Praziquantel decreases fecundity in Schistosoma mansoni adult worms that survive treatment: evidence from a laboratory life-history trade-offs selection study

Lamberton, P. H.L. , Faust, C. L. and Webster, J. P. (2017) Praziquantel decreases fecundity in Schistosoma mansoni adult worms that survive treatment: evidence from a laboratory life-history trade-offs selection study. Infectious Diseases of Poverty, 6, 110. (doi: 10.1186/s40249-017-0324-0) (PMID:28622767) (PMCID:PMC5472905)

143169.pdf - Published Version
Available under License Creative Commons Attribution.



Background: Mass 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. Methods: We 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 coinfected line (RS), under three treatment regimens: untreated, 25 mg/kg praziquantel, or 50 mg/kg praziquantel. Lifehistory 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. Results: Praziquantel 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. Conclusions: Our 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.

Item Type:Articles
Keywords:Biomphalaria, establishment, fecundity, mouse, praziquantel, resistance, Schistosoma mansoni, survival, trade-offs.
Glasgow Author(s) Enlighten ID:Faust, Christina and Lamberton, Professor Poppy
Authors: Lamberton, P. H.L., Faust, C. L., and Webster, J. P.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Infectious Diseases of Poverty
Publisher:BioMed Central
ISSN (Online):2049-9957
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Infectious Diseases of Poverty 6: 110
Publisher Policy:Reproduced under a Creative Commons license

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
730161SCHISTO-PERSISTPoppy LambertonEuropean Research Council (ERC)680088RI BIODIVERSITY ANIMAL HEALTH & COMPMED
721851ISSF Year 4 - Pilot ProjectsAnna DominiczakWellcome Trust (WELLCOTR)105614/Z/14/ZRI CARDIOVASCULAR & MEDICAL SCIENCES