Authors

A Sinha¹; S Kar¹; L Kori¹; C Chauhan¹; CP Yadav¹;  ¹ ICMR-National Institute of Malaria Research, India

Discussion

India is on track of malaria elimination by 2030 but emerging resistance to its first line antimalarials is one of the major roadblocks. Two instances of rapid development, spread & selection of drug resistant mutant parasites have already been evidenced (Chloroquine in whole of India & Artesunate+Sulfadoxine-Pyrimethamine (AS+SP) in India’s north-eastern states).
Looking at these rapid changes in SP drug resistance conferring mutation profile of P. falciparum, it becomes evident to systematically monitor the validated mutations in Pfdhfr & Pfdhps genes across India along with the AS+SP therapeutic efficacy studies. However, unfortunately, no systematic & robust countrywide surveillance has been reported for these parameters.
Therefore, we are presenting here the first exhaustive systematic review & data synthesis on the prevalence of WHO-validated SP-resistance markers in P. falciparum across India from 2008 to date. This systematic review covers published reports from the major databases including PubMed®, Web of Science^TM, Scopus®, Embase® & Google Scholar & presents a chronology of reported events of interest across India.
A total of 37 publications that had data collected between 2008 & 2018 were included in the analysis. Pfdhfr mutation data were obtained from 3438-3801 samples & that for Pfdhps from 2891-3596 samples.
The PfDHFR double mutants were the most prevalent (55%) overall. The overall prevalence of triple & quadruple mutations was 7% & 6%, respectively. The most common PfDHPS mutation is A437G with rising & near-100% prevalence in some states. For PfDHFR/PfDHPS quintuple & sextuple mutations, despite a low overall prevalence, some states had a prevalence of >30%.
This study gains importance in light of the flags raised towards emerging ‘artemisinin-resistance’ in eastern India & brings forward the SP-resistance hot-spots & emphasizes critical gaps, challenges & suggests malaria genetic surveillance till malaria is successfully eliminated.
The key question is whether the time has come for a change from AS+SP to AL in the rest of India? The evidence for the risks needs to be weighed but taking the risk of continuing AS+SP, particularly in the light of rising flags of artemisinin-resistance might be counterproductive & the decision needs to be made sooner rather than later.