Two-year longitudinal survey reveals high genetic diversity of Schistosoma mansoni with adult worms surviving praziquantel treatment at the start of mass drug administration in Uganda

Faust, C. L. et al. (2019) Two-year longitudinal survey reveals high genetic diversity of Schistosoma mansoni with adult worms surviving praziquantel treatment at the start of mass drug administration in Uganda. Parasites and Vectors, 12, 607. (doi: 10.1186/s13071-019-3860-6) (PMID:31881923) (PMCID:PMC6935072)

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Abstract

Background: A key component of schistosomiasis control is mass drug administration with praziquantel. While control interventions have been successful in several endemic regions, mass drug administration has been less effective in others. Here we focus on the impact of repeated praziquantel treatment on the population structure and genetic diversity of Schistosoma mansoni. Methods: We examined S. mansoni epidemiology, population genetics, and variation in praziquantel susceptibility in parasites isolated from children across three primary schools in a high endemicity region at the onset of the Ugandan National Control Programme. Children were sampled at 11 timepoints over two years, including one week and four weeks post-praziquantel treatment to evaluate short-term impacts on clearance and evidence of natural variation in susceptibility to praziquantel. Results: Prevalence of S. mansoni was 85% at baseline. A total of 3576 miracidia larval parasites, isolated from 203 individual children, were genotyped at seven loci. Overall, genetic diversity was high and there was low genetic differentiation, indicating high rates of parasite gene flow. Schistosome siblings were found both pre-treatment and four weeks post-treatment, demonstrating adult worms surviving treatment and natural praziquantel susceptibility variation in these populations at the beginning of mass drug administration. However, we did not find evidence for selection on these parasites. While genetic diversity decreased in the short-term (four weeks post-treatment), diversity did not decrease over the entire period despite four rounds of mass treatment. Furthermore, within-host genetic diversity was affected by host age, host sex, infection intensity and recent praziquantel treatment. Conclusions: Our findings suggest that praziquantel treatments have short-term impacts on these parasite populations but impacts were transient and no long-term reduction in genetic diversity was observed. High gene flow reduces the likelihood of local adaptation, so even though parasites surviving treatment were observed, these were likely to be diluted at the beginning of the Ugandan National Control Programme. Together, these results suggest that MDA in isolation may be insufficient to reduce schistosome populations in regions with high genetic diversity and gene flow.

Item Type:Articles
Additional Information:JPW currently funded by Biotechnology and Biological Sciences Research Council (BB/S013822/1), Global Challenges Research Fund (MR/ S01313X/1), Research England (CCF-17-7779) and European and Developing Countries Clinical Trials Partnership grants.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Crotti, Marco and Faust, Christina and Lamberton, Dr Poppy and Adekanle, Miss Elizabeth
Authors: Faust, C. L., Crotti, M., Moses, A., Oguttu, D., Wamboko, A., Adriko, M., Adekanle, E. K., Kabatereine, N., Tukahebwa, E. M., Norton, A. J., Gower, C. M., Webster, J. P., and Lamberton, P. H.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Science and Engineering > School of Engineering
Journal Name:Parasites and Vectors
Publisher:BioMed Central
ISSN:1756-3305
ISSN (Online):1756-3305
Published Online:01 January 2019
Copyright Holders:Copyright © The Authors 2019
First Published:First published in Parasites and Vectors 12:607
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172876SCHISTO-PERSISTPoppy LambertonEuropean Research Council (ERC)680088Institute of Biodiversity, Animal Health and Comparative Medicine
174071Cultural, social and economic influences on ongoing schistosomiasis transmission, despite a decade of mass treatment, and the potential for changePoppy LambertonMedical Research Council (MRC)MR/P025447/1Institute of Biodiversity, Animal Health and Comparative Medicine
300573Novel low cost diagnostic tools and their impact in AfricaJonathan CooperEngineering and Physical Sciences Research Council (EPSRC)EP/R01437X/1ENG - Biomedical Engineering