Treatment Of Latent Tuberculosis Infection Research Articles

Contact investigation in healthcare personnel exposed to pediatric patients with pulmonary tuberculosis at the pediatric ward, Vajira hospital, Thailand

BackgroundTuberculosis (TB) is an important public health problem, and airborne transmission is easily transmitted. Latent TB infection (LTBI) detection and treatment is the key strategy to prevent TB. ObjectiveThis study aimed to perform contact investigation of LTBI in healthcare personnel (HCPS) working with pediatric patients with active pulmonary TB and report the side effects of 12-week-isoniazid and rifapentine (3HP). MethodsThis contact investigation reviewed HCPS who were in close contact with pediatric pulmonary TB. Close contact with pulmonary TB is defined as contact for 8 h per day and 120 h per month, or contact in poor air ventilation spaces. HCPS who participated in this study were tested for the active TB and LTBI by history using physical examination, chest X-ray, and tested with interferon-gamma releasing assays (IGRAs). LTBI is defined as a positive IGRA without any evidence of active TB. ResultsA total of 82 HCPS, including 39 nurses (47%), 13 nursing assistance (16%), 12 pediatrician doctors (15%), 12 pediatric residents (15%), and 6 medical students (7%) had close contact with pediatric pulmonary TB. Of the total, 75 HCPS were women, and the mean age and standard deviation was 33 ± 10.4 years. IGRAs revealed positive results in 14 (17%) HCPS who were diagnosed with LTBI and treated with 3HP, of whom, 12 (86%) completed the LTBI treatment, but 2 discontinued the treatment due to the side effects of 3HP. No serious adverse events from 3HP were reported. The most reported side effect of 3HP was nausea and vomiting, occurring in 50% of the HCPS. No diagnosis of TB was seen after 1-year follow-up. ConclusionThis contact investigation in HCPS of the pediatric ward revealed a large number of LTBI. The LTBI treatment with 3HP showed favorable outcomes and showed minor side effects. Therefore, 3HP was preferred to treat LTBI.

Latent tuberculosis infection in liver transplant patients: a review.

Latent tuberculosis infection in liver transplant patients: a review.

LACTOFERRIN – A ROLE IN THE PROTECTIVE FUNCTIONS IN ADOLESCENTS WITH LATENT TUBERCULOSIS INFECTION

When evaluating the role of lactoferrin to improve the effectiveness of preventive treatment of latent tuberculosis infection in adolescents, it was found that the prescriptions of Lactoferrin imun + Colostrum contributed to a significantly more pronounced decrease in the frequency of hyperergic reactions in test with tuberculosis recombinant allergen (from 51.3% to 12.5% in the main group, from 50.7 % to 33.3% in the comparison group, p < 0.05), a decrease in the average size of the papule (from 17.6 mm to 8.2 mm in the main group and from 17.1 to 14.5 mm in the comparison group, p < 0.05). In patients of the main group, the restoration of free radical oxidation and antioxidant protection indicators to the level of healthy donors was established, while in the comparison group, the intensity of blood plasma chemiluminescence and the activity of myeloperoxidase in neutrophils remained elevated, while the activity of catalase and superoxidedismutase remained reduced. The level of lactoferrin during treatment in the main group increased to normal values (740 ng/ml, 95%CI 702.2-777.8), and in the control group remained reduced (440 ng/ml, 95%CI 411.5-478.5), p < 0.05. At the same time, the continuing level of positive reactions to tuberculosis recombinant allergen (Diaskintest®) against the background of normalization of the lactoferrin level indicates the high diagnostic capabilities of Diaskintest® to detect LTBI in adolescents

Contact Investigations With a Single Tuberculin Skin Test on Infants Exposed to Tuberculosis in a Postpartum Care Center During the Neonatal Period.

Tuberculosis (TB) exposure in congregate settings related to neonates is a serious medical and social issue. TB exposure happens during the neonatal period, but contact investigations for exposed infants are usually conducted after the neonatal period. Generally, recommendations for screening and managing close contact are different for neonates and children. Thus, there are challenges in contact investigations. We aimed to report contact investigations with a single tuberculin skin test (TST) on infants exposed to infectious TB in a postpartum care center. The index case was a healthcare worker with active pulmonary TB: sputum acid-fast bacilli smear negative, culture positive, and no cavitary lesion. All exposed infants underwent medical examinations and chest X-ray. After TB disease was ruled out, contacts received window period prophylaxis with isoniazid (INH) until three months after the last exposure. TST was performed only once after completing the prophylaxis. A total of 288 infants were selected as high-priority contacts. At the initial contact investigation, the age of infants ranged from 8 to 114 days. None of these exposed infants had TB disease. The prevalence of latent TB infection (LTBI) was 25.3% (73/288; 95% confidence interval [CI], 20.7-30.7). There were no serious adverse events related to the window period prophylaxis or LTBI treatment with INH. During the 1-year follow-up period, no infants progressed to overt TB disease. The size of TST induration in infants vaccinated with percutaneous Bacillus Calmette-Guérin (BCG) vaccine was significantly larger than that of infants vaccinated with intradermal BCG vaccine (median, 8 mm vs. 5 mm; P = 0.002). In multiple logistic regression analysis, independent factors associated with TST positivity (≥ 10 mm induration) were male (adjusted odds ratio [aOR], 2.98; 95% CI, 1.6-5.64), percutaneous BCG vaccination (aOR, 3.30; 95% CI, 1.75-6.48), TST reading between 60 and 72 hours after injecting purified protein derivative (aOR, 2.87; 95% CI, 1.53-5.49), and INH prophylaxis more than four weeks (aOR, 0.49; 95% CI, 0.25-0.94). A single TST at three months after the last TB exposure with INH prophylaxis could be used as a main protocol in contact investigations for infants exposed to infectious TB during the neonatal period in congregate settings in Korea.

Avaliação de tuberculose latente em adolescentes e adultos jovens vivendo com o vírus da imunodeficiência humana em um serviço de referência no Brasil

To avoid the occurrence of tuberculosis reactivation in people living with HIV (PLHIV) who have latent tuberculosis infection (LTBI), the therapeutical indications to this population were expanded in Brazil in 2018, with the recommendation of treatment for those with CD4 T lymphocyte count less than or equal to 350 cells/mm3, regardless of the result of the tuberculin test (TT). To evaluate the practical application of this recommendation, we decided to determine the prevalence of LTBI in PLHIV followed in our outpatient clinic. Ninety-nine adolescents and young adults living with HIV accompanied in a Reference Service were evaluated for the occurrence of LTBI with TT and TCD4 cell count application. The prevalence of LTBI was estimated at 7.1% considering the result of TT, and 18% when considering patients with CD4 lymphocyte count less than or equal to 350 cells/mm3. This difference reinforces the idea that the detection of patients with TCD4 lymphocytes less than or equal to 350 cells/mm3 effectively expands the indication for treatment of LTBI. However, only 4 (22.2%) of 18 patients with TCD4 less than or equal to 350 cells/mm3 adhered to the therapeutic proposal. The rebellious aspect inherent to this population, the failure to attend consultations and the refusal to use another drug were some of the reasons for the low adherence to treatment.

The cascade of care in testing and treatment of latent tuberculosis infection in liver transplant candidates.

Testing and treatment for latent tuberculosis infection (LTBI) can mitigate risk of active tuberculosis (TB) post-liver transplant (LT). Testing and treatment completion rates have been reported low in this population. Our study aims to quantify the proportion of LT candidates who completed LTBI care cascade in our center. A retrospective chart review was conducted on LT candidates from 2012 to 2021. Primary outcome was the proportion of patients who completed each cascade stage. Secondary outcome was an analysis of factors associated with positive and indeterminate LTBI testing. Of the 273 LT candidates, 265 (97.1%) were referred to transplant infectious disease (TID), 264 (96.7%) had orders for interferon-gamma release assay (IGRA), 262 (96%) underwent TID evaluation, and 259 (94.9%) completed IGRA. Twenty had LTBI, and 18 were treatment naïve and recommended for treatment. Of the 18, 15 (83.3%) agreed to therapy, 14 (77.8%) initiated treatment, and 12 (66.7%) completed treatment. No posttransplant TB reactivation occurred. Patients born in Asia, previous incarceration, past military service, and granuloma findings on chest imaging were likely to have positive IGRA (p<.05). Older age and travel to TB-endemic countries were likely to have indeterminate IGRA (p<.05). Indeterminate IGRAs were more common in QuantiFERON (QTF)-Gold Plus TB (15.3%) versus QTF-Gold TB (9.3%, p<.001). High rates of LTBI testing and treatment initiation and completion can be attributed to a standardized process that includes TID evaluation. Future studies in larger cohort are needed to better understand factors that can optimize the completion rates of LTBI treatment in LT candidates.

1441. LTBI screening cascade for non-US-born persons in a large health system assessed using EMR data

Abstract Background The majority of tuberculosis (TB) diagnosed in the US is reactivation TB in non-US-born (nUSb) persons. Guidelines recommend screening persons born in high TB burden countries for latent TB infection (LTBI) and treating if positive. We evaluated the LTBI cascade in primary care among nUSb persons in a large academic medical system in Washington State. Methods We used electronic medical record (EMR) data to evaluate the LTBI screening cascade. nUSb individuals were identified using the primary language recorded in the EMR. Place of birth is not routinely collected in the EMR. All persons with a non-English primary language who entered care and attended one or more primary care visits in UW clinics between April 2016- April2021 were identified and considered eligible for LTBI screening. Persons with a documented IGRA or tuberculin skin test were considered screened for LTBI. Prescription records were reviewed to determine LTBI treatment. Results 5148 persons with non-English primary language attended primary care visits 2016-2021 and considered eligible for LTBI screening. Eligible persons were 58.5% female, median age 41 (IQR 30-58). Primary WHO regions of origin were Asia (37%), the Americas (36%), and Africa (19%), with a minority from North Africa, Middle East, and Europe. 1012 (20%) had a documented history of LTBI testing (Quantiferon-GOLD (N=949) or tuberculin skin testing (N=63)). Among 296 (29%) persons with a positive test for LTBI, 140 (47%) were treated for LTBI. The highest proportion of persons tested for LTBI were patients attending the HIV clinic (120, 66%) and the International/Refugee clinic (227, 81%). The majority of eligible patients were seen outside these clinics (N=4687) in whom the percent of persons tested ranged from 3-18% (14% overall). LTBI cascade among non-US-born primary care patients IGRA: interferon-gamma release assay; TST: tuberculin skin test. Conclusion Although this subset underestimates the number of non-US-born individuals (since many non-US-born individuals use English as their primary language) eligible for screening, it nonetheless highlights the significant gap between actual and guideline-recommended screening in primary care, as well as further drop-off on the cascade from positive LTBI test to LTBI treatment. EMR platforms could be leveraged to prompt LTBI screening and treatment initiations in primary care to help achieve TB elimination goals in the US. Disclosures Adrienne E. Shapiro, MD, PhD, Vir Biotechnology: Support as a trial site paid to my institution and non-financial support for medical writing GlaxoSmithKline third party funding to Vir support H. Nina Kim, MD, MSc, Gilead Sciences: Grant/Research Support.

1439. Latent tuberculosis infection treatment location and association with care completion

Abstract Background Location and type of clinic where pediatric latent TB infection (LTBI) care is provided are associated with treatment completion and retention in care. Prior research has not evaluated joint clinical management occurring between care settings. Understanding care transfer dynamics and accessibility of clinics can inform pediatric LTBI care service delivery. Methods We conducted a retrospective cohort study of LTBI in children 0-17 years old who were prescribed outpatient treatment in two Boston-area health systems from 2017-2019. We defined “initial clinical setting” (categorized as primary care or TB/infectious diseases clinic) as the location where the first LTBI medication was prescribed. Through chart review, we determined if care was transferred to a different (“final”) clinic setting during treatment. We calculated driving time between a child’s home address and initial and final treatment clinics. The primary outcome was frequency of care transfer after starting treatment. In a secondary analysis, we used two multivariable logistic regression models (adjusted for age, sex, and use of rifamycin-based treatment) to evaluate associations between completion and distance to and type of initial and final treatment clinic. Results We identified 142 children who started LTBI treatment as outpatients; 110 started treatment in primary care clinics and 32 in TB/infectious diseases clinics. Overall, 20/142 (14%) transferred TB care to a different clinic after starting treatment. A total of 101/142 (71%) patients completed treatment. Neither initial treatment location nor driving time to initial clinic were significantly associated with treatment completion (Table 1). However, final treatment in a TB clinic was associated with higher odds of treatment completion than final treatment in a primary care clinic (aOR 2.71 [95%CI 1.06-6.91], P=0.04); time to clinic was not associated with completion (Table 2). Figure 1.Patient transfers after starting LTBI treatment.Table 1.Initial treatment location: Univariable and multivariable analysis of factors associated with treatment completion.1Adjusted for time to clinic and location of initial treatment as well as age, sex, and use of rifamycin-based treatment.Table 2.Final treatment location: Univariable and multivariable analysis of factors associated with treatment completion.1Adjusted for time to clinic and location of final treatment as well as age, sex, and use of rifamycin-based treatment. Conclusion Among children with LTBI in a large metropolitan area, more patients received treatment in primary care clinics than in TB clinics. Care transfers were relatively uncommon after starting treatment. A TB clinic as a final treatment location was associated with increased odds of treatment completion. Disclosures Jessica Haberer, MD, MS, Merck: Advisor/Consultant|Natera: Stocks/Bonds.

B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection.

Latent tuberculosis infection (LTBI) treatment is known to accelerate the decline in TB incidence, especially in high-risk populations. Mycobacterium tuberculosis (M. tb) expression profiles differ at different growth periods, and vaccines protective and therapeutic effects may increase when they include antigenic compositions from different periods. To develop a post-exposure vaccine that targets LTBI, we constructed four therapeutic DNA vaccines (A39, B37, B31, and B21) using different combinations of antigens from the proliferation phase (Ag85A, Ag85B), PE/PPE family (Rv3425), and latent phase (Rv2029c, Rv1813c, Rv1738). We compared the immunogenicity of the four DNA vaccines in C57BL/6j mice. The B21 vaccine stimulated the strongest cellular immune responses, namely Th1/Th17 and CD8+ cytotoxic T lymphocyte responses. It also induced the generation of strengthened effector memory and central memory T cells. In latently infected mice, the B21 vaccine significantly reduced bacterial loads in the spleens and lungs and decreased lung pathology. In conclusion, the B21 DNA vaccine can enhance T cell responses and control the reactivation of LTBI.

Practices and attitudes towards tuberculosis and latent tuberculosis infection screening in people living with HIV/AIDS among HIV physicians in Japan

BackgroundTuberculosis (TB) continues to be the leading cause of death for people living with HIV/AIDS (PLHIV), and HIV is the strongest known risk factor for progression to active TB disease for persons with latent TB infection (LTBI). Screening for active TB and LTBI, and TB preventive therapy (TPT) is recommended, however, clinical practices regarding LTBI screening for HIV positive population have not been uniform, resulting in low rates of LTBI screening and TPT uptake, in both low and high TB-burden countries. We sought to explore the practices and attitudes towards TB and LTBI screening in PLHIV among HIV physicians in Japan.MethodsWe conducted a cross-sectional survey whereby an on-line questionnaire was administered to physicians who are currently, or have the experience of, providing care and treatment for PLHIV in Japan.ResultsThe questionnaire was sent to a total of 83 physicians, of which 59 responded (response rate; 71.1%). 52.5% (31/59) conducted routine screening and 44.0% (26/59) conducted selectively screening for active TB among HIV/AIDS patients. As for LTBI, 54.2% (32/59) conducted routine screening and 35.6% (21/59) conducted selective screening for LTBI among PLHIV. “T-SPOT only” was the most frequently used method of screening (n = 33), followed by “QFT only” (n = 11). Criteria for LTBI screening included TB burden in the country of birth of the patient, previous contact with a TB patient, and CD4+ cell count. 83.1% (49/59) either “always” or “selectively” offered TPT to PLHIV diagnosed with LTBI, and among the 49 respondents who did provide TPT, 77.6% (38/49) chose 9-months isoniazid as their first choice. None chose regimen including rifampicin.ConclusionsOur study revealed that practices regarding TB and LTBI screening and treatment for PLHIV among HIV physicians were mixed and not necessarily in accordance with the various published guidelines. Building and disseminating scientific evidence that takes into consideration the local epidemiology of TB and HIV in Japan is urgently needed to assist physicians make decisions.

Using the Food and Drug Administration´s Sentinel System for surveillance of TB infection.

BACKGROUND: We examined patterns in care for individuals treated for latent TB infection (LTBI) in the US Food and Drug Administration´s Sentinel System.METHODS: Using administrative claims data, we identified patients who filled standard LTBI treatment prescriptions during 2008-2019. In these cohorts, we assessed LTBI testing, clinical management, and treatment duration.RESULTS: Among 113,338 patients who filled LTBI prescriptions, 80% (90,377) received isoniazid (INH) only, 19% (21,235) rifampin (RIF) only, and 2% (1,726) INH + rifapentine (RPT). By regimen, the proportion of patients with documented prior testing for TBI was 79%, 54%, and 91%, respectively. Median therapy duration was 84 days (IQR 35-84) for the 3-month once-weekly INH + RPT regimen, 60 days (IQR 30-100) for the 6- to 9-month INH regimen, and 30 days (IQR 2-60) for the 4-month RIF regimen.CONCLUSIONS: Among the cohorts, INH-only was the most commonly prescribed LTBI treatment. Most persons who filled a prescription for LTBI treatment did not have evidence of completing recommended treatment duration. These data further support preferential use of shorter-course regimens such as INH + RPT.

Expert consensus on diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases

Rheumatic diseases, a typical kind of autoimmune disease, are often treated with glucocorticoids, immunosuppressants, biological agents, and small-molecule targeted drugs, which often leads to immune dysfunction in patients and increases the risk of activation of latent tuberculosis infection. To regulate the screening, diagnosis, and prophylactic treatment of latent tuberculosis infection in patients with rheumatic diseases, reduce the risk of developing active tuberculosis and improve the prognosis, Peking University Shenzhen Hospital, Shenzhen Third People's Hospital and Peking Union Medical College Hospital jointly organized domestic experts in the field of rheumatology and tuberculosis to establish the expert consensus on the diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases. This consensus focuses on epidemiology, the importance of screening, screening methods, and prophylactic anti-tuberculosis treatment strategies for latent tuberculosis infection combined with rheumatic diseases.

Progress on diagnosis and treatment of latent tuberculosis infection.

One fourth of the global population has been infected with Mycobacterium tuberculosis, and about 5%-10% of the infected individuals with latent tuberculosis infection (LTBI) will convert to active tuberculosis (ATB). Correct diagnosis and treatment of LTBI are important in ending the tuberculosis epidemic. Current methods for diagnosing LTBI, such as tuberculin skin test (TST) and interferon-γ release assay (IGRA), have limitations. Some novel biomarkers, such as transcriptome derived host genes in peripheral blood cells, will help to distinguish LTBI from ATB. More emphasis should be placed on surveillance in high-risk groups, including patients with HIV infection, those using biological agents, organ transplant recipients and those in close contact with ATB patients. For those with LTBI, treatment should be based on the risk of progression to ATB and the potential benefit. Prophylactic LTBI regimens include isoniazid monotherapy for 6 or 9 months, rifampicin monotherapy for 4 months, weekly rifapentine plus isoniazid for 3 months (3HP regimen) and daily rifampicin plus isoniazid for 3 months (3HR regimen). The success of the one month rifapentine plus isoniazid daily regimen (1HP regimen) suggests the feasibility of an ultra-short treatment strategy although its efficacy needs further assessment. Prophylactic treatment of LTBI in close contact with MDR-TB patients is another challenge, and the regimens include new anti-tuberculosis drugs such as bedaquiline, delamanid, fluoroquinolone and their combinations, which should be carefully evaluated. This article summarizes the current status of diagnosis and treatment of LTBI and its future development direction.

“It’s too hard” – the management of latent TB in under-served populations in the UK: a qualitative study

BackgroundUK national guidance recommends systematic screening for latent tuberculosis infection (LTBI) in under-served populations, including people experiencing homelessness and people who use drugs. This is not routinely implemented in the UK, and the reasons for this policy-practice mismatch remain underexplored.MethodsSemi-structured qualitative interviews were conducted with 19 healthcare professionals from across the UK. Participants were recruited using purposive sampling and snowballing, identifying individuals with excellent knowledge of their regions practice and policy of LTBI management. The interviews were conducted online, and were audio recorded, with transcripts thematically analysed using a two-stage inductive coding process to explore perceived barriers and enablers to LTBI screening.ResultsMost participants had previous experience managing LTBI in under-served populations, but none were conducting systematic screening as per national guidance. We identified service provision challenges and low prioritisation of LTBI as the key explanatory themes driving this policy-practice mismatch. Lack of resource, and the complexity of clinical decision making were two key service level barriers. System and service inertia, and lack of cost effectiveness evidence led to LTBI being deprioritised. Service integration and promotion of WHO targets for TB elimination were highlighted as potential solutions.ConclusionIntegrating LTBI testing and treatment with existing health services for under-served populations could improve feasibility and efficacy. Promotion of UK TB elimination goals and generation of regional evidence to support commissioning for LTBI care is vital. Without such a multi-pronged approach inertia is likely to persist and the zeitgeist will remain: “it’s too hard”.

Determinants of latent tuberculosis infection and treatment interruption in long-term care facilities: A retrospective cohort study in Taiwan.

Latent tuberculosis infection (LTBI) treatment is challenging in long-term care facilities (LTCFs) residents due to the occurrence of medical complexities. However, factors associated with treatment interruption have not been extensively studied. This retrospective cohort study aimed to determine LTBI-associated factors and treatment interruption in LTCF residents and employees in Taiwan. From May 2017 through September 2020, the residents and employees of 20 LTCFs in Taipei, Taiwan, were screened for LTBI by using QuantiFERON-TB Gold In-Tube test. The LTBI individuals underwent directly observed preventive therapy (DOPT), including regimens of 9-month daily isoniazid (9H) and 3-month weekly isoniazid plus rifapentine (3HP). All the LTBI cases were followed up till treatment completion, death, or treatment interruption. Among 2207 LTCF subjects, 16.8% had LTBI. After controlling for other covariates, residents of public facilities had a significantly higher LTBI prevalence than those of private facilities (adjusted odds ratio [AOR]=1.43; 95% confidence interval [CI]: 1.08-1.88). Among 264 LTBI cases receiving preventive therapy, 52 (19.7%) had treatment interruption. LTBI cases receiving 3HP were less likely to have treatment interruption than those receiving 9H (AOR=0.22; 95% CI: 0.07-0.71). LTCF residents, particular those living in public facilities, had a high LTBI prevalence. 3HP with DOPT is considered the priority regimen for preventive therapy among LTBI cases in LTCFs.

Algorithms for Screening for Active Tuberculosis among Individuals with Latent Tuberculosis Infection in a Rural Community in China.

Screening for active tuberculosis (TB) among individuals with latent tuberculosis infection (LTBI) is important for the initiation and evaluation of TB preventive treatment. The performances of different tools and their combinations had rarely been studied in community-level screening among individuals with LTBI in China. This study aimed to explore appropriate algorithms for screening for active TB among individuals with LTBI in rural China. Three sputum samples were collected from each participant for smear microscopy, culture, and an Xpert MTB/RIF assay. Chest digital radiography and TB symptoms were investigated as well. The performances of different testing algorithms were compared with that of sputum culture as the gold standard. Overall, 1,564 study participants with LTBI were investigated, with a final diagnosis of 20 TB cases by sputum culture. Compared with other tests, the Xpert MTB/RIF assay detected 80.00% (95% confidence interval [CI], 58.40% to 91.93%) of culture-positive cases, with the highest sensitivity. When tests were combined using "or," "and," or "step" algorithms, the highest sensitivity reached 90.00% (95% CI, 69.90% to 97.21%) for the combination of the Xpert MTB/RIF assay and chest radiography, but the positive predictive value (PPV) decreased to 22.22% (95% CI, 14.54% to 32.41%). The Xpert MTB/RIF assay alone showed the best agreement with sputum culture, with a kappa value of 0.840. Pathogen molecular detection alone showed good performance compared to the other algorithms, for ruling out active TB in general LTBI, but the high cost might be a challenge for scaling it up. Identifying those with a high risk for progression to TB more precisely and establishing a cost-effective screening algorithm deserve further exploration. IMPORTANCE Enhancing community-wide active case screening in target LTBI populations is important for achieving the early treatment of active TB, and ruling active TB out is a prerequisite for initiating preventive treatment. The current study evaluated the performances of multiple tests and their combinations in screening for active TB among individuals with LTBI at the community level. Compared with the classical "TB symptoms and chest radiography" algorithm, the application of Xpert MTB/RIF improved the sensitivity from 45% to 80%. When the Xpert MTB/RIF assay was combined with chest radiography, the sensitivity was further improved to 90.00%, which achieved the World Health Organization (WHO) target product profiles. However, the algorithm requires caution as the PPV decreased from 88.89% for Xpert MTB/RIF alone to 22.22% for the combination. Xpert MTB/RIF alone offered remarkable sensitivity without compromising the PPV but would have major resource implications. Thus, identifying target populations for LTBI treatment more precisely and developing cost-effective and high-throughput screening tools and algorithms deserve further efforts.

Implementation of a Routine Screening Program for Latent Tuberculosis Infection among Patients with Acute Leukemia at a Canadian Cancer Center

Screening for latent tuberculosis infection (LTBI) in patients with hematological malignancy is recommended because of their increased risk of tuberculosis (TB). We assessed the utility of tuberculin skin test (TST) screening in patients with acute leukemia and subsequent outcomes of LTBI treatment. We retrospectively evaluated patients ≥16 years of age with acute leukemia from 2013-2014 with a TST planted and read prior to the initiation of antineoplastic chemotherapy treatment. Demographics, clinical information and treatment outcomes of LTBI therapy were compared between patients with positive TST (≥10 mm induration) and negative TST. A total of 389 patients with acute leukemia were included in the cohort. Of them, 37/389 (9.5%) had a positive TST. Only 3.4% (8/235) of individuals originating from North and South America as well as the Caribbean were TST positive, while 21% (20/95) of individuals from Asia were TST positive. Diagnostic imaging findings consistent with prior tuberculosis infection were higher in TST positive patients compared to TST negative ones (29.7% versus 9.4%, p < 0.0001). Furthermore, 31/38 patients (81.6%) who were TST positive received LTBI therapy, which was well tolerated. There was no significant difference in overall survival among those who received LTBI therapy compared to those who did not. No patients developed active TB. Universal screening with TST may be of low yield in individuals with acute leukemia unless patients originate from a TB endemic country. When therapy for LTBI is prescribed, patients with acute leukemia do not experience drug-induced liver toxicity and are likely to complete the intended duration of therapy, thus preventing the development of active tuberculosis.

Potential Impact of Long-Acting Products on the Control of Tuberculosis: Preclinical Advancements and Translational Tools in Preventive Treatment.

A key component of global tuberculosis (TB) control is the treatment of latent TB infection. The use of long-acting technologies to administer TB preventive treatment has the potential to significantly improve the delivery and impact of this important public health intervention. For example, an ideal long-acting treatment could consist of a single dose that could be administered in the clinic (ie, a "1-shot cure" for latent TB). Interest in long-acting formulations for TB preventive therapy has gained considerable traction in recent years. This article presents an overview of the specific considerations and current preclinical advancements relevant for the development of long-acting technologies of TB drugs for treatment of latent infection, including attributes of target product profiles, suitability of drugs for long-acting formulations, ongoing research efforts, and translation to clinical studies.

Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain

Tumor-necrosis-factor-α inhibitors (anti-TNF-α) are associated with an increased risk of tuberculosis (TB) disease, primarily due to reactivation of latent TB infection (LTBI). We assessed the performance of parallel LTBI screening with tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assays (QFT-GIT) before anti-TNF-α treatment in children with immune-mediated inflammatory disorders in a low TB-burden setting. We conducted a multicenter cohort study involving 17 pediatric tertiary centers in Spain. LTBI was defined as the presence of a positive TST and/or QFT-GIT result without clinical or radiological signs of TB disease. A total of 270 patients (median age:11.0 years) were included, mainly with rheumatological (55.9%) or inflammatory bowel disease (34.8%). Twelve patients (4.4%) were diagnosed with TB infection at screening (LTBI, n = 11; TB disease, n = 1). Concordance between TST and QFT-GIT results was moderate (TST+/QFT-GIT+, n = 4; TST−/QFT-GIT+, n = 3; TST+/QFT-GIT-, n = 5; kappa coefficient: 0.48, 95% CI: 0.36–0.60). Indeterminate QFT-GIT results occurred in 10 patients (3.7%) and were associated with young age and elevated C-reactive protein concentrations. Eleven of 12 patients with TB infection uneventfully completed standard LTBI or TB treatment. During a median follow-up period of 6.4 years, only 2 patients developed TB disease (incidence density: 130 (95% CI: 20–440) per 100,000 person-years), both probable de novo infections.Conclusion: A substantial number of patients were diagnosed with LTBI during screening. The dual strategy identified more cases than either of the tests alone, and test agreement was only moderate. Our data show that in children in a low TB prevalence setting, a dual screening strategy with TST and IGRA before anti-TNF-α treatment is effective.What is Known:• The optimal screening strategy for latent tuberculosis in children with immune-mediated inflammatory disorders remains uncertain.• Children receiving anti-TNF-α drugs are at increased risk of developing severe tuberculosis disease.What is New:• A dual screening strategy, using TST and an IGRA assay, identified more children with latent tuberculosis than either of the tests alone.• Identification and treatment of latent tuberculosis before initiation of anti-TNF-α therapy averted incident tuberculosis cases.

Optimizing tuberculosis screening for immigrants in southern New Brunswick: A pilot study protocol.

Immigrants from high tuberculosis-burdened countries have been shown to have an increased risk of latent tuberculosis infection (LTBI). To reduce the risk of increased tuberculosis cases in Canada, the country has a comprehensive immigration medical examination process that identifies individuals with active tuberculosis using chest X-ray; however, it fails to identify LTBI. The lack of LTBI identification is concerning because immigrants with LTBI are at an increased risk of developing active tuberculosis within their first few years of migration due to stressful experiences common to many immigrants. The goal of this pilot study is to improve the current LTBI screening protocols among immigrants from high tuberculosis incidence countries and to better prevent and manage tuberculosis cases, by introducing an LTBI screening pilot program. The objectives are threefold: 1) to screen LTBI in immigrants from high tuberculosis incidence countries, including immigrants identified as being at risk of LTBI by the NB health care system, using the QuantiFERON-TB Gold Plus interferon-gamma release assay (IGRA); 2) to offer LTBI treatment and supports to those identified as having LTBI; and 3) to assess immigrant and health care providers (HCPs) satisfaction of the LTBI screening pilot program. This cross-sectional study seeks to recruit 288 participants. Participants will be recruited via posters, social media platforms, invitations at immigrant wellness check-ups, presentations to local ethnocultural groups, and by snowball sampling. Consenting participants will be asked to submit a blood sample for LTBI screening; if positive, participants will be assessed and offered treatment for LTBI based on clinical assessment. Participants and HCPs' feedback will be gathered via short questionnaires. For the quantitative portion of the study, descriptive statistics will be used to summarize participant characteristics and feedback. Simultaneous logistic regression will be performed to identify variables associated with the IGRA test outcome and evidence of increased CD8 T-cell immune response among those found to be LTBI-positive. Qualitative results will be analyzed using inductive thematic analysis. The findings from this study will allow us to understand the role of the IGRA LTBI screening assay and its feasibility and acceptability by immigrants and HCPs in New Brunswick. The findings will additionally provide information on the enhancers and barriers of LTBI screening and management useful in determining how best to expand the LTBI screening program if deemed appropriate.