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A multinational study led by Burnet Institute researchers has identified natural immunity to malaria as a key factor in the clearance of the malaria parasite, but also as a potential driver of artemisinin-resistant malaria that’s exploding in the Greater Mekong subregion of South East 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 redefining of the concept 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 levels of naturally acquired malarial immunity impact on malaria resistant to artemisinin, which is the front line in treatment for malaria.
It demonstrates that in people with an acquired immunity to malaria, there’s an interaction between the antimalarial drugs and the immune system to clear the malaria from the bloodstream rapidly, and that this interaction is most pronounced in cases of 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.
“The problem is that high levels of immunity in a population can make it appear as though the drug is working effectively, which has the effect of masking emerging drug resistance.
“So people are taking the drugs and they seem to be getting better, but that’s partly because their immune system is making up the difference, so we’re underestimating how much drug resistance there might be.”
Dr Ricardo Ataide, first author of the study, said the study casts new light on the impact of malaria control activities in the region, including highly effective programs to promote the 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.
“When we think about drug resistance we tend to think about how the parasite modifies itself to promote resistance, but this research shows that the environment in the human host is also important in terms of driving the emergence of drug resistance.”
While the burden of malaria falls heaviest in Sub-Saharan Africa, drug-resistant malaria is spreading rapidly across the Greater Mekong subregion including Cambodia, Lao People’s Democratic Republic, Myanmar, Thailand and Vietnam.
The World Health Organization estimates there were 212 million cases of malaria globally in 2015, and around 430,000 deaths.
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Deputy Program Director, Maternal and Child Health