Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention
Abstract Background Sulfadoxine–pyrimethamine (SP) is a cornerstone of malaria chemoprophylaxis and is considered for programmes in the Democratic Republic of Congo (DRC). However, SP efficacy is threatened by drug resistance, that is conferred by mutations in the dhfr and dhps genes. The World Heal...
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doaj-43dc475688694ee4afe33ba734387cbc2020-12-20T12:39:01ZengBMCMalaria Journal1475-28752019-12-011811910.1186/s12936-019-3057-7Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemopreventionMarit van Lenthe0Renske van der Meulen1Maryvonne Lassovski2Adelaide Ouabo3Edwige Bakula4Colette Badio5Deogratias Cibenda6Lucy Okell7Erwan Piriou8Lynn Grignard9Kjerstin Lanke10Bhargavi Rao11Teun Bousema12Cally Roper13Médecins Sans Frontières (MSF)Médecins Sans Frontières (MSF)MSFMSFMSFMSFProgramme National de Lutte contre le Paludisme (PNLP) South KivuImperial CollegeMédecins Sans Frontières (MSF)London School of Hygiene and Tropical MedicineRadboud University Medical CentreMSFRadboud University Medical CentreLondon School of Hygiene and Tropical MedicineAbstract Background Sulfadoxine–pyrimethamine (SP) is a cornerstone of malaria chemoprophylaxis and is considered for programmes in the Democratic Republic of Congo (DRC). However, SP efficacy is threatened by drug resistance, that is conferred by mutations in the dhfr and dhps genes. The World Health Organization has specified that intermittent preventive treatment for infants (IPTi) with SP should be implemented only if the prevalence of the dhps K540E mutation is under 50%. There are limited current data on the prevalence of resistance-conferring mutations available from Eastern DRC. The current study aimed to address this knowledge gap. Methods Dried blood-spot samples were collected from clinically suspected malaria patients [outpatient department (OPD)] and pregnant women attending antenatal care (ANC) in four sites in North and South Kivu, DRC. Quantitative PCR (qPCR) was performed on samples from individuals with positive and with negative rapid diagnostic test (RDT) results. Dhps K450E and A581G and dhfr I164L were assessed by nested PCR followed by allele-specific primer extension and detection by multiplex bead-based assays. Results Across populations, Plasmodium falciparum parasite prevalence was 47.9% (1160/2421) by RDT and 71.7 (1763/2421) by qPCR. Median parasite density measured by qPCR in RDT-negative qPCR-positive samples was very low with a median of 2.3 parasites/µL (IQR 0.5–25.2). Resistance genotyping was successfully performed in RDT-positive samples and RDT-negative/qPCR-positive samples with success rates of 86.2% (937/1086) and 55.5% (361/651), respectively. The presence of dhps K540E was high across sites (50.3–87.9%), with strong evidence for differences between sites (p < 0.001). Dhps A581G mutants were less prevalent (12.7–47.2%). The dhfr I164L mutation was found in one sample. Conclusions The prevalence of the SP resistance marker dhps K540E exceeds 50% in all four study sites in North and South Kivu, DRC. K540E mutations regularly co-occurred with mutations in dhps A581G but not with the dhfr I164L mutation. The current results do not support implementation of IPTi with SP in the study area.https://doi.org/10.1186/s12936-019-3057-7MalariaDRCSulfadoxine–pyrimethamine (SP)Chemoprophylaxisdhpsdhfr |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marit van Lenthe Renske van der Meulen Maryvonne Lassovski Adelaide Ouabo Edwige Bakula Colette Badio Deogratias Cibenda Lucy Okell Erwan Piriou Lynn Grignard Kjerstin Lanke Bhargavi Rao Teun Bousema Cally Roper |
spellingShingle |
Marit van Lenthe Renske van der Meulen Maryvonne Lassovski Adelaide Ouabo Edwige Bakula Colette Badio Deogratias Cibenda Lucy Okell Erwan Piriou Lynn Grignard Kjerstin Lanke Bhargavi Rao Teun Bousema Cally Roper Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention Malaria Journal Malaria DRC Sulfadoxine–pyrimethamine (SP) Chemoprophylaxis dhps dhfr |
author_facet |
Marit van Lenthe Renske van der Meulen Maryvonne Lassovski Adelaide Ouabo Edwige Bakula Colette Badio Deogratias Cibenda Lucy Okell Erwan Piriou Lynn Grignard Kjerstin Lanke Bhargavi Rao Teun Bousema Cally Roper |
author_sort |
Marit van Lenthe |
title |
Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention |
title_short |
Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention |
title_full |
Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention |
title_fullStr |
Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention |
title_full_unstemmed |
Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention |
title_sort |
markers of sulfadoxine–pyrimethamine resistance in eastern democratic republic of congo; implications for malaria chemoprevention |
publisher |
BMC |
series |
Malaria Journal |
issn |
1475-2875 |
publishDate |
2019-12-01 |
description |
Abstract Background Sulfadoxine–pyrimethamine (SP) is a cornerstone of malaria chemoprophylaxis and is considered for programmes in the Democratic Republic of Congo (DRC). However, SP efficacy is threatened by drug resistance, that is conferred by mutations in the dhfr and dhps genes. The World Health Organization has specified that intermittent preventive treatment for infants (IPTi) with SP should be implemented only if the prevalence of the dhps K540E mutation is under 50%. There are limited current data on the prevalence of resistance-conferring mutations available from Eastern DRC. The current study aimed to address this knowledge gap. Methods Dried blood-spot samples were collected from clinically suspected malaria patients [outpatient department (OPD)] and pregnant women attending antenatal care (ANC) in four sites in North and South Kivu, DRC. Quantitative PCR (qPCR) was performed on samples from individuals with positive and with negative rapid diagnostic test (RDT) results. Dhps K450E and A581G and dhfr I164L were assessed by nested PCR followed by allele-specific primer extension and detection by multiplex bead-based assays. Results Across populations, Plasmodium falciparum parasite prevalence was 47.9% (1160/2421) by RDT and 71.7 (1763/2421) by qPCR. Median parasite density measured by qPCR in RDT-negative qPCR-positive samples was very low with a median of 2.3 parasites/µL (IQR 0.5–25.2). Resistance genotyping was successfully performed in RDT-positive samples and RDT-negative/qPCR-positive samples with success rates of 86.2% (937/1086) and 55.5% (361/651), respectively. The presence of dhps K540E was high across sites (50.3–87.9%), with strong evidence for differences between sites (p < 0.001). Dhps A581G mutants were less prevalent (12.7–47.2%). The dhfr I164L mutation was found in one sample. Conclusions The prevalence of the SP resistance marker dhps K540E exceeds 50% in all four study sites in North and South Kivu, DRC. K540E mutations regularly co-occurred with mutations in dhps A581G but not with the dhfr I164L mutation. The current results do not support implementation of IPTi with SP in the study area. |
topic |
Malaria DRC Sulfadoxine–pyrimethamine (SP) Chemoprophylaxis dhps dhfr |
url |
https://doi.org/10.1186/s12936-019-3057-7 |
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