title: The Impact of Hotspot-Targeted Interventions on Malaria Transmission in Rachuonyo South District in the Western Kenyan Highlands: A Cluster-Randomized Controlled Trial.
abstract: BACKGROUND
  Malaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area. Targeting hotspots may represent an efficacious strategy for reducing malaria transmission. We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities.
  
  
  RESULTS
  Twenty-seven serologically defined malaria hotspots were detected in a survey conducted from 24 June to 31 July 2011 that included 17,503 individuals from 3,213 compounds in a 100-km2 area in Rachuonyo South District, Kenya. In a cluster-randomized trial from 22 March to 15 April 2012, we randomly allocated five clusters to hotspot-targeted interventions with larviciding, distribution of long-lasting insecticide-treated nets, indoor residual spraying, and focal mass drug administration (2,082 individuals in 432 compounds); five control clusters received malaria control following Kenyan national policy (2,468 individuals in 512 compounds). Our primary outcome measure was parasite prevalence in evaluation zones up to 500 m outside hotspots, determined by nested PCR (nPCR) at baseline and 8 wk (16 June-6 July 2012) and 16 wk (21 August-10 September 2012) post-intervention by technicians blinded to the intervention arm. Secondary outcome measures were parasite prevalence inside hotpots, parasite prevalence in the evaluation zone as a function of distance from the hotspot boundary, Anopheles mosquito density, mosquito breeding site productivity, malaria incidence by passive case detection, and the safety and acceptability of the interventions. Intervention coverage exceeded 87% for all interventions. Hotspot-targeted interventions did not result in a change in nPCR parasite prevalence outside hotspot boundaries (p ≥ 0.187). We observed an average reduction in nPCR parasite prevalence of 10.2% (95% CI -1.3 to 21.7%) inside hotspots 8 wk post-intervention that was statistically significant after adjustment for covariates (p = 0.024), but not 16 wk post-intervention (p = 0.265). We observed no statistically significant trend in the effect of the intervention on nPCR parasite prevalence in the evaluation zone in relation to distance from the hotspot boundary 8 wk (p = 0.27) or 16 wk post-intervention (p = 0.75). Thirty-six patients with clinical malaria confirmed by rapid diagnostic test could be located to intervention or control clusters, with no apparent difference between the study arms. In intervention clusters we caught an average of 1.14 female anophelines inside hotspots and 0.47 in evaluation zones; in control clusters we caught an average of 0.90 female anophelines inside hotspots and 0.50 in evaluation zones, with no apparent difference between study arms. Our trial was not powered to detect subtle effects of hotspot-targeted interventions nor designed to detect effects of interventions over multiple transmission seasons.
  
  
  CONCLUSIONS
  Despite high coverage, the impact of interventions targeting malaria vectors and human infections on nPCR parasite prevalence was modest, transient, and restricted to the targeted hotspot areas. Our findings suggest that transmission may not primarily occur from hotspots to the surrounding areas and that areas with highly heterogeneous but widespread malaria transmission may currently benefit most from an untargeted community-wide approach. Hotspot-targeted approaches may have more validity in settings where human settlement is more nuclear.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01575613.
authors.affiliation: Radboud Institute for Health Sciences, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.|Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Teun
authors.initials: T
authors.lastname: Bousema
authors.affiliation: Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Gillian
authors.initials: G
authors.lastname: Stresman
authors.affiliation: Radboud Institute for Health Sciences, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Amrish Y
authors.initials: AY
authors.lastname: Baidjoe
authors.affiliation: MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Bradley
authors.affiliation: Department of Mathematical Sciences, University of Bath, Bath, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Knight
authors.affiliation: Radboud Institute for Health Sciences, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: William
authors.initials: W
authors.lastname: Stone
authors.affiliation: Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya.
authors.forename: Victor
authors.initials: V
authors.lastname: Osoti
authors.affiliation: Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya.
authors.forename: Euniah
authors.initials: E
authors.lastname: Makori
authors.affiliation: Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya.
authors.forename: Chrispin
authors.initials: C
authors.lastname: Owaga
authors.affiliation: Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya.
authors.forename: Wycliffe
authors.initials: W
authors.lastname: Odongo
authors.affiliation: Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya.
authors.forename: Pauline
authors.initials: P
authors.lastname: China
authors.affiliation: Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya.
authors.forename: Shehu
authors.initials: S
authors.lastname: Shagari
authors.affiliation: Malaria Research and Training Center, University of Sciences, Techniques and Technologies of Bamako, Bamako, Mali.
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.affiliation: Radboud Institute for Health Sciences, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.affiliation: Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya.
authors.forename: Simon
authors.initials: S
authors.lastname: Kariuki
authors.affiliation: Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Drakeley
authors.affiliation: Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.|Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stevenson
authors.affiliation: Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cox
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002648:Child; D002675:Child, Preschool; D009033:Culicidae / Q000254:growth & development / Q000469:parasitology*; D016054:DNA, Protozoan / Q000097:blood / Q000235:genetics; D004197:Disease Reservoirs; D005260:Female; D006790:Host-Parasite Interactions; D006801:Humans; D015994:Incidence; D007303:Insect Vectors / Q000254:growth & development / Q000469:parasitology*; D057148:Insecticide-Treated Bednets; D007306:Insecticides; D007630:Kenya / Q000453:epidemiology; D008288:Malaria / Q000175:diagnosis / Q000453:epidemiology / Q000469:parasitology / Q000517:prevention & control* / Q000635:transmission*; D008297:Male; D009032:Mosquito Control / Q000379:methods*; D010961:Plasmodium / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D016133:Polymerase Chain Reaction; D011156:Population Density; D015995:Prevalence; D019035:Rural Health Services; D016036:Seroepidemiologic Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D016054:DNA, Protozoan; D007306:Insecticides