Nyt fra tidsskrifterne

Tropical Medicine & International Health, Accepted Article.

In the face of vaccine dose shortages and logistical challenges, various deployment strategies are being proposed to increase population immunity levels to SARS-CoV-2. Two critical issues arise: how will the timing of delivery of the second dose affect both infection dynamics and prospects for the evolution of viral immune escape via a build-up of partially immune individuals. Both hinge on the robustness of the immune response elicited by a single dose, compared to natural and two-dose immunity. Building on an existing immuno-epidemiological model, we find that in the short-term, focusing on one dose generally decreases infections, but longer-term outcomes depend on this relative immune robustness. We then explore three scenarios of selection and find that a one-dose policy may increase the potential for antigenic evolution under certain conditions of partial population immunity. We highlight the critical need to test viral loads and quantify immune responses after one vaccine dose, and to ramp up vaccination efforts throughout the world.

Abstract Background To prevent antimicrobial resistance, both antimicrobial stewardship (AMS) and antifungal stewardship (AFS) in inpatient settings are needed in small/middle-sized hospitals as well as large hospitals. Methods We conducted the web-based, self-administered, nationwide cross-sectional study regarding AMS and AFS in inpatient settings in Japan, targeting hospitals that participated in a hospital epidemiology workshop conducted in July 2018. The questionnaire was composed of intervention protocols for use of broad-spectrum antimicrobials and antifungals within 7 or 28 d of beginning usage. These broad-spectrum antimicrobial and antifungal protocols were compared between large (≥501beds) and small/middle-sized (≤500 beds) hospitals. Results Of 240 hospitals surveyed, 39 (16%; 18 large and 21 small/middle-sized) responded. The number of hospitals that intervened in the use of broad-spectrum antimicrobials within 7 and 28 d were 17 (44%) and 34 (87%), respectively; those that intervened for antifungals were 3 (8%) and 10 (26%), respectively. Interventions for use of broad-spectrum antimicrobials within 7 d were significantly more frequent in small/middle-sized hospitals compared to large hospitals [13 (61. 9%) vs. 4 (22. 2%), odds ratio = 5.7, 95% confidence interval = 1.4–23.3, p = 0.023]. Conclusions Small/middle-sized hospitals had more frequent interventions within 7 d of broad-spectrum antimicrobial use than large hospitals. More effort to improve AFS is needed among all hospitals.

Abstract Background and purpose COVID-19 pandemic led to wide-spread use of face-masks, respirators and other personal protective equipment (PPE) by healthcare workers. Various symptoms attributed to the use of PPE are believed to be, at least in part, due to elevated carbon-dioxide (CO2) levels. We evaluated concentrations of CO2 under various PPE. Methods In a prospective observational study on healthy volunteers, CO2 levels were measured during regular breathing while donning 1) no mask, 2) JustAir® powered air purifying respirator (PAPR), 3) KN95 respirator, and 4) valved-respirator. Serial CO2 measurements were taken with a nasal canula at a frequency of 1-Hz for 15-min for each PPE configuration to evaluate whether National Institute for Occupational Safety and Health (NIOSH) limits were breached. Results The study included 11 healthy volunteers, median age 32 years (range 16–54) and 6 (55%) men. Percent mean (SD) changes in CO2 values for no mask, JustAir® PAPR, KN95 respirator and valve respirator were 0.26 (0.12), 0.59 (0.097), 2.6 (0.14) and 2.4 (0.59), respectively. Use of face masks (KN95 and valved-respirator) resulted in significant increases in CO2 concentrations, which exceeded the 8-h NIOSH exposure threshold limit value-weighted average (TLV-TWA). However, the increases in CO2 concentrations did not breach short-term (15-min) limits. Importantly, these levels were considerably lower than the long-term (8-h) NIOSH limits during donning JustAir® PAPR. There was a statistically significant difference between all pairs (p < 0.0001, except KN95 and valved-respirator (p = 0.25). However, whether increase in CO2 levels are clinically significant remains debatable. Conclusion Although, significant increase in CO2 concentrations are noted with routinely used face-masks, the levels still remain within the NIOSH limits for short-term use. Therefore, there should not be a concern in their regular day-to-day use for healthcare providers. The clinical implications of elevated CO2 levels with long-term use of face masks needs further studies. Use of PAPR prevents relative hypercapnoea. However, whether PAPR should be advocated for healthcare workers requiring PPE for extended hours needs to evaluated in further studies.

April 24, 2021, marks 1 year since the formation of the Access to COVID-19 Tools Accelerator (ACT-A) partnership. Its mission is to accelerate the development, production, and equitable access to COVID-19 tests, treatments, and vaccines, which is central to ending the acute phase of the COVID-19 pandemic. With the pandemic still raging, has ACT-A been successful so far? And what does the future hold?…

In an audit in 2015 of European intensive care units, central venous access was used in 70·7 per 100 patient days,1 and is also widely used in other clinical settings. It remains associated with considerable risks, in particular systemic infection, which can be severe and even lethal. In clinical studies, the most widely reported metric of this complication among patients is the number of catheter-related bloodstream infections (CRBSIs) per 1000 catheter days. In prospective studies across a range of clinical settings, reported rates are typically in the range of 1·0–2·7 CRBSI per 1000 central venous catheter days.

Doctors are reporting shortages of critical drugs and the need to ration care, pointing to public health failures. Lise Alves reports from São Paulo.

Soham Bandyopadhyay1 claimed that the UK Government's national lockdown, announced in November, 2020, to control COVID-19, was an institutionally racist policy. Claims of institutional racism are serious allegations and thus warrant critical appraisal. I therefore raise three points.

Bojorquez I, Cabieses B, Arósquipa C, et al. Migration and health in Latin America during the COVID-19 pandemic and beyond. Lancet 2021; 397: 1243–45—In this Comment, the date of the Ibero-American Summit has been corrected to April 21, 2021. This correction has been made to the online version as of April 15, 2021.

Infusion set use can be safely extended to 7 days with resultant cost and workload reductions.

A 66-year-old man attended our hospital with increasing shortness of breath, asthenia, and fever.

Antimicrobial resistance (AMR) is a major threat to human health globally. Surveillance is a key activity to determine AMR burden, impacts, and trends and to monitor effects of interventions. Surveillance systems require efficient capture and onward sharing of high-quality laboratory data. Substantial investment is being made to improve laboratory capacity, particularly in low-income and middle-income countries (LMICs) with high disease burdens. However, building capacity for effective laboratory data management remains an under-resourced area, which, unless addressed, will limit progress towards comprehensive AMR surveillance in LMICs.

I. G. Reed et al.

C. P. Popescu et al.

L. Staadegaard et al.

B. Breedlove…

by Lauren E. Parmley, Kieran Hartsough, Oliver Eleeza, Akopon Bertin, Bockarie Sesay, Amon Njenga, Mame Toure, Ginika Egesimba, Haja Bah, Alex Bayoh, Abdulraheem Yakubu, Ellen A. B. Morrison, Susan Michaels-Strasser After a decade of civil war and the 2014–2016 West African Ebola outbreak, Sierra Leone now faces the COVID-19 pandemic with a fragile health system. As was demonstrated during Ebola, preparedness is key to limiting a health crisis’ spread and impact on health systems and ensuring continued care for vulnerable populations including people living with HIV (PLHIV). To assess COVID-19 preparedness and inform interventions to ensure continuity of HIV services at health facilities (HFs) and community service points (CSPs), we conducted site readiness assessments in Freetown, the epicenter of COVID-19 in Sierra Leone. Data were collected at nine high-volume HIV HFs and seven CSPs in April 2020, a month after COVID-19 was declared a pandemic. CSPs comprised three community drop-in centers providing HIV counseling and testing services as well as HIV prevention services (e.g., condoms and lubricants) for key and priority populations and four community-based support groups serving PLHIV. At the time of assessment, CSPs did not provide antiretroviral therapy (ART) but were considered potential sites for expansion of differentiated service delivery (DSD)—a client-centered approach to HIV care—in the context of COVID-19. Overall, 5/9 HFs had trained staff on use of personal protective equipment (PPE) and prevention of COVID-19 transmission. Most had access to masks (5/9) and gloves (7/9) for management of suspected/confirmed COVID-19 cases, and 4/9 HFs had triage procedures for isolation of suspected cases. Conversely, few CSPs had access to masks (2/7) or gloves (2/7) and no staff were trained on PPE use or COVID-19 transmission. 7/9 HFs had adequate ART stock for multi-month dispensing though few had procedures for (3/9) or had trained staff in providing DSD (2/9). Among CSPs where measures were applicable, 2/4 had procedures for DSD, 1/3 had staff trained on DSD and none had adequate ART stock. Identification of gaps in COVID-19 preparedness is a critical step in providing support for infection control and modified service delivery. Findings from this assessment highlight gaps in COVID-19 preparedness measures at sites supporting PLHIV in Sierra Leone and indicate CSPs may require intensive supervision and training to ensure HIV services are uninterrupted while minimizing COVID-19 risk, especially if used as sites to scale up DSD.

by Rachael Phadnis, Champika Wickramasinghe, Juan Carlos Zevallos, Stacy Davlin, Vindya Kumarapeli, Veronica Lea, Juliette Lee, Udara Perera, Francisco Xavier Solórzano, Juan Francisco Vásconez Effective and rapid decision making during a pandemic requires data not only about infections, but also about human behavior. Mobile phone surveys (MPS) offer the opportunity to collect real-time data on behavior, exposure, knowledge, and perception, as well as care and treatment to inform decision making. The surveys aimed to collect coronavirus disease 2019 (COVID-19) related information in Ecuador and Sri Lanka using mobile phones. In Ecuador, a Knowledge, Attitudes and Practices (KAP) survey was conducted. In Sri Lanka, an evaluation of a novel medicine delivery system was conducted. Using the established mobile network operator channels and technical assistance provided through The Bloomberg Philanthropies Data for Health Initiative (D4H), Ministries of Health fielded a population-based COVID-19-specific MPS using Surveda, the open source data collection tool developed as part of the initiative. A total of 1,185 adults in Ecuador completed the MPS in 14 days. A total of 5,001 adults over the age of 35 in Sri Lanka completed the MPS in 44 days. Both samples were adjusted to the 2019 United Nations Population Estimates to produce population-based estimates by age and sex. The Ecuador COVID-19 MPS found that there was compliance with the mitigation strategies implemented in that country. Overall, 96.5% of Ecuadorians reported wearing a face mask or face covering when leaving home. Overall, 3.8% of Sri Lankans used the service to receive medicines from a government clinic. Among those who used the medicine delivery service in Sri Lanka, 95.8% of those who used a private pharmacy received their medications within one week, and 69.9% of those using a government clinic reported the same. These studies demonstrate that MPS can be conducted quickly and gather essential data. MPS can help monitor the impact of interventions and programs, and rapidly identify what works in mitigating the impact of COVID-19.

by Dani Zoorob, Shivam Shah, Danielle La Saevig, Courtney Murphy, Shaza Aouthmany, Kris Brickman Background Acute augmentation of stress and disruption of training, such as during the COVID-19 pandemic, may impact resident wellbeing. Objectives We investigated how residents in various specialties in the United States were impacted by COVID-19 on mental wellbeing and resilience levels, and the methodology for coping with the stress incurred. Methods In April 2020, the authors electronically surveyed 200 residency programs of all specialties nationally. The survey utilized two validated questionnaires to assess wellbeing and resilience, while investigating demographics and coping mechanisms. The authors used student t-test and ANOVA to quantitatively analyze the data. Results The sample consisted of 1115 respondents (with an 18% response rate). Male gender & Age >39 years were associated with more favorable average well-being indices (both p<0.01). Regarding resources, institutional support (IS) appeared favorable for resident well-being (IS 2.74, SD1.96 vs NoIS 3.71, SD2.29, p<0.01) & resilience (IS 3.72, SD0.70 vs NoIS 3.53, SD0.73, p = 0.05). The effects of mindfulness practices (MP) were not statistically significant for improvement of wellness (MP 2.87, SD 1.99 vs No MP 2.76, SD 2.15, p = 0.85) or resilience (MP 3.71, SD 0.70 vs No MP 3.72, SD 0.68, p = 0.87). Conclusions Findings highlight the critical importance of resident mental status in cases of augmented stress situations. Institutional support may contribute to promotion of resident wellbeing.

by Paulo Gonçalves, Emma Sáez-López, Sofia Carneiro, Maria João Simões Background The incidence of invasive meningococcal disease due to serogroup C (MenC) decreased in Portugal since the introduction of the conjugate vaccine (MCC) in the free market in 2001 and in the National Immunisation Plan in 2006. Considering the potential waning of the antibody response reported in the literature, the different vaccination schemes that were used in our country over the past decade, and that Neisseria meningitidis serogroup C continues to circulate, the Portuguese population may currently be at increased risk of infection. In the absence of national data, we evaluated the seroprotection level of the Portuguese population against MenC, in order to identify the protected fraction of the population and ponder on the necessity of a booster dose of the MCC vaccine. Methods We measured serum bactericidal antibody levels against MenC in a representative sample of the population (n = 1500) aged 2–64 years who participated in the 2015/2016 National Serological Survey. Results A total of 31.1% (466/1500, 95%CI: 29–33%) of the individuals studied were protected against MenC. The geometric mean titre was 6.5. The proportion of seroprotected was particularly low in children aged 2–4 years (…

by Xiu-Fen Yang, Meng-qi Li, Lu-lu Liao, Hui Feng, Si Zhao, Shuang Wu, Ping Yin Background The pandemic of coronavirus disease 2019 (COVID-19) has global impact, Wuhan in Hubei province is a high-risk area. And the older people in nursing homes are the most susceptible group to COVID-19. The aim of this study was to describe the practice and experience of the first-line medical team, to provide insights of coping with COVID-19 in China. Method This qualitative study used a descriptive phenomenological design to describe the experience of medical staff supported the nursing homes in Wuhan fighting against COVID-19. Unstructured interviews via online video were conducted with seven medical staffs who supported the nursing homes in Wuhan. Data were analyzed using content analysis in five main themes: for nursing homes, we interviewed the difficulties faced at the most difficult time, services for the older people, and prevention and management strategies, for the medical staff, the psychological experience were interviewed, and the implications for public health emergencies were also reported. Conclusions It is imperative that effective preventive and response measures be implemented to face the outbreak of COVID-19 and meet the care needs of older people in the context of COVID-19. Implications Findings will inform managers of some reasonable instructional strategies for implementing effective infection management. Nursing homes need to provide targeted services to help alleviating their bad psychology for residents.

Introduction Prisons are places with high vulnerability and high risk for the development of sexually transmitted infections. World Health Agencies recommend establishing intervention measures, such as information and education, on the prevention of diseases. Thus, technologies as tools for health education have been used to reduce sexually transmitted infections. However, no systematic review has investigated the effectiveness of these interventions. Therefore, this review’s objective is to examine the effect of educational technologies used for preventing sexually transmitted infections in incarcerated women. Methods and analysis Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be strictly followed. The following electronic databases will be searched: Scopus; Cumulative Index of Nursing and Allied Health, Education Resources Information Center, Embase, PsycINFO, PubMed/Medline, Web of Science and Google Scholar. Randomised clinical trials of interventions that used educational technologies to prevent sexually transmitted infections in incarcerated women will be searched in the databases from the beginning of 2020 until December by two researchers independently. A narrative synthesis will be constructed for all included studies, and if there are sufficient data, a meta-analysis will be performed using the Review Manager software (V.5.3). Continuous results will be presented as the weighted mean difference or the standardised mean difference with 95% CIs. Under the heterogeneity of the included studies, a random-effects or fixed-effects model will be used. The studies’ heterogeneity will be assessed by the I2 method. The sensitivity analysis will be carried out to examine the magnitude of each study’s influence on the general results. A significance level of p≤0.05 will be adopted. Ethics and disclosure Ethical approval is not required because no primary data will be collected. The results will be published in journals reviewed by peers. PROSPERO registration number CRD42020163820.

Objectives We aim to define the burden of rifampicin monoresistant tuberculosis (TB) at a tertiary care centre in northern India as well as determine the second-line drug susceptibilities (SL-DST) in a subset of patients. Methods A total of 3045 pulmonary (n=1883) and extrapulmonary (n=1162) samples from likely patients with TB were subjected to microscopy, culture and the Xpert MTB/RIF assay from March 2017 to June 2019. SL-DST testing by line probe assay version 2 for fluoroquinolones (FQs) and second-line injectable drugs were performed on 62 samples. Results Out of 3045 samples processed in our laboratory during the study period, 36.1% (1101/3045) were positive for Mycobacterium tuberculosis complex (MTBC) and 21.6% were rifampicin monoresistant (223/1032). The rate of rifampicin resistance in pulmonary samples was 23.5% (166/706) and in extrapulmonary cases, it was 17.4% (57/326). Out of 62 cases included for second-line testing, 48 were resistant to FQs (77.4%) while 11 were extensively drug resistant. Conclusions India urgently needs to arrest an emerging multidrug-resistant TB epidemic with associated resistance to FQs. A robust surveillance system is needed to execute the National Strategic Plan for 2017–2025.

Objective To provide evidence on the effect of the COVID-19 pandemic on the mental health of young people who grew up in poverty in low/middle-income countries (LMICs). Design A phone survey administered between August and October 2020 to participants of a population-based longitudinal cohort study established in 2002 comprising two cohorts born in 1994–1995 and 2001–2002 in Ethiopia, India (Andhra Pradesh and Telangana), Peru and Vietnam. We use logistic regressions to examine associations between mental health and pandemic-related stressors, structural factors (gender, age), and lifelong protective/risk factors (parent and peer relationship, wealth, long-term health problems, past emotional problems, subjective well-being) measured at younger ages. Setting A geographically diverse, poverty-focused sample, also reaching those without mobile phones or internet access. Participants 10 496 individuals were approached; 9730 participated. Overall, 8988 individuals were included in this study; 4610 (51%) men and 4378 (49%) women. Non-inclusion was due to non-location or missing data. Main outcome measures Symptoms consistent with at least mild anxiety or depression were measured by Generalized Anxiety Disorder-7 (≥5) or Patient Health Questionnaire-8 (≥5). Results Rates of symptoms of at least mild anxiety (depression) were highest in Peru at 41% (32%) (95% CI 38.63% to 43.12%; (29.49–33.74)), and lowest in Vietnam at 9% (9%) (95% CI 8.16% to 10.58%; (8.33–10.77)), mirroring COVID-19 mortality rates. Women were most affected in all countries except Ethiopia. Pandemic-related stressors such as health risks/expenses, economic adversity, food insecurity, and educational or employment disruption were risk factors for anxiety and depression, though showed varying levels of importance across countries. Prior parent/peer relationships were protective factors, while long-term health or emotional problems were risk factors. Conclusion Pandemic-related health, economic and social stress present significant risks to the mental health of young people in LMICs where mental health support is limited, but urgently needed to prevent long-term consequences.

Nature Medicine, Published online: 15 April 2021; doi:10.1038/s41591-021-01308-7 Comprehensive large-scale nucleic acid–testing strategies support China’s sustained containment of COVID-19…

Examining unmanipulated SARS-CoV-2-specific T cells is important for understanding primary and recall responses during COVID-19. Nguyen et al. analyze ex vivo CD8+ T cells specific for SARS-CoV-2 epitopes and find that immunodominant B7/N105-specific CD8+ T cells are present at high frequencies in blood samples from unexposed, acute COVID-19, and convalescence individuals, which is underpinned by diverse TCR repertoires.

by Shadnaz Asgari, Jelena Trajkovic, Mehran Rahmani, Wenlu Zhang, Roger C. Lo, Antonella Sciortino The COVID-19 pandemic compelled the global and abrupt conversion of conventional face-to-face instruction to the online format in many educational institutions. Urgent and careful planning is needed to mitigate negative effects of pandemic on engineering education that has been traditionally content-centered, hands-on and design-oriented. To enhance engineering online education during the pandemic, we conducted an observational study at California State University, Long Beach (one of the largest and most diverse four-year university in the U.S.). A total of 110 faculty members and 627 students from six engineering departments participated in surveys and answered quantitative and qualitative questions to highlight the challenges they experienced during the online instruction in Spring 2020. Our results identified various issues that negatively influenced the online engineering education including logistical/technical problems, learning/teaching challenges, privacy and security concerns and lack of sufficient hands-on training. For example, more than half of the students indicated lack of engagement in class, difficulty in maintaining their focus and Zoom fatigue after attending multiple online sessions. A correlation analysis showed that while semi-online asynchronous exams were associated with an increase in the perceived cheating by the instructors, a fully online or open-book/open-note exams had an association with a decrease in instructor’s perception of cheating. To address various identified challenges, we recommended strategies for educational stakeholders (students, faculty and administration) to fill the tools and technology gap and improve online engineering education. These recommendations are practical approaches for many similar institutions around the world and would help improve the learning outcomes of online educations in various engineering subfields. As the pandemic continues, sharing the results of this study with other educators can help with more effective planning and choice of best practices to enhance the efficacy of online engineering education during COVID-19 and post-pandemic.

by John Njuma Libwea, Mark A. Fletcher, Paul Koki Ndombo, Angeline Boula, Nadesh Taku Ashukem, Madeleine Ngo Baleba, Rachel Sandrine Kingue Bebey, Eric Gaston Nkolo Mviena, Jean Tageube, Marie Kobela Mbollo, Sinata Koulla-Shiro, Shabir Madhi, Berthe-Marie Njanpop-Lafourcade, Ali Mohammad, Elizabeth Begier, Joanna Southern, Rohini Beavon, Bradford Gessner Background The 13-valent pneumococcal conjugate vaccine (PCV13) entered Cameroon’s childhood national immunization programme (NIP) in July 2011 under a 3-dose schedule (6, 10, 14 weeks of age) without any catch-up. We described the impact of PCV13 onserotype distribution among pneumococcal meningitis cases over time. Methods We used laboratory-based sentinel surveillance data to identify meningitis cases among 2- to 59-month-old children with clinically-suspected bacterial meningitis (CSBM) admitted to hospitals in Yaoundé (August 2011-December 2018). Purulent meningitis cases had a cerebrospinal fluid (CSF) white blood cell (WBC) count ≥20 per mm3. Pneumococcal meningitis cases had S. pneumoniae identified from CSF, with serotyping by polymerase chain reaction. Years 2011-2014 were described as early PCV13 era (EPE) and years 2015-2018 as late PCV13 era (LPE) impact periods. Results Among children hospitalized with CSBM who had a lumbar puncture obtained, there was no significant change from the EPE versus the LPE in the percentage identified with purulent meningitis: 7.5% (112/1486) versus 9.4% (154/1645), p = 0.0846. The percentage of pneumococcal meningitis cases due to PCV13 vaccine-serotype (VST) decreased from 62.0% (31/50) during the EPE to 35.8% (19/53) in the LPE, p = 0.0081. The most frequent pneumococcal meningitis VSTs during the EPE were 6A/6B (30%) and 5 (6%), and during the LPE were 14 (13.2%), 3 (7.6%), 4 (5.6%) and 18C (5.6%). Conclusion Four to seven years after PCV13 introduction, the proportion of pneumococcal meningitis due to vaccine serotypes has declined, mainly due to reductions of serotypes 6A/6B, 1, 19A, and 23F; nevertheless, PCV13 VSTs remain common. Because the analyzed surveillance system was not consistent or population based, we could not estimate incidence or overall impact; this emphasizes the need for improved surveillance to document further the utility of PCV13 immunization in Cameroon.

by Avishek Chatterjee, Guangyao Wu, Sergey Primakov, Cary Oberije, Henry Woodruff, Pieter Kubben, Ronald Henry, Marcel J. H. Aries, Martijn Beudel, Peter G. Noordzij, Tom Dormans, Niels C. Gritters van den Oever, Joop P. van den Bergh, Caroline E. Wyers, Suat Simsek, Renée Douma, Auke C. Reidinga, Martijn D. de Kruif, Julien Guiot, Anne-Noelle Frix, Renaud Louis, Michel Moutschen, Pierre Lovinfosse, Philippe Lambin Objective To establish whether one can build a mortality prediction model for COVID-19 patients based solely on demographics and comorbidity data that outperforms age alone. Such a model could be a precursor to implementing smart lockdowns and vaccine distribution strategies. Methods The training cohort comprised 2337 COVID-19 inpatients from nine hospitals in The Netherlands. The clinical outcome was death within 21 days of being discharged. The features were derived from electronic health records collected during admission. Three feature selection methods were used: LASSO, univariate using a novel metric, and pairwise (age being half of each pair). 478 patients from Belgium were used to test the model. All modeling attempts were compared against an age-only model. Results In the training cohort, the mortality group’s median age was 77 years (interquartile range = 70–83), higher than the non-mortality group (median = 65, IQR = 55–75). The incidence of former/active smokers, male gender, hypertension, diabetes, dementia, cancer, chronic obstructive pulmonary disease, chronic cardiac disease, chronic neurological disease, and chronic kidney disease was higher in the mortality group. All stated differences were statistically significant after Bonferroni correction. LASSO selected eight features, novel univariate chose five, and pairwise chose none. No model was able to surpass an age-only model in the external validation set, where age had an AUC of 0.85 and a balanced accuracy of 0.77. Conclusion When applied to an external validation set, we found that an age-only mortality model outperformed all modeling attempts (curated on www.covid19risk.ai) using three feature selection methods on 22 demographic and comorbid features.

by Olivia L. McGovern, Mark Stenger, Sara E. Oliver, Tara C. Anderson, Cheryl Isenhour, Matthew R. Mauldin, Nia Williams, Eric Griggs, Tonny Bogere, Chris Edens, Aaron T. Curns, Joana Y. Lively, Yingtao Zhou, Songli Xu, Maureen H. Diaz, Jessica L. Waller, Kevin R. Clarke, Mary E. Evans, Elisabeth M. Hesse, Sapna Bamrah Morris, Robert P. McClung, Laura A. Cooley, Naeemah Logan, Andrew T. Boyd, Allan W. Taylor, Kristina L. Bajema, Stephen Lindstrom, Christopher A. Elkins, Christopher Jones, Aron J. Hall, Samuel Graitcer, Alexandra M. Oster, Alicia M. Fry, Marc Fischer, Laura Conklin, Runa H. Gokhale Background The Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), evolved rapidly in the United States. This report describes the demographic, clinical, and epidemiologic characteristics of 544 U.S. persons under investigation (PUI) for COVID-19 with complete SARS-CoV-2 testing in the beginning stages of the pandemic from January 17 through February 29, 2020. Methods In this surveillance cohort, the U.S. Centers for Disease Control and Prevention (CDC) provided consultation to public health and healthcare professionals to identify PUI for SARS-CoV-2 testing by quantitative real-time reverse-transcription PCR. Demographic, clinical, and epidemiologic characteristics of PUI were reported by public health and healthcare professionals during consultation with on-call CDC clinicians and subsequent submission of a CDC PUI Report Form. Characteristics of laboratory-negative and laboratory-positive persons were summarized as proportions for the period of January 17−February 29, and characteristics of all PUI were compared before and after February 12 using prevalence ratios. Results A total of 36 PUI tested positive for SARS-CoV-2 and were classified as confirmed cases. Confirmed cases and PUI testing negative for SARS-CoV-2 had similar demographic, clinical, and epidemiologic characteristics. Consistent with changes in PUI evaluation criteria, 88% (13/15) of confirmed cases detected before February 12, 2020, reported travel from China. After February 12, 57% (12/21) of confirmed cases reported no known travel- or contact-related exposures. Conclusions These findings can inform preparedness for future pandemics, including capacity for rapid expansion of novel diagnostic tests to accommodate broad surveillance strategies to assess community transmission, including potential contributions from asymptomatic and presymptomatic infections.

by Sebastien Kenmoe, Arnol Bowo-Ngandji, Cyprien Kengne-Nde, Jean Thierry Ebogo-Belobo, Donatien Serge Mbaga, Gadji Mahamat, Cynthia Paola Demeni Emoh, Richard Njouom Introduction Consideration of confounding factors about the association between Lower Respiratory Tract Infections (LRTI) in childhood and the development of subsequent wheezing has been incompletely described. We determined the association between viral LRTI at ≤ 5 years of age and the development of wheezing in adolescence or adulthood by a meta-analysis and a sensitivity analysis including comparable studies for major confounding factors. Methods We performed searches through Pubmed and Global Index Medicus databases. We selected cohort studies comparing the frequency of subsequent wheezing in children with and without LRTI in childhood regardless of the associated virus. We extracted the publication data, clinical and socio-demographic characteristics of the children, and confounding factors. We analyzed data using random effect model. Results The meta-analysis included 18 publications (22 studies) that met the inclusion criteria. These studies showed that viral LRTI in children ≤ 3 years was associated with an increased risk of subsequent development of wheezing (OR = 3.1, 95% CI = 2.4–3.9). The risk of developing subsequent wheezing was conserved when considering studies with comparable groups for socio-demographic and clinical confounders. Conclusions When considering studies with comparable groups for most confounding factors, our results provided strong evidence for the association between neonatal viral LRTI and the subsequent wheezing development. Further studies, particularly from lower-middle income countries, are needed to investigate the role of non-bronchiolitis and non-HRSV LRTI in the association between viral LRTI in childhood and the wheezing development later. In addition, more studies are needed to investigate the causal effect between childhood viral LRTI and the wheezing development later. Trial registration Review registration: PROSPERO, CRD42018116955; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018116955.

by Kevin Guedj, Mathieu Uzzan, Damien Soudan, Catherine Trichet, Antonino Nicoletti, Emmanuel Weiss, Hana Manceau, Alexandre Nuzzo, Olivier Corcos, Xavier Treton, Katell Peoc’h Background Severe acute respiratory syndrome caused by the novel coronavirus (SARS-CoV-2) is frequently associated with gastrointestinal manifestations. Herein we evaluated the interest in measuring the intestinal fatty acid-binding protein (I-FABP), a biomarker of intestinal injury, in COVID-19 patients. Methods Serum I-FABP was analyzed in 28 consecutive patients hospitalized for a PCR-confirmed COVID-19, in 24 hospitalized patients with non-COVID-19 pulmonary diseases, and 79 patients admitted to the emergency room for abdominal pain. Results I-FABP serum concentrations were significantly lower in patients with COVID-19, as compared to patients with non-COVID-19 pulmonary diseases [70.3 pg/mL (47–167.9) vs. 161.1 pg/mL (88.98–305.2), respectively, p = 0.008]. I-FABP concentrations in these two populations were significantly lower than in patients with abdominal pain without COVID-19 [344.8 pg/mL (268.9–579.6)]. I-FABP was neither associated with severity nor the duration of symptoms. I-FABP was correlated with polymorphonuclear cell counts. Conclusions In this pilot study, we observed a low I-FABP concentration in COVID-19 patients either with or without gastrointestinal symptoms, of which the pathophysiological mechanisms and clinical impact remain to be established. Further explorations on a larger cohort of patients will be needed to unravel the molecular mechanism of such observation, including the effects of malabsorption and/or abnormal lipid metabolism.

by Katherine Klise, Walt Beyeler, Patrick Finley, Monear Makvandi As social distancing policies and recommendations went into effect in response to COVID-19, people made rapid changes to the places they visit. These changes are clearly seen in mobility data, which records foot traffic using location trackers in cell phones. While mobility data is often used to extract the number of customers that visit a particular business or business type, it is the frequency and duration of concurrent occupancy at those sites that governs transmission. Understanding the way people interact at different locations can help target policies and inform contact tracing and prevention strategies. This paper outlines methods to extract interactions from mobility data and build networks that can be used in epidemiological models. Several measures of interaction are extracted: interactions between people, the cumulative interactions for a single person, and cumulative interactions that occur at particular businesses. Network metrics are computed to identify structural trends which show clear changes based on the timing of stay-at-home orders. Measures of interaction and structural trends in the resulting networks can be used to better understand potential spreading events, the percent of interactions that can be classified as close contacts, and the impact of policy choices to control transmission.

by Ariane Cristina Barboza Zanetti, Bruna Moreno Dias, Andrea Bernardes, Helaine Carneiro Capucho, Alexandre Pazetto Balsanelli, André Almeida de Moura, Rodrigo Soato, Carmen Silvia Gabriel Objective To analyze the incidence and preventability of adverse events related to health care in adult patients admitted to a Brazilian teaching hospital. Methods A retrospective cohort study, in which the incidence and preventability of adverse events related to health care were based on a two-stage retrospective review of 368 medical records (nurses and pharmacist review of medical records, followed by physicians review of triggered medical records) of adult patients whose hospitalizations occurred during 2015 in a high-complexity public teaching hospital located in Brazil. Data were collected from February 2018 to February 2019. Results A total of 266 adverse events were observed in 124 patients. The incidence of adverse events related to health care was 33.7% (95% CI 0.29–0.39), and the incidence density was 4.97 adverse events per 100 patient-days. Adverse events were responsible for 701 additional days of hospitalization, and the estimated length of additional hospital stay attributable to them was, on average, 6.8 days per event. The most common types of events were related to general care (60; 22.6%), medications (50; 18.8%), nosocomial infection (35; 13.2%), any other type (11; 4.1%), and diagnoses (2; 0.8%). Regarding the severity of adverse events, it was found that 168 (63.2%) were mild, 55 (20.7%) were moderate, and 43 (16.2%) were severe. In addition, it was estimated that 155 (58.3%) events were preventable. The length of a patient’s hospital stay was identified as a risk factor for the occurrence of adverse events (RR 1.20; 95% CI 1.04–1.39). Conclusions Through knowledge of the incidence, nature, severity, preventability, and risk factors for the occurrence of adverse events, it is possible to create the opportunities to prioritize the implementation of strategies for mitigating specific events based on reliable data and concrete information.

by Benjamin R. Bates, Adriana Tami, Ana Carvajal, Mario J. Grijalva Background COVID-19 threatens health systems worldwide, but Venezuela’s system is particularly vulnerable. To prevent the spread of COVID-19, individuals must adopt preventive behaviors. However, to encourage behavior change, we must first understand current knowledge, attitudes, and practices (KAPs) that inform response to this health threat. Methods We explored KAPs among Venezuelans using a cross-sectional, internet-based questionnaire. The questionnaire explored individuals’ knowledge about COVID-19; their attitudes toward the world’s and the Venezuelan authorities’ abilities to control it; and their self-reported practices. We also collected demographic data. Binomial logistic regression analyses were used to predict the adoption of preventive behaviors based on demographic variables, individual knowledge level, and individual attitudes. Results 3122 individuals completed the questionnaire. Participants had a high level of knowledge about COVID-19. They expressed high levels of optimism that the world would eventually control COVID-19, but they were very pessimistic about the public authorities in Venezuela. Most participants adopted preventive practices. Binomial regression suggests younger people, less educated people, and manual laborers hold lower levels of knowledge, and these groups, as well as men, were less likely to adopt preventive practices. Knowledge, by itself, had no association with optimism and little association with self-reported practices. Conclusions As other KAP studies in Latin America found, knowledge is not sufficient to prompt behavior change. Venezuelans’ pessimism about their own country’s ability should be explored in greater depth. Health promotion in Venezuela may wish to target the most at risk groups: men, younger people, less educated people, and manual laborers.

Abstract In patients who develop sepsis, whether due to primary, secondary or metastatic lesions, the skin is frequently affected. However, there are unresolved aspects regarding the general clinical manifestations in the skin or the prognosis and/or therapeutic implications. The main challenge in the approach to sepsis is its early diagnosis and management. In this review, we address the sepsis–skin relationship and the potential impact of early dermatological intervention on the septic patient through ten basic questions. We found little evidence of the participation of the dermatologist in sepsis alert programs. There are early skin changes that may alert clinicians on a possible sepsis, such as skin mottling or variations in acral skin temperature. In addition, the skin is an accessible and highly cost-effective tissue for etiological studies of some forms of sepsis (e.g., meningococcal purpura) and its involvement defines the prognosis of certain patients (e.g., infective endocarditis).

American Journal of Respiratory and Critical Care Medicine, Volume 203, Issue 8, Page 1025-1027, April 15, 2021.

American Journal of Respiratory and Critical Care Medicine, Volume 203, Issue 8, Page 1037-1041, April 15, 2021.

American Journal of Respiratory and Critical Care Medicine, Volume 203, Issue 8, Page 1041-1042, April 15, 2021.

American Journal of Respiratory and Critical Care Medicine, Volume 203, Issue 8, Page 1042-1043, April 15, 2021.

American Journal of Respiratory and Critical Care Medicine, Volume 203, Issue 8, Page 1045-1045, April 15, 2021.

Abstract Background The primary objective of the study is to describe the cellular characteristics of bronchoalveolar lavage fluid (BALF) of COVID-19 patients requiring invasive mechanical ventilation; the secondary outcome is to describe BALF findings between survivors vs non-survivors. Materials and methods Patients positive for SARS-CoV-2 RT PCR, admitted to ICU between March and April 2020 were enrolled. At ICU admission, BALF were analyzed by flow cytometry. Univariate, multivariate and Spearman correlation analyses were performed. Results Sixty-four patients were enrolled, median age of 64 years (IQR 58–69). The majority cells in the BALF were neutrophils (70%, IQR 37.5–90.5) and macrophages (27%, IQR 7–49) while a minority were lymphocytes, 1%, TCD3+ 92% (IQR 82–95). The ICU mortality was 32.8%. Non-survivors had a significantly older age (p = 0.033) and peripheral lymphocytes (p = 0.012) were lower compared to the survivors. At multivariate analysis the percentage of macrophages in the BALF correlated with poor outcome (OR 1.336, CI95% 1.014–1.759, p = 0.039). Conclusions In critically ill patients, BALF cellularity is mainly composed of neutrophils and macrophages. The macrophages percentage in the BALF at ICU admittance correlated with higher ICU mortality. The lack of lymphocytes in BALF could partly explain a reduced anti-viral response.

In the absence of a time machine, a single cell cannot be tested more than once in a destructive assay. Tian et al. instead develop clonal multi-omics to bypass this challenge and identify Bcor as a regulator of dendritic cell fate.

N. D. Hollis et al.

Abstract Background Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease’s complex etiology and the limitations of traditional microbiological diagnostic methods. Recent advances in next generation sequencing (NGS)-based metagenomics allow pan-pathogen detection in a single assay, and may have significant advantages over culture-based techniques. Results We conducted a cohort study of 159 CAP patients to assess the diagnostic performance of a clinical metagenomics assay and its impact on clinical management and patient outcomes. When compared to other techniques, clinical metagenomics detected more pathogens in more CAP cases, and identified a substantial number of polymicrobial infections. Moreover, metagenomics results led to changes in or confirmation of clinical management in 35 of 59 cases; these 35 cases also had significantly improved patient outcomes. Conclusions Clinical metagenomics could be a valuable tool for the diagnosis and treatment of CAP. Trial registration Trial registration number with the Chinese Clinical Trial Registry: ChiCTR2100043628.

Abstract Background Uganda's clinical management guidelines recommend a malaria laboratory test in all patients presenting with fever (history of fever or an axillary temperature ≥ 37.5 °C), and only those with a positive test receive anti-malarial treatment. However, the current practice in areas with declining malaria transmission remains unknown. This study assessed the clinicians’ diagnostic practices, the factors associated with recommending a test, and the risk of missing a malaria case when a test is not recommended in patients presenting with fever in Kampala, an area of declining malaria transmission in Uganda. Methods Between January and March 2020, 383 participants aged ≥ 12 years and presenting to Kisenyi Health Centre IV in Kampala district with fever were enrolled in the study. A questionnaire was administered during exit interviews, routine diagnostic practices were recorded from participant clinical notes, and a research blood slide was obtained for later reading. Results Of the enrolled participants, 356 (93%) had a malaria diagnostic test recommended by the clinician. Factors associated with increasing prevalence of having a test recommended included; history of overnight travel (adjusted prevalence ratio [aPR] 1.07, 95% confidence interval [CI] 1.02–1.13, p = 0.011), being married (aPR = 1.07, 95% CI 1.01–1.13, p = 0.022), and having tertiary education (aPR = 1.09 95% CI 1.01–1.17, p = 0.031). Among the 27 participants where a malaria diagnostic test was not recommended, 4 (14.8%) had a positive study smear. Conclusion Despite having significant declines in malaria transmission in Kampala in the last decade, clinicians at the study health facility highly adhered to the clinical management guidelines, recommending a malaria test in almost all patients presenting with fever. However, a significant proportion of malaria cases was missed when a test was not recommended. These results highlight the importance of laboratory testing for malaria in all patients who present with fevers and live in endemic settings even when the transmission has significantly declined.

Abstract Background Pregnant women are particularly vulnerable to malaria infections, increasing the risk of maternal–fetal complications, mainly in high-endemicity areas. However, few studies of malaria in pregnancy (MiP) have been carried out in Latin America, a region with low endemicity and transmission of both, Plasmodium falciparum and Plasmodium vivax. Despite the high malaria burden in Venezuela in the last years, no recent studies of MiP have been conducted. Hence, epidemiological and clinical characteristics of pregnant women with malaria in southern Venezuela are described herein. Methods A retrospective study in pregnant women attending at the “Ruíz y Páez” University Hospital Complex, Bolivar state, Venezuela, was carried out between February and October, 2019. Epidemiological, clinical, and laboratory information was analysed. Results Thirty-seven out of 52 pregnant women analysed were infected with P. vivax. Age ranged between 15 and 39 years, and adolescent pregnancies were common. Malaria infection was diagnosed mainly during the third trimester of pregnancy (63.4%). The distribution of symptoms and signs as well as clinical laboratory values was similar among Plasmodium spp. Although uncomplicated malaria was most frequent, 30% (13/52) had severe anaemia. A high proportion of studied women (44%) presented at least one complication during the pregnancy or delivery. Spontaneous abortion was recorded in four women, and three fetal deaths were observed. Six women had preterm delivery without any further complication. Conclusions A high prevalence of maternal–fetal complications was found in the studied population, highlighting the requirement for a careful medical follow up during the prenatal check-ups, which should include routinary malaria tests. Preventive measures as distribution of insecticide-treated mosquito net for pregnant women at risk should also be implemented. Those measures can help to reduce the negative impact of malaria on the newborn and mother.

Abstract Background Malaria transmission-blocking vaccines (TBVs) could help break the cycle of malaria transmission by conferring community rather than individual protection. When introducing new intervention strategies, uptake is dependent on acceptability, not just efficacy. In this exploratory study on acceptability of TBVs in Sierra Leone, it was hypothesized that TBVs would be largely acceptable to adults and health workers in areas with relatively few ongoing malaria interventions, and that (i) knowledge of malaria and vaccines, (ii) health behaviours associated with malaria and vaccines, and (iii) attitudes towards different vaccines types could lead to greater TBV acceptability. Methods This study used a mixed methods approach in Bo, Sierra Leone, to understand community knowledge, attitudes, and practices related to malaria and vaccination in general. This included: (i) a population-based cross-sectional survey (n=615 adults), (ii) 6 focus group discussions with parents, and (iii) 20 key informant interviews. The concept of a TBV was explained to participants before they were asked about their willingness to accept this vaccine modality as part of an integrated malaria elimination programme. Results This study found that most adults would be willing to receive a TBV vaccine. Respondents noted mostly positive past experiences with adult and childhood vaccinations for other infectious diseases and high levels of engagement in other malaria prevention behaviors such as bed nets. Perceived barriers to TBV acceptance were largely focused on general community-level distribution of a vaccine, including personal fears of vaccination and possible costs. After an explanation of the TBV mechanism, nearly all focus group and interview participants believed that community members would accept the vaccine as part of an integrated malaria control approach. Both parents and health workers offered insight on how to successfully roll-out a future TBV vaccination programme. Conclusions The willingness of community members in Bo, Sierra Leone to accept a TBV as part of an integrated anti-malarial strategy suggests that the atypical mechanism of TBV action might not be an obstacle to future clinical trials. This study’s findings suggests that perceived general barriers to vaccination implementation, such as perceived personal fears and vaccine cost, must be addressed in future clinical and implementation research studies.

Abstract Background The malaria control programme in Indonesia has successfully brought down malaria incidence in many parts in Indonesia, including Aceh Province. Clinical manifestation of reported malaria cases in Aceh varied widely from asymptomatic, mild uncomplicated to severe and fatal complications. The present study aims to explore the allelic diversity of merozoite surface protein 1 gene (msp1) and msp2 among the Plasmodium falciparum isolates in Aceh Province and to determine their potential correlation with the severity of malaria clinical manifestation. Methods Screening of over 500 malaria cases admitted to the hospitals in 11 districts hospital within Aceh Province during 2013–2015, identified 90 cases of P. falciparum mono-infection without any co-morbidity. The subjects were clinically phenotyped and parasite DNA was extracted and polymerase chain reaction (PCR) amplified for the msp1 and msp2 allelic subfamilies. Results Analysis of clinical manifestation revealed that fever-chill is the most frequent symptom. Based on WHO criteria showed 19 cases were classified as severe and 71 as mild malaria. Analysis of msp1 gene revealed the presence of K1 allele subfamily in 34 subjects, MAD20 in 42 subjects, RO33 in 1 subject, and mixed allelic of K1 + MAD20 in 5 subjects, K1 + RO33 in 4 subjects, and MAD20 + RO33 in 4 subjects. Analysis of msp2 gene revealed 34 subjects carried the FC27 allelic subfamily, 37 subjects carried the 3D7 and 19 subjects carried the mixed FC27 + 3D7. Analysis of multiplicity of infection revealed that msp1 alleles is slightly higher than msp2 with the mean of MOI were 2.69 and 2.27, respectively. Statistical analysis to determine the association between each clinical manifestation and msp1 and msp2 alleles revealed that liver function abnormal value was associated with the msp2 mixed alleles (odds ratio (OR):0.13; 95%CI: 0.03–0.53). Mixed msp1 of K1 + RO33 was associated with severe malaria (OR: 28.50; 95%CI: 1.59–1532.30). Conclusion This study found a strong association between severe malaria in Aceh with subjects carrying the msp1 mixed alleles of K1 and RO33. The liver function abnormal value associated with the msp2 mixed allelic subfamilies. Further study in different geographic areas is recommended.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presented as a mysterious infection causing global pandemic in a short time, gaining world-wide attention, imposing challenges to medical field, researchers, epidemiologists, and policy makers about the nature of the virus, and posing challenges for a successful vaccine outcome (Umakanthan et al., 2020). SARS-CoV-2 is transmitted via respiratory droplets from face-to-face contact or contaminated surfaces. Although the role of aerosol spread in humans remains unclear, this mode of transmission is still a major concern (Ganyani et al., 2020).