PMID- 31852480
OWN - NLM
STAT- MEDLINE
DCOM- 20200421
LR  - 20210110
IS  - 1475-2875 (Electronic)
IS  - 1475-2875 (Linking)
VI  - 18
IP  - 1
DP  - 2019 Dec 18
TI  - Markers of sulfadoxine-pyrimethamine resistance in Eastern Democratic Republic of 
      Congo; implications for malaria chemoprevention.
PG  - 430
LID - 10.1186/s12936-019-3057-7 [doi]
LID - 430
AB  - 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/microL 
      (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.
FAU - van Lenthe, Marit
AU  - van Lenthe M
AUID- ORCID: 0000-0002-1718-3347
AD  - Medecins Sans Frontieres (MSF), Amsterdam, The Netherlands. 
      marit.van.lenthe@amsterdam.msf.org.
FAU - van der Meulen, Renske
AU  - van der Meulen R
AD  - Medecins Sans Frontieres (MSF), Amsterdam, The Netherlands.
AD  - Radboud University Medical Centre, Nijmegen, The Netherlands.
FAU - Lassovski, Maryvonne
AU  - Lassovski M
AD  - MSF, Bukavu, Democratic Republic of Congo.
FAU - Ouabo, Adelaide
AU  - Ouabo A
AD  - MSF, North Kivu, Goma, Democratic Republic of Congo.
FAU - Bakula, Edwige
AU  - Bakula E
AD  - MSF, Bukavu, Democratic Republic of Congo.
FAU - Badio, Colette
AU  - Badio C
AD  - MSF, Bukavu, Democratic Republic of Congo.
FAU - Cibenda, Deogratias
AU  - Cibenda D
AD  - Programme National de Lutte contre le Paludisme (PNLP) South Kivu, Bukavu, 
      Democratic Republic of Congo.
FAU - Okell, Lucy
AU  - Okell L
AD  - Imperial College, London, UK.
FAU - Piriou, Erwan
AU  - Piriou E
AD  - Medecins Sans Frontieres (MSF), Amsterdam, The Netherlands.
FAU - Grignard, Lynn
AU  - Grignard L
AD  - London School of Hygiene and Tropical Medicine, London, UK.
FAU - Lanke, Kjerstin
AU  - Lanke K
AD  - Radboud University Medical Centre, Nijmegen, The Netherlands.
FAU - Rao, Bhargavi
AU  - Rao B
AD  - MSF, London, UK.
FAU - Bousema, Teun
AU  - Bousema T
AD  - Radboud University Medical Centre, Nijmegen, The Netherlands.
FAU - Roper, Cally
AU  - Roper C
AD  - London School of Hygiene and Tropical Medicine, London, UK.
LA  - eng
GR  - G1002387/MRC_/Medical Research Council/United Kingdom
GR  - MR/R015600/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20191218
PL  - England
TA  - Malar J
JT  - Malaria journal
JID - 101139802
RN  - 0 (Antimalarials)
RN  - 0 (Biomarkers)
RN  - 0 (Drug Combinations)
RN  - 37338-39-9 (fanasil, pyrimethamine drug combination)
RN  - 88463U4SM5 (Sulfadoxine)
RN  - Z3614QOX8W (Pyrimethamine)
SB  - IM
MH  - Adolescent
MH  - Antimalarials/*pharmacology
MH  - Biomarkers/blood
MH  - Chemoprevention/statistics & numerical data
MH  - Child
MH  - Child, Preschool
MH  - Democratic Republic of the Congo
MH  - Drug Combinations
MH  - *Drug Resistance
MH  - Female
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Malaria/*prevention & control
MH  - Male
MH  - Plasmodium/*drug effects
MH  - Pyrimethamine/*pharmacology
MH  - Sulfadoxine/*pharmacology
PMC - PMC6921399
OTO - NOTNLM
OT  - A581G
OT  - Chemoprophylaxis
OT  - DRC
OT  - I164L
OT  - IPTi
OT  - K540E
OT  - Malaria
OT  - Sulfadoxine-pyrimethamine (SP)
OT  - dhfr
OT  - dhps
COIS- The authors declare that they have no competing interests.
EDAT- 2019/12/20 06:00
MHDA- 2020/04/22 06:00
PMCR- 2019/12/18
CRDT- 2019/12/20 06:00
PHST- 2019/07/26 00:00 [received]
PHST- 2019/12/07 00:00 [accepted]
PHST- 2019/12/20 06:00 [entrez]
PHST- 2019/12/20 06:00 [pubmed]
PHST- 2020/04/22 06:00 [medline]
PHST- 2019/12/18 00:00 [pmc-release]
AID - 10.1186/s12936-019-3057-7 [pii]
AID - 3057 [pii]
AID - 10.1186/s12936-019-3057-7 [doi]
PST - epublish
SO  - Malar J. 2019 Dec 18;18(1):430. doi: 10.1186/s12936-019-3057-7.