Directly observed therapy for anti-relapse primaquine treatment

It worked. Really well.

Vivax malaria can relapse from liver stages (hypnozoites) adding to patient burden and further transmission. In tropical settings, upwards of 50-80% of patients may relapse within 1-3 months of the primary infection. Treating the dormant liver stages, which are unaffected by standard therapies, requires 14 days of treatment with primaquine. Adherence to therapy is generally regarded as poor – patients already feel better from the main therapy, primaquine has a number of side effects, and daily dosing for two weeks is a long regimen. Explaining the rationale for the therapy is important to ensure adherence but many health workers have little training or time for counseling and, in my experience, often altogether skip it.

Directly observed therapy (DOT) is exactly what it sounds like. It can be resource intensive but is a proven strategy for ensuring complete and effective treatment (particularly in tuberculosis control efforts). The powerhouse Mahidol University tropical diseases group conducted a randomized study of DOT primaquine in Thailand and followed the patients closely over the next three months to look for new infections.

Among those receiving DOT with primaquine the incidence rate of vivax malaria during follow-up was 3.4 cases / 10,000 person-days while in the self-administered group the rate of vivax was 13.5 cases / 10,000 person-days. No serious adverse events were reported. A quick number needed to treat calculation (with some assumptions about risks) reveals that in this setting the use of DOT primaquine in just 11 cases prevented 1 additional case over three months. The authors note the (already impressive) effect of DOT on subsequent P. vivax appearance is likely an underestimate. The self-administered adherence is inflated compared to the real world. Patients are more compliant under trial conditions (they know they are being studied) and a study follow-up visit at day 7 serves as a convenient reminder halfway through the treatment.

Takeuchi et al. also examined risk factors for vivax malaria reappearance and unfortunately devoted the entire discussion to these findings. I think more conversation about the DOT strategy itself – around questions of when, where, and how to use it in program settings – is the true point of interest in this work.

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