China has been estimated to have one million new cases of tuberculosis (TB) every year—more than any country except India. But the results of a Chinese study of TB infection published recently in The Lancet have shown that reliance on the 100-year-old tuberculin skin test (TST) has significantly overestimated the rate of latent TB infections in that country.
Conducted by researchers at the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, the study is the largest-ever prospective multicenter study to compare diagnostics for latent TB infection in China. The study screened more than 21,000 people, and aimed to identify at-risk populations to target for preventive intervention at the community level.
Comparative results among the same patients using the QuantiFeron-TB Gold (QFT) test from Qiagen NV, Hilden, Germany, provided a better understanding of disease burden. The study found a far lower prevalence of latent TB as measured using QFT than with TST. In particular, QFT testing found an overall TB infection rate of 18.8%, while TST testing found an overall rate of 28%.
The tuberculin skin test was first developed and described by the German physician Felix Mendel in 1908. In the Chinese study, the higher false positive rate created by the test was a result of several factors, including the nation’s use of the bacillus Calmette–Guérin (BCG) vaccination since the 1950s, with limited impact on reducing TB burden. BCG vaccination for newborns is recommended by the World Health Organization as a matter of TB control policy in many countries, including China.
Unlike the rates of latent TB infection detected by TST testing, the positive rates detected by QFT were not related to prior BCG vaccination. However, the QFT findings correlated with background active TB and suspect rates, as well as known risks for TB.
In light of the study’s new information about lower TB prevalence in China, the study authors suggest that community-based preventive intervention may be practical for individuals with latent TB who are at risk for developing active TB.
“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 tuberculosis are BCG vaccinated, it is clear that other tuberculosis control measures are needed. Screening of high-risk populations for latent tuberculosis infection with interferon-gamma release assays, and provision of preventive treatment for those testing positive and with high risks of developing disease, would be an important strategy to decease tuberculosis incidence.”
“This study by top experts in China provides powerful evidence that the accuracy of the screening test truly matters for individual patients and public health, and that tackling the issue of latent TB infections is critical to eradicating this deadly disease,” says Masae Kawamura, MD, senior director for QuantiFeron medical and scientific affairs at Qiagen. “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,” adds Kawamura. “This study demonstrates that China is leading Asia in TB elimination by doing the necessary research to determine the preventive interventions that are needed.”
Introduced in China in 2014, QFT is a laboratory-based interferon-gamma release assay (IGRA) that uses a patient blood sample to diagnose latent TB infection. QFT is faster, less labor-intensive, and more accurate than the TST, and improves the overall cost-effectiveness of TB control programs. For the recent Chinese study, the researchers selected QFT as the only IGRA to be used.
STUDY PROVIDES INSIGHTS ON TB CONTROL
The study reported in The Lancet represents the baseline phase of China’s first large-scale, multicenter study of the epidemiology of latent TB infection. The comparison study allowed detailed analysis of demographics and risk factors, along with robust comparisons within subgroups. The study’s follow-up phase is now under way, and patients with latent TB infection will be evaluated for rates of disease and associated risks. Generally, up to 10% of people with latent TB infection will develop active, contagious TB at some time. Already, independent experts report 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,” says Lee Reichman, MD, MPH, professor of medicine and executive director of the Global Tuberculosis Institute at the New Jersey Medical School at Rutgers University. “While most TB control efforts in China so far have not focused on prevention, the research findings can guide policymakers to focus appropriate preventive interventions on the right people, which is a smaller group and based on the risk factors found in the study.”
“Screening high-risk populations for latent TB infection using an IGRA and providing preventive treatment for those testing positive and with high risks of developing disease would be an important strategy to decrease TB incidence,” say the study authors. The study found higher latent TB rates in three vulnerable subpopulations—close contacts of active TB patients, the elderly, and smokers—and suggests that these groups “might be potential target populations for latent TB infection monitoring, with preventive intervention due to the observed higher risk of latent TB infection prevalence among them.”
TB control programs in the United States, Europe, and Japan have increasingly turned to QFT for screening vulnerable subpopulations for latent TB infection. More than 20 million QFT tests have been distributed since the launch of the first version.
In 2015, Qiagen expects to launch its fourth generation of the test, QuantiFeron-TB Gold Plus, in Europe and other markets where CE marking permits market entry. For further information, visit Qiagen.
Gao L, Lu W, Bai L, et al. Latent tuberculosis in rural China: baseline results of a population-based, multicenter, prospective cohort study. Lancet Infect Dis. 2015; published online first, February 10, 2015; doi: http://dx.doi.org/10.1016/S1473-3099(14)71085-0.