title: The seasonality of tuberculosis, sunlight, vitamin D, and household crowding.
abstract: BACKGROUND
  Unlike other respiratory infections, tuberculosis diagnoses increase in summer. We performed an ecological analysis of this paradoxical seasonality in a Peruvian shantytown over 4 years.
  
  
  METHODS
  Tuberculosis symptom-onset and diagnosis dates were recorded for 852 patients. Their tuberculosis-exposed cohabitants were tested for tuberculosis infection with the tuberculin skin test (n = 1389) and QuantiFERON assay (n = 576) and vitamin D concentrations (n = 195) quantified from randomly selected cohabitants. Crowding was calculated for all tuberculosis-affected households and daily sunlight records obtained.
  
  
  RESULTS
  Fifty-seven percent of vitamin D measurements revealed deficiency (<50 nmol/L). Risk of deficiency was increased 2.0-fold by female sex (P < .001) and 1.4-fold by winter (P < .05). During the weeks following peak crowding and trough sunlight, there was a midwinter peak in vitamin D deficiency (P < .02). Peak vitamin D deficiency was followed 6 weeks later by a late-winter peak in tuberculin skin test positivity and 12 weeks after that by an early-summer peak in QuantiFERON positivity (both P < .04). Twelve weeks after peak QuantiFERON positivity, there was a midsummer peak in tuberculosis symptom onset (P < .05) followed after 3 weeks by a late-summer peak in tuberculosis diagnoses (P < .001).
  
  
  CONCLUSIONS
  The intervals from midwinter peak crowding and trough sunlight to sequential peaks in vitamin D deficiency, tuberculosis infection, symptom onset, and diagnosis may explain the enigmatic late-summer peak in tuberculosis.
authors.affiliation: IFHAD: Innovation For Health and Development, United Kingdom Infectious Diseases and Immunity, Imperial College London Wellcome Trust Imperial College Centre for Global Health Research, London The Monsall Infectious Diseases Unit, North Manchester General Hospital, Manchester.
authors.forename: Tom
authors.initials: T
authors.lastname: Wingfield
authors.affiliation: IFHAD: Innovation For Health and Development, United Kingdom Laboratorio de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Perú
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Schumacher
authors.affiliation: Laboratorio de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Perú Infectious Diseases and Immunity, Imperial College London Wellcome Trust Imperial College Centre for Global Health Research, London.
authors.forename: Gurjinder
authors.initials: G
authors.lastname: Sandhu
authors.affiliation: IFHAD: Innovation For Health and Development, United Kingdom Asociación Benefica Prisma Laboratorio de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Perú
authors.forename: Marco A
authors.initials: MA
authors.lastname: Tovar
authors.affiliation: IFHAD: Innovation For Health and Development, United Kingdom Asociación Benefica Prisma.
authors.forename: Karine
authors.initials: K
authors.lastname: Zevallos
authors.affiliation: Laboratorio de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Perú
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Baldwin
authors.affiliation: IFHAD: Innovation For Health and Development, United Kingdom Asociación Benefica Prisma.
authors.forename: Rosario
authors.initials: R
authors.lastname: Montoya
authors.affiliation: Laboratorio de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Perú
authors.forename: Eric S
authors.initials: ES
authors.lastname: Ramos
authors.affiliation: IFHAD: Innovation For Health and Development, United Kingdom.
authors.forename: Chulanee
authors.initials: C
authors.lastname: Jongkaewwattana
authors.affiliation: IFHAD: Innovation For Health and Development, United Kingdom Medical Research Council Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lewis
authors.affiliation: Asociación Benefica Prisma School of Public Health, Johns Hopkins Bloomberg School of Hygiene and Public Health, Baltimore, Maryland.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.affiliation: Infectious Diseases and Immunity, Imperial College London Wellcome Trust Imperial College Centre for Global Health Research, London.
authors.forename: Jon S
authors.initials: JS
authors.lastname: Friedland
authors.affiliation: IFHAD: Innovation For Health and Development, United Kingdom Laboratorio de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Perú Infectious Diseases and Immunity, Imperial College London Wellcome Trust Imperial College Centre for Global Health Research, London.
authors.forename: Carlton A
authors.initials: CA
authors.lastname: Evans
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003441:Crowding; D005191:Family Characteristics; D005260:Female; D006801:Humans; D015994:Incidence; D059425:Interferon-gamma Release Tests; D008297:Male; D010568:Peru / Q000453:epidemiology; D012621:Seasons; D013472:Sunlight; D014374:Tuberculin Test; D014376:Tuberculosis / Q000453:epidemiology*; D014807:Vitamin D / Q000097:blood*
chemical_list: D014807:Vitamin D
keywords: crowding; household; seasonality; sunlight; tuberculosis; vitamin D