Nyt fra tidsskrifterne

by Frederik Boe Hüttel, Anne-Mette Iversen, Marco Bo Hansen, Bjarne Kjær Ersbøll, Svend Ellermann-Eriksen, Niels Lundtorp Olsen Ensuring the safety of healthcare workers is vital to overcome the ongoing COVID-19 pandemic. We here present an analysis of the social interactions between the healthcare workers at hospitals and nursing homes. Using data from an automated hand hygiene system, we inferred social interactions between healthcare workers to identify transmission paths of infection in hospitals and nursing homes. A majority of social interactions occurred in medication rooms and kitchens emphasising that health-care workers should be especially aware of following the infection prevention guidelines in these places. Using epidemiology simulations of disease at the locations, we found no need to quarantine all healthcare workers at work with a contagious colleague. Only 14.1% and 24.2% of the health-care workers in the hospitals and nursing homes are potentially infected when we disregard hand sanitization and assume the disease is very infectious. Based on our simulations, we observe a 41% and 26% reduction in the number of infected healthcare workers at the hospital and nursing home, when we assume that hand sanitization reduces the spread by 20% from people to people and 99% from people to objects. The analysis and results presented here forms a basis for future research to explore the potential of a fully automated contact tracing systems.

by Masaaki Takeuchi, Yukie Higa, Akina Esaki, Yosuke Nabeshima, Akemi Nakazono Background Adverse reactions are more common after the second injection of messenger RNA vaccines such as Pfizer/BioNTech’s BNT162b2. We hypothesized that the degree and severity of reactogenicity after the second injection reflects the magnitude of antibody production against the SARS CoV-2 virus spike protein (spike IgG). Methods and results Blood samples were obtained from 67 Japanese healthcare workers three weeks after the first injection and two weeks after the second injection of the BNT162b2 vaccine to measure spike IgG levels. Using questionnaires, we calculated an adverse event (AE) score (0–11) for each participant. The geometric mean of spike IgG titers increased from 1,047 antibody units (AU/mL) (95% confidence interval (95% CI): 855–1282 AU/mL) after the first injection to 17,378 AU/mL (95% CI: 14,622–20,663 AU/mL) after the second injection. The median AE score increased from 2 to 5. Spike IgG levels after the second injection were negatively correlated with age and positively correlated with spike IgG after the first injection. AE scores after the second injection were not significantly associated with log-transformed spike IgG after the second injection, when adjusted for age, sex, AE score after the first injection, and log-transformed spike IgG after the first injection. Conclusions Although the sample size was relatively small, reactogenicity after the second injection may not accurately reflect antibody production.

by Narendran Gopalan, Vignes Anand Srinivasalu, Ponnuraja Chinnayan, Banurekha Velayutham, Adhin Bhaskar, Ramesh Santhanakrishnan, Thirumaran Senguttuvan, Sridhar Rathinam, Mahilmaran Ayyamperumal, Kumar Satagopan, Dhanalakshmi Rajendran, Tamizhselvan Manoharan, Sekar Lakshmanan, Paulkumaran Paramasivam, Dhanalakshmi Angamuthu, Mangalambal Ganesan, John Washington Easudoss Arockia, Ramesh Babu Venkatesan, Venkatesan Lakshmipathy, Shivakumar Shanmugham, Balaji Subramanyam, Shakila Shankar, Jawahar Mohideen Shaheed, Baskaran Dhanaraj, Narayanan Paranji Ramiyengar, Soumya Swaminathan, Padmapriyadarsini Chandrasekaran Introduction Despite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment. Materials and method We extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application. Results Of 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p<0.001). In the multivariate analysis, the adjusted hazards ratios (HR) for an unfavorable response to TB therapy for extent of involvement, baseline cavitation and persistence (post treatment) were 1.21 (95% CI: 1.01–1.44), 1.73 (95% CI: 1.05–2.84) and 2.68 (95% CI: 1.4–5.12) respectively. A 3+ smear had an HR of 1.94 (95% CI: 0.81–4.64). Further probing into the interaction, among patients with 3+ and 2+ smears, HRs for cavitation were 3.26 (95% CI: 1.33–8.00) and 1.92 (95% CI: 0.80–4.60) while for >2 zones, were 3.05 (95% CI: 1.12–8.23) and 1.92 (95% CI: 0.72–5.08) respectively. Patients without cavitation, zonal involvement 2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting “minimal disease”, had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens.

by Pei-Chen Chen, Pei-Chen Li, Dah-Ching Ding Objectives Most research into the management of pelvic inflammatory disease (PID) is in younger women and focuses on sexually transmitted pathogens such as N. gonorrhoeae or C. trachomatis. Non-sexually transmitted bacterial pathogens and PID in older women are rarely examined. The objective of this study is to explore cervical culture pathogens in women of different age groups in a medical center in eastern Taiwan. Methods We enrolled patients whose medical records were diagnosed with PID (ICD-9-CM 614.0 [N70.01–03], 614.1[N70.11–13], 614.9 [N73.5, N73.9]) at our hospital from October 2014 to March 2020. Patients were divided into three groups according to age: the age…

by Pedro C. Álvarez-Esteban, Eustasio del Barrio, Oscar M. Rueda, Cristina Rueda This paper analyses COVID-19 patients’ dynamics during the first wave in the region of Castilla y León (Spain) with around 2.4 million inhabitants using multi-state competing risk survival models. From the date registered as the start of the clinical process, it is assumed that a patient can progress through three intermediate states until reaching an absorbing state of recovery or death. Demographic characteristics, epidemiological factors such as the time of infection and previous vaccinations, clinical history, complications during the course of the disease and drug therapy for hospitalised patients are considered as candidate predictors. Regarding risk factors associated with mortality and severity, consistent results with many other studies have been found, such as older age, being male, and chronic diseases. Specifically, the hospitalisation (death) rate for those over 69 is 27.2% (19.8%) versus 5.3% (0.7%) for those under 70, and for males is 14.5%(7%) versus 8.3%(4.6%)for females. Among patients with chronic diseases the highest rates of hospitalisation are 26.1% for diabetes and 26.3% for kidney disease, while the highest death rate is 21.9% for cerebrovascular disease. Moreover, specific predictors for different transitions are given, and estimates of the probability of recovery and death for each patient are provided by the model. Some interesting results obtained are that for patients infected at the end of the period the hazard of transition from hospitalisation to ICU is significatively lower (p < 0.001) and the hazard of transition from hospitalisation to recovery is higher (p < 0.001). For patients previously vaccinated against pneumococcus the hazard of transition to recovery is higher (p < 0.001). Finally, internal validation and calibration of the model are also performed.

by Yilma Markos Larebo, Desta Erkalo Abame Introduction The widespread use of face masks by the general public may help to prevent the spread of viruses. Face masks are thought to be a good strategy to protect against respiratory diseases such as the Coronavirus. Identifying student knowledge, attitude, and practice about the use of face masks is crucial to detect vulnerabilities and respond rapidly to avoid the spread of the infection. This study aimed to determine the knowledge, attitude, and practices of face mask utilization and associated factors in the COVID-19 pandemic among college students. Methods A cross-sectional study was performed from February to March 2021 among 764 students from Wachemo University, Southern Ethiopia. A multistage sampling technique was used in the study. The sample size for each department was allocated in proportion to the number of students in that department, and each respondent was chosen using a simple random sampling procedure. Data were collected using a pre-tested self-administered questionnaire and analyzed using SPSS version 26. To predict the relationship between the predictor and outcome variables, a logistic regression model was used. At a p-value of 0.05, statistical significance was declared. Results The study showed that the overall knowledge of the students was 223 (29.2%), their attitude was 673 (88.1%), and their practice was 684 (89.5%). The students from the college natural and computational sciences (AOR: 0.23; 95%CI: 0.13, 0.40) and students having good knowledge (AOR = 4.40; 95%CI; 2.13, 9.14) were found to be independently associated with face mask utilization. Conclusion When compared to other researches, the knowledge about the usage of face masks in this study was low, but the attitudes and practices were high. Authorities in areas that are in danger of a COVID-19 pandemic should plan and implement public awareness and education initiatives.

by Maria Kyprianidou, Eleana Tzira, Petros Galanis, Konstantinos Giannakou Introduction Vaccine hesitancy is identified as one of the top threats to global health. A significant drop of childhood vaccine coverage is reported worldwide. One of the key reasons that influenced mothers’ choice to postpone, or avoid children’s vaccination, is knowledge. This study aimed to assess the level of Cypriot mothers’ knowledge on certain aspects of vaccination of their children, examine the association between vaccination knowledge and selected socio-demographic factors, and lastly assess the association of mothers’ knowledge about vaccination with vaccination coverage and delay, compliance to the recommended schedules, vaccination during pregnancy and mother-pediatrician relationship. Methods An online-based cross-sectional study conducted to collect information about socio-demographic characteristics, child’s characteristics, vaccination, and vaccine knowledge, using a self-administered questionnaire. The survey was conducted between April 2020 and June 2020 and the study population included mothers over 18 years old with at least one child (…

by Yasue Fukuda, Shuji Ando, Koji Fukuda Countermeasures against the spread of COVID-19 have become an urgent issue in educational settings, where many group activities are necessary. Educators are key to preventing the spread of COVID-19 in educational settings. Infection prevention behavior requires comprehensive and complex measures such as self-restraint. disinfection care, hand washing, wearing masks and recommendation and implementation of vaccination. Improvement in the knowledge, skills, and preventive actions of educators vis-à-vis COVID-19 could allow for the continued provision of educational services while ensuring safety in educational settings. Therefore, the objective of this study was to explore the knowledge and preventive actions of educators regarding COVID-19 and vaccination awareness to provide appropriate support for educators. The study used data collected from 1,000 Japanese educators in January 2021 when the third wave of viral infections spread. Online surveys and multivariate linear regression analysis were used to determine age and whether respondents were being cared for by a doctor. We investigated the effects of factors on educators’ willingness to be vaccinated and changes in their behavior. This study found that factors such as age, gender, whether a respondent was under a physician’s care, and health literacy, affected the willingness of educators to receive vaccinations and engage in preventive actions. The study also suggests that the reliability of national government public relations efforts is lower than the reliability of local government public relations and that of information from family physicians, pharmacies, and mass media. It is therefore necessary to reexamine how information is disseminated by the national government and to increase the degree of trust in that information among the public. The findings of the study also revealed the importance of improving the provision of appropriate information and health literacy for the behavior of educators, not only during the initial outbreak, but also during the subsequent period of pandemic life.

by Satoshi Shimizutani, Eiji Yamada The COVID-19 pandemic is likely to have adverse effects on the economy through damage to migration and remittances. We use a unique monthly household panel dataset that covers the period both before and after the outbreak to examine the impacts of COVID-19 on a variety of household welfare outcomes in Tajikistan, where remittance inflows in recent years have exceeded a quarter of annual GDP. We provide several findings. First, after April 2020, the adverse effects of the pandemic on household welfare were significantly observed and were particularly pronounced in the second quarter of 2020. Second, in contrast to expectation, the pandemic had a sharp but only transitory effect on the stock of migrants working abroad in the spring. Some expected migrants were forced to remain in their home country during the border closures, while some incumbent migrants expecting to return were unable to do so and remained employed in their destination countries. Both departures and returns started to increase again from summer. Employment and remittances of the migrants quickly recovered to levels seen in previous years after a sharp decline in April and May. Third, regression analyses reveal that both migration and remittances have helped to mitigate the adverse economic outcomes at home during the “with-COVID-19” period, suggesting that they served as a form of insurance. Overall, the unfavorable effects of the COVID-19 pandemic were severe and temporary right after the outbreak, but households with migrants were more resilient against the pandemic.

by Mario A. Quiroz-Juárez, Armando Torres-Gómez, Irma Hoyo-Ulloa, Roberto de J. León-Montiel, Alfred B. U’Ren The current COVID-19 public health crisis, caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has produced a devastating toll both in terms of human life loss and economic disruption. In this paper we present a machine-learning algorithm capable of identifying whether a given patient (actually infected or suspected to be infected) is more likely to survive than to die, or vice-versa. We train this algorithm with historical data, including medical history, demographic data, as well as COVID-19-related information. This is extracted from a database of confirmed and suspected COVID-19 infections in Mexico, constituting the official COVID-19 data compiled and made publicly available by the Mexican Federal Government. We demonstrate that the proposed method can detect high-risk patients with high accuracy, in each of four identified clinical stages, thus improving hospital capacity planning and timely treatment. Furthermore, we show that our method can be extended to provide optimal estimators for hypothesis-testing techniques commonly-used in biological and medical statistics. We believe that our work could be of use in the context of the current pandemic in assisting medical professionals with real-time assessments so as to determine health care priorities.

by Carina Marquez, Andrew D. Kerkhoff, Jamie Naso, Maria G. Contreras, Edgar Castellanos Diaz, Susana Rojas, James Peng, Luis Rubio, Diane Jones, Jon Jacobo, Susy Rojas, Rafael Gonzalez, Jonathan D. Fuchs, Douglas Black, Salustiano Ribeiro, Jen Nossokoff, Valerie Tulier-Laiwa, Jacqueline Martinez, Gabriel Chamie, Genay Pilarowski, Joseph DeRisi, Maya Petersen, Diane V. Havlir Background COVID-19 vaccine coverage in the Latinx community depends on delivery systems that overcome barriers such as institutional distrust, misinformation, and access to care. We hypothesized that a community-centered vaccination strategy that included mobilization, vaccination, and “activation” components could successfully reach an underserved Latinx population, utilizing its social networks to boost vaccination coverage. Methods Our community-academic-public health partnership, “Unidos en Salud,” utilized a theory-informed approach to design our “Motivate, Vaccinate, and Activate” COVID-19 vaccination strategy. Our strategy’s design was guided by the PRECEDE Model and sought to address and overcome predisposing, enabling, and reinforcing barriers to COVID-19 vaccination faced by Latinx individuals in San Francisco. We evaluated our prototype outdoor, “neighborhood” vaccination program located in a central commercial and transport hub in the Mission District in San Francisco, using the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework during a 16-week period from February 1, 2021 to May 19, 2021. Programmatic data, city-wide COVID-19 surveillance data, and a survey conducted between May 2, 2021 and May 19, 2021 among 997 vaccinated clients ≥16 years old were used in the evaluation. Results There were 20,792 COVID-19 vaccinations administered at the neighborhood site during the 16-week evaluation period. Vaccine recipients had a median age of 43 (IQR 32–56) years, 53.9% were male and 70.5% were Latinx, 14.1% white, 7.7% Asian, 2.4% Black, and 5.3% other. Latinx vaccinated clients were substantially more likely than non-Latinx clients to have an annual household income of less than $50,000 a year (76.1% vs. 33.5%), be a first-generation immigrant (60.2% vs. 30.1%), not have health insurance (47.3% vs. 16.0%), and not have access to primary care provider (62.4% vs. 36.2%). The most frequently reported reasons for choosing vaccination at the site were its neighborhood location (28.6%), easy and convenient scheduling (26.9%) and recommendation by someone they trusted (18.1%); approximately 99% reported having an overall positive experience, regardless of ethnicity. Notably, 58.3% of clients reported that they were able to get vaccinated earlier because of the neighborhood vaccination site, 98.4% of clients completed both vaccine doses, and 90.7% said that they were more likely to recommend COVID-19 vaccination to family and friends after their experience; these findings did not substantially differ according to ethnicity. There were 40.3% of vaccinated clients who said they still knew at least one unvaccinated person (64.6% knew ≥3). Among clients who received both vaccine doses (n = 729), 91.0% said that after their vaccination experience, they had personally reached out to at least one unvaccinated person they knew (61.6% reached out to ≥3) to recommend getting vaccinated; 83.0% of clients reported that one or more friends, and/or family members got vaccinated as a result of their outreach, including 18.9% who reported 6 or more persons got vaccinated as a result of their influence. Conclusions A multi-component, “Motivate, Vaccinate, and Activate” community-based strategy addressing barriers to COVID-19 vaccination for the Latinx population reached the intended population, and vaccinated individuals served as ambassadors to recruit other friends and family members to get vaccinated.

American Journal of Respiratory and Critical Care Medicine, Volume 204, Issue 6, Page 626-627, September 15, 2021.

Objectives: Multiple randomized controlled trials exploring the outcomes of patients with ventilator-associated bacterial pneumonia and hospital-acquired bacterial pneumonia have noted that hospital-acquired bacterial pneumonia patients who require subsequent ventilated hospital-acquired bacterial pneumonia suffered higher mortality than either those who did not (nonventilated hospital-acquired bacterial pneumonia) or had ventilator-associated bacterial pneumonia. We examined the epidemiology and outcomes of all three conditions in a large U.S. database. Design: Retrospective cohort. Setting: Two hundred fifty-three acute-care hospitals, United States, contributing data (including microbiology) to Premier database, 2012–2019. Patients: Patients with hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia identified based on a slightly modified previously published International Classification of Diseases, 9th Edition/International Classification of Diseases, 10th Edition-Clinical Modification algorithm. Interventions: None. Measurements and Main Results: Among 17,819 patients who met enrollment criteria, 26.5% had nonventilated hospital-acquired bacterial pneumonia, 25.6% vHAPB, and 47.9% ventilator-associated bacterial pneumonia. Ventilator-associated bacterial pneumonia predominated in the Northeastern United States and in large urban teaching hospitals. Patients with nonventilated hospital-acquired bacterial pneumonia were oldest (mean 66.7 ± 15.1 yr) and most likely White (76.9%), whereas those with ventilator-associated bacterial pneumonia were youngest (59.7 ± 16.6 yr) and least likely White (70.3%). Ventilated hospital-acquired bacterial pneumonia was associated with the highest comorbidity burden (mean Charlson score 4.1 ± 2.8) and ventilator-associated bacterial pneumonia with the lowest (3.2 ± 2.5). Similarly, hospital mortality was highest among patients with ventilated hospital-acquired bacterial pneumonia (29.2%) and lowest in nonventilated hospital-acquired bacterial pneumonia (11.7%), with ventilator-associated bacterial pneumonia in-between (21.3%). Among survivors, 24.5% of nonventilated hospital-acquired bacterial pneumonia required a rehospitalization within 30 days of discharge, compared with 22.5% among ventilated hospital-acquired bacterial pneumonia and 18.8% ventilator-associated bacterial pneumonia. Unadjusted hospital length of stay after infection onset was longest among ventilator-associated bacterial pneumonia and shortest among nonventilated hospital-acquired bacterial pneumonia patients. Median total hospital costs mirrored length of stay: ventilator-associated bacterial pneumonia $77,657, ventilated hospital-acquired bacterial pneumonia $62,464, and nonventilated hospital-acquired bacterial pneumonia $39,911. Conclusions: Both hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia remain associated with significant mortality and cost in the United States. Our analyses confirm that of all three conditions, ventilated hospital-acquired bacterial pneumonia carries the highest risk of death. In contrast, ventilator-associated bacterial pneumonia remains most costly. Nonventilated hospital-acquired bacterial pneumonia survivors were most likely to require a readmission within 30 days of discharge. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http:/journals.lww.com/ccmjournal). Supported, in part, by a grant from Merck Sharp & Dohme, a subsidiary of Merck, Kenilworth, NJ. Portions of these data have been presented at the European Congress of Clinical Microbiology & Infectious Diseases 2021 annual conference. Dr. Zilberberg’s institution received funding from Merck Sharpe & Dohme, Spero Therapeutics, Lungpacer Medical, Tetraphase, Nabriva, and Melinta; she disclosed that she has stock in J&J. Dr. Nathanson’s institution received funding from EviMed, LLC; he disclosed his company, OptiStatim, LLC, and has had a consulting agreement with Spero Therapeutics. Dr. Puzniak disclosed work for hire and that she is an employee and stockholder of Merck & Co. Drs. Puzniak and Shorr received funding from Merck & Co. For information regarding this article, E-mail: evimedgroup@gmail.com This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Objectives: To evaluate whether a nurse navigator-led, multicomponent Sepsis Transition And Recovery program improves 30-day mortality and readmission outcomes after sepsis hospitalization. Design: Multisite pragmatic randomized clinical trial. Setting: Three hospitals in North Carolina from January 2019 to March 2020. PATIENTS: Eligible patients hospitalized for suspected sepsis and deemed high-risk for mortality or readmission by validated internal risk models. Interventions: Patients were randomized to receive usual care alone (i.e., routine transition support, outpatient care; n = 342) or additional Sepsis Transition And Recovery support (n = 349). The 30-day intervention involved a multicomponent transition service led by a nurse navigator through telephone and electronic health record communication to facilitate best practice postsepsis care strategies during and after hospitalization including: postdischarge medication review, evaluation for new impairments or symptoms, monitoring comorbidities, and palliative care approach when appropriate. Clinical oversight was provided by a Hospital Medicine Transition Services team. Measurements and Main Results: The primary outcome was a composite of mortality or hospital readmission at 30 days. Logistic regression models were constructed to evaluate marginal and conditional odds ratios (adjusted for prognostic covariates: age, comorbidity, and organ dysfunction at enrollment). Among 691 randomized patients (mean age = 63.7 ± 15.1 yr; 52% female), a lower percentage of patients in the Sepsis Transition And Recovery group experienced the primary outcome compared with the usual care group (28.7% vs 33.3%; risk difference, 4.7%; odds ratio, 0.80; 95% CI, 0.58–1.11; adjusted odds ratio, 0.80; 95% CI, 0.64–0.98). There were 74 deaths (Sepsis Transition And Recovery: 33 [9.5%] vs usual care: 41 [12.0%]) and 155 rehospitalizations (Sepsis Transition And Recovery: 71 [20.3%] vs usual care: 84 [24.6%]). Conclusions: In a multisite randomized clinical trial of patients hospitalized with sepsis, patients provided with a 30-day program using a nurse navigator to provide best practices for postsepsis care experienced a lower proportion of either mortality or rehospitalization within 30 days after discharge. Further research is needed to understand the contextual factors associated with successful implementation. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, internally by Atrium Health Acute Care Outcomes Research Network. Dr. Taylor reports grant support from National Institutes of Health (NIH) outside of the submitted work. Dr. Kowalkowski reports grant support from NIH and Patient-Centered Outcomes Research Institute outside of the submitted work. Drs. Taylor and Kowalkowski received funding from the National Institute of Nursing Research and the National Library of Medicine. Drs. Rios and Hetherington received support for article research from the NIH. Drs. Rios and Kowalkowski disclosed work for hire. Dr. McWilliams’ institution received funding from The Heineman Foundation; he disclosed he is the co-founder and administrative member of iEnroll, LLC. Drs. McWilliams’s and Hetherington’s institutions received funding from the NIH. Dr. Russo received funding from Moderna. The remaining authors have disclosed that they do not have any potential conflicts of interest. Trial Registration: ClinicalTrials.gov NCT03865602. For information regarding this article, E-mail: Stephanie.P.Taylor@AtriumHealth.org Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Objectives: The host response plays a central role in the pathophysiology of sepsis and severe injuries. So far, no study has comprehensively described the overtime changes of the injury-induced immune profile in a large cohort of critically ill patients with different etiologies. Design: Prospective observational cohort study. Setting: Adult ICU in a University Hospital in Lyon, France. Patients: Three hundred fifty-three septic, trauma, and surgical patients and 175 healthy volunteers were included in the REAnimation Low Immune Status Marker study. Interventions: None. Measurements and Main Results: Extensive immune profiling was performed by assessing cellular phenotypes and functions, protein, and messenger RNA levels at days 1–2, 3–4, and 5–7 after inclusion using a panel of 30 standardized immune markers. Using this immunomonitoring panel, no specificity in the immune profile was observed among septic, trauma, and surgical patients. This common injury-induced immune response was characterized by an initial adaptive (i.e., physiologic) response engaging all constituents of the immune system (pro- and anti-inflammatory cytokine releases, and innate and adaptive immune responses) but not associated with increased risk of secondary infections. In contrary, the persistence in a subgroup of patients of profound immune alterations at the end of the first week after admission was associated with increased risk of secondary infections independently of exposure to invasive devices. The combined monitoring of markers of pro-/anti-inflammatory, innate, and adaptive immune responses allowed a better enrichment of patients with risk of secondary infections in the selected population. Conclusions: Using REAnimation Low Immune Status Marker immunomonitoring panel, we detected delayed injury-acquired immunodeficiency in a subgroup of severely injured patients independently of primary disease. Critically ill patients’ immune status could be captured through the combined monitoring of a common panel of complementary markers of pro-/anti-inflammatory, innate, and adaptive immune responses. Such immune monitoring needs to be incorporated in larger study cohorts with more extensive immune surveillance to develop specific hypothesis allowing for identification of biological systems affecting altered immune function related to late infection in the setting of acute systemic injury. The REALISM Study Group is listed in Appendix 1. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Drs. Venet and Textoris contributed equally. Drs. Venet, Textoris, Blein, Cortez, Tan, Tipple, Quemeneur, Reynier, Leissner, Vedrine, Bouffard, Delwarde, Martin, Girardot, Truc, Moucadel, Pachot, Monneret, and Rimmele were involved in the study design and data analysis. Drs. Venet, Textoris, Blein, Rol, Canard, Cortez, Meunier, Reynier, Vedrine, Moucadel, Pachot, and Monneret, and Rimmele contributed to the acquisition of data and data analysis. Drs. Venet and Textoris drafted the article, and all authors were involved in the revision of the article and approved the final version. Supported, in part, by the Agence Nationale de la Recherche through a grant awarded to BIOASTER (grant number ANR-10-AIRT-03) and by bioMérieux, Sanofi, and GSK. All commercial and academic partners involved in the study agreed on the study design, collection, analysis, interpretation of data, writing of report, and decision to submit the article for publication. Drs. Textoris, Blein, Moucadel, and Pachot are employees of bioMérieux SA, an in vitro diagnostic company. Drs. Venet, Bouffard, Delwarde, Martin, Girardot, Truc, Monneret, and Rimmelé are employees of Hospices Civils de Lyon. Drs. Venet, Textoris, Blein, Moucadel, Pachot, Monneret, and Rimmelé work in a joint research unit, cofunded by the Hospices Civils de Lyon and bioMérieux. Drs. Venet, Textoris, Pachot, and Monneret are coinventors in patent applications covering the following markers: CX3CR1, CD127, interleukin-10, and S100A9. Drs. Tan and Tipple are employees of and hold stock and shares in GlaxoSmithKline. Dr. Cortez is an employee of Sanofi Pasteur. Dr. Cortez was an employee of Sanofi. Drs. Venet’s, Textoris’s, Blein’s, Rol’s, Canard’s, Tipple’s, Vedrine’s, Martin’s, Girardot’s, Truc’s, Griffiths’s, Pachot’s, and Rimmelé’s institutions received funding from the Agence Nationale de la Recherche through a grant awarded to BIOASTER (ANR-10-AIRT-03), bioMerieux, Sanofi, and GSK. Dr. Bodinier received funding from HCL. Drs. Quemeneur and Moucadel disclosed work for hire. Dr. Quemeneur disclosed that his partner is an employee of Bioaster. Dr. Martin disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest. The work was performed at Hospices Civils de Lyon. For information regarding this article, E-mail: fabienne.venet@chu-lyon.fr Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

No abstract available…

Objectives: Electronic cigarette or vaping product use–associated lung injury is a clinical entity that can lead to respiratory failure and death. Despite the severity of electronic cigarette or vaping product use–associated lung injury, the role of extracorporeal life support in its management remains unclear. Our objective was to describe the clinical characteristics and outcomes of patients with electronic cigarette or vaping product use–associated lung injury who received extracorporeal life support. Design: We performed a retrospective review of records of electronic cigarette or vaping product use–associated lung injury patients who received extracorporeal life support. Standardized data were collected via direct contact with extracorporeal life support centers. Data regarding presentation, ventilatory management, extracorporeal life support details, and outcome were analyzed. Setting: This was a multi-institutional, international case series with patients from 10 different institutions in three different countries. Patients: Patients who met criteria for confirmed electronic cigarette or vaping product use–associated lung injury (based on previously reported diagnostic criteria) and were placed on extracorporeal life support were included. Patients were identified via literature review and by direct contact with extracorporeal life support centers. Measurements and Main Results: Data were collected for 14 patients ranging from 16 to 45 years old. All had confirmed vape use within 3 months of presentation. Nicotine was the most commonly used vaping product. All patients had respiratory symptoms and radiographic evidence of bilateral pulmonary opacities. IV antibiotics and corticosteroids were universally initiated. Patients were intubated for 1.9 days (range, 0–6) prior to extracorporeal life support initiation. Poor oxygenation and ventilation were the most common indications for extracorporeal life support. Five patients showed evidence of ventricular dysfunction on echocardiography. Thirteen patients (93%) were placed on venovenous extracorporeal life support, and one patient required multiple rounds of extracorporeal life support. Total extracorporeal life support duration ranged from 2 to 37 days. Thirteen patients survived to hospital discharge; one patient died of septic shock. Conclusions: Electronic cigarette or vaping product use–associated lung injury can cause refractory respiratory failure and hypoxemia. These data suggest that venovenous extracorporeal life support can be an effective treatment option for profound, refractory respiratory failure secondary to electronic cigarette or vaping product use–associated lung injury. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Gupta contributed to the conception and design of the work as well as the acquisition, analysis, and interpretation of data. He drafted the article. Dr. Hayes, Dr. Tonna, Dr. Han, and Ms. Garcia made substantial contributions to the acquisition and interpretation of data for the work. Drs. Hsu, Bridges, Diaban, Bosma, Bhatt, Sakla, Bermudez, and Manetta made substantial contributions to the data acquisition of the work. Mr. Rycus made contributions to study conception and data acquisition. Dr. Harting made substantial contributions to the conception and design of the work as well as the acquisition, analysis, and interpretation of data. They have all contributed to drafting the work or revising it critically for important intellectual content. They have all approved the final version for publication and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and reported. Dr. Tonna is supported by a Career Development Award from the National Institutes of Health/National Heart, Lung, And Blood Institute (K23 HL141596). He received speaker fees and travel compensation from LivaNova and Philips Healthcare, unrelated to this work. Dr. Tonna’s institution received funding from LivaNova, Phillips Healthcare, and the National Heart, Lung, and Blood Institute; he received support for article research from the National Institutes of Health; he disclosed the off-label product use of extracorporeal membrane oxygenation. Dr. Bermudez received funding from Abbott acute mechanical circulatory support advisory board and Breethe/Abiomed. The remaining authors have disclosed that they do not have any potential conflicts of interest. A portion of these cases (six of 14) have been reported previously in individual reports or smaller series. Details regarding any overlapping patients are described in the methods section of the article. These data were presented, in part, at the Extracorporeal Life Support Organization Annual Meeting (2020) and the American Thoracic Society Annual Meeting (2020). Address requests for reprints to: Matthew T. Harting, MD, MS, Department of Pediatric Surgery, McGovern Medical School at the University of Texas Health Science Center and Children’s Memorial Hermann Hospital, 6431 Fannin St, MSB 5.233, Houston, TX 77030. E-mail: matthew.t.harting@uth.tmc.edu Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Background Venezuela accounted for 55% of the cases and 73% of the malaria deaths in the Americas in 2019. Bolivar state, in the southeast, contributes > 60% of the country's Plasmodium vivax and Plasmodium falciparum cases every year. This study describes the clinical–epidemiological characteristics of clinical malaria patients in this high-transmission area. Methods A prospective study was conducted on patients seeking medical attention in three medical centres in the state capital, Ciudad Bolivar, between June and October 2018. Malaria diagnosis was carried out using microscopy following national standards. Malaria-positive patients were examined for clinical symptoms, and haematological tests were performed at the time of diagnosis. Patients were followed up by telephone to evaluate malaria recurrences. Results Out of 287 patients, 200 (69.7%) were positive for P. vivax, 69 (24%) for P. falciparum, and 18 (6.3%) had mixed (P. vivax/P. falciparum) infections. Patients' median age was 33 years (IQR 20), 168 (69%) were men, and 40% practiced gold mining as the main occupation. Fever (96.5%), chills (91.3%), and headaches (90.6%) were the most frequent symptoms. At least one symptom associated with severe malaria was observed in 69 out of 161 patients with complete clinical evaluation (42.9%). Plasmodium vivax infections were found in 42 out of 69 (60.9%) severe cases; by contrast, P. falciparum and mixed malaria caused 34.8% (24/69) and 4.4% (3/69) of infections, respectively. Two patients died of cerebral malaria. Mean hemoglobin was lower in the patients infected with P. falciparum than those infected with P. vivax. Regardless of the parasite causing the infection, patients presented high levels of total bilirubin, aminotransferases (AST, ALT), and lactate dehydrogenase (LDH). Out of the 142 patients followed up by phone for three months (49.5% of the 287 patients), 35 (24.7%) reported recurrences. Conclusions The high malaria prevalence among young male adults practicing gold mining suggests that this occupation is a significant risk factor. The unexpected high prevalence of P. vivax patients with at least one criteria of severe clinical disease is a matter of concern. Whether it is the result of a lack of timely diagnosis and effective treatment should be explored.

Abstract Background Plasmodium falciparum erythrocyte binding antigen-175 (PfEBA-175) is a candidate antigen for a blood-stage malaria vaccine, while various polymorphisms and dimorphism have prevented to development of effective vaccines based on this gene. This study aimed to investigate the dimorphism of PfEBA-175 on both the Bioko Island and continent of Equatorial Guinea, as well as the genetic polymorphism and natural selection of global PfEBA-175. Methods The allelic dimorphism of PfEBA-175 region II of 297 bloods samples from Equatorial Guinea in 2018 and 2019 were investigated by nested polymerase chain reaction and sequencing. Polymorphic characteristics and the effect of natural selection were analyzed using MEGA 7.0, DnaSP 6.0 and PopART programs. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 and Foldx program. Results Both Bioko Island and Bata district populations, the frequency of the F-fragment was higher than that of the C-fragment of PfEBA-175 gene. The PfEBA-175 of Bioko Island and Bata district isolates showed a high degree of genetic variability and heterogeneity, with π values of 0.00407 & 0.00411 and Hd values of 0.958 & 0.976 for nucleotide diversity, respectively. The values of Tajima's D of PfEBA-175 on Bata district and Bioko Island were 0.56395 and − 0.27018, respectively. Globally, PfEBA-175 isolates from Asia were more diverse than those from Africa and South America, and genetic differentiation quantified by the fixation index between Asian and South American countries populations was significant (FST > 0.15, P < 0.05). A total of 310 global isolates clustered in 92 haplotypes, and only one cluster contained isolates from three continents. The mutations A34T, K109E, D278Y, K301N, L305V and D329N were predicted as probably damaging. Conclusions This study demonstrated that the dimorphism of F-fragment PfEBA-175 was remarkably predominant in the study area. The distribution patterns and genetic diversity of PfEBA-175 in Equatorial Guinea isolates were similar another region isolates. And the levels of recombination events suggested that natural selection and intragenic recombination might be the main drivers of genetic diversity in global PfEBA-175. These results have important reference value for the development of blood-stage malaria vaccine based on this antigen.

Human cytomegalovirus (HCMV) non-primary infections can occur in pregnant women and may result in congenital infection. Comprehensive studies investigating the frequency, characteristics, risk factors and immune response of non-primary infection in pregnancy are missing, while rate of vertical transmission is not known.

Reactivation of latent toxoplasmosis may be life-threatening in haematopoietic stem cell transplant (HSCT) recipients. We conducted an eight-year-long prospective study on the diagnosis and monitoring of reactivated toxoplasmosis in paediatric HSCT recipients. The primary objective was to determine the incidence of reactivated toxoplasmosis in a setting that withholds prophylaxis until engraftment. The second objective was to identify the subgroups of HSCT recipients particularly prone to reactivation who may benefit the most from regular PCR follow-up.

INTRODUCTION…

Abstract Background The number of persons infected with COVID-19 continues to increase with deaths reported daily across the globe. High income countries such as the US, the UK, Italy and Belgium have reported high COVID-19 related deaths but low-and-middle-income countries have recorded fewer deaths despite having poor healthcare system. This study aimed to investigate the association between malaria prevalence and COVID-19 mortality. Methods An ecological study was conducted with data from 195 countries. Spearman’s correlation was used to test the association between the population variables and COVID-19 mortality. Generalized linear model with Poisson distribution was used to determine the significant predictors of COVID-19 mortality. Results There was a significant positive correlation between median age, life expectancy, 65+ mortality and COVID-19 mortality while malaria prevalence, sex ratio and cardiovascular mortality were negatively correlated with COVID-19 mortality. Malaria prevalence, life expectancy and mortality rate were significant on multivariate regression analysis. Conclusion The results of this study support the hypotheses that there are reduced COVID-19 deaths in malaria endemic countries, although the results need to be proved further by clinical trials.

Abstract Background Shanghai, as a pilot city of China to achieve the goal of eliminating hepatitis C, its strategy of allocating medical resources is a pressing problem to be solved. This study aims to infer the time-spatial clustering patterns of HCV-infected cases, and grasp the dynamic genotype distribution of HCV, thereby inform elimination strategies of HCV with efficacy and efficiency. Methods Reported HCV cases including their demographic information in Shanghai city from 2005 to 2018 were released from the National Infectious Disease Reporting Information System, population data at community scale, geographical layers of hospitals, communities and districts were gathered from former research. Blood samples of HCV-infected individuals were collected during 2014–2018 from 24 sentinel hospitals, HCV-antibody test, qualitative nucleic acid test and NS5B/5’UTR gene amplification were performed accordingly to determine the genotypes of the specimen. Furthermore, global and local spatial self-correlation analysis of both acute and chronic HCV infections were conducted at community scale year by year, then time-spatial clusters of acute and chronic HCV infections and HCV genotype distribution of specimen collected from sentinel hospitals by districts were mapped by using Arcmap10.1. Results A total of 2631 acute HCV cases and 15,063 chronic HCV cases were reported in Shanghai from 2005 to 2018, with a peak in 2010 and 2017, respectively. The mean age of chronic HCV patients was 49.70 ± 14.55 years, 3.34 ± 0.32 years older than the acute (t = 10.55, P-value < 0.01). The spatial distribution of acute HCV infection formed one primary cluster (Relative Risk = 2.71), and the chronic formed one primary cluster and three secondary clusters with Relative Risk ranged from 1.94 to 14.42, meanwhile, an overlap of 34 communities between acute and chronic HCV clusters were found with time period spans varied from 6 to 12 years. Genotype 1 (N = 257, 49.71%) was the most prevalent HCV genotype in Shanghai, genotype 3 infections have increased in recent years. Baoshan district presented cluster of acute HCV and the highest proportion of genotype 2, Pudong new area was the cluster of chronic HCV and occupied the highest proportion of genotype 3. Conclusions Despite the low prevalence of HCV infection, it is still needed to push forward the elimination process in Shanghai, as there is a certain amount of HCV infected people waiting to be treated. The time-spatial clustering patterns and the dynamic of HCV genotype distribution together indicated a changing constitution of different transmission routes of HCV infection, thus, a focused strategy may be needed for high-risk population related to genotype 3 infection like drug users, in addition to an enforcement of the existing measures of preventing the iatrogenic and hematogenic transmission of HCV.

Abstract Background Limited data suggest that personal lubricants may damage the vaginal mucosal epithelium, alter the vaginal microbiota, and increase inflammation. We compared vaginal cytokine profiles and microbiota before and after vaginal lubricant use and condomless vaginal sex. Methods Reproductive-age women were recruited to a 10-week observational cohort study and were asked to self-collect vaginal samples and behavioral diaries daily. This nested case–control analysis utilized samples collected before and after self-reported condomless sexual activity with lubricants (22 case participants) and without lubricants (22 control participants). Controls were matched to cases on race/ethnicity. Microbiota composition was characterized by sequencing amplicons of the 16S rRNA gene V3–V4 regions. Cytokine concentrations were quantified using a magnetic bead 41-plex panel assay and read using a Bio-Plex 200 array reader. Wilcoxon signed-rank tests were used to assess baseline differences in vaginal cytokines between cases and controls as well as differences pre- and post-exposure. Linear mixed effects models were used to examine differences in relative post-to-pre change in each individual cytokine between matched cases and controls. Similar analyses were conducted for the microbiota data. Results Mean age was 29.8 years (SD 6.8), and 63.6% were African American. There were few statistically significant changes in cytokines or microbiota before and after exposure in cases or controls. In mixed-effects modeling, the mean relative post-to-pre change of cytokines was higher in cases vs. controls for macrophage derived chemokine (MDC) (p = 0.03). The microbiota data revealed no significant changes when measured by similarity scores, diversity indexes and descriptive community state types (CST) transition analyses. However, post sexual activity, the mean relative abundance of L. crispatus decreased for those who used lubricants (particularly those who were L. iners-dominated prior to exposure). Conclusions Although there were overall few differences in the vaginal microbiota and cytokine profiles of lubricant users and controls before and after condomless vaginal sex, there was a trend toward decreases in relative abundance of L. crispatus following use of lubricant. Future larger studies that take into account osmolarity and composition of lubricants may provide additional insights.

Abstract Background Rates of adherence to available recommendations for dose adjustments in patients with severe obesity are generally low. Hence, antimicrobials are often underdosed in these patients. Antimicrobial stewardship programmes can improve the use of antimicrobials in hospitalised patients. The aim of the study was to analyse the impact of an antimicrobial stewardship programme based on a computerised clinical decision support system for optimal dosing and antimicrobial use in inpatients with severe obesity. Methods This quasi-experimental retrospective study using interrupted time series was conducted in an academic centre in Canada from August 2008 to June 2018. The Antimicrobial Prescription Surveillance System was implemented in August 2010 (intervention 1) and specific rules targeting patients with class III obesity (body mass index ≥ 40 kg/m2) were added in June 2014 (intervention 2). Data were collected from all hospitalised adults receiving antimicrobials which required dose adjustment for severe obesity and were stratified by body mass index. Segmented regression analysis of interrupted time series was used to evaluate the impact of the Antimicrobial Prescription Surveillance System on the proportion of inappropriate days of therapy according to posology and on antimicrobial consumption. Results Overall, 65 205 antimicrobial prescriptions (68% non-obese, 25% class I-II obesity, and 7% class III obesity) were analysed. In patients with class III obesity, the intervention was associated with a decrease in the proportion of inappropriate days of therapy (trend after the first intervention, −0.8% per 2-month period [95% CI −1.1 to −0.5], p < 0.001; intercept, 11.3% [95% CI 8.2 to 14.5], p < 0.001), which led to a reduction of 35% over an eight-year period (from pre-intervention level of 19.1%). Intervention 1 resulted in a downward trend in antimicrobial consumption, followed by an increasing trend after intervention 2. In these patients, the most frequent interventions made by pharmacists targeted posology (46%). Conclusions Antimicrobial Prescription Surveillance System had a positive impact on dosing optimisation and antimicrobial consumption in patients with class III obesity. Improving antimicrobial prescriptions in these patients is important because suboptimal dosing could be associated with unfavourable outcomes.

Remdesivir is the only antiviral drug currently approved under emergency use authorization for the treatment of patients hospitalized for mild and moderate COVID-19 (Beigel et al., 2020). Isolated cases of cardiac rhythm abnormalities have been reported in patients on Remdesivir, including sinus bradycardia and QTc interval-prolongation (Gubitosa et al., 2020; Gupta et al 2020) warranting for close cardiac rhythm monitoring during Remdesivir administration.

Journal of Medical Virology, Accepted Article.

The skin microbiota plays an essential role in the protection against pathogens. It is our skin microbiota that makes us smell different from each other, rendering us more or less attractive to mosquitoes. Mosquitoes exploit skin bacterial odours to locate their hosts and are vectors of pathogens that can cause severe diseases such as malaria and dengue fever. A novel solution for long-lasting protection against insect vectors of disease could be attained by manipulating the bacterial commensals on human skin.

Interactions between the Anopheles mosquito vector and Plasmodium parasites shape how malaria is transmitted in endemic regions. The long association of these two organisms has led to evolutionary processes that minimize fitness costs of infection and benefit both players through shared nutrient resources, parasite immune suppression, and mosquito tolerance to infection. In this review we explore recent data describing how Plasmodium falciparum, the deadliest malaria parasite, associates with one of its most important natural mosquito hosts, Anopheles gambiae, and we discuss the implications of these findings for parasite transmission and vector control strategies currently in development.

Abstract Background Shanghai, as a pilot city of China to achieve the goal of eliminating hepatitis C, its strategy of allocating medical resources is a pressing problem to be solved. This study aims to infer the time-spatial clustering patterns of HCV-infected cases, and grasp the dynamic genotype distribution of HCV, thereby inform elimination strategies of HCV with efficacy and efficiency. Methods Reported HCV cases including their demographic information in Shanghai city from 2005 to 2018 were released from the National Infectious Disease Reporting Information System, population data at community scale, geographical layers of hospitals, communities and districts were gathered from former research. Blood samples of HCV-infected individuals were collected during 2014–2018 from 24 sentinel hospitals, HCV-antibody test, qualitative nucleic acid test and NS5B/5’UTR gene amplification were performed accordingly to determine the genotypes of the specimen. Furthermore, global and local spatial self-correlation analysis of both acute and chronic HCV infections were conducted at community scale year by year, then time-spatial clusters of acute and chronic HCV infections and HCV genotype distribution of specimen collected from sentinel hospitals by districts were mapped by using Arcmap10.1. Results A total of 2631 acute HCV cases and 15,063 chronic HCV cases were reported in Shanghai from 2005 to 2018, with a peak in 2010 and 2017, respectively. The mean age of chronic HCV patients was 49.70 ± 14.55 years, 3.34 ± 0.32 years older than the acute (t = 10.55, P-value < 0.01). The spatial distribution of acute HCV infection formed one primary cluster (Relative Risk = 2.71), and the chronic formed one primary cluster and three secondary clusters with Relative Risk ranged from 1.94 to 14.42, meanwhile, an overlap of 34 communities between acute and chronic HCV clusters were found with time period spans varied from 6 to 12 years. Genotype 1 (N = 257, 49.71%) was the most prevalent HCV genotype in Shanghai, genotype 3 infections have increased in recent years. Baoshan district presented cluster of acute HCV and the highest proportion of genotype 2, Pudong new area was the cluster of chronic HCV and occupied the highest proportion of genotype 3. Conclusions Despite the low prevalence of HCV infection, it is still needed to push forward the elimination process in Shanghai, as there is a certain amount of HCV infected people waiting to be treated. The time-spatial clustering patterns and the dynamic of HCV genotype distribution together indicated a changing constitution of different transmission routes of HCV infection, thus, a focused strategy may be needed for high-risk population related to genotype 3 infection like drug users, in addition to an enforcement of the existing measures of preventing the iatrogenic and hematogenic transmission of HCV.

Abstract Background Limited data suggest that personal lubricants may damage the vaginal mucosal epithelium, alter the vaginal microbiota, and increase inflammation. We compared vaginal cytokine profiles and microbiota before and after vaginal lubricant use and condomless vaginal sex. Methods Reproductive-age women were recruited to a 10-week observational cohort study and were asked to self-collect vaginal samples and behavioral diaries daily. This nested case–control analysis utilized samples collected before and after self-reported condomless sexual activity with lubricants (22 case participants) and without lubricants (22 control participants). Controls were matched to cases on race/ethnicity. Microbiota composition was characterized by sequencing amplicons of the 16S rRNA gene V3–V4 regions. Cytokine concentrations were quantified using a magnetic bead 41-plex panel assay and read using a Bio-Plex 200 array reader. Wilcoxon signed-rank tests were used to assess baseline differences in vaginal cytokines between cases and controls as well as differences pre- and post-exposure. Linear mixed effects models were used to examine differences in relative post-to-pre change in each individual cytokine between matched cases and controls. Similar analyses were conducted for the microbiota data. Results Mean age was 29.8 years (SD 6.8), and 63.6% were African American. There were few statistically significant changes in cytokines or microbiota before and after exposure in cases or controls. In mixed-effects modeling, the mean relative post-to-pre change of cytokines was higher in cases vs. controls for macrophage derived chemokine (MDC) (p = 0.03). The microbiota data revealed no significant changes when measured by similarity scores, diversity indexes and descriptive community state types (CST) transition analyses. However, post sexual activity, the mean relative abundance of L. crispatus decreased for those who used lubricants (particularly those who were L. iners-dominated prior to exposure). Conclusions Although there were overall few differences in the vaginal microbiota and cytokine profiles of lubricant users and controls before and after condomless vaginal sex, there was a trend toward decreases in relative abundance of L. crispatus following use of lubricant. Future larger studies that take into account osmolarity and composition of lubricants may provide additional insights.

Abstract Background Rates of adherence to available recommendations for dose adjustments in patients with severe obesity are generally low. Hence, antimicrobials are often underdosed in these patients. Antimicrobial stewardship programmes can improve the use of antimicrobials in hospitalised patients. The aim of the study was to analyse the impact of an antimicrobial stewardship programme based on a computerised clinical decision support system for optimal dosing and antimicrobial use in inpatients with severe obesity. Methods This quasi-experimental retrospective study using interrupted time series was conducted in an academic centre in Canada from August 2008 to June 2018. The Antimicrobial Prescription Surveillance System was implemented in August 2010 (intervention 1) and specific rules targeting patients with class III obesity (body mass index ≥ 40 kg/m2) were added in June 2014 (intervention 2). Data were collected from all hospitalised adults receiving antimicrobials which required dose adjustment for severe obesity and were stratified by body mass index. Segmented regression analysis of interrupted time series was used to evaluate the impact of the Antimicrobial Prescription Surveillance System on the proportion of inappropriate days of therapy according to posology and on antimicrobial consumption. Results Overall, 65 205 antimicrobial prescriptions (68% non-obese, 25% class I-II obesity, and 7% class III obesity) were analysed. In patients with class III obesity, the intervention was associated with a decrease in the proportion of inappropriate days of therapy (trend after the first intervention, −0.8% per 2-month period [95% CI −1.1 to −0.5], p < 0.001; intercept, 11.3% [95% CI 8.2 to 14.5], p < 0.001), which led to a reduction of 35% over an eight-year period (from pre-intervention level of 19.1%). Intervention 1 resulted in a downward trend in antimicrobial consumption, followed by an increasing trend after intervention 2. In these patients, the most frequent interventions made by pharmacists targeted posology (46%). Conclusions Antimicrobial Prescription Surveillance System had a positive impact on dosing optimisation and antimicrobial consumption in patients with class III obesity. Improving antimicrobial prescriptions in these patients is important because suboptimal dosing could be associated with unfavourable outcomes.

Abstract Background Legionella spp. are ubiquitous freshwater bacteria responsible for rare but potentially severe cases of Legionnaires’ disease (LD). Legionella sainthelensi is a non-pneumophila Legionella species that was first isolated in 1980 from water near Mt. St-Helens (USA). Although rare cases of LD caused by L. sainthelensi have been reported, very little data is available on this pathogen. Case presentation We describe the first documented case of severe bilateral pleuropneumonia caused by L. sainthelensi. The patient was a 35-year-old woman with Sharp’s syndrome treated with long-term hydroxychloroquine and corticosteroids who was hospitalized for an infectious illness in a university hospital in Reunion Island (France). The patient’s clinical presentation was complicated at first (bilateral pneumonia, multiloculated pleural effusion, then bronchopleural fistula) but her clinical condition eventually improved with the reintroduction of macrolides (spiramycin) in intensive care unit. Etiological diagnosis was confirmed by PCR syndromic assay and culture on bronchoalveolar lavage. Conclusions To date, only 14 documented cases of L. sainthelensi infection have been described worldwide. This pathogen is difficult to identify because it is not or poorly detected by urinary antigen and molecular methods (like PCR syndromic assays that primarily target L. pneumophila and that have only recently been deployed in microbiology laboratories). Pneumonia caused by L. sainthelensi is likely underdiagnosed as a result. Clinicians should consider the possibility of non-pneumophila Legionella infection in patients with a compatible clinical presentation when microbiological diagnostic tools targeted L. pneumophila tested negative.

Abstract Background Few studies on pharyngotonsillitis have examined the clinical presentation of different aetiologies where pathogens have been detected using molecular methods. We aimed to assess how well clinical signs and symptoms can predict (1) the presence or absence of a broad range of viruses and bacteria, and (2) reconsultations for a sore throat or a complication. Methods In this descriptive observational prospective study in primary health care 220 patients aged 15–45 with suspected pharyngotonsillitis were sampled from nose, throat and blood and screened for 20 bacteria and viruses using polymerase chain reaction (PCR), culture and serology. Odds ratios (OR) and predictive values with 95% confidence intervals (CI) were used to show association between microbiological findings and clinical signs and symptoms. Patients were followed up after 3 months by reviewing electronic medical records. Results Both cough and coryza were more common in patients with only viruses (67%) than in patients with only bacteria (21%) (p < 0.001), whereas tonsillar coating was more common in patients with only bacteria (53%) than in patients with only viruses (29%) (p = 0.006). Tonsillar coating (adjusted OR 6.0; 95% CI 2.5–14) and a lack of cough (adjusted OR 3.5; 95% CI 1.5–8.0) were significantly associated with Streptococcus pyogenes (group A streptococci; GAS) and with any bacterial finding. A Centor score of 3–4 had a positive predictive value of 49% (95% CI 42–57) for GAS and 66% (95% CI 57–74) for any bacterial findings. The use of rapid antigen detection test for GAS increased the positive predictive value for this group to 93%. Conclusions Signs and symptoms, both single and combined, were insufficient to rule in GAS or other pathogens. However, both cough and coryza were useful to rule out GAS. The results support the clinical approach of restricting rapid antigen detection testing to patients with 3–4 Centor criteria. The low carriage rate of bacteria among asymptomatic controls implied that most detections in patients represented a true infection.

Abstract Background The ongoing COVID-19 pandemic remains a major challenge for worldwide health care systems and in particular emergency medicine. An early and safe triage in the emergency department (ED) is especially crucial for proper therapy. Clinical symptoms of COVID-19 comprise those of many common diseases; thus, differential diagnosis remains challenging. Method We performed a retrospective study of 314 ED patients presenting with conceivable COVID-19 symptoms during the first wave in Germany. All were tested for COVID-19 with SARS-Cov-2-nasopharyngeal swabs. Forty-seven patients were positive. We analyzed the 267 COVID-19 negative patients for their main diagnosis and compared COVID-19 patients with COVID-19 negative respiratory infections for differences in laboratory parameters, symptoms, and vital signs. Results Among the 267 COVID-19 negative patients, 42.7% had respiratory, 14.2% had other infectious, and 11.2% had cardiovascular diseases. Further, 9.0% and 6.7% had oncological and gastroenterological diagnoses, respectively. Compared to COVID-19 negative airway infections, COVID-19 patients showed less dyspnea (OR 0.440; p = 0.024) but more dysgeusia (OR 7.631; p = 0.005). Their hospital stay was significantly longer (9.0 vs. 5.6 days; p = 0.014), and their mortality significantly higher (OR 3.979; p = 0.014). Conclusion For many common ED diagnoses, COVID-19 should be considered a differential diagnosis. COVID-19 cannot be distinguished from COVID-19 negative respiratory infections by clinical signs, symptoms, or laboratory results. When hospitalization is necessary, the clinical course of COVID-19 airway infections seems to be more severe compared to other respiratory infections. Trial registration: German Clinical Trial Registry DRKS, DRKS-ID of the study: DRKS00021675 date of registration: May 8th, 2020, retrospectively registered.

Abstract Background SARS-CoV-2 poses a considerable threat to those living in residential aged care facilities (RACF). RACF COVID-19 outbreaks have been characterised by the rapid spread of infection and high rates of severe disease and associated mortality. Despite a growing body of evidence supporting airborne transmission of SARS-CoV-2, current infection control measures in RACF including hand hygiene, social distancing, and sterilisation of surfaces, focus on contact and droplet transmission. Germicidal ultraviolet (GUV) light has been used widely to prevent airborne pathogen transmission. Our aim is to investigate the efficacy of GUV technology in reducing the risk of SARS-CoV-2 infection in RACF. Methods A multicentre, two-arm double-crossover, randomised controlled trial will be conducted to determine the efficacy of GUV devices to reduce respiratory viral transmission in RACF, as an adjunct to existing infection control measures. The study will be conducted in partnership with three aged care providers in metropolitan and regional South Australia. RACF will be separated into paired within-site zones, then randomised to intervention order (GUV or control). The initial 6-week period will be followed by a 2-week washout before crossover to the second 6-week period. After accounting for estimated within-zone and within-facility correlations of infection, and baseline infection rates (10 per 100 person-days), a sample size of n = 8 zones (n = 40 residents/zone) will provide 89% power to detect a 50% reduction in symptomatic infection rate. The primary outcome will be the incidence rate ratio of combined symptomatic respiratory infections for intervention versus control. Secondary outcomes include incidence rates of hospitalisation for complications associated with respiratory infection; respiratory virus detection in facility air and fomite samples; rates of laboratory confirmed respiratory illnesses and genomic characteristics. Discussion Measures that can be deployed rapidly into RACF, that avoid the requirement for changes in resident and staff behaviour, and that are effective in reducing the risk of airborne SARS-CoV-2 transmission, would provide considerable benefit in safeguarding a highly vulnerable population. In addition, such measures might substantially reduce rates of other respiratory viruses, which contribute considerably to resident morbidity and mortality. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12621000567820 (registered on 14th May, 2021).

Abstract Background Coccidioidomycosis is a systemic infection caused by dimorphic fungi Coccidioides spp. endemic to Southwestern United States and Central and South America. A history of residence and travel in these areas is essential for the diagnostic of coccidioidomycosis, which has highly variable symptoms ranging from asymptomatic to severe, disseminated infection, and even death. Immunocompromised patients of coccidioidomycosis experience a high risk of dissemination, chronic infection, and mortality. Meningitis is one of the most deleterious coccidioidomycosis and can cause various life-threatening complications. Case presentation Here we report a case of Coccidioides posadasii meningitis in a 49-year-old female who returned to China after one and a half years residence in Los Angeles, USA. The repeated routine cultures using CSF for bacteria or fungi were all negative. To hunt for an infectious etiology, the state-of-the-art technology metagenomic next-generation sequencing (mNGS) was then utilized, suggesting Coccidioides posadasii. Organizational pathological examination and polymerase-chain-reaction (PCR) results subsequently confirmed the mNGS detection. Conclusion To our knowledge, cases for coccidioidal meningitis have been rarely reported in China. While global travelling may spread this disease across continents and make the diagnosis more difficult. mNGS can detect almost all known pathogens with high sensitivity and specificity, especially for uncommon pathogen, such as Coccidioides posadasii in China.

Abstract Background Drug-resistant tuberculosis (DR-TB) remains a major public health concern worldwide. Bedaquiline, a novel diarylquinoline, was added to the WHO-recommended all-oral regimen for patients with multidrug-resistant tuberculosis. We performed a systematic review and meta-analysis to determine the effect of bedaquiline on tuberculosis treatment outcomes. Methods We searched the PubMed, Web of Science and EMBASE databases for relevant studies published up to March 12, 2021. We included studies in which some participants received bedaquiline and others did not. Stata version 16.0 (Stata Corp., College Station, Texas, USA) was used to analyze the results of the meta-analysis. Risk ratios (RRs) with 95% confidence intervals (95% CIs) were calculated to evaluate the effect of bedaquiline on drug-resistant tuberculosis. Between-study heterogeneity was examined by the I-squared test. Randomized controlled trials were assessed for quality using the Jadad scale, and cohort studies were assessed using the Newcastle–Ottawa scale. Results Eight studies, including 2 randomized controlled trials and 6 cohort studies involving a total of 21,836 subjects, were included. When compared with the control, bedaquiline treatment was associated with higher rates of culture conversion (risk ratio (RR):1.272 (1.165–1.389), P < 0.001). We found substantial evidence of a significant reduction in all-cause death (RR: 0.529 (0.454–0.616), P < 0.001)) in the bedaquiline treatment group. There was no significant reduction in treatment success (RR = 0.980 (0.948–1.013, P = 0.234)). Conclusions This study demonstrated that compared with patients who do not receive bedaquiline, this drug has the potential to achieve a higher culture conversion rate and a lower mortality risk among drug-resistant tuberculosis cases.

Abstract Background Ventilator associated pneumonia (VAP) caused by more than one microorganisms is not uncommon and may be potentially challenging, but the relevant data is scarce in ventilated neonates. We aimed to investigate the clinical characteristics and outcomes of polymicrobial VAP in the neonatal intensive care unit (NICU). Methods All neonates with definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and September 2020 were prospectively observed and enrolled for analyses. All clinical features, therapeutic interventions and outcomes were compared between the polymicrobial VAP and monomicrobial VAP episodes. Multivariate regression analyses were used to find the independent risk factors for treatment failure. Results Among 236 episodes of neonatal VAP, 60 (25.4%) were caused by more than one microorganisms. Polymicrobial VAP episodes were more likely to be associated with multidrug-resistant pathogens (53.3% versus 34.7%, P = 0.014), more often occurred in later days of life and in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. Otherwise most clinical characteristics of polymicrobial VAP were similar to those of monomicrobial VAP. The therapeutic responses and treatment outcomes were also comparable between these two groups, although modification of therapeutic antibiotics were significantly more common in polymicrobial VAP episodes than monomicrobial VAP episodes (63.3% versus 46.2%; P < 0.001). None of any specific pathogens was significantly associated with worse outcomes. Instead, it is the severity of illness, including presence of concurrent bacteremia, septic shock, and requirement of high-frequency oscillatory ventilator and underlying neurological sequelae that are independently associated with treatment failure. Conclusions Polymicrobial VAP accounted for 25.4% of all neonatal VAP in the NICU, and frequently occurred in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. In our cohort, most clinical features, therapeutic responses and final outcomes of neonates with monomicrobial and polymicrobial VAP did not differ significantly.

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Purpose of review The purpose of the review is to summarize recent advances in understanding the origins, drivers and clinical context of zoonotic disease epidemics and pandemics. In addition, we aimed to highlight the role of clinicians in identifying sentinel cases of zoonotic disease outbreaks. Recent findings The majority of emerging infectious disease events over recent decades, including the COVID-19 pandemic, have been caused by zoonotic viruses and bacteria. In particular, coronaviruses, haemorrhagic fever viruses, arboviruses and influenza A viruses have caused significant epidemics globally. There have been recent advances in understanding the origins and drivers of zoonotic epidemics, yet there are gaps in diagnostic capacity and clinical training about zoonoses. Summary Identifying the origins of zoonotic pathogens, understanding factors influencing disease transmission and improving the diagnostic capacity of clinicians will be crucial to early detection and prevention of further epidemics of zoonoses.

Purpose of review The COVID-19 pandemic is a global catastrophe that has led to untold suffering and death. Many previously identified policy challenges in planning for large epidemics and pandemics have been brought to the fore, and new ones have emerged. Here, we review key policy challenges and lessons learned from the COVID-19 pandemic in order to be better prepared for the future. Recent findings The most important challenges facing policymakers include financing outbreak preparedness and response in a complex political environment with limited resources, coordinating response efforts among a growing and diverse range of national and international actors, accurately assessing national outbreak preparedness, addressing the shortfall in the global health workforce, building surge capacity of both human and material resources, balancing investments in public health and curative services, building capacity for outbreak-related research and development, and reinforcing measures for infection prevention and control. Summary In recent years, numerous epidemics and pandemics have caused not only considerable loss of life, but billions of dollars of economic loss. The COVID-19 pandemic served as a wake-up call and led to the implementation of relevant policies and countermeasures. Nevertheless, many questions remain and much work to be done. Wise policies and approaches for outbreak control exist but will require the political will to implement them.

Purpose of review Due to the impact of the COVID-19 pandemic this past year, we have witnessed a significant acceleration in the science, technology, and policy of global health security. This review highlights important progress made toward the mitigation of Zika, Ebola, and COVID-19 outbreaks. These epidemics and their shared features suggest a unified policy and technology agenda that could broadly improve global health security. Recent findings Molecular epidemiology is not yet in widespread use, but shows promise toward informing on-the-ground decision-making during outbreaks. Point-of-care (POC) diagnostics have been achieved for each of these threats; however, deployment of Zika and Ebola diagnostics lags behind those for COVID-19. POC metagenomics offers the possibility of identifying novel viruses. Vaccines have been successfully approved for Ebola and COVID-19, due in large part to public-private partnerships and advance purchase commitments. Therapeutics trials conducted during ongoing epidemics have identified effective antibody therapeutics for Ebola, as well as steroids (both inhaled and oral) and a broad-spectrum antiviral for COVID-19. Summary Achieving global health security remains a challenge, though headway has been made over the past years. Promising policy and technology strategies that would increase resilience across emerging viral pathogens should be pursued.

Purpose of review The current article will review how the coronavirus disease 2019 pandemic has changed travel and travel medicine. Recent findings Travelers spread severe acute respiratory syndrome coronavirus 2 globally and continue to spread variants. The characteristics of the virus, the place, and time created a perfect storm that allowed the virus to quickly spread globally. The virus spread by every mode of travel with risk of transmission influenced by proximity to an infected person, duration of trip, physical characteristics of the space, and ventilation. Superspreading events were common; a small percentage of infected people accounted for most of transmission. The travel and tourist industry was devastated as lockdowns and quarantines severely restricted domestic and international travel. A trip includes multiple segments and shared sequential spaces, mostly indoors. Creating safe travel requires attention to all segments of a trip. Summary The coronavirus disease 2019 pandemic has affected every part of travel and travel medicine. The rapid development of multiple safe and effective vaccines and their deployment is allowing resumption of travel, yet many populations lack access to vaccines, and high levels of transmission continue in many areas. Providing documentation of vaccination or immunity in a consistent, verifiable, interoperable system is one of many active issues.

Purpose of review To examine the literature assessing safety of air travel relating to coronavirus disease 2019 (COVID-19) transmission from January 2020 to May 2021. The COVID-19 pandemic has had an unprecedented impact on air travel and global mobility, and various efforts are being implemented to determine a safe way forward. As the pandemic evolves, so do the challenges that force various stakeholders, including the aviation industry, health authorities, and governments, to reassess and adapt their practices to ensure the safety of travellers. Recent findings The literature was reviewed for multiple aspects of air travel safety during the COVID-19 pandemic. Recurring themes that surfaced included the pivotal role of commercial air travel in the geographic spread of COVID-19, the efficacy of travel restrictions and quarantines, inflight transmission risk and the role of preventive measures, the utility of pre and post flight testing, the development of effective vaccines and subsequent challenges of vaccine passports, and the ongoing threat of novel highly transmissible variants. Summary Much uncertainty lies ahead within the domains of these findings, and ongoing research, discourse and review will be necessary to navigate and determine the future direction and safety of air travel. Recovery will be slow, necessitating innovative, multipronged and collaborative solutions.

Purpose of review Antimicrobial resistance (AMR) in bacteria poses a major risk to global public health, with many factors contributing to the observed increase in AMR. International travel is one recognized contributor. The purpose of this review is to summarize current knowledge regarding the acquisition, carriage and spread of AMR bacteria by international travelers. Recent findings Recent studies have highlighted that travel is an important risk factor for the acquisition of AMR bacteria, with approximately 30% of studied travelers returning with an acquired AMR bacterium. Epidemiological studies have shown there are three major risk factors for acquisition: travel destination, antimicrobial usage and travelers’ diarrhea (TD). Analyses have begun to illustrate the AMR genes that are acquired and spread by travelers, risk factors for acquisition and carriage of AMR bacteria, and local transmission of imported AMR organisms. Summary International travel is a contributor to the acquisition and dissemination of AMR organisms globally. Efforts to reduce the burden of AMR organisms should include a focus on international travelers. Routine genomic surveillance would further elucidate the role of international travel in the global spread of AMR bacteria.

Purpose of review Artemisinin-based combination therapies (ACTs) are globally the first-line treatment for uncomplicated falciparum malaria and new compounds will not be available within the next few years. Artemisinin-resistant Plasmodium falciparum emerged over a decade ago in the Greater Mekong Subregion (GMS) and, compounded by ACT partner drug resistance, has caused significant ACT treatment failure. This review provides an update on the epidemiology, and mechanisms of artemisinin resistance and approaches to counter multidrug-resistant falciparum malaria. Recent findings An aggressive malaria elimination programme in the GMS has helped prevent the spread of drug resistance to neighbouring countries. However, parasites carrying artemisinin resistance-associated mutations in the P. falciparum Kelch13 gene (pfk13) have now emerged independently in multiple locations elsewhere in Asia, Africa and South America. Notably, artemisinin-resistant infections with parasites carrying the pfk13 R561H mutation have emerged and spread in Rwanda. Summary Enhancing the geographic coverage of surveillance for resistance will be key to ensure prompt detection of emerging resistance in order to implement effective countermeasures without delay. Treatment strategies designed to prevent the emergence and spread of multidrug resistance must be considered, including deployment of triple drug combination therapies and multiple first-line therapies.

Purpose of review Infection with the larval (metacestode) stage of Echinococcus multilocularis causes alveolar echinococcosis (AE), a serious hepatic disorder. The parasite has increased its infection extensity in wildlife and domestic dogs, mainly due to urbanization and spatial extension of wildlife hosts in Europe, Asia as well as North America, resulting in emerging infection risk for humans. Recent findings In hyperendemic areas such as Kyrgyzstan and China, ecological and socioeconomic changes have been associated with the unpredictable increase of AE cases. In North America, the appearance of the European-like genotype is of concern. In Europe, the annual increase of human case numbers reached a plateau even in hyperendemic situations. Therefore, we conclude that most of the exposed individuals are resistant to parasite invasion and/or to disease development. Thus, AE develops in a few healthy individuals, but preferentially in immunosuppressed patients. Summary In the future, improved diagnostic strategies will allow more precise estimations of transmission routes including the role of food, water and direct dog contact, which should yield improved public health recommendations. Finally, understanding protective innate and acquired immune mechanisms as well as parasite-driven immune-evasion processes will be essential to develop curative therapies in nonoperable patients and, futuristically, appropriate vaccines.