Annual Risk Of Tuberculosis Infection Research Articles

Tuberculosis Immunoreactivity Surveillance in Malawi (Timasamala)-A protocol for a cross-sectional Mycobacterium tuberculosis immunoreactivity survey in Blantyre, Malawi.

Tuberculosis (TB) transmission and prevalence are dynamic over time, and heterogeneous within populations. Public health programmes therefore require up-to-date, accurate epidemiological data to appropriately allocate resources, target interventions, and track progress towards End TB goals. Current methods of TB surveillance often rely on case notifications, which are biased by access to healthcare, and TB disease prevalence surveys, which are highly resource-intensive, requiring many tens of thousands of people to be tested to identify high-risk groups or capture trends. Surveys of "latent TB infection", or immunoreactivity to Mycobacterium tuberculosis (Mtb), using tests such as interferon-gamma release assays (IGRAs) could provide a way to identify TB transmission hotspots, supplementing information from disease notifications, and with greater spatial and temporal resolution than is possible to achieve in disease prevalence surveys. This cross-sectional survey will investigate the prevalence of Mtb immunoreactivity amongst young children, adolescents and adults in Blantyre, Malawi, a high HIV-prevalence city in southern Africa. Through this study we will estimate the annual risk of TB infection (ARTI) in Blantyre and explore individual- and area-level risk factors for infection, as well as investigating geospatial heterogeneity of Mtb infection (and its determinants), and comparing these to the distribution of TB disease case-notifications. We will also evaluate novel diagnostics for Mtb infection (QIAreach QFT) and sampling methodologies (convenience sampling in healthcare settings and community sampling based on satellite imagery), which may increase the feasibility of measuring Mtb infection at large scale. The overall aim is to provide high-resolution epidemiological data and provide new insights into methodologies which may be used by TB programmes globally.

Impact of Reversion of Mycobacterium tuberculosis Immunoreactivity Tests on the Estimated Annual Risk of Tuberculosis Infection.

A key metric in tuberculosis epidemiology is the annual risk of infection (ARI), which is usually derived from tuberculin skin test (TST) and interferon-γ release assay (IGRA) prevalence surveys carried out in children. Derivation of the ARI assumes that immunoreactivity is persistent over time; however, reversion of immunoreactivity has long been documented. We used a deterministic, compartmental model of Mycobacterium tuberculosis (Mtb) infection to explore the impact of reversion on ARI estimation using age-specific reversion probabilities for the TST and IGRA. Using empirical data on TST reversion (22.2%/year for persons aged ≤19 years), the true ARI was 2-5 times higher than that estimated from immunoreactivity studies in children aged 8-12 years. Applying empirical reversion probabilities for the IGRA (9.9%/year for youths aged 12-18 years) showed a 1.5- to 2-fold underestimation. ARIs are increasingly underestimated in older populations, due to the cumulative impact of reversion on population reactivity over time. Declines in annual risk did not largely affect the results. Ignoring reversion leads to a stark underestimation of the true ARI in populations and our interpretation of Mtb transmission intensity. In future surveys, researchers should adjust for the reversion probability and its cumulative effect with increasing age to obtain a more accurate reflection of the burden and dynamics of Mtb infection.

Comparing the Risk of M. Tuberculosis Infection among Men and Women in an African City

Background: Despite the well-known male bias in tuberculosis disease, the underlying reasons remained elusive. We examined whether male predominance in tuberculosis disease is result of higher risk of tuberculosis infection or not. If so, whether it is due to higher likelihood of exposure or higher susceptibility to infection among men. Methods: A household contact study and a prospective cohort study conducted in Kampala, Uganda, from 2013 to 2017 were used to estimate and compare prevalence and annual risk of tuberculosis infection among men and women. In household contact study, index tuberculosis cases and healthy index controls were asked to list their household contacts and extra-household contacts. All contacts were tested with tuberculin skin test to detect tuberculosis infection. In prospective cohort study, individuals with tuberculin skin test (TST) < 5 mm were enrolled and retested with the skin test at one year to detect new infection. Poisson regression with robust standard errors was used to estimate prevalence ratio and relative risk of tuberculous infection between men and women. Results: In household contact study, 123 index tuberculosis cases and 124 index controls listed 382 household contacts of tuberculosis cases, 624 extra-household contacts of tuberculosis cases, and 1044 contacts of controls. Of 1681 enrolled participants in cohort study, 1213 (72%) were retested with TST at one year. There was no sex difference in prevalence of tuberculosis infection among household contacts of tuberculosis cases, but men had a higher prevalence of tuberculosis infection among extra-household contacts of tuberculosis cases (prevalence ratio 1.25, 95% CI 1.06 – 1.48) and contacts of controls (prevalence ratio 1.53, 95% CI 1.30 – 1.81). Similarly, in cohort study, there was no sex difference in annual risk of tuberculosis infection when participant reported knowing tuberculosis cases, but men had a higher annual risk of tuberculosis infection when participants no known contact with tuberculosis (relative risk 1.94, 95% CI: 1.34, 2.80). Conclusion: Men have higher risk of acquiring tuberculous infection than women. Men and women may have the same susceptibility to tuberculosis infection given known exposure to tuberculosis cases. The observed difference in rate of infection may be partially explained by higher rates of exposure to undetected, infectious tuberculosis cases among men.

Decreased annual risk of tuberculosis infection in South Korean healthcare workers using interferon-gamma release assay between 1986 and 2005

BackgroundTuberculosis (TB) has been a major public health problem in South Korea. Although TB notification rate in Korea is gradually decreasing, still highest among the member countries of the Organization for Economic Cooperation and Development. To effectively control TB, understanding the TB epidemiology such as prevalence of latent tuberculosis infection (LTBI) and annual risk of TB infection (ARI) are important. This study aimed to identify the prevalence of LTBI and ARI among South Korean health care workers (HCWs) based on their interferon-gamma release assays (IGRA).MethodsThis was single center, cross-sectional retrospective study in a tertiary hospital in South Korea. We performed IGRA in HCWs between May 2017 and March 2018. We estimated ARI based on IGRA results. Logistic regression model was used to identify factors affecting IGRA positivity.ResultsA total of 3233 HCWs were analyzed. Median age of participants was 38.0 and female was predominant (72.6%). Overall positive rate of IGRA was 24.1% and IGRA positive rates age-group wise were 6.6%, 14.4%, 34.3%, and around 50% in the age groups 20s, 30s, 40s, and 50s and 60s, respectively. The ARIs was 0.26–1.35% between 1986 and 2005; rate of TB infection has gradually decreased in the last two decades. Multivariable analysis indicated that older age, healed TB lesion in x-ray, and male gender were risk factors for IGRA positivity, whereas working in high-risk TB departments was not.ConclusionsResults showed that ARI in South Korean HCWs gradually decreased over two decades, although LTBI remained prevalent. Our results suggest that the LTBI test result of HCWs might be greatly affected by age, rather than occupational exposure, in intermediate TB burden countries. Thus, careful interpretation considering the age structure is required.

Prevalence of Mycobacterium tuberculosis infection as measured by the QuantiFERON-TB Gold assay and ESAT-6 free IGRA among adolescents in Mwanza, Tanzania.

BackgroundThe prevalence of latent tuberculosis infection (LTBI) is vastly higher than that of tuberculosis (TB) disease and this enormous reservoir of individuals with LTBI impacts the global TB control strategy. Adolescents are at greatest risk of TB infection and are thus an ideal target population for a potential effective TB vaccine to be added to the current BCG programme as it could reduce the number of latent infections and consequently the number of adults with TB disease. However, LTBI rates are often unknown for this population. This study aims to estimate the magnitude of LTBI and to determine if Tanzanian adolescents would be a good population for a prevention of TB infection trial.MethodsThis was a descriptive cross-sectional study that recruited 193 adolescents aged 12 and 16 years from government schools and directly from the community in Mwanza Region, Tanzania. Socio-demographic characteristics were collected for all enrolled participants. Blood was drawn and tested using QuantiFERON-TB Gold In-Tube (QFT-GIT), and Early Secretory Antigenic Target-6–Free Interferon-gamma Release Assay (ESAT-6 free IGRA). Concordance between QFT-GIT and ESAT-6 free IGRA was evaluated using the McNemar’s test.ResultsOverall estimates of LTBI prevalence were 19.2% [95%CI, 14.1; 25.2] and 18.6% [95%CI, 13.6; 24.6] as measured by QFT-GIT IGRA and ESAT-6 free IGRA, respectively. The 16-year-old cohort had a higher LTBI prevalence (23.7% [95%CI, 16.1; 32.9]) as compared to 12-year-old cohort (14.6% [95%CI, 8.6; 22.7]) as measured by QFT-GIT IGRA. When measured by ESAT-6 Free IGRA, LTBI prevalence was 24.7% (95%CI, 16.9; 34.0) for the 16-year-old cohort and 12.5% (95%CI, 7.0; 20.3) among the 12-year-old cohort. According to both tests the prevalence of TB infection and the corresponding annual risk of tuberculosis infection (ARTI) and force of infection were high and increased with age. Of all enrolled participants, 97.4% had concordant results for QFT-GIT IGRA and ESAT-6 free IGRA (p = 0.65).ConclusionsThe prevalence of LTBI and the associated ARTI and force of infection among adolescents is high and increases with age in Mwanza Region. There was a high concordance between the QFT-GIT and the novel ESAT-6 free IGRA assays. These findings suggest Mwanza is a promising area to conduct novel TB vaccine research prevention of infection (POI) studies targeting adolescents.

Tuberculosis Infection in Women of Reproductive Age: A Cross-sectional Study at Antenatal Care Clinics in an Ethiopian City.

BackgroundKnowledge on tuberculosis (TB) infection epidemiology in women of reproductive age living in TB-endemic areas is limited. We used a composite definition of TB infection in a cohort of pregnant women recruited in an Ethiopian city as a model for TB exposure patterns, and to identify factors associated with TB infection. MethodsWomen seeking antenatal care at public health facilities underwent structured interviews, physical examination, and QuantiFERON-TB Gold-Plus (QFT) testing. Women with symptoms compatible with TB disease, and all human immunodeficiency virus (HIV)–positive women, were investigated for active TB by sputum bacteriological testing. TB infection (TB+) was defined as either positive QFT (≥ 0.35 IU/mL), self-reported previous active TB, or current active TB. Associations between TB infection and clinical, demographic, and socioeconomic characteristics were tested in multiple logistic regression analysis.ResultsAmong 1834 participants, 679 (37.0%) met criteria for TB+ (80 [4.4%] previous active TB, 5 [0.3%] current active TB, and 594 [32.4%] QFT-positive without previous or current active TB). Age (annual adjusted odds ratio [AOR], 1.069 [95% confidence interval {CI}, 1.045–1.093]) and HIV infection (AOR, 1.43 [95% CI, 1.033–1.988]) were independently associated with TB+. The relationship with increasing age was only observed in HIV-negative women, and translated to an estimated annual risk of TB infection of 2.1% in HIV-negative women.ConclusionsTB infection in women of reproductive age in Ethiopia was independently associated with HIV infection and increasing age, suggesting exposure to contagious TB and continuous acquisition of TB infection in this population.

The annual risk of tuberculosis infection in newly hired researchers and healthcare workers using interferon-gamma release assay in Japan

The tuberculosis (TB) notification rate in Japan is gradually decreasing but has not yet achieved “pre-elimination,” defined by the World Health Organization. To effectively tackle, control, and eliminate TB, estimating and monitoring the annual risk of TB infection (ARI) using tuberculin skin testing (TST) to understand the dynamics of TB epidemiology are significantly important. However, studies estimating ARIs using TST are few considering that Bacillus Calmette-Guérin vaccination coverage is high in Japan. This was a single-center, cross-sectional study conducted between January 2011 and December 2018 in Tokyo area where interferon-gamma release assays (IGRAs) were performed in newly hired researchers of Keio University School of Medicine and healthcare workers of Keio University Hospital to determine TB infection. We estimated the prevalence of TB infection and ARI based on their IGRA results. Among the 3908 subjects, 83 (2.124%) had positive IGRA results. Multiple logistic regression analysis revealed that age was a significant risk factor for positive IGRA result (adjusted odds ratio, 1.046). The ARIs were 0.049%–0.156% between 1986 and 2004, midyears of TB infection, but have not significantly decreased over approximately two decades. To decrease the risk of TB infection, advanced strategies to control and eliminate TB in Tokyo area are significantly required.

Estimating the annual risk of infection with Mycobacterium tuberculosis among adolescents in Western Kenya in preparation for TB vaccine trials

BackgroundAdolescents are a prime target group for tuberculosis (TB) vaccine trials that include prevention of infection (POI). The BCG vaccine is given at birth and does not prevent TB infection. TB infection, a critical endpoint for POI vaccine trials would need to be documented to estimate sample sizes in target populations.MethodsAdolescents aged 12–18 years of age were enrolled in an area under continuous demographic surveillance. A tuberculin skin test (TST) survey was conducted as part of a study on TB prevalence and incidence. All adolescents got TSTs at enrolment and returned after 72 h for reading. A TST of ≥10 mm if HIV negative or ≥ 5 mm if HIV positive, was considered positive.ResultsOf 4808 adolescents returning for TST readings (96% of those enrolled), mean age was 14.4 (SD 1.9), 4518(94%) were enrolled in school and 21(0.4%) gave a previous history of tuberculosis. Among adolescents with TST reactivity, the mean TST induration was 13.2 mm (SD 5.4). The overall prevalence of latent TB infection was 1544/4808 (32.1, 95% CI 29.2–35.1) with a corresponding annual risk of TB infection (ARTI) of 2.6% (95% CI 2.2–3.1). Risk factors for a positive TST included being male (OR 1.3, 95% CI 1.2,1.5), history of having a household TB contact (OR 1.5, 95% CI 1.2,1.8), having a BCG scar (OR 1.5,95% CI 1.2,1.8), living in a rural area (OR 1.4, 95% CI 1.1,1.9), and being out of school (OR 1.8, 95% CI 1.4,2.3).ConclusionWe conclude that the high TB transmission rates we found in this study, suggest that adolescents in this region may be an appropriate target group for TB vaccine trials including TB vaccine trials aiming to prevent infection.

Evaluation of purified protein derivates test at tuberculosis dispensary in Hatay, Turkey, applied to Turks and Syrian refugees (2012-2015).

The aim of the study was to evaluate results of purified protein derivates (PPD) test applied at the Tuberculosis Dispensary between 2012-2015 in Hatay, Turkey, where a large number of Syrian refugees have migrated since the Syrian civil war began in 2011. PPD test records from the Electronic Tuberculosis Management System at the Tuberculosis Dispensary from 2012-2015 were analyzed based on nationality, age groups, BCG scar availability, and PPD reaction. The annual risk of tuberculosis infection (ARTI) was calculated based on years for each age group in Turks and Syrian refugees and the trend was evaluated. Student-t, Chi-square, and Mantel-Haenszel tests were used in statistical analyses, p < 0.05 was considered significant. In total, 5,255 PPD tests were made, 15.5% were Syrian refugees. BCG scar was missing in 48.5% of Turks and 87.3% of refugees (p < 0.001). The 0-5 age group represented the lowest rate (Turks 3.2%, refugees 4.3%) and the 19-64 age group represented the highest rate (Turks 51.1%, refugees 54.1%) of positive PPD reaction among individuals without BCG scar. Among individuals without BCG scar, more positive PPD reactions developed in refugees of the 6-18 group than in Turks (Turks 16.9%, refugees 46.4%, p < 0.001). Among individuals with BCG scar, more positive PPD reactions developed among refugees of the 0-5 (Turks 7.8%, refugees 24.0%, p = 0.049) and 19-64 (Turks 36.6%, refugees 58.8%, p = 0.028) age groups. ARTIs between 2012-2015 were 0.2%, 1.0%, 1.3%, and 1.4% among Turks, (except 2012) 2.3%, 0.3%, 2.4% among refugees in the 0-5 age group, 1.1%, 2.0%, 1.7%, and 1.5% among Turks, and 8.5%, 6.6%, 7.3%, and 2.4% among refugees in the 6-18 age group, respectively. Higher positive PPD reactions and ARTIs were found among Syrian refugees, more specifically in the 6-18 age group.

Estimating the annual risk of tuberculosis infection in Japan from interferon-gamma release assay data

To assess tuberculosis transmission frequency at a population level, the age-dependent Mantoux test has been used widely to estimate the annual risk of infection (ARI) with Mycobacterium tuberculosis. However, the widespread Bacille Calmette-Guerin (BCG) immunization program implemented in Japan in the 20th century has made natural infections with M. tuberculosis difficult to distinguish from immune responses against this vaccine. Consequently, a recognized alternative method for measuring the frequency of primary infections, the interferon-gamma release assay (IGRA), which partially decays as a function of time after infection, is used. We aimed to estimate the ARI in Japan from IGRA data along with its response decay information using mathematical modeling. Devising a partial differential equation system, we computed the probability of IGRA positivity as a function of time and age, accounting for the time-varying force of infection and decay function of the IGRA response. Jointly estimating the force of infection and the parameters governing the decay function of the IGRA response, we found that the age-dependent increasing pattern of the IGRA response was captured by the proposed simple model, yielding estimates of the time-dependent force of infection. ARI decreased as a function of time in the study subjects for all geographic locations. By the year 2030, our model showed that the median age of infection is predicted to be delayed by 40–50 years compared with that in 1940. The geographic variations in the ARI were striking, ranging from under 0.1% to 0.6% in 2018, which echoes the longstanding notion of highly heterogeneous geographical tuberculosis transmission in Japan.

Latent tuberculosis infection in rural China: who will develop tuberculosis?

Screening people at risk of developing tuberculosis because of latent infection and offering preventive treatment to those with positive results is now regarded as one of the components of the WHO End TB Strategy. 1 Getahun H Matteelli A Abubakar I et al. Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries. Eur Respir J. 2015; 46: 1563-1576 Crossref PubMed Scopus (392) Google Scholar In The Lancet Infectious Diseases, Lei Gao and colleagues 2 Gao L Li X Liu J et al. Incidence of active tuberculosis in individuals with latent tuberculosis infection in rural China: follow-up results of a population-based, multicentre, prospective cohort study. Lancet Infect Dis. 2017; (published online July 14.)http://dx.doi.org/10.1016/S1473-3099(17)30402-4 Google Scholar present the results of a 2-year follow-up study in four rural regions of China, assessing patients with latent tuberculosis infection, defined by a positive tuberculin skin test (TST) or a positive interferon-γ release assay (IGRA) QuantiFERON-TB Gold In-Tube (QFT), which has been described in previous publications. 3 Gao L Lu W Bai L et al. Latent tuberculosis infection in rural China: baseline results of a population-based, multicentre, prospective cohort study. Lancet Infect Dis. 2015; 15: 310-319 Summary Full Text Full Text PDF PubMed Scopus (149) Google Scholar , 4 Gao L Bai L Liu J et al. Annual risk of tuberculosis infection in rural China: a population-based prospective study. Eur Respir J. 2016; 48: 168-178 Crossref PubMed Scopus (26) Google Scholar The authors report an incidence rate of tuberculosis of 0·87 (95% CI 0·68–1·07) per 100 person-years in people with QFT positivity and 0·50 (0·38–0·63) per 100 person-years in the group with a positive TST. 2 Gao L Li X Liu J et al. Incidence of active tuberculosis in individuals with latent tuberculosis infection in rural China: follow-up results of a population-based, multicentre, prospective cohort study. Lancet Infect Dis. 2017; (published online July 14.)http://dx.doi.org/10.1016/S1473-3099(17)30402-4 Google Scholar The main risk factors for the development of active tuberculosis during the observation period are male sex and a history of tuberculosis. Gao and colleagues conclude that targeted screening of population groups with a high risk of tuberculosis and provision of a preventive treatment might reduce the pool of future tuberculosis cases. Incidence of active tuberculosis in individuals with latent tuberculosis infection in rural China: follow-up results of a population-based, multicentre, prospective cohort studyOur results suggest that high-risk populations in communities in rural China, such as individuals at a high risk of disease reactivation from previous tuberculosis, should be targeted for latent infection screening and treatment with an interferon-γ releasing assay rather than a TST. Full-Text PDF

Racial inequality in the annual risk of Tuberculosis infection in the United States, 1910-1933.

Tuberculosis (TB) mortality rates in the USA fell rapidly from 1910 to 1933. However, during this period, racial disparities in TB mortality in the nation's expanding cities grew. Because of long delays between infection and disease, TB mortality is a poor indicator of short-term changes in transmission. We estimated the annual risk of TB infection (ARTI) in 11 large US cities to understand whether rising inequality in mortality reflected rising inequality in ARTI using city-level TB mortality data compiled by the US Department of Commerce from 1910 to 1933. We estimated ARTI for African-Americans and whites using pediatric extrapulmonary TB mortality data for African-Americans and whites in our panel of cities. We also estimated age-adjusted pulmonary TB mortality rates for these cities. We find that the ratio of ARTI for African-Americans vs. whites increased from 2·1 (95% CI = 1·7, 2·4) in 1910 to 4·2 (95% CI = 3·4, 5·2) in 1933. This change mirrored the increasing inequality in age-adjusted pulmonary TB mortality during this period. These findings may reflect the combined effects of migration, inequality in access to care, increasing population density, and racial residential segregation in northern cities during this period.

Prevalence of Latent Mycobacterium Tuberculosis Infection (LTBI) in Saudi Arabia; Population based survey

BackgroundThe annual risk of tuberculosis infection (ARTI) data in Saudi Arabia has not been updated since 1993. ObjectivesTo estimate the prevalence of latent TB infection (LTBI) and ARTI in a population-based sample in Saudi Arabia using Tuberculin skin test (TST) and QuantiFERON TB Gold in tube (QFT-GIT) test. MethodsA population-based cross sectional study was conducted between July 2010 and March 2013. Participants were randomly selected from the population served by the primary healthcare centers of the Ministry of National Guard Health Affairs in Riyadh, Jeddah, Alhassa and Dammam, Saudi Arabia. ResultsA total of 1369 participants were included. The overall prevalence of LTBI was similar using TST and QFT-GIT (9.3% and 9.1% respectively, p=0.872) but stratified prevalence rates were variable in all sociodemographic groups except marital status. Additionally, the prevalence rates of LTBI using either test alone showed significant differences by several sociodemographic and behavioral characteristics. The overall ARTI was 0.36% using TST and 0.35% using QFT-GIT. ConclusionsWe are reporting much lower estimates for the prevalence of LTBI and the ARTI in a population-based sample in Saudi Arabia relative to the data that have been used for more than two decades.

Diabetes incidence and projections from prevalence surveys in Fiji.

BackgroundType 2 diabetes mellitus (T2DM) incidence is traditionally derived from cohort studies that are not always feasible, representative, or available. The present study estimates T2DM incidence in Fijian adults from T2DM prevalence estimates assembled from surveys of 25–64 year old adults conducted over 30 years (n = 14,288).MethodsT2DM prevalence by five-year age group from five population-based risk factor surveys conducted over 1980–2011 were variously adjusted for urban-rural residency, ethnicity, and sex to previous censuses (1976, 1986, 1996, 2009) to improve representativeness. Prevalence estimates were then used to calculate T2DM incidence based on birth cohorts from the age-period (Lexis) matrix following the Styblo technique, first used to estimate annual risk of tuberculosis infection (incidence) from sequential Mantoux population surveys. Poisson regression of year, age, sex, and ethnicity strata (n = 160) was used to develop projections of T2DM prevalence and incidence to 2020 based on various scenarios of population weight measured by body mass index (BMI) change.ResultsT2DM prevalence and annual incidence increased in Fiji over 1980–2011. Prevalence was higher in Indians and men than i-Taukei and women. Incidence was higher in Indians and women. From regression analyses, absolute reductions of 2.6 to 5.1% in T2DM prevalence (13–26% lower), and 0.5–0.9 per 1000 person-years in incidence (8–14% lower), could be expected in 2020 in adults if mean population weight could be reduced by 1–4 kg, compared to the current period trend in weight gain.ConclusionsThis is the first application of the Styblo technique to calculate T2DM incidence from population-based prevalence surveys over time. Reductions in population BMI are predicted to reduce T2DM incidence and prevalence in Fiji among adults aged 25–64 years.Electronic supplementary materialThe online version of this article (doi:10.1186/s12963-016-0114-0) contains supplementary material, which is available to authorized users.

Identification of populations at high risk of tuberculosis infection in rural China: a population-based, multicentre, prospective study

BackgroundAcquisition and persistence of tuberculosis infection are important epidemiological measurements for evaluation of tuberculosis transmission in a community. However, prospective population data on the incidence of tuberculosis infection have been sparely reported in the global literature. MethodsWe conducted a population-based, multicentre, prospective study to investigate the annual risk of tuberculosis infection and its persistence in rural populations in China from July 2013 to June 2015, using yearly tests with tuberculin skin test (TST) and an interferon-γ release assay (IGRA). Findings15 907 eligible participants from four rural sites (Xiangtan, Hunan province; Zhongmu, Henan Province; Longxi, Gansu Province; Danyang, Jiangsu Province) who were identified as TST-negative (<10 mm) or IGRA-negative in a baseline survey were included in the first year's follow-up examination. 13 580 (85·4%) with completed questionnaires and tests results were included in this study. Annual seroconversion rates among the study sites ranged from 2·1% to 4·9% (average 3·1%) when assessed by IGRA and between 6·0% and 31·1% (14·5%) when assessed by TST. Infection persistence was successfully followed-up in 330 participants who underwent IGRA conversion during the second year of follow-up, 49·7% (164) were found to be consistently IGRA-positive. Both conversion and persistence of IGRA-positivity were increased significantly in association with increasing age (p<0·001 for trend). History of close contact with patients with active tuberculosis and smoking were positively associated with risk of IGRA conversion (adjusted OR 1·54, 95% CI 1·04–2·27, and 1·53, 1·13–2·05, respectively). InterpretationConsistent with published cross-sectional data, the prospective results provide stronger evidence that close contacts, older people, and smokers are high-risk populations for tuberculosis infection in rural China. These groups should be prioritised for tuberculosis control in China and areas with a similar epidemiological profile. The unexpectedly high annual infection rates based on TST could not be explained by local epidemiology and were probably overestimated because of the boosting effect of serial TST testing, BCG vaccination, or environmental mycobacteria. FundingNational Science and Technology Major Project of China (2013ZX10003004-002, 2014ZX10003001-001), and Program for Changjiang Scholars and Innovative Research Team in University of China (IRT13007).

Annual risk of tuberculosis infection in rural China: a population-based prospective study.

Prospective population data on the incidence of tuberculosis (TB) infection has been sparsely reported in the global literature.A population-based prospective study was conducted in rural China to investigate the annual risk of TB infection, and its persistence using serial tuberculin skin tests (TSTs) and an interferon-γ release assay. In total, 13 580 eligible participants from four rural sites, identified as TST negative (<10 mm) or QuantiFERON-TB Gold In-Tube (QFT) (an interferon-γ release assay) negative from a baseline survey, were included in the first year's follow-up examination.The annual conversion rate of QFT among the study sites ranged between 2.1% and 4.9% (average 3.1%), and the incidence of TST conversion ranged between 6.0% and 31.1% (average 14.5%). During the second year's follow-up, infection persistence was investigated using 390 subjects with QFT conversions. Among them, 49.7% (164 out of 330) were found to be consistently QFT positive. Both the conversion and the persistence of QFT positivity were found to be significantly increased with increasing age.In conclusion, the annual TB infection rate was suggested to be ∼1.5% based on persistent positive results after QFT conversion in rural China. Therefore, infection control among those high-risk populations, including the elderly, should be prioritised for TB control in China.

Estimating the annual risk of tuberculosis infection and disease in southeast of iran using the bayesian mixture method.

Background:Tuberculosis is still a public health concern in Iran. The main challenge in monitoring epidemiological status of tuberculosis is to estimate its incidence accurately.Objectives:We used a newly developed approach to estimate the incidence of tuberculosis in Sistan, an endemic area in southeast of Iran in 2012-13.Patients and Methods:This cross-sectional study was conducted on school children aged 6-9 years. We estimated a required sample size of 6350. Study participants were selected using stratified two-stage cluster sampling method and recruited in a tuberculin skin test survey. Indurations were assessed after 72 hours of the injection and their distributions were plotted. Prevalence and annual risk of tuberculosis infection (ARTI) were estimated using the Bayesian mixture model and some traditional methods. The incidence of active disease was calculated using the Markov Chain Monte Carlo technique.Results:We assumed weibull, normal and normal as the best distributions for indurations due to atypical reactions, BCG (Bacillus Calmette–Guérin) reactions and Mycobacterium tuberculosis infection, respectively. The estimated infection prevalence and ARTI were 3.6% (95%CI: 3.1, 4.1) and 0.48%, respectively. These estimates were lower than those obtained from the traditional methods. The incidence of active tuberculosis was estimated as 107 (87-149) per 100000 population with a CDR of 54% (40%-68%).Conclusions:Although the mixture model showed slightly lower estimates than the traditional methods, it seems that this method might generate more accurate results for deep exploration of tuberculosis endemicity. Besides, we found that Sistan is a high endemic area for tuberculosis in Iran with a low case detection rate.

Annual Risk of Tuberculosis Infection in Hellenic Air Force Recruits

Background:The annual risk of Tuberculosis infection (ARTI) is a key indicator in epidemiology, of the extent of transmission in a community. There have been several suggested methods in order to evaluate the prevalence of Tuberculosis infection using tuberculin skin data. This survey estimates the ARTI in young Hellenic air force recruits. The effect of BCG vaccination has also been investigated.Materials and Methods:During the period November 2006-November 2007 tuberculin skin tests were conducted to estimate the prevalence of mycobacterium tuberculosis infection and also to determine the ARTI. Tuberculin PPD-RT 23, dose 2 IU was used in 7.492 Greek air force military recruits with a mean age of 23.57 years. All recruits were examined for previous bacill Calmette-Guérin vaccination through BCG scar. A vast number of personal, epidemiological significance, data of the participants was collected.Results:The ARTI was 0.2%, in those who were not previously BCG vaccinated; this was derived from a tuberculin skin test cut-off point of 10 mm. There were not any statistically significant differences, neither between urban and rural population concerning the positivity of the tuberculin skin test, nor among the population in recent contact with immigrants from high-incidence countries.Conclusion:The estimated ARTI among non BCG vaccinated young Greek men is 0.2%.

Modeling the Role of Public Transportation in Sustaining Tuberculosis Transmission in South Africa

Current tuberculosis notification rates in South Africa are among the highest ever recorded. Although the human immunodeficiency virus epidemic has been a critical factor, the density of respiratory contacts in high-risk environments may be an important and underappreciated driver. Using a modified Wells-Riley model for airborne disease transmission, we estimated the risk of tuberculosis transmission on 3 modes of public transit (minibus taxis, buses, and trains) in Cape Town, South Africa, using exhaled carbon dioxide as a natural tracer gas to evaluate air exchange. Carbon dioxide measurements were performed between October and December of 2011. Environmental risk, reflected in the rebreathed fraction of air, was highest in minibus taxis and lowest in trains; however, the average number of passengers sharing an indoor space was highest in trains and lowest in minibus taxis. Among daily commuters, the annual risk of tuberculosis infection was projected to be 3.5%-5.0% and was highest among minibus taxi commuters. Assuming a duration of infectiousness of 1 year, the basic reproductive number attributable to transportation was more than 1 in all 3 modes of transportation. Given its poor ventilation and high respiratory contact rates, public transportation may play a critical role in sustaining tuberculosis transmission in South African cities.

Annual risk of tuberculosis infection in Sri Lanka: a low prevalent country with a high BCG vaccination coverage in the South-East Asia Region.

Despite its simplicity, efficiency and reliability, Sri Lanka has not used the Annual Risk of Tuberculosis Infection (ARTI) to assess the prevalence and efficiency of tuberculosis (TB) control. Hence, a national tuberculin survey was conducted to estimate the ARTI. A school-based, cross-sectional tuberculin survey of 4352 children aged 10 years irrespective of their BCG vaccination or scar status was conducted. The sample was selected from urban, rural and estate strata using two-stage cluster sampling technique. In the first stage, sectors representing three strata were selected and, in the second stage, participants were selected from 120 clusters. Using the mode of the tuberculin reaction sizes (15 mm) and the mirror-image technique, the prevalence and the ARTI were estimated. The prevalence of TB estimated for urban, rural and estate sectors were 13.9%, 2.2% and 2.3%, respectively. The national estimate of the prevalence of TB was 4.2% (95% CI = 1.7-7.2%). ARTI for the urban, rural and estate sectors were 1.4%, 0.2% and 0.2%, respectively, and the national estimate was 0.4% (95% CI = 0.2-0.7%). The estimated annual burden of newly infected or re-infected TB cases with the potential of developing into the active disease (400/100 000 population) was nearly 10-fold higher than the national new case detection rate (48/100 000 population). The national estimate of ARTI was lower than the estimates for many developing countries. The high-estimated risk for the urban sector reflected the need for intensified, sector-specific focus on TB control activities. This underscores the need to strengthen case detection. Repeat surveys are essential to determine the annual decline rate of infection.