Tuberculosis latente: diagnóstico y tratamiento actual / Latent tuberculosis: current diagnosis and treatment

Resumen La infección tuberculosa latente (TL) afecta al 23% de la población y constituye un reservorio de tuberculosis (TBC) ya que 10% progresa hacia una TBC. La TL se reconoce por pruebas como la tuberculina (PPD o TST) y los ensayos de liberación de Interferón gama (IGRAs). La sensibilidad de IGRAs (versión Quantiferon TB Gold plus) es 94% y del PPD 77%. La especificidad del Quantiferon TB Gold Plus es 97% y del PPD 68%. El valor predictivo de progresión a TBC activa de estas pruebas es bajo (PPD: 1,5%, IGRAs: 2,7%) pero mejora en personas de alto riesgo de contraer TBC (PPD: 2,4%, IGRAs: 6,8%). Las personas con pruebas negativas que posteriormente presentan viraje (prueba positiva) tienen mayor riesgo de progresión a TBC activa. Estas pruebas son útiles en el seguimiento de contactos intradomiciliarios, extranjeros de países con altas tasas de TBC, inmunosuprimidos, enfermedad renal crónica, diabetes, silicosis y secuelas pulmonares de TBC no tratada. En la terapia de TL se utiliza isoniazida (H) auto-administrada por plazos de 6 a 12 meses con eficacia protectora de 60% y riesgo de toxicidad hepática de 2% pero con baja adherencia (50-70%). La asociación de H con rifapentina en dosis única semanal durante 12 semanas tiene eficacia de 81%, adherencia de 82% y baja toxicidad hepática (0,4%). Nuevos biomarcadores de TL y vacunas que mejoren la inmunidad en TL se encuentran en estudio. El tratamiento de la TL puede reducir la incidencia de TBC a largo plazo.

Latent tuberculosis infection (LT) affects 23% of the population and constitutes a reservoir of tuberculosis (TB) as 10% progresses to TB. LT is recognized by tests such as tuberculin (PPD or TST) and Interferon gamma release assays (IGRAs). The sensitivity of IGRAs (Quantiferon TB Gold plus version) is 94% and PPD 77%. The specificity of Quantiferon TB Gold Plus is 97% and PPD 68%. The predictive value of progression to active TB of these tests is low (PPD: 1.5%, IGRAs: 2.7%) but improves in people at high risk of contracting TB (PPD: 2.4%, IGRAs: 6.8%). People with negative tests who subsequently turn around (positive) have a higher risk of progression to active TB. These tests are useful in the follow-up of intra-household contacts, foreigners from countries with high rates of TB, immunosuppressed, chronic kidney disease, diabetes, silicosis and pulmonary sequelae of untreated TB. In LT therapy, self-administered isoniazid (H) is used for periods from 6 to 12 months with protective efficacy of 60% and risk of liver toxicity of 2%, but with low adherence (50-70%). The association of H with rifapentine in a single weekly dose for 12 weeks has efficacy of 81%, adherence of 82% and low liver toxicity (0.4%). New LT biomarkers and vaccines that improve immunity in LT are under study. Treatment of LT may reduce the incidence of TB in the long term.

Factors influencing the initiation and adherence of LTBI treatment in healthcare workers: a systematic review.

Despite the importance of latent tuberculosis infection (LTBI) treatment and management in healthcare workers (HCWs), only a few studies have provided a comprehensive review of factors associated with the success rate of each stage of the LTBI treatment, as well as strategies to improve treatment adherence. This study investigated factors and determinants of patient losses at each stage of the entire cascade of LTBI in HCWs. Studies were extracted from PubMed, EBSCOhost, EMBASE, Cochrane Library, and ScienceDirect. Our study found poor completion rates of LTBI treatment in HCWs. The main reason for not visiting the outpatient clinic or not accepting treatment was related to the demographic characteristics, whereas adverse drug effects were the main reason for treatment discontinuation. These findings suggest that tailored interventions must be developed to improve the success rate at each stage of the LTBI treatment in HCWs.

Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring.

There is a crucial need for non-sputum-based TB tests. Here, we evaluate the performance of RISK6, a human-blood transcriptomic signature, for TB screening, triage and treatment monitoring. RISK6 performance was also compared to that of two IGRAs: one based on RD1 antigens (QuantiFERON-TB Gold Plus, QFT-P, Qiagen) and one on recombinant M. tuberculosis HBHA expressed in Mycobacterium smegmatis (IGRA-rmsHBHA). In this multicenter prospective nested case-control study conducted in Bangladesh, Georgia, Lebanon and Madagascar, adult non-immunocompromised patients with bacteriologically confirmed active pulmonary TB (ATB), latent TB infection (LTBI) and healthy donors (HD) were enrolled. ATB patients were followed-up during and after treatment. Blood RISK6 scores were assessed using quantitative real-time PCR and evaluated by area under the receiver-operating characteristic curve (ROC AUC). RISK6 performance to discriminate ATB from HD reached an AUC of 0.94 (95% CI 0.89-0.99), with 90.9% sensitivity and 87.8% specificity, thus achieving the minimal WHO target product profile for a non-sputum-based TB screening test. Besides, RISK6 yielded an AUC of 0.93 (95% CI 0.85-1) with 90.9% sensitivity and 88.5% specificity for discriminating ATB from LTBI. Moreover, RISK6 showed higher performance (AUC 0.90, 95% CI 0.85-0.94) than IGRA-rmsHBHA (AUC 0.75, 95% CI 0.69-0.82) to differentiate TB infection stages. Finally, RISK6 signature scores significantly decreased after 2 months of TB treatment and continued to decrease gradually until the end of treatment reaching scores obtained in HD. We confirmed the performance of RISK6 signature as a triage TB test and its utility for treatment monitoring.

Assessment of CD27 expression on T-cells as a diagnostic and therapeutic tool for patients with smear-negative pulmonary tuberculosis.

BACKGROUND: There is a global focus on illness diagnosis in smear-negative and latent tuberculosis infectious populations (SN-TB and LTBI). CD27 has been suggested to play a direct role in active TB. Little is known about smear-negative individuals. Here, we tried to investigate whether it has a role in smear-negative populations. The expression of CD27 and MTB-specific CD27 in CD4+ T cells ("CD27-CD4+" and "CD27-IFN-γ+CD4+") was evaluated in MTB-unexposed controls (HC), TB contacts (TB-C) and SN-TB individuals by flow cytometry. The sensitivity, specificity and AUC (area under curve) of "CD27-IFN-γ+CD4+" cells to distinguish SN-TBs from HCs and TB-Cs were determined by receiver operating characteristic (ROC) curve analysis. The clinical index was selected from the clinical laboratory and evaluated for correlation with "CD27-IFN-γ+CD4+" cells by Spearman statistical analysis. RESULTS: We observed that the percentages of "CD27-IFN-γ+CD4+" cells were significantly increased in the SN-TB group compared with the HC and TB-C groups (AUC was 0.88, sensitivity was 82.14%, specificity was 80.00%, and P < 0.0001). The percentage of "CD27-IFN-γ+CD4+" cells was negatively correlated with WBC (white blood cell count) (r = - 0.3019, P = 0.0182) and positively correlated with IgE (immunoglobulin E) (r = 0.2805, P = 0.0362). Furthermore, "CD27-IFN-γ+CD4+" cells were significantly decreased, especially in the > 50 years group, after clinical treatment. CONCLUSION: The present results demonstrated that the percentage of "CD27-IFN-γ+CD4+" cells might be a conceivable molecular indicator in the diagnosis of SN-TB and was influenced by its outcome of therapy.

Management of childhood and adolescent latent tuberculous infection (LTBI) in Germany, Austria and Switzerland.

BACKGROUND: Majority of active tuberculosis (TB) cases in children in low-incidence countries are due to rapid progression of infection (latent TB infection (LTBI)) to disease. We aimed to assess common practice for managing paediatric LTBI in Austria, Germany and Switzerland prior to the publication of the first joint national guideline for paediatric TB in 2017. METHODS: Online-based survey amongst pediatricians, practitioners and staff working in the public health sector between July and November 2017. Data analysis was conducted using IBM SPSS. RESULTS: A total of 191 individuals participated in the survey with 173 questionnaires included for final analysis. Twelve percent of respondents were from Austria, 60% from Germany and 28% from Switzerland. Proportion of children with LTBI and migrant background was estimated by the respondents to be >50% by 58%. Tuberculin skin test (TST) and interferon-γ-release-assay (IGRA), particularly Quantiferon-gold-test, were reported to be used in 86% and 88%, respectively. In children > 5 years with a positive TST or IGRA a chest x-ray was commonly reported to be performed (28%). Fifty-three percent reported to take a different diagnostic approach in children ≤ 5 years, mainly combining TST, IGRA and chest x-ray for initial testing (31%). Sixty-eight percent reported to prescribe isoniazid-monotherapy: for 9 (62%), or 6 months (6%), 31% reported to prescribe combination therapy of isoniazid and rifampicin. Dosing of isoniazid and rifampicin below current recommendations was reported by up to 22% of respondents. Blood-sampling before/during LTBI treatment was reported in >90% of respondents, performing a chest-X-ray at the end of treatment by 51%. CONCLUSION: This survey showed reported heterogeneity in the management of paediatric LTBI. Thus, regular and easily accessible educational activities and national up-to-date guidelines are key to ensure awareness and quality of care for children and adolescents with LTBI in low-incidence countries.

The knowns and unknowns of latent Mycobacterium tuberculosis infection.

Humans have been infected with Mycobacterium tuberculosis (Mtb) for thousands of years. While tuberculosis (TB), one of the deadliest infectious diseases, is caused by uncontrolled Mtb infection, over 90% of presumed infected individuals remain asymptomatic and contain Mtb in a latent TB infection (LTBI) without ever developing disease, and some may clear the infection. A small number of heavily Mtb-exposed individuals appear to resist developing traditional LTBI. Because Mtb has mechanisms for intracellular survival and immune evasion, successful control involves all of the arms of the immune system. Here, we focus on immune responses to Mtb in humans and nonhuman primates and discuss new concepts and outline major knowledge gaps in our understanding of LTBI, ranging from the earliest events of exposure and infection to success or failure of Mtb control.

CD4 response of QuantiFERON-TB Gold Plus for positive consistency of latent tuberculosis infection in patients on dialysis.

A significantly negative reversion in the QuantiFERON-TB Gold In-tube (QFT-GIT) test is reported in patients on dialysis, which makes the results unreliable. The CD4 and CD8 responses of the QFT-Gold plus (QFT-Plus) may have better positive consistency, but this needs to be investigated. We enrolled dialysis patients with baseline positive QFT-GIT0 results and conducted two rounds of follow-up paired QFT-GIT1&2 and QFT-Plus1&2 tests at an interval of 6 months. The positive consistency, concordance, and discordance of the QFT results were analyzed. A total of 236 patients on dialysis were screened, and 73 participants with positive QFT-GIT0 results were enrolled. The baseline QFT-GIT0 response was higher in the 1st QFT-Plus1(+) group than in the QFT-Plus1(-) group, but insignificantly different between the 1st QFT-GIT1(+) and QFT-GIT1(-) groups. The two assays had good correlation when concurrently tested. Fifty-three subjects completed a second round of the QFT-GIT2 and QFT-Plus2. Persistent positivity was higher with the QFT-Plus2 (81.8%) than with the QFT-GIT2 (58.8%, p = 0.040). The QFT-GIT1 and QFT-Plus1 CD4 responses were higher in patients with persistent positivity than in those with negative reversion, whereas the difference of the QFT-Plus TB1 and TB2 data, representative of the CD8 response, were similar between positive persistence and negative reversion. In conclusion, the QFT-Plus provides more reliable positive consistency than does the QFT-GIT. The CD4 interferon-γ response might play a role in maintaining positivity of LTBI.

Association of Mortality and Years of Potential Life Lost With Active Tuberculosis in the United States.

Importance: Active tuberculosis (TB) disease leads to substantial mortality but is preventable through screening and treatment for latent TB infection. Early mortality after TB diagnosis (≤1 year) is well described, but delayed mortality (>1 year) among patients with active TB is poorly understood. Objective: To compare early and delayed mortality and years of potential life (YPL) lost among patients with active TB disease vs an age-, sex-, and year of diagnosis-matched comparison cohort without active TB disease. Design, Setting, and Participants: This retrospective cohort study, conducted in the integrated health system of Kaiser Permanente Northern California, included patients with microbiologically confirmed active TB disease from January 1, 1997, to December 31, 2017, and a control cohort matched by age, sex, and year of diagnosis. Multivariable models were used to adjust for demographic and clinical characteristics. Patients with active TB disease prior to 1997 were excluded. Data were analyzed from January 1, 2019, to January 31, 2020. Exposure: Microbiologically confirmed TB disease. Main Outcomes and Measures: Early (≤1 year after TB diagnosis) and delayed (>1 year after TB diagnosis) all-cause mortality. Results: A total of 2522 patients who had active TB from 1997 to 2017 were identified, with 17 166 person-years of follow-up. The comparison cohort included 100 880 persons with 735 726 person-years of follow-up. In the active TB and comparison cohorts, similar percentages of persons were male (56.3% vs 55.6%), aged 45 to 64 years (33.7% vs 33.7%), and aged 65 years or older (24.7% vs 24.7%). Both early mortality (7.0%) and delayed mortality (16.3%) were higher among patients with active TB disease compared with those without active TB disease (1.1% and 12.0%, respectively). Patients with active TB disease had a significantly higher risk for early (adjusted hazard ratio [aHR], 7.29; 95% CI, 6.08-8.73) and delayed (aHR, 1.78; 95% CI, 1.61-1.98) mortality compared with the comparison cohort (P < .001). Active TB disease was associated with an adjusted -7.0 (95% CI, -8.4 to -5.5) YPL lost compared with the comparison cohort. Conclusions and Relevance: In this study, patients with active TB disease had significantly higher early and delayed all-cause mortality when adjusting for demographic and clinical characteristics. These findings suggest that TB prevention through screening and treatment of latent TB infection could reduce mortality and YPL lost due to active TB disease.

Ramadan and Culturally Competent Care: Strengthening Tuberculosis Protections for Recently Resettled Muslim Refugees.

To improve latent tuberculosis infection treatment completion rates, Tarrant County Public Health began providing after-dusk home delivery of a 12-dose latent tuberculosis infection regimen of weekly rifapentine plus isoniazid administered via directly observed preventive therapy during Ramadan, a month of prayer and daytime fasting observed by Muslims. In unadjusted difference-in-difference logistic regression analyses (n = 148), Muslim patients had lower treatment completion rates than non-Muslim patients during Ramadan prior to program implementation (68.8% vs 95.4%), whereas rates were comparable postimplementation (95.7% vs 96.4%; difference-in-difference P = .011). Similar results were found after adjusting for age and gender (pre: 71.4% vs 94.8%; post: 95.5% vs 96.3%; P = .032). These findings provide evidence of the need for and effectiveness of programmatic innovations tailored to the varying cultural norms of the widely diverse populations served by public health authorities and suggest that culturally competent clinical care may advance population health goals.

Factors associated with household contacts' tuberculosis testing and evaluation.

PURPOSE: No research has been done in New York City that shows the demographic characteristics of household contacts testing, evaluation, and treatment of LTBI. The objective of the study was to identify demographic factors associated with household contacts' TB testing, evaluation, and LTBI treatment. DESIGN AND METHODS: A retrospective analysis of the New York City (NYC) TB registry data that examined the factors (gender, age, country of birth, race/ethnicity, and borough of residence) associated with TB testing, evaluation, and LTBI treatment. The study sample included all household contacts of TB cases identified from 2010 to 2014 (N = 3,008). The data set was chosen when nurses were the primary case managers at chest centers in the department of health. Descriptive and inferential analysis was used to identify factors associated with testing, evaluation, and LTBI treatment. RESULTS: The demographic characteristics of household contacts associated with testing, evaluation, and LTBI treatment were consistent with those of TB cases in NYC from 2010 to 2014. Those not tested, not fully evaluated, and refusing LTBI treatment were most often aged 18-44 years and were non-US born. Males were significantly more likely than females not to be fully evaluated. Among racial/ethnic groups, Asian and Hispanic persons were at higher risk of not being fully evaluated, and residents of Queens had the highest risk among the five boroughs. In multivariate analyses, age was a significant predictor of behavior, such that the older the person the less likely to get TB testing or to accept LTBI treatment. Non-US country of birth was associated with lower likelihood of being fully evaluated but more likely to accept LTBI treatment when fully evaluated, while Asian or Hispanic race/ethnicity was associated with higher likelihood of both behaviors. CONCLUSIONS: Findings on age from this study will enable public health agencies and public health nurses to plan for effective strategies that will increase the number of household contacts who accept TB testing and evaluation, as well as the numbers who will accept and complete LTBI treatment.

Tuberculosis Screening, Testing, and Treatment of US Health Care Personnel: ACOEM and NTCA Joint Task Force on Implementation of the 2019 MMWR Recommendations.

: On May 17, 2019, the US Centers for Disease Control and Prevention and National Tuberculosis Controllers Association issued new Recommendations for Tuberculosis Screening, Testing, and Treatment of Health Care Personnel, United States, 2019, updating the health care personnel-related sections of the Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005. This companion document offers the collective effort and experience of occupational health, infectious disease, and public health experts from major academic and public health institutions across the United States and expands on each section of the 2019 recommendations to provide clarifications, explanations, and considerations that go beyond the 2019 recommendations to answer questions that may arise and to offer strategies for implementation.

Knowledge and stigma of latent tuberculosis infection in Brazil: implications for tuberculosis prevention strategies.

BACKGROUND: Tuberculosis (TB) elimination requires treatment of millions of persons with latent M. tuberculosis infection (LTBI). LTBI treatment acceptance depends on population-wide TB knowledge and low stigma, but limited data are available on the relationship between stigma and knowledge. We assessed knowledge of TB disease and LTBI throughout Brazil and examined their association with TB stigma and incidence. METHODS: We performed a nationwide survey with multi-stage probability design through AmericasBarometer from April-May 2017; the sample was representative of Brazil at regional and national levels. Knowledge of and stigma toward TB were assessed by validated survey questions. RESULTS: Survey-weighted responses of 1532 individuals suggest that 57% of the population knew LTBI can occur, and 90% would seek treatment for it. Regarding active TB, 85% knew TB symptoms, 70% reported they should avoid contact with someone with active TB, and 24% had stigma toward persons with TB (i.e., thought persons with tuberculosis should feel ashamed, or deserved their illness). In regression models adjusting for clinical and demographic variables, knowledge of LTBI was associated with increased stigma toward persons with TB (adjusted odds ratio [OR] = 2.13, 95% confidence interval [CI]: 1·25-3.63, for "should feel ashamed"; OR = 1·82, 95% CI: 1·15-2·89, for "deserve illness"). Adjusting for regional TB incidence did not affect this association. CONCLUSIONS: High proportions of this representative Brazilian population had knowledge of LTBI and were willing to seek treatment for it. However, such knowledge was associated with TB-specific stigma. Strategies to educate and implement treatment of latent tuberculosis must include efforts to decrease TB stigma.

Differential expression of circulating micro-RNAs in patients with active and latent tuberculosis. / Expresión diferencial de micro-ARN circulantes en pacientes con tuberculosis activa y latente.

OBJECTIVES: To analyze the differential expression of miR-21, miR-29a, miR-99b and miR-155 in serum samples from patients with latent tuberculosis (TB) and active TB compared to healthy controls. MATE RIALS AND METHODS: We used 28 serum samples (9 with active TB, 10 with latent TB and 9 healthy con trols) for the analysis of gene expression by RT-qPCR with Primers and TaqMan probes. The differential expression was calculated by the Livak method using a normalizing gene (RNU-48). RESULTS: Overex pression of miR-155 was found in people with latent tuberculosis, compared to healthy controls (0.63 vs. 0.01; p value = 0.032). CONCLUSION: The miR-155 could be considered a biomarker to differentiate latent TB from active disease. Studies with larger sample sizes are required to corroborate the findings.

OBJETIVO: El objetivo del estudio fue analizar la expresión diferencial de miR-21, miR-29a, miR-99b y miR-155 en muestras de suero de pacientes con tuberculosis (TB) latente y TB activa respecto a contro les sanos. MATERIALES Y MÉTODOS: Se utilizaron 28 muestras de suero (nueve con TB activa, diez con TB latente y nueve controles sanos) para el análisis de expresión génica mediante RT-qPCR con Primers y sondas TaqMan. Se calculó la expresión diferencial por el método de Livak utilizando un gen norma lizador (RNU-48). RESULTADOS: Se halló una sobreexpresión de miR-155 en personas con tuberculosis latente, respecto a los controles sanos (0,63 vs. 0,01; valor de p=0,032). CONCLUSIÓN: El miR-155 podría ser considerado un biomarcador para diferenciar TB latente de enfermedad activa. Se requieren estudios con mayores tamaños muestrales para corroborar nuestros hallazgos.

Solutions to improve the latent tuberculosis Cascade of Care in Ghana: a longitudinal impact assessment.

BACKGROUND: Loss of patients in the latent tuberculosis infection (LTBI) cascade of care is a major barrier to LTBI management. We evaluated the impact and acceptability of local solutions implemented to strengthen LTBI management of household contacts (HHCs) at an outpatient clinic in Ghana. METHODS: Local solutions to improve LTBI management were informed by a baseline evaluation of the LTBI cascade and questionnaires administered to index patients, HHCs, and health care workers at the study site in Offinso, Ghana. Solutions aimed to reduce patient costs and improve knowledge. We evaluated the impact and acceptability of the solutions. Specific objectives were to: 1) Compare the proportion of eligible HHCs completing each step in the LTBI cascade of care before and after solution implementation; 2) Compare knowledge, attitude, and practices (KAP) before and after solution implementation, based on responses of patients and health care workers (HCW) to structured questionnaires; 3) Evaluate patient and HCW acceptability of solutions using information obtained from these questionnaires. RESULTS: Pre and Post-Solution LTBI Cascades included 58 and 125 HHCs, respectively. Before implementation, 39% of expected < 5-year-old HHCs and 66% of ≥5-year-old HHCs were identified. None completed any further cascade steps. Post implementation, the proportion of eligible HHCs who completed identification, assessment, evaluation, and treatment initiation increased for HHCs < 5 to 94, 100, 82, 100%, respectively, and for HHCs ≥5 to 96, 69, 67, 100%, respectively. Pre and Post-Solutions questionnaires were completed by 80 and 95 respondents, respectively. Study participants most frequently mentioned financial support and education as the solutions that supported LTBI management. CONCLUSION: Implementation of locally selected solutions was associated with an increase in the proportion of HHCs completing all steps in the LTBI cascade. Tuberculosis programs should consider prioritizing financial support, such as payment for chest x-rays, to support LTBI cascade completion.

Resource implications of the latent tuberculosis cascade of care: a time and motion study in five countries.

BACKGROUND: The End TB Strategy calls for global scale-up of preventive treatment for latent tuberculosis infection (LTBI), but little information is available about the associated human resource requirements. Our study aimed to quantify the healthcare worker (HCW) time needed to perform the tasks associated with each step along the LTBI cascade of care for household contacts of TB patients. METHODS: We conducted a time and motion (TAM) study between January 2018 and March 2019, in which consenting HCWs were observed throughout a typical workday. The precise time spent was recorded in pre-specified categories of work activities for each step along the cascade. A linear mixed model was fit to estimate the time at each step. RESULTS: A total of 173 HCWs in Benin, Canada, Ghana, Indonesia, and Vietnam participated. The greatest amount of time was spent for the medical evaluation (median: 11 min; IQR: 6-16), while the least time was spent on reading a tuberculin skin test (TST) (median: 4 min; IQR: 2-9). The greatest variability was seen in the time spent for each medical evaluation, while TST placement and reading showed the least variability. The total time required to complete all steps along the LTBI cascade, from identification of household contacts (HHC) through to treatment initiation ranged from 1.8 h per index TB patient in Vietnam to 5.2 h in Ghana. CONCLUSIONS: Our findings suggest that the time requirements are very modest to perform each step in the latent TB cascade of care, but to achieve full identification and management of all household contacts will require additional human resources in many settings.

Latent tuberculosis in the general practice context.

BACKGROUND: Latent tuberculosis infection (LTBI) is an asymptomatic condition that may progress to active tuberculosis (TB), sometimes decades after exposure. Most people with active TB in Australia have not had recent contact and have been unaware of their risk. Tests for LTBI are available, allowing for diagnosis and preventive therapy to avoid active disease. OBJECTIVE: The aim of this article is to review current approaches to the diagnosis and management of LTBI, with particular focus on the Australian general practice setting. Groups at elevated risk of having LTBI and progressing to active disease are outlined. Recent research into the prevalence and distribution of LTBI in Australia is reviewed, and Australian guidelines for testing and treatment are summarised. DISCUSSION: LTBI occurs in an estimated 5% of all Australian residents. However, this is a particular issue for those born in TB-endemic countries. Approximately 17% of all overseas-born Australian residents, but only 0.4% of Australian-born residents, have LTBI. Appropriate diagnosis and management is an important long-term health promotion activity, and many people with LTBI can be managed safely and effectively in Australian general practice settings.

Latent Tuberculosis in Hematopoietic Stem Cell Transplantation: Diagnostic and Therapeutic Strategies to Prevent Disease Activation in an Endemic Population.

Latent tuberculosis infection (LTBI) affects one-fourth of the world´s population. Hematopoietic stem cell transplantation (HSCT) recipients are at an elevated risk of developing active tuberculosis infection (ATBI). In this retrospective study of donors and HSCT recipients who underwent transplantation between February 2000 and June 2018, our aim was to determine the prevalence of LTBI and ATBI and to describe diagnostic and therapeutic strategies in an HSCT population in an endemic region. The cohort of 409 participants included 125 allogeneic HSCT (allo-HSCT) recipients, 165 autologous HSCT (auto-HSCT) recipients, and 119 HSCT donors. Patients were evaluated pre-HSCT with tuberculin skin test and thoracic imaging. LTBI was diagnosed in 26.2% of the cohort. Cases represented 20% of the auto-HSCT population, 20% of the allo-HSCT population, and 41.2% of the donor population. Pre-HSCT evaluation to rule out ATBI was performed in 62.6% of the cohort; all results were negative. Isoniazid was administered to 73.3% of those with LTBI. Within subgroups, 91.7% of HSCT recipients and 51% of donors received treatment. The median duration of therapy pre-HSCT was 70 days in recipients and 48 days in donors. The incidence of post-HSCT ATBI was 0 at 1-year follow-up. The incidence of LTBI in our population was higher than expected and still might have been underestimated owing to diagnostic test limitations. The absence of incident ATBI suggests that recipients, as opposed to donors, must receive LTBI treatment. Prevention of infectious complications in the HSCT population should be prioritized to improve clinical outcomes. Prospective data from collaborative working groups is needed to determine the best diagnostic and therapeutic approaches in this vulnerable patient population.