Wednesday, 12 July 2017 16:38

Malaria infection decreases immune response to bacterial infection

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Published in mBiosphere

For many decades, children with malaria have been known to succumb to secondary infection with nontyphoidal Salmonella spp. (NTS). This observation led authors of a recent Clinical and Vaccine Immunology report to ask: how does Plasmodium falciparum infection negatively affect the immune response to invasive NTS infection? Their results demonstrate a link between P. falciparum infection and poor response to NTS.

CVIJournal: Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella during Current or Convalescent Plasmodium falciparum Infection in Malawian Children.

The research team, led by first author Tonney Nyirenda and senior scientist Wilson Mandala, designed a prospective study to monitor children experiencing different types of disease: febrile children suffering uncomplicated malaria, febrile children uninfected with malaria, or nonfebrile children uninfected with malaria. This allowed the researchers to compare the immune responses of children with malaria, children with a possible non-malarial infection, and children who were presumed to be healthy. 

2017.7.11Children with P. falciparum infection have reduced C3 deposition on Salmonella Typhimurium Source.

The researchers then looked at several immune responses to Salmonella Typhimurium, a nontyphoidal Salmonella enterica serovar, to see if there were differences between the groups. The malaria-infected children had less serum bactericidal and whole-blood bactericidal activity than the healthy children and febrile, non-malarial children, which was due in part to less complement C3 deposition (see figure, right). The loss of bactericidal activity was observed in blood from children with both current and recent P. falciparum infection, meaning even children recovering from malaria had less blood antibacterial activity. In some children, a normal immune response took over 30 days in convalescence to recover. 

Neutrophils are an important part of the response to intracellular pathogens, and so the research team examined the neutrophil respiratory burst activity (NRBA) from patients. They found that both the malaria-infected and the febrile, non-malaria-infected children had a lower NRBA in response to Salmonella Typhimurium compared to healthy children. This was surprising, because while P. falciparum infection inhibits neutrophil function, the results suggest nonmalarial febrile illness also inhibits this function. Since the other infections causing illness weren’t diagnosed, the researchers are unsure whether it’s the infecting microbe or the fever response that decreased neutrophil activity in these children.  

These results extend scientists’ understanding of the susceptibility of children with malaria to invasive NTS infection, a susceptibility observed for decades. Other factors, such as patient age, can also affect the immune response to Salmonella Typhimurium (older children have a stronger response). Understanding the mechanism by which susceptibility occurs may contribute to understanding other invasive bacterial infections in this population, and immune-boosting drugs may one day help decrease susceptibility in these children. For now, this increased susceptibility highlights the need to quickly diagnose invasive bacterial infections in children suffering from malaria, whose immune systems need extra help from antimicrobial drugs to fight off infection. 

Last modified on Wednesday, 12 July 2017 16:57
Julie Wolf

ASM Communications Social Media Specialist Julie Wolf spent her research career focused on medical mycology and infectious disease. Broadly interested in microbiology and scientific communication, she has taught at Long Island University and the community biolab Genspace and has written for the Scientista Foundation and Scholastic’s Science World magazine. Follow her on Twitter for more ASM and Microbiology highlights at @JulieMarieWolf.