title: Malaria morbidity and pyrethroid resistance after the introduction of insecticide-treated bednets and artemisinin-based combination therapies: a longitudinal study.
abstract: BACKGROUND
  Substantial reductions in malaria have been reported in several African countries after distribution of insecticide-treated bednets and the use of artemisinin-based combination therapies (ACTs). Our aim was to assess the effect of these policies on malaria morbidity, mosquito populations, and asymptomatic infections in a west African rural population.
  
  
  METHODS
  We did a longitudinal study of inhabitants of Dielmo village, Senegal, between January, 2007, and December, 2010. We monitored the inhabitants for fever during this period and we treated malaria attacks with artesunate plus amodiaquine. In July, 2008, we offered longlasting insecticide (deltamethrin)-treated nets (LLINs) to all villagers. We did monthly night collections of mosquitoes during the whole study period, and we assessed asymptomatic carriage from cross-sectional surveys. Our statistical analyses were by negative binomial regression, logistic regression, and binomial or Fisher exact test.
  
  
  RESULTS
  There were 464 clinical malaria attacks attributable to Plasmodium falciparum during 17,858 person-months of follow-up. The incidence density of malaria attacks averaged 5·45 (95% CI 4·90-6·05) per 100 person-months between January, 2007, and July, 2008, before the distribution of LLINs. Incidence density decreased to 0·41 (0·29-0·55) between August, 2008, and August, 2010, but increased back to 4·57 (3·54-5·82) between September and December, 2010--ie, 27-30 months after the distribution of LLINs. The rebound of malaria attacks were highest in adults and children aged 10 years or older: 45 (63%) of 71 malaria attacks recorded in 2010 compared with 126 (33%) of 384 in 2007 and 2008 (p<0·0001). 37% of Anopheles gambiae mosquitoes were resistant to deltamethrin in 2010, and the prevalence of the Leu1014Phe kdr resistance mutation increased from 8% in 2007 to 48% in 2010 (p=0·0009).
  
  
  CONCLUSIONS
  Increasing pyrethroid resistance of A gambiae and increasing susceptibility of older children and adults, probably due to decreasing immunity, caused the rebound and age shift of malaria morbidity. Strategies to address the problem of insecticide resistance and to mitigate its effects must be urgently defined and implemented.
  
  
  BACKGROUND
  Institut de Recherche pour le Développement and the Pasteur Institute of Dakar.
authors.affiliation: Research Unit on Emerging Infectious and Tropical Diseases, Institut de Recherche pour le Développement, Dakar, Senegal. jean-francois.trape@ird.fr
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Trape
authors.forename: Adama
authors.initials: A
authors.lastname: Tall
authors.forename: Nafissatou
authors.initials: N
authors.lastname: Diagne
authors.forename: Ousmane
authors.initials: O
authors.lastname: Ndiath
authors.forename: Alioune B
authors.initials: AB
authors.lastname: Ly
authors.forename: Joseph
authors.initials: J
authors.lastname: Faye
authors.forename: Fambaye
authors.initials: F
authors.lastname: Dieye-Ba
authors.forename: Clémentine
authors.initials: C
authors.lastname: Roucher
authors.forename: Charles
authors.initials: C
authors.lastname: Bouganali
authors.forename: Abdoulaye
authors.initials: A
authors.lastname: Badiane
authors.forename: Fatoumata Diene
authors.initials: FD
authors.lastname: Sarr
authors.forename: Catherine
authors.initials: C
authors.lastname: Mazenot
authors.forename: Aïssatou
authors.initials: A
authors.lastname: Touré-Baldé
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.forename: Pierre
authors.initials: P
authors.lastname: Druilhe
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.forename: Christophe
authors.initials: C
authors.lastname: Rogier
authors.forename: Cheikh
authors.initials: C
authors.lastname: Sokhna
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D009033:Culicidae; D004351:Drug Resistance; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007299:Insect Bites and Stings / Q000453:epidemiology; D057148:Insecticide-Treated Bednets; D008137:Longitudinal Studies; D008288:Malaria / Q000188:drug therapy / Q000453:epidemiology*; D008875:Middle Aged; D009017:Morbidity; D009032:Mosquito Control; D010961:Plasmodium / Q000187:drug effects; D015995:Prevalence; D011722:Pyrethrins / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D011722:Pyrethrins; C031327:artemisinin