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.

Latent Tuberculosis Infection Beliefs and Testing and Treatment Health Behaviors Amongst Non-US-Born South Asians in New Jersey: A Cross-Sectional Community Survey.

Latent tuberculosis infection (LTBI) remains a problem in the United States as reactivation leads to active TB disease particularly in persons with risk factors. The objective of this study is to assess the knowledge, attitudes and health behaviors related to testing and treatment of LTBI among non-US-born South Asians (SA) in New Jersey (NJ). A cross-sectional, community-based survey was the primary tool for gathering data. Eligibility criteria included being at least 18 years of age, self-identifying as SA, verbal consent for participation, and birth in a high TB endemic country. A hardcopy survey was distributed at local South Asian health fairs. The survey included questions about demographics, knowledge, beliefs on TB, and health behaviors (testing and treatment). Descriptive statistics were performed for all survey responses. Logistic regression models were constructed to assess the association of characteristics/beliefs and study outcomes. The survey sample size included 387 respondents. A total of 197 (54%) of respondents reported ever been tested for TB. Those who were tested for TB were generally younger, had higher educational levels, higher household incomes, and were more likely to have health insurance than those not ever tested for TB. Significantly more respondents who self-reported ever been tested for TB believed that TB was very or extremely serious (71.1% vs. 56.2%, p = 0.004). Also, significantly more respondents who self-reported ever been tested for TB believed that it was important to get tested (91.2% vs. 63.3%, p < 0.001). The survey analysis concluded that high-risk SA residents in NJ demonstrated a low rate of testing for TB.

Practical aspects of backward bifurcation in a mathematical model for tuberculosis.

In this work, we examine practical aspects of backward bifurcation for a data-based model of tuberculosis that incorporates multiple features which have previously been shown to produce backward bifurcation (e.g. exogenous reinfection and imperfect vaccination) and new considerations such as the treatment of latent TB infection (LTBI) and the BCG vaccine's interference with detecting LTBI. Understanding the interplay between these multiple factors and backward bifurcation is particularly timely given that new diagnostic tests for LTBI detection could dramatically increase rates of both LTBI detection and vaccination in the coming decades. By establishing analytic thresholds for the existence of backward bifurcation, we identify those aspects of TB's complicated pathology that make backward bifurcation more or less likely to occur. We also examine the magnitude of the backward bifurcation produced by the model and its sensitivity to various model parameters. We find that backward bifurcation is unlikely to occur. While increased vaccine coverage and/or increased detection and treatment of LTBI can push the threshold for backward bifurcation into the region of biological plausibility, the resulting bifurcations may still be too small to have any noticeable epidemiological impact.

Factors Associated with Non-Adherence to Tuberculosis Preventive Treatment among Adult Contacts of Pulmonary Tuberculosis Cases with Latent Tuberculosis Infection in Catalonia, Spain, in 2019-2021.

The aim of this study was to identify factors associated with non-adherence to tuberculosis (TB) preventive treatment among contacts with latent TB infection for new cases of pulmonary TB cases reported in Catalonia in 2019-2021. All contacts aged 18 years or older with a latent TB infection who received a TB preventive treatment were included in the study. The Chi square test and the odds ratios (OR) were used to assess the association between non-adherence to TB preventive treatment and the study variables; a p < 0.05 was considered statistically significant. Multiple logistic regression analysis was used to detect the independent factors associated with TB preventive treatment non-adherence; a p < 0.05 was considered statistically significant. The percentage of non-adherence to TB preventive treatment found in this study was 23.7%. A multivariable logistic regression analysis determined that the following factors were significantly associated with TB preventive treatment non-adherence among adult contacts: "exposure at school or workplace" (aOR = 3.34), "exposure to an index case without laboratory confirmation of TB" (aOR = 2.07), "immigrant contact" (aOR = 1.81), "male gender" (aOR = 1.75) and "exposure duration < 6 h per week or sporadic" (aOR = 1.60. By contrast, the factor "short-term TB preventive treatment regimen" (aOR = 0.38) was significantly associated with a lower treatment non-adherence. Adherence to TB preventive treatment should be improved among adult contacts of TB pulmonary cases with latent TB infection by recommending short-term treatment regimens and by developing health education activities, with a greater focus on contacts with factors associated with treatment non-adherence.

Monitoring tuberculosis contact tracing outcomes in Western Sydney, Australia.

Treatment of latent tuberculosis infection (LTBI) is an important component of strategies to achieve global tuberculosis (TB) elimination, but implementation is rarely monitored. This is a retrospective review of TB contact tracing outcomes at one of the busiest TB clinics in Australia, measured against the Centre for Disease Control and Prevention performance indicators. In total, 45 of 53 (85%) pulmonary TB cases had 171 close contacts, of whom 139 (81%) were evaluated with a tuberculin skin test (TST); 58 of 139 (42%) were positive at baseline. Among 57 close contacts of 16 sputum smear-positive TB cases, the elicitation, evaluation, initiation of LTBI treatment and completion rates were 93%, 86%, 14% and 100%, and among 114 close contacts of 37 sputum smear-negative pulmonary TB cases 81%, 83%, 16% and 89%, respectively. Of 79 contacts with an initial negative TST, 19 of 47 (40%) demonstrated TST conversion when retested; 5 of 19 (26%) were offered LTBI treatment. Four secondary TB cases were identified. One incident TB case developed a pleural effusion 5 months after TST conversion, despite LTBI treatment. Apart from young children, LTBI treatment was inconsistently initiated in household TB contacts. Safe and pragmatic treatment options, as well as functional monitoring frameworks, are essential to improve LTBI treatment implementation.