Previous Tuberculosis Disease Research Articles

Rifapentine and isoniazid for prevention of tuberculosis in people with diabetes (PROTID): protocol for a randomised controlled trial

BackgroundDiabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. In this trial, we will examine the efficacy and safety of TB preventive therapy against the development of TB disease in people with DM who have latent TB infection (LTBI), with a 12-week course of rifapentine and isoniazid (3HP).MethodsThe ‘Prevention of tuberculosis in diabetes mellitus’ (PROTID) consortium will randomise 3000 HIV-negative eligible adults with DM and LTBI, as evidenced by a positive tuberculin skin test or interferon gamma release assay, to 12 weeks of 3HP or placebo. Participants will be recruited through screening adult patients attending DM clinics at referral hospitals in Tanzania and Uganda. Patients with previous TB disease or treatment with a rifamycin medication or isoniazid (INH) in the previous 2 years will be excluded. The primary outcome is the occurrence of definite or probable TB disease; secondary outcome measures include adverse events, all-cause mortality and treatment completion. The primary efficacy analysis will be intention-to-treat; per-protocol analyses will also be carried out. We will estimate the ratio of TB incidence rates in intervention and control groups, adjusting for the study site using Poisson regression. Results will be reported as efficacy estimates (1-rate ratio). Cumulative incidence rates allowing for death as a competing risk will also be reported. Approximately 1000 LTBI-negative, HIV-negative participants will be enrolled consecutively into a parallel cohort study to compare the incidence of TB in people with DM who are LTBI negative vs positive. A number of sub-studies will be conducted among others to examine the prevalence of LTBI and active TB, estimate the population impact and cost-effectiveness of LTBI treatment in people living with DM in these African countries and address gaps in the prevention and therapeutic management of combined TB-DM.DiscussionPROTID is anticipated to generate key evidence to guide decisions over the use of TB preventive treatment among people with DM as an important target group for better global TB control.Trial registrationClinicalTrials.govNCT04600167. Registered on 23 October 2020

Previous tuberculosis disease as a risk factor for chronic obstructive pulmonary disease: a cross-sectional analysis of multicountry, population-based studies

BackgroundRisk factors for COPD in high-income settings are well understood; however, less attention has been paid to contributors of COPD in low-income and middle-income countries (LMICs) such as pulmonary tuberculosis....

Tracing TB: Are there predictors for active TB disease in patients with Xpert Ultra trace results?

ObjectivesThe Xpert MTB/Rif Ultra (Xpert Ultra; Cepheid, USA) has increased sensitivity compared with its predecessor (Gene Xpert), due to the addition of multicopy amplification targets and a novel trace call. The World Health Organization suggests that tuberculosis (TB) treatment should be initiated in HIV, paediatric, and extra-pulmonary TB patients with trace results. However, other factors such as previous TB disease may complicate the interpretation of trace results in high-burden TB settings. This study aimed to clarify the positive predictors for active TB disease in patients with trace results and to investigate if previous TB disease influences TB culture positivity. MethodsA retrospective descriptive study was performed on 290 patients with trace results, to determine what the positive predictors for active TB are by comparing clinical factors to TB culture. ResultsThe key findings of this study were that extra-pulmonary TB samples (OR, 2.7; p=0.012), no previous TB disease (OR, 4.5; p=0.001) and symptoms suggestive of TB (OR, 6.4; p<0.001) are independent predictors for active TB disease. ConclusionThis study found readily available clinical predictors that can aid clinicians with TB management decisions in patients with trace results.

RESPIRATORY SYMPTOMS AND LUNG FUNCTION AMONG ONLINE MOTORCYCLE TAXI DRIVERS

SESSION TITLE: Population-Wide Lung Health: Exposures and Risks SESSION TYPE: Original Investigations PRESENTED ON: 10/23/2019 10:45 AM - 11:45 AM PURPOSE: Online motorcycle taxi drivers have been heavily exposed to high concentration of hazardous air pollutants. It will cause harmful effects especially on the respiratory system. This study aimed to describe the respiratory symptoms and lung function among online motorcycle taxi drivers and risk factors that influence them. METHODS: A survey research design of 99 online motorcycle taxi drivers in Bekasi City was done. Lung function was measured using spirometer and predicted volume value from Pneumobile Project Indonesia. Risk factors and respiratory symptoms were collected using questionnaire. RESULTS: This study showed that 10,1% of subjects had restrictive lung function impairment and 5,1% had obstructive lung function impairment. Age had significant association with restrictive disorders (p= 0,006). The mean predicted forced vital capacity (FVC) was 3451 ml and the mean forced expiratory volume in one second (FEV1) was 2959 ml. There was a significant relationship between sex (p=0,001) and age (p=0,001) with the mean percent predicted forced vital capacity (%FVC). Age had significant association with the mean of percent predicted forced expiratory volume in one second (%FEV1) (p=0,039). However there were no significant relationship founded between sex, body mass index, safety equipment, history of smoking, duration of work, asthma history and previous tuberculosis disease with obstructive and restrictive lung function impairment. A proportion of respiratory symptoms among online motorcycle taxi drivers were cough (17,2%) and shortness of breath (6,1%). There were no significant relationship founded between respiratory symptoms and lung function result. CONCLUSIONS: This survey showed online motorcycle taxi drivers have respiratory symptoms and lung function impairment, however the causal relationship with the workplace environment is still unclear. Therefore, it will need further study to explore this findings. Moreover, education to the online motorcycle taxi drivers about the importance of using personal protective equipment will help them to protect respiratory systems from harmful gases. CLINICAL IMPLICATIONS: We report for the first time survey of online motorcycle taxi drivers in Indonesia which showed respiratory and impairment of lung function. Causal relationship with the workplace environment will be better explore with cohort study. Therefore, mask as personal protective equipment should be used in daily basis to protect them from air pollutants. DISCLOSURES: No relevant relationships by Triya Damayanti, source=Web Response No relevant relationships by Jaka Pradipta, source=Web Response no disclosure on file for Agus Susanto

Findings from a pilot project to assess the feasibility of active tuberculosis case finding among seniors in rural Sichuan Province, China, 2017.

BackgroundChina has a substantial tuberculosis (TB) disease burden and an aging population. Seniors have a higher risk of developing TB disease compared to younger age groups. Active case finding (ACF) could help identify seniors with TB disease.MethodsFrom March to June 2017, we included ACF during annual physical check-ups for persons aged ≥ 65 years in Bayi, Sichuan Province. Seniors with clinical TB symptoms (i.e., cough lasting ≥ 2 weeks and/or hemoptysis) or one or more risk factors (e.g., previous TB disease, diabetes, and heavy alcohol consumption) were offered chest x-rays. We used acid-Fast Bacilli smear and solid culture laboratory testing for TB confirmation. We calculated the yield (i.e., cases identified among seniors screened) and cost per new each TB case detected. Focus group-interviews were conducted with health care workers and seniors to evaluate project acceptability. Participation rates and acceptability were used to assess feasibility.ResultsOf the 2,393 seniors residing in Bayi, 2,049 (85.6%) were enrolled in the pilot project. Of these seniors, 794 (38.7%) presented with at least one TB risk factor and 74 (3.6%) had symptoms consistent with active TB disease. Three seniors (0.2%)–each presenting with at least one risk factor—were diagnosed with active TB. The project yielded 146 TB cases per 100,000 seniors screened; the cost per case detected was $4,897. Most workers supported ACF if additional resources and staff could be provided. Seniors appreciated the convenience of this integrated health service approach.ConclusionsAlthough the yield was lower than expected, ACF appeared feasible in Bayi. Targeting seniors with at least one known TB risk factor could help detect previously unidentified TB cases. However, similar projects in communities with a higher TB prevalence are needed to further evaluate the yield and required resources prior to implementation on a larger scale. Findings from our pilot project should be combined with data from these future ACF projects to improve TB screening criteria.

Tuberculosis and diabetes: bidirectional association in a UK primary care data set

BackgroundMany studies have found an increased risk of pulmonary tuberculosis (PTB) among those with diabetes mellitus (DM). However, evidence on whether the association is bidirectional remains sparse. This study investigates...

Incidence and determinants of tuberculosis infection among adult patients with HIV attending HIV care in north-east Ethiopia: a retrospective cohort study

ObjectiveThis study assessed the incidence of tuberculosis (TB) and its predictors among adults living with HIV/AIDS in government health facilities in north-east Ethiopia.SettingA 5-year retrospective cohort study was conducted from...

Differential Recognition of Mycobacterium tuberculosis-Specific Epitopes as a Function of Tuberculosis Disease History.

Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb). We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease. T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-γ enzyme-linked immunospot assay or intracellular cytokine staining. We identified a set of "type 2" T-cell epitopes that were recognized at 10-fold-lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those without previous TB. By contrast, "type 1" epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, "TB disease history-sensitive" type 2 epitopes were significantly (P < 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes. Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.

The Risk of Tuberculosis Reinfection Soon after Cure of a First Disease Episode Is Extremely High in a Hyperendemic Community

Elevated rates of reinfection tuberculosis in various hyperendemic regions have been reported and, in particular, it has been shown that in a high-incidence setting near Cape Town, South Africa, the rate of reinfection tuberculosis (TB) disease after cure of a previous TB disease episode is about four times greater than the rate of first-time TB disease. It is not known whether this elevated rate is caused by a high reinfection rate due, for instance, to living circumstances, or a high rate of progress to disease specific to the patients, or both. In order to address that question we analysed an extensive data set from clinics attended by TB patients in the high-incidence setting near Cape Town, South Africa and found that, in fact, the (average) rate of reinfection (as opposed to the rate of reinfection disease) after cure of a previous TB disease episode is initially about 0.85 per annum. This rate diminishes rapidly over time and after about ten years this rate is similar to the rate of infection in the general population. Also, the rate of progress to disease after reinfection is initially high but declines in subsequent years down to the figure typical for the general population. These findings suggest that the first few months after cure of a TB disease episode form a critical period for controlling reinfection disease in a hyperendemic setting and that monitoring such cured patients could pre-empt a reinfection progressing to active disease.

Prediction of the risk of active tuberculosis in HIV-infection with an interferon-γ release assay

BackgroundGlobally, tuberculosis remains the main cause of death in HIV-infected people. The spread of HIV/AIDS cannot be curbed without effective tuberculosis control strategies. Targeted treatment of latent tuberculosis infection is cost effective, but requires accurate diagnostic methods. QuantiFERON-TB Gold (QFT), an interferon-γ release assay, is promising, but its predictive value in HIV-infected patients is uncertain. We followed up a cohort of HIV-infected people to establish the incidence of tuberculosis by linking to a national tuberculosis database, and determined the predictive value of QFT. MethodsWe did a prospective 5-year cohort study in one medical centre and one regional hospital in Taiwan. HIV-infected adults attending outpatient clinics, from Jan 1, 2006, to Jan 31, 2010, were invited to participate after excluding active tuberculosis through absence of symptoms and a normal result of chest radiography. We used a questionnaire to obtain demographic information and information on past exposure to tuberculosis, previous tuberculosis disease, previous vaccination, HIV risk factors, CD4 cell counts, and HIV viral load testing within the past 3 months. At study entry, blood was taken for the QFT test. The cohort was followed up every 3 months, until development of active tuberculosis disease, death, or censoring on Dec 31, 2012. Cases of incident active tuberculosis were ascertained by linking participants to the national tuberculosis database registry. Patients were offered treatment if they tested positive. We used Kaplan-Meier survival analysis to explore risk factors. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios for development of incident active tuberculosis, and were adjusted for age and baseline CD4 cell count. FindingsWe enrolled 772 HIV-infected adults with a mean age of 36·8 years (SD 9·0), mostly men (744 [96·4%]), with a median CD4 cell count of 460 cells per μL (IQR 329–634), and a median log plasma HIV viral load of 3·40 copies per mL (IQR 1·74–3·97). HIV risk factors included being injecting drug users (517 [67%]), men who have sex with men (187 [24·2%]), and heterosexuals (62 [8%]). Almost a third (254 [32·9%]) were receiving antiretroviral treatment at study entry. Subsequently, 431 (60·3%) were placed on treatment during the study. The QFT was positive in 90 participants (11·7% [95% CI 9·5–14·0]) and indeterminate in 31 (4·0% [2·7–5·7]). 17 incident active tuberculosis cases (incidence rate 0·44 per 100 person-years) were recorded during 3843 person-years of follow-up (median 5·21 person-years), with two (11·8%) of 17 participants dying during the study. The median CD4 cell count at diagnosis of tuberculosis was 308 cells per μL (IQR 56–531). One patient had extrapulmonary tuberculosis and tested QFT negative. We found that people with a positive QFT had a five-fold risk (adjusted hazard ratio [HR] 5·02 [95% CI 1·75–14·42]; p=0·003) of developing active tuberculosis after ad justment for age, CD4 cell count, and HIV viral load. Individuals with an HIV viral load greater than or equal to 100 000 copies per mL had an eight-fold risk of developing active tuberculosis (adjusted HR 8·69 [1·21–62·23]; p=0·03). The negative predictive value of the QFT was 98·5% (95% CI 97·2–99·3). InterpretationA high negative predictive value of QFT for incident tuberculosis confirmed the safety of not treating those with negative tests. QFT accurately identifies patients who might benefit from treatment of latent tuberculosis infection, which is an important step towards halting the dual epidemic. FundingThis study was supported by grants from Kaohsiung Veterans General Hospital, Taiwan(VGHKS97-066); the National Science Council of Taiwan (NSC 100-2314-B-010-039, NSC102-2314-B-010-017); and the National Health Research Institute, Department of Health, Taiwan (NHRI-99A1-PDCO-0710101).

Contact screening in tuberculosis: can we identify those with higher risk?: Table 1–

To the Editor: Contact screening, as a strategy to identify recently infected individuals, is part of the tuberculosis (TB) elimination strategy. It follows risk stratification concerning the infectiousness of the index patient, the duration and proximity of exposure, and the susceptibility of the contact [1, 2]. For its optimisation it is important to know which risk factors are associated with Mycobacterium tuberculosis transmission in order to not over screen or lose at-risk contacts. In view of that, this study aims to identify potential risk factors for M. tuberculosis transmission among contacts of pulmonary TB patients, in a Portuguese TB reference centre. From January to December of 2011, all contacts of confirmed pulmonary TB patients, screened in the TB centre, were questioned about their exposure to the index patient through a questionnaire completed during the medical appointment. Both household and casual contacts were screened, independent of their cumulative exposure. Contacts excluded: those with exposure outdoors ( e.g. in the street); those with incomplete characterisation of exposure ( e.g. index patients for whom we did not know the symptomatic period); those non-compliant with screening ( e.g. contacts who failed tuberculin skin test (TST) reading); and those with a past history of M. tuberculosis infection or TB disease ( e.g. contact´s verbal report of previous TB disease, contact with a pulmonary TB patient or treatment for latent tuberculosis infection (LTBI)). Contacts of patients with a diagnosis of pulmonary TB were identified for screening at the moment of the index patient diagnosis. The index patient was asked to identify contacts within the family, social and work spheres. Furthermore, some other …

Tuberculosis in household contacts of multidrug-resistant tuberculosis patients

The burden of tuberculosis (TB) disease among household contacts of multidrug-resistant TB (MDR-TB) patients is poorly understood and might represent a target for transmission-interrupting interventions. This retrospective cohort study, conducted in Lima, Peru, from June to September 2008, estimated the incidence of TB disease among household contacts of MDR-TB patients in 358 households. Of 2112 household contacts in 80 households (22% of households), 108 (5%) developed TB disease during the study, giving an incidence rate of 2360 per 100 000 contact follow-up years for each of the first 3 years after exposure. Drug susceptibility tests (DST) were available for 50 diseased contacts, of whom 36 (80%) had MDR-TB. Forty-two pairs of index-contact DSTs were available, among which the contact had an identical or less resistant phenotype than the index case in 27 pairs. Multivariate Cox regression demonstrated that male contacts (hazard ratio [HR] 2.8, P < 0.05), with previous TB disease (HR 20.7, P < 0.001) and with associated (non-human immunodeficiency virus) comorbidities (HR 11.2, P < 0.001) were more likely to develop TB. The high percentage of diseased household contacts highlights an opportunity for household-level interventions to prevent transmission, whether or not these cases were all attributable to the index case.

Diagnosis and follow-up of treatment of latent tuberculosis; the utility of the QuantiFERON-TB Gold In-tube assay in outpatients from a tuberculosis low-endemic country

BackgroundInterferon-gamma (IFN-γ) Release Assays (IGRA) are more specific than the tuberculosis skin test (TST) in the diagnosis of latent tuberculosis (TB) infection (LTBI). We present the performance of the QuantiFERON®-TB Gold In-tube (QFT-TB) assay as diagnostic test and during follow-up of preventive TB therapy in outpatients from a TB low-endemic country.Methods481 persons with suspected TB infection were tested with QFT-TB. Thoracic X-ray and sputum samples were performed and a questionnaire concerning risk factors for TB was filled. Three months of isoniazid and rifampicin were given to patients with LTBI and QFT-TB tests were performed after three and 15 months.ResultsThe QFT-TB test was positive in 30.8% (148/481) of the total, in 66.9% (111/166) of persons with origin from a TB endemic country, in 71.4% (20/28) previously treated for TB and in 100% (15/15) of those diagnosed with active TB with no inconclusive results. The QFT-TB test was more frequently positive in those with TST ≥ 15 mm (47.5%) compared to TST 11-14 mm (21.3%) and TST 6-10 mm (10.5%), (p < 0.001). Origin from a TB endemic country (OR 6.82, 95% CI 1.73-26.82), recent stay in a TB endemic country (OR 1.32, 95% CI 1.09-1.59), duration of TB exposure (OR 1.59, 95% CI 1.14-2.22) and previous TB disease (OR 11.60, 95% CI 2.02-66.73) were all independently associated with a positive QFT-TB test. After preventive therapy, 35/40 (87.5%) and 22/26 (84.6%) were still QFT-TB positive after three and 15 months, respectively. IFN-γ responses were comparable at start (mean 6.13 IU/ml ± SD 3.99) and after three months (mean 5.65 IU/ml ± SD 3.66) and 15 months (mean 5.65 IU/ml ± SD 4.14), (p > 0.05).ConclusionOnly one third of those with suspected TB infection had a positive QFT-TB test. Recent immigration from TB endemic countries and long duration of exposure are risk factors for a positive QFT-TB test and these groups should be targeted through screening. Since most patients remained QFT-TB positive after therapy, the test should not be used to monitor the effect of preventive therapy. Prospective studies are needed in order to determine the usefulness of IGRA tests during therapy.

The Impact of Age on the Demographic, Clinical, Radiographic Characteristics and Treatment Outcomes of Pulmonary Tuberculosis Patients in Taiwan

The characteristics of pulmonary tuberculosis (TB) in the elderly are different from young patients. This leads to delay in diagnosis and higher mortality from TB in the aged population. The aim of this study was to investigate the impact of age on the demographic, clinical, radiographic characteristics, and treatment outcomes of pulmonary TB patients in Taiwan. We performed a retrospective analysis of the medical charts and chest radiographs of 83 elderly (> or =60 years old) and 74 young (< 60 years old) culture-proven pulmonary TB patients from 1 August 2003 to 31 July 2006. Elderly patients showed lower frequencies of infectious TB contact history, alcoholism, cavity, and positive acid-fast bacilli sputum smears. In contrast, the elderly population had higher frequencies of chronic obstructive lung disease, heart failure, stroke, dyspnea, lower lung field involvement, pleural effusion and mortality. There were no differences between these two groups regarding sex, initial body weight, previous TB disease, hospital admission, diabetes mellitus, end-stage renal disease, neoplasm, liver cirrhosis, upper lung field involvement, cure, and treatment completion. Furthermore, age of 60 and older, lower initial body weight less than 50 kg, coexisting medical diseases, and extensive radiographic disease were factors independently associated with unfavorable outcomes. Elderly patients with pulmonary TB are more likely to present with negative sputum smears, cavity-negative lesions, lower lung field involvement and pleural effusion on chest radiographs. The prognosis is poor for the elderly pulmonary TB patients with lower body weight, coexisting medical diseases, and extensive radiographic disease.

Latent Tuberculosis in HIV positive, diagnosed by the M. Tuberculosis Specific Interferon-γ test

BackgroundAlthough tuberculosis (TB) is a minor problem in Denmark, severe and complicated cases occur in HIV positive. Since the new M. tuberculosis specific test for latent TB, the QuantiFERON-TB In-Tube test (QFT-IT) became available the patients in our clinic have been screened for the presence of latent TB using the QFT-IT test. We here report the results from the first patients screened.MethodsOn a routine basis the QFT-IT test was performed and the results from 590 HIV positive individuals consecutively tested are presented here. CD4 cell count and TB risk-factors were recorded from patient files.Main findings27/590(4.6%) of the individuals were QFT-IT test positive, indicating the presence of latent TB infection. Among QFT-IT positive patients, 78% had risk factors such as long-term residency in a TB high endemic area (OR:5.7), known TB exposure (OR:4.9) or previous TB disease (OR:4.9). The prevalence of latent TB in these groups were 13%, 16% and 19% respectively. There was a strong correlation between low CD4 T-cell count and a low mitogen response (P < 0.001;Spearman) and more patients with low CD4 cell count had indeterminate results.ConclusionWe found an overall prevalence of latent TB infection of 4.6% among the HIV positive individuals and a much higher prevalence of latent infection among those with a history of exposure (16%) and long term residency in a high endemic country (13%). The QFT-IT test may indeed be a useful test for HIV positive individuals, but in severely immunocompromised, the test may be impaired by T-cell anergy.