title: Serological markers for monitoring historical changes in malaria transmission intensity in a highly endemic region of Western Kenya, 1994-2009.
abstract: BACKGROUND
  Monitoring local malaria transmission intensity is essential for planning evidence-based control strategies and evaluating their impact over time. Anti-malarial antibodies provide information on cumulative exposure and have proven useful, in areas where transmission has dropped to low sustained levels, for retrospectively reconstructing the timing and magnitude of transmission reduction. It is unclear whether serological markers are also informative in high transmission settings, where interventions may reduce transmission, but to a level where considerable exposure continues.
  
  
  METHODS
  This study was conducted through ongoing KEMRI and CDC collaboration. Asembo, in Western Kenya, is an area where intense malaria transmission was drastically reduced during a 1997-1999 community-randomized, controlled insecticide-treated net (ITN) trial. Two approaches were taken to reconstruct malaria transmission history during the period from 1994 to 2009. First, point measurements were calculated for seroprevalence, mean antibody titre, and seroconversion rate (SCR) against three Plasmodium falciparum antigens (AMA-1, MSP-119, and CSP) at five time points for comparison against traditional malaria indices (parasite prevalence and entomological inoculation rate). Second, within individual post-ITN years, age-stratified seroprevalence data were analysed retrospectively for an abrupt drop in SCR by fitting alternative reversible catalytic conversion models that allowed for change in SCR.
  
  
  RESULTS
  Generally, point measurements of seroprevalence, antibody titres and SCR produced consistent patterns indicating that a gradual but substantial drop in malaria transmission (46-70%) occurred from 1994 to 2007, followed by a marginal increase beginning in 2008 or 2009. In particular, proportionate changes in seroprevalence and SCR point estimates (relative to 1994 baseline values) for AMA-1 and CSP, but not MSP-119, correlated closely with trends in parasite prevalence throughout the entire 15-year study period. However, retrospective analyses using datasets from 2007, 2008 and 2009 failed to detect any abrupt drop in transmission coinciding with the timing of the 1997-1999 ITN trial.
  
  
  CONCLUSIONS
  In this highly endemic area, serological markers were useful for generating accurate point estimates of malaria transmission intensity, but not for retrospective analysis of historical changes. Further investigation, including exploration of different malaria antigens and/or alternative models of population seroconversion, may yield serological tools that are more informative in high transmission settings.
authors.affiliation: Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA. vsm0@cdc.gov.
authors.forename: Jacklyn
authors.initials: J
authors.lastname: Wong
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Hamel
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Drakeley
authors.forename: Simon
authors.initials: S
authors.lastname: Kariuki
authors.forename: Ya Ping
authors.initials: YP
authors.lastname: Shi
authors.forename: Altaf A
authors.initials: AA
authors.lastname: Lal
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Nahlen
authors.forename: Peter B
authors.initials: PB
authors.lastname: Bloland
authors.forename: Kim A
authors.initials: KA
authors.lastname: Lindblade
authors.forename: Vincent
authors.initials: V
authors.lastname: Were
authors.forename: Kephas
authors.initials: K
authors.lastname: Otieno
authors.forename: Peter
authors.initials: P
authors.lastname: Otieno
authors.forename: Chris
authors.initials: C
authors.lastname: Odero
authors.forename: Laurence
authors.initials: L
authors.lastname: Slutsker
authors.forename: John M
authors.initials: JM
authors.lastname: Vulule
authors.forename: John E
authors.initials: JE
authors.lastname: Gimnig
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007630:Kenya / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000635:transmission*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000276:immunology; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D012189:Retrospective Studies; D016036:Seroepidemiologic Studies; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; C041595:circumsporozoite protein, Protozoan