Abstract
BackgroundMass drug administration of praziquantel is the World Health Organization’s endorsed control strategy for schistosomiasis. A decade of annual treatments across sub-Saharan Africa has resulted in significant reductions of infection prevalence and intensity levels, although ‘hotspots’ remain. Repeated drug treatments place strong selective pressures on parasites, which may affect life-history traits that impact transmission dynamics. Understanding drug treatment responses and the evolution of such traits can help inform on how to minimise the risk of drug resistance developing, maximise sustainable control programme success, and improve diagnostic protocols.MethodsWe performed a four-generation Schistosoma mansoni praziquantel selection experiment in mice and snails. We used three S. mansoni lines: a praziquantel-resistant isolate (R), a praziquantel-susceptible isolate (S), and a co-infected line (RS), under three treatment regimens: untreated, 25 mg/kg praziquantel, or 50 mg/kg praziquantel. Life-history traits, including parasite adult-worm establishment, survival, reproduction (fecundity), and associated morbidity, were recorded in mice across all four generations. Predictor variables were tested in a series of generalized linear mixed effects models to determine which factors had a significant influence on parasite life-history traits in definitive hosts under different selection regimes.ResultsPraziquantel pressure significantly reduced adult-worm burdens across all generations and isolates, including within R-lines. However, previous drug treatment resulted in an increase in adult-worm establishment with increasing generation from P1 to F3. The highest worm numbers were in the co-infected RS line. Praziquantel treatment decreased adult-worm burden, but had a larger negative impact on the mean daily number of miracidia, a proxy for fecundity, across all three parasite isolates.ConclusionsOur predicted cost of resistance was not supported by the traits we measured within the murine host. We did not find evidence for negative adult worm density-dependent effects on fecundity. In contrast, of the adult worms that survived treatment, even low doses of praziquantel significantly reduced adult-worm fecundity. Such reductions in worm fecundity post treatment suggest that egg - based measures of drug efficacy, such as Kato-Katz, may overestimate the short-term effect of praziquantel on adult - worm burdens. These findings have important implications for S. mansoni transmission control, diagnostic protocols, and the potential for undetected selection toward drug resistance.
Highlights
Mass drug administration of praziquantel is the World Health Organization’s endorsed control strategy for schistosomiasis
Worm establishment and survival Adult worm numbers were measured between days 47–62 post infection, equating to 5–20 days post praziquantel treatment
Cull day post treatment affected the establishment and survival of adult worms in a univariate model (IRR: 0.96; 95% Confidence interval (CI): 0.94, 0.99), it was not significant once included in multivariate models or present as a predictor in the best fit model
Summary
Mass drug administration of praziquantel is the World Health Organization’s endorsed control strategy for schistosomiasis. Repeated drug treatments place strong selective pressures on parasites, which may affect life-history traits that impact transmission dynamics. The majority of human intestinal schistosomiasis infections are caused by Schistosoma mansoni, a species found predominantly in Africa and South America. When faeces contaminate freshwater water through poor or lack of sanitation, the eggs hatch into miracidia. These miracidia infect Biomphalaria snail species where they reproduce asexually to produce cercariae. These cercariae are directly infective to humans; people are exposed when they contact infected water sources when bathing, swimming, fishing, and doing other water-based activities
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