title: Defining clinical malaria: the specificity and incidence of endpoints from active and passive surveillance of children in rural Kenya.
abstract: BACKGROUND
  Febrile malaria is the most common clinical manifestation of P. falciparum infection, and is often the primary endpoint in clinical trials and epidemiological studies. Subjective and objective fevers are both used to define the endpoint, but have not been carefully compared, and the relative incidence of clinical malaria by active and passive case detection is unknown.
  
  
  METHODS
  We analyzed data from cohorts under active and passive surveillance, including 19,462 presentations with fever and 5,551 blood tests for asymptomatic parasitaemia. A logistic regression model was used to calculate Malaria Attributable Fractions (MAFs) for various case definitions. Incidences of febrile malaria by active and passive surveillance were compared in a subset of children matched for age and location.
  
  
  RESULTS
  Active surveillance identified three times the incidence of clinical malaria as passive surveillance in a subset of children matched for age and location. Objective fever (temperature≥37.5°C) gave consistently higher MAFs than case definitions based on subjective fever.
  
  
  CONCLUSIONS
  The endpoints from active and passive surveillance have high specificity, but the incidence of endpoints is lower on passive surveillance. Subjective fever had low specificity and should not be used in primary endpoint. Passive surveillance will reduce the power of clinical trials but may cost-effectively deliver acceptable sensitivity in studies of large populations.
authors.affiliation: Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre for Geographic Medicine Research, Kilifi, Kenya. Aolotu@kilifi.kemri-wellcome.org
authors.forename: Ally
authors.initials: A
authors.lastname: Olotu
authors.forename: Gregory
authors.initials: G
authors.lastname: Fegan
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Williams
authors.forename: Philip
authors.initials: P
authors.lastname: Sasi
authors.forename: Edna
authors.initials: E
authors.lastname: Ogada
authors.forename: Evasius
authors.initials: E
authors.lastname: Bauni
authors.forename: Juliana
authors.initials: J
authors.lastname: Wambua
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Steffen
authors.initials: S
authors.lastname: Borrmann
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
mesh_terms: D002675:Child, Preschool; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D003140:Communicable Disease Control; D003362:Cost-Benefit Analysis; D005260:Female; D005334:Fever; D005843:Geography; D006801:Humans; D015994:Incidence; D007223:Infant; D007630:Kenya; D008288:Malaria / Q000175:diagnosis* / Q000453:epidemiology*; D008297:Male; D015233:Models, Statistical; D010963:Plasmodium falciparum / Q000378:metabolism*; D012044:Regression Analysis; D012424:Rural Population