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Title: Lymphatic filariasis control in an HIV endemic area in northern Malawi
Author: Tafatatha, Terence Thawe
ISNI:       0000 0004 7659 1433
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2018
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Lymphatic filariasis (LF) and human immunodeficiency virus (HIV) are major public health problems in Malawi. Coinfections are widespread and there is possibility of important interactions between these two pathogens with consequences for LF control and elimination. There is little available evidence on co-infection and interaction of LF and HIV infections and the study set out to investigate associations and interactions between these two pathogens and determine possible consequences for LF control and elimination through annual mass drug administration (MDA). This thesis presents results from adult study participants in two rural sites in Karonga district, northern Malawi, a region endemic for both LF and HIV. Stored blood samples and data from two geographically separate studies were used. One was a clinical trial of anti-filarial agent dosing regimens in Songwe in the northern part of the district (the Songwe clinical trial), and the other a whole population annual HIV sero-survey with longitudinal follow up data from the southern part of the district (the Karonga Health and Demographic Surveillance System or KHDSS). The main objectives were: 1. To determine the prevalence of LF and HIV co-infections as quantified by the Og4C3 ELISA in a large cross-sectional study in Karonga district, rural northern Malawi. 2. To investigate whether higher and/or more frequent doses of albendazole and ivermectin were more effective in eliminating Wuchereria bancrofti microfilariae than the World Health Organisation (WHO) approved standard regimen. 3. To determine the relationship of circulating filarial antigen (CFA) and microfilaria count (MF) by HIV status. 4. To monitor the impact of Mass Drug Administration (MDA) on LF antigenaemia by HIV status by following a cohort of LF antigen positive individuals identified in objective one. 5. To assess the contribution of insecticide treated bed nets (ITNs) to changes in CFA. These objectives were met through three filarial research studies using data from two distinct geographical locations: Study 1, cross-sectional assessment of the relationship of HIV and markers of LF infection; Study 2, clinical trial of anti-filarial dosing regimens and Study 3, longitudinal assessment of the impact of MDA on LF antigenaemia by HIV status. In study 1 (cross-sectional assessment), 1,851 consecutive adult volunteers from the Songwe area of Karonga district were screened for HIV and LF infection. Overall CFA prevalence was 24.1% (447/1851) while CFA prevalence was 25.4% (43/169) in HIV-positive and 23.6% (351/1487) in HIV-negative participants (p=0.57). Geometric mean concentrations (GMC) of CFA were 859 and 1660 antigen units per ml of blood (Ag/ml) respectively, geometric mean ratio (GMR) 0.85, 95% CI 0.49-1.50. In addition, a further 7,863 adults from the KHDSS part of the district had an overall CFA prevalence of 23.8% (1875/7863), a CFA prevalence of 20.9% (86/411) in HIV-positive and 24.0% (1789/7452) in HIV-negative participants (p=0.15) at baseline. GMC CFA was 630 and 839 Ag/ml respectively (GMR 0.75, 95% CI 0.60-0.94). In the HIV-positive group, antiretroviral therapy (ART) use was associated with a lower CFA prevalence, 12.7% (18/142) vs. 25.3% (67/265), (OR 0.43, 95% CI 0.24-0.76). Prevalence of CFA decreased with duration of ART use, 15.2% 0-1 year (n=59), 13.6% > 1-2 years (n=44), 10.0% > 2-3 years (n=30) and 0% > 3-4 years treatment (n=9), p < 0.01 ?2 for linear trend. In study 2 (clinical trial), seventy individuals with confirmed circulating LF antigen had microfilarial counts > 80 microfilariae/ml and were randomised as part of a controlled open label clinical trial. The clinical trial compared three modified treatment groups to standard dosage of ivermectin and albendazole in adults. Participants were followed up every six months for two years for repeat microfilarial counts and safety assessments. All treatment groups achieved a significant reduction of microfilariae levels by 12 and 24 months of follow up. Doubling the standard dose and giving it twice yearly showed a non-significant tendency towards faster and more complete clearance. There were no serious adverse reactions. In study 3 (longitudinal assessment), the cohort was derived from study 1 and comprised of 1722 baseline CFA positive individuals who had a follow up blood sample and a random sample of 939 baseline CFA negative individuals. Of the 1722 baseline CFA positive individuals, 524 (30.4%) remained CFA-positive, a clearance rate of 325/1000 person years of follow up while all but two of the 939 CFA-negative individuals at baseline remained negative at follow up, an incidence of 1/1000 person years of follow up. Using logistic regression, two doses of annual MDA was independently associated with decreased CFA positivity while bed net ownership and HIV status were not associated with CFA positivity. In the HIV-positive subgroup, ART use did not show any association with CFA positivity at follow up. This is the first investigation of this magnitude into HIV and LF co-infection in Malawi and it adds significantly to existing knowledge in the field. The cross-sectional study of two distinct LF-exposed populations confirms that there is no evidence that HIV infection has an impact on LF epidemiology that will interfere with LF control measures. A significant association of ART use with lower CFA prevalence merits further investigation to understand this apparent beneficial impact of ART. At follow up, MDA effectively reduced CFA prevalence and worm burden and the effectiveness of MDA treatment is unaffected by HIV co-infection and ART status.
Supervisor: Taegtmeyer, Miriam ; French, Neil Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral