Post-doctoral fellow Ashenafi Assefa, PhD, and Jonathan Parr, MD, MPH, assistant professor of medicine in infectious diseases, researchers with the Institute for Global Health and Infectious Diseases (IGHID) working in the IDEEL (the Infectious Disease Epidemiology and Ecology) Lab assess the pros and cons of a new strategy to simplify malaria treatment, both published today in The Lancet.
The majority of malaria cases worldwide are caused by Plasmodium falciparum and P. vivax. Unlike P. falciparum, P. vivax can form hypnozoites, dormant parasites in the liver that can reactivate weeks or months following an acute infection. The World Health Organization currently recommends addition of treatment with primaquine to eliminate the liver stage, also known as ‘radical cure.’ But this treatment may cause toxicity in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetic disorder that affects red blood cells.
In a trial published today in The Lancet, K. Thiemer and colleagues from the Menzies School of Health Research and Charles Darwin University designed a novel strategy to simplify malaria treatment in co-endemic areas, by assessing the use of primaquine radical cure in P. falciparum patients, in an effort to reduce the risk of subsequent P. vivax.
Post-doctoral fellow Ashenafi Assefa, PhD, and Jonathan Parr, MD, MPH, assistant professor of medicine in infectious diseases, researchers with the Institute for Global Health and Infectious Diseases (IGHID) working in the IDEEL (the Infectious Disease Epidemiology and Ecology) Lab, assessed the pros and cons of this new strategy that links P. vivax anti-relapse therapy to the routine treatment of uncomplicated P. falciparummalaria. Their review was also published today in The Lancet.
“In my home country Ethiopia, people often consider the two species differently, viewing P. vivax as a mild chronic infection and P. falciparum as a dangerous emergency,” explained Assefa. “However, we know P. vivax malaria can cause severe complications and have important implications for school and work absenteeism.”
The randomized controlled trial analyzed 495 participants from Bangladesh, Indonesia, and Ethiopia. Participants received routine artemisinin-combination therapy for P. falciparum, and were randomized to receive a 0.25 mg/kg single dose of primaquine to prevent onward transmission of P. falciparum, or a 1 mg/kg per day high-dose radical cure regimen for 7 days.
In participants with at least 70% (G6PD) enzyme activity, the strategy significantly reduced the incidence of P. vivax infection (from 11% to 25%) and hemolysis. Participants only reported relatively mild gastrointestinal toxicity and complaints, probably a result of primaquine administration with food provided by study staff.
“Thoughtful, cross-cutting strategies are critical to malaria elimination efforts,” said Parr. Linking P. vivax radical cure to routine P. falciparum management offers efficiencies when used in the right context.”
But while the trial’s results are encouraging, Ashenafi and Parr note challenges for real-world implementation in settings like Ethiopia, where the majority of the study participants were enrolled. These include logistical challenges and costs associated with screening each patient. They also acknowledge that proper storage of materials, quality monitoring, and training are crucial to avoid diagnostic errors that can lead to life-threatening toxicity. Adherence is another challenge because many patients will stop short of even a shortened 7-day regimen for P. vivax radical cure if malaria symptoms improve after starting artemisinin combination therapy. Furthermore, the effectiveness of primaquine for radical cure has previously been shown to wane in the absence of directly observed therapy, as was done during the trial.
Still, the study provides data supporting a new strategy that could help some countries affected by both P. falciparum and P. vivax move toward malaria elimination. New approaches are especially important now, during a time when the fight against malaria is threatened by insecticide, diagnostic and treatment resistance. Creative methods that consider operational feasibility are needed.