Availability of drugs for the treatment of multidrug-resistant/rifampicin-resistant tuberculosis in the World Health Organization European Region, October 2023.

The BPaLM regimen (bedaquiline, pretomanid, linezolid and moxifloxacin) recently recommended by the World Health Organization offers short, safe, and effective treatment for multidrug-resistant/rifampicin-resistant tuberculosis (TB). In a survey with national TB focal points in 18 central and western European countries to explore barriers for the implementation of BPaLM, only three reported full availability of pretomanid, a necessary component of this regimen. Implementation barriers included financing and procurement. Solutions on national and supranational level are needed to guarantee universal access.

[Treatment of MDR, pre-XDR, XDR and rifampicin resistant tuberculosis or in case of intolerance to at least rifampicin in Austria, Germany and Switzerland - Amendment dated 19.09.2023 to the Sk2-Guideline: Tuberculosis in adulthood of the German Central Committee against Tuberculosis (DZK) on behalf of the German Respiratory Society (DGP)]. / Therapie bei MDR-, prä-XDR-, XDR-Tuberkulose und Rifampicin-Resistenz oder bei Medikamentenunverträglichkeit gegenüber mindestens Rifampicin.

In December 2022, based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB). The evaluation of both, these recommendations, and the latest study data, makes it necessary to update the existing guidelines on the treatment of at least rifampicin-resistant tuberculosis for the German-speaking region, hereby replacing the respective chapters. A shortened MDR-TB treatment of at least 6 month using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Germany, Austria, and Switzerland under certain conditions. This recommendation applies to TB cases with proven rifampicin resistance, including rifampicin monoresistance. For treatment of pre-extensively drug resistant TB (pre-XDR-TB), an individualized treatment for 18 months adjusted to resistance data continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in pre-XDR TB if all prerequisites are met. The necessary prerequisites for the use of BPaLM and BPaL are presented in this amendment to the S2k guideline for 'Tuberculosis in adulthood'.

[Recommendations for Contact Tracing for Tuberculosis - Update 2023]. / Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose ­ Update 2023.

The aim of contact tracing for tuberculosis is in addition to active case finding the detection of chains of infection and the prevention of the further spread of the disease. In this context, a careful selection of contact persons is necessary, depending on the type and duration of contact, to identify persons who are recently infected and therefore to increase the benefit of a preventive therapy and to avoid unnecessary testing of persons who are not at risk of infection. Since the last update of the recommendations on contact tracing, data on the use of interferon-y release assays (IGRAs) in children has been improved markedly. These are the preferred test in contact tracing of adults. For children, both IGRAs and the tuberculin skin test can be used equivalently. Rifampicin for 4 months, rifampicin and isoniazid for 3 months, or isoniazid for 9 months are recommended as preventive therapy in cases of confirmed infection.The implementation of the contact tracing in different age groups as well as legal framework conditions and socio-medical aspects and challenges are dealt with in detail. In addition, special cases, such as environmental screening in day-care centers, schools, or other community facilities, are discussed separately.

[Tuberculosis Infection Control & Hygiene - Recommendations of the DZK]. / Infektionsprävention & Hygiene bei Tuberkulose ­ Empfehlungen des DZK.

Preventing the spread of the disease is an essential goal in the care and treatment of tuberculosis. In addition to early diagnosis and effective therapies, isolation of infectious patients and adequate hygiene measures are of particular importance for infection prevention. The present recommendations replace the previous recommendations "tuberculosis infection control" from 2012 and take into account the current national and international recommendations and as well as new scientific findings. After a description of the infection and the transmission pathways, the necessary prevention and hygiene measures in health care facilities are comprehensively presented. Since the last revision of the recommendations on infection prevention, international recommendations and the KRINKO recommendation on ending isolation have been changed. In accordance with this, under certain conditions in the case of sensitive tuberculosis, de-isolation in health care facilities can take place after 14 days without taking the sputum findings into account. The second part of the recommendations explains in detail the measures to be taken in special situations and areas, such as general practitioners, ambulance services and care facilities. Here, the recommendations on respiratory protection have been simplified; for staff, an FFP2 mask is now generally considered sufficient.

[Recommendations for contact tracing for tuberculosis - update 2023]. / Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose ­ Update 2023.

The aim of contact tracing for tuberculosis is in addition to active case finding the detection of chains of infection and the prevention of the further spread of the disease. In this context, a careful selection of contact persons is necessary, depending on the type and duration of contact, to identify persons who are recently infected and therefore to increase the benefit of a preventive therapy and to avoid unnecessary testing of persons who are not at risk of infection. Since the last update of the recommendations on contact tracing, data on the use of interferon-y release assays (IGRAs) in children has been improved markedly. These are the preferred test in contact tracing of adults. For children, both IGRAs and the tuberculin skin test can be used equivalently. Rifampicin for 4 months, rifampicin and isoniazid for 3 months, or isoniazid for 9 months are recommended as preventive therapy in cases of confirmed infection.The implementation of the contact tracing in different age groups as well as legal framework conditions and socio-medical aspects and challenges are dealt with in detail. In addition, special cases, such as environmental screening in day-care centers, schools, or other community facilities, are discussed separately.

Quantifying progression and regression across the spectrum of pulmonary tuberculosis: a data synthesis study.

BACKGROUND: Prevalence surveys show a substantial burden of subclinical (asymptomatic but infectious) tuberculosis, from which individuals can progress, regress, or even persist in a chronic disease state. We aimed to quantify these pathways across the spectrum of tuberculosis disease. METHODS: We created a deterministic framework of untreated tuberculosis disease with progression and regression between three states of pulmonary tuberculosis disease: minimal (non-infectious), subclinical (asymptomatic but infectious), and clinical (symptomatic and infectious). We obtained data from a previous systematic review of prospective and retrospective studies that followed and recorded the disease state of individuals with tuberculosis in a cohort without treatment. These data were considered in a Bayesian framework, enabling quantitative estimation of tuberculosis disease pathways with rates of transition between states and 95% uncertainty intervals (UIs). FINDINGS: We included 22 studies with data from 5942 individuals in our analysis. Our model showed that after 5 years, 40% (95% UI 31·3-48·0) of individuals with prevalent subclinical disease at baseline recover and 18% (13·3-24·0) die from tuberculosis, with 14% (9·9-19·2) still having infectious disease, and the remainder with minimal disease at risk of re-progression. Over 5 years, 50% (40·0-59·1) of individuals with subclinical disease at baseline never develop symptoms. For those with clinical disease at baseline, 46% (38·3-52·2) die and 20% (15·2-25·8) recover from tuberculosis, with the remainder being in or transitioning between the three disease states after 5 years. We estimated the 10-year mortality of people with untreated prevalent infectious tuberculosis to be 37% (30·5-45·4). INTERPRETATION: For people with subclinical tuberculosis, classic clinical disease is neither an inevitable nor an irreversible outcome. As such, reliance on symptom-based screening means a large proportion of people with infectious disease might never be detected. FUNDING: TB Modelling and Analysis Consortium and European Research Council.

The natural history of untreated pulmonary tuberculosis in adults: a systematic review and meta-analysis.

Stages of tuberculosis disease can be delineated by radiology, microbiology, and symptoms, but transitions between these stages remain unclear. In a systematic review and meta-analysis of studies of individuals with untreated tuberculosis who underwent follow-up (34 cohorts from 24 studies, with a combined sample of 139 063), we aimed to quantify progression and regression across the tuberculosis disease spectrum by extracting summary estimates to align with disease transitions in a conceptual framework of the natural history of tuberculosis. Progression from microbiologically negative to positive disease (based on smear or culture tests) in participants with baseline radiographic evidence of tuberculosis occurred at an annualised rate of 10% (95% CI 6·2-13·3) in those with chest x-rays suggestive of active tuberculosis, and at a rate of 1% (0·3-1·8) in those with chest x-ray changes suggestive of inactive tuberculosis. Reversion from microbiologically positive to undetectable disease in prospective cohorts occurred at an annualised rate of 12% (6·8-18·0). A better understanding of the natural history of pulmonary tuberculosis, including the risk of progression in relation to radiological findings, could improve estimates of the global disease burden and inform the development of clinical guidelines and policies for treatment and prevention.

[Tuberculosis in adulthood - The Sk2-Guideline of the German Central Committee against Tuberculosis (DZK) and the German Respiratory Society (DGP) for the diagnosis and treatment of adult tuberculosis patients]. / Tuberkulose im Erwachsenenalter.

In Germany tuberculosis is a rare disease and usually well treatable. Worldwide it is one of the most common infectious diseases with approximately 10 million new cases every year. Even with low incidences in Germany, tuberculosis is an important differential diagnosis especially due to international developments and migration movements. With a decreasing experience there's a continuous demand on accurate and up-to-date information. This guideline covers all aspects of microbiological diagnostics, basic principles of standard therapy, treatment of extrapulmonary tuberculosis, management of side effects, special features of diagnosis and treatment of resistant tuberculosis, and treatment in TB-HIV coinfection. Also, it explains when treatment in specialized centers is required, aspects of care and legal regulations and the diagnosis and preventive therapy of latent tuberculosis infection. The update of the S2k guideline "Tuberculosis in Adults" is intended to serve as a guideline for prevention, diagnosis, and treatment of tuberculosis for all those involved in tuberculosis care and to help meet the current challenges in dealing with tuberculosis in Germany.

Risk Assessment for Patients with Chronic Respiratory Conditions in the Context of the SARS-CoV-2 Pandemic Statement of the German Respiratory Society with the Support of the German Association of Chest Physicians.

Assessing the risk for specific patient groups to suffer from severe courses of COVID-19 is of major importance in the current SARS-CoV-2 pandemic. This review focusses on the risk for specific patient groups with chronic respiratory conditions, such as patients with asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF), sarcoidosis, interstitial lung diseases, lung cancer, sleep apnea, tuberculosis, neuromuscular diseases, a history of pulmonary embolism, and patients with lung transplants. Evidence and recommendations are detailed in exemplary cases. While some patient groups with chronic respiratory conditions have an increased risk for severe courses of COVID-19, an increasing number of studies confirm that asthma is not a risk factor for severe COVID-19. However, other risk factors such as higher age, obesity, male gender, diabetes, cardiovascular diseases, chronic kidney or liver disease, cerebrovascular and neurological disease, and various immunodeficiencies or treatments with immunosuppressants need to be taken into account when assessing the risk for severe COVID-19 in patients with chronic respiratory diseases.