We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs.
In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.
Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate.
P. falciparum gametocytes may persist after treatment with sulphadoxine-pyrimethamine (SP) plus artesunate (AS) and contribute considerably to malaria transmission. We determined the efficacy of SP+AS plus a single dose of primaquine (PQ, 0.75 mg/kg) on clearing gametocytaemia measured by molecular methods.
                The study was conducted in Mnyuzi, an area of hyperendemic malaria in north-eastern Tanzania. Children aged 3-15 years with uncomplicated P. falciparum malaria with an asexual parasite density between 500-100,000 parasites/microL were randomized to receive treatment with either SP+AS or SP+AS+PQ. P. falciparum gametocyte prevalence and density during the 42-day follow-up period were determined by real-time nucleic acid sequence-based amplification (QT-NASBA). Haemoglobin levels (Hb) were determined to address concerns about haemolysis in G6PD-deficient individuals.
                108 individuals were randomized. Pfs25 QT-NASBA gametocyte prevalence was 88-91% at enrolment and decreased afterwards for both treatment arms. Gametocyte prevalence and density were significantly lower in children treated with SP+AS+PQ. On day 14 after treatment 3.9% (2/51) of the SP+AS+PQ treated children harboured gametocytes compared to 62.7% (32/51) of those treated with SP+AS (p<0.001). Hb levels were reduced in the week following treatment with SP+AS+PQ and this reduction was related to G6PD deficiency. The Hb levels of all patients recovered to pre-treatment levels or greater within one month after treatment.
                PQ clears submicroscopic gametocytes after treatment with SP+AS and the persisting gametocytes circulated at densities that are unlikely to contribute to malaria transmission. For individuals without severe anaemia, addition of a single dose of PQ to an efficacious antimalarial drug combination is a safe approach to reduce malaria transmission following treatment.
                Controlled-Trials.com ISRCTN61534963.