Paving the way for universal radical cure

P. vivax forms dormant liver stages (hypnozoites) that reactivate weeks or months following an acute infection. Recurrent infections can be associated with a febrile illness, a cumulative risk of severe anaemia, direct and indirect mortality and are the most important source of onward transmission of the parasite. The only hypnozoitocidal drug that is widely available is primaquine (PQ), which can potentially cause severe drug-induced haemolysis in glucose-6-dehydrogenese (G6PD) deficient patients. The risk of haemolysis after PQ depends on the dose administered and the G6PD activity of the individual exposed. The risk of serious haemolysis associated with G6PD deficiency makes clinicians reluctant to prescribe PQ without prior testing, which is often unavailable. In many locations the effectiveness of the 14-day unsupervised PQ treatment is extremely poor, resulting in a high risk of relapse. The recent FDA and TGA approval of tafenoquine (TQ), a single dose radical cure, provides the opportunity to overcome low adherence, however introduction into endemic markets will not happen in the near future. In the meantime PQ remains the drug of choice and efforts to shorten treatment regimens while maintaining efficacy and safety have been proven successful and provide an opportunity to increase adherence. In the recently completed IMPROV trial we showed that a 7-day high dose PQ course is non-inferior to a 14-day course in preventing P. vivax recurrences. Further there is a strong rationale for eradicating P. vivax hypnozoites from the liver in patients presenting with uncomplicated P. falciparum infection in co-endemic regions, potentially expanding the target population for radical cure and making a case for universal radical cure.

The recently completed IMPROV trial and studies planned for 2019 which aim to evaluate prospectively the benefit of radical cure in P. falciparum patients provide the network and opportunity for a larger scale follow up study to assess the effectiveness of a shortened high dose PQ course as universal radical cure. This however requires preparatory data collection to ensure usefulness of outcomes for national malaria control programs and a better understanding of the potential impact.

1. Suitable partners will be identified based on previous studies and new collaborators will be approached. Suggested sites will undergo a feasibility assessment, that will include but is not limited to i) review of hospital/health facility records to ensure co-endemicity of P. vivax and P. falciparum, ii) review of healthcare facility capacity to identify patients who are returning for care (e.g. through patient ID cards) and iii) evidence of a high proportion of health seeking behaviour at the participating facility.
2. Surveillance data will be collected retrospectively in at least 4 of the selected sites in Indonesia and PNG and will be used to estimate the risks of patient representing with P. vivax after initial vivax infection as well as the risk of patients presenting with P. vivax after P. falciparum infection. This will inform the study design for a large cluster randomized effectiveness study.
3. A series of interviews with national malaria control programs will be conducted in the first half of 2019 via phone/skype. Additional face to face interviews will be conducted in conjunction with the annual meeting of the Vivax Working Group (VxWG) of the Asia Pacific Malaria Elimination Network (APMEN). Interviews are aimed to gain a better understanding of individual country requirements and what additional evidence country partners need to introduce universal radical cure. We will aim to recruit a master student to support this activity.

Drug-based Strategies
P. vivax

Nov 2018 — Oct 2023

$15,000

Asia, Eastern
Asia, Southeastern
Asia, Southern
Oceania

Australian Centre for Research Excellence in Malaria Elimination (ACREME)