title: Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting.
abstract: BACKGROUND
  Children who are young, malnourished, and infected with HIV have significant risk of tuberculosis (TB) morbidity and mortality following TB infection. Treatment of TB infection is hindered by poor detection and limited pediatric data.
  
  
  OBJECTIVE
  Identify improved testing to detect pediatric TB infection.
  
  
  METHODS
  This was a prospective community-based study assessing use of the tuberculin skin test and IFN-γ release assays among children (n = 1,343; 6 mo to <15 yr) in TB-HIV high-burden settings; associations with child characteristics were measured.
  
  
  RESULTS
  Contact tracing detects TB in 8% of child contacts within 3 months of exposure. Among children with no documented contact, tuberculin skin test and QuantiFERON-TB Gold In-Tube positivity was greater than T-SPOT.TB. Nearly 8% of children had IFN-γ release assay positive and skin test negative discordance. In a model accounting for confounders, all tests correlate with TB contact, but IFN-γ release assays correlate better than the tuberculin skin test (P = 0.0011). Indeterminate IFN-γ release assay results were not associated with age. Indeterminate QuantiFERON-TB Gold In-Tube results were more frequent in children infected with HIV (4.7%) than uninfected with HIV (1.9%), whereas T-SPOT.TB indeterminates were rare (0.2%) and not affected by HIV status. Conversion and reversion were not associated with HIV status. Among children infected with HIV, tests correlated less with contact as malnutrition worsened.
  
  
  CONCLUSIONS
  Where resources allow, use of IFN-γ release assays should be considered in children who are young, recently exposed, and infected with HIV because they may offer advantages compared with the tuberculin skin test for identifying TB infection, and improve targeted, cost-effective delivery of preventive therapy. Affordable tests of infection could dramatically impact global TB control.
authors.affiliation: 1 Section on Retrovirology and Global Health, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Mandalakas
authors.forename: H Lester
authors.initials: HL
authors.lastname: Kirchner
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.forename: Robert P
authors.initials: RP
authors.lastname: Gie
authors.forename: H Simon
authors.initials: HS
authors.lastname: Schaaf
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
authors.forename: Harleen M S
authors.initials: HM
authors.lastname: Grewal
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Hesseling
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D042241:Early Diagnosis; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007223:Infant; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000209:etiology*; D008297:Male; D008403:Mass Screening / Q000379:methods*; D009169:Mycobacterium tuberculosis; D011446:Prospective Studies; D013019:South Africa; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000209:etiology*
keywords: HIV; IFN-γ release tests; latent tuberculosis infection; pediatrics; tuberculin test