The battle against colistin-resistant E. coli and the need for a one health approach.

Promoting the judicious use of antibiotics is crucial. Physicians and veterinarians must adhere to evidence-based guidelines and prescribe antibiotics only when necessary [26]. Improved diagnostic tools can help identify the most appropriate treatment options.

The association of SARS-CoV-2 infection and tuberculosis disease with unfavorable treatment outcomes: A systematic review.

BACKGROUND: Whether SARS-CoV-2 infection and its management influence tuberculosis (TB) treatment outcomes is uncertain. We synthesized evidence on the association of SARS-CoV-2 coinfection (Coinfection Review) and its management (Clinical Management Review) on treatment outcomes among people with tuberculosis (TB) disease. METHODS: We systematically searched the literature from 1 January 2020 to 6 February 2022. Primary outcomes included: unfavorable (death, treatment failure, loss-to-follow-up) TB treatment outcomes (Coinfection and Clinical Management Review) and/or severe or critical COVID-19 or death (Clinical Management Review). Study quality was assessed with an adapted Newcastle Ottawa Scale. Data were heterogeneous and a narrative review was performed. An updated search was performed on April 3, 2023. FINDINGS: From 9,529 records, we included 11 studies and 7305 unique participants. No study reported data relevant to our review in their primary publication and data had to be contributed by study authors after contact. Evidence from all studies was low quality. Eight studies of 5749 persons treated for TB (286 [5%] with SARS-CoV-2) were included in the Coinfection Review. Across five studies reporting our primary outcome, there was no significant association between SARS-CoV-2 coinfection and unfavorable TB treatment outcomes. Four studies of 1572 TB patients-of whom 291 (19%) received corticosteroids or other immunomodulating treatment-were included in the Clinical Management Review, and two addressed a primary outcome. Studies were likely confounded by indication and discordant findings existed among studies. When updating our search, we still did not identify any study reporting data relevant to this review in their primary publication. INTERPRETATION: No study was designed to answer our research questions of interest. It remains unclear whether TB/SARS-CoV-2 and its therapeutic management are associated with unfavorable outcomes. Research is needed to improve our understanding of risk and optimal management of persons with TB and SARS-CoV-2 infection. TRIAL REGISTRATION: Registration: PROSPERO (CRD42022309818).

Migration and medical screening for tuberculosis.

Vulnerable populations, such as migrants and refugees, have an increased risk of tuberculosis disease, especially in the first years after arrival in the host country. The presence of migrants and refugees in Brazil exponentially grew over the period between 2011 and 2020, and approximately 1.3 million migrants from the Global South were estimated to be residing in Brazil, most of whom from Venezuela and Haiti. Tuberculosis control programs for migrants can be divided into pre- and post-migration screening strategies. Pre-migration screening aims to identify cases of tuberculosis infection (TBI) and can be carried out in the country of origin (pre-entry) or in the destination country (at entry). Pre-migration screening can also detect migrants at an increased risk of developing tuberculosis in the future. High-risk migrants are then followed up in post-migration screening. In Brazil, migrants are considered a priority group for the active search for tuberculosis cases. However, there is no recommendation or plan regarding screening for TBI in migrants and refugees. Ensuring prevention, diagnosis, and treatment for TBI and tuberculosis disease in migrant populations is an important aspect of tuberculosis control and elimination. In this review article, we address epidemiological aspects and access to health care for migrants in Brazil. In addition, the migration medical screening for tuberculosis was reviewed.

The path to tuberculosis elimination: a renewed vision.

Tuberculosis (TB) elimination and pre-elimination, with thresholds of 1 and 10 incident cases per million population, respectively, were considered achievable for low TB incidence countries in the 1990s, when they were conceived. However, it has since become clear that, even in low TB incidence settings with effective programmes and sufficient resources, achieving pre-elimination in the next decade will require a dramatic acceleration of efforts. In this review, we describe the history of the TB elimination concept and existing country experiences, as well as the interventions available to accelerate the progress towards this threshold. We then propose a framework for near-term progress towards the more aspirational goal of TB pre-elimination. This framework consists of five stages (high incidence, moderate incidence, low incidence, nearing pre-elimination and pre-elimination) that are benchmarked to specific levels of TB incidence in each country. Using this framework, countries can set 5-year targets of achieving certain reductions in TB incidence and/or reaching the next stage, through the use of strategies tailored to both local epidemiology and available organisation and infrastructure. TB elimination remains as an aspirational goal in all stages, but certain activities can be prioritised in the short term to make more rapid progress, ensure local-level buy-in and increase accountability. As TB pre-elimination is approached, certain ethical and social concerns are likely to rise in importance; these concerns are also discussed. Our aim in setting this framework is to guide clinicians, public health experts and decision makers in taking actionable next steps in the trajectory towards TB pre-elimination and elimination.

Impact of COVID-19 on diagnosis of tuberculosis, multidrug-resistant tuberculosis, and on mortality in 11 countries in Europe, Northern America, and Australia. A Global Tuberculosis Network study.

OBJECTIVES: Although evidence is growing on the overall impact of the COVID-19 pandemic on tuberculosis (TB) services, global studies based on national data are needed to better quantify the extent of the impact and the countries' preparedness to tackle the two diseases. The aim of this study was to compare the number of people with new diagnoses or recurrence of TB disease, the number of drug-resistant (DR)-TB, and the number of TB deaths in 2020 vs 2019 in 11 countries in Europe, Northern America, and Australia. METHODS: TB managers or directors of national reference centers of the selected countries provided the agreed-upon variables through a validated questionnaire on a monthly basis. A descriptive analysis compared the incidence of TB and DR-TB and mortality of the pre-COVID-19 year (2019) vs the first year of the COVID-19 pandemic (2020). RESULTS: Comparing 2020 vs 2019, lower number of TB cases (new diagnosis or recurrence) was notified in all countries (except USA-Virginia and Australia), and fewer DR-TB notifications (apart from France, Portugal, and Spain). The deaths among TB cases were higher in 2020 compared to 2019 in most countries with three countries (France, The Netherlands, USA-Virginia) reporting minimal TB-related mortality. CONCLUSIONS: A comprehensive evaluation of medium-term impact of COVID-19 on TB services would benefit from similar studies in multiple settings and from global availability of treatment outcome data from TB/COVID-19 co-infected patients.

Rapid Diagnosis of XDR and Pre-XDR TB: A Systematic Review of Available Tools

Introduction: No previous systematic reviews have comprehensively investigated the features of Xpert MTB/XDR and other rapid tests to diagnose pre-XDR/XDR-TB. The aim of this systematic review is to assess existing rapid diagnostics for pre-XDR/XDR-TB from a point-of-care perspective and describe their technical characteristics (i.e., sensitivity, specificity, positive and negative predictive values). Methods: Embase, PubMed, Scopus, and Web of Science were searched to detect the articles focused on the accuracy of commercially available rapid molecular diagnostic tests for XDR-TB according to PRISMA guidelines. The analysis compared the diagnostic techniques and approaches in terms of sensitivity, specificity, laboratory complexity, time to confirmed diagnosis. Results: Of 1298 records identified, after valuating article titles and abstracts, 97 (7.5%) records underwent full-text evaluation and 38 records met the inclusion criteria. Two rapid World Health Organization (WHO)-endorsed tests are available: Xpert MTB/XDR and GenoType MTBDRsl (VER1.0 and VER 2.0). Both tests had similar performance, slightly favouring Xpert, although only 2 studies were available (sensitivity 91.4–94; specificity 98.5–99; accuracy 97.2–97.7; PPV 88.9–99.1; NPV 95.8–98.9). Conclusions: Xpert MTB/XDR could be suggested at near-point-of-care settings to be used primarily as a follow-on test for laboratory-confirmed TB, complementing existing rapid tests detecting at least rifampicin-resistance. Both Xpert MTB/XDR and GenoType MTBDRsl are presently diagnosing what WHO defined, in 2021, as pre-XDR-TB. (AU)

Breathing Back Better. A State of the Art on the Benefits of Functional Evaluation and Rehabilitation of Post-Tuberculosis and Post-COVID Lungs

Currently, tuberculosis (TB) and COVID-19 account for substantial morbidity and mortality worldwide, not only during their acute phase, but also because of their sequelae. This scoping review aims to describe the specific aspects of post-TB and post-COVID (long-COVID-19) sequelae, and the implications for post-disease follow-up and rehabilitation.In particular, evidence on how to identify patients affected by sequelae is presented and discussed. A section of the review is dedicated to identifying patients eligible for pulmonary rehabilitation (PR), as not all patients with sequelae are eligible for PR. Components of PR are presented and discussed, as well as their effectiveness.Other essential components to implement comprehensive rehabilitation programmes such as counselling and health education of enrolled patients, evaluation of cost-effectiveness of PR and its impact on health systems as well as research priorities for the future are included in this scoping review. (AU)

Rapid Diagnosis of XDR and Pre-XDR TB: A Systematic Review of Available Tools.

INTRODUCTION: No previous systematic reviews have comprehensively investigated the features of Xpert MTB/XDR and other rapid tests to diagnose pre-XDR/XDR-TB. The aim of this systematic review is to assess existing rapid diagnostics for pre-XDR/XDR-TB from a point-of-care perspective and describe their technical characteristics (i.e., sensitivity, specificity, positive and negative predictive values). METHODS: Embase, PubMed, Scopus, and Web of Science were searched to detect the articles focused on the accuracy of commercially available rapid molecular diagnostic tests for XDR-TB according to PRISMA guidelines. The analysis compared the diagnostic techniques and approaches in terms of sensitivity, specificity, laboratory complexity, time to confirmed diagnosis. RESULTS: Of 1298 records identified, after valuating article titles and abstracts, 97 (7.5%) records underwent full-text evaluation and 38 records met the inclusion criteria. Two rapid World Health Organization (WHO)-endorsed tests are available: Xpert MTB/XDR and GenoType MTBDRsl (VER1.0 and VER 2.0). Both tests had similar performance, slightly favouring Xpert, although only 2 studies were available (sensitivity 91.4-94; specificity 98.5-99; accuracy 97.2-97.7; PPV 88.9-99.1; NPV 95.8-98.9). CONCLUSIONS: Xpert MTB/XDR could be suggested at near-point-of-care settings to be used primarily as a follow-on test for laboratory-confirmed TB, complementing existing rapid tests detecting at least rifampicin-resistance. Both Xpert MTB/XDR and GenoType MTBDRsl are presently diagnosing what WHO defined, in 2021, as pre-XDR-TB.

Breathing Back Better! A State of the Art on the Benefits of Functional Evaluation and Rehabilitation of Post-Tuberculosis and Post-COVID Lungs.

Currently, tuberculosis (TB) and COVID-19 account for substantial morbidity and mortality worldwide, not only during their acute phase, but also because of their sequelae. This scoping review aims to describe the specific aspects of post-TB and post-COVID (long-COVID-19) sequelae, and the implications for post-disease follow-up and rehabilitation. In particular, evidence on how to identify patients affected by sequelae is presented and discussed. A section of the review is dedicated to identifying patients eligible for pulmonary rehabilitation (PR), as not all patients with sequelae are eligible for PR. Components of PR are presented and discussed, as well as their effectiveness. Other essential components to implement comprehensive rehabilitation programmes such as counselling and health education of enrolled patients, evaluation of cost-effectiveness of PR and its impact on health systems as well as research priorities for the future are included in this scoping review.

Post-tuberculosis lung disease: a comparison of Brazilian, Italian, and Mexican cohorts.

OBJECTIVE: To evaluate lung function in a cohort of patients with a history of pulmonary tuberculosis in Brazil, as well as to evaluate the decline in lung function over time and compare it with that observed in similar cohorts in Mexico and Italy. METHODS: The three cohorts were compared in terms of age, smoking status, pulmonary function test results, six-minute walk test results, and arterial blood gas results. In the Brazilian cohort, pulmonary function test results, six-minute walk test results, and arterial blood gas results right after the end of tuberculosis treatment were compared with those obtained at the end of the follow-up period. RESULTS: The three cohorts were very different regarding pulmonary function test results. The most common ventilatory patterns in the Brazilian, Italian, and Mexican cohorts were an obstructive pattern, a mixed pattern, and a normal pattern (in 58 patients [50.9%], in 18 patients [41.9%], and in 26 patients [44.1%], respectively). Only 2 multidrug-resistant tuberculosis cases were included in the Brazilian cohort, whereas, in the Mexican cohort, 27 cases were included (45.8%). Mean PaO2 and mean SaO2 were lower in the Mexican cohort than in the Brazilian cohort (p < 0.0001 and p < 0.002 for PaO2 and SaO2, respectively). In the Brazilian cohort, almost all functional parameters deteriorated over time. CONCLUSIONS: This study reinforces the importance of early and effective treatment of drug-susceptible tuberculosis patients, because multidrug-resistant tuberculosis increases lung damage. When patients complete their tuberculosis treatment, they should be evaluated as early as possible, and, if post-tuberculosis lung disease is diagnosed, they should be managed and offered pulmonary rehabilitation because there is evidence that it is effective in these patients.

Country-specific lockdown measures in response to the COVID-19 pandemic and its impact on tuberculosis control: a global study.

The objective of this study was to describe country-specific lockdown measures and tuberculosis indicators collected during the first year of the COVID-19 pandemic. Data on lockdown/social restrictions (compulsory face masks and hand hygiene; international and local travel restrictions; restrictions to family visits, and school closures) were collected from 24 countries spanning five continents. The majority of the countries implemented multiple lockdowns with partial or full reopening. There was an overall decrease in active tuberculosis, drug-resistant tuberculosis, and latent tuberculosis cases. Although national lockdowns were effective in containing COVID-19 cases, several indicators of tuberculosis were affected during the pandemic.

Drug resistant TB - latest developments in epidemiology, diagnostics and management.

AIM: The aim of this review is to inform the reader on the latest developments in epidemiology, diagnostics and management. EPIDEMIOLOGY: Drug-resistant Tuberculosis (DR-TB) continues to be a current global health threat, and is defined by higher morbidity and mortality, sequelae, higher cost and complexity. The WHO classifies drug-resistant TB into 5 categories: isoniazid-resistant TB, rifampicin resistant (RR)-TB and MDR-TB, (TB resistant to isoniazid and rifampicin), pre-extensively drug-resistant TB (pre-XDR-TB) which is MDR-TB with resistance to a fluoroquinolone and finally XDR-TB that is TB resistant to rifampicin, plus any fluoroquinolone, plus at least one further priority A drug (bedaquiline or linezolid). Of 500,000 estimated new cases of RR-TB in 2020, only 157 903 cases are notified. Only about a third of cases are detected and treated annually. DIAGNOSTICS: Recently newer rapid diagnostic methods like the GeneXpert, whole genome sequencing and Myc-TB offer solutions for rapid detection of resistance. TREATMENT: The availability of new TB drugs and shorter treatment regimens have been recommended for the management of DR-TB. CONCLUSION: Despite advances in diagnostics and treatments we still have to find and treat two thirds of the drug resistant cases that go undetected and therefore go untreated each year. Control of TB and elimination will only occur if cases are detected, diagnosed and treated promptly.

Delamanid-containing regimens and multidrug-resistant tuberculosis: A systematic review and meta-analysis.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening condition needing long poly-chemotherapy regimens. As no systematic reviews/meta-analysis is available to comprehensively evaluate the role of delamanid (DLM), we evaluated its effectiveness and safety. METHODS: We reviewed the relevant scientific literature published up to January 20, 2022. The pooled success treatment rate with 95% confidence intervals (CI) was assessed using a random-effect model. We assessed studies for quality and bias, and considered P<0.05 to be statistically significant. RESULTS: After reviewing 626 records, we identified 25 studies that met the inclusion criteria, 22 observational and 3 experimental, with 1276 and 411 patients, respectively. In observational studies the overall pooled treatment success rate of DLM-containing regimens was 80.9% (95% CI 72.6-87.2) with no evidence of publication bias (Begg's test; P >0.05). The overall pooled treatment success rate in DLM and bedaquiline-containing regimens was 75.2% (95% CI 68.1-81.1) with no evidence of publication bias (Begg's test; P >0.05). In experimental studies the pooled treatment success rate of DLM-containing regimens was 72.5 (95% CI 44.2-89.8, P <0.001, I2: 95.1%) with no evidence of publication bias (Begg's test; P >0.05). CONCLUSIONS: In MDR-TB patients receiving DLM, culture conversion and treatment success rates were high despite extensive resistance with limited adverse events.

History of prevention, diagnosis, treatment and rehabilitation of pulmonary sequelae of tuberculosis.

Tuberculosis (TB), known as the White Plague' is of great significance to humanity for the magnitude of morbidity and mortality it has generated over centuries from the very start of human civilization. In this Review, we will describe the history of prevention (vaccination and management of TB infection), diagnosis, treatment and pulmonary rehabilitation of post-treatment sequelae. The article leads the reader through the main discoveries which paved the way to the modern approach to TB prevention and care. The history of Bacille Calmette-Guérin (BCG) vaccine and of the diagnosis and treatment of TB infection are presented, together with that of diagnosis and treatment of TB disease. Pivotal was in 1882 the discovery by Robert Koch of the aetiological agent of TB, and his pioneering work in culturing the bacillus and developing tuberculin. Also of enormous importance was, in 1895, the discovery of the X-rays by Wilhelm Conrad Röntgen, discovery which paved the way to the development of the modern imaging technologies. To complement this, the more recent history of rehabilitation of post-treatment sequelae is summarized, given the importance this issue has on patients' wellbeing and Quality of Life.

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.