Background: Neurocysticercosis (NCC) is the main cause of epilepsy in Taenia solium endemic rural communities. NCC diagnosis is difficult due to unavailability and unaffordability of serologic assays and neuroimaging. This study aimed to assess the performance of a cheap, novel T. solium lateral-flow point-of-care (TS POC) test for the diagnosis of NCC in a community setting. Methods: A diagnostic accuracy study with prospective data collection, using a two-stage design was conducted in Sinda district of the Eastern province of Zambia between December 2017 and June 2019. Eligible participants were tested with the TS POC test. Thereafter, participants with a TS POC CC+ result and a subset of participants with a TS POC CC− result were subjected to serological testing for reference assays, and cerebral computed tomography (CT) for the reference diagnosis of NCC. Findings: A total of 1249 participants were tested with the TS POC of which 177 (14%) were positive. Of the 151 TS POC CC+ and 82 TS POC CC− participants with cerebral CT examination, 35 TS POC CC+ and 10 TS POC CC−, respectively, had NCC. The sensitivity of the TS POC CC strip was 26% (uncertainty interval [UI] 15–41) for any type of NCC, which was similar to that estimated for the rT24H-EITB (23%, UI 8–48) and the serum antigen ELISA (30%, UI 11–58). The specificity was 88% (UI 85–90) for the TS POC, 89% (UI 79–94) for the rT24H-EITB, and 82% (UI 71–89) for the antigen ELISA. For NCC with active stage lesions, sensitivity was >99% (UI 58-->99) for the TS POC, 76% (UI 40–94) for the rT24H-EITB and 76% (UI 39–94) for the antigen ELISA. Interpretation: The TS POC CC had a promising sensitivity for diagnosis of participants with active NCC lesions within a community-based setting. Accuracy for NCC at any stage was limited for all tests (TS POC, rT24H-EITB and antigen ELISA). With further development the TS POC CC may enable a better detection and faster referral of NCC patients who may benefit from antiparasitic treatment. Funding: European and Developing Countries Clinical Trials Partnership (EDCTP) and the German Federal Ministry of Education and Research (BMBF). © 2024 The Authors

INTRODUCTION: To examine the long-term health and economic impact of a lifestyle diabetes prevention program in people with high risk of developing type 2 diabetes in Germany. RESEARCH DESIGN AND METHODS: We assessed the lifetime cost-effectiveness of a 2-year pragmatic lifestyle program for preventing type 2 diabetes targeting German adults aged 35-54 and 55-74 years old with hemoglobin A1c (HbA1c) from 6.0% to 6.4%. We used the Centers for Disease Control and Prevention RTI Diabetes Cost-Effectiveness Model to run a simulation on the program effectiveness. We estimated incremental health benefits in quality-adjusted life years (QALYs) and costs using an established simulation model adapted to the German context, from a healthcare system and societal perspective. The cost-effectiveness of the program was measured by incremental cost-effectiveness ratios (ICERs) in cost per QALY. We projected the number of type 2 diabetes cases prevented by participation rate if the program was implemented nationwide. RESULTS: The lifestyle program would result to more QALYs and higher costs. The lifetime ICERs were 14 690€ (35-54 years old) and 14 372€ (55-74 years old) from a healthcare system perspective and cost saving (ICER=-3805€) and cost-effective (ICER=4579€), respectively, from a societal perspective. A total of 10 527 diabetes cases would be prevented over lifetime if the program was offered to all eligible people nationwide and 25% of those would participate in the program. CONCLUSIONS: Implementing the lifestyle intervention for people with HbA1c from 6.0% to 6.4% could be a cost-effective at standard willingness to pay level strategy for type 2 diabetes prevention. The intervention in the younger cohort could be cost saving from a societal perspective. The successful implementation of a lifestyle-based diabetes prevention program could be an important component of a successful National Diabetes Strategy in Germany.

BACKGROUND: The United States Preventive Services Task Force recommends annual alcohol screening and brief behavioral intervention (alcohol SBI) with general adult and pregnant populations. Implementation of alcohol SBI in primary care has encountered numerous barriers to adapting procedures and infrastructure to support its routine delivery. This collection of case studies describes the implementation strategies used by 4 academic health system teams that were funded by the Centers for Disease Control and Prevention to implement alcohol SBI within healthcare systems to prevent alcohol-exposed pregnancies. METHODS: We used constructs from the Framework for Reporting Adaptations and Modifications-Expanded (FRAME) to describe planned and unplanned adaptations to implementation strategies, and the SBIRT (Screening, Brief Intervention, and Referral to Treatment) Program Matrix to identify key questions, challenges, and recommendations for improving alcohol SBI implementation. Participating systems were 2 regional affiliates of a national reproductive healthcare organization, an integrated non-profit healthcare system, and an urban medical center and its affiliated network of community health centers. RESULTS: Planned adaptations included expanding the target population for brief interventions to include patients drinking at low levels who could become pregnant, modifying workflows and systems to support routine screening, and customizing training content and logistics. Unplanned adaptations included varying site recruitment and pre-implementation awareness-building strategies to enhance local receptivity of systems with decentralized management, and pivoting from in-person to virtual training during the COVID-19 pandemic. Fewer unplanned adaptations were observed for health systems with centralized management structures and practice teams that were fully engaged in implementation planning, training, roll-out, and problem-solving. CONCLUSIONS: Unplanned adaptations were observed across the 4 cases and emphasized the importance of flexible, adaptive designs when implementing evidence-based practice in dynamic settings. Participation of the health system in planning, including decisions to modify electronic health records and workflows, supported adapting to unplanned circumstances to achieve implementation goals.

BACKGROUND: Alcohol-exposed pregnancies, which can lead to fetal alcohol spectrum disorders (FASDs), is one of the most common preventable causes of lifelong intellectual and developmental disabilities in the U.S. Healthcare teams can play a critical role in preventing FASDs; however, they are currently unprepared to do so. Training can remediate this problem. This article explores the different approaches to the education and training of healthcare providers around FASD prevention used by six Centers for Disease Control (CDC)-funded programs, and how they have been adapted to (1) the specific needs of the healthcare professionals and/or the clinical setting and (2) the challenges posed by the COVID-19 pandemic. METHODS: This article offers an in-depth description and comparison of the models utilized by the programs described, detailing the challenges of each model as well as the adaptations made. Interdisciplinary collaboration and review highlights these models and offers a variety of solutions and lessons learned that can be implemented in similar practice settings and/or educational initiatives. RESULTS: Based on organizational structure (i.e., national organization, educational institution, and clinical settings) and program purpose, different methods were employed for FASD education. Some programs were focused on FASD prevention through staff training and alcohol screening and brief intervention/clinical intervention and others were focused on broadscale professional education and awareness. Improvements were made on an ongoing basis as challenges related to COVID-19, staff shortages, and patient and clinician discomfort were identified, resulting in modifications to content and delivery modality (e.g., online forums and use of social media). CONCLUSION: FASD prevention education is wrought with a variety of challenges related to stigma, discomfort, and misinformation, which these programs encountered in a variety of ways.

Background: The first licensed malaria vaccine, RTS,S/AS01<inf>E</inf>, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy. Method(s): Between Sept 28, 2017, and Sept 25, 2018, 1500 children aged 5-17 months were randomly assigned (1:1:1:1:1) to receive four different RTS,S/AS01<inf>E</inf> regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov, NCT03281291. Finding(s): We observed significant and similar vaccine efficacy (25-43%; 95% CI union 9-53) against first new infection for all four RTS,S/AS01<inf>E</inf> regimens across both follow-up periods (12 months and 20 months). Each RTS,S/AS01<inf>E</inf> regimen significantly reduced the mean number of new infections in the 20-month follow-up period by 1.1-1.6 infections (95% CI union 0.6-2.1). Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria (68%; 95% CI 50-80) than in those who were uninfected (37%; 23-48) at the first vaccination (p=0.0053). Interpretation(s): All tested dosing regimens blocked some infections to a similar degree. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation. Funding(s): GlaxoSmithKline Biologicals SA, PATH, Bill & Melinda Gates Foundation, and the German Federal Ministry of Education and Research. Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

BACKGROUND: The first licensed malaria vaccine, RTS,S/AS01(E), confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy. METHODS: Between Sept 28, 2017, and Sept 25, 2018, 1500 children aged 5-17 months were randomly assigned (1:1:1:1:1) to receive four different RTS,S/AS01(E) regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov, NCT03281291. FINDINGS: We observed significant and similar vaccine efficacy (25-43%; 95% CI union 9-53) against first new infection for all four RTS,S/AS01(E) regimens across both follow-up periods (12 months and 20 months). Each RTS,S/AS01(E) regimen significantly reduced the mean number of new infections in the 20-month follow-up period by 1·1-1·6 infections (95% CI union 0·6-2·1). Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria (68%; 95% CI 50-80) than in those who were uninfected (37%; 23-48) at the first vaccination (p=0·0053). INTERPRETATION: All tested dosing regimens blocked some infections to a similar degree. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation. FUNDING: GlaxoSmithKline Biologicals SA, PATH, Bill & Melinda Gates Foundation, and the German Federal Ministry of Education and Research.

Pre-exposure prophylaxis (PrEP) is an effective tool in protecting persons from acquiring HIV infection through sex or injection drug use. However, awareness and willingness to use PrEP among Black gay, bisexual, and other men who have sex with men (BMSM) remain suboptimal compared to White MSM (WMSM) in the United States. Our aims were to (1) assess the factors associated with PrEP awareness and willingness to use PrEP among MSM and (2) compare the PrEP perceptions among BMSM versus non-Black MSM. Data were drawn from two cross-sectional behavioral surveys in Baltimore, MD: Behavioral Surveillance Research (BESURE) conducted in 2017, and Safe Spaces 4 Sexual Health (SS4SH), conducted in 2018 and 2019. Descriptive statistics were used to summarize the study population. We used Poisson regression models to identify variables associated with awareness of PrEP and willingness to use PrEP. PrEP perceptions were assessed via 13 items scored on a 5-point Likert scale. Finally, we conducted a post-hoc exploratory bivariate analysis of the relationship between PrEP perception and willingness to use PrEP, stratified by race/ethnicity. A total of 261 MSM participated in this study. Many of the participants were aware of PrEP (75.1%). Factors associated with greater PrEP awareness included having greater than a high school education (aRR 1.22, 95% CI 1.04, 1.43); and earning more than $25,000 annually (aRR 1.24, 95% CI 1.08, 1.42). Participants who had received money in exchange for sex one or more times were less likely to be aware of PrEP (aRR 0.59, 95% CI 0.36, 0.95). More than half of the participants were willing to use PrEP (55.3%). In bivariate and multivariable analyses, demographic or behavioral characteristics were not significantly associated with willingness to use PrEP. Higher agreement with the following statements was associated with lower willingness to use PrEP: "Having to take a pill every day is difficult" (RR 0.89, 95% CI 0.82-0.97) and, "I am concerned about the side effects of PrEP" (RR 0.89, 95% CI 0.82-0.96), and "PrEP is for people who have riskier sex lives than I do" (RR 0.86, 95% CI 0.78-0.95). Conversely, higher willingness to use PrEP was associated with comfortable having sex without a condom (RR 1.11, 95% CI 1.02-1.21), less anxious about sex (RR 1.12, 95% CI 1.02-1.24), and my friends think that I should take PrEP (RR 1.19, 95% CI 1.07-1.32). We found BMSM compared to non-Black MSM had higher mean scores related to taking a daily pill (p = 0.041), concerns about side effects (p = 0.012), concerns about people thinking they had HIV (p = 0.001), concerns about the financial costs of PrEP (p = 0.038) and caution when dealing with healthcare organizations/medical mistrust (p = 0.019). Perceptions with a statistically significant lower score among BMSM versus non-Black MSM included statements such as, comfortable having sex without a condom (p = 0.003) and less anxious about sex (p < 0.001). We conclude HIV prevention strategies, programs, and interventions should be cognizant of PrEP perceptions that facilitate or hinder PrEP uptake in Baltimore City, MD.

OBJECTIVES: Leptospira, the spirochaete causing leptospirosis, can be classified into >250 antigenically distinct serovars. Although knowledge of the animal host species and geographic distribution of Leptospira serovars is critical to understand the human and animal epidemiology of leptospirosis, current data are fragmented. We aimed to systematically review, the literature on animal host species and geographic distribution of Leptospira serovars to examine associations between serovars with animal host species and regions and to identify geographic regions in need of study. METHODS: Nine library databases were searched from inception through 9 March 2023 using keywords including Leptospira, animal, and a list of serovars. We sought reports of detection of Leptospira, from any animal, characterised by cross agglutinin absorption test, monoclonal antibody typing, serum factor analysis, or pulsed-field gel electrophoresis to identify the serovar. RESULTS: We included 409 reports, published from 1927 through 2022, yielding data on 154 Leptospira serovars. The reports included data from 66 (26.5%) of 249 countries. Detections were from 144 animal host species including 135 (93.8%) from the class Mammalia, 5 (3.5%) from Amphibia, 3 (2.1%) from Reptilia, and 1 (0.7%) from Arachnida. Across the animal host species, Leptospira serovars that were detected in the largest number of animal species included Grippotyphosa (n = 39), Icterohaemorrhagiae (n = 29), Pomona (n = 28), Australis (n = 25), and Ballum (n = 25). Of serovars, 76 were detected in a single animal host species. We created an online database to identify animal host species for each serovar by country. CONCLUSIONS: We found that many countries have few or no Leptospira serovars detected from animal host species and that many serovars were detected from a single animal species. Our study highlights the importance of efforts to identify animal host species of leptospirosis, especially in places with a high incidence of human leptospirosis. We provide an updated resource for leptospirosis researchers.

Together with plague, smallpox and typhus, epidemics of dysentery have been a major scourge of human populations for centuries(1). A previous genomic study concluded that Shigella dysenteriae type 1 (Sd1), the epidemic dysentery bacillus, emerged and spread worldwide after the First World War, with no clear pattern of transmission(2). This is not consistent with the massive cyclic dysentery epidemics reported in Europe during the eighteenth and nineteenth centuries(1,3,4) and the first isolation of Sd1 in Japan in 1897(5). Here, we report a whole-genome analysis of 331 Sd1 isolates from around the world, collected between 1915 and 2011, providing us with unprecedented insight into the historical spread of this pathogen. We show here that Sd1 has existed since at least the eighteenth century and that it swept the globe at the end of the nineteenth century, diversifying into distinct lineages associated with the First World War, Second World War and various conflicts or natural disasters across Africa, Asia and Central America. We also provide a unique historical perspective on the evolution of antibiotic resistance over a 100-year period, beginning decades before the antibiotic era, and identify a prevalent multiple antibiotic-resistant lineage in South Asia that was transmitted in several waves to Africa, where it caused severe outbreaks of disease.

One Health is an integrative and systemic approach to health, based on the understanding that human, animal and ecosystem health are inextricably linked. These interconnections and vulnerabilities were once more clearly demonstrated by the COVID-19 pandemic. This led the heads of the United Nations Food and Agriculture Organization (FAO), the United Nations Environment Programme (UNEP), the World Health Organization (WHO), and the World Organization for Animal Health (WOAH; founded as OIE), to enhance their science-based cross-sectoral collaboration by creating a multidisciplinary One Health High-Level Expert Panel (OHHLEP) to provide technical and scientific advice on One Health issues. Out of over 700 applications from all over the world, the four international partners FAO, WHO, WOAH and UNEP selected 26 experts from 24 countries as members of the OHHLEP. The multisectoral and transdisciplinary expertise present in OHHLEP members covers a wide range including animal, human and environmental health, biodiversity conservation and social sciences. The panel was conceived following a proposal by the French and German governments at the Paris Peace Forum in November 2020. It drew on the already existing FAO-OIE-WHO Tripartite intersectoral cooperation on One Health issues. In 2021, UNEP joined to form the Tripartite plus UNEP which was formally transformed into the ‘Quadripartite Collaboration for One Health’ in March 2022 and which now acts as the partner for engaging with OHHLEP. This is the first time that a global advisory panel on One Health has been created as a centre for expert advice.

Ludwig van Beethoven (1770‒1827) is one of the most renowned and admired composers in the development of Western Classical music. He was perhaps the greatest contributor to the musical style transition from Classical (roughly 1750‒1820), with linear compositional styles, to Romantic (roughly 1798‒1837), with dramatic expansion of orchestra size and development of lyrical, less formulaic melodic styles. The German composer’s contributions vastly widened the scope and development of the concerto, quartet, sonata, and symphony. In March 1827, after a prolonged illness, Beethoven died at age 56 in his apartment in Vienna. Discussions of Beethoven’s health have been voluminous, fraught with controversy, and limited by an absence of evidence, characteristic of the first half of the 19th century before the availability of radiologic and microbiologic diagnostics. Starting at age 28, the composer suffered hearing deficits that were initially characterized as tinnitus and high-frequency hearing loss. Letters, journals, and other documents of that era indicate that, in his final decade of his life, Beethoven’s health and hearing progressively declined, yet he produced many works that were expansive and departing from the more conservative structure of his earlier works.

BACKGROUND: Neurocysticercosis is a common cause of epilepsy in Taenia solium-endemic areas in sub-Saharan Africa but is often undiagnosed because of an absence of affordable diagnostic tools. This study evaluated the diagnostic accuracy of a T solium cysticercosis antibody-detecting lateral-flow point-of-care assay (TS POC test) for the neuroimaging-based diagnosis of neurocysticercosis. METHODS: Patients with epileptic seizures or severe progressive headache were recruited consecutively from three hospitals in southern Tanzania. All patients were tested with the TS POC test. All patients positive for cysticercosis on the TS POC test and every tenth patient who was negative for cysticercosis received a brain CT examination and underwent reference testing for T solium cysticercosis (ie, rT24H-EITB, LLGP-EITB, and antigen ELISA). The primary outcome of the study was the sensitivity of the TS POC test for the diagnosis of neurocysticercosis. FINDINGS: Of the 601 recruited participants, 102 (17%) tested positive for cysticercosis with the TS POC test. Overall, 48 (62%) of the 77 patients positive for cysticercosis and five (17%) of the 29 patients negative for cysticercosis on the TS POC test had CT-confirmed neurocysticercosis. The TS POC test yielded a sensitivity of 49% (uncertainty interval [UI] 41-58) for neurocysticercosis. Sensitivity was similar to that of the rT24H-EITB (44%, UI 37-51) and the antigen ELISA (50%, 43-56). For the subset of neurocysticercosis cases with at least one active (ie, vesicular) lesion, sensitivity was above 98% for the TS POC test, the rT24H-ETIB, and the antigen ELISA. INTERPRETATION: The TS POC test showed promising results for the diagnosis of neurocysticercosis in patients with vesicular lesions, which need to be confirmed in a larger study. This test could be considered to support policies on screening patients with suspected neurocysticercosis in clinical settings, which would allow appropriate referral for neuroimaging and early treatment. FUNDING: German Federal Ministry of Education and Research and the European & Developing Countries Clinical Trials Partnership. TRANSLATION: For the Swahili translation of the abstract see Supplementary Materials section.

Objectives The COVID-19 pandemic has had a substantial impact on health systems. The WHO Antimicrobial Resistance (AMR) Collaborating Centres Network conducted a survey to assess the effects of COVID-19 on AMR surveillance, prevention and control.Methods From October-December 2020, WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) national focal points completed a questionnaire including Likert-scales and open-ended questions. Data were descriptively analysed, income/regional differences were assessed, and free-text questions were thematically analysed.Results Seventy-three countries across income levels participated. During the COVID-19 pandemic, 67% reported limited ability to work with AMR partnerships; decreases in funding were frequently reported by low- and middle-income countries (LMICs; p&lt;0.01). Reduced availability of nursing, medical and public health staff for AMR was reported by 71%, 69% and 64%, respectively, whereas 67% reported stable cleaning staff availability. The majority (58%) reported reduced reagents/consumables, particularly LMICs (p&lt;0.01). Decreased numbers of cultures, elective procedures, chronically ill admissions and outpatients and increased intensive care unit admissions reported could bias AMR data. Reported overall infection prevention and control (IPC) improvement could decrease AMR rates, whereas increases in selected inappropriate IPC practices and antibiotic prescribing could increase rates. Most did not yet have complete data on changing AMR rates due to COVID-19.Conclusions This was the first survey to explore the global impact of COVID-19 on AMR among GLASS countries. Responses revealed universal patterns but also captured country variability. Although focus is understandably on COVID-19, gains in detecting and controlling AMR, a global health priority, cannot afford to be lost.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by a working group belonging to the WHO AMR Surveillance and Quality Assessment Collaborating Centres Network. It was led by the coordinator of the Network at the Robert Koch Institute in Berlin, Germany, who received funding from the Global Protection Programme (GHPP) at the German Federal Ministry of Health.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The anonymous survey was conducted as part of routine public health work by the WHO Antimicrobial Resistance (AMR) Surveillance and Quality Assessment Collaborating Centres Network. No human subjects, samples or data were involved for this research purpose. As per the policy in Germany, the survey protocol was reviewed and waived by the data protection institutional review board of the Network coordinator at Robert Koch Institute, Berlin, Germany.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe aggregated data is avaiable on a case-by-case basis upon consultation with the WHO AMR Surveillance and Quality Assessment Collaborating Centres Network coordinator (Robert Koch Institute, Berlin, Germany)

BACKGROUND: To respond to the need to establish infodemic management functions at the national public health institute in Germany (Robert Koch Institute, RKI), we explored and assessed available data sources, developed a social listening and integrated analysis framework, and defined when infodemic management functions should be activated during emergencies. OBJECTIVE: We aimed to establish a framework for social listening and integrated analysis for public health in the German context using international examples and technical guidance documents for infodemic management. METHODS: This study completed the following objectives: identified (potentially) available data sources for social listening and integrated analysis; assessed these data sources for their suitability and usefulness for integrated analysis in addition to an assessment of their risk using the RKI's standardized data protection requirements; developed a framework and workflow to combine social listening and integrated analysis to report back actionable infodemic insights for public health communications by the RKI and stakeholders; and defined criteria for activating integrated analysis structures in the context of a specific health event or health emergency. RESULTS: We included and classified 38% (16/42) of the identified and assessed data sources for social listening and integrated analysis at the RKI into 3 categories: social media and web-based listening data, RKI-specific data, and infodemic insights. Most data sources can be analyzed weekly to detect current trends and narratives and to inform a timely response by reporting insights that include a risk assessment and scalar judgments of different narratives and themes. CONCLUSIONS: This study identified, assessed, and prioritized a wide range of data sources for social listening and integrated analysis to report actionable infodemic insights, ensuring a valuable first step in establishing and operationalizing infodemic management at the RKI. This case study also serves as a roadmap for others. Ultimately, once operational, these activities will inform better and targeted public health communication at the RKI and beyond.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic once more demonstrated the close connection between humans, animals, and the shared environment. Although still under investigation, the closest relatives of this virus exist in animals, and the factors leading to spillover remain to be fully understood. This interconnectedness again highlighted the need for a One Health approach. Although the One Health concept is not new and has been at the forefront of interdisciplinary and multisectoral discussions for years, there is now an increased interest for this approach to be applied and translated into action. Following a proposal made by the French and German Ministers for Foreign Affairs at the November 2020 Paris Peace Forum, 4 global partners, the Food and Agriculture Organization (FAO), the World Organization for Animal Health (OIE), the United Nations Environment Programme (UNEP), and the World Health Organization (WHO), in May 2021 established the interdisciplinary One Health High-Level Expert Panel (OHHLEP) (https://www.who.int/groups/one-health-high-level-expert-panel) to enhance their cross-sectoral collaboration. The creation of OHHLEP represents a recognition at the highest level of the urgency and complexities surrounding One Health and the intent to take this concept forward into policies and concrete actions.

Whole genome sequencing (WGS) of Salmonella supports both molecular typing and detection of antimicrobial resistance (AMR). Here, we evaluated the correlation between phenotypic antimicrobial susceptibility testing (AST) and in silico prediction of AMR from WGS in Salmonella enterica (n = 1321) isolated from human infections in Canada. Phenotypic AMR results from broth microdilution testing were used as the gold standard. To facilitate high-throughput prediction of AMR from genome assemblies, we created a tool called Staramr, which incorporates the ResFinder and PointFinder databases and a custom gene-drug key for antibiogram prediction. Overall, there was 99% concordance between phenotypic and genotypic detection of categorical resistance for 14 antimicrobials in 1321 isolates (18,305 of 18,494 results in agreement). We observed an average sensitivity of 91.2% (range 80.5100%), a specificity of 99.7% (98.6100%), a positive predictive value of 95.4% (68.2100%), and a negative predictive value of 99.1% (95.6100%). The positive predictive value of gentamicin was 68%, due to seven isolates that carried aac(3)-IVa, which conferred MICs just below the breakpoint of resistance. Genetic mechanisms of resistance in these 1321 isolates included 64 unique acquired alleles and mutations in three chromosomal genes. In general, in silico prediction of AMR in Salmonella was reliable compared to the gold standard of broth microdilution. WGS can provide higher-resolution data on the epidemiology of resistance mechanisms and the emergence of new resistance alleles. 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Hispanic or Latino* (Hispanic) persons are disproportionately affected by HIV in the United States. In 2019, Hispanic persons accounted for 18% of the U.S. population, but for 29% of new diagnoses of HIV infection (1). The Ending the HIV Epidemic in the U.S. (EHE) initiative aims to reduce new HIV infections by 90% by 2030 (2). Preexposure prophylaxis (PrEP), medication taken to prevent acquisition of HIV, is an effective strategy for preventing HIV infection.(†) To examine PrEP awareness and referral to providers among Hispanic persons, CDC analyzed 2019 National HIV Prevention Program Monitoring and Evaluation HIV testing data. Approximately one quarter (27%) of Hispanic persons tested for HIV at CDC-funded sites (n = 310,954) were aware of PrEP, and 22% of those who received a negative HIV test result and were eligible for referral (111,644) were referred to PrEP providers. PrEP awareness and referrals among Hispanic persons were lower compared with those among non-Hispanic White persons. Among Hispanic persons, significant differences were found in PrEP awareness and referrals by age, gender, race, population group, geographic region, and test setting. HIV testing programs can expand PrEP services for Hispanic persons by implementing culturally and linguistically appropriate strategies that routinize PrEP education and referral, collaborating with health care and other providers, and addressing social and structural barriers.

To be effective, a negative-pressure, air-purifying, particulate-removing, half-facepiece respirator (particulate respirator) must form a good seal against the wearer’s face. This fact has long been recognized by those in the respiratory protection n community. As one historical example, in 1911, German investigators conducted studies on fit (Brown 1937). However, the current National Institute for Occupational Health and Safety (NIOSH) respirator approval program does not evaluate particulate respirator fit characteristics. Therefore, it is difficult to predict which particulate respirator model will be the best fit in a particular population. Having particulate respirators with good fit characteristics is extremely important today. With the resurgence of tuberculosis (TB) in the United States in the 1990s, the use of particulate respirators in healthcare has increased due to surgical masks only providing barrier protection against droplets that include large respiratory particles. Most surgical masks lack an adequate face seal and do not effectively filter small particles from the air or aerosols, allowing for leakage around the mask and subsequent exposure (Umer et al. 2020). Therefore, surgical masks do not provide adequate protection against infectious respiratory diseases since they are transmitted via droplets and aerosols. With this increased use of particulate respirators in healthcare, supplies of particulate respirators, including N95 filtering facepiece respirators (FFRs), can become depleted during a pandemic or widespread outbreak of infectious respiratory illnesses (Institute of Medicine 2006). However, previous shortages pale in comparison to those caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The resulting respirator shortage left doctors, nurses, and other frontline workers dangerously ill-equipped to care for COVID-19 patients while protecting themselves from being infected with SARS-CoV-2. The shortages were so severe that even with the availability of hundreds of NIOSH-approved particulate respirator models, under an emergency use authorization, the U.S. Food and Drug Administration (FDA) allowed certain non-NIOSH approved particulate respirators to be used in healthcare for protection against COVID-19 (FDA 2020). Many employers had to buy whatever respirators they could find, resulting in healthcare workers having to wear particulate respirators with which they were unfamiliar. With the need to wear these respirators immediately to care for COVID-19 patients, some healthcare workers may have increased their risk of exposure and infection by wearing respirators with poor fit characteristics. In addition to healthcare workers, particulate respirator wearers in other industries may be at risk from overexposure to various contaminants. A 2001 survey of over 40,000 establishments designed to represent all private-sector establishments revealed that only about 57% of those requiring the use of tight-fitting facepiece respirators performed fit testing (BLS/ NIOSH 2003). Having particulate respirators that meet a standard such as the new ASTM F3407-20 Standard Test Method for Respirator Fit Capability (RFC) for Negative-Pressure Half-Facepiece Particulate Respirators would reduce the number of employees who may be overexposed due to wearing a particulate respirator with poor fit characteristics.

BACKGROUND: People who inject drugs (PWID) lag behind other key populations in HIV care continuum outcomes. The impacts of criminal justice reform and increasing drug treatment access on HIV have been underexplored. METHODS: We developed agent-based models (ABM) of sexual partnerships among PWID and non-PWID, and injection equipment-sharing partnerships among PWID in five US cities (Baltimore, Boston, Miami, New York City, San Francisco) over 3 years. The first set of ABM projected changes in partnership discordance among PWID as a function of decreasing ZIP code-level incarceration rates. The second set projected discordance as a function of increasing ZIP code-level drug treatment access. ABM were parameterized and validated overall, and by city and PWID race/ethnicity (Black, Latino, White) using National HIV Behavioral Surveillance data, administrative ZIP code-level data, surveillance reports and prior literature. Informed by research on prisoner release and community-level HIV prevalence, reductions in incarceration rates were fixed at 5% and 30% and respectively projected to increase ZIP code-level HIV prevalence by 2% and 12%. Increases in drug treatment access were fixed at 30% and 58%. RESULTS: In each city, a 30% reduction in ZIP code-level incarceration rates and 12% increase in ZIP code-level HIV prevalence significantly increased sero-discordance among at least one racial/ethnic group of PWID by 1-3 percentage points. A 5% reduction in incarceration rates, and 30% and 58% increases in drug treatment access, led to isolated significant changes in sero-discordance among Black and White PWID that were less than 1 percentage point. CONCLUSION: Reductions in incarceration rates may lead to short-term increases in sero-discordant partnerships among some PWID by increasing community-level HIV prevalence. Efforts to increase HIV testing, engagement in care and community reintegration post release, should be strengthened in the wake of incarceration reform. Additional research should confirm these findings and explore the lack of widespread impacts of drug treatment in this study.

Although non-Hispanic American Indian and Alaska Native (AI/AN) persons account for 0.7% of the U.S. population,* a recent analysis reported that 1.3% of coronavirus disease 2019 (COVID-19) cases reported to CDC with known race and ethnicity were among AI/AN persons (1). To assess the impact of COVID-19 among the AI/AN population, reports of laboratory-confirmed COVID-19 cases during January 22(†)-July 3, 2020 were analyzed. The analysis was limited to 23 states(§) with >70% complete race/ethnicity information and five or more laboratory-confirmed COVID-19 cases among both AI/AN persons (alone or in combination with other races and ethnicities) and non-Hispanic white (white) persons. Among 424,899 COVID-19 cases reported by these states, 340,059 (80%) had complete race/ethnicity information; among these 340,059 cases, 9,072 (2.7%) occurred among AI/AN persons, and 138,960 (40.9%) among white persons. Among 340,059 cases with complete patient race/ethnicity data, the cumulative incidence among AI/AN persons in these 23 states was 594 per 100,000 AI/AN population (95% confidence interval [CI] = 203-1,740), compared with 169 per 100,000 white population (95% CI = 137-209) (rate ratio [RR] = 3.5; 95% CI = 1.2-10.1). AI/AN persons with COVID-19 were younger (median age = 40 years; interquartile range [IQR] = 26-56 years) than were white persons (median age = 51 years; IQR = 32-67 years). More complete case report data and timely, culturally responsive, and evidence-based public health efforts that leverage the strengths of AI/AN communities are needed to decrease COVID-19 transmission and improve patient outcomes.

INTRODUCTION: Men who have sex with men (MSM) in the United States (US) are disproportionately affected by HIV. We estimated the impact of past interventions and contribution of different population groups to incident MSM HIV infections. SETTING: Baltimore, US METHODS:: We used a deterministic model, parameterised and calibrated to demographic and epidemic Baltimore MSM data, to estimate the fraction of HIV infections among MSM averted by condoms and antiretroviral therapy (ART) over 1984-2017 and the fraction of infections acquired and transmission contributed by MSM from different demographic groups and disease and care continuum stages over 10-year periods from 1988 to 2017, using population attributable fractions (PAFs). RESULTS: Condom use and ART averted 19% (95% uncertainty interval: 14-25%) and 23% (15-31%) of HIV infections that would have occurred since 1984 and 1996, respectively. Over 2008-2017, 46% (41-52%) of incident infections were acquired by, and 35% (27-49%) of transmissions contributed by MSM aged 18-24 years old (who constitute 27% of all MSM, 19% of HIV+ MSM). MSM with undiagnosed HIV infection, those with diagnosed infection but not in care, and those on ART contributed to 41% (31-54%), 46% (25-56%), and 14% (7-28%) of transmissions, respectively. CONCLUSION: Condoms and ART have modestly impacted the HIV epidemic among Baltimore MSM to date. Interventions reaching MSM with diagnosed infection who are not in care should be implemented since the largest percentage of HIV transmissions among Baltimore MSM are attributed to this group.

At the transition of the 18th into the 19th century, large numbers of deaths in Europe, especially those in urban areas, were associated with tuberculosis. During those two centuries, many celebrated artists, musicians, and literary giants were lost to the disease. Romanticism—Europe’s dominant artistic, musical, and intellectual movement that began in the late 18th century and waned after 1850—emphasized individualism and emotion. Characteristic themes included the goodness of people, from which urban life detracted, and the simplicities of childhood and all things natural. A popular myth arose that this movement was favored by tuberculosis, which putatively augmented one’s creative faculties. Classicists viewed this belief as consistent with what ancient Greek physicians had called the spes phthisica—an earnest hope of recovery from tuberculosis that drove heightened sensitivity and great creativity despite overwhelming illness. Portrayals of this view appear in Alexander Dumas's La Dame aux Camélias, Victor Hugo's Les Misérables, Giuseppe Verdi's La traviata, and Giacomo Puccini's La bohème. | | Among German writers of the Romantic era who had tuberculosis were Johann Wolfgang von Goethe (1749–1832; best known to English speakers for his poetic drama Faust), Friedrich Schiller (1759–1805; trained as a physician and author of “An die Freude”—the Ode to Joy in the final movement of Beethoven’s Ninth Symphony), and Georg Philipp Friedrich von Hardenberg (1772–1801; principal poet-theoretician of Early German Romanticism). Goethe received his tuberculosis diagnosis when in his early 20s and recovered fully after several years of convalescence. In contrast, Schiller died of pulmonary tuberculosis at age 46 after a period of increasing lethargy.

AIMS: Although risk scores to predict type 2 diabetes exist, cost-effectiveness of risk thresholds to target prevention interventions are unknown. We applied cost-effectiveness analysis to identify optimal thresholds of predicted risk to target a low-cost community-based intervention in the USA. METHODS: We used a validated Markov-based type 2 diabetes simulation model to evaluate the lifetime cost-effectiveness of alternative thresholds of diabetes risk. Population characteristics for the model were obtained from NHANES 2001-2004 and incidence rates and performance of two noninvasive diabetes risk scores (German diabetes risk score, GDRS, and ARIC 2009 score) were determined in the ARIC and Cardiovascular Health Study (CHS). Incremental cost-effectiveness ratios (ICERs) were calculated for increasing risk score thresholds. Two scenarios were assumed: 1-stage (risk score only) and 2-stage (risk score plus fasting plasma glucose (FPG) test (threshold 100 mg/dl) in the high-risk group). RESULTS: In ARIC and CHS combined, the area under the receiver operating characteristic curve for the GDRS and the ARIC 2009 score were 0.691 (0.677-0.704) and 0.720 (0.707-0.732), respectively. The optimal threshold of predicted diabetes risk (ICER < $50,000/QALY gained in case of intervention in those above the threshold) was 7% for the GDRS and 9% for the ARIC 2009 score. In the 2-stage scenario, ICERs for all cutoffs >/= 5% were below $50,000/QALY gained. CONCLUSIONS: Intervening in those with >/= 7% diabetes risk based on the GDRS or >/= 9% on the ARIC 2009 score would be cost-effective. A risk score threshold >/= 5% together with elevated FPG would also allow targeting interventions cost-effectively.

Correct and consistent condom use and human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) are protective against sexual transmission of HIV (1,2). The incidence of HIV infection among Hispanic/Latino men who have sex with men (MSM) in the United States is increasing (3). HIV risk among Hispanic/Latino MSM differs based on their place of birth and years of U.S. residence (4). Data from CDC's National HIV Behavioral Surveillance (NHBS)* for 2011-2017 were analyzed to assess changes in sexual risk behaviors among Hispanic/Latino MSM by place of birth and years of U.S. residence. Overall, condomless anal sex during the previous 12 months increased from 63% in 2011 to 74% in 2017, and PrEP use during the previous 12 months increased from 3% in 2014 to 24% in 2017. Regardless of place of birth, nearly 75% of Hispanic/Latino MSM reported condomless anal sex during 2017. However, because of PrEP use, <60% of non-U.S.-born Hispanic/Latino MSM and <50% of U.S.-born Hispanic/Latino MSM reported unprotected anal sex (condomless anal sex and no PrEP use) during 2017. Results indicate that PrEP can be a vital tool for reducing HIV transmission among Hispanic/Latino MSM, especially those who have condomless anal sex. Interventions to prevent HIV acquisition, including increasing PrEP uptake, could address cultural and linguistic needs of Hispanic/Latino MSM, as well as other barriers to prevention of HIV infection typically faced by all MSM.

Nationally representative data from mother-child dyads that capture human milk composition (HMC) and associated health outcomes are important for advancing the evidence to inform federal nutrition and related health programs, policies, and consumer information across the governments in the United States and Canada as well as in nongovernment sectors. In response to identified gaps in knowledge, the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH sponsored the "Workshop on Human Milk Composition-Biological, Environmental, Nutritional, and Methodological Considerations" held 16-17 November 2017 in Bethesda, Maryland. Through presentations and discussions, the workshop aimed to 1) share knowledge on the scientific need for data on HMC; 2) explore the current understanding of factors affecting HMC; 3) identify methodological challenges in human milk (HM) collection, storage, and analysis; and 4) develop a vision for a research program to develop an HMC data repository and database. The 4 workshop sessions included 1) perspectives from both federal agencies and nonfederal academic experts, articulating scientific needs for data on HMC that could lead to new research findings and programmatic advances to support public health; 2) information about the factors that influence lactation and/or HMC; 3) considerations for data quality, including addressing sampling strategies and the complexities in standardizing collection, storage, and analyses of HM; and 4) insights on how existing research programs and databases can inform potential visions for HMC initiatives. The general consensus from the workshop is that the limited scope of HM research initiatives has led to a lack of robust estimates of the composition and volume of HM consumed and, consequently, missed opportunities to improve maternal and infant health.

INTRODUCTION: HIV prevalence is high among men who have sex with men (MSM) in Baltimore, Maryland, United States, and the levels of viral suppression among HIV-positive MSM are relatively low. The HIV Prevention Trials Network 078 trial seeks to increase the levels of viral suppression among US MSM by increasing the rates of diagnosis and linkage to care and treatment. We estimated the increases in viral suppression needed to reach different HIV incidence reduction targets, and the impact of meeting diagnosis and treatment targets. METHODS: We used a mathematical model of HIV transmission among MSM from Baltimore, US, parameterised with behavioural data and fitted to HIV prevalence and care continuum data for Baltimore wherever possible, to project increases in viral suppression needed to reduce the HIV incidence rate among Baltimore MSM by 10, 20, 30 or 50% after 2, 5 and 10 years. We also projected HIV incidence reductions achieved if US national targets - 90% of people living with HIV (PLHIV) know their HIV serostatus, 90% of those diagnosed are retained in HIV medical care and 80% of those diagnosed are virally suppressed - or UNAIDS 90-90-90 targets (90% of PLHIV know their status, 90% of those diagnosed receive antiretroviral therapy (ART), 90% of those receiving ART are virally suppressed) are each met by 2020. RESULTS: To reduce the HIV incidence rate by 20% and 50% after five years (compared with the base-case at the same time point), the proportion of all HIV-positive MSM who are virally suppressed must increase above 2015 levels by a median 13 percentage points (95% uncertainty interval 9 to 16 percentage points) from median 49% to 60%, and 27 percentage points (22 to 35) from 49% to 75% respectively. Meeting all three US or 90-90-90 UNAIDS targets results in a 48% (31% to 63%) and 51% (38% to 65%) HIV incidence rate reduction in 2020 respectively. CONCLUSIONS: Substantial improvements in levels of viral suppression will be needed to achieve significant incidence reductions among MSM in Baltimore, and to meet 2020 US and UNAIDS targets. Future modelling studies should additionally consider the impact of pre-exposure prophylaxis for MSM.

OBJECTIVES: Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) increase the risk of HIV transmission among men who have sex with men (MSM). Diagnosis of NG/CT may provide an efficient entry point for prevention of HIV through the delivery of pre-exposure prophylaxis (PrEP); however, the additional population-level impact of targeting PrEP to MSM diagnosed with NG/CT is unknown. DESIGN: An agent-based simulation model of NG/CT and HIV cocirculation among MSM calibrated against census data, disease surveillance reports and the US National HIV Behavioral Surveillance study. SETTING: Baltimore City, Maryland, USA. INTERVENTIONS: PrEP implementation was modelled under three alternative scenarios: (1) PrEP delivery at NG/CT diagnosis (targeted delivery), (2) PrEP evaluation at NG/CT screening/testing and (3) PrEP evaluation in the general community (untargeted). MAIN OUTCOME: The projected incidence of HIV after 20 years of PrEP delivery under two alternatives: when equal numbers of MSM are (1) screened for PrEP or (2) receive PrEP in each year. RESULTS: Assuming 60% uptake and 60% adherence, targeting PrEP to MSM diagnosed with NG/CT could reduce HIV incidence among MSM in Baltimore City by 12.4% (95% uncertainty range (UR) 10.3% to 14.4%) in 20 years, relative to no PrEP. Expanding the coverage of NG/CT screening (such that individuals experience a 50% annual probability of NG/CT screening and evaluation for PrEP on NG/CT diagnosis) can further increase the impact of targeted PrEP to generate a 22.0% (95% UR 20.1% to 23.9%) reduction in HIV incidence within 20 years. When compared with alternative implementation scenarios, PrEP evaluation at NG/CT diagnosis increased impact of PrEP on HIV incidence by 1.5(95% UR 1.1 to 1.9) times relative to a scenario in which PrEP evaluation happened at the time of NG/CT screening/testing and by 1.6 (95% UR 1.2 to 2.2) times relative to evaluating random MSM from the community. CONCLUSIONS: Targeting MSM infected with NG/CT increases the efficiency and effectiveness of PrEP delivery. If high levels of sexually transmitted infection screening can be achieved at the community level, NG/CT diagnosis may be a highly effective entry point for PrEP initialisation.

A century ago, the world was ensnared in the Great War, 1914–1918, now known as the First World War. During that war, an estimated 9 million combatants and as many as 7 million civilians died, and it brought to an end the German, Russian, Austro-Hungarian, and Ottoman Empires. Infectious diseases played a prominent role in that war, resulting in more casualties than did war-inflicted wounds. With several decades of knowledge about bacterial organisms, armies had implemented sanitation measures such as latrines and water purification methods to control diarrheal and dysenteric diseases. Vaccine successes had been documented for smallpox and typhoid. However, louse-borne typhus killed 2–3 million soldiers and civilians on the Eastern Front, and the war’s end in November 1918 was hastened by an influenza pandemic that had begun in January 1918 and eventually claimed the lives of an estimated 50 million. | | Because of the huge numbers of casualties, control of media was important for maintaining positive public opinion and support for the war efforts; all combatant countries developed central censorship and propaganda offices. The United States entered the war in April 1917, fully two-and-a-half years into the conflict, and created its own Committee on Public Information and its own Censorship Board. For the Austro-Hungarian forces, the central censorship and propaganda institution was the War Press Office, or Kriegspressequartier, which eventually included more than 750 writers, journalists, photographers, and filmmakers, and some 150 visual artists. Painters and photographers worked in the field of combat, many as military officers, and sketched quick impressions, which they could later render more elaborate or refined, when they were away from the dangers of the front. Among these many painters was a young artist, Ernst Liebenauer (1884–1970), who had studied under reknowned realist Christian Griepenkerl at the Wiener Akademie der Bildenden Künste (Viennese Academy of Fine Arts) and later at the Spezialschule für Historienmalerei (Special School for Historical Painting) under another well-known Austrian portrait and landscape painter, Franz Rumpler. During the war, Liebenauer focused on military subjects, but after the war, he became a painter of landscapes, still life, portraits, and mythical scenes. He was best known as an illustrator of children’s books and fairy tales, including versions of Daniel Defoe’s Robinson Crusoe and the works of the Brothers Grimm.

Mycobacterium chimaera was identified as a species within the Mycobacterium avium complex in 2004. Until recently, it was predominantly seen in immunocompromised patients. In 2015, an outbreak of disseminated M. chimaera disease was described in European patients after undergoing open-heart surgery in which contaminated heater-cooler water units were used. Using whole genomic sequencing and phylogenetic analysis, investigators found a highly clonal outbreak from the German manufacturing site of the heater-cooler water units. This outbreak has now proven to be world-wide. Patients present with fever, fatigue, and weight loss months to many years after surgery. They are found to have systemic manifestations, including endocarditis, pancytopenia, renal dysfunction, chorioretinitis, and hepatitis. Preliminary reports suggest a high mortality rate despite aggressive treatment. In some patients, the predominant laboratory abnormalities are elevations in liver function tests, leading to diagnostic hepatobiliary work-ups, including liver biopsy. The pathologic changes in the liver have not yet been described. Herein, we report the clinicopathologic findings of the largest series of M. chimaera liver disease in the United States to date: 7 cases within a large, multihospital health care network. Five (71%) patients died of disease, despite aggressive treatment. Liver function test abnormalities were predominantly biliary: mean values of alkaline phosphate 288 U/L, aspartate aminotransferase 79 U/L, alanine aminotransferase 64 U/L. All 7 biopsies showed a consistent and characteristic dual pattern of injury: small, ill-formed collections of sinusoidal histiocytes with rare multinucleated giant cells, and scattered architectural changes of venous outflow obstruction. Two (29%) cases showed mild pericellular fibrosis. Nodular regenerative hyperplasia was seen in 2 (29%) cases, consistent with a sinusoidal/venous obstructive pattern of injury. We postulate that the sinusoidal location of the granulomas contributes to the venous obstructive changes. Recognition of this characteristic dual pattern of injury can allow pathologists to suggest the diagnosis and prompt the appropriate diagnostic and therapeutic interventions.

BACKGROUND: Pre-exposure prophylaxis (PrEP) greatly reduces the risk of HIV acquisition, but its optimal delivery strategy remains uncertain. Clinics for sexually transmitted infections (STIs) can provide an efficient venue for PrEP delivery. METHODS: To quantify the added value of STI clinic-based PrEP delivery, we used an agent-based simulation of HIV transmission among men who have sex with men (MSM). We simulated the impact of PrEP delivery through STI clinics compared with PrEP delivery in other community-based settings. Our primary outcome was the projected twenty-year reduction in HIV incidence among MSM. RESULTS: Assuming PrEP uptake and adherence of 60% each, evaluating STI clinic attendees and delivering PrEP to eligible MSM reduced HIV incidence by 16% [95% uncertainty range: 14% - 18%] over 20 years, an impact that was 1.8 [1.7-2.0] times as great as that achieved by evaluating an equal number of MSM recruited from the community. Comparing strategies where an equal number of MSM received PrEP in each strategy (i.e., evaluating more individuals for PrEP in the community-based strategy, since MSM attending STI clinics are more likely to be PrEP eligible), the reduction in HIV incidence under the STI clinic-based strategy was 1.3 [1.3-1.4] times as great as that of community-based delivery. CONCLUSIONS: Delivering PrEP to MSM who attend STI clinics can improve efficiency and effectiveness. If high levels of adherence can be achieved in this population, STI clinics may be an important venue for PrEP implementation.