CD4 T cell activation as a predictor for treatment failure in Ugandans with Plasmodium falciparum malaria.
Host immunity plays an important role in response to antimalarial therapy but is poorly understood. To test whether T cell activation is a risk factor for antimalarial treatment failure, we studied CD4(+) and CD8(+) T cell activation in 31 human immunodeficiency virus-negative Ugandan patients 5-37 years of age who were treated for uncomplicated Plasmodium falciparum malaria. Increased CD4(+) T cell activation, as indicated by co-expression of HLA-DR and CD38, was an independent risk factor for treatment failure (hazard ratio = 2.45, 95% confidence interval = 1.02-5.89, P = 0.05) in multivariate analysis controlling for age, baseline temperature, and pre-treatment parasite density. The results provide insight into the role of cellular immunity in response to antimalarial therapy and underscore the need to investigate the mechanisms behind immune activation.
Eggena
Mark P
MP
Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA.
Hopkins
Heidi
H
Barugahare
Banson
B
Okello
Martin
M
Ssali
Francis
F
Mugyenyi
Peter
P
Rosenthal
Philip J
PJ
Cao
Huyen
H
Dorsey
Grant
G
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D001831:Body Temperature; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000276:immunology; D011739:Pyrimethamine / Q000627:therapeutic use; D012307:Risk Factors; D013413:Sulfadoxine / Q000627:therapeutic use; D017211:Treatment Failure; D014454:Uganda
D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine