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

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...

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Published inEmerging infectious diseases Vol. 23; no. 8; pp. 1300 - 1307
Main Authors Rutledge, Gavin G, Marr, Ian, Huang, G Khai Lin, Auburn, Sarah, Marfurt, Jutta, Sanders, Mandy, White, Nicholas J, Berriman, Matthew, Newbold, Chris I, Anstey, Nicholas M, Otto, Thomas D, Price, Ric N
Format Journal Article
LanguageEnglish
Published United States U.S. National Center for Infectious Diseases 01.08.2017
Centers for Disease Control and Prevention
Subjects
Adult
after Treatment with Artemether/Lumefantrine
Analysis
Antimalarials - therapeutic use
Artemether, Lumefantrine Drug Combination
artemether-lumefantrinem
Artemisinins - therapeutic use
DNA sequencing
Drug Combinations
Drug Resistance
Ethanolamines - therapeutic use
Fluorenes - therapeutic use
Genomes
Genomic Characterization of Recrudescent
Genomics
Health aspects
Humans
Hydroxychloroquine - therapeutic use
Infection
Malaria
Malaria - drug therapy
Malaria - parasitology
Male
parasitaemia
parasites
Plasmodium falciparum
Plasmodium malariae
Plasmodium malariae - genetics
Primaquine - therapeutic use
recrudescence
Recurrence
Australia
United Kingdom
artemether/lumefantrine
haplotype
parasitemia
parasites
recrudescence
Plasmodium malariae
Australia
malaria
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Summary: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.
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ISSN:1080-6040
1080-6059
DOI:10.3201/eid2308.161582