The effect of altitude on parasite density case definitions for malaria in northeastern Tanzania

OBJECTIVES 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 4000 parasites per mu l at altitudes < 600 m (high transmission intensity) was most appropriate, compared with 1000 parasites per mu l 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.