Extended TB surveillance needed for specific IGRA-negative individuals

Certain individuals initially testing negative for tuberculosis (TB) by interferon-gamma release assay (IGRA) may later contract the infection and therefore require extended follow-up due to increased risk, as reported in a study from Singapore.

Data from the National Tuberculosis Programme (NTBP) showed that several risk factors among IGRA-negative contacts were independently associated with high TB risk.

The risk factors were older age (≥50 vs 0–25 years: adjusted odds ratio [aOR], 6.85, 95 percent confidence interval [CI], 2.71–17.31; p<0.001), Malay ethnicity (vs Chinese: aOR, 2.37, 95 percent CI, 1.42–3.93; p<0.001), pre-existing comorbidities (diabetes: aOR, 1.89, 95 percent CI, 1.10–3.28; p=0.020; end-stage renal failure: aOR, 14.65, 95 percent CI, 3.39–63.25; p<0.001), contact with smear-positive index cases (aOR, 1.74, 95 percent CI, 1.04–2.91; p=0.030), a “family” relationship with the index case (aOR, 3.48, 95 percent CI, 1.37–8.86; p=0.001), and exposure to an index case in a dormitory or nursing home setting (aOR, 5.04, 95 percent CI, 1.25–20.38 and aOR, 3.82, 95 percent CI, 1.28–8.86; p=0.020 for both). [Int J Infect Dis 2024;doi:10.1016/j.ijid.2024.107166]

The analysis included 60,377 IGRA-negative contacts (median age 35.4 years, 51.7 percent male, 61.0 percent Chinese) linked to 7,737 index cases (median age 56.5 years, 64.4 percent male, 59.5 percent Chinese) identified over a 9-year period.

Of the contacts, 150 (0.3 percent) contracted TB disease, with a median time to onset of 92 weeks following exposure to index case; 58 (39 percent) of them were culture-positive.

The present data are generally consistent with published evidence on the factors associated with the risk of TB transmission to contacts, the investigators noted. [Epidemiol Infect 2018;146:345-353; Trop Med Int Health 2018;23:1058-1070; Clin Infect Dis 2020;70:1562-1572]

“In addition to confirming the role of age and comorbidities, our analysis suggests risk factors specific to the Singapore context which can help optimize contact tracing strategies, follow-up, and preventive treatment for TB in subgroups at the highest risk of infection,” they said.

“For example, given that the median time to develop TB disease in this population of IGRA-negative contacts was 92 weeks, with 75 percent of contacts only diagnosed after 189 weeks from index case notification, it may be cost-effective to deploy additional resources to extend follow-up to 24 months for [high-risk] IGRA-negative contacts,” according to the investigators.

They also highlighted the importance of reviewing the optimal time to repeat the IGRA test beyond the window period in order to minimize the proportion of IGRA false-negative results.

“In the context of Singapore's ambitious goal to reduce TB incidence to 10 per 100,000 by 2040, enhancing contact tracing under the NTBP may prove invaluable,” the investigators said.