Genomic Characterization of Recrudescent Plasmodium malariae after Treatment with Artemether/Lumefantrine

Emerg Infect Dis. 2017 Aug;23(8):1300-1307. doi: 10.3201/eid2308.161582. Epub 2017 Aug 15.

Abstract

Plasmodium malariae is the only human malaria parasite species with a 72-hour intraerythrocytic cycle and the ability to persist in the host for life. We present a case of a P. malariae infection with clinical recrudescence after directly observed administration of artemether/lumefantrine. By using whole-genome sequencing, we show that the initial infection was polyclonal and the recrudescent isolate was a single clone present at low density in the initial infection. Haplotypic analysis of the clones in the initial infection revealed that they were all closely related and were presumably recombinant progeny originating from the same infective mosquito bite. We review possible explanations for the P. malariae treatment failure and conclude that a 3-day artemether/lumefantrine regimen is suboptimal for this species because of its long asexual life cycle.

Keywords: Australia; Plasmodium malariae; artemether/lumefantrine; haplotype; malaria; parasitemia; parasites; recrudescence.

MeSH terms

  • Adult
  • Antimalarials / therapeutic use*
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins / therapeutic use*
  • Drug Combinations
  • Drug Resistance
  • Ethanolamines / therapeutic use*
  • Fluorenes / therapeutic use*
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Malaria / drug therapy*
  • Malaria / parasitology*
  • Male
  • Plasmodium malariae* / genetics
  • Primaquine / therapeutic use
  • Recurrence

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins
  • Drug Combinations
  • Ethanolamines
  • Fluorenes
  • Hydroxychloroquine
  • Primaquine