Treatment of MDR, Pre-XDR, XDR, and Rifampicin-Resistant Tuberculosis or in Case of Intolerance to at Least Rifampicin in Austria, Germany, and Switzerland.

Based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB) in December 2022. The new recommendations and the latest study data made it necessary to update the existing guideline on the treatment of at least rifampicin-resistant TB (RR-TB) for the German-speaking countries, replacing the respective chapters of the treatment guidelines published in 2022. A shortened treatment of proven RR-TB and multidrug-resistant TB for at least 6 months using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Austria, Germany, and Switzerland under certain conditions considering the existing barriers for the implementation of the new treatment regimen. For the treatment of pre-extensively drug-resistant (pre-XDR-) TB, an individualized treatment for 18 months continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in selected pre-XDR-TB cases, provided that all prerequisites are met. The necessary requirements for using BPaLM and BPaL are presented in detail in this amendment to the consensus-based TB treatment guideline for adult patients.

[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.

[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.

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.

Complications of influenza in 272 adult and pediatric patients in a German university hospital during the seasonal epidemic 2017-2018.

BACKGROUND: The influenza season 2017-2018 of the northern hemisphere was the highest since 2001 and was caused predominantly by influenza B virus. METHODS: We performed a retrospective analysis of all patients in a university hospital in northern Germany with laboratory-confirmed influenza during the winter season 2017-2018 and analyzed underlying conditions, complications, and outcome. RESULTS: A total of 272 cases of influenza were diagnosed: 70 influenza A (25.7%), 201 influenza B (73.9%), and 1 co-infection. Of 182 adults, 145 were hospitalized, 73 developed pneumonia, 11 developed myocardial infarction, two a transient ischemic attack, one a stroke, and one perimyocarditis. Eleven of the 145 hospitalized adult patients (7.6%) died, ten of them because of pneumonia. All of them had preexisting diseases. Pneumonia was associated with a mortality of 13.7%. Underlying cardiac insufficiency was correlated with higher mortality (7/51 with versus 4/126 patients without cardiac insufficiency; p < 0.05). Ninety cases of influenza were diagnosed in 89 children (30 A, 60 B), one child had first influenza B, then influenza A. Twenty-eight children (31%) were hospitalized, 15 children developed one or more complications (lower respiratory tract infections, meningeal irritations, febrile seizures, otitis media, myositis). No child died. Influenza vaccination status was known in 149 adult patients, pneumonia occurred more frequently in non-vaccinated individuals (43/90; 47.8%) than in vaccinated patients (18/59; 30.5%, p < 0.05). CONCLUSION: Patients with influenza should be monitored for secondary pneumonia and myocardial infarction, and vaccination should be enforced especially in patients with coronary heart disease and cardiac insufficiency.

[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.

Longitudinal detection of SARS-CoV-2-specific antibody responses with different serological methods.

Serological testing for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is used to detect ongoing or past SARS-CoV-2 infections. To study the kinetics of anti-SARS-CoV-2 antibodies and to assess the diagnostic performances of eight serological assays, we used 129 serum samples collected on known days post symptom onset (dpso) from 42 patients with polymerase chain reaction-confirmed coronavirus disease 2019 (COVID-19) and 54 serum samples from healthy blood donors, and children infected with seasonal coronaviruses. The sera were analyzed for the presence of immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) antibodies using indirect immunofluorescence testing (IIFT) based on SARS-CoV-2-infected cells. They were further tested for antibodies against the S1 domain of the SARS-CoV-2 spike protein (IgG, IgA) and against the viral nucleocapsid protein (IgG, IgM) using enzyme-linked immunosorbent assays. The assay specificities were 94.4%-100%. The sensitivities varied largely between assays, reflecting their respective purposes. The sensitivities of IgA and IgM assays were the highest between 11 and 20 dpso, whereas the sensitivities of IgG assays peaked between 20 and 60 dpso. IIFT showed the highest sensitivities due to the use of the whole SARS-CoV-2 as substrate and provided information on whether or not the individual has been infected with SARS-CoV-2. Enzyme-linked immunosorbent assays provided further information about both the prevalence and concentration of specific antibodies against selected antigens of SARS-CoV-2.

[COVID-19: epidemiology and clinical facts]. / COVID-19: Epidemiologische und klinische Fakten.

Until July 31, 2020, about 17.6 million SARS-CoV­2 infections and 680,000 deaths from COVID-19 were reported. SARS-CoV­2 is most likely transmitted by droplets and probably by aerosols. Patients become infectious 2-3 days before the onset of symptoms, and persons with asymptomatic infections are also infectious. COVID-19 affects the upper respiratory tract, lungs (pneumonia, acute respiratory distress syndrome [ARDS]), heart, liver, gastrointestinal tract, and other organs. SARS-CoV­2 uses ACE2 a receptor to enter host cells. Vasculitis, endothelial damage, thromboembolic events and organ failure are accompanied by a massive cytokine response. Elderly people and those with pre-existing diseases are particularly vulnerable. An efficient antiviral therapy is not yet available. Severely ill patients may benefit from dexamethasone and early treatment of complications. Candidate vaccines are currently being tested in clinical studies.

A phase III, open-label, single-arm, study to evaluate the safety and immunogenicity of a trivalent, surface antigen inactivated subunit influenza virus vaccine produced in mammalian cell culture (Optaflu®) in healthy adults.

Vaccination is an essential tool in reducing the impact of seasonal influenza infections. The viral strains responsible for seasonal outbreaks vary annually, and preventive vaccines have to be adapted accordingly. The aim of this study was to evaluate the safety, clinical tolerability and the antibody response to each of the three influenza vaccine antigens after vaccination with a cell-derived, trivalent, surface antigen, inactivated influenza vaccine (TIVc), as measured by single radial haemolysis (SRH) or haemagglutination inhibition (HI) assay in accordance with European Union licensing guidelines in place for years 2013/2014. This phase 3, open-label, single-arm study enrolled 126 healthy adults divided into two age groups (63 subjects aged 18 to ≤ 60 years and 63 subjects aged ≥ 61 years). Antibody titres were measured before and 21 days after vaccination. Adverse events were determined using diary cards, interviews and reviews of the available medical records. One subject was lost to follow-up and three subjects had protocol deviations. Following vaccination, protective HI antibody titres (≥ 1:40) were detected in 100%, 97%, and 94% of the younger adults (18-≤ 60 years) and in 97%, 95%, and 80% of the older adults (≥ 61 years) against the A (H1N1), A (H3N2), and B influenza strains respectively. The antibody response licensing criteria were met in both age groups. Solicited adverse events were reported by 57% subjects 18 to ≤ 60 years and 35% subjects ≥ 61 years. Among the younger adults 51% had local and 27% had systemic adverse events, whereas of the older subjects 29% had local and 13% had systemic adverse events (mainly injection site pain or headache in both age groups). Unsolicited adverse events at least possibly related to the vaccine were mild and detected in 3% of the younger adults and none of the older adults. Overall, the trivalent, surface antigen, inactivated subunit influenza virus vaccine produced in mammalian cell culture proved to be safe and immunogenic in younger and older healthy adults.

Tuberculosis-associated hemophagocytic lymphohistiocytosis with subsequent unmasking cryptococcal immune reconstitution inflammatory syndrome (IRIS) in an HIV-negative man.

A 22-year-old HIV-negative man from Ghana was diagnosed with severe hemophagocytic lymphohistiocytosis (HLH) induced by multiorgan tuberculosis with peritoneal, hepatic, pericardial, myocardial, pleural, pulmonary, and bone manifestation. His body mass index was 12.9 m2/kg. Bioptic material of a peritoneal biopsy grew M. tuberculosis, sensitive to all first-line antituberculous drugs. HLH resolved with antituberculous therapy, without additional anti-inflammatory therapy being given. The initial CT scan of his brain was normal. After 5 months of antituberculous treatment, he developed a paralysis of the left arm. A cerebral MRT showed ring-enhanced lesions. Blood cultures and lumbar puncture revealed Cryptococcus neoformans var. grubi. The HIV test was repeatedly negative. Antituberculous treatment was continued for a total of 9 months, and additional treatment with antifungal therapy was established. He recovered fully after 14 months of antifungal treatment.

Tuberculosis and Takayasu arteritis: case-based review.

This report presents a case of co-occurrence of Takayasu arteritis (TA) and multiorgan tuberculosis (TB) in a 20-year-old female and provides a review of 18 previously reported cases of co-occurring TA and TB. All patients were between 9 and 24 years of age. Most reports describe a concomitant diagnosis of active TB and TA. TB lymphadenitis was described in 11 cases (57.9%), and microbiologically confirmed in 4 of these. All patients received antituberculous therapy and most received corticosteroids (89.5%). In our and two other cases, TA relapses necessitating additional immunosuppressive therapy were observed.

Performance Analysis of Serodiagnostic Tests to Characterize the Incline and Decline of the Individual Humoral Immune Response in COVID-19 Patients: Impact on Diagnostic Management.

Serodiagnostic tests for antibody detection to estimate the immunoprotective status regarding SARS-CoV-2 support diagnostic management. This study aimed to investigate the performance of serological assays for COVID-19 and elaborate on test-specific characteristics. Sequential samples (n = 636) of four panels (acute COVID-19, convalescent COVID-19 (partly vaccinated post-infection), pre-pandemic, and cross-reactive) were tested for IgG by indirect immunofluorescence test (IIFT) and EUROIMMUN EUROLINE Anti-SARS-CoV-2 Profile (IgG). Neutralizing antibodies were determined by a virus neutralization test (VNT) and two surrogate neutralization tests (sVNT, GenScript cPass, and EUROIMMUN SARS-CoV-2 NeutraLISA). Analysis of the acute and convalescent panels revealed high positive (78.3% and 91.6%) and negative (91.6%) agreement between IIFT and Profile IgG. The sVNTs revealed differences in their positive (cPass: 89.4% and 97.0%, NeutraLISA: 71.5% and 72.1%) and negative agreement with VNT (cPass: 92.3% and 50.0%, NeutraLISA: 95.1% and 92.5%) at a diagnostic specificity of 100% for all tests. The cPass showed higher inhibition rates than NeutraLISA at VNT titers below 1:640. Cross-reactivities were only found by cPass (57.1%). Serodiagnostic tests, which showed substantial agreement and fast runtime, could provide alternatives for cell-based assays. The findings of this study suggest that careful interpretation of serodiagnostic results obtained at different times after SARS-CoV-2 antigen exposure is crucial to support decision-making in diagnostic management.

Distinguishing Incubation and Acute Disease Stages of Mild-to-Moderate COVID-19.

While numerous studies have already compared the immune responses against SARS-CoV-2 in severely and mild-to-moderately ill COVID-19 patients, longitudinal trajectories are still scarce. We therefore set out to analyze serial blood samples from mild-to-moderately ill patients in order to define the immune landscapes for differently progressed disease stages. Twenty-two COVID-19 patients were subjected to consecutive venipuncture within seven days after diagnosis or admittance to hospital. Flow cytometry was performed to analyze peripheral blood immune cell compositions and their activation as were plasma levels of cytokines and SARS-CoV-2 specific immunoglobulins. Healthy donors served as controls. Integrating the kinetics of plasmablasts and SARS-CoV-2 specific antibodies allowed for the definition of three disease stages of early COVID-19. The incubation phase was characterized by a sharp increase in pro-inflammatory monocytes and terminally differentiated cytotoxic T cells. The latter correlated significantly with elevated concentrations of IP-10. Early acute infection featured a peak in PD-1+ cytotoxic T cells, plasmablasts and increasing titers of virus specific antibodies. During late acute infection, immature neutrophils were enriched, whereas all other parameters returned to baseline. Our findings will help to define landmarks that are indispensable for the refinement of new anti-viral and anti-inflammatory therapeutics, and may also inform clinicians to optimize treatment and prevent fatal outcomes.

[Screening of Mothers in a COVID-19 Low-Prevalence Region: Determination of SARS-CoV-2 Antibodies in 401 Mothers from Rostock by ELISA and Confirmation by Immunofluorescence]. / Mütter-Screening in einem COVID-19-Niedrig-Pandemiegebiet: Bestimmung SARS-CoV-2-spezifischer Antikörper bei 401 Rostocker Müttern mittels ELISA und Immunfluoreszenz-Bestätigungstest.

BACKGROUND: In children, the infection with SARS-CoV-2, the cause of COVID-19, tends to be clinically inapparent more often or less severe than in adults. The spread of this infection from children poses a danger to vulnerable adults. Therefore, child care institutions and schools currently are widely closed. METHODS: Since the status of infection tends to be congruent in mothers and their children, we tested 401 mothers of children between 1 and 10 years in the city of Rostock (State of Mecklenburg-Westpomerania, northeast of Germany), for the presence of RNA of SARS-CoV-2 in throat swabs, and of antibodies against SARS-CoV-2 in serum. RESULTS: In none of the mothers tested, RNA of this virus was detected in the throat swab. In the ELISA test, IgG antibodies were positive in one serum sample, IgA antibodies were positive in 11, and borderline in 3 serum samples. All 401 sera were negative in the indirect immunofluorescence test (IIFT) with FITC-labeled IgG, IgA, und IgM antibodies. CONCLUSION: At the time of this study, neither SARS-CoV-2 RNA, nor specific antibodies against SARS-CoV-2 were detectable in the mothers tested in Rostock.

RE: 'Streptococcus pluranimalium: A novel human pathogen?'

Streptococcus pluranimalium as a novel human pathogen has been reported by several authors in various contexts. In all reported cases in humans the microorganism was detected by the Vitek2®. The great advances with the introduction of new analytical techniques such as MALDI-TOF or 16S rRNA analysis enabled a more detailed discrimination of pathogens such as these nonhemolytic streptococci. In the cases of such similar gene sequences such techniques are absolutely essential to identify the exact strain for this highly conserved 16S rRNA gene. However, until now neither a sequence analysis of the 16S rRNA gene nor PCR nor MALDI-TOF techniques could define Streptococcus pluranimalium in humans. We conclude that according to our best present knowledge there exists no conclusive evidence for a human infection of Streptococcus pluranimalium even when using most advanced and exact identification techniques until now.

[BCGitis with Involvement of Lung, Liver and Bone Marrow after Immunotherapy of Urothelial Cancer]. / BCGitis mit Lungen-, Leber- und Knochenmarksbeteiligung nach Immuntherapie eines Urothelkarzinoms.

Medical history A 77-year-old patient with transurethral resection of a bladder tumor was transferred due to persistent fever and progressive dyspnea despite antibiotic therapy for suspected urinary tract infection. Repeating the medical history revealed that a BCG immunotherapy of his non-muscle-invasive bladder carcinoma was performed the day before fever developed. Therefore, BCGitis was suspected. Examinations Laboratory parameters showed pancytopenia, elevated liver enzymes, eleveated C-reactive protein and hypoxemia. The CT scan showed multiple miliary lesions of the lung, the bone marrow biopsy revealed granuloma. Diagnosis M. bovis BCG was cultured from urine and bronchoalveolar lavage fluid. Therapy and course Therapy with isoniazide, rifampine, ethambutol and initially prednisolone caused rapid improvement. Conclusion BCGitis is a rare complication of BCG immunotherapy of non-muscle-invasive bladder carcinoma.