Abstract
Artemisinin is the frontline fast-acting anti-malarial against P. falciparum. Emergence and spread of resistant parasite in eastern-India poses a threat to national malaria control programs. Therefore, the objective of our study is to evaluate the artesunate-sulfadoxine-pyrimethamine efficacy in Central India. 180 monoclonal P. falciparum-infected patients received standard ASSP therapy during August 2015–January 2017, soon after diagnosis and monitored over next 42-days. Artemisinin-resistance was assessed through in-vivo parasite clearance half-life (PC1/2), ex-vivo ring-stage survivability (RSA), and genome analysis of kelch13 and other candidate gene (pfcrt, pfmdr1, pfatpase 6, pfdhfr and pfdhps). Of 180 P. falciparum positive patients, 9.5% showed increased PC1/2 (> 5.5 h), among them eleven isolates (6.1%) showed reduced sensitivity to RSA. In 4.4% of cases, parasites were not cleared by 72 h and showed prolonged PC1/2(5.6 h) (P < 0.005) along with significantly higher RSA (2.2%) than cured patients (0.4%). None of day-3 positive isolates contained the pfkelch13 mutation implicated in artemisinin resistance. Parasite recrudescence was observed in 5.6% patients, which was associated with triple dhfr–dhps (A16I51R59N108I164–S436G437K540G581T613) combination mutation. Emergence of reduced sensitivity to artesunate-sulfadoxine-pyrimethamine, in central India highlighted the risk toward spread of resistant parasite across different parts of India. Day-3 positive parasite, featuring the phenotype of artemisinin-resistance without pfkelch13 mutation, suggested kelch13-independent artemisinin-resistance.
Highlights
Artemisinin is the frontline fast-acting anti-malarial against P. falciparum
Global mortality and morbidity associated with malaria were considerably reduced after the introduction of artemisinin-based combination therapy (ACT), but emergence and subsequent spread of artemisinin-resistant parasites in the Greater Mekong sub-region had seriously threatened the global malaria control and elimination p rogress[11,12,13,14]
Artemisinin resistance is characterized by drug failure reflected in slow parasite clearance as assessed by increased in vivo parasite clearance half-life (PC1/2) along with reduced sensitivity of ex-vivo ring-stage parasites to a rtemisinin[15,16,17]
Summary
Artemisinin is the frontline fast-acting anti-malarial against P. falciparum. Emergence and spread of resistant parasite in eastern-India poses a threat to national malaria control programs. Artemisinin-resistance was assessed through in-vivo parasite clearance half-life (PC1/2), ex-vivo ring-stage survivability (RSA), and genome analysis of kelch[13] and other candidate gene (pfcrt, pfmdr[1], pfatpase 6, pfdhfr and pfdhps). Emergence of reduced sensitivity to artesunate-sulfadoxine-pyrimethamine, in central India highlighted the risk toward spread of resistant parasite across different parts of India. The emergence and spread of partial artemisinin resistant parasites were previously reported from West Bengal-an eastern state of I ndia[27,28]. Prevalence of mutations in molecular markers (pfdhfr and pfdhps) associated with partner drug resistance (sulfadoxine–pyrimethamine) was previously reported from different parts of India including central India[8,29,30,31,32,33]. The aim of this study was to critically examine the ASSP efficacy through in-vivo, ex-vivo and genome-wide variation studies in central India
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