title: Helminths and skewed cytokine profiles increase tuberculin skin test positivity in Warao Amerindians.
abstract: The immune regulatory mechanisms involved in the acquisition of Mycobacterium tuberculosis infection in children are largely unknown. We investigated the influence of parasitic infections, malnutrition and plasma cytokine profiles on tuberculin skin test (TST) positivity in Warao Amerindians in Venezuela. Pediatric household contacts of sputum smear-positive tuberculosis (TB) cases were enrolled for TST, chest radiograph, plasma cytokine analyses, QuantiFERON-TB Gold In-Tube (QFT-GIT) testing and stool examinations. Factors associated with TST positivity were studied using generalized estimation equations logistic regression models. Of the 141 asymptomatic contacts, 39% was TST-positive. After adjusting for age, gender and nutritional status, TST positivity was associated with Trichuris trichiura infections (OR 3.5, 95% CI 1.1-11.6) and low circulating levels of T helper 1 (Th1) cytokines (OR 0.51, 95% CI 0.33-0.79). Ascaris lumbricoides infections in interaction with Th2- and interleukin (IL)-10-dominated cytokine profiles were positively associated with TST positivity (OR 3.1, 95% CI 1.1-8.9 and OR 2.4, 95% CI 1.04-5.7, respectively). A negative correlation of QFT-GIT mitogen responses with Th1 and Th2 levels and a positive correlation with age were observed (all p < 0.01). We conclude that helminth infections and low Th1 cytokine plasma levels are significantly associated with TST positivity in indigenous Venezuelan pediatric TB contacts.
authors.affiliation: Laboratorio de Tuberculosis, Instituto de Biomedicina, Caracas, Venezuela. lillyverhagen@hotmail.com
authors.forename: L M
authors.initials: LM
authors.lastname: Verhagen
authors.forename: P W M
authors.initials: PW
authors.lastname: Hermans
authors.forename: A
authors.initials: A
authors.lastname: Warris
authors.forename: R
authors.initials: R
authors.lastname: de Groot
authors.forename: M
authors.initials: M
authors.lastname: Maes
authors.forename: J A
authors.initials: JA
authors.lastname: Villalba
authors.forename: B
authors.initials: B
authors.lastname: del Nogal
authors.forename: S
authors.initials: S
authors.lastname: van den Hof
authors.forename: L
authors.initials: L
authors.lastname: Mughini Gras
authors.forename: D
authors.initials: D
authors.lastname: van Soolingen
authors.forename: E
authors.initials: E
authors.lastname: Pinelli
authors.forename: J H
authors.initials: JH
authors.lastname: de Waard
mesh_terms: D000818:Animals; D017164:Ascaris lumbricoides / Q000302:isolation & purification; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000276:immunology*; D005191:Family Characteristics; D005260:Female; D006373:Helminthiasis / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D044342:Malnutrition / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D044382:Population Groups; D015995:Prevalence; D011933:Reagent Kits, Diagnostic; D012307:Risk Factors; D014258:Trichuris / Q000302:isolation & purification; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D014687:Venezuela / Q000453:epidemiology
chemical_list: D016207:Cytokines; D011933:Reagent Kits, Diagnostic