title: Can changes in malaria transmission intensity explain prolonged protection and contribute to high protective efficacy of intermittent preventive treatment for malaria in infants?
abstract: BACKGROUND
  Intermittent preventive (or presumptive) treatment of infants (IPTi), the administration of a curative anti-malarial dose to infants whether or not they are known to be infected, is being considered as a new strategy for malaria control. Five of the six trials using sulphadoxine-pyrimethamine (SP) for IPTi showed protective efficacies (PEs) against clinical malaria ranging from 20.1 - 33.3% whilst one, the Ifakara study, showed a protective efficacy of 58.6%.
  
  
  METHODS
  The possible mechanisms that could explain the differences in the reported PE of IPTi were examined by comparing output from a mathematical model to data from the six published IPTi trials.
  
  
  RESULTS
  Under stable transmission, the PE of IPTi predicted by the model was comparable with the observed PEs in all but the Ifakara study (ratio of the mean predicted PE to that observed was 1.02, range 0.39 - 1.59). When a reduction in the incidence of infection during the study was included in the model, the predicted PE of IPTi increased and extended into the second year of life, as observed in the Ifakara study.
  
  
  CONCLUSIONS
  A decrease in malaria transmission during the study period may explain part of the difference in observed PEs of IPTi between sites and the extended period of protection into the second year of life observed in the Ifakara study. This finding of continued benefit of interventions in settings of decreasing transmission may explain why rebound of clinical malaria was absent in the large scale trials of insecticide-treated bed nets.
authors.affiliation: Department of Infectious and Tropical Disease, London School of Hygiene and Tropical Medicine, London, UK. Roly.gosling@gmail.com
authors.forename: Roly D
authors.initials: RD
authors.lastname: Gosling
authors.forename: Azra C
authors.initials: AC
authors.lastname: Ghani
authors.forename: Jaqueline L
authors.initials: JL
authors.lastname: Deen
authors.forename: Lorenz
authors.initials: L
authors.lastname: von Seidlein
authors.forename: Brian M
authors.initials: BM
authors.lastname: Greenwood
authors.forename: Daniel
authors.initials: D
authors.lastname: Chandramohan
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage*; D004338:Drug Combinations; D006801:Humans; D007223:Infant; D008288:Malaria / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission*; D008962:Models, Theoretical; D020011:Protective Agents / Q000008:administration & dosage*; D011739:Pyrimethamine / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D013413:Sulfadoxine / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D020011:Protective Agents; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine