title: Expanding the hygiene hypothesis: early exposure to infectious agents predicts delayed-type hypersensitivity to Candida among children in Kilimanjaro.
abstract: BACKGROUND
  Multiple lines of evidence suggest that infections in early life prevent the development of pathological immune responses to allergens and autoantigens (the hygiene hypothesis). Early infections may also affect later immune responses to pathogen antigen.
  
  
  METHODS
  To evaluate an association between early infections and immune responses to pathogen antigen, delayed-type hypersensitivity (DTH) to Candida albicans was evaluated among 283 2- to 7-year-old children in Kilimanjaro, Tanzania. A questionnaire and physical examination were used to characterize variables reflecting early exposure to infectious agents (family size, house construction materials, BCG vaccination, hospitalization history). Logistic regression was used to evaluate the association between early exposure to infectious agents and DTH to C. albicans.
  
  
  RESULTS
  Triceps skinfold thickness (OR: 1.11; 95% CI: 1.01, 1.22) and age (OR: 1.27; 95% CI: 1.04, 1.55) were positively associated with DTH to C. albicans. Adjusted for age and sex, large family size (OR: 2.81; 95% CI: 1.04, 7.61), BCG vaccination scar (OR: 3.10; 95% CI: 1.10, 8.71), and hospitalization during infancy with an infectious disease (OR: 4.67; 95% CI: 1.00, 21.74) were positively associated with DTH to C. albicans.
  
  
  CONCLUSIONS
  Early life infections were positively associated with later DTH to C. albicans. This result supports an expansion of the hygiene hypothesis to explain not only pathological immune responses to allergens, but also appropriate immune responses to pathogens. Immune system development may be responsive to early infections as an adaptive means to tailor reactivity to the local infectious disease ecology.
authors.affiliation: Department of Anthropology, University of Washington, Seattle, Washington, United States of America. kwander@u.washington.edu
authors.forename: Katherine
authors.initials: K
authors.lastname: Wander
authors.forename: Kathleen
authors.initials: K
authors.lastname: O'Connor
authors.forename: Bettina
authors.initials: B
authors.lastname: Shell-Duncan
mesh_terms: D000485:Allergens / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage; D002176:Candida albicans / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005191:Family Characteristics; D005260:Female; D006801:Humans; D061148:Hygiene Hypothesis; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D008297:Male; D012882:Skin Tests; D013636:Tanzania
chemical_list: D000485:Allergens; D001500:BCG Vaccine