Lassa fever is a serious epidemic viral disease in West Africa affecting an estimated 2 million people annually with about 5000-10,000 deaths, although supporting data is sparse. Lassa fever significantly affects neonates, children, and pregnant women, however, comprehensive data on its impact in these populations are lacking. We reviewed the available literature on Lassa fever to assess its prevalence and impact in these populations and implications for vaccine development. Clinical features in children were similar to those observed in adults, with complications such as bleeding. Altered mental status, anasarca (swollen baby syndrome), bleeding, and poor urine output were risk factors for death. The case fatality rate (CFR) in 16 paediatric studies ranged from 6 % to 63 % and was 66.7 % and 75.0 % in two neonatal studies. In a systematic review of studies on pregnant women the CFR was 33.73 %. The adverse foetal outcomes included miscarriage, stillbirth, and intrauterine death associated with maternal death. Since Lassa fever significantly affects neonates, children, and pregnant women, developing a safe and effective, single-dose vaccine for these high-risk populations is vital. Currently, there are four clinical trials assessing Lassa virus vaccines. Only one of these trials is enrolling children aged ≥18 months, and exclude pregnant and breast-feeding women. It is essential that pregnant and breast-feeding women and young children are included in clinical trials that incorporate robust safety surveillance and risk mitigation measures. In our review, potential approaches to address the specific gaps in the areas of diagnosis, management, and prevention of Lassa fever in these specific populations, such as disease surveillance systems and vaccine development, were identified. A comprehensive strategy with investment focused on addressing specific knowledge gaps will be essential in protecting the health of these specific populations in Lassa virus endemic regions.

This article reports changes to virus taxonomy and taxon nomenclature that were approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in April 2024. The entire ICTV membership was invited to vote on 203 taxonomic proposals that had been approved by the ICTV Executive Committee (EC) in July 2023 at the 55th EC meeting in Jena, Germany, or in the second EC vote in November 2023. All proposals were ratified by online vote. Taxonomic additions include one new phylum (Ambiviricota), one new class, nine new orders, three new suborders, 51 new families, 18 new subfamilies, 820 new genera, and 3547 new species (excluding taxa that have been abolished). Proposals to complete the process of species name replacement to the binomial (genus + species epithet) format were ratified. Currently, a total of 14,690 virus species have been established.

CONTEXT: Laboratory-based hepatitis C virus (HCV) clearance cascades are an important tool for health departments to track progress toward HCV elimination, but a laboratory-based definition of HCV clearance has not yet been validated. OBJECTIVE: To compare agreement between a laboratory-based HCV clearance definition with a clinical cure definition. DESIGN: Observational. SETTING: New York City Department of Health and Mental Hygiene HCV surveillance system data and New York City hepatitis C linkage-to-care program data. PARTICIPANTS: Linkage-to-care program participants who were diagnosed with hepatitis C and enrolled in the linkage-to-care program from July 1, 2016, through June 30, 2020. MAIN OUTCOME MEASURE: Percent agreement between a laboratory-based HCV clearance definition (surveillance system) and a clinical cure definition (program data). RESULTS: Among 591 program participants with known treatment outcome, the laboratory-based HCV clearance definition and clinical cure definition were concordant in 573 cases (97%). CONCLUSIONS: A laboratory-based HCV clearance definition based on public health surveillance data can be a reliable source for monitoring HCV elimination.

The Advisory Committee on Immunization Practices (ACIP) recommended that dengue pre-vaccination screening tests for Dengvaxia administration have at least 98% specificity and 75% sensitivity. This study evaluates the performance of commercial anti-DENV IgG tests to identify tests that could be used for pre-vaccination screening. First, for seven tests, we evaluated sensitivity and specificity in early convalescent dengue virus (DENV) infection, using 44 samples collected 7-30 days after symptom onset and confirmed by RT-PCR. Next, for the five best-performing tests and two additional tests (with and without an external test reader) that became available later, we evaluated performance to detect past dengue infection among a panel of 44 specimens collected in 2018-2019 from healthy 9- to 16-year-old children from Puerto Rico. Finally, a full-scale evaluation was done with the four best-performing tests using 400 specimens from the same population. We used virus focus reduction neutralization test and an in-house DENV IgG ELISA as reference standards. Of seven tests, five showed ≥75% sensitivity in detecting anti-DENV IgG in early convalescent specimens with low cross-reactivity to the Zika virus. For the detection of previous DENV infections, the tests with the highest performance were the Euroimmun NS1 IgG ELISA (sensitivity 84.5%, specificity 97.1%) and CTK Dengue IgG rapid test R0065C with the test reader (sensitivity 76.2% specificity 98.1%). There are IgG tests available that can be used to accurately classify individuals with previous DENV infection as eligible for dengue vaccination to support safe vaccine implementation. IMPORTANCE: The Advisory Committee on Immunization Practices (ACIP) has set forth recommendations that dengue pre-vaccination screening tests must exhibit at least 98% specificity and 75% sensitivity. Our research rigorously assesses the performance of various commercial tests against these benchmarks using well-characterized specimens from Puerto Rico. The findings from our study are particularly relevant given FDA approval and ACIP recommendation of Sanofi Pasteur's Dengvaxia vaccine, highlighting the need for accurate pre-vaccination screening tools.

BACKGROUND: The COVID-19 pandemic underscored the need for rapid and accurate diagnostic tools. In August 2020, the Abbott BinaxNOW COVID-19 Antigen Card test became available as a timely and affordable alternative for SARS-CoV-2 molecular testing, but its performance may vary due to factors including timing and symptomatology. This study evaluates BinaxNOW diagnostic performance in diverse epidemiological contexts. METHODS: Using RT-PCR as reference, we assessed performance of the BinaxNOW COVID-19 test for SARS-CoV-2 detection in anterior nasal swabs from participants of two studies in Puerto Rico from December 2020 to May 2023. Test performance was assessed by days post symptom onset, collection strategy, vaccination status, symptomatology, repeated testing, and RT-PCR cycle threshold (Ct) values. RESULTS: BinaxNOW demonstrated an overall sensitivity of 84.1% and specificity of 98.8%. Sensitivity peaked within 1-6 days after symptom onset (93.2%) and was higher for symptomatic (86.3%) than asymptomatic (67.3%) participants. Sensitivity declined over the course of infection, dropping from 96.3% in the initial test to 48.4% in testing performed 7-14 days later. BinaxNOW showed 99.5% sensitivity in participants with low Ct values (≤ 25) but lower sensitivity (18.2%) for participants with higher Cts (36-40). CONCLUSIONS: BinaxNOW demonstrated high sensitivity and specificity, particularly in early-stage infections and symptomatic participants. In situations where test sensitivity is crucial for clinical decision-making, nucleic acid amplification tests are preferred. These findings highlight the importance of considering clinical and epidemiological context when interpreting test results and emphasize the need for ongoing research to adapt testing strategies to emerging SARS-CoV-2 variants.

BACKGROUND: Dengue fever remains a significant public health challenge in tropical and subtropical regions, with its transmission dynamics being influenced by both environmental factors and human mobility. The Dominican Republic, a biodiversity hotspot in the Caribbean, has experienced recurrent dengue outbreaks, yet detailed understanding of the virus's transmission pathways and the impact of climatic factors remains limited. This study aims to elucidate the recent transmission dynamics of the dengue virus (DENV) in the Dominican Republic, utilizing a combination of genomic sequencing and epidemiological data analysis, alongside an examination of historical climate patterns. METHODS: We conducted a comprehensive study involving the genomic sequencing of DENV samples collected from patients across different regions of the Dominican Republic over a two-year period. Phylogenetic analyses were performed to identify the circulation of DENV lineages and to trace transmission pathways. Epidemiological data were integrated to analyze trends in dengue incidence and distribution. Additionally, we integrated historical climate data spanning several decades to assess trends in temperature and their potential impact on DENV transmission potential. RESULTS: Our results highlight a previously unknown north-south transmission pathway within the country, with the co-circulation of multiple virus lineages. Additionally, we examine the historical climate data, revealing long-term trends towards higher theoretical potential for dengue transmission due to rising temperatures. CONCLUSION: This multidisciplinary study reveals intricate patterns of dengue virus transmission in the Dominican Republic, characterized by the co-circulation of multiple DENV lineages and a novel transmission pathway. The observed correlation between rising temperatures and increased dengue transmission potential emphasizes the need for integrated climate-informed strategies in dengue control efforts. Our findings offer critical insights for public health authorities in the Dominican Republic and similar settings, guiding resource allocation and the development of preparedness strategies to mitigate the impacts of climate change on dengue transmission.

PROBLEM/CONDITION: Dengue is the most prevalent mosquitoborne viral illness worldwide and is endemic in Puerto Rico. Dengue's clinical spectrum can range from mild, undifferentiated febrile illness to hemorrhagic manifestations, shock, multiorgan failure, and death in severe cases. The disease presentation is nonspecific; therefore, various other illnesses (e.g., arboviral and respiratory pathogens) can cause similar clinical symptoms. Enhanced surveillance is necessary to determine disease prevalence, to characterize the epidemiology of severe disease, and to evaluate diagnostic and treatment practices to improve patient outcomes. The Sentinel Enhanced Dengue Surveillance System (SEDSS) was established to monitor trends of dengue and dengue-like acute febrile illnesses (AFIs), characterize the clinical course of disease, and serve as an early warning system for viral infections with epidemic potential. REPORTING PERIOD: May 2012-December 2022. DESCRIPTION OF SYSTEM: SEDSS conducts enhanced surveillance for dengue and other relevant AFIs in Puerto Rico. This report includes aggregated data collected from May 2012 through December 2022. SEDSS was launched in May 2012 with patients with AFIs from five health care facilities enrolled. The facilities included two emergency departments in tertiary acute care hospitals in the San Juan-Caguas-Guaynabo metropolitan area and Ponce, two secondary acute care hospitals in Carolina and Guayama, and one outpatient acute care clinic in Ponce. Patients arriving at any SEDSS site were eligible for enrollment if they reported having fever within the past 7 days. During the Zika epidemic (June 2016-June 2018), patients were eligible for enrollment if they had either rash and conjunctivitis, rash and arthralgia, or fever. Eligibility was expanded in April 2020 to include reported cough or shortness of breath within the past 14 days. Blood, urine, nasopharyngeal, and oropharyngeal specimens were collected at enrollment from all participants who consented. Diagnostic testing for dengue virus (DENV) serotypes 1-4, chikungunya virus, Zika virus, influenza A and B viruses, SARS-CoV-2, and five other respiratory viruses was performed by the CDC laboratory in San Juan. RESULTS: During May 2012-December 2022, a total of 43,608 participants with diagnosed AFI were enrolled in SEDSS; a majority of participants (45.0%) were from Ponce. During the surveillance period, there were 1,432 confirmed or probable cases of dengue, 2,293 confirmed or probable cases of chikungunya, and 1,918 confirmed or probable cases of Zika. The epidemic curves of the three arboviruses indicate dengue is endemic; outbreaks of chikungunya and Zika were sporadic, with case counts peaking in late 2014 and 2016, respectively. The majority of commonly identified respiratory pathogens were influenza A virus (3,756), SARS-CoV-2 (1,586), human adenovirus (1,550), respiratory syncytial virus (1,489), influenza B virus (1,430), and human parainfluenza virus type 1 or 3 (1,401). A total of 5,502 participants had confirmed or probable arbovirus infection, 11,922 had confirmed respiratory virus infection, and 26,503 had AFI without any of the arboviruses or respiratory viruses examined. INTERPRETATION: Dengue is endemic in Puerto Rico; however, incidence rates varied widely during the reporting period, with the last notable outbreak occurring during 2012-2013. DENV-1 was the predominant virus during the surveillance period; sporadic cases of DENV-4 also were reported. Puerto Rico experienced large outbreaks of chikungunya that peaked in 2014 and of Zika that peaked in 2016; few cases of both viruses have been reported since. Influenza A and respiratory syncytial virus seasonality patterns are distinct, with respiratory syncytial virus incidence typically reaching its annual peak a few weeks before influenza A. The emergence of SARS-CoV-2 led to a reduction in the circulation of other acute respiratory viruses. PUBLIC HEALTH ACTION: SEDSS is the only site-based enhanced surveillance system designed to gather information on AFI cases in Puerto Rico. This report illustrates that SEDSS can be adapted to detect dengue, Zika, chikungunya, COVID-19, and influenza outbreaks, along with other seasonal acute respiratory viruses, underscoring the importance of recognizing signs and symptoms of relevant diseases and understanding transmission dynamics among these viruses. This report also describes fluctuations in disease incidence, highlighting the value of active surveillance, testing for a panel of acute respiratory viruses, and the importance of flexible and responsive surveillance systems in addressing evolving public health challenges. Various vector control strategies and vaccines are being considered or implemented in Puerto Rico, and data from ongoing trials and SEDSS might be integrated to better understand epidemiologic factors underlying transmission and risk mitigation approaches. Data from SEDSS might guide sampling strategies and implementation of future trials to prevent arbovirus transmission, particularly during the expansion of SEDSS throughout the island to improve geographic representation.

Phaeoacremonium is a genus of dematiaceous fungi that rarely causes human infections. We describe a case of subcutaneous infection in a 70-year-old diabetic man with lesions on the dorsum of the one foot. The agent was isolated, and for the final identification we performed matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and DNA sequencing. After diagnosis, the patient underwent curettage of the cyst and received 100mg of Itraconazole, twice daily for 6 months. Clinical resolution of the lesion was observed after treatment. This is the first case of infection by Phaeoacremonium venezuelense reported in Costa Rica.

Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.

BACKGROUND: A better understanding of SARS-CoV-2 infection risk among Hispanic and Latino populations and in low-resource settings in the United States is needed to inform control efforts and strategies to improve health equity. Puerto Rico has a high poverty rate and other population characteristics associated with increased vulnerability to COVID-19, and there are limited data to date to determine community incidence. OBJECTIVE: This study describes the protocol and baseline seroprevalence of SARS-CoV-2 in a prospective community-based cohort study (COPA COVID-19 [COCOVID] study) to investigate SARS-CoV-2 infection incidence and morbidity in Ponce, Puerto Rico. METHODS: In June 2020, we implemented the COCOVID study within the Communities Organized to Prevent Arboviruses project platform among residents of 15 communities in Ponce, Puerto Rico, aged 1 year or older. Weekly, participants answered questionnaires on acute symptoms and preventive behaviors and provided anterior nasal swab samples for SARS-CoV-2 polymerase chain reaction testing; additional anterior nasal swabs were collected for expedited polymerase chain reaction testing from participants that reported 1 or more COVID-19-like symptoms. At enrollment and every 6 months during follow-up, participants answered more comprehensive questionnaires and provided venous blood samples for multiantigen SARS-CoV-2 immunoglobulin G antibody testing (an indicator of seroprevalence). Weekly follow-up activities concluded in April 2022 and 6-month follow-up visits concluded in August 2022. Primary study outcome measures include SARS-CoV-2 infection incidence and seroprevalence, relative risk of SARS-CoV-2 infection by participant characteristics, SARS-CoV-2 household attack rate, and COVID-19 illness characteristics and outcomes. In this study, we describe the characteristics of COCOVID participants overall and by SARS-CoV-2 seroprevalence status at baseline. RESULTS: We enrolled a total of 1030 participants from 388 households. Relative to the general populations of Ponce and Puerto Rico, our cohort overrepresented middle-income households, employed and middle-aged adults, and older children (P<.001). Almost all participants (1021/1025, 99.61%) identified as Latino/a, 17.07% (175/1025) had annual household incomes less than US $10,000, and 45.66% (463/1014) reported 1 or more chronic medical conditions. Baseline SARS-CoV-2 seroprevalence was low (16/1030, 1.55%) overall and increased significantly with later study enrollment time (P=.003). CONCLUSIONS: The COCOVID study will provide a valuable opportunity to better estimate the burden of SARS-CoV-2 and associated risk factors in a primarily Hispanic or Latino population, assess the limitations of surveillance, and inform mitigation measures in Puerto Rico and other similar populations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/53837.

Over the past 70 years, significant advances have been made in determining the causes of death in populations not served by official medical certification of cause at the time of death using a technique known as Verbal Autopsy (VA). VA involves an interview of the family or caregivers of the deceased after a suitable bereavement interval about the circumstances, signs and symptoms of the deceased in the period leading to death. The VA interview data are then interpreted by physicians or, more recently, computer algorithms, to assign a probable cause of death. VA was originally developed and applied in field research settings. This paper traces the evolution of VA methods with special emphasis on the World Health Organization's (WHO)'s efforts to standardize VA instruments and methods for expanded use in routine health information and vital statistics systems in low- and middle-income countries (LMICs). These advances in VA methods are culminating this year with the release of the 2022 WHO Standard Verbal Autopsy (VA) Toolkit. This paper highlights the many contributions the late Professor Peter Byass made to the current VA standards and methods, most notably, the development of InterVA, the most commonly used automated computer algorithm for interpreting data collected in the WHO standard instruments, and the capacity building in low- and middle-income countries (LMICs) that he promoted. This paper also provides an overview of the methods used to improve the current WHO VA standards, a catalogue of the changes and improvements in the instruments, and a mapping of current applications of the WHO VA standard approach in LMICs. It also provides access to tools and guidance needed for VA implementation in Civil Registration and Vital Statistics Systems at scale.

This report introduces a Brighton Collaboration (BC) case definition for autoimmune hepatitis (AIH), which has been classified as a priority adverse event of special interest (AESI), as there were possible cases seen following COVID-19 vaccination. The case definition was developed by a group of subject matter and BC process experts to facilitate safety data comparability across pre- and post-licensure clinical trials, as well as pharmacovigilance activities in multiple settings with diverse resources and healthcare access. The usual BC case definition development process was followed in an expedited manner, and took two months to complete, including finalising the manuscript for publication, instead of the usual 1 year development time. It includes a systematic review of the literature and an expert consensus to define levels of diagnostic certainty for AIH, and provides specific guidelines for data collection and analysis. Histology, serological and biochemical tests and exclusion of alternate diagnosis were considered necessary to define the levels of certainty (definitive, probable and possible). AEFI reports of suspected AIH were independently classified by the WG members to test its useability and these classifications were used to finalise the case definition. The document underwent peer review by external AIH experts and a Reference Group of vaccine safety stakeholders in high-, low- and middle-income countries to ensure case definition useability, applicability, and scientific integrity. The expedited process can be replicated for development of other standardised case definitions for priority AESIs for endemics and epidemics. While applicable to cases reported following immunisation, the case definition is independent of lapsed time following vaccination and, as such, can also be used to determine background incidence for vaccinated and unvaccinated control groups in studies of causal association. While use of this case definition is also appropriate for the study of safety of other products including drugs, it is not meant to guide clinical case management.

During May 2022-April 2023, dengue virus serotype 3 was identified among 601 travel-associated and 61 locally acquired dengue cases in Florida, USA. All 203 sequenced genomes belonged to the same genotype III lineage and revealed potential transmission chains in which most locally acquired cases occurred shortly after introduction, with little sustained transmission.

IMPORTANCE: Influenza virus infection during pregnancy is associated with severe maternal disease and may be associated with adverse birth outcomes. Inactivated influenza vaccine during pregnancy is safe and effective and can protect young infants, but recent evidence, particularly after the 2009 novel influenza A (H1N1) pandemic, is limited. OBJECTIVE: To evaluate the effectiveness of influenza vaccination during pregnancy against laboratory-confirmed influenza-associated hospitalizations and emergency department (ED) visits in infants younger than 6 months. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, test-negative case-control study using data from the New Vaccine Surveillance Network from the 2016 to 2017 through 2019 to 2020 influenza seasons. Infants younger than 6 months with an ED visit or hospitalization for acute respiratory illness were included from 7 pediatric medical institutions in US cities. Control infants with an influenza-negative molecular test were included for comparison. Data were analyzed from June 2022 to September 2023. EXPOSURE: Maternal influenza vaccination during pregnancy. MAIN OUTCOMES AND MEASURES: We estimated maternal vaccine effectiveness against hospitalizations or ED visits in infants younger than 6 months, those younger than 3 months, and by trimester of vaccination. Maternal vaccination status was determined using immunization information systems, medical records, or self-report. Vaccine effectiveness was estimated by comparing the odds of maternal influenza vaccination 14 days or more before delivery in infants with influenza vs those without. RESULTS: Of 3764 infants (223 with influenza and 3541 control infants), 2007 (53%) were born to mothers who were vaccinated during pregnancy. Overall vaccine effectiveness in infants was 34% (95% CI, 12 to 50), 39% (95% CI, 12 to 58) against influenza-associated hospitalizations, and 19% (95% CI, -24 to 48) against ED visits. Among infants younger than 3 months, effectiveness was 53% (95% CI, 30 to 68). Effectiveness was 52% (95% CI, 30 to 68) among infants with mothers who were vaccinated during the third trimester and 17% (95% CI, -15 to 40) among those with mothers who were vaccinated during the first or second trimesters. CONCLUSIONS AND RELEVANCE: Maternal vaccination was associated with reduced odds of influenza-associated hospitalizations and ED visits in infants younger than 6 months. Effectiveness was greatest among infants younger than 3 months, for those born to mothers vaccinated during the third trimester, and against influenza-associated hospitalizations.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

BACKGROUND: Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment. METHODS: To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student's t-test followed by pathway analysis and comparison between the different omics modalities. RESULTS: Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection. CONCLUSION: This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

Mental and behavioral health conditions among school-aged children, including substance use disorders and overall emotional well-being, are a public health concern in the United States. Timely data on seasonal patterns in child and adolescent conditions can guide optimal timing of prevention and intervention strategies. CDC examined emergency department (ED) visit data from the National Syndromic Surveillance Program for 25 distinct conditions during January 2018-June 2023 among U.S. children and adolescents aged 5-17 years, stratified by age group. Each year, during 2018-2023, among persons aged 10-14 and 15-17 years, the number and proportion of weekly ED visits for eight conditions increased in the fall school semester and remained elevated throughout the spring semester; ED visits were up to twice as high during school semesters compared with the summer period. Among children aged 5-9 years, the number and proportion of visits increased for five mental and behavioral health conditions. Seasonal increases in ED visits for some conditions among school-aged children warrant enhanced awareness about mental distress symptoms and the challenges and stressors in the school environment. Systemic changes that prioritize protective factors (e.g., physical activity; nutrition; sleep; social, community, or faith-based support; and inclusive school and community environments) and incorporate preparedness for increases in conditions during back-to-school planning might improve child and adolescent mental health.

Palau had no reported evidence of COVID-19 community spread until January 2022. We chart reviewed hospitalized patients who had a positive SARS-CoV-2 test result during early community transmission. Booster vaccinations and early outpatient treatment decreased hospitalizations. Inadequate hospital infection control practices contributed to iatrogenic COVID-19 and preventable deaths.

BACKGROUND: We evaluated dengue presentation by age, the performance of the 2015 Pan American Health Organization (PAHO) case criteria in identifying dengue cases, and variables to improve specificity. METHODS: Patients with fever ≤7 days (N = 10 408) were recruited from 2 emergency departments from May 2012 through December 2015. Serum samples were tested for dengue, chikungunya, and nasopharyngeal swabs for respiratory viruses. Smoothing splines assessed differences in the frequencies of signs/symptoms by age. Least absolute shrinkage and selection operator regressions identified the variables that best predicted dengue. RESULTS: Among 985 dengue cases, children aged <5 years were least likely to have leukopenia, but most likely to have rash and petechiae. Adults had the highest odds of aches/pains and headaches/retro-orbital pain. The 2015 PAHO criteria had sensitivity of 93% and specificity of 25%. Specificity could be improved by requiring at least 2 of the following criteria: vomiting/nausea, petechiae, rash, or leukopenia (specificity 68%, sensitivity 71%) or by using 2015 PAHO criteria plus either (1) aspartate aminotransferase >50 IU/L or platelet count <100 000 platelets/μL (specificity 81%, sensitivity 56%) or (2) itchy skin or absence of rhinorrhea or cough (specificity 51%, sensitivity 82%). CONCLUSIONS: The 2015 PAHO dengue case criteria had excellent sensitivity but poor specificity. This can be improved by adding signs/symptoms associated with dengue diagnosis.

Reproductive coercion is any behavior that attempts to control the autonomous reproductive decision-making of an intimate partner. Very little research has focused on males who perpetrate reproductive coercion. Using a diverse community sample of young adults, we examined the prevalence of lifetime reproductive coercion perpetration and its relationship with other forms of intimate partner violence (IPV). Results demonstrated that approximately 6.4% of the men reported perpetrating reproductive coercion in their lifetime. Chi-square analyses demonstrated that men who reported sexual (16.2%), physical (11.1%), or psychological (59.1%) IPV perpetration, relative to men who did not, reported a significantly higher prevalence of reproductive coercion perpetration.

We report a dengue outbreak in Key Largo, Florida, USA, from February through August 2020, during the COVID-19 pandemic. Successful community engagement resulted in 61% of case-patients self-reporting. We also describe COVID-19 pandemic effects on the dengue outbreak investigation and the need to increase clinician awareness of dengue testing recommendations.

The US-Affiliated Pacific Islands (USAPIs) experience many health disparities, including high rates of non-communicable disease and limited health resources, making them particularly vulnerable when SARS-CoV-2 began circulating globally in early 2020. Therefore, many USAPIs closed their borders early during the COVID-19 pandemic to give them more time to prepare for community transmission. Routine virtual meetings were established and maintained throughout the pandemic to support preparedness and response efforts and to share information among USAPIs and support partners. Data collected from these regular virtual meetings were gathered and disseminated through routine regional situational reports. These situational reports from March 27, 2020 to November 25, 2022 were reviewed to develop a quantitative dataset with qualitative notes that were used to summarize the COVID-19 response in the USAPIs. The initial surges of COVID-19 in the USAPIs ranged from August 2020 in Guam to August 2022 in the Federated States of Micronesia. This prolonged time between initial surges in the region was due to varying approaches regarding travel requirements, including fully closed borders, repatriation efforts requiring pre-travel quarantine and testing, quarantine requirements upon arrival only, and vaccine mandates. Delaying community transmission allowed USAPIs to establish testing capacity, immunize large proportions of their populations, and use novel COVID-19 therapeutics to reduce severe disease and mortality. Other essential components to support the USAPI regional COVID-19 response efforts included strong partnership and collaboration, regional information sharing and communication efforts, and trust in health leadership among community members. Valuable lessons learned from the USAPIs during the COVID-19 pandemic can be used to continue to strengthen systems within the region and better prepare for future public health emergencies.

Candida auris is an emerging fungal pathogen of rising concern due to its increasing incidence, its ability to cause healthcare-associated outbreaks and antifungal resistance. Genomic analysis revealed that early cases of C. auris that were detected contemporaneously were geographically stratified into four major clades. Clade II, also termed East Asian clade, consists of the initial isolates described from cases of ear infection, is less frequently resistant to antifungal drugs and to date, the isolates from this group have not been associated with outbreaks. Here, we generate nearly complete genomes (“telomere-to-telomere”) of an isolate of this clade and of the more widespread Clade IV. By comparing these to genome assemblies of the other two clades, we find that the Clade II genome appears highly rearranged, with 2 inversions and 9 translocations resulting in a substantially different karyotype. In addition, large subtelomeric regions have been lost from 10 of 14 chromosome ends in the Clade II genomes. We find that shorter telomeres and genome instability might be a consequence of a naturally occurring loss-of-function mutation in DCC1 exclusively found in Clade II isolates, resulting in a hypermutator phenotype. We also determine that deleted subtelomeric regions might be linked to clade-specific adaptation as these regions are enriched in Hyr/Iff-like cell surface proteins, novel candidate cell surface proteins, and an ALS-like adhesin. The presence of these cell surface proteins in the clades responsible for global outbreaks causing invasive infections suggests an explanation for the different phenotypes observed between clades.IMPORTANCE Candida auris was unknown prior to 2009 and since then it has quickly spread around the world, causing outbreaks in healthcare facilities and representing a high fraction of candidemia cases in some regions. The emergence of C. auris is a major concern, since it is often multidrug-resistant, easily spread between patients, and causes invasive infections. While isolates from three global clades cause invasive infections, isolates from Clade II primarily cause ear infections and have not been implicated in outbreaks, though cases of Clade II infections have been reported on different continents. Here, we describe genetic differences between Clade II and Clades I, III and IV, including a loss-of-function mutation in a gene associated with telomere length maintenance and genome stability, and the loss of cell wall proteins involved in adhesion and biofilm formation, that may suggest an explanation for the lower virulence and potential for transmission of Clade II isolates.

Candida auris is an emergent fungal pathogen of rising public health concern due to increasing reports of outbreaks in healthcare settings and resistance to multiple classes of antifungal drugs. While distantly related to the more common pathogens C. albicans and C. glabrata, C. auris is closely related to three rarely observed and often multidrug-resistant species, C. haemulonii, C. duobushaemulonii and C. pseudohaemulonii. Here, we generated and analyzed near complete genome assemblies and RNA-Seq-guided gene predictions for isolates from each of the four major C. auris clades and for C. haemulonii, C. duobushaemulonii and C. pseudohaemulonii. Our analyses mapped seven chromosomes and revealed chromosomal rearrangements between C. auris clades and related species. We found conservation of genes involved in mating and meiosis and identified both MTLa and MTLα C. auris isolates, suggesting the potential for mating between clades. Gene conservation analysis highlighted that many genes linked to drug resistance and virulence in other pathogenic Candida species are conserved in C. auris and related species including expanded families of transporters and lipases, as well as mutations and copy number variants in ERG11 that confer drug resistance. In addition, we found genetic features of the emerging species that likely underlie differences in virulence and drug response between these and other Candida species, including genes involved in cell wall structure. To begin to characterize the species-specific genes important for antifungal response, we profiled the gene expression of C. auris in response to voriconazole and amphotericin B and found induction of several transporters and metabolic regulators that may play a role in drug resistance. This study provides a comprehensive view of the genomic basis of drug resistance, potential for mating, and virulence in this emerging fungal clade.

Diagnostic testing for Zika virus (ZIKV) or dengue virus (DENV) infection can be accomplished by a nucleic acid detection method; however, a negative result does not exclude infection due to the low virus titer during infection depending on the timing of sample collection. Therefore, a ZIKV- or DENV-specific serological assay is essential for the accurate diagnosis of patients and to prevent potential severe health outcomes. A retrospective study design with dual approaches of collecting human serum samples for testing was developed. All serum samples were extensively evaluated by using both non-infectious virus-like particles (VLPs) and soluble non-structural protein 1 (NS1) in the standard immunoglobulin M (IgM) antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). Both VLP- and NS1-MAC-ELISAs were found to have similar sensitivity for detecting anti-premembrane/envelope and NS1 antibodies from ZIKV-infected patient sera. Group cross reactive (GR)-antibody-ablated homologous fusion peptide-mutated (FP)-VLPs consistently showed higher P/N values than homologous wild-type VLPs. Therefore, FP-VLPs were used to develop the algorithm for differentiating ZIKV from DENV infection. Overall, the sensitivity and specificity of the FP-VLP-MAC-ELISA and the NS1-MAC-ELISA were each higher than 80% with no statistical significance. A novel approach to differentiate ZIKV from DENV infection serologically has been developed. The accuracy can reach up to 95% when combining both VLP and NS1 assays. In comparison to current guidelines using neutralization tests to measure ZIKV antibody, this approach can facilitate laboratory screening for ZIKV infection, especially in regions where DENV infection is endemic and capacity for neutralization testing does not exist.

Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (Clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in over 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; Clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single healthcare facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 339 years; outbreak-causing clusters from Clades I, III, and IV originated 34-35 years ago. We observed high rates of antifungal resistance in Clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in Clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris.Importance In less than a decade, C. auris has emerged in healthcare settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.

Candida auris has emerged as a multidrug-resistant pathogen of great clinical concern. Approximately 90% of clinical C. auris isolates are resistant to fluconazole, the most commonly prescribed antifungal agent, yet it remains unknown what mechanisms underpin this fluconazole resistance. To identify novel mechanisms contributing to fluconazole resistance in C. auris, the fluconazole-susceptible C. auris clinical isolate AR0387 was passaged in media supplemented with fluconazole to generate derivative strains which had acquired increased fluconazole resistance in vitro. Comparative analysis of comprehensive sterol profiles, [3H]-fluconazole uptake, sequencing of C. auris genes homologous to genes known to contribute to fluconazole resistance in other species of Candida, and the relative expression of C. auris ERG11, CDR1, and MDR1 were performed. All fluconazole-evolved derivative strains were found to have acquired mutations in the zinc-cluster transcription factor-encoding gene, TAC1B, and a corresponding increase in CDR1 expression relative to the parental clinical isolate, AR0387. Mutations in TAC1B were also identified in a set of 304 globally distributed C. auris clinical isolates representing each of the four major clades. Introduction of the most common mutation found among fluconazole-resistant clinical isolates of C. auris into the fluconazole-susceptible isolate AR0387, was confirmed to increase fluconazole resistance by 8-fold, and the correction of the same mutation in a fluconazole-resistant isolate, AR0390, decreased fluconazole MIC by 16-fold. Taken together, these data demonstrate that C. auris can rapidly acquire resistance to fluconazole in-vitro, and that mutations in TAC1B significantly contribute to clinical fluconazole resistance.IMPORTANCE Candida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and commonly resistant to antifungals. While the vast majority of clinical C. auris isolates are highly resistant to fluconazole, an essential part of the available antifungal arsenal, very little is known about the mechanisms contributing to resistance. In this work, we show that mutations in the transcription factor TAC1B significantly contribute to clinical fluconazole resistance. These studies demonstrate that mutations in TAC1B can arise rapidly in vitro upon exposure to fluconazole, and that a multitude of resistance-associated TAC1B mutations are present among the majority of fluconazole-resistant C. auris isolates from a global collection and appear specific to a subset of lineages or clades. Thus, identification of this novel genetic determinant of resistance significantly adds to the understanding of clinical antifungal resistance in C. auris.

Concurrent separate human outbreaks of Salmonella enterica serotype Reading occurred in 2017-2019 in the United States and Canada, which were both linked to the consumption of raw turkey products. In this study, a comprehensive genomic investigation was conducted to reconstruct the evolutionary history of S. Reading from turkeys, and to determine the genomic context of outbreaks involving this rarely isolated Salmonella serotype. A total of 988 isolates of U.S. origin were examined using whole genome-based approaches, including current and historical isolates from humans, meat, and live food animals. Broadly, isolates clustered into three major clades, with one apparently highly adapted turkey clade. Within the turkey clade isolates clustered into three subclades, including an “emergent” clade that only contained isolates dated 2016 or later, including many of the isolates from these outbreaks. Genomic differences were identified between emergent and other turkey subclades suggesting that the apparent success of currently circulating subclades clade is, in part, attributable to plasmid acquisitions conferring antimicrobial resistance, gain of phage-like sequences with cargo virulence factors, and mutations in systems that may be involved in beta-glucuronidase activity and resistance towards colicins. U.S. and Canadian outbreak isolates were found interspersed throughout the emergent subclade and the other circulating subclade. The emergence of a novel S. Reading turkey subclade, coinciding temporally with expansion in commercial turkey production and with U.S. and Canadian human outbreaks, indicates that emergent strains with higher potential for niche success were likely vertically transferred and rapidly disseminated from a common source.Importance Increasingly, outbreak investigations involving foodborne pathogens are confounded by the inter-connectedness of food animal production and distribution, necessitating high-resolution genomic investigations to determine their basis. Fortunately, surveillance and whole genome sequencing, combined with the public availability of these data, enable comprehensive queries to determine underlying causes of such outbreaks. Utilizing this pipeline, it was determined that a novel clone of Salmonella Reading has emerged that coincides with increased abundance in raw turkey products and two outbreaks of human illness in North America. The rapid dissemination of this highly adapted and conserved clone indicates that it was likely obtained from a common source and rapidly disseminated across turkey production. Key genomic changes may have contributed to its apparent continued success in the barn environment, and ability to cause illness in humans.