title: CD4 T cell activation as a predictor for treatment failure in Ugandans with Plasmodium falciparum malaria.
abstract: 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.
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Eggena
authors.forename: Heidi
authors.initials: H
authors.lastname: Hopkins
authors.forename: Banson
authors.initials: B
authors.lastname: Barugahare
authors.forename: Martin
authors.initials: M
authors.lastname: Okello
authors.forename: Francis
authors.initials: F
authors.lastname: Ssali
authors.forename: Peter
authors.initials: P
authors.lastname: Mugyenyi
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Huyen
authors.initials: H
authors.lastname: Cao
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
mesh_terms: 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
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine