RP-Department of Pre-clinical Sciences

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    Distinct Pattern of Class and Subclass Antibodies in Immune Complexes of Children with Cerebral Malaria and Severe Malarial Anaemia.
    (Parasite Immunology Journal, 2008) Mibei, Erick Kipsang; Otieno, W. O.; Orago, A. S.; Stoute, J. A.
    Plasmodium falciparum infection can lead to deadly complications such as severe malaria-associated anaemia (SMA) and cerebral malaria (CM). Children with severe malaria have elevated levels of circulating immune complexes (ICs). To further investigate the quantitative differences in antibody class/subclass components of ICs in SMA and CM, we enrolled 75 children with SMA and 32 children with CM from hospitals in western Kenya and matched them to 74 and 52 control children, respectively, with uncomplicated symptomatic malaria. Total IgG IC levels were always elevated in children with malaria upon enrollment, but children with CM had the highest levels of any group. Conditional logistic regression showed a borderline association between IgG4-containing IC levels and increased risk of SMA (OR = 3.11, 95% CI 1.01-9.56, P = 0.05). Total IgG ICs (OR = 2.84, 95% CI 1.08-7.46, P = 0.03) and IgE-containing ICs (OR = 6.82, OR 1.88-24.73, P < or = 0.01) were associated with increased risk of CM. These results point to differences in the contribution of the different antibody class and subclass components of ICs to the pathogenesis of SMA and CM and give insight into potential mechanisms of disease.
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    Immune Complex Levels in Children with Severe Plasmodium Falciparum Malaria.
    (The American Society of Tropical Medicine, 2000-05) Mibei, Erick Kipsang; Orago, A. S.; Stoute, J. A.
    Malaria infection leads to the formation of circulating immune complexes. However, it is unclear whether these complexes play a role in the pathogenesis of complicated Plasmodium falciparum malaria. This study aimed at determining if there are differences in the levels of immune complexes between children with severe malaria-associated anemia and cerebral malaria and between each of these two groups and their respective uncomplicated symptomatic malaria or healthy asymptomatic controls. Children with severe malaria-associated anemia and cerebral malaria had significantly higher immune complex levels than their respective controls, but there were no significant differences in the levels between the two severe malaria groups. In addition, there was an inverse relationship between the hemoglobin levels and immune complex levels in the severe anemia controls, suggesting that immune complexes may contribute to erythrocyte destruction in these children. These results suggest that immune complex levels alone cannot account for the differences in the distinct clinical presentation between severe malaria-associated anemia and cerebral malaria.
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    The levels of CD16/Fc gamma receptor IIIA on CD14+ CD16+ monocytes are higher in children with severe Plasmodium falciparum anemia than in children with cerebral or uncomplicated malaria.
    (PubMed, 2010) Ogonda, Frederick L. A.; Orago, A. S.; Otieno, M.; Adhiambo, C.; Otieno, W.; Stoute, J. A.
    Fc gamma receptor IIIA (CD16/Fc gamma RIIIA) on monocytes/macrophages may play an important role in the pathogenesis of severe malarial anemia (SMA) by promoting phagocytosis of IgG-coated uninfected red cells and by allowing the production of tumor necrosis factor alpha (TNF-alpha) upon cross-linking by immune complexes (ICs). However, not much is known about the differential expression of this receptor on monocytes of children with severe malaria and uncomplicated malaria. Therefore, we investigated the expression of CD16/Fc gamma RIIIA on monocytes of children with SMA, cerebral malaria (CM), and their age-matched uncomplicated malaria controls by flow cytometry. Since CD14 low (CD14(+)) monocytes are considered more mature and macrophage-like than CD14 high (CD14(++)) monocytes, we also compared the level of expression of CD16/Fc gamma RIIIA according to the CD14 level and studied the relationship between CD16/Fc gamma RIIIA expression and intracellular TNF-alpha production upon stimulation by ICs. CD16/Fc gamma RIIIA expression was the highest overall on CD14(+) CD16(+) monocytes of children with SMA at enrollment. At convalescence, SMA children were the only ones to show a significant decline in the same parameter. In contrast, there were no significant differences among groups in the expression of CD16/Fc gamma RIIIA on CD14(++) CD16(+) monocytes. A greater percentage of CD14(+) CD16(+) monocytes produced TNF-alpha upon stimulation than any other monocyte subset, and the amount of intracellular TNF-alpha correlated positively with CD16/Fc gamma RIIIA expression. Furthermore, there was an inverse correlation between hemoglobin levels and CD16/Fc gamma RIIIA expression in children with SMA and their controls. These data suggest that monocytes of children with SMA respond differently to Plasmodium falciparum infection by overexpressing CD16/Fc gamma RIIIA as they mature, which could enhance erythrophagocytosis and TNF-alpha production.
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    Patient related barriers to adequate blood pressure control among adult hypertensive patients seen at Kiambu County Hospital, Kenya
    (East and Central Africa Medical Journal, 2020) Kibore Mogondo, Antony; Moturi, George; Thigiti, Joseph
    Introduction: Hypertension is a key precursor to cardiovascular and renal disease globally. According to WHO, Prevalence of hypertension was about 40 % globally in 2015 and 45% in Sub Saharan Africa in 2015. Despite much emphasis on treatment of the syndrome, the related blood pressure control remains poor or inadequate. Objective: The study sought to establish the patient related barriers to adequate blood pressure control among adult hypertensive patients in Kiambu Count Hospital in Kenya. Methods: A cross -sectional descriptive study method approach was used to examine sample of 330 patients selected through consecutive sampling technique in the medical outpatient chronic disease clinic. Multivariate logistic regression analysis was used to determine variables associated with inadequate or poorly controlled hypertension among adult patients. Results: Most of the patients were females (71.5%). However, the presence of inadequate blood pressure control was significantly higher among males (P-value= 0.009). Regularly taking of hypertension drugs for the last 6 months was significantly associated with adequate blood pressure control (p-value=0.033). The other barriers including single status, inadequate knowledge, employment and time duration since diagnosis of hypertension did not significantly affect blood pressure control status. Discussion: Males were 54% more likely to have inadequate blood pressure control compared to females (AOR=0.543; 95%CI=0.323-0.914). Patients with low adherence to treatment were 11% more likely to have inadequate blood pressure control than those with high adherence rate (AOR=1.093; 95%CI=0.224-5.332) though the association was not significant (p-value=0.912). Conclusion: Male gender was a major barrier to adequate blood pressure control. Patients who well adhered to treatment scheme for a duration of six months preceding the study had their blood pressure better controlled than those who did not. Male hypertensive patients need to be followed up to ensure they adhere to drug treatment in order to reduce the rates of inadequate blood pressure control and other related complications.
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    Uptake of Chronic Kidney Disease Preventive Measures among Diabetic and Hypertensive Patients at the Nyeri County Referral Hospital, Kenya
    (IJRESM, 2023) Wakhungu, Liner; Githemo, Grace; Wala, Jonathan
    The rise in chronic kidney disease (CKD) prevalence worldwide is alarming. It is associated with substantial mortality and morbidity, thus demanding special consideration as one of the increasing public health concerns. Hypertension and diabetes pose the highest risk for CKD development. The study objective was to establish the factors that influence CKD preventive practices among diabetes and hypertension patients at Nyeri County Referral Hospital (NCRH). Data was obtained from 190 participants by the use of a questionnaire. Data was analyzed using SPSS and presented using descriptive statistics. Chi-square was used to test for association among variables while multiple regression analysis was used to test for the predictors of CKD prevention uptake. The findings revealed that 84.2% of the participants had good CKD prevention uptake. Gender χ2 (1) = 6.243, p= .012 age χ2 (4) = 13.146, p= .011, and income χ2 (4) = 25.467, p <0.001 were significantly associated with CKD preventive practice uptake. Health care provider communicating to DM/HTN patients in a language they could understand χ2 (2) = 18.102, p<0.001, accessing all the laboratory services within the hospital χ2 (2) = 8.469, p=.014 and being able to obtain the prescribed drugs from the hospital pharmacy χ2 (2) = 6.361, p=.043 were significantly associated with CKD prevention uptake. The predictors for CKD prevention uptake included gender, income, age, and being well informed about the disease condition. In conclusion 84.2% of the participants had good CKD prevention uptake and this was influenced by factors stated above. The study recommends that health care providers in Nyeri County Referral Hospital should provide CKD prevention health education program especially to the at-risk population. The health care services should also be made available, accessible and affordable to diabetic and hypertensive patients.