title: Epidemiology of drug-resistant malaria in Republic of Congo: using molecular evidence for monitoring antimalarial drug resistance combined with assessment of antimalarial drug use.
abstract: In Congo, urgent efforts are needed to help with the revision of the national antimalarial drug policy. Despite its high resistance level, chloroquine (CQ) is still extensively used as the first-line treatment for uncomplicated Plasmodium falciparum malaria. The study was conducted in children under 5 years with uncomplicated malaria in Pointe-Noire and Brazzaville, the two largest cities that contain approximately 60% of the population of Congo. We investigated by polymerized chain reaction and sequencing methods the frequency distribution of molecular markers for antimalarial drug resistance, including mutations in P. falciparum chloroquine resistance transporter (pfcrt) gene associated with CQ resistance and mutations in dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes conferring resistance to sulphadoxine/pyrimethamine (SP) among pre-treatment P. falciparum isolates, as well as assessing antimalarial drug use in the community. pfcrt (K76T) mutation was present in most isolates (96.4%, n = 138) and high frequency (69.2%, n = 133) of triple-mutant dhfr-S108N, N51I, C59R was observed. The quintuple mutant (dhfr-S108N, N51I, C59R and dhps-A437G or S436A, K540E) considered as molecular marker for SP treatment failure was not found because dhps-K540E mutation was absent in isolates tested; this is a clear evidence for the excellent efficacy of SP that we previously described in the same population. The complete absence of the dhps-K540E mutation is a deterrent component for using this molecular marker as an early warning tool for SP resistance testing in that population. Poor compliance issues related to the antimalarial drug use including inappropriate manufacturing practices reported in this study require intensive attention and should be taken into account when implementing drug policy change. If Congo changes its treatment policy from CQ to SP monotherapy, this will not last long. The strategy of combining SP with other affordable and effective antimalarial drugs such as the artemisinin derivatives to improve efficacy and to delay the development of parasite resistance is essential.
authors.affiliation: National Malaria Control Programme, Division for Disease Control, Ministry of Health, Brazzaville, Congo. basilensimba@aol.com
authors.forename: Basile
authors.initials: B
authors.lastname: Nsimba
authors.forename: Sayeh
authors.initials: S
authors.lastname: Jafari-Guemouri
authors.forename: David A
authors.initials: DA
authors.lastname: Malonga
authors.forename: André M
authors.initials: AM
authors.lastname: Mouata
authors.forename: Jeannine
authors.initials: J
authors.lastname: Kiori
authors.forename: Frédéric
authors.initials: F
authors.lastname: Louya
authors.forename: Dominique
authors.initials: D
authors.lastname: Yocka
authors.forename: Maurice
authors.initials: M
authors.lastname: Malanda
authors.forename: Rémy
authors.initials: R
authors.lastname: Durand
authors.forename: Jacques
authors.initials: J
authors.lastname: Le Bras
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use; D003223:Congo / Q000453:epidemiology; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009154:Mutation; D010349:Patient Compliance; D016133:Polymerase Chain Reaction / Q000379:methods; D015995:Prevalence; D015800:Protozoan Proteins; D011739:Pyrimethamine / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D016896:Treatment Outcome; D014504:Urban Health
chemical_list: D000962:Antimalarials; D015415:Biomarkers; D004338:Drug Combinations; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine