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Title: Use of cotrimoxazole prophylactic treatment in HIV exposed children and its impact on malaria
Author: Mbeye, Nyanyiwe
ISNI:       0000 0004 5362 7827
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2014
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The rapidly growing population of HIV exposed children entails widespread use of cotrimoxazole prophylactic treatment (CPT) to protect them from HIV opportunistic infections given their increased susceptibility compared to non-HIV exposed children. A number of studies have reported that CPT also provides protection against malaria but estimates of its effectiveness vary and there is little information on the impact of the prevalence of antifolate resistance mutations on its effect. Since daily CPT provides prophylaxis against malaria, it could modulate the development of malaria-specific immunity and increase the incidence of malaria after it is stopped (a rebound effect). Moreover, factors that influence CPT adherence in this group are not known. This thesis reviewed studies that examined the effect of CPT provided at the age of 6 weeks to 14 months on malaria incidence in children in Sub-Saharan Africa (systematic review) and investigated the incidence of malaria and other morbidities during and after CPT in the first two years of life in HIV exposed children in southern Malawi (cohort study). Lastly, CPT adherence was explored using narrative and grounded theory approaches (qualitative study). Results The systematic review included 3 Randomised Controlled Trials (RCTs) and four cohort studies fulfilling the eligibility criteria, with a total of 5,978 children (1,692 HIV exposed; 2,800 non-HIV exposed; 1,486 HIV-infected). Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined Incidence Rate Ratio (IRR) = 0·37, 95% CI 0·21, 0·66) but there was substantial between-study heterogeneity (I-squared=94%, p<0·001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d’Ivoire. In the cohort study of 500 HIV exposed and 500 non-HIV exposed children matched on age and residence; the incidence of uncomplicated malaria was 65% lower in year 1 in the HIV exposed group (IRR = 0.35, 95% CI 0.25, 0.49, p<0.001). In year 2 after CPT was stopped, the incidence was similar to that in non-HIV exposed group (IRR = 0.94, 95% CI 0.53, 1.68, p=0.839) among the first 315 children that had completed the follow-up period at the time of the analysis. The same pattern was observed for all-cause morbidity and hospital admissions where a lower risk was observed during year 1 and similar estimates between the groups were obtained in year 2. In the qualitative study, Participation in the cohort study empowered HIV infected women to make decisions about their children’s health and develop useful strategies to promote uptake of CPT. The women themselves, their families, the communities in which they lived and the health care system related and influenced each other through social interaction which played a role in influencing actions either positively or negatively. Despite negative influences that might have arisen at any level, the determination of the individual to take a health related action and the realisation that the recommended action would prevent any negative outcomes motivated the mothers to believe that they could successfully do something to prevent any negative health outcomes on their children. Conclusions CPT significantly reduced the incidence of malaria in children in the systematic review and metaanalysis as well as in HIV exposed children in the cohort study in year 1. Marked reductions in the incidence of severe malaria, all-cause morbidity and hospital admissions during the period in which it was given were observed in the cohort study. Although the cohort study was not able to show any benefits on all-cause mortality, CPT was associated with significant reductions in mortality in the systematic review. The follow up in year 2 is on going but preliminary results suggest that the incidence of malaria does not increase after cessation of CPT at 14 months of age. The improved health outcomes of HIV infected women motivate the women to continue administering CPT to their children despite any deterring factors that might arise.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available