Latent tuberculosis and COVID-19 disease

Since the start of the COVID-19 pandemic in 2020, there has been chaos in the world. With the COVID-19 cases rising, many other medical diseases have been ignored and not prioritized. One of these crucial diseases is Tuberculosis (TB). TB is a highly infectious bacterial respiratory disease. Every year there are millions of cases that are registered all around the world. TB is seen in two forms, an active and a latent form. In both of the states, the individual with TB is immunocompromised. This is of great importance, as COVID-19 is known to readily infect individuals in an immunocompromised state more than those with a healthy immune system. Although a little investigation about coexisting infections with COVID-19 and TB is conducted, it is important to consider many factors that can be beneficial to help treat these patients with both conditions effectively and promptly. A few of these factors are pathophysiological relation, diagnostic measurements, effects of each condition on the other, and approaches to treatment. Through a literature review of available information, we summarized the knowledge regarding the correlation between Latent TB infection and COVID-19 infection. The main objective of this publication is to provide a brief overview of how the two conditions overlap with one another. The article also provides a clinical review of how to approach these two conditions in a scenario where an individual is found to be infected with both Latent TB and COVID-19.

ImmunoStart: preparing patients for immunosuppression

Objectives Patients with immune-mediated inflammatory disease (IMID) present an increased risk of infection. Here, we present the concept of a preventive consultation called ImmunoStart and the first results of its implementation in the care pathway of patients with IMID. Methods Relevant information about vaccination history, TB exposition and other infectious risks are collected through blood sampling, complete anamnesis, chest X-Ray and Mantoux test. During ImmunoStart consultation, vaccination schedules, specific treatments and risk considerations are discussed. Results Between October 2016 and February 2020, 437 patients were seen at the ImmunoStart consultation, mainly referred by rheumatologists (56%), dermatologists (25%), and gastroenterologists (18%). A total of 421 (96%) patients needed at least one vaccine (a mean of 3.3 vaccines per patient). Live attenuated vaccine was indicated for 45 patients (10%), requiring them to reduce or interrupt their immunosuppressive drug(s). Ninety-two patients (21%) were treated for latent TB infection. Conclusion This preventive consultation provides a centralized and systematic setting for the direct management of patients with IMID in need of vaccination, treatment of latent disease and specific advice regarding their immunomodulating treatments.

Latent tuberculosis screening and treatment in HIV: highly acceptable in a prospective cohort study

BackgroundPeople living with HIV (PLWH) are at increased risk of reactivation of latent TB infection (LTBI). Although UK and international guidelines identify this group as a priority for LTBI screening and treatment, data on attitudes of PLWH to this policy recommendation are lacking.MethodsA five-point, Likert-style questionnaire was administered to PLWH to assess views and intentions towards accepting LTBI screening and treatment. Subsequent Immune Gamma Release Assay (IGRA) testing was offered, and chemoprophylaxis if required. Influencing demographic and psychological associations with planned, and actual, testing and treatment uptake, were assessed using multivariable logistic regression.Results444/716 (62%) patients responded. 417/437 (95.4%) expressed intention to accept LTBI testing. The only significant association was the perceived importance of testing to the individual (aOR 8.98, 95% CI 2.55–31.67). 390/393 (99·2%) accepted appropriate IGRA screening; 41/390 (10·5%) were positive. 397/431 (92.1%) expressed intention to accept chemoprophylaxis, associated with perceived importance of treatment (aOR 3.52, 95% CI 1.46–8.51), a desire to have treatment for LTBI (aOR 1.77, 95% CI 0.99–3.15), and confidence in taking treatment (aOR 3.77, 95% CI 1.84–7.72). Of those offered chemoprophylaxis, 36/37 (97·3%) accepted and 34/36 (94·4%) completed treatment. There were no correlates with actual screening acceptance.ConclusionsLTBI is common amongst PLWH, highlighting the importance of robust screening and treatment programmes. This study shows that screening and treatment for LTBI is highly acceptable to PLWH and provides strong, objective, evidence for policy-makers developing guidelines in this cohort.

Combination of HLA-DR on Mycobacterium tuberculosis-Specific Cells and Tuberculosis Antigen/Phytohemagglutinin Ratio for Discriminating Active Tuberculosis From Latent Tuberculosis Infection

BackgroundNovel approaches for tuberculosis (TB) diagnosis, especially for distinguishing active TB (ATB) from latent TB infection (LTBI), are urgently warranted. The present study aims to determine whether the combination of HLA-DR on Mycobacterium tuberculosis (MTB)-specific cells and TB antigen/phytohemagglutinin (TBAg/PHA) ratio could facilitate MTB infection status discrimination.MethodsBetween June 2020 and June 2021, participants with ATB and LTBI were recruited from Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort), respectively. The detection of HLA-DR on MTB-specific cells upon TB antigen stimulation and T-SPOT assay were simultaneously performed on all subjects.ResultsA total of 116 (54 ATB and 62 LTBI) and another 84 (43 ATB and 41 LTBI) cases were respectively enrolled from Qiaokou cohort and Caidian cohort. Both HLA-DR on IFN-γ+TNF-α+ cells and TBAg/PHA ratio showed discriminatory value in distinguishing between ATB and LTBI. Receiver operator characteristic (ROC) curve analysis showed that HLA-DR on IFN-γ+TNF-α+ cells produced an area under the ROC curve (AUC) of 0.886. Besides, TBAg/PHA ratio yield an AUC of 0.736. Furthermore, the combination of these two indicators resulted in the accurate discrimination with an AUC of 0.937. When the threshold was set as 0.36, the diagnostic model could differentiate ATB from LTBI with a sensitivity of 92.00% and a specificity of 81.82%. The performance obtained in Qiaokou cohort was further validated in Caidian cohort.ConclusionsThe combination of HLA-DR on MTB-specific cells and TBAg/PHA ratio could serve as a robust tool to determine TB disease states.

Tuberculosis contact investigation following the stone-in-the-pond principle in the Netherlands – Did adjusted guidelines improve efficiency?

Background In low tuberculosis (TB) incidence countries, contact investigation (CI) requires not missing contacts with TB infection or disease without unnecessarily evaluating non-infected contacts. Aim We assessed whether updated guidelines for the stone-in-the-pond principle and their promotion improved CI practices. Methods This retrospective study used surveillance data to compare CI outcomes before (2011–2013) and after (2014–2016) the guideline update and promotion. Using negative binomial regression and logistic regression models, we compared the number of contacts invited for CI per index patient, the number of CI scaled-up according to the stone-in-the-pond principle, the TB and latent TB infection (LTBI) testing coverage, and yield. Results Pre and post update, 1,703 and 1,489 index patients were reported, 27,187 and 21,056 contacts were eligible for CI, 86% and 89% were tested for TB, and 0.70% and 0.73% were identified with active TB, respectively. Post update, the number of casual contacts invited per index patient decreased statistically significantly (RR = 0.88; 95% CI: 0.79–0.98), TB testing coverage increased (OR = 1.4; 95% CI: 1.2–1.7), and TB yield increased (OR = 2.0; 95% CI: 1.0–3.9). The total LTBI yield increased from 8.8% to 9.8%, with statistically significant increases for casual (OR = 1.2; 95% CI: 1.0–1.5) and community contacts (OR = 2.0; 95% CI: 1.6–3.2). The proportion of CIs appropriately scaled-up to community contacts increased statistically significantly (RR = 1.8; 95% CI: 1.3–2.6). Conclusion This study shows that promoting evidence-based CI guidelines strengthen the efficiency of CIs without jeopardising effectiveness. These findings support CI is an effective TB elimination intervention.

Presentation, diagnosis, and treatment of a cerebellar tuberculoma: illustrative case

BACKGROUND Central nervous system (CNS) tuberculomas are a feared complication of tuberculosis (TB) infection. These lesions can present in varying manners and are associated with significant morbidity and mortality. Prompt diagnosis and treatment of the lesion and the underlying infection are critical in the care of these patients. The authors presented a case of a 45-year-old Yemeni immigrant presenting with a 3-month history of severe right temporo-occipital headaches with photophobia and night sweats. Imaging showed a rim-enhancing lesion in the right cerebellar hemisphere. OBSERVATIONS Laboratory tests were unremarkable and within normal limits. QuantiFERON testing was negative, ruling out latent TB infection. The patient received a suboccipital craniotomy, and resection of the cerebellar lesion showed caseating granuloma formation, which was positive for acid-fast bacilli and Fite stain. LESSONS CNS tuberculomas are an important differential to consider in patients with a history of primary TB, regardless of active disease or immunocompetent status. Resection of these lesions remains a viable treatment option that is safe and effective.

Tuberculosis

The failure to control tuberculosis (TB) in recent times stems, at least in part, from complacency towards TB control in the 1970s and 1980s and the subsequent devastating impact of the HIV-1 pandemic, the rising emergence of drug resistance as well as the growing disparity in disease burden between developed and developing countries. Progress has also been hindered by the slow development of more effective tools such as point-of-care diagnostics and treatments for active and latent disease, preventive vaccines, and laboratory assays of disease progression, immune protection, and cure. This lack of progress is, in turn, related to a poor understanding of the fundamental relationship between Mycobacterium tuberculosis and the human host and especially the nature of what is referred to as ‘latent TB infection’. An increased focus on understanding the mechanics and drivers of transmission together with a concerted effort to translate research findings into policy and practice contextualized to local needs and resources is required. This chapter reviews recent advances in tackling tuberculosis, highlighting key unmet needs and strategies for an accelerated effort to achieve control.

Differential Diagnosis of Latent Tuberculosis Infection and Active Tuberculosis: A Key to a Successful Tuberculosis Control Strategy

As an ancient infectious disease, tuberculosis (TB) is still the leading cause of death from a single infectious agent worldwide. Latent TB infection (LTBI) has been recognized as the largest source of new TB cases and is one of the biggest obstacles to achieving the aim of the End TB Strategy. The latest data indicate that a considerable percentage of the population with LTBI and the lack of differential diagnosis between LTBI and active TB (aTB) may be potential reasons for the high TB morbidity and mortality in countries with high TB burdens. The tuberculin skin test (TST) has been used to diagnose TB for > 100 years, but it fails to distinguish patients with LTBI from those with aTB and people who have received Bacillus Calmette–Guérin vaccination. To overcome the limitations of TST, several new skin tests and interferon-gamma release assays have been developed, such as the Diaskintest, C-Tb skin test, EC-Test, and T-cell spot of the TB assay, QuantiFERON-TB Gold In-Tube, QuantiFERON-TB Gold-Plus, LIAISON QuantiFERON-TB Gold Plus test, and LIOFeron TB/LTBI. However, these methods cannot distinguish LTBI from aTB. To investigate the reasons why all these methods cannot distinguish LTBI from aTB, we have explained the concept and definition of LTBI and expounded on the immunological mechanism of LTBI in this review. In addition, we have outlined the research status, future directions, and challenges of LTBI differential diagnosis, including novel biomarkers derived from Mycobacterium tuberculosis and hosts, new models and algorithms, omics technologies, and microbiota.