Contacts Of Active Tuberculosis Cases Research Articles

The Impact of Diabetes and Prediabetes on Prevalence of Mycobacterium tuberculosis Infection Among Household Contacts of Active Tuberculosis Cases in Ethiopia.

It is uncertain whether diabetes affects the risk of developing latent tuberculosis infection (LTBI) following exposure to Mycobacterium tuberculosis (Mtb). We assessed the relationship of diabetes or prediabetes and LTBI among close and household contacts (HHCs) of patients with active pulmonary tuberculosis (TB) disease in Addis Ababa, Ethiopia. In this cross-sectional study, we performed interferon-γ release assays, TB symptom screening, and point-of-care glycolated hemoglobin (HbA1c) testing among HHCs of active TB cases. Diabetes status was classified into diabetes (HbA1c ≥6.5% or self-reported diagnosis), prediabetes (5.7%-6.4%), and euglycemia (≤5.6%). Multivariable logistic regression was used to determine the association of diabetes with LTBI. Among 597 study participants, 123 (21%) had dysglycemia including diabetes (n = 31) or prediabetes (n = 92); 423 (71%) participants were diagnosed with LTBI. Twelve of 31 (39%) HHCs with diabetes were previously undiagnosed with diabetes. The prevalence of LTBI among HHCs with diabetes, prediabetes, and euglycemia was 87% (27/31), 73% (67/92), and 69% (329/474), respectively. In multivariable analysis adjusted for age, sex, and HIV status, the odds of LTBI among HHCs with diabetes were 2.33 (95% confidence interval [CI], .76-7.08) times the odds of LTBI without diabetes. When assessing interaction with age, the association of diabetes and LTBI was robust among participants aged ≥40 years (adjusted odds ratio [aOR], 3.68 [95% CI, .77-17.6]) but not those <40 years (aOR, 1.15 [95% CI, .22-6.1]). HHCs with diabetes may be more likely to have LTBI than those with euglycemia. Further investigations are needed to assess mechanisms by which diabetes may increase risk of LTBI after Mtb exposure.

61586 Impact of Diabetes and Pre-diabetes on Prevalence of Infection with Mycobacterium tuberculosis among Household Contacts of Active Tuberculosis Cases in Ethiopia

ABSTRACT IMPACT: This work examines the association between diabetes mellitus and latent tuberculosis infection among a cohort of household contacts exposed to active tuberculosis in Ethiopia, focusing attention on the need for further translational research to determine the mechanisms of susceptibility to Mycobacterium tuberculosis infection among individuals with diabetes and pre-diabetes. OBJECTIVES/GOALS: Diabetes mellitus (DM) is an established risk factor for active TB disease, but there is limited understanding of the relationship of DM and latent tuberculosis (LTBI). We sought to determine the relationship between DM or pre-DM with LTBI among household or close contacts (HHCs) of active TB cases in Ethiopia. METHODS/STUDY POPULATION: We conducted a cross-sectional study of the HHCs of index active TB cases enrolled in an ongoing TB Research Unit (TBRU) study in Addis Ababa, Ethiopia. HHCs of individuals with laboratory-confirmed TB had QuantiFERON ®-TB Gold Plus (QFT) and glycated hemoglobin (HbA1c) tests performed. LTBI was defined as a positive QFT and lack of symptoms. HbA1C results were used to define no DM (HbA1c &lt;5.7), pre-DM (HbA1c 5.7-6.5%), and DM (HbA1c &gt;6.5% or prior history of diabetes). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) after adjustment for age, sex and HIV status as potential confounders. RESULTS/ANTICIPATED RESULTS: Among 466 HHCs, the median age was 29 years (IQR 23-38), 58.8% were female, 3.4% were HIV-positive, and median BMI was 20.9 kg/m^2 (IQR 18.9-23.8). Overall, 329 HHCs (70.6%) had LTBI, 26 (5.6%) had DM and 73 (15.7%) had pre-DM. Compared to HHC without DM, the prevalence of LTBI was higher in those with pre-DM (68.9% vs. 72.6%; OR 1.19, 95% CI 0.69-2.13) and those with DM (88.5%; OR 3.45, 95% CI 1.17-14.77). In multivariable analysis, there was a trend towards increased LTBI risk among HHCs with DM vs. without DM (OR 2.16, 95% CI 0.67-9.70) but the difference was not statistically significant. Among HHCs with LTBI, the median IFN-? response to TB1 antigen was modestly greater in those with DM (5.3 IU/mL; IQR 3.0-7.8) and pre-DM (5.4 IU/mL; IQR 2.0-8.4) compared to HHCs without DM (4.3 IU/mL; IQR 1.4-7.7). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results suggest that DM may increase the risk of LTBI among HHCs recently exposed to active TB. Among those with LTBI, increased IFN-? antigen response in the presence of DM and pre-DM may indicate an exaggerated but ineffectual response to TB. Further investigation is needed to assess how dysglycemia impacts susceptibility to M. tuberculosis.

Tuberculosis: where and how fast are stone quarry workers infected?

Abstract Background In 2018 an annual tuberculosis (TB) screening program targeting stone quarry workers was implemented in two municipalities in Northern Portugal. These have been hotspots for TB (76 and 59 cases per 100 000 population per year in 2012-2016, well above the 18 cases per 100 000 population observed in Portugal in 2016), with 30% of active TB cases occurring among stone quarry workers. Screening in this setting is recommended by the World Health Organization, as exposure to silica and silicosis increase the risk of TB. Occupational health services, TB outpatient centers, the hospital, a laboratory, primary health care and public health services work closely together with employers, employees, municipal council and the community promoting meetings and continuous training. Screening activities included a symptom questionnaire, chest X-ray and sputum exam; and, after exclusion of active TB, interferon-gamma release assay (IGRA) for latent tuberculosis infection (LTBI). Preventive treatment was offered. Objective Assess annual rate of TB infection Methods Workers without history of TB/LTBI were IGRA tested in 2018, and retested in 2019. Annual rate of infection was calculated as the proportion of workers IGRA negative in 2018 becoming positive in 2019. Results In 2018-2019, 274 workers were screened yearly. In 2018, 22 were diagnosed with LTBI and 26 had previous history of TB/LTBI. Out of 226 IGRA negative workers in 2018, 19 tested positive in 2019 (8.4% annual rate of infection). These individuals were not identified as close contacts of any new TB case and no cases of active TB were reported in their stone quarries. Some active TB cases were regular customers of specific bars. Conclusions Active transmission of TB seems to be occurring among stone quarry workers. Workers that converted from IGRA negative to positive had no co-workers with active TB in the study period, suggesting they could have been infected away from the workplace, possibly in community public places. Key messages Stone quarry workers in a high-risk TB sub-region were infected at an 8.4% annual rate, and could have been infected in community public places such as bars. Besides screening close contacts and at workplace, more efforts should be made identifying social contacts of active TB cases.

Tuberculin Skin Testing versus Interferon-Gamma Release Assay among Users of a Public Health Unit in Northeast Portugal

The screening of groups with a high risk for developing tuberculosis (TB) is a priority in order to control this disease. Since there is no gold standard for the diagnosis of latent TB infection (LTBI), both the tuberculin skin test (TST) and the interferon-gamma release assays (IGRA) have been used for this purpose. The aim of this study was to determine the proportion of LTBI by using the TST and the IGRA tests, and to assess the risk factors related with discordant results between tests across several risk groups advised for screening in Northeast Portugal. Data were collected from the database of patients with suspected LTBI and advised for the screening in a public health unit (January 2014 to December 2015). The proportion of LTBI was computed using both tests. Logistic regression models assessed risk factors for a positive test and for discordant results between tests. The adjusted odds ratio (OR) and respective 95% confidence interval (95% CI) were obtained. Out of 367 patients included in the analysis, 79.8% had a positive TST and 46.0% of them had a positive IGRA. In comparison with contacts of active TB cases, healthcare workers and inmates presented higher odds of TST positivity (OR 4.38, 95% CI 1.59–12.09 and OR 4.74, 95% CI 1.45–15.49, respectively), but immunocompromised people presented lower odds of TST positivity (OR 0.14; 95% CI 0.06–0.31). Instead, healthcare workers (OR 0.44, 95% CI 0.24–0.80) and immunocompromised people (OR 0.24, 95% CI 0.10–0.56) presented lower odds of a positive IGRA. There were 42.0% concordant positive results, 16.1% concordant negative results, and 41.9% discordant results, with healthcare workers presenting higher odds of discordant results (OR 3.34, 95% CI 1.84–6.05). The proportion of LTBI estimated by TST and IGRA among people advised for screening in our setting is high, highlighting the need of preventive strategies. Among healthcare workers, TST results should be read with caution as the higher proportion of discordant results with a positive TST suggests the impact of the booster reaction in this group.

Factors associated with tuberculosis disease among children who are household contacts of tuberculosis cases in an urban setting in Malaysia

BackgroundWith the rise in prevalence of childhood tuberculosis (TB) globally, contact tracing should be a powerful strategy for early diagnosis and management, especially in children who are household contacts of active TB cases. Here, we aimed to determine the prevalence and factors associated with TB disease in children who are household contacts of TB cases.MethodsWe used a cross-sectional study with data from the Malaysian TB Information System (TBIS) recorded from 1 January 2014 to 31 December 2017. All children aged 0–14 years who were registered in the TBIS with at least one household contact of TB cases were included in the study. Multiple logistic regression analysis was performed to calculate the adjusted odds ratio (adj. OR) and for adjusting the confounding factors.ResultsA total of 2793 children were included in the study. The prevalence of active TB was 1.5% (95% confidence interval [CI]: 1.31, 1.77%). Children aged < 5 years [adj. OR 9.48 (95% CI: 3.41, 26.36) p < 0.001] with positive tuberculin skin test [adj. OR 395.73 (95% CI: 134.17, 1167.13), p < 0.001] and investigation period of > 6 weeks [adj. OR 7.48 (95% CI: 2.88, 19.43), p < 0.001] had significantly higher odds for TB disease.ConclusionsThe prevalence of TB disease in children who were household contacts of TB cases is relatively low. However, contact tracing programmes should not only focus on children aged < 5 years and with positive tuberculin skin test results, but also be empowered to reduce the investigation period.

Polymorphisms in TLR4 and TNFA and Risk of Mycobacterium tuberculosis Infection and Development of Active Disease in Contacts of Tuberculosis Cases in Brazil: A Prospective Cohort Study.

The role of genetic polymorphisms in latent tuberculosis (TB) infection and progression to active TB is not fully understood. We tested the single-nucleotide polymorphisms (SNPs) rs5743708 (TLR2), rs4986791 (TLR4), rs361525 (TNFA), rs2430561 (IFNG) rs1143627 (IL1B) as risk factors for tuberculin skin test (TST) conversion or development of active TB in contacts of active TB cases. Contacts of microbiologically confirmed pulmonary TB cases were initially screened for longitudinal evaluation up to 24 months, with clinical examination and serial TST, between 1998 and 2004 at a referral center in Brazil. Data and biospecimens were collected from 526 individuals who were contacts of 177 active TB index cases. TST conversion was defined as induration ≥5 mm after a negative TST result (0 mm) at baseline or month 4 visit. Independent associations were tested using logistic regression models. Among the 526 contacts, 60 had TST conversion and 44 developed active TB during follow-up. Multivariable regression analysis demonstrated that male sex (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.1-4.6), as well as SNPs in TLR4 genes (OR: 62.8, 95% CI: 7.5-525.3) and TNFA (OR: 4.2, 95% CI: 1.9-9.5) were independently associated with TST conversion. Moreover, a positive TST at baseline (OR: 4.7, 95% CI: 2.3-9.7) and SNPs in TLR4 (OR: 6.5, 95% CI: 1.1-36.7) and TNFA (OR: 12.4, 95% CI:5.1-30.1) were independently associated with incident TB. SNPs in TLR4 and TNFA predicted both TST conversion and active TB among contacts of TB cases in Brazil.

Two interferon gamma release assays for predicting active tuberculosis: the UK PREDICT TB prognostic test study.

Despite a recent decline in the annual incidence of tuberculosis (TB) in the UK, rates remain higher than in most Western European countries. The detection and treatment of latent TB infection (LTBI) is an essential component of the UK TB control programme. To assess the prognostic value and cost-effectiveness of the current two interferon gamma release assays (IGRAs) compared with the standard tuberculin skin test (TST) for predicting active TB among untreated individuals at increased risk of TB: (1) contacts of active TB cases and (2) new entrants to the UK from high-TB-burden countries. A prospective cohort study and economic analysis. Participants were recruited in TB clinics, general practices and community settings. Contacts of active TB cases and migrants who were born in high-TB-burden countries arriving in the UK were eligible to take part if they were aged ≥ 16 years. Outcomes include incidence rate ratios comparing the incidence of active TB in those participants with a positive test result and those with a negative test result for each assay, and combination of tests and the cost per quality-adjusted life-year (QALY) for each screening strategy. A total of 10,045 participants were recruited between May 2010 and July 2015. Among 9610 evaluable participants, 97 (1.0%) developed active TB. For the primary analysis, all test data were available for 6380 participants, with 77 participants developing active TB. A positive result for TSTa (positive if induration is ≥ 5 mm) was a significantly poorer predictor of progression to active TB than a positive result for any of the other tests. Compared with TSTb [positive if induration is ≥ 6 mm without prior bacillus Calmette-Guérin (BCG) alone, T-SPOT®.TB (Oxford Immunotec Ltd, Oxford, UK), TSTa + T-SPOT.TB, TSTa + IGRA and the three combination strategies including TSTb were significantly superior predictors of progression. Compared with the T-SPOT.TB test alone, TSTa + T-SPOT.TB, TSTb + QuantiFERON® TB Gold In-Tube (QFT-GIT; QIAGEN GmbH, Hilden, Germany) and TSTb + IGRA were significantly superior predictors of progression and, compared with QFT-GIT alone, T-SPOT.TB, TSTa + T-SPOT.TB, TSTa + QFT-GIT, TSTa + IGRA, TSTb + T-SPOT.TB, TSTb + QFT-GIT and TSTb + IGRA were significantly superior predictors of progression. When evaluating the negative predictive performance of tests and strategies, negative results for TSTa + QFT-GIT were significantly poorer predictors of non-progression than negative results for TSTa, T-SPOT.TB and TSTa + IGRA. The most cost-effective LTBI testing strategies are the dual-testing strategies. The cost and QALY differences between the LTBI testing strategies were small; in particular, QFT-GIT, TSTb + T-SPOT.TB and TSTb + QFT-GIT had very similar incremental net benefit estimates. This study found modest differences between tests, or combinations of tests, in identifying individuals who would go on to develop active TB. However, a two-step approach that combined TSTb with an IGRA was the most cost-effective testing option. The two-step TSTb strategy, which stratified the TST by prior BCG vaccination followed by an IGRA, was the most cost-effective approach. The limited ability of current tests to predict who will progress limits the clinical utility of tests. The implications of these results for the NHS England/Public Health England national TB screening programme for migrants should be investigated. This study is registered as NCT01162265. The National Institute for Health Research Health Technology Assessment programme.

2300 Association between source case cavitation on chest radiograph and QuantiFERON-TB Gold In-Tube conversion among close contacts of active tuberculosis cases in Brazil

OBJECTIVES/SPECIFIC AIMS: QuantiFERON-TB Gold In-Tube (QFT) conversion from negative to positive, is regarded as a marker of recent latent tuberculosis infection and may be predictive of incident active tuberculosis (TB) disease. However, it remains unclear how conversion is influenced by individual and environmental factors, including the infectiousness of the source case to whom the contact was exposed. We aimed to examine the effect of infectiousness of TB in the source case, as measured by presence of cavitation on chest X-ray, on the incidence of QFT conversion among close contacts of the pulmonary TB index case, after adjusting for potential confounding by contact and source case characteristics. METHODS/STUDY POPULATION: The Regional Prospective Observational Research for Tuberculosis (RePORT)-Brazil is an ongoing prospective cohort study that enrolls close contacts of culture-confirmed pulmonary TB patients and follows them for 24 months for development of active TB. Demographic, clinical, and diagnostic information are obtained at baseline and during follow-up at clinical visits and by telephone. QFT testing is performed at baseline and repeated after 6 months if the baseline QFT is negative. A positive IFN-γ value is defined as &gt;0.35 IU/mL, as recommended by the manufacturer and the CDC, and QFT conversion is defined as a negative QFT at baseline followed by a positive QFT at 6 months. RESULTS/ANTICIPATED RESULTS: Among 260 enrolled contacts with nonpositive baseline QFT results and 6 months of follow-up, 198 (76%) were retested with QFT 6 months after enrollment. Of those retested, 26 (13%) converted to positive. Presence of any cavitation in the source case, based on chest radiography, was significantly associated with QFT-conversion (ORunadjusted=2.4, 95% CI: 1.0–5.7). Additional univariate analyses revealed that QFT conversion was associated with black and brown race (compared with white race) of the contact, current smoking and current alcohol use in the source case. After adjusting for potential confounders (age, sex, and race of the contact and current smoking of the source case), the association between source case cavitation and QFT conversion remained (ORadjusted=2.5 95% CI: 1.0–6.2). As of December 6, 2017, none of the QFT-retested contacts had developed active TB, with a median follow-up of 12.3 months (IQR: 7.1–13.1). We anticipate that ongoing enrollment and follow-up may yield cases of active TB; future analyses will provide greater precision for examining predictors of QFT-conversion and its association with incident TB. DISCUSSION/SIGNIFICANCE OF IMPACT: Our preliminary results agree with published literature suggesting the infectiousness of TB in the index case is a predictor of incident LTBI. Along with recent LTBI, immune suppression, HIV co-infection, and type 2 diabetes are considered risk factors for progression to active TB disease. Because only a small proportion of persons progress from LTBI to active TB disease, it is not appropriate to treat all persons with LTBI. Thus, more research is needed to identify groups at highest risk for QFT-conversion and incident TB disease, so these groups can be targeted for TB prevention, interventions, and facilitate a decline in TB incidence and mortality.

Risk of tuberculous infection in adolescents and adults in a rural community in Ethiopia.

The incidence of tuberculosis (TB) in sub-Saharan Africa is one of the highest in the world. To evaluate the prevalence of TB, the annual risk of tuberculous infection (ARTI) and associated risk factors in rural Ethiopia. A tuberculin skin test was performed among 2743 individuals in a rural community of Ethiopia around Ginci town, west of Addis Ababa, to estimate the prevalence of tuberculin reactivity and to assess factors associated with tuberculous infection. Among 2743 volunteer participants, test results were available for 2640, 691 (26.2%) of whom had an identifiable bacille Calmette-Guérin (BCG) scar; 221 (8.3%) reported household contact with a known TB case. The overall prevalence of TST reactions of ⩾ 10 mm was 29.7%. The ARTI was estimated at 1.7%. Tuberculin reactivity varied with age, sex, income and history of household contact with a TB case. Presence of BCG scar was not related to tuberculin reactivity. Our findings indicate that despite an effective TB control programme, TB transmission rates are still high in rural Ethiopia. Provision of isoniazid prophylaxis in close contacts of active TB cases among the poorest population groups may reduce TB incidence.

Household Contact Screening Adherence among Tuberculosis Patients in Northern Ethiopia.

BackgroundHousehold contacts of active tuberculosis cases are at high risk of getting tuberculosis disease. Tuberculosis detection rate among contacts of household members is high. Hence, this study investigated household contact screening adherence and associated factors among tuberculosis patients in Amhara region, Ethiopia.MethodsA cross-sectional study was conducted from April 10 - June 30, 2013 in five urban districts of Amhara region, where 418 patients receiving treatment at tuberculosis clinic were interviewed. All patients were interviewed using structured and pre-tested questionnaire. Bringing at least one household contact to TB clinic was regarded as adherent to household contacts screening. Bivariate and multiple logistic regressions were used to investigate association.ResultsThe overall adherence to household contact screening in Amhara region was 33.7%. Adherence was higher among Muslims than Christians. Adherence was high if patient took health education from Health Care Worker [AOR: 3.22, 95% CI: 1.88 to 5.51] and 2.17 times higher if patient had sufficient knowledge on tuberculosis [AOR: 2.17, 95% CI: 1.29 to 3.67] during interview. Relationship with contact was a significant [AOR: 0.4, 95% CI: 0.2 to 0.9] social related factor.ConclusionOne third of tuberculosis patients adhered to household contact screening in health facilities during their treatment course. Promoting knowledge of tuberculosis in the community and continuous health education to tuberculosis patients are recommended.

How can we achieve better prevention of progression to tuberculosis among contacts?

To the Editor : Strategies for control and elimination of tuberculosis (TB) in low-incidence settings are directed toward treatment of recently acquired latent tuberculosis infection (LTBI) in TB contacts [1]. To identify this target population for preventive treatment the development of more specific, in vitro assays for LTBI, the interferon (INF)-γ release assays (IGRAs), has offered an alternative method for LTBI diagnosis. Although IGRAs are increasingly recommended in national guidelines, evidence that positive IGRA results are prognostic for developing TB is still limited [2, 3], especially outside of prospective studies with well-defined inclusion criteria. Therefore, we investigated progression towards active TB among IGRA positive contacts of active TB cases under routine field conditions and calculated the positive predictive value (PPV) for progression and the number needed to treat (NNT) with preventive treatment to prevent one incident TB case. Additionally, we introduced different cut-off values for IGRA positivity and compared the computed progression rates. Among all contacts with a positive tuberculosis-specific IGRA we describe the uptake of preventive treatment. Our study covered a population of 3.2 million with a reported TB incidence of 7.5 cases per 100 000 population in 2008. From 2008 to 2010, we prospectively recruited all IGRA-positive contacts of newly detected sputum smear and/or culture positive notified TB cases at 12 local public health authorities (LPHAs) in Hesse, Germany. Only contacts with a history of TB disease were excluded. The German recommendations for contact investigations, published in 2007 [4], served as the basis for the LPHAs investigations: a dual-step approach in which IGRA is only performed if the tuberculin skin test (TST) is positive. However, LPHAs deviated from this recommendation and performed TST in less than 27% of all IGRA tested contacts. All our study participants, namely all IGRA-positive contacts, were …

A Quantitative Benefit-Risk Analysis of Isoniazid for Treatment of Latent Tuberculosis Infection Using Incremental Benefit Framework

BackgroundWe undertook a quantitative benefit-risk analysis of a targeted isoniazid (INH) therapy for latent tuberculosis (TB) infection for different groups of contacts of active TB cases. MethodsWe developed a decision-analytic model to compare the treatment of latent TB infection in subgroups of contacts to no treatment over a 6-year time horizon in a Canadian setting. Contacts were stratified into 32 groups on the basis of five binary variables: type of contact (close or casual), tuberculin skin test (TST) results (positive or negative at 5 mm cutoff), Bacillus Calmette-Guérin vaccination status, place of birth (foreign- or Canadian-born), and age group (cutoff 35 years). Risk of TB reactivation was calculated for each subgroup from a longitudinal registry of contacts, adjusted for several potential confounders and comorbid conditions. We calculated the quality-adjusted life-years gained because of delayed or prevention of active TB via treatment of latent TB infection versus quality-adjusted life-years lost because of the adverse events to INH. ResultsA targeted policy based on adopting INH therapy only in subgroups with positive expected incremental net health benefit resulted in a different treatment decision than the current guidelines in five subgroups comprising 3.9% of the contacts. Namely, the targeted policy comprised no INH therapy in casual contacts with a positive vaccination history even with a positive TST result and INH therapy in foreign-born close contacts younger than 35 years even with a negative TST result. ConclusionsFrom a benefit-risk viewpoint, INH treatment of contacts should be tailored on the basis of risk assessment algorithms that consider a range of factors at the time of screening.

Evaluation of an interferon-gamma release assay in young contacts of active tuberculosis cases

In a cross-sectional study in a hospital in Tehran in 2006-08 the QuantiFERON-TB interferon-gamma release assay (QTB) was compared with the tuberculin skin test (TST) in 59 young people (aged < 20 years) with close contact with immunocompetent cases of proven pulmonary tuberculosis. After 1 year follow-up 10 subjects had progressed to tuberculosis disease and received treatment; TSTwas positive in 30% and QTB in 100%. Of the 49 non-progressive subjects, TST was positive in 10.4% and QTB in 16.3%. The agreement between TST and QTB assay in non-progressive subjects was poor (K = 0.43). False positive and false negative rates for TST were 40.0% and 9.3% respectively; positive and predictive values were 60.0% and 90.7%. We suggest adding the interferon assay to the skin test in the decision to perform chest X-ray or to start chemoprophylaxis at least in younger subjects (aged < 20 years).

The presence of a booster phenomenon among contacts of active pulmonary tuberculosis cases: a retrospective cohort

BackgroundAssuming a higher risk of latent tuberculosis (TB) infection in the population of Rio de Janeiro, Brazil, in October of 1998 the TB Control Program of Clementino Fraga Filho Hospital (CFFH) routinely started to recommend a two-step tuberculin skin test (TST) in contacts of pulmonary TB cases in order to distinguish a boosting reaction due to a recall of delayed hypersensitivity previously established by infection with Mycobacterium tuberculosis (M.tb) or BCG vaccination from a tuberculin conversion. The aim of this study was to assess the prevalence of boosted tuberculin skin tests among contacts of individuals with active pulmonary tuberculosis (TB).MethodsRetrospective cohort of TB contacts ≥ 12 years old who were evaluated between October 1st, 1998 and October 31st 2001. Contacts with an initial TST ≤ 4 mm were considered negative and had a second TST applied after 7–14 days. Boosting reaction was defined as a second TST ≥ 10 mm with an increase in induration ≥ 6 mm related to the first TST. All contacts with either a positive initial or repeat TST had a chest x-ray to rule out active TB disease, and initially positive contacts were offered isoniazid preventive therapy. Contacts that boosted did not receive treatment for latent TB infection and were followed for 24 months to monitor the development of TB. Statistical analysis of dichotomous variables was performed using Chi-square test. Differences were considered significant at a p < 0.05.ResultsFifty four percent (572/1060) of contacts had an initial negative TST and 79% of them (455/572) had a second TST. Boosting was identified in 6% (28/455). The mean age of contacts with a boosting reaction was 42.3 ± 21.1 and with no boosting was 28.7 ± 21.7 (p = 0.01). Fifty percent (14/28) of individuals whose test boosted met criteria for TST conversion on the second TST (increase in induration ≥ 10 mm). None of the 28 contacts whose reaction boosted developed TB disease within two years following the TST.ConclusionThe low number of contacts with boosting and the difficulty in distinguishing boosting from TST conversion in the second TST suggests that the strategy of two-step TST testing among contacts of active TB cases may not be useful. However, this conclusion must be taken with caution because of the small number of subjects followed.

Cost-effectiveness of isoniazid chemoprevention in close contacts

The aim of the present study was to perform a cost-effectiveness analysis in young and middle-aged adults with latent tuberculosis (TB) infection in Germany. A Markov model simulated the progression of 20- and 40-yr-old close contacts of active TB cases over 20 yrs. Health and economic outcomes of isoniazid (INH) chemoprevention versus no intervention were compared. The analysis determined the incremental cost-effectiveness ratio in terms of cost per quality-adjusted life year and the difference between numbers of TB cases and of TB-related deaths. INH chemoprevention prevented 79% of expected TB cases in both age groups, and saved 9,482 and 9,142 in the lower and higher age groups, respectively, per case prevented. Quality-adjusted life expectancy was slightly extended by 8 days in the lower age group and 7 days in the higher age group, at a cost saving of 417 and 375, respectively, per person. Annual savings were 20,862 and 18,742 per 1,000 contacts, respectively. The number needed to be treated to prevent one TB case in the lower age group was 23 and 25 in the higher age group. The programme also prevented three TB-related deaths in the younger and two in the older cohort. The results are highly sensitive to treatment-cost assumptions. In conclusion, isoniazid chemoprevention in Germany is a highly cost-effective approach for reducing the burden of tuberculosis in recently converted young and middle-aged adults.

Predictive model to identify positive tuberculosis skin test results during contact investigations.

Budgetary constraints in tuberculosis (TB) control programs require streamlining contact investigations without sacrificing disease control. To develop more efficient methods of TB contact investigation by creating a model of TB transmission using variables that best predict a positive tuberculin skin test among contacts of an active TB case. After standardizing the interview and documentation process, data were collected on 292 consecutive TB cases and their 2941 contacts identified by the Alabama Department of Public Health between January and October 1998. Generalized estimating equations were used to create a model for predicting positive skin test results in contacts of active TB cases. The model was then validated using data from a prospective cohort of 366 new TB cases and their 3162 contacts identified between October 1998 and April 2000. Tuberculin skin test result. Using generalized estimating equations to build a predictive model, 7 variables were found to significantly predict a positive tuberculin skin test result among contacts of an active TB case. Further testing showed this model to have a sensitivity, specificity, and positive predictive value of approximately 89%, 36%, and 26%, respectively. The false-negative rate was less than 10%, and about 40% of the contact workload could be eliminated using this model. Certain characteristics can be used to predict contacts most likely to have a positive tuberculin skin test result. Use of such models can significantly reduce the number of contacts that public health officials need to investigate while still maintaining excellent disease control.

The Epidemiology of Tuberculosis in the U.S. Air Force, 1987

In preparation for a major revision of the Air Force tuberculosis (TB) prevention and control program, we reviewed tuberculosis cases treated at Air Force hospitals and the U.S. Air Force tuberculin skin testing program for 1987. The highest rates of active TB cases and infection were observed in the Pacific overseas region. Active tuberculosis cases occurred most frequently in white male retirees and in Asian dependent females. Nineteen cases (9% of total TB cases) occurred in children under the age of 5. Only 46-60% of individuals with a positive Purified Protein Derivative-Tuberculin were placed on isoniazid (INH) chemoprophylaxis. Flying status personnel were less likely to have either active disease or TB infection than non-flying active duty members. Based upon these findings, Air Force tuberculosis prevention and control program efforts should de-emphasize screening of low risk active duty populations and stress timely reporting and case finding, compliance with therapy, and initiation of INH chemoprophylaxis in accordance with existing guidelines. Young children who are contacts of active TB cases should receive special emphasis.