Resistance to Antimalarial Monotherapy Is Cyclic.

Rachel Weitzman,Abraham O Samson,Naamah Bloch,Avi Rosenfeld,Ortal Calfon-Peretz,Moshe Amitay,Karin Ben Zaken,Trishna Saha

doi:10.3390/jcm11030781

Rachel Weitzman, Abraham O Samson + Show 6 more

Open Access

https://doi.org/10.3390/jcm11030781

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Abstract

Malaria is a prevalent parasitic disease that is estimated to kill between one and two million people—mostly children—every year. Here, we query PubMed for malaria drug resistance and plot the yearly citations of 14 common antimalarials. Remarkably, most antimalarial drugs display cyclic resistance patterns, rising and falling over four decades. The antimalarial drugs that exhibit cyclic resistance are quinine, chloroquine, mefloquine, amodiaquine, artesunate, artemether, sulfadoxine, doxycycline, halofantrine, piperaquine, pyrimethamine, atovaquone, artemisinin, and dihydroartemisinin. Exceptionally, the resistance of the two latter drugs can also correlate with a linear rise. Our predicted antimalarial drug resistance is consistent with clinical data reported by the Worldwide Antimalarial Resistance Network (WWARN) and validates our methodology. Notably, the cyclical resistance suggests that most antimalarial drugs are sustainable in the end. Furthermore, cyclic resistance is clinically relevant and discourages routine monotherapy, in particular, while resistance is on the rise. Finally, cyclic resistance encourages the combination of antimalarial drugs at distinct phases of resistance.

Highlights

Malaria is a pernicious parasitic infection transmitted by anopheline mosquitoes
Drug resistance is partially alleviated through combination therapy of antimalarials, and Artemisinin-based combination therapies (ACTs) have been recommended by the World Health Organization (WHO) as a first-line treatment for P. falciparum malaria in countries where resistance has compromised the efficacy of other drugs [2]
Resistance to ACTs has increased in western Cambodia, which could be disastrous for global malaria control [3]

Summary

Introduction

Malaria is a pernicious parasitic infection transmitted by anopheline mosquitoes. Four species of Plasmodium commonly infect humans, but only one, Plasmodium falciparum (P.falciparum), accounts for most cases of morbidity and mortality [1]. Malaria is a pernicious parasitic infection transmitted by anopheline mosquitoes. Drug resistance has emerged in all classes of antimalarials, and it is responsible for considerable malaria-related mortality, on the African continent. Drug resistance is partially alleviated through combination therapy of antimalarials, and Artemisinin-based combination therapies (ACTs) have been recommended by the World Health Organization (WHO) as a first-line treatment for P. falciparum malaria in countries where resistance has compromised the efficacy of other drugs [2]. Resistance to ACTs has increased in western Cambodia, which could be disastrous for global malaria control [3]. Drug resistance is a survival mechanism through which the Plasmodium parasite endures, and several drug resistance mechanisms have been reported [5]

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