Long-Incubation-Time Gamma Interferon Release Assays in Response to Purified Protein Derivative, ESAT-6, and/or CFP-10 for the Diagnosis of Mycobacterium tuberculosis Infection in Children

Abstract

The diagnosis of childhood active tuberculosis (aTB) and latent Mycobacterium tuberculosis (M. tuberculosis) infection (LTBI) remains a challenge, and the replacement of tuberculin skin tests (TST) with commercialized gamma interferon (IFN-␥) release assays (IGRA) is not currently recommended. Two hundred sixty-six children between 1 month and 15 years of age, 214 of whom were at risk of recent M. tuberculosis infection and 51 who were included as controls, were prospectively enrolled in our study. According to the results of a clinical evaluation, TST, chest X ray, and microbiological assessment, each children was classified as noninfected, having LTBI, or having aTB. Long-incubation-time purified protein derivative (PPD), ESAT-6, and CFP-10 IGRA were performed and evaluated for their accuracy in correctly classifying the children. Whereas both TST and PPD IGRA were suboptimal for detecting aTB, combining the CFP-10 IGRA with a TST or with a PPD IGRA allowed us to detect all the children with aTB with a specificity of 96% for children who were positive for the CFP-10 IGRA. Moreover, the combination of the CFP-10 IGRA and PPD IGRA detected 96% of children who were eventually classified as having LTBI, but a strong IFN-␥ response to CFP-10 (defined as >500 pg/ml) was highly suggestive of aTB, at least among the children who were <3 years old. The use of long-incubation-time CFP-10 IGRA and PPD IGRA should help clinicians to quickly identify aTB or LTBI in young children.

Is secretion of IFN‐gamma in response to Mycobacterium tuberculosis antigens in youngest children sufficient to play a role in TB diagnostics?

“…[35][36][37][38] In an observational study held among patients with positive QFT- T-lymphocytes with pure protein derivative (PPD) and specific TB antigens (ESAT-6 and CFP-10), showed that among children below 3 years of age, individuals with ATB produced significantly higher amounts of IFN-ɣ than those diagnosed with LTBI. 39 No such dependency was proved in other age groups. The authors concluded that exceptionally high IFN-ɣ concentrations in youngest children with active tuberculosis may reflect increasing bacterial load in recently infected individuals, and the lack of secondary suppression observed in older children and adults in the course of disease development.…”

“…The younger the individual was and the higher IFN‐ɣ level measurement, the higher the risk of developing active tuberculosis . Interestingly, Schepers et al who focused on IFN‐ɣ level measurement after incubating T‐lymphocytes with pure protein derivative (PPD) and specific TB antigens (ESAT‐6 and CFP‐10), showed that among children below 3 years of age, individuals with ATB produced significantly higher amounts of IFN‐ɣ than those diagnosed with LTBI . No such dependency was proved in other age groups.…”

Comparison of pro‐inflammatory cytokines of non‐healing and healing cutaneous leishmaniasis

“…These findings confirmed that PPD could be considered an appropriate antigen for negative controls. Intriguingly, the IFN‐ γ responses to PPD in all of the healing and non‐healing patients were very low, indicating that no participant was recently infected with TB or some of the Mycobacteria , thus avoiding false‐positive results being attributed to the above‐mentioned infection . Furthermore, our findings showed that the PBMCs of non‐healing patients were not totally unresponsive to SLA or PHA, although these responses were not sufficient.…”

TB or not TB? Diagnostic difficulties in HIV-positive versus HIV-negative tuberculosis patients with an immigration background in Germany

“…This result can be unsatisfactory considering that onequarter of the world's population contains TB within themselves due to contact (and even higher population parts in endemic regions). Therefore TST and IGRA should not be seen as [15][16][17][18][19][20] In particular, TST is useful applied to adult immigrants for highly endemic countries whereas IGRA is useful in children and adolescents born to immigrants from highly endemic countries that grew up in Germany or other lowrisk countries. However, it has to be taken in account that children aged younger than 5 years IGRAs may yield false negative results.…”

“…However, it has to be taken in account that children aged younger than 5 years IGRAs may yield false negative results. [16][17][18][19][20] PCR is valuable because the result is achieved promptly contrary to culture. However, it must be considered that a negative result does not rule out TB.…”