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.

Aplicación y utilidad actual de las técnicas de interferón-g en el diagnóstico de la tuberculosis / Up-to-date applicability of interferon-g release assays for the diagnosis of tuberculosis

La utilización de las técnicas de inmunodiagnóstico in vitro basadas en la liberación de interferón-g tras la estimulación con antígenos específicos de Mycobacterium tuberculosis (IGRA) ha supuesto una mejora en la precisión del diagnóstico de la infección tuberculosa. Los IGRA tienen una reconocida mayor especificidad que la prueba de la tuberculina, y en pacientes inmunodeprimidos pueden presentar un mayor número de resultados positivos. Los IGRA presentan una mayor correlación con la exposición a M. tuberculosis que la prueba de la tuberculina; no obstante, sus valores predictivos positivo y negativo son similares. Sin embargo, dada su mayor especificidad permiten reducir el número de tratamientos preventivos innecesarios. Además, estas técnicas in vitro se ven menos afectadas que la prueba de la tuberculina por los diferentes estados de inmunodepresión. En esta revisión se discute la utilidad y aplicabilidad de los IGRA en diferentes grupos de pacientes: estudios de contactos, población pediátrica, inmunodeprimidos, trabajadores sanitarios y pacientes con tuberculosis activa. Además se incluyen nuevas perspectivas tecnológicas en el diagnóstico de la infección tuberculosa y de la tuberculosis activa

Utility of the in-vitro immunodiagnostic methods, based on the detection of interferon-g released by T-cells after specific Mycobacterium tuberculosis antigen stimulation (IGRA), has been an improvement in the accuracy of the latent tuberculosis infection diagnosis. IGRA have a well-known higher specificity than the tuberculin skin testing (TST). Moreover, they can obtain a larger number of positive results than the TST in immunocompromised patients. IGRA have shown a high correlation with M. tuberculosis exposure, but their positive and negative predictive value are similar than those obtained by TST. Nevertheless, given their high specificity, they allow reducing number of unnecessary preventive treatments. In addition, these in-vitro techniques are less affected than TST by the different immunosuppressing status. In this review is discussed up-to-date applicability of IGRA in different patient groups: contact studies, pediatric population, immunosuppressed patients, health care workers and active tuberculosis patients. Furthermore, it has been included possible future directions for latent tuberculosis infection and active tuberculosis diagnosis

[FACTORS ASSOCIATED WITH CHANGES IN THE NUMBER OF LATENT TUBERCULOSIS INFECTION NOTIFICATIONS IN JAPAN: NATIONWIDE SURVEY FINDINGS].

PURPOSE: To investigate factors contributing to the drastic increase and subsequent decrease in latent tuberculosis infection (LTBI) notifications in 2011 (n = 10,046) and 2012 (n = 8,771), respectively, in Japan. METHODS: We conducted cross-sectional surveys in all 495 health centers in Japan in 2012 and 2013 using a semi-structured questionnaire that contained questions regarding the number of contacts listed for contact investigation, interferon-gamma release assay (IGRA) results, and incident of possible false positive IGRA results. RESULTS: Both the numbers and proportion of patients investigated using IGRA tended to increase from 2009 to 2012. However, the numbers and proportion of IGRA-positive patients, as well as that of those with borderline IGRA results, increased in 2011 and have decreased since 2012. In the 2012 survey, only 34 health centers (8%) reported questionable IGRA results. DISCUSSION: The removal of the age limit for LTBI treatment in 2010 may have contributed to the increase in the number of LTBI notifications in 2011, as the increase was particularly remarkable in the elderly age group. The increase in the proportion of positive and borderline IGRA results was likely partly due to expanded IGRA coverage that included more medical staff and the older population, which have a relatively high prevalence of tuberculosis infection, as well as a change from second-generation to third-generation QuantiFERON (QFT®) IGRA that offered increased sensitivity. The decrease in the number of outbreak incident cases and infectious patients may have contributed to the decrease in the number of LTBI notifications in 2012. CONCLUSION: Factors such as the increase in the number of patients undergoing IGRA, increase in the number of positive or borderline results due to QFT changes, and decrease in the number of tuberculosis outbreak incidents and infectious patients likely contributed to the increase and decrease in the number of LTBI notifications in 2011 and 2012, respectively.

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.

Interferon-gamma release assays for tuberculosis: current and future applications.

Interferon-gamma release assays (IGRAs) represent the first new tool to diagnose latent tuberculosis infection for more than 100 years. They have advantages over the traditional tuberculin skin test which has a poor specificity due to false-positive responses in people who are BCG vaccinated as there is a cross-reactivity of proteins present in both BCG and the tuberculin skin test. IGRAs rely on the concept of detecting the ex vivo release of the cytokine IFN-γ, a key anti-Mycobacterium tuberculosis cytokine, from T cells which react specifically to antigens from M. tuberculosis. T cells are sensitized to the antigens in vivo, and then react when they encounter the same proteins ex vivo. The readouts are used to determine presence of sensitized cells, acting as a surrogate for latent tuberculosis infection. IGRAs are now being incorporated into national guidance for diagnosis and research is ongoing into next-generation versions of the test.