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Scientists at Indiana University School of Medicine have identified various types of bacteria found in the stomach that are linked to an increased risk of severe malaria in both humans and mice. Their research, recently published in Nature Communications, may pave the way for innovative approaches targeting gut bacteria to prevent severe malaria and its associated fatalities.
Malaria is a life-threatening infectious disease caused by parasites transmitted through the bites of infected mosquitoes. According to the latest World Malaria Report by the World Health Organization, an estimated 619,000 people succumbed to malaria globally in 2021, with 76% of those fatalities occurring in children aged 5 or younger.
Dr. Nathan Schmidt, an associate professor of pediatrics at IU School of Medicine specializing in pediatric infectious diseases and global health, expressed that while significant progress has been made in malaria treatment and prevention, including the development of new vaccines, antimalarial drugs, and mosquito population control measures, novel strategies are urgently needed as progress in reducing malaria-related deaths has plateaued in recent years.
Schmidt emphasized the absence of approaches targeting gut microbiota and highlighted the potential of their research as an exciting opportunity to address this gap.
In a pivotal 2016 study published in PNAS, Schmidt and his team discovered that gut microbiota can influence the severity of malaria in experimental models. This revelation spurred their determination to identify specific microorganisms, known as “Bacteroides,” in the intestinal tract that play a role in this effect.
In their latest study, the researchers observed a notable association between mice harboring particular species of Bacteroides and an increased risk of severe malaria. A similar correlation was also found in the intestinal tracts of children suffering from severe malaria.
While most of the Schmidt lab’s research has been conducted using mouse models of malaria, a collaboration with colleagues in the field enabled the team to extend their observations by studying around 50 children with malaria in Uganda. They plan to further their clinical observations by working with a cohort of over 500 children with malaria.
This collaboration was made possible through the combined efforts of Dr. Chandy John, Dr. Ruth Namazzi, and Dr. Robert Opoka from IU School of Medicine, Makerere University, and Global Health Uganda, respectively. They are collectively examining how severe malaria may impact the neurodevelopment of children from households with a history of severe malaria. Some of these children may not display any symptoms of illness but carry the malaria parasite in their blood, allowing researchers to explore risk factors associated with the development of severe malaria, including variations observed in the microbiome.
Dr. John, the Ryan White Professor of Pediatrics at IU School of Medicine, emphasized the importance of Schmidt’s findings, suggesting that they indicate certain bacteria or combinations of bacteria in the gut may predispose a child to severe malaria. This opens the door to considering how these combinations in the gut could potentially be modified to protect children from severe malaria.
In addition to studying the expanded cohort in Uganda, Schmidt and his team will collaborate with researchers in Malawi and Mali to gain a broader understanding of the relationships between gut microbiota and malaria across Africa.
Schmidt concluded by stating that, beyond their efforts to assess the contribution of gut bacteria to severe malaria in diverse African populations, they have initiated pre-clinical efforts to target gut bacteria that lead to susceptibility to severe malaria. Their ultimate goal is to advance a treatment into clinical practice.
