Interferon-γ release assays for diagnostic evaluation of tuberculosis

A multicenter cohort study evaluated the diagnostic performance of four interferon gamma release assays (IGRAs) in over 800 patients presenting with suspected active tuberculosis across English hospitals. Researchers compared traditional tests—T-SPOT.TB and QFT-GIT—to newer second-generation assays designed to incorporate novel M. tuberculosis antigens. The within-patient testing design minimized variability and allowed a robust head-to-head comparison of test characteristics.

The study found that T-SPOT.TB had moderately high sensitivity (81.4%) and specificity (86.2%), whereas QFT-GIT showed lower sensitivity (67.3%) and slightly lower specificity (80.4%). These findings align with prior reports indicating limited diagnostic accuracy of existing IGRAs in distinguishing active tuberculosis from latent infection or other conditions. In practical terms, neither T-SPOT.TB nor QFT-GIT demonstrated sufficient predictive values to function as reliable rule-in or rule-out tools in routine care.

By contrast, the second-generation IGRAs achieved sensitivity near 90% and negative predictive values approaching 90%, significantly outperforming older tests. This improvement was particularly notable in smear-negative and extrapulmonary tuberculosis cases, where conventional diagnostics often struggle. However, specificity was modest (around 80%), highlighting the persistent challenge of false positives in low-prevalence populations.

Importantly, the proportion of indeterminate results was lower for second-generation assays, suggesting they may be more robust in diverse clinical settings, including among patients with HIV and diabetes. The study also showed that adjusting test cutoffs did not meaningfully improve accuracy, underscoring that current assays are unlikely to achieve major gains simply by changing interpretive thresholds.

Overall, this work provides compelling evidence that while traditional IGRAs remain limited in their clinical utility, newer assays offer incremental benefits that could inform diagnostic pathways. These findings are relevant for clinicians, policymakers, and laboratories considering the adoption of advanced immunodiagnostic tools to support tuberculosis management.

References:

1. Whitworth, H.S., Badhan, A., Boakye, A.A., Takwoingi, Y., Rees-Roberts, M., Partlett, C., Lambie, H., Innes, J., Cooke, G., Lipman, M. and Conlon, C., 2019. Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study. The Lancet Infectious Diseases, 19(2), pp.193-202.

Tuberculosis in Nigeria

A study in a national TB reference hospital in Nigeria examined how age and gender influence susceptibility to tuberculosis (TB) and drug-resistant TB (DR-TB). Individuals aged 40 or younger were four times more likely to develop DR-TB than older individuals, with 80% of DR-TB cases occurring in this age group. Gender disparities were also evident, as males were generally more susceptible to TB. Among DS-TB cases, 68.3% were male and 31.7% were female, while in DR-TB cases, the male proportion dropped to 55%, suggesting that drug-resistant infections are more evenly distributed between genders.[1]

Beyond age and gender, other factors such as geography, occupation, and environment played a role in TB susceptibility. Urban residency was common in both DS-TB (71.67%) and DR-TB (60%) cases, while a family history of TB was more prevalent in DR-TB patients. Occupational exposure varied, with artisans and business professionals most affected by DS-TB, whereas DR-TB cases included drivers, housewives, and community volunteers. The study also highlighted gaps in BCG vaccination, with only 10% of DR-TB patients having BCG scars compared to 65% of asymptomatic household contacts. Additionally, environmental and dietary factors like raw meat handling and unpasteurized milk consumption may contribute to TB resistance, underscoring the importance of vaccination and lifestyle interventions.[1]

A cross-sectional study conducted from September to December 2018 examined 352 adult volunteers from rural, semi-urban, and urban areas. Participants underwent risk screening using a modified WHO STEPS instrument. The demographic distribution was balanced between males and females, with most individuals being over 40 years old and married or cohabiting. Many participants had no family history of diabetes or tuberculosis, and hypertension was uncommon. However, obesity was more prevalent among urban dwellers. Nearly all participants had received BCG vaccination, and there were no significant differences in CD4+ T lymphocyte counts, hemoglobin levels, or C-reactive protein profiles among the groups. However, total cholesterol levels varied significantly, with rural participants exhibiting slightly higher HDL-C levels.[2]

The study assessed pre-diabetes (PDM) and latent tuberculosis infection (LTBI), finding higher PDM rates in urban areas and higher LTBI rates in rural areas. A small subset of participants had both conditions (PDM-LTBI), with prevalence notably higher among those with LTBI. Bivariate analysis identified age, smoking, family history of diabetes, abdominal obesity, hypertension, and lack of BCG vaccination as risk factors for PDM, while LTBI was also linked to educational level and family history of TB. Logistic regression confirmed that older age, smoking, family history of diabetes, and absence of BCG vaccination significantly predicted both conditions. Adults aged 50-59 years were at the highest risk for concurrent PDM and LTBI, while BCG vaccination was found to significantly reduce this risk.[2]

References:

1. Madaki, S., Mohammed, Y., Rogo, L.D., Yusuf, M. and Bala, Y.G., 2024. Age and gender in drug resistance tuberculosis: a cross-sectional case study at a national tuberculosis reference hospital in Nigeria. Journal of Global Antimicrobial Resistance, 39, pp.175-183.

2. Akinshipe, B.O., Yusuf, E.O., Akinshipe, F.O., Moronkeji, M.A. and Nwaobi, A.C., 2019. Prevalence and Determinants of Pre-diabetes and Latent Tuberculosis Infection Among Apparently Healthy Adults in Three Communities in Southern Nigeria. International Journal of Immunology, 7(2), pp.23-32.