title: The Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA): study protocol for a randomised controlled trial.
abstract: BACKGROUND
  The Hygiene Hypothesis proposes that infection exposure protects against inflammatory conditions. Helminths possess allergen-like molecules and may specifically modulate allergy-related immunological pathways to inhibit responses which protect against them. Mass drug administration is recommended for helminth-endemic communities to control helminth-induced pathology, but may also result in increased rates of inflammation-mediated diseases in resource-poor settings. Immunological studies integrated with implementation of helminth control measures may elucidate how helminth elimination contributes to ongoing epidemics of inflammatory diseases. We present the design of the Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA), a cluster-randomised trial evaluating the risks and benefits of intensive versus standard anthelminthic treatment for allergy-related diseases and other health outcomes.
  
  
  METHODS
  The setting is comprised of island fishing communities in Mukono district, Uganda. Twenty-six communities have been randomised in a 1:1 ratio to receive standard or intensive anthelminthic intervention for a three-year period. Baseline characteristics were collected immediately prior to intervention rollout, commenced in February 2013. Primary outcomes are reported wheeze in the past 12 months and atopy (skin prick test response and allergen-specific immunoglobulin (asIg) E concentration). Secondary outcomes are visible flexural dermatitis, helminth infections, haemoglobin, growth parameters, hepatosplenomegaly, and responses to vaccine antigens. The trial provides a platform for in-depth analysis of clinical and immunological consequences of the contrasting interventions.
  
  
  CONCLUSIONS
  The baseline survey has been completed successfully in a challenging environment. Baseline characteristics were balanced between trial arms. Prevalence of Schistosoma mansoni, hookworm, Strongyloides stercoralis and Trichuris trichiura was 52%, 23%, 13%, and 12%, respectively; 31% of Schistosoma mansoni infections were heavy (>400 eggs/gram). The prevalence of reported wheeze and positive skin prick test to any allergen was 5% and 20%, respectively. Respectively, 77% and 87% of participants had Dermatophagoides- and German cockroach-specific IgE above 0.35 kUA/L. These characteristics suggest that the LaVIISWA study will provide an excellent framework for investigating beneficial and detrimental effects of worms and their treatment, and the mechanisms of such effects.
  
  
  BACKGROUND
  This trial was registered with Current Controlled Trials (identifier: ISRCTN47196031) on 7 September 2012.
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, PO Box 49, Entebbe, Uganda. maggie.nampijja@gmail.com.
authors.forename: Margaret
authors.initials: M
authors.lastname: Nampijja
authors.affiliation: London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. emily.webb@lshtm.ac.uk.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Webb
authors.affiliation: Vector Control Division, Ministry of Health, PO Box 1661, Kampala, Uganda. james.kaweesa@yahoo.co.uk.
authors.forename: James
authors.initials: J
authors.lastname: Kaweesa
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, PO Box 49, Entebbe, Uganda. kizindorobert@yahoo.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Kizindo
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, PO Box 49, Entebbe, Uganda. namutebimilly49@yahoo.com.
authors.forename: Milly
authors.initials: M
authors.lastname: Namutebi
authors.affiliation: Entebbe Hospital, PO Box 29, Entebbe, Uganda. esthersanyu22@gmail.com.
authors.forename: Esther
authors.initials: E
authors.lastname: Nakazibwe
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, PO Box 49, Entebbe, Uganda. odurugloria@yahoo.com.
authors.forename: Gloria
authors.initials: G
authors.lastname: Oduru
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, PO Box 49, Entebbe, Uganda. pkabubi2010@gmail.com.
authors.forename: Prossy
authors.initials: P
authors.lastname: Kabuubi
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, PO Box 49, Entebbe, Uganda. Joyce.Kabagenyi@mrcuganda.org.
authors.forename: Joyce
authors.initials: J
authors.lastname: Kabagenyi
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, PO Box 49, Entebbe, Uganda. dennison.kizito@mrcuganda.org.
authors.forename: Dennison
authors.initials: D
authors.lastname: Kizito
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, PO Box 49, Entebbe, Uganda. Lawrence.Muhangi@mrcuganda.org.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Muhangi
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, PO Box 49, Entebbe, Uganda. mirriam_akello@yahoo.com.
authors.forename: Mirriam
authors.initials: M
authors.lastname: Akello
authors.affiliation: Laboratory for Medical Microbiology and Immunology, St Elisabeth Hospital, Postbus 90151, 5000 LC, Tilburg, the Netherlands. J.Verweij@elisabeth.nl.
authors.forename: Jaco J
authors.initials: JJ
authors.lastname: Verweij
authors.affiliation: Uganda Virus Research Institute, PO Box 49, Entebbe, Uganda. bnerimanaomi@yahoo.com.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nerima
authors.affiliation: Vector Control Division, Ministry of Health, PO Box 1661, Kampala, Uganda. edmuheki@gmail.com.
authors.forename: Edridah
authors.initials: E
authors.lastname: Tukahebwa
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, PO Box 49, Entebbe, Uganda. alison.elliott@mrcuganda.org.|London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. alison.elliott@mrcuganda.org.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Elliott
mesh_terms: D015766:Albendazole / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D002985:Clinical Protocols; D003876:Dermatitis, Atopic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D004334:Drug Administration Schedule; D006454:Hemoglobins / Q000378:metabolism; D006790:Host-Parasite Interactions; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007428:Intradermal Tests; D011223:Praziquantel / Q000008:administration & dosage* / Q000009:adverse effects; D012107:Research Design; D012130:Respiratory Hypersensitivity / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D012135:Respiratory Sounds / Q000187:drug effects / Q000276:immunology; D012550:Schistosoma mansoni / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity; D012555:Schistosomiasis mansoni / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D017171:Strongyloides stercoralis / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity; D013322:Strongyloidiasis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D013997:Time Factors; D016896:Treatment Outcome; D014257:Trichuriasis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D014258:Trichuris / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity; D014454:Uganda
chemical_list: D000871:Anthelmintics; D015415:Biomarkers; D006454:Hemoglobins; D007073:Immunoglobulin E; D011223:Praziquantel; D015766:Albendazole