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Evaluating the potential impact of mass praziquantel administration for HIV prevention in Schistosoma haematobium high-risk communities.

ABSTRACT: Genital infection with Schistosoma haematobium is prevalent in sub-Saharan Africa. Epidemiological studies have observed that genital schistosomiasis is associated with an increased odd of HIV infection among women. We used mathematical modeling to explore the potential impact of mass preventive chemotherapy against schistosomiasis on HIV transmission in three sub-Saharan Africa countries: Angola, Kenya, and Zambia. We developed a model of female genital schistosomiasis (FGS) and HIV transmission dynamics, fitting it to data of HIV and S. haematobium prevalences as well as co-infection. We simulated targeted mass drug administration (MDA) with praziquantel to school-age children and mass treatment of the entire community. We estimated that, in S. haematobium high-risk communities, targeted annual treatment of school-age children could reduce HIV prevalence by 20% (95% CI: 12-31%) in Angola, 16% (95% CI: 10-32%) in Kenya, and 6% (95% CI: 3-18%) in Zambia after the first 20 years of intervention; and would reduce HIV incidence by 15% (95% CI: 13-32%) in Angola, 22% (95% CI: 18-42%) in Kenya, and 9% (95% CI: 3-22%) in Zambia. Extending the intervention to adults could reduce HIV prevalence by an additional 2.2% (95% CI: 0.2-12.0%) in Angola, 1.8% (95% CI: 0.1-5.2%) in Kenya, and 0.3% (95% CI: 0.1-2.1%) in Zambia; and would reduce HIV incidence by an additional 1.8% (95% CI: 0.0-14.4%) in Angola, 6.1% (95% CI: 0.5-12.6%) in Kenya, and 0.8% (95% CI: 0.0-2.7%) in Zambia. We showed that the exacerbation of HIV transmission due to FGS and the probability of developing FGS as a result of childhood infection with S. haematobium, were the most important factors in determining the effectiveness of praziquantel MDA for reducing HIV transmission. Praziquantel MDA may be an innovative measure for reducing schistosomiasis and HIV transmission in sub-Saharan Africa, the effectiveness of which varies with HIV prevalence.

SUBMITTER: Ndeffo Mbah ML

PROVIDER: S-EPMC4316832 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Evaluating the potential impact of mass praziquantel administration for HIV prevention in Schistosoma haematobium high-risk communities.

Ndeffo Mbah Martial L ML Gilbert Jennifer A JA Galvani Alison P AP

Epidemics 20140429

Genital infection with Schistosoma haematobium is prevalent in sub-Saharan Africa. Epidemiological studies have observed that genital schistosomiasis is associated with an increased odd of HIV infection among women. We used mathematical modeling to explore the potential impact of mass preventive chemotherapy against schistosomiasis on HIV transmission in three sub-Saharan Africa countries: Angola, Kenya, and Zambia. We developed a model of female genital schistosomiasis (FGS) and HIV transmissio ...[more]

PMID: 24928666

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Project description:Previous studies suggest that protective immunity against Schistosoma haematobium is primarily stimulated by antigens from dying worms. Praziquantel treatment kills adult worms, boosting antigen exposure and protective antibody levels. Current schistosomiasis control efforts use repeated mass drug administration (MDA) of praziquantel to reduce morbidity, and may also reduce transmission. The long-term impact of MDA upon protective immunity, and subsequent effects on infection dynamics, are not known. A stochastic individual-based model describing levels of S. haematobium worm burden, egg output and protective parasite-specific antibody, which has previously been fitted to cross-sectional and short-term post-treatment egg count and antibody patterns, was used to predict dynamics of measured egg output and antibody during and after a 5-year MDA campaign. Different treatment schedules based on current World Health Organisation recommendations as well as different assumptions about reductions in transmission were investigated. We found that antibody levels were initially boosted by MDA, but declined below pre-intervention levels during or after MDA if protective immunity was short-lived. Following cessation of MDA, our models predicted that measured egg counts could sometimes overshoot pre-intervention levels, even if MDA had had no effect on transmission. With no reduction in transmission, this overshoot occurred if protective immunity was short-lived. This implies that disease burden may temporarily increase following discontinuation of treatment, even in the absence of any reduction in the overall transmission rate. If MDA was additionally assumed to reduce transmission, a larger overshoot was seen across a wide range of parameter combinations, including those with longer-lived protective immunity. MDA may reduce population levels of immunity to urogenital schistosomiasis in the long-term (3-10 years), particularly if transmission is reduced. If MDA is stopped while S. haematobium is still being transmitted, large rebounds (up to a doubling) in egg counts could occur.

Project description:BackgroundTreatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against schistosomiasis. The antimalarial drug mefloquine shows antischistosomal activity in animal models and clinical trials, which calls for further investigations.MethodologyWe comparatively assessed the efficacy and tolerability of the following treatments against Schistosoma haematobium in school-aged children in Côte d'Ivoire: (i) praziquantel (40 mg/kg; standard treatment); (ii) mefloquine (25 mg/kg) combined with praziquantel (40 mg/kg); and (iii) mefloquine-artesunate (3× (100 mg artesunate +250 mg mefloquine)) combined with praziquantel (40 mg/kg) (treatments administered on subsequent days). Two urine samples were collected before, and on days 21-22 and 78-79 after the first dosing.Principal findingsSixty-one children were present on all examination time points and had complete datasets. No difference in efficacy was observed between the three treatment groups on either follow-up. On the 21-22 day posttreatment follow-up, based on available case analysis, cure rates of 33% (95% confidence interval (CI) 11-55%), 29% (95% CI 8-50%), and 26% (95% CI 5-48%) were observed for praziquantel, mefloquine-artesunate-praziquantel, and mefloquine-praziquantel, respectively. The corresponding egg reduction rates were 94% and above. On the second follow-up, observed cure rates ranged from 19% (praziquantel) to 33% (mefloquine-artesunate-praziquantel), and egg reduction rates were above 90%. Praziquantel monotherapy was the best tolerated treatment. In the mefloquine-artesunate-praziquantel group, adverse events were reported by 91% of the participants, and in the mefloquine-praziquantel group, 95% experienced adverse events. With the exception of abdominal pain at moderate severity, adverse events were mild.Conclusions/significanceThe addition of mefloquine or mefloquine-artesunate does not increase the efficacy of praziquantel against chronic S. haematobium infection. Additional studies are necessary to elucidate the effect of the combinations against acute schistosomiasis.

Project description:BackgroundSub-Saharan Africa carries most of the global burden of schistosomiasis. To optimize disease control and reduce morbidity, precise data are needed for control measures adapted to the local epidemiological situation. The objective of this study is to provide baseline information on schistosomiasis dynamics, including praziquantel (PZQ) treatment outcome in children and young adults living in the vicinity of Lambaréné, Gabon.MethodsEligible volunteers were included into a prospective longitudinal study. Urine filtration technique was used to detect eggs in urine for schistosomiasis diagnosis. Subjects were treated with 60 mg of PZQ once per month for three consecutive months, and the outcome was assessed by cure rate (CR) and egg reduction rate (ERR).ResultsA total of 328 volunteers were enrolled in the study with a mean (± SD) age of 12.2 ± 4.7 years-old. The female-to-male ratio was 0.99. Out of 258 participants in total, 45% had schistosomiasis during the survey and 43% presented with heavy infections. The incidences of haematuria and schistosomiasis were 0.11 and 0.17 person-years, respectively. After the first and third dose of PZQ, overall ERR of 93% and 95% were found, respectively; while the CR were 78% and 88%, respectively. Both ERR (100 vs 88%) and CR (90 vs 68%) were higher among females than males after the first dose. The CR increased for both groups after the third dose to 95% and 80%, respectively. After the first PZQ dose, ERR was higher for heavy compared to light infections (94 vs 89%), while the CR was higher for light than for heavy infections (87 vs 59%). After the third PZQ dose, ERR increased only for light infections to 99%, while CR increased to 98% and 75% for light and for heavy infections, respectively. The reinfection rate assessed at a mean of 44.6 weeks post-treatment was 25%.ConclusionsThe prevalence of schistosomiasis is moderate in communities living in the vicinity of Lambaréné, where a subpopulation with a high risk of reinfection bears most of the burden of the disease. To improve schistosomiasis control in this scenario, we suggest education of these high-risk groups to seek themselves a one-year PZQ treatment. Trial registration clinicaltrials.gov Identifier NCT02769103. Registered 11 May 2016, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT02769013.

Dataset Information

Evaluating the potential impact of mass praziquantel administration for HIV prevention in Schistosoma haematobium high-risk communities.

Publications

Evaluating the potential impact of mass praziquantel administration for HIV prevention in Schistosoma haematobium high-risk communities.

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