In the Journals

Added primaquine reduced gametocyte carriage in P. falciparum malaria

Patients from Senegal who were treated with primaquine for Plasmodium falciparum malaria showed significantly lower gametocyte carriage compared with those who received artemisinin combination therapy alone, according to recently published findings.

However, hemoglobin concentrations fell more among patients who were glucose-6-phosphate dehydrogenase-deficient than in those who were not.

“WHO recommends the addition of a single low-dose of primaquine (0.25 mg/kg) to artemisinin combination therapy for treatment of uncomplicated Plasmodium falciparum malaria as a component of pre-elimination or elimination programs,” Roger C. Tine, of the department of medical parasitology and faculty of medicine, University Cheikh Anta Diop, Dakar, Senegal, and colleagues wrote. “Primaquine has been used for over 60 years in treating Plasmodium vivax and as a P. falciparum gametocytocide. However, countries in sub-Saharan Africa have been reluctant to use primaquine due to a lack of evidence about safety of the low-dose regimen in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency.”

Tine and colleagues randomly assigned 274 patients with Plasmodium falciparum malaria to receive either an artemisinin combination therapy alone (n = 139) or with primaquine (n = 135). The researchers used a rapid test to determine patients’ G6PD status, and followed patients for 28 days to record gametocyte carriage, adverse events and hemoglobin concentration. The main endpoint was change in hemoglobin after 7 days.

Twenty percent (n = 52) of patients were G6PD deficient. At 7 days, both groups showed similar hemoglobin reductions, with a –0.04 g/dL difference in the artemisinin plus primaquine group compared with the artemisinin alone group (95% CI, –0.23 to 0.31), the researchers reported.

Primaquine showed different effects by G6PD status. In G6PD-deficient patients who received primaquine, hemoglobin dropped by a mean of 0.63 g/dL more than in those who received artemisinin combination therapy alone (95% CI, 0.03-1.24), Tine and colleagues wrote. In patients with normal G6PD status who received primaquine, however, the mean reduction in hemoglobin was 0.22 g/dL less than in those who did not (95% CI, –0.08 to 0.52; P = .01).

One patient with normal G6PD status developed moderately severe anemia after treatment with primaquine (Hb < 8 g/dL). A more common adverse effect was dark urine. Overall, primaquine was associated with a significant reduction in gametocyte carriage: 1.08 days in the artemisinin alone group compared with 0.29 in the primaquine group, a 73% reduction (95% CI, 24%-90%).

“This study provides additional evidence that the currently recommended single dose of primaquine is well-tolerated,” the researchers wrote. “However, the way in which primaquine should be delivered in elimination settings is still under debate. Further studies are therefore needed in order to determine the tolerability and acceptability of low-dose primaquine in [mass drug administration] programs, and in patients with [hemoglobin] lower than 8g/dL. Additional safety data on vulnerable groups may be needed to support the use of primaquine in elimination programs in Africa.” – by Andy Polhamus

Disclosure: The researchers report no relevant financial disclosures.

Patients from Senegal who were treated with primaquine for Plasmodium falciparum malaria showed significantly lower gametocyte carriage compared with those who received artemisinin combination therapy alone, according to recently published findings.

However, hemoglobin concentrations fell more among patients who were glucose-6-phosphate dehydrogenase-deficient than in those who were not.

“WHO recommends the addition of a single low-dose of primaquine (0.25 mg/kg) to artemisinin combination therapy for treatment of uncomplicated Plasmodium falciparum malaria as a component of pre-elimination or elimination programs,” Roger C. Tine, of the department of medical parasitology and faculty of medicine, University Cheikh Anta Diop, Dakar, Senegal, and colleagues wrote. “Primaquine has been used for over 60 years in treating Plasmodium vivax and as a P. falciparum gametocytocide. However, countries in sub-Saharan Africa have been reluctant to use primaquine due to a lack of evidence about safety of the low-dose regimen in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency.”

Tine and colleagues randomly assigned 274 patients with Plasmodium falciparum malaria to receive either an artemisinin combination therapy alone (n = 139) or with primaquine (n = 135). The researchers used a rapid test to determine patients’ G6PD status, and followed patients for 28 days to record gametocyte carriage, adverse events and hemoglobin concentration. The main endpoint was change in hemoglobin after 7 days.

Twenty percent (n = 52) of patients were G6PD deficient. At 7 days, both groups showed similar hemoglobin reductions, with a –0.04 g/dL difference in the artemisinin plus primaquine group compared with the artemisinin alone group (95% CI, –0.23 to 0.31), the researchers reported.

Primaquine showed different effects by G6PD status. In G6PD-deficient patients who received primaquine, hemoglobin dropped by a mean of 0.63 g/dL more than in those who received artemisinin combination therapy alone (95% CI, 0.03-1.24), Tine and colleagues wrote. In patients with normal G6PD status who received primaquine, however, the mean reduction in hemoglobin was 0.22 g/dL less than in those who did not (95% CI, –0.08 to 0.52; P = .01).

One patient with normal G6PD status developed moderately severe anemia after treatment with primaquine (Hb < 8 g/dL). A more common adverse effect was dark urine. Overall, primaquine was associated with a significant reduction in gametocyte carriage: 1.08 days in the artemisinin alone group compared with 0.29 in the primaquine group, a 73% reduction (95% CI, 24%-90%).

“This study provides additional evidence that the currently recommended single dose of primaquine is well-tolerated,” the researchers wrote. “However, the way in which primaquine should be delivered in elimination settings is still under debate. Further studies are therefore needed in order to determine the tolerability and acceptability of low-dose primaquine in [mass drug administration] programs, and in patients with [hemoglobin] lower than 8g/dL. Additional safety data on vulnerable groups may be needed to support the use of primaquine in elimination programs in Africa.” – by Andy Polhamus

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Disclosure: The researchers report no relevant financial disclosures.