title: Multiple causes of an unexpected malaria outbreak in a high-transmission area in Madagascar.
abstract: BACKGROUND
  The malaria burden in Madagascar dropped down last decade, largely due to scale-up of control measures. Nevertheless, a significant rise of malaria cases occurred in 2011-2012 in two regions of the rainy South-Eastern Madagascar, where malaria is considered as mesoendemic and the population is supposed to be protected by its acquired immunity against Plasmodium. A multidisciplinary investigation was conducted in order to identify the causes of the outbreak.
  
  
  METHODS
  In March 2012, a cross-sectional study was conducted in 20 randomly selected clusters, involving the rapid diagnostic testing of all ≥6 month-old members of households and a questionnaire about socio-demographic data and exposure to malaria control interventions. Changes in environmental conditions were evaluated by qualitative interview of local authorities, climatic conditions were evaluated by remote-sensing, and stock outs of malaria supplies in health facilities were evaluated by quantitative means. Two long-lasting insecticidal nets (LLINs) were sampled in each cluster in order to evaluate their condition and the remanence of their insecticidal activity. The entomological investigation also encompassed the collection Anopheles vectors in two sites, and the measure of their sensitivity to deltamethrin.
  
  
  RESULTS
  The cross-sectional survey included 1615 members of 440 households. The mean Plasmodium infection rate was 25.6 % and the mean bed net use on the day before survey was 71.1 %. The prevalence of Plasmodium infections was higher in 6-14 year-old children (odds ratio (OR) 7.73 [95 % CI 3.58-16.68]), in rural areas (OR 6.25 [4.46-8.76]), in poorest socio-economic tercile (OR 1.54 [1.13-2.08]), and it was lower in individuals sleeping regularly under the bed net (OR 0.51 [0.32-0.82]). Stock outs of anti-malarial drugs in the last 6 months have been reported in two third of health facilities. Rainfalls were increased as compared with the three previous rainy seasons. Vectors collected were sensitive to pyrethroids. Two years after distribution, nearly all LLINs collected showed a loss of physical integrity and insecticide activity,
  
  
  CONCLUSIONS
  Increased rainfall, decreasing use and reduced insecticide activity of long-lasting insecticide-treated nets, and drug shortages may have been responsible for, or contributed to, the outbreak observed in South-Eastern Madagascar in 2011-2012. Control interventions for malaria elimination must be sustained at the risk of triggering harmful epidemics, even in zones of high transmission.
authors.affiliation: Institut Pasteur de Madagascar, Avaradoha, BP 1274, 101, Antananarivo, Madagascar. thomask@pasteur.mg.|Unité de recherche sur les maladies infectieuses et tropicales émergentes (URMITE)-UMR 6236, 27 boulevard Jean Moulin, 13385, Marseille Cedex 05, France. thomask@pasteur.mg.|Fondation Mérieux, 17 rue Bourgelat, 69002, Lyon, France. thomask@pasteur.mg.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kesteman
authors.affiliation: Institut Pasteur de Madagascar, Avaradoha, BP 1274, 101, Antananarivo, Madagascar. armarafal@gmail.com.|Direction de Veille Sanitaire et de Surveillance Epidémiologique, Ministère de la Santé, Antananarivo, Madagascar. armarafal@gmail.com.
authors.forename: Solofoniaina A
authors.initials: SA
authors.lastname: Rafalimanantsoa
authors.affiliation: Institut Pasteur de Madagascar, Avaradoha, BP 1274, 101, Antananarivo, Madagascar. rhmahefa@yahoo.fr.|Direction de Veille Sanitaire et de Surveillance Epidémiologique, Ministère de la Santé, Antananarivo, Madagascar. rhmahefa@yahoo.fr.
authors.forename: Harimahefa
authors.initials: H
authors.lastname: Razafimandimby
authors.affiliation: Direction de Lutte contre le Paludisme, Ministère de la Santé Publique, Antananarivo, Madagascar. andokevin@yahoo.fr.
authors.forename: Heriniaina H
authors.initials: HH
authors.lastname: Rasamimanana
authors.affiliation: Institut Pasteur de Madagascar, Avaradoha, BP 1274, 101, Antananarivo, Madagascar. rvmalala@pasteur.mg.
authors.forename: Vaomalala
authors.initials: V
authors.lastname: Raharimanga
authors.affiliation: Direction de Lutte contre le Paludisme, Ministère de la Santé Publique, Antananarivo, Madagascar. rabefan2009@yahoo.fr.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ramarosandratana
authors.affiliation: Direction de Lutte contre le Paludisme, Ministère de la Santé Publique, Antananarivo, Madagascar. aratsimbasoa@gmail.com.
authors.forename: Arsene
authors.initials: A
authors.lastname: Ratsimbasoa
authors.affiliation: Institut Pasteur de Madagascar, Avaradoha, BP 1274, 101, Antananarivo, Madagascar. ratov@pasteur.mg.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Ratovonjato
authors.affiliation: Institut Pasteur de Madagascar, Avaradoha, BP 1274, 101, Antananarivo, Madagascar. nohal_elissa@yahoo.com.
authors.forename: Nohal
authors.initials: N
authors.lastname: Elissa
authors.affiliation: Institut Pasteur de Madagascar, Avaradoha, BP 1274, 101, Antananarivo, Madagascar. laurence@pasteur.mg.
authors.forename: Laurence
authors.initials: L
authors.lastname: Randrianasolo
authors.affiliation: US Centers for Disease Control and Prevention, Atlanta, GA, USA. alyssafinlay@gmail.com.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Finlay
authors.affiliation: Institut Pasteur de Madagascar, Avaradoha, BP 1274, 101, Antananarivo, Madagascar. christophe.rogier@gmail.com.|Unité de recherche sur les maladies infectieuses et tropicales émergentes (URMITE)-UMR 6236, 27 boulevard Jean Moulin, 13385, Marseille Cedex 05, France. christophe.rogier@gmail.com.|Institute for Biomedical Research of the French Armed Forces (IRBA), BP 73, 91223, Brétigny-Sur-Orge Cedex, France. christophe.rogier@gmail.com.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rogier
authors.affiliation: Institut Pasteur de Madagascar, Avaradoha, BP 1274, 101, Antananarivo, Madagascar. milijaon@pasteur.mg.
authors.forename: Milijaona
authors.initials: M
authors.lastname: Randrianarivelojosia
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004196:Disease Outbreaks; D005260:Female; D006801:Humans; D007223:Infant; D057148:Insecticide-Treated Bednets; D008270:Madagascar / Q000453:epidemiology; D008288:Malaria / Q000188:drug therapy / Q000453:epidemiology* / Q000635:transmission*; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use; D010961:Plasmodium / Q000502:physiology; D011722:Pyrethrins / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000962:Antimalarials; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin
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