Submicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya.

<h4>Background</h4>Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine re...

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Autores principales:	Mayke J A M Oesterholt, Michael Alifrangis, Colin J Sutherland, Sabah A Omar, Patrick Sawa, Christina Howitt, Louis C Gouagna, Robert W Sauerwein, Teun Bousema
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b3b98ca949fb46a2a1c518955fc44f99
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spelling	oai:doaj.org-article:b3b98ca949fb46a2a1c518955fc44f992021-11-25T06:17:29ZSubmicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya.1932-620310.1371/journal.pone.0004364https://doaj.org/article/b3b98ca949fb46a2a1c518955fc44f992009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19194499/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites. In the present study, we determine the association between parasite mutations, submicroscopic P. falciparum gametocytemia and malaria transmission to mosquitoes.<h4>Methodology/principal findings</h4>Samples from children treated with SP alone or in combination with artesunate (AS) or amodiaquine were genotyped for SNPs in the dhfr and dhps genes. Gametocytemia was determined by microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification (Pfs25 QT-NASBA). Transmission was determined by membrane-feeding assays. We observed no wild type infections, 66.5% (127/191) of the infections expressed mutations at all three dhfr codons prior to treatment. The presence of all three mutations was not related to higher Pfs25 QT-NASBA gametocyte prevalence or density during follow-up, compared to double mutant infections. The proportion of infected mosquitoes or oocyst burden was also not related to the number of mutations. Addition of AS to SP reduced gametocytemia and malaria transmission during follow-up.<h4>Conclusions/significance</h4>In our study population where all infections had at least a double mutation in the dhfr gene, additional mutations were not related to increased submicroscopic gametocytemia or enhanced malaria transmission. The absence of wild-type infections is likely to have reduced our power to detect differences. Our data further support the use of ACT to reduce the transmission of drug-resistant malaria parasites.Mayke J A M OesterholtMichael AlifrangisColin J SutherlandSabah A OmarPatrick SawaChristina HowittLouis C GouagnaRobert W SauerweinTeun BousemaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 2, p e4364 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mayke J A M Oesterholt Michael Alifrangis Colin J Sutherland Sabah A Omar Patrick Sawa Christina Howitt Louis C Gouagna Robert W Sauerwein Teun Bousema Submicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya.
description	<h4>Background</h4>Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites. In the present study, we determine the association between parasite mutations, submicroscopic P. falciparum gametocytemia and malaria transmission to mosquitoes.<h4>Methodology/principal findings</h4>Samples from children treated with SP alone or in combination with artesunate (AS) or amodiaquine were genotyped for SNPs in the dhfr and dhps genes. Gametocytemia was determined by microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification (Pfs25 QT-NASBA). Transmission was determined by membrane-feeding assays. We observed no wild type infections, 66.5% (127/191) of the infections expressed mutations at all three dhfr codons prior to treatment. The presence of all three mutations was not related to higher Pfs25 QT-NASBA gametocyte prevalence or density during follow-up, compared to double mutant infections. The proportion of infected mosquitoes or oocyst burden was also not related to the number of mutations. Addition of AS to SP reduced gametocytemia and malaria transmission during follow-up.<h4>Conclusions/significance</h4>In our study population where all infections had at least a double mutation in the dhfr gene, additional mutations were not related to increased submicroscopic gametocytemia or enhanced malaria transmission. The absence of wild-type infections is likely to have reduced our power to detect differences. Our data further support the use of ACT to reduce the transmission of drug-resistant malaria parasites.
format	article
author	Mayke J A M Oesterholt Michael Alifrangis Colin J Sutherland Sabah A Omar Patrick Sawa Christina Howitt Louis C Gouagna Robert W Sauerwein Teun Bousema
author_facet	Mayke J A M Oesterholt Michael Alifrangis Colin J Sutherland Sabah A Omar Patrick Sawa Christina Howitt Louis C Gouagna Robert W Sauerwein Teun Bousema
author_sort	Mayke J A M Oesterholt
title	Submicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya.
title_short	Submicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya.
title_full	Submicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya.
title_fullStr	Submicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya.
title_full_unstemmed	Submicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya.
title_sort	submicroscopic gametocytes and the transmission of antifolate-resistant plasmodium falciparum in western kenya.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/b3b98ca949fb46a2a1c518955fc44f99
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Submicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya.

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