Utility of the QuantiFERON-TB Gold In-Tube assay for the diagnosis of tuberculosis in Moroccan children.

SETTING: The utility of interferon-gamma release assays (IGRAs), such as the QuantiFERON-TB Gold In-Tube (QFT-GIT) test, in diagnosing active tuberculosis (TB) in children is unclear and depends on the epidemiological setting. OBJECTIVE: To evaluate the performance of QFT-GIT for TB diagnosis in children living in Morocco, an intermediate TB incidence country with high bacille Calmette-Gurin vaccination coverage. DESIGN: We prospectively recruited 109 Moroccan children hospitalised for clinically suspected TB, all of whom were tested using QFT-GIT. RESULTS: For 81 of the 109 children, the final diagnosis was TB. The remaining 28 children did not have TB. QFT-GIT had a sensitivity of 66% (95%CI 5277) for the diagnosis of TB, and a specificity of 100% (95%CI 88100). The tuberculin skin test (TST) had lower sensitivity, at 46% (95%CI 3360), and its concordance with QFT-GIT was limited (69%). Combining QFT-GIT and TST results increased sensitivity to 83% (95%CI 6992). CONCLUSION: In epidemiological settings such as those found in Morocco, QFT-GIT is more sensitive than the TST for active TB diagnosis in children. Combining the TST and QFT-GIT would be useful for the diagnosis of active TB in children, in combination with clinical, radiological and laboratory data.

Pott's disease in Moroccan children: clinical features and investigation of the interleukin-12/interferon-γ pathway.

SETTING: Tuberculosis spondylodiscitis (TS), or Pott's disease, an extra-pulmonary form of tuberculosis (TB), is rare and difficult to diagnose in children. Some cases of severe TB in children were recently explained by inborn errors of immunity affecting the interleukin-12/interferon-gamma (IL-12/IFN-γ) axis. OBJECTIVE: To analyse clinical data on Moroccan children with TS, and to perform immunological and genetic explorations of the IL-12/IFN-γ axis. DESIGN: We studied nine children with TS diagnosed between 2012 and 2014. We investigated the IL-12/IFN-γ circuit by both whole-blood assays and sequencing of the coding regions of 14 core genes of this pathway. RESULTS: A diagnosis of TS was based on a combination of clinical, biological, histological and radiological data. QuantiFERON(®)-TB Gold In-Tube results were positive in 75% of patients. Whole-blood assays showed normal IL-12 and IFN-γ production in all but one patient, who displayed impaired decreased response to IL-12. No candidate disease-causing mutations were detected in the exonic regions of the 14 genes. CONCLUSIONS: TS diagnosis in children remains challenging, and is based largely on imaging. Further investigations of TS in children are required to determine the role of genetic defects in pathways that may or may not be related to the IL-12/IFN-γ axis.

[Human genetics of tuberculosis]. / Génétique humaine de la tuberculose.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major public health problem worldwide, resulting in 8.7 million new cases and 1.4 million deaths each year. One third of the world's population is exposed to M. tuberculosis and, after exposure, most, but not all, individuals become infected. Among infected subjects, only a minority (∼10%) will eventually develop clinical disease, which is typically either a primary, often extra-pulmonary, TB in children, or a reactivation, pulmonary TB in adults. Considerable genetic epidemiological evidence has accumulated to support a major role for human genetic factors in the development of TB. Numerous association studies with various candidate genes have been conducted in pulmonary TB, with very few consistent results. Recent genome-wide association studies revealed only a modest role for two inter-genic polymorphisms. However, a first major locus for pulmonary TB was mapped to chromosome 8q12-q13 in a Moroccan population after a genome-wide linkage screen. Using a similar strategy, two other major loci controlling TB infection were recently identified. While the precise identification of these major genes is ongoing, the other fascinating observation of these last years was the demonstration that TB can also reflect a Mendelian predisposition. Following the findings obtained in the syndrome of Mendelian susceptibility to mycobacterial diseases, several children with complete IL-12Rß1 deficiency, were found to have severe TB as their sole phenotype. Overall, these recent findings provide the proof of concept that the human genetics of TB involves a continuous spectrum from Mendelian to complex predisposition with intermediate major gene involvement. The understanding of the molecular genetic basis of TB will have fundamental immunological and medical implications, in particular for the development of new vaccines and treatments.