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$37.5uC) gave consistently higher MAFs than case
definitions based on subjective fever.
Conclusion: 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.
