Credit: Molecular Systems Biology (2025). DOI: 10.1038/s44320-025-00135-z

Researchers have uncovered new evidence that challenges long-standing beliefs about asymptomatic malaria infections. The study, led by Monash University's Professor Diana Hansen and published in Molecular Systems Biology, focused on Plasmodium vivax, the most widespread malaria parasite and a major obstacle to global elimination efforts.

While people in malaria-endemic regions often carry the parasite without showing symptoms, these "silent" infections were traditionally seen as beneficial—thought to help maintain immunity and prevent future illness. However, these new findings suggest that these sub-clinical infections may actually impair the immune system.

Using a systems immunology approach, the team analyzed blood samples from individuals with both symptomatic and asymptomatic P. vivax infections. They found that both groups showed signs of immune dysfunction, particularly in monocytes—cells that play a key role in fighting infections.

In symptomatic cases, monocyte-related genes were strongly suppressed, and critical immune cells were depleted. Even in asymptomatic individuals, gene activity linked to monocyte function and inflammation was disrupted.

The study also identified increased activity in anti-inflammatory pathways and immune checkpoint receptors, further suggesting that the immune system is actively suppressed during infection.

"Our results show that asymptomatic malaria is not as harmless as previously believed, " said Professor Hansen, Co-Head of the Infection Discovery Program at Monash University's Biomedicine Discovery Institute.

"Even without symptoms, the infection can suppress key immune functions, potentially reducing the body's ability to eliminate the parasite, fight off other diseases, or respond effectively to vaccines."

The research marks a significant step forward in understanding malaria's complex relationship with the immune system, and provides a compelling case for rethinking public health strategies in malaria-endemic regions. Rather than ignoring asymptomatic cases, the findings support the need for screening and treatment to reduce transmission and improve overall health outcomes.

"These insights offer a new framework for malaria control, " said Professor Hansen. "Subclinical infections may be silently undermining immune protection, and addressing them could be crucial for both individual and community health."

More information: Stephanie I Studniberg et al, Systems approach identifies monocyte imbalance in symptomatic and asymptomatic P. vivax malaria, Molecular Systems Biology (2025). DOI: 10.1038/s44320-025-00135-z  Journal information: Molecular Systems Biology