2015/09/12 by Cherie Priya Dhar, Blanca Elena Gonzalez, Blanca E. Gonzalez +3
Medicine · Immunology and Microbiology · #Tuberculosis Research and Epidemiology #Immunodeficiency and Autoimmune Disorders #Diagnosis and treatment of tuberculosis
paper · doi:10.1097/inf.0000000000000829
To the Editors: We read the recent article “Evaluation of QuantiFeron-TB Gold In-tube and Tuberculin Skin Test Among Immigrant Children Being Screened for Latent Tuberculosis Infection” by Howley et al1 with great interest. This study supports the use of interferon gamma release assays (IGRAs) over the tuberculin skin test (TST) in foreign-born children for the diagnosis of latent tuberculosis infection (LTBI). Among 2-to-14-year-old children (N = 2520), presumably Bacillus Calmette–Guérin (BCG) vaccinated, immigrating to the US from tuberculosis endemic areas, the TST and QuantiFERON-TB Gold In-Tube (QFT) had poor agreement. The TST was positive (>10 mm) in 26% of children; of these, 17% had a positive QFT. Conversely, 2% of children had a negative TST and positive QFT. The dilemma of choosing the best test for BCG-vaccinated international adoptees is complex. Following institutional review board approval, we performed a retrospective chart review of children evaluated at the International Adoption Clinic of Rainbow Babies and Children’s Hospital, Cleveland, Ohio, between January 2007 and December 2012. Thirty-four children (median age 26.5 months, range 0.5–11 years) were studied. The majority were adopted from China, Russia and Ethiopia. Though only 33% had confirmed receipt of BCG-vaccine, all children arrived from countries where neonatal BCG vaccination is in routine practice. LTBI was diagnosed in 15 children; 13 had positive TST but negative IGRA, 1 had both positive IGRA and TST and 1 had a positive IGRA but no TST performed. The 2 children with positive IGRAs were 4-year-old and 6-year-old siblings whose mother had died of tuberculosis. Contrary to the study by Howley et al,1 where family history of TB was known and chest radiographs of family members were available, most of our patients had unknown family histories. Recognizing the high risk of LTBI in young international adoptees, we elected to optimize sensitivity of testing by utilizing both TST and IGRA. The study by Howley et al1 provides additional evidence of the advantages of IGRAs in BCG-vaccinated children. Basu Roy et al2 demonstrated that young age was a predictor of indeterminate IGRA results, but noted that indeterminate results occur at clinically insignificant rates. Mandalakas et al3 did not find correlation between age and indeterminate results but demonstrated that IGRAs correlate better with recent tuberculosis contact than the TST among children as young as 6 months of age. In a meta-analysis by Sun et al,4 the specificity of the IGRA was higher for BCG-vaccinated children than the TST (89% vs. 49%). Should we hesitate to use IGRAs in young BCG-vaccinated children? The American Academy of Pediatrics Committee of Infectious Disease now recommends IGRA as an alternative to the TST in BCG-vaccinated children over 5 years of age,5 but for 2-to-4-year-old children, the recommendation is lukewarm and left to the discretion of experts. Our clinical experience supports more liberal use of IGRAs in BCG-vaccinated children as young as 2 years of age in whom good follow-up can be assured. Reliance on IGRAs could improve the positive predictive value of testing and the quality of care afforded to pediatric patients by reducing the use of unnecessary medications, chest radiography, clinician visits and parental anxiety associated with LTBI. Cherie Priya Dhar, MD Adolescent Medicine Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Blanca Elena Gonzalez, MD Center for Pediatric Infectious Diseases Cleveland Clinic Children’s Hospital Cleveland, Ohio Therese Dragga, RN Denise Bothe, MD Developmental Behavioral Pediatrics University Hospitals Rainbow Babies and Children’s Hospital Cleveland, Ohio Anna M. Mandalakas, MD Global TB Program Baylor College of Medicine and Texas Children’s Hospital Houston, Texas