Trends in diagnostic methods and treatment of latent tuberculosis infection in a tertiary care center from 2000 to 2017.

Screening for latent tuberculosis infection (LTBI) is indicated before immunosuppressive therapies but is complicated by lack of a gold standard and limited by, e.g., immunosuppression. This study aimed to investigate a series of patients diagnosed with LTBI during screening before immunosuppressive therapy, describing how the use of diagnostic tests and treatment evolved over time. This retrospective cohort study included all individuals diagnosed with LTBI during screening before intended immunosuppressive therapy in a tertiary care hospital between January 2000 and December 2017. Evidence for LTBI, including history, tuberculin skin test (TST), QuantiFERON (QFT) result and suggestive lesions on chest radiography (CXR), and CT scan if available, was analyzed. The study included 295 individuals with LTBI, with median follow-up of 3.8 years (IQR 1.7-7.4 years). During screening, TST, QFT, and CXR were positive in 80.8%, 53.4%, and 22.7%, respectively. Chest CT revealed lesions associated with past tuberculosis infection in around 70%, significantly more frequent than CXR. In patients diagnosed with LTBI, we observed that the use of TST declined over time whereas the use of QFT increased, and that isoniazid was replaced with rifampicin as preferential treatment. Preventive treatment was started in 82.3%, of whom 88.6% completed treatment. During follow-up, no individuals developed active tuberculosis. The diagnosis of LTBI was based on history, TST, QFT, and/or CXR in nearly every possible combination, but mostly on TST and QFT. The most striking trends were the decreased use of TST, increased use of QFT, and the replacement of isoniazid with rifampicin for treatment.

Evaluating a 24-year tuberculosis screening in first-grade elementary schoolers in a low-burden area.

AIM: Early diagnosis of tuberculosis infection can significantly contribute to the control of the disease. The aim of the present study was to describe the tuberculin skin test (TST) trends over a 24-year period (1990-2013) and explore the value of universal tuberculosis screening in a low-burden area. METHODS: All first graders that underwent TST during the 24-year study period (1990-2013) on the island of Crete, Greece, were retrospectively included in the study. RESULTS: A total of 82 402 children (92.3% of Greek nationality; 51.0% male) underwent TST, of whom 335 (0.41%, 95% CI 0.37-0.46) were found to have positive TST while 0.27% of the study population had a TST between 5 and 9 mm. The tuberculin index declined significantly between 1990-1994 and 2010-2013 (0.67 vs 0.26; RR 2.73, 95% CI 1.82-4.09; p < 0.0001). Positive TST result was significantly higher in the immigrant than the native group (0.66% vs 0.24%; RR 3.76 95%, CI 2.89-4.84; p < 0.0001). In the last study years, 386 children (488 native; 153 immigrant) should be tested for one to be found TST positive. CONCLUSION: Our findings question the massive tuberculin testing in low-burden areas and point to selective screening of high-risk groups.

Survey of rheumatologists on the use of the Philippine Guidelines on the Screening for Tuberculosis prior to use of Biologic Agents.

BACKGROUND: The use of biologic agents has become an important option in treating patients with rheumatoid arthritis. However, these drugs have been associated with an increased risk of tuberculosis (TB) reactivation. Local guidelines for TB screening prior to the use of biologic agents were developed to address this issue. AIM: This study is a survey describing the compliance of Filipino rheumatologists to these guidelines. METHOD: Eighty-seven rheumatologists in the Philippines were given the questionnaire and responses from 61 rheumatologists were included in the analysis. RESULTS: All respondents agree that patients should be screened prior to giving the biologic agents. Local guidelines recommend screening with tuberculin skin test (TST) and chest radiograph. However, cut-off values considered for a positive TST and timing of initiation of biologic agents after starting TB prophylaxis and treatment varied among respondents. In addition, screening of close household contacts were only performed by 41 (69.5%) respondents. There were 11 respondents who reported 16 patients developing TB during or after receiving biologic agents, despite adherence to the guidelines. CONCLUSION: This survey describes the compliance rate of Filipino rheumatologists in applying current local recommendations for TB screening prior to initiating biologic agents. The incidence of new TB cases despite the current guidelines emphasizes the importance of compliance and the need to revise the guidelines based on updated existing literature.

Recomendaciones de vacunación con bacilo de Calmette-Guérin en niños con infección tuberculosa latente / Recommendations for bacillus Calmette-Guérin vaccination in children with latent tuberculosis infection

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Advances in diagnosis and treatment of latent tuberculosis infection.

In the United States, latent tuberculosis infection (LTBI) affects between 10 and 15 million people, of whom 10% may develop active tuberculosis disease. People at increased risk for tuberculosis reactivation include recent immigrants from countries with a high incidence of tuberculosis, children younger than age 5, people who have been infected with Mycobacterium tuberculosis within the past 2 years, or people with immunosuppression for a variety of reasons. Appropriate diagnosis and treatment of LTBI are critical for controlling and eventually eliminating tuberculosis as a public health problem. Although the tuberculin skin test is the traditional diagnostic measure for LTBI, reduced specificity has promoted the development and utilization of the interferon-γ release assays as an in vitro blood test with specific antigens to M. tuberculosis (QuantiFERON-TB Gold In-Tube test and the T.SPOT-TB test are commercially available). Despite the rise of the new diagnostic tests, however, there is still no gold standard for diagnosing LTBI, and epidemiologic risks and comorbidities need to be taken into account before initiating therapy. Current diagnostic tests combined with recommended treatment regimens are valuable tools that, when used correctly, promise to hurry the elimination of tuberculosis.

Purified protein derivatives of tuberculin--past, present, and future.

The tuberculin skin test, which involves monitoring the immune reaction to an injection of purified protein derivative (PPD), has been the most widely used method for detecting infection with Mycobacterium tuberculosis since its development in 1930s. Until recently, the molecular composition of PPD was unknown. This thwarted the discovery of improved skin testing reagents and drastically hindered efforts to define the mechanism of action. Proteomic evaluation of PPD combined with a detailed analysis in the guinea pig model of tuberculosis led to further definition of the molecular composition of PPD. This communication reviews the history and current status of PPD, in addition to describing candidate next-generation PPD reagents, based on the use of an individual protein or protein cocktails.

Cribado tuberculínico: prevención de la tuberculosis / Tuberculin screening: tuberculosis prevention

El cribado tuberculínico se utiliza para identificar, evaluar y poder tratar a las personas que tienen mayor riesgo de padecer una infección tuberculosa latente o de desarrollar la enfermedad tuberculosa una vez infectados por el M. tuberculosis. Se revisan los criterios, las indicaciones y la metodología del cribado tuberculínico para la detección de la infección tuberculosa y otras medidas disponibles en Atención Primaria para la prevención de la tuberculosis en la infancia y adolescencia, incluyendo el estudio de contactos de personas con infección tuberculosa y el tratamiento de la exposición a la tuberculosis y de la tuberculosis latente(AU)

Tuberculin skin testing is used to identify, evaluate, and treat people who are at higher risk for latent tuberculosis infection or for developing tuberculosis disease after the infection by M. tuberculosis. We review the criteria, indications and methodology of tuberculin skin testing for the detection of tuberculosis infection and other measures available in primary care for the prevention of tuberculosis in childhood and adolescence, including the study of contacts of people with tuberculosis infection and the treatment of exposure to tuberculosis and of latent tuberculosis infection(AU)

Interferon-γ release assays for diagnosis of latent tuberculosis infection: evidence in immune-mediated inflammatory disorders.

PURPOSE OF REVIEW: To provide a narrative synthesis of evidence on interferon-gamma release assays (IGRAs) for the diagnosis of latent tuberculosis infection (LTBI) in individuals with immune-mediated inflammatory disorders (IMIDs). RECENT FINDINGS: Only a few studies have evaluated IGRAs in IMIDs, and most were small and varied considerably with respect to the use of immunosuppressive medications and types of IMIDs. Current evidence does not clearly suggest that IGRAs are better than tuberculin skin test (TST) in identifying individuals with IMID who could benefit from LTBI treatment. To date, no studies have been done on the predictive value of IGRAs in IMID patients. Important questions remain unanswered as to the impact of immunosuppressive medications and the impact of type of IMID on IGRA performance. SUMMARY: Despite the lack of clear evidence, there is an increasing tendency for guidelines to prefer IGRA over TST in IMIDs or to recommend both TST and IGRA to enhance sensitivity. We believe the use of either test is acceptable for LTBI screening. Clinicians could consider starting with IGRAs in individuals with a history of Bacille Calmette-Guérin (BCG) vaccination after infancy or with repeated BCG vaccinations. When the index of suspicion for LTBI is high, both IGRA and TST could be performed, especially prior to initiating TNF-α inhibitor therapy. Regardless of the test used, it is important to remember that in the face of immune-suppression, both IGRA and TST can be falsely negative and are thus only diagnostic aids - they will need to be interpreted with other clinical and risk factor data.

Concordancia de las pruebas de tuberculina e Interferón gamma en población reclusa / Concordance of tuberculin test and Interferon gamma release assays in the prison population

Objetivo: Estudiar en población penitenciaria la concordancia de la prueba de la tuberculina (PT) y las pruebas de interferón gamma (IFG). Material y Métodos: Estudio prospectivo realizado en una prisión en mayo-junio de 2009. Se estudian los ingresos sin antecedente de tuberculosis (TB) o con PT previa negativa o no realizada. Se realizó IDR de Mantoux (positivo ³ 10 mm) y extracción sanguínea para prueba de IFG (QuantiFERON®-TB Gold). En los infectados, se realizó despistaje de TB. Se pasó un cuestionario y se solicitó consentimiento informado. El estudio fue aprobado por un Comité Ético ajeno a instituciones penitenciarias. La concordancia entre PT e IFG se basó en el índice Kappa. Resultados: Se incluyeron 181 casos. El 62% eran extranjeros, el 17% vacunados por BCG, el 8,4% UDI y el 4% VIH+. En los extranjeros había más vacunados, menos UDI y menos infectados por VIH que en autóctonos (p=0,02, p=0,02, y p=0,01, respectivamente). La PT fue positiva en el 24% y la IFG en el 26%. Hubo información de ambas en 149 (82%) casos. El 15,8% fueron discordantes. El índice Kappa fue de 0,6 (0,4-0,7). La concordancia varió según subgrupos, siendo mayor en autóctonos (kappa= 0,8) y menor en vacunados (kappa=0,4) e inmigrantes (kappa=0,5). Conclusión: La concordancia global fue moderada-buena, pero en vacunados e inmigrantes fue menor. El nivel de discordancia aconseja ampliar el estudio, así como evaluar que prueba predice mejor el riesgo de progresión a TB y el coste-beneficio de ambas en la población reclusa de nuestro país(AU)

Objective: To study the agreement of Tuberculin Skin Tests (TST) and Interferon Gamma Release Assays (IGRA) when screening tuberculosis infection amongst inmates recently admitted to prison. Materials and Methods: Prospective study conducted in a prison during the months of May and June 2009. Inmates without a TB history, with previous TST negatives or without prior TSTs were included. Participants signed an informed consent form and the study was approved by an independent Ethical Committee. TST (positive 10 >= mm) and IGRA (Quantiferon TB-Gold) were performed and standardized data collection was carried out. The agreement between both tests was analysed using the Kappa index. Results: A total of 181 people were included. 62% were foreign-born, 17% had previous BCG vaccination, 8.4% were IDUs and 4% HIV-infected. Foreign born subjects were more frequently vaccinated and presented less drug use and HIV infection than people born in Spain. (p=0.02, p=0.02 and p=0.01 respectively). TST results were positive in 24% and IGRA in 26%. Both tests were performed in 149 people (82%). Discordant results were observed in 15.8%. Agreement of the Kappa coefficient was 0.6 (CI 0.4-0.7). Agreement was better in the native population (K=0.8) and worse in BCG vaccinated (K=0.4) and foreign-born subjects (K=0.8) Conclusion: Overall agreement was moderate and was less amongst vaccinated subjects and those born abroad. Extension of the study could be useful to evaluate which test better predicts the risk of progression to active TB and the cost-benefit of both tests among the prison population(AU)

Recent advances in testing for latent TB.

After more than a century of relying on skin testing for the diagnosis of latent TB infection, clinicians now have access to blood-based diagnostics in the form of interferon γ release assays (IGRAs). These tests are generally associated with higher sensitivity and specificity for diagnosis of latent TB infection. This article reviews the indications for testing and treatment of latent TB infection in the overall context of a TB control program and describes how IGRAs might be used in specific clinical settings and populations, including people having close contact with an active case of TB, the foreign born, and health-care workers.

Assessment of latent tuberculosis infection in Takayasu arteritis with tuberculin skin test and Quantiferon-TB Gold test.

A possible relationship between Takayasu arteritis (TA) and tuberculosis (TB) has been suggested. An increased frequency of tuberculin skin test (TST) was observed in TA patients. Quantiferon-TB Gold test (QFT) is a new in vitro assay measuring interferon-gamma response to M. tuberculosis antigens and helpful in diagnosing latent TB infection. The aim of this study was to investigate latent TB infection among TA patients by the use of both TST and QFT Gold test. Ninety-four (male/female: 7/87) TA patients fulfilling ACR 1990 TA criteria from three different university hospitals in Turkey and 107 control subjects without inflammatory diseases were included in the study. Data about medical history (TA and TB) were collected for both groups. TST and QFT were performed. TST values > or =5 mm for TA patients and > or =15 mm for controls was accepted as TST positivity. Even though TA group was older (40 +/- 12 vs. 32 +/- 8, P < 0.001), there was no significant difference between TA patients and controls regarding demographic characteristics. Six TA patients and one control had a history of previous TB infection (P = 0.054). Although TST positivity was higher in TA group [55 patients (62.5%) vs. 24 controls (41.4%), P = 0.008], QFT positivity was similar between two groups [21 patients (22.3%) vs. 24 controls (22.4%), P > 0.05]. QFT was negative in two of six TA patients with previous TB history. Rate of latent TB infection in TA patients measured with QFT is no more than controls. QFT seems to be a good and favorable test compared with TST in detecting LTBI in TA.

Advances in the diagnosis of tuberculosis.

Tuberculosis ranges among the leading causes of morbidity and mortality worldwide. A diagnostic approach to a patient with possible tuberculosis includes a detailed medical history and clinical examination as well as radiological, microbiological, immunological, molecular-biological and histological investigations, where available. Recently, important advances have been achieved in these fields that have led to substantial improvements in the accuracy and the timing of the diagnosis of tuberculosis. Novel methods allow for a better identification of latently infected individuals who are at risk of developing active tuberculosis, they also offer the possibility for a rapid diagnosis of active tuberculosis in patients with negative sputum smears for acid-fast bacilli and enable prompt identification of drug-resistant strains of Mycobacterium tuberculosis directly from respiratory specimen with a high accuracy. In addition, promising methods that will further optimize the diagnosis of tuberculosis are under development. In the future, therapeutic interventions based on the results of novel diagnostic procedures can be made earlier leading to improvements in patient care.

Estudio multicéntrico de prevalencia de infección tuberculosa latente en los internados en prisiones españolas / Multi-centre study of the prevalence of latent tuberculosis infection amongst inmates in spanish prisons

Objetivo: Estudiar la prevalencia de infección tuberculosa latente (ITL) entre los presos internados en las prisiones españolas. Material y Método: Estudio multicéntrico, observacional y transversal; muestreo por conglomerado bietápico. Se recogieron variables sociodemográficas, penitenciarias y clínico-serológicas. Se realizó análisis univariante, bivariante y multivariante mediante regresión logística con las variables que mostraron significación estadística. Se calculó la odds ratio con intervalo de confianza del 95%. Resultados: 378 pacientes. Se dispuso de intradermorreacción de Mantoux (IDRM) valorable en el 90,2%. 91,2% hombres, 37,8% extranjeros con edad media de 35,9±10,3 años. Mediana de estancia en prisión: 2 años y el 28,7% había estado > 5 años en prisión. El 49,6% ingresó en prisión en 2006 o antes. El 24,5% tenía antecedentes de uso de drogas intravenosas (UDI). El 50,4% presentaba ITL que se asoció a: edad > 40 años (63,2 vs 43,8%; IC: 1,39-3,49; OR: 2,20; p=0,001); haber estado > 5 años en prisión (71,2 vs 41,3%; IC: 2,13-5,75; OR: 3,50; p<0,001); estar en prisión desde 2006 o antes (58,1 vs 42,6%; IC: 1,22-2,88; OR:1,87; p=0,004); estar infectado por el VHC+ (66,3 vs 45,3%; IC:1,40-4,0; OR: 2,37; p=0,001). El modelo de regresión logística confirmó la asociación independiente de la ITL con: a) edad > 40 años (OR:1,76; IC: 1,08-2,87; p=0,024); y b) estancia > 5 años en prisión (OR: 2,50; IC: 1,41-4,43; p=0,002). Conclusiones: La prevalencia de ITL en prisión es muy alta, sobre todo en los mayores de 40 años y los que están más de cinco años en prisión. Para evitar el riesgo de progresión a tuberculosis, se recomienda tratar a los infectados que lo precisen y mantener los programas de control de esta patología(AU)

Aims: To study the prevalence of latent tuberculosis infection (LTBI) amongst inmates in Spanish prisons. Materials and Methods: Multi-centre, cross-sectional study; two stage sampling. Socio-demographic, prison and clinical variables were gathered. A univariate, bivariate and multivariate analysis was carried out using logistic regression with the variables that showed statistical significance. The odds ratio was calculated with a confidence interval of 95%. Results: 378 patients. The Mantoux test (PPD) assessable in 90.2% was available. 91.2% men, 37.8% foreigners with average age of 35.9±10.3 years. Average stay in prison: 2 years, 28.7% had been > 5 years in prison. 49.6% entered prison in 2006 or before. 24.5% had a history of intravenous drug use (IDU). 50.4% presented LTBI that was associated with: age > 40 years (63.2 vs 43.8%; CI: 1.39-3.49; OR: 2.20; p=0.001); stay of > 5 years in prison (71.2 vs 41.3%; CI: 2.13-5.75; OR: 3.50; p<0.001); in prison since 2006 or before (58.1 vs 42.6%; CI: 1.22- 2.88; OR:1.87; p=0.004); infected with HCV+ (66.3 vs 45.3%; CI:1.40-4.0; OR: 2.37; p=0.001). The logistic regression model confirmed the independent association of LTBI with: a) age > 40 years (OR: 1.76; CI: 1.08-2.87; p=0.024); and length of prison stay > 5 years (OR: 2.50; CI: 1.41-4.43; p=0.002). Conclusions: The prevalence of LTBI in prison is very high, especially amongst inmates over 40 and those who have been in prison for more than five years. To prevent the risk of progression to tuberculosis, treatment is recommended for those who require it along with the maintenance of control programmes for this pathology(AU)

Prueba de la tuberculina y riesgo de tuberculosis. No sólo el tamaño es importante / The tuberculin skin test and risk of tuberculosis: size is not the only issue

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Diagnosis of latent Mycobacterium tuberculosis infection: is the demise of the Mantoux test imminent?

Tuberculosis is responsible for more then 2 million deaths worldwide each year and vies with HIV as the world's most fatal infectious disease. In many developing countries, attempts to control the spread of infection rely solely on identification and treatment of those with active disease, ignoring subclinical infection. However, in developed countries, large efforts are also expended to identify and give prophylactic drugs to people with latent tuberculosis infection. Until recently, the 100-year-old tuberculin skin test (Mantoux) has been the only available diagnostic test for latent tuberculosis infection, despite its many well-known limitations. Advances in scientific knowledge have led to the development of tests for tuberculosis that measure the production of interferon-gamma by T-cells stimulated in vitro with Mycobacterium tuberculosis-specific antigens. These interferon-gamma tests are highly specific and unaffected by prior Bacille Calmette-Guérin vaccination or immune reactivity to most atypical mycobacteria. They are more sensitive than the tuberculin skin test in detecting people with active tuberculosis, and their results correlate more closely with M. tuberculosis exposure risk factors than the tuberculin skin test in people likely to have latent tuberculosis infection. Science has caught up with one of the oldest diagnostic tests still in use worldwide, and the adoption of new, tuberculosis-specific interferon-gamma-based tests should move us one step closer to better control of this insidious pathogen.

Tuberculin skin testing among economically disadvantaged youth in a federally funded job training program.

Low income, medically underserved communities are at increased risk for tuberculosis. Limited population-based national data are available about tuberculous infection in young people from such backgrounds. To determine the prevalence of a positive tuberculin skin test among economically disadvantaged youth in a federally funded job training program during 1995 and 1996, the authors evaluated data from medical records of 22,565 randomly selected students from over 100 job training centers throughout the United States. An estimated 5.6% of students had a documented positive skin test or history of active tuberculosis. Rates were highest among those who were racial/ethnic minorities, foreign born, and (among foreign-born students) older in age (p < 0.001). Weighted rates (adjusting for sampling) were 1.3% for white, 2.2% for Native American, 4.0% for black, 9.6% for Hispanic, and 40.7% for Asian/Pacific Islander students; rates were 2.4% for US-born and 32.7% for foreign-born students. Differences by geographic region of residence were not significant after adjusting for other demographic factors. Tuberculin screening of socioeconomically disadvantaged youth such as evaluated in this study provides important sentinel surveillance data concerning groups at risk for tuberculous infection and allows recommended public health interventions to be offered.