title: Analysis of Preventive Interventions for Malaria: Exploring Partial and Complete Protection and Total and Primary Intervention Effects.
abstract: Event dependence, the phenomenon in which future risk depends on past disease history, is not commonly accounted for in the statistical models used by malaria researchers. However, recently developed methods for the analysis of repeated events allow this to be done, while also accounting for heterogeneity in risk and nonsusceptible subgroups. Accounting for event dependence allows separation of the primary effect of an intervention from its total effect, which is composed of its primary effect on risk of disease and its secondary effect mediated by event dependence. To illustrate these methods and show the insights they can provide, we have reanalyzed 2 trials of seasonal malaria chemoprevention (SMC) in Boussé, Burkina Faso, and Kati, Mali, in 2008-2009, as well as a trial of intermittent preventive treatment of malaria in infants in Navrongo, Ghana, in 2000-2004. SMC completely protects a large fraction of recipients, while intermittent preventive treatment in infants provides modest partial protection, consistent with the rationale of these 2 different chemopreventive approaches. SMC has a primary effect that is substantially greater than the total effect previously estimated by trials, with the lower total effect mediated by negative event dependence. These methods contribute to an understanding of the mechanisms of protection from these interventions and could improve understanding of other tools to control malaria, including vaccines.
authors.forename: Matthew
authors.initials: M
authors.lastname: Cairns
authors.forename: Yin Bun
authors.initials: YB
authors.lastname: Cheung
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Kwaku Poku
authors.initials: KP
authors.lastname: Asante
authors.forename: Seth
authors.initials: S
authors.lastname: Owusu-Agyei
authors.forename: Diadier
authors.initials: D
authors.lastname: Diallo
authors.forename: Amadou T
authors.initials: AT
authors.lastname: Konate
authors.forename: Alassane
authors.initials: A
authors.lastname: Dicko
authors.forename: Daniel
authors.initials: D
authors.lastname: Chandramohan
authors.forename: Brian
authors.initials: B
authors.lastname: Greenwood
authors.forename: Paul
authors.initials: P
authors.lastname: Milligan
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D002050:Burkina Faso / Q000453:epidemiology; D002675:Child, Preschool; D005260:Female; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007223:Infant; D053208:Kaplan-Meier Estimate; D008288:Malaria / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission; D008297:Male; D008302:Mali / Q000453:epidemiology; D008954:Models, Biological; D015233:Models, Statistical; D011322:Primary Prevention / Q000379:methods*; D012008:Recurrence; D012621:Seasons
chemical_list: D000962:Antimalarials
keywords: cure models; event dependence; heterogeneity; malaria; repeated events