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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.

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.

Little is known about the relationship between the COVID-19 and tuberculosis (TB). The aim of this study is to describe a group of patients who died with TB (active disease or sequelae) and COVID-19 in two cohorts. Data from 49 consecutive cases in 8 countries (cohort A) and 20 hospitalised patients with TB and COVID-19 (cohort B) were analysed and patients who died were described. Demographic and clinical variables were retrospectively collected, including co-morbidities and risk factors for TB and COVID-19 mortality. Overall, 8 out of 69 (11.6%) patients died, 7 from cohort A (14.3%) and one from cohort B (5%). Out of 69 patients 43 were migrants, 26/49 (53.1%) in cohort A and 17/20 (85.0%) in cohort B. Migrants: (1) were younger than natives; in cohort A the median (IQR) age was 40 (27–49) VS. 66 (46–70) years, whereas in cohort B 37 (27–46) VS. 48 (47–60) years; (2) had a lower mortality rate than natives (1/43, 2.3% versus 7/26, 26.9%; p-value: 0.002); (3) had fewer co-morbidities than natives (23/43, 53.5% versus 5/26–19.2%) natives; p-value: 0.005). The study findings show that: (1) mortality is likely to occur in elderly patients with co-morbidities; (2) TB might not be a major determinant of mortality and (3) migrants had lower mortality, probably because of their younger age and lower number of co-morbidities. However, in settings where advanced forms of TB frequently occur and are caused by drug-resistant strains of M. tuberculosis, higher mortality rates can be expected in young individuals.

Resumen Introduccion La diabetes mellitus (DM), una enfermedad muy frecuente en Mexico, es un factor de riesgo bien conocido para el desarrollo de tuberculosis (TB). Sin embargo, se desconoce en que medida la DM predispone al desarrollo de reacciones adversas (RA) a los farmacos anti-tuberculosis y/o si predispone a un peor resultado en pacientes con pacientes con TB multirresistente (TB-MR) y TB extremadamente resistente (TB-XR). El objetivo principal de este estudio fue describir los resultados del tratamiento anti-tuberculosis, el impacto de la DM y la prevalencia de RA en una cohorte de pacientes con TB pulmonar MR/XR tratados en el centro de referencia nacional para TB, en la Ciudad de Mexico. Resultados Entre 2010 y 2015 se incluyeron 90 pacientes —73 con TB-MR (81,1%), 11 con TB pre-XR (12,2%) y 6 (6,7%) con TB-XR—, 49 (54,4%) de los cuales tenian DM y 3 con co-infeccion por el virus de la inmunodeficiencia humana (VIH) (3,3%). El diagnostico se realizo mediante cultivo y pruebas de farmaco-sensibilidad (PFS) en el 98% de los pacientes y mediante prueba molecular en un caso. La presencia de DM se asocio con un mayor riesgo de RA graves, tales como nefrotoxicidad (odds ratio [OR] = 6,5; intervalo de confianza del 95% [IC 95%]: 1,9-21,8) e hipotiroidismo (OR = 8,8; IC 95%: 1,8-54,2), aunque no con peor resultado del tratamiento. Conclusiones Nuestros datos sugieren que la DM no tiene un impacto sobre los resultados del tratamiento anti-tuberculosis de segunda linea, pero los pacientes con DM tienen mayor riesgo de presentar RA graves secundarias al tratamiento, tales como nefrotoxicidad e hipotiroidismo.

Introduction Diabetes mellitus (DM), a very common disease in Mexico, is a well-known risk factor for tuberculosis (TB). However, it is not known by which extent DM predisposes to adverse events (AE) to anti-TB drugs and/or to worse outcomes in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB). The main objective of this study was to describe the outcomes of TB treatment, the impact of DM and the prevalence of AE in a cohort of patients with MDR-/XDR pulmonary TB treated at the national TB referral centre in Mexico City. Results Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (12.2%) and 6 (6.7%) with XDR-TB, including 49 (54.4%) with DM, and 3 with Human Immunodeficiency Virus (HIV) co-infection (3.3%). In 98% of patients, diagnosis was made by culture and drug susceptibility testing, while in a single case the diagnosis was made by a molecular test. The presence of DM was associated with an increased risk of serious drug-related AEs, such as nephrotoxicity (Odds Ratio [OR]=6.5; 95% Confidence Interval [95% CI]: 1.9–21.8) and hypothyroidism (OR=8.8; 95% CI: 1.8–54.2), but not for a worse outcome. Conclusions Our data suggest that DM does not impact second-line TB treatment outcomes, but patients with DM have a higher risk of developing serious AEs to drug-resistant TB treatment, such as nephrotoxicity and hypothyroidism.

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.

Summary WHO estimates that 9 million people developed active tuberculosis in 2013 and 1·5 million people died from it. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis continue to spread worldwide with an estimated 480 000 new cases in 2013. Treatment success rates of MDR and XDR tuberculosis are still low and development of new, more effective tuberculosis drugs and adjunct therapies to improve treatment outcomes are urgently needed. Although standard therapy for drug-sensitive tuberculosis is highly effective, shorter, more effective treatment regimens are needed to reduce the burden of infectious cases. We review the latest WHO guidelines and global recommendations for treatment and management of drug-sensitive and drug-resistant tuberculosis, and provide an update on new drug development, results of several phase 2 and phase 3 tuberculosis treatment trials, and other emerging adjunct therapeutic options for MDR and XDR tuberculosis. The use of fluoroquinolone-containing (moxifloxacin and gatifloxacin) regimens have failed to shorten duration of therapy, and the new tuberculosis drug pipeline is sparse. Scale-up of existing interventions with increased investments into tuberculosis health services, development of new antituberculosis drugs, adjunct therapies and vaccines, coupled with visionary political leadership, are still our best chance to change the unacceptable status quo of the tuberculosis situation worldwide and the growing problem of drug-resistant tuberculosis.

Multi-drug and extensively drug-resistant tuberculosis (MDR/XDR-TB) are considered a serious threat for TB control and elimination. The outcome of these patients is still largely unsatisfactory as of today, with treatment success rates being consistently below 50% at global level.The World Health Organization (WHO) recommends that management of MDR-TB cases is supported by a specialized team, including complementary medical professionals able to cover several perspectives (clinical, both for adults and children; surgical; radiological; public health; psychological; nursing, among others). Implementation of such a body (known as Consilium in most of the former Soviet Union countries) is often a pre-requisite to apply for international TB control funding and concessionally priced medicines to treat M/XDR-TB cases.The primary objective of the ERS/WHO TB Consilium is to provide clinical consultation for drug-resistant TB and other difficult-to-treat TB cases, including co-infection with HIV and paediatric cases. Through technical guidance to clinicians managing complex TB cases, the main contribution and outcome of the initiative will be a public health response aimed at achieving correct treatment of affected patients and preventing further development of drug resistance. The Consilum's secondary objective is to ensure monitoring and evaluation of clinical practices on the ground (diagnosis, treatment and prevention).

The number of international migrants worldwide has continued to grow rapidly over the past fifteen years and the trend is expected to continue, making the health matters associated with migration a crucial public health challenges faced by governments and societies. Multidrug-resistant tuberculosis is a paradigm of transmissible diseases that do not respect borders and poses a multifaceted and complex challenge on migrant health. The guiding principles for the health response are the respect of equity and human rights as well as the accurate analysis of epidemiological trends and determinants of TB in migrants. The action framework “Towards tuberculosis elimination: an action framework for low-incidence countries” includes regulations for cross border migration among the top eight interventions for TB elimination in low incidence countries. Political commitment is the essential requirement, and currently, the limiting factor, to draft regulations for cross-border collaboration, establish cross-border referral systems with contact tracing and information sharing. The e-platform TB Consilium hosted by European Respiratory Society in collaboration with World Health Organization – Euro is an example of a tool that can be used to exchange information for clinical management and surveillance.