title: Associations between antibodies to a panel of Plasmodium falciparum specific antigens and response to sub-optimal antimalarial therapy in Kampala, Uganda.
abstract: BACKGROUND
  Antibodies are important in the control of blood stage Plasmodium falciparum infection. It is unclear which antibody responses are responsible for, or even associated with protection, partly due to confounding by heterogeneous exposure. Assessment of response to partially effective antimalarial therapy, which requires the host to assist in clearing parasites, offers an opportunity to measure protection independent of exposure.
  
  
  METHODS
  A cohort of children aged 1-10 years in Kampala, Uganda were treated with amodiaquine+sulfadoxine-pyrimethamine for uncomplicated malaria. Serum samples from the time of malaria diagnosis and 14 days later were analyzed for total IgG to 8 P. falciparum antigens using a quantitative indirect ELISA. Associations between antibody levels and risk of treatment failure were estimated using Cox proportional hazard regression.
  
  
  RESULTS
  Higher levels of antibodies to apical membrane antigen 1 (AMA-1), but to none of the other 7 antigens were significantly associated with protection against treatment failure (HR 0.57 per 10-fold increase in antibody level, CI 0.41-0.79, p = 0.001). Protection increased consistently across the entire range of antibody levels.
  
  
  CONCLUSIONS
  Measurement of antibody levels to AMA-1 at the time of malaria may offer a quantitative biomarker of blood stage immunity to P. falciparum, a tool which is currently lacking.
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors.forename: Chris E
authors.initials: CE
authors.lastname: Keh
authors.forename: Aashish R
authors.initials: AR
authors.lastname: Jha
authors.forename: Bridget
authors.initials: B
authors.lastname: Nzarubara
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
authors.forename: Sheetij
authors.initials: S
authors.lastname: Dutta
authors.forename: Michael
authors.initials: M
authors.lastname: Theisen
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Bryan
authors.initials: B
authors.lastname: Greenhouse
mesh_terms: D000913:Antibodies, Protozoan / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000276:immunology*; D013045:Species Specificity; D016896:Treatment Outcome; D014454:Uganda
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000962:Antimalarials