Roll out the radical cure with primaquine for vivax elimination: development grant

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What does it take to roll-out radical cure with primaquine regimens of vivax malaria in Cambodia, Laos, Vietnam, and Bangladesh? Without radical cure more than half of all patients with vivax malaria suffer one or often many repeated relapses. Not only does relapse cause suffering, loss of income and misery, people with relapsing malaria are also infectious and contribute to the continued transmission of vivax malaria. Vivax malaria relapse can be prevented by the administration of drug regimens which include primaquine. These drug regimens are underused because they can potentially trigger hemolysis (rupturing of red blood cells) in people with an inborn error in an enzyme (G6PD), which can be severe enough to require blood transfusions. Two important developments make it now easier to administer radical cure for vivax malaria. First, several companies have developed point-of-care sophisticated devices (biosensors) to measure G6PD enzyme activity. Using biosensors health care providers can detect patients with an enzyme deficiency and exclude them from treatment with primaquine. Second, a recent study has shown that a 7-day primaquine regimen is as safe and as good at clearing vivax malaria as the traditional 14-day drug regimen. We think that patients are more likely to complete a 7-day course than a 14-day course. These two developments, biosensors and 7-day primaquine regimens, should lead to the widespread uptake of radical cure with primaquine. However, many health care providers and the policymakers (who make the guidelines health care providers follow) are not aware of these recent developments. Furthermore, the currently available evidence may not convince them. One way to convince them may be to start discussions on the preparation and eventual results from large demonstration trials. We are planning a large trial in which all vivax patients in selected villages receive a primaquine regimen. We will compare the incidence of vivax malaria in villages where primaquine radical cure is routinely used with the incidence of vivax malaria in villages where primaquine is not used, according to current national guidelines. We expect that people with G6PD deficiency can be reliably detected at the point of care and excluded, that the primaquine regimens are well tolerated in G6PD-normal patients and that continuous treatment of vivax cases with radical cure will reduce and eventually stop the transmission of vivax malaria. The demonstration trial is a major undertaking and critically depends on the choice of an appropriate G6PD test, the right primaquine regimen, the agreement of the proposed study community and the policy makers. To make sure the conditions are promising we are proposing here the funding of a development grant. We are planning to use the grant for a multidisciplinary preparatory study. The three main component of the proposed study are: 1) To interview relevant policymakers and stakeholders on what they think of the roll-out of the radical cure and what evidence would convince them to support the roll-out. 2) We will compare the performance of the available G6PD biosensors with the traditional standard tests in the diagnosis of the enzyme deficiency and select the best-performing biosensors that can be reliably and feasibly used by village health workers. The village health workers already diagnose patients with vivax malaria using rapid diagnostic test. In addition, they will diagnose G6PD deficiency using the biosensors to make sure that biosensors are helpful in field conditions.3. We will explore which is the acceptability by health workers and patient adherence to the primaquine regimen at the village level.4) We will find out the most appropriate sites for the trial.At the end of the study we expect to have accumulated enough knowledge to undertake a large demonstration trial in our target countries.