Immunological Diagnosis of Tuberculosis Based on Recombinant Antigens ESAT-6 and CFP-10 in Children from an Endemic Area in Northeast Brazil

Abstract

Diagnostic tests for tuberculosis (TB) using interferon gamma (IFN‐γ) responses produced by T lymphocytes after stimulation by early secretory antigen target 6 (ESAT‐6), culture filtrate protein 10 (CFP‐10) or purified protein derivate (PPD) were carried out using ELISA (enzyme‐linked immunosorbent assay) in whole blood culture supernatants from children with suspected TB disease (n = 21), latent TB infection (LTBI; n = 17) and negative controls (NC; n = 21) from Recife, Pernambuco, Brazil. The results were analysed using the ROC (receiver operating characteristic) curves and the areas under the curve (AUC) generated varied from 0.5 to 1.0 with higher values indicating increased discriminatory ability. Comparisons of AUCs were made using non‐parametric assumptions, and the differences were considered significant if P < 0.05. The ROC curve showed a statistical difference (P = 0.015) between the LTBI and NC groups with an AUC of 0.731, TB disease and NC (AUC = 0.780; P = 0.002) and a group with TB (latent infection + disease, n = 38) and NC (AUC = 0.758; P = 0.001) when the antigen used was ESAT‐6. No statistical difference was found between the groups when CFP‐10 or PPD was used. In conclusion, the ESAT‐6 test may be the most appropriate for diagnosis of childhood TB, both LTBI and TB disease, when associated with epidemiological and clinical data, especially in endemic areas such as Brazil.

Mycobacterium tuberculosis Sonicate–Induced IFNγ, CXCL10 and IL10 can Differentiate Severity in Tuberculosis

“…We observed that CFP10‐induced IFNγ levels in patients with TB were of a higher magnitude than those induced by ESAT6; however, the CFP10‐induced IFNγ response did not discriminate between TB and EC groups. This corresponds with previous reports that have shown that CFP10 does not discriminate between active TB and uninfected controls [30–32]. In addition, as antigens related to ESAT6 and CFP10 are present in some NTMs that are likely to be present in this high TB endemic region, it is possible that because of cross‐reactivity to these, the discriminatory power of ESAT6 and CFP10 for identification of M. tuberculosis –infected individuals may be reduced.…”

“…In endemic regions, IFNγ can also be regulated by the natural exposure to M. tuberculosis or NTMs as well as BCG vaccination [34, 35]. Similar MTBs‐stimulated IFNγ responses in EC and TB could also be attributed to cross‐reactivity with MTBs in BCG‐vaccinated study subjects [29–32].…”

The TB-specific CD4+ T cell immune repertoire in both cynomolgus and rhesus macaques largely overlap with humans

“…Of these antigens, a subset has been shown to be protective in animal models (Rv3619c, Rv3620c, Rv2608), highly immunogenic in humans (Rv3875, Rv3874, Rv0288, Rv1196) and strongly recognized in the initial stages of infection in humans (Rv0288 and Rv3875) [121,122]. We show that several of these antigens, including Rv3875 (ESAT-6) and Rv3874 (CFP10), which are immunodominant in humans [123–130], are also immunodominant in rhesus macaques. Our results therefore support the feasibility of evaluation in NHPs of vaccines based on these antigens.…”

Tuberculose Latente Em Indivíduos De Uma Unidade Prisional Do Centro Oeste Do Brasil

“…As diferenças estatísticas entre os grupos foram avaliadas utilizando-se o teste de t Student, sendo consideradas significantes p<0,05. Centros penitenciários constituem comunidades que apresentam ambientes dinâmicos, em que os grupos de risco favorecem o desenvolvimento e a disseminação da TB (11,30). No Brasil, a população encarcerada total em 2010 era constituída por 496.251 indivíduos, e a proporção de pessoas em regime de reclusão foi de 253 por 100.000 habitantes.…”