Falciparum malaria in the north of Laos: the occurrence and implications of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene haplotype SVMNT

Abstract

Summaryobjective The Pfcrt-gene encodes a transmembrane protein located in the Plasmodium falciparum digestive vacuole. Chloroquine resistant (CQR) strains of African and Southeast Asian origin carry the Pfcrt-haplotype (c72-76) CVIET, whereas most South American and Papua New Guinean CQR stains carry the SVMNT haplotype.method Eighty-eight samples from an area with reported in vivo Chloroquine and in vitro Amodiaquine-resistance were screened for the K76T mutation and their Pfcrt-haplotype (c72-76) using a new SSOP-ELISA.results Hundred percent of the analysed samples showed the K76T mutation which is highly associated with in vivo drug failure. This very high rate of a CQR-marker is alarming in an area were CQ is still used as first line drug. The distribution of the three main Pfcrt-haplotypes was as follows: 68% CVIET, 31% SVMNT, 0% CVMNT.conclusions These data show, for the first time, the South American/PNG -haplotype (SVMNT) on mainland Southeast Asia. SVMNT-haplotype and others might be associated with a decreased efficacy of Amodiaquine and could therefore be potential markers for of amodiaquine resistance (AQR). If there is a correlation between AQR and the SVMNT-haplotype as suggested, 31% prevalence of a potential resistance marker is cause for concern.

Alta frecuencia de mutaciones puntuales en pfcrt de Plasmodium falciparum y emergencia de nuevos haplotipos mutantes en Colombia

“…This concurs with reports of the distribution of this gene in other geographic regions worldwide (1,17,18).…”

Pfcrt mutant haplotypes may not correspond with chloroquine resistance

“…In recent years, in addition to the conventional in vivo and in vitro methods, the molecular markersbased approach to study and elucidate antimalarial drug resistance has proved useful [22][23][24][25][26]29,30,32]. In this study, we described the distribution of pfcrt K76T and pfmdr1 N86Y mutations in the study area and attempted to evaluate the correlation of these mutations with in vivo clinical outcomes.…”

“…In areas that have low levels of complex and multiclonal malaria infections, the inbreeding of malaria parasites having mutant genotypes could spread the antimalarial drug resistance at an extraordinary rate [28]. The prevalence of the SVMNT haplotype in highly malaria-endemic study areas indicates the wide spread of chloroquineresistant P. falciparum, which might have evolved due to prolonged use of antimalarial amodiaquine in malaria chemotherapy [29][30][31]. Studies have shown that P. falciparum mutant pfcrt haplotypes have selective advantage in competitive mosquito infections by protecting immature gametocytes from chloroquine [32].…”

Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine

“…One likely influence is the history of AQ and CQ use in these regions and the consequent selective pressure for pfcrt and pfmdr1 polymorphisms of one type or another. Haplotypes of pfcrt-encoding polymorphisms similar to those of the pfcrt alleles in South America and PNG have been reported from East Timor, Indonesia, the Philippines, Laos, India, and Iran (40)(41)(42)(43)(44)(45)(46)(47)(48)(49). In many of these regions AQ was widely used in the 1940s (50) and early 1950s before the advent of CQR (Fig.…”