Increased levels of inflammatory mediators in children with severe Plasmodium falciparum malaria with respiratory distress.
BACKGROUND
Respiratory distress (RD), a symptom of underlying metabolic acidosis, has been identified as a major risk factor for mortality in children with severe malaria in Africa, yet the molecular mediators involved in the pathogenesis of RD have not been identified.


METHODS
We studied circulating levels of mediators of inflammation--including the cytokines tumor necrosis factor (TNF)- alpha and interleukin (IL)-10; the chemokines macrophage inflammatory protein (MIP)-1 alpha , MIP-1 beta , and IL-8; and the immune activation marker neopterin--in children with RD, severe malarial anemia (SMA), cerebral malaria (CM), and uncomplicated malaria (UM).


RESULTS
Children with RD had significantly higher plasma levels of TNF- alpha , IL-10, and neopterin and a significantly higher TNF- alpha : IL-10 ratio than those without RD. In addition, the results demonstrated that, relative to UM, CM was associated with increased levels of TNF- alpha and decreased levels of MIP-1 alpha , whereas SMA was associated with decreased levels of IL-10. Circulating levels of neopterin were inversely correlated with hemoglobin, whereas levels of MIP-1 beta were positively correlated with parasitemia.


CONCLUSIONS
We conclude that distinct clinical presentations of severe malaria are associated with specific patterns of inflammatory mediators. In particular, we show, to our knowledge for the first time, that patients with malaria and RD have a strong and unbalanced proinflammatory response that may be involved in the pathogenesis of the underlying metabolic acidosis.
Awandare
Gordon A
GA
Immunology Department, Noguchi Memorial Institute for Medical Research, University of Ghana Medical School, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
Goka
Bamenla
B
Boeuf
Philippe
P
Tetteh
John K A
JK
Kurtzhals
Jorgen A L
JA
Behr
Charlotte
C
Akanmori
Bartholomew D
BD
D000818:Animals; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology; D008297:Male; D018512:Parasitemia; D010963:Plasmodium falciparum; D012120:Respiration Disorders / Q000209:etiology*; D013223:Statistics as Topic
D016207:Cytokines; D006454:Hemoglobins