Gametocyte Carriage, Antimalarial Use, and Drug Resistance in Cambodia, 2008-2014

Abstract

Gametocytes are the malaria parasite stages responsible for transmission from humans to mosquitoes. Gametocytemia often follows drug treatment, especially as therapies start to fail. We examined Plasmodium falciparum gametocyte carriage and drug resistance profiles among 824 persons with uncomplicated malaria in Cambodia to determine whether prevalent drug resistance and antimalarial use has led to a concentration of drug-resistant parasites among gametocyte carriers. Although report of prior antimalarial use increased from 2008 to 2014, the prevalence of study participants presenting with microscopic gametocyte carriage declined. Gametocytemia was more common in those reporting antimalarial use within the past year, and prior antimalarial use was correlated with higher IC₅₀s to piperaquine and mefloquine, as well as to increased pfmdr1 copy number. However, there was no association between microscopic gametocyte carriage and parasite drug resistance. Thus, we found no evidence that the infectious reservoir, marked by those carrying gametocytes, is enriched with drug-resistant parasites.

Figure 1.

Gametocyte prevalence (A) and reported antimalarial use (B and C) in persons presenting with uncomplicated falciparum malaria in Cambodia from 2008 to 2014. Gametocyte prevalence (gray bars) refers to the proportion of study participants with gametocytemia detected by microscopy at enrollment. Antimalarial use denotes reported usage over the previous 12-month (recent antimalarial use in the preceding 7 days (WR1576) or 28–30 days (WR1877 and WR1396 were exclusion criteria). Artemisinin-based combination therapies (ACTs) reported included dihydroartemisinin–piperaquine or artesunate–mefloquine combinations, and non-ACT use was predominantly chloroquine for vivax malaria. Artesunate and artemether were included with ACTs, whereas antimalarial use reported as unknown is denoted as missing data.

Figure 2.

Relationship of antimalarial use within the past year (A) and gametocyte carriage (B) to drug resistance profiles based on ex vivo IC₅₀s and molecular markers of resistance. Red lines mark threshold for classifying parasites as resistant based on WHO-defined cutoffs (chloroquine and mefloquine) or the upper quartile for piperaquine resistance. This figure appears in color at www.ajtmh.org.