Abstract Background Respiratory syncytial virus (RSV) primarily affects the respiratory tract, with a high burden among older adults. We aimed to estimate the prevalence and characteristics of RSV-associated respiratory infections in community-dwelling older adults across Europe. Methods A prospective, observational study was conducted in six European countries over three consecutive RSV seasons (October 2021 until April 2024). Non-RSV vaccinated participants (age ≥60 years) presenting with symptoms of acute respiratory infection (ARI) at general practitioners and outpatient clinics/outpatient hospitals were recruited. Respiratory syncytial virus and other respiratory viruses were detected using a combined nasal and throat swab. Diary cards and regular phone contacts were used to collect information on onset and resolution of symptoms. The prevalence of RT-PCR confirmed RSV-ARI (cRSV-ARI) was estimated, as well as symptom duration, underlying comorbidities, prevalence of RT-PCR confirmed RSV lower respiratory tract disease (cRSV-LRTD), complications, hospitalizations, and co-infections. Results A total of 2573 participants were enrolled (139 with cRSV-ARI). The prevalence of cRSV-ARI varied by season: 3.6% in Season 1, 9.3% in Season 2, and 4.2% in Season 3. The most frequently reported upper respiratory, lower respiratory, and systemic symptoms were nasal congestion/rhinorrhea, cough, and fatigue (cRSV-ARI: 83.1%, 97.8%, and 64.0%; non-cRSV-ARI: 78.0%, 95.0%, and 68.2%). The overall prevalence of cRSV-LRTD was 3.9% in Season 1, 12.5% in Season 2, and 7.3% in Season 3. Conclusions This study highlights the substantial burden of RSV among older adults in Europe and reflects the shift in RSV epidemiology due to the COVID-19 pandemic, indicating a return to prepandemic seasonality trends. Clinical Trial Registration Not applicable

While higher pyrazinamide and isoniazid exposures and slow NAT2 acetylator status were each associated with increased hepatotoxicity, only pyrazinamide exposure was associated when considering pharmacokinetic variables together. Rifampin exposure was not associated with hepatotoxicity, supporting further evaluation of doses up to 20 mg/kg/day in a larger trial.

Medical historians typically situate the origins of the antimicrobial era during the early germ period at the turn of the 20th century. They have regarded the development of chemical compounds designed to treat infectious diseases by killing their causative germ as the beginning of the antimicrobial era. Scholars, however, had been speculating about the causal relationship between germs and diseases for centuries beforehand. One of them also addressed the practical applications of this theory. The Italian physician Fracastoro proposed in 1546 that infectious diseases could be treated by administering substances to antagonize disease causing germs. He claimed that health could be restored to people who became ill with infections by nullifying the responsible germs at a time when investigators could not see germs or investigate their ability to cause disease. The long genealogy of antimicrobial therapy from its conception to its fruition took place over the span of several centuries.

Tularemia is caused by the gram-negative bacterium Francisella tularensis. Although rare, tularemia during pregnancy has been associated with pregnancy complications; data on efficacy of recommended antimicrobials for treatment are limited. We performed a systematic literature review to characterize clinical manifestations of tularemia during pregnancy and examine maternal, fetal, and neonatal outcomes with and without antimicrobial treatment. We searched 9 databases, including Medline, Embase, Global Health, and PubMed Central, using terms related to tularemia and pregnancy. Articles reporting cases of tularemia with ≥1 maternal or fetal outcome were included. Of 5891 articles identified, 30 articles describing 52 cases of tularemia in pregnant patients met inclusion criteria. Cases were reported from 9 countries, and oropharyngeal and ulceroglandular tularemia were the most common presenting forms. A plurality (46%) of infections occurred in the second trimester. Six complications were observed: lymph node aspiration, lymph node excision, maternal bleeding, spontaneous abortion, intrauterine fetal demise, and preterm birth. No deaths among mothers were reported. Of 28 patients who received antimicrobial treatment, 1 pregnancy loss and 1 fetal death were reported. Among 24 untreated patients, 1 pregnancy loss and 3 fetal deaths were reported, including one where F. tularensis was detected in placental and fetal tissues. Pregnancy loss and other complications have been reported among cases of tularemia during pregnancy. However, risk of adverse outcomes may be lower when antimicrobials known to be effective are used. Without treatment, transplacental transmission appears possible. These data underscore the importance of prompt recognition and treatment of tularemia during pregnancy.

Francisella tularensis, the causative agent of tularemia, is endemic throughout the Northern Hemisphere and requires as few as 10 organisms to cause disease, making this potential bioterrorism agent one of the most infectious bacterial pathogens known. Aminoglycosides, tetracyclines, and, more recently, fluoroquinolones are used for treatment of tularemia; however, data on the relative effectiveness of these and other antimicrobial classes are limited. Nine databases, including Medline, Global Health, and Embase, were systematically searched for articles containing terms related to tularemia. Articles with case-level data on tularemia diagnosis, antimicrobial treatment, and patient outcome were included. Patient demographics, clinical findings, antimicrobial administration, and outcome (eg, intubation, fatality) were abstracted using a standardized form. Of the 8878 publications identified and screened, 410 articles describing 870 cases from 1993 to 2023 met inclusion criteria. Cases were reported from 35 countries; more than half were from the United States, Turkey, or Spain. The most common clinical forms were ulceroglandular, oropharyngeal, glandular, and pneumonic disease. Among patients treated with aminoglycosides (n = 452 [52%]), fluoroquinolones (n = 339 [39%]), or tetracyclines (n = 419 [48%]), the fatality rate was 0.7%, 0.9%, and 1.2%, respectively. Patients with pneumonic disease who received ciprofloxacin had no fatalities and the lowest rates of thoracentesis/pleural effusion drainage and intubation compared to those who received aminoglycosides and tetracyclines. Aminoglycosides, fluoroquinolones, and tetracyclines are effective antimicrobials for treatment of tularemia, regardless of clinical manifestation. For pneumonic disease specifically, ciprofloxacin may have slight advantages compared to other antimicrobials.

Journal Article Corrected proof Beyond Diagnosis: Xpert Cycle Threshold Values as Predictors of Tuberculosis Transmission Get access Lauren Linde, Lauren Linde Department of Epidemiology, Boston University, School of Public Health, Boston, Massachusetts, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Meredith B Brooks, Meredith B Brooks Department of Global Health, Boston University, School of Public Health, Boston, Massachusetts, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Leonardo Martinez Leonardo Martinez Department of Epidemiology, Boston University, School of Public Health, Boston, Massachusetts, USA Correspondence: L. Martinez, Department of Epidemiology, Boston University School of Public Health, 715 Albany St, Boston, MA 02118 (leomarti@bu.edu). https://orcid.org/0000-0003-0954-8489 Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinical Infectious Diseases, ciad791, https://doi.org/10.1093/cid/ciad791 Published: 03 January 2024 Article history Received: 20 December 2023 Editorial decision: 22 December 2023 Accepted: 28 December 2023 Published: 03 January 2024 Corrected and typeset: 22 January 2024