Plasmodium falciparum Malaria and Salmonella Infections in Gambian Children

Mabey, David; Brown, Aisling; Greenwood, Brian

doi:10.1093/infdis/155.6.1319

Cited by 198 publications

(164 citation statements)

References 9 publications

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“…The clinical association between malaria and NTS bacteremia in African children is well recognized (38,39), yet the underlying mechanisms of this association are poorly understood. Our findings suggest that the high levels of complement consumption in malaria, particularly in severe malarial anemia (40), could underlie this association, together with direct inhibition of oxidative burst activity resulting from ingestion of malaria-parasitized red blood cells or hemozoin by phagocytes (41).…”

Section: Discussionmentioning

confidence: 99%

Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans

Gondwe

Molyneux

Goodall

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

121

133

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Bacteremia caused by nontyphoidal strains of Salmonella is endemic among African children. Case-fatality rates are high and antibiotic resistance increasing, but no vaccine is currently available. T cells are important for clearance of Salmonella infection within macrophages, but in Africa, invasive Salmonella disease usually manifests in the blood and affects children between 4 months and 2 y of age, when anti- Salmonella antibody is absent. We have previously found a role for complement-fixing bactericidal antibody in protecting these children. Here we show that opsonic activity of antibody and complement is required for oxidative burst and killing of Salmonella by blood cells in Africans. Induction of neutrophil oxidative burst correlated with anti- Salmonella IgG and IgM titers and C3 deposition on bacteria and was significantly lower in African children younger than 2 y compared with older children. Preopsonizing Salmonella with immune serum overcame this deficit, indicating a requirement for antibody and/or complement. Using different opsonization procedures, both antibody and complement were found to be necessary for optimal oxidative burst, phagocytosis and killing of nontyphoidal Salmonella by peripheral blood cells in Africans. Although most strains of African nontyphoidal Salmonella can be killed with antibody and complement alone, phagocytes in the presence of specific antibody and complement can kill strains resistant to killing by immune serum. These findings increase the likelihood that an antibody-inducing vaccine will protect against invasive nontyphoidal Salmonella disease in African children.

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Section: Discussionmentioning

confidence: 99%

Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans

Gondwe

Molyneux

Goodall

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

121

133

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“…Cardiac arrhythmias were not found to be responsible for deaths in Gambian children. 109 Superimposed bacterial infections (pneumonia, septicemia, and urinary tract infections) often cause death in nonimmune adults with malaria, and although Salmonella septicemia was associated with malaria infection in Gambian children, 110 superimposed infections only rarely cause death in children with severe and complicated malaria. 6,7 POST-MORTEM FINDINGS Gross brain abnormalities.…”

Section: Pathophysiology Of Fatal Malariamentioning

confidence: 99%

Pathophysiology of fatal falciparum malaria in African children.

Newton¹,

Taylor²,

Whitten³

1998

Am J Trop Med Hyg

122

121

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Abstract. Children living in sub-Saharan Africa bear the brunt of the mortality from falciparum malaria, yet there is a dearth of relevant post-mortem data. Clinical studies from centers in Africa suggest that the pathophysiology of severe malaria is different in children and adults. Three overlapping clinical syndromes, metabolic acidosis manifesting as hyperpnea, cerebral malaria, and severe anemia, are responsible for nearly all the deaths in African children. Despite improvements in antimalarial treatment, there has not been a significant reduction in mortality. We review the pathology and pathophysiology of fatal falciparum malaria in African children. Many questions remain, the answers to which would facilitate the development and evaluation of new approaches to the management of this disease.Severe and complicated Plasmodium falciparum infections continue to threaten the survival of young children in sub-Saharan Africa: one in 15 children on the Kenyan coast will have experienced an episode of severe malaria before the age of five, 1 and 1% of Gambian children less than five years of age will die of malaria. 2 The annual death toll is estimated to be one million children across the continent; 90% of the annual worldwide malaria mortality. 3 Although most children die in the community, on the Kenyan coast it is estimated that more than 40% die in a hospital (Marsh K, unpublished data) and one-third of pediatric hospital admissions and one-third of pediatric hospital deaths in Malawi can be attributed to malaria. 4

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“…A number of epidemiological studies suggest the existence of malaria-induced immune suppression. In endemic areas, an association of malaria with a higher incidence of other infectious diseases [3][4][5] and reduced immune responses to vaccination during malaria infections [6,7] is found.…”

Section: Introductionmentioning

confidence: 99%

Role of TGF‐β and PGE₂in T cell responses during Plasmodium yoelii infection

et al. 2007

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During an acute blood-stage malaria infection, T cell responses to malaria and other bystander antigens are inhibited. Plasmodium infection induces strong cytokine responses that facilitate parasite clearance but may interfere with T cell functions, as some of the soluble immune mediators induced are also general inhibitors of T cell responses. Using a malaria mouse model, we have analyzed the cytokines produced by dendritic cells in response to P. yoelii infection that have potential T cell inhibitory activity. We found that during acute infection DC migrate to the spleen and secrete TGF-b, prostaglandin E 2 (PGE 2 ) and IL-10. We have analyzed the role of these general T cell inhibitors in a particular T cell response of evident importance in malaria infections: the CD8 + T cells generated against the liver-stage of the disease. During blood-stage infection, inhibition of the activity of TGF-b and PGE 2 restores the CD8 + T cell responses generated by sporozoites, increasing protection against re-infection. Our findings suggest that the strong cytokine response induced by blood-stage P. yoelii infection affects host T cell responses, inhibiting protective CD8 + T cells against the liver-stage of the disease.

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Plasmodium falciparum Malaria and Salmonella Infections in Gambian Children

Cited by 198 publications

References 9 publications

Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans

Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans

Pathophysiology of fatal falciparum malaria in African children.

Role of TGF‐β and PGE₂in T cell responses during Plasmodium yoelii infection

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Plasmodium falciparum Malaria and Salmonella Infections in Gambian Children

Cited by 198 publications

References 9 publications

Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans

Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans

Pathophysiology of fatal falciparum malaria in African children.

Role of TGF‐β and PGE2 in T cell responses during Plasmodium yoelii infection

Contact Info

Product

Resources

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Role of TGF‐β and PGE₂in T cell responses during Plasmodium yoelii infection