Return of chloroquine sensitivity to Africa? Surveillance of African Plasmodium falciparum chloroquine resistance through malaria imported to China

Abstract

BackgroundChloroquine (CQ) was the cornerstone of anti-malarial treatment in Africa for almost 50 years, but has been widely withdrawn due to the emergence and spread of resistance. Recent reports have suggested that CQ-susceptibility may return following the cessation of CQ usage. Here, we monitor CQ sensitivity and determine the prevalence of genetic polymorphisms in the CQ resistance transporter gene (pfcrt) of Plasmodium falciparum isolates recently imported from Africa to China.MethodsBlood samples were collected from falciparum malaria patients returning to China from various countries in Africa. Isolates were tested for their sensitivity to CQ using the SYBR Green I test ex vivo, and for a subset of samples, in vitro following culture adaptation. Mutations at positions 72–76 and codon 220 of the pfcrt gene were analyzed by sequencing and confirmed by PCR-RFLP. Correlations between drug sensitivity and pfcrt polymorphisms were investigated.ResultsOf 32 culture adapted isolates assayed, 17 (53.1%), 6 (18.8%) and 9 (28.1%) were classified as sensitive, moderately resistant, and highly resistant, respectively. In vitro CQ susceptibility was related to point mutations in the pfcrt gene, the results indicating a strong association between pfcrt genotype and drug sensitivity. A total of 292 isolates were typed at the pfcrt locus, and the prevalence of the wild type (CQ sensitive) haplotype CVMNK in isolates from East, South, North, West and Central Africa were 91.4%, 80.0%, 73.3%, 53.3% and 51.7%, respectively. The only mutant haplotype observed was CVIET, and this was almost always linked to an additional mutation at A220S.ConclusionsOur results suggest that a reduction in drug pressure following withdrawal of CQ as a first-line drug may lead to a resurgence in CQ sensitive parasites. The prevalence of wild-type pfcrt CQ sensitive parasites from East, South and North Africa was higher than from the West and Central areas, but this varied greatly between countries. Further surveillance is required to assess whether the prevalence of CQ resistant parasites will continue to decrease in the absence of widespread CQ usage.

Assessment of Plasmodium falciparum drug resistance molecular markers from the Blue Nile State, Southeast Sudan

“…Chloroquine resistance mutations is not reversible. However, when chloroquine pressure is removed sensitive strains dominate [32,33] so the low percentage may indicate this phenomenon. This percentage of resistance is still high for reinstitution of chloroquine which requires resistance level not exceeding 10% [34].…”

Efficacy of Artemisinin-lumefantrine for the treatment of uncomplicated malaria after more than a decade of its use in Kenya

“…In the early 1940s, chloroquine (CQ) was the drug of choice for the treatment of malaria in many countries having been confirmed as an anti-malarial drug with a quick metabolism, good curative effect including affordable cost [7][8][9][10]. The first case of P falciparum resistance to CQ was noted in the Thai-Cambodia border in Southeast Asia in 1957 and in 1959, the resistance observed in the Venezuela-Cambodia border in Northern South America and finally span to other countries around the world [11][12].…”

Clinical efficacy of artemisinin-lumefantrine and status of antifolate drug resistance markers in western Kenya

“…In the early 1940s, chloroquine (CQ) was the drug of choice for the treatment of malaria in many countries having been confirmed as one of the most important anti-malarial drug with quick metabolism, good curative effect including affordable cost [5][6][7][8]). Resistance to CQ on P. falciparum isolates were first observed in Thai-Cambodia border in Southeast Asia in 1957 and Venezuela-Combodia border in Northern South America in 1959 and eventually spreading to other countries around the world [9][10].…”