TY - JOUR
T1 - Distinct clinical and immunologic profiles in severe malarial anemia and cerebral malaria in Zambia
AU - Thuma, Philip E.
AU - Van Dijk, Janneke
AU - Bucala, Rick
AU - Debebe, Zufan
AU - Nekhai, Sergei
AU - Kuddo, Thea
AU - Nouraie, Mehdi
AU - Weiss, Günter
AU - Gordeuk, Victor R.
N1 - Funding Information:
This work was supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (grants 1 R01 AI44857 and AI051306); the National Heart, Lung, and Blood Institute and the Office of Research on Minority Health at the National Institutes of Health (grant UH1-HL03679); and the National Institute of Research Resources, Howard University General Clinical Research Center (grant MO1-RR10284).
PY - 2011/1/15
Y1 - 2011/1/15
N2 - Background. The mechanisms of severe malarial anemia and cerebral malaria, which are extreme manifestations of Plasmodium falciparum malaria, are not fully understood. Methods. Children aged <6 years from southern Zambia presenting to the hospital with severe malarial anemia (n = 72), cerebral malaria (n = 28), or uncomplicated malaria (n = 66) were studied prospectively. Children with overlapping severe anemia and cerebral malaria were excluded. Results. Low interleukin 10 concentrations had the strongest association with severe anemia (standard β = .61; P < .001) followed by high tumor necrosis factor α and sFas concentrations, low weight-for-age z scores, presence of stool parasites, and splenomegaly (standard β = .15-.25; P ≤ .031); most of these factors were also associated with lower reticulocytes. Greater parasitemia was associated with higher interleukin 10 and tumor necrosis factor α concentrations, whereas sulfadoxizole/pyrimethamine therapy and lower weight-for-age z scores were associated with lower interleukin 10 levels. Thrombocytopenia and elevated tissue plasminogen activator inhibitor 1 levels had the strongest associations with cerebral malaria (standard β = .37 or .36; P < .0001), followed by exposure to traditional herbal medicine and hemoglobinuria (standard β = .21-.31; P ≤ .006). Conclusions. Predictors of severe malarial anemia (altered immune responses, poor nutrition, intestinal parasites, and impaired erythropoiesis) differed from those of cerebral malaria (thrombocytopenia, herbal medicine, and intravascular hemolysis). Improved preventive and therapeutic measures may need to consider these differences.
AB - Background. The mechanisms of severe malarial anemia and cerebral malaria, which are extreme manifestations of Plasmodium falciparum malaria, are not fully understood. Methods. Children aged <6 years from southern Zambia presenting to the hospital with severe malarial anemia (n = 72), cerebral malaria (n = 28), or uncomplicated malaria (n = 66) were studied prospectively. Children with overlapping severe anemia and cerebral malaria were excluded. Results. Low interleukin 10 concentrations had the strongest association with severe anemia (standard β = .61; P < .001) followed by high tumor necrosis factor α and sFas concentrations, low weight-for-age z scores, presence of stool parasites, and splenomegaly (standard β = .15-.25; P ≤ .031); most of these factors were also associated with lower reticulocytes. Greater parasitemia was associated with higher interleukin 10 and tumor necrosis factor α concentrations, whereas sulfadoxizole/pyrimethamine therapy and lower weight-for-age z scores were associated with lower interleukin 10 levels. Thrombocytopenia and elevated tissue plasminogen activator inhibitor 1 levels had the strongest associations with cerebral malaria (standard β = .37 or .36; P < .0001), followed by exposure to traditional herbal medicine and hemoglobinuria (standard β = .21-.31; P ≤ .006). Conclusions. Predictors of severe malarial anemia (altered immune responses, poor nutrition, intestinal parasites, and impaired erythropoiesis) differed from those of cerebral malaria (thrombocytopenia, herbal medicine, and intravascular hemolysis). Improved preventive and therapeutic measures may need to consider these differences.
UR - http://www.scopus.com/inward/record.url?scp=79851506686&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79851506686&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiq041
DO - 10.1093/infdis/jiq041
M3 - Article
C2 - 21288821
AN - SCOPUS:79851506686
SN - 0022-1899
VL - 203
SP - 211
EP - 219
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -