摘要：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 (PC
1/2), 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 PC
1/2 (> 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 PC
1/2(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 (A
16
I
51
R
59
N
108I
164–S
436
G
437K
540
G
581
T
613
) 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.
