Cargando…

The changing landscape of Plasmodium falciparum drug resistance in the Democratic Republic of Congo

BACKGROUND: Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to underst...

Descripción completa

Detalles Bibliográficos
Autores principales: Deutsch-Feldman, Molly, Aydemir, Ozkan, Carrel, Margaret, Brazeau, Nicholas F., Bhatt, Samir, Bailey, Jeffrey A., Kashamuka, Melchior, Tshefu, Antoinette K., Taylor, Steve M., Juliano, Jonathan J., Meshnick, Steven R., Verity, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805465/
https://www.ncbi.nlm.nih.gov/pubmed/31640574
http://dx.doi.org/10.1186/s12879-019-4523-0
_version_ 1783461390958198784
author Deutsch-Feldman, Molly
Aydemir, Ozkan
Carrel, Margaret
Brazeau, Nicholas F.
Bhatt, Samir
Bailey, Jeffrey A.
Kashamuka, Melchior
Tshefu, Antoinette K.
Taylor, Steve M.
Juliano, Jonathan J.
Meshnick, Steven R.
Verity, Robert
author_facet Deutsch-Feldman, Molly
Aydemir, Ozkan
Carrel, Margaret
Brazeau, Nicholas F.
Bhatt, Samir
Bailey, Jeffrey A.
Kashamuka, Melchior
Tshefu, Antoinette K.
Taylor, Steve M.
Juliano, Jonathan J.
Meshnick, Steven R.
Verity, Robert
author_sort Deutsch-Feldman, Molly
collection PubMed
description BACKGROUND: Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to understand how resistant malaria may be spreading within the DRC, using samples from nation-wide population-representative surveys. METHODS: We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known variants in the pfdhps and pfcrt genes associated with resistance. We compared the proportion of mutant parasites in 2013 to those previously reported from adults in 2007, and identified risk factors for carrying a resistant allele using multivariate mixed-effects modeling. Finally, we fit a spatial-temporal model to the observed data, providing smooth allele frequency estimates over space and time. RESULTS: The proportion of co-occurring pfdhps K540E/A581G mutations increased by 16% between 2007 and 2013. The spatial-temporal model suggests that the spatial range of the pfdhps double mutants expanded over time, while the prevalence and range of pfcrt mutations remained steady. CONCLUSIONS: This study uses population-representative samples to describe the changing landscape of SP resistance within the DRC, and the persistence of chloroquine resistance. Vigilant molecular surveillance is critical for controlling the spread of resistance.
format Online
Article
Text
id pubmed-6805465
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-68054652019-10-24 The changing landscape of Plasmodium falciparum drug resistance in the Democratic Republic of Congo Deutsch-Feldman, Molly Aydemir, Ozkan Carrel, Margaret Brazeau, Nicholas F. Bhatt, Samir Bailey, Jeffrey A. Kashamuka, Melchior Tshefu, Antoinette K. Taylor, Steve M. Juliano, Jonathan J. Meshnick, Steven R. Verity, Robert BMC Infect Dis Research Article BACKGROUND: Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to understand how resistant malaria may be spreading within the DRC, using samples from nation-wide population-representative surveys. METHODS: We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known variants in the pfdhps and pfcrt genes associated with resistance. We compared the proportion of mutant parasites in 2013 to those previously reported from adults in 2007, and identified risk factors for carrying a resistant allele using multivariate mixed-effects modeling. Finally, we fit a spatial-temporal model to the observed data, providing smooth allele frequency estimates over space and time. RESULTS: The proportion of co-occurring pfdhps K540E/A581G mutations increased by 16% between 2007 and 2013. The spatial-temporal model suggests that the spatial range of the pfdhps double mutants expanded over time, while the prevalence and range of pfcrt mutations remained steady. CONCLUSIONS: This study uses population-representative samples to describe the changing landscape of SP resistance within the DRC, and the persistence of chloroquine resistance. Vigilant molecular surveillance is critical for controlling the spread of resistance. BioMed Central 2019-10-22 /pmc/articles/PMC6805465/ /pubmed/31640574 http://dx.doi.org/10.1186/s12879-019-4523-0 Text en © The Author(s). 2019 Open AccessThis 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.
spellingShingle Research Article
Deutsch-Feldman, Molly
Aydemir, Ozkan
Carrel, Margaret
Brazeau, Nicholas F.
Bhatt, Samir
Bailey, Jeffrey A.
Kashamuka, Melchior
Tshefu, Antoinette K.
Taylor, Steve M.
Juliano, Jonathan J.
Meshnick, Steven R.
Verity, Robert
The changing landscape of Plasmodium falciparum drug resistance in the Democratic Republic of Congo
title The changing landscape of Plasmodium falciparum drug resistance in the Democratic Republic of Congo
title_full The changing landscape of Plasmodium falciparum drug resistance in the Democratic Republic of Congo
title_fullStr The changing landscape of Plasmodium falciparum drug resistance in the Democratic Republic of Congo
title_full_unstemmed The changing landscape of Plasmodium falciparum drug resistance in the Democratic Republic of Congo
title_short The changing landscape of Plasmodium falciparum drug resistance in the Democratic Republic of Congo
title_sort changing landscape of plasmodium falciparum drug resistance in the democratic republic of congo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805465/
https://www.ncbi.nlm.nih.gov/pubmed/31640574
http://dx.doi.org/10.1186/s12879-019-4523-0
work_keys_str_mv AT deutschfeldmanmolly thechanginglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT aydemirozkan thechanginglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT carrelmargaret thechanginglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT brazeaunicholasf thechanginglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT bhattsamir thechanginglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT baileyjeffreya thechanginglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT kashamukamelchior thechanginglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT tshefuantoinettek thechanginglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT taylorstevem thechanginglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT julianojonathanj thechanginglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT meshnickstevenr thechanginglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT verityrobert thechanginglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT deutschfeldmanmolly changinglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT aydemirozkan changinglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT carrelmargaret changinglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT brazeaunicholasf changinglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT bhattsamir changinglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT baileyjeffreya changinglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT kashamukamelchior changinglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT tshefuantoinettek changinglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT taylorstevem changinglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT julianojonathanj changinglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT meshnickstevenr changinglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo
AT verityrobert changinglandscapeofplasmodiumfalciparumdrugresistanceinthedemocraticrepublicofcongo