title: Interpreting malaria age-prevalence and incidence curves: a simulation study of the effects of different types of heterogeneity.
abstract: BACKGROUND
  Individuals in a malaria endemic community differ from one another. Many of these differences, such as heterogeneities in transmission or treatment-seeking behaviour, affect malaria epidemiology. The different kinds of heterogeneity are likely to be correlated. Little is known about their impact on the shape of age-prevalence and incidence curves. In this study, the effects of heterogeneity in transmission, treatment-seeking and risk of co-morbidity were simulated.
  
  
  METHODS
  Simple patterns of heterogeneity were incorporated into a comprehensive individual-based model of Plasmodium falciparum malaria epidemiology. The different types of heterogeneity were systematically simulated individually, and in independent and co-varying pairs. The effects on age-curves for parasite prevalence, uncomplicated and severe episodes, direct and indirect mortality and first-line treatments and hospital admissions were examined.
  
  
  RESULTS
  Different heterogeneities affected different outcomes with large effects reserved for outcomes which are directly affected by the action of the heterogeneity rather than via feedback on acquired immunity or fever thresholds. Transmission heterogeneity affected the age-curves for all outcomes. The peak parasite prevalence was reduced and all age-incidence curves crossed those of the reference scenario with a lower incidence in younger children and higher in older age-groups. Heterogeneity in the probability of seeking treatment reduced the peak incidence of first-line treatment and hospital admissions. Heterogeneity in co-morbidity risk showed little overall effect, but high and low values cancelled out for outcomes directly affected by its action. Independently varying pairs of heterogeneities produced additive effects. More variable results were produced for co-varying heterogeneities, with striking differences compared to independent pairs for some outcomes which were affected by both heterogeneities individually.
  
  
  CONCLUSIONS
  Different kinds of heterogeneity both have different effects and affect different outcomes. Patterns of co-variation are also important. Alongside the absolute levels of different factors affecting age-curves, patterns of heterogeneity should be considered when parameterizing or validating models, interpreting data and inferring from one outcome to another.
authors.affiliation: Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland. amanda.ross@unibas.ch
authors.forename: Amanda
authors.initials: A
authors.lastname: Ross
authors.forename: Thomas
authors.initials: T
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D006801:Humans; D015994:Incidence; D007223:Infant; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology / Q000517:prevention & control*; D008875:Middle Aged; D015233:Models, Statistical; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D015995:Prevalence; D012307:Risk Factors