title: The effectiveness of non-pyrethroid insecticide-treated durable wall lining to control malaria in rural Tanzania: study protocol for a two-armed cluster randomized trial.
abstract: Despite considerable reductions in malaria achieved by scaling-up long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), maintaining sustained community protection remains operationally challenging. Increasing insecticide resistance also threatens to jeopardize the future of both strategies. Non-pyrethroid insecticide-treated wall lining (ITWL) may represent an alternate or complementary control method and a potential tool to manage insecticide resistance. To date no study has demonstrated whether ITWL can reduce malaria transmission nor provide additional protection beyond the current best practice of universal coverage (UC) of LLINs and prompt case management.
  
  
  
  A two-arm cluster randomized controlled trial will be conducted in rural Tanzania to assess whether non-pyrethroid ITWL and UC of LLINs provide added protection against malaria infection in children, compared to UC of LLINs alone. Stratified randomization based on malaria prevalence will be used to select 22 village clusters per arm. All 44 clusters will receive LLINs and half will also have ITWL installed on interior house walls. Study children, aged 6 months to 11 years old, will be enrolled from each cluster and followed monthly to estimate cumulative incidence of malaria parasitaemia (primary endpoint), time to first malaria episode and prevalence of anaemia before and after intervention. Entomological inoculation rate will be estimated using indoor CDC light traps and outdoor tent traps followed by detection of Anopheles gambiae species, sporozoite infection, insecticide resistance and blood meal source. ITWL bioefficacy and durability will be monitored using WHO cone bioassays and household surveys, respectively. Social and cultural factors influencing community and household ITWL acceptability will be explored through focus-group discussions and in-depth interviews. Cost-effectiveness, compared between study arms, will be estimated per malaria case averted.
  
  
  
  This protocol describes the large-scale evaluation of a novel vector control product, designed to overcome some of the known limitations of existing methods. If ITWL is proven to be effective and durable under field conditions, it may warrant consideration for programmatic implementation, particularly in areas with long transmission seasons and where pyrethroid-resistant vectors predominate. Trial findings will provide crucial information for policy makers in Tanzania and other malaria-endemic countries to guide resource allocations for future control efforts.
  
  
  
  NCT02533336 registered on 13 July 2014.
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania. mtoveg2002@gmail.com.
authors.forename: George
authors.initials: G
authors.lastname: Mtove
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mugasa
authors.affiliation: Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Louisa A
authors.initials: LA
authors.lastname: Messenger
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Malima
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Peter
authors.initials: P
authors.lastname: Mangesho
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Franklin
authors.initials: F
authors.lastname: Magogo
authors.affiliation: US President's Malaria Initiative, Atlanta, GA, USA.|Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Plucinski
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Ramadhan
authors.initials: R
authors.lastname: Hashimu
authors.affiliation: Kilimanjaro Christian Medical College, Moshi, Tanzania.
authors.forename: Johnson
authors.initials: J
authors.lastname: Matowo
authors.affiliation: National Institute for Medical Research, Headquarters, Dar es Salaam, Tanzania.
authors.forename: Donald
authors.initials: D
authors.lastname: Shepard
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Bernard
authors.initials: B
authors.lastname: Batengana
authors.affiliation: Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Jackie
authors.initials: J
authors.lastname: Cook
authors.affiliation: Kilimanjaro Christian Medical College, Moshi, Tanzania.|National Institute for Medical Research, Headquarters, Dar es Salaam, Tanzania.
authors.forename: Basiliana
authors.initials: B
authors.lastname: Emidi
authors.affiliation: Brandeis University, Heller School, Waltham, Massachusetts, USA.
authors.forename: Yara
authors.initials: Y
authors.lastname: Halasa
authors.affiliation: Kilimanjaro Christian Medical College, Moshi, Tanzania.
authors.forename: Robert
authors.initials: R
authors.lastname: Kaaya
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Aggrey
authors.initials: A
authors.lastname: Kihombo
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Lindblade
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Geofrey
authors.initials: G
authors.lastname: Makenga
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Robert
authors.initials: R
authors.lastname: Mpangala
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Abraham
authors.initials: A
authors.lastname: Mwambuli
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Ruth
authors.initials: R
authors.lastname: Mzava
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Abubakary
authors.initials: A
authors.lastname: Mziray
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: George
authors.initials: G
authors.lastname: Olang
authors.affiliation: PMI Africa Indoor Residual Spraying Project, Abt Associates, London, UK.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Oxborough
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Seif
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Edward
authors.initials: E
authors.lastname: Sambu
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Samuels
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: Wema
authors.initials: W
authors.lastname: Sudi
authors.affiliation: Phoenix Ordinary LLC, Bridgewater, New Jersey, USA.
authors.forename: John
authors.initials: J
authors.lastname: Thomas
authors.affiliation: Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Weston
authors.affiliation: President's Malaria Initiative, United States Agency for International Development, Washington DC, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Alilio
authors.affiliation: Translating Research into Action Project (TRAction) University Research Co., LLC, Bethesda, Maryland, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Binkin
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: John
authors.initials: J
authors.lastname: Gimnig
authors.affiliation: Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Immo
authors.initials: I
authors.lastname: Kleinschmidt
authors.affiliation: US President's Malaria Initiative, Atlanta, GA, USA.|Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: McElroy
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Moulton
authors.affiliation: President's Malaria Initiative, United States Agency for International Development, Washington DC, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Norris
authors.affiliation: Translating Research into Action Project (TRAction) University Research Co., LLC, Bethesda, Maryland, USA.
authors.forename: Trenton
authors.initials: T
authors.lastname: Ruebush
authors.affiliation: President's Malaria Initiative, United States Agency for International Development, Washington DC, USA.
authors.forename: Meera
authors.initials: M
authors.lastname: Venkatesan
authors.affiliation: Department of Disease Control, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Rowland
authors.affiliation: Kilimanjaro Christian Medical College, Moshi, Tanzania.
authors.forename: Franklin W
authors.initials: FW
authors.lastname: Mosha
authors.affiliation: National Institute for Medical Research, Amani Research Centre, Muheza, Tanzania.
authors.forename: William N
authors.initials: WN
authors.lastname: Kisinza
mesh_terms: D000740:Anemia / Q000453:epidemiology; D001681:Biological Assay; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D016000:Cluster Analysis; D004781:Environmental Exposure / Q000032:analysis* / Q000517:prevention & control; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007305:Insecticide Resistance; D007306:Insecticides / Q000008:administration & dosage*; D008288:Malaria / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission; D008297:Male; D009032:Mosquito Control / Q000379:methods*; D017063:Outcome Assessment, Health Care; D018512:Parasitemia / Q000453:epidemiology; D015995:Prevalence; D012424:Rural Population; D011795:Surveys and Questionnaires; D013636:Tanzania / Q000453:epidemiology
chemical_list: D007306:Insecticides
keywords: Cluster randomized controlled trial; Entomological inoculation rate; Insecticide resistance management; Insecticide-treated wall lining; Long-lasting insecticidal nets; Malaria control