History Of Active Tuberculosis Research Articles

People Living With HIV Have More Intact HIV DNA in Circulating CD4+ T Cells if They Have History of Pulmonary Tuberculosis.

A primary barrier to curing HIV is the HIV reservoir. The leading infectious cause of death worldwide for people living with HIV is tuberculosis (TB), but we do not know how TB impacts the HIV reservoir. Participants in identification and validation cohorts were selected from previously enrolled studies at Groupe Haïtien d'Étude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) in Port au Prince, Haiti. Intact and non-intact proviral DNA were quantified using droplet digital PCR of peripheral blood mononuclear cell (PBMC)-derived CD4+ T cells. Kruskal-Wallis tests were used to compare medians with tobit regression for censoring. In the identification cohort, we found that people living with HIV with a history of active pulmonary TB (n=19) had higher levels of intact provirus than people living with HIV without a history of active TB (n=47) (median 762; IQR, 183-1173 vs 117; IQR, 24-279 intact provirus per million CD4, respectively; P=0.0001). This difference also was seen in the validation cohort (n=31), (median 102; IQR, 0-737 vs 0; IQR, 0-24.5 intact provirus per million CD4, P=0.03) for TB vs no-TB history groups, respectively. The frequencies of CD4+ T cells with any detectable proviral fragment was directly proportional to the levels of interleukin-1 beta (r=0.524, P= 0.0025) and interleukin-2 (r=0.622, P=0.0002). People living with HIV with a history of active pulmonary TB have more HIV pro-virus in their circulating CD4+ T cells, even years after TB cure. We need to characterize which CD4+ T cells are harboring intact provirus to consider the impact of T cell-targeting HIV cure interventions for people living in TB-endemic areas.

Latent Tuberculosis Infection Testing Practices in a Large US Integrated Healthcare System.

Tuberculosis (TB) is a public health threat, with >80% of active TB in the United States occurring due to reactivation of latent TB infection (LTBI). We may be underscreening those with high risk for LTBI and overtesting those at lower risk. A better understanding of gaps in current LTBI testing practices in relation to LTBI test positivity is needed. This study, conducted between 1 January 2008 and 31 December 2019 at Kaiser Permanente Southern California, included individuals aged ≥18 years without a history of active TB. We examined factors associated with LTBI testing and LTBI positivity. Among 3 816 884 adults (52% female, 37% White, 37% Hispanic, mean age 43.5 years [standard deviation, 16.1]), 706 367 (19%) were tested for LTBI, among whom 60 393 (9%) had ≥1 positive result. Among 1 211 971 individuals who met ≥1 screening criteria for LTBI, 210 025 (17%) were tested for LTBI. Factors associated with higher adjusted odds of testing positive included male sex (1.32; 95% confidence interval, 1.30-1.35), Asian/Pacific Islander (2.78, 2.68-2.88), current smoking (1.24, 1.20-1.28), diabetes (1.13, 1.09-1.16), hepatitis B (1.45, 1.34-1.57), hepatitis C (1.54, 1.44-1.66), and birth in a country with an elevated TB rate (3.40, 3.31-3.49). Despite being risk factors for testing positive for LTBI, none of these factors were associated with higher odds of LTBI testing. Current LTBI testing practices may be missing individuals at high risk of LTBI. Additional work is needed to refine and implement screening guidelines that appropriately target testing for those at highest risk for LTBI.

Financial incentives for reduced alcohol use and increased isoniazid adherence during tuberculosis preventive therapy among people with HIV in Uganda: an open-label, factorial randomised controlled trial

Alcohol use is common among people with HIV and is a risk factor for tuberculosis disease and non-adherence to isoniazid preventive therapy (IPT). Few interventions exist to reduce alcohol use and increase IPT adherence in sub-Saharan Africa. The aim of this study was to test the hypothesis that financial incentives conditional on point-of-care negative urine alcohol biomarker testing and positive urine isoniazid testing would reduce alcohol use and increase isoniazid adherence, respectively, in people with HIV who have latent tuberculosis infection and hazardous alcohol use. We conducted an open-label, 2×2 factorial randomised controlled trial in Uganda. Eligible for the study were non-pregnant HIV-positive adults (aged ≥18 years) prescribed antiretroviral therapy for at least 6 months, with current heavy alcohol use confirmed by urine ethyl glucuronide (biomarker of recent alcohol use) and a positive Alcohol Use Disorders Identification Test-Consumption (AUDIT-C; ≥3 for women, ≥4 for men) for the past 3 months' drinking, no history of active tuberculosis, tuberculosis treatment, or tuberculosis preventive therapy, and a positive tuberculin skin test. We randomly assigned participants (1:1:1:1) initiating 6 months of IPT to: no incentives (group 1); or incentives for recent alcohol abstinence (group 2), isoniazid adherence (group 3), or both (group 4). Escalating incentives were contingent on monthly point-of-care urine tests negative for ethyl glucuronide (groups 2 and 4), or positive on IsoScreen (biomarker of recent isoniazid use; groups 3 and 4). The primary alcohol outcome was non-hazardous use by self-report (AUDIT-C <3 for women, <4 for men) and phosphatidylethanol (PEth; past-month alcohol biomarker) <35 ng/mL at 3 months and 6 months. The primary isoniazid adherence outcome was more than 90% bottle opening of days prescribed. We performed intention-to-treat analyses. This trial is registered with ClinicalTrials.gov (NCT03492216), and is complete. From April 16, 2018, to Aug 2, 2021, 5508 people were screened, of whom 680 were randomly assigned: 169 to group 1, 169 to group 2, 170 to group 3, and 172 to group 4. The median age of participants was 39 years (IQR 32-47), 470 (69%) were male, 598 (90%) of 663 had HIV RNA viral loads of less than 40 copies per mL, median AUDIT-C score was 6 (IQR 4-8), and median PEth was 252 ng/mL (IQR 87-579). Among 636 participants who completed the trial with alcohol use endpoint measures (group 1: 152, group 2: 159, group 3: 161, group 4: 164), non-hazardous alcohol use was more likely in the groups with incentives for alcohol abstinence (groups 2 and 4) versus no alcohol incentives (groups 1 and 3): 57 (17·6%) of 323 versus 31 (9·9%) of 313, respectively; adjusted risk difference (aRD) 7·6% (95% CI 2·7 to 12·5, p=0·0025). Among 656 participants who completed the trial with isoniazid adherence endpoint measures (group 1: 158, group 2: 163, group 3: 168, group 4: 167), incentives for isoniazid adherence did not increase adherence: 244 (72·8%) of 335 in the isoniazid incentive groups (groups 3 and 4) versus 234 (72·9%) of 321 in the no isoniazid incentive groups (groups 1 and 2); aRD -0·2% (95% CI -7·0 to 6·5, p=0·94). Overall, 53 (8%) of 680 participants discontinued isoniazid due to grade 3 or higher adverse events. There was no significant association between randomisation group and hepatotoxicity resulting in isoniazid discontinuation, after adjusting for sex and site. Escalating financial incentives contingent on recent alcohol abstinence led to significantly lower biomarker-confirmed alcohol use versus control, but incentives for recent isoniazid adherence did not lead to changes in adherence. The alcohol intervention was efficacious despite less intensive frequency of incentives and clinic visits than traditional programmes for substance use, suggesting that pragmatic modifications of contingency management for resource-limited settings can have efficacy and that further evaluation of implementation is merited. National Institute on Alcohol Abuse and Alcoholism. For the Runyankole translation of the abstract see Supplementary Materials section.

Disseminated Congenital Tuberculosis in Neonates: A Case Series.

Congenital tuberculosis (CTB) is an uncommon yet, well-defined condition. CTB has a non-specific clinical presentation, making the diagnosis difficult. The rarity of CTB in neonates is due to the difficulty in distinguishing between congenital and postnatally acquired infection, and non-specific symptoms in the newborn, which are often misdiagnosed. Though it has a low incidence, it has significant mortality if the diagnosis is delayed. We are presenting two cases of CTB in newborns who showed signs of disease in the first few days of life. The diagnosis was suspected based on chest computed tomography, magnetic resonance imaging brain, cerebrospinal fluid studies, intrauterine growth restriction, non-response to standard treatment and a maternal history of active tuberculosis. These cases highlight the significance of having a high suspicion of CTB and timely treatment for better outcomes.

Prevalence of Latent Tuberculous Infection in Patients With Nontuberculous Mycobacterial Lung Disease and Colonization: A Prospective Study in an Intermediate Tuberculosis Burden Country.

BackgroundControlling latent tuberculosis infection (LTBI) is important in eliminating tuberculosis (TB); however, the prevalence of LTBI has rarely been studied in patients with nontuberculous mycobacterial (NTM) lung disease (LD) and colonization (LC).MethodsWe prospectively recruited subjects with NTM isolated from sputum mycobacterial cultures from December 2011 to June 2019. NTM-LD and NTM-LC were defined according to the American Thoracic Society guidelines. Patients with negative cultures were recruited as controls. Patients with a history of active TB or positive TB cultures were excluded. LTBI was confirmed using a QuantiFERON-TB Gold In-tube test. The prevalence and factors associated with LTBI were analyzed.ResultsA total of 406 participants were enrolled, including 171 in the NTM-LD group, 153 in the NTM-LC group, and 82 in the control group. The prevalence of LTBI was higher in the NTM-LD and NTM-LC groups than in the controls (21.6%, 20.9%, and 6.1%; P = .006). Multivariable analysis showed that old age (adjusted odds ratio [aOR], 1.021, per year increment; P = .042), NTM-LD (aOR, 4.030; P = .005), NTM-LC (aOR, 3.610; P = .011, compared with the controls), and pulmonary cavitary lesions (aOR, 3.393; P = .034) were independently associated with LTBI.ConclusionsThe prevalence of LTBI was higher in the patients with NTM-LD and NTM-LC than in the controls. Old age, pulmonary cavitation, and NTM isolated from sputum were associated with a higher risk of LTBI.

Impact of Positive Interferon-Gamma Release Assay on IVF-ET Pregnancy Outcomes in Infertile Patients With Untreated Prior Tuberculosis: A Prospective Cohort Study.

Introduction: Tuberculosis (TB) is a major infectious disease that seriously endangers human health and female reproduction. In our previous study, 10.4% of infertile patients preparing for In vitro fertilization and embryo transfer (IVF-ET) had prior pulmonary TB (PTB) as detected on chest X-ray (CXR) screening. Among them, 81.8% did not receive anti-TB treatment. It remains unclear whether infertile women with untreated prior PTB have latent TB infection (LTBI) and whether LTBI affects IVF-ET outcomes. In this study, we aim to analyze the relationship between LTBI and pregnancy outcomes following IVF-ET in patients with untreated prior PTB.Methods and Analysis: We designed a prospective cohort study of 1,200 infertile women with CXR findings suggestive of old-healed untreated TB, who are preparing for IVF-ET. Patients with a history of active TB and anti-TB treatment will be excluded. Interferon-gamma release assay (IGRA) will be used in patients with CXR findings suggestive of old-healed untreated TB to construct a cohort of IGRA-positive and IGRA-negative patients. Participants will undergo IVF-ET. General information, including age, body mass index, infertility causes, and controlled ovarian hyperstimulation protocol, will be recorded. Participants will be followed up during pregnancy. The primary outcome is live birth. Secondary outcomes include the numbers of retrieved oocytes, high-quality embryo rate, clinical pregnancy, number of active TB cases during pregnancy, and miscarriage.Ethics and Dissemination: The study was approved by the Ethics Committee of Peking University Third Hospital [approval number (2020)218-01; approval date: June 19, 2020]. The research results will be disseminated through scientific/medical conferences and published in academic journals.Trial Registration: ClinicalTrials.gov; identifier: NCT04443283.

1648. CD4 T Lymphocyte and Monocyte Activation within One Year After Treatment Completion for Pulmonary Tuberculosis: A Pilot Study

BackgroundPersons with active tuberculosis (TB) have increased immune activation, which declines with TB treatment. Whether residual immune activation is present after completion of TB treatment is unknown. We conducted immunophenotyping of T cells and monocytes from individuals who had completed TB treatment, and compared them to controls without history of active TB.MethodsCross-sectional study of HIV-uninfected individuals 40 to 70 years old recruited in Lima, Peru. For this analysis, we included 6 individuals who had completed treatment for pulmonary TB within the past year, and 10 healthy controls without history of active TB (6 QuantiFERON®-TB positive; 4 QuantiFERON®-TB negative). Participants provided blood for T cell and monocyte immunophenotyping using multi-parameter flow cytometry, including expression of cell surface activation markers.ResultsThere were no significant differences in age, sex, or comorbidities between patients previously treated for TB and controls without history of active TB. Median time since TB treatment completion was 4 months (range, 2 – 9) for the previously treated group. Compared to controls, persons previously treated for TB had increased CD4+ to CD8+ ratio (2.4 vs. 1.3; p=0.03), increased proportion of CD4+ T cells co-expressing HLA-DR and CD38 activation markers (5.8% vs. 3.1%; p=0.02), increased CD4+ T cell ICAM-1 expression (56.3% vs. 33.2%; p=0.03), as well as increased density of HLA-DR in monocytes (HLA-DR MFI; 7572 vs. 3917; p=0.03).ConclusionIn this pilot study, individuals who recovered from pulmonary TB exhibited increased CD4+ T cell and monocyte activation phenotypes within one year of TB treatment completion. These results suggest residual immune activation after clinical TB cure.Disclosures Carl Fichtenbaum, MD, Amgen (Grant/Research Support, outside the submitted work)Clinical Care Options (Other Financial or Material Support, outside the submitted work)Cytodyn (Grant/Research Support, outside the submitted work)Gilead Sciences (Grant/Research Support, outside the submitted work)Janssen (Grant/Research Support, outside the submitted work)Merck (Grant/Research Support, outside the submitted work)ViiV Healthcare (Research Grant or Support, outside the submitted work)

Prevalence of positive IGRAs and innate immune system in HIV-infected individuals in Japan

IntroductionHuman immunodeficiency virus (HIV) infected individuals are at increased risk of developing active tuberculosis (TB). TB incidence remains higher than in non-HIV subjects after antiretroviral therapy (ART) initiation. This study was conducted to estimate the prevalence of positive IGRA, reflecting latent tuberculosis infection and/or a history of active TB, in HIV-infected individuals after ART initiation in Japan. MethodsTwo IGRAs (Interferon (IFN)-γ release assays), QuantiFERON®-TB Gold Plus (QFT-Plus) and T-Spot®.TB (TSPOT), were used. We also analyzed the TB associated risk factors for the IGRAs results and the role of CD4+ T-cells, CD8+ T-cells and NK cells for producing IFN-γ. We also analyzed the risk factors for positive IGRA responses and the role of CD4+ T-cells, CD8+ T-cells and NK cells for producing IFN-γ. ResultsOne hundred eight-four subjects were prospectively enrolled. Median age was 49 years. The positivity rates of QFT-Plus and TSPOT were 7.6% [95%CI 4.6–12.4] and 2.7% [95%CI 1.2–6.2], respectively, with significant difference. TB-associated risk factors and NK cells ≥300/μL were selected as independently significant factors by multivariate logistic regression. The NK cell count revealed significant linear regression with IFN-γ production responding to TB-specific antigens. ConclusionsThe prevalence of positive IGRAs was 2.7%–7.6%. QFT-Plus would be practical for a higher positivity rate and reflect TB risk factors. The innate immune system, referring to IFN-γ production, plays an important role in the immune response to TB-specific antigens even after initiating ART.

Active tuberculosis in inflammatory bowel disease patients under treatment from an endemic area in Latin America.

BACKGROUNDThere has been an increase in cases of inflammatory bowel disease (IBD) in recent years. There is also greater access and availability of immunosuppressive and biological agents, which increase the risk of opportunistic infection despite improving the quality of life and promoting mucosal healing. Tuberculosis (TB) remains a public health problem, and it has a high incidence in several countries. Therefore, knowledge of the risk of developing TB in patients with IBD is important.AIMTo evaluate the risk of active TB in patients with IBD under treatment from an endemic area in Latin America.METHODSA standard questionnaire included demographic variables, clinical aspects of IBD disease, history of active TB during treatment, active TB characteristics and evolution, initial screening and results and time from the start of anti-tumor necrosis factor alpha (TNFα) to TB development.RESULTSAzathioprine, anti-TNFα and the combination of these two drugs were associated with a higher risk of active TB incidence. The TNFα blockers increased the relative risk of developing active TB compared to other treatments. All four multivariable models showed that the use of TNFα blockers alone or in combination with azathioprine was an important risk factor for the incidence of active TB. After adjustment for sex, age, type of IBD and latent TB, anti-TNFα with azathioprine increased the relative risk to 17.8 times more than conventional treatment. Late TB, which was diagnosed 3 mo after the start of anti-TNFα, was the most frequent.CONCLUSIONTreatment with anti-TNFα increased the risk of active TB in IBD patients from an endemic area in Latin America. This risk was increased when anti-TNFα was combined with azathioprine. The time from the beginning of the treatment to the active TB diagnosis suggests a new TB infection.

Lung Function and Respiratory Symptoms after Tuberculosis in an American Indian Population. The Strong Heart Study.

Rationale: Permanent lung function impairment after active tuberculosis infection is relatively common. It remains unclear which spirometric pattern is most prevalent after tuberculosis.Objectives: Our objective was to elucidate the impact of active tuberculosis survival on lung health in the Strong Heart Study (SHS), a population of American Indians historically highly impacted by tuberculosis. As arsenic exposure has also been related to lung function in the SHS, we also assessed the joint effect between arsenic exposure and past active tuberculosis.Methods: The SHS is an ongoing population-based, prospective study of cardiovascular disease and its risk factors in American Indian adults. This study uses tuberculosis data and spirometry data from the Visit 2 examination (1993-1995). Prior active tuberculosis was ascertained by a review of medical records. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and FEV1/FVC were measured by spirometry. An additional analysis was conducted to evaluate the potential association between active tuberculosis and arsenic exposure.Results: A history of active tuberculosis was associated with reduced percent predicted FVC and FEV1, an increased odds of airflow obstruction (odds ratio = 1.45, 95% confidence interval = 1.08-1.95), and spirometric restrictive pattern (odds ratio = 1.73, 95% confidence interval = 1.24-2.40). These associations persisted after adjustment for diabetes and other risk factors, including smoking. We also observed the presence of cough, phlegm, and exertional dyspnea after a history of active tuberculosis. In the additional analysis, increasing urinary arsenic concentrations were associated with decreasing lung function in those with a history of active tuberculosis, but a reduced odds of active tuberculosis was found with elevated arsenic.Conclusions: Our findings support existing knowledge that a history of active tuberculosis is a risk factor for long-term respiratory impairment. Arsenic exposure, although inversely associated with prior active tuberculosis, was associated with a further decrease in lung function among those with a prior active tuberculosis history. The possible interaction between arsenic and tuberculosis, as well as the reduced odds of tuberculosis associated with arsenic exposure, warrants further investigation, as many populations at risk of developing active tuberculosis are also exposed to arsenic-contaminated water.

A cross sectional study on knowledge, attitude and practice towards tuberculosis among health care workers

Health care providers play a major role in the management of tuberculosis (TB). The knowledge, attitude and practice towards TB in health care providers will have an impact on the treatment success or failure. Studies have reported that inadequate knowledge of the health care providers led to the delivery of improper counselling content to the recipients. We assessed the knowledge, attitude and practice (KAP) towards tuberculosis among health care workers in and around Chennai. A cross sectional study was conducted among 382 health care workers of the chest and tuberculosis department of government hospitals and directly observed treatment short-course clinics. The principal investigator administered a structured and validated questionnaire to the study participants. Around 500 healthcare workers were approached, and 382 showed interest to sign the informed consent. A majority (70%) of the study participants were between the age group 20-30 years. There was a highly significant difference (P = 0.006) in response to this between participants who had a history of active tuberculosis and undergone treatment for the same, and the participants with no history of TB. There was a significant difference between the study population based on their qualification and profession (P = 0.001 and P = 0.007 respectively) in using the Revised National Tuberculosis Control Program guideline for reference. The knowledge attitude and practice towards TB was good in more than 80% of the respondents, yet there is room to improve. Structured periodic training towards TB will further improve the KAP of health care workers.

Tuberculosis Infection in Chinese Patients with Giant Cell Arteritis

Giant cell arteritis (GCA) is a medium- and large-vessel vasculitis with an onset age after 50 years. Takayasu arteritis (TA), which is also a large-vessel vasculitis with an onset age earlier than 40 years, was suggested to be associated with tuberculosis (TB). However, the association between GCA and TB was rarely reported. This study was to retrospectively analyze clinical data of GCA patients at Peking Union Medical College Hospital and elucidate the association between GCA and TB. Ninety-one patients diagnosed with GCA were included in the study. A total of 20 patients (22.0%) had a history of active tuberculosis and received anti-tuberculosis therapy. On comparing the clinical features of patients with GCA and concomitant TB and those without TB, obvious weight loss (P = 0.011), lower percentage of dyslipidemia (P = 0.042), higher percentage of anti-phospholipid antibodies (P = 0.010), and lower white blood cells (P = 0.006) were noted in the TB group. In conclusion, this study demonstrated the percentage of TB history in patients with GCA was higher than that in the Chinese general population. Clinicians should recognize the possibility of comorbid TB in patients with obvious weight loss and relatively lower white blood cell count.

Effectiveness of Canada's tuberculosis surveillance strategy in identifying immigrants at risk of developing and transmitting tuberculosis: a population-based retrospective cohort study

In Canada, tuberculosis disproportionately affects the foreign-born population. The national tuberculosis medical surveillance programme aims to prevent these cases. Individuals referred for further in-country surveillance (referrals) have a history of active tuberculosis or have features of old, healed tuberculosis on chest radiograph; those not referred (non-referrals) do not undergo surveillance. We aimed to examine the risk of transmission arising from referrals versus non-referrals. We did this population-based retrospective cohort study of foreign-born migrants (aged 15-64 years) to Alberta, Canada, between Jan 1, 2002, and Dec 31, 2013. We obtained information about year of arrival and country of citizenship from Immigration, Refugees and Citizenship Canada, and data for tuberculosis cases and their contacts from the Alberta Tuberculosis Registry. The outcome of interest was culture-positive pulmonary tuberculosis. We compared the incidence of pulmonary tuberculosis and the odds of transmission among referrals versus non-referrals. By use of conventional and molecular epidemiological techniques, we defined transmission as either a secondary case or a tuberculin skin-test (TST) conversion among close contacts. We used multivariate logistic regression to determine the independent association between referral for tuberculosis surveillance and transmission. Between 2002 and 2013, there were 223 225 foreign-born migrants to Alberta, of whom 5500 (2%) were referrals and 217 657 (98%) were non-referrals. 3805 (69%) referrals and 115 226 (53%) non-referrals were from countries with a tuberculosis incidence of more than 150 per 100 000 populations, or sub-Saharan Africa. 234 foreign-born individuals were diagnosed with culture-positive pulmonary tuberculosis between Jan 1, 2004, and Dec 31, 2013. The incidence of culture-positive pulmonary disease was nine times higher in referrals (n=50) than all non-referrals (n=184; incidence rate ratio 9·1, 95% CI 6·7-12·5) and five times higher in referrals than non-referrals from high-risk countries (n=167; 5·0, 3·6-6·8). 71 total transmission events arose from the individuals with culture-positive pulmonary tuberculosis-three (4%) from referrals and 68 (96%) from non-referrals. No secondary cases were attributable to a referral source case, whereas 18 secondary cases were attributable to 11 different non-referral source cases. Three TST conversions were attributable to three different referral source cases compared with 50 conversions from 31 different non-referral source cases. That is, three (6%) referrals transmitted tuberculosis compared with 42 (22%) non-referrals (adjusted odds ratio of 0·19, 95% CI 0·054-0·66; p=0·009). Despite a much higher incidence of pulmonary tuberculosis in referrals than non-referrals, referrals were 80% less likely to transmit tuberculosis. Rather than a focus on referrals, Canada could consider screening and treatment of latent tuberculosis in all migrants from high-risk countries-a group that accounted for 100% of secondary cases. Canadian Institutes of Health Research.

Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial

Tuberculosis remains one of the world's deadliest transmissible diseases despite widespread use of the BCG vaccine. MTBVAC is a new live tuberculosis vaccine based on genetically attenuated Mycobacterium tuberculosis that expresses most antigens present in human isolates of M tuberculosis. We aimed to compare the safety of MTBVAC with BCG in healthy adult volunteers. We did this single-centre, randomised, double-blind, controlled phase 1 study at the Centre Hospitalier Universitaire Vaudois (CHUV; Lausanne, Switzerland). Volunteers were eligible for inclusion if they were aged 18-45 years, clinically healthy, HIV-negative and tuberculosis-negative, and had no history of active tuberculosis, chemoprophylaxis for tuberculosis, or BCG vaccination. Volunteers fulfilling the inclusion criteria were randomly assigned to three cohorts in a dose-escalation manner. Randomisation was done centrally by the CHUV Pharmacy and treatments were masked from the study team and volunteers. As participants were recruited within each cohort, they were randomly assigned 3:1 to receive MTBVAC or BCG. Of the participants allocated MTBVAC, those in the first cohort received 5 × 10(3) colony forming units (CFU) MTBVAC, those in the second cohort received 5 × 10(4) CFU MTBVAC, and those in the third cohort received 5 × 10(5) CFU MTBVAC. In all cohorts, participants assigned to receive BCG were given 5 × 10(5) CFU BCG. Each participant received a single intradermal injection of their assigned vaccine in 0·1 mL sterile water in their non-dominant arm. The primary outcome was safety in all vaccinated participants. Secondary outcomes included whole blood cell-mediated immune response to live MTBVAC and BCG, and interferon γ release assays (IGRA) of peripheral blood mononuclear cells. This trial is registered with ClinicalTrials.gov, number NCT02013245. Between Jan 23, 2013, and Nov 6, 2013, we enrolled 36 volunteers into three cohorts, each of which consisted of nine participants who received MTBVAC and three who received BCG. 34 volunteers completed the trial. The safety of vaccination with MTBVAC at all doses was similar to that of BCG, and vaccination did not induce any serious adverse events. All individuals were IGRA negative at the end of follow-up (day 210). After whole blood stimulation with live MTBVAC or BCG, MTBVAC was at least as immunogenic as BCG. At the same dose as BCG (5×10(5) CFU), although no statistical significance could be achieved, there were more responders in the MTBVAC group than in the BCG group, with a greater frequency of polyfunctional CD4+ central memory T cells. To our knowledge, MTBVAC is the first live-attenuated M tuberculosis vaccine to reach clinical assessment, showing similar safety to BCG. MTBVAC seemed to be at least as immunogenic as BCG, but the study was not powered to investigate this outcome. Further plans to use more immunogenicity endpoints in a larger number of volunteers (adults and adolescents) are underway, with the aim to thoroughly characterise and potentially distinguish immunogenicity between MTBVAC and BCG in tuberculosis-endemic countries. Combined with an excellent safety profile, these data support advanced clinical development in high-burden tuberculosis endemic countries. Biofabri and Bill & Melinda Gates Foundation through the TuBerculosis Vaccine Initiative (TBVI).

Evaluation of immunological parameters in purified protein derivative positive tuberculin workers.

According to the occupationally risk of infection in staff workers who have direct contact with mycobacterium species, we investigated their immunological parameters and compared with healthy purified protein derivative (PPD) negative volunteers. Materials and Methods : We investigated 20 PPD positive volunteers working at Tuberculin Unit of Razi Vaccine and Serum Research Institute and PPD negative healthy controls with no exposure or history of active tuberculosis. The percentages of circulating lymphocyte subpopulations were detected by flowcytometry. IL-4 and IFN-γ production levels were measured by ELISA in supernatants of PPD-stimulated peripheral blood mononuclear cells (PBMCs) culture. Results : Tuberculin workers showed an increase in IFN-γ level and significant decrease of CD4+ T cells percentage and CD4/CD8 ratio compared to PPD negative normal individuals. However the IL-4 production and percentage of other lymphocyte population has been unchanged. These observations suggest that the immunological parameters of tuberculin workers with PPD positive reaction, who are occupationally exposed to mycobacterium antigens, could be changed. Future studies will be directed towards cytokine networking and regulatory lymphocytes, which will help us validate the significant data presented in this study.

AB0518 High percentage of dermoconversion in patients with rheumatoid arthritis under biological therapy

BackgroundMexico is a high burden tuberculosis (Tb) country. Inflammatory rheumatic diseases such as rheumatoid arthritis have an increased risk of Tb associated with both RA activity itself and treatment requirement,...

Mycobacterium tuberculosis Infections in Solid Organ Transplantation

Mycobacterium tuberculosis Infections in Solid Organ Transplantation

Tuberculose em indígenas da Amazônia brasileira: estudo epidemiológico na região do Alto Rio Negro

To describe the sociodemographic, clinical, and epidemiological characteristics of reported tuberculosis cases among indigenous individuals of São Gabriel de Cachoeira, State of Amazonas, Brazil, and to identify the factors associated with mortality during treatment; and to estimate the prevalence of latent tuberculosis infection (LTBI) and associated factors and obtain information on the therapeutic course and the individual perceptions regarding acquistion of tuberculosis in the district of Iauaretê. Firstly, a retrospective epidemiological study (1997 to 2007) was conducted using data from the Brazilian Notifiable Diseases Surveillance System (SINAN). Next, a cross-sectional study (2010) was conducted with respiratory symptomatic subjects and contacts of Iauaretê. Seven hundred and twenty-three new cases were reported, with incidence of 273.4/100 000 and mortality of 13.2/100 000. There was a predominance of males (57%), aged > 45 years (37.6%), people with no schooling (42.7%), and cases from rural areas (76.9%). Patients aged 0 to 20 years were at lower risk of death when compared to those aged > 45 years (OR = 0.3; IC95%: 0.1 a 0.9). In Iauaretê, with 15.3% of the reported cases, 184 people were interviewed. A prevalence of LTB of 76.1% was reported. Tuberculin skin test > 5 mm was associated with the > 15-year old age group, history of active tuberculosis, and radiological alterations. A previous history of tuberculosis was cited by 54 people (29.3%). The main explanation for the disease was "puffing/poisoning" (24.1%). The therapeutic course included industrialized drugs (42.6%), medicinal plants/roots, shamanism, and prayer (42.7%). The risk of tuberculosis infection and disease in this population was high. Despite the reduced incidence resulting from recent efforts, tuberculosis control requires closer surveillance of contacts and improvement in communication strategies between health teams and indigenous populations.

Role of the QuantiFERON-TB gold in tube in ruling out tuberculosis in end stage renal disease patients receiving hemodialysis

BackgroundIt is difficult to diagnose tuberculosis (TB) in dialysis patients because of the high rate of extrapulmonary TB in these patients compared with the general population. Recently, a new diagnostic test called QuantiFERON(QFT) has been developed and shown promise as a diagnostic tool for active TB diseases and latent TB infection. The aim of the present study was to analyze the performance of QuantiFERON-TB Gold in tube (QFT-G) in end stage renal disease patients receiving hemodialysis. MethodsQuantiFERON Gold in tube (QFT-GIT) were prospectively performed in 50 end stage renal disease (ESRD) cases undergoing hemodialysis (HD), including 6 patients with active TB and evaluated the utility of this test in dialysis patients. ResultsAmong 50 dialysis patients, positive QFT results occurred in 10 (20%), negative QFT results occurred in 25 (50%) and indeterminate QFT results occurred in 15 (30%). All six active TB patients had positive QFT results, and none of the 25 patients with negative results had active TB. Among 7 patients with a history of active TB, 2 (28.5%) had positive results. Although the indeterminate rate was relatively high, no patient with an indeterminate result had active TB. Among 30 cases after excluding the patients with previous TB and indeterminate results, the sensitivity of the QFT is 100% (6 of 6) and the specificity is 91.6% (22 of 24 cases). ConclusionsOur data suggest that the QFT test is a useful supplementary tool for the diagnosis of active TB even in dialysis patients. Negative and indeterminate results on this test may be used to exclude the presence of active TB.

Tuberculosis-specific T-cell response after recent treatment and remote cure

To the Editors: Tuberculosis (TB) remains a major global health problem. A major factor contributing to the current TB epidemic is the resistance of Mycobaterium tuberculosis to first-line anti-TB treatment. Therefore, there is a need for an appropriate and reliable tool to evaluate treatment efficacy. Several studies using the T-SPOT®. TB assay (Oxford Immunotec Ltd, Oxford, UK) reported a decline in the number of spots after successful anti-TB treatment, particularly in the 6-kDa early secretory antigenic target (ESAT-6) panel [1–3]; however, to our knowledge, no data have been published on cured TB patients who contracted TB before isoniazid and rifampicin became available. Therefore, the naturally long-term range of ESAT-6- and culture filtrate protein (CFP)-10-specific T-cell responses in patients with TB who did not receive modern anti-TB treatment is not known. Because most patients in prior studies were born in high-burden, TB-endemic countries, the T-cell kinetics might be influenced by reinfection. Therefore, the aim of this report is to compare the ESAT-6- and CFP-10-specific T-cell responses in a low-burden country with a low risk of reinfection between patients with a history of active TB before 1955, and patients with recently treated active TB. Venous blood for T-SPOT®. TB was collected from 24 outpatient subjects with a history of active TB before 1955 (group 1), obtained by clinical history-taking, patients’ medical records or documentation of a sanatorium admission. 16 of these patients had been admitted to a sanatorium, two patients underwent surgery and six patients were treated at home with para-aminosalicylic acid therapy or bedrest. Furthermore, 27 patients with recent active TB (group 2) were prospectively enrolled between March and May 2008. Active TB was defined as fulfilling one or more of the following criteria: 1) positive culture for M. tuberculosis (n=22); 2) positive PCR for M. …