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.

Targeting Non-Replicating Mycobacterium tuberculosis and Latent Infection: Alternatives and Perspectives (Mini-Review)

Latent tuberculosis infection (LTBI) represents a major challenge to curing TB disease. Current guidelines for LTBI management include only three older drugs and their combinations—isoniazid and rifamycins (rifampicin and rifapentine). These available control strategies have little impact on latent TB elimination, and new specific therapeutics are urgently needed. In the present mini-review, we highlight some of the alternatives that may potentially be included in LTBI treatment recommendations and a list of early-stage prospective small molecules that act on drug targets specific for Mycobacterium tuberculosis latency.

Active TB infection and its associated factors among HIV-1 infected patients at Jimma medical center, Southwest Ethiopia

Background Human immune deficiency virus (HIV) increases the susceptibility to primary infection or reinfection and the risk of tuberculosis (TB) reactivation for patients with latent TB. There was no current report on the rate of active TB infection among HIV-1 infected patients in our teaching and referral hospital. Therefore, this study was aimed to determine the prevalence and factors associated with active TB infection among HIV-1 infected patients. Methods Hospital-based retrospective cross-sectional study was conducted at the Anti-Retroviral Therapy (ART) chronic follow-up clinic. Systematic random sampling was used to include the patients. A structured questionnaire was used to collect data. Data were analyzed using SPSS version 25. Descriptive statistics were used to describe the findings and multivariate logistic regression was performed to identify factors associated with active TB infection. Result 150 HIV-1 infected patients (female 54.7%) were included. The median (interquartile range, IQR) age of the patients was 33.5 (25.7, 40.0) years. Twenty-six (17.3%) of the patients had developed active TB infection, which was independently associated with the WHO clinical stage III and IV (AOR: 9.67, 95% confidence interval (CI); 2.21–42.37), p = 0.003). The use of isoniazid preventive therapy (IPT) (AOR: 0.123, 95CI; 0.034–0.44, p = 0.001) and having good adherence to ART medications (AOR: 0.076, 95CI; 0.007–0.80, p = 0.032) was associated with the reduced risk of active TB infection among HIV-1 infected patients. Conclusions Advanced WHO clinical stages increased the risk of active TB infection, while the use of IPT and good adherence to ART medications reduced the risk of active TB infection. Therefore, patients with advanced WHO clinical stage should be screened for TB infection, and starting IPT for the candidate patients should be strengthened to reduce the burden of active TB incidence. ART medication adherence should also be supported.

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.

1406. Hepatitis B and C Prevalence in Patients with Active and Latent Tuberculosis in an Ethnically Diverse Area of London, UK

Background North West London has one of the highest tuberculosis (TB) rates in the UK, at 24.8 per 10,000. The UK prevalence of hepatitis B virus (HBV) is 0.1-0.5% and for hepatitis C virus (HCV) is 0.5-1%. Chronic infection with HBV or HCV can lead to an increased risk of adverse treatment outcomes, such as drug-induced liver injury (DILI) in patients with active or latent TB. National guidelines recommend routinely screening for HBV/HCV prior to initiating TB treatment. Our objectives were to 1) evaluate the HBV/HCV screening practice in local TB clinics, 2) establish the prevalence of HBV/HCV in patients receiving TB treatment. Methods Retrospective analysis of laboratory and medical records of patients treated for active or latent TB identified from the London TB register and clinic records from 01/01/2018 to 31/12/2020 from London North West NHS Trust. Results 1409 patients received treatment for TB during the time period of interest; 574 (40.7%) had active disease and 835 (59.3%) had latent infection. 966/1409 patients (68.56%) were screened for HBV and HCV. 55.9% of the active TB group and 77.2% of the latent infection group were tested. 66 (6.8%) patients had isolated anti-HBc positivity, 22 (2.3%) were HBV surface antigen positive and 8 (0.8%) were HCV-antibody positive. HBV surface antigens were more prevalent in active TB patients: 9/321 (2.80%) with active TB versus 13/645 (2.02%) with latent TB. 36/321 (11.21%) active TB patients had HBV core antibodies compared to 30/645 (4.65%) latent TB patients (p < 0.001). Three patients started antiviral treatment following their viral hepatitis diagnosis (one with HBV, two with HCV). Conclusion The prevalence of chronic HBV in the study population was higher than the estimated UK prevalence. Fifteen diagnoses of hepatitis were new, allowing specialist referral for monitoring of fibrosis and development of hepatocellular carcinoma. Three patients required hepatitis treatment. 6.8% of patients were positive for anti-HBc and therefore identified as being at future risk of HBV reactivation if requiring immunosuppressive therapies.TB disproportionately affects marginalised communities; screening for viral hepatitis in TB clinic represents an opportunity to target these hard-to-reach groups to maximise the impact of public health interventions. Disclosures All Authors: No reported disclosures

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.

Tuberculosis amidst COVID-19 pandemic in India: unspoken challenges and the way forward

India is home to the most significant number of tuberculosis (TB) cases around the globe. The COVID-19 crisis has deeply perturbed most of the essential TB services in India. Regulating TB is difficult in a densely populated country like India due to latent TB infection in millions of Indians, which can reactivate at any point in the future. Due to the ongoing pandemic, healthcare workers have been diverted to activities implemented for effective COVID-19 management, leaving a meager workforce to help deal with TB management. Integrating TB and COVID-19 to augment India’s health outreach is the need of the hour to diminish the effect of the COVID-19 crisis on TB. Increasing overall testing capacity, active screening, implementation of strategies for easy identification of TB hotspots, and ensuring uninterrupted drug supply for treatment through heedful planning of local and regional distribution and transportation will especially help cater to the vulnerable population who are at a high risk of suffering from adverse outcomes of TB. Lessons learnt in the battle against COVID-19 can most definitely help in providing insights to fulfill the goal of eliminating TB from India.