According to World Health Organization WHO, Tuberculosis (TB) is the second cause of death from infectious disease worldwide. During 2021, 10.6 million people were infected with TB, and 1.6 million people died. TB is caused by pathogens belonging to the Mycobacterium tuberculosis complex (MTBC), mainly by Mycobacterium tuberculosis (M.tb). Members of this complex are acid-fast bacilli, which can cause intrapulmonary and extra pulmonary TB, and can be divided into various lineages, based on genomic markers. The main public health threat comes from drug resistant M.tb strains, which are responsible for about 25% of TB death and treatment failure worldwide. Treating drug resistant TB patients significantly raises the costs of TB treatment. This study provides an overview of the demographic and drug susceptibility characteristics of newly diagnosed TB patients in Israel in 2021. The State of Israel has a very low level of TB endemicity and is at a pre-elimination phase. Notably, only 11.7% of the newly diagnosed TB patients were born in Israel. In this report, of the 154 new laboratory-confirmed TB patients, 66.7% had pulmonary TB, while 16% had extrapulmonary TB. Males accounted for 52% of the patients, with the most prevalent age group being 21-40. Most patients were citizens of Israel (53.9%), while 37.7% had no Israeli citizenship. Among non-citizens, there was a predominance of males and patients aged 21-40. The susceptibility profile showed a high resistance rate to streptomycin (18.2%) and to a lower extent to isoniazid (13.6%), pyrazinamide (8.4%), rifampicin (7.8%), and ethambutol (3.2%). Only 2 cases of XDR-TB and 10 MDR-TB strains were detected in Israel in 2021, with both XDR strains and 5 out of 10 MDR strains belonging to the Beijing lineage. Most of Beijing isolates were resistant to at least one tested drug. Genomic sequencing of 134 out of 156 strains and bioinformatics analysis using the MTBseq program and WHO mutation catalogue shows a good match with only 9 discrepancies between phenotypic and genotypic susceptibility profiles in first line drugs. The most common lineage is Delhi-Cas (23%) followed by the Beijing lineage (17%). Most patients from the Delhi-Cas lineage were born in Africa, while patients with Beijing isolates were born in different countries. Minimum spanning tree analysis identified 15 clusters. The study highlights the need for ongoing surveillance of TB using molecular and phenotypic tools to further decreasing the spreading level of the disease and develop effective treatment strategies.

Tuberculosis (TB) is the second-most prevalent cause of mortality resulting from infectious diseases worldwide. It is caused by bacteria belonging to the Mycobacterium tuberculosis complex (MTBC). In Israel, TB incidence is low, acknowledged by the WHO as being in a pre-elimination phase. Most cases occur among immigrants from high TB incidence regions like the Horn of Africa and the former Soviet Union (FSU), with occasional outbreaks. The outbreak described in this report occurred between 2018 and 2024, increasing the incidence rate of TB in the region. Control of this outbreak posed challenges due to factors including a diverse population (including Ethiopian immigrants, Israeli-born citizens, and immigrants from other countries), economic and social barriers, and hesitancy to disclose information. The unique multidisciplinary team formed to address these challenges, involving the local TB clinic, district health ministry, health maintenance organization (HMO) infectious disease consultant, neighborhood clinic, and National Mycobacterium Reference Laboratory (NMRL), achieved effective treatment and containment. Whole genome sequencing (WGS) proved pivotal in unraveling patient connections during the outbreak. It pinpointed those patients overlooked in initial field investigations, established connections between patients across different health departments, and uncovered the existence of two distinct clusters with separate transmission chains within the same neighborhood. This study underscores collaborative efforts across sectors that successfully contained a challenging outbreak.

Rapid and accurate detection of drug-resistant tuberculosis (DR-TB) is critical for effective treatment and containment. The Xpert^® MTB/XDR (GXXDR) assay is designed to detect Mycobacterium tuberculosis complex (MTBC) and resistance to isoniazid and second-line anti-TB drugs directly from clinical specimens. We evaluated the clinical performance of GXXDR using 61 MTBC-positive specimens with available phenotypic drug susceptibility testing results. GXXDR results were compared to a phenotypic drug susceptibility test (pDST) and whole-genome sequencing (WGS) to assess sensitivity, specificity, and concordance. Resistance to isoniazid, fluoroquinolones, amikacin, capreomycin, and ethionamide was analyzed. Sensitivity comparisons between GXXDR, WGS, pDST, and manufacturer data were performed using Fisher’s exact and Tango tests. GXXDR demonstrated a high specificity for most drugs and a strong sensitivity for isoniazid (93.8%) and fluoroquinolone (92.3%), consistent with manufacturer reports. In contrast, the sensitivity for amikacin (58.3%), capreomycin (35.7%), and ethionamide (27.3%) was significantly lower than stated by the manufacturer (91.9%, 84.0% and 64.7%, respectively), likely due to resistance mutations outside the assay’s target regions. Sensitivity concordance of GXXDR with WGS was high for all drugs, except ethionamide. The GXXDR assay enables rapid and reliable detection of isoniazid and fluoroquinolone resistance in clinical settings, though sensitivity for certain second-line drugs may be affected by regional genetic diversity. These findings underscore the importance of integrating local epidemiological data to optimize molecular diagnostics for DR-TB.