Antimalarial Drug Resistance of Plasmodium falciparum in northwest Madagascar

Alysala Malik, VP&S Class of 2025

Name: Alysala Malik
School: Vagelos College of Physicians & Surgeons, Class of 2025
Mentor: David Fidock, PhD and Milijaona Randrianarivelojosia, PhD

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Malaria parasites, notably Plasmodium falciparum, are among the top five causes of mortality in Madagascar. Following widespread parasite resistance to chloroquine in the 1970s, artemisinin-based combination therapies were adopted as first-line treatment worldwide. However artemisinin efficacy is now threatened by emerging resistance, and monitoring is crucial to a unified global effort to monitor resistance patterns and inform drug policy. This collaboration with the Institut Pasteur de Madagascar (IPM) was initiated to test for the emergence of drug- resistant P. falciparum parasites in northwest Madagascar. Capacity strengthening of the Parasitology Unit at IPM was a major focus, with the aim of creating a sustainable system of collecting Plasmodium isolates, culture- adapting parasite lines, and amplifying the genes of pfmdr1, pfk13, and most importantly pfcrt for which resistance to piperaquine is mediated via point mutations. Plasmodium sp isolates were collected at a primary health center in Antanimbary, Madagascar (284 km northwest of Antananarivo). Venous blood samples arrived in Antananarivo within 24 hours and the species of Plasmodium infection was determined by microscopy. Samples presenting singularly with P. falciparum and with a parasitemia > 0.2% were placed into culture. Following RNA extraction and cDNA synthesis, reverse-transcriptase PCR was performed to amplify the drug resistance-associated genes of pfcrt, pfmdr1, and pfk13. Samples were sent to GenoScreen in France and sequences are currently being analyzed. Next steps are to assess ex-vivo drug susceptibilities to artemisinin derivatives and their partner drugs used in current combination therapies to identify mutations causal for drug resistance and loss of drug efficacy.