Tuberculosis Disease Research Articles

Trends in Viral Vector-Based Vaccines for Tuberculosis: A Patent Review (2010-2023).

Tuberculosis (TB) is an ancient global public health problem. Several strategies have been applied to develop new and more effective vaccines against TB, from attenuated or inactivated mycobacteria to recombinant subunit or genetic vaccines, including viral vectors. This review aimed to evaluate patents filed between 2010 and 2023 for TB vaccine candidates. It focuses on viral vector-based strategies. A search was carried out in Espacenet, using the descriptors "mycobacterium and tuberculosis" and the classification A61K39. Of the 411 patents preliminarily identified, the majority were related to subunit vaccines, with 10 patents based on viral vector platforms selected in this study. Most of the identified patents belong to the United States or China, with a concentration of patent filings between 2013 and 2023. Adenoviruses were the most explored viral vectors, and the most common immunodominant Mycobacterium tuberculosis (Mtb) antigens were present in all the selected patents. The majority of patents were tested in mouse models by intranasal or subcutaneous route of immunization. In the coming years, an increased use of this platform for prophylactic and/or therapeutic approaches for TB and other diseases is expected. Along with this, expanding knowledge about the safety of this technology is essential to advance its use.

Screening hemodialysis patients for tuberculosis in Sudan

ObjectivesTo estimate the prevalence of latent tuberculosis infection (LTBI) and the need for TB preventive treatment (TPT) among hemodialysis (HD) patients in Sudan. MethodsWe screened patients in a single HD center by two-step tuberculin skin test (TST), symptom survey, physical examination and chest radiography (CXR). ResultsThe survey included 204 patients, five of whom (2.5%) had history of previously treated TB. The proportion of TST positive patients was 12.3% after the first test and increased to 21.1% after the second test. Patients previously treated for TB were more likely to have positive TST (80 vs 20.1%, p = 0.01). We screened 184 patients for TB disease; 16.3% were symptomatic, 15.8% had CXR abnormality and 6.5% were symptomatic with CXR abnormality. Additionally, 13.6% of patients had physical signs consistent with extra-pulmonary TB without symptoms or CXR abnormality. Based on these findings, high probability of pulmonary and extra-pulmonary TB was found in 38.6% and 13.6% of patients respectively and they were referred for bacteriological confirmation. We diagnosed LTBI and prescribed TPT to 9.2% of screened patients. ConclusionIn this cohort of Sudanese HD patients, 21.1% were positive after two-step TST and 52.2% were considered to have high probability of TB disease.

Tuberculosis-related Mood Disorders: Probiotics as a Next-Generation Strategy

Introduction: Tuberculosis-related mood disorders are well-known but least researched. As frequent comorbidity of tuberculosis (TB), depression is linked to poor adherence to treatment for a number of illnesses. The exact causal mechanism and pathways behind TB disease and associated mental illnesses are unclear. The disease's severity and duration impact the occurrence of depression, and MDR-TB enhances this risk. To summarise the information on the association between depression and unfavourable outcomes of TB treatment, we carried out a narrative review. Objective: The objective of this study is to provide an overview of probiotics as a cutting-edge treatment for mood disorders linked to tuberculosis. Methods: A systematic stepwise online database research was done for systematic reviews, original studies, and review papers published on probiotics and mental disorders associated with tuberculosis in PubMed/MEDLINE, Google Scholar, and Web of Science. The reference lists for these articles were also used as sources for the bibliography Results: The gut microbiota and the brain are connected by neuroendocrine-immune pathways. The diversity and abundance of microbiota Proteobacteria, Actinobacteria Bacteroides, and Firmicutes are reduced in tuberculosis patients. Through the stimulation of different immunological responses or visceral sensory pathways, these changes in the gut microbiome may be a contributing factor in emotional instability and mood disorders. Probiotics also lessen the stress response caused by cortisol, in addition to releasing neurotransmitters, including GABA, serotonin, noradrenaline, acetylcholine, and dopamine, in various brain regions. Probiotics are the most prevalent in the sensory brain network of the brain, which controls the brain's core processing of emotions and sensations. In addition, they produce short-chain fatty acids (SCAFs) from the bacterial fermentation of fibre in the colon, such as butyrate, which inhibits histone deacetylase, binds to G protein-coupled receptors, and serves as an energy metabolite. Butyrate plays a significant role in maintaining brain health by having antimanic and antidepressant effects. Several clinical research on patients with MDD has revealed that probiotics have favourable effects on depressive symptoms. Conclusion: The central dopamine system, inflammation, the BDNF system, and the gut-brain axis are all recognised to play crucial roles in the pathogenesis of MDD. Commercial probiotics that generate butyrate-producing SCFAs and those resistant to metabolic disorders (such as Bacteroidetes) may be beneficial for tuberculosis-related MDD during and after treatment. In this situation, using bacteria that produce SCFA could be a cutting-edge method of treating clinical MDD.

TB disease yield from household contact screening of TB index patients in Pakistan.

<sec><title>OBJECTIVES</title>The national guidelines recommend contact screening of a subset of patients with the TB index and their household contacts (HHCs). Thus, many contacts with TB remain unscreened.</sec><sec><title>METHODS</title>We collected prospective data under programmatic conditions in Karachi, Pakistan, from January 2018 to December 2019. We screened all HHCs of all patients using the TB index. We disaggregated the data into guideline-eligible or ineligible index patients and contacts. We calculated TB disease yields for different groups of index patients and contacts.</sec><sec><title>RESULTS</title>Of 39,168 HHCs from 6,450 index patients, 21,035 completed clinical assessments for TB, and 416 were diagnosed with all forms of TB. HHCs of patients with clinically diagnosed pulmonary TB (PTB) were as likely to be diagnosed with TB as the HHCs of patients with bacteriologically confirmed PTB (adjusted OR 1.28, 95% CI 0.94-1.75). The yield of TB disease among child contacts (3.4%) was significantly higher than that among adult contacts (0.5%) (P < 0.001).</sec><sec><title>CONCLUSIONS</title>Broadening household contact screening criteria could increase the yield of contact tracing and improve the diagnosis of TB. However, further studies are required to establish the feasibility and cost-effectiveness of this approach, including studies from more diverse settings.</sec>.

The International Consensus for Early TB framework (ICE-TB): Implications from a low-incidence setting.

<sec><title>BACKGROUND</title>In recent years, there has been increasing recognition of the public health significance of the spectrum of TB disease presentation, and the existing classification systems of asymptomatic infection and symptomatic TB have been limited in terms of explanatory power. Accordingly, in 2022-2023, a new International Consensus framework for Early TB (ICE-TB) was developed, categorising the spectrum of TB infection and disease into five states based on the presence or absence of macroscopic pathology, host infectiousness, and symptoms and signs.</sec><sec><title>METHODS</title>We used the ICE-TB framework to re-analyse existing notification data for 2022 within a low-incidence setting to explore the potential utility and future challenges for its public health application.</sec><sec><title>RESULTS</title>Existing notification data were sufficient to allow substantial reclassification of currently recognised active disease states, but did not systematically capture Mycobacterium tuberculosis infection or subclinical TB. Fifty percent of existing TB notifications would be classified as 'Clinical, infectious', with the potential need to consider further subclassification.</sec><sec><title>CONCLUSION</title>Our exploration highlighted limitations in existing classification systems and diagnostic approaches and should encourage researchers and programmatic implementers to emphasise person-centred and programmatic needs in the development of new tools for TB management.</sec>.

Coexistence of Bronchiectasis Related with Rheumatoid Arthritis and Posttuberculosis Lung Disease - An Everpresent Issue

Abstract The lung is a common site of involvement both in TB and rheumatoid arthritis (RA) disease, caused by disease itself or therapy. After completion of antiTB treatment, post TB lung disease (PTLD) residual changes persist and affect heath, survival and quality of life, mainly in patients with associated collagen diseases, as RA. Bronchiectasis are described in both RA and PTLD. The purpose of this prevalence study of bronchiectasis, performed among 92 RA hospitalized patients, from June 2017 to June 2019, consists in a pictorial assessment of the lung involvement changes, noticed on chest radiography and/or computed tomography, described in relation with TB sequelae, severity and duration of RA disease. Results. A high prevalence of imagistic abnormalities was found in 77.2% of cases (n=71/92). Bronchiectasis was a frequent imagistic chest finding (24/71; 33.8%), having a lower frequency among all study group patients (n=24/92; 26%), mostly older nonsmoker females. Conclusions. In a high TB burden, as Romania, the prevalence of bronchiectasis is related with advanced RA disease, being strongly correlated with persistent respiratory symptoms (p=0.009), and coexisting PTLD calcified nodular lung sequelae (p=0.001).

Impact of fine particulate pollution exposures on respiratory health in a megacity of Pakistan

Air pollution poses a substantial barrier to global environmental sustainability and citizen well-being. However, there is a lack of research that specifically examines the effects of short-term exposure to PM2.5 and its components on health outcomes in developing nations in Asia, regions often cited as having some of the most severe urban air quality issues globally. The present study evaluated the associations between PM2.5 components and hospital admissions (HA) and emergency room visits (ERV) for respiratory diseases in the megacity of Karachi, Pakistan. We measured PM2.5 constituents, including black carbon (BC) and ionic species (sulfate - SO42−; nitrate - NO3−; and ammonium - NH4+) at two sites (August 2008 to August 2009) in Karachi. The HA and ERV, respiratory disease outcome data, were collected from three local, large tertiary care hospitals. We assessed the lag structure of excess risk (ER) of the pollutants-outcomes association (0–6 single and cumulative lag days) using time-series quasi-Poisson models after adjusting for temperature, humidity, and day of the week. Among a total 13,827 patients, the highest ERs for all respiratory urgent care use (UCU) were observed for PM2.5 (10.3, 95% CI: 2.59%-18.59), NH4+ (9.58%, 95% CI: 1.50%–18.30%), air quality index (9.11%, 95%CI: 2.54%–16.09%) and SO42− (7.26%, 95% CI: 1.03%–13.87%) within 0–4 lag days. Additionally, patients with chronic obstructive pulmonary disease (COPD), tuberculosis (TB), or other pulmonary diseases and older or male patients were more vulnerable to these pollutants. This first study in Pakistan found that PM2.5 and its constituents were associated with respiratory HAs and ERVs for the inhabitants of the megacity of Karachi. These associations varied by different PM constituents, disease subtypes, age, and gender. Our results provide important information to policymakers for developing regulations for improving air quality and public health. Further studies are urgently needed in other developing countries to disentangle the air pollution health effects.

Epidemiological, clinical and evolutive profile of tuberculosis patients: Case of the region of Guelmim in Morocco

Background and aimTuberculosis is an infectious, contagious disease caused mainly by Mycobacterium tuberculosis. The objective of our study is to describe the epidemiological, clinical and evolutionary profiles of tuberculosis patients at the Diagnostic Center for Tuberculosis and Respiratory Diseases (DCTRD) in the Guelmim region, Morocco. MethodsThis is a retrospective study examining the medical records of tuberculosis patients at the Guelmim DCTRD from January 1, 2018, to April 28, 2022. ResultsA total of 825 cases were collected, comprising 488 cases of ETB and 337 cases of PTB. The median age of ETB patients was 31.5 [21–47] years, compared to 37 [26.5–52] years for PTB patients. ETB was more common than PTB in both age groups (<10 and ≥ 10 years) (p < 0.001). Females were more affected by ETB in 73 % of cases. Clinical signs were more prevalent in PTB than in ETB patients (p < 0.001). Tobacco and alcohol consumption were higher in the PTB group than in the ETB group (p < 0.001). Asthma and diabetes were more prevalent in the ETB group at 58 % and 51 %, respectively (p < 0.001). HIV serology was largely negative in both groups, with a non-negligible proportion of unknown status (p < 0.001). Therapeutic outcomes were favorable in 61 % of PTB patients versus 39 % of ETB patients (p < 0.001). ConclusionOur study highlighted the predominance of ETB. PTB patients had more clinical signs and tobacco/alcohol consumption. HIV serology was mostly negative, and therapeutic outcomes were favorable, suggesting a need for better management.

Prevalence and epidemiological profile of pulmonary tuberculosis among elderly population residing in old age homes in Salem district, Tamilnadu

BackgroundTuberculosis mostly affects adults in their most productive years. However, all age groups are at risk. One of the high risk groups for tuberculosis is the elderly population due to factors like physiological ageing related changes, presence of comorbidities and immunodeficiency. Objective1. To estimate the prevalence of pulmonary tuberculosis among the elderly population residing in selected old age homes.2. To assess the epidemiological profile of pulmonary tuberculosis among the elderly population residing in selected old age homes. MethodologyAn analytical cross sectional study was carried out among elderly inmates (N – 300) of selected 10 old age homes in Salem district of Tamilnadu. A pre tested semi-structured questionnaire was used as a study tool for data collection. Investigations like CBNAAT and X ray were carried out on individuals with presumptive symptoms. ResultsAmong 300 participants, about 50.7% were between 61 and 70 Years and 60.7% were females. Nearly 4.3% were current smokers, 28.7% were hypertensive and 20.6% were diabetic About 15.6% had cough, 11.2% had fever and 4.8% had hemoptysis Prevalence of tuberculosis was 2.6% (260 per 10,000 popultion) in this study. Tuberculosis was reported more in Females, those with presumptive symptoms, underweight individuals, those living in dormitory and those with comorbidity. ConclusionThe results indicate that the key population should be concentrated for routine screening for tuberculosis. Pro-active interventions to seek and diagnose TB disease among older adults are more effective than traditional passive case-finding as we march towards elimination of tuberculosis in India.

A pharmacometric multistate model for predicting long-term treatment outcomes of patients with pulmonary TB.

Studying long-term treatment outcomes of TB is time-consuming and impractical. Early and reliable biomarkers reflecting treatment response and capable of predicting long-term outcomes are urgently needed. To develop a pharmacometric multistate model to evaluate the link between potential predictors and long-term outcomes. Data were obtained from two Phase II clinical trials (TMC207-C208 and TMC207-C209) with bedaquiline on top of a multidrug background regimen. Patients were typically followed throughout a 24 week investigational treatment period plus a 96 week follow-up period. A five-state multistate model (active TB, converted, recurrent TB, dropout, and death) was developed to describe observed transitions. Evaluated predictors included patient characteristics, baseline TB disease severity and on-treatment biomarkers. A fast bacterial clearance in the first 2 weeks and low TB bacterial burden at baseline increased probability to achieve conversion, whereas patients with XDR-TB were less likely to reach conversion. Higher estimated mycobacterial load at the end of 24 week treatment increased the probability of recurrence. At 120 weeks, the model predicted 55% (95% prediction interval, 50%-60%), 6.5% (4.2%-9.0%) and 7.5% (5.2%-10%) of patients in converted, recurrent TB and death states, respectively. Simulations predicted a substantial increase of recurrence after 24 weeks in patients with slow bacterial clearance regardless of baseline bacterial burden. The developed multistate model successfully described TB treatment outcomes. The multistate modelling framework enables prediction of several outcomes simultaneously, and allows mechanistically sound investigation of novel promising predictors. This may help support future biomarker evaluation, clinical trial design and analysis.

TB prevention activities in the WHO European Region.

TB preventive treatment (TPT) is the primary available healthcare intervention to reduce the risk of progression from TB infection to TB disease. The WHO Regional Office for Europe established the European Prevention and Systematic Screening Initiative to End TB (PASS) to scale up activities related to the programmatic management of TPT. In the absence of a system to measure and monitor preventive activities, a baseline assessment survey was carried out to provide a reference to monitor the scale-up of the intervention. This was a semi-structured survey including 52 questions that was developed, implemented in the WHO-hosted LimeSurvey data form and sent to focal points in the 55 countries and territories in the European Region between September and October 2023. The questions covered TPT, systematic screening and infection prevention and control. A total of 28 questionnaires were returned, corresponding to an overall 51% response rate. Most national policies for TPT and TB screening are in line with the latest WHO guidelines. However, implementation of TB screening, prevention, and infection control activities is lagging. Results are presented separately for high-priority and low-priority countries. The survey identified several important areas that the PASS initiative will focus on to accelerate efforts towards reaching the targets set at the 2027 UN High-Level Meeting on TB for preventive therapy in the European Region. This will require a massive scale-up of efforts and larger investments, as well as coordinated approaches and interventions across the 'cascade' of prevention, from the identification of target populations to the completion of treatment.

Outcomes of people with TB reported to the WHO Global Clinical Platform of COVID-19.

TB is a leading infectious cause of death worldwide. The COVID-19 pandemic raised concerns that the burden of TB disease and death would increase due to the synergy between the two conditions. We used individual-level data submitted to the WHO Global Clinical Platform for COVID-19 on hospitalised patients to explore associations of TB with mortality using multivariable logistic regression. Data were available from 453,233 persons with COVID-19 and known TB status and mortality outcomes from 62 countries (96% SARS-CoV-2 test-positive). Of these, 48% were male, and the median age was 53 years (IQR 38-67). There were 8,214 cases with current TB reported by 46 countries, mainly from Africa. Of people with current TB, 31.4% were admitted with severe illness, and 24.5% died. Current TB was independently associated with higher mortality when adjusted for age, sex, HIV status, illness severity at hospital admission, and underlying conditions (adjusted RR 1.47, 95% CI 1.35-1.61). Current or past TB were independent risk factors for in-hospital mortality regardless of illness severity at admission. Caveats for interpretation include changes during the data collection period (viral variation, vaccination coverage) and opportunistic sampling. However, the platform exemplifies how timely, coordinated global reporting can inform our understanding of health emergencies and the vulnerable populations affected.

Resolution of tuberculosis blood RNA signatures fails to discriminate persistent sputum culture positivity after eight weeks of anti-tuberculous treatment.

Concerted efforts aim to reduce the burden of 6 months anti-tuberculous treatment for tuberculosis (TB). Treatment cessation at 8 weeks is effective for most but incurs increased risk of disease relapse. We tested the hypothesis that blood RNA signatures or C-reactive protein (CRP) measurements discriminate 8-week sputum culture status, as a prerequisite for a biomarker to stratify risk of relapse following treatment cessation at this time point. We identified blood RNA signatures of TB disease or cure by systematic review. We evaluated these signatures and CRP measurements in a pulmonary TB cohort, pre-treatment, at 2 and 8 weeks of treatment, and sustained cure after treatment completion. We tested biomarker discrimination of 8-week sputum culture status using area under the receiver operating characteristic curve (AUROC) analysis and, secondarily, assessed correlation of biomarker scores with time-to-culture positivity at 8 weeks of treatment. 12 blood RNA signatures were reproduced in the dataset from 44 individuals with sputum culture positive pulmonary TB. These normalised over time from TB treatment initiation. 11/44 cases with blood RNA, CRP and sputum culture results were sputum culture positive at 8 weeks of treatment. None of the contemporary blood RNA signatures discriminated sputum culture status at this time point or correlated with bacterial load. CRP achieved modest discrimination with AUROC of 0.69 (95% confidence interval 0.52-0.87). Selected TB blood RNA signatures and CRP do not provide biomarkers of microbiological clearance to support TB treatment cessation at 8 weeks. Resolution of blood transcriptional host-responses in sputum culture-positive individuals suggests Mycobacterium tuberculosis may colonise the respiratory tract without triggering a detectable immune response.

Sociocultural dimensions of research on public health roles for community pharmacists in tuberculosis disease control in a developing country

Sociocultural dimensions of research on public health roles for community pharmacists in tuberculosis disease control in a developing country

New Approach to Mapping Regional Vulnerability in Controlling Tuberculosis Disease in Indonesia

New Approach to Mapping Regional Vulnerability in Controlling Tuberculosis Disease in Indonesia

Making family medicine work: Rural community-based and interprofessional medical education.

At the University of the Free State, the 5-year MBChB curriculum had to be complemented with community-based education exposure to meet the requirements of the Health Professions Council of South Africa. Following the faculty leadership's vision, an interprofessional training experience was conceptualised and implemented by a project team from the three schools in the Faculty of Health Sciences (Medicine, Nursing, and Health and Rehabilitation Sciences). For the past decade, 4th-year medical students participated in the 2-week rotation in the rural southern Free State province, of which 1 week is spent with students from other health professions programmes in a structured interprofessional learning experience. The other week focuses on the realities of nurse-driven primary healthcare services in a resource-deprived area, including exposure to the programme-guided care for patients with tuberculosis (TB) or chronic diseases, care for pregnant women and for babies, including vaccinations.

New genetic biomarkers from transcriptome RNA-sequencing for Mycobacterium tuberculosis complex and Mycobacterium avium complex infections by bioinformatics analysis

The study aims to accurately identify differentially expressed genes (DEGs) and biological pathways in mycobacterial infections through bioinformatics for deeper disease understanding. Differentially expressed genes (DEGs) was explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Unique DEGs were submitted on least absolute shrinkage and selection operator (LASSO) regression analysis. 1,057 DEGs from two GSE datasets were identified, which were closely connected with NTM/ latent TB infection (LTBI)/active TB disease (ATB). It was demonstrated that these DEGs are mainly associated with detoxification processes, and virus and bacterial infections. Moreover, the METTL7B gene was the most informative marker for distinguishing LTBI and ATB with an area under the curve (AUC) of 0.983 (95%CI: 0.964 to 1). The significantly upregulated HBA1/2 genes were the most informative marker for distinguishing between individuals of IGRA-HC/NTM and LTBI (P < 0.001). Moreover, the upregulated HBD gene was also differ between IGRA-HC/NTM and ATB (P < 0.001). We have identified gene signatures associated with Mycobacterium infection in whole blood, which could be significant for understanding the molecular mechanisms and diagnosis of NTM, LTBI, or ATB.

Correlation Between Livable Housing, BCG Immunization Coverage, and Population Density with Child Tuberculosis Incidence in East Java Province 2020-2022

Introduction: Mycobacterium tuberculosis bacteria can cause tuberculosis disease. In 2022, East Java Province reported 8,398 cases of child tuberculosis with a discovery coverage of 105.6%. This study aims to describe the distribution of child tuberculosis incidence in East Java Province by mapping and analyzing the correlation between livable houses, BCG immunization coverage, and population density with the incidence of child tuberculosis in 38 districts/cities in East Java Province from 2020 to 2022. Methods: This was a descriptive approach with a population correlation study design using the Spearman correlation statistical test. Secondary records from the East Java Health Profile 2020, 2021, and 2022 were used in this study. Thirty-eight districts/cities in the province of East Java comprised the study's population. Results and Discussion: This study showed that there has been a positive correlation between BCG immunization coverage in 2020 (r=0.043); 2021 (r=0.140); 2022 (r=0.214) and population density 2020 (r=0.082); 2021 (r=0.102); and 2022 (r=0.174) with the incidence of child tuberculosis. Meanwhile, the correlation between livable houses and the incidence of child tuberculosis is negative in 2020 (r=-0.990) and 2022 (r=-0.047) but positive in 2021 (r=0.078). Conclusion: The increase in BCG immunization coverage and population density aligns with the increase in child tuberculosis cases. Meanwhile, an increase in the percentage of access to livable houses is followed by a decrease in the incidence of child tuberculosis.

Effects of the Beijing genotype on latent tuberculosis infection, TB disease risk, and clustering of TB cases

BackgroundThe Beijing genotype of Mycobacterium tuberculosis (Mtb) has sparked debate regarding its virulence and transmissibility. This study contributes to this discussion by assessing its effect on the risk of latent tuberculosis infection (LTBI), active tuberculosis (TB) disease among contacts, and clustering of known TB cases. MethodsWe conducted a retrospective cohort study using the records of 4457 culture-confirmed TB patients and their contacts (20,448) reported to the Florida Department of Health between 2009 and 2023. Univariate and multivariate analyses were used to evaluate the effect of the Beijing strain on LTBI, active TB risk among contacts, and case clustering. ResultsOur study revealed no significant difference in transmissibility between the Beijing and non-Beijing genotypes among contacts. LTBI prevalence was 19.9%, slightly higher in non-Beijing than Beijing genotypes (20.2% vs. 15.5%, p < 0.001). The prevalence of active TB was 1.8%, with no significant difference between the Beijing and non-Beijing genotypes (1.4% vs. 1.8%, p = 0.296). Increased LTBI risk was associated with older age, male sex, Hispanic ethnicity, multidrug-resistant TB exposure, household exposure, and a longer exposure duration. Active TB risk was higher for males, HIV-positive individuals, and contacts with more prolonged exposure to index cases. The Beijing genotype was associated with increased TB case clustering (aOR = 1.98, 95%CI: 1.53, 2.55, p < 0.001) as compared to the non-Beijing genotypes. US birthplace (aOR = 2.75, 95%CI: 2.37, 3.19, p < 0.001), pulmonary disease (aOR = 1.27, 95%CI: 1.04, 1.56, p < 0.020), cavitary TB (aOR = 1.25, 95% CI: 1.08, 1.44, p < 0.003), previous year alcohol use (aOR = 1.68, 95%CI: 1.38, 2.04, p < 0.001), and recreational drug use (aOR = 1.32, 95%CI: 1.04, 1.67, p < 0.024) were also associated with an increased risk of TB case clustering. ConclusionWhile the Beijing genotype did not increase the risk of LTBI or active TB among contacts, it showed a higher tendency for case clustering. Hence, interventions should prioritize populations where this genotype is prevalent.

Detection of Mycobacterium tuberculosis transrenal DNA in urine samples among adults in Peru

Diagnosis of pulmonary tuberculosis (TB) relies on a sputum sample, which cannot be obtained from all symptomatic individuals. Mycobacterium tuberculosis (Mtb) transrenal DNA (trDNA) has been detected in urine, an easily obtainable, noninvasive, alternative sample type. However, reported sensitivities have been variable and likely depend on collection and assay procedures and aspects of trDNA biology. We analyzed three serial urine samples from each of 75 adults with culture-confirmed pulmonary TB disease in Lima, Peru for detection of trDNA using short-fragment real-time PCR. Additionally, we examined host, urine, and sampling factors associated with detection. Overall per-sample sensitivity was 38 % (95 % Confidence Interval [CI] 30–45 %). On an individual level (i.e., any of the three samples positive), sensitivity was 73 % (95 % CI: 62–83 %). Sensitivity was highest among samples from patients with smear-positive TB, 92 % (95 % CI: 62–100 %). Specificity from a single sample from each of 10 healthy controls was 100 % (95 % CI: 69–100 %). Adjusting our assay positivity threshold increased individual-level sensitivity to 88 % (95 % CI: 78–94 %) overall without affecting the specificity. We did not find associations between Mtb trDNA detection and individual characteristics or urine sample characteristics. Overall, our results support the potential of trDNA detection for TB diagnosis.