A molecular map of chloroquine resistance in Mali

Abstract

Plasmodium falciparum chloroquine resistance (CQR) transporter point mutation (PfCRT 76T) is known to be the key determinant of CQR. Molecular detection of PfCRT 76T in field samples may be used for the surveillance of CQR in malariaendemic countries. The genotype-resistance index (GRI), which is obtained as the ratio of the prevalence of PfCRT 76T to the incidence of CQR in a clinical trial, was proposed as a simple and practical molecular-based addition to the tools currently available for monitoring CQR in the field. In order to validate the GRI model across populations, time, and resistance patterns, we compiled data from the literature and generated new data from 12 sites across Mali. We found a mean PfCRT 76T mutation prevalence of 84.5% (range 60.9-95.1%) across all sites. CQR rates predicted from the GRI model were extrapolated onto a map of Mali to show the patterns of resistance throughout the participating regions. We present a comprehensive map of CQR in Mali, which strongly supports recent changes in drug policy away from chloroquine.

Molecular Analysis of Chloroquine and Sulfadoxine-Pyrimethamine Resistance-Associated Alleles in Plasmodium falciparum Isolates from Nicaragua

“…33 Nicaragua is an active partner in the Amazon Network for Monitoring Antimalarial Drug Resistance along with the collaboration of PAHO, and continued partnership in this network will enhance surveillance efforts to monitor emergence of CQ-and SP-resistant parasites in this region. A targeted and responsive molecular surveillance infrastructure can strengthen the overall malaria control program in areas at risk for epidemics by promptly determining if parasites harboring resistance alleles are being introduced or are circulating in the population.…”

“…Low transmission and absence of in vivo antimalarial resistance in Nicaragua mean that genotype resistance and genotype failure indices cannot be validated in this setting, as has been validated in other regions such as Mali. 33 Given the progress that Nicaragua has made towards malaria elimination in many parts of the country and the low number of P. falciparum cases in the country, a directed molecular Siuna CVMNK CNCNI SAKAA *Alleles described by amino acids in key positions for each gene as in Table 2. Amino acid changes indicating polymorphism are underlined.…”

PfCRT and its role in antimalarial drug resistance

“…This decline was most notable in Malawi, where within ten years of CQ withdrawal wild type parasites have re-expanded and parasites possessing pfcrt K76T have become undetectable by standard methods [8, 71], although minority parasite populations possessing pfcrt K76T are still circulating [72]. Household surveys from Africa reveal that pfcrt K76T rates are decreasing in areas of low CQ use, however, this drug continues to be widely used at high rates in many African countries, thus keeping mutant pfcrt (typically with the 72-76 haplotype CVIET) at fairly high levels [73-75]. Of note, other forms of mutant pfcrt (harboring the 72-76 haplotype SVMNT) remain highly prevalent in South America in the absence of CQ pressure.…”

Characterization of Plasmodium falciparum genes associated with drug resistance in Hodh Elgharbi, a malaria hotspot near Malian–Mauritanian border

“…The problem of human population movement is further compounded by the presence of populations leading a nomadic lifestyle in this agropastoral area. The situation in Mali near the border area is quite similar in terms of malaria epidemiology and chloroquine resistance [17, 18]. …”