A clinical and molecular study of artesunate + sulphadoxine-pyrimethamine in three districts of central and eastern India

Abstract

BackgroundArtesunate + sulphadoxine-pyrimethamine (AS + SP) is recommended throughout India as the first-line treatment for uncomplicated falciparum malaria. Due to the presence of several eco-epidemiological zones of malaria and variable drug pressure, it is necessary to evaluate the efficacy of this combination in different regions of India. The objective of this study was to use clinical and molecular methods to monitor the efficacy of AS + SP in three diverse sites.MethodsThe study was undertaken in three high endemic sites of central and eastern India. Patients with uncomplicated falciparum malaria were enrolled and followed for 28 days. Molecular genotyping was conducted for merozoite surface protein (msp1 and msp2) to differentiate between re-infection and recrudescence and for the dhfr and dhps genes to monitor antifolate drug resistance.ResultsIn all, 149 patients were enrolled at the three sites. The crude cure rates were 95.9%, 100%, and 100% in Ranchi, Keonjhar, and West Garo Hills respectively. PCR-corrected cure rates were 100% at all sites. In dhfr, 27% of isolates had triple mutations, while 46% isolates were double-mutants. The most prevalent mutation was S108N followed by C59R. 164 L mutation was observed in 43/126 (34%) isolates. In dhps, most (76%) of the isolates were wild-type. Only 2.5% (2/80) isolates showed double mutation. dhfr-dhps two locus mutation were observed in 16% (13/80) isolates. Parasite clearance time was not related with antifolate mutations.ConclusionsAS + SP combination therapy remained effective against falciparum malaria despite common mutations promoting resistance to antifolate drugs. Although the prevalence of double and triple mutations in dhfr was high, the prevalence of dhfr-dhps two locus mutations were low. Even isolates with dhfr triple and dhfr-dhps two locus mutations achieved adequate clinical and parasitological response.

Prevalence of PfDHFR and PfDHPS Mutations Associated with Drug Resistance Among Pregnant Women Receiving IPTp-SP at Msambweni County Referral Hospital, Kwale County, Kenya

“…Although a study in DRC reported a conservative prevalence of 60% (23) at 59R, other studies found slightly higher prevalence (87%-98%) at this codon (10,21,22,24,26,29), compared to 78% demonstrated in this study. In agreement with our study, investigations elsewhere found a prevalence of ≥97% at 108N (10,(21)(22)(23)(24)26,27,29). In contrast to average prevalence (66%-68%) reported in India and Gabon (24,26), prevalence of >90% at PfDHPS437G was reported in this study, western Kenya and parts of central Africa.…”

“…Studies elsewhere have documented quadruple mutations (65%) in Equatorial Guinea (22) and 48% in DRC (23), and triple mutations (92%) in Gabon (24) and 61-71% in Burkina Faso (25) as the most prevalent. Similar to India, where double mutation was the most prevalent (26,27), a study in Brazil reported double mutation as most prevalent but did not find quintuple or quadruple mutations (28).…”

Comparative assessment on the prevalence of mutations in the Plasmodium falciparum drug-resistant genes in two different ecotypes of Odisha state, India

“…This is important, as treatment in case of failure to the antimalarial CQ and SP has now become very common in almost all malaria endemic regions of the globe including India (Cui et al, 2015; Klein, 2013). In Odisha, high level of resistance to both CQ and SP has been reported from many malarious districts including Keonjhar, Sundargarh, Anugul and Sambalpur districts (Mohanty et al, 2009; Peterson et al, 1988; Srivastava et al, 2013; Sutar et al, 2011), with no report from the Deogarh district.…”

Polymorphism in drug resistance genes dihydrofolate reductase and dihydropteroate synthase in Plasmodium falciparum in some states of India

“…A single mutation in pfdhfr or pfdhps gene is not enough to cause treatment failure and multiple mutation combinations in these two genes were associated with failure of SP as anti-malarial therapy [ 15 , 16 ]. Various parts of India reported single, double, triple and quadruple mutant pfdhfr gene [ 17 – 22 ]. However, double mutation at codon 59 and 108 in pfdhfr gene was predominant throughout India [ 17 – 22 ].…”