title: The effect of altitude on parasite density case definitions for malaria in northeastern Tanzania.
abstract: OBJECTIVE
  Malaria clinical trials need precise endpoints to measure efficacy. In endemic areas where asymptomatic parasitaemia is common, 'fever plus parasitaemia' may not differentiate between malaria cases and non-cases. Case definitions based on parasite cut-off densities may be more appropriate but may vary with age and transmission intensity. This study examines appropriate case definitions from parasitological surveys conducted over a broad range of transmission intensities, using altitude as a proxy for transmission intensity.
  
  
  METHODS
  Cross-sectional data collected from 24 villages at different altitudes in an endemic area of northeastern Tanzania were used to calculate malaria-attributable fractions using a modified Poisson regression method. We modelled fever as a function of parasite density and determined the optimum cut-off densities of parasites to cause fever using sensitivity and specificity analyses.
  
  
  RESULTS
  The optimum cut-off density varied by altitude in children aged under 5 years: a case definition of 4,000 parasites per mul at altitudes <600 m (high transmission intensity) was most appropriate, compared with 1,000 parasites per mul at altitudes >600 m (low transmission intensity). In children aged over 5 years and adults, there was little variation by altitude and a case definition of any parasites plus fever was the most appropriate.
  
  
  CONCLUSIONS
  Locally appropriate case definitions of malaria should be used for research purposes. In our setting, these varied independently with age and transmission intensity.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. clare.chandler@lshtm.ac.uk
authors.forename: Clare I R
authors.initials: CI
authors.lastname: Chandler
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Drakeley
authors.forename: Hugh
authors.initials: H
authors.lastname: Reyburn
authors.forename: Ilona
authors.initials: I
authors.lastname: Carneiro
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000531:Altitude; D002648:Child; D002675:Child, Preschool; D019353:Endemic Diseases; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D007223:Infant; D008288:Malaria / Q000175:diagnosis / Q000453:epidemiology / Q000469:parasitology*; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D010270:Parasite Egg Count; D018512:Parasitemia / Q000453:epidemiology / Q000469:parasitology; D012423:Rural Health; D013636:Tanzania / Q000453:epidemiology