Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention

Autor: Maryvonne Lassovski, Renske van der Meulen, Bhargavi Rao, Colette Badio, Edwige Bakula, Teun Bousema, Lynn Grignard, Cally Roper, Marit van Lenthe, Deogratias Cibenda, Lucy C Okell, Adelaide Ouabo, Kjerstin Lanke, Erwan Piriou
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Plasmodium
Drug Resistance
DHPS
Drug resistance
Chemoprophylaxis
THERAPY
0302 clinical medicine
Sulfadoxine–pyrimethamine (SP)
1108 Medical Microbiology
I164L
Outpatient clinic
Medicine
dhfr
030212 general & internal medicine
Child
MUTATION
INTERMITTENT PREVENTIVE TREATMENT
Rapid diagnostic test
PLASMODIUM-FALCIPARUM
biology
3. Good health
Drug Combinations
PREGNANCY
Infectious Diseases
Pyrimethamine
Child
Preschool
Democratic Republic of the Congo
Female
Life Sciences & Biomedicine
0605 Microbiology
medicine.drug
AFRICA
lcsh:Arctic medicine. Tropical medicine
Adolescent
lcsh:RC955-962
030231 tropical medicine
MOLECULAR MARKERS
Chemoprevention
1117 Public Health and Health Services
lcsh:Infectious and parasitic diseases
03 medical and health sciences
dhps
Antimalarials
All institutes and research themes of the Radboud University Medical Center
Tropical Medicine
parasitic diseases
Sulfadoxine
Humans
lcsh:RC109-216
Genotyping
DRUG-RESISTANCE
Science & Technology
business.industry
Research
Infant
Newborn
DRC
Infant
Plasmodium falciparum
A581G
biology.organism_classification
medicine.disease
Virology
Sulfadoxine/pyrimethamine
Malaria
K540E
IPTi
Sulfadoxine-pyrimethamine (SP)
lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4]
Parasitology
business
Biomarkers
Zdroj: Malaria Journal
Malaria Journal, 18, 1
Malaria Journal, Vol 18, Iss 1, Pp 1-9 (2019)
Malaria Journal, 18
Malar J
ISSN: 1475-2875
Popis: 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 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.
Databáze: OpenAIRE
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