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

作　　者：Poppy H.L.Lamberton Christina L.Faust Joanne P.Webster 

机构地区：[1]Institute for Biodiversity,Animal Health,and Comparative Medicine&Wellcome Centre for Molecular Parasitology,College of Medical,Veterinary&Life Sciences,University of Glasgow,G128QQ,Glasgow,UK [2]London Centre for Neglected Tropical Disease Research,Department of Infectious Disease Epidemiology,School of Public Health,Imperial College London,St Mary’s Campus,W21PG,London,UK [3]Centre for Endemic,Emerging and Exotic Diseases,The Royal Veterinary College,University of London,London AL97TA,UK

出　　处：《Infectious Diseases of Poverty》2017年第1期988-998,共11页贫困所致传染病（英文）

基　　金：PHLL and CLF are currently funded by PHLL’s European Research Council Starting Grant[680,088 SCHISTO_PERSIST];PHLL is also funded by a Wellcome Trust ISSF Grant[105,614/Z/14/Z];a Lord Kelvin Adam Smith Leadership Fellowship;JPW’S current Schistosoma research is funded by a ZELS research grant(combined BBSRC,MRC,ESRC,NERC,DSTL&DFID:BB/L018985/1);a BBSRC Impact Accelerator Grant(BB/GCRF-IAA/19);a SCORE research grant(The University of Georgia Research Foundation,funded by the Bill and Melinda Gates Foundation:RR374-053/4785426);During the experiment study PHLL was funded by a Medical Research Council PhD studentship and JPW was funded by a Royal Society University Research Fellowship.Funding for the laboratory facilities was given from the Schistosomiasis Control Initiative。

摘　　要：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 adul

关 键 词：Schistosoma mansoni BIOMPHALARIA Mouse PRAZIQUANTEL Resistance Establishment Survival FECUNDITY Trade-offs 

分 类 号：R53[医药卫生—内科学]