Plasmodium falciparumresistant to chloroquine and to pyrimethamine in Comoros

Abstract

P l a s m o d iu m f a l c ip a r u m r e s is t a n t t o c h l o r o q u in e AND TO PYRIMETHAMINE IN COMOROSRANDRIANARIVELOJOSIAThis in vivo study w a s carrie d out in February an d M a rch 2 0 0 1 in M o ro n i. C h lo roq uin e treatm ent fa ile d in 2 3 children (7 6 .6 %; 9 5 % confide nce interval: 5 7 . 7 to 9 0 .1 %). Subsequent g e no typ ing show ed that all P. falciparum isolates (1 0 0 %) harboured a tyrosine residue at position 8 6 in p fM D R l. 8 3 .3 % ( 2 5 /3 0 ) o f these isolates harboured a mutation a t position 7 6 in pfCRT an d half ( 1 5 /3 0 ) of these isolates also harboured a mutation at position 1 0 8 in pfDHFR. C h lo roq uin e resistance is a real concern in the C om oros U nion. The prevalence o f pfDHFR mutant parasites is alarm ing. The alternative drugs proposed as a replacem ent for chloroquine as first-line treatm ent in C om oros, and the strategy to m onitor the drug susceptibility o f Plasm odium sp in this part of the Indian O c e a n sub-region are discussed. KEY WORDS :Comoros, chloroquine, malaria, Plasmodium falciparum, resistance. has been the recommended first-line treatment for mala ria for the last four decades. Local populations with limited income, frequently use a chloroquine auto-medi cation in case of fever. Recent reports from peripheral health districts of the archipelago (Grande Comore, Anjouan and Mohéli) have shown an increasing rate of chloroquine treatment failure, which now exceeds 30 % (Silai, unpublished data). This probably reflects increasing prevalence of chloroquine-resistant P. f a l ciparu m parasites in the Comoros. However, in order to change the national treatment policy, evidencebased information is needed. R ésu m é : R é s is t a n c e d e P l a s m o d i u m f a l c ip a r u m àComoros. Above all, the aim was to document chloroquine effectiveness and the prevalence of the pfCRT mutation K76T associated in other settings with chloroquine-resistance (Fidock et al., 2000; Djimde et al., 2001). MATERIALS AND METHODSI n vivo t e s t a n d Thirty-two children with uncomplicated P. fa lc ip a r u m malaria were included. Two were excluded during the followup, because they were given a quinine injection on Day 1 or Day 2 by a private health worker in their vil lage with parental consent because they had fever ("hot skin" according to local terminology). Thirty children (nine females and 21 males) aged between eight months and nine years (mean age: 3 .6 years; median age: 3.25 years; 95 % confidence interval: 2.78-4.42 years) were monitored for 14 days following WHO protocol (WHO, 1996). Before the administration of chloroquine on Day 0, a fingerprick blood sample was collected on filter paper. The air-dried filter paper was placed in an individual plastic bag and shipped to Institut Pasteur de Madagascar. The samples were kept at -20° C until use. DNA EXTRACTION AND PCR (POLYMERASE CHAIN r e a c t i o n )Mutations in the pfcrt and in p fm d r1 genes were detected by the Malaria Research Group at the Institut Pasteur de Madagascar in Octob...

Genetic Structure ofPlasmodium falciparumand Elimination of Malaria, Comoros Archipelago

“…However, the study of Pfcrt and Pfdhfr resistance–associated mutations differed markedly, explainable only by contrasting levels of drug selective pressure among islands. Indeed, the prevalence of the K76T mutation on the Pfcrt gene was high in both Grande Comore and Moheli as found in previous studies ( 32 , 33 ) but substantively lower in Anjouan and significantly higher in Mayotte where chloroquine use was massive during 1975–2007 ( 7 , 34 ). Similarly, the prevalence of Pfdhfr triple mutants was higher in Moheli than in Anjouan and the prevalence of Pfdhfr double or triple mutants higher in Marseille than in Grande Comore.…”

Plasmodium falciparumDrug Resistance in Madagascar: Facing the Spread of Unusualpfdhfrandpfmdr-1Haplotypes and the Decrease of Dihydroartemisinin Susceptibility

“…In vitro CQ resistance was moderate in Madagascar (29,33,45), although the level of therapeutic efficacy was declining. During that time, the rate of CQ resistance was high in the Comoros Islands (22,23,30). Likewise, pyrimethamine resistance was absent in Madagascar (28, 32) but was present at high levels in the Comoros Islands (23).…”

K13-Propeller Polymorphisms in Plasmodium falciparum Isolates from Patients in Mayotte in 2013 and 2014

“…The government of the Union of Comoros introduced artemether-lumefantrine as first-line therapy for uncomplicated P. falciparum malaria and officially withdrew the use of chloroquine and sulfadoxine-pyrimethamine in 2004 (4,5). Unfortunately, the ACT regimen did not lead to a decrease of malaria incidence, with approximately 100,000 annual malaria cases recorded from 2006 to 2012.…”