Relapsing Infections Could Challenge Malaria Eradication

November 6, 2015

An international study found that 4 out of 5 children in Papua New Guinea (PNG) aged five to 10 years old were susceptible to recurring infection with the malaria parasite Plasmodium vivax. Courtesy of Mayeta Clark/Walter and Eliza Hall Institute

Eliminating malaria in the Asia-Pacific could prove more challenging than previously thought, with new research showing that most childhood malaria infections in endemic areas are the result of relapsed, not new, infections.

An international study found that four out of five children in Papua New Guinea (PNG) aged five to 10 years old were susceptible to recurring infection with the malaria parasite Plasmodium vivax, which can 'hide' undetected in the liver. P. vivax is the most widespread malaria parasite worldwide, and the predominant cause of malaria in the vast majority of countries outside Africa.

The discovery has significant repercussions for the country's - and region's - malaria control program, as well as other areas globally where P. vivax is a significant cause of malaria, such as Central and South America, South and Southeast Asia and the Middle East.

The research study was led by Dr. Leanne Robinson from the Walter and Eliza Hall Institute and Papua New Guinea Institute of Medical Research and professor Ivo Mueller from the Walter and Eliza Hall Institute and Barcelona Centre for International Health Research in Spain.

Robinson says the research showed relapsing infections with P. vivax were responsible for 80 percent of infections in PNG children aged five to 10 years.

"Our research has shown that one of the biggest problems in realising malaria eradication is relapsing P. vivax infections, which are critical for sustained transmission in the region," Robinson says. "Children treated with drugs that targeted the liver and blood stages of infection had 80 per ent fewer malaria infections than those treated with drugs that only targeted the blood stage of infection."

Robinson says P. vivax malaria was problematic for global malaria control efforts, especially in PNG and the Asia-Pacific where it is the major cause of infection and illness in young children. "P. vivax parasites are able to hide in the liver for long periods of time before 'reawakening' to cause disease and continue the transmission cycle," she says. "Mass drug administration that includes a drug that kills parasites in the liver is likely to be a highly effective strategy for eliminating malaria in PNG."

Mueller says mathematical modeling showed current programs would be unable to achieve elimination because the programs could not identify and treat children with dormant liver infections. "We need a better way of identifying children who are chronically infected with malaria so that they can be treated," he said. "It is the only way to stop the malaria transmission cycle in PNG, and is likely to be the case for eliminating malaria in other parts of the Asia-Pacific and Americas."

Mueller and an international team of collaborators successfully secured a AUD$1.15 million grant through the Global Health Innovative Technology (GHIT) Fund to accelerate development of a test that identifies people with dormant malaria parasites in their liver. GHIT is a public-private partnership between Japanese pharmaceutical companies, the Japanese government and the Bill & Melinda Gates Foundation to leverage Japanese biotechnology capabilities to fight neglected disease.

The team will work with Japan's Ehime University, Switzerland's Foundation for Innovative New Diagnostics (FIND), and Japanese biotech CellFree Sciences Co. Ltd. to develop biomarkers for P. vivax malaria that could drive the development of new diagnostic tools. This is only the second diagnostic project supported by the GHIT Fund and the first to be led by an Australian institute.

Mueller says the GHIT Fund was a great model for bringing together the best minds, technologies and resources to develop new diagnostics and treatments for diseases that are devastating the developing world, such as malaria. "The funding will support development of a diagnostic test to identify people with chronic malaria infections so that we can effectively treat them, which will be critical for achieving malaria eradication in PNG and in the Asia-Pacific region," he says.

The research study, published in PLOS Medicine, was supported by the TransEPI consortium, funded by The Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation Grant, Cellex Foundation, International Centers of Excellence in Malaria Research and Victorian Government Operational Infrastructure Support Scheme. Preliminary work on the diagnostic test was supported by Australian Department of Foreign Affairs and Trade (DFAT) through FIND.

Source: Walter and Eliza Hall Institute