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Effect of three years’ seasonal malaria chemoprevention on molecular markers of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine and amodiaquine in Ouelessebougou, Mali

BACKGROUND: In 2012, seasonal malaria chemoprevention (SMC) was recommended as policy for malaria control by the World Health Organization (WHO) in areas of highly seasonal malaria transmission across the Sahel sub-region in Africa along with monitoring of drug resistance. We assessed the long-term...

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Autores principales: Mahamar, Almahamoudou, Sumner, Kelsey M., Levitt, Brandt, Freedman, Betsy, Traore, Aliou, Barry, Amadou, Issiaka, Djibrilla, Dembele, Adama B., Kanoute, Moussa B., Attaher, Oumar, Diarra, Boubacar N., Sagara, Issaka, Djimde, Abdoulaye, Duffy, Patrick E., Fried, Michal, Taylor, Steve M., Dicko, Alassane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822718/
https://www.ncbi.nlm.nih.gov/pubmed/35135546
http://dx.doi.org/10.1186/s12936-022-04059-z
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author Mahamar, Almahamoudou
Sumner, Kelsey M.
Levitt, Brandt
Freedman, Betsy
Traore, Aliou
Barry, Amadou
Issiaka, Djibrilla
Dembele, Adama B.
Kanoute, Moussa B.
Attaher, Oumar
Diarra, Boubacar N.
Sagara, Issaka
Djimde, Abdoulaye
Duffy, Patrick E.
Fried, Michal
Taylor, Steve M.
Dicko, Alassane
author_facet Mahamar, Almahamoudou
Sumner, Kelsey M.
Levitt, Brandt
Freedman, Betsy
Traore, Aliou
Barry, Amadou
Issiaka, Djibrilla
Dembele, Adama B.
Kanoute, Moussa B.
Attaher, Oumar
Diarra, Boubacar N.
Sagara, Issaka
Djimde, Abdoulaye
Duffy, Patrick E.
Fried, Michal
Taylor, Steve M.
Dicko, Alassane
author_sort Mahamar, Almahamoudou
collection PubMed
description BACKGROUND: In 2012, seasonal malaria chemoprevention (SMC) was recommended as policy for malaria control by the World Health Organization (WHO) in areas of highly seasonal malaria transmission across the Sahel sub-region in Africa along with monitoring of drug resistance. We assessed the long-term impact of SMC on Plasmodium falciparum resistance to sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) over a 3-year period of SMC implementation in the health district of Ouelessebougou, Mali. METHODS: In 8 randomly selected sub-districts of Ouelessebougou, Mali, children aged 0–5 years were randomly selected during cross-sectional surveys at baseline (August 2014) and 1, 2 and 3 years post-SMC, at the beginning and end of the malaria transmission season. Blood smears and blood spots on filter paper were obtained and frequencies of mutation in P. falciparum genes related to resistance to SP and AQ (Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt) were assessed by PCR amplification on individual samples and PCR amplification followed by deep sequencing on pooled (by site and year) samples. RESULTS: At each survey, approximately 50–100 individual samples were analysed by PCR amplification and a total of 1,164 samples were analysed by deep sequencing with an average read depth of 18,018–36,918 after pooling by site and year. Most molecular markers of resistance did not increase in frequency over the period of study (2014–2016). After 3 years of SMC, the frequencies of Pfdhps 540E, Pfdhps 437G and Pfcrt K76T remained similar compared to baseline (4.0 vs 1.4%, p = 0.41; 74.5 vs 64.6%, p = 0.22; 71.3 vs 67.4%, p = 0.69). Nearly all samples tested carried Pfdhfr 59R, and this proportion remained similar 3 years after SMC implementation (98.8 vs 100%, p = 1). The frequency of Pfmdr1 N86Y increased significantly over time from 5.6% at baseline to 18.6% after 3 years of SMC (p = 0.016). Results of pooled analysis using deep sequencing were consistent with those by individual analysis with standard PCR, but also indicated for the first time the presence of mutations at the Pfdhps A581G allele at a frequency of 11.7% after 2 years of SMC, as well as the Pfdhps I431V allele at frequencies of 1.6–9.3% following 1 and 2 years of SMC, respectively. CONCLUSION: Two and 3 years of SMC implementation were associated with increased frequency of the Pfmdr1 N86Y mutation but not Pfdhps 540E, Pfdhps 437G and Pfcrt K76T. The first-time detection of the Pfdhps haplotype bearing the I431V and A581G mutations in Mali, even at low frequency, warrants further long-term surveillance.
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spelling pubmed-88227182022-02-08 Effect of three years’ seasonal malaria chemoprevention on molecular markers of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine and amodiaquine in Ouelessebougou, Mali Mahamar, Almahamoudou Sumner, Kelsey M. Levitt, Brandt Freedman, Betsy Traore, Aliou Barry, Amadou Issiaka, Djibrilla Dembele, Adama B. Kanoute, Moussa B. Attaher, Oumar Diarra, Boubacar N. Sagara, Issaka Djimde, Abdoulaye Duffy, Patrick E. Fried, Michal Taylor, Steve M. Dicko, Alassane Malar J Research BACKGROUND: In 2012, seasonal malaria chemoprevention (SMC) was recommended as policy for malaria control by the World Health Organization (WHO) in areas of highly seasonal malaria transmission across the Sahel sub-region in Africa along with monitoring of drug resistance. We assessed the long-term impact of SMC on Plasmodium falciparum resistance to sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) over a 3-year period of SMC implementation in the health district of Ouelessebougou, Mali. METHODS: In 8 randomly selected sub-districts of Ouelessebougou, Mali, children aged 0–5 years were randomly selected during cross-sectional surveys at baseline (August 2014) and 1, 2 and 3 years post-SMC, at the beginning and end of the malaria transmission season. Blood smears and blood spots on filter paper were obtained and frequencies of mutation in P. falciparum genes related to resistance to SP and AQ (Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt) were assessed by PCR amplification on individual samples and PCR amplification followed by deep sequencing on pooled (by site and year) samples. RESULTS: At each survey, approximately 50–100 individual samples were analysed by PCR amplification and a total of 1,164 samples were analysed by deep sequencing with an average read depth of 18,018–36,918 after pooling by site and year. Most molecular markers of resistance did not increase in frequency over the period of study (2014–2016). After 3 years of SMC, the frequencies of Pfdhps 540E, Pfdhps 437G and Pfcrt K76T remained similar compared to baseline (4.0 vs 1.4%, p = 0.41; 74.5 vs 64.6%, p = 0.22; 71.3 vs 67.4%, p = 0.69). Nearly all samples tested carried Pfdhfr 59R, and this proportion remained similar 3 years after SMC implementation (98.8 vs 100%, p = 1). The frequency of Pfmdr1 N86Y increased significantly over time from 5.6% at baseline to 18.6% after 3 years of SMC (p = 0.016). Results of pooled analysis using deep sequencing were consistent with those by individual analysis with standard PCR, but also indicated for the first time the presence of mutations at the Pfdhps A581G allele at a frequency of 11.7% after 2 years of SMC, as well as the Pfdhps I431V allele at frequencies of 1.6–9.3% following 1 and 2 years of SMC, respectively. CONCLUSION: Two and 3 years of SMC implementation were associated with increased frequency of the Pfmdr1 N86Y mutation but not Pfdhps 540E, Pfdhps 437G and Pfcrt K76T. The first-time detection of the Pfdhps haplotype bearing the I431V and A581G mutations in Mali, even at low frequency, warrants further long-term surveillance. BioMed Central 2022-02-08 /pmc/articles/PMC8822718/ /pubmed/35135546 http://dx.doi.org/10.1186/s12936-022-04059-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Mahamar, Almahamoudou
Sumner, Kelsey M.
Levitt, Brandt
Freedman, Betsy
Traore, Aliou
Barry, Amadou
Issiaka, Djibrilla
Dembele, Adama B.
Kanoute, Moussa B.
Attaher, Oumar
Diarra, Boubacar N.
Sagara, Issaka
Djimde, Abdoulaye
Duffy, Patrick E.
Fried, Michal
Taylor, Steve M.
Dicko, Alassane
Effect of three years’ seasonal malaria chemoprevention on molecular markers of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine and amodiaquine in Ouelessebougou, Mali
title Effect of three years’ seasonal malaria chemoprevention on molecular markers of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine and amodiaquine in Ouelessebougou, Mali
title_full Effect of three years’ seasonal malaria chemoprevention on molecular markers of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine and amodiaquine in Ouelessebougou, Mali
title_fullStr Effect of three years’ seasonal malaria chemoprevention on molecular markers of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine and amodiaquine in Ouelessebougou, Mali
title_full_unstemmed Effect of three years’ seasonal malaria chemoprevention on molecular markers of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine and amodiaquine in Ouelessebougou, Mali
title_short Effect of three years’ seasonal malaria chemoprevention on molecular markers of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine and amodiaquine in Ouelessebougou, Mali
title_sort effect of three years’ seasonal malaria chemoprevention on molecular markers of resistance of plasmodium falciparum to sulfadoxine-pyrimethamine and amodiaquine in ouelessebougou, mali
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822718/
https://www.ncbi.nlm.nih.gov/pubmed/35135546
http://dx.doi.org/10.1186/s12936-022-04059-z
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