title: A cohort study of the effectiveness of insecticide-treated bed nets to prevent malaria in an area of moderate pyrethroid resistance, Malawi.
abstract: BACKGROUND
  Insecticide-treated bed nets (ITNs) are the cornerstone of malaria control in sub-Saharan Africa but their effectiveness may be compromised by the spread of pyrethroid resistance among malaria vectors. The objective of this investigation was to assess the effectiveness of ITNs to prevent malaria in an area of Malawi with moderate pyrethroid resistance.
  
  
  METHODS
  One deltamethrin ITN was distributed in the study area for every two individuals in each household plus one extra ITN for households with an odd number of residents. A fixed cohort of 1,199 children aged six to 59 months was seen monthly for one year and at sick visits to measure malaria infection and use of ITNs. Insecticide resistance among malaria vectors was measured. The effect of ITN use on malaria incidence was assessed, adjusting for potential confounders using generalized estimating equations accounting for repeated measures.
  
  
  RESULTS
  There were 1,909 infections with Plasmodium falciparum over 905 person-years at risk (PYAR), resulting in an observed incidence of 2.1 infections per person-year (iPPY). ITNs were used during 97% of the PYAR. The main vector was Anopheles funestus: mortality in WHO tube assays after exposure to 0.05% deltamethrin was 38% (95% confidence interval (CI) 29-47), and resistance was due to elevated oxidase enzymes. After adjusting for potential confounders, the incidence of malaria infection among ITN users was 1.7 iPPY (95% CI 1.5-2.1) and among non-bed net users was 2.6 iPPY (95% CI 2.0-3.3). Use of ITNs reduced the incidence of malaria infection by 30% (rate ratio 0.7; 95% CI, 0.5-0.8) compared to no bed nets.
  
  
  CONCLUSIONS
  ITNs significantly reduced the incidence of malaria infection in children in an area with moderate levels of pyrethroid resistance and considerable malaria transmission. This is the first study to show that ITNs provide protection in areas where pyrethroid-resistant An. funestus is the major malaria vector. Malaria control programmes should continue to distribute and promote ITNs in areas with low to moderate pyrethroid resistance; however, insecticide resistance may intensify further and it is not known whether ITNs will remain effective at higher levels of resistance. There is an urgent need to identify or develop new insecticides and technologies to limit the vulnerability of ITNs to insecticide resistance.
authors: Division of Parasitic Diseases and Malaria, US Centers for Disease Control and Prevention, 1600 Clifton Rd. NE MS A-06, Atlanta, GA, 30333, USA. kil2@cdc.gov.
authors: Kim A
authors: KA
authors: Lindblade
authors: Malaria Alert Centre, Malawi College of Medicine, Blantyre, Malawi. dmwandama@mac.medcol.mw.
authors: Dyson
authors: D
authors: Mwandama
authors: Malaria Alert Centre, Malawi College of Medicine, Blantyre, Malawi. tmzilahowa@mlw.medcol.mw.
authors: Themba
authors: T
authors: Mzilahowa
authors: Division of Parasitic Diseases and Malaria, US Centers for Disease Control and Prevention, 1600 Clifton Rd. NE MS A-06, Atlanta, GA, 30333, USA. lsteinhardt@cdc.gov.
authors: Laura
authors: L
authors: Steinhardt
authors: Division of Parasitic Diseases and Malaria, US Centers for Disease Control and Prevention, 1600 Clifton Rd. NE MS A-06, Atlanta, GA, 30333, USA. jgimnig@cdc.gov.
authors: John
authors: J
authors: Gimnig
authors: Division of Parasitic Diseases and Malaria, US Centers for Disease Control and Prevention, 1600 Clifton Rd. NE MS A-06, Atlanta, GA, 30333, USA. hyy9@cdc.gov.
authors: Monica
authors: M
authors: Shah
authors: Malaria Alert Centre, Malawi College of Medicine, Blantyre, Malawi. abauleni@mac.medcol.mw.
authors: Andy
authors: A
authors: Bauleni
authors: Division of Parasitic Diseases and Malaria, US Centers for Disease Control and Prevention, 1600 Clifton Rd. NE MS A-06, Atlanta, GA, 30333, USA. vsm0@cdc.gov.
authors: Jacklyn
authors: J
authors: Wong
authors: Division of Parasitic Diseases and Malaria, US Centers for Disease Control and Prevention, 1600 Clifton Rd. NE MS A-06, Atlanta, GA, 30333, USA. fwk2@cdc.gov.
authors: Ryan
authors: R
authors: Wiegand
authors: Division of Parasitic Diseases and Malaria, US Centers for Disease Control and Prevention, 1600 Clifton Rd. NE MS A-06, Atlanta, GA, 30333, USA. bsr7@cdc.gov.
authors: Paul
authors: P
authors: Howell
authors: National Malaria Control Programme, Ministry of Public Health, Lilongwe, Malawi. zoyaj2003@yahoo.co.uk.
authors: John
authors: J
authors: Zoya
authors: National Malaria Control Programme, Ministry of Public Health, Lilongwe, Malawi. chiphwanyajohn@yahoo.com.
authors: John
authors: J
authors: Chiphwanya
authors: Malaria Alert Centre, Malawi College of Medicine, Blantyre, Malawi. dmathang@mac.medcol.mw.
authors: Don P
authors: DP
authors: Mathanga
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007303:Insect Vectors / Q000187:drug effects; D007305:Insecticide Resistance; D057148:Insecticide-Treated Bednets / Q000706:statistics & numerical data*; D007306:Insecticides / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000517:prevention & control*; D008295:Malawi / Q000453:epidemiology; D008297:Male; D011722:Pyrethrins / Q000494:pharmacology
chemical_list: D007306:Insecticides; D011722:Pyrethrins
references: Biometrics. 1986 Mar;42(1):121-30
references: 3719049
references: Malar J. 2012 Mar 19;11:74
references: 22423618
references: Stat Med. 1998 Jul 30;17(14):1643-58
references: 9699236
references: PLoS Med. 2011 Sep;8(9):e1001091
references: 21909249
references: Malar J. 2007 Oct 31;6:142
references: 17973989
references: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):68-77
references: 12749488
references: Malar J. 2008 Oct 29;7:221
references: 18959777
references: Trends Parasitol. 2002 Jan;18(1):12-6
references: 11850008
references: Am J Trop Med Hyg. 1998 Jan;58(1):1-6
references: 9452282
references: S Afr Med J. 2005 Nov;95(11):871-4
references: 16344885
references: Emerg Infect Dis. 2012 Feb;18(2):272-8
references: 22305090
references: Am J Trop Med Hyg. 2005 Nov;73(5):859-64
references: 16282294
references: PLoS One. 2010 Jul 29;5(7):e11872
references: 20686697
references: Am J Trop Med Hyg. 2013 Nov;89(5):840-849
references: 24062477
references: Ann Soc Belg Med Trop. 1993 Dec;73(4):291-4
references: 8129474
references: PLoS Med. 2011 Sep;8(9):e1001088
references: 21909247
references: Bull World Health Organ. 1987;65(6):869-77
references: 3325185
references: Demography. 2001 Feb;38(1):115-32
references: 11227840
references: Malar J. 2006 Dec 19;5:125
references: 17177993
references: Bull World Health Organ. 1987;65(1):39-45
references: 3555879
references: Med Vet Entomol. 2000 Jun;14(2):181-9
references: 10872862
references: PLoS One. 2012;7(2):e31943
references: 22384107
references: Malar J. 2014 Mar 01;13:76
references: 24581394
references: Philos Trans R Soc Lond B Biol Sci. 2014 May 12;369(1645):20130431
references: 24821917
references: Antimicrob Agents Chemother. 2000 Mar;44(3):697-704
references: 10681341
references: Malar J. 2010 Dec 31;9:380
references: 21194470
references: Parasit Vectors. 2014 Aug 23;7:390
references: 25150975
references: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):16-22
references: 12749481
references: Trends Parasitol. 2011 Feb;27(2):91-8
references: 20843745
references: Cochrane Database Syst Rev. 2000;(2):CD000363
references: 10796535
references: PLoS One. 2012;7(3):e32929
references: 22479349
references: Am J Trop Med Hyg. 2003 Apr;68(4 Suppl):121-7
references: 12749495
references: PLoS Med. 2014 Mar 18;11(3):e1001619
references: 24642791
references: Malar J. 2007 May 02;6:52
references: 17474975
references: Bull World Health Organ. 2003;81(5):324-33
references: 12856050
references: Trans R Soc Trop Med Hyg. 2011 May;105(5):247-53
references: 21353689
references: J Vector Borne Dis. 2003 Mar-Jun;40(1-2):1-8
references: 15119065
references: Am J Trop Med Hyg. 1999 Apr;60(4):687-92
references: 10348249
references: Med Vet Entomol. 1989 Jul;3(3):253-62
references: 2519670
references: Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19063-70
references: 23118337
references: Parasitol Today. 1988 Jul;4(7):S15-7
references: 15463084
references: Trans R Soc Trop Med Hyg. 1988;82(2):212-5
references: 3055456
references: Proc Annu Meet N J Mosqu Exterm Assoc. 1946 Apr;33:65-9
references: 20251718