Novel interferon-gamma assays for diagnosing tuberculosis in young children in India

Abstract

SUMMARY SETTING The tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) are used as supportive evidence to diagnose active tuberculosis (TB). Novel IGRAs could improve diagnosis, but data are lacking in young children. DESIGN Children (age ≤ 5 years) with suspected TB were prospectively screened at a tertiary hospital in Pune, India; the children underwent TST, and standard (early secretory antigenic target 6 and culture filtrate protein 10) and enhanced (five additional novel antigens) enzyme-linked immunospot (ELISpot) assays. RESULTS Of 313 children (median age 30 months) enrolled, 92% had received bacille Calmette-Guérin vaccination, 53% were malnourished and 9% were coinfected with the human immunodeficiency virus (HIV); 48 (15%) had TB, 128 (41%) did not, and TB could not be ruled out in 137 (44%). The sensitivity of enhanced (45%) and standard (42%) ELISpot assays for diagnosing TB was better than that of TST (20%) (P ≤ 0.03); however, enhanced ELISpot was not more sensitive than the standard ELISpot assay (P= 0.50). The specificity of enhanced ELISpot, standard ELISpot and TST was respectively 82% (95%CI 74–89), 88% (95%CI 81–94) and 98% (95%CI 93–100). Rv3879c and Rv3615c, previously reported to be promising antigens, failed to improve the diagnostic performance of the ELISpot assay. CONCLUSION The TST and the standard and novel ELISpot assays performed poorly in diagnosing active TB among young children in India.

<p>Prevalence, Associated Risk Factors and Rifampicin Resistance Pattern of Pulmonary Tuberculosis Among Children at Debre Markos Referral Hospital, Northwest, Ethiopia</p>

“…In this study, the prevalence of pulmonary tuberculosis among children is 5.73% (22/384), which is similar to the finding in Tanzania (5.2%). 34 However, it is higher than the findings reported in Zambia (1.58%), 35 Mozambique (1.65), 36 South Africa (1.3%), 37 and lower than reports from India (15%), 38 Zimbabwe (8.7%), 39 Greenland (8.5%), 40 South Africa (13%), 41 Uganda (10%), 42 Ethiopia (13.6%), 43 Bangladesh (32.97%) 44 and Nigeria (32%). 45 The reason for variation might be due to the difference in the prevalence of tuberculosis in the general population, methods of sputum sample collection and diagnosis.…”

Risk Factors for False-Negative Interferon-γ Release Assay Results in Culture-Confirmed Childhood TB

“…For example, first, age was associated with the IGRA results. [20][21][22] In addition, body mass index < 16.0 kg/m 2 ), HIV infection, race, HLA allele, and smoking habit were also associated with negative IGRA results. 6,15,23,24 Second, Sharninghausen et al 15 found that anemia (less hemoglobin) was an independent risk factor for an indeterminate IGRA result.…”

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

“…TB effectiveness for diagnosing pediatric tuberculosis as only adults were studied; substantial differences have been reported between immune responses to MTB in children versus adults. [ 41 , 42 ] Third, the impact of nontuberculous mycobacterial (NTM) infection was not considered here even though patients infected with M. kansasii, M. szulgai or M. marinum may also have positive IGRA results, since NTM also harbor genes encoding ESAT-6 and CFP-10 antigens. [ 7 ]…”