High Risk Of Active Tuberculosis Research Articles

Prospective cohort study on tuberculosis incidence and risk factors in the elderly population of eastern China

BackgroundTuberculosis continues to be a significant public health concern in China, particularly among the elderly population. This study aimed to assess the risk factors of tuberculosis among elderly individuals in China through a cohort study, focusing on this high-risk population. MethodsThe population-based census was strategically designed to cover diverse regions and demographics across the city. The survey captured demographic and lifestyle information, as well as a clinical examination. Participants were prospectively followed up over a specified duration to monitor the incidence of tuberculosis cases. ResultsAfter a follow-up period of more than 7 years, 246 individuals developed tuberculosis, resulting in an incidence rate of 92.21 per 100,000 person-years (95 % CI 81.2–104.3). In multivariate analysis, the following factors were found to have significant associations with active tuberculosis. Increasing age correlated with a higher risk of active tuberculosis (AHR = 1.03 per 1-year increase in age, 95%CI: 1.01, 1.04, P < 0.001). Males continued to have a higher risk compared to females (HR = 2.73, 95%CI: 2.08, 3.58, P < 0.001). Individuals with a normal Body Mass Index (BMI) faced nearly three times higher risk compared to their obese counterparts (HR = 2.87, 95 % CI: 1.51, 5.46, P = 0.001). Conversely, those with an underweight BMI had a ten-fold higher risk compared to the obese group (HR = 9.89, 95 % CI: 4.92, 19.85, P < 0.001). Elderly individuals who quit smoking had a 1.35-fold increased risk compared to non-smokers (HR = 1.35, 95%CI: 1.12, 1.64, P < 0.001). ConclusionsTuberculosis incidence among the elderly population in China remained alarmingly high. This finding emphasizes the urgent need for implementing proactive case detection measures specifically tailored to address the specific needs of this vulnerable demographic, particularly in individuals who are male, have a history of former or current smoking, and have a low BMI. Moreover, we must not underestimate the influence of former smoking on tuberculosis risk.

Healthcare workers' acceptance of and adherence to latent tuberculosis treatment.

Healthcare workers (HCWs) with latent tuberculosis infection (LTBI) have a high risk of active tuberculosis and need systematic LTBI screening and treatment. However, acceptance and adherence rates of LTBI treatment are low. To examine the specific reasons for the loss at each LTBI treatment-cascade stage: acceptance, continuation and completion of LTBI treatment in HCWs. This retrospective descriptive study was conducted among 61 HCWs with an interferon-gamma release assay-confirmed LTBI diagnosis who were prescribed LTBI treatment at a tertiary hospital in the Republic of Korea. Data were analysed using Pearson's chi-square, Fisher's exact, independent t-test and Mann-Whitney U-test. A word cloud analysis was used to describe the perceived meaning of LTBI in HCWs. HCWs who refused or discontinued LTBI treatment perceived LTBI as 'not a big deal', whereas HCWs who completed LTBI treatment had a high-risk perception of the LTBI prognosis, such as 'frightened about adverse prognosis'. Determinants of non-adherence to the recommended LTBI treatment included a busy work schedule, side effects of anti-tuberculosis agents and the inconvenience of regularly taking anti-tuberculosis agents. To ensure LTBI treatment adherence in HCWs, effective interventions that are customized to each stage of the LTBI treatment should be developed, with due consideration of the stage-specific perceived facilitators and barriers in the LTBI treatment cascade.

Atypical Pulmonary Tuberculosis as the First Manifestation of Advanced HIV Disease-Diagnostic Difficulties.

Tuberculosis (TB) is the leading cause of morbidity, hospitalisations, and mortality in people living with HIV (PLWH). The lower CD4+ T-lymphocyte count in the course of HIV infection, the higher risk of active TB, and the higher odds for atypical clinical and radiologic TB presentation. These HIV-related alterations in TB presentation may cause diagnostic problems in patients not knowing they are infected with HIV. We report on a patient without any background medical conditions, who was referred to a hospital with a 4-month history of chest and feet pains, mild dry cough, fatigue, reduced appetite, and decreasing body weight. Chest X-ray revealed mediastinal lymphadenopathy, bilateral reticulonodular parenchymal opacities, and pleural effusion. A preliminary diagnosis of lymphoma, possibly with a superimposed infection was established. Further differential diagnostic process revealed pulmonary TB in the course of advanced HIV-1 disease, with a CD4+ T-lymphocyte count of 107 cells/mm3. The patient completed anti-tuberculous therapy and successfully continues on antiretroviral treatment. This case underlines the importance of screening for HIV in patients with newly diagnosed TB.

The utility of repeat Xpert MTB/RIF testing to diagnose tuberculosis in HIV-positive adults with initial negative result

Background: Amongst HIV-positive adults in South Africa with initial negative Xpert results, we compared the yield from repeating Xpert MTB/RIF (“Xpert”) on sputum to guideline-recommended investigation for tuberculosis (TB). Methods: A systematic sample of adults attending for HIV care were enrolled in a cohort exploring TB investigation pathways. This substudy was restricted to those at highest risk of TB (CD4&lt;200 cells/mm3 or unknown) who had a negative initial Xpert result. At attendance for the Xpert result, a repeat sputum sample was stored, and further investigations facilitated per national guidelines. Participants were reviewed monthly, with reinvestigation if indicated, for at least three months, when sputum and blood were cultured for mycobacteria, and the stored sputum tested using Xpert. We defined TB as “confirmed” if Xpert, line probe assay or Mycobacterium tuberculosis culture within six months of enrolment were positive, and “clinical” if TB treatment was started without microbiological confirmation. Results: Amongst 227 participants with an initial negative Xpert result (63% female, median age 37 years, median CD4 count 100 cells/mm3), 28 (12%) participants had TB diagnosed during study follow-up (16 confirmed, 12 clinical); stored sputum tested positive on Xpert in 5/227 (2%). Amongst 27 participants who started TB treatment, the basis was bacteriological confirmation 11/27 (41%); compatible imaging 11/27 (41%); compatible symptoms 2/27 (7%); and unknown 3/27 (11%). Conclusions: Amongst HIV-positive individuals at high risk of active TB with a negative Xpert result, further investigation using appropriate diagnostic modalities is more likely to lead to TB treatment than immediately repeating sputum for Xpert. TB diagnostic tests with improved sensitivity are needed.

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.

Risk of active tuberculosis infection in kidney transplantation recipients: A matched comparative nationwide cohort study

Large-scale evidence comparing the risk of Mycobacterium tuberculosis (TB) between kidney transplant (KT) recipients and dialysis patients is warranted. This is a nationwide retrospective cohort study based on the claims database of South Korea where a moderate prevalence of TB is reported. We included incident KT recipients from 2011 to 2015 and compared their active TB risks with 1:1 matched dialysis and general population control groups, respectively. The risk of incident active TB was assessed by multivariable Cox regression. Associations between active TB and posttransplant death or death-censored graft failure were investigated. The number of matched subjects included in each of the study groups was 7462. The KT group showed a significantly higher risk of active TB than the general population group (hazard ratio [HR] 3.39 [1.88-6.10]), whereas it showed a similar risk to that of the dialysis group (HR 0.98 [0.73-1.31]). In KT patients, active TB was a significant risk factor for both death (HR 2.33 [1.24-4.39]) and death-censored graft failure (HR 2.26 [1.39-3.67]). Although KT recipients may not have to burden the additional risk of active TB when compared with dialysis patients in recent medicine, active TB should not be overlooked as it is associated with a worse prognosis in posttransplant patients.

Association of Vitamin D Receptor Polymorphism (rs2228570, rs1544410, rs7975232, and rs731236) and Macrophage Migration Inhibitory Factor -173 G/C (rs755622) with the Susceptibility of Active Pulmonary Tuberculosis in Makassar, Indonesia

BACKGROUND: The study of Vitamin D Receptor (VDR) and Macrophage Migration Inhibitory Factor (MIF) polymorphisms, associated with active pulmonary tuberculosis (ATB) presents varying results. AIMS: This study aimed to investigate the association between VDR rs2228570, rs1544410, rs7975232, rs731236 and MIF -173 G/C (rs755622) single nucleotide polymorphism (SNP), with susceptibility of developing ATB, and positivity of Interferon Gamma Release Assay (IGRA) results (in household contact). METHODS AND MATERIAL: This study involved 83 ATB and 73 household contacts in Makassar. We checked IGRA based on ELISA in household contacts by using QuantiFERON TB Gold Plus test, and we found that 61.64% (n = 45) of household contacts had positive IGRA. Polymorphism examination was carried out by Sanger sequencing. RESULTS: VDR rs2228570 T/T and T/C-T/T were significantly associated with higher risk of active tuberculosis. VDR rs7975232 G/G genotype was associated with an increased risk of developing active TB compared to T/T-T/G. Haplotype analysis of VDR rs2228570, rs1544410, rs7975232, rs731236 and combination with MIF rs755622 demonstrated that TGGTG was observed to have a higher risk of tuberculosis. CONCLUSIONS: The combination of VDR and MIF variants may contribute to the susceptibility of active tuberculosis disease.

The Risk of Developing Tuberculosis in Cancer Patients Is Greatest in Lymphoma: A Large Population-Based Study

Introduction: Patients with cancer, especially those diagnosed with hematological malignancies, are considered at higher risk for tuberculosis (TB). Several studies reported that Hodgkin lymphoma (HL) patients have the highest risk for TB among patients with hematological malignancies. These data are relatively old and based mostly on series of patients with malignancies or with TB but often lack statistical rigor and not based on large population-based studies.According to the Israeli regulations, every new diagnosis of cancer must be reported to the Israel National Cancer Registry (INCR) and every new diagnosis of TB to the Israel National Tuberculosis Registry (INTR). We combined both databases and studied epidemiological features of TB among patients with cancer in Israel, in which the incidence of TB in the general population is relatively low. The study objectives were to examine whether patients with hematological malignancies are at increased risk to develop active TB, compared to patients with solid tumors, and to examine whether patients with HL have a higher risk of active TB than patients with other hematological malignancies.Methods: The study population consists of all newly diagnosed cancer cases reported to the INCR from 1993-2013. These data were linked with data from the INTR for the same period. HIV patients were excluded from both databases. Hematologic malignancies were categorized into 5 groups: acute leukemia, HL, non-Hodgkin lymphoma (NHL), myelodysplastic syndrome/myeloproliferative neoplasm and plasma cell dyscrasia. Incidence rates per 100,000 person-years were calculated. Logistic regression was used to analyze the risk of TB following cancer diagnosis among patients with different malignancies.Results: Of 465,429 patients who were diagnosed with cancer during 1993-2013, 676 patients were notified to have TB but in only 321 patients the diagnosis of TB followed cancer diagnosis. The cumulative incidence of TB following cancer diagnosis was 14.4 per 100,000 person-years (PY). The rate of TB incidence following cancer diagnosis was 27.2/100,000 PY for persons diagnosed with hematological malignancies, and 12.7/100,000 PY among those with non-hematological malignancies (p<0.001). The highest TB incidence was found among patients with lymphoma (30.1 TB cases per 100,000 PY). Among lymphoma patients, a higher incidence rate was found in NHL patients than among HL patients, however the difference was not significant (32.1 vs . 21.6, respectively, p=0.378). Accounting for sex, age at diagnosis and ethnicity in logistic regression, the risk of TB among lymphoma patients is significantly higher than in other malignancies (Odds ratio 2.61, p=0.002) and there is no added significant risk for patients with HL (Odds ratio 1.33, p=0.464).Conclusions: 1) In this population-based study of more than 450,000 patients diagnosed with cancer, the incidence of TB following a cancer diagnosis is higher among patients with hematological malignancies than in patients with solid tumors. 2) Lymphoma patients have the highest risk to develop TB. 3) In contrast to common perception, we did not find that patients with HL are at increased risk to develop TB relative to NHL patients. 4) These data suggest for a heightened awareness for latent TB among newly diagnosed patients with lymphoma and for active TB among patients with a background of lymphoma who present with fever or respiratory complains. DisclosuresNo relevant conflicts of interest to declare.

1650. Clinical Features and Risk Factors of Active Tuberculosis in Patients with Behçet’s Disease

BackgroundUnderstanding the clinical characteristics and risk factors of active tuberculosis (ATB) in Behçet’s disease (BD) is of great significance to improve the treatment efficacy and guide the preventive treatment. However, the relevant studies are very limited.MethodsWe retrospectively reviewed medical records of BD patients admitted to our institute from 2010 to 2019. BD patients with ATB were enrolled as the case group, and the control group was selected by random number sampling from the remaining BD patients. Multivariate logistic regression analysis was performed to explore the potential risk factors of ATB in BD patients.Figure 1. Flowchart of the study ResultsTwenty-one ATB cases were identified from 386 BD patients, including four (19.0%) microbiologically confirmed and 17 (81.0%) clinically diagnosed. ATB patients can present with systemic symptoms (fever, night sweating, unexplained weight loss) and/or symptoms related to the infection site. Logistic regression analysis revealed that ESR>60mm/h (OR=13.710, 95%CI (1.101, 170.702)), increased IgG (OR=1.226, 95%CI (1.001, 1.502)), and positive T-SPOT.TB (OR=7.793, 95%CI (1.312, 48.464), for 24-200 SFC/106PBMC; OR=17.705 (2.503, 125.260), for >200 SFC/106PBMC) were potential risk factors for ATB in BD patients.Table 1. Past medical history and medication of BD patients with and without ATB Table 2. Clinical presentation and laboratory results of BD patients with and without ATB Table 3. Potential risk factors for ATB in BD patients ConclusionWhen BD patients have fever, night sweating, unexplained weight loss, or manifestations rarely occurred in BD, the diagnosis of ATB should be considered. Significantly elevated T-SPOT.TB indicates a high risk of ATB in BD patients.Disclosures All Authors: No reported disclosures

Acceptability and Feasibility of a Nurse-Led, Community Health Worker Partnered Latent Tuberculosis Medication Adherence Model for Homeless Adults.

Homeless adults are at increased risk of latent tuberculosis infection (LTBI), which can lead to active tuberculosis (TB) disease. The purpose of this study was to assess acceptability and feasibility of a six-month, nurse-led, community health worker-partnered short-course treatment (3HP) LTBI adherence model for a high risk, LTBI positive, homeless population. Informed by our community advisory board (CAB) and community-based participatory research principles (CBPR), a qualitative study was undertaken and used focus group discussions to identify perspectives of homeless men and women who had undergone LTBI treatment (N = 11, Mage = 51.2, SD 8.60, range 35–60). Three themes formed, which were engaging and recruiting LTBI intervention participants, delivering an LTBI intervention, and retaining LTBI intervention participants. Within those themes, barriers (e.g., lack of LTBI treatment readiness, substance use, etc.), and facilitators (e.g., LTBI and TB health education, familiarity with homeless population, etc.) were discussed to facilitate program recruitment, program delivery and program retention. These findings provide a greater understanding of how to effectively utilize a nurse-led, Community Health Worker (CHW) intervention delivery method to not only improve 3HP LTBI medication adherence, but also decrease substance use, improve mental health, and decrease unstable housing among this vulnerable population at high risk for active tuberculosis.

Risk of active tuberculosis among COPD patients treated with fixed combinations of long-acting beta2 agonists and inhaled corticosteroids

ObjectivesTo investigate the incidence of active tuberculosis (TB) among COPD patients using fluticasone/salmeterol or budesonide/formoterol, and to identify any differences between these two groups of patients.MethodsThe study enrolled COPD patients from Taiwan NHIRD who received treatment with fluticasone/salmeterol or budesonide/formoterol for > 90 days between 2004 and 2011. The incidence of active TB was the primary outcome.ResultsAmong the intention-to-treat population prior to matching, the incidence rates of active TB were 0.94 and 0.61% in the fluticasone/salmeterol and budesonide/formoterol groups, respectively. After matching, the fluticasone/salmeterol group had significantly higher rates of active TB (adjusted HR, 1.41, 95% CI, 1.17–1.70) compared with the budesonide/formoterol group. The significant difference between these two groups remained after a competing risk analysis (HR, 1.45, 95% CI, 1.21–1.74). Following propensity score matching, the fluticasone/salmeterol group had significantly higher rates of active TB compared with the budesonide/formoterol group (adjusted HR, 1.45, 95% CI, 1.14–1.85). A similar trend was observed after a competing risk analysis (HR, 1.44, 95% CI, 1.19–1.75). A higher risk of active TB was observed in the fluticasone/salmeterol group compared with the budesonide/formoterol group across all subgroups, but some differences did not reach statistical significance.ConclusionFluticasone/salmeterol carried a higher risk of active TB compared with budesonide/formoterol among COPD patients.

Incidence of tuberculosis and the need of prophylactic treatment in persons living with HIV in Stockholm during the era of anti-retroviral therapy 1996–2013

Background: The aim of this observational cohort study was to determine the incidence and risk factors of active tuberculosis (TB) in persons living with HIV in a low endemic setting over a 17-year time period when combination antiretroviral therapy (ART) has been available. We thereby aimed to understand the usefulness of TB chemoprophylaxis among HIV patients with latent TB.Methods: All 2127 adult patients diagnosed with HIV January 1996–December 2013 at the Karolinska University Hospital in Stockholm County were eligible. After exclusion of 259 patients transferred to other clinics, 1868 were followed until TB diagnosis, death or end of study period (December 2013). The median follow-up time was 7.9 years (interquartile range, 3.9–11.5).Results: Active TB was diagnosed in 92 patients, corresponding to an incidence rate of 6.2 cases (95% CI 5.1–7.6) per 1000 person-years with a significant decline over time. The majority (52%) of TB cases were diagnosed within 1 month from HIV diagnosis. Being a migrant from a TB-endemic region, was the only patient characteristic associated with significantly higher risk of active TB (Hazard Ration, HR: 8.54, 95% confidence interval, CI: 3.09–23.61 in a multivariate regression analysis controlling for route of HIV transmission, year of HIV diagnosis and CD4-cell count and viral load at HIV diagnosis. The number needed to treat to prevent one case of TB among patients in this high-risk group was 22 (95% CI 26–47).Conclusion: The incidence of active TB in persons living with HIV in Stockholm County declined significantly after the introduction of ART but was still 80 times higher than in the general population at the end of the study period. The therapeutic gain of chemoprophylaxis in low endemic settings should be weighed against costs and side effects.

Latent tuberculous infection among foreign-born individuals applying to shelters in the metropolitan area of Milan.

Screening for latent tuberculous infection (LTBI) of groups at high risk of active tuberculosis (TB) is a key component of the End TB Strategy. To conduct a retrospective descriptive analysis of LTBI rates among foreign-born individuals applying to shelters in the metropolitan area of Milan, Italy. All foreign-born individuals registering for accommodation centres in the city of Milan from November 2009 to April 2017 were screened for active TB and LTBI. Individuals aged <36 years with a tuberculin skin test (TST) induration of >10 mm were offered confirmatory testing with QuantiFERON®-TB Gold In-Tube (QFT-GIT). Of the 2666 TST-positive migrants aged <36 years who underwent LTBI confirmation testing, 1322 (49.6%) tested negative, 1339 (50.2%) were positive and five (0.2%) had indeterminate results. In the multivariate analysis, TB incidence in the country of origin and age were significantly associated with QFT-GIT positivity. Although estimated TB incidence in Eritrea, Morocco and Romania was 100/100 000 person-years (py), the probability of being QFT-GIT-positive in individuals from these countries were not statistically significantly different from individuals from countries with TB incidence > 250/100 000 person-years. Our data showed a high proportion of LTBI among individuals coming from intermediate TB burden countries.

Missed opportunities for tuberculosis prevention among patients accessing a UK HIV service.

United Kingdom guidelines recommend screening for and treatment of latent tuberculosis infection (LTBI) in HIV-positive patients at high risk of active tuberculosis (TB) disease, but implementation is suboptimal. We investigated potential missed opportunities to identify and treat LTBI among HIV-positive patients accessing a large HIV outpatient service in London. Case records of all adult patients attending our service for HIV care diagnosed with active TB between 2011 and 2015 were reviewed to determine whether they met criteria for LTBI screening and whether screening was undertaken. Twenty-five patients were treated for TB. Of 15 (60%) patients who started TB treatment ≥6 months after HIV diagnosis, 14 (93%) met UK guideline-recommended criteria for LTBI screening and treatment; only one (7%) had been screened for LTBI. Eight of these 15 (53%) patients had additional risk factors for TB which are not reflected in current UK guidelines. Of 15 patients treated for TB ≥6 months after diagnosis of HIV, 14 (93%) had not been screened for LTBI, suggesting missed opportunities for TB prevention. People living with HIV may benefit from a broader approach to LTBI screening which takes into account additional recognised TB risk factors and ongoing TB exposure.

The utility of repeat Xpert MTB/RIF testing to diagnose tuberculosis in HIV-positive adults with initial negative result.

Background: Amongst HIV-positive adults in South Africa with initial negative Xpert results, we compared the yield from repeating Xpert MTB/RIF ("Xpert") on sputum to guideline-recommended investigation for tuberculosis (TB). Methods: A systematic sample of adults attending for HIV care were enrolled in a cohort exploring TB investigation pathways. This substudy was restricted to those at highest risk of TB (CD4<200 cells/mm 3 or unknown) who had a negative initial Xpert result. At attendance for the Xpert result, a repeat sputum sample was stored, and further investigations facilitated per national guidelines. Participants were reviewed monthly, with reinvestigation if indicated, for at least three months, when sputum and blood were cultured for mycobacteria, and the stored sputum tested using Xpert. We defined TB as "confirmed" if Xpert, line probe assay or Mycobacterium tuberculosis culture within six months of enrolment were positive, and "clinical" if TB treatment was started without microbiological confirmation. Results: Amongst 227 participants with an initial negative Xpert result (63% female, median age 37 years, median CD4 count 100 cells/mm 3), 28 (12%) participants had TB diagnosed during study follow-up (16 confirmed, 12 clinical); stored sputum tested positive on Xpert in 5/227 (2%). Amongst 27 participants who started TB treatment, the basis was bacteriological confirmation 11/27 (41%); compatible imaging 11/27 (41%); compatible symptoms 2/27 (7%); and unknown 3/27 (11%). Conclusions: Amongst HIV-positive individuals at high risk of active TB with a negative Xpert result, further investigation using appropriate diagnostic modalities is more likely to lead to TB treatment than immediately repeating sputum for Xpert. TB diagnostic tests with improved sensitivity are needed.

End-stage Renal Disease and Risk of Active Tuberculosis: a Nationwide Population-Based Cohort Study.

BackgroundThe converging epidemics of tuberculosis (TB) and end-stage renal disease (ESRD) have generated a significant public health burden, however, previous studies have been limited to a small number of patients. This nationwide cohort study aimed to assess the rate of developing active TB among patients receiving dialysis for ESRD.MethodsThe Korean national health insurance database was used to identify patients receiving dialysis for new-onset ESRD during 2004–2013, who were propensity score matched to an equivalent number of non-dialysis subjects from the general population. The incidences of active TB in the ESRD and control cohorts were calculated for 2004–2013, and multivariable Cox proportional hazards model was used to evaluate the ESRD-related risk of active TB.ResultsDuring 2004–2013, 59,584 patients received dialysis for newly diagnosed ESRD. In the dialysis and control cohorts, 457 (0.8%) and 125 (0.2%) cases of active TB were detected, respectively. Patients with ESRD were associated with a significantly higher risk of active TB compared to the controls (incidence rate ratio, 4.80). The ESRD cohort had an independently elevated risk of active TB (adjusted hazard ratio, 4.39; 95% confidence interval, 3.60–5.37).ConclusionWe found that patients receiving dialysis for ESRD had an elevated risk of active TB. These results highlight the need for detailed and well-organised guidelines for active TB screening among patients with ESRD.

Association of autophagy-related IRGM polymorphisms with latent versus active tuberculosis infection in a Chinese population

The autophagy-related immunity-related GTPase family M protein, IRGM, plays an important role in the defense against tuberculosis (TB) infection. IRGM polymorphisms are associated with TB infection susceptibility, and recent studies demonstrate host genetic differences between active and latent TB. Here, we investigated the association between IRGM polymorphisms and TB infection type in a Chinese population. We recruited 268 and 321 patients with confirmed or latent TB, respectively, and 475 TB-free healthy controls. Three single nucleotide polymorphisms, rs10065172, rs10051924, and rs13361189 within IRGM were genotyped using TaqMan-based assays. Interferon-gamma release levels were tested by T-SPOT. rs10065172 (P = 0.024, OR 0.67 (95% CI 0.48-0.95)), rs10051924 (P = 0.01, OR 0.64 (95% CI 0.46-0.90)), and rs13361189 (P = 0.055, OR 0.72 (95% CI 0.51-1.01)) were associated with a protective role against latent TB progression. Haplotype analysis showed that TCC was protective for latent TB (P = 0.022, OR 0.74 (95% CI 0.57-0.96)) whereas TTC conferred a higher risk of active TB. Additionally, patients with the rs10065172 TT genotype had a higher response to TB specific antigens. Thus, IRGM polymorphism differences between latent and active TB suggests that genetic differences in autophagy might partly affect host TB infection status.

Latent Tuberculosis Infection Screening and 2-Year Outcome in Antiretroviral-Naive HIV-Infected Patients in a Low-Prevalence Country.

Diagnosis and treatment of latent tuberculous infection decrease the incidence of tuberculosis (TB) in HIV-infected patients. To evaluate the diagnostic yield of two IFN-γ release assays and tuberculin skin testing for the screening of latent infection in HIV-infected patients. We performed a prospective study in 29 referral centers for HIV care in France. Asymptomatic, antiretroviral-naive patients infected with HIV-1 who consented to participate underwent two commercial tests (T-SPOT.TB and QuantiFERON-TB Gold In-Tube ELISA test [QFT]) and skin test at enrollment and were followed up for clinical events during 24 months. Between March 2009 and 2011, 506 patients were included, of whom 415 performed the three tests. Median age was 38 years (interquartile range, 31-45 yr), with median CD4 cell count of 466/μL (337-615 μL), and HIV viral load of 4.5 log10 copies/ml (3.6-4.9 log10 copies/ml). At least one IFN-γ release assay was positive for 55 (13.5%) patients: QFT (n = 43), T-SPOT.TB (n = 34), both (n = 22). Skin test was positive (>5 mm) in 66 (15.9%) patients, with intertest agreement at 81 to 86%. On multivariate analysis, positive IFN-γ release assay was only correlated with country of birth (8.4% for France vs. 17.9% for high-prevalence countries, P = 0.004). Of the 55 patients with positive IFN-γ release assay, 8 (14.5%) developed active TB, all within 120 days. No other case of active TB was diagnosed. Once active TB was excluded, IFN-γ release assay-based latent infection prevalence was 11.8%. Systematic screening for latent TB infection by IFN-γ release assay identifies a population at high risk of active TB over the next months. An extensive diagnostic work-up for active TB must follow positive IFN-γ release assay, before considering treatment of latent infection. Clinical trial registered with www.clinicaltrials.gov (NCT00805272).

Efficacy Of Ruxolitinib In Korean Myelofibrosis Patients and Cases Complicated TB Lymphadenitis During The Treatment

IntroductionRuxolitinib is a selective JAK 1/2 inhibitor, which shows an excellent treatment outcome in myelofibrosis (MF) patients. Main side effect of JAK 1/2 inhibitors is an increased risk of infection. JAK1/2 inhibition may interfere with the differentiation of interferon-γ (IFN-γ) producing Th1 cells and IFN-γ is a key cytokine involved in protective immunity against Mycobacterium tuberculosis(TB). During COMPORT-II trial, a case of disseminated TB with ruxolitinib was reported. Here, we analyze the efficacy and safety of ruxolitinib in Korean MF patients and report cases of TB lymphadenitis during the treatment. MethodsForty-nine patients diagnosed with PMF, PPV-MF or PET-MF have been enrolled and at this time twenty patients are evaluable (median age; 63 years, 37-80). Starting dose of ruxolitinib was determined based on each patient's baseline platelet count (20 mg bid/d for a baseline platelet more than 200,000/µL, 15 mg bid/d for 100,000-200,000/uL). To determine the efficacy of ruxolitinib, we serially assessed the spleen size by palpation, myelofibrosis symptom assessment using MFSAF and BM examination with JAK2V617Fmutation allele burden. Among 20 evaluable patients, 16 assessed IFN-γ release assays (IGRAs, quantiFERON-TB Gold test) before starting ruxolitinib. ResultsOf total twenty patients, 12 (60.0%), 3 (15.0%) and 5 (25.0%) were PMF, PPV-MF and PET-MF, respectively. By DIPSS, 13 (65.0%) was Int-2 risk, 3 (15.0%) and 4 (20.0%) were Int-1 and high risk. Eleven patients started with 20 mg bid/d (median baseline platelet: 302,000/uL, 206,000-814,000) and nine were 15 mg bid/d (median; 139,000/uL, 100,000-194,000). Median baseline total symptom score (TSS) was 12 (1-36) and palpable spleen length was 19 cm (1-30). JAK2V617Fmutation was positive in 13 (65.0%) patients (median allele burden; 87.1%, 26.2-93.7). Median time of ruxolitinib exposure was 2.0 ms. (0.8-6.2). Two patients increased TSS following ruxolitinib treatment, however, median maximal reduction in TSS was above 90.9% (27.8-100) and 64.7% of patients showed more than 50% reduction of TSS with ruxolitinib. In an aspect of spleen length, all except two patients showed decreased palpable spleen length. Median maximal reduction in spleen length was 70.2% (0-100) and 72.2% of patients showed more than 35% reduction in spleen length with ruxolitinib. Three patients (15.0%) experienced gr. 3/4 thrombocytopenia and one (5.0%) gr. 3 neutropenia. Among patients who assessed pre-treatment IGRAs, only one revealed positive IGRAs. Since there was no evidence of active TB in symptom and radiologic examination, he was diagnosed as latent TB infection (LTBI) and started 9 ms.-isoniazid (INH) treatment. He had a huge hepatosplenomegaly combined with large amount of ascites which needed frequent paracentesis, hence, we started ruxolitinib with INH treatment. He showed no evidence of active TB and achieved negative IGRAs result on 5 ms. of ruxolitinib treatment. On 1 m. and 5 ms. of ruxolirinib treatment, two patients developed pyrexia and neck masses which were diagnosed as TB lymphadenitis. All of them had no previous history of TB and showed negative results in pre-treatment IGRAs and radiologic examinations. First patient discontinued ruxolitinib by herself and eventually died of MF progression 2 ms. later. Second patient continued ruxolitinib treatment with TB medication and there was no evidence of active TB or MF progression on 5 ms. of ruxolitinib treatment. ConclusionsRuxolitinib was generally well tolerated and showed an excellent treatment outcome in Korean MF patients. By 2008 WHO report, intermediate burden of TB cases exist in Korea, hence, TB is still endemic in Korea. According to 2011 Korean Guidelines for TB, LTBI should be treated in patients receiving immunosupressive agents including TNF-α inhibitors. Although further prospective investigations on the incidence of TB with JAK 1/2 inhibitors in TB endemic countries are warranted, it seems to be reasonable to check the possibility of LTBI before starting JAK 1/2 inhibitors. LTBI confirmed patients receiving JAK 1/2 inhibitors may be deemed a high risk of active TB and consider LTBI treatment. Furthermore, it is necessary to use a caution for active TB infection during the treatment of JAK 1/2 inhibitors in such countries. Disclosures:No relevant conflicts of interest to declare.

Patient Preference for Latent Tuberculosis Infection Preventive Treatment: A Discrete Choice Experiment

ObjectivesTo quantify patient preferences when making decisions as to whether to accept latent tuberculosis infection (LTBI) preventive treatment, using a discrete choice experiment (DCE). MethodsA DCE survey was developed and administered to LTBI patients. Each patient was given 10 random choices along with two fixed choices to check consistency. Two hypothetical treatment options and one opt-out option were presented in each choice task. Latent class analysis was conducted to estimate preferences for six key treatment attributes. ResultsAmong the 214 respondents, 194 (90.7%) who provided valid DCE responses and complete sociodemographic information were included. Results consistently suggested that respondents were averse to higher risk of active tuberculosis and side effects and longer treatment. A three-latent-class model with five covariates was chosen. Forty-seven percent of the respondents were assigned to class 1, 32% to class 2, and 21% to class 3. Although all six attributes were shown to significantly influence the respondents' treatment decision, the risk of active tuberculosis, chance of liver damage, and frequency of clinic visits were the most important ones. Significant preference heterogeneity was observed in two attributes: frequency of clinic visits (P < 0.01) and chance of liver damage developing (P < 0.01). Class 1 individuals were most likely to have children. Class 2 had the highest employment rate. Class 3 respondents tended to choose the opt-out option on DCE tasks and were more likely to be born outside Canada, have higher education, and be unemployed. ConclusionRespondents consistently preferred preventive treatment with higher effectiveness, fewer side effects, and shorter length. Substantial preference heterogeneity existed among respondents.