Prevalence of Latent Tuberculosis Infection among Patients Undergoing Regular Hemodialysis in Disenfranchised Communities: A Multicenter Study during COVID-19 Pandemic.

Background and Objectives: Due to their weakened immune response, hemodialysis (HD) patients with latent tuberculosis infection (LTBI) are at higher risk for active tuberculosis (TB) disease and are more subject to patient-to-patient transmission within dialysis units. Consequently, current guidelines advocate screening these patients for LTBI. To our knowledge, the epidemiology of LTBI in HD patients has never been examined before in Lebanon. In this context, this study aimed to determine LTBI prevalence among patients undergoing regular HD in Northern Lebanon and to identify potential factors associated with this infection. Notably, the study was conducted during the COVID-19 pandemic, which is likely to have catastrophic effects on TB and increase the risk of mortality and hospitalization in HD patients. Materials and Methods: A multicenter cross-sectional study was carried out in three hospital dialysis units in Tripoli, North Lebanon. Blood samples and sociodemographic and clinical data were collected from 93 HD patients. To screen for LTBI, all patient samples underwent the fourth-generation QuantiFERON-TB Gold Plus assay (QFT-Plus). Multivariable logistic regression analysis was used to identify the predictors of LTBI status in HD patients. Results: Overall, 51 men and 42 women were enrolled. The mean age of the study population was 58.3 ± 12.4 years. Nine HD patients had indeterminate QFT-Plus results and were therefore excluded from subsequent statistical analysis. Among the remaining 84 participants with valid results, QFT-Plus was positive in 16 patients, showing a positivity prevalence of 19% (95% interval for p: 11.3%, 29.1%). Multivariable logistic regression analysis showed that LTBI was significantly associated with age [OR = 1.06; 95% CI = 1.01 to 1.13; p = 0.03] and a low-income level [OR = 9.29; 95% CI = 1.62 to 178; p = 0.04]. Conclusion: LTBI was found to be prevalent in one in five HD patients examined in our study. Therefore, effective TB control measures need to be implemented in this vulnerable population, with special attention to elderly patients with low socioeconomic status.

Tuberculosis Outbreak in a State Prison System - Washington, 2021-2022.

During 2014-2020, no tuberculosis (TB) cases were reported within the Washington state prison system. However, during July 2021-June 2022, 25 TB cases were reported among persons incarcerated or formerly incarcerated in two Washington state prisons. Phylogenetic analyses of whole genome sequencing data indicated that Mycobacterium tuberculosis isolates from all 11 patients with culture-confirmed TB were closely related, suggesting that these cases represented a single outbreak. The median infectious period for 12 patients who were considered likely contagious was 170 days. As of November 15, 2022, the Washington State Department of Corrections (WADOC) and Washington State Department of Health (WADOH), with technical assistance from CDC, had identified 3,075 contacts among incarcerated residents and staff members at five state prisons, and 244 contacts without a known TB history received a diagnosis of latent TB infection (LTBI). Persons who were evaluated for TB disease were isolated; those receiving a diagnosis of TB then initiated antituberculosis therapy. Persons with LTBI were offered treatment to prevent progression to TB disease. This ongoing TB outbreak is the largest in Washington in 20 years. Suspension of annual TB screening while limited resources were redirected toward the COVID-19 response resulted in delayed case detection that facilitated TB transmission. In addition, fear of isolation might discourage residents and staff members from reporting symptoms, which likely also leads to delayed TB diagnoses. Continued close collaboration between WADOC and WADOH is needed to end this outbreak and prevent future outbreaks.

Impact of COVID-19 Pandemic on Tuberculosis Preventive Services and Their Post-Pandemic Recovery Strategies: A Rapid Review of Literature.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has disrupted tuberculosis (TB) care and prevention around the world. The aim of this study is to review literature on the impact of COVID-19 on TB preventive services and discuss their policy options during and after the pandemic. METHODS: We conducted a rapid review of scientific literature on the impact of COVID-19 on TB preventive services and their recovery strategies. After conducting a line-by-line open coding, their codes were applied in the descriptive theme building process, which was guided by the End TB strategy. TB preventive measures were selected and classified into five analytical categories: 1) vaccination against TB, 2) detection and treatment of latent TB infection (LTBI), 3) screening and diagnostics, 4) active case finding and contact tracing, and 5) surveillance. RESULTS: We identified 93 articles, of which 65 were research articles. During the pandemic, we observed decrease in Bacillus Calmette-Guérin (BCG) coverage, TB diagnostic services, case finding activities, and LTBI management. TB case detection was declined, which was not resumed to the pre-pandemic level after loosening the lock-down. Several recommendations were highlighted: 1) secure BCG stocks and its supply chains, 2) consider catch-up activities of routine immunization and LTBI screening, 3) maintain minimal TB health services, infection prevention and control, and surveillance, 4) leverage laboratory capacity and contact tracing mechanisms, 5) consider simultaneous testing for TB and COVID-19, and 6) Incorporate digital health technologies. CONCLUSIONS: Our findings and lessons learnt from the pandemic can aid in the development of future national TB control program.

Contact investigation of tuberculosis in Brunei Darussalam: Evaluation and risk factor analysis.

INTRODUCTION: We evaluated the yield of tuberculosis (TB) contact investigation in Brunei Darussalam, and identified the associated factors for latent TB infection (LTBI) diagnosis, as well as for initiating and completing LTBI treatment. METHODS: Data were extracted and digitalised for all close contacts of pulmonary TB (PTB) cases at the National TB Coordinating Centre from January 2009 to December 2018. Generalising estimating equations logistic regression models were used to determine the associated factors. Manual matching against electronic health records system was done to identify contacts who had progressed to active TB disease. RESULTS: Among 10 537 contacts, 9.9% (n=1047) were diagnosed as LTBI, out of which 43.0% (n=450) initiated LTBI treatment. Among those who initiated, 74.0% (n=333) completed LTBI treatment. Contact factors associated with LTBI diagnosis include being male (adjusted OR (aOR)=1.18 (95% CI 1.03 to 1.34)), local (aOR=0.70 (95% CI 0.56 to 0.88)) and a household contact (aOR=1.59 (95% CI 1.26 to 1.99)). Contacts of index cases who were <60 years old and diagnosed as smear positive PTB (aOR=1.62 (95% CI 1.19 to 2.20)) had higher odds of being diagnosed with LTBI. Local LTBI cases had higher odds of initiating LTBI treatment (aOR=1.86 (95% CI 1.26 to 2.73)). Also, LTBI cases detected from local (aOR=2.32 (95% CI 1.08 to 4.97)) and smear positive PTB index cases (aOR=2.23 (95% CI 1.09 to 4.55)) had higher odds of completing LTBI treatment. Among 1047 LTBI cases, 5 (0.5%) had progressed to active PTB within 1-8 years post-LTBI diagnosis. DISCUSSION: LTBI burden is disproportionately high towards foreign nationals, with higher odds of LTBI diagnosis but lower odds of treatment initiation. Determining the reasons of not initiating LTBI treatment will be useful to help improve LTBI treatment uptake. Establishing digital databases and building TB laboratory capacity for molecular typing would be useful to determine the contribution of LTBI or reactivation towards TB incidence in Brunei.

GIVE statistic for goodness of fit in instrumental variables models with application to COVID data.

Since COVID-19 outbreak, scientists have been interested to know whether there is any impact of the Bacillus Calmette-Guerin (BCG) vaccine against COVID-19 mortality or not. It becomes more relevant as a large population in the world may have latent tuberculosis infection (LTBI), for which a person may not have active tuberculosis but persistent immune responses stimulated by Mycobacterium tuberculosis antigens, and that means, both LTBI and BCG generate immunity against COVID-19. In order to understand the relationship between LTBI and COVID-19 mortality, this article proposes a measure of goodness of fit, viz., Goodness of Instrumental Variable Estimates (GIVE) statistic, of a model obtained by Instrumental Variables estimation. The GIVE statistic helps in finding the appropriate choice of instruments, which provides a better fitted model. In the course of study, the large sample properties of the GIVE statistic are investigated. As indicated before, the COVID-19 data is analysed using the GIVE statistic, and moreover, simulation studies are also conducted to show the usefulness of the GIVE statistic along with analysis of well-known Card data.

Prevalence of latent tuberculosis infection among pre-clinical and clinical medical students using QuantiFERON-TB gold plus and tuberculin skin test at a teaching hospital in Thailand: A cross-sectional study.

BACKGROUND: Healthcare workers are considered to be at a higher risk of acquiring tuberculosis (TB) infection than the general population. Clinical medical students are part of the healthcare team and clinical practice are done during their clinical rotation. They could be exposed to similar occupational risks as the healthcare workers. Most students who become infected have latent tuberculosis infection (LTBI) and may not exhibit any clinical symptoms. Some students with LTBI can progress to TB disease during clinical rotations in the hospitals. Therefore, screening for LTBI in this population represents hospital aspect of public health strategy and infection control in medical school in high TB burden countries. OBJECTIVE: We aimed to determine the prevalence of LTBI among fourth-year medical students and sixth-year medical students by using QuantiFERON-TB Gold Plus (QFT-Plus) and Tuberculin Skin Test (TST). METHODS: A cross-sectional study of fourth-year medical students (n = 73) and sixth-year medical students (n = 85) was conducted at the School of Medicine, Chulalongkorn University, Bangkok, Thailand. The medical students (n = 158) who met the eligibility criteria were recruited into the study. LTBI was detected by using QFT-Plus and some of the participants had a tuberculin skin test (TST). The TST was interpreted after 48-72 h. The participants who tested positive by QFT-Plus were considered to have LTBI. Demographic information and data on occupational TB exposure were collected via a questionnaire. A multivariate logistic regression was used to test for associations between independent variables and results of the QFT-Plus. RESULTS: A total of 158 participants were included in this study. The overall prevalence of LTBI was 6.3% (n = 10) as determined by QFT-Plus. The LTBI prevalence was higher in the sixth-year medical students (9.4%) compared to the fourth-year medical students (2.7%). Higher risk of LTBI was associated with sixth-year medical students (odds ratio, 3.69 [95%CI, 0.75-17.96]), but this was not significant. Moreover, history of occupational TB exposure without PPE yielded an odds ratio of 2.98 [95%CI, 0.68-13.12] but it was not statistically significant due to the small sample size. One hundred thirty-nine (88%) participants were BCG vaccinated as per the national vaccination requirements. No abnormal chest X-rays were found for any of the positive participants. Of the 158 participants, 41 (25.9%) of them had TST. Of the 41 participants, 6 (14.6%) tested positive at a cut-off of ≥ 10 mm for TST, which was concordant with QFT-Plus results. The agreement between the two tests was 0.57 using kappa coefficients. CONCLUSION: The screening of TB infection in new healthcare workers (HCWs), especially medical students, is essential to reduce future nosocomial TB incidences in the hospitals. This study showed that there was a high prevalence of LTBI among sixth-year medical students compared to fourth-year medical students. Our results suggest that tendency of higher LTBI prevalence might be associated with advanced clinical years, thus tailored public health education strategy and infection control in tertiary care hospitals for new healthcare workers in TB endemic countries may prevent nosocomial TB disease from developing in the future. Therefore, active surveillance should be done for all new HCWs, and TB preventive therapy should be administered to recent converters.

Predicting Airborne Infection Risk: Association Between Personal Ambient Carbon Dioxide Level Monitoring and Incidence of Tuberculosis Infection in South African Health Workers.

BACKGROUND: High rates of tuberculosis (TB) transmission occur in hospitals in high-incidence countries, yet there is no validated way to evaluate the impact of hospital design and function on airborne infection risk. We hypothesized that personal ambient carbon dioxide (CO2) monitoring could serve as a surrogate measure of rebreathed air exposure associated with TB infection risk in health workers (HWs). METHODS: We analyzed baseline and repeat (12-month) interferon-γ release assay (IGRA) results in 138 HWs in Cape Town, South Africa. A random subset of HWs with a baseline negative QuantiFERON Plus (QFT-Plus) underwent personal ambient CO2 monitoring. RESULTS: Annual incidence of TB infection (IGRA conversion) was high (34%). Junior doctors were less likely to have a positive baseline IGRA than other HWs (OR, 0.26; P = .005) but had similar IGRA conversion risk. IGRA converters experienced higher median CO2 levels compared to IGRA nonconverters using quantitative QFT-Plus thresholds of ≥0.35 IU/mL (P < .02) or ≥1 IU/mL (P < .01). Median CO2 levels were predictive of IGRA conversion (odds ratio [OR], 2.04; P = .04, ≥1 IU/mL threshold). Ordinal logistic regression demonstrated that the odds of a higher repeat quantitative IGRA result increased by almost 2-fold (OR, 1.81; P = .01) per 100 ppm unit increase in median CO2 levels, suggesting a dose-dependent response. CONCLUSIONS: HWs face high occupational TB risk. Increasing median CO2 levels (indicative of poor ventilation and/or high occupancy) were associated with higher likelihood of HW TB infection. Personal ambient CO2 monitoring may help target interventions to decrease TB transmission in healthcare facilities and help HWs self-monitor occupational risk, with implications for other airborne infections including coronavirus disease 2019.

Impact of the COVID-19 pandemic on contact tracing of patients with pulmonary tuberculosis.

BACKGROUND: The COVID-19 pandemic could have negative effects on tuberculosis (TB) control. The objective was to assess the impact of the pandemic in contact tracing, TB and latent tuberculosis infection (LTBI) in contacts of patients with pulmonary TB in Catalonia (Spain). METHODS: Contact tracing was carried out in cases of pulmonary TB detected during 14 months in the pre-pandemic period (1 January 2019 to 28 February 2020) and 14 months in the pandemic period (1 March 2020 to 30 April 2021). Contacts received the tuberculin skin test and/or interferon gamma release assay and it was determined whether they had TB or LTBI. Variables associated with TB or LTBI in contacts (study period and sociodemographic variables) were analyzed using adjusted odds ratio (aOR) and the 95% confidence intervals (95% CI). RESULTS: The pre-pandemic and pandemic periods showed, respectively: 503 and 255 pulmonary TB reported cases (reduction of 50.7%); and 4676 and 1687 contacts studied (reduction of 36.1%). In these periods, the proportion of TB cases among the contacts was 1.9% (84/4307) and 2.2% (30/1381) (P = 0.608); and the proportion of LTBI was 25.3% (1090/4307) and 29.2% (403/1381) (P < 0.001). The pandemic period was associated to higher LTBI proportion (aOR = 1.3; 95% CI 1.1-1.5), taking into account the effect on LTBI of the other variables studied as sex, age, household contact and migrant status. CONCLUSIONS: COVID-19 is affecting TB control due to less exhaustive TB and LTBI case detection. An increase in LTBI was observed during the pandemic period. Efforts should be made to improve detection of TB and LTBI among contacts of TB cases.

Clinical and Epidemiological Correlates of Low IFN-Gamma Responses in Mitogen Tube of QuantiFERON Assay in Tuberculosis Infection Screening During the COVID-19 Pandemic: A Population-Based Marker of COVID-19 Mortality?

Background: The clinical and epidemiological implications of abnormal immune responses in COVID-19 for latent tuberculosis infection (LTBI) screening are unclear. Methods: We reviewed QuantiFERON TB Gold Plus (QFT-Plus) results (36,709 patients) from July 2016 until October 2021 in Asturias (Spain). We also studied a cohort of ninety hospitalized patients with suspected/confirmed COVID-19 pneumonia and a group of elderly hospitalized patients with COVID-19 who underwent serial QFT-Plus and immune profiling testing. Results: The indeterminate QFT-Plus results rate went from 1.4% (July 2016 to November 2019) to 4.2% during the COVID-19 pandemic. The evolution of the number of cases with low/very low interferon-gamma (IFN-gamma) response in the mitogen tube paralleled the disease activity and number of deaths during the pandemic waves in our region (from March 2020 to October 2021). The percentages of positive QFT-plus patients did not significantly change before and during the pandemic (13.9% vs. 12.2%). Forty-nine patients from the suspected/confirmed COVID-19 pneumonia cohort (54.4%) had low/very low IFN-gamma response to mitogen, 22 of them (24.4%) had severe and critical pneumonia. None received immunosuppressants prior to testing. Abnormal radiological findings (P = 0.01) but not COVID-19 severity was associated with low mitogen response. Immune profiling showed a reduction of CD8 + T cells and a direct correlation between the number of EMRA CD8 + T-cells and IFN-gamma response to mitogen (P = 0.03). Conclusion: Low IFN-gamma responses in mitogen tube of QFT-Plus often occur in COVID-19 pneumonia, which is associated with a low number of an effector CD8 + T-cell subset and does not seem to affect LTBI screening; however, this abnormality seems to parallel the dynamics of COVID-19 at the population level and its mortality.

Targeting screening and treatment for latent tuberculosis infection towards asylum seekers from high-incidence countries - a model-based cost-effectiveness analysis.

BACKGROUND: Enhancing tuberculosis (TB) prevention and care in a post-COVID-19-pandemic phase will be essential to ensure progress towards global TB elimination. In low-burden countries, asylum seekers constitute an important high-risk group. TB frequently arises post-immigration due to the reactivation of latent TB infection (LTBI). Upon-entry screening for LTBI and TB preventive treatment (TPT) are considered worthwhile if targeted to asylum seekers from high-incidence countries who usually present with higher rates of LTBI. However, there is insufficient knowledge about optimal incidence thresholds above which introduction could be cost-effective. We aimed to estimate, among asylum seekers in Germany, the health impact and costs of upon-entry LTBI screening/TPT introduced at different thresholds of country-of-origin TB incidence. METHODS: We sampled hypothetical cohorts of 30-45 thousand asylum seekers aged 15 to 34 years expected to arrive in Germany in 2022 from cohorts of first-time applicants observed in 2017-2019. We modelled LTBI prevalence as a function of country-of-origin TB incidence fitted to data from observational studies. We then used a probabilistic decision-analytic model to estimate health-system costs and quality-adjusted life years (QALYs) under interferon gamma release assay (IGRA)-based screening for LTBI and rifampicin-based TPT (daily, 4 months). Incremental cost-effectiveness ratios (ICERs) were calculated for scenarios of introducing LTBI screening/TPT at different incidence thresholds. RESULTS: We estimated that among 15- to 34-year-old asylum seekers arriving in Germany in 2022, 17.5% (95% uncertainty interval: 14.2-21.6%) will be latently infected. Introducing LTBI screening/TPT above 250 per 100,000 country-of-origin TB incidence would gain 7.3 (2.7-14.8) QALYs at a cost of €51,000 (€18,000-€114,100) per QALY. Lowering the threshold to ≥200 would cost an incremental €53,300 (€19,100-€122,500) per additional QALY gained relative to the ≥250 threshold scenario; ICERs for the ≥150 and ≥ 100 thresholds were €55,900 (€20,200-€128,200) and €62,000 (€23,200-€142,000), respectively, using the next higher threshold as a reference, and considerably higher at thresholds below 100. CONCLUSIONS: LTBI screening and TPT among 15- to 34-year-old asylum seekers arriving in Germany could produce health benefits at reasonable additional cost (with respect to international benchmarks) if introduced at incidence thresholds ≥100. Empirical trials are needed to investigate the feasibility and effectiveness of this approach.

[Friend or Foe? Evaluation of BCG Vaccine and Latent Tuberculosis Infection Effect in Patients Diagnosed with COVID-19 Infection]. / Dost mu Düsman mi? COVID-19 Enfeksiyonu Tanili Hastalarda BCG Asisi ve Latent Tüberküloz Enfeksiyonu Etkisinin Degerlendirilmesi.

While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread rapidly worldwide, some issues such as the uncertainty of the disease progress, whether intensive care will be needed, and risk classification are still important for clinicians. It is notable that in countries where latent tuberculosis infection (LTBI) is common and participating in the national Bacillus Calmette-Guerin (BCG) vaccination program, the case-fatality rates are relatively low throughout the world. In this study, it was aimed to evaluate the effects of the BCG vaccine and LTBI status on the course of the disease in patients diagnosed with coronavirus-19 (COVID-19) infection and to compare the LTBI rate with people with and without COVID-19 infection. The patients diagnosed with COVID-19 infection who were hospitalized during a period of seven months between May 1st to December 1st, 2020 were investigated by the QuantiFERON-TB Gold Plus (QFT-Plus) test in the blood samples for the presence of LTBI. For the comparison of the patients diagnosed with COVID-19 and people without COVID-19 infections in terms of LTBI rate retrospectively; all consecutive patients who were sent blood samples to the mycobacteriology laboratory for the QFT-Plus test between January 2016 and December 2019 were included in the study. Demographic, clinical, radiological, laboratory, and follow-up data of the patients were obtained from the electronic patient file. A total of 170 patients (n= 9 8 male [57.6%], n= 72 female [42.3%], mean age= 53.5 ± 15.8 years) were enrolled. Twenty-five patients' (25/170 [14.7%]) QFT-plus tests were positive. When the cases with positive QFT-Plus test (n= 25) and the cases with negative QFT-Plus test (n = 145) were compared in terms of disease severity respectively; it was determined that mild/moderate patients were 18/25 (72%) and 108/145 (74.5%), severe patients were 7/25 (28%) and 37/145 (25.5%) (p= 0.988). When these two groups were compared in terms of the clinical course respectively; the need for intensive care was 6/25 (24%) and 34/145 (23.4%) (p= 1.00), oxygen therapy requirement was 13/25 (52%) and 49/145 (33.8%) (p= 0.128), and death was 5/25 (20%) and 18/145 (12.4%) (p= 0.341). QFT-Plus positivity was 25/170 (14.7%) in patients diagnosed with COVID-19, while in control group it was 198/496 (39.9%) (OR= 0.259, 95% CI [0.164-0.411], p<0.001). When the values were evaluated quantitatively, in the COVID-19 patient group, QFT-Plus T1/T2 (IU/ml) interferon (IFN)-É£ was 0.87 ± 1.52/0.62 ± 1.53, while in the control group it was 1.52 ± 3.69/1.50 ± 3.33 (p= 0.032, p= 0.04). There was no significant difference in the parameters investigated between 82 (48.2%) patients with BCG vaccine and those 88 (51.8%) without BCG vaccine. Although it was not statistically significant in our study, increased oxygen therapy requirement and higher mortality rates in the QFT-Plus positive group were remarkable. The detection of statistically significantly lower LTBI rates and T1-T2/IFN-É£ values in the COVID-19 group supported that SARS-CoV-2 infection may suppress lymphocyte functions in patients and IFN-É£ response. We believe that the results of our study are remarkably valuable, but more clinical studies are needed to elucidate the relationship between BCG vaccine, LTBI, and COVID-19 infection.

Latent Tuberculosis Infection among Health Workers in Germany-A Retrospective Study on Progression Risk and Use of Preventive Therapy.

Despite the decline in tuberculosis incidence (TB) in Germany, health workers (HW) are at greater risk of becoming infected with Mycobacterium tuberculosis. To date, little is known about the risk of progression of latent tuberculosis infections (LTBI) and the use of Tuberculosis Preventive Therapy (TPT) among HW. Routine data from the German Statutory Institution for Accident Insurance and Prevention for Health and Welfare Services (BGW) were analysed and a retrospective survey was conducted. A self-administered questionnaire was sent to 1711 HW who had received recognition of an LTBI as an occupational disease between the years 2009 and 2018. The response rate was 42.3% after correcting for those with no actual address (20.4%). We included 575 HW in the data analysis of the retrospective survey. The cumulative incidence of progression, the incidence density and the associated 95% confidence interval (95% CI) were calculated. Three progressive cases were identified in the analysis of the routine data. In the survey cohort, three HW developed TB during the observation period of 5.4 years on average (standard deviation: 2.8 years; interquartile range: 5.0 years). The cumulative TB incidence was 0.52% in the survey group (95% CI: 0.14% to 1.65%). The incidence density was 0.97 cases per 1000 person years (95% CI: 0.25 to 3.10). One-third of the respondents underwent TPT. Significant differences were observed between age and activity groups in the use of TPT, but not between the genders, year of diagnosis or the reason for performing the screening. The data indicate that the risk of progression of an LTBI is low for HW. However, one-third of the HW had undergone TPT. Information about the expected progression risk is important so that it can be weighed against the risk of side effects of TPT.

Cost-effectiveness analysis of 3 months of weekly rifapentine and isoniazid compared to isoniazid monotherapy in a Canadian arctic setting.

OBJECTIVE: To assess the cost effectiveness of once weekly rifapentine and isoniazid for 12 weeks (3HP) to the current standard care for latent tuberculosis (TB) infection (LTBI) in Iqaluit, Nunavut. DESIGN: A cost-effectiveness analysis using a Markov model reflecting local practices for LTBI treatment. SETTING: A remote Canadian arctic community with a high incidence of TB. PARTICIPANTS: Hypothetical patients with LTBI. INTERVENTIONS: The cost effectiveness of 3HP was compared with the existing standard of care in the study region which consists of 9 months of twice weekly isoniazid (9H) given by directly observed therapy. OUTCOME MEASURES: Effectiveness was measured in quality-adjusted life years (QALYs) with model parameters were derived from historical programmatic data, a local implementation study of 3HP and published literature. Costs from the perspective of the Nunavut healthcare system were measured in 2019 US dollars and were obtained primarily from local, empirically collected data. Secondary health outcomes included estimated TB cases and TB deaths averted using 3HP versus 9H. One way and probabilistic sensitivity analyses were performed. RESULTS: The 3HP regimen was dominant over 9H: costs were lower (US$628 vs US$924/person) and health outcomes slightly improved (20.14 vs 20.13 QALYs/person). In comparison to 9H, 3HP treatment resulted in fewer TB cases (27.89 vs 30.16/1000 persons) and TB deaths (2.29 vs 2.48/1000 persons). 3HP completion, initiation and risk of fatal adverse events were the primary drivers of cost effectiveness. CONCLUSION: In a remote Canadian arctic setting, using 3HP instead of 9H for LTBI treatment may result in cost savings and similar or improved health outcomes.

Is chemoprophylaxis necessary for all latent tuberculosis infection patients receiving IL-17 inhibitors? A cohort study.

The tuberculosis (TB) burden is high in China, with a 32% prevalence of latent tuberculosis infection (LTBI) in Beijing. Screening for LTBI and the chemoprophylaxis of positive patients are recommended prior to biologic therapy. To evaluate the TB-related safety of secukinumab (SEC) in a cohort of plaque psoriasis patients with LTBI receiving different treatments. Plaque psoriasis patients eligible for SEC treatment were screened for TB. LTBI patients (QuantiFeron-TB test positive, QFT+) receiving SEC were closely monitored by chest radiograph, ESR or hs-CRP, and blood counts every 12 to 20 weeks for active TB infection. QFT_patients receiving SEC treatment were screened for LTBI every 6 to 12 months. Of 42 patients treated with SEC, 19 were QFT+ (45.24%). A QFT_patient became QFT+ after 6 months treatment. Two patients started SEC treatment from 2015 to 2016 and were followed up 268 and 216 weeks later, respectively. Three patients received chemoprophylaxis, 17 did not because of safety concerns or being unable to complete the process. During the 16- to 268-week follow-up, no signs of TB reactivation were observed in the 20 LTBI patients receiving SEC. Plaque psoriasis patients with LTBI who received no chemoprophylaxis could be safely treated with SEC.

Preliminary observations on IGRA testing for TB infection in patients with severe COVID-19 eligible for immunosuppressive therapy.

COVID-19, the novel coronavirus pandemic, has already spread around the globe affecting more than 18 million people. As previously observed with other coronaviruses, SARS-CoV-2 deeply dysregulate the immune system eliciting respiratory failure and a state of systemic hyperinflammation in severely ill individuals. Immunotherapy is often used to downgrade the detrimental effects of the disease sustained by high-level of cytokines. Those treatments, however, are known to undermine patients' ability to contain tuberculosis (TB) infection. This study aims to describe interferon-γ release assay (IGRA) results in severe COVID-19 patients eligible for immunosuppressive treatment. Aggregate data were gathered from five hospitals in Milan, Italy, from March 1 to May 15, 2020 and retrospectively analyses. Results were summarized using absolute frequencies and percentages and compared using a two-sided Chi-squared test. Overall, 462 COVID-19 patients were eligible for immunosuppressive therapy, among which 335 were tested using IGRA testing. More than one-third of them (122/335; 36.4%) had an indeterminate IGRA result because of insufficient immune response to mitogen control, 19 (5.7%) tested positive and 194 (57.9) negative. The majority of patients with lymphocytopenia (i.e., total lymphocyte count [TLC] below 1000 cells/mm3) had indeterminate IGRAs (81/155; 52.3%). The proportion becomes even higher in patients with severe lymphocytopenia (i.e., TLC<500 cells/mm3) (36/57; 63%). Our results suggest a possible negative impact of COVID-19 related immune dysregulation on TB infection assessment and management. Close monitoring of individuals with or without retesting of individuals with indeterminate IGRAs and further basic science investigations should to be sought to better comprehend their implication on TB epidemiology.

The paradigm shift in the approach to management of latent tuberculosis infection in high tuberculosis burden countries.

Introduction: Addressing the reservoir of Latent Tuberculosis Infection (LTBI) is critical to TB elimination because if left untreated LTBI can progress to active TB disease. This additional burden can prevent achieving the global targets of TB elimination. Management of LTBI has been a low priority target for National TB Elimination Programs (NTEP) due to various challenges in the field settings.Areas covered: This article reviews the most recent advances in the field of LTBI management including newer diagnostics, treatments, vaccines, programmatic challenges, and gaps and suggests a way forward that can be adopted by NTEPs for LTBI. We searched the electronic databases of PubMed, Scopus, and Web of Science for studies published between 2010 to 2020 using MeSH terms: Latent TB Diagnosis, TB preventive therapy, Vaccines, LTBI, and HIV/ COVID.Expert opinion: NTEPs of developing countries should offer a better, point-of-care diagnostic, and effective treatment for LTBI to reduce the number of new TB cases arising from people infected with M.tb. Awareness about LTBI should be increased among the health system staff and the public. More funding is needed to advance research as well as implement the newer findings in the NTEP to achieve the End TB targets by 2035.

Role of latent tuberculosis infections in reduced COVID-19 mortality: Evidence from an instrumental variable method analysis.

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, there has been significant interest in the potential protective effect of the Bacillus Calmette-Guerin (BCG) vaccine against COVID-19 mortality. This effect has been attributed to innate immune responses induced by BCG vaccination. However, these studies ignore an important fact: according to World Health Organization estimates, about a quarter of the world's population may have latent tuberculosis infection (LTBI), a condition in which there is no evidence of clinically active tuberculosis but persistent immune responses are stimulated by Mycobacterium tuberculosis antigens. Thus, both LTBI and BCG induce lifelong immunity and may provide immunological protection against COVID-19. In this study, the relationship between LTBI and reduced COVID-19 mortality was analyzed using the instrumental variable method. The results showed with robust statistical support that LTBI was also associated with reduced COVID-19 mortality.