Pivotal Study Supports Modern Blood Test Over Common Skin Test for Latent Tuberculosis Screening

A groundbreaking study in China finds, by comparison with results from a highly accurate commercial test, that screening with a still commonly used tuberculin skin test (TST) for latent Mycobacterium tuberculosis (TB) infection (LTBI) clearly results in unacceptably high numbers of false positives and overestimation of infection rates. Determination of lower prevalence rates is critical for increasing effectiveness and efficiency of LTBI screening as a tool in reducing the TB public health burden.

China has been estimated to have 1 million new cases of TB every year, more than any country except India. The new study, China’s largest-ever population-based prospective multicenter clinical LTBI diagnostics study, by researchers at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, showed that reliance on the 100-year-old TST significantly overestimates LTBI rates, compared to results from the same patients using the highly accurate, interferon-gamma release assay (IGRA)-based QuantiFERON-TB Gold (QFT) test from QIAGEN N.V. (Venlo, Netherlands and Hilden, Germany). Their findings support reducing China's TB burden by providing follow-up treatment for at-risk patients identified using modern IGRA technology.

Upon screening over 21,000 people in rural China, the results showed a far lower overall LTBI rate of 18.8% as measured by QFT compared to 28% by TST. The higher false positive rate of TST is due to several factors, including the use of Bacille Calmette-Guérin (BCG) vaccination in China since the 1950s, which has had only a very limited impact on reducing TB burden. Unlike TST, positive rates of QFT were not related to prior BCG vaccination, but correlated with background active TB and suspect rates, as well as known risks for TB. BCG vaccination is recommended by the World Health Organization (WHO) as a matter of TB control policy to newborns in many countries, including China.

"The present study represents a first step in China to address the important topic of development of tuberculosis control strategies," noted the study authors, "On the basis of evidence suggesting that BCG vaccination does not confer protection in adults, and the basic observation that most people in China who develop active TB are BCG vaccinated, it is clear that other TB control measures are needed."

This study by top experts in China provides strong evidence that accuracy of LTBI screening is critical for eradicating TB. “Consistent with other studies, QuantiFERON-TB Gold proved highly accurate and more reliable than the century-old skin test for correctly identifying TB infection. The findings offer valuable insights for TB control efforts, both in China and other areas of the world," said Dr. Masae Kawamura, MD, Senior Director, QuantiFERON Medical and Scientific Affairs, QIAGEN, "This study demonstrates that China is leading Asia in TB elimination by doing the necessary research to determine the preventive interventions that are needed."

The study was conducted also to identify vulnerable, at-risk populations to target for LBTI screening at the community level, enabling community-based preventive interventions for individuals effectively identified as being at risk for developing active TB. Higher LTBI rates were found in 3 subpopulations that may be potential target populations for LTBI monitoring: close contacts of active TB patients, the elderly, and smokers.

The report presents the baseline phase of China's first large-scale, multi-center study of LTBI epidemiology. It allowed detailed analysis of demographics and risk factors, along with robust comparisons within subgroups. The study's follow-up phase is now underway, and patients with LTBI will be evaluated for rates of disease and associated risks. Generally, up to 10% of people with LTBI will develop active, contagious TB at some point.

Independent experts note important implications for TB control: "The study shows that historical estimates of latent TB infection in China, as high as 44.5% of the population, were overinflated by TST as compared to IGRA," said Dr. Lee Reichman, MPH, Executive Director of the Global Tuberculosis Institute, New Jersey Medical School, Rutgers University, "While most TB control efforts in China so far have not focused on prevention, the research findings can guide policy makers to focus appropriate preventive interventions on the right people, which is a smaller group and based on the risk factors found in the study."

Qiagen’s QFT, introduced in China in 2014, is a modern standard with demonstrated clinical reliability for LTBI diagnosis, and is faster, less labor-intensive, and far more accurate than TST. Leading TB control programs worldwide are replacing TST with QFT because its superior performance and simpler administration as a laboratory-based blood test improve overall healthcare and the cost-effectiveness of TB control programs.

QIAGEN is currently launching QuantiFERON-TB Gold Plus (QFT-Plus) in Europe and other markets as a 4th-generation test with CE-IVD marking.

The study was published online February 10, 2015 in the journal the Lancet.

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