In the Lancet Infectious Disease, Lei Gao and colleagues1 report the results of a large multicentre, prospective cohort study of the prevalence of latent tuberculosis infection in China. The study was done in registered residents (aged ≥5 years) of four sites in rural China with diverse climates, population profiles, and incidences of tuberculosis. Eligible participants were identified by door-to-door survey and the screening process included a questionnaire about demographics and risk factors for tuberculosis, a tuberculin skin test, an interferon-γ release assay (QuantiFERON [QFT]), and digital chest radiography for participants older than 15 years.
The age-standardised and sex-standardised rate of tuberculin skin-test positivity (≥10 mm) was 28% in 21 022 participants (ranging from 15% to 42% according to study site), whereas the QFT positivity rate was lower at 19% (range 13–20%). Factors significantly associated with a positive skin test were male sex, increasing age, middle-school and high-school education, higher family income (≥600 RMB), history of smoking, consumption of alcohol, presence of a BCG scar, a body-mass index (BMI) of less than 18·5 kg/m2, and history of close contact with a patient with tuberculosis.
Factors associated with QFT positivity were male sex, increasing age (≥20 years), a history of smoking, close contact with a patient with tuberculosis, and a BMI of 28 kg/m2 or more. Half of participants with a positive tuberculin skin test had a positive QFT test, whereas three-quarters of those with QFT positivity also had positive skin tests. Skin-test-only positivity was significantly associated with male sex, ages of 60 years and older, and BCG vaccination, whereas QFT-only positivity was associated with male sex and with old age (≥60 years), probably because of the decreasing tuberculin sensitivity of elderly individuals, but not with BCG vaccination. The rate of confirmed and suspected pulmonary tuberculosis at screening varied between 4·1 per 1000 population and 28·8 per 1000 population. 360 (40%) of 910 participants with a positive skin test had a history of close contact with a patient with tuberculosis compared with 250 (27%) of 913 participants with QFT positivity, which is similar to findings from other studies.2, 3
The findings of Gao and colleagues' study show important differences between the four study sites, mainly in the frequency of skin-test positivity. At two sites, the rate of skin-test positivity was double or triple that of QFT positivity, whereas at two sites, both rates were similar. The differences are attributable to the differences in risk of exposure to non-tuberculous mycobacteria, which seem to be more prevalent at the site with a maritime climate than at the other study sites.
The great merit of this study is that it reports data for a very large general population sample in China, which is probably similar to populations in many other rural regions in countries with a medium to high incidence of tuberculosis. The findings show not only the risk factors associated with latent tuberculosis, but also the differences in prevalence according to the definition of latent infection, by tuberculin skin test or QFT test. In this context, the frequently quoted classic assertion that a third of the world's population is infected with Mycobacterium tuberculosis,4, 5 which relies on population surveys done with tuberculin skin tests, is probably an overestimate, and figures using more specific tests, such as interferon-γ release assays, should be closer to the reality, particularly in populations that are largely covered by BCG vaccination. The findings also show that the baseline rate of QFT positivity is very different between regions and correlates with the background prevalence of tuberculosis. Data for the rate of positivity of interferon-γ release assays in unselected populations are scarce and the reported frequency varies between 0·5% in young unexposed adults in low-incidence countries,6 8% in elderly unexposed adults,7 and 25% in immigrants from high-incidence countries.8 The rates in the present study are therefore in the same range as those recorded in exposed populations from high-incidence countries.
A naive but interesting idea is that screening of whole population groups for latent tuberculosis infection, and offering of preventive therapy to all individuals with a positive test result, might contribute to the eradication of tuberculosis by decreasing the pool of infected people at risk of reactivation. Screening for latent infection and consequent application of preventive therapy seems to be one component of the elimination strategy, at least in countries with a low or medium prevalence of tuberculosis.9 Such an approach has been used in small communities, such as Alaskan Eskimos,10 but is clearly not feasible and probably not cost-effective in large communities. WHO has issued the recommendations of a working group that analysed the cost-effectiveness of screening and preventive treatment for latent tuberculosis infection in different populations according to risk of reactivation.11 The conclusions are that systematic screening and preventive treatment are justified in populations groups with the highest risk of development of tuberculosis, if infected, but this approach is restricted to people with diverse immune deficiencies (eg, HIV, anti-tumour necrosis factor, dialysis, transplantation, silicosis), and adult and child contacts of pulmonary tuberculosis. A general policy of preventive treatment of all carriers of a positive skin test or interferon-γ release assay is unrealistic and not cost-effective, because of the risk of adverse events.
Follow-up of the population screened in Gao and colleagues' study will increase our knowledge about the risk factors associated with tuberculosis and might help to define more precisely individuals will benefit from screening and preventive therapy.
I declare no competing interests.
- Gao, L, Lu, W, Bai, L..., and for the LATENTTB-NSTM study team. Latent tuberculosis infection in rural China: baseline results of a population-based, multicentre, prospective cohort study. Lancet Infect Dis. 2015; (published online Feb 11.) http://dx.doi.org/10.1016/S1473-3099(14)71085-0.
- Fox, GJ, Barry, SE, Britton, WJ, and Marks, GB. Contact investigation for tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2013; 41: 140–156
- Erkens, CG, Dinmohamed, AG, Kamphorst, M et al. Added value of interferon-gamma release assays in screening for tuberculous infection in the Netherlands. Int J Tuberc Lung Dis. 2014; 18: 413–420
- Sudre, P, ten Dam, G, and Kochi, A. Tuberculosis: a global overwiew of the situation today. Bull World Health Organ. 1992; 70: 149–159
- Zumla, A, Atun, R, Maeurer, M et al. Eliminating tuberculosis and tuberculosis-HIV co-disease in the 21st century: key perspectives, controversies, unresolved issues, and needs. J Infect Dis. 2012; 205: S141–S146
- Mancuso, JD, Mazurek, GH, Tribble, D et al. Discordance among commercially available diagnostics for latent tuberculosis infection. Am J Respir Crit Care Med. 2012; 185: 427–434
- Hinks, TS, Varsani, N, Godsiff, DT et al. High background rates of positive tuberculosis-specific interferon-gamma release assays in a low prevalence region of UK: a surveillance study. BMC Infect Dis. 2012; 12: 339
- Sarivalasis, A, Zellweger, J, Faouzi, M, Daher, O, Deslarzes, C, and Bodenmann, P. Factors associated with latent tuberculosis among asylum seekers in Switzerland: a cross-sectional study in Vaud County. BMC Infect Dis. 2012; 12: 285
- Diel, R, Loddenkemper, R, Zellweger, JP et al. Old ideas to innovate tuberculosis control: preventive treatment to achieve elimination. Eur Respir J. 2013; 42: 785–801
- Comstock, GW, Baum, C, and Snider, DE Jr. Isoniazid prophylaxis among Alaskan Eskimos: a final report of the Bethel Isoniazid studies. Am Rev Respir Dis. 1979; 119: 827–830
- WHO. Guidelines on the management of latent tuberculosis infection. http://apps.who.int/iris/bitstream/10665/136471/1/9789241548908_eng.pdf?ua=1&ua=1; 2015. ((accessed Jan 27, 2015).)
Source: The Lancet Infectious Disease