Asymptomatic malaria is not as harmless as it seems

Australian and Indonesian researchers have shown that persistent, asymptomatic malaria infections are not innocuous as previously believed. Instead, these infections suppress the immune system, preventing it from eradicating parasites from the bloodstream.

Malaria remains one of the most serious infectious diseases of humans, with over 200 million clinical cases and 600,000 deaths estimated in 2020. Some people can develop immunity to the malaria parasite Plasmodium falciparum after many years of repeated infections. In these patients, a small number of parasites continue to live silently in the bloodstream but do not cause fever-like symptoms.

“These infections have historically been viewed as beneficial because they were thought to offer protection against symptomatic disease,” said study co-leader Associate Professor Diana Hansen, from the Walter and Eliza Hall Institute of Medical Research (WEHI).

“Based on this assumption, asymptomatic malaria is often left untreated in countries where malaria is endemic, despite our poor understanding of the real impact that these persistent infections have on people.”

Studies have reported that asymptomatic infections are responsible for up to half of new transmissions, often sliding under the radar and sabotaging efforts of malaria elimination programs. To investigate the impact of asymptomatic disease, the WEHI-led research team analysed the white blood cells of patients carrying asymptomatic and symptomatic infections in an endemic area of Indonesia.

The team found that patients with chronic asymptomatic malaria infections upregulated genes that suppressed the immune system, making more proteins to help the parasites survive. Because the immune system is suppressed and cannot work at full capacity, Hansen said, the body cannot take control of the parasites and clear them from the bloodstream — which could have critical implications for the administration of malaria vaccines and elimination strategies around the world.

“In an immunosuppressed individual carrying an asymptomatic malaria infection, the effectiveness of the malaria vaccine is reduced as the immune system does not have the capacity to be trained appropriately,” Hansen said.

“If we were to treat individuals with asymptomatic malaria infections, we would also reduce the invisible parasite reservoir that perpetuates transmission and deters efforts of malaria elimination campaigns.”

The team’s findings, published in the journal Molecular Systems Biology, thus provide an alternative view to the belief that asymptomatic malaria infections are beneficial in helping reduce the risk of severe disease, and suggest that treating chronic infections could enhance vaccine effectiveness and reduce transmission. The new information provides a framework to consider new polices supporting screening and treatment of asymptomatic malaria in endemic areas around the world.

Image credit: ©stock.adobe.com/au/mycteria

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