Enhanced TB Test Uncovers Hidden Infections in Households

Conventional tuberculosis (TB) culture methods may be overlooking a substantial number of asymptomatic infections capable of contributing to ongoing transmission, according to a longitudinal study. Researchers found that enhanced culture assays detecting differentially culturable tubercle bacteria (DCTB) identified significantly more Mycobacterium tuberculosis infections than standard laboratory methods, particularly among household contacts.

Despite advances in molecular diagnostics, TB remains one of the world’s leading infectious killers. Conventional culture techniques can fail to detect certain populations of viable bacteria that require specialised growth conditions, potentially leaving infected individuals undiagnosed and allowing transmission to continue within households and communities.

Enhanced Culture Improved Detection

Researchers conducted a prospective cohort study involving 293 patients with confirmed pulmonary tuberculosis, 701 household contacts, and 122 participants from control households in two districts of South Africa.

Participants were followed for 16 months, with sputum samples collected at regular intervals. Samples were analysed using both conventional mycobacterial growth indicator tube (MGIT) culture and enhanced DCTB assays designed to recover bacterial populations that do not grow under standard laboratory conditions.

At enrolment, conventional culture identified M. tuberculosis in 85% of index cases and 16% of household contacts. Among samples that tested negative using routine culture, DCTB assays detected additional infections in 21 index patients and 26 household contacts.

Hidden Reservoir of Asymptomatic Infection

Over the course of follow-up, the enhanced assays identified 61 additional TB-positive household contacts who were not detected using conventional culture.

Overall, conventional testing identified 233 TB-positive household contacts during the study period, 84% of whom were asymptomatic. DCTB assays detected a further 94 positive household contacts, with 79 of these individuals also showing no symptoms.

The findings suggest that asymptomatic individuals harbouring viable M. tuberculosis may represent a larger reservoir of infection than previously recognised.

Better Understanding of Household Transmission

Researchers also performed whole-genome sequencing on cultured isolates to investigate transmission within households.

Using conventional culture alone, evidence of household transmission was identified in 16 of 104 TB-positive households. Incorporating DCTB-positive samples revealed an additional 19 transmission events that would otherwise have been missed.

However, no evidence of intrahousehold transmission was found in approximately two-thirds of TB-positive households, suggesting that many infections may have originated outside the home or through more complex transmission pathways.

Implications for TB Control

The authors conclude that DCTB assays substantially improve the detection of viable M. tuberculosis, particularly among asymptomatic household contacts who may otherwise remain undiagnosed.

They suggest that incorporating enhanced culture methods into TB diagnostic and surveillance programmes could strengthen contact tracing, improve identification of subclinical infection, and provide a more complete picture of transmission dynamics. Earlier detection of these hidden infections could ultimately support more effective TB control strategies, particularly in high-burden settings.

The researchers note that further studies will be needed to determine how best to integrate DCTB assays into routine clinical practice and to assess their impact on long-term transmission and disease prevention.

Reference

Sewcharran A et al. Assessment of differentially culturable tubercle bacteria assays for the detection of tuberculosis infection in asymptomatic household contacts and the implications for intra-household transmission: a longitudinal cohort study. The Lancet Microbe, 2026; DOI: 10.1016/j.lanmic.2026.101412.