Treatment Of Latent Tuberculosis Infection Research Articles

Health economic analyses of latent tuberculosis infection screening and preventive treatment among people living with HIV in lower tuberculosis incidence settings: a systematic review.

Introduction: In lower tuberculosis (TB) incidence countries (<100 cases/100,000/year), screening and preventive treatment (PT) for latent TB infection (LTBI) among people living with HIV (PLWH) is often recommended, yet guidelines advising which groups to prioritise for screening can be contradictory and implementation patchy. Evidence of LTBI screening cost-effectiveness may improve uptake and health outcomes at reasonable cost. Methods: Our systematic review assessed cost-effectiveness estimates of LTBI screening/PT strategies among PLWH in lower TB incidence countries to identify model-driving inputs and methodological differences. Databases were searched 1980-2020. Studies including health economic evaluation of LTBI screening of PLWH in lower TB incidence countries (<100 cases/100,000/year) were included. Study quality was assessed using the CHEERS checklist. Results: Of 2,644 articles screened, nine studies were included. Cost-effectiveness estimates of LTBI screening/PT for PLWH varied widely, with universal screening/PT found highly cost-effective by some studies, while only targeting to high-risk groups (such as those from mid/high TB incidence countries) deemed cost-effective by others. Cost-effectiveness of strategies screening all PLWH from studies published in the past five years varied from US$2828 to US$144,929/quality-adjusted life-year gained (2018 prices). Study quality varied, with inconsistent reporting of methods and results limiting comparability of studies. Cost-effectiveness varied markedly by screening guideline, with British HIV Association guidelines more cost-effective than NICE guidelines in the UK. Discussion: Cost-effectiveness studies of LTBI screening/PT for PLWH in lower TB incidence settings are scarce, with large variations in methods and assumptions used, target populations and screening/PT strategies evaluated. The limited evidence suggests LTBI screening/PT may be cost-effective for some PLWH groups but further research is required, particularly on strategies targeting screening/PT to PLWH at higher risk. Standardisation of model descriptions and results reporting could facilitate reliable comparisons between studies, particularly to identify those factors driving the wide disparity between cost-effectiveness estimates. Registration: PROSPERO CRD42020166338 (18/03/2020).

Completion Rate and Safety of Programmatic Screening and Treatment for Latent Tuberculosis Infection in Elderly Patients With Poorly Controlled Diabetic Mellitus: A Prospective Multicenter Study.

BackgroundPoor control of diabetes mellitus (DM) increases active tuberculosis (TB) risk. Understanding risk factors for latent TB infection (LTBI) in this population and intervention completion rates is crucial for policy making.MethodsUnder a collaborative multidisciplinary team consisting of public health professionals, endocrinologists, and pulmonologists, patients aged >45 years with poorly controlled DM (pDM), defined as having a glycated hemoglobin level of ≥9% within the preceding year, were enrolled by endocrinologists from 2 hospitals; these patients underwent LTBI screening by using QuantiFERON (QFT). Once-weekly isoniazid and rifapentine for 12 weeks (3HP) or daily isoniazid for 9 months (9H) was administered by pulmonologists. QFT-positivity predictors were evaluated using logistic regression. Completion rates and safety were also investigated.ResultsAmong 980 patients with pDM (age: 64.2 ± 9.7 years), 261 (26.6%) were QFT-positive. Age, DM duration, chronic kidney disease stage ≥3, and dipeptidyl peptidase-4 inhibitor use, not using metformin, were associated with QFT-positivity. Preventive therapy (3HP: 138; 9H: 62) was administered in 200 (76.6%) QFT-positive patients. The completion rates of 3HP and 9H were 84.1% and 79.0%, respectively (P = .494). Nine (6.5%) and zero patients in the 3HP and 9H groups, respectively, developed systemic drug reactions (P = .059); 78.3% and 45.2% had ≥1 adverse drug reactions (P < .001); and post-treatment QFT conversion rates were 32% and 20%, respectively (P = .228).ConclusionsLTBI prevalence exceeds 25% in elderly patients with pDM. Under care from a collaborative multidisciplinary team, the completion rate of preventive therapy, regardless of regimen could approach, or even exceed 80% in this population.

Risk of active tuberculosis in migrants diagnosed with cancer: a retrospective cohort study in British Columbia, Canada

ObjectivesTo describe the association between types of cancer and active tuberculosis (TB) risk in migrants. Additionally, in order to better inform latent TB infection (LTBI) screening protocols, we assessed proportion...

Guidelines on controlling latent tuberculosis infection to support tuberculosis elimination.

Objectives Latent TB infection (LTBI) affects 25% of the world’s population. As long as this reservoir exists, the elimination of TB will not be feasible. The Assembly of the World Health Organization adopted the “Global End TB” strategy for the elimination of TB in 2014. The objective of this review is to present strategies for risk groups that are candidates for the detection and treatment of LTBI.Material and method There is sufficient evidence of screening in: immunocompromised people (HIV-infected, biological therapies, alternative renal therapy, organ transplantation), recent immigrants, inmates in prison, people injecting drugs and homeless people, and workers from at-risk settings. Tests to diagnose LTBI include tuberculin skin test (TST) and gamma release assay interferon (IGRA). There is no reference test and the choice of one or the other will depend on logistical considerations, such as avoiding injection (TST) or not needing a second visit (IGRA). Treatment of LTBI is based on the use of isoniazide and rifampicin in short period of 3 or 4 months, using associations of rifampicin and isoniazide or rifampicin alone.Discussion Given the estimated high prevalence of LTBI, renewed efforts are required to reduce the number of people with LTBI that includes a registration and monitoring system to observer progress, increased testing, and the use of short treatment guidelines.

Completion and Adverse Drug Events of Latent Tuberculosis Infection Treatment in Patients Receiving Dialysis: Predictors and Impacts of Different Regimens in a Prospective Cohort Study.

Although patients with end-stage renal disease receiving maintenance hemodialysis are at high risk for tuberculosis, the optimal treatment regimen for latent tuberculosis infection (LTBI) in this group has scarcely been studied for predictors of completion rate and adverse drug events (ADE). We prospectively enrolled dialysis patients for LTBI intervention from three medical centers in Taiwan. LTBI treatments were 3 months of weekly rifapentine plus isoniazid (3HP) and 9 months of daily isoniazid (9H). Completion rate, ADE, and reasons for treatment termination were recorded. Factors associated with treatment termination and ADE were analyzed using multivariate logistic regression. In all, 91 treatment courses (41 9H and 50 3HP) were surveyed. The completion rates were 61% for 9H and 82% for 3HP (P = 0.046). Use of 9H and development of ADE with a grade of ≥2 (≥grade 2 ADE) were associated with treatment termination. Hypersensitivity occurred in 29.2% of subjects in the 3HP group and 10.8% in the 9H group (P = 0.035) and independently correlated with 3HP regimen, diabetes mellitus (DM), and peritoneal dialysis (PD). Similarly, the independent predictors of ≥grade 2 ADE were use of 3HP regimen, presence of DM, and use of PD, whereas ≥grade 3 ADE were associated with eosinophil counts of >700/mm3 after 2 weeks of LTBI treatment even after adjustment for age and gender. In conclusion, for patients on dialysis, 3HP showed a higher rate of completion but also a higher rate of ≥grade 2 ADE than 9H. In addition, DM and PD were risk factors for ≥grade 2 ADE. Eosinophilia after 2-week treatment might be an alert for severe ADE.

Cost-effectiveness of the latent tuberculosis screening program for migrants in Stockholm Region

IntroductionThe majority of tuberculosis (TB) cases in Sweden occur among migrants from endemic countries through activation of latent tuberculosis infection (LTBI). Sweden has LTBI-screening policies for migrants that have not been previously evaluated. This study aimed to assess the cost-effectiveness of the current screening strategy in Stockholm.MethodsA Markov model was developed to predict the costs and effects of the current LTBI-screening program compared to a scenario of no LTBI screening over a 50-year time horizon. Epidemiological and cost data were obtained from local sources when available. The primary outcomes were incremental cost-effectiveness ratio (ICER) in terms of societal cost per quality-adjusted life year (QALY).ResultsScreening migrants in the age group 13–19 years had the lowest ICER, 300,082 Swedish Kronor (SEK)/QALY, which is considered cost-effective in Sweden. In the age group 20–34, ICER was 714,527 SEK/QALY (moderately cost-effectives) and in all age groups above 34 ICERs were above 1,000,000 SEK/QALY (not cost-effective). ICER decreased with increasing TB incidence in country of origin.ConclusionScreening is cost-effective for young cohorts, mainly between 13 and 19, while cost-effectiveness in age group 20–34 years could be enhanced by focusing on migrants from highest incidence countries and/or by increasing the LTBI treatment initiation rate. Screening is not cost-effective in older cohorts regardless of the country of origin.

Screening for hepatitis B virus infection among refugees diagnosed with latent tuberculosis in an Italian community.

Refugees are a growing population in the EU-27 area with specific health needs that are to be addressed in the most rapid and effective way at their arrival in the host country. Screening for Hepatitis B Virus infection is offered to specific categories and it could be useful and effective to extend its indications. The aim of this study was to define the epidemiological profile regarding Hepatitis B Virus infection in re-fugees hosted in the Asylum Seekers Centers of Verona (Italy), diagnosed with latent tuberculosis infection and eligible for chemoprophylaxis. We conducted a retrospective study in 715 refugees diagnosed with latent tuberculosis infection from January 1st, 2015 to December 31st, 2017. Screening for Hepatitis B Virus infection was offered to la-tent tuberculosis infection patients who were due to commence treatment. Subjects were tested for Hepatitis B surface Antigen and Hepatitis B core antigen total antibodies. None of the screened patients reported previous vaccination for hepatitis B. Among the 715 refugees diagnosed with latent tuberculosis infection, 593 were eligible for treatment for latent tuberculosis infection. Of these, 211 (35.6%) accepted to be screened for Hepatitis B Virus infection. One hundred and ninety-five of the 211 (92.4%) came from African countries, and 16 (7.6%) from Asia; the majority (80.9%) were males. Median age was 23 years (95% CI 22-24). Of the 211, 58 individuals (27.5%) were Hepatitis B surface Antigen and Hepatitis B core antigen total antibodies positive; 74 (35.1%) were Hepatitis B surface Antigen negative and Hepatitis B core antigen total antibodies positive; and 79 (37.4%) were Hepatitis B surface Antigen and Hepatitis B core antigen total antibodies negative. Male gender and African origin were associated with a lower probability of being Hepatitis B surface Antigen- and Hepatitis B core antigen total antibodies-negative. Screening for Hepatitis B Virus is of paramount importance not only for the control and prevention of infection, but also in terms of long-term healthcare issues. Making screening more systematic can have an important impact on public health, while always considering cost-effectiveness and promotion of awareness among ethnic groups in order to gain their compliance to treatment/vaccination.

Tuberculosis: Development of New Drugs and Treatment Regimens

Tuberculosis (TB) still becomes a public health crisis. Drug-resistant TB (DR-TB) becomes a concern as the increasing DR-TB cases in countries with high TB burden. The 2017 World Health Organization (WHO) guideline recommended a combination of TB treatment consisting of 2 months of intensive phase with isoniazid (H), rifampisin (R), pyrazinamid (Z), and ethambutol (E), followed by 4 months of continuation phase with HR daily. WHO has updated DR-TB treatment guidelines several times. In 2016, WHO recommended shorter regimen and individual regimen based on certain conditions. The most updated 2020 WHO guideline recommended the short regimen consisting of all oral drugs as well as changes in the grouping of medicines used in DR-TB regimens in longer/individual regimens. Bedaquiline, delamanid, pretomanid, and sutezolid are new drugs which have been studied for their uses as anti-TB drugs (ATD). Bedaquilin and delamanid, which have passed phase 3 trials, have been approved and recommended by WHO for DR-TB treatment. Repurposed drugs have been used for DR-TB treatment during the time of evaluation of drugs list and regimens for DR-TB treatment. Fluoroquinolones, clofazimine, linezolid, carbapenem, amoxicillin/clavulanic acid are repurposed drugs. TB and DR-TB management will be updated at any time, based on the latest findings in studies, to evaluate and improve the effectiveness of current treatments. Prevention of active TB disease by the treatment of latent TB infection (LTBI) is also a critical component of the end TB strategy by WHO. Therefore, the development of new drugs for the LTBI treatment is also needed.

Tele-TB: Using TeleMedicine to Increase Access to Directly Observed Therapy for Latent Tuberculosis Infection.

Treatment of latent tuberculosis infection (LTBI) decreases risk of progression to active tuberculosis. Traditional treatment regimens required either daily isoniazid for 9 months, with historically poor compliance, or 12-week directly observed therapy (DOT) with isoniazid and rifapentine, with improved compliance but additional challenges of coordinating weekly clinic visits, further complicated if patients must travel a great distance for care. Our referral area is complicated by congested traffic often resulting in one-way commutes, which can exceed 2 hours. These travel times would be prohibitive for conducting weekly in-clinic DOT. In an effort to improve access to DOT, we implemented TeleMedicine LTBI DOT (vDOT) within a military pediatric infectious diseases clinic. Patients aged 24 months or older diagnosed with LTBI were referred for possible enrollment into our vDOT clinic. All patients without contraindications for receiving isoniazid and/or rifapentine were offered LTBI treatment via weekly vDOT or daily treatment with isoniazid or rifampin. The first visit for vDOT patients was performed in person to discuss treatment options, demonstrate use of TeleMedicine software, and ensure the patient was able to take the medications. Baseline information about patients and travel time to our facility was determined. To date, 16 patients have completed LTBI therapy using vDOT. Average one-way travel time to our facility for patients was 51 minutes. Actual time spent in most vDOT encounters was less than 10 minutes. Appointments were arranged to take place outside usual school and work hours so patients could complete vDOT with minimal interruptions to daily life, resulting in 100% treatment compliance and completion. Conducting LTBI DOT using TeleMedicine is a viable and time-saving measure that still allows for high levels of patient compliance and treatment completion while minimizing interruptions to academic and work schedules.

Effects of programmatic interventions to improve the management of latent tuberculosis: a follow up study up to five months after implementation

BackgroundLess than 19% of those needing tuberculosis (TB) preventive treatment complete it, due to losses in several steps of the cascade of care for latent TB infection. A cluster randomized trial of a programmatic public health intervention to improve management of latent TB infection in household contacts was conducted in Rio de Janeiro. Interventions included contact registry, initial and in-service training, and a TB booklet. We conducted a follow-up study starting one month after the conclusion of this trial, to measure the effect of interventions implemented, and to identify remaining barriers and facilitators to latent TB infection treatment, from different perspectives.MethodsIn two health clinics in Rio de Janeiro that received the interventions in the trial, data for the latent TB infection cascade of care for household contacts was collected over a five-month period. The number of household contacts initiating treatment per 100 index-TB patients was compared with the cascade of care data obtained before and during the intervention trial. Semi-structured open-ended questionnaires were administered to healthcare workers, household contacts and index-TB patients regarding knowledge and perceptions about TB and study interventions.ResultsIn this follow-up study, 184 household contacts per 100 index-TB patients were identified. When compared to the intervention period, there were 65 fewer household contacts per 100 index-TB patients, (95% CI -115, − 15) but the number starting latent TB infection treatment was sustained (difference -2, 95% CI -8,5). A total of 31 index-TB patients, 22 household contacts and 19 health care workers were interviewed. Among index-TB patients, 61% said all their household contacts had been tested for latent TB infection. All health care workers said it was very important to test household contacts, and 95% mentioned that possessing correct knowledge on the benefits of latent TB infection treatment was the main facilitator to enable them to recommend this treatment.ConclusionIn this follow-up study, we observed a sustained effect of interventions to strengthen the latent TB infection cascade of care on increasing the number of household contacts starting latent TB infection treatment.

Progress in diagnosis and treatment of latent tuberculosis infection

Progress in diagnosis and treatment of latent tuberculosis infection

Trend and treatment outcomes of latent tuberculosis infection among migrant persons in Japan: retrospective analysis of Japan tuberculosis surveillance data

BackgroundScreening for latent tuberculosis infection (LTBI) among migrant population has become a critical issue for many low tuberculosis (TB) burden countries. Evidence regarding effectiveness of LTBI programs are limited, however, partly because of paucity of national data on treatment outcomes for LTBI. In Japan, notification of LTBI is mandatory, and its treatment outcome is reported as part of Japan’s national TB surveillance system. We thus conducted a detailed analysis of LTBI among foreign-born persons, to update the epidemiological trend of newly notified LTBI between 2007 and 2018, and to examine the treatment regimen and outcome of those notified in 2016 and 2017, focusing specifically on the potential risk factors for lost to follow-up.MethodsWe extracted and analyzed the data of newly notified LTBI patients from the Japan Tuberculosis Surveillance System to examine the overall trend of notification and by age groups and modes of detection between 2007 and 2018, and the cohort data for treatment regimen and outcomes of foreign-born persons notified with LTBI in 2016 and 2017. Trends and proportions were summarized descriptively, and logistic regression analysis was conducted to identify potential risk factors for lost to follow-up. Comparisons were made with the Japan-born patients where appropriate, using chi-squared tests.ResultsBoth the number and proportion of LTBI among foreign-born persons have been constantly increasing, reaching 963 cases in 2018. Cohort analysis of the surveillance data indicated that the proportion of those on shorter regimen was higher among the foreign- than Japan-born patients (5.5% vs. 1.8%, p < 0.001). The proportion of those who have been lost to follow-up and transferred outside of Japan combined was higher among the foreign- than Japan-born patients (12.0% vs, 8.2%, p < 0.001). Risk factors for lost to follow-up were being employed on a temporal basis, and job status unknown (adjusted odds ratios 3.11 and 4.09, 95% confidence intervals 1.34–7.26 and 1.60–10.48, respectively).ConclusionsMigrant population face greater risk of interrupting LTBI treatment, and interventions to improve adherence are a critical component of programmatic management of LTBI. Further studies are needed to explore the cultural and socioeconomic situation in which foreign-born persons undergo LTBI treatment in Japan.

Risk of Tuberculosis Development in Patients with Rheumatoid Arthritis Receiving Targeted Therapy: a Prospective Single Center Cohort Study.

BackgroundPatients with rheumatoid arthritis (RA) undergoing targeted therapy have a higher risk of developing tuberculosis (TB). This requires diagnosis and treatment of latent tuberculosis infection (LTBI). We aimed to evaluate whether diagnosis and treatment of LTBI in RA are effective in Korea, and to estimate the risk of TB development by calculating the incidence rate of active TB among RA patients receiving targeted therapy.MethodsWe analyzed data from two prospective cohort studies of RA patients who received biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase (JAK) inhibitor. We selected new starters of targeted therapy and classified them into three groups receiving tumor necrosis factor (TNF) inhibitor, non-TNF inhibitor, and JAK inhibitor, respectively. We then compared LTBI prevalence, treatments, and active TB incidence during first-line therapy in each group.ResultsA total of 765 RA patients (574 TNF inhibitor users, 132 non-TNF inhibitor users, and 59 JAK inhibitor users) were included in this study. Observation periods were 1,255.2 person-years (PYs), 264.7 PYs, and 53.3 PYs, respectively. All 765 patients underwent LTBI screening, and the positivity rate was 26.5% (n = 203). Of the 203 LTBI-positive patients, 189 (93.1%) received treatment. Only one patient, who was in the TNF inhibitor group, and was negative for the interferon gamma release assay (IGRA), did not receive LTBI treatment and developed active TB during follow-up.ConclusionAlthough the prevalence of LTBI in RA patients who started targeted therapy was slightly elevated, the Korean guidelines specifying LTBI screening and treatment were effective in preventing latent TB from becoming active.

Latent TB Infection in USSOF: A Refresher and Update

Tuberculosis (TB) causes approximately 2 million deaths annually worldwide, with 2 billion persons estimated to be actively infected with TB. While rates of active TB disease in the US military are low, military service in TB-endemic countries remains an uncommon, but important source of infection. United States Special Operations Forces (USSOF) and enablers often operate in TB-endemic countries and, as an inherent risk of their mission sets, are more likely to have high-risk exposure to TB disease. Military medical authorities have provided excellent diagnostic guidance; the Centers for Disease Control and Prevention (CDC) recently updated preferred regimens for the treatment of latent TB infection (LTBI). This review serves as a refresher and update to the management of LTBI in USSOF to optimize medical readiness through targeted testing and short treatment regimens.

1643. A scoping review of pediatric latent tuberculosis care cascades: Initial steps are lacking

BackgroundEach year an estimated 1 million children develop and ~200,000 die from tuberculosis (TB). The WHO has named identification and treatment of latent tuberculosis infection (LTBI) one of the cornerstones of efforts to eliminate TB by 2030. Identification and treatment of pediatric LTBI requires completion of a complex care cascade. While attention has been given to LTBI care cascades in adults, to date there has been no attempt to map literature on the pediatric LTBI care cascade.Facilitators and barriers to retention in steps of the pediatric LTBI care cascadeMethodsWe systematically searched PubMed, CINAHL, Cochrane and Embase databases for papers and abstracts describing screening, diagnosis, and treatment of pediatric LTBI. We categorized literature using seven step-offs in the pediatric LTBI care cascade, extrapolated from prior studies focused on adults: 1) intention to screen to initial test, 2) initial test to receipt of results, 3) receipt to referral for evaluation, 4) referral to completion of evaluation, 5) completion to treatment recommendation, 6) recommendation to treatment acceptance/initiation, and 7) initiation to treatment completion. Our aim was to assess factors that facilitated and inhibited completion of each cascade step, and to identify knowledge gaps in this literature.ResultsWe identified 137 studies that met inclusion criteria. Most studies described multiple step-offs in the care cascade, although the focus of most (120/137 studies) was on initiation and completion of LTBI therapy (the final step in the care cascade). Several effective strategies to improve medication adherence were described, including selective use of nursing visits, directly observed therapy, shorter treatment regimens, and peer counseling. Reports of facilitators and barriers for retention in upstream step-offs in the cascade were scarce, revealing a lack of published evidence for how to retain children from pre-screening to treatment initiation (Table). ConclusionWhile existing literature describes LTBI treatment initiation and completion in children, our analysis reveals a lack of data guiding retention of children from LTBI screening through treatment initiation. This review highlights the need to further understand early steps of the care cascade, in order to help alleviate the burden of TB in children.DisclosuresJessica Haberer, MD, MS, Merck (Consultant)

1665. Using Electronic Health Records to Describe TB in Community Health Settings: a Cohort Analysis in a Large Safety-Net Population

BackgroundOver 80% of tuberculosis (TB) cases in the United States are attributed to reactivation of latent TB infection (LTBI). Eliminating TB in the United States requires expanding identification and treatment of LTBI. Centralized electronic health records (EHRs) are an unexplored data source to identify persons with LTBI. We explored EHR data to evaluate TB and LTBI screening and diagnoses within OCHIN, Inc., a U.S. practice-based research network with a high proportion of Federally Qualified Health Centers.MethodsFrom the EHRs of patients who had an encounter at an OCHIN member clinic between January 1, 2012 and December 31, 2016, we extracted demographic variables, TB risk factors, TB screening tests, International Classification of Diseases (ICD) 9 and 10 codes, and treatment regimens. Based on test results, ICD codes, and treatment regimens, we developed a novel algorithm to classify patient records into LTBI categories: definite, probable or possible. We used multivariable logistic regression, with a referent group of all cohort patients not classified as having LTBI or TB, to identify associations between TB risk factors and LTBI.ResultsAmong 2,190,686 patients, 6.9% (n=151,195) had a TB screening test; among those, 8% tested positive. Non-U.S. –born or non-English–speaking persons comprised 24% of our cohort; 11% were tested for TB infection, and 14% had a positive test. Risk factors in the multivariable model significantly associated with being classified as having LTBI included preferring non-English language (adjusted odds ratio [aOR] 4.20, 95% confidence interval [CI] 4.09–4.32); non-Hispanic Asian (aOR 5.17, 95% CI 4.94–5.40), non-Hispanic black (aOR 3.02, 95% CI 2.91–3.13), or Native Hawaiian/other Pacific Islander (aOR 3.35, 95% CI 2.92–3.84) race; and HIV infection (aOR 3.09, 95% CI 2.84–3.35).ConclusionThis study demonstrates the utility of EHR data for understanding TB screening practices and as an important data source that can be used to enhance public health surveillance of LTBI prevalence. Increasing screening among high-risk populations remains an important step toward eliminating TB in the United States. These results underscore the importance of offering TB screening in non-U.S.–born populations.Disclosures All Authors: No reported disclosures

1651. Describing the Tuberculosis Infection Cascade of Care Based on Electronic Health Record Data

BackgroundAppropriate screening of individuals to detect latent tuberculosis infection (LTBI) is a critical step for achieving tuberculosis (TB) elimination in the US; >80% of TB cases are attributed to LTBI reactivation. TB infection testing and treatment must engage community health clinics where populations at risk seek care. However, there are significant data knowledge gaps in the current LTBI cascade of care (CoC) in this setting. We used an electronic health record (EHR) database from OCHIN, Inc., to characterize the LTBI CoC and identify potential future interventions.MethodsWe extracted a cohort of patients from 2012–2016 EHR data; we stratified by whether patients were at risk for TB based on meeting at least one of the following criteria: non-US born or non-English language preference, homelessness, encounter at correctional facility, history of close contact with a TB case, or being immunocompromised. Along each step of the LTBI CoC, we determined the proportions with a test for TB infection, with available test results, with a positive test, with an LTBI diagnosis, and with LTBI treatment prescribed. We used Χ 2 tests to compare the LTBI CoCs among patients at risk with those classified as not at risk.ResultsOf nearly 2.2 million patient records, 701,467 (32.0%) met criteria for being at risk for TB; 84,422 at risk (12.0%) were tested; 65,562 (77.7%) had available results, of whom 9,624 (14.7%) were positive. Among those with positive results, 6,958 (72.3%) had an LTBI diagnosis, of whom 1,732 (24.9%) were prescribed treatment. Among those classified as not at risk, fewer were tested (66,773 [4.5%], p< 0.001) and had positive results (2,500 [3.7%], p< 0.0001). Among those with positive results, 1,998 (80.0%) had an LTBI diagnosis, of whom 395 (19.8%) initiated treatment.ConclusionThis study highlights gaps in the LTBI CoC, and where interventions are most needed. The largest gaps were in testing patients at risk, as 88% were not tested, and treatment, as 75% diagnosed with LTBI were not treated. Just under half (44%) of all TB tests appeared to be performed in persons with little risk for TB; this is a substantial amount of testing given very few begin treatment. Resources could be redirected to increase screening and treatment among populations at risk.Disclosures All Authors: No reported disclosures

The contribution of stigma to the transmission and treatment of tuberculosis in a hyperendemic indigenous population in Brazil

BackgroundThe Guarani-Kaiowá are Brazil's second-largest indigenous group. Average annual tuberculosis (TB) incidence rates among the Guarani-Kaiowá are nearly 400/100,000 in Mato Grosso do Sul state, ten times the national average. Although stigma is considered crucial for TB control in indigenous communities, few studies have investigated TB stigma among indigenous populations. This study sought to understand the role of TB-related stigma and perceptions of TB in maintaining hyperendemic TB transmission in the Guarani-Kaiowá communities.MethodsVarious forms of stigma were explored through semi-structured interviews with 19 patients, 11 relatives, and 23 community members. Patients were identified from the registry of the healthcare service. Community members, selected by snowball sampling, were matched by gender and village of residence. Interviews were conducted in Guarani and Portuguese and later translated into English. Framework analysis was performed using NVivo.ResultsTraditional beliefs of a weakening of the body allowing the disease to enter were common, but the exact mechanism of transmission was unknown. Strong community/public stigma associated TB with uncleanliness, abuse, and irresponsibility. Anticipated stigma led to significant treatment delays for fear of exclusion and losing employment. While most patients felt supported by their families, nearly all patients related experienced/enacted stigma in the community such as gossip, avoidance, and social exclusion, leading to long-lasting internalized/self-stigma. Secondary stigmatization of relatives was widespread, and blanket latent TB infection (LTBI) treatment of patients’ households was a contributing factor in treatment delay. The healthcare service unnecessarily added to stigmatization by enforcing separate utensils and sleeping arrangements for patients.ConclusionsOur findings suggest that stigma is a driver for treatment delay and continued transmission of TB in the community. The stigmatization of TB was rooted in a poor understanding of TB transmission, partly because of incorrect orientation by the healthcare service. Interventions to reduce TB-associated stigma are urgently needed.

Interferon gamma release assay tests are associated with persistence and completion of latent tuberculosis infection treatment in the United States: Evidence from commercial insurance data.

Risk-targeted testing and treatment of latent tuberculosis infection (LTBI) is a critical component of the United States' (US) tuberculosis (TB) elimination strategy, but relatively low treatment completion rates remain a challenge. Both treatment persistence and completion may be facilitated by diagnosing LTBI using interferon gamma release assays (IGRA) rather than tuberculin skin tests (TST). We used a national sample of administrative claims data to explore associations diagnostic test choice (TST, IGRA, TST with subsequent IGRA) and treatment persistence and completion in persons initiating a daily dose isoniazid LTBI treatment regimen in the US private healthcare sector between July 2011 and March 2014. Associations were analyzed with a generalized ordered logit model (completion) and a negative binomial regression model (persistence). Of 662 persons initiating treatment, 327 (49.4%) completed at least the 6-month regimen and 173 (26.1%) completed the 9-month regimen; 129 (19.5%) persisted in treatment one month or less. Six-month completion was least likely in persons receiving a TST (42.2%) relative to persons receiving an IGRA (55.0%) or TST then IGRA (67.2%; p = 0.001). Those receiving an IGRA or a TST followed by an IGRA had higher odds of completion compared to those receiving a TST (aOR = 1.59 and 2.50; p = 0.017 and 0.001, respectively). Receiving an IGRA or a TST and subsequent IGRA was associated with increased treatment persistence relative to TST (aIRR = 1.14 and 1.25; p = 0.027 and 0.009, respectively). IGRA use is significantly associated with both higher levels of LTBI treatment completion and treatment persistence. These differences are apparent both when IGRAs alone were administered and when IGRAs were administered subsequent to a TST. Our results suggest that IGRAs contribute to more effective LTBI treatment and consequently individual and population protections against TB.

Tuberculosis screening and management of latent tuberculosis infection prior to biologic treatment in patients with immune-mediated inflammatory diseases: A longitudinal population-based analysis using claims data.

Background and AimScreening for tuberculosis before treating with biologic agents is recommended in patients with immune‐mediated inflammatory diseases (IMIDs). We conducted this study to identify adherence to the recommended practice in a real‐world setting in Japan.MethodsWe used a community‐based insurance claims database in a city in the Greater Tokyo Area in Japan. Between July 2012 and January 2019, we enrolled patients with IMIDs in the age range 15 to 74 years who had initiated biologic therapy. Tuberculosis screening was defined as (a) interferon‐γ release assay and/or a tuberculin skin test (IGRA/TST) and (b) IGRA/TST and X‐ray and/or CT scan (X‐ray/CT) within 2 months before starting biologic agents. We analyzed the proportions of patients who underwent tuberculosis screening and their association with the patient‐ and treatment‐related factors and treatment for latent tuberculosis infection (LTBI).ResultsOf 421 patients presumed to have initiated biologic therapy, 202 (48%) underwent IGRA/TST and 169 (40%) underwent IGRA/TST and X‐ray/CT. Patients aged 65 to 74 years were more likely to undergo tuberculosis screening than those aged 45 to 64 years. Compared to infliximab, IGRA/TST was less frequently performed in patients treated with etanercept, adalimumab, golimumab, abatacept, and tocilizumab. Treatment for LTBI was provided to 67 (16%) patients. Proportions of patients receiving LTBI treatment did not significantly differ according to the screening status.ConclusionThere was low adherence to the recommendations for tuberculosis screening and prophylactic treatment before biologic therapy. It is necessary to continue alerting clinical practitioners to the importance of screening for tuberculosis and treatment for LTBI.