PREDICTORS OF HIV AND PULMONARY, TB INFECTIONS AMONG. .. INJECTION DRUG USERS IN MOMBASA COUNTY, KENYA VALENTINE BUDAMBULA P97/13136/09 A THESIS SUBMITTED IN FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN PUBLIC HEALTH IN THE SCHOOL OFPUBLICHEALTH,KENYATTA UNIVERSITY DECEMBER, 2015 ENYA U IVE ii DECLARATION This thesis is my original work and has not been presented for a degree in any other University. SigruJ.ture~ .• ~· . VALENTINE BUDAMBULA Department of Community Health This thesis has been submitted for examination with our approval as University supervisors. Signature ..tk.:." . Date.91• (!~lf:p( r; . PROF. MICHAEL OTIENO KENYA TTA UNIVERSITY Department of Medical Laboratory Sciences - Signature . DR. TOM WERE MASINDE MULIRO ·UNIVERSITY OF SCIENCE AND TECHNOLOGY- Department of Medical Laboratory Sciences III DEDICATION This is a special dedication to my family members who have shaped my life. To my husband Joseph Luttson, thank you for your incalculable support, I salute thee. To my father, the late Aaron Leonid Budambula (BA, Makerere University), who believed in girl child education, Rest in Peace. To my mother Zerephata, the first lady of the Budambula dynasty and a great matriarch, I salute thee. And to my sister Prof. Nancy Budambula-Mong'are who is indeed a distinguished woman without limits, I salute thee. My special tribute to Mrs. Elizabeth Kipsang, my high school teacher (Kapsabet Girls High School), for her immense love and psychosocial support, I salute thee. My accolades to Mrs. Florence Lwoyelo (Director, Nurseconsult Services) for encouraging and empowering me to pursue post graduate education, I salute thee. IV ACKNOWLEDGEMENT I take this opportunity to thank God, my Ebenezer for thus this far He has brought me. I convey my sincere gratitude to my supervisors Prof. Michael Otieno and Dr. Tom Were whose support, patience and guidance have made this thesis to be successful. Further, I am grateful to the staff and management of Bomu Hospital especially Mr. Musa Mwamzuka, Ms. Ann Mwashumbe (both laboratory technicians), Ms Caroline Kai (TB clinic) and Dr. Aabid A. Ahmed (the Chief Executive Officer). I am deeply indebted to all the PWID in Mombasa who took their time to participate in the study, and to Mr. Nasser Ahmed, a rehabilitated former IDU and currently a community health worker who served as a link between the IDUs and 1. My sincere appreciation to research assistants Ms. Linet Makena and Ms. Nancy Odhiambo as well as to the NASCOP team hosted at Bomu especially Ms. Caroline Omeddo. My sincere gratitude goes to the Technical University of Mombasa (TUM) for both monetary (staff development and partial research funding) and non monetary support. I acknowledge the gui~ance I received from the then TOM director of research, Dr. Charles Matoka. This study was made possible through the funding received from the National Commission for Science, Technology and Innovation (NACOSTI) grant number NCST151003/065. To NACOSTI, thank you for making my dream come true. Since it is not possible to thank each and every individual, I am forever indebted to many who have contributed positively to this work both directly or indirectly through prayers, moral support and encouragement. To all the above I saY,Ahsante sana. vTABLE OF CONTENTS Declaration .ii Dedication Statement iii Acknowledgement .iv Table of Contents v List of Figures x List of Plates xi List of Appendices xii Abbreviation! Acronyms , .. . . . . . .. . .. . . . . . . . .. . . . . . . . . . .. . . . . . . . .. . .. . . . . . . . . xiii Definition of Terms xvii Abstract.. xviii CHAPTER ONE: INTRODUCTION 1 1.1 Background to the Study 1 1.2 Statement of the Problem .4 1.3 Research Questions 6 1.4 Null Hypotheses 6 1.5 General Objective 7 1.6 Specific Objectives 7 1.7 Justification , 7 1.8 Limitations 8 1.9 Conceptual Framework. 8 CHAPTER TWO: LITERATURE REVIEW IO 2.1 Over View on Drugs Abused by Participants 10 2.lJ Narcotics '" .11 2.1.1.2 Morphine and Codeine 12 2.1.1.3 Heroin 13 2.1.1.3.1 Effects of Heroin .16 2.1.2 Stimulants 17 2.1.2.1 Cocaine -." 17 2.1.2.1.1 Forms of Cocaine 18 2.1.2.1.2 Effects of cocaine .20 Vl 2. J .2.2 Khat 21 2.1.2.2.2 Effects of Khat.. 24 2.1.2.3 Nicotine 25 2.1.2.3.1 Effects of nicotine .28 2.13 Cannabinoids 29 2.1.3.1 Effects of Marijuana 33 2.1.4 Benzodiazepines .34 2.1.4.1 Effects Rohypnol ' .36 2.1.5 Alcohol. 37 2.1.5.1 Effects of Alcohol.. , 39 2.2 Socio-demographic Characteristics .40 2.3 Drug Use Patterns .48 2.4 Nutrition 53 2.5 Tuberculosis 58 2.6mv 61 2.6.1mv and Injection Drug Use 62 2.6.2 Hl V Subtypes: Global Outlook. 64 2.6.3mv Subtypes in Kenya .- 66 2.6.4 HlV Subtypes in the IDU population 67 2.7 Drugs and Immunity 68 2.8 Other Common Co-morbidities 69 2.8.1 Hepatitis B and C , 69 2.8.1.1 Hepatitis B 69 2.8.1.2 Hepatitis C 69 2.8.2 Tetanus 70 2.8.3 Dermatological disorders 70 2.9 Prevention and Management of Drug Use and Addiction 71 2.9.1 Demand Reduction 72 2.9..2Supply Reduction 72 2.9.3 Harm Reduction 73 2.9.4 Rehabilitation , 78 VII 2.10 Challenges 78 2.11 Conclusion 79 CHAPTER THREE: MATERIALS AND METHODS 81 3.1 Study Design 81 3.2 Variables 81 3.3 Target and Study Population 81 3.4 Study Site 81 3.5 Sample Size 84 3.6 Sampling Procedure 85 3.6.1 Respondent Driven Sampling , .85 3.6.2 Snowball Sampling 86 3.6.3 Makeshift Outreach Method 86 3.7. Data Collection Methods 87 3.7.1 Interview Schedule 87 3.7.2 Anthropometric Measurements 87 3.7.3 Tuberculosis Diagnostic Methods 89 3.7.3.1 Collection of Sputum 90 3.7.3.2 TB Sputum for Acid Fast Bacteria (AFB) Microscopy 90 3.7.3.3 Drug Susceptibility Testing , .- 91 3.7.4 Hl V Testing 93 3.7.4.1 Blood Collection " 93 3.7.4.2 RNAExtraction and Quantitation ofHIV-l Viral Load 94 3.7.4.3 Reverse Transcriptase-PCR 94 3.7.4.4 DNA Purification and Sequencing 95 3.7.5 Hematological Profile 96 3.7.6 CD4+ T Cell Enumeration 96 3.8 Vital Signs : 97 3.8.1 Body Temperature 97 3.8.2 Blood Pressure 97 3.9 Pilot Study 97 3.10 Inclusion Criteria '" 98 VlIl 3. J ) Exclusion Criteria 98 3.13 Ethical Consideration 98 3.14 Data Analysis 99 CHAPTER FOUR: RESULTS AND DISCUSSION IOI 4.1 TIle Social-demographic Characteristics and Sexual Practices of the PWID in Mombasa County '" .10] 4.2 Drug Use Patterns of my Infected and non Infected IDUs of Mombas a County ]09 4.3 Association of Socio-demographic, Sexual Practice and Drug Use Patterns in Relation to my Status 113 4.4 Nutritional Measures of the PWID in Mombasa County .117 4.5 The Prevalence of Pulmonary TB Infections among my Uninfected and Infected IDUs in Mombasa County .124 4.6 The HlV Subtypes that Cause my Infections in IDUs Living in Mombasa County , , .129 OlAPTER FIVE: CONCLUSION AND RECOMMENDA TIONS .......•........ ~132 5.1 Conclusion 132 5.2 Recommendations 133 5.3 General recommendations ] 37 5.4 Suggested Further Research 139 REFERENCES 140 APPENDICES ] 88 Appendix 1: Map of Kenya and Mombasa County 188 Appendix 2: Interview Schedule , , , .. , 189 Appendix 3: ERC Clearance 193 Appendix 4: Ministry of Health, Mombasa County Clearance .195 Appendix 5: Consent Form- English Version ] 96 Appendix 6: Consent Form- Swahili Version 197 Appendix 7.:PCR Protocol 198 Appendix 8: Work Plan 199 Appendix 9: Budget: Data Collection Costs 200 IX LIST OF TABLES Table 3.1: Critical concentrations of first-line drugs 92 Table 4.1: Socio-dernographic characteristics ofPWID in Mombasa, Kenya, 2012-2013 102 Table 42: Sexual practices ofPWID in Mombasa, Kenya, in2012-2013 103 Table 4.3: Drug use patterns among IDUs in Mombasa, Kenyan in 2012-2013 110 Table 4.4: Association of the socio-demographic characteristics, sexual . practices and drug use patterns in relation to IDUs Hl V status, . in Mombasa County 2012-2013 115 Table 4.5: Nutritional Status ofHIV-l infected and uninfected IDUs in Mombasa County, 2012-2013 .119 Table 4.6: Predictors of malnutrition in HlV-I infected and uninfected injection drug users in Mombasa County, 2012-201 120 Table 4.7: Tuberculosis prevalence rate among PWID in Mombasa County, 2012-2013 125 Table 4.8: Predictors of tuberculosis among IDV-l uninfected IDUs in Mombasa County, 2012-2013 .126 Table 4.9: Predictors of tuberculosis among HlVvl infected PWID in Mombasa County, 2012-2013 .127 Table 4.10: HIV subtypes circulating in Mombasa IDUs 130 xLIST OF FIGURES Figure 1.1: The Conceptual Framework 9 Figure 2.1: Chemical structure of heroin (diacetylmorphine) , 13 Figure 2.2: Chemical structure of Cocaine 18 Figure 2.3: Chemical structure of Cathinone , 22 Figure 2.4: Chemical structure ofCathine 24 Figure 2.5: Chemical structure of Nicotine 27 Figure 2.6: Chemical structure of Tetrahydrocannabinol.. .30 Figure 2.7: Chemical Structure of Rohypnol (Flunitrazepam) .35 Figure 2.8: Chemical structure of Ethyl Alcohol .38 Figure 3.1: Map of Kenya and Mombasa County , 83 XI LIST OF PLATES Plate 2.1: Opium poppies (Papaver somniferumj 12 Plate 2.2: Coca Plant (Erythroxylum coca) .l9 Plate 2.3: Khat Plant (Catha edulis) .23 Plate 2.4: Tobacco plant (Nicotiana tabacum) .26 Plate 2.5: Marijuana Plant (Cannabis sativa Linneaeus) .31 XII LIST OF APPENDICES Appendix 1: Map of Kenya and Mombasa County J 99 Appendix 2: Interview schedule 200 Appendix 3: Ethical review clearance .204 Appendix 4: Ministry of Health clearance .206 Appendix 5: Consent form- English version 207 Appendix 6: Consent form- Swahili version 208 Appendix 7: HIV testing protocol.. , 209 Appendix 8: Work plan 210 Appendix 9: Budget 211 AFB AIDS ART ARV BMI BMT CDC CESAR CI CMI CNS CRF DEA DFSA DST ECDC EMCDDA ERC FANTA FAO FDA GABA XlII ABBREVIATION/ACRONYMS Acid Fast Bacteria Acquired Immune Deficiency Syndrome Antiretroviral Therapy Antiretroviral Body Mass Index Buprenorphine Maintenance Treatment Centre for Disease Control Centre for Substance Abuse Confidence Interval Cell Mediated Immunity Central Nervous System Circulating Recombinant Forms Drug Enforcement Administration Drug Facilitated Sexual Assault Drug Sensitivity Test European Centre for Disease Prevention and Control European Monitoring Centre for Drugs and Drug Addiction Ethics Review Committee Food and Nutrition Technical Advisor Food and Agriculture Organization Food and Drug Administration Gamma aminobutyric acid GABAA HBC HBV HCV mv IBM ICHRA IDSA IDU XIV Gamma-aminobutyric acid-A High-Burden Countries Hepatitis B virus Hepatitis C Virus Human Immunodeficiency Virus International Business Machines International Centre for Health Interventions and Research in Africa Infectious Diseases Society of America Intravenous Drug Use! Injection Drug Use IDUs Intravenous Drug users! Injection Drug Users lliRA International Harm Reduction Association IQR Inter-Quartile Range IRIN Integrated Regional Information Networks KAIS Kenya AIDS Indicator Survey KFSSG Kenya Food Security Steering Group KNBS Kenya National Bureau of Statistics LJ Lowenstein-Jensen UvlIC Low and Middle Income Countries MDR Multidrug Resistant METHOIDE Methamphetamine and Other Illicit Drug Education MMT MOH NACADA Methadone Maintenance Treatment Ministry of Health National Agency for the Campaign against Drug Abuse NACC NASCOP NCDs NIDA NIH NMDA NPlN NTFIC NUUA OR OST PLWA PLVlHA PWID RDS SA SAMHSA SIF SIV SNEP SPSS SW SSA xv National AIDS Control Council National AIDS and STI Control Programme Non Communicable Diseases National Institute on Drug Abuse National Institutes of Health N-methyl-D-aspartate National Prevention Information Network National Tobacco Free Initiative Committee New South Wales' Drug User & AIDS Association's Odds Ratio Opioid Substitution Treatment People Living With AIDS People Living With mV/AIDS People Who Inject Drugs Respondent Driven Sampling South Africa Substance Abuse and Mental Health Services Administration Supervised Injecting Facilities Simian Immunodeficiency Virus Syringe and Needle Exchange Programme Statistical Programme for Social Scientists Sex Worker Sub Saharan Africa TB VCT THC TISS UNAIDS UNODC USA USAID USDA WFP WHES WHO WHR XVI Tuberculosis .Voluntary Counseling and Testing Tetrahydrocannabinol Tata Institute of Social Sciences Joint United Nations Programme on HlV and AIDS United Nations Office on Drugs and Crime United States of America United States Agency for International Development United States Department of Agriculture World Food Programme World Hunger Education Service World Health Organization Waist to Hip Ratio XVll DEFINITION OF TERMS Intravenous/injection drug user: A person who uses recreational drugs that are administered via the vein. The two terms have been used interchangeably in this study. Blood loaning: A practice in which an IDU who cannot afford to purchase heroin injects the blood of another IDU who recently injected, in the belief that the blood contains heroin and thus can prevent withdrawal symptoms. Cooker: Any small container, usually a spoon or a bottle cap, used to dissolve the injectable drug, most often in powder form. Drugs: A chemical, often an illegal substance that causes addiction, habituation, or a marked change in consciousness. Flush-blood: the practice of deliberately drawing blood into a syringe and reinjecting the blood-drug mixture. Recreational drug use: The non medicinal use of a substance (legal, controlled, or illegal) with the intention of enhancing life (increasing euphoria, blocking unhappy memories, or creating pleasure). Undernutrition: Insufficient provision of energy and nutrients, such as good quality protein with an adequate balance of essential amino acids, vitamins and minerals, and an inability to meet the requirements of the body to ensure growth, maintenance, and specific functions. Serosorting: A decision to share or not to share injection equipment based on the partner's Hl V status. Sex fur police protection: Occurs when vulnerable groups like injection drug users offer sex to policemen in order to avoid being arrested. XVlll ABSTRACT Both injection drug use (IDU) and HfV are major global public health problems. The link between IDU and Hl V arises from high risk injecting and precarious sexual behaviour. Data on the socio-demographics, drug use patterns, tuberculosis (TB) prevalence, nutritional status and Hl V sub-types is inadequately documented in Kenyan IDUs. This cross sectional study sought to determine the factors that predict HIV and Pulmonary TB among IDUs in Mombasa County. At Bomu Hospital 371 IDUs (HIV infected, n= 157) were enrolled using respondent driven sampling, snowball and make shift methods. The study was approved by Kenyatta University Ethics Review Committee and conducted according to the Helsinki declaration. Written informed consent was obtained from each participant. Structured interview schedule was used to capture the socio-demographic characteristics and drug use patterns. Nutritional status determined using anthropometric indices. One spot and two early morning sputa were obtained on three consecutive days for TB microscopy and culture. HIV status was established by two parallel rapid antibody tests. mV-I pro-viral DNA was extracted from plasma, amplified using gag-pol primers and amplicons were sequenced from Stanfurd HIVdb database. Using SPSS version 20, Pearson's Chi-square, Fisher's exact, Mann-Whitney tests and binary logistic regression were utilized as appropriate. Socio- demographic predictors of Hl V-1 infection were being female, sex work or working in entertainment venues, having more than five sexual partners, sex without a condom, sex for police protection and exposure to SIl, all at P <0.0001. In addition marital separation and sex for drugs increased the odds ofHIV infection at P <0.001. Although heroin was the most common drug at 81.7%, a vast majority of IDUs were polysubstance users. Use of Rohypnol for recreational purposes was rampant at 55.3%. Alcohol, khat and cocktail consumption predicted higher odds of Hl V infection at P <0.0001,0.007 and 0.004 respectively. On the other hand, any use of heroin or cocaine, having injected for more than three years as well as polydrug use of heroin or cocaine alongside any other four substances were predictive of Hl V infection, all at P <0.0001. High levels of undernutrition were reported in this sub-population with Hl V infected IDUs faring worse on height and MUAC at P <0.001 and P <0.0001 correspondingly. Additionally, having a CD4 count of less than 500 cells/ul. increased the odds of undernourishment. A CD4 of less than 500 cells/ul. and or BMJ equal or below 18.5 kglm1augmented the odds of contracting TB irrespective of HIV status. Nonetheless mv infected IDUs were at a higher risk of TB infection than the uninfected at P <0.0001. There were nine Hl V sub-types including their recombinant forms circulating namely AI, A2_AG, AID, A2C, ABDU, B, C, D and G with Al being the most dominant. This study has demonstrated the association between drug use, TB and Hl V infections, therefore there is need to integrate H1V and TB screening as well as nutrition supplementation in drug prevention and management programmes. These findings will influence the planning and resource allocation for targeted intervention among IDUs both at National and County Government levels in order to mitigate the impact of drug abuse as well as achieve the MDGs one to six. In addition, continuous surveillance of themv and TB epidemiology is imperative. These interventions are key to Kenya's achievement of zero new H1V infections and AIDS-related deaths initiative. CHAPTER ONE: INTRODUCTION 1.1 Background to the study Injection Drug Users (IDUs) also known as People Who Inject Drugs (PWID) are among the groups most affected by the Human Immunodeficiency virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) since the epidemic began almost over three decades ago. The link between injection drug use and HIV arises from sharing of needles, syringes, water mixing spoons, practicing flashblood and engaging in high risk sexual behaviour (McCurdy et af., 2010; Uuskula et al., 2010; Ulibarri et aI., 2011; CDC, 2012a; NASCOP, 2012a). Consequently, injection drug use is one of the most efficient avenues of transmitting HIV and other blood-borne pathogens like Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV), that spread rapidly through IDU populations and their sexual partners (Cavlek et aI., 2011; Orsetti et aI., 2013; WHO,2013a). Although injection drug use has previously been perceived as a European and Asian problem, evidence indicates that drug use is on the increase on the African continent. In particular the coastal cities of Nigeria, Tanzania, Kenya and South Africa are the most affected (UNODC, 20 13a). Due to the illicit nature of drug use and the associated stigma, it is difficult to obtain the exact data on PWID (Needle et al., 2005) however, Mombasa is estimated to have an IDU population of about 26,000 persons (IRIN, 2012; NASCOP, 2012a). Previous studies carried out and reports show that there is steady increase of injection drug use in Kenya (Odek-Ogunde et al., 2003; Beckerleg and Hundt, 2004; Ndetei,.2004; Needle et al., 2005; Beckerleg et al., 2006; Deveau et al; 2006). Currently 2coastal towns (Mombasa, Lamu and Malindi) as well as Nairobi are the most affected (IRIN, 2012; NASCOP, 2012a). Globally the most common injectable drugs are amphetamines, opioids (including, heroin) and cocaine (UNODC, 2011a). In Kenya, the commonly used injecting drugs include heroin, cocaine and methamphetamine (NACADA, 2012). In Mombasa, heroin has been a street drug for over 30 years. During the 1980s, heroin (the brown sugar version) quickly spread from Mombasa to smaller coastal towns like Malindi and Watamu (Beckerleg et al., 2006). Brown sugar was mostly used through inhalation of its vapour. In 1998, the injectable heroin (white crest) started to replace brown sugar. Hence by the late 1990s, heroin users were shifting from brown sugar to white crest (Beckerleg, 2004). High risk injecting trends and sexual behaviour has been extensively documented among PWIDs. These include sharing of syringes, needles and water mixing spoons, practicing of flashblood, blood loaning, unprotected sex with partners of unknown HIV status and anal sex (McCurdy et al., 2006; McCurdy et al., 2010; Cavlek et al., 2011). Additionally, multiple sexual partnerships, sex for drugs, group sex, sex for money to buy drugs or for drugs, sex for police protection is well documented in this sub-population (Parry et al., 2008; Williams et al., 2009; Brodish et aI., 2011; Majidpour et aI., 2012). Moreover, most PWID face drug-driven impaired judgment which reduces their negotiation power for safer sex (McCurdy et al., 2010; Uuskula et aI., 2010; Ulibarri et al., 20] 1; NASCOP, 20 12a). As a result the prevalence rate of HIV among IDUs globally is alarmingly high. 3In Kenya for instance, previously the HlV prevalence among IDUs ranged between 43% - 49% (Deveau et al., 2006; Needle and Zhao, 2010) as opposed to the then national adult prevalence of 7.1 % (KAIS, 2007). Currently this prevalence has come down to 18% but remains high when compared to the national adult prevalence of 6.2% (NASCOP, 2013). Drug abuse has been linked to poor nutritional status attributed to impaired nutrient absorption or altered appetite or metabolism (Hendricks et al., 2010; Vogenthaler et al., 2010; Tang et al., 2011). Undernutrition increases the risk of Hl V transmission or acquisition by compromising ones immune status as well as gut and genital mucosal integrity (Weiser et al., 2008; Olsen et al., 2014). Drug use, HfV infections and undernutrition lower immunity thus increasing the risk of reactivating latent tuberculosis (TB) to active TB infection in addition to exacerbating progression of HIV to AIDS (Drake, 2010; Shalini et al., 2012; Mamani et 01.,2013; Padmanesan et of, 2013). Both IDUs and non-IDUs are at a risk of developing TB due to the overlap of epidemiological and social factors associated with both drug use, Hl V and TB (Deiss et al., 2009; CDC, 2012d; Ruutel et 01.,2012). Globally, nearly 2 billion people are infected with TB. People living with mY/AIDS (PLWHA) are more likely to develop active TB in a given year than HlV sero-negative persons due to their weakened the immune system (USAID, 2013; WHO, 2013a). Currently about 34 million people are living with HIV and at least one third are co-infected with TB. Kenya ranks thirteenth on the list of twenty two TB High Burden Countries (HBCs) in the world and has the fifth highest burden in Africa, These 22 HBCs account for 80% of the global TB burden (WHO, 2013b). In 4Kenya, the prevalence ofTB among HIV sero-positive patients was 44% in 2009 (WHO, 2009a; CDC, 2011a) and presently it ranges between 38.3% and 39% (MOH, 2012; MOH, 2013). The HIV-TB co-infection is a major problem in Sub-Saharan Africa (SSA) and is commonly called the deadly duo. TB infections enhance Hl V replication at the same time accelerates Hl V progression to AIDS. The overlap of HIV- TB co-infection with MDR- TB and extensively drug-resistant TB presents a tremendous challenge and threatens progress in controlling TB and HIVI AIDS as well as in eliminating the mortality associated with these diseases (USAID, 2013; WHO, 2013b). In Kenya, out of the total samples received and processed, 225 were resistant to both Isoniazid and Rifampicin (MOH, 2012). Elsewhere, outbreaks of drug-susceptible and MDR-TB have been reported among PWID (Deiss et al., 2009) but this data is scanty in Kenya. 1.2 Statement of the Problem Despite the fact that previous studies have shown that PWID are more predisposed to HIY than the general population, injection drug use remains a major public health challenge. Approximately, there 16 million PWID globally out of which 3 million are HIV infected. Globally, injection drug use accounts for at least 10% of new HIV infections (Riley et al., 2005; WHO, 2013a). The HIV prevalence among PWIDs in Kenya estimated to be 18.3% is by far much higher than the national prevalence of 6.2% (NASCOP, 2008, NASCOP, 2013, NASCOP, 2014). In addition, an estimated 4% of new my infections are linked to injection drug use with Coastal Kenya leading at 17% 5(NASCOP, 2008). The high risk of HIV acquisition and transmission in PWID largely arises from unhygienic injecting and precarious sexual practices. Although injection drug use is a global problem, Africa is a more recent victim as it acts as a conduit of drugs from South America en route to Europe and Asia. In the process some of the drugs find their way into the local market due to laxity in enforcing drug related laws as well as corruption (UNODC, 2013a). In Kenya, more so Mombasa, drug abuse has been linked to the proximity of the port, corruption, poverty, pouching, radicalization and breakdown in family structure. People who inject drugs like other drug users are undernourished. Undernourishment arises from food insecurity, misplaced priorities, reduced food intake and mal- absorption(Anema et aI., 2010 and Tang et al., 2011). Under nutrition on its own leads to reduced CD4 and CD8 T-lymphocyte number (Drake 2010). This impairs cell-mediated immunity (CM!) which is the principle host defense against TB (Shalini et al., 20]2). Undernutrition irrespective of the cause increases the risk of opportunistic infections and exacerbates progression from HIV to AIDS (Cegielski et al., 2010; Padmanesan et at, 2013). Due to overlap of epidemiological factors like poverty and overcrowding, PWID are therefore at a greater risk of contracting both HIV as well as TB infections (Deiss et aI., 2009; Ruutel et af., 2012). In addition, criminalization of drug use has led to marginalization of IDUs. Therefore, IDUs who are infected with either HIV or TB or both are less likely to access healthcare 6and adhere to respective drug regiments. Poor adherence reduces efficacy of medicinal drugs at the same time increases the probability of developing multi-drug resistance (Muture et aI., 2011; CDC, 2012a; ELF, 2012; Dutta et al., 2013). In this regard, the IDU, HIV, malnutrition and TB burden is immense as well as complex. Elsewhere, determinants of HIV and TB among PWID have been identified as socio- demographics, drug use patterns, low BMl and low CD4. However, these factors are scantly documented in the Kenyan context. Unless these factors are identified and dealt with through targeted interventions, Kenya may not achieve most of the sustainable development goals. 1.3 Research questions 1. What are the social-demographic characteristic of an IDU population? 2. What are the drug use patterns ofIDUs? 3. What is the nutritional status ofIDUs? 4. What is the TB prevalence rate in IDUS? 5. What are the HIV subtypes causing HIV infections in IDUs? 1.4 ,Null hypotheses I. Social-demographic characteristics are similar between HIV infected and uninfected IDUs. 2. Drug use patterns are invariable between HIV infected and uninfected IDUs. 3. Nutritional status is incomparable between HIV infected and uninfected IDUs. 74. TB infection rate does not vary with HlV infection ill IDUs. 5. Single HIY subtype do not cause HIY infection in IDUs. 1.5 General objective To determine the factors that predicts HIY and Pulmonary TB infections among lDUs in Mombasa County. 1.6 Specific objectives 1. To describe the social demographic characteristics ofIDUs in Mombasa County. 2. To determine drug use patterns of the IDUs in Mombasa County. 3. To assess the nutritional status of the lDUs in Mombasa County. 4. To establish the TB prevalence in the IDUs in Mombasa County. 5. To identify the HIY subtypes causing HIY infections in the IDUs in Mombasa County. 1.7 Justification Due to scanty information on the impact of injection drug use on the upsurge of HIY infections and related co-morbidities among the PWID in Kenya, the study was necessary in order to identify the predictors of HIY and TB among IDUs. This was further necessitated by the fact that risk of TB infections among IDl!s is due to an overlap of epidemiological and social factors associated with both drug use, HIV and TB. In addition, the adequate control of the HIV and TB syndemic in IDUs, non-IDUs and the non drug users is the key to the long-term TB elimination target set for 2050. It was 8therefore important to delineate the factors that predict HIV and TB infections in the IDU subpopulation by establishing the epidemiology of HlV and TB among IDUs in Kenya. Findings of this study will contribute to planning and resource allocation for targeted intervention among IDUs both at National and County Government levels in order to mitigate the impact of drug use as wellas achieve the MDGs one to six. 1.8 Limitations Due to stigma and the illegal nature of drug use, drug users in Kenya are hidden and were difficult to reach. It was even more difficult to access and enroll female IDUs. Tills limitation was overcome by working closely with various psychosocial support groups of sex workers. Since the study design was cross-sectional, it is difficult to know the time- point of HIV acquisition. A longitudinal approach would have yielded detailed information on sexual practices and drug use patterns. Drug llse patterns were self- reported as no urinalysis was carried out, hence the complete set of injection and non- injection drugs used by the study participants are unknown. Furthermore, self-reported exposure to STIs and sexual practices may be confounded by recall bias. 1.9 Conceptual framework Injection drug use in Kenya has become increasingly recognized as a public health problem, particularly in light of its association with needle sharing and undernutrition. IDUs are vulnerable to undernutrition, overcrowding and poverty. These increase the risk for both TB and HIV/AIDS infections. Most IDUS on one hand are less likely not to adhere to both antiretroviral and anti TB drugs while on the other hand they are more 9likely to engage in high risk sexual behaviour such as sex work (either heterosexuality or homosexuality or bisexuality or group). Consequently, the prevalence rate oflITV and TB in the IDU population is significantly higher than that of the general population. These factors are illustrated in Figure 1.1 Independent variables High risk injecting & sexual nractices Impaired judgment Mono or Polysubstance Use STIs Female Gender Dependent variables HIV & Co-morbidities e.g. HBV,HCV&TB Intermediate variables Dependent variable TB, Faster disease progression & high mortality rate Under Nutrition, low CD4 count & poor adherence Figure 1.1 Conceptual Framework (Source: literature review) 10 CHAPTER TWO: LITERATURE REVIEW 2.1 Over View on Drugs Abused by Participants Drug abuse refers to the harmful or hazardous use of psychoactive substances for mood- altering purposes. 1t can also be defined as the use of illicit drugs or the abuse of prescription or over-the-counter drugs for purposes other than those for which they are indicated or in a manner or in quantities other than directed (Medline Medical Encyclopedia, 2014; WHO,2014a). Addiction is the repeated use of a psychoactive substance or substances, to the extent that the user (referred to as an addict) is periodically or chronically intoxicated, shows a compulsion to take the preferred substance (or substances), has great difficulty in voluntarily ceasing or modifying substance use, and exhibits determination to obtain psychoactive substances by almost any means (WHO, 2014a). It can also be defined as a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences. It is considered a brain disease because drugs change the brain, its structure and how it works. These changes can be long lasting and harmful, often leading to self-destructive behaviours (NIDA, 2012). Based on these definitions, the study focused on recreational drugs in the context of use of illegal substance(s) and pharmacological preparation (s) that is (are) taken voluntarily for personal pleasure or satisfaction rather than medicinal purposes. In addition the term drug and substance have been used as synonyms. Borrowing from both National Institute on Drug Abuse (NIDA) and Drug Enforcement Administration (DEA) recreational drugs 11 classification systems, drugs in this study were discussed under following topics: narcotics, stimulants, cannabinoids, depressants and alcohol. Dissociative anesthetics, hallucinogens, inhalants and anabolic steroids have not been discussed as use of these drugs was not reported by the participants (DEA 20]]; NIDA, 20]2). 2.1.1 Narcotics The word narcotic is derived from the Greek word narke (meaning stupor) and is used.to descnbe opium, opium-based derivatives and synthetic substitutes. They include opium, heroin, morphine, codeine and other opioid derivatives (DEA Museum, 2012; Opium, 2014). Narcotics have been useful in the practice of medicine for relief of intense pain since they are the most effective analgesics known. Although narcotic substances are available for medical use like in treatment of pain, epilepsy and opioid dependence, their access is controlled and limited (WHO, 2010). With respect to the context of this study, the literature review was restricted to recreational use of heroin but with a brief introduction to opium and morphine. Opium, the first opioid, is derived from the sap of opium poppies (Papaver somniferumj and is obtained as the dried milky juice (Plate 2.1). Its use dates back to around 3400 BC among the Sumarians who lived in lower Mesopotamia (now western Iraq). By 1300 BC, the Egyptians were cultivating poppies for the production of opium. The opium they produced was an extremely popular commodity that they traded it as far away as Greece and central Europe (Rosso, 2010; Flaseha, 2011). During the 18th century physicians in the United States of America (U.S.A) used opium as panacea (Hays, 2011). 12 Plate 2.1: Opium poppies (Papaver somniferum) Source: Plant & Flower Encyclopedia (Botany.com) 2.1.1.2 Morphine and Codeine In 1805, morphine was used as a cure for opium addiction smce its addictive characteristics were not known. Morphine was used widely as a painkiller during the American Civil War and many soldiers became addicted. Codeine, a less powerful form of opium but can be synthesized was first isolated in 1830 in France by Jean-Pierre Robiquet to replace raw opium for medical purposes. It was used mainly as a cough remedy (DEAMuseum, 2012; UNODC, 2014a). 13 2.1.1.3 Heroin In 1874, German scientists developed a formula for a painkiller that they thought would be less addictive than morphine. They simply added two acetyls to morphine to form diacetylmorphine (commonly known as heroin). It was produced and marketed commercially in 1898 by Bayer Pharmaceutical Company as a panacea. Heroin is also converted into morphine once in the body. When used in medicine, it is typically used to treat severe pain, such as that resulting from a heart attack or a severe injury (Bergstrom, 2002; Scott, 2012). The chemical structure of heroin is illustrated in figure 2.1. HC-C-O 3 II o Figure 2.1: Chemical structure of heroin (diacetylmorphine) Source: EMCDDA, 2013a Currently United Nations Office on Drug and Crime (UNODC) estimates that there are between 12 and 21 million opiate users worldwide. Globally heroin is the most commonly used opiate. Heroin is manufactured from opium poppies cultivated in four primary source areas namely South America, Southeast and Southwest Asia and Mexico. 14 Europe and Asia have been reported as the key opiate consumption markets. Afghanistan remains the highest producer of opium with an estimated acreage of about 123,000 ha in 2012, that is74% of global cultivation (UNODC, 2013a). Although heroin is not cultivated in Africa, it remains the most commonly used illicit injection drug in Tanzania and Kenya (Ross et a/., 2008; Brodish et al., 201 I; Ratliff et al., 2013). Heroin is distributed in three forms namely brown, white and black tar heroin. It can be injected into a vein ("mainlining") or a muscle, smoked in a water pipe or standard pipe, mixed in a marijuana roll or regular cigarette, inhaled as smoke through a straw ("chasing the dragon,") or snorted as powder. It can also be injected under the skin also known as skin popping (Ciccarone, 2009; NIDA 20 13a; Drug policy Alliance, 2014). Brown heroin also known as brown sugar is pr.oduced mainly in the Golden Crescent (Afghanistan, Pakistan and Iran). It is less refined and burns at a lower temperature than white heroin making it ideal for smoking. When smoking, a small amount of heroin is placed on a piece of silver foil and heated from below. The heroin turns into a liquid and gives off a curl of smoke. This curly smoke is inhaled through a rolled tube of paper or straw, a practice referred to as chasing the dragon (Ciccarone, 2009; CESAR, 2013; NUDA, 2014; UNODC, 2014b). White heroin is the most refined heroin often referred to as grade four heroin. It is produced mainly in the Golden Triangle (Burma, Laos and Thailand). The process of preparing heroin for injection can be done either heating heroin mixed with water in a 15 spoon over a flame ("cooking"). Alternatively it can be by dropping the heroin powder with water directly into a syringe and then applying flame from a lighter directly to the syringe (CESAR, 2013; Ciccarone, 2009; NUUA, 2014; UNODC, 2014b). Black tar heroin is sticky like roofing tar or hard like coal. It is predominantly produced in Mexico and sold in areas west of Mississippi River. The dark color associated with black tar heroin results from crude processing methods which leave behind impurities. This impure heroin is usually dissolved, diluted and injected (Maxwell and Spence 2008; Dickson et al., 2010; NIDA 2014). Black tar heroin use among PWID has been linked to an increased number of cases of wound botulism, tetanus and necrotizing soft-tissue infections due to Clostridia (Kimura 2007; Yuan, 2011). Those who inject heroin use a set of paraphernalia like hypodermic needles, small cotton balls, spoons or bottle caps for heating or liquefying the drugs and a "tie-off" that the user wraps around their arm to make the veins protrude. Paraphernalia for sniffing or smoking include razor blades, straws and pipes (EMCDDA, 2013a; Palmateer et al., 2014). Following injection, heroin crosses the blood-brain barrier within 20 seconds, with almost 70 % of the dose reaching the brain. Once heroin enters the brain, it is converted tomorphine and binds to opioid receptors. There are three main opioid receptors: delta, kappa and mu. They occur throughout the central nervous system (CNS), in some sensory nerves, on mast cells and in a few gastrointestinal tract (GIT) cells. Opioid receptors are alsolocated in the brain stem which is important for vital processes like breathing. blood pressure and arousal (EMCDDA, 2013a; CESAR, 2013; Feng et al., 2012). 16 2.1.1.3.1 Effects of Heroin Apart from analgesia, positive effects of diamorphine include drowsiness, euphoria and a sense of detachment. Negative effects include respiratory depression, weakened immune system, nausea, vomiting and decreased motility in the gastrointestinal tract. Moreover, heroin use leads to cough reflex suppression, hypothermia, tooth decay, inflammation of the gums, constipation, muscular weakness, partial paralysis, memory loss, impaired intellectual performance, introversion, depression as well as pustules on the face (Blum et al., 2013; EMCDDA, 2013a, NlDA, 2013b). Besides, heroin addiction has been linked to reduced sexual capacity, menstrual disturbance in women, inability to achieve sexual orgasm (in both women and men), drug induced anorexia, insomnia and coma (Schmidt et al., 2013; UNODC 2014c). Long term effects include tolerance, physical dependence and overdose. Heroin is associated with far more accidental overdoses and fatal poisonings than any other scheduled substance (Bang-Ping, 2009; Chekuri, 2011; Cioe et al., 2013; EMCDDA, 2013a; NIDA, 2013b). Sinceheroin is addictive, sudden cessation of use in tolerant subjects leads to withdrawal syndrome also known as cold turkey. This may occur within 6 to 24 hours of discontinuation of the drug. However time frame can fluctuate with the degree of tolerance as well as the amount of the last consumed dose. Withdrawal symptoms include coldsweats, general malaise, anxiety, depression, akathisia, priapism and extra sensitivity of the genitals in females (Kenny, 2009; NIDAb, 2013). Further, excessive yawning or sneezing, cramps, watery eyes, rhinorrhea, insomnia, myalgia, bone aches and chills have JCEriYA A U IV•..••ul 17 been reported. Nausea, vomiting, diarrhea, fever, cramp-like pains and involuntary spasms in the limbs are also common (EMCDDA, 2013a; Hartney, 2014). 2.1.2 Stimulants Stimulants are drugs that excite any bodily function through stimulation of the brain and central nervous system. They include cocaine, amphetamine, methylenedioxy- methamphetamine (MDMA), methamphetamine and methylphenidate. This study focused on cocaine, khat and nicotine. 2.].2.1 Cocaine Coca is one of the oldest and most potent stimulants of natural origin. The ancient Incas in the Andes chewed coca leaves to get their hearts racing and to speed their breathing in order to counter the effects of Jiving on thin mountain air as far back as 3000 BC Natives in this region chewed or brewed coca leaves into tea for refreshment and to relieve fatigue similar to the customs of drinking tea or coffee (Gonzales, 2010; DEA Museum, 2012). Coca did not find use in Western medicine until the late 19th century when American drug companies began to research on new medicines (Gonzales, 2010; Gootenber, 2010; DEA Museum, 201.2). It was first extracted from coca leaves in 1859 by German chemist Albert Niemann. Later pure cocaine was isolated in the 1880s and used as a local anesthetic in eye surgery. Many of its therapeutic applications are now obsolete due to the development of safer drugs (Gootenber, 2010; Rankin, 2010). 18 Cultivation of coca is concentrated in Colombia, Peru and Bolivia. In 2011, the UNODC estimated that the area under coca cultivation in 2010 amounted to 149 000 hectares (UNODC, 2011a). Erythroxylum Erythroxylum coca (Plate 2.2) is the most popular species in South America (Plowman, 2008; Hirst, 2014). Cocaine consignments to Europe appear to be transited through Argentina, Brazil, Ecuador, Venezuela and Mexico. In recent years, alternative routes through West Africa have been detected. Coastal cities of East Africa are some of the most provenance regions (Parry et al., 2009; Peltzer et al., 2009; EMCDDA and Europol, 2010; NACADA, 2010). 2.1.2.1.1 Forms of Cocaine Cocaine (C)7H2IN04), whose chemical structure is shown in Figure 2.2 is usually distributed in three forms. These are cocaine paste, the salt form (cocaine hydrochloride also known as white crystalline powder) and freebase cocaine or crank: cocaine which is a waxy solid that may be white, yellowish, or greyish. The physiological and psychoactive effects of cocaine are similar regardless of its form (NIDA, 20 l3c; Watson 2014). o "C-O-CH3 oO-~-{) Figure 2.2: Chemical structure of Cocaine Source: EMCDDA, 2013b 19 Plate 2.2: Coca Plant (ErydlToxylum coca) Source: DEA Museum, 2012 Cocaine paste also known as pasta basica de cocaina is the first crude extraction product of coca leaves thus it is the least pure form of cocaine. The leaves are mashed with an alkali like sodium bicarbonate and kerosene and then sulfuric acid or sometimes potassium permanganate. The result is off-white or light-brown paste containing 40 to 70 percent cocaine, as well as other alkaloids, benzoic acid, kerosene residue and sulfuric acid (NIDA, 2013c; UNODC, 2013a; Watson 2014). 20 Powdered form of cocaine (cocaine hydrochloride) is more pure than paste cocaine. It can either be snorted or dissolved in water and injected into the bloodstream. It is odourless and cannot be smoked because it is mostly destroyed by heat (Andreasen et aI., 2009; EMCDDA, 20] 0; Hall et al., 2012; NIDA, 2012; Watson 20]4). Crank cocaine (freebase cocaine) was first developed during the cocaine boom of the 1970's. It remains the most popular drug, as it is inexpensive to produce thus cheaper to purchase than powder cocaine. Powder cocaine when chemically changed to create crank cocaine can be smoked or snorted but cannot be injected as it is not water soluble. It is called "crack" because of the crackling sound it makes when smoked or rock (from forms ofsmaJl white oryellowish rocks) and is the purest form of cocaine (CESAR, 2013; NIDA, 20I3c). Cocaine irrespective of the version is a CNS stimulant that increases levels of dopamine in brain circuits regulating pleasure and movement. Normally, dopamine is released by neurons in these circuits in response to potential rewards. It is then recycled back into the cell that released it thus shutting off the signal between neurons. Cocaine prevents the dopamine from being recycled causing excessive amounts to build up in the synapse. This amplifies the dopamine signal and ultimately disrupts normal brain communication. It is this flood of dopamine that causes cocaine's characteristic euphoria (Blaylock et aI., 2011; Blaylock et al., 2012; NIDA, 2013c; Xiea, 2014). 2.1.2.1.2 Effeds of cocaine Cocaine produces euphoria, appetite suppression, altered metabolism, agitation, anxiety, constricts blood vessels, irregular menses in women, increased energy, mental alertness, 21 tremors, irritability, aggressiveness and paranoia (Dinis-Oliveira, 2012; NIDA, 20 13c). It also triggers hypertension, hyperthermia, tachycardia, arrhythmias, acute coronary syndrome, myocardial infarction, increased risk of coronary diseases, cardiomyopathy, stroke and psychosis (Ersche et al., 2010; CESAR, 2013; EMCDDA, 2013b) Repeated use of cocaine leads to tolerance, addiction, loss of the sense of smell, nosebleeds, severe bowel gangrene as a result of reduced blood flow, Fournier's gangrene, priapism and undernutrition (Ersche et al., 2012a; Khan et la., 2013; Nidimusili et aI., 2013). Cocaine is more dangerous when combined with other drugs. For example, the combination of cocaine and heroin (known as a speedball if injected or moonrocks when snorted) carries a particularly high risk of fatal overdose (NIDA, 2013c; Trujilloa, 2011). The withdrawal symptoms associated with cocaine are unlike those related to opiates. The body does not become physiologically dependent, but they may produce a state of acute unease or discomfort, enhanced anxiety, depression, fatigue, insomnia and craving for more cocaine (El Hage et al., 2012; UNODC, 2014d). 2.1.2.2 Khat Khat is a stimulant drug derived from Catha edulis, a native plant of East Africa and southern Arabia. It is also known by street names like qat, quat, gat, jaad, chat and miraa. Most- of the effects of chewing khat come from the two phenylalkylamines (cathinone and Cathine) which are structurally related to amphetamine (EMCDDA, 2011a; Brenneisen et al., 2012). Khat (Plate 2.3) is not scheduled under the Controlled Substances Act of the United States, but since cathinone, is a Schedule I drug (a 22 controlled substance with no recognized therapeutic use), the Federal Government considers Khat use illegal (NIDA, 2013). In Kenya, khat has been listed as a drug by the National Authority for the Campaign against Alcohol and Drug Abuse (NACADA, 20]3). The principal active component in khat is S-cathinone, otherwise known as alpha aminopropiophenone or S-(-)-2-amino-l-phenyl-l-propanone (Figure 2.3). Cathinone is labile and is transformed within a few days of harvesting to a dimer (3,6-dimethyl-2,5- diphenylpyrazine). It is considered a natural amphetamine as it produces sympathomimetic and central nervous system stimulation analogous to the effects of ampbetamine (Waleed, 2011; Wabe et al., 2012; CESAR, 2013). o Figure 2.3: Chemical structure of Cathinone Source: EMCDDA, 20l3c 23 Plate 2.3: Khat Plant (Catha edulis) Source: DEA Museum, 2012 Cathine (a norpseudoephedrine and phenylpropanolamine), is a further psychoactive substance that arises from the metabolism of cathinone in plants (Figure 2.4). Cathine has a milder psychostimulant action than cathinone and the effects last are short lived, so the user must chew leaves almost continuously. Although it plays only a minor role in the action of khat, cathine is responsible for the systemic effects like hypertension. The fresh leaves contain a higher proportion of desirable cathinone but on drying, it breaks down into Cathine (Krizevskiab et al., 2008; Dagne et al., 2010; EMCDDA, 2013c). 24 The constituents of khat have been shown to exert their effects on dopamine and noradrenalin. It has also been postulated that like amphetamine cathinone releases serotonin in the CNS. This increases the activity of the dopaminergic pathways. High accumulation of dopamine in the brain can cause halluc.inations, schizophrenia, and hypertension (EMCDDA; 20] Ia; CESAR, 2013; NIDA, 2013). OH-- Figure 2.4: Chemical structure of Catbine Source: EMCDDA, 2013a 2.1.2.2.2 Effects of Khat Khat alleviates fatigue, reduces appetite while levels of alertness, euphoria, arousal and motor activity are increased. Users can quickly develop a psychological dependency to the drug, which increases their confidence, friendliness and contentment. Hallucinations, insomnia, grandiose delusions, elevated blood pressure, impaired memory and cognitive flexibility as well as paranoia have also been noted as side effects of using khat (CESAR, 2013; Getahun et al., 2010; NIDA, 2013; UNODC, 2014e). This may be followed by depression, irritability, anorexia and difficulty in sleeping. Continuous use of high doses 25 may evoke psychotic reactions, spermatorrhoea, constipation and unne retention (EMCDDA 2011, Zeleke et al., 20]3; NACADA, 2014). It is unclear whether khat causes tolerance, physical dependency, addiction or withdrawal but long-term users have reportedmild depression, nightmares and trembling after ceasing to chew (NIDA, 2013). 2.1.2.3 Nicotine Nicotine is named after the tobacco plant Nicotiana tabacum, which in turn is named after Jean Nicot, a French ambassador to Portugal. He used to send tobacco from Brazil toParis in 1560 as well as promoted its medicinal use (Van Hoof, 2011). Tobacco began growing in the Andes of South America about 6,000 B.c. It was used for religious and medicinal practices although not on daily basis. Tobacco was hailed as a panacea as there were claims it was effective against a host of disorders (Borio, 2010; Zagorevski and Newman, 2012; Hirst, 2014). Tobacco.is native to the subtropical and tropical Americas but there are a few species indigenous to selected areas of Africa. There are over sixty species but the most common are Nicotiana tabacum (Plate 2.4) and Nicotiana rustica (Moon et al., 2009; Denduangboripant et al., 2010; Van Hoof, 201]; Encyclopaedia of Life, 2012). 26 Plate 2.4: Tobacco plant (Nicotiana tabacum) Source: Encyclopaedia Britannica Online Tobacco leaves and the smoke generated when they are burned contain over four thousand chemicals, the best known of which is nicotine (the active ingredient responsible for addiction). Nicotine was first extracted in 1807 in Italy by the researcher Gaspare Cerioli, who called it tobacco's "essential oil." The French chemist Louis- Nicolas Vauquelin made the same discovery in 1809 without knowledge of Cerioli's work. However it is Physician Wilhelm Heinrich Posselt and chemist Karl Ludwig Reimann, who accomplished significant work in the extraction of nicotine (Erowid, 2010; 27 Nordqvist, 2013). Nicotine (3-[(2S)-I-methylpyrrolidin-2-yl] pyridine), as shown ill Figure 2.5 is a colorless oily liquid alkaloid. Figure 2.5: Chemical structure of Nicotine Source: Pubchem In Africa, the tobacco story began when it was imported from America by the Portuguese. In 1560 Portuguese and Spaniards shipped tobacco to East Africa, where it spread to Central and West Africa. By 1650s South Africa European settlers grew tobacco and used it as a form of currency (BAT, 2010; Borio, 2010). In Kenya, tobacco production can be traced back to 1935 when a tobacco industry was started by white settlers in the then Nyanza province (Campaign for Tobacco Free Kids, 2013). In Kenya, volume and value sales of tobacco have continued to increase with time partly due to rising urbanization and changes in lifestyle especially among females where 28 smoking has became more acceptable. However, after passing the Tobacco Control Act in 2007, the Kenyan govermnent began implementing enforcement of anti-smoking campaigns. Smoking prevalence dropped for the first time in 2012, after rising steadily before. Despite the decrease, non-communicable diseases (NCDs) for which tobacco is a risk factor currently account for more than 55% of the mortality in the country and 50% of the public-hospital admission (NACADA, 2012; Euromonitor, 2013). As nicotine enters the body, it is distributed quickly through the bloodstream and crosses the blood-brain barrier. On average it takes about seven seconds for the substance to reach the brain when inhaled. Nicotine exerts its neurophysiologic action principally through the brain's reward center by binding to nicotinic receptors. The nicotine molecule increases dopamine levels in the reward circuits of the brain thus activating the reward system and generating feelings of pleasure (Whirl-Carrillo et al., 2012). 2.1.2.3.1 Effects of nicotine In general, nicotine has a psycho stimulatory effect on the CNS at low doses via enhancing the actions of norepinephrine and dopamine in the brain. At higher doses, nicotine enhances the effect of serotonin and opiate activity. It exerts a calming and depressing effect (Manoranjan et aI., 2011; Garduno et aI., 2013; Koranda et al., 2013). Nicotine-induced stimulation of the sympathetic nervous system causes palpitations, increased blood pressure and coronary blood flow leading to cardiovascular diseases (Chen et al., 2012; D'Alessandro et aI., 2012; Jones et aI., 2013). Smoking increases the risk of respiratory, gastrointestinal, skin diseases and skeletal muscle tremors as well as a 29 number of tobacco-related cancers in addition to reproductive disorders (Al-Wadei et al., 2012; Chakraborty et al., 2014; Harte; 2014; Merritt et al., 2013; Lavezzi et al., 2014). Chronic nicotine use has been linked to tooth discoloration, tooth decay and gum diseases (like gingivitis) and reduced appetite as nicotine mutes taste buds as well as depresses appetite (Yann et al., 20]]; CDC, 2013a; Pilhatsch et al., 2014). 2.1.3 Cannabinoids Cannabinoids refers to a group of substances that are structurally related to tetrahydrocannabinol or that bind to cannabinoid receptors (NIDA, 2014). The principal constituents of Cannabis are delta-9-tetrahydrocannabinol (D9-THC) and cannabidiol. The former is the main psychoactive ingredient and it produces transient psychotic symptoms as well as impaired memory in a dose-dependent manner. Cannabidiol does not induce hallucinations or delusions but antagonises the cognitive impairment and psychotogenic effects caused by D9- THC (Di Forti et al., 2009; Murray et aI., 2009). Theoldest known written record on Cannabis use comes from the Chinese Emperor Shen Nung in 2727 B.c. In 1545 Cannabis spread to the western hemisphere where Spaniards imported it to Chile as fiber. In North America cannabis, in the form of hemp, was grown onmany plantations for use in rope, clothing and paper (Gumbiner, 2011; DEA Museum, 2012). There are over 200 street names for marijuana including pot, herb, dope, reefer, grass, weed, ganja, Mary Jane and chronic (NIDA 2013; Drugfree world, 2014). Over the course of time, marijuana has evolved into four species, Cannabis sativa, C indica, e. ruderalis and C. chinensis. C. sativa and C. indica are both found in Asia but 30 Cannabis sativa is the dominant variety in Africa (Craker and Gardner, 2010; Abel et al., 2011). Cannabis sativa variety Linneaeus, (Plate 2.5) commonly known as marijuana (with Tetrahydrocannabinol as the principle ingredient, figure 2.6) is a dioecious plant (Craker and Gardner, 2010; EMCDDA, 2013d). Figure 2.6: Chemical structure of tetrahydrocannabinol Source: EMCDDA, 2013d According to UNODC world report on drugs, Cannabis sativa l. remains the most widely used illicit substance globally, with an estimated annual prevalence in 2010 of 2.6-5.0% of the adult population (between 119 million and 224 million users aged 15-64 years). There was a minor increase in the prevalence of cannabis users (180.6 million or 3.9% of the population aged 15-64) as compared with previous estimates in 2009. The highest prevalence of cannabis use being reported in Oceania (Australia and New Zealand) at 9.1- 14.6%, followed by North America (10.8%), Western and Central Europe (7.0 %) and West and Central Africa (5.2-13.5%» while in Kenya 1.2% of the population use marijuana (NACADA, 2012; UNODC, 20 13a). 31 Plate 2.5: Marijuana Plant (Cannabis sativa Linneaeus) Source: Encyclopaedia Britannica Online Globally, Cannabis sativa is distributed in five forms namely, bh~g (a paste of leaves of the plant or dried leaves), ganja (dried flowering stem of the plant), charas (processed from live buds), hashish (extracted from the resin covering the plant) and hash oil which is thick oil that is obtained from hashish (National Cannabis Prevention and Information Centre, 2012; NIDA, 2014). It can be smoked in cigarettes or in clay pipes (most common method in religious settings and rural areas) and in water pipes like the traditional hookah (UNODC and TISS, 2011). Bhang consists of the dried seeded mixture of mature leaves and flowering shoots of both female and male plants, wild or cultivated. It can be ingested orally (by adding to tea and other beverages) or mixed with a combination of sugar, spices and fruit or smoked (alone 32 or mixed with cigarette). It is the weakest of all cannabis preparations and has a low THe concentration (DEA Museum, 2012; Drugfree world, 2014; Narconon, 2014). Ganja (Sinsemilla) consists of the dried unfertilized flowering tops of the cultivated female cannabis plant, which become coated with a resinous exudation, chiefly from the glandular hairs as consequence of being deprived of the opportunity of setting seed. As the female plants begin to form flowers, all the large leaves on the stem and branches are also removed. The smaller leaves and the bracts of inflorescence become agglutinated into a mass called ganja (UNODC, 2014c). Charas is processed from live Cannabis buds. Like ganja, it is smoked, but its THC concentration is far higher. In comparison to bhang and ganja, charas is more potent as it contains a relatively large amount of resin. Hash oil (also known as wax, nectar, full melt, honey or budder) is a resinous matrix of cannabinoids obtained from the Cannabis plant by solvent extraction which is formed into a hardened or viscous mass. Hash oil is more potent than marijuana because of its high THC content although it varies depending on the plant (Druglibrary, 2010; Hashish Centre, 2013). Hashish is the most potent form of cannabis preparations being at least twice or as many as strong as 10 times marijuana (Encyclopaedia Britannica, 2012). It is produced by collecting and compressing trichomes (fine growths on cannabis plants that produce a sticky resin). Hashish is consumed by heating it in a pipe, hookah, bong, bubbler, vaporizer or hot knife (placed between the tips of two heated knife blades). It can be 33 smoked,mixed with cannabis buds or tobacco, cooked in foods or smoked as bottle tokes (DEA Museum, 2012; Hashish Centre, 2013; Narconon, 2014; UNODC, 2014d). Whenone inhales marijuana, THC is absorbed into the bloodstream and later the brain. It then binds to and activates cannabinoid receptors which are activated by a neurotransmitter called anandamide. Like THC, anandamide is a cannabinoid, but found within the immune system of all animaJs, humans included. The THC then mimics the actions of anandamide, meaning that THC binds with cannabinoid receptors and activates neurons, which causes adverse effects on the mind and body. High concentrations of cannabinoid receptors exist in the hippocampus, cerebellum and basal ganglia. The hippocampus sits within the temporal lobe and is important for short-term memory. When the THC binds with the cannabinoid receptors inside the hippocampus, it interferes with the recollection of recent events. The THC also affects coordination, which the t4 m cerebellum controls. The basal ganglia direct unconscious muscle movements, which is Ianother reason why motor coordination is impaired when under the influence ofmarijuana (EMCDDA, 2008; Bonsor, 2011; NlDA, 2014). 2.1.3.1 Effects of Marijuana Potential consequences include euphoria, slowed thinking and reaction time, risk of developing psychiatric disorders, confusion, impaired balance and coordination., cough, frequent respiratory infections, impaired memory and learning ability. It has also been shown to cause increased heart rate, cardiovascular disease, anxiety, panic attacks, male infertility, low birth weight infants, preterm birth, foetal growth restriction, increased risk 34 of infant mortality, tolerance and addiction (Sharma et al., 2012; Brown and Graves, 2013; Hall and Degenhardt, 2013; NIDA, 20t3; NIDA, 2014; Volkow, et al., 2014). In addition, it impairs human reproductive potential by disrupting menstrual cycle, suppressing oogenesis and impairing embryo development in women. In men it increases ejaculation disorders, reduces sperm count and motility, it leads to loss of libido and impotence (Bari et al., 20] 1; Amoako et al., 2013). High risk sexual behaviour, non- adherence to ART and poly-drug use has also been reported among marijuana users (Andrade et al., 2013; Mimiaga et al., 20 13). 2.1.4 Benzodiazepines Benzodiazepines are sedative-hypnotics used to treat anxiety, insomnia, sleep disorders andseizure disorders. Members of this class include Flunitrazepam (Rohypnol, illustrated in Figure 2.7), alpranzolam (Xanax), bromazepam chlordiazepoxide (Librium) , lorazepam (Atavan) and diazepam like valium which are central nervous system depressants. Some of the street names of Rohypnol include Date rape drug, La roche, R2, Rib, Roach, Roofenol, Roofies, Rope, Rophies, Ruffles and The forget pill (CESAR, 2013). This study focused on recreational use of Rohypnol although medicinal use has beenhighlighted. 35 F _N N~ I 0 H3C Figure 2.7: Chemical Structure of Rohypnol (Flunitrazepam) Source: Drug Bank, 2010 2.1.4 Rohypnol Hoffman- La Roche, a Swiss pharmaceutical company was the first company to describe and develop benzodiazepines in the 1950s. Roche modified the basic benzodiazepine structure and introduced a munber of tranquilizers ]960s and ] 970s, including Rohypnol in 1975 (Wick, 2013; Helmenstine, 2014). The medicinal use of flunitrazepam as a hypnotic is intended to be for short-term treatment of chronic or .severe insomniacs not responsive to other hypnotics (CESAR, 2013; Helmenstine, 2014). Since the initial composition of Rohypnol tablets was odorless, tasteless, and dissolve undetected in liquid, they were used to facilitate sexual assault. In the mid-I 990s, reports surfaced that Rohypnol was being used in drug-facilitated sexual assault (DFSA) and it became known as a date-rape drug. When mixed with alcohol, Rohypnol incapacitates and induces amnesia, making one more vulnerable and unable to fight back or negotiate with rapists. In addition one may be confused or unable to remember the rape when the 36 drugwears off. This delays reporting of the crime, hinders law enforcement response and early medical intervention (Gemma and Fitzgerald, 2010). In response to reports implicating Rohypnol in DFSA, the manufacturer reformulated the tablets to oblong green tablets that have a dye which turns blue when dissolved in liquid thus making the drug more easily detected in drinks (Badiye et al., 2012; DEA Museum, 2012; CESAR, 2013). The use of Rohypnol for recreational studies has been reported in various studies both globally and locally (Brodish et al., 2011; Fulton et al.20] l ; Imer et 01.,2012; Kahuthia-Gathu et al., 2013; Lee et al., 2014). Rohypnol binds nonspecific ally to benzodiazepine receptors BNZI (which mediates sleep) and BNZ2, which affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to garnma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to this site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell (Drug Bank, 2010; EMCDDA, 2013). 2.1.4.1 Effects Robypnol It has powerful hypnotic, sedative, anxiolytic and skeletal muscle relaxant properties. It acts by depressing the CNS activity and brain function. This depressed CNS activity manifests as sedation, sleep, muscle relaxation, reduced anxiety and blood pressure. 37 When mixed with alcohol, another CNS depressant, unconsciousness, stupor, respiratory depression and death are more likely to occur. Overdose can cause drowsiness, memory impairment, low blood pressure, dizziness, headaches, nightmares, confusion, tremors and death (SAMHSA, 2010; Treweek et al., 2010). Regular use of Rohypnol results in increased tolerance while sudden cessation leads to withdrawal effects characterized by restlessness, anxiety, tremors, hallucinations, and convulsions. One may also experience headaches, muscle pain, tension, numbness, tingling of extremities, loss of identity, delirium and shock (SAMHSA, 20] 0; CESAR, 2013). Heroin users utilize Rohypnol to enhance the effects of low-quality heroin or to relieve withdrawal symptoms. In contrast to cocaine users who take Rohypnol to soften the negative effects of coming down from a binge (DEA, 2011; Roncero, 2013). 2.1.5 Alcohol Alcohol (ethyl alcohol, ethanol or grain alcohol) is produced by the fermentation of yeast, sugars, fruits and starches. Ethyl alcohol (Figure 2.8) is the intoxicating ingredient found in alcoholic beverages like beer, wine and distilled spirits. Slang terms include booze, bubbly, firewater, joy juice, sauce and liquid courage (NIDA, 2012; CESAR 2013). 38 Figure 2.8: Chemical structure of Ethyl AJcohol Source: Pubchem According to the World Health Organization (WHO), the harmful use of alcohol is a global problem which compromises both individual and social development. It causes harm far beyond the physical and psychological health of the drinker as it affects the well-being and health of people around the drinker. Indeed it is a socio-medical problem and results in 2.5 million deaths each year. An intoxicated person can harm others or put them at risk of traffic accidents or violent behaviour, Of negatively affect co-workers, relatives, friends or strangers. Thus, the impact of the harmful use of alcohol penetrates deep into society (WHO, 2011a). The current use of alcohol among 15-65 year olds in Kenya is estimated to be at 13.6% at national level and 10.6% in the coastal region (NACADA,2012). Ethanol appears to act by modifying cell membranes rather than by binding to specific receptor sites on neurons like other compounds. Alcohol dissolves in the lipid layer of 39 cellular membranes' causing an increase in its fluidity. This change may modify the actions of specific receptors or ion channels, resulting in the many behavioural effects of ethanol. Gamma aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) are receptors that are associated with the effects of alcohol. The inhibitory effects of ethanol may result from an enhancement of GABA receptor function, increasing the effects of this inhibitory receptor which causes relaxation, relief from anxiety, ataxia and lowering of inhibitions. A blockade of NMDA receptor function interferes with the effects of this excitatory receptor. However, pinpointing a site of action of alcohol effects is difficult because the drug affects virtually all neurochemical and endocrine systems (Drugfsank, 20]3; Adermark et al., 2014; Trudel et al., 2014). 2.1.5.1 Effects of Alcohol When one consumes alcohol, it is absorbed in the stomach, enters the bloodstream and goes to all the tissues. The effects of alcohol are dependent on a variety of factors like a person's size, weight, age, and sex, as well as the amount of food and alcohol consumed (Kokavec et aI., 2009; CESAR, 2013; Van Zanten et al., 2013). Effects of alcohol intake include dizziness, confidence, slurred speech, disturbed sleep, nausea, vomiting, impaired judgment and coordination as well as aggressiveness including domestic violence and child abuse. It can also lead to reduced performance, hangovers (characterized by headache, nausea, dizziness and fatigue) and accidents (Coskunpinar et al., 2013; Kask et al, 2013; National Institute on Alcohol Abuse and Alcoholism-NJAAA, 2013). Prolonged and heavy use of alcohol leads to alcoholism. It has been strongly linked to systemic failure, malnutrition, cancer and suicide (Andrade and Gin, 2009; Canula et al., 40 20ll; NACADA, 20]2). Mothers who drink alcohol during pregnancy may give birth to infants with foetal alcohol syndrome who later may suffer from mental and physical retardation (Ornoy and Ergaz 2010; Flak et al., 2013). Additionally, children of alcoholic parents are at greater risk than other children of becoming alcoholics (Handley and Chassin, 2013; Hussong et aI., 2012; NACADA, 2010). Sudden cessation of long term, extensive alcohol intake is likely to produce withdrawal symptoms like severe anxiety, tremors, hallucinations and convulsions (NlAAA, 2013). In Kenya alcohol use and abuse is associated with domestic violence, marital separation, child neglect, dropping out of school, loss of livelihood, idleness and crime (Githui, 2011; Birech et a/., 2013; Chweya and Auya, 2014). These factors are also determinants of drug abuse and HlV epidemiological trends as discussed in the next sub-topic. 2.2 Socio-demographic Characteristics Social and economic factors shape the risky behaviours and health of drug users. They affect health indirectly by shaping individual drug-use behaviour and directly by affecting the availability of resources, access to social welfare systems, marginalization as well as adherence to medication. Drug-related activity has been associated with age, familial dysfunction, reduced productivity, unemployment, poverty, drug-related violence and gang activity (Peltzer et al., 2010; Van Wyk, 2011, Trenz et af., 2013). Worldwide, most studies report the mean or median age of IDUs to be at about 30 years (Cavlek et aI., 2011; Ulibarri et aI., 2011; Majidpour et al., 2012). These reports are 41 similar to findings of several studies in Africa (Needle et al., 2008; Parry et al., 2009; Nsimba, et al., 2013) and Kenya (Brodish et al., 2011; Tun et al., 20] 1). Young people are particularly at risk for psychoactive substance use, as they are at a stage in life when patterns of behaviour are being formed. They are most likely to be influenced by peers and role models who may be involved in the use of substances (UNODC, 2011b; WHO, 2013h). That is partly why UNODC advocates for prevention strategies that target working with families, schools, and communities. Such strategies ensure that children and youth, especially the most marginalized and poor, grow and stay healthy into adulthood (UNODC, 20 13b). Drug education if provided in school-based and mass education programmes (like faith based institutions) has been found to reduce riskof drug abuse (NACADA, 2012; Sabin and Ersin, 2014). Lower educational level is an important predictor of one becoming an IDU. Low educational level can be due to not enrolling in scbool at all, dropping out of school or not progressing to higher levels. Dropping out from school is one of the social disruption variables and a proxy indicator for initiation into drug use (Noroozi et al., 2012). Studies have demonstrated that PWID with low level of education are more likely to share needles and less likely to participate in my interventions in contrast to those with higher educational attainment (Swe et al., 2010; CDC, 2012c, Gajendra et al., 2012; Medhi et al, 2012). This trend has been documented in Kenya, therefore the Kenya government's free primary education and subsidized secondary should be supported by all as it aids in keeping young people in school (Brodish et al., 2011; NACADA, 2012). 42 TheHlV prevalence among female IDUs (FIDUs) has been found to be higher than that ofmale IDUs. This HIV gender disparity is replicated in the Kenyan general population. For example, the 2012 Kenya AIDS Indicator Survey (KAlS) showed that although the adult (persons between 15 to 64 years) HIV prevalence had dropped to 5.6%, a higher proportion of women (6.9%) in the same age bracket were infected compared to their male (4.4%) counterparts (NASCOP, 2013). In addition, a study carried out in Nairobi show that females among the urban poor have remained more vulnerable to HIV-l infection because they are more excluded from mainstream economic activities and thus more affected by the ravages of poverty (Madise et al., 2012). This gender variation could be attributed to social, cultural and biological factors. Social factors that increase the risk of HIV infection include poverty, low levels of education, intergeneration dating, early sexual 'debut and marital status. Moreover, most females have limited negotiating power in terms of safer sex such as consistent condom use due to male domination of sexual roles. Stereotyped gender relationships are a major barrier for females in terms of maintaining safer sex practices with their partners (Amomkul et 01.,2009; Ulibarri et al., 2011 ;'Munyuwiny et aI., 2013; NASCOP, 2013). Although this may be a problem for females in general, but for FIDUs it is even more severe since they are marginalized by society. As a result the FIDUs often have strong feelings of powerlessness, low levels of self-esteem and self-confidence. They also experience impaired judgment while under the influence of drugs and extra sensitivity of the genitals in females during heroin withdrawal episodes. In addition, many FIDUs 43 engage in precarious sexual and injecting practices. Moreover, many FIDUs have a history of physical and sexual abuse (Ulibarri et al., 20]1; Moraros et al., 2012). Globally studies and reports show that females who have been abused are more likely to use drugs and have multiple sex partners (Moraros et 01., 2012; UNODC, 2012). The same scenario has been documented in Africa (Ross et aI., 2008; McCurdy et al., 2010) and Kenya as well (NASCOP, 2012a). On the other hand cultural practices like early marriages, female genital mutilation, wife inheritance and wife sharing heighten the risk ofHlV infection in women (Sesay, 2010; Kemboi eta!., 2011; Maleche and Day, 2011). Women's biological susceptibility to HIV can be linked to large surface area of the body parts like cervix, vagina and possibly the uterus where HIV transmission occurs in women. As compared to men, small tears occur on the penis, foreskin and urethra. In addition, HIV concentration is higher in semen than vaginal secretions and during sex a significant amount of seminal fluid enters the woman's body. Furthermore, delicate tissue of the genital tract can be damaged during intercourse, leading to increased abrasions and vaginal bleeding, consequently increased risk of transmission. Moreover, the warmth and moistness of the vagina provide HIV with an ideal place for micro-organisms to grow (Stoecklein and Osuka; 2012; Ghosh et al., 2013). Studies show that low levels of estrogen may increase a wornan's.risk for transmission of my because it makes the vaginal wall thinner. Thinning occurs during menstruation and menopause enabling HIV to penetrate more easily thus increasing vulnerability. Furthermore, increase in progesterone level that occurs due to pregnancy or use of 44 progesterone based contraceptives has been linked to increased risk of Hl V acquisition. On the other hand women under 24 may be at higher risk of mv infection because they may have an immature cervix and genital tract. These are characterized by thinner cells lining that tear more easily during sexual intercourse. This creates a conducive environment for HIV to penetrate more easily into the vaginal wall of younger women than in older ones. Furthermore, older women who have gone through menopause are at increased risk of infection because their lining of their uterus is thinner and their vagina drier (Carias et al., 2012; Stoecklein and Osuka, 2012; Grant et al., 2013). Ingeneral, women are more prone to STls than men as symptoms of STls are often more difficult to detect meaning STIs are not treated early enough. The presence of STIs like candidiasis, herpes simplex virus 2 (HSV-2), bacterial vaginosis, chlamydia and the human papilloma virus (HPV) increase the risk of HIV infection (Hilber et al., 2010; Cohen et al., 20ll; Djoba, 2014). Vaginal practices like douching and vaginal structural modification alters or destroys the friendly bacteria that protect the vagina. Douching is the practice of washing the vagina before and after sex using water, soap, lemon juice, antiseptics or other consumer douching products. Use of antiseptic or acidic liquids such as rubbing alcohol or lemon juice can irritate the lining of the vagina and create microscopic tears that HIV can pass through (Hilber et a/., 2011; Low et al., 20 II). In SSA, vaginal practices are widespread with prevalence reportedly ranging from 6 to 98%. It has been reported in over 98 studies in 24 countries, many of which also focus on traditional medicine to preserve health and wellbeing according to local health beliefs 45 (Redmond, 2011). In Kenya, vaginal washing using soap, acidic and or drying agents has been reported among female sex workers. This has been shown to augment the odds of HlV acquisition by almost three to four times (McClelland, 2008; Masese et al; 2012). Familial dysfunction like separation and divorce as well as being single (never married) predict a higher risk of Hl V infection among IDUs. These has been reported by several studies in the USA (Heinz et al., 2009; Khan et al., 2012), Middle East (Majidpour et aI., 2012), Africa (Drissa et aI., 2013; Kagaayi et aI., 2014) and Kenya (Tun et ai., 2014). Moreover singlehood through separation, divorce or widowhood is associated with higher rates of HlV infections in the general population (CDC, 20]2b). ln the Kenyan general population, marital separation has been shown to increase the risk ofHl V acquisition as reported in the KAlS report of 2012 (NASCOP, 2013). In addition children from dysfunctional families are vulnerable to sexual abuse, delinquency and are more likely to lack emotional security, trust as well as healthy parent-child relationship. These factors increase vulnerability to homelessness, sex work and substance abuse (Barth, 2009; UNODC, 2009; Massey et al., 20]4). Furthermore, children of parents who are already drug users are likely to end up using drugs. At the same time drug use affects parenting skills and such parents may end up applying inappropriate disciplinary measures which may also trigger substance abuse among the children (NACADA, 20] 0; NACADA, 20]2; Niccols et al., 20]2). To break this vicious cycle of generational substance abuse, family skills training programmes that 46 aim at strengthening the famiJy protective factors need to be implemented at community level (Niccols et al., 2012; Kumpfer, 2013; Tlale and Dreyer, 2013). Homeless PWID as well as those in precarious housing conditions are likely to engage in unhygienic injecting practices such as sharing injecting equipment and re-using cleaned needles (Grebely and Dore 2011). At the same time they are more vulnerable to rape, sexual assault and harassment (Mayhew et 01., 2009). In addition they are less likely to bargain for safer sex and access primary health care. The homeless and marginally housed HfV-positive IDUs are less likely to adherence to ARYs. Worldwide, the link between hornelessness, injection drug use, undernutrition and HlY risk has been extensively documented (Hendricks et al., 2010; Tang et 01., 2011; Cunningham, 2012; Neaigus et al., 2013, Noor et al., 2013; Yogenthaler et al., 2013; Havinga et al, 2014). In Kenya, the use of psychoactive substances among street children for survival and the high HJY 'prevalence in this sub-population has been extensively documented in most urban centres (Embleton et al., 2012; Embleton et al., 2013; Oino and Sorre, 2013; Oino et aI., 2014). There is therefore need to incorporate interventions that promote family relationships, family values and expectations in community based programmes. Sex work IS associated with a host of psychosocial vulnerabilities like exposure to childhood physical and sexual abuse, interpersonal violence in adulthood and substance use which are risk factors for my infection. The relationship between sex work and drug use is complex and inter-dependant. Drugs can be used to boost self confidence, 47 prolonged sexual performance as well as cope with the long and late working hours. On the other hand drug users are likely to engage in transactional sex that is sex for drugs, police protection or for money to purchase drugs. In addition substance use also helps female sex workers (FSW) feel assertive while talking with men especially when soliciting for clients (Ross et al., 2008; McCurdy et 01., 2010; Uuski.ila et 01., 2010; Ulibarri et 01.,2011; Moraros et 01.,2012). Female sex workers who inject drugs are also vulnerable to extortion either in cash or kind from law enforcers and pimps. This causes them to engage more in high risk sexual practices as they are more financially rewarding. Overall these multiple sexual partnerships, sex with persons of unknown HIV status, sexual assault and rape is a good recipe for Hl V acquisition or transmission. Additionally, drug-driven impaired judgment, sex under duress and increased genital sensation during heroin withdrawal episodes reduce their negotiation power for safer sex (Ross et 01., 2008; McCurdy et al., 2010; Ulibarri et aI., 2011; NASCOP, 20l2a). Overall sex work is associated with socio-demographic disadvantages like minority ethnic status, low income, homelessness and low education level which are also predictors of drug use as well as STIs including Hl V infection in both IDU and general population (Swe et 01., 2010; Gajendra et 01., 2012; Noroozi et 01., 2012; Boden et 01., 2013;Myers et al., 2013) These relationship is replicated in Africa (Kabbash et aI., 2012; Ademolaer 01.,2014) and Kenya (Tegang et 01.,2010; Ngugi et 01.,2013). 48 The relationship between poverty and drug abuse is a complex phenomenon and is affected by many contributing factors. Beyond the insufficiency of money, poverty develops certain mindset, activities, behaviours and life conditions. These attitudes and conditions can contribute toward drug usage. Poverty deprives the people from material resources due to lack of sufficient income and as a result loose prestige and status in the society(Niazi et aI., 2009; Farmer and Hanratty, 2011). Social inequalities induce social exclusion, deprivation, marginalization and hopelessness which induce drug abuse. lllicit drug use can be reduced by decreasing economic and social inequality as the prevalence of drug use seems to be higher in countries with greater levels of inequality such as the USA and lower in countries with less inequality such as Japan and the Scandinavian countries (pickett and Wilkinson, 20] 0; Wilkinson and Pickett, 2010; Sutin et aI., 2013; ThompsonJr et aI., 2013; UNODC, 2013b). In Iran poverty, living in poor neighbourhoods or polluted suburbs and low level of leisure facilities have been identified as predictors of drug use (Nadjme and Nouzar, 2014). In most African countries where poverty is widespread, youths roam the streets in search of employment consequently some resort to begging as well as high risk sexual behaviour and drug abuse (Fareo, 2012; Mbwambo et al., 2012). Similar scenario has been reported in Kenya (Chesang, 2013; Korir, 2013). 2.3 Drug use patterns 2.3.1Mode of administration A route of drug administration is a method in which a drug is taken into the body and differs from the point at which the drug interacts and affects an individual. It is 49 determined primarily by the properties of the drug (for example, water or lipid solubility and ionization) and therapeutic objectives like desirability of a rapid onset of action or needfor long-term administration or restriction to a local site. Reasons for preferring one route over another, depends on the desired effect (like speed and intensity), effect on mood or behaviour, convenience, avoiding possible harms (for example infections and overdose), need to protect the veins, avoiding injection marks or personal preference (Harrella et al., 2012; Vorobjov et al., 2012). Routes of drug administration can be categoried as topical, enteral and parenteral. Topical administration entails direct application of the drug to the area that it is needed like smokingand snorting. Enteral routes involve the digestive tract like orally taking the drug or using a suppository. Parental routes make use of other internal pathways such as subcutaneous, intravenous and intramuscular (FDA, 2009; Verma et al., 2010). Smoking is one of the most common routes of drug administration. Whenever someone smokes, the smoke goes to the lungs and is rapidly absorbed into the bloodstream. This makes it one of the fastest ways for someone to experience euphoria as the chemicals are transferred to' the necessary bodily receptors in five to ten seconds (NIDA, 2011; Surratt et al., 201 1). On the other hand, during snorting about 30 to 60% of the snorted chemicals enter the bloodstream through the mucus membrane in the nose. The rest is swallowed andmoves down to the stomach where it finally reaches the bloodstream. The euphoria is experienced within about 15 minutes (EMCDDA, 2010; EMCDDA, 2013t). 50 Oral ingestion allows the drug to move from the mouth to the stomach where it is absorbed by the stomach lining and then enters the bloodstream. Swallowing is one of the safest ways to take drugs as the substance is be slowly absorbed through the stomach lining resulting in effects which are less extreme and therefore less dangerous. Secondly, an individual's digestive system is designed to induce vomiting if that person ingests anything risky (Verma et al., 2010; SAMHSA, 2012). One of the riskier methods of drug intake is the use of suppositories where the substance is absorbed through the mucus membrane in the rectum. Since the mucus membranes around the rectum are very sensitive, the substance taken it can burn the lining causing irreparable damage. Additionally, inserting anything into the anus can result in the lower colon being perforated (Verma et aI., 2010; CESAR, 2013). Parenteral route of administration is a recent development in the drug scene and involves injecting of drugs directly into the blood stream. This can be either subcutaneous (injecting into the soft tissue beneath the skin), intravenous (injecting into a vein) or intramuscular which entails injecting into a muscle (FDA, 2009; Verma et aI., 2010). Injecting route is more popular as the full effects are felt within 3 to 5 seconds. It also bypasses many of the body's defenses and delivers the drug to the brain. That is why injecting is more dangerous as substances which would have normally been rejected by the stomach or blocked by the skin can easily enter into the bloodstream. Consequently, increased chance of infection, scarring of the veins, arterial damage, hemorrhaging, distal 51 ischemia, gangrene, endarteritis, thrombosis and death due to overdose may occur (Verma et aI., 20 J 0; Novak and Kral, 2011; Vorobjov et aI., 2011; Surratt et aI., 2{)1J). Studies demonstrate that there is an increased chance of addiction for those who take drugs via injections and smoking. This is because the heightened feelings that they experience may lead them to come back and repeat the action simply to relive the previous emotions. This may explain why tobacco smoking and injecting heroin are most often associated with dependence among users. Cigarette smoking has been extensively reported among PWID although the reason for this relationship is unclear (Marshall et al., 20] l a; Harrell et al., 2012 Methoide, 2014). 2.3.2Mooosubstance versus polysubstaoce use People who use drugs (PWUD) rarely limit their use to one substance and the increasing prevalence of polysubstance use has been shown to contribute to the already devastating HIV epidemic (Wechsberg et aI., 2008; Floyd et al., 2010). The WHO defines polydrug abuse as the concurrent or sequential abuse of more than one drugor type of drug, with dependence upon at least one and usually with the intention of enhancing, potentiating, or counteracting the effects of another drug. The term is also used more loosely to include the unconnected use of two or more drugs by the same person(WHO, 2014b). It occurs when an individual abuses several substances over a short period of time, often inan attempt to enhance the effect of a single drug to create a more intense high. Other 52 individuals take a drug to counteract the effects of a drug they had taken previously like taking sedatives to come off a stimulant effects. Some combination drug users have patterned use like alcoholics who use cocaine only after they have reached a certain state ofintoxication so as to avoid overuse and addicts who speed-ball (a mixture cocaine and heroin)for intravenous use. Polydrug use can also be due to changes in price, availability, legalityor fashion (EMCDDA, 2009). Interactions between different drugs consumed close together in time can lead to increased toxicity. This can occur due to additive or potentiation effects, pharmacokinetic factors like reduced metabolism leading to higher blood concentrations of the drug or to other interactions, such as the production of a new metabolite derived from the drugs or products. The effects of certain psychoactive substances can also lead to increased risk behaviourwith another substance (EMCDDA, 2009). Theabuse of multiple substances continues to be a major public health concern in Europe (EMCDDA, 2009; Irner et al., 2012), United States of America (Harrell et al., 2012; Ogbu et al., 201.4), Latin America (Reyes et aI., 2012) and other countries in the world. In Africa poly substance abuse is well documented in South Africa ((Floyd et aI., 2010; Trenz et aI., 2013) and the Republic of Tanzania (Nsimba et aI., 2013). Although literature on polydrug abuse is scanty in Kenya, the phenomenon bas recently been reported 'among IDUs in Nairobi (Tun et al., 2014) and Malindi (Brodish et al., 2012), 53 Studiesshow that risky sexual behaviour in terms of a higher number of sexual partners andhigher number of self-reported STls is influenced by the type of drug used as well as route of administration (Celentano et 01., 2008; Vorobjov et 01., 2012). Poly substance useincreases the likelihood of sexually transmitted HIV and other STIs (Mimiaga et aI., 2008; Mayer et 01., 2012). 2.4Nutrition Undernutrition is defined as insufficient provision of energy and nutrients, such as good qualityprotein with an adequate balance of essential amino acids, vitamins and minerals, andan inability to meet the requirements of the body to ensure growth, maintenance, and specific functions (FAO, 2010; White el 01., 2012; WHES, 2012). Globally, between 842 and 870 million people or around one in eight people in the world are estimated to be suffering from chronic hunger, regularly not getting enough food to conduct an active life with Sub-Saharan Africa being the most affected region (WHES, 2012; FAO, 2014). It is estimated that 42% of the people living in the horn of Africa are food insecure and undernourished (FAO, 2010; USDA, 2012; USAID, 2014). In addition 50% of the population of Nairobi (2 million people) is food-insecure. Similarly the Coastal region of Kenya has been classified by Kenya Food Security Steering Group- KFSSG as a food insecure (GOK, 2013). In countries like Canada and India, reports show that between 30% and 70% of drug- using individuals report some level of food insecurity and undernutrition (Anerna et al., 2010; Tang et 01., 2011). Other studies show that, regardless of HIV status, nutritional 54 intakeof IDUs is well below the recommended dietary allowance for vitamins A, C, and E, calcium and zinc in addition to low body mass index (Hendricks et al., 2009; Hendricks et al., 2010; Karajibani et al., 2012; Strike et al., 20] 2). Factors that influence nutritional status of a given population include food availability (sufficient quantities of food available on a consistent basis), food accessibility (ability to produce one's own food or buy it) and food use or quality which is the appropriate use of food based on nutritional knowledge and care as well as adequate acess to water and sanitation (Ajao et al., 2010; Kimani-Murage et al., 20]]; Saaka and Osman, 2013; CIRAD,2014; WHO, 2014c). Predictors of injection drug use; like poor educational attainment, homelessness or unstable housing, unemployment or being on welfare or low income, lack of food preparation and storage facilities, mental illness, high risk sexual and injecting behaviour, social ostracization and frequent incarceration overlap with the determinants of food security and nutritional status of any given population (Hendricks et al., 2009; Hendricks et al., 2010; Brodish et al., 20] 1; Tang et al., 2011; Vogenthaler et al., 2013). In addition these social predictors are associated with many negative social medical outcomes like elevated risk of acquiring sexually transmitted infections and blood borne pathogens like Hlv, Hepatitis Band C (Majidpour et al., 2012). Undernutrition among mv -positive drug users exacerbates an already compromised immune system (as the body lacks anti-oxidants which mop up harmful free radicals and 55 the nutrients needed to maintain immunity) and mitigates the effectiveness of antiretrovirals, ultimately decreasing the survival chances (Van Gaalen and Wahl, 2009; Hendricks,201O). In addition, undernutrition irrespective ofHIV status increases the risk ofHIV transmission through sex and drug risk routes by compromising an individual's immune-status as well as gut and genital mucosal integrity (Weiser et aI., 2008). At the same time infections increase the risk of undernutrition because sick people eat less, absorb fewer nutrients, lose nutrients (through diarrhoea and vomiting) and have increasednutrient needs especially fever. In addition, infections weaken the linings of the gut and respiratory systems making them weak and therefore can easily be invaded by pathogens (Krawinkel, 2012; MacArthur and DuPont, 2012). Infections like HIV may result in undernutrition as a result of insufficient dietary intake, malabsorption and altered metabolism. Lack of sufficient food intake and/or malabsorption leads to weight loss, which further exacerbates the hypercatabolic nature ofmv infection and ultimately reduces the chances of survival (Koethe et al., 20] 0; Andrade et al., 2012). People living with HIV/AIDS experience weight loss, loss of muscle tissue and body fat, vitamin and mineral deficiencies. When the body mounts its acute phase immune response to HlV infection, it releases pro-oxidant cytokines and other oxygen-reactive species. These cytokines produce several results including cachexia which is characterized by involuntary weight loss due to depletion of host adipose ti~sue and skeletal muscle mass that is not associated with starvation (Braun and Marks,2010;·Akiibinu et aI., 2012; Mody et al., 2014). 56 Inaddition it leads to anorexia resulting into lower food intake and fever which increases energy expenditure. An augmentation in circulating inflammatory cytokines has been implicated as a uniting pathogenic mechanism of cachexia and associated anorexia Consequently this leads to reduced immune competence and increased susceptibility to secondary infections (Braun and Marks, 2010; Shalini et aI., 2012; Mody et aI., 2014). If the infection is prolonged, muscle wasting occurs because muscle tissue is broken down to provide the amino acids with the immune protein and enzymes they need. These processes increase energy requirements of people living with mY/AIDS during the asymptomatic phase by 10 percent over the level of energy intake recommended for healthy, non-HIV-infected people of the same age, sex and physical activity level (Martins et al., 20 II; Sunguya et aI., 20] l). AmongHrtls undernutrition is due to food insecurity, reduced food intake and food malabsorption (NIH, 2012; Strike et aI., 2012; DRUG INFO, 2013). In the USA between 30 to 70% of drug using individuals report some level of food insecurity (Strike et aI., 2012). Reduced food intake is attributed to hunger suppression, selective appetite, distorted food taste and altered metabolic processes resulting in an imbalance between fat intake and storage. This has been reported among people who chew khat, heroin and cocaine users as well as tobacco smokers (Murray et aI., 2008; Douglas et al., 2011; Mineur et al., 2011; Neale et al., 2012; Ersche et al., 2012b; Ersche et al., 2013; Rubinstein andLow, 2013). 57 Overall drug addiction modifies eating habits, often causing individuals to adopt poor dietary patterns such as an irregular eating schedule, eating fewer meals per week, skipping meals or fasting to prolong the effects of drugs (Neale et aI., 2012). Poor nutrient absorption is partly attributed to withdrawal symptoms like loss of appetite, nausea, vomiting, diarrhoea nutrient maldigestion and direct nutrient loss (WHO 2009a; Nel, 20]0; Smith et al., 2012). Most IDUs face competing demands between addiction and subsistence, which in return hinder access to groceries and food selection. As a result major components of IDU diets have been reported as foods of low nutritive value which are mostly cheap and easy to prepare foods, high-fat diets or ready to eat sweet and salty snacks while the minor components are fruits, vegetables, grains and dairy products and hence undernutrition (Hendricks et al., 2010; Alves et al., 2011; Saeland et al., 2011). Under nutrition enhances susceptibility to infection in both Hl V infected and uninfected persons with the former faring worse. Malnourishment is associated with an increased risk of progression from latent to active TB because of the negative impact of micro and macronutrient deficiencies on the cell-mediated immune system. Low BMI is a risk factor for TB. In HlV mono infected patients a higher BMI is associated with better survival outcomes and a lower BMI is a predictor of mortality (Knut et al., 2010; Maro et 01.,2010; Padmanesan et al., 2010; Semba et al., 2010). 58 It is important to note that under nutrition irrespective of the cause reduces CD4 and CD8 f-lymphocyte number leading to impaired cell-mediated immunity (CMJ) which is the principle host defense against TB (Drake, 2010; Shalini et al., 2012). Both IDU and HlYlAIDS are characterized with undernutrition which is a predictor of the health status of a population and exacerbates progression from HlV to AIDS (Shannon et al., 2011; Shaliniet al., 2012; Padmanesan et al, 2013). Although information on food security and nutrition status of African as well as Kenyan populations are well documented (FAa 2010; USDA, 2012; GOK, 2013; USAID 2014) data on the same for the IDU subpopulation in this region is scanty. To the best knowledge of the researcher there is no documented study on nutritional status and food security of injection and non injection drug users in Africa as well as Kenya. 2.5 Tuberculosis Tuberculosis is one of the world's deadliest diseases and it is estimated that one third of the world's population is infected with TB. In 2013 alone, 9 million people around the world had active TB and around 1.5 million TB-related deaths were reported 360 000 of whom were HlY -positive. Tuberculosis is slowly declining each year and it is estimated that 37 million liveswere saved between 2000 and 2013 through effective diagnosis and treatment. Since most deaths from TB are preventable, the death toll from the disease is still unacceptably high and efforts to combat it must be accelerated if the 20] 5 global MDG targets are' to be met (CDC, 2014; WHO, 2014d). N'l ITA U IVERS TY'=LI RA V;: ---.......... - 59 Kenya ranks thirteenth on the list of twenty two TB High Burden Countries (HBCs) in theworld and has the fifth highest burden in Africa. These 22 HBCs account for 80% of the global TB burden (WHO, 2013b). In 2013, Kenya observed a sharp decline of TB cases, having a total number of 89,760 a 9.48% decline from the 99,159 cases observed in 2012. Additionally, there was a reduction in the prevalence of TB among HIV sero- positive patients from 44% in 2009 (WHO, 2009a; CDC, 2011a) to between 38.3% and 39%(MOH, 2012; MOH, 2013). Globally it has been shown that both IDUs and non IDUs are at high risk of contracting tuberculosis irrespective of their HIV status (Haileyesus et ai., 2013). Recreational drug use is a risk factor for TB as a result of the overlap of epidemiological and social factors associated with both drug use and TB (Deiss et aI., 2009; CDC, 2012d; Ruutel et aI., 2012). Most IDUs are faced with undernutrition, poverty, homelessness and overcrowding which are also risk factors for both HIV/AIDS and TB infections (Arema et aI., 2010; Tang et aI., 2011; Strike et aI., 2012). Although the higher risk of TB observed in IDUs is usually the result of associated HIV infection, the non IDUs are at a higher risk attributable to the sharing of drug equipment such as marijuana water pipes, smoking and living in cramped conditions or in dwellings with poor ventilation (Deiss et aI., 2009; Getahun et al., 2012). Furthermore, PLWHA who inject drugs have been found to be 85% more likely to have Hlv-associated tuberculosis than those who were not injecting drug users. This higher TB rates among PWID support evidence that IDUs are at higher risk of TB (Odendal, 60 2011; Baddeley, 2013). Since there are very few mono-substance users, polysubstance use contributes to the already devastating HlV epidemic which in turn affects the epidemiology of TB (Kalichman et al., 2006; Kedia et al., 2007; Wechsberg et al., 2008;Floyd et al., 2010). Furthermore drug use, HlV infections and undernutrition lower immunity thus increasing the risk of reactivating Mycobacterium tuberculosis infection. Low body mass index (BMI< 18.5 kg/m") and anaemia have been shown to predict high mortality among TB patients. Moreover, patients with poor weight gains during TB treatment are at an increased risk of treatment failure, relapse and premature death (Drake, 2010; Shalini et al., 20]2; Mamani et al., 2013; McDennid et aI., 2013; Padmanesan et aI., 2013). In South Africa, drug-related activity has been associated with poverty, reduced productivity, unemployment, familial dysfunction, political instability, drug-related violence, gang activity, escalating rates of blood-borne illness such as HlV/AIDS, TB infections, injury, and premature death (Parry et al., 2009; Peltzer et al., 20]0; Van Wyk, 2011;Trenz et aI., 2013). In Tanzania, mus have been shown to be at high risk for both TB and HIV with outbreaks of drug-susceptible and multidrug resistant TB being reported in this sub population (Gupta et al., 2014). At the time of this study, data on TB among IDUs in Kenya was not available nevertheless drug use has been identified as a predictor of poor adherenceto TB treatment in the general population (Muture et aI., 20] 1). 61 Since PLWHA are more likely to develop active TB in a given year than mv sero- negativepersons due to their weakened immune system, TB screening is critical for the IOU subpopulation (Hwang et al., 2009; USAID, 2013; WHO, 2013a). Recognizing the important relationship between TB and drug use, the WHO, Joint United Nations Programmeon mY/AIDS (UNAIDS) and the UNODC recently issued a set of guidelines tobetter coordinate TB care among drug users (WHO, UNODC and UNAIDS, 2012). 2.6IDV Despitethe global massive expansion of Hl V interventions, HlV burden remains a major public health challenge. In 2013, 35.0 million people were living with HIV up from 29.8 million in 2001 due to continuing new infections, people living longer with HlV and generalpopulation growth. In the same year, 1.5 million people died of AIDS which is a 35% decrease since 2005. This decline is partly due to antiretrovira1 treatment (ART) scale-up(UNAIDS, 2014). Sub-Saharan Africa, the hardest hit region is home to 71% of people living with HIV. In 2013 alone, there were 24.7 million people living with HIV in SSA with women accounting for 58% of the total number of people infected. Swaziland has the highest mv prevalence rate (27.4%) in the world. This high rate in SSA is fueled by poverty, extensive sexual networks of men, cultural practices, unemployment, labour migration and displacement as a result of conflicts (Fox, 2010; Coburn et al., 2013; Ramjee and Daniels,2013; UNAIDS, 2014). 62 Although Kenya has one of the largest Hl V epidemics in the world, it is still widely regarded as one of sub-Saharan Africa's success stories where mv prevention is concerned. Annual new Hl V infections are roughly one third of what they were at the peak of the country's epidemic in 1993. For example, in 2012 there were an estimated 100,000 new HlV infections in Kenya. Furthermore, during the same period the HlV prevalence among adults aged 15 to 64 years decreased nationally from 7.2% as measured in KAlS 2007 to 5.6%. At the same time, the distribution of HlV infections varied across the country with Mombasa region reporting an Hl V prevalence of 4.3% from7.1% in 2007 (NACC and NASCOP, 2012; UNAIDS, 2013; NASCOP, 2014). 2.6.1 HIV and Injection Drug Use Inthe context of Hl V epidemiology, people who inject drugs are classified as the most at risk populations (MARPs). Their vulnerability is attributed to precarious injecting practices, high risk sexual activities, under utilizatition of health services and poor adherence to treatment (Uuskula et al., 2010; Cavlek et al., 2011; Muture et al., 2011; Ulibarri et al., 2011; CDC, 20 12d; Orsetti et al., 2013; WHO, 2013a). Sharing mainly occurs because the needles and syringes are either not enough, available, accessible or affordable to IDUs. The accessibility of new needles and or syringes is hindered by various structural factors like refusal by pharmacy operators to sell needles or syringes to IDUs. Furthermore, geographic locations (like distance between shooting galleries and pharmacies), perceptions about stigma and concerns about confidentiality hinders accessibity. Sometimes sharing occurs due to drug impaired judgment or as a sign 63 ofbrotherhood (Chakrapani et al., 2011). In addition, when heroin is scarce or resources are limited, some IDUs seek partnerships with others to enhance their ability to raise funds to purchase drugs and such efforts often lead to group injection (Mateu-Gelabert et al., 2010). High risk sexual activities among PWID include multiple sex partnerships, having unprotected sex with partners of unknown HIY status and engaging in sex for drugs or for money to purchase drugs as well as survival. Besides, sex for police protection, group sex, anal sex, sexual assaIt, unconsented sex and partner sexual violence have been reported in this population (Mayhew et al., 2009; Swe et al., 2010). The higher prevalence of HIY among women than men, together with a lower prevalence of HCY provides evidence of sexual transmission of HIY among IDUs. This is of considerable concern given that SSA has the world's largest population of individuals living with my (Bowring et aI., 2012; UNAIDS, 2012). In Africa unsafe sexual and injecting practices among IDUs are welJ documented. For example in South Africa, drug use has been linked to increased risk of HIY acquisition and transmission with IDUs being more at risk than the non- IDUs. In Egypt, high risk behaviours like multiple partnerships with men who have sex with men, female sex workers and other regular or casual partners has been reported (Soliman et al., 2010). Closer home, Tanzania has been identified as one of the sub-Saharan African countries experiencing significant changes in the patterns of illicit drug use. These include both 64 non-injecting and injecting drug use in addition to increasing prevalence of unsafe injection and sexual practices. For example blood flashing and sharing, sex for drugs as well as sexual multiple partnerships has been reported among PWID in Tanzania (McCurdy et 01.,2010; Atkinson et 01., 2011; Bowring et al., 2012). High risk injection practices have been documented among Kenyan IDUs. These practices include syringe and needle sharing, using pre-filled needles and syringes, front orback loading, sharing of preparation water, sharing equipment and drawing drugs from a common container (Brodish et al., 2011; NASCOP, 2012a; TlID et al., 2014). Precarious sexual tendencies like multiple sexual partnerships with persons of unknown HlV status have been reported. These include rape, sexual assault, unprotected sex which couldbe consented or unconsented due to drug impairment, sex for police protection, sex for drugs and sex for money to buy drugs as well as survival (Tegang et 01., 2010; Brodish et 01.,2011; NACADA, 2012; Kahuthia-Gathu et 01.,2013; NASCOP, 2013). 2.6.2HIV Subtypes: Global Outlook There are two types ofHIV which have been distinguished genetically and antigenically. The Hlv-I sub-type is the cause of the worldwide pandemic while mV-2 is predominantly found in West Africa. The HIV-2, which is transmitted in the same ways as HlV-1 is less lethal than HIV -1 but otherwise clinically the diseases are very similar. HIV-I and HIV-2 are thought to have arisen from two natural hosts both harboring Simian Immunodeficiency Virus (SlY). The closest relative of HIV-I is SIVcp2 which infects wild-living chimpanzees (Pan troglodytes troglodytes) and gorillas (Gorilla 65 gorilla gorilla) in west central Africa while HIV-2 is SIVsrnm harbored by sooty mangabeys,Cercocebus atys (Sharp and Hahn, 2010; Sharp and Hahn, 2011). Thereare three sub-groups ofHIV-I, M (main or major), N (new) and a (outlier). Type o IDV-I is mostly found in Cameroon and Gabon while the rare N sub-group is found in Cameroon. It is very likely that SIVcpz infected humans on separate occasions to give rise to the three sub-groups. In addition, there are at least ten different HIV-I subtypes withinthe M group and they are designated A to K (Hunt, 2010; Sharp and Hahn, 2011; Kerinaet aI., 2013). Most sub-types are found in sub-Saharan Africa with A and D dominating Central and Eastern Africa and C in Southern Africa (lung et aI., 2012; Kiwelu et aI., 2012). This subtypeC is also predominant in India and Nepal. It is also the cause of most infections worldwide and is linked to mother to child HIV transmission (Zhanga et aI., 2009; Shen et al., 2011; Alcantara. et al., 2012). Sub type B is majorly in North America, Latin America, the Caribbean, Europe, Japan and Australia (lunqueira et aI., 2011; Abecasis et a/., 2013; Mendoza etal., 2014). Type E has been isolated in Thailand and central Africa while type F is predominant in Brazil and Romania. On the other hand, type G has been reported in Russia and Gabon while type H is found in Zaire and in Cameroon (Alcantara et aI., 2012; Fayemiwo et aI., 2014). Subtype K has been isolated in the Congo and Cameroon (Sharp and Hahn, 2011). Although subtype I was a name given to an apparent sub-type found in Cyprus but the name is no longer used since it is now classified as a recombinant (Hunt, 2010; Kousiappa et aI., 2011). 66 In some countries, mosaics (recombinants) between different subtypes have been found. These arise when two different subtypes infect a person at the same time and recombination occurs. For example, the former subtype I is a circulating recombinant form (or CRF) that is a recombinant of subtypes A, G, H and K. In addition, the polymerase genes of HIV -1 strains from Ghana are made up of recombinants of several CRF 02-AG strains from Ghana, Senegal and Cameroon (Sagoe et al., 2009; Kerina et al., 2013; Palm et al., 2013). Based on laboratory studies, different HIV -1 subtypes can be transmitted by different routes. For example, type B may be transmitted more effectively by homosexual intercourse and via blood (as in injection drug use) whereas types C and E may be transmitted more via a heterosexual route. This is because types C and E replicate better in Langerhans' cells found in the mucosa of the cervix, vagina and penis while type B replicates better in the rectal mucosa. It also appears that type E is more readily transmitted between sexual partners than type B (Haaland et al., 2009; Almeida et al., 20]2; King et al., 2Q13). Subtype D appears to be more virulent than subtype A. In addition subtypes D and C seem to be transmitted more effectively from mother to child than subtype A (Krivine et al., 2009; Hunt, 2010; Ryland et al., 20J 0; Zhang et al., 2010). 2.6.3 HIV Subtypes in Kenya InKenya, HIV -1 subtype A has been reported as the dominant strain in southern part of the country with over 30% recombinants while subtype C is more predominant in 67 northernpart. Subtypes A, B, C, D and G together with their recombinants have also been descnbed in various parts of the country. Irrespective of the region, subtype A remains theprincipal strain but there is an increase in the prevalence of subtype C (Khamadi et al., 2009; Lihana et aI., 2009; Kageha et aI., 2012; Lihana et aI., 2012; Muriuki, 2012; Kiptoo et aI., 2013; Nyamache et al., 2013; Bezemer et aI., 2014). Kenya appears to havean array of subtypes that co-circulate courtesy of increased human migration in and aroundEast and Central Africa (Hue et a/., 2012; Lihana et al., 2012). 2.6.4HIV Subtypes in the IDU population Due to both high risk sexual and injecting practices, IDUs are likely to have diversified illV types and recombinants. Globally the explosive outbreak of Hl v-I circulating recombinant forms among IDUs has been extensively documented for example in Afghanistan, China, Greece, India and Taiwan (Sanders-Buell et al., 2010; Yen-lu et aI., 2010;Sarkar et al., 2011; Paraskevis et al., 20] l ; Han et aI., 2013). In Kenya investigation on the molecular epidemiology of different HIV-I subtypes and their associated risk factors among IDUs is limited. Despite this constraint, Osman et at. (2013) has reported subtypes AI, B and C to be circulating among IDUs in Mombasa. Mombasa which is a coastal cosmopolitan city has the largest number ofMARPS. These include PWIDs, men who have sex with men (MSM) and sex workers (NASCOP, 2012a). Due to their high risk injecting and sexual behaviour the probability of HIV co- infections as well as super infections is high. This key sub-population does not operate in 68 exclusionbut instead acts as a bridge to the general population thus fueling HlV epidemicsin the region. 2.7Drugs and Immunity Previous and ongoing studies as well as reports indicate that drug use diminishes immunity. For example, use of opiates (like heroin and opium) affects several components of the immune system and thus modulates host immunity increasing susceptibility to infections (Ramsin et al., 2008; Haghpanah et al., 2010). In addition, nicotineuse has been shown to suppress the immune system there by increasing the risk of infection and poor disease prognosis (Comer et aI., 2014; Padmanesan et al., 2013; Van Zyl-Smit et al., 2014). Furthermore, cathinone and cathine reduces post-translational modifications of intracellular signal transducers in T-lymphocytes, B-Iymphocytes, naturalkiller cells and monocytes leading to impaired immunity (Bredholt, 2013). Weakened immunity can be as a direct result of using drugs or indirectly due to binging which causes the user to be ill and dehydrated. The impact of dehydration, mental and physical exhaustion, sleeplessness and lack of food depletes the immune system (Molina et 01.,2010). Diminished immune system in addition to sharing of drug equipment such as marijuana water pipes, smoking as well as living in poorly ventilated dweIIings increases the risk of acquiring tuberculosis (Deiss et al., 2009; Getahun et aI., 2012). Beside PWID are less likely to access healthcare facilities as well as adhere to long term TBand HlV therapy (Dutta et al., 2013; Singer, 2014). Therefore, drug use, exposure to HIV and TBas well. as undernutrition combined or separately leads to reduced immunity 69 and thus inability to resist or withstand infections. By and large drug use reduces quality oflife and productivity in addition to increased risk of contracting infections as well as prematuredeath. Moreover, drug users are more likely to develop mental disorders even after rehabilitation. Consequently, recreational drug use should be dealt with as a socio- medicalproblem and not a criminal offence. 2.8Other Common Co-morbidities 2.8.1Hepatitis Band C 2.8.1.1Hepatitis B The term hepatitis simply means inflammation of the liver and humans are the only reservoir of hepatitis B virus (HBV). The virus is transmitted by percutaneous and pennucosal exposure to infected blood and other body fluids, mainly semen and vaginal fluid.This can happen through sexual contact with an infected person or sharing needles, syringes, or other drug-injection equipment. Hepatitis B can also be passed from an infectedmother to her baby at birth (WHO, 20Bc; Hoffmann et al., 2014; Moezzi et aI., 2014; Ramezani .et al., 20]4). Hepatitis B can be prevented via vaccination which is 95% effectivein preventing infection (CDC, 2013d; WHO, 20I3d). 2.8.1.2Hepatitis C Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). The HCV is most commonly transmitted through exposure to infectious blood. This can occur through: receipt of contaminated blood transfusions, blood products, organ transplants, injections given with contaminated' syringes and needle-stick injuries in health-care settings, 70 recreational injection drug use, beauty treatments and being born to a hepatitis C-infected mother(CDC, 20Bc; Villar et al., 2013; WHO, 20Be; Ramezani et al., 2014). Thereis no vaccine for Hepatitis C but can be prevented by avoiding behaviours that can spread the disease, especially sharing drug needles or personal items such as toothbrushes, razors, and nail clippers with an infected person· (CDC 2012c; Hepatitis Foundation international, 2013; WHO, 20 Be). 2.8.2Tetanus Tetanusis an acute illness caused by the toxin of Clostridium tetani. Soil, street dust and intestinal content of animals and humans are the normal habitat of the organism, but contamination of any wound can result in tetanus. Tetanus among PWID has been reported worldwide (CDC, 2011). Drug injection provides several potential sources for infectionwith C. tetani, including the drug itself, its adulterants like contaminated heroin, injection equipment and unwashed skin. Although recommendations to prevent transmission of HIV among IDUs may limit infection from contaminated injection equipment, these measures may not be effective against spores inoculated from the skin or contained in the drug (WHO, 2009a; Health Protection Agency, 20 II). So far, there is nocure for tetanus but it can be prevented by the administration of tetanus toxoid (WHO, 2009a;CDC, 2013e, WHO, 20BfWHO, 2013g). 2.8.3Dermatological disorders Skin and soft tissue bacterial infections are a common complication of IDU due to injection of drugs into the fatty layer under the skin. Additionally, leakage of drugs out of 71 veinsduring injection (extravasation) and necrosis as a result of toxic materials in drugs as well as increased numbers of bacteria on the skin surface lead to dermatological disorders. Continued use of intravenous drugs can damage both the skin at the site of injection as well as internal organs. A case in point is recurrent suppurative skin infections as a result of subcutaneous administration of drugs being associated with AmyloidA amyloidosis which leads to progressive loss of renal function (WHO, 2009a; Tomlinson,2010; Nayer, 2014). Although skin infections usually present as areas of redness, warmth and tenderness (inflammation), the appearance in IDUs is often atypical. Infections usually affect the armsor legs as these are the sites used most frequently for injection. Unusual sites may be involved like the abdomen, back, groin, scrotum and neck due to injecting in the jugular or femoral veins. A more recent study carried out in Glasgow, United Kingdom reported a high prevalence (60%) of skin disease and surprisingly high rates of leg ulceration (15%) among PWID (WHO, 2009a; EMCDDA, 2011b; Coull et al., 2014). 2.9 Prevention and Management of drug use and addiction It is time for drug abuse to be seen as public health problem aed not a criminal problem. The consequences of drug abuse and addiction are costly in terms of preventable health care, law enforcement and crime among other costs. In Kenya, it has been note that drug treatment reduces likelihood of HIV infection by 6 fold in injecting drug users at the same time presents opportunities for screening, counseling, and referral (NACADA, 2012). According to UNODC, for every dollar spent on prevention, at least ten can be 72 savedin future health, social and crime costs (UNODC, 2013b). The best approach to reducingthe tremendous toll from substance abuse is to prevent the damage before it occurs.These strategies include demand reduction, supply reduction and harm reduction. 2.9.1 Demand reduction Reducingdemand consists of creating an environment where the vast majority of people whohave never taken drugs continue to resist any pressures to do so, and making it easier forthose that do to stop. Drug and substance abuse prevention intervention programmes shouldtarget risk factors and enhancing protective factors at all levels therefore reducing demand for drugs. Moderators that need to be promoted in order to prevent drug use include but are not limited to substance and drug abuse awareness, improvement of school enrollment and retention rate, drug resistance skills, personal self-management skills,general social skills, positive peer pressure, good parenting skills, strengthening of the family fabric, poverty eradication and wealth creation as demonstrated in Srikala and Kishore (2010), Mahmoudi and Moshayedi (2012), Niccols et al. (20]2), Crowley et al. (20]4) and Massey et al, (2014). 2.9.2 Supply reduction The basic goals of supply reduction and drug law enforcement agencies are to minimize the supply of drugs to illicit markets and to increase the price and inconveniences of acquiring drugs. A fundamental aspect of the drug market is that supply responds to demand and vise versa in accordance with basic economic theory. By targeting to reduce production, distribution, and sales of drug at street level, distributing and selling illicit 73 drugwill be more risky and shortage of drug will increase the price to drug users. In addition,this strategy should be directed towards regulating and enforcing access to legal drugsand substances, particularly those that are of a high probability for abuse, including pharmaceuticals and other precursors and essential chemicals (UNODC and TISS, 20]]; Werbet al., 201]; Sabin and Matusitz, 2012; Werb et al., 20]3; Sahin and Ersin, 2014). 2.9.3 Harm reduction Harm reduction refers to approaches to psychoactive drug use that aim to reduce the harmsassociated with drug use for people who are unable or unwilling to abstain. The prevention of harm is given the highest priority rather than achieving indefinite abstinence from illicit drug use regardless of the unintended negative consequences. Its approach to drugs is based on a strong commitment to public health and human rights (International Harm Reduction Association- IHRA, 2010; UNODC and TISS. 2011). Comprehensive harm- reduction services benefits people who use drugs, their families andthe community as is associated with reversal of a rapidly emerging epidemic of HIV amongPWID (Sharrnin, 20]3; Huang et al., 2014). The concept of harm reduction and minimization for drug users was born in 1986 with the realization that the Hl V virus was being spread through the sharing of syringes amongst heroin injecting users. To reduce the risk of an increase in AIDS cases, Australia took the bold step and led the world into implementing the availability and distribution of new syringes to IDUs. As a result, Australia has the lowest incidence of HIV amongst 74 injecting drug users in the world, less than 2% compared to figures up to 90% in some othercountries (Commonwealth of Australia, 2011). Theharm-reduction approach applies various strategies which include but are not limited to addiction counseling, STIs treatment and HIV testing including linkage, educational interventions, needle syringe exchange programmes, detoxification, oral substitution therapy-OST (like methadone and buprenorphine treatment) and Supervised Injecting Facilities [SlFs]. Research indicates that majority of PWUD have an underlying mental health condition, significant emotional or psychological difficulty and thus require both addiction and general counseling (Munro and Allan, 2011; UNODC and TISS, 2011; NIDA, 20l2). A goodcounseling programme incorporates family therapy as drug addiction does not only affect the. user's life but the whole family (Centre for Addiction and Mental Health - CAMH, 2010). Studies show family therapy results in lower relapse rates, increased happiness in the family and better functioning in children of addicted parents (Munro and .Allan,2011; UNODC and TISS, 2011; Evans et aI., 20]2). Screening of STIs and respective treatment in addition to HlV testing and linkage is an important aspect of harm reduction as some STIs cause open wounds or ulcers to form in the genital area. These openings provide a way for HIV to enter the blood stream. Although some STIs don't cause open wounds but the presence of the STI causes the body to increase the concentration of CD4 cells in the genital area which provide HIV with a favourable target for infection. In addition, people infected with STIs have 75 increasedconcentrations of HIV in their genital fluids, increasing the possibility of HIV transmission(CDC, 2010; Cohen et 01., 20]2; Zhang et 01., 2013a). It is imperative to preventand manage STIs including HIV infections in this sub-population as most PWID tendto engage in precarious sexual practices, Peereducation is a strategy whereby individuals from a target group provide information or training to their peers. These groups can be determined by socio-demographic characteristics (like age, education, type of work) or by risk-taking behaviour (like injection drug use, sex work and sexual orientation). Peer networks increase the credibility and effectiveness of the message being presented (Research to Prevention, 2010; UNODC, 2011b; Jain et 0/., 2014). Syringe and needle exchange programmes (SNEP) exemplify harm reduction because theyreduce the harms from drug use to drug users, their families and community without requiring a change in the consumption of drugs. These programmes work on the philosophy of providing sterile and new needles and syringes to mus in exchange of old usedand potentially infected ones. The exchange component has multiple benefits as it ensures that all the used injecting equipments have been collected from the mus and destroyed under supervision, minimizing the risk of reuse and accidental exposure. Secondly, it provides an opportunity for frequent contact with mus, during which not just needles and syringes but education and other services can be delivered (Global Commission on Drug Policies, 2011; UNODC and T1SS, 2011). Furthermore, SNEP 76 encouragethe entry of PWID into drug detoxification and treatment programmes (Alkiviadiset al., 2010; O'Gurek and Kirchner, 2010; Aspinall et al., 2014). Detoxificationservices can help to ensure that withdrawal is safe and comfortable and warndrug users of the risk of an overdose on relapse. It is a prelude to treatment and not distincta form of treatment (Global Commission on Drug Policy, 2011; Katz et al., 2011; Chandraand Madison, 2012; NIDA, 2012). Methadoneand buprenorphine treatment have been endorsed by the WHO and UNAIDS asopioid substitution treatment (OST) for heroin dependence (WHO, 2009b; UNAlDS, 20].1; UNODC, 2013c; Wu and Clark, 2013). Both epitomize harm reduction because theyreduce the harms ·of street heroin use without requiring the drug user to abstain from theuse of mood altering drugs. The effectiveness of OST in treating opiate addiction, reducingdrug use, reducing the frequency of sharing potentially HIV-contarninated .syringesand needles, and preventing HfV infection has been well documented. Strong evidence indicates that appropriate doses of methadone or buprenorphine relieve cravings,block the effect of illicit opioids and prevent withdrawal. Reduce frequency of injectingdrugs, reuse of syringes and needles has also been reported (Kimber et aI., 2010; ECDC, 2011; MacArthur et al., 2012; Wang et al., 2014). Researchinto treatments for stimulant (like amphetamine and cocaine) addicts lags far behindas compared to treatments for heroin dependence. Dexamphetamine substitute treatmentfor amphetamine dependence shows promise and appears to be effective and 77 safe. Use of dextroamphetamine has been associated with higher rates of sustained amphetamineand cocaine abstinence (Castells et 01.,2010; Galloway et 01.,2011). Supervised Injecting Facilities also known as Supervised Injection Sites (SIS), Safe Injection Site, Safer Injection Facility (SIF), Drug Consumption Facility (DCF), Drug Consumptionrooms (DCR) or Medically Supervised, Injection Center (MSIC) are legally sanctioned and medically supervised facilities where injection drug users are allowed to injectpre-obtained drugs in a more protected, hygienic and less stressful environment comparedwith most other private and public settings. The first injection room appeared inBern, Switzerland, in 1986. In the decade that followed, SIFs spread to other cities in Switzerland as well as cities in Germany and the Netherlands. Since 2000, SIFs have been introduced in Spain (Madrid and Barcelona), Australia (Sydney) and Canada (Vancouver). These facilities are exempted from the application of the criminal code or otherlegislation that governs the use of controlled substances (Csete, 2010; Davies, 20 10; Hedrichet 01.,2010; UNODC, 2012). Theiraim is to establish contact with hard-to-reach populations of drug users, provide an environment for more hygienic drug use, reduce morbidity and mortality risks associated with drug use. (in particular street-based drug injecting), lessen overdose episodes and promote drug users' access to other social, health and drug treatment services (Salmon et al.,2010; Marshall et 01.,2011 b; De Vel-Palumbo et 01.,2013; EMCDDA, 2013g). 78 It is imperative to note that promoting harm minimization does not condone illicit drug use.It acknowledges that many people are not able to give up drug use without help. It is a means of reducing the risk of harm to a person so that they are kept alive and if they eventually decide to stop their drug use, they will not suffer serious consequences from theirdrug use (DeBeck et 01.,20] 1). Despite good evidence for its effectiveness in HfV prevention, several countries remain resistant to harm reduction (Rhodes et 01.,2010). 2.9.4 Rehabilitation TheWHO defines rehabilitation as the process by which an individual with a substance use disorder achieves an optimal state of health, psychological functioning, and social well-being. The general intent is to enable the patient to cease substance abuse, in order toavoid the psychological, legal, financial, social, and physical consequences that can be caused, especially by extreme abuse. Drug users have a right to voluntary rehabilitation. After rehabilitation they are expected to be socially reintegrated into the wider community (Gifford, 2014; Reif et 01.,2014; WHO, 2014b). 2.10Challenges Globally, harm reduction strategies addressing drug issues are so unpopular amongst politicians, policemen, magistrates and bureaucrats. In many countries publicly supporting an innovative harm reduction strategy like SIF is considered political suicide. Tbe Global Commission on Drug Policy has been urging politicians to courageously speakout on effective drug policies (Global Commission on Drug Policy, 2011). 79 Thesituation is not better in Kenya as most decision makers like politicians (primarily lawmakers), police (law enforcement officers), magistrates and judges (criminal justice authorities),technocrats, bureaucrats and religious leaders are not willing to support harm reduction strategies in letter and spirit. The criminalization of drug use promotes arbitraryarrests of PWID which it leads congestion in prisons which in return facilitates druguse among inmates, some who are first time users (Kinyanjui and Atwoli, 2013). Peoplewho inject drugs are likely not to optimally adhere to long term treatment. This hasbeen attributed to delayed access to health facilities, competing comorbid diseases, stigma, discrimination, poverty, criminalization of drug use and poorer long-term adherence(Cayla et al., 2009; Muture et al., 2011; DeSilva et al., 2013). In addition, the potentialinteractions between methadone and buprenorphine with substances of abuse as wellas medicinal drugs like Nevirapine, efavirevz, and Rifampicin reduce the efficacy of OST (Lee et al., 2012; McCance-Katz et al., 20] 3; Vilas-Boas et al., 2013). Besides, in Kenya there are limited government funded rehabilitation centres and most clients seeking rehabilitative services end up being held in lID suitable venues like the medical or psychiatric wards. Besides most government funded rehabilitation centres do not admit FIDUs. Moreover, MAT is mostly available in privately owned facilities. 2.11 Conclusion Since drug and substance abuse is a socio-medical problem, public health interventions aimed at improving the health of drug users must address the social factors that 80 accompany and exacerbate the health consequences of illicit drug use. People who use drugshave the same human rights as people who have never used drugs. These rights includethe right to the highest attainable standard of health, to social services, to work, to benefit from scientific progress, to freedom from arbitrary detention and freedom from cruelinhuman as well as degrading treatment. 81 CHAPTER THREE: MATERIALS AND METHODS 3.1 Study Design This study was carried out in Mombasa County with an objective of determining the predictors of HIV and puJrnonary TB among PWID. It was a cross sectional study which focused on assessing a representative subpopulation of PWID at one specific point in time.Disease and exposure status were measured simultaneously. This study design has been used for similar studies like in Cavlek et al. (2011), Majidpour et al. (2012) and Karajibani et at. (2012). 3.2 Variables The independent variables (risk factors) were high risk injecting and sexual practices, mono or polysubstance use and exposure to ST1s while the dependent variables HIV infection, low BM1, Jaw CD4 count, TB and HIV sub-types. 3.3 Target and Study Population The target population was a community living in a cosmopolitan coastal city while the study population was PWID living in Mombasa County, Kenya. 3.4 Study Site. The study was carried out in purposively Mombasa County based on the fact that it bas the largest number of PWID in Kenya. Mombasa acts as a conduit of drugs from South America en route to Europe and Asia and in the process some of the drugs find their way 82 into the local market. The IDU participants were recruited from Bomu Hospital as it has supportgroups for recreational drug users as well as PLWHA. Mombasa is a cosmopolitan coastal city with the largest port in East Africa and lies between latitudes 3° 80' and 4° ]0' S and longitudes 39° 60' and 39° 80' E, with a total landmass of 229.6 km2 and inshore waters covering 65 km2 (as shown in Figure 3.J and Appendix 1). Mombasa County has a population of939,370 people of which 486.,924 are male and 452,446 are female (KNBS, 20] 0). The County consists of 6 constituencies namely, Kisauni, Mvita, Changamwe, Likoni, Jomvu and Nyali (IEBC, 2012). The cosmopolitan nature of Mombasa combined with the presence of a youthful population has created a suitable environment for commercial sex, child tourism and recreational druguse (Kahuthia-Gathu et al., 2013; Korir, 2013). Bomu Hospital is a registered non-governmental healthcare organization situated in Changamwe Sub-County close to the Moi International Airport (at latitudes 40 l ' 28' South of Equator and longitude 39° 46'57" East of the Greenwich Meridian), It is a project of the Mkomani Clinic Society (MCS). In addition, MCS runs three other satellite clinics in South Coast, Mariakani and at Wema Centre in Kisauni Sub-County. Bomu Hospital offers a large range of programmes like separate Comprehensive Care Centres foradults and children (MOH, 2011; Bomu Hospital, 2013). 83 1.75 3.5 I I I I t 7 Kilometers I Legend • City Constituency Kisauni .~ s Figure 3.1: Map of Kenya and Mombasa County Source: Courtesy of Regional Centre for Mapping of Resources for Development 84 Currently,Bomu provides free comprehensive medical services to more than 23,500 PLWHA from all over the Coast region through the hospital and its satellite clinics that areassisted by the President's Emergency Plan for AIDS Relief (PEPFAR) funding. Otherdonors include United States Agency for International Development (USAlD), KenyaFamily Health Program, Japanese International Cooperation Agency, Canadian International Development Agency, Pathfinder's International, European Union, International Center For Reproductive Health, The Planned Parenthood Federation of America, African Palliative Care Association, Academy for Educational DevelopmentJIntemational Center for AIDS care and treatment Programs, New York Universityand the Center for Disease Control (Bomu Hospital, 2013). 3.5 Sample Size Samplesize determination is influenced by study design, prevalence of the attribute, accessibilityto the participants, ethical issues and availability of financial resources. An optimum sample is one that fulfills the requirements of efficiency, representativeness, reliabilityand flexibility. At per time this study was designed, the H1Y prevalence among PWID ranged between 43% - 49% (Deveau et al., 2006; Needle and Zhao, 20]0). Both authorsreported this as an underestimate. The prevalence of my in PWID was estimated to50% and the formula below was used (Mugenda and Mugenda, 2003). .. 85 D =the desired sample size (since the target population is greater than 10,000). z = the standard normal deviant (as per area under normal curve at confidence level 95%), p = the proportion ill the target population estimated to have the attributes being measured. q= l-p d= the level of statistical significance set n= (1.96f (0.5). (1- 0.5) (0.05) 2 n "" 384 participants. A total of 384 participants were to be recruited. Due to circumstances beyond the control of the researcher like the general elections in 2013 and arbitrary eviction of drug users from their havens by the County government, only 371 rDUs were enrolled. 3.6 Sampling Procedure Respondent driven sampling (RDS), traditional snowball sampling and makeshift outreach methods were used to recruit IDUs. 3.6.1 Respondent driven sampling The RDS method is based on snowball sampling and allows researchers to make estimates about hidden population such as the injection drug users, sex workers. and men 86 who have sex with men. This sampling technique has been used by several researchers (Atkinson et al., 2011; Ulibarri et al., 2011; Medhi et al., 2012). Recruitment using RDS was initiated with a number of purposefully selected "seeds" (individuals belonging to the study population who have influence over other members being interviewed). Each seed was given three uniquely coloured coupons with which to recruit peers (other eligible PWID) into the study. These recruited peers were considered as the first wave of participants. Each participant in the first wave who completed the interview was then provided six coupons with which to recruit their peers. Successive waves of recruitment continued until the waves died (no more participants were being enrolled) before the desired sample size was achieved. At this stage only 142 PWID had been recruited. SnowbalJ sampling and makeshift outreach methods were then used. 3.6.2 Snowball sampling SnowbalJ sampling is a non-probability recruitment technique that is appropriate to use in hidden populations. The recruited PWID were asked to assist researchers in identifying other potential subjects. The chain referral system continued until it was exhausted. This method has been used by researchers targeting similar groups (Rafiey et al., 2009; Atkinson et al., 2011; Shannon et al., 2011; Suohu et al., 2012). 3.6.3 Makeshift outreach method To cover up for the deficit, makeshift outreach method was used. This involved direct recruitment from drug havens by a rehabilitated former IDU Among others, the method 87 haspreviously been used by Gyarmathy et al, (2009), Williams et al, (2009) and Suohu et al, (2012). 3.7. Data Collection Methods The roUs were defined as persons who injected drugs for recreational purpose at least once a day regularly in the last one month prior to the commencement of study. Observation of the needJe scars was a necessary criterion for their enrollment. Data collection methods varied depending on the objective as follows: 3.7.1 Interview Schedule Structured interview schedule was used to capture the socio-demographic characteristics and drug use pattems. The information was collected by research assistants who are trained community health workers. They read the questions exactly as they appeared on the interview schedule to the participants in English or Swahili. TIle choices of answers to the questions were both fixed (close-ended) as well as open-ended as shown in Appendix 2. 3.7.2 Anthropometric Measurements Nutritional status was determined using anthropometric measurements which included weight, standing height, bust, waist circumference, hip circumference and mid- upper arm circumference as per anthropometry procedures manual by National Health and Nutritional Examination Survey (CDC, 2009). In addition, in order to assess the heamogloblin level a full haemogram was carried out. 88 Heightwas measured in centimeters using Health 0 Meter PORTROD, Professional Wall MountedHeight Rod. Participants were asked to remove their shoes, stand straight with both feet facing flat-forward and their back against the wall. To measure weight (in kilograms), each respondent was requested to remove their shoes, purse and anything else thatwas heavy. The respondent stood on the scale platform, facing the vertical portion of thescale with weight evenly distributed between both feet (CDC, 2009). Todetermine bust circumference, a tape measure was placed around the back and across thenipples. It was wrapped around loosely. The waist circumference was determined by first identifying the lowest point of the last rib and the crest of the ilium (top of the hip bone). Once the upper hip bone was located, a tape measure was placed around the abdomenhorizontally and at the belly button or just above it. The tape measure was snug but tight enough not to cause compressions on the skin. The hip circumference was obtained by positioning the tape measure horizontally around the maximum circumference of the buttocks. For women this was at groin level while for men it was 2 - 4 inches below the navel. All measurements were recorded in centimeters. Waist. hip ratio (WHR) was obtained by dividing waist circumference by hip circumference. The mid-upper arm circumference (MUAC) was obtained using MUAC tape measure. With the arm bent and held against the torso, the summit of the shoulder (the acromium) to the tip of the elbow (the olecranon) was measured; the mid-point was marked and this iswhere the circumference measure was then taken. The arm was left to hang in a relaxed position and the armband (strip) was contacting the entire circumference of arm, this was " 89 doneby applying finger pressure. It was not so tight to cause the skin to bulge around the tape and neither was there any space left between the tape and the skin. The circumference was recorded to the nearest millimeter (eDe, 2009; WHO, 2011b). Body mass index (BMI) also referred to as Quetelet index, is a statistical measurement which compares a healthy body weight based on how tall a person is. It was determined using the universally formula of kg/m". Based on the WHO guidelines, a BMl of less than ]8.5 kg/rrr' was considered underweight indicator of undernutrition, while a BMJ greater than 25 was considered overweight and above 30 was considered as obese (FANTA, 2013). To determine the heamogloblin (Hb) level, approximately 5 ml of venipunctnre blood was drawn a full haemogram was carried out using Midray Analyzer CSC-5380, Mindray Medical International Limited). Haemoglobin that was equal or more than 12 g/dl, for women and 13 g/dL for men was considered as non-anaemia while Hb of less than 12 g/dL in women or. 13 g/dL in men was classified as anaemia (WHO, 20 11c). 3.7.3 Tuberculosis Diagnostic Methods All the participants received health education on TB and those who had a self reported history of persistent cough for more than two weeks, fever, chest discomfort and sweating at night were screened for TB infection ceDe, 20l2f). The screening process was carried out by a registered medical practitioner while the sputum was obtained by a 90 registered laboratory technologist. The TB samples were handled at a Physical Containment Level 3 (APe3) laboratory which had bio-safety cabinets. 3.7.3.1 Collection of Sputum The patients were given instructions on how to collect the sputum. One spot and two early morning 5 ml specimens of sputum were obtained on three different consecutive days for TB diagnosis (WHO, 2008a). This was done in a Sputum Collection Booth (model VCM-1500N 2 ) to prevent TB from spreading. 3.7.3.2 TB Sputum for Acid Fast Bacteria (AFB) Microscopy Using an application stick, the most mucoid part of the sputum was placed on the slide in an oval shape (2-3 em in length and] -2cm width). Carbol Fuchsin was applied on the slidewhich was gently heated until it steamed. The hot slide was allowed to sit for 3 to 5 minutes and afterwards rinsed with tap water. The slide was flooded with a decolorizor (3% hydrochloric acid in isopropyl alcohol) and rinsed subsequently with tap water. The slide was next flooded with Methylene Blue (in order to provide a contrasting background), rinsed with tap water and blot dried. The non-acid-fast bacteria picked up Methylene Blue, to become blue while the acid-fast bacteria retained Carbol Fuchsin colour and appeared red when viewed under the microscope. A drop of oil was put on one end of the smear and the slide was viewed under oil immersion lens (Af'Hl, 2009)" The findings were reported as negative where no AFB was found in at least 100 fields and exact figure out of 100 in slides with ]-9 AFB per 100 fields while slides with 10-99 • '". 91 AFBper 100 fields were reported as (+). On the other hand, slides with 1-10 AFB per fieldwith count of at least SO fields were reported as (++) while slides with more than 10 AFBper field with count of at least 20 fields were reported as (+++) as guided in APHL (2009). A bacteriologically confirmed TB case was defined as a positive by smear microscopy, culture or WHO-approved rapid diagnostics such as Xpert MTBIRIF (WHO, 20l3i). The clients who tested TB positive were enrolled into the TB programme at Bomu Hospital or Coast PGH for treatment and psycho-social support. Infectious waste was collected in an autoclavable bag and autoclaved before incineration. 3.7.3.3 Drug Susceptibility Testing Drug susceptibility testing (DST) of Mycobacterium tuberculosis was carried out after culture was isolated from clinical specimens. Lowenstein-Jensen (LJ) media was used for mycobacterial culture. A homogeneous suspension of growth was inoculated into growth control (GC) tubes and drug-containing LJ media tubes. The proportion method (critical proportion of 1% of growth for all the four drugs) was used to determine the percentage of growth (number of colonies) of a defined inoculum on a drug-free GC media versus growth on culture media containing the critical concentration of an anti- TB drug (Table 3.1). This was followed by incubation of the media at 36 ± 1°C. The inoculated media were examined for contamination after 1 week of incubation and for DST interpretation after 4 and 6 weeks of incubation. Results after 4 weeks were considered as provisional while after 6 weeks were definitive and interpretation of results was based on the later. 92 Drug Isoniazid Rifampicin Ethambutol Pyrazinamide --- Critical concentration (ug/ml) 0.2 40 2 4 Table 3.1: Critical concentrations of first-line drugs Source: (WHO, 2008b). A strain was considered to be resistant if the medium containing the critical concentration of the corresponding drug showered more colonies than the growth control (GC) with the 1% inoculum. The result was interpreted and reported as susceptible or resistant. Borderline cases (about 1% growth on drug-containing medium) were reported as resistant and retested (WHO, 2008b). Growth of more than 20 colonies on control rubes and no growth on drug tubes were reported as sensitive to all drugs. Growth of more than 20 colonies on control tubes and number of colonies on Isoniazid, Rifampicin, Ethambutol and Pyrazinamide tubes of more than or equal number of colonies on control corresponding tubes of 1/100 was reported as resistant to Isoniazid, Rifampicin, Ethambutol and Pyrazinamide respectively. Growth of more than 20 colonies and number of colonies on Isoniazid, Rifampicin, Ethambutol and Pyrazinamide tubes of less number of colonies on respective control tubes 11100 was considered as sensitive to Isoniazid, Rifampicin, Ethambutol and Pyrazinamide correspondingly. In cases where there was no growth on control tubes or lessthan 20 colonies on GC and no growth on drug tubes, it was reported as invalid result and the process was repeated. Multi drug resistant TB was defmed as resistance to 93 isoniazid and rifampicin, with or without resistance to other first-line drugs (WHO, 2008b;WHO, 2012b; TB CARE 1,2014). 3.7.4 HIV Testing All the participants received free my education after which they were allowed to make personal informed choices on either to undergo an HIV test or not. Upon obtaining written informed consent, they completed the interview schedule after which each participant underwent pre-test HIV counseling. Provider-Initiated HIV Testing and Counseling was carried out by trained YCT counselors. The HIV testing was purely on voluntary basis and those who decided not to undergo the test at this stage were not included in the study. 3.7.4.1 Blood Collection Approximately, 5 ml of venipuncture blood was drawn from each participant in EDTA anticoagulant tubes and used for conducting other tests cited within this study like full haemograrn, CD4 count and viral load. A drop of the blood was used for HlV testing. The HfV -I status was determined using Determine ™ (Abbott Laboratories, Tokyo, Japan) and positive serological results were confirmed by Unigold" (Trinity Biotech PJc. Bray, Ireland) as per the Kenya National Guidelines for my Testing and Counseling (NASCOP, 2010). The results were ready within 5 to 10 minutes. Each participant received post test counseling and those who tested HIY positive were referred to the Comprehensive Care Centre and enrolled into the Hl V ART treatment and psychosocial 94 support program at Bomu hospital or Coast General Hospital. All participants were encouraged to join the recreational drug users support group hosted by Bomu hospital. 3.7.4.2 RNA Extraction and Quantitation of HIV-l Viral Load The HIV-I viral load was quantified using the automated Abbott m Sample Preparation System (m2000sp) that has automated sample extraction, amplification and detection according to the manufacturer's instructions (Abbott Molecular Inc., Illinois, U.S.A). This was achieved via RNA extraction from 0.2 mL of plasma using the 0.2 mL plasma RNA extraction and master mix addition protocol by the Abbott m2000sp sample preparation system. The master mix containing the viral RNA (vRNA) was then transferred to Abbott m2000rt instrument for viral load detection using the program for O.2mL RNA amplification with a lower limit of quantitation at 150 (2.18 logl O) copies/nil of plasma. This method has been previously by Thao et at. (2012). 3.7.4.3 Reverse Transcriptase-Pf.R To convert vRNA to cDNA, 5 ul. from the remaining BilL of the RNA extract in the Abbott m2000sp deep well plate was used as a template and 0.16 J.lMeach of primers; Nyupol_7 (5 '-GGGAATTTTCTTCAGAGCAG-3') and Nyupol_8 (5'- TCTTCTGTCAATGGCCATTGT-3'). This was performed by one-step RT-PCR in a 25 ul, reaction consisting of; 0.5 ul. SuperScriptTM III one step RTlPlatinumH Taq high Fidelity Enzyme Mix in a 1x reaction buffer mixture containing Mg2+ and deoxyribonucleotide triphosphates (dNTPs) (lnvitrogen, Carlsbad, CA). Thennocycling conditions for reverse transcriptase PCR were set with an initial cycle RT step at 5SOC for 95 30 min and 94°C for 2 min, followed by 40 cycles of PCR at 94°C for 15 see, 46°C for 30 see,nOc for 1 min and an extension at 7i)c for 5 min. The amplified viral cDNk encording the partial pol-gag gene was nested in a 25 ~L master mix reaction consisting of 1X P 1.5mM MgCI-.2, 1U/~L Taq polymerase (KemTaq®), 200 ~M of each dNTP (Invitrogen, Carlsbad, CA), 3~1 of template DNA and0.5 ~M of each inner primer; Nyupol_9 (5'-TCCTT AACTTCCCTCAAATCAeT~3') and Nyupol_lO (5' -CTGGCACGGTTTCAATAGGACT-3'). Amplification was done with an initial denaturation of 94°C for 4 minutes followed by 40 cycles of 94°C for 15seconds, 46°e for 30 seconds, and noe for 1min, with a final extension of noe for 5minutes. The resulting PCR products were electrophoresed in 1.5% ethidium bromide stained agarose gel and visualized under ultraviolet light. Presence of 297 bp fragment was indicative of successful amplification. 3.7.4.4 DNA Purification and Sequencing The resulting PCR amplicons were purified with QIAquick PCR purification kit (Qiagen, Valencia. CA) following manufacturer's instructions (5.7.3). Direct sequencing of the PCR amplification products was performed using the inner primers (Nyupol_9 and Nyupol_lO) with the Big Dye Terminator sequencing chemistry in both directions. The sequencing products were analyzed on an ABI PRlSM® 3100 Genetic Analyzer and DNA base calling performed using the DNA Sequencing Analysis software V3.7. The sequence data was then imported into the Genetyx-Windows computer software version 96 9.1.0 (Genetyx Corporation, Tokyo, Japan) to assemble the two sequence segments into a single contiguous sequence. 3.7.5 Hematological Profile Full haemogram was determined usmg a BC-3200 mindray haematologic analyser (Mindray Inc., NJ). These included: leucocyte counts (total leukocytes, and numbers and percentages of lymphocytes, monocytes, neutrophils, eosinophils and basophils); erythrocyte indices (red blood cells [RBC], haemoglobin [Hb] levels, haematocrit [Hct], mean corpuscular Hb [MCH], mean corpuscular Hb concentration [MCHC], mean cell volume [MCV] and red cell width [RDW]); and thrombocyte indices (platelets. mean platelet volume [:MPV],PCT and platelet width [PDW]). 3.7.6 CD4+ T Cell Enumeration Baseline CD4+ T cell counts were determined using a FACSCalibur flow cytometer (Becton-Dickinson, NJ) equipped with automated acquisition and analysis software. This was done by placing 5 JlI of whole blood samples in a tube and RBC lysis buffer was added. After 5 minutes incubation, the cells were washed and fluorescent-tagged antibodies anti-CD3, anti-CD4, anti-CD19 and anti-CD45 were added. The cells were incubated for 30 minutes after which the samples were washed and CD4+ T cells enumerated on the flow cytometer. Individual test results were reviewed to confirm the accuracy of the automated software analysis. 97 3.8Vital Signs 3.8.1 Body Temperature It was measured using a clinical thermometer which was placed under arm with the bulb in the center of the armpit. The ann was pressed against the body for 5 minutes. The thermometer was removed and readings recorded in degrees Celsius. Pulse rate which is thebeat of the heart that can be felt in any artery that lies close to the skin per minute. It was determined by placing the tips of the index and second fmgers of one hand on the insidewrist of the participants hand. The fingers were positioned just below the base of thethumb to take the radial pulse at the wrist for one minute. 3.8.2Blood Pressure To obtain blood pressure, participants were asked to remove any constricting clothing from their upper left arm, to sit straight up in a chair with their feet resting flat on the floor and not cross their legs. The blood pressure cuff was loosened and slid on their Jeft arm through it until it was positioned about 112 inch above the elbow. The cuff was inflated by rapidly pumping the inflation bulb until the correct pressure was reached. The inflation bulb was slowly released until the numbers came to rest, then the current blood pressure readings were recorded. 3.9 Pilot Study A pilot study was carried out from Bomu Hospital (Wema centre satellite clinic in Kisanni Sub-County) to assess whether the proposed methods and procedures were applicable. This was to help in testing logistics that could have exposed any deficiencies 98 to the main study. The quality and the efficiency of the main study were improved. The participants from this centre were not included in the actual study. 3.10 Inclusion Criteria 1. Only individuals who had practiced injection drug use in the last Imonth were included in this IDU study. 2. These individuals were all adults. 3. They must have consented to voluntarily participate and undergo an HIV test. 4. Those with visible needle scars. 3.11Exclusion Criteria 1. Other drug users who were non IDUs were excluded from the study. 2. Injecting drug users who were minors were not included. 3. Participant who were not willing to give a written consent or undergo an HIV test were excluded. 4. Those without needle scars were excluded. 3.13EthicaJ Consideration Thestudy was conducted according to the Helsinki Declarations and ethical approval for the study was sought and granted from Kenyatta University Ethical Review Committee (PKUO 19/116 of 2012, Appendix 4). Permission was granted from Ministry of Health, Mombasa County (MOH Ref ADMJ/5/371121 , Appendix 5). Written informed consent 99 either in English or Swahili was obtained from each participant before enrolment (Appendix 6 and 7 respectively). Confidentiality was ensured as no individual name was used instead the participants were assigned study numbers. The participants benefited from free health education on HIV, tuberculosis, hepatitis Band C, STIs, personal hygiene and nutrition. The HlV positive, TB positive as well as Hl V-TB co-infected participants were referred to the comprehensive care unit of either Bomu Hospital or the Coast General Provincial hospital depending on participant's preference. All participants were encouraged to join the recreational drug users support group hosted at Bomu Hospital. 3.14Data Analysis Data analyses were conducted using SPSS, version 19 (IBM SPSS Inc., New York, USA), all tests were two-tailed and P231 100 (46.7) 88 (56.1) 174-231 41(19.2) 39(24.8) 116-173 40 (18.7) 18 (11.5) 0-115 33 (15.4) 12 (7.6) 214 14 (6.5) 31.7 (9.1) 157 86 (54.8) 30.6 (6.6) 111 (51.9) 58(27.1) 45 (21.0) 80 (51.0) 39 (24.8) 38 (24.2) 66 (30.8) 138 (64.5) 10 (4.7) 35 (22.3) 112 (71.3) 10(6.4) 57 (26.6) 26 (12.1) 86 (40.2) 42 (19.6) 3(1.4) ]7(10.8) 28(17.8) 44 (28.0) 66 (42.0) 2 (1.3) 43 (20.1) 20 (9.3) 151 (70.6) 43 (27.4) 36 (22.9) 78 (49.7) ]72 (80.4) 42(19.6) ]35 (86.0) 22 (14.0) 102 (47.7) 66 (30.8) 5 (2.3) 17 (7.9) 4 (1.9) 20 (9.3) 34 (21.7) 20 (12.7) 32 (20.4) 13 (8.3) 41 (26.1) ]7 (10.8) <0.0001 0.271a 0.741 0.170 <0.0001 <0.0001 0.167 <0.0001 0.015 Table 4.1: Socio-demographic characteristics of IDUs in Mombasa, 2012-2013 Data are presented as numbers and proportions (%) of subjects, unless otherwise indicated. Statistical analyses were conducted using the Pearson's chi-square or Fisher's exact tests as appropriate. "Mann-Whitney test. bChi-square test was based only on cells with at least 5 counts. 'Others constituted fishermen, house helps, beggars, garbage collectors, clerks, masons, artisans and petty thieves. PSV, passenger service vehicles (Matatu drivers, taxi drivers, conductors and touts). dAs at September 30th 2013, US$ was equivalent to KShs. 86.8. Values in bold indicate significant P-values. 106 Sexual practices were examined among IDUs presenting with or without HIV infection. Sexual orientation did not differ significantly between the groups (P=O.225). However, the proportion of IDUs reporting early age of sexual debut (P<0.0001), at least two sexual partners (P20 43 (20.1) 19 (12.1) Number of sexual partners 0 25 (11.7) 5 (3.2) I 91 (42.5) 49 (31.2) <0.0001 2-5 88 (41.1) 73 (46.5) >5 10 (4.7) 30 (19.1) Hadpenetrative sex in the past year 165(77.1) 144 (91.7) <0.0001 Had sex without condom 19 (8.9) 49 (31.2) <0.0001 Had sex for police protection 6 (2.8) 37 (23.6) <0.0001 Had sex for drugs 20 (9.3) 39 (24.8) O.05 for all) as shown in table 4.3. 110 Category HIV(-] pHIV(+] 214Participants (n) Injection drugs Cocaine Heroin Heroin -cocaine Oilier injection drugs Diazepam (valium) Flunitrazepam (rohypnol) Frequency of injection, per day Once Twice Thrice >3 times Duration of injection <6 mos. 6-11 mos. 1-3 yrs, >3 yrs. Non-injection drugs Alcohol Bhang Brown sugar" Cigarette Cocktail" Diazepam Khat Rohypnol tablets Poiysubstance use Group I 6 (2.8) 5 (3.2) Group II 50 (23.4) 25 (15.9) Group III 7] (33.2) 39 (24.8) Group IV 67 (3] .3) 37 (23.6) Group V 19 (8.9) 39 (24.8) Group VI ] (0.5) 12 (7.6) Needle and syringe sharing 50 (23.4) 50 (31.8) 0.076 Flushing of blood 43 (20.1) 15 (9.6) 0.006 Table 4.3: Drug use patterns among IDUs in Mombasa, Kenyan in 2012-2013 ]9 (8.9) 191 (89.3) 4 (1.9) 16 (7.5) 12 (5.6) 13 (6.1) 75(35.0) 95 (44.4) 31 (14.5) 40 (18.7) 30 (14.0) 76 (35.5) 68 (31.8) 37 (17.3) 102 (47.7) 30 (14.0) 144 (67.3) 54 (25.2) 2 (0.9) 51 (23.8) 114 (53.3) ]57 42 (26.8) 112 (71.3) 3 (1.9) 10 (6.4) 2 (1.3) 25(15.9) 36 (22.9) 76 (48.4) 20 (12.7) 8 (5.1) 21 (13.4) 62 (39.5) 66 (42.0) 82 (52.2) 81 (5l.6) 19 (12.1) 110 (70.1) 64 (40.8) 4 (2.5) 61 (38.9) 91 (58.0) <0.0001 <0.0001 0.837 0.004 0.001 <0.0001 0.464 0.643 0.651 0.002 0.002 0.265 0.999 0.089 0.086 0.103 3 years [OR, 6.509 (2.716-15.598); P5 Had penetrative sex Sex without a condom Sex for police protection Sex for drugs' STl Injecting drugs Any use ofheroin Any use of cocaine Duration of injection 6-11 mos. 1-3 yrs. >3 yrs. Needle and syringe sharing Flushing of blood Non-injecting drugs Alcohol Cocktail Khat Polysubstance use Group V 3.045 (1.631-5.684) <0.0001 Group VI 15.195(1.870-123.473) 0.011 Table 4.4: Association of the socio-demographic characteristics, sexual practices and drug use patterns in relation to IDUs HIV status, in Mombasa County 2012-2013 Characteristic OR (95% CI) 2.676 (1.487-4.817) 2.897 (1.457-5.762) 8.900 (2.610-30.350) 14.765 (3.979-54.794) 0.354 (0.150-0.837) 0.377 (0.171-0.831) 0.426 (0.218-0.829) 0.451 (0210-0.969) 2.730 (1.340-5.560) 3.766 (1.348-10.520) 11.375 (3.312-39.072) 3.072 (1.552-6.083) 3.683 (1.986-6.833) 8.888 (3.515-22.479) 2.762 (1.492-5.114) 5.520 (3.364-9.056) 3.253 (1.823-5.803) 3.509 (J .895-6.499) 3.072 (1.149-8.213) 3.869 (1.633-9.168) 6.509 (2.716-15.598) 1.712 (1.052-2.788) 0.462 (0.238-0.897) 4.618 (2.810-7.590) 1.916 (1.197-3.067) 2.009 (1.251-3.224) 0.001 0.002 <0.0001 <0.0001 0.018 0.016 0.012 0.041 0.006 0.011 <0.0001 0.001 <0.0001 <0.0001 0.001 <0.0001 <0.0001 <0.0001 0.025 0.002 <0.0001 0.031 0.024 <0.0001 0.007 0.004 Binary logistic regression was conducted such that all HIV infected injection drug users (n=157) were modeled against all of the HIV negative injection drug users (n=214) controlling for age, education, employment, religion and residence. Data are presented as odds ratios (OR) and 95% confidence interval (CI)~ SW, sex worker; STI, sexually transmitted infections; Group V, heroin or cocaine and any other four substances; Group VI, heroin or cocaine and any other five substances. ,. 116 An overlap of socio-demographic characteristics, sexual practices and substance use patterns predicted rnv infections in this study. These include the female gender, marital separation, sex work or working in entertainment and beauty therapy venues, having had penetrative sex in the last one year, early sexual debut, high risk sexual behaviour (like multiple sexual partnership arising from sex for money, sex for police protection and sex for drugs as well as unprotected sex), exposure to STI and high risk injecting practices (like sharing of needles and syringes). The increased risk of HlV acquisition arising from the overlap between sex work and drug use has been widely documented. Female sex workers who are drug dependent are more likely to engage in transactional sex while under the influence of substances in addition to being acquiesced to clients' demands for unprotected sex, especially if offered more money or drugs (Strathdee et 01., 2008; Patterson et 01., 2012; Shannon et al., 2014). In some cases, drug use is involuntary because pimps and managers coerce sex workers into drug use as a means of control especially for under age users (Goldenberg et 01.,2012). Owing to the fact that both sex work and drug use are illegal, sex workers who use drugs are more vulnerable to police harassment like frequent arbitrary arrests or police misconduct like extortion and blackmail. They also face the risk of physical as well as sexual abuse which increases the odds of HlV acquisition and reduced probability of seeking medical attention (Cottler et 01.,2014; Odinokova et aI., 2014). Although heroin was the most common drug, a vast majority of IDUs utilized more than one substance. In addition, consumption of khat, cocktail or alcohol and poly substance 117 use was predictive of HIV infection. While many IDUs in this study used heroin, a depressant that tends to inhibit libido, especially in large quantities or with long-term use, they additionally consumed stimulant-type drugs such as khat, bhang and cocktail that increased sexual desire (Blum et al., 2013, Tadesse et al., 2013; Berhanu et al,. 2014). 4.4 Nutritional Measures of the PWID in Mombasa County Nutritional analyses showed that body height was significantly higher among HIY-1 negative individuals compared to HIV-I positive individuals (P=O.OOl). However, body weight, hip circumference, waist circumference, bust circumference, waist-to-hip ratio, and bust-to-waist ratio did not differ significantly between the HIV-l negative and positive study groups (P>0.05 for all comparisons). Although the mid-upper-arm circumferences were significantly lower in the HIV-l positive group (P0.05 for both comparisons). Finally, haemoglobin (Hb) levels were significantly lower in the HJV-J positive individuals compared to the HIV-I negative groups (P=O.002). Consistent with the low Hb levels in the HIV -1 infected group, the proportions of individuals with anaemia was significantly higher in the HV-I positive IDUs compared to the mV-J negative IDUs (29.3% vs. 19.2%; P=O.026) as shown in table 4.5. 118 Additional regression analyses for identifying the predictors of malnutrition (BMl<18.5 kg/nr') indicated that malnutrition in the HlV negative IDU subpopulation was significantly associated with the CD4+ T cell count 2350<500 cells/ul. (OR, 3.718; 95% CI, 1.264-10.932; P=O.017) and CD4+ T cells/ul. <350 cells/ul, (OR, 2.761; 95% CI, 1.204-6.334; P=0.016). Among the HIV positive IDUs malnutrition was associated with CD4+ T cell count 2350<500 cells/ul, (OR, 2.031; 95% CI, 0.936-4.407; P=O.073) and <350 cells/ul. (OR, 2.972; 95% CI, 1.117-7.910; P=0.029) (Table 4.7). However, HIV-l viral loads 21,000<10,000 (OR, 1.808; 95% CI, 0.675-4.848; P=0.239); 210,000<100,000 (OR, 0.998; 95% CI, 0.394-2.526; P=0.997) and >100,000 (OR, 0.565; 95% Cl, 0.568-4.312; P=0.387) were not significantly associated with malnutrition in the HIV positive IDUs (Table 4.6). 119 IDU Characteristic HIV-l Negative, HIV-l Positive, p n=214 n=157 Height, m l.71 (0.09) l.69 (0.11) 0.001 Weight, kg 54.0 (9.0) 53.0 (8.0) 0.295 Hip circumference, ern 90.0 (7.8) 90.0 (8.0) 0.381 Waist circumference, 76.0 (7.0) 75.0 (9.0) 0.122 cm Bust circumference, ern 85.0 (7.3) 85.0 (7.0) 0.898 Waist-to-hip ratio 0.83 (0.09) 0.83 (0.08) 0.487 Bust-to-waist ratio l.12 (0.11) l.13 (0.10) 0.265 MUAC,cm 26.0 (3.0) 24.0 (2.8) <0.0001 M<23.0; F<22.0cm, n 24 (11.2) 13 (8.3) (%) 0.385 Normal, n (%) 190 (88.8) 144 (91.7) BMI, kg/m' 18.69 (2.77) 18.75 (2.17) 0.277 <18.5, n (%) 101 (47.2) 64 (40.8) 0.245~18.5,n (%) 113 (52.8) 93 (59.2 Haemoglobin, g/elL 12.60 (2.30) 12.30 (2.50) 0.002 Anaemia, n (%) 41 (19.2) 46 (29.3) 0.026 Table 4.5: Nutritional status of Hfv-I infected and uninfected IDDs in Mombasa County, 2012-2013 Data are presented as medians (interquartile range, IQR) for continuous variables or number of subjects (n) and proportions (percentages, %) for categorical variables. Statistical analyses were conducted using the Mann Whitney U test for continuous variables and Fisher's exact test for comparing proportions between the groups. Bl\lI: basal metabolic index. MUAC: mid upper arm circumference. Body mass index (8MI kg/rrr'): Non-malnourished (2:18.50) and malnourished «18.50) (FANTA, 2013). MUAC cut-offs for malnutrition: males, <23.0 cm and females <22.0 em (UNICEF, 20] I). Anaemia was defined using haemoglobin (Hb, g/dL) cut-offs previously established by (WHO, 2011c) as follows: non-pregnant women (~15.00 yrs), Hb<12.0 g/dl.; and men «~15.00 yrs), Hb <13.0 g/dL). Since this is the first known study to assess nutritional status of PWID in Kenya, the findings of this study were compared to results of studies carried out in the general population in Mombasa and IDU subpopulations outside Kenya. The low height found among the HIV infected injection drug users in comparison to HIV uninfected injection 120 drug users signify loss of body height, a common feature in people living with IllV/AIDS (McComsey et al., 2010). Similar results were reported among PWID in Chennai, South India showing that HlV infected injection drug users presented with lower body height relative to the HfV uninfected injection drug users (Tang et al., 2011). In addition, the low body heights observed in the current study also parallel previous clinical studies in the USA among HIV infected non-drug using persons aged between 4 and 24 years as wen as in Chinese adults showing marked reductions in body height (Jacobson et a/., 2010; Zhang et aI., 2013b). Although the mechanisms governing the loss in body height are poorly defined, it appears that loss of bone mineral density underlies the low body height in the HlV infected injection drug users. This premise is supported by previous studies showing heightened bone mineral loss in Senegalese adults living with mY/AIDS (Cournil et al., 20] 2). It is also possible that chronic use of protease inhibitors contribute to bone mineral loss. This suggestion is supported by previous studies in France and Japan showing that long-term use of protease inhibitors is associated with loss of bone mineral density in adults on anti- retroviral treatment (Duvivier et aI., 2009; Kinai, et aI., 2014). The lack of significant differences in the standard nutritional measures of body weight, hip circumference, waist circumference, bust circumference, waist-to-hip ratio, bust-to- waist ratio, and BM! between the HlV infected and uninfected injection drug users observed in this study may be related to the fact that these measures approximate both lean and fat body mass. These results are similar to a previous study among drug users 121 living in three US cities (Baltimore, Boston, Providence) that reported low waist circumference in both mv infected and uninfected IDUs which was associated with low BMI as well as low body fat (Tang et aI., 2010). These fmdings suggest a lack of abdominal obesity that is measured as high waist circumference and waist to hip circumference ratio in both HIV infected and uninfected IDUs (WHO, 20] lb). However, the lower mid-upper-arm circumference (MUAC), a nutritional marker for wasting or acute malnutrition, in the HlV infected injection drug users suggests that the mid-arm-circumference is a better surrogate for assessing acute malnutrition in HIV infected IDUs. This proposition is supported by previous studies among non-drug using population of Hl V infected adults in Guinea-Bissau showing that MUAC was an independent predictor of death while in Indian, MUAC as a marker was found to be 94.6% sensitive and 71.2% specific among adolescents (Dasgupta et al., 2010~Oliveira et al., 2012). The Iow haemoglobin levels and associated high rates of anaemia in the HIV infected injection drug users is indicative of increased anaemia burden in this population. Although anaemia appears to occur in both HlV infected and uninfected injection drug users, it is possible that consumption of foods of low nutritive value, a common practice among injection drug users increases the risk of developing anaemia (Hendricks et aI., 2010; Alves et al., 2011; Saeland et al., 2011; Karajibani et al., 2012). However, the higher frequency of anaemia in the mv infected .injection drug users is partly consistent with NASCOP guidelines on management of opportunistic infections (NASCOP, 2012c) 122 indicating that the burden of anaemia is higher in the people living HIV IAIDS in the country. Consistent with these results previous clinical studies in Brazil and India showed higher rates of anaemia in the HIV infected injection drug users (Solomon et aI., 2008; Brunetta et al., 2013). The mechanisms driving the increased anaemia burden in the HIV infected injection drug using people are largely undefined. This is supported by previous studies in Indonesian HIV infected adults showing that high prevalence of chronic diseases and/or iron deficiency is associated with increased risk of anaemia (Wisaksana et aI., 2011), and previous studies in India, Cambodia and South Africa among HIV infected adults illustrating that long-term use of antiretroviral drugs such as zidovudine is associated with increased risk of anaemia (Nigam et al., 2013; Phe et al., 2013; Simbarashe et aI., 2013). Overall, the implications of these results are that incorporation of iron supplements in the nutritional management schedules for HIV infected IDUs wiJI reduce the risk of anaemia and other related co-morbidities leading to improved quality of life. In order to assess the predictors of malnutrition in both HIV infected and uninfected IDUs, binary logistic regression was conducted as shown in table 4.6. Findings illustrating that low CD4+ T cells counts are predictive of high rates of malnutrition in both mv infected and uninfected IDUs indicate suppression of cell mediated immunity, a frequent sequel of malnourished persons (Franca et al., 2009). Similar results have been reported in injection drug using patients from Brazil and the general adult population from Germany (Brunetta et al., 2013; Iliakis and Kressig, 2014). The low 123 CD4 count may result from malnutrition and HIV infection .driven reduction in the CD4+ T cell numbers (Shalini et al., 2012). This assertion is parallel to previous studies in South Africa showing correlations between the CD4 cell count and BMI among adults living with HIV/AIDS (Venter et al., 2009; Evans et al., 2013). Overall, the present study revealed that IDUs experience high levels of malnutrition with HlV infected IDUs suffering even higher burden of malnutrition. Malnutrition in the injection drug using population is largely attributable to reduced dietary intake, malabsorption and or altered metabolism. Decreased dietary intake is due to abdominal pain, anorexia, chaotic lifestyles, depression, diarrhoea, poverty, food insecurity, mouth sores, nausea and vomiting (Anema et 01., 2010~ Smith et 01., 2012~ Strike et al., 20]2). Malabsorption can be linked to the Hl V-induced mucosal changes, effects of drugs on I absorption of specific nutrients and opportunistic gastrointestinal infections (Martins et al., 2011; Sunguya et aI., 2011; Krawinkel, 2012). In contrast, altered metabolism is associated with the effects of injection drugs and substance consumption (like heroin and khat), fever or cytokine-induced increase in the basal metabolic rate, hormonal deficiencies, increased breakdown of lean body mass, and effects of medications on metabolism (Hendricks et al., 2010; Douglas et aI., 2011; Mineur et al., 2011; Neale et aI., 2012; Ersche et al., 2013; Rubinstein and Low, 2013). 124 Characteristic B WaJd OR (95% CI) P-value mv-i Uninfected IDUs CD4+ Tcells/pL 2:500 (Ref) 2:350<500 <350 1.313 1.016 5.694 5.751 3.718 (l.264-1O.932) 2.761 (1.204-6.334) 0.017 0.016 urv-r Infected IDUs CD4+ Tcells/pL ~500 (Ref) ~350<500 <350 Vimlload (copies/mL) Undetectable100,000 0.709 3.213 2.031 (0.936-4.407) 0.073 1.089 4.756 2.972 (1.117-7.910) 0.029 0.592 1.386 1.808 (0.675-4.848) 0.239 -0.002 0 0.998 (0.394-2.526) 0.997 0.448 0.75 1.565 (0.568-4.312) 0.387 Table 4.6: Predictors of malnutrition in Hl'v-I infected and uninfected injection drug users in Mombasa County, 2012-2013 Data are presented as odds ratios (OR) and 95% confidence interval (Cl). Binary logistic regression was conducted using BMI<18.5 kg/nr' (malnourished) as the dependent variable and B~18.5 kglm2 as the reference group controlling for age and gender in HIV negative rous and age, gender and ART use in the HIV positive roUs. The CD4+ T cells were categorized using a combined CDC classification system and NASCOP thresh- hold for initiating anti-retroviral therapy for HIV-infected adults and adolescents into three groups: 1) 2:500 cells/ul.; 2) 350-499 cells/ul.; and 3) <350 cells/ul. (eDC, ]992; NA.~COP. 2012b). Infected IDUs in Mombasa County 4.5 The Prevalence of Pulmonary TB Infections among HIV Uninfected and A total of 39 pulmonary TB cases were detected among the study participants with the HJV-I infected individuals (18.5%) presenting with significantly higher rates compared to the lllV-1 uninfected individuals (4.5%) at (P<0.0001). Sensitivity testing of the thirty nine Mycobacterium tuberculosis isolates against anti-mycobacterial first line drugs 125 treatment demonstrated that all of the isolates were sensitive to ethambutol, pyrazinamide, rifampicin and isoniazid. A synopsis of the pulmonary TB prevalence rate is illustrated in table 4.7. Characteristic HIV-l Uninfected, n=214 HIV -1 Infected, n=157 Tuberculosis rates *Mycobacterium tuberculosis sensitivity to TB drugs Ethambutol 10 (100.0) 29 (100.0) Pyrazinamide 10 (100.0) 29 (100.0) Rifampicin 10 (100.0) 29 (100.0) Isoniazid 10 (100.0) 29 (100.0) 10 (4.7) 29 (18.5) <0.0001 Table 4.7: Tuberculosis prevalence rate among PWID in Mombasa County, 2012- 2013 Data presented are number and proportions (%) of subjects. Statistical analysis was performed using the Fisher's exact test. *antimycobacterial sensitivities were performed on all the TB positive cases. The findings showing higher prevalence rates of TB in the HfV infected mus indicate that HIV -1 infection increases the risk of TB infection. However, the presence of TB in the mV-1 uninfected IDUs, suggests that injection drug use is also a risk factor of acquiring TB. The results illustrating TB prevalence rates of 29% in the HIV -1 infected IDUs from Mombasa parallels previous findings of showing a 33.9% TB prevalence among IDUs from Chennai, India (Solomon et 01., 2008). The higher risk of TB in the HIV-l infected IDUs is attributable to the lower CD4+ T cell counts detected in this group. The reduced CD4+ T cells consequently cause lowered cellular immunity that is paramount for elimination of Mycobacterium bacilli (Shalini et al., 2012). It is also· 126 likely that injection drug use which is associated with weakened cellular immunity increase the risk ofTB infection (Deiss et al., 2009; Getahun et al., 2012). Nevertheless, the Mycobacterium tuberculosis isolates from both groups were sensitive to all the first line anti-TB drugs. These results deviate from findings of a previous study which isolated MDR TB from injection drug users in Tanzania (Gupta et al., 2014). In Kenya. the reasons underlying the continued sensitivity of anti-TB treatment in this most at risk population may be linked to the intensive surveillance and follow-up of TB cases in the general population by Division of Leprosy, Tuberculosis and other Lung Diseases (MOPHS, 2010). In addition, a declining trend of TB cases as well as high sputum conversion rate (ranging between 88% and 97%) to first line of treatment in the general population has been reported in Kenya (Kwange and Budambula, 2010; Sitienei et aI., 2013). However, it is also possible that severe TB cases and MDR TB among lOUs were not obtained due to the fact that sick injection drug users are less likely to access heaIthcare (Dutta et al., 2013). Regression analyses to identify the predictors of TB in the HlV -1 infected and uninfected injection drug users was carried out and presented in Tables 4.8 and 4.9 respectively. Findings indicated that the probability of having TB infection among those presenting with malnutrition was at least four times in both HlV-l uninfected (OR, 4.599; 95% Cl, 0.946-22.357; P> 0.059) and infected (OR, 4.077; 95% cr, 1.505-11.049; P=0.006) injection drug users. However, additional risk factors for TB did not show significant associations with TB infection in the Hl'V-I uninfected (cigarette smoking, alcohol 127 consumption, anaemia and CD4+ T cell status) and infected (cigarette smoking, alcohol consumption, anaemia, CD4+ T cell and viral load status) injection drug users (P>0.05). Results indicating a higher probability of having TB infection in both HIV -1 infected and uninfected IDUs presenting with lower BMI «18.5 kg/nr') indicate that malnutrition is an important risk factors for TB infection in this key population. This finding is similar to previous studies showing in the Kenyan general population low BMI was common among TB patients (Sitienei et al., 2014). Malnutrition is associated with depressed cellular immunity (lowering host defense against tuberculosis) and this could be responsible for the acquisition of Mycobacterium tuberculosis, an intra-cellullar pathogen (Drake, 2010; Duggal et al., 2012; Padmanesan et al, 2013). Among HlV-I infected IDUs, malnutrition and reduced CD4+ T cells concomitantly worsen cellular immune responses increasing the risk of acquiring and developing disease against intra-cellular pathogens such asMycobacterium tuberculosis. This study demonstrated that pulmonary TB is an important problem in the IDU sub- population in Mombasa. In this, key population, TB is associated with HlV and malnutrition which are also a common burden in IDUs (Hendricks et aI., 2010; Tang et al.• 20ll). Without adequate. control of the TB-illV syndemic, the long-term TB elimination target set for 2050 may not be reached. 128 Characteristic pB Wald OR (95% en Mablutritioll B~18.5 kg/nr' (Ref) BMI<18.5 kg/nr' Smoking No (Ref) Yes Alcohol No (Ref) Yes Anaemia No (Ref) Yes CD4+ TcelTs (xJ(fjpL) 2:500 (Ref) 2:350<500 <350 1.526 0.072 0.203 0.732 0.180 1.222 3.527 0.011 0.057 0.890 0.027 0.920 4.599 (0.946-22.357) 1.075 (0.275-4.200) 0.816 (0.155-4.297) 2.079 (0.455-9.505) 1.197 (0.138-10.383) 3.395 (0.279-41.245) 0.059 0.917 0.8\1 0.345 0.870 0.337 Table 4.8: Predictors of tuberculosis among HIV-l uninfected IDUs in Mombasa County,2012-2013 Data are presented as odds ratios (OR) and 95% confidence interval (Cl). Binary logistic regression analysis was conducted by entering tuberculosis status as the dependent variable, risk factors (malnutrition, smoking, alcohol, anaemia, and CD4+ T cells) as independent variables, and controlling for age and gender. Ref, reference. BMI, basal metabolic index. . 129 Characteristic B Wald OR (95% CI) p Malnutritioll BMI218.5 kg/m' (Ref) BMI<18.5 kg/m' Smoking No (Ref) Yes Alcohol No (Ref) Yes Anaemia No (Ref) Yes CD4+ T cells (xJ(f /J1l) 2:500 (Ref) ~350<500 <350 Viralload/mL Undetectable100,000 0.784 l.216 2.190 (0.544-8.828) 0.270 Table 4.9: Predictors of tuberculosis among HIV~l infected PWID in Mombasa County,2012-2013 1.405 7.634 0.0064.077 (1.505-11.049) 0.027 1.027 (0.375-2.815) 0.9590.003 0.803 2.231 (0.697-7.141) 0.1761.827 0.292 0.328 0.5671.340 (0.492-3.646) 0.655 0.927 0.248 0.180 1.334 1.801 1.924 (0.634-5.843) 2.526 (0.653-9.779) Data are presented as odds ratios (OR) and 95% confidence interval (Cl). Binary logistic regression analysis was conducted by entering tuberculosis status as the dependent variable, risk factors (malnutrition, smoking, alcohol, anaemia, and CD4+ T cells) as independent variables, and controlling for age and gender. Ref, reference. BMI, basal metabolic index. 4.6 The HIV Subtypes that Cause HIV Infections in IDUs Living in Mombasa County Seventy six (48.4%) of the one-hundred and fifty seven HIV-J infected IDUs were successfully' sequenced. Genotype analysis identified the following sub-types: Al 130 (56.6%), C (15.8%), D (14.5%), A2-C (1.3%), ABDU (1.3%), B (1.3%) and G (1.3%) as illustrated in Table 4.10. Subtype Male Female Total Al 18(58.1) 25 (55.6) 43 (56.6) C 9 (20.0) 3 (9.7) 12 (15.8) D 7 (15.6) 4 (12.9) 11 (14.5) A2 AG 2 (6.5) 2(4.4) 4 (5.3) AJD I (3.2) 1 (3.2) 2 (2.6) AlC 0(0.0) 1 (3.2) 1 (1.3) ABDU 0(0.0) 1 (3.2) 1 (1.3) B 0(0.0) 1 (3.2) 1 (1.3) G 1 (2.2) 0(0.0) 1 (1.3) Table 4.10: HIV-l subtypes circulating in IDUs from Mombasa County. 2012-2013 Data presented are number and proportions (%) of participants. Note: A2_AG, A1D, A2C and ABDU are circulating recombinants forms (CRFs). The high prevalence of subtype Al detected in the IIIV-1 infected injection drug users signifies the dominance of this subtype transmission within the injection drug users from Mombasa, Although subtype Al was the most frequent, the rate was lower relative to previous cross-sectional studies in Mombasa (same area as the present study) showing 89.7% prevalence in anti-retroviral treatment-exposed injection drug users (Osman et al., 20U) and 70.6% prevalence among anti-retroviral treatment-naive individuals from the general population (Sigaloff et al., 2012). This evident variation in the prevalence of the Al sub-type between the current study and previous studies from the same study area may be attributable to the rapidly evolving epidemiology of HIV -1 subtypes in this most- at-risk-population that is frequently exposed to multiple subtypes. 131 This fact is related to the high rates of C, D and circulating recombinant forms detected in the present study compared to the previous studies in the same study area. Based on review of studies carried out in different regions in Kenya on HIV sub-types (Kageha et al., 2012; Khamadi et aI., 2009; Kiptoo et aI., 2013; Lihana et aI., 2009; Muriuki, 2012; Nyamache et al., 2013; Osman et al., 2013; Sigaloff et al., 2012), the present study is the first to report the presence of sub-type B in the country. This further supports the preposition that there is changing epidemiology of circulating HIV -1 subtypes in Kenya. 132 CHAPTER FIVE: CONCLUSION AND RECOMMENDATIONS 5.1 Conclusion. From the study, it was hypothesized that social-demographic characteristics are similar between HlV infected and uninfected IDUs. However the study findings imply that the female gender, being separated or divorced, widowhood, early sex debut, sex work, working in entertainment and beauty therapy sectors, exposure to STr and risky sexual practices were statistically more significant in the HlV infected group than uninfected IDUs. Therefore the null hypothesis is rejected and it is concluded that social- demographic characteristics vary between Hl V infected and non-infected IDUs. Longer duration of injection use, needle and syringe sharing, injecting heroin or cocaine in addition to using alcohol, khat, and cocktail as well as polydrug use increased the risk of exposure to HlV, The null hypothesis that proposed drug use patterns are invariable between HlV infected and uninfected IDUs is rejected and the researcher concludes drug use patterns differ between Hl V infected and uninfected IDUs. Although low anthropometric measurements and aneamia were common in the IDUs irrespective of their HIV status, the HIV infected IDUs fared worse than the uninfected. The null hypothesis that had proposed stating that the nutritional status was incomparable between HIV infected and non-infected IDUs is accepted. Based on the findings it is concluded that in terms of nutrition, the mv positive injection drug users are more malnourished than the infected IDUs. 133 The significant high .proportions of TB in 'HlV positive in comparison to the negative IDUs imply that HIV infected IDUs are at an elevated risk of acquiring TB infections. The null hypothesis is rejected and based on findings of the study it is concluded that TB infection rate do vary with mv infection in the IDU subpopulation. The assortment of HIV -1 subtypes and recombinants that co-circulate among PWID in Mombasa courtesy of high risk injecting and sexual practices point to the changing epidemiology of circulating HIV-i subtypes in Kenya. The proposed hypothesis is rejected and supported by the findings of this present study, it is concluded t~1atan array ofHIV-l sub-types and recombinants co-circulate in IDUs in Mombasa County. Overall, the study demonstrated multiple trajectories of drug injection behaviours. By understanding socio-economic factors, drug use patterns, nutritional status, TB as well as HIV trends among users in this subpopulation forms the basis of preventive and therapeutic interventions. - 5.2 Recommendations From this study, empowerment of youths and women is recommended through the Ministry of Labour, Social Security and Services. Although the national government has already set aside funds to benefit the youths and women, the most vulnerable categories like those who dropped out of primary and secondary schools are yet to benefit. Empowerment is crucial as this will curtail idleness, drug abuse and high risk sexual behaviour. In addition both public and private funded rehabilitation centres ought to 134 integrate vocational training skills in their rehabilitation packages so as rehabilitated IDUs are empowered in order to prevent reversion to drug use, idleness and high risk sexual behaviour. The County government, non-governmental organizations (NGOs), community and faith based organizations (CBOs and FBOs respectively) should plan for targeted activities that will aim at educating sex workers. In addition, they should be empowered to venture into alternative income generating activities. Given that female IDUs are vulnerable to HIV infections; it is recommended that the County government of Mombasa to design female friendly IDU services as currently none of the public funded rehabilitation centres admit female clients. In view of the fact that female exposure to HIV has a direct implication on mother to child HIV transmission, there is need to put in place appropriate interventions targeting FIDUs. The NGOs, CBOs and FBOs in Mombasa, should upscale targeted programmes that promote family unit as it moderates the probability of one engaging in drugs as well as high risk sexual behaviour. The County government should invest in friendly drop-in centres for IDUs, non rDUs and their partners in order ensure accessible compressive primary health care services (PHC). In addition, integrated approaches are required in advocating for behaviour 135 change and early diagnosis as well as treatment of STIs in order to curb the high H1V rates among the mus and their sexual partners by extension. The Nationa Authority for the Campaign against Alcohol and drugs in conjunction with Mombasa based NGOs and CBOs should start monitoring drug use patterns. For example, seasons when drugs are consumed most, type of drug( s) taken, polydrug use as well as mode of administration. This will help in developing targeted interventions like integrating prevention of alcohol, cocktail and khat consumption in injection drug use and mv intervention programs. In addition the Pharmacy and Poisons Board should flex its muscles and withdraw licenses or black list the pharmacy operators who dispense prescription drugs Rohypnol and valium on over the counter basis. Overall to moderate drug use, the National government ought to step up the war against drugs by targeting the drug supply chain starting with the barons, distributors and peddlers so as to reduce supply of drugs in the market. In accordance with the law of supply and demand, reduced supply will lead to increase in drug prices and fear of being arrested hence reduced demand. Since malnutrition is an important correlate of the Immune status of PWID, it is recommended to Ministry of Health (MaR) to facilitate food assistance and. micronutrient supplementation programmes as well as nutritional education to roUs in 136 order to improve their nutritional status and immunological outcomes, especially, among themv infected IDUs as an adjunct for the antiretroviral therapy regimens. It is recommended to the County of government to integrate active TB screening into drug prevention and management programmes as well as in targeted outreach activities. These services should work in close tandem with the MOR in order to facilitate early diagnosis and effective treatment of TB among injecting drug users. This will also help in the achievement of MDG 6C and MDG 1C that seeks to halt the TB burden as well as reduce by half the proportion of population below minimum level of dietary energy consumption respectively. 'In addition, continued surveillance for MDR-TB by the MOR ought to be up scaled to reach the hidden subpopulations like roUs that are unlikely to utilize PHC services. To both the National and County governments, the up-scale HIV education is recommended in order to reduce infection and re-infection rates within the IDU sub- population as well as the general population. This will contribute greatly towards achieving MDG 7 that calls for the halting and reversing of the spread ofHIV/AIDS and the achievement of universal access to treatment for RIV/AIDS. As part of way forward, it is recommended that the National government, research stations and independent researchers to work together in continuous surveillance of tile HIVepidemiology . 137 5.3 General recommendations The researcher recommends health education to the public that should be initiated and facilitated by both National and County governments. This can be achieved through substance and drug abuse awareness starting at an early age for example at primary school level. Such an approach can form the basis of responding to substance use before one starts using substances. In addition, this strategy could help to discourage or stop use in those who are already experimenting or using. Such programmes can be extended to proprietors and workers of entertainment venues as well as beauty parlours. Substance and drug abuse awareness will help in reducing demand for drugs which in return will lead to supply reduction. Additionally, it is imperative for police education programs to be designed in order to align policing with public health efforts targeting vulnerable populations (MARPS). This will minimize incidents of sex for police protection as well as arbitrary arrests from law enforcers since fear of arrest drives PWID away from HlV testing and primary healthcare services. Moreover it disrupts antiretroviral therapy resulting in elevated illV viral load and subsequent IllV trans-mission as well as increased antiretroviral resistance. Other state actors like lawmakers (including but not limited to Members of Parliament and Members of County Assemblies) and criminal justice authorities (like magistrates and judges) should also be provided with educational programs on human rights and public health interventions. 138 Both the County and National government are advised to support harm reduction interventions by developing policy and guidelines on harm reduction at the same time implementing them. These interventions may include counseling, syringe and needle exchange programmes (SNEP), methadone assisted treatment (MAT) and provision of safe injecting facilities (SIF). The County government is advised not to ignore the plight of PWID or persecute them through arbitrary arrests but instead facilitate their voluntary rehabilitation. This can be achieved through partnership with NGOs, CBOs, and FBOs as well as the private sector. Additionally, the community and affected families need to be encouraged to accept back the rehabilitated IDUs. This will help to break the vicious cycle of rejection and stigma associated with IDU. As a parting to all the parties mentioned in these recommendations, people who use drugs have the same human rights as people who have never used drugs. These rights include the right to the highest attainable standard of health, to social services, to work, to freedom from arbitrary detention and freedom from cruel inhuman as well as degrading treatment. A time has come for all mankind to stop focusing on the sin but what happens to the sinner. - J\TTAUN V R ITY-LI RA ~; -~-. - •. e _ .••--:--:--' 139 5.4 Suggested Further Research Since this was a cross sectional study no causal relationships could be established. Therefore further research needs to be carried out using a longitudinal and experimental approach. There is a possibility that drug use pattern was not well captured due to the structure of the interview schedule. In future studies it is advisable an elaborate list of drugs should be included so that the participants can respond to the items on the list. In addition, both drug use patterns and exposure to STIs were self-reported and hence may be confounded by recall bias. Future studies should include toxicological analysis of urine in order to a certain the complete set of injecting and non-injecting drugs used by the study participants. Moreover, future studies should include comparative groups like non-injecting drug users and non drug users. Although both MUAC and BMJ are good nutritional markers, it is imperative that additional nutritional markers like biochemical, body composition measurements and dietary intake assessment be examined. It is suggested further research be carried out on TB and HIV epidemiological patterns in both high risk as well as general population. While the present study has shed light on predictors of HlV and Pulmonary TB among PWID, more studies need to be carried out to reinforce or refute the findings of this study. 140 REFERENCES Abdala N, White E, Toussova OV, Krasnoselskikh TV, Verevochkin S, Kozlov AP and Heimer R. (2010). Comparing sexual risks and patterns of alcohol and drug use between injection drug users (IDUs) and non-IDUs who report sexual partnerships with lDUs in St. Petersburg, Russia. BMC Public Health, 10:676. Abecasis AB, Annemarie MW, Dimitris P, Jurgen V, Kristof T, David AV, Albert J , Asjo B, Balotta C, Beshkov D, Camacho RJ, Clotet B, De Gascun C, Griskevicius A, Grossman Z, Hamouda 0, Horban A, Kolupajeva T, Korn K, Kostrikis GL, Kucherer C, Liitsola K, Linka M, Nielsen C, Otelea D, Paredes R, Poljak M, Puchhammer-Stock E, Schmit JC, Sonnerborg A, Stanekova D, Stanojevic M, Struck D, Boucher CAB and Vandamme AM (2013). HIV-l subtype distribution and its demographic determinants in newly diagnosed patients in Europe suggest highly compartmentalized epidemics. Retrovirology, 10 (7). Abel WD, Sewell C and Eldemire-Shearer D (2011). Decriminalization of marijuana: is this a realistic public mental health policy for Jamaica? West Indian Medical Journal, 60(3). Ademola LA, Omoregie PI and Edoni ER (2014). Sexual Practices of Female Sex Workers Who Inject Drugs in Osogbo, Nigeria. International Scholarly Research Notices, 2014(2014). '. Adermark L, Soderpalm B and Burkhardt 1M (2014). Brain region specific modulation of ethanol-induced depression of GABAergic neurons in the brain reward system by the nicotine receptor antagonist mecamylamine. Alcohol, 48(5):455-461. . Ajao KO, Ojofeitimi EO, Adebayo AA, Fatusi AO and Afolabi OT (2010). Influence of Family Size, Household Food Security Status, and Child Care Practices on the Nutritional Status of Under-five Children in Ile-Ife, Nigeria. African Journal of Reproductive Health, 14(4): 123-132. Akiibinu MO, Adekunle M and Ayodele 00 (2012). Micronutrients and Markers of Oxidative Stress in Symptomatic HIV-Positive/AIDS Nigerians: A Call For Adjuvant Micronutrient Therapy, 3(2): 7-11. Alcantara KC, Reis MNG, Cardoso LPV, Bello G and Stefani MMA (2013). Increasing heterosexual transmission of HIV -1 subtype C in Inland Central. Western Brazilian Journal of Medical Virology, 85: 396-404. Alkiviadis GN, Andrea JL and Maria MO (2010). Syringe Exchange Programs: Impact on Injection Drug Users and the Role of the Pharmacist from a U.S. Perspective. Journal of American Pharmacists Association, 50(2): 148-157. 141 Almeida EM, Rubia M, Dennis MJ, Tiago G, Caroline PB, Gonzalo B, Morgado MG and Guimaraes ML (20l2). Temporal dynamics of HIV-l circulating subtypes in distinct exposure categories in southern Brazil. Virology Journal, 9:306. Alves D, Costa AF, Custodio D, Natario L, Ferro-Lebres V and Andrade F(201!). Housing and employment situation, body mass index and dietary habits of heroin addicts in methadone maintenance treatment. Association jar the Application of Neuroscientific Knowledge to Social Aims, 13(1):1592-1638. Al-Wadei H., Al-Wadei MH and Schuller HM (2012). Cooperative Regulation of Non- Small Cell Lung Carcinoma by Nicotinic and Beta-Adrenergic Receptors: A Novel Target for Intervention. PLoS ONE, 7(1). Amoako AA, Marczylo TH, Marczylo EL, Elson J, Willets 1M,Taylor AH and Konje JC (2013). Anandamide modulates human sperm motility: implications for men with asthenozoospermia and oligoasthenoteratozoospermia. Journal of Human Reproductive Sciences, 28(8):2058-2066 Andrade J and Gin KG (2009). Alcohol and the heart. Issue: British Columbia Medical Journal, 51(5): 200-205. Amomkul PN, Vandenhoudt H, Nasokho P, Odhiambo F, Mwaengo D, Hightower A, . Buve A, Misore A,Vulule J, Vitek C, Glynn J, Greenberg A, Slutsker L, De Cock KM (2009). HIV Prevalence and Associated Risk Factors among Individuals Aged 13.-.34 Years in Rural Western Kenya. PLoS ONE 4(7) Andrade CS, Jesus RP, Andrade TB, Oliveira NS, Nabity SA, Ribeiro GS (2012). Prevalence and Characteristics Associated with Malnutrition at Hospitalization among Patients with Acquired Immunodeficiency Syndrome in Brazil. PLoS ONE, 7(11) Andrade LF, Carroll KM and Petry NM (2013). Marijuana use is associated with risky sexual behaviours in treatment-seeking polysubstance abusers. American Journal of Drug Alcohol Abuse, 39(4):266-271. Andreasen MF, Christian L and Elisabet K (2009). Adulterants and Diluents in Heroin, Amphetamine, and Cocaine Found on the Illicit Drug Market in Aarhus, Denmark. The Open Forensic Science Journal, 2:16-20. Anema A, Wood E, Weiser SD, Qi J, Montaner JS and Kerr T (2010). Hunger and associated harms among injection drug users in an urban Canadian setting. Substance Abuse Treatment and Prevention Policy, 5:20. . Association of Public Healt Laboratories,' (2009). AFB Smear Microscopy. httpJ/www.aphl.org/aphlprograms/infectious/tuberculosisrrBCoreCurriculum/Document sfTBAFBSmearMicroscopyTrainerNotes\. pdf 142 Atkinson J, McCurdy S, Williams M, Mbwambo J and Kilonzo G (2011). mv risk behaviours, perceived severity of drug use problems, and prior treatment experience in a sample of young heroin injectors in Dar es Salaam, Tanzania. African Journal of Drug Alcohol Studies, 10:1-9. Ayenew F, Tadesse T and Azale T (2012). Alcohol and khat use as risk factors for HlV infection among visitors to voluntary counselling and testing centres in Northwest Ethiopia. Tropical Doctor, 42:99-100. Baddeley A. (2013). Measuring TB burden and access to TB services for people who inject drugs in the WHO European Region, 2010 and 20] 1. http://www.ihra.net!files/2013/091l3/Annabel Baddeley - 714.pdf. Badiye A and Mansi G (2012). A Review on Abuse as Date Rape Drug. Helix, 3:161-]64 Bang-Ping J (2009). Sexual dysfunction in men who abuse illicit drugs: a preliminary report. Journal of Sexual Medicine, 6(4):1072-1080. Bad M, Battista N, Pirazzi V and Maccarrone M (2011).The manifold actions of endocannabinoids on female and male reproductive events. Frontiers in Bioscience, 1(16):498-516. Barth PR. (2009). Preventing Child Abuse and Neglect with Parent Training: Evidence and Opportunities. Preventing Child Maltreatment, 19 (2). BAT (2010). History of tobacco in Africa. Accessed on 2nd July 20] 4 via http://www.bat!careers.com/grouphr/ siteslBA T 8VEHSC .nsf/vwPages WebLiveID08 VF CLL?opendocument&SKN= 1 Beckerleg S, Telfer M and Sadiq A. (2006). A Rapid Assessment of Heroin use in Mombasa, Kenya. Substance Use and Misuse, 41(6-7): 1029-1044. Beckerleg, S (2004). How cool is heroin use at the Kenyan Coast? Journal of Drugs, Education and Policy. 3:159-169. Beckerleg, S and Hundt, GL (2004). The characteristics and recent growth of heroin injecting in a Kenyan coastal town. Addiction Research and Theory, 12(1): 41-53. Bergstrom, J (2002). From The Beginning: The Chronology of Heroin Use ht1p:llwww.mapinc.org/drugnews/v02/n2154/a08.html Berhanu M, Aregash E and Alyi M (2014). Socio-Economic Impact of Khat in Mana District, Jimma Zone, South Westem Ethiopia. Discourse Journal of Agriculture and Food Sciences, 2(2): 21-32. 143 Bezemer Dl, Faria NR, Hassan A, Hamers RL, Mutua G, Anzala 0, Mandaliya K,Cane p. Berkley JA, Rinke de Wit TF, Wallis C, Graham SM, Price MA, Coutinho RA, Sanders EJ (2014). mv Type 1 transmission networks among men having sex with men and heterosexuals in Kenya. AIDS Research and Human Retroviruses, 30(2): 118-126. Birech J, Kabiru J, Misaro J and Kariuki D (2013). Alcohol Abuse and the Family: A Case Study of the Nandi Community of Kenya. International Journal of Humanities and Social Science. 3 (15). Blaylock BL, Gould RW, Banala A, Grundt P, Luedtke RR, Newman AH and Nader MA (201]). Influence of cocaine history on the behavioural effects of dopamine D3 receptor- selective compounds in monkeys. Neuropsychopharmacology, 36: 1104-1113. Blaylock BL and Michael AN (2012). Dopamine D3 Receptor Function and Cocaine Exposure. Neuropsychopharmacology Reviews, 37: 297-298. Blum J, Hana G, Urs G, Otto S, Sylvie P, Anita R, Gerhard AW, Stefan JB and Walter M (2013). Acute effects of heroin on emotions in heroin-dependent patients. The American Journal on Addictions, 22 (6): 598-604. Bogenschutz MP, Samara LR, Tonigan JS, Vogel HS, Nowinski J, Hume D and Arenella PB (2014). 12-step facilitation for the dually diagnosed: A randomized clinical trial. Journal of Substance Abuse Treatment, 46 (4): 403-411. Bomu Hospital (2013). Accessed http://www .mkomani. orglbranches.htrnl. on April 2014 'via Bonsor K and Nicholas G (2011). How Marijuana Works. Accessed on 19th April 2014 via http://science.howstllffworks.comlmarij uana.htm>. Borio, G (2010). The History of Tobacco Part I. Accessed on 12th April 2014 vta http://www.historian.orglbysubject/tobaccol.htm. Botany.com. (2014). Plant Encyclopedia to Identify Plants, Flowers, Trees & More. Accessed on 3n1 April2013 via http://www.botany.com/indexl.html. Bowring AL, Luhmann N, Pont S, Debaulieu C, Derozier S, Asouab F, Toufik A,van Gemerta C, Dietzea P and Stoove M (2013). An urgent need to scale-up injecting drug harm reduction services in Tanzania: prevalence' of blood-borne viruses among drug users ill Temeke District, Dar-es-Salaam.lnternational Journal o.f Drug Policy, 24( 1):78- 81. Braithwaite RS, Nucifora KA, Kessler J, Toohey C, Mentor SM, Dhler LM, Roberts MS and Bryant K (2014). Impact of Interventions Targeting Unhealthy Alcohol Use in Kenya 144 on HIV Transmission and AIDS-Related Deaths. Alcoholism: Clinical and Experimental Research, 38: 1059-1067. Braun TP ann Daniel LM (2010). Pathophysiology and treatment of inflammatory anorexia in chronic disease. Journal of Cachexia Sarcopenia Muscle, 1(2):l35-145. Bredholt T, Ersveer E, Erikstein BS, Sulen A, Reikvam H, Aarstad ill, Johannessen AN, Vintermyr OH, Bmsemd (2) and Gjertsen BT(2013). Distinct single cell signal transduction signatures in leukocyte subsets stimulated with khat extract, amphetamine- like cathinone, cathine or norephedrine. BMC Pharmacology and Toxicology, 14:35. Brenneisen R, Fisch HU, Koelbing D, Geisshusler S and Kalix P (2012). Amphetamine- like effects in hwnans of the khat alkaloid Cathinone. British Journal of Clinical Pharmacology, 211(2): 144-149 Brodish P, Kavita S, Rinyuri A, Njeru C, Kingola N, Mureithi P, Sambisa W and Weir S (2011). Evidence of high-risk sexual behaviours among injection drug users in the Kenya PLACE Study. Drug and Alcohol Dependence, 119(1-2): 138-141. Brown HL and Graves CR (2013). Smoking and marijuana use in pregnancy. Clinical Obstetrics Gynecology, 56(1):107-113. Brunetta DM, De Santis, Vilar GC, Fernando C, Brandao RA, Muniz RZA, de Lima GMN. Amorelli-Chacelb ME, Covas DT and Machado AA (2013). Hematological particularities and co-infections in injected drug users with AIDS. Brazilian Jou17101of Infectious Diseases, 17(6): 654-656. CAMH, (2010). Addiction Centre for Addiction and Mental Health. Accessed on zs" April 2014 via http://www.camh.ca/en/hospital/health _information/a _z_mental_health _ and~addiction _informationldrug-use-addictionIPages/addictiou.aspx. Camila P, Pereira da Silva Marchini AM, Barbara MAM, Reis de Vasconcellos LM Fernandes da Rocha R and Marchini L (2011). Negative Effects of Alcohol Intake and Estrogen Deficiency Combination on Osseointegration in a Rat Model. Journal of Oral Imp/ontology, 37(6): 633-639. Campaign for Tobacco Free Kids, 2013. Golden Leaf, Barren Harvest: The Costs of Tobacco Farming. Accessed on 12th April 2014 via http://www.ash.org.uk/files/documents/ASH 330.pdf.. Carias A, McRaven M, Anderson M, Henning T, Kersh E, Smith J, Butler K, Vishwanathan S, McNicholl 1M, Hendry RM, Veazey R and Hope T (2012)_ HlV interactions and the perils of epithelial thinning in the female reproductive tract. Retrovirology , 9(2): 363. 145 Castells X, Casas M, Perez-Mafia C, Roncero C, Vidal X and Capella D (2010). Efficacy of psychostimulant drugs for cocaine dependence. Cochrane Database of Systematic Reviews, 17(2). Cavlek VT, Jelena M, Ljiljana K and Branko K (2011). Hepatitis C Virus Antibody Status, Sociodemographic Characteristics, and Risk Behaviour among Injecting Drug Users in Croatia. Central European Journal of Public Health, 19 (1): 26-29 Cayla JA, Rodrigo T, Juan R, Jose AC, Rafael V, Jose MG, Rafael B, Marti C and the Working Group on Completion of Tuberculosis Treatment in Spain (Study ECUTTE).(2009). Tuberculosis treatment adherence and fatality in Spain. Respiratory Research, 10:121 eDC, (1992). Centers for Disease Control and Prevention. 1992 revised classification system for HfV infection and expanded surveillance case definition for AIDS among adolescents and adults. Morbidity and Mortality Weekly Report, 18 (41):1-19. CDC, (2009). Anthropometry Procedures Manual, National Health and Nutritional Examination Survey. Accessed on 18th July 2014 via http://www.cdc.gov/nchs/data I nhanes/nhanes 09 101B0dyMeasures 09.pdf. CDC, (2010). Centers for Disease Control and Prevention. The Role of STD Detection and Treatment in HfV Prevention - CDC Fact Sheet. Accessed on 29th April 20]4 via lmp:Uwww.cdc.gov/stdlhiv/stdfact-std-hiv.htm. CDC, (201] a). mv Testing and Treatment mmong Tuberculosis Patients in Kenya, 2006-2009. Morbidity and Mortality Weekly Report. 59(46);1514-1517. CDC, (201lb). Tetanus surveillance. Morbidity and Mortality Weekly Report. 60(1.2):365-369. CDC, (2012a). Multidrug Resistant Tuberculosis. Accessed on 8th April 2014 via http://www.cdc.gov/tb/publications/factsheets/drtb/mdrtb.htrn. CDC, (2012b). National Center for mY/AIDS, Viral Hepatitis, STD, and TB Prevention, Division of STD Prevention. Accessed on 10th January 2013 via http://www .cdc.gov/nchhstp/about.htrn. CDC, (2012c). Hl V Infection and HlV-Associated Behaviours Among Injecting Drug Users - 20 Cities, United States, 2009. Morbidity and Mortality Weekly Report, 61(08); 133-138. CDC, (2012d). Integrated Prevention Services for mv Infection, Viral Hepatitis, Sexually Transmitted Diseases, and Tuberculosis for Persons Who Use Drugs Illicitly: 146 CDC, (20 12e). Hepatitis C Information for the Public. Accessed on 21st August 2013 via http://vvww.cdc.gov/hepatitis/c/cfag.htm. CDC, (2012f). Tuberculosis. Accessed on 6th June 2012 via http://www.cdc.gov/tb/ topiclbasics/default.htm. Summary Guidance from CDC and the U.S. Department of Health and Human Services. Morbidity and Mortality Weekly Report, 61(5): 1-46. CDC, (2013). Health Effects of Cigarette Smoking. Accessed on 21 st August 2013 via http://www.cdc.gov/tobacco/data statistics/fact sheets/healtheffects/effects cig smoking CDC, (20 13b). Hepatitis B Information for the Public. Accessed on 2nd April 2014 http://www.cdc.gov/hepatitislb/. CDC, (20 13c). Hepatitis C Information for the Public. Accessed on 2nd April 2014 http://www.cdc.gov/hepatitis/c/. CDC, (2013d). Vaccines and Preventable Diseases: Hepatitis B Vaccination. Accessed on 2nd Apri12014.http://www.cdc.gov/vaccines/ypd-vac/hepb/ . CDC, (20 13e). Vaccines and Preventable Diseases:Tetanus (Lockjaw) Vaccination. Accessed on 2nd April 2014. http://www.cdc.gov/vaccines/vpd-vac/tetanus/. CDC, (2014). Tuberculosis Data and Statistics. Accessed on 14th Jan 2014. bttp:/Iwww.cdc.gov/tb/statisticsl. Celentano DD, Latimore AD and Mehta SH (2008). Variations in sexual risks in drug users: Emerging themes in a behavioural context. Current HIV IAIDS Report. 5(4): 212- 218. Cegielski JP, Arab Land Cornoni-Huntley J (2013). Nutritional risk factors for tuberculosis among adults in the United States, 1971-1992. American Journal of Epidemiogy, 176(5):409-422. CESAR, (2013). Center for Substance Abuse Research. Accessed on I" August 2013 via http://www.cesar.wnd.edu/. Chakraborty A, Gupta A, Singh AK and Patni P (2014). Effect of oxidative phytochemicals on nicotine-stressed UMNSAHlDF-1 cell line. Journal of Traditional Complementary Medicine, 4: 126-131 Chakrapani V, Newman PA, Murali S and Dubrow R (2011). Social-structural contexts of needle and syringe sharing behaviours of Hlv-positive injecting drug users in .Manipur, India: a mixed methods investigation. Harm Reduction Journal. 8(9). 147 Chandra K and Madison J (2012). Withdrawal Symptoms Hindering Harm-Minimization and Drug Detoxification Efforts: Experiences of Injecting Drug Users in Nepal. Journal of HIJl/AlDS and Social Services, 11 :3. Chekuri V, Gerber D, Brodie A and Krishnadas R (2011). Premature ejaculation and other sexual dysfunctions in opiate dependent men receiving methadone substitution treatment. Addictiont Behaviour, 37(1): 124-126. Chen H, Saad S, Sandow SL and Bertrand PP (2012). Cigarette smoking and brain regulation of energy homeostasis. Frontiers in Pharmacology. 25(3):147. . Chesang, KR ( 2013). Drug Abuse Among The Youth In Kenya. International Journal of Scientific and Technology Research, 2(6). Chweya M and Auya S (2014). Socio- Economic Effects of Alcoholism on Families in .Mukuru Slum, Nairobi County. International Journal of Innovation and Scientific Research, 9(1): 35-39. Ciccarone, D (2009). Heroin in brown, black and white: Structural factors and medical consequences in the US heroin market. International Journal of Drug Policy, 20(3): 277- 282. Cioe PA, Anderson BJ and Stein MD (2013). Change in symptoms of erectile dysfunction in depressed men initiating buprenorphine therapy. Journal of Substance Abuse Treatment, 45(5):451-456. CIRAD, (2014). Food security. Centre de cooperation internationale en recherche agronomique pour le developpement. Accessed on 23rd/June 2014 via http://www.cirad.fr/en/research-operations/research-topics/food-security/what-s-cirad- doing. Cleland CM, Des Jarlais DC, Perlis IE, Stimson G and Poznyak V (2007). HlV risk behaviours among female IDUs in developing and transitional countries. BMC Public Health, 7:271. Coburn BJ, Okano JT and Blower S (2013). Current drivers and geographic patterns of IDV in Lesotho: implications for treatment and prevention in Sub-Saharan Africa. 13MC Medicine, 11 :224. Cohen CR, Lingappa JR, Baeten lM, Ngayo MO, Spiegel CA, Hong T, Donnell D, Celurn C, Kapiga S, Delany Sand Bukusi EA (2012). Bacterial Vaginosis Associated with Increased Risk of Female-to-Male Hl v-I Transmission: A Prospective Cohort Analysis among African Couples. PLoS Medicine, 9(6). 148 Comer DM, Joseph SE and Ennis M (2014). Inflammatory and cytotoxic effects of acrolein, nicotine, acetylaldehyde and cigarette smoke extract on human nasal epithelial cells. BMC Pulmonary Medicine, 14: 32. Commonwealth of Australia (2011). The National Drug Strategy: 2010-2015: A frame work for alcohol, tobacco and other drugs, Ministerial Council on Drug Strategy, Perth. http://www.nationaldrugstrategy.gov.au/intemetldrugstrategy/publishing.nsf/ContentlDB 4076D49FI3309FCA257854007BAF30/$File/nds20 15.pdf. Connor J, Psutka R, Cousins K, Gray A and Kypri K (2013). Risky Drinking, Risky Sex: A National Study of New Zealand University Students. Alcoholism Clinical Experience Research, 37(11):1971-1978. Coskunpinar A, Allyson LD, Karyadi AK, Chung SK and Melissa AC (2013). Mechanisms Underlying the Relationship between Negative Affectivity and Problematic Alcohol Use. Journal of Experimental Psychopathology, 4 (3): 263-278. CottIer LB, O'Leary CC, Nickel KB, Reingle 1M and Isom D (2014). Breaking the blue wan of silence: risk factors for experiencing police sexual misconduct among female offenders. American Journal of Public Health, 104: 338-344. Coull AF, Atherton L, Taylor A and Watterson AE (2014). Prevalence of skin problems and leg ulceration in a sample of young injecting drug users. Harm Reduction Journal 1l(22). Cournil A, Eymard-Duvemay S, Diouf A, Moquet C, Coutherut J, Ngom Gueye NF, Carnes C,- Taverne B, Bork K, Sow PS, Delaporte E and ANRS 1215 Study Group' (2012). Reduced Quantitative Ultrasound Bone Mineral Density in Hlv-Infected Patients on Antiretroviral Therapy in SenegaL PLoS ONE, 7(2). Craker LE. & Zoe G.(2014). The Botany of Cannabis. Accessed on 19th April 2014 via http://www.motherearthliving.comlnatural-healthlbotany-of-carmabis . Crowley D, Jones DE, Coffman DL, Greenberg and MT (2014). Can We Build an Efficient Response to the Prescription Drug Abuse Epidemic? Assessing the Cost Effectiveness of Universal Prevention in the PROSPER Trial. Journal of Preventive Medicine, 6:712-717. Csete J (2010). From the Mountaintops. What the World Can Learn from Drug Policy Change in Switzerland. Open Society Foundations, USA. ISBN: 978-1-936133-34-5. Accessed on 25th June via http://www.opensocietvfoundations.org/sites/default Ifileslfrom-the-mountaintops-english-20110524 O.pdf 149 Cunningham J (2012). Homelessness, Orphaned Status, IDU and Sexual Risk in HTV Prevention, HIV/AIDS, Orphaned and Vulnerable Children and Youth, Young People Most-at-risk ofHIV. AIDS, 26(1):111-113. D'Alessandro AI, Boeckelmann I, Hammwhoner M and Goette A (2012) Nicotine, cigarette smoking and cardiac arrhythmia: an overview. European Journal of Preventive Cardiology, 19(3):297-305. Dagne E, Yirga A, Eshetu K and Yoseph A (2010). Determination of Levels of Cathine in Khat (Catha edulis) Leaves and its Detection in Urine of Khat Chewers: A Preliminary Report. Ethiopian E Journalfor Research and Innovation Foresight. 2(1):7-22. Dasgupta A, Butt A, Saha TK, Basu G, Chattopadhyay A and Mukherjee A (2010). Assessment of malnutrition among adolescents: can BMl be replaced by MUAC? Indian Journal Community Medicine, 35:276-279. Davies G (2010). A Critical Evaluation of the Effects of Safe Injection Facilities. The Journal of Global Drug Policy and Practice, 1(3). De Vel-Palumbo M, Matthew-Simmons F, Shanahan M and Ritter A (2013)". Supervised Injecting Facilities: What the literature tells us. Drug Policy Modelling Program Bulletin Series, 22 (2). DEA 2011 Drug Enforcement Administration. Accessed on io" April 20]4 VIa http://www.usa.gov/directory/federalldrug-enforcement-administration.shtml. -DEA Museum, 2012. Drug Enforcement Administration. Accessed on 10th April 2014 via http://www.deamuseum.orgiccplhistory.html. DeBeck K, Kerr T, Bird L, Zhang R, Marsh D, Tyndall M, Montaner J and Wood E (2011). Injection drug use cessation and use of North America's first medically supervised safer injecting facility. Drug and Alcohol Dependence, 113:172-176. Denduangboripant J, Piteekan T and Nantharat M (2010). Genetic polymorphism between tobacco cultivar groups revealed by amplified fragment length polymorphism analysis. Journal of Agricultural Science, 2(2): 41-48. Deiss RG, Rodwell TC and Garfein RS (2009). Tuberculosis and illicit drug use: review and update. Clinical Infectious Diseases, 48: 72-82. DeSilva MB, Allen L, XuKeyi G. Zhong L, Cheng F, Mohamad B, Harrold M, Yueying H, Gill CJ, Wubin X, Vian T, Haberer J, Bangsberg D and Sabin L (2013). Feasibility and Acceptability of a Real-Time Adherence Device among HIV-Positive IDU Patients in China. AIDS Research and Treatment. 2013(2013):957862 150 Deveau C, Levine Band Beckerleg S (2006). Heroin Use in Kenya and Findings from a Community Based Outreach Programme to Reduce the Spread of HIV/AIDS. African Journal of Drug and Alcohol Studies, 5(2): 95-106. Di Forti M, Morgan C, Dazzan P, Pariante C, Mondelli V, Marques TR Handley R, Luzi S, Russo M, Paparelli A, Butt A, Stilo SA, Wiffen B, Powell 1and Murray RM (2009). High-potency cannabis and the risk of psychosis. British Journal of Psychriatry; 195:488- 91. Dickson AJ, Shawn P, Vorce BL and Marilyn RP (2010). Multiple-Drug Toxicity Caused by the Coadministration of 4-Methylmethcathinone (Mephedrone) and Heroin. Journal of Analytical Toxicology. 34(3):162-168. Dinis-Oliveira, RJ, Carvalho F, Duarte lA, Proenca JB, Santos A and Magalhaes T (2012). 'Clinical and forensic signs related to cocaine abuse', Current Drug Abuse Review, 5(1): 64-83. Djoba, SJF (2014). Chlamydia trachomatis, Human Immunodeficiency. Virus (HIV) Distribution and Sexual Behaviours across Gender and Age Group in an African Setting. PLoS ONE, 9(3). Douglas H, Boyle M and Lintzeris N (2011). The health impacts of khat: a qualitative study among Somali-Australians. Medical Journal of Australia. 19;195(11-12):666-669. Drake lV (2010). Nutrition and Immunity, Part 1. Micronutrient Information Center. Oregon State University. http://1pi.ore gonstate. eduJss 1O/nutrition.html 21106/2013. last updated 2010. Drissa S, Yentema 0, Arijit N, Foro A and Brewer T (2014). What lies behind gender inequalities in HIV/AIDS in sub-Saharan African countries: evidence from Kenya, Lesotho and Tanzania. Health Policy Plan, 29(7):938-949. Druginfo, (2013). Accessed on 19th May via 2014 http://www.drugabuse.gov/about- nidalorganization. Drugbank, (2013). Ethanol. Accessed on z= April 2014 VIa http://www.drugbank.caldrugslD B0089 8. Drugfree world, (2014). The Truth About Marijuana: Its Background. Accessed on 19th April 2014 via http://www.drugfreeworJd.org/drugfacts/marijuanaiit-s-background.html. Druglibrary, (2010). Guide to the Different Types of Hash from Around the World. Accessed on 19th April 2014 via http://www.druglibrary.orgischaffer/. 151 Dutta A, Wirtz A, Stanciole A, Oelrichs R, Semini I, Baral S, Pretorius S, Haworth C, Hader S, Beyrer C and Cleghorn (2013). The Global Epidemics among People Who Inject Drugs.Washington, DC: World Bank. eISBN: 978-0-8213-9777-0. Duvivier Cl, Kolta S, Assoumou L, Ghosn J, Rozenberg S, Murphy RL, Katlama C, Costagliola and ANRS 121 Hippocampe study group (2009). Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnuc1eoside reverse transcriptase inhibitor regimens in HIV-l infected naive patients. AIDS, 23(7):817-824. ECDC, (2011). European Centre for Disease Prevention and Control and European Monitoring Centre for Drugs and Drug Addiction. Prevention and control of infectious diseases among people who inject drugs. Accessed on 26th April 2011 via http://www.eurosurveillance.org/ViewArticle.aspx?Articleld=1996') . EI Hage C, Rappeneau V, Etievant A, Morel A-L, Scama H, Zimmer L,Berod A (2011). Enhanced Anxiety Observed in Cocaine Withdrawn Rats Is Associated with Altered Reactivity of the Dorsomedial Prefrontal Cortex. PLoS ONE, 7(8). ELF, (2012). European Lung Foundation, Multidrug-Resistant Tuberculosis. http://www .europeanlung. org/en/news-and-events/news/professional- focus-christoph- lange. Embleton L, Ayuku D, Atwoli L, Vreeman R and Braitstein P (2012). Knowledge, Attitudes, and Substance Use Practices Among Street Children in Western Kenya. Substance Use and Misuse, 47(11): 1234-1247. - Embleton L, Mwangi A, Vreeman R, Ayuku D and Braitstein P (2013). The epidemiology of substance use among street children in resource-constrained settings: a systematic review and meta-analysis. Addiction, 108(10):1722-1733. EMCDDA, (2008). European Monitoring Centre for Drugs and Drug Addiction. A cannabis reader: global issues and local experiences, Monograph series 8, Volume 2, European Monitoring Centre for Drugs and Drug Addiction, Lisbon. Accessed on April 2014 via http://www.emcdda.europa.eu/attachements.cfinlatt 53399 EN emcdda--cannabis-mon-voI2-ch9-web.pdf. EMCDDA, (2009). Polydrug Use: Patterns and Responses. Accessed on 21st March 2014 via http://www.emcdda.europa.eu/attachements.cfm/att 101612 EN TDAN 090 02ENC.pdf. EMCDDA and Europol (2010). Cocaine. A European Union perspective in the global context, EMCDDA-Europol joint publications, Publications Office of the European Union, Luxembourg. Accessed on 6th April 2014 via http://www.emcdda.europa. eui attachements.cfm/att 1016I2 EN TDAN09002ENC.pdf. 152 EMCDDA, (2010). European Monitoring Centre for Drugs and Drug Addiction. Trends In Injecting Drug Use In Europe. Accessed on 1st April 2014 via http://www.emcdda: europa.eulattachements.cfmJatt 108590 EN EMCDDA S1l0 injecting.pdf. EMCDDA, (2010). Levamisole as a cocaine adulterant. In 2010 Annual report. Accessed on 5th April 2014 via http://www.emcdda.europa.euJonline/annual-report/2010 /boxes / p66. EMCDDA, (20lla). Prevention and control of infectious diseases among people who inject drugs. Accessed on 17th April 2014 http://ecdc.europa.eu/en/publications/ publications/Ill 012 guidance ecdc-emcdda.pdf. EMCDDA, (201Ib). Khat. Accessed on 15th April 2014 via http://www.emcdda .europa .en/publicationsfdrug-profilesfkhat. EMCDDA, (2013a). Heroin. Accessed on 19th April 2014 VIa http://www.emcdda. europa.eu/publications/drug-profiles/heroin. EMCDDA, (2013b). Cocaine. Accessed on 18th April 2014 via http://www.erncdda. europa.euJpublications/drug-profiles /cocaine. EMCDDA, (20 13c). Cannabis. Accessed on 19th April 20J 4 Via http://www.emcddaeuropa.eu/publications/drug-profiles/cannabis. EMCDDA, (2013d). Khat. Accessed on 19th April 2014 via http://www.emcdda. europa.eu/publications/drug-profileslkhat. EMCDDA, (20 Be). Benzodiazepine. Accessed on 21st April 2014 Via http://www.emcdda.europa.eu/publications/drug-profiles/benzodiazepine. EMCDDA, (20 13f). Drug profiles. Accessed on 30th April 2014 via http://www. emcdda. europa. eu/drug-profiles. EMCDDA, (20 13g). Harm reduction. Accessed on 13th April 2014 via http://www. emcdda.europa.eu/themes/harm-reduction. Encyclopaedia Britannica, (2012). Accessed on 2nd April 2014 via http://www. britannica.comlchecked/topic/172024/drug-use/40524/Types-of-cannabis-preparations. Encyclopcedia Britannica Online Accessed on 30th July 2014 VIa bttp ://www.britanni ca.comlEBchecked/media/4 7] 6/Cannabis-sativa>. Encyclopaedia of Life, 2012. Nicotiana tabacum. Accessed on 2nd July 2014 VIa http://eo1.org/pages/581050/hierarchy entries/50310302/overview. 153 Ersche, KD (2013). Neurobiological Correlates of the Familial Risk for Stimulant Drug Dependence. Neuropsychopharmacology Review, 38:238-239. Ersche KD, Jones PS, Williams GB, Turton AJ, Robbins TW and Bullmore ET (2012a). Abnormal Brain Structure Implicated in Stimulant Drug Addiction. Science, 335: 601- 604. Ersche KD, Turton AJ, Chamberlain SR, Miiller U, Bullmore ET and Robbins TW (2012b). Cognitive dysfunction and anxious-impulsive personality traits are endophenotypes for drug dependence. American Journal of Psychiatry, 169: 926-936. Ersche KD, Bullmore ET, Craig KJ, Shabbir SS, Ulrich Muller, Suckling J, Merlo-Pich EY, MD, and Robbins TW(2010). Influence of Compulsivity of Drug Abuse on Dopaminergic Modulation of Attentional Bias in Stimulant Dependence. Archives of General Psychiatry, 67(6): 632-644. Erowid 2010. Nicotine Timeline. Accessed on 2nd July 2014 via httns:llwww.erowid.org Ichemicals/nicotine/nicotine timeline.php. Euromonitor, 2013. Euromonitor International Tobacco in Kenya. Accessed on 1'1 April 2014 via http://www.ellIomonitor.com/img/logo-euromonitor-international.png. Evans D, McNamara L, Mhairi M, Selibas K, Van Amsterdam D, Baines N, Webster T and Sann I (2013). Impact of nutritional supplementation on immune response, body mass index and bioelectrical impedance in HIV-positive patients starting antiretroviral therapy. Nutrition Journal 12:111 Evans P, Turner S and Trotter C (2012). The Effectiveness of Family and Relationship. Therapy: A Review of the Literature. Melbourne: PACFA. Accessed on 28th April 2014 via www.pacfa.org.au. FANTA, (2013). BMl and BMl-for-Age Look-Up Tables for Children and Adolescents 5-18 Years of Age and BMl Look-Up Tables for Non-Pregnant, Non-Lactating Adults > 19 Years of Age. Accessed on zs" April via http://www.fantaproiect.orgltoolslbl:ni-109k· ltp~tables_ FAO, (2010). The state of food insecurity in the world: addressing food insecurity in protracted crises. Accessed on 4th Nov 2013 via bttp:l/www.fao.org/fileadmin/user uploadlagnlpdf/N-interno-rev2.pdf. FAO, (2014). The multiple dimensions of food security. Accessed on 23rd/June 2014 via http://www .fao.org/publications/sofi/2 0131en/. 154 Farmer S. and Hanratty B (2011). The relationship between subjective wellbeing, low income and substance use amongst schoolchildren in the north west of England: A cross sectional study. Journal of Public Health, 34(4):512-522. . Fayemiwo SA, Odaibo GN, Sankale JL, Oni AA, Bakare RA, Olaleye OD and Kanki P (2014). Diverse genetic subtypes of mY-1 among female sex workers in Ibadan, Nigeria. African Journal of Clinical and Experimental Microbiology, 15(1) FDA, (2009). Route of Administration. Accessed on 24~ June 2014 via . bttp:!Iwww.fda. govlDrugslDevelopmentApprovalProcess/F ormsSubmissionRequirement slElectronicSubmissionslDataS tandardsMan uaimonographs/ucm071667 .htm. Feng Yl, He X, Yang Y, Chao D, Lazarus LH and Xia Y. (2012). Current research on opioid receptor ftmction. Current Drug Targets,13(2):230-46. Flak AL, Su S, Bertrand J, Denny CH, Kesmodel US and Cogswell :ME (2014). The Association of Mild, Moderate, and Binge Prenatal Alcohol Exposure and Child Neuropsychological Outcomes: A meta-analysis. Alcoholism Clinical and Experimental Research,38(1):214-26. Flascha Carl, (2011). On Opium: Its History, Legacy and Cultural Benefits. Prospect Journal in Culture, History, Science and Technology. Accessed on 26th July 2013 http://prospectjoumal.org/20 11105/251on-opium- its-history-Iegacy-and-cultural-benefits/. Floyd LJ, Hedden S, Lawson A, Salama C, Moleko AG and Latimer W (2010). The association between poly-substance use, coping, and sex trade among black South African substance users. Substance Use and Misuse, 45:1971-1987. Fox AM, (2010). The·Social Determinants of my Serostatus in Sub-Saharan Africa: An Inverse Relationship Between Poverty and Hl'V? Accessed on 4th Jan 2015 via http://www.publichealthreports.org/issueopen.cfm?articleID=24 79. Franca TGD, Ishikawa LLW, .Zorzella-Pezavento SFG, Chiuso-Minicucci F, da Cunha, MLRS and Sartori A(2009). Impact of malnutrition on immunity and infection. JOUYhol of Venomous Animals and Toxins including Tropical Diseases, 15(3): 374-390. Fulton HG, Barrett SP, MacIsaac C and Stewart HS (2011). The relationship between self-reported substance use and psychiatric symptoms in low-threshold methadone maintenance treatment clients. Harm Reduction Journal, 8:18. Gajendra KM, Jagadish M, Ramesh SP, Rajatashuvra A, Senjam GS, Akoijam SB and Goswami P (2012). Factors associated with ever my testing among injecting drug users (IDUs) in two my high prevalent States of India. Indian Journal of Medical Research, 136:64-71 155 Galloway GP, Buscemi R, Coyle JR, Flower K, Siegrist JD, Fiske LA, Baggott MJ, Li L, Polcin D, Chen CYA and Mendelson J(2011). A Randomized, Placebo-Controlled Trial of Sustained-Release Dextroamphetamine for Treatment of Methamphetamine Addiction. Clinical Pharmacology Therapy, 89(2): 276-282. Garduno J, Galindo-Charles L, Jimenez-Rodriguez J, Elvira G, Dagoberto T, Mihailescu S and Hernandez-Lopez S (2012). Presynaptic (l4~2 Nicotinic Acetylcholine Receptors Increase Glutamate Release and Serotonin Neuron Excitability in the Dorsal Raphe Nucleus. The Journal of Neuroscience , 32(43): 15148-15157. Gemma and Fitzgerald, 2010. Flunitrazepam: the Date Rape Drug. Accessed on 19th Apri12014 via http://www.chm.bris.ac.uk/motm/rohypnollrohypnolh.htm. Getahun H, Gunneberg C, Sculier D, Verster A and Raviglione M (2012). Tuberculosis and Hl V in people who inject drugs: evidence for action for TB, HIV, prison and harm reduction services. Current Opinion in HIV and AIDS, 7: 345-53. Getahun W, Teferi G and Fikru T (2010). Regular Khat (Catha edulis) chewing is associated with elevated diastolic blood pressure among adults in Butajira, Ethiopia: A comparative study. BMC Public Health, 10:390 Gifford, S. (2012). Differences Between Outpatient and Inpatient Treatment Programs. Accessed on 3rd May 2014 via http://psychcentraLcomilib/differences-between- outpatient~and-inpatient-treatment-programs/0007 531. Gibson DR, Zhang G, Cassady D, Pappas L, Mitchell J and Kegeles SM (2010). - Effectiveness of HlV prevention social marketing with injecting drug users. American Journal of Public Health, 100:1828-1830. Githui, DM (2011). Drinking Culture and Alcohol Management in Kenya: An Ethical Perspective. European Journal of Business and Management, 3(4): 1'32- 145 Global Commission on Drug Policy, (2012). The War on Drugs and HIV/AIDS. How the Criminalization of Drug Use Fuels the Global Pandemic. Accessed on 16th May 20J4 via http://www.globalcommissjonondmgs.org/category/news. Government of Kenya, (2013). Kenya Food Security Steering Group (KFSSG) October to December 2013 Short Rains Season Assessment Report. Accessed on 14th Jan 2015 via http://www.disasterriskreduction.netlfileadminluser _upload! droughtldocs/20 13- 2014%20SRA %20Report_ FinaLpdf. Goldenberg SM, Rangel G, Vera A, Vera A, Patterson TL, Abramovitz D, Silverman JG, Anita Raj, and Steffanie A Strathdee (2012). Exploring the impact of underage sex work among female sex workers in two Mexico-US border cities. AIDS Behaviour, 16: 969- 81. 156 Gonzales MJ (2010). Andean Cocaine: The Making of a Global Drug (review). Journal of Interdisciplinary History. 41(1):170-171. Ghosh M, Rodriguez-Garcia M and Wira CR (2013). Immunobiology of genital tract trauma: endocrine regulation of HIV acquisition in women following sexual assault or genital tract mutilation. American Journal of Reproductive Immunology, 69 (l): 51-60. Grant CH, Clark EA and Wong AH (2013). The intracellular progesterone receptor regulates CD4+ T cells and T cell-dependent antibody responses. Journal of Leukocyte .Biology, 93 :369-375. Grebely J and Dore JG (2011). Prevention of Hepatitis C Virus in Injecting Drug Users: A Narrow Window of Opportunity. Journal of Infectious Diseases, 203(5):571-574. Gumbiner J (2011). History of Cannabis 111 http://chineseculture.about.comllibrary/clipartlblscliparts.htm. Ancient China. Gupta A, Mbwambo J and Bruce RD (2014). None Active Case Finding for Tuberculosis among Injection Drug Users in Medication Assisted Treatment in Dar es SaJaam, Tanzania. International Journal of Tuberculosis and Lung Diseases,18(7):793-798. Gyarmathy VA, Neaigus A and Ujhelyi E (2009). Vulnerability to drug-related infections and co-infections among injecting drug users in Budapest, Hungary. European Journal of Public Health, 19(3): 260-265. Haaland RE, Hawkins PA, Salazar-Gonzalez J, Amber J, Tichacek A, Manigart 0, Mulenga J, Keele BF, Shaw GM, Hahn BH, Allen SA, Derdeyn CA and Hunter E (2009)". Inflammatory Genital Infections Mitigate a Severe Genetic Bottleneck in Heterosexual . Transmission of Subtype A and C HIV -1. PLoS Pathogens, 5(1). Haghpanah T, Mohammadreza A and Kouros D (2010). A Review on Hematological Factors in Opioid-Dependent People (Opium and Heroin) after the Withdrawal Period. Journal of Addiction and Health, 2(1-2): 9-16. Haileyesus G, Baddeley A and Ravigiione M (2013). Managing tuberculosis in people V.1lO use and inject illicit drugs. Bulletin of the World Health Organization, 91:154-156. Hall W and Degenhardt L(20 13). The adverse health effects of chronic cannabis use. Drug Testing and Analysis, 6(1):39-45. Hall AB, Coy SL, Nazarov EG and Vouros P (2012). Rapid Separation and Characterization of Cocaine and Cocaine Cutting Agents by DifferentiaJ Mobility Spectrometry-Mass Spectrometry. Journal of Forensic Sciences, 57: 750-756. 157 Han X, An M, Zhao B, Duan S, Yang S. Li H and Wang X (2013). High Prevalence of HJV·l Intersubtype B9/C Recombinants among Injecting Drug Users in Dehong, China. PLoS ONE. 8(5) Handley ED and Chassin L (2013). Alcohol-specific parenting as a mechanism of parental drinking and alcohol use disorder risk on adolescent alcohol use onset. Journal of Studies on Alcohol and Drugs, 74(5):684-693. Harrella PT, Trenza RC, Scherera M, Ropelewskia LR & Latimera WW (2012). Cigarette smoking, illicit drug use, and routes of administration among heroin and cocaine users. Addiction Behaviour, 37(5): 678-681. Harte, CB (2014). Concurrent relations among cigarette smoking status, resting heart rate variability, and erectile response. Journal of Sexual Medicine, 11(5): 1230-1239. Hartney, E (2014). What to Expect from Heroin Withdrawal and How to Feel Better. Accessed on 16th April 2014 via http://addictions.about.com/od/dailylifewithaddiction /a! What- To-Expect-From-Heroin- Withdrawal.htrn. Hashish Centre, (2013). Hashish Facts. Accessed on 19th April 2014 VIa http://www.hashish-center.comlhashishfacts.html. Havinga P, Van der Velden C, de Gee A and Van der Poe A (2014). Differences in sociodemographic, drug use and health characteristics between never, former and current injecting, problematic hard-drug users in the Netherlands. Harm Reduction Journal, 11:6. Hays, J (2011). Opium, Morphine And Heroin And Their History. Accessed on 1st Dee 2013 via http://factsanddetails.com/world/cat54/sub348/itemI219.html. Health Protection Agency, (2011). Accessed on 25th April 2014 VIa http://www.hpa.org.uk/webcIHPAwebFileIHPAweb_C/1317131377664. Hedrich D, Kerr T and Dubois-Arber F (2010). Drug consumption facilities in Europe and beyond. In The European MonitoringCentre for Drugs and Drug Addiction. http://www.erncdda.europa.eulattachernents.cfinlatt_l 01273_EN_emcdda-hann%2Ored- rnon-chll-web.pdf. Heinz AJ, Wu J, Witkiewitz K, Epstein DH and Preston KL (2009). Marriage and relationship closeness as predictors of cocaine and heroin use. Addiction Behaviours, 34(3):258-263. Helrnenstine AM, (2014). Rohypnol Fast Facts. Accessed on 19t11April 2014 via bttp://chemistry.about.comlod/drugs/a/rohypnoIfacts.htm. 158 Hendricks K and Gorbach S (2009). Nutrition issues in chronic drug users living with mv infection. Addiction Science Clinical Practice, 5:16-23. Hendricks KM, Erzen lID, Wanke CA and Tang AM (2010). Nutrition issues in the Hlv- infected injection drug user: findings from the nutrition for healthy living cohort. Journal of American College of Nutrition, 29(2):136-143. Hepatitis Foundation international (2013). Hepatitis C. Accessed on 17th April 2014 via http://www.hepti.orgIHEPATITIS/Hepatitis-C.html Hilber AM, Francis SC, Chersich M, Scott P, Redmond S, Bender N, Miotti Temmennan M and Low N (2010) Intravaginal Practices, Vaginal Infections and HIV Acquisition: Systematic Review and Meta-Analysis. PLoS ONE, 5(2). Hirst, KK (2014). Tobacco History: Origins and Domestication of Nicotiana in Plant Domestication. Accessed on 19th April 2014 via http://arc.haeology.about.comlodlt erms/g I Tobacco-History.htm. Hoffmann CJ, Mashabela F, Cohn S, Hoffmann JD, Lala S, Martinson NA and Chaisson RE. (2014). Maternal hepatitis B and infant infection among pregnant women living with Hl.V in South Africa. Journal of International AIDS Society, 22( 17) Huang Y-F, Yang J-Y, Nelson KE, Kuo H-S, Lew-Ting C-Y, Chang-Hsun C, Feng-Yee C and Hui-Rong L (2014) Changes in HIV Incidence among People Who Inject Drugs in Taiwan following Introduction of a Harm Reduction Program: A Study of Two Cohorts. PLoS Medicine, 11(4). Hue S, Hassan AS, Nabwera H, Sanders EJ, Pillay D, Berkley JA and Cane PA (2012). HfV type 1 in a rural coastal town in Kenya shows multiple introductions with many subtypes and much recombination. AiDS Research and Human Retroviruses, 28(2):220- 224. Hunt, R (2010). Human Immunodeficiency Virus and AIDS: Types, Sub-types and Co- receptors. In Microbiology and Immunology Online. Accessed on 19th April 2014 via http://pathmicro.med.sc.edu/Jechlrelhiv6.htm. Hussong AM, Jones DJ, Stein GL, Baucom DH and Boeding S (2011). An internalizing pathway to alcohol use and disorder. Psychology of Addictive Behaviors, 25(3):390-404. Hwang LY, Grimes CZ, Beasley RP and Graviss EA (2009). Latent tuberculosis infections in hard-to reach drug using population - detection, prevention and control. Tuberculosis, 89(1):41-45. IBM, (20]2). The International Business Machines Corporation. Accessed on 22fl(1Jan 2013 via http://www.ibm.coml. \ 159 IEBC, (2012). Constituency boundaries. Accessed on 2nd April 2014 via http://W\vw.iebc .or. kef. lliRA, (2010). A position statement from the International Harm Reduction Association. Accessed on zs" April 2014 via http://www.ihra.net/files/2010/05/31IlHRA HRStatement. pelf. Iliakis D and Kressig RW (2014). The relationship between malnutrition and immune. Therapeutische Umschau, 71(1):55-61. IRIN, (2012). Integrated Regional Information Networks. KENYA: Needles to be distributed to injecting drug users. 2012. Accessed on 2nd July 20]4 via http://www.irinnews.org/report/95601/kenya-need1es-to-be-dlstributed-to-injecting-dmg- users. IRIN, (2013). HIV/AIDS: Criminalization of drug use fuelling HIV. Accessed on 2nd July 2014 via http://www.irinnews.org/report/95746/hiv-aids-criminalization-of-dmg- use-fuelling-hiv. lmer TB, Teasdale WT, Tine N, Vedal S and Olofsson M (2012): Substance Use During Pregnancy and Postnatal Outcomes, Journal of Addictive Diseases, 31: 1, 19-28. Jacobson DL, Lindsey JC, Gordon CM, Moye J, Hardin DS et al. (20 lO). Total body and spinal bone mineral density across Tanner stage in perinatally Hl V-infected and uninfected children and youth in PACTG 1045. AIDS, 24(5): 687-696. Jain B, Suneeta K, Sowmya R, Shmtika S, Vijay G and Neeraj D.(2014). Effect of peer- led outreach activities on injecting risk behaviour among male drug users in Haryana, India. Harm Reduction Journal, 11:3 Jones MR, Apelberg BJ, Samet JM and Navas-Acien A (2013). Smoking, Menthol Cigarettes, and Peripheral Artery Disease in U.S. Adults. Nicotine Tobacco Research, 15(7):1183-1189. Jung M, Leye N, Vidal N, Fargette D, Diop H, Kane CT, Gascuel 0 and Peeters M (2012). The Origin and Evolutionary History ofHIV-1 Subtype C in Senegal. PLoS ONE, 7(3) Junqueira DM, de Medeiros RM, Matte MCC, Arau' jo LAL and Chies JAB(20]]). Reviewing the History ofHIV-l:Spread of Subtype B in the Americas. PLoS ONH, 6(11). Kabbash AI, Abdul-Rahman, Shehata YA and Omar AAR. HIV infection and related risk bebaviours among female sex workers in greater Cairo, Egypt. Eastern Mediterranean Health Journal, 18 (9). 160 Kagaayi J, Gray RH, Whalen C, Fu P, Neuhauser D, Kigozi G, Nalugoda F, Reynolds SJ, Maria J. Wawer and Mendel E. Singer (2014). Indices to Measure Risk of H1V Acquisition in Rakai, Uganda. PLoS ONE, 9(4) Kageha S, Liliana RW, Okoth V, Mwau M, Okoth FA, Songok EM, Ngaira 1M,Khamadi SA (2012). HIV type 1 subtype surveillance in central Kenya. AIDS Research and Human Retroviruses, 28(2):228-231. Kahuthia-Gathu R, Okwarah P, Gakunju R and Thungu J (2013). Trends and emerging drugs in Kenya: A case study in Mombasa and Nairobi County. Journal of Applied Biosciences, 67:5308-5325. Karajibani M, Montazerifar F and Shakiba M. (2012). Evaluation of Nutritional Status in Drug Users Referred to the Center of Drug Dependency Treatment in Zahedan. International Journal of High Risk Behaviiors and Addiction, 1(1):18-21. Kalichrnan SC, Simbayi LC, Kagee A, Toefy Y, Jooste S and Cain D.(2006). Associations of poverty, substance use, and mv transmission risk behaviours in three South African communities. Social Sciences and Medicine, 62:1641-1649. Kask K, Markina A and Podana Z (2013). The Effect of Family Factors on Intense Alcohol Use among European Adolescents: A Multilevel Analysis. Psychiatry Journal, 2013 (2013):250215 Kaushik KS, Kapila K and Praharaj AK (2011). Shooting up: the interface of microbial infections and drug abuse. Journal of Medical Microbiology, 60(4):408-22. Kemboi GJ, Onkware K and Ntabo OM (2011). Socio-cultural factors that perpetuate the spread ofHIV among women and girls in Keiyo District, Kenya. International Journal of Sociology and Anthropology, 3(5):147-152. Gootenber P (2010). Andean Cocaine: The Making of a Global Drug. The University of North Carolina Press, Chapel Hill, 448 pp. ISBN: 978-0807859056. Kenny JP, Chen SA, Kitamura 0, Athina M and George FK (2009). Conditioned Withdrawal Drives Heroin Consumption and Decreases Reward Sensitivity. The Journal of Neuroscience, 26(22): 5894-5900. Kenna D, Babill S and Muller F (2013). HIV Diversity and Classification, Role in Transmission: Advances in Infectiou Diseases, 3(2): 146-156. Keshtkar A, Majdzadeh R, Nedjat S, Gholipour M, Badakhshan A, Qorbani M, Vakili M, Salari H (2012). Characteristics of high-risk sexual behaviours for human 161 immunodeficiency virus infection among Iranian drug abusers. Journal of Addiction Medicine, 6(2):153-158. Khamadi SA, Lihana RW, Osman S, Mwangi J, Muriuki J, Lagat N, Okoth FA and Songok EM (2009). Genetic diversity of HlV type 1 along the coastal strip of Kenya. AIDS Research and Human Retroviruses, 25(9):919-923. Khan M. Berger A, Hemberg J, O'Neill A, Typhanye PD and Kristina Smyrk (2012). Non-Injection and Injection Drug Use and STlfHIV Risk in the United States: The Degree to which Sexual Risk Behaviours Versus Sex with an STI-Infected Partner Account for Infection Transmission among Drug Users. AIDS and Behaviour, 17 (3): 1185-1194. Khan P, Mukhtar S, Anjum F, Tripathi B, Sriprasad S, Dickinson K and Madaan S. (2013). Fournier's gangrene associated with intradermal injection of cocaine. Journal of Sexual Medicine, 10(4): 1184-1186. Kim SG, Jung JB, Dixit D, Rovner R Jr, Zack JA, Baldwin GC and Vatakis DN (2013). Cocaine exposure enhances permissiveness of quiescent T cells to HIV infection. Journal of Leukocyte Biology, 94(4):835-843. . Kimani-Murage EW, Holding PA, Jean-Christophe F, Ezeh, AC Madise NJ, Kahurani, EN and. Zulu EM (2011). Food Security and Nutritional Outcomes among Urban Poor Orphans in Nairobi, Kenya. Journal of Urban Health, 88(2). Kimber Jo, Copeland L, Hickman M, Macleod J, McKenzie J and Mclendon M (2010). Survival and cessation in injecting drug users: prospective observational study of outcomes and effect of opiate substitution treatment British Medical Journal, 341 :c3172 Kimura CA, Higa JI, Levin RM, Simpson G and Vargas Y. (2007). Outbreak of Necrotizing Fasciitis Due to Clostridium sordellii among Black-Tar Heroin Users. 040rd Journals Medicine Clinical Infectious Diseases, 38 (9): 87-9l. Kinai E, Nishijima T, Mizushima D, Watanabe K, Aoki T and Honda H(2014). AIDS Research and Human Retroviruses, 30(6): 553-559. King DFL, Siddiqui AA, Buffa V, Fischetti L, Gao Y, Stieh D and McKay PF (2013). Mucosal Tissue Tropism and Dissemination of illY -1 Subtype B Acute Envelope- Expressing Chimeric Virus. Journal of Virology, 87(2):890. Kinyanjui DW and Atwoli L (2013). Substance use among inmates at the Eldoret prison in Western Kenya. BMC Psychiatry, 13:53. 162 Kiptoo M, Brooks J, Lihana RW, Sandstrom P, Ng'ang'a Z, Kinyua J, Lagat N, Okoth F, Songok EM (2013). HIV-I drug resistance-associated mutations among HIV-l infected drug-narve antenatal clinic attendees in mral Kenya. BMC Infectious Diseases, 13 :517. KNBS, (2010). Kenya National Bureau of Statistics, Population and Housing Census .2009. Nairobi: Ministry of State for Planning and National Development and Vision 2030. Accessed on 29th April 2014 via http://statistics.knbs .or.ke/nada/index.php/catalog/S S . Kiwelu IE, Novitsky V, Margolin L, Baca J and Manongi R (2012) HIV-I Subtypes and Recombinants in Northern Tanzania: Distribution of Viral Quasispecies. PLoS One 7: e4760S. Knut L, Williams BG, Cegielski P and Dye C (2010). A consistent log-linear relationship between tuberculosis incidence and body mass index. International Journal ofEpidemiology, 39 (1): 149-15S. Koethe JR and Heimburger DC (2013). Nutritional aspects of HIV-associated wasting in sub-Saharan Africa. American Journal of Clinical Nutrition, 91: 1138-1142. Kokavec A, Lindner AJ, Ryan JE and Crowe SF (2009). Ingesting alcohol prior to food can alter the activity of the hypothalamic-pituitary-adrenal axis. Pharmacology, Biochemisy and Behavior, 93(2): 170-6. Koranda JL, Cone 11, McGehee DS, Roitman MF, Beeler JA and Zhuang X (2014). Nicotinic receptors regulate the dynamic range of dopamine release in vivo. Journal of Neurophysiology. 111 (1): 103-111. Korir, W (2013). An analysis of drug abuse along the coastal regron of Kenya. International NGG Journal, 8(7): 153-158. Kousiappa I, Charis A, Hezka J, Yiota L, Othonos K and Demetriades 1(2011). AIDS Research and Human Retroviruses. 27(11): 1183-1199. Krawinkel, MB (2012). Interaction of nutrition and infections globally: an overview. Annals of Nutrition and Metabolism, 61(1):39-45. Krivine A, Odile L, Firtion G, Finkielsztejn L and Jullien V. (2009). Does HIV-1 Subtype D Have a Higher Risk of Vertical Transmission than Other HIV Subtypes? The Journal of Infectious Diseases, 199:1S53- 1554. Krizevskiab R, Nativ D, Einat B, Ilana D, Uzi Rand Lewinsohna E. (2008). Quantitative stereoisomeric determination of phenylpropylamino alkaloids in khat (Catha edulis Forsk.) using chiral GC-MS.Israel Journal of Plant Sciences, 56 (3). 163 Kumpfer, LK (2014). Family Based Interventions for the Prevention of Substance Abuse and Other Impulse Control Disorders in Girls. Addiction; 2014 (2014). Kwange SO and Budambula N (2010). Effectiveness of anti-tuberculosis treatment among patients receiving highly active antiretroviral therapy at Vihiga district hospital in 2007. Indian Journal of Medical Microbiology, 28:21-25 Lavezzi MA Coma MF, Alfonsi G and Matturri L (2014). Possible role of the a7 nicotinic receptors in mediating nicotine's effect on developing lung-implications in unexplained human perinataJ death. BMC Pulmonary Medicine, 14:11 Lee H, Jih-Heng L, Li-Tzy W, Jin-Song W, Cheng-Fang Y and Hsin-Pei T (2012). Survey of methadone-drug interactions among patients of methadone maintenance treatment program in Taiwan. Substance Abuse Treatment, Prevention and Policy 20 l Z, 7:11. Lee SC, Klein-SW, Doyon S and Welsh C (2014). Comparison of toxicity associated with nonmedical use of benzodiazepines with buprenorphine or methadone. Drug & AlcoholDependence. 138: 118-123. Lihana RW, Khamadi SA, Lwembe RM, Kinyua JG, Muriuki JK, Lagat NJ, Okoth' FA, Makokha EP and Songok EM (2009). HIV-l subtype and viral tropism determination for evaluating antiretroviral therapy options: an analysisof archived Kenyan blood samples. BMC Infectious Diseases, 9:215. Liliana RW, Ssemwanga D, Abimiku A and Ndembi N. (2012). Update on HlV-I . diversity in Africa: a decade in review. AIDS Review, (2):83-100. Low N, Chersich MF, Schmidlin K, Egger M and Francis SC (2011) Intravaginal Practices, Bacterial Vaginosis, and HfV Infection in Women: Individual Participant Data Meta-analysis. PLoS Medicine, 8(2). MacArthur JG, Minozzi S, Martin N, Vickerman P, Deren S and Bruneau J. (2012). Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis. British Medical Journal, 2012;345:e5945 MacArthur RD and DuPont HL (2012). Etiology and Pharmacologic Management of . Noninfectious Diarrhea in HlV-Infected Individuals in the Highly Active Antiretroviral Therapy Era. Clinical Infectious Diseases, 55(6):860-867. Madise IN, Ziraba AK, Inungu J, Khamadi SA, Ezeh A, Zulu EM, Kebaso J, Okoth V and Mwau M (2012). Are slum dwellers at heightened risk of HIV infection than other urban residents? Evidence from population-based HIV prevalence surveys in Kenya. Health Place, 18(5):1144-1152. ( 164 Mahmoudi A and Moshayedi M (2012). Life Skills Education for Secondary Education. Life Science Journal, 9(3). Majidpour AMD, Majidpour MDS and Quassemi MM (20] 2). Prevalence of hepatitis B virus (fill V), hepatitis C virus (HCV) and human immune-deficiency virus (ill V) infections among intravenous drug users (IDUs) in the ¥AH-o-MEHR Harm Reduction Center of Tehran, Iran Journal of AIDS and HIV Research, 4(6):152-158. Maleche A and Day E (2011). Traditional cultural practices and HlV: reconciling culture and human rights. Working Paper for the Third Meeting of the Technical Advisory Group of the Global Commission on HlV and the Law, 7-9 July 2011. 2011. Accessed on 10 May 2014 via http://kelinkenya.org/wp-content/uploads/20 1011O/traditional-cultural- practiceshiv-reconciling-culture-andhuman-rights.pdf. Mamani M, Mohammad MM, Saadat T, Ronak M and Ka-myab A (2013). Latent and Active Tuberculosis: Evaluation of Injecting Drug Users. Iranian Red Crescent Medical Journal, 15(9). Manoranjan S. D'Souza and Markou A (2011). Neuronal Mechanisms Underlying Development of Nicotine Dependence: Implications for Novel Smoking-Cessation Treatments. Addiction Science & Clinical Practice, 6(1): 4-6. Maro I, Lahey T, MacKenzie T, Mtei Land Bakari M (2010). Low BM! and falling BM! predict Hl'V-associated tuberculosis: A prospective study in Tanzania. International Journal ofTuberculosis and Lung Disease, 14: 1447-1453. Marshall MM, Kirk GD, Caporaso NE, McCormack MC and Merlo CA (201la). Tobacco use and nicotine dependence among Hl V-infected and uninfected injection drug users. Addictive Behaviours, 36:61-67. Marshall BDL, Milloy MJ, Wood E, Montaner JSG and Kerr T (2011b). Reduction in overdose mortality after the opening of North America's first medically supervised safer injecting facility: a retrospective population-based study. The Lancet, 377(9775), 1429- 1437. Masese L, McClelland RS, Gitau R, Wanje G, Shafi J, Kashonga F et al. (20l3). A pilot study of the feasibility of a vaginal washing cessation intervention among Kenyan female. sex workers.London. Sexually Transmitted Infections, 89(3):217-222. Massey SH, Compton MT and Kaslow NJ. (2014), Attachment security and problematic substance use in low-income, suicidal, African American women. The American Journal on Addictions, 23: 294-299. 165 Martins VJB, Toledo FTMM; Grillo, LP; Do Canno PFM and Martins PA (2011). Long- Lasting Effects of Undernutrition. International Journal of Environtal Research and Public Health, 8: 1817-1846. Mathers BM, Degenhardt L, Phillips B, Wiessing L and Hickman M, (2008). Global epidemiology of injecting drug use and HIV among people who inject drugs: a systematic review. Lancet, 372(9651):1733-1745. Maxwell JC and Spence RT (2008). An Exploratory Study ofInhalers and Injectors who Used Black Tar Heroin. Journal of Maintenance in the Addictions, 3(1), 61-82. Mayer KH, Bush T, Henry K, Overton ET, Hammer J and Richardson J. (2012). Ongoing sexually transmitted disease acquisition and risk-taking behaviour among US mv -infected patients in primary care: implications for prevention interventions.· Sexully Transmitted Diseases, 39: 1-7. . Mayhew S, Collumbien M, Qureshi A, Platt L, Rafiq Nand FaiseI A (2009). Protecting the unprotected: mixed-method research on drug use, sex work and rights in Pakistan's fight against HIV IAIDS. Sexually Transmitted Infections, 85(2):31-36. Mateu-Gelabert P, Milagros S, MeyIakhs P, Wendel T and Friedman SR (2010). Strategies to avoid opiate withdrawal: Implications for HCV and HIV risks. International Journal of Drug Policy, 21(3):179-185. Mbwambo J, McCurdy AS, Myers B, Lambdin B, Kilonzo GPand Kaduri P (2012). Drug trafficking, use, and HIV risk: The need for comprehensive interventions, SAHARA-J: Journal of Social Aspects ofHIV/AIDS, 9(3): 154-159. McCance-Katz EF, Gruber VA, Beatty G, Lum P, Ma Q and Difrancesco R (2013). Interaction of Disulfiram with Antiretroviral Medications: Efavirenz Increases While Atazanavir Decreases Disulfiram Effect on Enzymes of Alcohol Metabolism. American Journal of Addiction, 23(2):137-144. McClelland RS, Lavreys L, Hassan WM, Mandaliya x, Ndinya-Achola JO, Baeten JM and (2008). Vaginal washing and increased risk of HlV-I acquisition among African women: a 10-year prospective study. Journal of Infectious Diseases, 195: 698-702. McComsey GA, Tebas P, Shane E, Michael T, Yin E, Turner O. et al. (2010). Bone Disease in HIV Infection: A Practical Review and Recommendations for HIY Care Providers. Clinical and Infectious Diseases, 51 (8): 937-946. McCurdy SA, Ross MW, Kilonzo GP, Leshabari MT and Williams ML (2006). HlV/AIDS and injection drug use in the neighborhoods of Dar es Salaam, Tanzania. Drug and alcohol dependence, 82 (1),23-27. 166 McCurdy SA, Ross MW, Williams ML, Kilonzo GP, Leshabari MT (2010). Flashblood: blood sharing among female injecting drug users in Tanzania. Addiction, 105(6):1062-70. McDennid 1M, Hennig BJ, van der Sande M, Hill AV, Whittle HC and Jaye A. (2013). Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11- year retrospective cohort study. RMe Infectious Disease, 13:48. Mcllwraith F, Betts KS, Jenkinson R, Hickey S, Burns Land Alati R (2013). Is Low BM! Associated With Specific Drug Use Among Injecting Drug Users? Substance Use and Misuse, 49 (4): 374-382. Medhi KG, Jagadish M, Ramesh SP, Rajatashuvra A and Senjam GS(2012). Factors associated with ever HIV testing among injecting drug users (IDUs) in two HIV high prevalent States ofIndia. Indian Journal of Medical Research, 136: 64-71 Medline Medical Encyclopedia, 2014. Accessed on 1st April 2014 via. http://www.nlm.nih.gov/medlineplus/ency/article/001522.htm. Mendoza Y, Bello G, Castillo Mewa J, Marnnez AA and GonzaIez C(2014). Molecular Epidemiology of HIV-l in Panama: Origin of Non-B Subtypes in Samples Collected from 2007 to 2013. PLoS ONE 9(1): e85153. Merritt T, Mazela J and Merritt A (2013). Tobacco smoking and its consequences on reproductive health: the impact of a lifestyle choices including cigarette smoke exposure on fertility and birth defects. Przeglad Lekarski, 70(10):779-783. Methoide, (2013). Heroin overview: Origin and History. Accessed on I" April 20]4 via http://methoide.fcm.arizona.edu/infocenterlindex.cfm%3Fstid%3 D174 Methoide, (2014). Methamphetamine and Other Illicit Drug Education. Accessed on l st April 2014 via http://methoide.fcm.arizona.edu/ Miller CL, Fielden SJ, Tyndall MW, Zhang R, Gibson K and Shannon K (20] I). Individual and structural vulnerability among female youth who exchange sex for survival. Journal of Adolescent Health, 49(1 ):36-41. Mimiaga MJ, Reisner SL, Grasso C, Crane HM, Safren SA and Kitahata MM (2013). Substance Use Among HIV-Infected Patients Engaged in Primary Care in the United States: Findings From the Centers for AIDS Research Network of Integrated Clinical Systems Cohort. American Journal of Public Health, 103(8): 1457-1467. Mineur YS, Abizaid A, Rao Y, Salas R, DiLeone RJ, Gimdisch D and Diano S(2011). Nicotine decreases food intake through activation of POMC neurons. Science, 10J32(6035):1330-1332. 167 Mizuno Y, David WP, Metsch LR, Gomez CA, Knowlton AR and Latka ME (20] l ). Is Injection Serosorting Occurring among HIV-Positive Injection Drug Users? Comparison by Injection Partner's HIV Status. Urban Health, 88(6): 1031-1043. Moezzi M, Imani R, Khosravi N, Pourheidar B, Ganji F, Karimi A (2014). Hepatitis B seroprevalence and risk factors in adult population of chaharmahal and bakhtiari province in 2013. Hepatitis Monthly, 3;14(5):e17398. MOH, (2011). Bomu Medical Hospital (Changamwe). http://www.ehealth.or.ke/ facilitieslfacility.aspx?fas= 11258. MOR, (2012). Division of Leprosy Tuberculosis and Lung Disease, Annual Report. Accessed on 2nd July 2014 via http://www.nltp.co.ke/docs IDLTLD Annual report 2012.pdf. MOR, (2013). TB quarterly bulletin Q4, Issue I,Volume IlDecember 2013. Accessed on 2nd July 2014 via http://www.nltp.co.ke/docs/04 NTLD-U bulletin.pdf. Molina PE, Happel Kl, Zhang P, Kolls JK and Nelson S (2010). Focus On: Alcohol and The Immune System. Alcohol and Health, 33(1). Moon HS, Nifong 1M, Nicholson JS, Heineman A, Lion K and Hoeven R. (2014). Microsatellite-based Analysis of Tobacco (Nicotiana tabacum L.) Genetic Resources'. Accessed on 8th March 2014 via bttp://handle.nal.usda.govIl0113/37345. MOPHS, (2010). Ministry of Public Health Sanitation. National Monitoring and Evaluation Plan. DLTLD/ October, 2010. Accessed on 8th March 2014 VIa http://www.nltp.co.ke/docsIDLTLD M E plan for SP 2011-2015.pdf. Moraros J, Falconer J, Rogers M and Lemstra M (2012). Risk Factors Associated with Higher Injection Drug Use and HlV Rates: Findings from Saskatchewan, Canada. Journal of AIDS and Clinical Research, S1:009. Morris CN and Ferguson AG (2006). Estimation of the sexual transmission of HIV in Kenya and Uganda on the trans-Africa highway: the continuing role for prevention in high risk groups. Sexually transmitted infections, 82:368-371. ~enda 0 and Mugenda A (2003). Research Methods: Qualitative and Quantitative. Approaches, Acts Press, Nairobi-Kenya. Munro A and Allan J (2011). Can family-focussed interventions improve problematic substance use in Aboriginal communities? A role for social work. Australian Social Work 64(2): 169-182. 168 Munyuwiny S, Kamweya A, Nyandieka L, Murimi N and Ong'ayo OM (2013). Factors Associated with HIV Risk Sexual Behaviour among Female Domestic Workers in Nairobi, Kenya. African Journal of Health Science, 25:104-119 Muriuki, JM (2012). HIV-1 subtypes and coreceptor usage in a population from Northem Kenya (Master's Thesis at Kenyatta University, Kenya). Accessed on 19th April20J4 via http://ir-library.ku.ac.ke/bitstream/handlel1234 56789/415 9/J ohn%25 2OMartin.PdfOlo3 Fsequence %3. Murray MR, Morrison PD, Henquet C and Di Forti M (2008). Cannabis, the mind and society: The harsh realities. Nature Reviews Neuroscience, 8(11):885-95. Mntnre BN, Keraka NM, Kimuu PK, Kabiru EW, Ombeka VO and Oguya F (2011). Factors associated with default from treatment among tuberculosis patients in nairobi province, Kenya: A case control study. BMC Public Health, 11:696. Myers B, Kline TL, Browne FA, Camey T, Parry C and Jolmson K (2013). Ethnic Differences in Alcohol and Drug Use and Related Sexual Risks for nrv among Vulnerable Women in Cape Town, South Africa: Implications for Interventions. BMC Public Health, 13:174. NACADA, (2010). The Role of Parents in Prevention and Control of Alcohol and Drug Accessed on 12th April 2014 via http://www.nacada.go.ke/documents-and- resources/category/8-research-survey-findings%3Fdownloads. NACADA, (2012). Rapid Situation Assessment Of The Status Of Drug And Substance Abuse In Kenya, 2012. Accessed on 12th April 2014 via http://www.nacada.go.ke/ documents-and-resources/category/8-research-survey- findings %3Fdownloads. NACADA, (2013). Abused Substances. Accessed on 15th April 2014 via http://www.nacada.go.ke/khat. NACADA, (2014). Socio-economic and perceived health effects of khat chewing among persons aged 10-65 years in selected counties in Kenya. Policy Brief No. NAC/13/2014. Accessed on 15\h April 2014 via http://www.nacada.go.ke/documents-and- resources/category/8-research-survey- findings%3 Fdownloads. \ NACC and NASCOP (2012). Kenya AIDS Epidemic Update 2011. Accessed on 6thApril 20] 4 via http://www.nascop.or.kellibrary/3d1FINAL %20Kenya%20Update%2020 12, %2030%20May.pdf. Nadjme J and Nouzar N (2014). Etiology of Drug Abuse: A Narrative Analysis. Journal of Addiction, 2014 (2014). 169 Narconon, (2014). Marijuana information. Accessed on 19th April 2014 VIa http://www.narconon.org/drug-infonnationlmarijuana-pot.html. NASCOP, (2008). National AIDS and SID Control Programme, Ministry of Health, Kenya. July 2008. Kenya AIDS Indicator Survey 2007: Preliminary Report. Nairobi, Kenya. Accessed on 30th March 2014 via http://nascop.or.ke/library/3dlPreliminary %2520 Report%2520for%2520Kenya%2520AIDS%2520indica. NASCOP, (2010). National AIDS and STI Control Programme, Ministry of Public Health and Sanitation, Kenya. Guidelines for HIV Testing and Counselling and Kenya. Accessed on 30th March 2014 via http://nascop.or.ke/libraryIHTC /National %20 Guidelines%20 for%20HTC%20in%20Kenya%2020 10.pdf. NASCOP, (2012a). Rapid Situational Assessment of HfV Prevalence and Related Risky Behaviours among Injecting Drug Users in Nairobi and Coast Provinces of Kenya. Accessed on r" April 2014 via http://nascop.or.ke/librarylMarps /MARPs%2520BOOK %2520REPOR T%2520 .pdf. NASCOP) (2012b). Guidelines for antiretroviral therapy in Kenya 2011. National AIDS and STI Control Programme, Ministry of Health, Kenya. Accessed on 101b April 2014 via http://nascop.or.ke/library/ART%2520guidelineslFinal%2520guidelines%2520re % 2520 prin~10252011. NASCOP, (2012c). National Manual for the Management of HIV-related Opportunistic. Accessed on n'" April 2014 via http://nascop.or.ke/library/ART%2520guidelines /National %2520Manual %2520for%2520the%2520. NASCOP, (2013). National AIDS and STI Control Programme, Ministry of Health, Kenya. September 2013. Kenya AIDS Indicator Survey 2012: Preliminary Report. Nairobi, Kenya. Accessed on n" April 2014 via http://nascop.or.kellibrary/3d / Preiiminary%20Report%2 Ofor%20Kenya%20AIDS%20indicator%20survey%2020 12.p. Ndetei, DM (2004). Study on the Assessment of the Linkages Between Drug Abuse, Injecting Drug Abuse and Hiv/Aids in Kenya: A Rapid Situation Assessment (Rsa). Nairobi, Kenya, UN Office on Drugs and Crime (UNDOC). Accessed on 8th January via https:/lwww.unodc.org/pdfIWDR_2005/volume_l_chap3.pdf. Neaigus A, Reilly KH, Jenness SM, Hagan H, Wendel T and Gelpi-Acosta C (2013). \ Dual HIV Risk: Receptive Syringe Sharing and Unprotected Sex Among HIV-Negative Injection Drug Users in New York City. AIDS Behavior, 17(7):2501-9. Neale J, Nettleton S, Pickering L and Fischer J (2012). Eating patterns among heroin users: a qualitative study with implications for nutritional interventions. Addiction, 107(3):635-41. 170 NeL ED (2010). Diarrhoea and malnutrition. South Africa Journal of Clinical Nutrition, 23(1):15-18. Needle RH, Burrows D, Friedman SR, Dorabjee J, Touze G and Badrieva L (2005). Effectiveness of community-based outreach in preventing HfV/AIDS among injecting drug users. International Journal of Drug Policy, 16(5); 45-47 Needle RH and Zhao L (2010). illV Prevention among Injection Drug Users: Strengthening U.S. Support for Core Interventions. A Report of the CSIS Global Health Policy Center. Accessed on 1st April 2014 via http://csis.org/files/ publication! 100408_ Needle _IDVPrevention _web.pdf. NIAAA, 2013. National Institute on Alcohol Abuse and Alcoholism. Alcohol Facts and Statistics. Accessed on lst April 2014 via http://www.niaaa.nih.gov/aicohol- health/overview-alcohol-consumption!a1cohol-facts-and-statistics. Niazi MR, Ullah K, Khallid Z and Waseem I (2009). Is Poverty to be Blamed for Narcotic Abuse? A Case Study of Pakistan. International Journal of Basic & Applied Sciences, 09 (l0). Niccols A, Milligan K, Sword W, Thabane L, Henderson J and Smith A (2012). Integrated programs for mothers with substance abuse issues: A systematic review of studies reporting on parenting outcomes. Harm Reduction Journal, 9: 14. NIDA, (2012). National Institute on Drug Abuse, The Science of Drug Abuse and Addiction. Accessed on 1st April 2014 viahttp://www.nlm.nih.gov /medlineplus/ency /article/OO1522.htm. Nida, (2013a). mode oh heroin injection Accessed on 2nd April 2014 via http://www. drugabuse. gov/pub1ications/drugfactslheroin. Nida, (2013b). effects of heroin Accessed on 2nd April 2014 via http://www. drugabuse. gov/publications/drugfacts/heroin. NIDi\, (2013c). DrugFacts: Cocaine. Accessed on 3rd' April 2014 via http://www. drugabuse. gov/publicatiolls/drugfacts/cocaine. NIDA, (2014). DrugFacts: Marijuana. Accessed on 1st April 2014 via (http://www. drugabuse. gov/publications/dru gfacts/marijuana). Nidimusili AJ, Mennella J and Shaheen K. (2013). Small intestinal ischemia with pneumatosis in a young adult: what could be the cause? Case Reports in Gastrointestinal Medicine, 2013(2013). 171 Nigam JS, Bharti IN, Kumar D and Sharma A (2013). A Comparison of Hemoglobin Levels in Untreated and Treated Groups of ill V Patients on ART Including Zidovudine. Pathology Research International, 2013(2013). NlH, (2011). National Institutes of Health, Opiate withdrawal. Accessed on 15th February 2014 via http://www.n1m.nih.gov/medlineplus/ency/article/000949.htm. NIH, 2012. Opiate withdrawal Accessed on accessed on 26th July 20J3 http://www.nlm.nih.gov/medlineplus/ency/article/000949.htm. Nayer A (2014). Amyloid A amyloidosis: frequently neglected renal disease in injecting drug users. Journal ofNephropathology, 3(l):26-28. Ngugi EN, Roth E, Mastin T, Nderiru MG and Yasmin S (2012). Female sex workers in Africa: Epidemiology overview, data gaps, ways forward. Journal of Social Aspects of HIVIAIDS, 9 (3). Noor SW, Ross MW, Lai 0 and Risser JM (2013). Clustered drug and sexual Hl V risk among a sample of middle-aged injection drug users, Houston, Texas. AIDS Care. 25(7):895-903. Noroozi M, Nedjat S, Golestan Band Majdzadeh R (2012). What are differences between non-injecting and injecting drug addicts? International Journal of Preventive Medicine. 3:414~·>419. Nordqvist, C (2013). What is nicotine? Accessed on 2nd July 2014 http://www. medical newstoday.comlarticles/240820.php. " Novak SP and Kral AH (2011). Comparing injection and non-injection routes of administration for heroin, methamphetamine, and cocaine users in the United States. Journal of Addiction Disorders, 30:248-257. Nsimba SE, Kayombo EJ, Massele AY, Laurent Y and Lusajo M (2013). Characteristics of drug abusers inan urban community of Tanzania. American Journal of Research Communication, 1(7) NUUA, (20] 4). Brown heroin, white smack with a tan or the real deal? Accessed all l " "" April 2014 via http://www.nuaa.org.aulindex.php?option=colTI_content &view=articlc "&id=] 04&Itemid. Nyamache AK, Muigai AW and Khamadi SA (2013). Circulating trends of non-B HIV type 1 subtypes among Kenyan i.ndividuals. AIDS Research and Human Retroviruses, 29(2):400-3. .kENYAlTA ~NIVEIJS'T'I UB 172 Odek-Ogunde M, Lore Wand Owiti FR (2003). Risky behaviours among injecting drug users in Kenya. Paper presented at 1.4111International Conference on the Reduction or Drug Related Harm, April 2003, Chiang Mai, Thailand. Odendal, L (2011). Indonesia: Injecting drug use a major risk factor for HIY-associatcd TB. http://www.aidsmap.comJIndonesia-Injecting-drug-use-a-major-risk-factor-for-Hl y- associated- TB/page/2122520/ Odenwald M, Lingenfelder B, Wolfgang P, Farhan AH and Abdirisak MW(20 1J). A pilot study on community-based outpatient treatment for patients with chronic psychotic disorders in Somalia: Change in symptoms, functioning and co-morbid khat use International Journal of Men tal Health Systems, 6:8. Odinokova V, Rusakova M, Urada LA, Silverman JG and Raj A (20\4). Police sexual coercion and its association with risky sex work and substance use behaviours among female sex workers in St Petersburg and Orenburg, Russia. International Journal of Drug Policy, 25: 96-104. Ogbu CU, Lotfipour Sand Chakravarthy B (2014). Addressing the Spectrum of Polysubstance Abuse: Alcohol, Opioids and Benzodiazepines Require Coordinated Engagement by Society, Patients, and Physicians. Western Journal of Emergency Medicine, 16(1):17-19. O'Gurek TD and Kirchner TJ (2010). Needle Exchange for HIV/AIDS:An Effective Public Health Policy. Journal of Lancaster General Hospital. Summer 2010 - Vo!.5, NO.2. Accessed on 29th April 2014 via http://\-v.:ww.jlgh.org!Past-lsslies/Volllllle-5-::: Issue-2INeedle-Exchange-for-HIV-AIDS--An-Effective-Public-.aspx. Oino GP, Towett G and Ngunzo FK (2014). Patterns and Dynamics of Psychoactive Substance 'Use among Street Children in Eldoret Municipality, Kenya. International Journal of innovation and Scientific Research, 7(2): 163-170. Oino P and Sorre B (2013). The Danger of IllV/AIDS Prevalence among Street Children on the Public in Kenya: Experiences from Eldoret Municipality. International Journal o] Science and Research, 2 (3). Oliveira I, Andersen A and Furtado A (2012). Assessment of simple risk markers for early mortality among Hl V-infected patients in Guinea-Bissau: a cohort study. British MedicalJournal, Open, 2(e001587). Olsen :MF, Alemseged A, Kzestel P, Tesfaye M, Yilma D and Girma T(20] 4). Effects of nutritional supplementation for HIV patients starting antiretroviral treatrnent: randornised controlled trial in Ethiopia. British Medical Journal, 348 (g3187). 173 Opium, (2014). History of Opium. Accessed on 1st April 20)4 vra http://www.opium.orglllistory-of-opiurn.htmi . Ornoy A and Ergaze Z (2010). Alcohol Abuse in Pregnant Women: Effects on the Fetus and Newborn, Mode of Action and Maternal Treatment. International Journal of Environmental Research and Public Health, 7:364-379. Orsetti E, Staffolani S, Gesuita R, De Iaco G, Marchionni E and Brescini L(20Ll). Changing characteristics and risk factors of patients with and without incident Hev infection among HI V-infected individuals. Infection, 41 (5):987-990. Osman S, Lihana RW, Kibaya RM, Ishizaki A, Bi X, Okoth FA, Ichimura H and Lwembe RM (20 l3). Diversity of HfV type 1 and drug resistance mutations among injecting drug users in Kenya. AIDS Research and Human Retroviruses, 29( 1): 187-190. Palm AA, Esbjornsson J, Mansson F, Kvist A, Per-Erik I and Biague A(2013). Faster progression to AIDS and AIDS-related death among seroincident individuals infected with recombinant HIV-l A3/CRF02 AG compared to sub subtype A3. Journal of Infectious Diseases. 209(5):721-728 . Padmanesan N, Wood J, Macintyre CR and Mathai D (2013). Risk Factors for Tuberculosis. Pulmonary Medicine, 2013(2013). Palmateer N, Hutchinson S, McAllister G and Murrro A(2014).D. Risk of transmission assoc.iated with sharing drug injecting paraphernalia: analysis of recent hepatitis C virus (HCV) infection using cross-sectional survey data. Journal of Viral Hepatitis, 2 \: 25-32. Paraskevis D, Nikolopoulos G, Tsiara C, Paraskeva D and Antoniadou A (2011). Hl V-I outbreak among injecting drug users in Greece, 2£)11: a preliminary report EuniSurveillance, 16(36). PatTY C, Petersen P, Carney T, Dewing S and Needle R (2008). Rapid assessment of drug use and sexual HIV risk patterns among vulnerable drug-using populations in Cape Town, Durban and Pretoria, South Africa. SAHARA Journal, 5:113-119. Parry CD, Carney T, Peterson P, Dewing S and Needle R (2009). Hlv-risk behaviour among injecting or non-injecting drug users in Cape Town, Durban, and Pretoria, South Africa. Substance use and misuse, 44(6):886-904. Patterson TL, Volkmann T and Gallardo M (2012). Identifying the HIV transm ission bridge: which men are having unsafe sex with female sex workers and with their own wives or steady partners? Journal of Acquired Immune Deficiency Syndrome, 60: 414- 420. 174 Peltzer K, Ramlagan S, Johnson BD and Phaswana-Mafuya N (2010). Illicit drug use and treatment in South Africa: a review. Substance Use and Misuse, 45: 2221-2243. Phe T, Thai S, Veng C, Sok S and Lynen L (2013) Risk Factors of Treatment-Limiting Anaemia after Substitution of Zidovudine for Stavudine in HIV-Infected Adult Patients on Antiretroviral Treatment. PLoS ONE, 8(3): e60206. Pickett EK and Wilkinson RG (2010). Inequality: an under acknowledged source of mental illness and distress. The British Journal o] Psychiatry, 197: 426-428. Pilhatsch M, Scheuing H, Kraemer N, Kobiella A and Bidlingmaier M (2014). Nicotine administration in healthy non-smokers reduces appetite but does not alter plasma ghrelin, Human Psychopharmacology-Clinical and Experimental, 29:384-387. Plowman, T (2008). The identification of coca (Erythroxylum species): 1860-1910. Botanical Journal of the Linnean Society. DOl: 10.11l1/j.l 095-8339 .1982.tb00368.x. http://onlinelibrary.wiley.comldoi/IO.IIllh.l 095-8339 .l982.tb00368.x/abstract Pubchern, (2014). Accessed on 19th April 2014 via http://pubcheni.ncbi. nlm.nih. goyl summary/summary.cgi?cid=89594#itabs-2d. Public Health England, (2013). Tetanus: information for health professionals. Accessed on 29th April 2014 via http://www.hpa.org.uk Iwebcl HPA webFilel HPAweb C/1194947374762. Quach AL, Wanke CA, Schmid CH, Gorbach SL and Mwamburi DM(2008). Drug Use and Other Risk Factors Related to Lower Body "Mass Index among Hl v-Iufected Individuals. Drug Alcohol Dependence, 95(1-2): 30-36. Rafiey H, Narenjiha H, Shirinbayan P, Noori R, Javadipour M, Roshanpajouh M, Samie: Maud, Assari S (2009). Needle and syringe sharing among Iranian drug injectors. Harm Reduction Journal, 6:21 Ramezani A, Amirmoezi R, Yolk JE, Aghakhani A and Zarinfar N (2014). Hey, HBV, and HIV seroprevalence, coinfections, and related behaviours among male injection drug users in Arak, Iran. AlDS Care, 26(9): 1122-1126. Ramjee G and Daniels B (2013). Women and HlV m Sub-Saharan Africa. A1DS Research and Therapy, 10:30. Ramsin 8, Trescot AM, Datta S, Buenaventura R, Adlaka R and Sehgal N (2008). Opioid Complications and Side Effects. Pain Physician, 11:S105-S 120. Rankin, M (2010). Andean Cocaine: The Making of a Global Drug. Journal of' World Hist01Y, 21(3):566-568. 175 Redmond S, Kenter E, Garside R, Low N, Egger M and Martin HA (2011). Patterns of vaginal practices across Sub-Saharan Africa and their correlation with HIV - a systematic review. Social science and medicine, 74(9):1311-1323. Reif S, Preethy G, Braude L, Dougherty RH, Daniels AS and Ghose SS (2014). Residential Treatment for Individuals With Substance Use Disorders: Assessing the Evidence. Psychiatric Services, 65:301-312. Research to Prevention, (2010). Peer Education Rigorous Evidence -Usable Results. Accessed on 29th April 2014 via http://www.jhsph.edu/research/centers-and- institutes/research-to-prevention/publications/peereducation.pdf. Reyes JC, Perez CM, Colon HM, Dowell MH and Cumsille F (2013). Prevalence and Patterns of Polydrug Use ill Latin America: Analysis of Population-based Surveys in Six Countries. Review of European Studies, 50). Rhodes T, Sarang A, Vickerman P and Hickman M. (2010). Policy resistance to harm reduction for drug users and potential effect of change. British Medical Journal. 341 :c3439. Roncero C, Martinez-Luna N, Daigre C, Grau-L6pez Land Gonzalvo B (2013). Psychotic symptoms of cocaine self-injectors in a harm reduction program. Substance Abuse, 34(2):118-121. Ross MW, McCurdy SA, Kilonzo GP, Williams ML and Leshabari MT (2008). Drug use careers and blood-borne pathogen risk behaviour in male and female Tanzanian heroin injectors. American Journal of Tropical Medicine and-Hygiene, 79(3): 338-343. Rosso, MA (2010). Poppy and Opium in Ancient Times: Remedy or Narcotic? Biomedicine International, 1: 81-87 Rubinstein Marcelo and Low MJ (2011). The Smoking Gun III Nicotine-Induced Anorex..ia.Cell Metabolism, 14(2): 145-147. Rnutel 'RK, Parker D, Sobolev I and Helle-Mai L(2012). Tuberculosis Knowledge among Injecting Drug Users Visiting Syringe Exchange Programme in Tallinn, Estonia. Central European Journal of Public Health, 20(4): 248-25 Ryland EG, Tang Y, Christie CD and Feeney ME (2010). Sequence Evolution of HIV-J following Mother-to-Child Transmission. Journal of Virology, 84(23): 12437-12444 Saaka M and Osman SM (2013). Does Household Food Insecurity Affect the Nutritional Status of Preschool Children Aged 6-36 Months? International Journal of' Population Research, 2013(2013) 176 Saeland M, Haugen M and Eriksen F (2011). High sugar consumption and poor nutrient intake among drug addicts in Oslo, Norway. British Journal of Nutrition, 105(4):(j 18- 624. Sagoe KW, Dwidar M, Adiku TK and Arens MQ (2009). HIV-l CRF 02 AG polymerase genes in Southern Ghana are mosaics of different 02 AG strains and the protease gene cannot infer subtypes. Virology Journal 2009, 6:27. Sahin I and Ersin (2014). The Effectiveness of School-Based Drug Resistance Education Program in the United States. European Scientific Journal, 10(5):1857-7881. Sahin, 1. and Matusitz J (2013). Using Network Theory to Improve Outcomes for Drug Law Enforcement Agencies. Journal ofPolicy Practice, 12(2):125-142. Salmon AM, Van Beek I, Amin J, Kaldor J and Maher L (2010). The impact or a supervised injecting facility on ambulance call-outs in Sydney, Australia. Addiction, ]05(4),676-683. SAMHSA, (2010). Substance Abuse and Mental Health Services Administration, Drug Abuse Warning Network, 2010: National Estimates of Drug-Related Emergency Department Visits. Accessed on 29th April 2014 via bttp:llwww.samhsrt. gov/di!.ta/2k13/DA WN2kl OED IDAWN2kl OED.hlm. SAMHSA, (2012). Substance Abuse and Mental Health Services Administration, Center for Behavioural Health Statistics and Quality. Treatment Episode Data Set (TEDS): 2000-2010. National Admissions to Substance Abuse Treatment Services. DASIS Series S--61, HHS Publication No. (SMA) 12-4701. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2012. I Sanders-Buell E, Bose M, Abdul N, Todd CS and Stanekzai MR (2010). Distinct Circulating Recombinant Hfv-I Strains Among Injecting Drug Users and Sex Workers in Afghanistan. AIDS research and human retroviruses, 26(5). Sarkar R, Reshmi P, Baishali B, Ranajoy M, Satarupa Sand Sarkar K (20 II). Genetic Characterization of Hl V-I Strains among the Injecting Drug Users in Nagaland, India. The Open Virology Journal, 5: 96-102 Sesay, W (2010). Female bodies: Gender inequalities, vulnerability, HIV and AIDS in Kenya. Advancing Women in Leadership Journal, 30(17). Shannon K, Kerr T and Milloy M (2011). Severe food insecurty is associated with elevated unprotected sex among HIV-seropositive injection drug users independent of HAART use. AIDS, 25:2037-2042. 177 Shannon K, Strathdee SA and Goldenberg SM(2014). Global epidemiology of HIV among female sex workers: influence of structural determinants. Lancet, 385(9962):71- 73 Schmidt A, Borgwardt S, Hana G, Wiesbeck GA and Schmid 0 (2013). Acute Effects or Heroin on Negative Emotional Processing: Relation of Amygdala Activity and Stress- Related Responses. Journal 0.( Biological Psychiatry, 76(4):289-296. Scott, 1. (2012). Hundred-year history of heroin, from cough medicine to underworld narcotic. Accessed on 2617/2013 via http://www.historytodav.comlian-scott/heroin- hl1ndred~year-habit. Semba RD, Darnton-Hill I and de Pee S (2010). Addressing tuberculosis in the context of malnutrition and HIV coinfection. Food and Nutrition Bulletin, 31(4):S345-364. ( Shalini D, Das Chugh T and Shalini AK. (2012). HIV and Malnutrition: Effects on Immune System. Clinical and Developmental immunology, 2012(2012). Sharma P, Pratima M and Bharath MS. (2012). Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications. Iran Journal of Psychiatry, 7(4): 149-156. Shartnin, S (2011). Drug Use and Harm Reduction Model: Responding to the Health Challenge ofInjecting Drug Users in Bangladesh. International Journal 0.( Social Science Studies, 1(2). Sharp PM and Hahn BH (2010). The evolution of HIV-l and the ongin of AfDS. Philosophical Transactions of the Royal Society, 365(1552):2487-2494. Sharp PM and Hahn BH (2011). Origins of HIV and the AIDS Pandemic. Cold Sprmg Harhor Perspectives inMedicine, 1(1):a006841. Shen C, Craigo J, Ding M, Chen Y and Gupta P (201 I). Origin and Dynamics or Hl V- i Subtype C Infection in India. PLoS ONE, 6(10): e25956. Sigaloff KC, Mandaliya K, Hamers RL, Otieno F, Jao 1M and Lyagoba F (2012). Short communication: High prevalence of transmitted antiretroviral drug resistance among newly Hl.V type 1 diagnosed adults in Mombasa, Kenya. AlDS Research and Human Retroviruses, 28(9):1033-1037. Simbarashe T, Mhairi, Brennan AT, Sanne I, MacPhail AP and Fox MP. (20 \:l). Anaemia among HIV-Infected Patients Initiating Antiretroviral Therapy in South Africa: Improvement in Hemoglobin regardless of Degree of Immunosuppression and the Initiating ART Regimen," Journal of Tropical Medicine, 2013(2013). 178 Singer M (2014). The Infectious Disease Syndemics of Crack Cocaine. The Journal o] Equity in Health, 3(1'),32-44. Sitienei J, Nyambati V and Borus P(20l3). The Epidemiology of Smear Positive Tuberculosis in Three TBIHIV High Burden Provinces of Kenya (2003 -20n()) Epidemiology Research International, 2013 (2013). ./ Sitienei JK, Kipruto H, BonIS P, Nyambati V, Sitienei JC, Kihara A and Kosge: RJ(2014). Predictors of Low Body Mass Index Among Patients with Smear Positive Pulmonary Tuberculosis in Kenya. International Journal of Tropical Disease (~.Heal/h. 4(4): 427-436. Soliman C, Rahman IA, Shawky S, Bahaa T, Elkarnhawi Sand EI Sattar AA (2010). HIV prevalence and risk behaviours of male injection drug users in Cairo, Egypt. All),', 2:S33-38. Solomon SS, Hawcroft CS, Narasimhan P, Subbaraman Rand Srikrishnan AK (2008). Comorbidities among HlV-infected injection drug users in Chennai, India. Indian Journal of Medical Research, 127: 447-452. Srikala Band Kishore KKV (2010). Empowering adolescents with life skills education in schools - School mental health program: Does it work? Indian Journal oj Psychiatry, 52(4): 344-349. Smith HS, Smith JM and Seidner P (2012). Opioid-induced nausea and vomiting. Annal, of Palliative Medicin, 1(2). Stoecklein VM, Osuka A and Lederer JA (2012). Trauma equals danger=damage control by the immune system. Journal of Leukocyte Biology, 92(3):539-551. Strathdee SA, Philbin MM and Semple SJ (2008). Correlates of injection drug use among female sex workers in two Mexico-US border cities. Drug and Alcohol Dependence, 92:132-140. Strike C, Rudzinski K, Ptterson J and Millson M (2012). Frequent food insecurity among injection drug users: correlates and concerns. BMC Public Health, 12: 1058. Sunguya BF, Krishna CP, Otsuka K, Yasuoka J, Mluncle JB and Urassa DP (20 I I) Undernutrition among HIV-positive children in Dar es Salaam, Tanzania: antirerroviral therapy alone is 110tenough. BMC Public Health, 11 :869. Suohu KjHumtsce C, Saggurti N, Saban-val Sand Mahapatra B (2012). Understanding the association between injecting and sexual risk behaviours of injecting drug users in Manipur and Nagaland, India. Harm Reduction Journal. 18;9:40. 179 Surratt H, Kurtz Sl+and Cicero TJ (2011). Alternate Routes of Administration and Risk for HIV among Prescription Opioid Abusers. Journal of Addictive Diseases. 30(4) 334- 341. Sutin AR, Evans MK and Zonderman AB (2013). Personality traits and illicit substances the moderating role of poverty. Drug and Alcohol Dependence, 1;]3] (3):247-251. Swe AL, Kay K.N and Rashid AK (2010). Risk behaviours among HTV positiveinjecting drug users in Myanmar.a case control study. Harm Reduction Journal, 7:] 2 Tadesse N, Tadesse AA, Mengesha ZB and Kefyalew AA (2013). High prevalence 01 HIV/AIDS risky sexual behaviours among street youth in Gondar town: a community based cross sectional study. BA1e Research Notes, 6:234. Tang MA, Forrester JE, Spiegelman D, Flanigan T, Dobs A, Skinner S and Wanke C (2010). Heavy injection drug use is associated with lower percent body fat in a ITIu1ti- ethnic cohort of Hl'V-positive and HIV-negative drug users from three U.S cities. American Journal of Drug Alcohol Abuse, 36(1): 78-86. Tang MA, Bhatnagar T, Ramachandran R, Dong K, Skinner S, Kumar MS, Wanke C/\ (201]). Malnutrition in a population of HIV-positive and HIV-negative drug users living in Chennai, South India. Drug and Alcohol Dependence, l ; I] 8( 1): 73-77. TB Alliance, 2012. The TB Pandemic. Accessed on 29th April 2014 via http://w''\vw.tbaUiance.orgl. Tegang SP, Abdallah S, Emukule G, Luchters S, Kingola N, Barasa M, Mucheke Sand Mwarogo P (2010). Concurrent sexual and substance-use risk behaviours among female sex workers in Kenya's Coast Province: Findings from a behavioural monitoring SlIIVC:V Journal a/Social Aspects ofJ-!JV/AJDS. 7(4). Thao Ie TL, Lindan CP, Brickley DB and Giang Ie T (2006). Changes in high-risk bebaviours over time among young drug users in South Vietnam: a three-province sruclv. A1DS and behaviour, 10:S47-56. Tbao VP, Thuy L, Torok EM, Yen NTB, Chau TT and Jurriaans S (2012). HIY-I drug resistance in anrirerroviral-naive individuals with HIV -I-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam. Antiviral Therapy, 17905-913. ThompsonJr RG, Wall MM, Greenstein E, Grant BF and Hasin DS (2013). Substance- Use Disorders and Poverty as Prospective Predictors of First-Time Homelessness in the United States. American Journal of Public Health, 103(S2):S282-S288. Hale LDN and Dreyer SE (2013). Contextual Influences of Substance Abuse Problems among School Children. Mediterranean Journal of Social Sciences, 4(13). 180 Tobin KE, German D, Spikes P, Patterson J and Latkin C (2011). A comparison of the social and sexual networks of crack-using and non-crack using African American men who have sex with men. Journal of Urban Health, 88(6):1052-62. Tomlinson CA (2010). Effects of IV Drug Abuse http://www.livestrong.cC..m/ articlell95207 -effects-of-iv-drug-abusel. Trenz RC, Scherer M, Duncan If, Harrell PT, Moleko AG and Latimer WW (2013). Latent class analysis of polysubstauce use, sexual risk behaviours, and infectious disease among South African drug users. Drug and Alcohol Dependence, 132(3 ):44 j -448. Treweek BJ, Amanda JR and Kim DJ (2010). Superadditive Effects of Ethanol and Flunitrazepam: Implications of Using Immunopharmacotherapy as a Thcrapeui ic. Molecular Pharmaceutics, 7 (6),2056-2068. Trujilloa KA, Smith ML and Guaderrama MM (201]). Powerful Behavioural lnteractions between Methamphetamine and Morphine. Pharmacal Biochem Behaviour .Ionmal, 99(3): 451-458. . Tun W, Sheehy M, Broz D, Okal J, Muraguri N, Raymond HF, Musyoki H, Kim f\A, Muthui M and Geibel S (20]4). Hl V and STI Prevalence and Injection Behaviour Among People Who Inject Drugs in Nairobi: Results from a 2011 Bio-behavioural Study Using Respondent-Driven Sampling. AIDS Behavior, 19( 1):24-35. Ulibarri DM., Strathdee SA, Ulloa EC, Lozada R, Fraga MA, Rodriguez eM, De I,;) Torre A, Amaro H, O'Campo P and Patterson It (2011). Injection Drug Use as a Mediator Between Client-perpetrated Abuse and HIV Status among Female Sex Workers in IwoMexico- US Border Cities. AiDS Behavior, 15: 179-185. \JNAIDS, (2011). Methac\one substitution therapy helps prevent new HIV infections in Belarus. Accessed on 29th April 2014 via http://www.unaids.org/en/ resources Ipresscentre/feahlrestories/20 Il1march/20 110302ll1ethadonebelarus( UNAIDS, (20121' Global report: UNAIDS report on the global AIDS epidemic 2012. Accessed on 6 June 2014 via http://www.unaicis.org/en/media/unaids/eontentassets /documents/epidemiology/2012/gr20 12/20121120 UNAlDS Global Report 2012 with _annexes en.pdf UNAIDS, (2013), Global Report. Accessed on 8th June 20 I~ h!!u.:I/www .lUlaids .org/en/sites/de fau lt/fi les/en/ media/una ids/con ten tassets/docum ent:;Iep I demiology /20] 3/gr20] 3/unaids _global Jeport _20] 3__en .pdf. 181 UNAIDS, (2014). Fast-Track - Ending the AIDS epidemic by 2030. Accessed on 2nd Ian 2015. http://www.unafds.org/sites/defaultlfiles/media_assetIJC2686_ WAD201 4report _en.pdf. UNICEF, (2011). Measuring malnutrition: individual assessment of acute malnutrition Accessed on 28u1 May 2014 via http://www.unicef.org/nutritioncillster/files /rnod« measuring_ malnutrition- fact_ sheet.doc. UNODC and TISS (2011). Counselling in Targeted Intervention for Injecting Drug Users: A Resource Guide. A publication of United Nations Office on Drugs and Crime, Regional Office for South Asia AND Tata Institute of Social Sciences, Murnbai. Accessed on 26th April 2013 via httQ;LLw_y{w~11Jlod~.QIg[gOClJmel1ts/soJ!.tb_iJ5jil( TrainingmanuaJslA Resource Guide.pdf. UNODC, (2009). Guide to implementing family skills training programmes for drug. abuse prevention. Accessed on 3rd Dee 2013 via http://www.unodc.org /documents /prevention/famil y -guidelines- E.pd f. UNODC, (2011a). World drug report 2011, United Nations Office on Drugs and Crime. Vienna. Accessed on 20 March 2014 via http://wvvw .unodc.org/documents/datcHHld- analysis/WDR20IllWorlcl Drug Report 2011 ebook.pdf. UNODC, (20 11b). Counselling in targeted intervention for injecting drug users. Accessed on 5th April 2014 via http://www.unodc.org/docllments/sollJlEL<; ia/ TrainingmanuaLsI A Resource Guide.pdf. UNODC, (2012). Association of Drug Use Pattern with Vulnerability and Service Uptake. Accessed on 21s1 April 2014 via h.tm;/Lwyw.unodc.org/documents/ so!ubasial publications/research. UNODC, (2013a). World Drug Report 2013 (United Nations publication, Sales No. E.13 .XI.6). Accessed on 19th April 2014 via http://www .unodc.org/\lI1odc IseclU'5 D Impossible to tell Single 0Married Widowed o Separated D Other Catholic D Divorced 3. Religion: D D D Muslim Atheist 4. Income/Month (Ksh): D <5000 ___ J D500 \-\0. OO() D 10. Age offirst sexual encouriter ------------------- 11. Have you ever been forced to have sex without using a condom? DYes D No 12. During the last 12 months, how many times have you avoided arrest by providing the police officer with a sexual favouO None D twice D 3-5 times D > 5 times 13. In the last 12 months have you had sex in exchange for drugs Yes D 0 D 14. If yes, how many times? D Once D twice D 3-5 times D > 5 times 190 15. Have you ever be~n diagnosed with a STI within the last Yes No Six months I year -- 2-3 years----_. r---- -_.- -"'- >3 years t6. If yes, which STl were you diagnosed with? o Syphilis 0 Gonorrhea D Trichomoniasis DChlamydia D Herpes D Others (specify _ PART B: ANTHROPOMETRIC DATA Measurement Unit 1 Weight (kg) 2 Standing Height (ern) 3 Wai st Circumference , (ern) 4 Buttocks (Hip) Circumference (ern) ~~ 5 Mid- Upper Ann Circumference (cm) ..- 6 Bust (ern) PART C: KNO'VLEDGE, ATTITUDE AND PRACTICES 17. Which injection drug (s) do you use? a) b) c) _ d _ 18. Which non injecting drug do use? a) b) c) _ d) _ 19. When did you start injecting? D< 6 months D6-11 months D 1-3 yrs D .; 3 \'1 191 20. How many times do you inject per day? D ONCE THRICE D >3 TI.MES D NO DNO 23. Have you ever practiced Flashblood? DYESD NO 24. Name some of the health related risks associated with needle/syringe sharing or flashblood D TWICE D D YES 22. Have you ever heard of Flashblood? DYES 21 .Have you ever shared syringes? '2 ,'3----------_. , --------------.---- -_._---_ ...__ ..--._ ... 25. Do you know of any drug rehabilitation centre? 26. If yes name some of them DYES D NO ; 2 ; 3--------------- ------_._-_. 27. Would you like to be referred to a rehabilitation centre for treatment? D Y1-::S D NO If yes, Rea son --------------:--------------------------------------- --- ---- -- -'--- ------ --- --- ---- ---- ----- ---..-- . Jf no, Reason------------------------------------------------------------------------------- ------ --- --..---------- PART D: MEDICAL HISTORY [) SELF REPORTED MEDICAL HISTORY 28. Have you experienced any of the following in the last TWO weeks? Fever D Vomiting D Diarrhoea D Headache D Coughing 0 29. Have you been 011 any medication in the last TWO weeks? D YES D NU 30. If yes please specify ARVs ~]tjbiotics D Others .__ . ._ . 31. When did you start using ARV;.?D < 6 months D 6-- 11 months D \-3 yrs D >~)T<; JJ) MEDICAL EXAMINATION 32. Vital signs Vital sign Reading Temperature ,......-_. - -~--•...•...•---.~-- Pulse rate Blood pressure 192 33. TB Screening ~d testing a) Physical screening 1 Chest examination ~Coughing --1 b) Sputum Analysis AFB (-VE) AFB (+VE) -.--.---.-.--- .. - -- ..._-- --- i On spot sputum Early morning sputum -'---1 ---) Early morning sputum I I 34. Drug Sensitivity Testing Drug Sensitive Resistant Borderline Comment Isoniazid Rifampicin Ethambutol Pyrazinamide 193 Appendix 3: ERe clearance a·'f~ .:J ~I \ t '. •-\j"'-'..!'~r-' KEl'\'YA1TA l'l':IVI:RSI1Y nl-1IO' RI:VlI:W C•.),\1.\1ITln: r3X: 1\7"Z4~/1\7":;7" Email: ~1r.r£..-.;h!l1.nl1~I"'l!!.k\l ..)f. ~,~ ~uJ:D:_··~·~:"I~I;IJ)·'.!Lbl.,tl·.k{· \\·d~ ..itc: ~'.:.\..':~.\:':'~·.I.I.: 1\_:.~:~ I'. l '. I~'x oJ ~S·i-l. :'\;lirc,h. ~'l~'l\l\ .;: ,....I.: '~'.J I .: '·"I"lIlilll' Blul,,,,,IJ ••,,, Schnol ••f I'uhlic Ilc~11 h. "''''":1111;1 l:nh·cl~.ity ".0. 1.lux ~311~4. r;"irnhi. DC3r .\1~. Valentine ,\ f'l'I.!, ',\TIl'1\' i':i1,\Htf:f> "" III) 19.11h ,)1' 2(' 12 . 'IllV Il'ullllUlI :11'.'TII ,.". iIIfl·,·ti"" ;"'" '''~, I intrnvenous t.lru!,!US('I'S in 1\1olUha,,:\. Kenya. \'l'rsioll ~. TIlt: arrlicJltion lx-forc the commrttcc is witha research (DJ,ic ·,II\'/PuI1l1l"1:"',\ 'I B l-o-iuf"',IIO" amol1:.!sl intnt\l'rltuu~ clrllJ! 1I~t..'I-Sin ;\lf1mha~u.Kt·l1~a·. Vcrxiou ,I, Pall'd I!)" ,\tl\': :~1."I:!: " \'akllti!l~ Blld:utlt'lIl:t Sl.'h,,-,IC'I f'III'Iil' 1Ie:)"". K1.'nv;ut:l \ "n ive r-sitv r.o. 1'<,,, ·1:',:"1.1. :-i:lir01'i. 3. srn; The connniuce l1a~ (,.'•...1fl~idl'rl..'d tlrc research pr •..'tttK(~1 ill .H,:~\"t'\.bn~\' \\':~Ii lh •.. h:~'!I":I\:,1 I'!':',,,:, Re5c';ll'chri.."lh:y 1.st"~th:'ll7,'!..,1,::;) :l1ld lhl.'"Kell~·:tlla l1niv(.'I''\iry I'Ii1h','" J\t'\'!l:\\' l"'!!I!1!il:"l' \,UI~::,ll!h'''', i '" is (""1the view th.11 ;l.',.:,:linsl thl' tt..."lll.,,,,jl1;'<:clcmcnt s ot I'L'ViL-W, ANn :\rrROVJ:r\ th"t the research may proceed for" period of ,..•Nf. yl':Ir [r o tn (.,10 ,f1l11l'.:~l' 1:'. 194 i. r'n'~rl'ss rt1r'011S are submitted to the Kl'~r~t' cvcrv .:;i:--' l~k\Jt!:,~ :I~~~~'\ 1.:1' [.. \',": r . :,\.IlJlIlitt~d:l1 th~ end of litc'llIdy. ii. Serious :Itld unexpected adverse events rcl.ucd t~~ tilt.' C~"JldIKI('I Ih\.~':llhi\ .I~, :'\ I",': 10 liti< lxxrrd iI11111,'di:lk\l' they occur. iii. Ck~lr:lIh.'~ mus: h' \....I ttined ior t'~':ln"T'('n:ltic'!l('\f :t!iy L'il"lc':.:ic'l: !::~l:Lri.d \'I;! ((\IH1try i.c, KCH~\1. When replying, kindly quote the application number at",,",.:. If you acccpt the decision reached and advice :lIId conditions ;.:i\'cl1 plea:;e ,i:.:" in the '~Kl' pr,", ,ell'.! below and return 10 KU·ERe a copy of the letter. EEQ.L1:'IJPl..m;I~.K. <;:;JKONYO Ct-IAtRMAN J:11{1CS RJ:Vll:W COMMI1TEE b.. 1, I .\h.\.·:~:,:·.·:~'.~ :~·.'.'::! :· :1 :ICCC.,t the .i.Ivic« :,i"el1 ;111.1\\'111 rult rll th« conditions therein. Signaturc.. :if~~·f~:~~~~7:".;-,. ....(~:.I( .. ~l' I .'. cc. \'ir<:·Ch:IIIC('IIN Director: 11I.'litulc Il)1 I\cs-:it rcl I S,:it,lttt' a!ld Tl'lltlll'il':,I' KENYATTll ' •.un'•....u... 195 Appendix 4: Ministry~of Health, Mombasa County Clearance RI."Ii,.\"., .' •• ~ ~f'-!..:...:.. l\-lINISTRY OF PUBLIC HEALTH & SANITATIO;-.i Telegrams: "PROVMED". MOJ\IBASA Tel: .Ylomhasa: 2226006/2212867 "Fax:2226006 F.mail: pdph~coa5t!li;yahoo.com When replying please quote OvrTCEOF TIIF. PROVINCIAl. OIRF(,TOI·: Of PUBLIC II[ALTII ...., S,\:\IT.·\TIO'i SEltVICE~ f('().\~T I'ROVI:'JCE P. O. BOX 90133-8111110 MO"R·\S.·\ Ref: A))l\1.3/S/37/121 D:Jtl': li"I.JULY 2012 District Medical Officers of Health :.. MombaS!170 zirnehifadhiwa kwa ajili yakukufidia endapo utadhurika kutokana na urafiti huu. Kamn unafikiria kwamba ulidhurika kutokana na utafiti huu wasiliana na mtafiti mkuu. Kwa kuweka sahihi jina langu nathibitisha yafuatayo:- 1. Nimesoma (ama nimesomewa) karatasi hii ya kutoa idhini ya kukubali, 1Ia masvvali yangu yote yamejibiwa na nimeridhika. . ·2. Nia, mitindo.hatari pamoja na faida zinazoambatana 11a utafiti huu zirneclczwa kw ;Jngll 3. Nakubali na kuruhusu timu ya utafiti kutumia na kugawahabari za kiafya ama ,1I1li! yoyote ya habari zitakazo kusanywa kutokana na utafiti huu. 4. Nimekubali kwa hiyari kushiriki kwenye utafiti huu. 5.' Nimeelezwa kwamba ninaweza kukoma kushiriki wakati wowote. Jina la mshiriki Sahihi----------------------- ------- Mtafiti mkuu Sahihi Tarehe .__ Tarehe.------- ------.------ Zaidi; wasiliana na wafuatao 1. Mtafiti mkuu: Valentine Budambula kwa nambari ya rununu, 07222822448 2. KU-ERC: Kupitia barua pepe kuerc.chairman@kl!~'Jcke 198 Appendix 7: peR protocol QL\.quick peR Purification Kit Protocol This protocol is designed to purify single- or double-stranded DNA fragments from PCR and other enzymatic reactions. For cleanup of other enzvmatic reactions, follow the protocol as described L'f peR samples or use the :MinElute Reaction Cleanup Kit. Fragments ranging from 1OJ bp to 10 kb are purified from primers, nucleotides, polymerases, and salts us-ing QfAquick spin columns in a rnicrocentrifug e. Impor-tant points before starting 1. Add ethanol (96-100%) to Buffer PE before use (see bortl e label for volume). 11. All centrifugation steps are carried out at 17,900 x g (13,000 rpm) in a conventional rable.op microcentrifuge at room temperature. Ill. Add 1:250 volume pH indicator I to Buffer PB (i.e., add 1.20 ul pH indicator J (0.30 mJ Buffer PB or add 600 pI pH indicator 1 to 150 ml Buffer PB). The yellow CciC'f of Buffer PB with pH indicator I indicates a pH of=7.5. IV. Add pH indicator I to entire buffer contents. Do not add pH indicator 1 to buffer aliquots v If the purified PCR product is to be used in sensitive microarrav applications. it rnav t c beneficial ,0 use Buffer PB without the addition of pH indicator 1. Procedure 1. Add 5 volumes of Buffer PB to 1 volume of the PeR sample and mix. I: is no: necessarv to remove mineral oil or kerosene. For example, add 500 ul of Buffer PB to 100 .LlI PCR sample (not including oil). 2. If pH indicator I has beein added to Buffer PB, check that the color of the mixture is vellow If the color of the mixture is orange or \'101et, add 10 p.1of 3 M sodium acetate'. pH ~ ~. R:1d mix. The color of the mixture will turn to vellow. 3. Place a Ql.Aquick spin column in a provided 2 rnl collection tube. 4. To bind DNA, apply the sample to the QIAquick COIUDlll and centrifuge for 30-60 s. 5. Discard flow-through. Place the QIAqulck column back into the same tube. C0l1("C(il'!1rules are re-used to reduce plastic waste. 6. To wash, add 0,75 ml Buffer Pf to the QIAquick column and centrifuge lor -'0--0,) s. 7. Discard flow-through and place the QIAquick column back in the same rube. Centrifu] C ~:l<" column for an additional 1 min. ThIPORTA_ 'I: Residual ethanol £rom Buffer PE \\;11 not be completelv removed unless -h(' flow-throug h is discarded before this additional centrifugation. PCR Purification 8. Place QIAquick column in a clean 1.5 nil microcenrrifuge tube 9. To clute D~A, add SOpI. Buffer EB (10 mM Tris'CI, pH 8.5) or water (rH -.0-S.5) to IlL- center of the Ql.Aquick membrane and centrifuge the column for 1 min. Alternari ve lv, for increased D~A concentration, add 30 ul, elution buffer to the center of the QlAquick membrane, let the column stand for 1 nun, and then centrifuge. [\IPORT A.'H: Ensure that the elution buffer is dispensed directly onto the QlA.quil'k membrane for complete elution of bound DNA. The average eluate: volume is ~8 ul, from 50llli elution buffer volume, and 18 ~ from 30fll. duti<:n buffer. 199 App di 8 W k Ien IX : or plan ~ept Nov- July Aug-Dec Aug Sept- --- EVENT Jan July- Ian 14 2010- June 2012 2012 2013- IDee July ~O14 lOee Aug 2012 June ~0I3 ~O14 2011 Proposal '-,,,. " processmg Y' ',1: Clearance : ,,:",'; -- , by ERe " "" ", :" Training of , I research i. ' "assistants .' ~. '.' -.-;Jl, ••..• 1-'-----Data collection : HlV gene- "" ' I " ; , typing " " [Data .'- ~ -." . -- . .- --.- --... j analysis " ' " Thesis ".. " ' . Iwriting - , I Manuscript preparation '- 1---- Results " Presentation I I Thesis \i submission II i Thesis 1 i I defense I j 200 A di 9 BUDGET DATA COLLECTION COSTS.ppen IX : ,.' . , Item Description Cos t(Ks hs ) 1 Photocopy (Consent forrrs 400 copies K shs. 3 1,200.00 2 Photocopy (questionnaire) 400 copies x 5 pages xKshs.3 6,000.00 3 Email/airtirre 8,000.00 4 Determine kits 4 pkts @ 6000 24,000.00 5 Unigold 2 pkts @ 8000 16. 00000 6 surgical gloves 8 pkts @ 600 4, 800.00 7 syringes 450 @ 17 7,650.00 _ ..... .... - ..-- ._... " ' .n ,w .... - ... _e.··.· "." 8 needles 450 @10 4,500.00 9 Slides 200 pieces @ Kshs 30 6,000.00 10 G Iycene envelops 150 @ 12 I, 800.00 11 filter papers (for DBS) 300 @16 ~, 800.00 12 Ziplock bag; Assorted 3,600.00 13 Desiccants Assorted 3,500.00 14 Humidity indicator 1 tin 2, 500.00 15 EIDA tubes 450 @ 20 9,000.00 16 Plain tubes 450 @2 20 9,000.00 17 Cryovials 9 boxes @ 1900 17, ]00.00 18 Pippe1tes 196 pieces @ 60 11, 760.00 19 Field visits 2 fuel tanks! month for 6 month 48, 000.00 20 Field assistants 2 research assistants and 2 lab 80,000.00 21 Field assistants 2 IOU field mobilizers 40,000.00 22 CD4 Testing 361 IDU @ 1000 36],000.00 23 Full haerrogram 36] IDU @ 400 144,400.00 24 Bus fare reimbursement 36] rDU@ 250 90,250.00 201 ITEM , Cost Kshs - 1 UltraPure DNAselRNAse-Free Distilled Water (l xu.Slitre) 2,376.00 2 One-Step Reverse transcriptase 34,956.00 3 AmpIiTaq Gold DNA PoLymerase, with Gold Buffer- {Chemically modified enzyme for automated Hot Start PCR. IncludeslOx PCR Gold Buffer (500mM KCl, 150mM TrislHCl 32,883.00 pH 8.0) and 25mM MgCl 2 solution for 200 x 50pl reactions} - 4 MicroAmp Optical 96-Well Reaction Plate (1 PKT/IO) 1024100 --- 5 AmpliTaq Gold PCR Master Mix (200 rxs) Each tube of AmpliTaq Gold PO~ Master Mix is at 2X the recommended usage concentration, and contains the following: AmpliTaq Gold 50,440.00- DNA Polymerase 250 U (0.05 U/pI-) GeneAmp PCR Gold Buffer, 30 mM Tris/HCI, pH 8.05, 100 mM KCI dNTP, 400 pM each MgC!2, 5 mM Stabilizers ._.- 6 BigDye ® Terminator v l ,1 Ready Reaction Cycle Sequencingr-- Kit [200pL Tube ofBigOye® Terminator v.l.I Ready Reaction 44,405.00 Mix,Tube M13 (-21) Primer,Tube pGEM Control DNA, ImL Tube of 5x Sequencing Buffer] 7 0.2 mL Polypropylene PCR Tubes (2xCase of250) 34,073.00 j 15 mL Polypropylene Centrifuge Tubes (l xcase of 500) I 8 56.706B 9 DNA MW Marker, 100 bp Ladder (lOObp-1.5kb (lx250!-l1) 40,120:..~)Q_._ 10 Powder-less h~nd Gloves (Large) (case of 1000) 7,480.0o__ ._ 11 20 ul micropipette tips (500) I3260.0.9_J 12 IQOOul micropipette tips (500) 1,955.00 _ I 13 200 !-llmicropipette tips (1000) 1,955~~ __. Eppendorff microcentrifuge tubes (l.5mL, assorted colours and 14 ~!erile) (1 bag) 1,955.00 -- ]5 ]OXTBE (1 litre) 8,840.00 16 Ethidium bromide (5 g) 11,90000 17 Denatured Ethanol (molecular biology grade, 1 litre) 6,120.00 --- BUDGET: HIV GENOTYPING EXPENDITURE 202 - --I .18 Sodium Acetate (molecular biology grade, 500g) 4,250.00 19 Highly deionized (HiDi) Formamide (l00 ml) 4,335.00 20 POP 6 polymer (3m!) 5,525.00 21 Sequencing tray (96 well sequencing plate, 3 sets) 19,720.00 I 22 Bench fee 130,900.00 23 One-step Rtase 50,150.00.--- 24 PRIMER SET-1 25 5'·GGAAACCAAAAA TGATAGGGGGAA TTGGAGG-3' 12,750.00 26 5'·TGACTTGCCCAATTTAGTTTTCCCACT AA-3' 9,775.00 --1 27 5'-GTAGGACCTACACCTGTTCAACATAATTGGAAG-]' .j, I 28 5'-CCCATCCAAAGAAATGGAGGAGGTTCTTTCTGATG-3' 9227_~·~ I...-...__. - --- I PRIMER SET-2 ~ I 29 5'-TCCTT AACTTCCCTCAAATCACT -3' ! 30 5'-CTGGCACGGTTTCAATAGGACT-3' 9,775.00 I~ I I I 31 5'·GGGAATTTTCTTCAGAGCAG-3 , -~ I 32 5'-TCTTCTGTCAA TGGCCATTGT -3' _~}_2~~__ II- ~.---.~-.,......... -~-- -- IPRJMER SET-3 -J 33 5'-TCTTAGGAGCAGCAGCAGGAAGCACT ATGGG-3' I I -- -------.-. ---I I 34 5'-AACGACAAAGGTGAGTATCCCTGCCT AA-3' 9,775.00 I 35 5'-ACAA TTATTGTCTGGT ATAGTGCAACAGCA-3' ! 36 5'-TCCTACTA TCATT ATGAA TATTTTTATATA-3' 9,775.00 --I J 203 PRIMER SET-4 37 5'-GGGTCACCAT AITCTTGGG-3' 38 5'-CA (AlG) AGACAAAAGAAAATTGG-3' 9,775.00 39 5'-GAACAAGAGCTACAGCATGGG-3' 40 5'-CCACTGCATGGCCTGAGGATG-3' 9,775.00 41 Research Assistants (2) @, 20,000 per month 40,000.00 SUB-TOTAL 705,495.00 PLUS DATA COLLECTION COSTS 904,860.00 GRAND TOTAL 1,610,355.00