New research findings as World Malaria Day observed

Burnet Institute

25 April, 2017

Image: Associate Professor Freya Fowkes (right) in the laboratory with research officer Dr Ricardo Ataide

As the world celebrated World Malaria Day, new Burnet research has identified natural immunity as a potential driver of artemisinin-resistant malaria in the Greater Mekong subregion of Southeast Asia.

The research led by Associate Professor Freya Fowkes in collaboration with colleagues from the University of Melbourne and the Mahidol-Oxford Research Unit, and published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), could also prompt a redefinition of artemisinin resistance.

By quantifying genetic markers of drug resistance and looking at multiple measures of the immune response, the study aimed to understand how variations in naturally acquired malarial immunity affect malaria resistance to artemisinin.

Artemisinin and its derivatives are powerful medicines known for their ability to swiftly reduce the number of Plasmodium parasites in the blood of patients with malaria. Artemisinin-based combination therapies are recommended by the World Health Organization (WHO) as the first-line treatment for uncomplicated P. falciparum malaria.

The study demonstrated that in people with an acquired immunity to malaria the immune system interacts with antimalarial drugs to clear the infection from the bloodstream rapidly, an interaction most pronounced in drug-resistant malaria infection.

“If a person has low levels of immunity and is infected with artemisinin-resistant malaria, they will be very poor at clearing the drug-resistant parasites,” Associate Professor Fowkes said.

“But people with high levels of natural immunity will still clear the infection, even if the malaria has some resistance to artemisinin.

Naturally acquired malaria immunity may help its hosts, but complicates the picture for research, Burnet scientists have found.

“So the study shows clearly for the first time the importance of the immune system in clearing infection, especially when you have drug-resistant malaria,” Associate Professor Fowkes said.

This means that in populations with high levels of immunity it may appear as though antimalarials are working effectively, when in fact, the host’s immunity is doing all the work. According to Associate Professor Fowkes this can have the effect of masking emerging drug resistance and lead to an underestimation of drug resistance levels.

Dr Ricardo Ataide, first author of the study, said the research cast new light on the impact of malaria control activities in the Greater Mekong subregion, including highly effective programs to promote use of insecticide-treated bed nets.

“These activities have helped to reduce the burden of malaria, which means that the level of immunity in populations living in those areas has also dropped,” he said.

“So in areas where malaria transmission and immunity is decreasing, there will be less clearance and greater transmission of drug resistant parasites. That’s a big problem."

Dr Ataide said there were important lessons in this research for sub-Saharan Africa where the burden of malaria fell most heavily, with 90 per cent of the world’s malaria cases and 92 per cent of malaria deaths in 2015, according to the WHO.

“If drug resistance hits Africa, especially now that immunity is coming down in Africa due to all the control efforts, it’s potentially going to have a very negative effect, so we need to be prepared for it,” he said.

“And that’s one of the best aspects of this research – being able to inform organisations like the WHO about the need to focus attention on countries where most of the control measures are being undertaken, because if the parasites are going to appear anywhere, that’s where they are going to appear.”

Image: A village in Myanmar

One of the strengths of the study was that it was conducted across multiple populations from throughout the Greater Mekong subregion, including Cambodia, Lao People’s Democratic Republic, Myanmar, Thailand and Vietnam, rather than on single study sites as previously.

Dr Ataide described the role of immunity in this context as a variable that needed to be quantified and accounted for in the development of new treatments.

“You cannot do clinical trials and drug efficacy trials without having a component that tells you the immunity of the population, otherwise you are missing a very important confounder,” he said.

“This study highlights the importance of vaccines. The sooner we can develop and distribute high efficacy vaccines as an additional tool in our fight against malaria, the better.”

Malaria causes an estimated 430,000 deaths each year, 212 million cases in 2015 and a child dying every 60 seconds from the mosquito-borne disease, WHO figures report.

This year’s global theme for World Malaria Day is prevention, a critical strategy for reducing the toll. To read more about Burnet’s malaria programs, click here.

Contact Details

For more information in relation to this news article, please contact:

Professor Freya J.I. Fowkes

Deputy Program Director, Maternal, Child and Adolescent Health




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