This study aims to understand availability of school-based infectious disease surveillance data (e.g., COVID-19 cases, student absences) based on experiences during the COVID-19 pandemic using a national sample of public K-12 schools (n = 1,602). Based on surveys administered to school administrators throughout the 2021-2022 school year, we found high levels of missingness data for school-level COVID-19 cases, quarantines, and student absenteeism, increasing missingness over time, and variations in missingness by school characteristics (e.g., school size) and protocols (e.g., having a school-based system to report at-home COVID-19 tests). For the same sample of schools, using data requests to health departments, we found similarly high levels of missingness of school-level COVID-19 case data and varying approaches in data collection. Developing nationally standardized case definitions-and systems to surveil or collect and monitor school-based infectious disease outcomes early in a public health emergency-may be helpful in producing actionable data.

PURPOSE: The COVID-19 pandemic disrupted pediatric health care in the United States, and this disruption layered on existing barriers to health care. We sought to characterize disparities in unmet pediatric health care needs during this period. METHODS: We analyzed data from Wave 1 (October through November 2020) and Wave 2 (March through May 2021) of the COVID Experiences Survey, a national longitudinal survey delivered online or via telephone to parents of children aged 5 through 12 years using a probability-based sample representative of the US household population. We examined 3 indicators of unmet pediatric health care needs as outcomes: forgone care and forgone well-child visits during fall 2020 through spring 2021, and no well-child visit in the past year as of spring 2021. Multivariate models examined relationships of child-, parent-, household-, and county-level characteristics with these indicators, adjusting for child's age, sex, and race/ethnicity. RESULTS: On the basis of parent report, 16.3% of children aged 5 through 12 years had forgone care, 10.9% had forgone well-child visits, and 30.1% had no well-child visit in the past year. Adjusted analyses identified disparities in indicators of pediatric health care access by characteristics at the level of the child (eg, race/ethnicity, existing health conditions, mode of school instruction), parent (eg, childcare challenges), household (eg, income), and county (eg, urban-rural classification, availability of primary care physicians). Both child and parent experiences of racism were also associated with specific indicators of unmet health care needs. CONCLUSIONS: Our findings highlight the need for continued research examining unmet health care needs and for continued efforts to optimize the clinical experience to be culturally inclusive.

Marburg virus (MARV) and Ravn virus (RAVV), collectively called marburgviruses, cause Marburg hemorrhagic fever (MHF) in humans. In July 2007, 4 cases of MHF (1 fatal) occurred in miners at Kitaka Mine in southern Uganda. Later, MHF occurred in 2 tourists who visited Python Cave, ≈50 km from Kitaka Mine. One of the tourists was from the United States (December 2007) and 1 was from the Netherlands (July 2008); 1 case was fatal (1,2,3). The cave and the mine each contained 40,000–100,000 Rousettus aegyptiacus bats (Egyptian fruit bats). | | Longitudinal investigations of the outbreaks at both locations were initiated by the Viral Special Pathogens Branch of the Centers for Disease Control and Prevention (CDC, Atlanta, GA, USA, and Entebbe, Uganda) in collaboration with the Uganda Wildlife Authority (UWA) and the Uganda Virus Research Institute (UVRI). During these studies, genetically diverse MARVs and RAVVs were isolated directly from bat tissues, and infection levels of the 2 viruses were found to increase in juvenile bats on a predictable bi-annual basis (4,5). However, investigations at Kitaka Mine were stopped when the miners exterminated the bat colony by restricting egress from the cave with papyrus reed barriers and then entangling the bats in fishing nets draped over the exits. The trapping continued for weeks, and the entrances were then sealed with sticks and plastic. These depopulation efforts were documented by researchers from UVRI, the CDC, the National Institute of Communicable Diseases (Sandringham, South Africa), and UWA during site visits to Kitaka Mine (Technical Appendix Figure). In August 2008, thousands of dead bats were found piled in the forest, and by November 2008, there was no evidence of bats living in the mine; whether 100% extermination was achieved is unknown. CDC, UVRI, and UWA recommended against extermination, believing that any results would be temporary and that such efforts could exacerbate the problem if bat exclusion methods were not complete and permanent (6,7).

STUDY QUESTION: Does the fertility status of an individual act as a biomarker for their future health? SUMMARY ANSWER: Data support an association between reproductive health and overall health for men and women. WHAT IS ALREADY KNOWN: Various chronic conditions, such as diabetes, obesity and cancer, can compromise fertility, but there are limited data for the converse situation, in which fertility status can influence or act as a marker for future health. Data reveal an association between infertility and incident cardiovascular disease and cancer in both men and women. STUDY DESIGN SIZE AND DURATION: A National Institute of Child Health and Human Development-Centers for Disease Control and Prevention workshop in April 2016 was convened that brought together experts in both somatic diseases and conditions, and reproductive health. Goals of the workshop included obtaining information about the current state of the science linking fertility status and overall health, identifying potential gaps and barriers limiting progress in the field, and outlining the highest priorities to move the field forward. PARTICIPANTS/MATERIALS SETTING AND METHODS: Approximately 40 experts participated in the workshop. MAIN RESULTS AND THE ROLE OF CHANCE: While the etiology remains uncertain for infertility, there is evidence for an association between male and female infertility and later health. The current body of evidence suggests four main categories for considering biological explanations: genetic factors, hormonal factors, in utero factors, and lifestyle/health factors. These categories would be key to include in future studies to develop a comprehensive and possibly standardized look at fertility status and overall health. Several themes emerged from the group discussion including strategies for maximizing use of existing resources and databases, the need for additional epidemiologic studies and public health surveillance, development of strategies to frame research so results could ultimately influence clinical practice, and the identification of short and long-term goals and the best means to achieve them. LIMITATIONS REASONS FOR CAUTION: Further research may not indicate an association between fertility status and overall health. WIDER IMPLICATIONS OF THE FINDINGS: Currently medical care is compartmentalized. Reproductive medicine physicians treat patients for a short period of time before they transition to others for future care. Going forward, it is critical to take an interdisciplinary patient care approach that would involve experts in a broad range of medical specialties in order to more fully understand the complex interrelationships between fertility and overall health. If infertility is confirmed as an early marker of chronic disease then screening practices could be adjusted, as they are for patients with a family history of malignancy. STUDY FUNDING/COMPETING INTERESTS: Funding for the workshop was provided by the Fertility and Infertility Branch, National Institute of Child Health and Human Development, National Institutes of Health and the Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control. There are no conflicts of interest to declare. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the National Institutes of Health. TRIAL REGISTRATION NUMBER: Not applicable.

Introduction: The virus formerly known as monkeypox virus, now called mpoxv, belongs to the Orthopoxvirus genus and can cause mpox disease through both animal-to-human and human-to-human transmission. The unexpected spread of mpoxv among humans has prompted the World Health Organization (WHO) to declare a Public Health Emergency of International Concern (PHEIC). Methods: We conducted a literature search to identify the gaps in biosafety, focusing on five main areas: how the infection enters the body and spreads, how much of the virus is needed to cause infection, infections acquired in the lab, accidental release of the virus, and strategies for disinfecting and decontaminating the area. Discussion: The recent PHEIC has shown that there are gaps in our knowledge of biosafety when it comes to mpoxv. We need to better understand where this virus might be found, how much of it can spread from person-to-person, what are the effective control measures, and how to safely clean up contaminated areas. By gathering more biosafety evidence, we can make better decisions to protect people from this zoonotic agent, which has recently become more common in the human population. © Stuart D. Blacksell et al. 2023; Published by Mary Ann Liebert, Inc.

BACKGROUND: Key population HIV programmes in sub-Saharan Africa require epidemiological information to ensure equitable and universal access to effective services. We aimed to consolidate and harmonise survey data among female sex workers, men who have sex with men, people who inject drugs, and transgender people to estimate key population size, HIV prevalence, and antiretroviral therapy (ART) coverage for countries in mainland sub-Saharan Africa. METHODS: Key population size estimates, HIV prevalence, and ART coverage data from 39 sub-Saharan Africa countries between 2010 and 2023 were collated from existing databases and verified against source documents. We used Bayesian mixed-effects spatial regression to model urban key population size estimates as a proportion of the gender-matched, year-matched, and area-matched population aged 15-49 years. We modelled subnational key population HIV prevalence and ART coverage with age-matched, gender-matched, year-matched, and province-matched total population estimates as predictors. FINDINGS: We extracted 2065 key population size data points, 1183 HIV prevalence data points, and 259 ART coverage data points. Across national urban populations, a median of 1·65% (IQR 1·35-1·91) of adult cisgender women were female sex workers, 0·89% (0·77-0·95) were men who have sex with men, 0·32% (0·31-0·34) were men who injected drugs, and 0·10% (0·06-0·12) were women who were transgender. HIV prevalence among key populations was, on average, four to six times higher than matched total population prevalence, and ART coverage was correlated with, but lower than, the total population ART coverage with wide heterogeneity in relative ART coverage across studies. Across sub-Saharan Africa, key populations were estimated as comprising 1·2% (95% credible interval 0·9-1·6) of the total population aged 15-49 years but 6·1% (4·5-8·2) of people living with HIV. INTERPRETATION: Key populations in sub-Saharan Africa experience higher HIV prevalence and lower ART coverage, underscoring the need for focused prevention and treatment services. In 2024, limited data availability and heterogeneity constrain precise estimates for programming and monitoring trends. Strengthening key population surveys and routine data within national HIV strategic information systems would support more precise estimates. FUNDING: UNAIDS, Bill & Melinda Gates Foundation, and US National Institutes of Health.

We describe a strain of Lassa virus representing a putative new lineage that was isolated from a cluster of human infections with an epidemiologic link to Togo. This finding extends the known range of Lassa virus to Togo.

This review summarizes the recent Global Meningococcal Initiative (GMI) regional meeting, which explored meningococcal disease in North America. Invasive meningococcal disease (IMD) cases are documented through both passive and active surveillance networks. IMD appears to be decreasing in many areas, such as the Dominican Republic (2016: 18 cases; 2021: 2 cases) and Panama (2008: 1 case/100,000; 2021: <0.1 cases/100,000); however, there is notable regional and temporal variation. Outbreaks persist in at-risk subpopulations, such as people experiencing homelessness in the US and migrants in Mexico. The recent emergence of β-lactamase-positive and ciprofloxacin-resistant meningococci in the US is a major concern. While vaccination practices vary across North America, vaccine uptake remains relatively high. Monovalent and multivalent conjugate vaccines (which many countries in North America primarily use) can provide herd protection. However, there is no evidence that group B vaccines reduce meningococcal carriage. The coronavirus pandemic illustrates that following public health crises, enhanced surveillance of disease epidemiology and catch-up vaccine schedules is key. Whole genome sequencing is a key epidemiological tool for identifying IMD strain emergence and the evaluation of vaccine strain coverage. The Global Roadmap on Defeating Meningitis by 2030 remains a focus of the GMI.

Lujo virus (LUJV), a highly pathogenic arenavirus, was first identified in 2008 in Zambia. To aid the identification of effective therapeutics for LUJV, we developed a recombinant reporter virus system, confirming reporter LUJV comparability with wild-type virus and its utility in high-throughput antiviral screening assays. Using this system, we evaluated compounds with known and unknown efficacy against related arenaviruses, with the aim of identifying LUJV-specific and potential new pan-arenavirus antivirals. We identified six compounds demonstrating robust anti-LUJV activity, including several compounds with previously reported activity against other arenaviruses. These data provide critical evidence for developing broad-spectrum antivirals against high-consequence arenaviruses.

This article reports the changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in March 2021. The entire ICTV was invited to vote on 290 taxonomic proposals approved by the ICTV Executive Committee at its meeting in October 2020, as well as on the proposed revision of the International Code of Virus Classification and Nomenclature (ICVCN). All proposals and the revision were ratified by an absolute majority of the ICTV members. Of note, ICTV mandated a uniform rule for virus species naming, which will follow the binomial 'genus-species' format with or without Latinized species epithets. The Study Groups are requested to convert all previously established species names to the new format. ICTV has also abolished the notion of a type species, i.e., a species chosen to serve as a name-bearing type of a virus genus. The remit of ICTV has been clarified through an official definition of 'virus' and several other types of mobile genetic elements. The ICVCN and ICTV Statutes have been amended to reflect these changes.

INTRODUCTION: Relatively limited data are available regarding paediatric COVID-19. Although most children appear to have mild or asymptomatic infections, infants and those with comorbidities are at increased risk of experiencing more severe illness and requiring hospitalisation due to COVID-19. The recent but uncommon association of SARS-CoV-2 infection with development of a multisystem inflammatory syndrome has heightened the importance of understanding paediatric SARS-CoV-2 infection. METHODS AND ANALYSIS: The Paediatric Emergency Research Network-COVID-19 cohort study is a rapid, global, prospective cohort study enrolling 12 500 children who are tested for acute SARS-CoV-2 infection. 47 emergency departments across 12 countries on four continents will participate. At enrolment, regardless of SARS-CoV-2 test results, all children will have the same information collected, including clinical, epidemiological, laboratory, imaging and outcome data. Interventions and outcome data will be collected for hospitalised children. For all children, follow-up at 14 and 90 days will collect information on further medical care received, and long-term sequelae, respectively. Statistical models will be designed to identify risk factors for infection and severe outcomes. ETHICS AND DISSEMINATION: Sites will seek ethical approval locally, and informed consent will be obtained. There is no direct risk or benefit of study participation. Weekly interim analysis will allow for real-time data sharing with regional, national, and international policy makers. Harmonisation and sharing of investigation materials with WHO, will contribute to synergising global efforts for the clinical characterisation of paediatric COVID-19. Our findings will enable the implementation of countermeasures to reduce viral transmission and severe COVID-19 outcomes in children. TRIAL REGISTRATION NUMBER: NCT04330261.

On April 10, 2020, just 2 days before the anticipated declaration of the end of the North Kivu and Ituri Ebola virus disease (EVD) outbreak in DR Congo, and 53 days after the last confirmed case of EVD had been reported, a new case was confirmed. Sequencing of patient samples from the case in April and six others that followed indicated that these cases were likely to have come from a reintroduction of the virus from a persistently infected survivor.1 This group of cases marked the second flare-up linked to an EVD survivor during this outbreak. In November, 2019, a relapse case in North Kivu resulted in widespread transmission across multiple health zones, helping to extend the outbreak by at least 3 months.

INTRODUCTION: Great strides in responding to the HIV epidemic have led to improved access to and uptake of HIV services in Guyana, a lower-middle-income country with a generalized HIV epidemic. Despite efforts to scale up HIV treatment and adopt the test and start strategy, little is known about costs of HIV services across the care cascade. METHODS: We collected cost data from the national laboratory and nine selected treatment facilities in five of the country's ten Regions, and estimated the costs associated with HIV testing and services (HTS) and antiretroviral therapy (ART) from a provider perspective from January 1, 2016 to December 31, 2016. We then used the unit costs to construct four resource allocation scenarios. In the first two scenarios, we calculated how close Guyana would currently be to its 2020 targets if the allocation of funding across programs and regions over 2017-2020 had (a) remained unchanged from latest-reported levels, or (b) been optimally distributed to minimize incidence and deaths. In the next two, we estimated the resources that would have been required to meet the 2020 targets if those resources had been distributed (a) according to latest-reported patterns, or (b) optimally to minimize incidence and deaths. RESULTS: The mean cost per test was US$15 and the mean cost per person tested positive was US$796. The mean annual cost per of maintaining established adult and pediatric patients on ART were US$428 and US$410, respectively. The mean annual cost of maintaining virally suppressed patients was US$648. Cost variation across sites may suggest opportunities for improvements in efficiency, or may reflect variation in facility type and patient volume. There may also be scope for improvements in allocative efficiency; we estimated a 28% reduction in the total resources required to meet Guyana's 2020 targets if funds had been optimally distributed to minimize infections and deaths. CONCLUSIONS: We provide the first estimates of costs along the HIV cascade in the Caribbean and assessed efficiencies using novel context-specific data on the costs associated with diagnostic, treatment, and viral suppression. The findings call for better targeting of services, and efficient service delivery models and resource allocation, while scaling up HIV services to maximize investment impact.

Crimean-Congo Hemorrhagic Fever (CCHF) is the most widely distributed tick-borne viral infection in the world. Strikingly, reported mortality rates for CCHF are extremely variable, ranging from 5 to 80% (1). CCHF virus (CCHFV, Nairoviridae) exhibits extensive genomic sequence diversity across strains (2, 3). It is currently unknown if genomic diversity is a factor contributing to variation in its pathogenicity. We obtained complete genome sequences of CCHFV directly from the tick reservoir. These new strains belong to a solitary lineage named Europe 2 that is circumstantially reputed to be less pathogenic than the epidemic strains from Europe 1 lineage. We identified a single tick-specific amino acid variant in the viral glycoprotein region that dramatically reduces its fusion activity in human cells, providing evidence that a GPC variant, present in ticks, have severely impaired function in human cells.

Remdesivir is a broad-spectrum antiviral nucleotide prodrug that has been clinically evaluated in Ebola virus patients and recently received emergency use authorization (EUA) for treatment of COVID-19. With approvals from the Federal Select Agent Program and the Centers for Disease Control and Prevention's Institutional Biosecurity Board, we characterized the resistance profile of remdesivir by serially passaging Ebola virus under remdesivir selection; we generated lineages with low-level reduced susceptibility to remdesivir after 35 passages. We found that a single amino acid substitution, F548S, in the Ebola virus polymerase conferred low-level reduced susceptibility to remdesivir. The F548 residue is highly conserved in filoviruses but should be subject to specific surveillance among novel filoviruses, in newly emerging variants in ongoing outbreaks, and also in Ebola virus patients undergoing remdesivir therapy. Homology modeling suggests that the Ebola virus polymerase F548 residue lies in the F-motif of the polymerase active site, a region that was previously identified as susceptible to resistance mutations in coronaviruses. Our data suggest that molecular surveillance of this region of the polymerase in remdesivir-treated COVID-19 patients is also warranted.

On April 10, 2020, a total of 53 days after the last patient with Ebola virus disease (EVD) had been isolated and more than 23 months since the start of the 10th EVD outbreak in the Democratic Republic of Congo (DRC), a new confirmed case was reported in the Beni health zone. This case, and the six that followed, brought the total to 3462 cases — the second-largest Ebola outbreak in history. Although the outbreak was declared over on June 25, 2020, additional cases attributable to persistently infected survivors may occur. Therefore, surveillance and rapid-response capacity should be maintained, not only for a duration equivalent to two incubation periods (42 days) after the last confirmed case tested negative, but also for at least 90 additional days of enhanced surveillance.

In the United States, immunization recommendations and their associated schedules are developed by the Advisory Committee on Immunization Practices (ACIP). To assist with the translation process and better harmonize the outcomes of existing clinical decision support tools, the Centers for Disease Control and Prevention (CDC) created clinical decision support for immunization (CDSi) resources for each set of ACIP recommendations. These resources are continually updated and refined as new vaccine recommendations and clarifications become available and will be available to health information systems for a coronavirus disease 2019 (COVID-19) vaccine when one becomes available for use in the United States Objectives: To assess awareness of CDSi resources, whether CDSi resources were being used by immunization-related health information systems, and perceived impact of CDSi resources on stakeholders' work Design: Online surveys conducted from 2015-2019 including qualitative and quantitative questions Participants: The main and technical contact from each of the 64 CDC-funded immunization information system (IIS) awardees, IIS vendors, and electronic health record vendors Results: Awareness of at least one resource increased from 75% of respondents in 2015 to 100% in 2019. Use of at least one CDSi resource also increased from 47% in 2015 to 78% in 2019. About 80% or more of users of CDSi are somewhat or very highly satisfied with the resources and report a somewhat or very positive impact from using them Conclusion: As awareness and use of CDSi resources increases, the likelihood that patients receive recommended immunizations at the right time will also increase. Rapid and precise integration of vaccine recommendations into health information systems will be particularly important when a COVID-19 vaccine becomes available to help facilitate vaccine implementation.

Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence- only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth.

Newborn screening (NBS) identifies infants at risk for congenital disorders for which early intervention has been shown to improve outcomes (1). State public health programs are encouraged to screen for disorders on the national Recommended Uniform Screening Panel (RUSP), which increased from 29 disorders in 2005 to 35 in 2018.* The RUSP includes hearing loss (HL) and critical congenital heart defects, which can be detected through point-of-care screening, and 33 disorders detected through laboratory screening of dried blood spot (DBS) specimens. Numbers of cases for 33 disorders on the RUSP (32 DBS disorders and HL) reported by 50 U.S. state programs were tabulated. The three subtypes of sickle cell disease (SCD) listed as separate disorders on the RUSP (S,S disease; S,beta-thalassemia; and S,C disease) were combined for the current analysis, and the frequencies of the resulting disorders were calculated relative to annual births. During 2015-2017, the overall prevalence was 34.0 per 10,000 live births. Applying that frequency to 3,791,712 live births in 2018,(†) approximately 12,900 infants are expected to be identified each year with one of the disorders included in the study. The most prevalent disorder is HL (16.5 per 10,000), and the most prevalent DBS disorders are primary congenital hypothyroidism (CH) (6.0 per 10,000), SCD (4.9 per 10,000), and cystic fibrosis (CF) (1.8 per 10,000). Notable changes in prevalence for each of these disorders have occurred since the previous estimates based on 2006 births (2). The number of infants identified at a national level highlights the effect that NBS programs are having on infant health through early detection, intervention, and potential improved health, regardless of geographic, racial/ethnic, or socioeconomic differences.

Genomic surveillance of bacterial meningitis pathogens is essential for effective disease control globally, enabling identification of emerging and expanding strains and consequent public health interventions. While there has been a rise in the use of whole genome sequencing, this has been driven predominately by a subset of countries with adequate capacity and resources. Global capacity to participate in surveillance needs to be expanded, particularly in low and middle-income countries with high disease burdens. In light of this, the WHO-led collaboration, Defeating Meningitis by 2030 Global Roadmap, has called for the establishment of a Global Meningitis Genome Partnership that links resources for: N. meningitidis (Nm), S. pneumoniae (Sp), H. influenzae (Hi) and S. agalactiae (Sa) to improve worldwide co-ordination of strain identification and tracking. Existing platforms containing relevant genomes include: PubMLST: Nm (31,622), Sp (15,132), Hi (1,935), Sa (9,026); The Wellcome Sanger Institute: Nm (13,711), Sp (>24,000), Sa (6,200), Hi (1738); and BMGAP: Nm (8,785), Hi (2,030). A steering group is being established to coordinate the initiative and encourage high-quality data curation. Next steps include: developing guidelines on open-access sharing of genomic data; defining a core set of metadata; and facilitating development of user-friendly interfaces that represent publicly available data.

Candida auris is a difficult to eradicate yeast that has caused outbreaks in healthcare facilities. We report a cluster of five patients in one intensive care unit who were colonized or infected in 2017. The initial two patients were recipients of liver transplants who had cultures that grew C. auris within three days of each other in June 2017 (days 43 and 30 post-transplant). Subsequent screening cultures identified two additional patients with C. auris colonization. Respiratory and urine cultures from a fifth patient yielded C. auris. All isolates were fluconazole-resistant but susceptible to echinocandins. Whole genome sequencing showed the strains were clonal, suggesting in-hospital transmission, and related but distinct from NY/NJ strains, consistent with a separate introduction. However, no source or contact was found. Two of the five patients died. C. auris infection likely contributed to one patient death by infecting a vascular aneurysm at the graft anastomosis. Strict infection control precautions were initiated to control the outbreak. Our experience reveals that while severe disease from C. auris can occur in transplant recipients, outbreaks can be controlled using recommended infection control practices. We have had no further patients infected with C. auris to date.

In recent years, phylogenetic analysis of HIV sequence data has been used in research studies to investigate transmission patterns between individuals and groups, including analysis of data from HIV prevention clinical trials; in molecular epidemiology; and in public health surveillance programs. Phylogenetic analysis can provide valuable information to inform HIV prevention efforts, but it also has risks, including stigma and marginalization of groups, or potential identification of HIV transmission between individuals. In response to these concerns, an interdisciplinary working group was assembled to address ethical challenges in United States-based HIV phylogenetic research. The working group developed recommendations regarding (1) study design; (2) data security, access, and sharing; (3) community engagement; (4) legal issues; and (5) communication and dissemination. The working group also identified areas for future research and scholarship to promote ethical conduct of HIV phylogenetic research.

St. Louis encephalitis virus (SLEV) is a flavivirus that circulates in an enzootic cycle between birds and mosquitoes and can also infect humans to cause febrile disease and sometimes encephalitis. Although SLEV is endemic to the United States, no activity was detected in California during the years 2004 through 2014, despite continuous surveillance in mosquitoes and sentinel chickens. In 2015, SLEV-positive mosquito pools were detected in Maricopa County, Arizona, concurrent with an outbreak of human SLEV disease. SLEV-positive mosquito pools were also detected in southeastern California and Nevada in summer 2015. From 2016 to 2018, SLEV was detected in mosquito pools throughout southern and central California, Oregon, Idaho, and Texas. To understand genetic relatedness and geographic dispersal of SLEV in the western United States since 2015, we sequenced four historical genomes (3 from California and 1 from Louisiana) and 26 contemporary SLEV genomes from mosquito pools from locations across the western US. Bayesian phylogeographic approaches were then applied to map the recent spread of SLEV. Three routes of SLEV dispersal in the western United States were identified: Arizona to southern California, Arizona to Central California, and Arizona to all locations east of the Sierra Nevada mountains. Given the topography of the Western United States, these routes may have been limited by mountain ranges that influence the movement of avian reservoirs and mosquito vectors, which probably represents the primary mechanism of SLEV dispersal. Our analysis detected repeated SLEV introductions from Arizona into southern California and limited evidence of year-to-year persistence of genomes of the same ancestry. By contrast, genetic tracing suggests that all SLEV activity since 2015 in central California is the result of a single persistent SLEV introduction. The identification of natural barriers that influence SLEV dispersal enhances our understanding of arbovirus ecology in the western United States and may also support regional public health agencies in implementing more targeted vector mitigation efforts to protect their communities more effectively.

BACKGROUND: During 2017, a multi-state outbreak investigation occurred following the confirmation of Seoul virus (SEOV) infections in people and pet rats. A total of 147 humans and 897 rats were tested. METHODS: In addition to IgG and IgM serology and traditional RT-PCR, novel quantitative RT-PCR primers/probe were developed, and whole genome sequencing was performed. RESULTS: Seventeen people had SEOV IgM, indicating recent infection; seven reported symptoms and three were hospitalized. All patients recovered. Thirty-one facilities in 11 US states had SEOV infection, and among those with >/=10 rats tested, rat IgG prevalence ranged 2-70% and SEOV RT-PCR positivity ranged 0-70%. Human lab-confirmed cases were significantly associated with rat IgG positivity and RT-PCR positivity (p=0.03 and p=0.006, respectively). Genomic sequencing identified >99.5% homology between SEOV sequences in this outbreak, and these were >99% identical to SEOV associated with previous pet rat infections in England, the Netherlands, and France. Frequent trade of rats between home-based ratteries contributed to transmission of SEOV between facilities. CONCLUSIONS: Pet rat owners, breeders, and the healthcare and public health community should be aware and take steps to prevent SEOV transmission in pet rats and to humans. Biosecurity measures and diagnostic testing can prevent further infections.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tri-segmented, tick-borne nairovirus that causes disease of ranging severity in humans. The CCHFV M segment encodes a complex glycoprotein precursor (GPC) that undergoes extensive endoproteolytic cleavage, giving rise to two structural proteins (Gn and Gc) required for virus attachment and entry, and to multiple non-structural proteins (NSm, GP160, GP85, and GP38). The functions of these non-structural proteins remain largely unclear. Here, we investigate the role of NSm during infection by generating a recombinant CCHFV lacking the complete NSm domain (10200NSm) and observing CCHFV NSm replication in cell lines and pathogenicity in Ifnar(-/-) mice. Our data demonstrate that the NSm domain is dispensable for viral replication in vitro, and, despite the delayed onset of clinical signs, CCHFV lacking this domain caused severe or lethal disease in infected mice.

Key to the success of orangutan conservation management practices is the prevention of the introduction of infectious diseases to the remaining populations. Previous reports of Entamoeba spp. positive orangutans are of concern as Entamoeba spp. infection has been linked to morbidity and mortality in primates. It remains to be determined if the Entamoeba species infecting orangutans is the pathogenic Entamoeba histolytica. Orangutan fecal samples have been collected from orangutans from sites in Sumatra (Bukit Lawang, Ketambe, and Suaq, 241 samples from 64 individuals), and two sites in Kalimantan (Sebangau and Tuanan, 129 samples from 39 individuals). All samples were from wild orangutans except for a proportion from Sumatra which were from semi-wild (108 samples, 10 individuals). E. histolytica-specific nested PCR assays were carried out on the fecal samples. A total of 36 samples from 17 individuals tested positive for E. histolytica. When compared with published sequences using NCBI BLAST the E. histolytica positive samples showed a 98-99% concordance. The majority (76%, n = 36) of the positive isolates came from semi-wild orangutans in Bukit Lawang. This study supports the growing body of evidence that contact with humans is an important risk factor for infection of wild primates with E. histolytica.

The error-prone nature of ribonucleic acid (RNA)-dependent RNA polymerases drives the diversity of RNA virus populations. Arising within this diversity is a subset of defective viral genomes that retain replication competency, termed defective interfering (DI) genomes. These defects are caused by aberrant viral polymerase reinitiation on the same viral RNA template (deletion DI species) or the nascent RNA strand (copyback DI species). Defective interfering genomes have previously been shown to alter the dynamics of a viral population by interfering with normal virus replication and/or by stimulating the innate immune response. In this study, we investigated the ability of artificially produced DI genomes to inhibit Nipah virus (NiV), a highly pathogenic biosafety level 4 paramyxovirus. High multiplicity of infection passaging of both NiV clinical isolates and recombinant NiV in Vero cells generated an extensive DI population from which individual DIs were identified using next-generation sequencing techniques. Assays were established to generate and purify both naturally occurring and in silico-designed DIs as fully encapsidated, infectious virus-like particles termed defective interfering particles (DIPs). We demonstrate that several of these NiV DIP candidates reduced NiV titers by up to 4 logs in vitro. These data represent a proof-of-principle that a therapeutic application of DIPs to combat NiV infections may be an alternative source of antiviral control for this disease.

Three genome sequences of Buffalopox virus (BPVX) were retrieved from a human and two buffaloes scab samples. Phylogenomic analysis of the BPXV indicates that it shares a most recent common ancestor with Lister and closely related vaccine strains when compared to potential wild-type VACV strains (like Horsepox virus).

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

BACKGROUND: An alarming rise in reported Lassa fever cases continues in west Africa. Liberia has the largest reported per capita incidence of Lassa fever cases in the region, but genomic information on the circulating strains is scarce. The aim of this study was to substantially increase the available pool of data to help foster the generation of targeted diagnostics and therapeutics. METHODS: Clinical serum samples collected from 17 positive Lassa fever cases originating from Liberia (16 cases) and Guinea (one case) within the past decade were processed at the Liberian Institute for Biomedical Research using a targeted-enrichment sequencing approach, producing 17 near-complete genomes. An additional 17 Lassa virus sequences (two from Guinea, seven from Liberia, four from Nigeria, and four from Sierra Leone) were generated from viral stocks at the US Centers for Disease Control and Prevention (Atlanta, GA) from samples originating from the Mano River Union (Guinea, Liberia, and Sierra Leone) region and Nigeria. Sequences were compared with existing Lassa virus genomes and published Lassa virus assays. FINDINGS: The 23 new Liberian Lassa virus genomes grouped within two clades (IV.A and IV.B) and were genetically divergent from those circulating elsewhere in west Africa. A time-calibrated phylogeographic analysis incorporating the new genomes suggests Liberia was the entry point of Lassa virus into the Mano River Union region and estimates the introduction to have occurred between 300-350 years ago. A high level of diversity exists between the Liberian Lassa virus genomes. Nucleotide percent difference between Liberian Lassa virus genomes ranged up to 27% in the L segment and 18% in the S segment. The commonly used Lassa Josiah-MGB assay was up to 25% divergent across the target sites when aligned to the Liberian Lassa virus genomes. INTERPRETATION: The large amount of novel genomic diversity of Lassa virus observed in the Liberian cases emphasises the need to match deployed diagnostic capabilities with locally circulating strains and underscores the importance of evaluating cross-lineage protection in the development of vaccines and therapeutics. FUNDING: Defense Biological Product Assurance Office of the US Department of Defense and the Armed Forces Health Surveillance Branch and its Global Emerging Infections Surveillance and Response Section.