A Mathematical Model for the Impact of 3HP and Social Programme Implementation on the Incidence and Mortality of Tuberculosis: Study in Brazil.

In this paper, we presented a mathematical model for tuberculosis with treatment for latent tuberculosis cases and incorporated social implementations based on the impact they will have on tuberculosis incidence, cure, and recovery. We incorporated two variables containing the accumulated deaths and active cases into the model in order to study the incidence and mortality rate per year with the data reported by the model. Our objective is to study the impact of social program implementations and therapies on latent tuberculosis in particular the use of once-weekly isoniazid-rifapentine for 12 weeks (3HP). The computational experimentation was performed with data from Brazil and for model calibration, we used the Markov Chain Monte Carlo method (MCMC) with a Bayesian approach. We studied the effect of increasing the coverage of social programs, the Bolsa Familia Programme (BFP) and the Family Health Strategy (FHS) and the implementation of the 3HP as a substitution therapy for two rates of diagnosis and treatment of latent at 1% and 5%. Based of the data obtained by the model in the period 2023-2035, the FHS reported better results than BFP in the case of social implementations and 3HP with a higher rate of diagnosis and treatment of latent in the reduction of incidence and mortality rate and in cases and deaths avoided. With the objective of linking the social and biomedical implementations, we constructed two different scenarios with the rate of diagnosis and treatment. We verified with results reported by the model that with the social implementations studied and the 3HP with the highest rate of diagnosis and treatment of latent, the best results were obtained in comparison with the other independent and joint implementations. A reduction of the incidence by 36.54% with respect to the model with the current strategies and coverage was achieved, and a greater number of cases and deaths from tuberculosis was avoided.

Explaining age disparities in tuberculosis burden in Taiwan: a modelling study.

BACKGROUND: Tuberculosis (TB) burden shows wide disparities across ages in Taiwan. In 2016, the age-specific notification rate in those older than 65 years old was about 100 times as much as in those younger than 15 years old (185.0 vs 1.6 per 100,000 population). Similar patterns are observed in other intermediate TB burden settings. However, driving mechanisms for such age disparities are not clear and may have importance for TB control efforts. METHODS: We hypothesised three mechanisms for the age disparity in TB burden: (i) older age groups bear a higher risk of TB progression due to immune senescence, (ii) elderly cases acquired TB infection during a past period of high transmission, which has since rapidly declined and thus contributes to little recent infections, and (iii) assortative mixing by age allows elders to maintain a higher risk of TB infection, while limiting spillover transmission to younger age groups. We developed a series of dynamic compartmental models to incorporate these mechanisms, individually and in combination. The models were calibrated to the TB notification rates in Taiwan over 1997-2016 and evaluated by goodness-of-fit to the age disparities and the temporal trend in the TB burden, as well as the deviance information criterion (DIC). According to the model performance, we compared contributions of the hypothesised mechanisms. RESULTS: The 'full' model including all the three hypothesised mechanisms best captured the age disparities and temporal trend of the TB notification rates. However, dropping individual mechanisms from the full model in turn, we found that excluding the mechanism of assortative mixing yielded the least change in goodness-of-fit. In terms of their influence on the TB dynamics, the major contribution of the 'immune senescence' and 'assortative mixing' mechanisms was to create disparate burden among age groups, while the 'declining transmission' mechanism served to capture the temporal trend of notification rates. CONCLUSIONS: In settings such as Taiwan, the current TB burden in the elderly may be impacted more by prevention of active disease following latent infection, than by case-finding for blocking transmission. Further studies on these mechanisms are needed to disentangle their impacts on the TB epidemic and develop corresponding control strategies.

Determinants of losses in the latent tuberculosis cascade of care in Brazil: A retrospective cohort study.

BACKGROUND: The present study evaluated factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of tuberculosis (TB) patients, in a referral center from a highly endemic region in Brazil. METHODS: Contacts of 1672 TB patients were retrospectively studied between 2009 and 2014. Data on TB screening by clinical investigation, radiographic examination and tuberculin skin test (TST) were extracted from medical records. Losses in the cascade of care and TB incidence within 2-year follow-up were calculated. RESULTS: From a total of 1180 TB contacts initially identified, only 495 were examined (58% loss), and 20 were diagnosed with active TB at this stage. Furthermore, 435 persons returned for TST result interpretation and 351 (∼81%) were TST positive. Among those with positive TST, 249 (73%) were treated with isoniazid for 6 months whereas 51 abandoned therapy early. Three individuals who did not receive LTBI treatment, one with incomplete treatment and another who completed treatment developed active TB. A logistic regression analysis revealed that increases in age were associated with losses in the LTBI cascade independent of other clinical and epidemiological characteristics. CONCLUSIONS: Major losses occur at initial stages and older patients are at higher risk of not completing the LTBI cascade of care.

A population-based study of tuberculosis incidence among rheumatic disease patients under anti-TNF treatment.

INTRODUCTION: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. The advent of immunobiologic therapy with TNF inhibitors agents, has been associated with a significant increase in incident cases of tuberculosis in this population. OBJECTIVE: To estimate the incidence of tuberculosis in patients receiving TNF inhibitors therapy for rheumatic diseases. As secondary objectives, we sought to evaluate mortality and the clinical impact of screening for latent tuberculosis infection. METHODS: This retrospective study included patients with rheumatic diseases of Public Health System from the Brazilian state, a high TB incidence area, who received prescriptions of TNF inhibitors agents between 2006 and 2016. RESULTS: A total of 5853 rheumatic disease patients were included. Patients were predominantly women (68.7%) aged 49.5 (± 14.7) years old. Forty-three cases of TB were found (2.86 cases per 1000 person-years; 18 times higher than in the general population). Adalimumab and certolizumab users presented a higher risk for TB development compared to etanercept users (RR: 3.11, 95%CI 1.16-8.35; 7.47, 95%CI 1.39-40.0, respectively). In a subgroup of patients, screening for latent tuberculosis infection was performed in 86% of patients, and 30.2% had a positive tuberculin skin test. Despite latent TB treatment, TB was diagnosed in 2 out of 74 (2.7%) patients. Overall, TB diagnosis did not increase mortality. CONCLUSION: In this population-based study of rheumatic disease patients from a high incident area, TNF inhibitor exposure was associated with an 18-time increased TB incidence. Adalimumab and certolizumab were associated with greater and earlier TB diagnosis compared to etanercept.

Epidemiology of tuberculous lymphadenitis in Denmark: A nationwide register-based study.

BACKGROUND: Tuberculous lymphadenitis (TBLA) is the most common extrapulmonary manifestation of tuberculosis (TB), often claimed to be reactivation. We aimed to describe the epidemiology of TBLA in Denmark, as it has not previously been investigated specifically although extrapulmonary TB has been associated with an increased long-term mortality and delays in the diagnosis. METHODS: Register-based study of all patients notified with TBLA in Denmark from 2007 through 2016 utilizing six different nationwide registers. Patients were identified through the national TB surveillance register, and the diagnosis evaluated based on microbiology, pathology and/or clinical assessment. RESULTS: In total, 13.5% (n = 489) of all TB patients in Denmark had TBLA with annual proportions from 9.4 to 15.7%. Most patients were immigrants between 25-44 years. Incidence rates ranged from as high as 1,014/100,000 for Nepalese citizens to as a low as 0.06/100,000 for Danes. Danes had a significant higher median age and significant more risk factors and comorbidities, as well as an increased overall mortality, compared with immigrants (p<0.05). A significant and much higher proportion of unique MIRU-VNTR genotypes were seen among TBLA patients compared to other TB manifestations. CONCLUSION: In Denmark, TBLA is a common manifestation of TB, especially in young immigrants from high-incidence countries. In Danes, it is a rare disease manifestation and associated with higher morbidity and mortality. To our knowledge, this is the first study suggesting that TBLA is predominantly associated with reactivation of latent TB infection based on genotyping although this remains to be clarified.

Mycobacterium tuberculosis recombinant protein Rv2626c expressed in Streptomyces lividans. Physico-chemical and Immunological characterization as potential vaccine antigen

Mycobacterium tuberculosis (Mtb) is a leading cause of death globally. Latent tuberculosis infection threatens 1.7 billion people. Mtb latency is mediated by a group of proteins, mainly coded by the Dormancy Safety Regulator (DosR). The protein Rv2626c is the strongest regulated member of this operon. Previous results, including ours, indicate a strong potential of Rv2626c as antigen in a new multiple tuberculosis vaccine. Objectives of this study were to purify the rRv2626c protein and characterize it physico-chemically and immunologically. The purified protein migrates as a sole band after a non-reductive PAGE-silver staining. Under reductive conditions, the dimer isoform appearing at 30.9 kDa prevails over the monomer 15.6 kDa. Mass spectrometry corroborates electrophoresis results regarding dimer molecular weight, of approximately 32 kDa. Six of its digested peptides matched those of HRP-1 protein (Rv2626c) of Mtb whereas 92.1 percent of its amino acid sequence contains three mutations and the addition of an amino acid. With respect to native Mtb protein, 12 of the 13 main epitopes are conserved. Antigenicity was corroborated in volunteers, the antibody responses were significantly higher in a number of infected tuberculosis patients in comparison to healthy Mantoux negative donors as well as in mice immunized with reference Rv2626c, while the immune identification pattern was as expected. The purified protein was able to elicit strong immune response in mice and the resulting antibodies recognized the reference Rv2626c protein. Lastly, the productive specific yield of the Streptomyces lividans strain is sustainable. Taking these results altogether, corroborates our rRv2626c as a promising candidate as antigen for new tuberculosis vaccine formulations(AU)

Mycobacterium tuberculosis (Mtb) es una de las principales causas de muerte globalmente, la tuberculosis latente amenaza a 1,7 mil millones de personas. En combinación con el VIH-SIDA y otras enfermedades, la tuberculosis puede ser reactivada. La latencia de Mtb está mediada por un grupo de proteínas, principalmente codificadas por el Regulador de Seguridad de Latencia (DosR). La proteína Rv2626c es el miembro más fuertemente regulado de este operón. Los resultados previos, incluidos los nuestros, indican una gran potencialidad de Rv2626c como antígeno en una nueva vacuna múltiple contra la tuberculosis. Los objetivos de este estudio fueron purificar la proteína Rv2626c y caracterizarla fisicoquímica e inmunológicamente. La proteína purificada migra como una banda única después de PAGE con tinción de plata en condiciones no reductoras. En condiciones reductoras, el dímero, de 30,9 kDa, es la isoforma prevaleciente sobre el monómero, de 15,6 kDa. La espectrometría de masas corrobora el peso molecular del dímero, de aproximadamente 32 kDa. Seis de sus péptidos digeridos coincidieron con los de la proteína Rv2626c de Mtb, mientras que se confirmó coincidencia del 92,1 por ciento de su secuencia de aminoácidos, detectándose tres mutaciones y la adición de un aminoácido. Con respecto a la proteína Mtb nativa, se conservan 12 de los 13 epítopes principales. La antigenicidad se corroboró en voluntarios, las respuestas de anticuerpos fueron significativamente mayores en un número de pacientes infectados con tuberculosis en comparación con los donantes negativos de Mantoux sanos, así como en ratones inmunizados con la referencia Rv2626c, mientras que el patrón de identificación inmune fue el esperado. La proteína purificada fue capaz de provocar una fuerte respuesta inmune en ratones y los anticuerpos resultantes reconocieron la proteína de referencia Rv2626c. Por último, el rendimiento productivo específico de la cepa de Streptomyces lividans es sostenible. Tomando estos resultados en conjunto, corrobora nuestra rRv2626c como un candidato prometedor como antígeno para nuevas formulaciones de vacunas contra la tuberculosis(AU)

Tuberculosis incidence among infected contacts detected through contact tracing of smear-positive patients.

BACKGROUND: The contacts of people with pulmonary tuberculosis (PTB) have a high risk of becoming infected and developing tuberculosis (TB). Our aim was to determine the incidence of TB and its risk factors in a cohort of contacts with latent TB infection (LTBI) detected through contact tracing of smear-positive PTB cases. METHODS AND FINDINGS: We performed a population-based retrospective cohort study including contacts that had LTBI, and were contacts of people with PTB who started treatment between 2008 and 2014. We followed up contacts until they developed TB or until the end date for follow-up (31st December 2016). We used Kaplan-Meier curves to compute incidence at 2 and 5 years, and Cox regression to compute hazard ratios (HR) and their 95% confidence intervals (CI). We analyzed 3097 close contacts of 565 PTB cases. After exclusion of 81 co-prevalent TB cases, 953 contacts had LTBI, of which 14 developed TB. Their risk of developing TB after two and five years was 0.7% (CI: 0.3-1.6) and 1.8% (CI: 1.1-3.1) respectively. Contacts who had not been referred for LTBI treatment had a 1.0% (CI: 0.2-4.0) risk at 5 years. Risk of developing TB at 5 years was 1.2% (CI: 0.5-3.0) among people who completed treatment, and 11.1% (CI: 5.1-23.3) for those who did not. Risk factors for TB were not completing LTBI treatment (HR 9.4, CI: 2.9-30.8) and being female (HR 3.5, CI: 1.1-11-3). CONCLUSIONS: LTBI treatment plays a fundamental role in decreasing the risk of developing TB. It is necessary to achieve a maximum contact tracing coverage and the highest possible compliance with LTBI treatment.

Tuberculin conversion and tuberculosis disease in infants and young children from the Drakenstein Child Health Study: A call to action.

Although tuberculosis (TB) is widely acknowledged as a major driver of global morbidity and mortality in adults, the disease's impact on children has been underappreciated. Global estimates of mortality among children aged <5 years, derived largely from vital registration and verbal autopsy records, have excluded paediatric TB as a contributing cause.

Burden of non-adherence to latent tuberculosis infection drug therapy and the potential cost-effectiveness of adherence interventions in Canada: a simulation study.

OBJECTIVE: Pharmaceutical treatment of latent tuberculosis infection (LTBI) reduces the risk of progression to active tuberculosis (TB); however, poor adherence tempers the protective effect. We aimed to estimate the health burden of non-adherence, the maximum allowable cost of hypothetical new adherence interventions to be cost-effective and the potential value of existing adherence interventions for patients with low-risk LTBI in Canada. DESIGN: A microsimulation model of LTBI progression over 25 years. SETTING: General practice in Canada. PARTICIPANTS: Individuals with LTBI who are initiating drug therapy. INTERVENTIONS: A hypothetical intervention with a range of effectiveness was evaluated. Existing drug adherence interventions including peer support, two-way text messaging support, enhanced adherence counselling and adherence incentives were also evaluated. PRIMARY AND SECONDARY OUTCOME MEASURES: Simulation outcomes included healthcare costs, TB incidence, TB deaths and quality-adjusted life years (QALYs). Base case results were interpreted against a willingness-to-pay threshold of $C50 000/QALY. RESULTS: Compared with current adherence levels, full adherence to LTBI drug therapy could reduce new TB cases from 90.3 cases per 100 000 person-years to 35.9 cases per 100 000 person-years and reduce TB-related deaths from 7.9 deaths per 100 000 person-years to 3.1 deaths per 100 000 person-years. An intervention that increases relative adherence by 40% would bring the population near full adherence to drug therapy and could have a maximum allowable annual cost of approximately $C450 per person to be cost-effective. Based on estimates of effect sizes and costs of existing adherence interventions, we found that they yielded between 900 and 2400 additional QALYs per million people, reduced TB deaths by 5%-25% and were likely to be cost-effective over 25 years. CONCLUSION: Full adherence could reduce the number of future TB cases by nearly 60%, offsetting TB-related costs and health burden. Several existing interventions are could be cost-effective to help achieve this goal.

Benefit of treatment of latent tuberculosis infection in individual patients.

We aimed to develop a decision aid that estimates whether treatment of latent tuberculosis infection (LTBI) is likely to have a net gain in quality-adjusted life-years for an individual. A Markov model was developed which incorporated personalised estimates for risk of tuberculosis (TB) reactivation, TB death, quality-of-life impairments and treatment side-effects. The net effect of LTBI treatment was quantified in terms of quality-adjusted life-years gained or lost. Analyses were conducted for a representative set of hypothetical patients. LTBI treatment was estimated to be beneficial when the annual risk of TB reactivation exceeded 13/100,000 to 93/100,000 for females aged 10-75 years and 15/100,000 to 119/100,000 for males aged 10-75 years; the numbers needed to treat to avoid one case of TB were 93, 77, 85 and 72, respectively, at these threshold levels. LTBI treatment was estimated to confer a positive net benefit across a broad range of patients with characteristics typically seen in a low incidence setting for TB. Use of the decision aid has the potential to facilitate and increase confidence with LTBI treatment decisions by providing clinicians and patients with personalised estimates of likely net benefit.

Longevity loss among cured tuberculosis patients and the potential value of prevention.

BACKGROUND: Evidence of substantial, quantifiable and preventable burdens of mortality hazard even after anti-tuberculosis treatment and cure would be a compelling, concrete, and useful measure of the value of prevention. METHODS: We compared years of potential life lost between a cohort of 3 933 cured tuberculosis (TB) patients and 9 166 persons with latent tuberculous infection. We constructed a regression model to predict the expected years of potential life lost in each cohort and for demographic subgroups. RESULTS: Among decedents, a history of fully treated TB is associated with a predicted average 3.6 more years of potential life loss than a comparable population without active TB. Greater longevity losses were predicted among those identified as White and Hispanic than among Black and Asian counterparts. CONCLUSION: We found significant differences in predicted longevity of treated TB survivors relative to a similar group without active TB. These excess losses are substantial: a total of 14 158 life-years or the equivalent of more than 188 75-year lifespans. These findings illustrate an important opportunity cost associated with each preventable TB case - an average of 3.6 potential years of life. We conclude that substantial preventable mortality burdens remain despite adequate anti-tuberculosis treatment, a compelling rationale for more widespread and systematic use of prevention.

Modeling the potential impact of host population survival on the evolution of M. tuberculosis latency.

Tuberculosis (TB) is an infectious disease with a peculiar feature: Upon infection with the causative agent, Mycobacterium Tuberculosis (MTB), most hosts enter a latent state during which no transmission of MTB to new hosts occurs. Only a fraction of latently infected hosts develop TB disease and can potentially infect new hosts. At first glance, this seems like a waste of transmission potential and therefore an evolutionary suboptimal strategy for MTB. It might be that the human immune response keeps MTB in check in most hosts, thereby preventing it from achieving its evolutionary optimum. Another possible explanation is that long latency and progression to disease in only a fraction of hosts are evolutionary beneficial to MTB by allowing it to persist better in small host populations. Given that MTB has co-evolved with human hosts for millenia or longer, it likely encountered small host populations for a large share of its evolutionary history and had to evolve strategies of persistence. Here, we use a mathematical model to show that indeed, MTB persistence is optimal for an intermediate duration of latency and level of activation. The predicted optimal level of activation is above the observed value, suggesting that human co-evolution has lead to host immunity, which keeps MTB below its evolutionary optimum.

Modeling the spread of tuberculosis in semiclosed communities.

We address the problem of long-term dynamics of tuberculosis (TB) and latent tuberculosis (LTB) in semiclosed communities. These communities are congregate settings with the potential for sustained daily contact for weeks, months, and even years between their members. Basic examples of these communities are prisons, but certain urban/rural communities, some schools, among others could possibly fit well into this definition. These communities present a sort of ideal conditions for TB spread. In order to describe key relevant dynamics of the disease in these communities, we consider a five compartments SEIR model with five possible routes toward TB infection: primary infection after a contact with infected and infectious individuals (fast TB), endogenous reactivation after a period of latency (slow TB), relapse by natural causes after a cure, exogenous reinfection of latently infected, and exogenous reinfection of recovered individuals. We discuss the possible existence of multiple endemic equilibrium states and the role that the two types of exogenous reinfections in the long-term dynamics of the disease could play.

Chemoprophylaxis with isoniazid in liver transplant recipients.

A patient receiving a liver graft needs to be treated with immunosuppressive drugs to avoid rejection. These kinds of drugs predispose the patient to the reactivation of latent infections such as tuberculosis (TB). Therefore, it is necessary to establish treatment regimens to prevent this. We retrospectively analyzed all consecutive patients undergoing liver transplantation (LT) at our center between January 1, 2000 and December 31, 2010. Latent tuberculosis infections (LTBIs) were diagnosed with positive tuberculin skin test results. After LT, infected patients were treated with isoniazid for 6 months; the treatment began soon after transplantation, and the patients were followed until the end of the study. During this period, 53 patients had LTBI data. All these patients were treated with isoniazid after LT. The median observation period after LT was 52 months (range = 12-129 months). No cases of TB reactivation were reported during follow-up. Only 4 patients presented alterations in liver enzymes related to this treatment, and they showed clear improvement after the treatment was stopped. None of these patients showed severe graft dysfunction. In conclusion, preventive isoniazid appears to be a safe drug for use in LTBI patients after LT. The treatment may be established just after LT without important graft dysfunction or severe consequences for the patient.

Tuberculosis in ageing: high rates, complex diagnosis and poor clinical outcomes.

BACKGROUND: worldwide, the frequency of tuberculosis among older people almost triples that observed among young adults. OBJECTIVE: to describe clinical and epidemiological consequences of pulmonary tuberculosis among older people. METHODS: we screened persons with a cough lasting more than 2 weeks in Southern Mexico from March 1995 to February 2007. We collected clinical and mycobacteriological information (isolation, identification, drug-susceptibility testing and IS6110-based genotyping and spoligotyping) from individuals with bacteriologically confirmed pulmonary tuberculosis. Patients were treated in accordance with official norms and followed to ascertain treatment outcomes, retreatment, and vital status. RESULTS: eight hundred ninety-three tuberculosis patients were older than 15 years of age; of these, 147 (16.5%) were 65 years of age or older. Individuals ≥ 65 years had significantly higher rates of recently transmitted and reactivated tuberculosis. Older age was associated with treatment failure (OR=5.37; 95% CI: 1.06-27.23; P=0.042), and death due to tuberculosis (HR=3.52; 95% CI: 1.78-6.96; P<0.001) adjusting for sociodemographic and clinical variables. CONCLUSIONS: community-dwelling older individuals participate in chains of transmission indicating that tuberculosis is not solely due to the reactivation of latent disease. Untimely and difficult diagnosis and a higher risk of poor outcomes even after treatment completion emphasise the need for specific strategies for this vulnerable group.

Analysis of undiagnosed tuberculosis-related deaths identified at post-mortem among HIV-infected patients in Russia: a descriptive study.

BACKGROUND: Tuberculosis remains a serious public health threat and economic burden in Russia with escalating rates of drug resistance against a background of growing HIV-epidemic. Samara Oblast is one of the regions of the Russian Federation where more than 1% of the population is affected by the HIV-epidemic; almost half of the cases are concentrated in the largely-industrial city of Togliatti with a population of 800 000. METHODS: We conducted a retrospective analysis of errors leading to death of HIV-positive patients in general health care hospitals in Togliatti, Russia, in 2008. All (n = 29) cases when tuberculosis was established at autopsy as a cause of death were included. RESULTS: Median length of hospital stay was 20 days; in 11 cases the death occurred within the first 24 hours of admission. All cases were known to be HIV-positive prior to admission, however HAART was not initiated for any case, and no relevant tests to assess severity of immunosupression were performed despite their availability. No appropriate diagnostic algorithms were applied to confirm tuberculosis. Major gaps were identified in the work of hospital and consulting physicians including insufficient records keeping. In almost all patients earlier regular HIV-relevant tests were not performed due to poor compliance of patients, many of whom abused alcohol and drugs. CONCLUSIONS: We conclude that introduction of prompt and accurate diagnostics tests, adequate treatment protocols and intensive training of physicians in management of AIDS and TB is vital. This should include reviewing standards of care for HIV-positive individuals with accompanying social problems.

[The global importance of tuberculosis]. / Tuberkulose - weltweite Bedeutung.

In the western industrialized world tuberculosis has receded from its peak with an annual mortality of 1 % some 150 to 250 years ago to currently 10 to 20 new cases annually per 100,000 population. The introduction of chemotherapy in the 1950s reduced case fatality from some 70 % to a small fraction. Nowadays, the indigenous elderly and immigrants from high-prevalence countries contribute most of tuberculosis morbidity in the industrialized world. In contrast, tuberculosis remains a major public health problem in most resource-constrained countries and has substantially increased in sub-Saharan Africa as a result of the impact of HIV infection. The World Health Organization estimates that each year over 9 million new cases emerge in the world. Because of weak infrastructures low-income countries continue to experience shortages in the drug supply, facilitating the emergence of strains resistant to first-line drugs which are difficult or impossible to treat. The primordial task for the international community is to assist in strengthening the necessary infrastructures and to help ensuring that patients have unrestricted and uninterrupted access to antituberculosis medications and antiretroviral drugs.

Detection and management of latent tuberculosis in liver transplant patients.

The optimal means for detecting and managing liver transplantation (LT) patients with latent tuberculosis (TB) are not well defined. Our study aims were to (1) determine the frequency and risk factors of latent TB in a large cohort of consecutive adult LT candidates and (2) determine the safety and efficacy of isoniazid treatment in LT recipients with latent TB. A review of patients assessed for latent TB by skin testing using purified protein derivative (PPD; January 2004 to September 2008) or with the interferon-γ release assay QuantiFERON-TB Gold (QFT; March 2008 to October 2009) was undertaken. The baseline clinical features and outcomes of subjects with latent TB and subjects without latent TB were compared. Twenty-five of 420 subjects (6.0%) were positive for PPD. In comparison, 11 of 119 subjects (9.2%) had a positive QFT assay, and 15 others (13%) had indeterminate results. Both PPD-positive and QFT-positive subjects were less likely to be Caucasian than subjects without latent TB (p < 0.001). The 3-year survival rate of the 25 LT recipients with latent TB was similar to that of the 296 LT recipients without latent TB (78.7% versus 74.6%, P = 0.58). Fifteen of the 25 latent TB patients received isoniazid at a mean of 0.67 months after LT. Although isoniazid was discontinued in 8 subjects because of possible side effects, none of the 25 latent TB patients developed TB reactivation after transplantation with a mean follow-up of 33 months. In conclusion, both QFT testing and PPD testing demonstrate similar rates of detecting latent TB infection in American LT candidates, but QFT testing also leads to a moderate rate of indeterminate test results. Early isoniazid chemoprophylaxis after LT is poorly tolerated and is frequently discontinued.