Challenging MDR-TB clinical problems - The case for a new Global TB Consilium supporting the compassionate use of new anti-TB drugs.

MDR-TB is a growing challenge worldwide, and an obstacle to TB elimination. It is apparent that TB is being replaced by small but growing number of resistant cases with an anticipated 2 million cases of MDR-TB within the next two decades. One of the potential causes of MDR-TB is iatrogenic and we risk losing our new drugs through inexperience and repetition of basic errors of adding single active drugs to failing regimens. Discussion of MDR-TB cases with senior colleagues is not only best practice; it is now embedded in the WHO and many national and local guidelines.TB Consilia act as gatekeepers to the new drugs, monitor guideline adherence and mandate active drug safety monitoring. TB Consilia are also excellent educational tools.TB Consilia are now recommended by funding bodies, the WHO and manufacturers of drugs available for compassionate use in the hope that these drugs will be protected and will continue to be useful in the future. This article briefly discusses Consilia, their origin and evolution and gives some examples of how they operate. Keywords: TB, MDR-TB, TB Consilium, Prevention, New TB drugs, Compassionate use, Alderott

Do we need a new Fleming époque: The nightmare of drug-resistant tuberculosis.

Tuberculosis represents an important clinical and public health problem globally, particularly in low- and middle-income countries. During the last 20 years, two relevant events has changed the epidemiology of the disease: the spread of the TB/HIV co-infection and the emergence and spread of the multi-drug resistance tuberculosis (i.e., tuberculosis caused by strains resistant to at least isoniazid and rifampicin). The latter phenomenon has been generated by the inappropriate management of the anti-tuberculosis drugs. Currently, the World Health Organization estimates at least 600,000 MDR-TB cases worldwide, particularly in China, India, South Africa, and in former Soviet Union countries. Unfortunately, new difficult-to-treat MDR-TB cases have been described, named XDR- or TDR-TB (extensively or totally drug-resistant tuberculosis, respectively). Numerous observational retrospective studies proved the poorer prognostic profile of the MDR-TB cases when compared with drug-susceptible tuberculosis. The clinical management of the patients with an XDR and beyond pattern is complicated owing to the poorest, expensive, and toxic therapeutic options. MDR-TB is currently under-reported because of methodological issues, mainly related to the poor proficiency of laboratory testing. National public health strategies should reduce the increase of tuberculosis cases without therapeutic alternatives. Furthermore, research and development activities, based on continuous and sustained funding, should be improved, together with the implementation and the scale-up of effective infection control measures in healthcare settings and in the community. © 2013 Asian-African Society for Mycobacteriology

How We Treat Drug-Susceptible Pulmonary Tuberculosis: A Practical Guide for Clinicians

Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide and pulmonary TB (PTB) is the main variant responsible for fueling transmission of the infection. Effective treatment of drug-susceptible (DS) TB is crucial to avoid the emergence of Mycobacterium tuberculosis-resistant strains. In this narrative review, through a fictional suggestive case of DS PTB, we guide the reader in a step-by-step commentary to provide an updated review of current evidence in the management of TB, from diagnosis to post-treatment follow-up. World Health Organization and Centre for Diseases Control (CDC) guidelines for TB, as well as the updated literature, were used to support this manuscript

Disseny d'una cambra frigorífica al municipi de Seròs

El present projecte tracta del disseny, per a la posterior construcció, d'una cambra frigorífica destinada al refredament de la fruita recent recol·lectada. El principal objectiu d'aquesta cambra es poder conservar la fruita freda durant posc dies per poder-la distribuir arreu d'Espanya quan convingui, tot i que també té com a avantatge que el propietari pot recol·lectar els fruits durant els dies festius i guardar-los en bones condicions tèrmiques

Prevalence of bacteriologically confirmed pulmonary tuberculosis in South Africa, 2017-19 : a multistage, cluster-based, cross-sectional survey

DATA SHARING : Individual, deidentified participant data, including data dictionaries, may be shared. Templates of the informed consent forms may be shared upon request. The data will be available following publication, with no end date, and will be shared with anyone who wishes to access them with a clear data sharing agreement, for any purpose of analyses. For data access, please contact the corresponding author and the tuberculosis programme at the National Department of Health in South Africa.BACKGROUND : Tuberculosis remains an important clinical and public health issue in South Africa, which has one of the highest tuberculosis burdens in the world. We aimed to estimate the burden of bacteriologically confirmed pulmonary tuberculosis among people aged 15 years or older in South Africa. METHODS : This multistage, cluster-based, cross-sectional survey included eligible residents (age ≥15 years, who had slept in a house for ≥10 nights in the preceding 2 weeks) in 110 clusters nationally (cluster size of 500 people; selected by probability proportional-to-population size sampling). Participants completed face-to-face symptom questionnaires (for cough, weight loss, fever, and night sweats) and manually read digital chest X-ray screening. Screening was recorded as positive if participants had at least one symptom or an abnormal chest X-ray suggestive of tuberculosis, or a combination thereof. Sputum samples from participants who were screen-positive were tested by the Xpert MTB/RIF Ultra assay (first sample) and Mycobacteria Growth Indicator Tube culture (second sample), with optional HIV testing. Participants with a positive Mycobacterium tuberculosis complex culture were considered positive for bacteriologically confirmed pulmonary tuberculosis; when culture was not positive, participants with a positive Xpert MTB/RIF Ultra result with an abnormal chest X-ray suggestive of active tuberculosis and without current or previous tuberculosis were considered positive for bacteriologically confirmed pulmonary tuberculosis. FINDINGS : Between Aug 15, 2017, and July 28, 2019, 68 771 people were enumerated from 110 clusters, with 53 250 eligible to participate in the survey, of whom 35 191 (66·1%) participated. 9066 (25·8%) of 35 191 participants were screen-positive and 234 (0·7%) were identified as having bacteriologically confirmed pulmonary tuberculosis. Overall, the estimated prevalence of bacteriologically confirmed pulmonary tuberculosis was 852 cases (95% CI 679–1026) per 100 000 population; the prevalence was highest in people aged 35–44 years (1107 cases [95% CI 703–1511] per 100 000 population) and those aged 65 years or older (1104 cases [680–1528] per 100 000 population). The estimated prevalence was approximately 1·6 times higher in men than in women (1094 cases [95% CI 835–1352] per 100 000 population vs 675 cases [494–855] per 100 000 population). 135 (57·7%) of 234 participants with tuberculosis screened positive by chest X-ray only, 16 (6·8%) by symptoms only, and 82 (35·9%) by both. 55 (28·8%) of 191 participants with tuberculosis with known HIV status were HIV-positive. INTERPRETATION : Pulmonary tuberculosis prevalence in this survey was high, especially in men. Despite the ongoing burden of HIV, many participants with tuberculosis in this survey did not have HIV. As more than half of the participants with tuberculosis had an abnormal chest X-ray without symptoms, prioritising chest X-ray screening could substantially increase case finding.Global Fund, Bill & Melinda Gates Foundation, USAID.http://www.thelancet.com/infectionhj2023Medical Microbiolog

Compassionate use of new drugs in children and adolescents with multidrug-resistant and extensively drug-resistant tuberculosis: early experiences and challenges

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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

Worldwide Effects of Coronavirus Disease Pandemic on Tuberculosis Services, January–April 2020

Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic

Combining bedaquiline and delamanid to treat multidrug-resistant tuberculosis

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