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Photo Simone D. McCourtie, World Bank
Researchers conducted an individual patient data meta-analysis using data from 1,747 patients, across Indonesia, Brazil, Vietnam, Thailand, Peru, Colombia, Ethiopia, and India, between 2000 to 2022, to examine the utility and validity of blood methaemoglobin as a measure for people having recurrent vivax malaria.
Plasmodium vivax malaria is dangerous because parasites can lay dormant in the liver for weeks or years and then cause serious recurrence or death. The prodrugs primaquine and tafenoquine are the only available treatments to prevent relapsing malaria, but their optimal dosing remains unclear.
Analysis of the data showed that methaemoglobin levels during treatment for vivax malaria can be used to predict population-level treatment efficacy. However, further research is needed to determine if this marker can be used to predict recurrence at an individual patient level.
The paper, titled Read the publication 'Methaemoglobin as a surrogate marker of primaquine antihypnozoite activity in Plasmodium vivax malaria: a systematic review and individual patient data meta-analysis', has been published in PLOS Medicine.
Researchers observed an increasing dose-response relationship between weight-adjusted primaquine dose and methaemoglobin levels measured on day seven. They found that, for a fixed primaquine dose regimen, a doubling of day seven methaemoglobin was associated with an estimated 30% reduction in the risk of vivax recurrence. Using day seven methaemoglobin levels as a surrogate endpoint for recurrent malaria could reduce sample sizes needed in future studies by about 40% and shorten the follow-up duration by 94%.
First author Dr Ihsan Fadilah, based at Oxford University Clinical Research Unit Indonesia and Centre for Tropical Medicine and Global Health, said much more work was needed.
He said: “This study could be used to refine guidelines for the design of exploratory trials or to consider incorporating methaemoglobin measurement in malaria control programmes. It highlights a promising, measurable approach to optimise malaria treatment efficacy, which could eventually inform policy in specific settings.”