Subclinical tuberculosis: a meta-analysis of prevalence and scoping review of definitions, prevalence and clinical characteristics.

BACKGROUND: This scoping review aimed to characterise definitions used to describe subclinical tuberculosis (TB), estimate the prevalence in different populations and describe the clinical characteristics and treatment outcomes in the scientific literature. METHODS: A systematic literature search was conducted using PubMed. We included studies published in English between January 1990 and August 2022 that defined "subclinical" or "asymptomatic" pulmonary TB disease, regardless of age, HIV status and comorbidities. We estimated the weighted pooled proportions of subclinical TB using a random-effects model by World Health Organization reported TB incidence, populations and settings. We also pooled the proportion of subclinical TB according to definitions described in published prevalence surveys. RESULTS: We identified 29 prevalence surveys and 71 other studies. Prevalence survey data (2002-2022) using "absence of cough of any duration" criteria reported higher subclinical TB prevalence than those using the stricter "completely asymptomatic" threshold. Prevalence estimates overlap in studies using other symptoms and cough duration. Subclinical TB in studies was commonly defined as asymptomatic TB disease. Higher prevalence was reported in high TB burden areas, community settings and immunocompetent populations. People with subclinical TB showed less extensive radiographic abnormalities, higher treatment success rates and lower mortality, although studies were few. CONCLUSION: A substantial proportion of TB is subclinical. However, prevalence estimates were highly heterogeneous between settings. Most published studies incompletely characterised the phenotype of people with subclinical TB. Standardised definitions and diagnostic criteria are needed to characterise this phenotype. Further research is required to enhance case finding, screening, diagnostics and treatment options for subclinical TB.

High all-cause mortality and increasing proportion of older adults with tuberculosis in Texas, 2008-2020.

Pulmonary tuberculosis (PTB) elimination efforts must consider the global growth of the ageing population. Here we used TB surveillance data from Texas, United States (2008-2020; total n = 10656) to identify unique characteristics and outcomes in older adults (OA, ≥65 years) with PTB, compared to young adults (YA, 18-39 years) or middle-aged adults (40-64 years). We found that the proportion of OA with PTB increased from 15% in 2008 to 24% in 2020 (trend p < 0.05). Diabetes was highly prevalent in OA (32%) but not associated with adverse outcomes. Death was 13-fold higher in OA compared to YA and was 7% at the time of diagnosis which suggests diagnostic delays. However, once TB was suspected, we found no differences in culture, smear, or nucleic acid detection of mycobacteria (although less lung cavitations) in OA. During treatment, OA had less drug-resistant TB, few adverse reactions and adhered with TB treatment. We recommend training healthcare workers to 'think TB' in OA, for prompt treatment initiation to diminish deaths. Furthermore, OA should be added as a priority group to the latent TB treatment guidelines by the World Health Organization, to prevent TB disease in this highly vulnerable group.

Sociodemographic and clinical risk factors associated with in-hospital tuberculosis mortality in Türkiye, 2008-2018.

Introduction: Tuberculosis (TB) is an infectious disease that can be fatal if left untreated or poorly treated, and it is associated with many morbidities. Deaths may provide better understanding of the associated factors and help guide interventions to reduce mortality. In this study, it was aimed to reveal some of the features that predict hospital mortality in patients with TB and to present some alarming findings for clinicians. Materials and Methods: Patients who had been hospitalized with the diagnosis of TB between January 2008 and December 2018 were included and analyzed retrospectively. In-hospital mortality because of any TB disease after the initiation of treatment in patients admitted to the TB Ward and the primary cause of mortality were taken as endpoint. Result: A total of 1321 patients with a mean age of 50.1 years were examined. Total mortality was 39.4% (521 deaths) and 13.1% were in-hospital deaths (173 deaths). Of the deaths, 61.8% (n= 107) occurred during the first month after TB treatment were started. On univariate analysis, age over 48.5 years, Charlson comorbidity index, extension of radiological involvement, hypoalbuminemia and lymphopenia were most predictive variables with higher odds ratios (respectively, p<0.001 for all). Conclusions: In-hospital tuberculosis disease mortality is related with older age, cavitary or extensive pulmonary involvement, low albumin levels, unemployment, cigarette smoking and especially those with concomitant malignancy and chronic pulmonary disease.

Death after cure: Mortality among pulmonary tuberculosis survivors in rural Uganda.

OBJECTIVES: To determine the incidence of mortality and its predictors among pulmonary tuberculosis (PTB) survivors treated at a rural Ugandan tertiary hospital. METHODS: We conducted a retrospective chart review of data between 2013 and 2023. We included all people that met the World Health Organisation's definition of tuberculosis cure and traced them or their next of kin to determine vital status (alive/deceased). We estimated the cumulative incidence of mortality per 1000 population, crude all-cause mortality rate per 1000 person-years, and median years of potential life lost for deceased individuals. Using Cox proportional hazard models, we investigated predictors of mortality. RESULTS: Of 334 PTB survivors enrolled, 38 (11.4%) had died. The cumulative incidence of all-cause mortality was 113.7 per 1000 population, and the crude all-cause mortality rate was 28.5 per 1000 person-years. The median years of potential life lost for deceased individuals was 23.8 years (IQR: 9.6-32.8). Hospitalization (adjusted hazard ratio (aHR): 4.3, 95% CI: 1.1-16.6) and unemployment (aHR: 7.04, 95% CI: 1.5-31.6) at TB treatment initiation predicted mortality. CONCLUSION: PTB survivors experience post high mortality rates after TB cure. Survivors who were hospitalized and unemployed at treatment initiation were more likely to die after cure. Social protection measures and long-term follow-up of previously hospitalized patients could improve the long-term survival of TB survivors.

Admissions by tuberculosis in a regional reference Center. A complex and worrying scenario.

OBJECTIVES: To characterize clinical aspects, evaluate the diagnostic opportunity, and identify factors associated with mortality in patients hospitalized for tuberculosis (TB). METHODS: Retrospective study of patients admitted for TB to a Regional Hospital in Chile between 2011 and 2019. RESULTS: 142 TB events required hospitalization in this period (38.2% of total cases). All risk groups were identified, with a significant increase in patients with diabetes mellitus. The pulmonary location was the most frequent (71.1%), followed by disseminated forms (16.2%). The sensitivity of microscopy smear in cases of pulmonary TB (isolated or combined) was 78.8% and lower in cases of bronchoalveolar lavage (58.3%). PCR was only occasionally applied (< 10%) with a sensitivity of 100% in sputum samples. Its use increased progressively and reached a positivity of 33% (6 out of 18 cases) in cases with negative sputum staining. The median time between symptom onset and diagnosis was prolonged (9 weeks), and 32.5% of all regional events were diagnosed at the hospital. Dose adjustments (22.1%), corticosteroid use (25%), and treatment interruptions were frequent (11%). Lethality reached 19%, and by multivariate analysis, only shock was associated with a fatal outcome. CONCLUSIONS: In this case series, the diagnosis of TB cases was delayed, scarcely diagnosed by molecular methods, highly concentrated at the hospital level, required admission in a large percentage of cases, and had a high case-fatality rate.

Impact of pathobiological diversity of Mycobacterium tuberculosis on clinical features and lethal outcome of tuberculosis.

BACKGROUND: Mycobacterium tuberculosis population in Russia is dominated by the notorious Beijing genotype whose major variants are characterized by contrasting resistance and virulence properties. Here we studied how these strain features could impact the progression of pulmonary tuberculosis (TB) concerning clinical manifestation and lethal outcome. RESULTS: The study sample included 548 M. tuberculosis isolates from 548 patients with newly diagnosed pulmonary TB in Omsk, West Siberia, Russia. Strains were subjected to drug susceptibility testing and genotyping to detect lineages, sublineages, and subtypes (within Beijing genotype). The Beijing genotype was detected in 370 (67.5%) of the studied strains. The strongest association with multidrug resistance (MDR) was found for epidemic cluster Beijing B0/W148 (modern sublineage) and two recently discovered MDR clusters 1071-32 and 14717-15 of the ancient Beijing sublineage. The group of patients infected with hypervirulent and highly lethal (in a mouse model) Beijing 14717-15 showed the highest rate of lethal outcome (58.3%) compared to Beijing B0/W148 (31.4%; P = 0.06), Beijing Central Asian/Russian (29.7%, P = 0.037), and non-Beijing (15.2%, P = 0.001). The 14717-15 cluster mostly included isolates from patients with infiltrative but not with fibrous-cavernous and disseminated TB. In contrast, a group infected with low virulent 1071-32-cluster had the highest rate of fibrous-cavernous TB, possibly reflecting the capacity of these strains for prolonged survival and chronicity of the TB process. CONCLUSIONS: The group of patients infected with hypervirulent and highly lethal in murine model 14717-15 cluster had the highest proportion of the lethal outcome (58.3%) compared to the groups infected with Beijing B0/W148 (31.4%) and non-Beijing (15.2%) isolates. This study carried out in the TB high-burden area highlights that not only drug resistance but also strain virulence should be considered in the implementation of personalized TB treatment.

Risk factors for early TB treatment interruption among newly diagnosed patients in Malaysia.

TB treatment interruption has resulted in delayed sputum conversion, drug resistance, and a high mortality rate and a prolonged treatment course, hence leading to economic and psychosocial affliction. To date, there are limited studies investigating the physico-social risk factors for early treatment interruptions. This prospective multicenter cohort study aimed to investigate the risk factors for early treatment interruption among new pulmonary tuberculosis (TB) smear-positive patients in Selangor, Malaysia. A total of 439 participants were recruited from 39 public treatment centres, 2018-2019. Multivariate Cox proportional hazard analyses were performed to analyse the risk factors for early treatment interruption. Of 439 participants, 104 (23.7%) had early treatment interruption, with 67.3% of early treatment interruption occurring in the first month of treatment. Being a current smoker and having a history of hospitalization, internalized stigma, low TB symptoms score, and waiting time spent at Directly Observed Treatment, Short-course centre were risk factors for early treatment interruption. An appropriate treatment adherence strategy is suggested to prioritize the high-risk group with high early treatment interruption. Efforts to quit smoking cessation programs and to promote stigma reduction interventions are crucial to reduce the probability of early treatment interruption.

Active pulmonary tuberculosis and coronavirus disease 2019: A systematic review and meta-analysis.

OBJECTIVE: The proportion of COVID-19 patients having active pulmonary tuberculosis, and its impact on COVID-19 related patient outcomes, is not clear. We conducted this systematic review to evaluate the proportion of patients with active pulmonary tuberculosis among COVID-19 patients, and to assess if comorbid pulmonary tuberculosis worsens clinical outcomes in these patients. METHODS: We queried the PubMed and Embase databases for studies providing data on (a) proportion of COVID-19 patients with active pulmonary tuberculosis or (b) severe disease, hospitalization, or mortality among COVID-19 patients with and without active pulmonary tuberculosis. We calculated the proportion of tuberculosis patients, and the relative risk (RR) for each reported outcome of interest. We used random-effects models to summarize our data. RESULTS: We retrieved 3,375 citations, and included 43 studies, in our review. The pooled estimate for proportion of active pulmonary tuberculosis was 1.07% (95% CI 0.81%-1.36%). COVID-19 patients with tuberculosis had a higher risk of mortality (summary RR 1.93, 95% CI 1.56-2.39, from 17 studies) and for severe COVID-19 disease (summary RR 1.46, 95% CI 1.05-2.02, from 20 studies), but not for hospitalization (summary RR 1.86, 95% CI 0.91-3.81, from four studies), as compared to COVID-19 patients without tuberculosis. CONCLUSION: Active pulmonary tuberculosis is relatively common among COVID-19 patients and increases the risk of severe COVID-19 and COVID-19-related mortality.

Mortality during tuberculosis treatment in South Africa using an 8-year analysis of the national tuberculosis treatment register.

In 2011, the South African HIV treatment eligibility criteria were expanded to allow all tuberculosis (TB) patients lifelong ART. The impact of this change on TB mortality in South Africa is not known. We evaluated mortality in all adults (≥ 15 years old) treated for drug-susceptible TB in South Africa between 2009 and 2016. Using a Cox regression model, we quantified risk factors for mortality during TB treatment and present standardised mortality ratios (SMR) stratified by year, age, sex, and HIV status. During the study period, 8.6% (219,618/2,551,058) of adults on TB treatment died. Older age, male sex, previous TB treatment and HIV infection (with or without the use of ART) were associated with increased hazard of mortality. There was a 19% reduction in hazard of mortality amongst all TB patients between 2009 and 2016 (adjusted hazard ratio: 0.81 95%CI 0.80-0.83). The highest SMR was in 15-24-year-old women, more than double that of men (42.3 in 2016). Between 2009 and 2016, the SMR for HIV-positive TB patients increased, from 9.0 to 19.6 in women, and 7.0 to 10.6 in men. In South Africa, case fatality during TB treatment is decreasing and further interventions to address specific risk factors for TB mortality are required. Young women (15-24-year-olds) with TB experience a disproportionate burden of mortality and interventions targeting this age-group are needed.

Pulmonary mycobacterial infection is associated with increased mortality in patients with acute respiratory distress syndrome.

ABSTRACT: Although pulmonary mycobacterial infection is associated with acute respiratory distress syndrome (ARDS) in critically ill patients, its clinical implication on patients with ARDS has not been clearly elucidated. The aim of study was to investigate the clinical significance of pulmonary mycobacterial infection in patients with ARDS.Between January 2014 and April 2019, medical records of 229 patients with ARDS who met the Berlin criteria and received invasive mechanical ventilation in medical intensive care unit were reviewed. Clinical characteristics and the rate of mortality between patients with and without pulmonary mycobacterial infection were compared. Factors associated with a 28-day mortality were analyzed statistically.Twenty two (9.6%) patients were infected with pulmonary mycobacteria (18 with tuberculosis and 4 with non-tuberculous mycobacteria). There were no differences in baseline characteristics, the severity of illness scores. Other than a higher rate of renal replacement therapy required in those without pulmonary mycobacterial infection, the use of adjunctive therapy did not differ between the groups. The 28- day mortality rate was significantly higher in patients with pulmonary mycobacterial infection (81.8% vs 58%, P = .019). Pulmonary mycobacterial infection was significantly associated with 28-day mortality (hazard ratio 1.852, 95% confidence interval 1.108-3.095, P = .019).Pulmonary mycobacterial infection was associated with increased 28-day mortality in patients with ARDS.

Impact of the diagnostic test Xpert MTB/RIF on patient outcomes for tuberculosis.

BACKGROUND: The World Health Organization (WHO) recommends Xpert MTB/RIF in place of smear microscopy to diagnose tuberculosis (TB), and many countries have adopted it into their diagnostic algorithms. However, it is not clear whether the greater accuracy of the test translates into improved health outcomes. OBJECTIVES: To assess the impact of Xpert MTB/RIF on patient outcomes in people being investigated for tuberculosis. SEARCH METHODS: We searched the following databases, without language restriction, from 2007 to 24 July 2020: Cochrane Infectious Disease Group (CIDG) Specialized Register; CENTRAL; MEDLINE OVID; Embase OVID; CINAHL EBSCO; LILACS BIREME; Science Citation Index Expanded (Web of Science), Social Sciences citation index (Web of Science), and Conference Proceedings Citation Index - Social Science & Humanities (Web of Science). We also searched the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the Pan African Clinical Trials Registry for ongoing trials. SELECTION CRITERIA: We included individual- and cluster-randomized trials, and before-after studies, in participants being investigated for tuberculosis. We analysed the randomized and non-randomized studies separately.  DATA COLLECTION AND ANALYSIS: For each study, two review authors independently extracted data, using a piloted data extraction tool. We assessed the risk of bias using Cochrane and Effective Practice and Organisation of Care (EPOC) tools. We used random effects meta-analysis to allow for heterogeneity between studies in setting and design.  The certainty of the  evidence in the randomized trials was assessed by GRADE. MAIN RESULTS: We included 12 studies: eight were randomized controlled trials (RCTs), and four were before-and-after studies. Most included RCTs had a low risk of bias in most domains of the Cochrane 'Risk of bias' tool. There was inconclusive evidence of an effect of Xpert MTB/RIF on all-cause mortality, both overall (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.75 to 1.05; 5 RCTs, 9932 participants, moderate-certainty evidence), and restricted to studies with six-month follow-up (RR 0.98, 95% CI 0.78 to 1.22; 3 RCTs, 8143 participants; moderate-certainty evidence). There was probably a reduction in mortality in participants known to be infected with HIV (odds ratio (OR) 0.80, 95% CI 0.67 to 0.96; 5 RCTs, 5855 participants; moderate-certainty evidence). It is uncertain whether Xpert MTB/RIF has no or a modest effect on the proportion of participants starting tuberculosis treatment who had a successful treatment outcome (OR) 1.10, 95% CI 0.96 to 1.26; 3RCTs, 4802 participants; moderate-certainty evidence). There was also inconclusive evidence of an effect on the  proportion of participants who were treated for tuberculosis (RR 1.10, 95% CI 0.98 to 1.23; 5 RCTs, 8793 participants; moderate-certainty evidence). The proportion of participants treated for tuberculosis who had bacteriological confirmation was probably higher in the Xpert MTB/RIF group (RR 1.44, 95% CI 1.29 to 1.61; 6 RCTs, 2068 participants; moderate-certainty evidence). The proportion of participants with bacteriological confirmation who were lost to follow-up pre-treatment was probably reduced (RR 0.59, 95% CI 0.41 to 0.85; 3 RCTs, 1217 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: We were unable to confidently rule in or rule out the effect on all-cause mortality of using Xpert MTB/RIF rather than smear microscopy. Xpert MTB/RIF probably reduces mortality among participants known to be infected with HIV. We are uncertain whether Xpert MTB/RIF has a modest effect or not on the proportion treated or, among those treated, on the proportion with a successful outcome. It probably does not have a substantial effect on these outcomes. Xpert MTB/RIF probably increases both the proportion of treated participants who had bacteriological confirmation, and the proportion with a laboratory-confirmed diagnosis who were treated. These findings may inform decisions about uptake alongside evidence on cost-effectiveness and implementation.

ANTECEDENTES: La Organización Mundial de la Salud (OMS) recomienda la Xpert MTB/RIF en lugar de la baciloscopia para diagnosticar la tuberculosis (TB) y muchos países la han adoptado en sus algoritmos de diagnóstico. Sin embargo, no está claro si la mayor exactitud de la prueba se traduce en mejores desenlaces de salud. OBJETIVOS: Evaluar el impacto de la Xpert MTB/RIF en los desenlaces de las personas sometidas a pruebas para la tuberculosis. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en las siguientes bases de datos, sin restricción de idioma, desde 2007 hasta el 24 de julio de 2020: Registro especializado del Grupo Cochrane de Enfermedades infecciosas (Cochrane Infectious Disease Group [CIDG]); CENTRAL; MEDLINE OVID; Embase OVID; CINAHL EBSCO; LILACS BIREME; Science Citation Index Expanded (Web of Science), Social Sciences citation index (Web of Science), y Conference Proceedings Citation Index ­ Social Science & Humanities (Web of Science). También se buscaron ensayos en curso en la Plataforma de registros internacionales de ensayos clínicos de la OMS, en ClinicalTrials.gov y en el Pan African Clinical Trials Registry. CRITERIOS DE SELECCIÓN: Se incluyeron ensayos aleatorizados individuales y por conglomerados, y estudios tipo antes y después (before­after studie), con participantes sometidos a pruebas para la tuberculosis. Los estudios aleatorizados y no aleatorizados se analizaron por separado. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, extrajeron los datos de cada estudio mediante una herramienta de extracción de datos analizada. El riesgo de sesgo se evaluó mediante las herramientas de Cochrane y del Grupo Cochrane para una Práctica y organización sanitarias efectivas (Effective Practice and Organisation of Care [EPOC]). Se utilizó el metanálisis de efectos aleatorios para considerar la heterogeneidad entre los estudios en cuanto al contexto y el diseño. La certeza de la evidencia en los ensayos aleatorizados se evaluó mediante el método GRADE. RESULTADOS PRINCIPALES: Se incluyeron 12 estudios: ocho eran ensayos controlados aleatorizados (ECA) y cuatro eran estudios tipo antes y después. La mayoría de los ECA incluidos tenían un bajo riesgo de sesgo en la mayoría de los dominios de la herramienta Cochrane "Risk of bias". Hubo evidencia no concluyente de un efecto de la Xpert MTB/RIF sobre la mortalidad por todas las causas, tanto en general (razón de riesgos [RR] 0,89; intervalo de confianza [IC] del 95%: 0,75 a 1,05; cinco ECA, 9932 participantes, evidencia de certeza moderada), como limitada a los estudios con seguimiento de seis meses (RR 0,98; IC del 95%: 0,78 a 1,22; tres ECA, 8143 participantes; evidencia de certeza moderada). Probablemente hubo una reducción de la mortalidad en los participantes que se sabía que estaban infectados por el VIH (odds ratio [OR] 0,80; IC del 95%: 0,67 a 0,96; cinco ECA, 5855 participantes; evidencia de certeza moderada). No está claro si la Xpert MTB/RIF no tiene efectos o tiene un efecto modesto sobre la proporción de participantes que inician el tratamiento de la tuberculosis y que tienen un desenlace exitoso del tratamiento (OR 1,10; IC del 95%: 0,96 a 1,26; tres ECA, 4802 participantes; evidencia de certeza moderada). También hubo evidencia no concluyente de un efecto sobre el porcentaje de participantes que recibieron tratamiento para la tuberculosis (RR 1,10; IC del 95%: 0,98 a 1,23; cinco ECA, 8793 participantes; evidencia de certeza moderada). Es probable que la proporción de participantes tratados por tuberculosis que tuvieron confirmación bacteriológica fuera mayor en el grupo de Xpert MTB/RIF (RR 1,44; IC del 95%: 1,29 a 1,61; seis ECA, 2068 participantes; evidencia de certeza moderada). Es probable que se redujera la proporción de participantes con confirmación bacteriológica que se perdió durante el seguimiento previo al tratamiento (RR 0,59; IC del 95%: 0,41 a 0,85; tres ECA, 1217 participantes; evidencia de certeza moderada). CONCLUSIONES DE LOS AUTORES: No fue posible descartar con seguridad el efecto sobre la mortalidad por todas las causas del uso de Xpert MTB/RIF en lugar de la baciloscopia. La Xpert MTB/RIF probablemente reduce la mortalidad en los participantes que se sabe que están infectados por el VIH. No hay certeza con respecto a si la Xpert MTB/RIF tiene un efecto modesto o no en la proporción tratada o, entre los tratados, en la proporción con un desenlace exitoso. Probablemente no tenga un efecto importante sobre estos desenlaces. La Xpert MTB/RIF probablemente aumenta la proporción de participantes tratados que tenían confirmación bacteriológica, así como la de aquellos con un diagnóstico confirmado por el laboratorio que fueron tratados. Estos hallazgos podrían servir de base para las decisiones sobre la adopción de la prueba, junto con la evidencia sobre la coste­efectividad y la aplicación.

A severity-of-illness score in patients with tuberculosis requiring intensive care.

BACKGROUND: We previously retrospectively validated a 6-point severity-of-illness score aimed at identifying patients at risk of dying of tuberculosis (TB) in the intensive care unit (ICU). Parameters included septic shock, HIV infection with a CD4 count <200 cells/µL, renal dysfunction, a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (P/F) <200 mmHg, a chest radiograph demonstrating diffuse parenchymal infiltrates, and no TB treatment on admission. OBJECTIVES: To prospectively validate the severity-of-illness scoring system in patients with TB requiring intensive care, and to refine and simplify the score in order to expand its clinical utility. METHODS: We performed a prospective observational study with a planned post hoc retrospective analysis, enrolling all adult patients with confirmed TB admitted to the medical ICU of a tertiary hospital in Cape Town, South Africa, from 1 February 2015 to 31 July 2018. The admission data of all adult patients with TB requiring admission to the ICU were used to calculate the 6-point severity-of-illness score and a refined 4-point score (based on the planned post hoc analysis). Descriptive statistics and χ2 or Fisher's exact tests (where indicated) were performed on dichotomous categorical variables, and t-tests on continuous data. Patients were categorised as hospital survivors or non-survivors. RESULTS: Forty-one of 78 patients (52.6%) died. The 6-point scores of non-survivors were higher than those of survivors (mean (standard deviation (SD)) 3.5 (1.3) v. 2.7 (1.2); p=0.01). A score ≥3 v. <3 was associated with increased mortality (64.0% v. 32.1%; odds ratio (OR) 3.75; 95% confidence interval (CI) 1.25 - 10.01; p=0.01). Post hoc, a P/F ratio <200 mmHg and no TB treatment on admission failed to predict mortality, whereas any immunosuppression did. A revised 4-point score (septic shock, any immunosuppression, acute kidney injury and lack of lobar consolidation) demonstrated higher scores in non-survivors than survivors (mean (SD) 2.8 (1.1) v. 1.6 (1.1); p<0.001). A score ≥3 v. ≤2 was associated with increased mortality (78.4% v. 29.3%; OR 8.76; 95% CI 3.12 - 24.59; p<0.001). CONCLUSIONS: The 6-point severity-of-illness score identified patients at increased risk of death. We were able to derive and retrospectively validate a simplified 4-point score with superior predictive power.

The risk of pulmonary tuberculosis after traumatic brain injury.

After traumatic brain injury (TBI), an inflammatory response in the brain might affect the immune system. The risk of pulmonary infection reportedly increases in patients with TBI. We aimed to evaluate the risk of tuberculosis (TB) in patients with TBI in Taiwan. All participants were selected from the intensive care unit (ICU). Patients with TBI were defined as patients in ICU with intracranial injury, and comparison cohort were patients in ICU without TBI diagnosis. There was a significant difference in TB risk between the patients with TBI and the comparison cohort according to age and the Charlson's comorbidity index (CCI) score. Thus, we divided patients based on CCI into three groups for further analysis: mild (CCI = 0), moderate (CCI = 1/2), severe (CCI > 2). Mild-CCI group had a lower TB incidence rate (0.74%) and longer time to TB development (median: 2.43) than the other two groups. Moderate-CCI group had 1.52-fold increased risk of TB infection (p < 0.0001) compared with mild-CCI group. In the severe-CCI group, patients aged ≥ 80 years had 1.91-fold risk of TB compared with mild-CCI group (p = 0.0481). Severe-CCI group had significantly higher mortality than the mild-CCI group (p = 0.0366). Patients with TBI and more comorbidities had higher risk of TB infection with higher mortality rate.

Utility of Bronchiectasis severity index (BSI) as prognostic tool in patients with post tubercular bronchiectasis: An experience from a tertiary care hospital in North India.

BACKGROUND: Bronchiectasis severity Index (BSI) score which predicts the severity of the disease along with future exacerbations and mortality rate has been well validated in European patients; however there is paucity of data evaluating its validity in Indian patients. The authors therefore decided to evaluate the utility of BSI to predict exacerbations and mortality rate in patients with post tubercular bronchiectasis presenting to our facility. METHODS: The study was a retrospective observational study done in patients with bronchiectasis secondary to tuberculosis. These patients were followed up for 4 years. BSI was calculated from different variables and descriptive statistics along with regression analysis were used to evaluate utility of BSI. RESULTS: A total of 48 patients of post tubercular bronchiectasis were included in the study. Majority of our patients belonged to severe bronchiectasis group seen in 23 patients (48%) while those with mild and moderate bronchiectasis were seen in 13 (27%) and 12 (25%) patients respectively. The exacerbation rate in mild group was comparable to the predicted BSI exacerbation at 1 year while the predicted and observed rates were statistically significant for moderate and severe bronchiectasis group (p value < 0.05). Mortality rates at 1 year were comparable in all the groups of bronchiectasis while it was comparable only in mild and moderate group bronchiectasis at 4 years. CONCLUSION: Bronchiectasis severity index seems to predict mortality at 1 year in post tuberculosis bronchiectasis. However, it under predicts 1 year and 4 year exacerbation rates. Hence BSI may not be useful as a prognostic tool in Indian patients with bronchiectasis. Larger multi-centred studies may be required to further evaluate the clinical utility of BSI among Indian population.

Noncompliance of treatment among tuberculosis patients in intensive phase at Kalutara District of Sri Lanka.

BACKGROUND: Tuberculosis (TB) is an ancient disease and remains to be a public health problem all over the world. Noncompliance of treatment among TB patients affect the control of disease, leading to increased burden of the disease, mortality, drug resistant and relapse. Assessing the factors associated with noncompliance of TB treatment will be useful to reduce the noncompliance and burden. OBJECTIVES: To assess the factors associated with noncompliance of treatment among TB patients in intensive phase at Kalutara District, Sri Lanka. METHODS: A descriptive cross-sectional study was conducted among the new TB patients registered at District Chest Clinic (DCC), Kalutara for a period of six months. A questionnaire was administered for total study population registered during the data collection period. The relevant data were abstracted from registers and records maintaining at the DCC. RESULTS: Data were collected from 252 patients [males = 160 (63.5%) and females = 92 (36.5%)]. The percentage of noncompliance was 18.3% (n = 46) among newly diagnosed TB patients. Only 13.5% (n = 34) of TB patients visited Directly Observed Treatment, short-course (DOTS) provider daily. Majority (61.9%, n = 156) of DOTS providers did not observe for drug intake. The factors significantly associated with noncompliance for TB treatment were (1) not observing the drug intake by DOTS providers, (2) side effects of the drugs, (3) educational level, (4) living environment and (5) absent of a care giver. CONCLUSIONS: Noncompliance of treatment is still a common problem among TB patients. Special emphasis should be made on TB patients based on the factors associated with the noncompliance of the treatment. DOTS providers should adhere to DOTS policy.

Mortality predictors among patients with HIV-associated pulmonary tuberculosis in Northeast China: A retrospective cohort analysis.

The coexistence of pulmonary tuberculosis (PTB) and human immunodeficiency virus (HIV) infection leads to high morbidity and mortality in these populations. Although antiretroviral therapy (ART) has decreased TB incidence in HIV-infected patients, this coexistence still prevails in China. Patients with HIV-PTB admitted to Beijing You An Hospital from 2014 to 2018 were retrospectively enrolled, and information on demographics, clinical characteristics, and laboratory findings were extracted from medical records. Predictors of death, including age (adjusted hazard ratio [AHR]: 1.03; 95% confidence interval [CI]: 1.00-1.05), tobacco use (AHR: 2.76; 95% CI: 1.54-4.94), history of tuberculosis (AHR: 3.53; 95% CI: 1.82-6.85), not being on ART (AHR: 2.94; 95% CI: 1.31-6.63), extrapulmonary tuberculosis (AHR: 2.391; 95% CI: 1.37-4.18), sputum smear positivity (AHR: 2.84; 95% CI: 1.61-4.99), CD4+ T cell count ≤ 50 cells/µl (AHR: 3.45; 95% CI: 1.95-6.10), and initiating ART ≥ 8 weeks after the initiation of antituberculous therapy (odds ratio: 3.30; 95% CI: 1.09-10.04). By contrast, there were no deaths among the six patients who began ART within 8 weeks after the initiation of antituberculous therapy. Age, tobacco use, not being on ART, extrapulmonary tuberculosis, sputum smear positivity, and CD4+ T cell count ≤50 cells/µl predict those patients at high risk of death among HIV-infected patients with PTB, and the time of initiating ART after the initiation of antituberculous therapy is also important for prognosis.

CXCL17 Is a Specific Diagnostic Biomarker for Severe Pandemic Influenza A(H1N1) That Predicts Poor Clinical Outcome.

The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.

Risk factors for death during treatment in pulmonary tuberculosis patients in South India: A cohort study.

OBJECTIVE: Identifying the risk factors for deaths during tuberculosis (TB) treatment is important for achieving the vision of India's National Strategic Plan of 'Zero Deaths' by 2025. We aimed to determine the proportion of deaths during TB treatment and its risk factors among smear positive pulmonary TB patients aged more than 15 years. STUDY DESIGN: We performed a cohort study using data collected for RePORT India Consortium (Regional Prospective Observational Research in Tuberculosis). SETTING: Revised TB Control Program (RNTCP) in three districts of South India. PARTICIPANTS: The cohort consisted of newly diagnosed drug sensitive patients enrolled under the Revised National TB Control Program during 2014-2018 in three districts of southern India. Information on death was collected at homes by trained project staff. PRIMARY OUTCOME MEASURES: We calculated 'all-cause mortality' during TB treatment and expressed this as a proportion with 95% confidence interval (CI). Risk factors for death were assessed by calculating unadjusted and adjusted relative risks with 95% CI. RESULTS: The mean (SD) age was of the 1167 participants was 45 (14.5) years and 79% of them were males. Five participants (0.4%) were HIV infected. Among the males, 560 (61%) were tobacco users and 688 (75%) reported consuming alcohol. There were 47 deaths (4%; 95% CI 3.0-5.3) of which 28 deaths (60%) occurred during first two months of treatment. In a bi-variable analysis, age of more than 60 years (RR 2.27; 95%CI: 1.24-4.15), male gender (RR 3.98; 95% CI: 1.25-12.70), alcohol use in last 12 months (RR 2.03; 95%CI: 1.07-3.87), tobacco use (RR 1.87; 95%CI: 1.05-3.36) and severe anaemia (RR 3.53: 95%CI: 1.34-9.30) were associated with a higher risk of death. In adjusted analysis, participants with severe anaemia (<7gm/dl) had 2.4 times higher risk of death compared to their counterparts. CONCLUSION: Though deaths during TB treatment was not very high, early recognition of risk groups and targeted interventions are required to achieve zero TB deaths.

COVID-19 case fatality rate and tuberculosis in a metropolitan setting.

In this study, we aimed to assess the relationship between tuberculosis case rate and COVID-19 case fatality rate (CFR) among districts within a tuberculosis-endemic metropolitan area. We analyzed data from 43 districts in Lima, Peru. We used districts as the units of observation. Linear regressions were used to investigate the relationship between COVID-19 CFRs and tuberculosis case rates. The mean COVID-19 CFR in each district for reporting Weeks 5-32 was used as the dependent variable. Independent variable was the mean rate of confirmed pulmonary tuberculosis cases for 2017-2019 period. Analyses were adjusted by population density, socioeconomic status, crowded housing, health facility density, and case rates of hypertension, diabetes mellitus, and HIV infection. The mean COVID-19 CFR in Lima was 4.0% ± 1.1%. The mean tuberculosis rate was 16.0 cases per 10,000 inhabitants. In multivariate analysis, tuberculosis case rate was associated with COVID-19 CFR (ß = 1.26; 95% confidence interval: 0.24-2.28; p = .02), after adjusting for potential confounders. We found that Lima districts with a higher burden of tuberculosis exhibited higher COVID-19 CFRs, independent of socioeconomic, and morbidity variables.

Análise espacial dos óbitos por tuberculose pulmonar no estado do Amazonas / Spatial analysis of deaths from pulmonary tuberculosis in the state of Amazonas / Análisis espacial de muertes por tuberculosis pulmonar en el estado de las Amazonas

Objetivo: analisar a distribuição dos óbitos por tuberculose pulmonar no estado do Amazonas. Método: trata-se de um estudo ecológico com dados secundários do Sistema de Informação de Mortalidade, durante o período de 2007 a 2017. O software QGIs foi utilizado para elaborar um mapa digital e o software RStudio para as análises estatísticas. Na análise dos dados foi aplicado a regressão linear múltipla, o índice de Moran Global e o teste multiplicador de Lagrange. Resultados: identificou-se 1.267 casos de óbitos por tuberculose pulmonar no estado do Amazonas. A maioria dos óbitos ocorreram no sexo masculino (64,64%); solteiros (47,43%); com faixa etária ≥ 60 anos (51,14%); raça/cor parda (71,11%). Verificou-se que não existe autocorrelação espacial através do índice de Moran Global (0.0094). Conclusão: A distribuição espacial dos óbitos ocorreu de forma heterogênea nas diferentes regiões do estado Amazonas, apresentando elevadas taxas de mortalidade durante o período de 2007 a 2017.(AU)

Objective: to analyze the distribution of deaths from pulmonary tuberculosis in the state of Amazonas. Method: it is an ecological study with secondary data from the Mortality Information System, during the period from 2007 to 2017. The QGIs software was used to create a digital map and the RStudio software for statistical analysis. In the data analysis, multiple linear regression, the Moran Global index and the Lagrange multiplier test were applied. Results: 1,267 cases of deaths from pulmonary tuberculosis were identified in the state of Amazonas. Most deaths occurred in males (64.64%); singles (47.43%); aged ≥ 60 years (51.14%); race / brown color (71.11%). It was found that there is no spatial autocorrelation using the Moran Global index (0.0094). Conclusion: The spatial distribution of deaths occurred heterogeneously in different regions of the state of Amazonas, with high mortality rates during the period from 2007 to 2017.(AU)

Objetivo: analizar la distribución de muertes por tuberculosis pulmonar en el estado de Amazonas. Método: se trata de un estudio ecológico con datos secundarios del Sistema de Información de Mortalidad, durante el período de 2007 a 2017. Se utilizó el software QGIs para crear un mapa digital y el software RStudio para análisis estadístico. En el análisis de datos se aplicó regresión lineal múltiple, el índice Moran Global y la prueba del multiplicador de Lagrange. Resultados: se identificaron 1.267 casos de defunciones por tuberculosis pulmonar en el estado de Amazonas. La mayoría de las muertes ocurrieron en hombres (64,64%); solteros (47,43%); edad ≥ 60 años (51,14%); raza / color marrón (71,11%). Se encontró que no existe autocorrelación espacial usando el índice Moran Global (0.0094). Conclusión: La distribución espacial de las defunciones ocurrió de manera heterogénea en diferentes regiones del estado de Amazonas, con altas tasas de mortalidad durante el período 2007 a 2017.(AU)