title: Evaluation of the prognostic value of IFN-gamma release assay and tuberculin skin test in household contacts of infectious tuberculosis cases in Senegal.
abstract: BACKGROUND
  Chemoprophylaxis of contacts of infectious tuberculosis (TB) cases is recommended for TB control, particularly in endemic countries, but is hampered by the difficulty to diagnose latent TB infection (LTBI), classically assessed through response to the Tuberculin Skin Test (TST). Interferon-gamma release assays (IGRA) are proposed new tools to diagnose LTBI, but there are limited data on their ability to predict the development of active TB disease. To address this, we investigated the response to TST and IGRA in household contacts of infectious TB cases in a TB high-burden country and the potential correlation with development of TB.
  
  
  RESULTS
  Prospective household contacts study conducted in two health centres in Dakar, Senegal. A total of 2679 household contacts of 206 newly detected smear and/or culture positive index TB cases aged 18 years or greater were identified A TST was performed in each contact and an ESAT6/CFP10 ELISPOT assay performed in a random sample of those. Contacts were followed-up for 24 months. TB was diagnosed in 52 contacts, an incidence rate of 9.27/1000 person-years. In univariable analysis, the presence of positive TST (> or = 10 mm) and ELISPOT (>32 SFC/million PBMC) responses at baseline were associated with active TB during follow-up: Rate Ratio [RR] = 2.32 (95%CI:1.12-4.84) and RR = 2.09 (95%CI:0.83-5.31), respectively. After adjustment for age, sex and proximity to index case, adjusted RRs were 1.51 (95%CI:0.71-3.19) and 1.98 (95%CI:0.77-5.09), respectively. Restricting analysis to the 40 microbiologically confirmed cases, the adjusted RR for positive ELISPOT was 3.61 (95%CI:1.03-12.65). The median ELISPOT response in contacts who developed TB was 5-fold greater than in those who did not develop TB (p = 0.02).
  
  
  CONCLUSIONS
  TST and IGRAs are markers of a contact of the immune system with tubercle bacilli. In a TB endemic area, a high ELISPOT response may reflect increased bacterial replication that may subsequently be associated with development of TB disease and may have a prognostic value. Further longitudinal data are needed to assess whether IGRAs are reliable markers to be used for targeting chemoprophylaxis.
authors.affiliation: Institut de Recherche pour le Développement, Programme Tuberculose, Dakar, Senegal. lienhardtc@who.int
authors.forename: Christian
authors.initials: C
authors.lastname: Lienhardt
authors.forename: Katherine
authors.initials: K
authors.lastname: Fielding
authors.forename: Abdoul A
authors.initials: AA
authors.lastname: Hane
authors.forename: Aliou
authors.initials: A
authors.lastname: Niang
authors.forename: Cheikh T
authors.initials: CT
authors.lastname: Ndao
authors.forename: Farba
authors.initials: F
authors.lastname: Karam
authors.forename: Helen
authors.initials: H
authors.lastname: Fletcher
authors.forename: Fatou
authors.initials: F
authors.lastname: Mbow
authors.forename: Jules-François
authors.initials: JF
authors.lastname: Gomis
authors.forename: Raymond
authors.initials: R
authors.lastname: Diadhiou
authors.forename: Roger
authors.initials: R
authors.lastname: Diadhiou
authors.forename: Maxime
authors.initials: M
authors.lastname: Toupane
authors.forename: Tandakha
authors.initials: T
authors.lastname: Dieye
authors.forename: Souleymane
authors.initials: S
authors.lastname: Mboup
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005191:Family Characteristics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D015994:Incidence; D007371:Interferon-gamma / Q000032:analysis* / Q000378:metabolism*; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D012675:Senegal / Q000453:epidemiology; D013997:Time Factors; D014374:Tuberculin Test / Q000379:methods*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000453:epidemiology; D055815:Young Adult
chemical_list: D007371:Interferon-gamma
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