PHD-School of Health Sciences

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This collections contains bibliographic information and abstracts of PHD theses and dissertation in the School of Health Sciences held in Kenyatta University Library

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Browsing PHD-School of Health Sciences by Author "Kabiru, Ephantus W."

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    Efficacy of Crude Extracts from Allium Sativum, Callistemon Citrinus and Moringa Stenopetala of Kenya against Leishmania Major
    (2014-02-22) Kinuthia, Geoffrey Kariuki; Kabiru, Ephantus W.; Gikonyo, Nicholas K.; Anjili, C. O.
    Cutaneous leishmaniasis (CL) is endemic in more than 80 countries worldwide and it causes skin ulcers and disfigurement. Leishmania major causes CL in Kenya and its drugs are expensive, toxic and require prolonged use. Multidrug combination therapy prevents drug resistance and reduces toxicity. Herbal extracts can be safe and cheaper. This study investigated in vitro and in vivo efficacy of single and blends of crude aqueous and methanolic extracts from Moringa stenopetala, Callistemon citrinus, and Allium sativum against L. major. Controls were contemporary Leishmania drugs pentostam and liposomal amphotericin B, and phosphate buffered saline. Dry ground test materials were soaked in H2O at 70oC for 1½ hours, filtered, and freeze dried. Similarly, ground test materials were soaked in 500 ml of analytical grade methanol for 72 hours at room temperature, filtered and concentrated using rotary evaporator. T-test and ANOVA were used for data analysis. P-value of < 0.05 was considered significant. The minimum inhibitory concentrations (MICs) of aqueous extracts of M. stenopetala (A), C. citrinus (B), and A. sativum (C) ranged from 3 to 5mg/ml while IC50 from 297.79 to 575.75μg/ml against L. major promastigotes as compared to MICs of 12.50 and 6.25μg/ml and IC50 of 0.26 and 0.82μg/ml for pentostam and liposomal amphotericin B respectively. MICs of methanolic extracts of M. stenopetala (H), C. citrinus (G), and A. sativum (F) ranged from 1 to 5mg/ml with IC50 of 572.69 to 1752.92μg/ml against L. major promastigotes. The extracts’s cytotoxicity against vero cells ranged from 467.11 to 2105.93μg/ml as compared to 60.95μg/ml and 108.58μg/ml for pentostam and liposomal amphotericin B respectively. Methanolic extracts of C. citrinus and aqueous A. sativum extracts stimulated production of 20μM nitric oxide in BALB/c mice peritoneal macrophages signifying their immuno-modulatory role. Blends of M. stenopetala & C. citrinus (AB), M. stenopetala & A. sativum (AC) and C. citrinus & A. sativum (BC) at concentrations based on MICs of individual extracts, were active at ratios 1:1, 1:9 and 1:1 with promastigotes’ viabilities of 33.82%, 17.41% and 60.74 % respectively. The ratios and promastigotes viabilities for methanolic blends were, FG (1:1; 31.32%), FH (1:9; 34.59%) and GH (9:1; 7.44%). The IC50 for any blends of two extracts ranged from 174μg/ml to 1314μg/ml against L. major promastigotes. There was strong synergistic (1:9) and additive (1:1 and 2:8) interactions for the blend AC. Blend BC interacted additively at ratio 1:1. Blend AC at 125μg/ml had infection rate (IR) of 71% and multiplication index (MI) of 48.20% for L. major amastigotes in vitro, and compared well to pentostam at 12.50μg/ml with IR of 67% and MI of 47.51%. Methanolic blends of three different extracts were more efficacious with MIs of 33.48 to 38.24%. Oral aqueous and methanolic A. sativum extracts (A and F) reduced the foot pad lesion sizes significantly (P < 0.05) in infected BALB/c mice. Oral blend BC reduced the footpad lesion size significantly (P < 0.05) like Leishmania control drugs. Oral blends BC and AC reduced spleen amastigotes in mice by 48.33% and 60.94% corresponding to total LDUs of 6.35±0.66 and 4.80±0.95 respectively. Oral/ip blend HGF (2:2:1) had amastigotes inhibition rate of 63.95% compared to 66.40% and 60.62% for pentostam and liposomal amphotericin B respectively. In conclusion, aqueous and methanolic crude extracts of C. citrinus, A. sativum and M. stenopetala were less toxic but active against L. major in vitro and in vivo and their blends that had additive or synergistic interaction lowered L. major survival. This study recommends that Kenyatta University in collaboration with relevant stakeholders to consider developing natural products based on these results for the management of CL in poverty stricken leishmaniases endemic areas of Kenya.
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    Isolation of recurrent mycobacteium isolates from sputum smear negative relapse at the central reference tuberculosis laboratory in Nairobi, Kenya
    (2011-08-15) Wahogo, Josephine N; Orago, Alloys S.S.; Kabiru, Ephantus W.
    Pregnant women have increased susceptibility to malaria infection. In these women, malaria parasites are frequently found sequestered in the placental intervillous spaces, a condition referred to as placental malaria (PM). Placental malaria threatens the health of the mother and the child's life by causing intrauterine growth retardation, abortions, still births and reduction in gestational age. An estimated 24 million pregnant women in SubSaharan Africa are at risk. Mechanisms responsible for increased susceptibility in pregnant women are not fully understood. Baboons are susceptible to Plasmodium knowlesi and have similar host pathogen interactions and reproductive physiology similar to humans, making them attractive for the development as a model for studying mechanisms underlying development of placental malaria. This study exploited the susceptibility of baboons to Plasmodium knowlesi infection to develop a non-human primate (baboon) model for studying PM. The main objective of the study was to demonstrate PM and characterize immunological mechanisms underlying the pathogenesis of PM in baboons infected with Plasmodium knowlesi. The pregnancies of three time mated adult female baboons and their gestational levels (one in its second trimester and two in their third trimester) were confirmed by ultrasonography. On the 150th day of gestation, the pregnant baboons were infected with Plasmodium knowlesi H strain parasites together with four non pregnant controls. Peripheral parasitaemia development was monitored on a daily basis from two days post inoculation. Collection of sera, plasma, mononuclear cells and haematological samples was done on a weekly basis. Peripheral blood mononuclear cells (PBMC) were stimulated in culture with concanavalin A and P. knowlesi antigens and their proliferation quantified. Sera cytokine and immunoglobulin concentrations were measured by ELISA using respective enzyme conjugated antibodies. Two pregnant baboons aborted (one on day 6 and the other on day 7 post infection) and cesarean section was only done on one baboon. Smears prepared from placental blood demonstrated the presence Plasmodium knowlesi parasites in all the sampled placentas. On average, the pregnant baboons had more than 29 fold higher placental parasitaemia than simultaneous peripheral parasitaemia. This shows that Plasmodium knowlesi preferentially sequesters in the baboon placenta just like Plasmodium falciparum does in humans. Two baboons that had high placental parasitaemia experienced abortion, which is a sequele of human placental malaria. Results indicate that PM in this model is associated with significant (P < 0.05) suppression of immunoglobulin G, Interferon gamma, and interleukin 6 responses. Tumour necrosis factor alpha responses were significantly upregulated (P < 0.05) while immunoglobulin M, interleukin 10, interleukin 12, interleukin 4 and PBMC proliferation responses did not differ from controls (P > 0.05). These data are consistent with some findings from human studies, showing the feasibility of this model for studying mechanisms underlying placental malaria. The study has contributed valuable data to be used in further studies and the development of preventative, control and therapeutic measures against PM in women