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Background Unrest in Myanmar in August 2017 resulted in the movement of over 700,000 Rohingya refugees to overcrowded camps in Cox's Bazar, Bangladesh. A large outbreak of diphtheria subsequently began in this population. Methods and findings Data were collected during mass vaccination campaigns (MVCs), contact tracing activities, and from 9 Diphtheria Treatment Centers (DTCs) operated by national and international organizations. These data were used to describe the epidemiological and clinical features and the control measures to prevent transmission, during the first 2 years of the outbreak. Between November 10, 2017 and November 9, 2019, 7,064 cases were reported: 285 (4.0%) laboratory-confirmed, 3,610 (51.1%) probable, and 3,169 (44.9%) suspected cases. The crude attack rate was 51.5 cases per 10,000 person-years, and epidemic doubling time was 4.4 days (95% confidence interval [CI] 4.2-4.7) during the exponential growth phase. The median age was 10 years (range 0-85), and 3,126 (44.3%) were male. The typical symptoms were sore throat (93.5%), fever (86.0%), pseudomembrane (34.7%), and gross cervical lymphadenopathy (GCL; 30.6%). Diphtheria antitoxin (DAT) was administered to 1,062 (89.0%) out of 1,193 eligible patients, with adverse reactions following among 229 (21.6%). There were 45 deaths (case fatality ratio [CFR] 0.6%). Household contacts for 5,702 (80.7%) of 7,064 cases were successfully traced. A total of 41,452 contacts were identified, of whom 40,364 (97.4%) consented to begin chemoprophylaxis; adherence was 55.0% (N = 22,218) at 3-day follow-up. Unvaccinated household contacts were vaccinated with 3 doses (with 4-week interval), while a booster dose was administered if the primary vaccination schedule had been completed. The proportion of contacts vaccinated was 64.7% overall. Three MVC rounds were conducted, with administrative coverage varying between 88.5% and 110.4%. Pentavalent vaccine was administered to those aged 6 weeks to 6 years, while tetanus and diphtheria (Td) vaccine was administered to those aged 7 years and older. Lack of adequate diagnostic capacity to confirm cases was the main limitation, with a majority of cases unconfirmed and the proportion of true diphtheria cases unknown. Conclusions To our knowledge, this is the largest reported diphtheria outbreak in refugee settings. We observed that high population density, poor living conditions, and fast growth rate were associated with explosive expansion of the outbreak during the initial exponential growth phase. Three rounds of mass vaccinations targeting those aged 6 weeks to 14 years were associated with only modestly reduced transmission, and additional public health measures were necessary to end the outbreak. This outbreak has a long-lasting tail, with Rt oscillating at around 1 for an extended period. An adequate global DAT stockpile needs to be maintained. All populations must have access to health services and routine vaccination, and this access must be maintained during humanitarian crises., Author(s): Jonathan A. Polonsky 1,2,*, Melissa Ivey 3, Md. Khadimul Anam Mazhar 4, Ziaur Rahman 5, Olivier le Polain de Waroux 1,6,7,8,9, Basel Karo 6,10, Katri Jalava 4, Sirenda Vong [...]

Introduction: Lung infections are associated with a high mortality rate in immunocompromised patients. Achieving an accurate and rapid diagnosis is vital to help guide management, and thus improve survival. Objective: To establish the diagnostic yield, clinical value, and safety of bronchoscopy with bronchoalveolar lavage (BAL) in immunocompromised adult patients with pulmonary infiltrates. Methods: This retrospective study included all immunocompromised adult patients who underwent bronchoscopy with BAL for investigation of radiologically confirmed pulmonary infiltrates at a tertiary care hospital between January 01, 2014, and June 30, 2021. Clinically significant findings of BAL were defined as a positive microbiological result of a potential pathogen determined using routine culture, acid-fast bacilli smear, mycobacterial culture, tuberculosis PCR, fungal culture, Aspergillus antigen, and multiplex PCR panel and/or positive cytology. Results: A total of 103 unique patients were included (mean ± SD age: 44.5 ± 14.1 years), of which the majority were male (60.2%). The BAL diagnostic yield was 52.4% (95% CI: 42.6–62.2%). In the multiple logistic regression model, positive BAL was predicted by symptom of sputum (aOR 4.01, 95% CI: 1.27–12.70, P = 0.018). Almost half of the procedures (43.7%, 95% CI: 33.9–53.4%) resulted in a change in the management plan, with positive BAL findings more than twice as likely to result in a change (OR 2.39, 95% CI: 1.07–5.33, P = 0.033). Only three (2.9%) procedures resulted in complications and required ventilator support and/or oxygen escalation. Conclusions: BAL is a safe clinical tool that can be useful in impacting clinical management in a significant proportion of immunocompromised patients with pulmonary infiltrates. [ABSTRACT FROM AUTHOR]

While complex intra- and interspecies microbial community dynamics are apparent during chronic infections and likely alter patient health outcomes, our understanding of these interactions is currently limited. For example, Pseudomonas aeruginosa and Staphylococcus aureus are often found to coinfect the lungs of patients with cystic fibrosis (CF), yet these organisms compete under laboratory conditions. Recent observations that coinfection correlates with decreased health outcomes necessitate we develop a greater understanding of these interbacterial interactions. In this study, we tested the hypothesis that P. aeruginosa and/or S. aureus adopts phenotypes that allow coexistence during infection. We compared competitive interactions of P. aeruginosa and S. aureus isolates from mono- or coinfected CF patients employing in vitro coculture models. P. aeruginosa isolates from monoinfected patients were more competitive toward S. aureus than P. aeruginosa isolates from coinfected patients. We also observed that the least competitive P. aeruginosa isolates possessed a mucoid phenotype. Mucoidy occurs upon constitutive activation of the sigma factor AlgT/U, which regulates synthesis of the polysaccharide alginate and dozens of other secreted factors, including some previously described to kill S. aureus. Here, we show that production of alginate in mucoid strains is sufficient to inhibit anti-S. aureus activity independent of activation of the AlgT regulon. Alginate reduces production of siderophores, 2-heptyl-4-hydroxyquinolone-N-oxide (HQNO), and rhamnolipids—each required for efficient killing of S. aureus. These studies demonstrate alginate overproduction may be an important factor driving P. aeruginosa coinfection with S. aureus.

Background: From 2003 to 2008, a total of 25 cross-sector, multidisciplinary community partnerships funded through the Active Living by Design (ALbD) national program designed, planned, and implemented policy and environmental changes, with complementary programs and promotions. Purpose: This paper describes the use of concept mapping methods to gain insights into promising active living intervention strategies based on the collective experience of community representatives implementing ALbD initiatives. Methods: Using Concept Systems software, community representatives (n=43) anonymously generated actions and changes in their communities to support active living (183 original statements, 79 condensed statements). Next, respondents (n=26, from 23 partnerships) sorted the 79 statements into self-created categories, or active living intervention approaches. Respondents then rated statements based on their perceptions of the most important strategies for creating community changes (n=25, from 22 partnerships) and increasing community rates of physical activity (n=23, from 20 partnerships). Cluster analysis and multidimensional scaling were used to describe data patterns. Results: ALbD community partnerships identified three active living intervention approaches with the greatest perceived importance to create community change and increase population levels of physical activity: changes to the built and natural environment, partnership and collaboration efforts, and land-use and transportation policies. The relative importance of intervention approaches varied according to subgroups of partnerships working with different populations. Conclusions: Decision makers, practitioners, and community residents can incorporate what has been learned from the 25 community partnerships to prioritize active living policy, physical project, promotional, and programmatic strategies for work in different populations and settings. [ABSTRACT FROM AUTHOR]