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Eliminating the most widespread form of malaria will only be possible if public health programmes treat people with parasites lying dormant in their liver, a study suggests.

More than 2.5 billion people, mostly in Asia, the Horn of Africa and Latin America, live at risk of malaria caused by the Plasmodium vivax parasite. Not only is this strain of malaria widespread, it is also persistent: when it enters a victim’s liver, it can remain dormant without causing any symptoms for years after the initial infection, says the study in PLOS Medicine.

The study found that four-fifths of cases of P. vivax malaria in Papua New Guinean children occur when the parasite re-emerges and causes a relapse. There is currently no way to identify people with the dormant ‘hypnozoite’ form of the parasite, researchers warn.

“Unless we somehow find a way to attack the reservoir of hypnozoites in the liver, it will be near impossible to eliminate vivax malaria.”

Leanne Robinson, Papua New Guinea Institute of Medical Research.

“Unless we somehow find a way to attack the reservoir of hypnozoites in the liver, it will be near impossible to eliminate vivax malaria,” says Leanne Robinson, lead author of the study and researcher at the Papua New Guinea Institute of Medical Research.

To assess what proportion of malaria infections occur due to relapses, researchers treated one group of children with drugs that kill parasites in both the blood and liver, while giving another group a placebo and a drug that attacks the blood stage of the parasite.

Based on the results, the researchers developed transmission models to assess whether giving malaria drugs to entire communities would be effective at preventing recurrent Pvivax infections.

They also modelled the potential impact of tafenoquine — a promising relapse-phase drug that is still in clinical trials.

“Our mathematical models showed that the only approach currently available to really reduce vivax prevalence [in Papua New Guinea] is mass administration of both a blood and liver stage drug,” Robinson says.

Regina Rabinovich, director of the Malaria Elimination Initiative at the Barcelona Institute for Global Health, says she is “excited about these results”.

“Once [tafenoquine] meets regulatory requirements and is available, it will help solve part of the delivery problem,” says Rabinovich. “This affects elimination strategies far beyond Papua New Guinea.”

Robinson and her colleagues plan to do similar studies in other Plasmodium vivax endemic countries.

“There are different strains of Plasmodium vivax all over the world and those strains have different patterns of relapse, so that would obviously change the scenario compared to what we’ve seen in Papua New Guinea,” she says. One country in their sights — Guatemala — had more than 4,800 cases of malaria in 2014 alone, the study says.

But despite efforts to scale up prevention and control measures such as providing more mosquito nets and microscopy centres in high-risk areas in the country, “we’ve not seen a significant reduction of cases since 2012”, says Norma Padilla, the head of entomology and ecology of parasitic diseases at the Universidad del Valle in Guatemala.

“This study provides valuable information to accelerate elimination in areas like Guatemala, where conventional approaches don’t seem to be reducing cases as expected,” she says. 


Leanne J. Robinson and others Strategies for understanding and reducing the Plasmodium vivax and Plasmodium ovale hypnozoite reservoir in Papua New Guinean children: a randomised placebo-controlled trial and mathematical model (PLOS Medicine, 27 October 2015)