Tuberculosis: Is the landscape changing?

Robert Heinrich Herman Koch, a German physician and microbiologist, received Nobel Prize in 1905 for identifying the specific causative agent of tuberculosis (TB). During his time it was believed that TB was an inherited disease. However he was convinced that the disease was caused by a bacterium and was infectious, tested his postulates using guinea pigs, and found the causative agent to be slow growing mycobacterium tuberculosis. TB is the second most common cause of death from infectious diseases after HIV/AIDS. Drug-resistant TB poses serious challenge to effective management of TB worldwide. Multidrug-resistant TB accounted for about half a million new cases and over 200,000 deaths in 2013. Whole-genome sequencing (first done in 1998) technologies have provided new insight into the mechanism of drug resistance. For the first time in 50 y, new anti TB drugs have been developed. The World Health Organization (WHO) has recently revised their treatment guidelines based on 32 studies. In United States, latent TB affects between 10 and 15 million people, 10% of whom may develop active TB disease. QuantiFERON TB Gold and T-SPOT.TB test are used for diagnosis. Further research will look into the importance of newly discovered gene mutations in causing drug resistance.

Comparing the tuberculin skin test and T-SPOT.TB blood test in children.

BACKGROUND: Interferon-γ-release assays (IGRAs) have been developed for the diagnosis of tuberculosis infection, but few data are available for children. There currently is no reference standard for the diagnosis of tuberculosis infection. OBJECTIVE: To compare the performance of 1 IGRA, the T-SPOT.TB assay with the tuberculin skin test (TST) in children with different epidemiologic risk factors for tuberculosis. METHODS: We conducted a prospective study of 210 patients referred to 3 pediatric tuberculosis clinics, including those with no risk factors for tuberculosis (low risk, n = 27), risk factors but no identifiable source case (intermediate risk, n = 78), contact with a known source case (high risk, n = 74), and active disease (n = 31). Children were tested with TST and T-SPOT.TB. Concordance analyses were performed, and assay outcomes were modeled by multivariate logistic regression. RESULTS: For 13 children with culture-confirmed tuberculosis disease, sensitivity of TST and T-SPOT.TB was 77% and 92%, respectively, and concordance was 69%. For high-risk children, concordance was 94% for BCG-unimmunized children and 88% for BCG-immunized children. For intermediate-risk children, concordance was 74% for BCG-unimmunized children and 33% for BCG-immunized children. For low-risk children, concordance was 74% for BCG-unimmunized children and 20% for BCG-immunized children. Multivariate analysis revealed that contact with a source case was associated with T-SPOT.TB result, but age and BCG immunization were not. CONCLUSIONS: T-SPOT.TB is comparable to the TST in the diagnosis of tuberculosis disease and identification of high-risk children with tuberculosis infection and is more specific than the TST in children who have received the BCG vaccine.