Challenges for achieving safe and effective radical cure of Plasmodium vivax: a round table discussion of the APMEN Vivax Working Group

Abstract

The delivery of safe and effective radical cure for Plasmodium vivax is one of the greatest challenges for achieving malaria elimination from the Asia–Pacific by 2030. During the annual meeting of the Asia Pacific Malaria Elimination Network Vivax Working Group in October 2016, a round table discussion was held to discuss the programmatic issues hindering the widespread use of primaquine (PQ) radical cure. Participants included 73 representatives from 16 partner countries and 33 institutional partners and other research institutes. In this meeting report, the key discussion points are presented and grouped into five themes: (i) current barriers for glucose-6-phosphate deficiency (G6PD) testing prior to PQ radical cure, (ii) necessary properties of G6PD tests for wide scale deployment, (iii) the promotion of G6PD testing, (iv) improving adherence to PQ regimens and (v) the challenges for future tafenoquine (TQ) roll out. Robust point of care (PoC) G6PD tests are needed, which are suitable and cost-effective for clinical settings with limited infrastructure. An affordable and competitive test price is needed, accompanied by sustainable funding for the product with appropriate training of healthcare staff, and robust quality control and assurance processes. In the absence of quantitative PoC G6PD tests, G6PD status can be gauged with qualitative diagnostics, however none of the available tests is currently sensitive enough to guide TQ treatment. TQ introduction will require overcoming additional challenges including the management of severely and intermediately G6PD deficient individuals. Robust strategies are needed to ensure that effective treatment practices can be deployed widely, and these should ensure that the caveats are outweighed by the benefits of radical cure for both the patients and the community. Widespread access to quality controlled G6PD testing will be critical.

Unsupervised primaquine for the treatment of Plasmodium vivax malaria relapses in southern Papua: A hospital-based cohort study

“…vivax will require practicable, safe, and effective radical cure of both blood and liver stage infections. Building stronger health systems, educating patients on the importance of treatment adherence, and supervision of therapy will be critical for improving the outcomes of primaquine radical cure for P. vivax [ 1 , 40 ]. However, ultimately, a hypnozoitocidal treatment regimen is needed, which is more amenable to high prescriber and patient adherence than the current prolonged, and potentially toxic, course of primaquine.…”

“…The primary comparison was between patients treated without primaquine and those treated with either a low or high total dose of primaquine—in other words, with a potentially curative regimen. All prespecified subgroup analyses were limited to patients receiving either no primaquine or high-dose primaquine (hospital protocol) and included: [ 1 ] individual age categories (1 to <5 years, 5 to <15 years, and ≥15 years), [ 2 ] patients initially treated as outpatients, [ 3 ] patients treated during, or 12 months before and after, the largest primaquine stock outage from July 2007 to February 2008, and [ 4 ] patients prescribed either no primaquine or a total primaquine dose greater than 7 mg/kg. Since a longer period of follow-up will result in a greater proportion of recurrent episodes of vivax malaria attributable to reinfection, subanalyses were also conducted in which follow-up was restricted to 3 months; during this period, relapsing infections will have constituted the majority of recurrences.…”

“…Primaquine is the only licensed drug known to be active against Plasmodium vivax hypnozoites. It is critically important for preventing relapses and thus reducing the global burden of vivax malaria [ 1 ]. The World Health Organization (WHO) recommends a total dose of 3.5–7 mg/kg primaquine divided over 14 days for the treatment of vivax malaria in those who are not deficient in the glucose-6-phosphate dehydrogenase (G6PD) enzyme [ 2 ].…”

Barriers to routine G6PD testing prior to treatment with primaquine

“…Guides for the interviews were developed based on discussions between national malaria program officers, malaria researchers and healthcare providers [ 19 ]. The interviews for policy makers included questions on policy, operational, regulatory, financial, and managerial aspects of G6PD acceptability and testing.…”

Approach to the Patient With Malaria

“…Female patients should be examined by quantitative spectrophotometric testing and those <70% of normal G6PD activity excluded from primaquine PART. 18 The early evidence of safety regarding G6PD-deficient patients showed a self-limiting AHA with sustained daily primaquine therapy. Those studies, however, were conducted in otherwise healthy African-American adult male volunteers with the relatively mild African A-variant of G6PD deficiency.…”