LTBI Screening Research Articles

European guidelines for the management of tuberculosis screening in migrants: a systematic review

Abstract Background This systematic review assesses the current available evidence across the WHO European region on the effectiveness and cost-effectiveness of the different approaches used for TB screening and also explores the facilitators and barriers that migrants face during screening programs. Methods We conducted an extensive, comprehensive, and systematic literature search across multiple databases, including MEDLINE, Cochrane, Scopus, and ISI Web of Knowledge, without any restrictions on publication date or language. In addition, we reviewed grey literature and reports from WHO. The data were meticulously analyzed using RStudio, with a focus on screening effectiveness indicators, such as infection and disease detection rates, uptake, coverage, and cost-effectiveness economic analyses. Results Our review included 43 studies covering over 8 million migrants from 11 countries. The findings demonstrate that while screening uptake was high, coverage varied, and completion rates for preventive treatments were low. Economic analyses supported the high cost-effectiveness of the screening programs, particularly when integrating both active TB and LTBI screening strategies. Conclusions The implementation of uniform screening protocols could potentially streamline efforts, reduce TB transmission, and offer substantial public health and economic benefits, making this research highly relevant for policymakers and healthcare providers. Key messages • An important strength of this study lies in its pioneering approach of current recommendations regarding screening for latent tuberculosis infection and active TB within the WHO European region. • This is the first study that provides a comprehensive overview of screening interventions across 11 countries and incorporates studies with large sample sizes (n > 8 million migrants).

#833 Spectrum of tuberculosis after kidney transplantation: a case-control study in a middle-endemic area

Abstract Background and Aims Tuberculosis (TB) is the leading cause of infectious-disease death worldwide. Post-transplant TB is a problem in successful long-term outcome of kidney transplantation recipients (KT) and is often associated with high morbidity and mortality. The aim of this study was to assess the clinical features, risk factors, and outcome of TB after kidney transplantation in a middle-prevalence area. Method We performed a retrospective analysis of a cohort of adult KT recipients from 2015 to 2020 at the Annaba University Hospital with follow-up until October 2022. Results Among 152 KT recipients evaluated, 8 developed TB, the prevalence was 5.26%. Median time to diagnosis was 28.4 months, with 25% of the cases occurring in the first Two year. Pulmonary TB represented 75% of the cases, including disseminated disease. Two patients received isoniazid prophylaxis for latent TB infection and developed active infection. Median duration of treatment was 12 months. However TB was associated with a significant reduction in patient and graft survival (74% vs. 90.2% in 5 years for patient survival, P=0.001; and 58.6% vs. 80.2% in 5 years for graft survival, P<0.001). Death and graft loss occurred in the first 6 months after diagnosis in one-third of the patients, 38.8% of them with disseminated disease. Disseminated disease was significantly associated with mortality compared to local disease (41.8% vs. 9.7%, P=0.035). It should also be pointed out that Algeria is a country with an intermediate level of tuberculosis endemicity. Conclusion TB is the archetype of opportunistic infection in KT, with significant impact on patient and graft survival. Our results emphasize the need for systematic screening for LTBI in all patients awaiting transplant. Treatment challenges in KT recipients with TB, drug interactions, drug toxicities and therapeutical adherence must be considered.

Latent tuberculosis infection in Korean patients with multiple sclerosis and neuromyelitis optica spectrum disorder

BackgroundLatent tuberculosis infection (LTBI) is defined as an immune response to Mycobacterium tuberculosis infection that does not manifest clinically as active tuberculosis (TB). Since some immunotherapies can alter cellular immunity, LTBI screening has been recommended for patients with multiple sclerosis (pwMS) before initiation of long-term immunotherapies. In this study, we investigated the frequency of LTBI in Korean pwMS and patients with neuromyelitis optica spectrum disorder (pwNMOSD) and reported the long-term observation of untreated LTBI under various immunotherapies. MethodsWe enrolled pwMS or pwNMOSD who visited the Neurology department of the National Cancer Center between 2017 and 2021. LTBI was determined based on positive results of interferon-gamma release assay (IGRA) using QuantiFERON Gold Plus test and no evidence of active TB. Annual chest X-ray and careful monitoring for TB symptoms were performed until April 2023 or the time of follow-up loss. ResultsAmong 531 patients who underwent the IGRA test, 25 pwMS (10.5%) and 42 pwNMOSD (14.3%) were diagnosed with LTBI. Of the 67 patients with LTBI, 59 patients (24 pwMS and 35 pwNMOSD) declined to receive preventive anti-TB drugs. None of the 59 with untreated LTBI demonstrated TB reactivation during 74.8 person-years in pwMS and 166.1 person-years in pwNMOSD. In addition, eight patients who completed the treatment for LTBI experienced no TB reactivation for a median of 5.5 years. ConclusionThe LTBI prevalence in Korean pw MS and pwNMOSD was 10.5% and 14.3%, respectively, which was much higher than that in pwMS from Western countries. Notably, none of the 59 patients with untreated LTBI showed TB reactivation over 240 person-years even under long-term immunotherapies, indicating the need for additional research to stratify the risk of LTBI-reactivation.

Development and validation of a prediction algorithm to identify birth in countries with high tuberculosis incidence in two large California health systems.

ObjectiveThough targeted testing for latent tuberculosis infection (“LTBI”) for persons born in countries with high tuberculosis incidence (“HTBIC”) is recommended in health care settings, this information is not routinely recorded in the electronic health record (“EHR”). We develop and validate a prediction model for birth in a HTBIC using EHR data.Materials and methodsIn a cohort of patients within Kaiser Permanente Southern California (“KPSC”) and Kaiser Permanent Northern California (“KPNC”) between January 1, 2008 and December 31, 2019, KPSC was used as the development dataset and KPNC was used for external validation using logistic regression. Model performance was evaluated using area under the receiver operator curve (“AUCROC”) and area under the precision and recall curve (“AUPRC”). We explored various cut-points to improve screening for LTBI.ResultsKPSC had 73% and KPNC had 54% of patients missing country-of-birth information in the EHR, leaving 2,036,400 and 2,880,570 patients with EHR-documented country-of-birth at KPSC and KPNC, respectively. The final model had an AUCROC of 0.85 and 0.87 on internal and external validation datasets, respectively. It had an AUPRC of 0.69 and 0.64 (compared to a baseline HTBIC-birth prevalence of 0.24 at KPSC and 0.19 at KPNC) on internal and external validation datasets, respectively. The cut-points explored resulted in a number needed to screen from 7.1–8.5 persons/positive LTBI diagnosis, compared to 4.2 and 16.8 persons/positive LTBI diagnosis from EHR-documented birth in a HTBIC and current screening criteria, respectively.DiscussionUsing logistic regression with EHR data, we developed a simple yet useful model to predict birth in a HTBIC which decreased the number needed to screen compared to current LTBI screening criteria.ConclusionOur model improves the ability to screen for LTBI in health care settings based on birth in a HTBIC.

Latent Tuberculosis Infection Diagnosis among Household Contacts in a High Tuberculosis-Burden Area: a Comparison between Transcript Signature and Interferon Gamma Release Assay.

ABSTRACTDiagnosis of latent tuberculosis infection (LTBI) using biomarkers in order to identify the risk of progressing to active TB and therefore predicting a preventive therapy has been the main bottleneck in eradication of tuberculosis. We compared two assays for the diagnosis of LTBI: transcript signatures and interferon gamma release assay (IGRA), among household contacts (HHCs) in a high tuberculosis-burden population. HHCs of active TB cases were recruited for our study; these were confirmed to be clinically negative for active TB disease. Eighty HHCs were screened by IGRA using QuantiFERON-TB Gold Plus (QFT-Plus) to identify LTBI and uninfected cohorts; further, quantitative levels of transcript for selected six genes (TNFRSF10C, ASUN, NEMF, FCGR1B, GBP1, and GBP5) were determined. Machine learning (ML) was used to construct models of different gene combinations, with a view to identify hidden but significant underlying patterns of their transcript levels. Forty-three HHCs were found to be IGRA positive (LTBI) and thirty-seven were IGRA negative (uninfected). FCGR1B, GBP1, and GBP5 transcripts differentiated LTBI from uninfected among HHCs using Livak method. ML and ROC (Receiver Operator Characteristic) analysis validated this transcript signature to have a specificity of 72.7%. In this study, we compared a quantitative transcript signature with IGRA to assess the diagnostic ability of the two, for detection of LTBI cases among HHCs of a high-TB burden population; we concluded that a three gene (FCGR1B, GBP1, and GBP5) transcript signature can be used as a biomarker for rapid screening.IMPORTANCE The study compares potential of transcript signature and IGRA to diagnose LTBI. It is first of its kind study to screen household contacts (HHCs) in high TB burden area of India. A transcript signature (FCGR1B, GBP1, & GBP5) is identified as potential biomarker for LTBI. These results can lead to development of point-of-care (POC) like device for LTBI screening in a high TB burdened area.

Assessment of latent tuberculosis infection pre-immunomodulatory therapy; 5 year experience in a UK centre

• A 5 year retrospective review of 367 LTBI referrals to a UK TB service. • 51% were referred pre-immunomodulatory therapy with 25 different agents. • They were older and had more negative & indeterminate screening IGRAs than ‘traditional’ LTBI referrals. • 57% either didn’t initiate or couldn’t complete chemoprophylaxis. An ever greater variety of immunomodulatory agents with potential to reactivate latent TB infection are being used in clinical practice. We set out to describe the experience of assessing and mitigating TB reactivation risk for patients planning to start immunomodulatory biological or small molecule inhibitor (SMI) therapies referred to a TB service in a high income low TB prevalence setting. Retrospective clinical case note review of patients referred to the infectious diseases TB service of Sheffield Teaching Hospitals following LTBI screening between 1 September 2015 and 30 September 2020. 367 patients had been referred and assessed. 179 patients referred for new entrant or contact screening and 188 (51%) patients were being worked up pre-immunomodulatory therapy with 25 different biologic/SMIs for more than 20 conditions. This group were older (median age 56.2 vs 32.6 years, p < 0.0001), and more likely to have had a negative or indeterminate screening IGRA (25.5% vs 4.1%, p < 0.0001). 155/188 were diagnosed with LTBI, of whom 58% commenced chemoprophylaxis (50 isoniazid, 40 rifampicin/isoniazid) and they were significantly younger than those who did not (median age 48.7 vs 70.6 years, p = 0.0004). 75% completed chemoprophylaxis with 7% stopping early due to altered liver function tests and 10% due to other adverse effects. No differences were observed between isoniazid or rifampicin/isoniazid treated groups. Increased age, less reliable screening IGRAs and adverse effects of chemoprophylaxis in the face of a widening variety of agents make management of LTBI in patients pre-immunomodulatory therapy complex. Better tests and treatments are required.

Tuberculosis incidence in country of origin is a key determinant of the risk of active tuberculosis in people living with HIV: Data from a 30-year observational cohort study.

People living with HIV (PLWH) are at high risk of active tuberculosis (TB) but this risk in the era of antiretroviral treatment (ART) remains unclear. It is critical to identify the groups who should be prioritised for latent TB (LTBI) screening. In this study we identified the risk factors associated with developing incident TB disease, by analysing a 30-year observational cohort. We evaluated PLWH in Leicester, UK, between 1983 and 2017 to ascertain those who developed active TB and the timing of this in relation to HIV diagnosis; whether before, concurrently with, or more than 3months after the diagnosis of HIV (incident TB). Predictors of incident TB were ascertained using Cox proportional hazards models. In all, 325 out of 2158 (15.1%) PLWH under care had had active TB; 64/325 (19.7%) prior to HIV diagnosis, 161/325 (49.5%) concurrently with/within 3months of HIV diagnosis and 100/325 (30.8%) had incident TB. Incident TB risk was 4.57/1000 person-years. Increased TB incidence in the country of birth was associated with an increased risk of developing incident TB [50-149/100000 population, adjusted hazard ratio (AHR) = 3.10, 95% CI: 0.94-10.20; 150-249/100000 population, AHR = 7.14, 95% CI: 3.46-14.74; 250-349/100000 population, AHR = 5.90, 95% CI: 2.32-14.99; ≥350/100000 population, AHR = 3.96, 95% CI: 1.39-11.26]. Tuberculosis risk remains high among PLWH and is related to TB incidence in the country of birth. Further work is required to determine whether specific groups of PLWH should be targeted for programmatic LTBI screening, and whether it will result in high uptake and completion of chemoprophylaxis and is cost-effective for widespread implementation.

Cost-effectiveness of testing for latent tuberculosis infection in people with HIV.

The aim of this study was to estimate the cost-effectiveness of screening strategies for predicting LTBI that progresses to active tuberculosis (TB) in people with HIV. We developed a decision-analytical model that constituted a decision tree covering diagnosis of LTBI and a Markov model covering progression to active TB. The model represents the lifetime experience following testing for LTBI, and discounting costs, and benefits at 3.5% per annum in line with UK standards. We undertook probabilistic and one-way sensitivity analyses. UK National Health Service and Personal Social Service perspective in a primary care setting. Hypothetical cohort of adults recently diagnosed with HIV. Interferon-gamma release assays and tuberculin skin test. Cost per quality-adjusted life year (QALY). All strategies except T-SPOT.TB were cost-effective at identifying LTBI, with the QFT-GIT-negative followed by TST5mm strategy being the most costly and effective. Results indicated that there was little preference between strategies at a willingness-to-pay threshold of £20 000. At thresholds above £40 000 per QALY, there was a clear preference for the QFT-GIT-negative followed by TST5mm, with a probability of 0.41 of being cost-effective. Results showed that specificity for QFT-GIT and TST5mm were the main drivers of the economic model. Screening for LTBI has important public health and clinical benefits. Most of the strategies are cost-effective. These results should be interpreted with caution because of the paucity of studies included in the meta-analysis of test accuracy studies. Additional high-quality primary studies are needed to have a definitive answer about, which strategy is the most effective.

Cost effectiveness of three months of rifapentine and isoniazid for latent tuberculosis in Syrian refugees

BackgroundLatent Tuberculosis infection (LTBI) has a large global burden especially among refugees. We aimed to test the cost effectiveness of weekly rifapentine plus isoniazid for 3 months (3HP) versus nine months of daily isoniazid (INH-9) to treat LTBI in Syrian refugees residing in Turkey. MethodsWe used a Markov state transition model to estimate the incremental cost-effectiveness of 3HP relative to INH-9 using a simulated cohort of Syrian refugees. Both cost and effectiveness were assessed assuming that LTBI screening would be performed, with treatment of those who screen positive. Costs were measured in 2017 US dollars, and effectiveness was estimated as quality adjusted life years (QALYs) gained. An annual discount rate of 3% was applied to future costs and QALYs over the analytical time horizon of 20 years. ResultsPer 100 individuals screened at age 30 in the base case scenario, treating LTBI with 3HP rather than INH-9 resulted in a gain of 0.08 QALYs (95% uncertainty interval: -0.007, 0.221) and savings of $1421 ($483, $3478). Assuming a value of $100000 per QALY, the incremental net monetary benefit of 3HP was $9772 ($639, $24517). Findings were robust to sensitivity analyses except when treating older individuals. Conclusions3HP is likely to save costs and improve health compared to INH-9 when used for LTBI treatment among Syrian refugees in Turkey.

Utility of the monocyte to lymphocyte ratio in diagnosing latent tuberculosis among HIV-infected individuals with a negative tuberculosis symptom screen.

Latent Tuberculosis Infection (LTBI) remains a major driver of the TB epidemic, and individuals with Human Immuno-deficiency Virus (HIV) are particularly at a heightened risk of developing LTBI. However, LTBI screening among HIV-infected individuals in resource limited setting is largely based on a negative symptom screen, which has low specificity. In a cross sectional diagnostic study, 115 HIV infected participants with a negative symptom screen will be consented and enrolled. They will be requested to donate 5 ml of blood for complete blood count (CBC) and interferon gamma release assay (IGRA) testing. In a nested prospective study, the 115 participants will be initiated on Tuberculosis Preventive Therapy and the CBC testing repeated after 3 months. In the analysis of study finding, the monocyte to lymphocyte ratio (MLR) will be derived from the dividend of the absolute monocyte and lymphocyte counts. The optimal MLR positivity cut-off for elevated or normal MLR will be the highest value of Youden's index, J (sensitivity + specificity-1). The MLR will be cross tabulated with the IGRA status to determine the sensitivity, specificity, negative and positive predictive values of the MLR. The area under the receiver operating characteristic (ROC) curve will be determined to give the overall diagnostic accuracy of MLR. The baseline and 3 month CBC will be used to determine the change in MLR, and a random effect logistic regression will be used to determine factors associated with the change in the MLR. If positive results are realized from this study, the MLR could become an inexpensive alternative biomarker with potential to improve the specificity of the negative symptom screen in identifying individuals that should be targeted for TB preventive therapy.

Tuberculosis risk in patients with rheumatologic disease treated with biologic drugs.

The risk of tuberculosis is higher in cases who have used antiTNF treatments. However, it is not clearly known whether there is a relationship between other biologic agents and the risk of developing tuberculosis or not. We aimed to investigate the prevalence of active tuberculosis among patients with rheumatic disease treated with biologic drugs. The study was performed at a tertiary referral center from January 2015 to December 2019. A total of 2000 patients with rheumatic diseases were screened and 461 patients were enrolled in the study due to regular records. They were underwent LTBI screening tests and were followedup at least 1 year after TNF inhibitor treatment initiation. The median age of all patients was 48 (min-max: 19-80). 283 patients (61.3%) were female and 178 (38.7%) were male. The most common diseases were ankylosing spondylitis (67.2%), rheumatoid arthritis (26%) and psoriatic arthritis (5.2%). Anti-TNF treatments were given to 85.2% of all cases and other biologic treatments were given to 14.8%. Tuberculin skin test was applied to 429 patients and 70.4% positivity was found. Quantiferon-TB test was applied to 93 patients and 20.4% positivity was found. 320 patients were treated for LTBI due to positive tuberculin skin test and/or positive quantiferon-TB test. TB was developed in only one patient out of 393 patients who were treated with anti-TNF treatments and the the prevalence of TB development was found 255/100.000. The incidence of tuberculosis was quite low in our patients with rheumatic disease who were receiving anti-TNF treatment compared to previous studies. Also, in patients who were using other biological treatments, no TB cases were developed.

Efficacy and safety of weekly rifapentine and isoniazid for tuberculosis prevention in Chinese silicosis patients: a randomized controlled trial

ObjectiveThe aim was to evaluate the efficacy, safety and completion rate of 3-month, once-weekly rifapentine and isoniazid for tuberculosis (TB) prevention among Chinese silicosis patients. MethodsMale silicosis patients without human immunodeficiency virus infection, aged 18 years to 65 years, with or without latent TB infection, were randomized 1:1 to receive rifapentine/isoniazid under direct observation (3RPT/INH group) or were untreated (observation group). Active TB incidence was compared between the two groups with 37 months of follow-up. Safety profile and complete rates were evaluated. ResultsA total of 1227 adults with silicosis were screened; 513 eligible participants were enrolled and assigned to 3RPT/INH (n = 254) vs. observation (n = 259). Twenty-eight participants were diagnosed with active TB, and 9 and 19 in the 3RPT/INH group and observation groups, respectively. In the intention-to-treat analysis, the cumulative active TB rate was 3.5% (9/254) in the 3RPT/INH group and 7.3% (19/259) in the observation group (log rank p 0.055). On per protocol analysis, the cumulative active TB rates were 0.7% (1/139) and 7.3% (19/259), respectively (log rank p 0.01). Owing to an unexpected high frequency of adverse events (70.4%) and Grade 3 or 4 AEs (7.9%), the completion rate of the 3RPT/INH regimen was 54.7% (139/254). Twenty-six (10.8%) participants had flu-like systemic drug reactions; five (2.1%) experienced hepatotoxicity. DiscussionWeekly rifapentine/isoniazid prophylaxis prevented active TB among Chinese people with silicosis when taken, irrespective of LTBI screening; efficacy was reduced by lack of compliance. The regimen must be used with caution because of the high rates of adverse effects. Clinical trial registrationClinicalTrials.gov number: NCT02430259

Evaluation of a routine screening program with tuberculin skin testing on rates of detection of latent tuberculosis infection and prevention of active tuberculosis in patients with multiple myeloma at a Canadian cancer centre.

Chemotherapy-induced T cell dysfunction, resulting from treatment of multiple myeloma (mm), enhances the risk for reactivation of latent tuberculous infection (ltbi). However, routine screening for ltbi has its limitations. The objective of the present study was to assess the number of patients treated for ltbi both before and after the introduction of a consistent tuberculin skin test (tst) screening program for patients with mm at our cancer centre. This retrospective observational study analyzed adult patients with mm treated with autologous hematopoietic stem-cell transplantation from 1 January 2013 to 31 December 2014, for whom tst was consistently performed at our cancer facility. Baseline demographic characteristics of patients who received tst testing and ltbi therapy were compared with those of a pre-intervention cohort of patients (1 January 2008 to 31 December 2009) who were not tested. During the post-intervention period, 170 patients with mm had a tst. In 14 patients (8.2%) results were positive, and 11 of the 14 received ltbi therapy. Of another 12 patients with radiographic imaging changes consistent with prior granulomatous disease and negative tst results, 2 were treated. No cases of tuberculosis (tb) reactivation were noted in individuals who completed ltbi therapy. One case of active tb was diagnosed in a patient with a negative tst. In contrast, in the pre-intervention matched cohort of 170 patients, no tsts were performed, and no cases of active tb were documented. Patients with mm could benefit from a consistent tst testing policy coupled with subsequent ltbi therapy. However, universal testing might not be required. A targeted program combining evaluation of host risk factors, imaging findings, and screening tests might optimize ltbi diagnosis and management, and thus be effective in preventing the development of active tb in at-risk patients with mm.

Incidencia de tuberculosis en pacientes que reciben fármacos anti-TNFα

Introduction: tuberculosis (TB) is a frequent complication in patients receiving tumor necrosis factor-alpha (TNF-a) blockers. It occurs upon the reactivation of a latent infection or the progression of a recent infection.Objective: to learn about the incidence of TB in a population receiving tumor necrosis factor-alpha (TNF-a) blockers, to analyze the presentation of this condition and to conduct a latent infection research prior to the initiation of therapy.Method: retrospective cohort study. Patients receiving tumor necrosis factor-alpha (TNF-a) blockers between 2010 and 2016 were included in the study. Data were obtained from the IT systems of the National Resources Fund and the National Tuberculosis Program. The incidence of TB was calculated and the cases developing TB were described.Results: 991 treatments were included for 980 patients in total. 9 cases of TB were reported. Global incidence was 419.9 (IC 95% 191.9-591.2) out of 100,000 people per year. Cases of TB were only seen in patients treated with adalimumab. Screening for LTBI upon initiation of the drug was heterogeneous and the disseminated forms of TB prevailed (6/9) over isolated pulmonary affectation (3/9). In all cases anti- TNFa was suspended when TB was diagnosed, and it was not reinitiated.Conclusions: the incidence of TB in patients receiving tumor necrosis factor-alpha (TNF-a) blockers was 16.5 times greater than in the general population. Disseminated forms of TB prevailed, and some cases occurred in individuals who had received LTBI therapy prior to the initiation of the drug, suggesting the risk persists as long as there is exposure to the drug.

Protocol for a cluster randomised control trial evaluating the efficacy and safety of treatment for latent tuberculosis infection in recent migrants within primary care: the CATAPuLT trial

BackgroundThe identification and treatment of LTBI is a key component of the WHO’s strategy to eliminate TB. Recent migrants from high TB-incidence countries are recognised to be at risk TB reactivation, and many high-income countries have focused on LTBI screening and treatment programmes for this group. However, migrants are the group least likely to complete the LTBI cascade-of-care. This pragmatic cluster-randomised, parallel group, superiority trial investigates whether a model of care based entirely within a community setting (primary care) will improve treatment completion compared with treatment in specialist TB services (secondary care).MethodsThe CATAPuLT trial (Completion and Acceptability of Treatment Across Primary Care and the community for Latent Tuberculosis) randomised 34 general practices in London, England, to evaluate the efficacy and safety of treatment for LBTI in recent migrants within primary care. GP practices were randomised to either provide management for LTBI entirely within primary care (GPs and community pharmacists) or to refer patients to secondary care. The target recruitment number for individuals is 576. The primary outcome is treatment completion (defined as taking at least 90% of antibiotic doses). The secondary outcomes assess adherence, acceptance of treatment, the incidence of adverse effects including drug-induced liver injury, the rates of active TB, patient satisfaction and cost-effectiveness of LTBI treatment. This protocol adheres to the SPIRIT Checklist.DiscussionThe CATAPuLT trial seeks to provide implementation research evidence for a patient-centred intervention to improve treatment completion for LTBI amongst recent migrants to the UK.Trial registrationNCT03069807, March 2017, registered retrospectively.

1392. Tuberculosis Disease in Recipients of Organ-Transplantation, California 2010–2017

BackgroundTuberculosis (TB) disease in persons who have received organ transplantation causes high morbidity, but the epidemiology and clinical features of this problem remain poorly described.MethodsUsing California TB registry data from 2010–2017, we describe clinical features of all TB cases occurring in patients who previously received solid-organ transplantation. We compared TB cases with and without transplant, and examined mortality controlling for age.ResultsDuring 8 years of observation, the California TB Registry recorded 116 cases of post-transplant TB. A majority of patients with post-transplant TB were >45 year old (84%), nonwhite (90%), and born outside of the United States (84%). Of 116 cases, 48 (41%) had pulmonary disease, while 68 (59%) had extra-pulmonary or both pulmonary and extra-pulmonary disease, compared with 69% and 31%, respectively, in non-transplant-associated TB (P < 0.01). Common sites of extrapulmonary disease in transplant patients included pleura (19%), cervical lymph nodes (12%), and bone (12%). Controlling for age, transplant cases were nearly twice as likely to die as non-transplant-associated TB cases (OR = 1.92, CI = 1.13, 3.25). Among 49 post-transplant TB cases with a positive TB skin test (TST) or interferon-gamma release assay (IGRA), 12 (24%) had the test performed > 6 months prior to TB diagnosis.ConclusionOur findings suggest that post-transplant TB disease is more likely to be extra-pulmonary and result in death than non-transplant-associated TB, and that opportunities may exist for preventing TB disease through screening and treatment for LTBI in this population.Disclosures All authors: No reported disclosures.

Mycobacterium tuberculosis: Active disease and latent infection in a renal transplant cohort.

Our aim was threefold: first, to determine the incidence of active TB in our cohort, second to investigate the risk factors for active TB and third, to understand current screening practices. The ultimate goal was to use our findings to inform development of local and national guidelines. The records of all adult patients who underwent renal transplantation at our centre from 2005 to 2014 were retrospectively reviewed to assess current screening practices, the risks for and burden of active TB. A total of 660 individuals underwent renal transplantation during this period, totalling 3647 person years of follow up. Two patients were diagnosed with active TB after renal transplant, resulting in an incidence of 55 per 100 000 person-years. Of 656 transplant recipients, 102 (15.5%) were born in high TB incidence countries and 89 (13.5%) had an interferon gamma release assay (IGRA) at any point. Individuals born in high TB risk countries had a much higher incidence of active TB (353 per 100 000 person-years). Ten individuals had positive IGRA tests, of whom two were treated for active TB, two received chemoprophylaxis and six were not treated. In the absence of formal guidelines, IGRA-based screening for LTBI was infrequently performed. Our data suggest that screening and treatment of renal transplant recipients born in high incidence countries is an important preventive measure.

Estimated Impact of World Health Organization Latent Tuberculosis Screening Guidelines in a Region With a Low Tuberculosis Incidence: Retrospective Cohort Study.

Latent tuberculosis infection (LTBI) screening and treatment is a key component of the World Health Organization (WHO) EndTB Strategy, but the impact of LTBI screening and treatment at a population level is unclear. We aimed to estimate the impact of LTBI screening and treatment in a population of migrants to British Columbia (BC), Canada. This retrospective cohort included all individuals (N = 1 080 908) who immigrated to Canada as permanent residents between 1985 and 2012 and were residents in BC at any time up to 2013. Multiple administrative databases were linked to identify people with risk factors who met the WHO strong recommendations for screening: people with tuberculosis (TB) contact, with human immunodeficiency virus, on dialysis, with tumor necrosis factor-alpha inhibitors, who had an organ/haematological transplant, or with silicosis. Additional TB risk factors included immunosuppressive medications, cancer, diabetes, and migration from a country with a high TB burden. We defined active TB as preventable if diagnosed ≥6 months after a risk factor diagnosis. We estimated the number of preventable TB cases, given optimal LTBI screening and treatment, based on these risk factors. There were 16 085 people (1.5%) identified with WHO strong risk factors. Of the 2814 people with active TB, 118 (4.2%) were considered preventable through screening with WHO risk factors. Less than half (49.4%) were considered preventable with expanded screening to include people migrating from countries with high TB burdens, people who had been prescribed immunosuppressive medications, or people with diabetes or cancer. The application of WHO LTBI strong recommendations for screening would have minimally impacted the TB incidence in this population. Further high-risk groups must be identified to develop an effective LTBI screening and treatment strategy for low-incidence regions.

Latent tuberculosis infection and renal transplantation – Diagnosis and management

BackgroundTuberculosis (TB) continues to be the commonest infectious disease cause of death worldwide. Tuberculosis is an important infectious disease cause of morbidity and death in renal transplant recipients. Tuberculosis can also cause loss of kidney allograft. ObjectivesThe purpose of this viewpoint is to highlight the issues related to prevention, diagnosis and treatment of tuberculosis in renal transplant recipients. MethodsThe PubMed database was searched for publications and guidelines on diagnosis and management of LTBI in renal transplantation. Publications on renal allograft recipients with LTBI and TB in post-operative period were also analysed. Specialist Society guidelines were also used. FindingsTuberculosis is one of the most important infectious disease-related causes of morbidity and death in transplant recipients. LTBI in allograft recipients continues to be a clinical management problem. It can occur either from donor kidney or from endogenous reactivation of latent tuberculosis infection or from acquiring new Mycobacterium tuberculosis infection. Tuberculosis can also cause loss of kidney allograft. ConclusionsKidney transplantation is now universally performed in high and low Tuberculosis endemic countries. A high index of awareness of the possibility of TB disease or LTBI is required prior to renal transplant aligned to reduce renal allograft damage, morbidity and death due to tuberculosis. WHO Management recommendations for LTBI screening and treatment should be followed.

A case report of mucocutaneous tuberculosis after orthotopic liver transplantation: a challenging diagnosis

BackgroundMycobacterium tuberculosis is responsible for high morbidity and mortality in immune-compromised hosts.Case presentationWe present a rare case of cutaneous tuberculosis after orthotopic liver transplantation without involvement of any other organs.ConclusionTB risk-factors assessment, careful LTBI screening and treatment according to national guidelines, as well as a reduction in missed opportunity for prevention are necessary to avoid MTB related disease in fragile patients.