Coinfections and Immune Responses in Malaria

Malaria infection induces profound alterations in host immunity, metabolic homeostasis and mucosal integrity that together predispose to opportunistic bacterial infections. Haemolysis and parasite-driven immunoregulation, notably via interleukin-10 and haem oxygenase-1, impair neutrophil oxidative burst and macrophage function, while disruption of gut barrier integrity and shifts in the intestinal microbiota favour translocation and overgrowth of enteric pathogens. Coinfections with non-typhoidal Salmonella and other Gram-negative bacteria synergise with severe anaemia and microcirculatory disturbances to increase morbidity and mortality. Understanding the bidirectional interactions between Plasmodium spp., the immune system and commensal communities is central to refining antimicrobial stewardship, improving diagnostic targeting and developing adjunctive therapies that restore immune competence and microbial balance.

Research from Nature Portfolio

Murine models of Plasmodium infection have provided foundational insight into how malaria reshapes intestinal ecology and susceptibility to enteric pathogens. In one model, infection with Plasmodium berghei ANKA induced epithelial detachment, increased gut permeability and marked dysbiosis characterised by loss of Firmicutes and enrichment of Proteobacteria; the degree of microbial shift correlated with cerebral malaria severity. A complementary study using Plasmodium yoelii demonstrated that malaria-associated mucosal inflammation disrupts colonisation resistance to Salmonella Typhimurium, with 16S rRNA analysis confirming that altered community structure directly promotes pathogen overgrowth, highlighting the gut microbiota as a key mediator of systemic co-infections.

Coinfections and Immune Responses in Malaria publication trend

The graph below shows the total number of articles in coinfections and immune responses in malaria across all publications each year (not limited to Nature Index journals).

Technical terms

Haemolysis: Destruction of red blood cells releasing haem and iron, which can impair immune cell function.

Neutrophil oxidative burst: Rapid production of reactive oxygen species by neutrophils to kill pathogens.

Dysbiosis: Disruption of the normal balance of microbial communities in the gut.

Colonisation resistance: Ability of commensal microbiota to prevent pathogen overgrowth.

Interleukin-10 (IL-10): An anti-inflammatory cytokine that modulates immune responses and can suppress antimicrobial functions.

Pharmacokinetics–pharmacodynamics (PK-PD): Study of drug absorption, distribution and effect relationships to optimise dosing.

References

1. Azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a phase II randomised controlled trial. BMC Medicine (2024).
2. Intestinal injury and the gut microbiota in patients with Plasmodium falciparum malaria. PLOS Pathogens (2023).
3. The Prevalence of Malaria and Bacteremia Co-Infections among Febrile Patients: A Systematic Review and Meta-Analysis. Tropical Medicine and Infectious Disease (2022).
4. Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function. PLOS Pathogens (2014).
5. Plasmodium berghei ANKA causes intestinal malaria associated with dysbiosis. Scientific Reports (2015).
6. Inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal Salmonella during concurrent malaria parasite infection. Scientific Reports (2015).
7. Infection-related hemolysis and susceptibility to Gram-negative bacterial co-infection. Frontiers in Microbiology (2015).