Prevalence and temporal changes of mutations linked to antimalarial drug resistance in Plasmodium falciparum and Plasmodium vivax in Palawan, Philippines

Jennifer Luchavez,Alison Paolo N Bareng,Ralph Reyes,Freya Spencer,Ma Lourdes Macalinao,Chris Drakeley,Lynn Grignard,Kim Fornace,Julius Clemence R Hafalla,Fe Esperanza Espino

doi:10.1016/j.ijid.2021.12.318

Abstract

ObjectiveThis study provides 2016 data on the prevalence of key single nucleotide polymorphisms (SNPs) associated with antimalarial drug resistance in Palawan, Philippines. Findings were combined with historical data to model temporal changes in the prevalence of these SNPs in Plasmodium isolates. MethodsPlasmodium isolates were genotyped using drug resistance markers pfmdr1, pfcrt, pfdhfr, pfdhps, kelch-13, pvmdr1, pvdhfr, and pvdhps. Temporal trends in the probability of mutations were estimated as a function of time using a binomial generalised linear model. ResultsAll samples sequenced for Plasmodium falciparum chloroquine markers pfmdr1 and pfcrt had wild-type alleles. Varying mutation patterns were observed for the sulphadoxine/pyrimethamine markers pfdhps and pfdhfr; complete quintuplet mutations were not found. No SNPs were observed for the artemisinin marker kelch-13. For Plasmodium vivax, differing patterns were detected for pvmdr1, pvdhfr, and pvdhps. ConclusionsThe study findings suggest that the current drugs remain effective and that there is limited importation and establishment of resistant parasites in the area. Clear temporal trends were recognised, with prominent decreases in the proportions of pfcrt and pfmdr mutations detected within the past 15 years, consistent with a change in antimalarial drug policy. Continuous surveillance of antimalarial drug resistance is important to support malaria elimination efforts.

Highlights

Malaria remains one of the world’s greatest public health challenges, and in 2019, it was responsible for nearly 229 million cases and 409,000 deaths worldwide
In order to provide recent data for the Philippines, this study presents findings on the prevalence of mutations based on the genetic markers pfmdr1, pfcrt, pfdhfr, pfdhps, pfk13, pvmdr1, pvdhfr, and pvdhps from samples collected in the Philippines as part of a research study to employ enhanced surveillance methodologies in the country (Reyes et al, 2021)
Analysis of single nucleotide polymorphisms (SNPs) in P. falciparum resistance markers mdr1 and crt, genes associated with CQ resistance in P. falciparum, were successfully amplified and sequenced in 90 and 51 samples, respectively

Summary

Introduction

Malaria remains one of the world’s greatest public health challenges, and in 2019, it was responsible for nearly 229 million cases and 409,000 deaths worldwide. Despite current innovative strategies to accelerate global control and elimination, including in the Philippines, that have seen a huge decline in malaria cases and deaths over the past years (World Health Organization, 2019), the emergence and spread of antimalarial drug resistance threatens effective treatment in endemic countries (Menard and Dondorp, 2017). Since the late 1990s, the Philippines has monitored the efficacy of first line antimalarial drugs for P. falciparum following the WHO protocol for Therapeutic Efficacy Surveillance (TES) (UCSF Global Health Group, 2014). Drug resistance genotyping of TES isolates has been limited, results have led to revisions of the National Malaria Control Program (NMCP) treatment guidelines for falciparum malaria in 2002, from the use of CQ alone to CQ plus SP combination (UCSF Global Health Group, 2014). Based on WHO guidelines (World Health Organization, 2015), the Philippines has revised its P. vivax treatment policy from CQ to AL in 2018

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