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Phenotypic and genotypic monitoring of Schistosoma mansoni in Tanzanian schoolchildren five years into a preventative chemotherapy national control programme.

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Title: Phenotypic and genotypic monitoring of Schistosoma mansoni in Tanzanian schoolchildren five years into a preventative chemotherapy national control programme.
Authors: Gower, CM
Gehre, F
Marques, SR
Lamberton, PHL
Lwambo, NJ
Webster, JP
Item Type: Journal Article
Abstract: BACKGROUND: Schistosoma mansoni is a parasite of profound medical importance. Current control focusses on mass praziquantel (PZQ) treatment of populations in endemic areas, termed Preventative Chemotherapy (PC). Large-scale PC programmes exert prolonged selection pressures on parasites with the potential for, direct and/or indirect, emergence of drug resistance. Molecular methods can help monitor genetic changes of schistosome populations over time and in response to drug treatment, as well as estimate adult worm burdens through parentage analysis. Furthermore, methods such as in vitro drug sensitivity assays help phenotype in vivo parasite genotypic drug efficacy. METHODS: We conducted combined in vitro PZQ efficacy testing with population genetic analyses of S. mansoni collected from children from two schools in 2010, five years after the introduction of a National Control Programme. Children at one school had received four annual PZQ treatments and the other school had received two mass treatments in total. We compared genetic differentiation, indices of genetic diversity, and estimated adult worm burden from parasites collected in 2010 with samples collected in 2005 (before the control programme began) and in 2006 (six months after the first PZQ treatment). Using 2010 larval samples, we also compared the genetic similarity of those with high and low in vitro sensitivity to PZQ. RESULTS: We demonstrated that there were individual parasites with reduced PZQ susceptibility in the 2010 collections, as evidenced by our in vitro larval behavioural phenotypic assay. There was no evidence, however, that miracidia showing phenotypically reduced susceptibility clustered together genetically. Molecular analysis also demonstrated a significant reduction of adult worm load over time, despite little evidence of reduction in parasite infection intensity, as measured by egg output. Genetic diversity of infections did not reduce over time, despite changes in the genetic composition of the parasite populations. CONCLUSIONS: Genotypic and phenotypic monitoring did not indicate a selective sweep, as may be expected if PZQ treatment was selecting a small number of related "resistant" parasites, but there was evidence of genetic changes at the population level over time. Genetic data were used to estimate adult worm burdens, which unlike parasite infection intensity, showed reductions over time, suggesting the relaxation of negative density-dependent constraints on parasite fecundity with PZQ treatment. We thereby demonstrated that density-dependence in schistosome populations may complicate evaluation and monitoring of control programmes.
Issue Date: 2-Dec-2017
Date of Acceptance: 13-Nov-2017
URI: http://hdl.handle.net/10044/1/54646
DOI: https://dx.doi.org/10.1186/s13071-017-2533-6
ISSN: 1756-3305
Publisher: BioMed Central
Journal / Book Title: Parasites & Vectors
Volume: 10
Issue: 1
Copyright Statement: © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Sponsor/Funder: Bill & Melinda Gates Foundation
Bill & Melinda Gates Foundation
The Royal Society
Funder's Grant Number: 36202
RR374-053/4785416
EGAP RG090679
Keywords: Density-dependence
Drug resistance
Neglected tropical diseases
Population genetics
Praziquantel
Schistosomiasis
1108 Medical Microbiology
1117 Public Health And Health Services
Mycology & Parasitology
Tropical Medicine
Publication Status: Published
Article Number: 593
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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