Long-term outcomes of the global tuberculosis and COVID-19 co-infection cohort.

BACKGROUND: Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19. METHODS: We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both. RESULTS: Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53). CONCLUSIONS: In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes.

COVID-19: The question of genetic diversity and therapeutic intervention approaches.

Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), is the largest pandemic in modern history with very high infection rates and considerable mortality. The disease, which emerged in China's Wuhan province, had its first reported case on December 29, 2019, and spread rapidly worldwide. On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic and global health emergency. Since the outbreak, efforts to develop COVID-19 vaccines, engineer new drugs, and evaluate existing ones for drug repurposing have been intensively undertaken to find ways to control this pandemic. COVID-19 therapeutic strategies aim to impair molecular pathways involved in the virus entrance and replication or interfere in the patients' overreaction and immunopathology. Moreover, nanotechnology could be an approach to boost the activity of new drugs. Several COVID-19 vaccine candidates have received emergency-use or full authorization in one or more countries, and others are being developed and tested. This review assesses the different strategies currently proposed to control COVID-19 and the issues or limitations imposed on some approaches by the human and viral genetic variability.

Atmospheric Pollution and Hospitalization for Cardiovascular and Respiratory Diseases in the City of Manaus from 2008 to 2012.

OBJECTIVE: To relate the levels of air pollution and hospital admissions for cardiovascular and respiratory diseases in the city of Manaus in Brazil from 2008 to 2012. METHOD: This is an ecological time-series study among children (under 5 years of age) and elderly (above 60 years of age). Data on the daily number of hospitalizations for cardiovascular and respiratory diseases, pollutants (PM2.5), temperature, and humidity were used. Poisson generalized additive models were used to estimate the association between variables. Increases in hospitalizations for cardiovascular and respiratory diseases were estimated for the interquartile range (IQR) daily mean level of each variable studied, with a confidence interval of 95%. RESULTS: Respiratory diseases and children: -0.40% (95% CI: -1.11, 0.30), 0.59% (95% CI: -0.35, 1.52), and 0.47% (95% CI: -3.28, 4.21) for PM2.5, temperature, and humidity, respectively. Respiratory diseases and elderly: 0.19% (95% CI: -0.93, 1.31), -0.10% (95% CI: -1.85, 1.65), and -6.17% (95% CI: -13.08, 0.74) for PM2.5, temperature, and humidity, respectively. Cardiovascular diseases and elderly: -0.18% (95% CI: -0.86, 0.50), -0.04% (95% CI: -1.10, 1.03), and -3.37% (95% CI: -7.59, 0.85) for PM2.5, temperature, and humidity, respectively. CONCLUSIONS: The time-series study found no significant association between PM2.5, temperature, humidity, and hospitalization, unlike the evidences provided by the present academic literature. Since there is no air quality monitoring network in Manaus and the option available in the present study was to reproduce some information obtained from remote sensing, there is a need for implementation of ground monitoring stations for health and environmental studies in the region.

Comparison of effectiveness and safety of imipenem/clavulanate- versus meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB.

No large study to date has ever evaluated the effectiveness, safety and tolerability of imipenem/clavulanate versus meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to compare the therapeutic contribution of imipenem/clavulanate versus meropenem/clavulanate added to background regimens to treat MDR- and XDR-TB cases.84 patients treated with imipenem/clavulanate-containing regimens showed a similar median number of antibiotic resistances (8 versus 8) but more fluoroquinolone resistance (79.0% versus 48.9%, p<0.0001) and higher XDR-TB prevalence (67.9% versus 49.0%, p=0.01) in comparison with 96 patients exposed to meropenem/clavulanate-containing regimens. Patients were treated with imipenem/clavulanate- and meropenem/clavulanate-containing regimens for a median (interquartile range) of 187 (60-428) versus 85 (49-156) days, respectively.Statistically significant differences were observed on sputum smear and culture conversion rates (79.7% versus 94.8%, p=0.02 and 71.9% versus 94.8%, p<0.0001, respectively) and on success rates (59.7% versus 77.5%, p=0.03). Adverse events to imipenem/clavulanate and meropenem/clavulanate were reported in 5.4% and 6.5% of cases only.Our study suggests that meropenem/clavulanate is more effective than imipenem/clavulanate in treating MDR/XDR-TB patients.

Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB.

No large study has ever evaluated the efficacy, safety and tolerability of meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to evaluate the therapeutic contribution, effectiveness, safety and tolerability profile of meropenem/clavulanate added to a background regimen when treating MDR- and XDR-TB cases.Patients treated with a meropenem/clavulanate-containing regimen (n=96) showed a greater drug resistance profile than those exposed to a meropenem/clavulanate-sparing regimen (n=168): in the former group XDR-TB was more frequent (49% versus 6.0%, p<0.0001) and the median (interquartile range (IQR)) number of antibiotic resistances was higher (8 (6-9)versus 5 (4-6)). Patients were treated with a meropenem/clavulanate-containing regimen for a median (IQR) of 85 (49-156) days.No statistically significant differences were observed in the overall MDR-TB cohort and in the subgroups with and without the XDR-TB patients; in particular, sputum smear and culture conversion rates were similar in XDR-TB patients exposed to meropenem/clavulanate-containing regimens (88.0% versus 100.0%, p=1.00 and 88.0% versus 100.0%, p=1.00, respectively). Only six cases reported adverse events attributable to meropenem/clavulanate (four of them then restarting treatment).The nondifferent outcomes and bacteriological conversion rate observed in cases who were more severe than controls might imply that meropenem/clavulanate could be active in treating MDR- and XDR-TB cases.

Brazilian Thoracic Society recommendations for the diagnosis and monitoring of asbestos-exposed individuals.

Asbestos was largely used in Brazil. It is a mineral that induces pleural and pulmonary fibrosis, and it is a potent carcinogen. Our objective was to develop recommendations for the performance of adequate imaging tests for screening asbestos-related diseases. We searched peer-reviewed publications, national and international technical documents, and specialists' opinions on the theme. Based on that, the major recommendations are: Individuals exposed to asbestos at the workplace for ≥ 1 year or those with a history of environmental exposure for at least 5 years, all of those with a latency period > 20 years from the date of initial exposure, should initially undego HRCT of the chest for investigation. Individuals with pleural disease and/or asbestosis should be considered for regular lung cancer monitoring. Risk calculators should be adopted for lung cancer screening, with a risk estimate of 1.5%.

An Evaluation of the Impact of Air Pollution on the Lung Functions of High School Students Living in a Ceramic Industrial Park Zone.

Santa Gertrudes (SG) and Rio Claro (RC), Sao Paulo, Brazil, are located in a ceramic industrial park zone, and their particulate matter with an aerodynamic diameter of less than 10 µm (PM10) concentration levels has been among the highest in recently monitored cities in Brazil. Local PM10 was mostly composed of silica. A cross-sectional study was designed to evaluate the lung functions of public high school students in SG, RC, and São Pedro (SP) (control location), Brazil, in 2018. The prevalence of asthma, mean PM10, FVC (forced vital capacity), and FEV1 (forced expiratory volume in the first second) were compared between the locations, and regression analyses were performed. A total of 450 students were included (SG: 158, RC: 153, and SP: 139). The mean FVC% (SG: 95.0% ± 11.8%, RC: 98.8% ± 12.9%, SP: 102.4% ± 13.8%, p < 0.05), the mean FEV1% (SG: 95.7% ± 10.4%, RC: 99.7% ± 12.0%, SP: 103.2% ± 12.0%, p < 0.05) and the mean PM10 (SG: 77.75 ± 38.08 µg/m3, RC: 42.59 ± 23.46 µg/m3, SP: 29.52 ± 9.87 µg/m3, p < 0.01) differed between locations. In regression models, each increase in PM10 by 10 µg/m3 was associated with a decrease in FVC% by 1.10% (95% CI 0.55%-1.65%) and a decrease in FEV1% by 1.27% (95% CI 0.75%-1.79%). Exposure to high levels of silica-rich environmental PM10 was found to be associated with lower FVC and FEV1.

Environmental air pollution: respiratory effects.

Environmental air pollution is a major risk factor for morbidity and mortality worldwide. Environmental air pollution has a direct impact on human health, being responsible for an increase in the incidence of and number of deaths due to cardiopulmonary, neoplastic, and metabolic diseases; it also contributes to global warming and the consequent climate change associated with extreme events and environmental imbalances. In this review, we present articles that show the impact that exposure to different sources and types of air pollutants has on the respiratory system; we present the acute effects-such as increases in symptoms and in the number of emergency room visits, hospitalizations, and deaths-and the chronic effects-such as increases in the incidence of asthma, COPD, and lung cancer, as well as a rapid decline in lung function. The effects of air pollution in more susceptible populations and the effects associated with physical exercise in polluted environments are also presented and discussed. Finally, we present the major studies on the subject conducted in Brazil. Health care and disease prevention services should be aware of this important risk factor in order to counsel more susceptible individuals about protective measures that can facilitate their treatment, as well as promoting the adoption of environmental measures that contribute to the reduction of such emissions.

Screening for Tuberculosis in Migrants: A Survey by the Global Tuberculosis Network.

Tuberculosis (TB) does not respect borders, and migration confounds global TB control and elimination. Systematic screening of immigrants from TB high burden settings and-to a lesser degree TB infection (TBI)-is recommended in most countries with a low incidence of TB. The aim of the study was to evaluate the views of a diverse group of international health professionals on TB management among migrants. Participants expressed their level of agreement using a six-point Likert scale with different statements in an online survey available in English, French, Mandarin, Spanish, Portuguese and Russian. The survey consisted of eight sections, covering TB and TBI screening and treatment in migrants. A total of 1055 respondents from 80 countries and territories participated between November 2019 and April 2020. The largest professional groups were pulmonologists (16.8%), other clinicians (30.4%), and nurses (11.8%). Participants generally supported infection control and TB surveillance established practices (administrative interventions, personal protection, etc.), while they disagreed on how to diagnose and manage both TB and TBI, particularly on which TBI regimens to use and when patients should be hospitalised. The results of this first knowledge, attitude and practice study on TB screening and treatment in migrants will inform public health policy and educational resources.

Relationship between air pollution and hospitalizations for congestive heart failure in elderly people in the city of São Paulo.

To evaluate the effects of air pollutants on hospitalizations of elderly people for congestive heart failure (CHF) in the city of São Paulo, stratified by sex, exploring lag structures, from 2000 to 2013. Ecological time series study using information on hospitalization of elderly patients for CHF (ICD-10th: I50) obtained from DATASUS for the city of São Paulo. Information on O3, PM10, NO2, SO2, CO, temperature and humidity was obtained from CETESB. Descriptive analyses, Pearson correlation, and generalized linear Poisson regression model were applied to estimate the effects of pollutants. The interquartile variations of O3 (52.45 µg/m3), PM10 (24.28 µg/m3), NO2 (7.63 µg/m3), SO2 (50.22 µg/m3), and CO (1.28 ppm) were associated with increased hospitalizations for CHF. Air pollutants continue to be a factor that contributes to the increase in the number of hospitalizations due to CHF.

Usefulness of Mycobacterium tuberculosis molecular typing in a tuberculosis low-endemic agro-industrial setting of Brazil.

To highlight the transmission and major phylogenetic clades of Mycobacterium tuberculosis, a retrospective study was carried out at two health facilities in a small agro-industrial area in Sao Paulo, Brazil, that has a low tuberculosis incidence rate. IS6110-RFLP and spoligotyping were performed on the isolates, with the former revealing that 31.3% (35/112) of strains were clustered. Epidemiological links were found in 16 of the 35 clustered patients and were associated with transmission among patients living in public housing. Spoligotyping grouped 62.8% of the strains. The T genetic family predominated among the isolates. Of interest is that five strains had a pattern characteristic of African or Asian origin (ST535), and two others were of the rare localized type ST1888 (BRA, VEN). In addition, three new types--1889, 1890, and 1891--were identified. Spoligotyping showed that some ST may be circulating to or from Brazil, and RFLP revealed ongoing transmission in inadequately ventilated public-housing buildings. This may point to a failure in tuberculosis control policy.

Risk factors for tuberculosis: diabetes, smoking, alcohol use, and the use of other drugs.

Tuberculosis continues to be a major public health problem. Although efforts to control the epidemic have reduced mortality and incidence, there are several predisposing factors that should be modified in order to reduce the burden of the disease. This review article will address some of the risk factors associated with tuberculosis infection and active tuberculosis, including diabetes, smoking, alcohol use, and the use of other drugs, all of which can also contribute to poor tuberculosis treatment results. Tuberculosis can also lead to complications in the course and management of other diseases, such as diabetes. It is therefore important to identify these comorbidities in tuberculosis patients in order to ensure adequate management of both conditions.

New and repurposed drugs to treat multidrug- and extensively drug-resistant tuberculosis.

Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. The objective of this review was to summarize what has been achieved to date, as far as new and repurposed drugs are concerned, with a special focus on delamanid, bedaquiline, pretomanid, clofazimine, carbapenems, and linezolid. After more than 40 years of neglect, greater attention has recently been paid to the need for new drugs to fight the "white plague", and promising results are being reported.

Evaluation of peak expiratory flow in adolescents and its association with inhalable particulate in a Brazilian medium-sized city.

INTRODUCTION: High particulate matter (PM10) concentrations are associated with increased incidence of respiratory symptoms and decreased lung function. This study evaluates the air pollution effects in children's and adolescents' lung function using peak expiratory flow (PEF) measurements over a given period, in an area exposed to industrial emissions. METHODOLOGY: This was a panel study. The effects of air pollution on respiratory symptoms and PEF were investigated in 117 children and adolescents from three public schools in areas of exposure to air pollution from a mining company in a Brazilian medium-sized city, from 2008 to 2009. The average daily PM10, temperature and humidity were recorded by the monitoring network in the region. Association between daily records of PEF and PM10 was assessed in mixed-effect regression models, controlling for temperature, humidity, and body mass index. RESULTS: About 60,000 PEF measurements were performed. Increases of 14µg/m3 in PM10 were associated with decreased PEF in the morning (-1.04%, 95%CI -1.32; -0.77) and evening (-1.2%, 95%CI -1.49, -0.92). DISCUSSION: We found a significant negative association between particulate matter and peak expiratory flow rate in this population, and these remained significant even after adjusted for temperature, humidity, body mass index, coughing, wheezing and coryza. CONCLUSION: Adverse effects were found and it suggests an association between increase in PM10 and reduced lung function.

Air pollution from biomass burning and asthma hospital admissions in a sugar cane plantation area in Brazil.

OBJECTIVE: To evaluate the association between the total suspended particles (TSPs) generated from preharvest sugar cane burning and hospital admission due to asthma (asthma hospital admissions) in the city of Araraquara. DESIGN: An ecological time-series study. Total daily records of asthma hospital admissions (ICD 10th J15) were obtained from one of the main hospitals in Araraquara, São Paulo State, Brazil, from 23 March 2003 to 27 July 2004. The daily concentration of TSP (microg/m(3)) was obtained using Handi-vol equipment (Energética, Brazil) placed in downtown Araraquara. The local airport provided the daily mean figures of temperature and humidity. The daily number of asthma hospital admissions was considered as the dependent variable in Poisson's regression models and the daily concentration of TSP was considered the independent variable. The generalised linear model with natural cubic spline was adopted to control for long-time trend. Linear terms were used for weather variables. RESULTS: TSP had an acute effect on asthma admissions, starting 1 day after TSP concentrations increased and remaining almost unchanged for the next four days. A 10 microg/m(3) increase in the 5-day moving average (lag1-5) of TSP concentrations was associated with an increase of 11.6% (95% CI 5.4 to 17.7) in asthma hospital admissions. CONCLUSION: Increases in TSP concentrations were definitely associated with asthma hospital admissions in Araraquara and, despite using sugar cane alcohol to reduce air pollution from automotive sources in large Brazilian urban centres, the cities where sugar cane is harvested pay a high toll in terms of public health.

The challenge of the new tuberculosis drugs.

Tuberculosis (TB) continues to cause more deaths worldwide than any other single infectious disease. Even though tuberculosis appears to be decreasing in incidence globally for some time, the proportion of drug resistance is increasing, contributing to greater complexity, morbidity and mortality as well as cost. Since the advent of rifampicin in the 1960s, and the implementation of standard quadruple anti-tuberculosis regimen in the late 1970s, no new drugs have been changed the first line regimen. This regimen is effective however it is pill burden, and duration has not received investment and innovation. Drug-resistant regimens are long and frequently poorly tolerated due to significant toxicity. This review is an update on what is new in the treatment of drug-susceptible and drug-resistant tuberculosis, new TB drugs currently being used and studied in clinical trials are also mentioned. Fortunately, there have been many significant advances in this field in recent years. The horizon is changing with the new WHO shorter multidrug-resistant tuberculosis regimens and with the increasing availability of new or repurposed drugs like bedaquiline, delamanid, clofazimine and linezolid. These drugs pose new challenges relating to their rational use to prevent selection of resistant strains of Mycobacterium tuberculosis even before a new regimen has been studied. The availability of these new drugs is offering hope and new possibilities for saving patients who had few or no treatment options. Their use and combination into effective regimens need to be studied; trials are in progress. It is hoped that soon we will be able to treat sensitive and drug-resistant cases with a universal regimen, this would revolutionise treatment and take us another step closer towards elimination.

The impact of sugar cane-burning emissions on the respiratory system of children and the elderly.

We analyzed the influence of emissions from burning sugar cane on the respiratory system during almost 1 year in the city of Piracicaba in southeast Brazil. From April 1997 through March 1998, samples of inhalable particles were collected, separated into fine and coarse particulate mode, and analyzed for black carbon and tracer elements. At the same time, we examined daily records of children (<13 years of age) and elderly people (>64 years of age) admitted to the hospital because of respiratory diseases. Generalized linear models were adopted with natural cubic splines to control for season and linear terms to control for weather. Analyses were carried out for the entire period, as well as for burning and nonburning periods. Additional models were built using three factors obtained from factor analysis instead of particles or tracer elements. Increases of 10.2 microg/m3 in particles

Environmental air pollution: respiratory effects / Poluição do ar ambiental: efeitos respiratórios

ABSTRACT Environmental air pollution is a major risk factor for morbidity and mortality worldwide. Environmental air pollution has a direct impact on human health, being responsible for an increase in the incidence of and number of deaths due to cardiopulmonary, neoplastic, and metabolic diseases; it also contributes to global warming and the consequent climate change associated with extreme events and environmental imbalances. In this review, we present articles that show the impact that exposure to different sources and types of air pollutants has on the respiratory system; we present the acute effects—such as increases in symptoms and in the number of emergency room visits, hospitalizations, and deaths—and the chronic effects—such as increases in the incidence of asthma, COPD, and lung cancer, as well as a rapid decline in lung function. The effects of air pollution in more susceptible populations and the effects associated with physical exercise in polluted environments are also presented and discussed. Finally, we present the major studies on the subject conducted in Brazil. Health care and disease prevention services should be aware of this important risk factor in order to counsel more susceptible individuals about protective measures that can facilitate their treatment, as well as promoting the adoption of environmental measures that contribute to the reduction of such emissions.

RESUMO A poluição do ar ambiental é um dos principais fatores de risco de morbidade e mortalidade global. Ela tem impacto direto na saúde humana, sendo responsável pelo aumento de incidência e de óbitos por doenças cardiorrespiratórias, neoplásicas e metabólicas; também contribui para o aquecimento global e para as consequentes alterações do clima associadas a eventos extremos e aos desequilíbrios ambientais. Nesta revisão, apresentamos artigos que evidenciam o impacto da exposição a diferentes fontes e tipos de poluentes do ar no sistema respiratório; apresentamos os efeitos agudos — como aumento de sintomas e no número de atendimentos em serviços de emergência, internações e óbitos — e crônicos — como o aumento da incidência de asma, DPOC e câncer de pulmão, assim como o declínio acelerado da função pulmonar. Também são apresentados e discutidos os efeitos da poluição atmosférica em populações mais suscetíveis e dos efeitos associados à realização de exercícios físicos em ambientes poluídos. Por fim, apresentamos os principais estudos brasileiros sobre o assunto. Os serviços de atenção à saúde e de prevenção de doenças devem ficar atentos a esse importante fator de risco para orientar indivíduos mais suscetíveis sobre medidas de proteção que possam facilitar seu tratamento, além de estimular a adoção de medidas ambientais que contribuam para a redução dessas emissões.