Recent Latent Tuberculosis Infection Research Articles

Comparison of QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-Tube tests for patients with active and latent tuberculosis: A prospective cohort study

IntroductionWe aimed to determine the diagnostic performance and clinical value of the QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold Plus (QFT-Plus) tests in patients with active tuberculosis (TB) or latent TB infection (LTBI). MethodsWe prospectively enrolled 140 patients, including 63 with active TB and 77 with LTBI, between March 2017 and October 2018. QFT-GIT and QFT-Plus were performed simultaneously in all subjects. ResultsQFT-Plus and QFT-GIT test results showed significant agreement, in both active TB and LTBI patients, in terms of the interferon-γ concentration and interpretation result. QFT-Plus had higher sensitivity than QFT-GIT for predicting active TB (82.5% vs. 77.8%) and showed fewer false-negative and indeterminate results in both active TB and LTBI patients due to its “TB2 tube”. The QFT-Plus TB2-TB1 value was higher in the active TB group than in the LTBI group. The QFT-Plus TB1-Nil and TB2-Nil values were useful in predicting remote LTBI, rather than recent LTBI. ConclusionsQFT-Plus showed good agreement with QFT-GIT in both active TB and LTBI patients, and higher sensitivity for predicting active TB than QFT-GIT. The QFT-Plus TB2 tube results, which reflect CD8+ T cell immunity, may improve predictive accuracy and detection of the immune response associated with active TB and LTBI.

A new mathematical model to identify contacts with recent and remote latent tuberculosis.

Tuberculosis (TB) elimination programmes need to target preventive treatment to groups with an increased risk of TB activation, such as individuals with a latent tuberculosis infection (LTBI) acquired recently. Current diagnostic tests for LTBI have poor predictive values for TB activation and there is, at present, no reference method to evaluate new LTBI diagnostic and prognostic tools. Thus, our objective was to develop a mathematical model, independent of currently available diagnostic tests, to estimate the individual probability of recent and/or remote LTBI.Estimations of recent LTBI were based on the contagiousness of index case, proximity and time of exposure, and environmental factors. Estimation of remote LTBI was based on country of origin, previous stays in high-risk environments or known exposure to TB. Individual probabilities were calculated and compared with tuberculin skin test (TST) and interferon-γ release assay results for 162 contacts of 42 index TB cases.Probabilities of remote LTBI were 16% for European/American contacts and 38% for African/Asian contacts. The probability of recent LTBI was 35% for close contacts to smear microscopy positive index cases. A higher probability of remote LTBI was seen among TST-positive contacts.This model may, with further validation, be used as an independent tool to evaluate new diagnostic markers for recent LTBI.

Serum antibody profiles in individuals with latent Mycobacterium tuberculosis infection.

One‐third of the world's humans has latent tuberculosis infection (LTBI), representing a large pool of potentially active TB. Recent LTBI carries a higher risk of disease progression than remote LTBI. Recent studies suggest important roles of antibodies in TB pathology, prompting us to investigate serum antibody profiles in a cohort with LTBI. In this single‐center prospective observational study, we analyzed IgG‐antibody concentrations against five major Mycobacterium tuberculosis (Mtb) antigens (including 6 kDa early secretory antigenic target (ESAT6), CFP10, and antigen 85A, which are expressed mainly in the growth phase; and mycobacterial DNA‐binding protein 1 (MDP1) and alpha‐crystallin like protein (Acr), which are expressed in the dormant phases) in individuals with recent (n=13) or remote (n=12) LTBI, no Mtb infection (n=19), or active TB (n=15). Antibody titers against ESAT6 and MDP1 were significantly higher in individuals with recent LTBI than in those with no Mtb infection or remote LTBI. All pairwise antibody titers against these five major antigens were significantly correlated throughout the stages of Mtb infection. Five individuals with recent LTBI had significantly higher antibody titers against ESAT6 (P = 0.03), Ag85A (P = 0.048), Acr (P = 0.057), and MDP1 (P = 0.0001) than in individuals with remote LTBI; they were also outside the normal range (+2 SDs). One of these individuals was diagnosed with active pulmonary TB at 18‐month follow‐up examination. These findings indicated that concentrations of antibodies against both multiplying and dormant Mtb are higher in recent LTBI and that individuals with markedly higher antibody titers may be appropriate candidates for prophylactic therapy.

Understanding the burden of tuberculosis among American Indians/Alaska Natives in the U.S.: a validation study.

We validated cases of active tuberculosis (TB) recorded in the Indian Health Service (IHS) National Patient Information Reporting System (NPIRS) and evaluated the completeness of TB case reporting from IHS facilities to state health departments. We reviewed the medical records of American Indian/Alaska Native (AI/AN) patients at IHS health facilities who were classified as having active TB using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes from 2006 to 2009 for clinical and laboratory evidence of TB disease. Individuals were reclassified as having active TB disease; recent latent TB infection (LTBI); past positive tuberculin skin test (TST) only; or as having no evidence of TB, LTBI, or a past positive TST. We compared validated active TB cases with corresponding state records to determine if they were reported. The study included 596 patients with active TB as per ICD-9-CM codes. Based on chart review, 111 (18.6%) had active TB; 156 (26.2%) had LTBI; 104 (17.4%) had a past positive TST; and 221 (37.1%) had no evidence of TB disease, LTBI, or a past positive TST. Of the 111 confirmed cases of active TB, 89 (80.2%) resided in participating states; 81 of 89 (91.2%) were verified as reported TB cases. ICD-9-CM codes for active TB disease in the IHS NPIRS do not accurately reflect the burden of TB among AI/ANs. Most confirmed active TB cases in the IHS health system were reported to the state; the national TB surveillance system may accurately represent the burden of TB in the AI/AN population.

Key Role of Effector Memory CD4+T Lymphocytes in a Short-Incubation Heparin-Binding Hemagglutinin Gamma Interferon Release Assay for the Detection of Latent Tuberculosis

The treatment of latent tuberculosis infection (LTBI) in target populations is one of the current WHO strategies for preventing active tuberculosis (TB) infection and reducing the Mycobacterium tuberculosis reservoir. Therefore, powerful LTBI screening tools are indispensable. A gamma interferon release assay (IGRA) in response to the stimulation of peripheral blood mononuclear cells by the latency antigen native heparin-binding hemagglutinin (nHBHA-IGRA) has proven its potential for this purpose. We have evaluated its possible optimization through a reduction of incubation time from 96 to 24 h, while compensating for this by adding interleukin 7 (IL-7) to the medium. We have also investigated the phenotypes of the gamma interferon (IFN-γ)-producing cells after both short and long incubation times. One hundred thirty-one nonimmunocompromised patients were recruited from 3 Brussels-based university hospitals. They were divided into 1 of 4 subgroups according to their M. tuberculosis infection status (LTBI, TB infection, undetermined M. tuberculosis infection status, and noninfected controls). The novel 24-h nHBHA-IGRA was performed for all subjects, and a simultaneous 96-h classical HBHA-IGRA was performed for 79 individuals. The results showed a good correlation between the two tests, and the novel 24-h nHBHA-IGRA maintained the principal advantages of the classical test, namely, a high specificity for LTBI diagnosis, an absence of interference of Mycobacterium bovis BCG vaccination during infancy, and a relative discrimination between LTBI and TB infection. Whereas the commercialized IGRAs show a greater sensitivity for recent than for remote M. tuberculosis infections, the 24-h nHBHA-IGRA appears to have comparable diagnostic powers for recent and remote LTBI. The IFN-γ detected by the 24-h nHBHA-IGRA was mainly secreted by effector memory CD4(+) T lymphocytes, a finding suggestive of continuous HBHA presentation during latency.

Tuberculosis in healthcare workers – a narrative review from a German perspective

IntroductionDespite the decline of tuberculosis in the population at large, healthcare workers (HCW) are still at risk of infection.MethodsIn a narrative review the TB risk in HCW and preventive measures are described, with the focus on epidemiology and Occupational Safety and Health (OSH) regulations in Germany.ResultsThere is an increased risk of infection not only in pneumology and laboratories with regular contact with tuberculosis patients or infectious materials. Epidemiological studies have also verified an increased risk of infection from activities that involve close contact with patients’ breath (e.g. bronchoscopy, intubation) or close contact with patients in need of care in geriatric medicine or geriatric nursing. In occupational disease claim proceedings on account of tuberculosis, the burden of proof can be eased for insured persons who work in these or other comparable fields. Forgoing evidence of an index person as a source of infection has led to a doubling of the rate of cases of tuberculosis recognised as an occupational disease and has halved the duration of occupational disease claim proceedings in Germany. For several years now, it has been possible to use the new interferon-y release assays (IGRAs) to diagnose a latent tuberculosis infection (LTBI) with significantly greater validity than with the traditional tuberculin skin test (TST). However, variability of the IGRAs around the cut-off poses problems especially in serial testing of HCWs. At around 10%, LTBI prevalence in German healthcare workers is lower than had been assumed. It can make sense to treat a recent LTBI in a young healthcare worker so as to prevent progression into active tuberculosis. If the LTBI is occupational in origin, the provider of statutory accident insurance can cover the costs of preventive treatment. However, little is known about disease progression in HCWs with positive IGRA sofar.ConclusionTB screening in HCWs will remain an important issue in the near future even in low incidence, high income countries, as active TB in HCWs is often due to workplace exposure. The IGRAs facilitate these screenings. However, variability of IGRA results in serial testing of HCWs need further investigations.

Latent Tuberculosis in Healthcare Workers: Time to Act

Latent Tuberculosis in Healthcare Workers: Time to Act

Lower prevalence of tuberculosis infection in BCG vaccinees: a cross-sectional study in adult prison inmates

ObjectivesTo address whether the effect of BCG vaccination against tuberculosis (TB) infection lasts to adulthood.MethodsA cross-sectional study on the prevalence of latent TB infection (LTBI) among HIV-negative men, using QuantiFERON-TB...

Evaluation of Interferon-Gamma Release Assays in the Diagnosis of Recent Tuberculosis Infection in Health Care Workers

BackgroundHealth care workers (HCWs) are a group at risk of latent tuberculosis infection (LTBI). The aims of this study were to determine IFN-γ response by QuantiFERON-TB GOLD In Tube (QFN-G-IT) and T-SPOT.TB in HCWs, comparing the results with tuberculin skin test (TST); and to analyze the capacity of IFN-γ tests to detect recent versus remote LTBI with a prolonged stimulation test (PST).Methodology/Principal FindingsA total of 147 HCWs were enrolled; 23 of whom were BCG vaccinated. 95 HCWs (64.6%) had a previous positive TST and were not retested; and 52 HCWs had a previous negative TST or were tested for the first time. When we analysed individuals without previous positive TST, the number of positive results for T-SPOT.TB was 12/52 (23.1%); and for QFN-G-IT, 9/52 (17.3%). The global concordance (κ) between T-SPOT.TB and QFN-G-IT with TST was 0.754 and 0.929 respectively. Of individuals with previous positive TST, T-SPOT.TB and QFN-G-IT were negative in 51.6% (49/95) and 62.1% (59/95) respectively, decreasing the concordance to 0.321 and 0.288, respectively. In non-BCG vaccinated HCWs with previous positive TST a positive IFN-γ test was associated with degree of exposure and diameter of TST. PST was performed in 24 HCW with previous positive TST and negative IFN-γ tests. PST was developed in 3 cell cultures stimulated with medium alone, ESAT-6 and CFP-10, respectively. In the third and sixth day of incubation period, part of the supernatants were replaced with complete medium supplemented with (rIL)-2. On day 9, ELISPOT assay was performed. In 14 samples PST was not valid due to not having enough cells. In 8 cases, the response was negative, and in 2 cases positive, suggesting that these patients were infected with Mycobacterium tuberculosis in some point in the past.ConclusionsBoth IFN-γ tests showed a similar number of positive results, and concordance between the tests was excellent. None of the tests was affected by prior BCG vaccination. IFN-γ tests are a useful tool for detecting recent infection in HCW population.

Les nouveaux tests immunologiques dans le diagnostic de la tuberculose (TB or not TB)

Targeted testing and treatment of individuals with latent tuberculosis infection (LTBI), at high risk of progression to active tuberculosis (ATB), are key elements in the battle against tuberculosis, both in France and in many parts of the world. Though the finding of tubercle bacilli is the essential examination for the diagnosis of ATB, there is no indisputable test for LTBI. The help currently given to the diagnosis of LTBI by the degree of positivity of the tuberculin skin test (TST) is limited, both operationally and logistically, in populations vaccinated with BCG or sensitised by atypical mycobacteria, and by its low sensitivity in those immuno-suppressed persons who are at greatest risk of progression. Moreover the TST has other operational limitations linked to return visits, repeat testing causing a boosting effect and subjective interpretation. A new approach follows the availability of two biological tests for the diagnosis of LTBI (QuantiFERON-TB and T-SPOT-TB) that measure the in-vitro production of interferon gamma (IFN-gamma) by the blood mononuclear cells in response to M. tuberculosis specific antigens (ESAT-6 and CFP10). This revue analyses the published studies, undertaken with varying numbers of patients, that evaluate the diagnostic accuracy of these two tests in comparison with TST. However, validation is handicapped by the lack of a "gold standard" for the diagnosis of LTBI. These studies demonstrate similar levels of specificity for the two biological tests. They are statistically higher than those for TST, particularly in populations vaccinated by BCG. On the other hand, their sensitivity was at least equivalent to that of TST and, in certain studies, superior with T-SPOT-TB. Finally, several studies in contacts have been undertaken with the aim of measuring the concordance between these biological tests and TST. The essential finding is of a very good correlation between positivity of the biological tests and the degree of exposure of the contacts. These tests have additional operational advantages over TST: completed in one visit, results available in 24 hours, absence of inter and intra observer divergence, detection of potential immuno-depression and avoidance of boosting by repeat testing. Currently, however, these biological tests present several operational limits: lower sensitivity in severe disease, incomplete data in immuno-suppressed subjects and in children, lack of predictive value for future development of ATB, lack of distinction between LTBI and ATB. Numerous clinical studies are under way, in France and elsewhere, in order to reduce these limitations and to allow the appropriate incorporation of these tests into protocols for the diagnosis of tuberculosis. These two biological tests should, in the near future, replace or complement TST in the diagnosis of recent LTBI, leading to their optimal incorporation into the decision making processes of the national plans for the control of tuberculosis.

Adrenal‐to‐caudate transplantation

Tuberculosis (TB) elimination programmes need to target preventive treatment to groups with an increased risk of TB activation, such as individuals with a latent tuberculosis infection (LTBI) acquired recently. Current diagnostic tests for LTBI have poor predictive values for TB activation and there is, at present, no reference method to evaluate new LTBI diagnostic and prognostic tools. Thus, our objective was to develop a mathematical model, independent of currently available diagnostic tests, to estimate the individual probability of recent and/or remote LTBI. Estimations of recent LTBI were based on the contagiousness of index case, proximity and time of exposure, and environmental factors. Estimation of remote LTBI was based on country of origin, previous stays in high-risk environments or known exposure to TB. Individual probabilities were calculated and compared with tuberculin skin test (TST) and interferon-γ release assay results for 162 contacts of 42 index TB cases. Probabilities of remote LTBI were 16% for European/American contacts and 38% for African/Asian contacts. The probability of recent LTBI was 35% for close contacts to smear microscopy positive index cases. A higher probability of remote LTBI was seen among TST-positive contacts. This model may, with further validation, be used as an independent tool to evaluate new diagnostic markers for recent LTBI.