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Single-Dose Primaquine to Block Transmission of Falciparum Malaria

Summary and Comment |
November 21, 2013

Single-Dose Primaquine to Block Transmission of Falciparum Malaria

  1. Mary E. Wilson, MD

A single dose of primaquine ≥0.4mg/kg reduced duration of gametocyte carriage; even lower doses (including the WHO-recommended 0.25 mg/kg) should be assessed.

  1. Mary E. Wilson, MD

Artemisinin combination therapy rapidly clears asexual-stage parasites but has inadequate activity against mature gametocytes, the parasite stage responsible for onward transmission. Gametocytes can persist in the blood for at least 14 days after treatment. Primaquine, the only available drug active against mature Plasmodium falciparum gametocytes, can cause dose-dependent hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. However, reduced doses may clear gametocytes.

To assess dose response and safety, investigators conducted a double-blind trial in Uganda. Children aged 1 to 10 years with uncomplicated falciparum malaria and normal G6PD levels were randomized to receive artemether–lumefantrine twice daily for 3 days, with a single dose of placebo or primaquine (0.1 mg/kg, 0.4 mg/kg, or the standard 0.75 mg/kg) on day 3. Gametocyte counts were measured for 14 days — and hemoglobin concentration for 28 days — after treatment initiation.

Among the 468 participants, the mean number of days of gametocyte carriage after treatment initiation was 6.6, 6.3, 8.0, and 12.4 for those receiving primaquine 0.75 mg/kg, 0.4 mg/kg, and 0.1 mg/kg and placebo, respectively. The mean gametocyte circulation time was significantly longer in the placebo and 0.1-mg/kg groups than in the 0.75-mg/kg group. Primaquine was not associated with hemolysis or an increase in adverse events in the study population.

Comment

The WHO has recommended the use of primaquine (at a dose recently reduced from 0.75 mg/kg to 0.25 mg/kg) along with artemisinin combination therapy in malaria-elimination programs and to interrupt the spread of artemisinin resistance. This study suggests that relatively low doses of primaquine (≥0.4 mg/kg) can speed gametocyte clearance and should block transmission, but did not assess the newly recommended 0.25-mg/kg dose. Future trials should evaluate this dose and establish whether gametocytes that persist after primaquine treatment remain infectious to mosquitoes. The authors also note that a trial of low-dose primaquine is warranted in individuals with G6PD deficiency.

  • Disclosures for Mary E. Wilson, MD at time of publication Editorial boards Clinical Infectious Diseases; Infectious Diseases in Clinical Practice; RSTMH International Health; UpToDate Leadership positions in professional societies International Society of Travel Medicine (Chair, Scientific Program Committee for 2013 Meeting)

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