We compared the number of Aedes aegypti females per trap and the number of detections of this mosquito species per week during 8 wk in 3 types of autocidal gravid traps, the Centers for Disease Control and Prevention (CDC) Autocidal Gravid Ovitrap (AGO), Biogents Gravid Aedes Trap (GAT), and Singapore Gravitrap (SGT), in central Puerto Rico. These traps use the same principles for attracting gravid Ae. aegypti females as traditional ovitraps, such as dark colors, standing water, and decomposing plant materials. The traps differ in size, AGO being the biggest and SGT the smallest. Average captures of female Ae. aegypti per trap per week were 11.1, 7.2, and 1.7 in AGO, GAT, and SGT traps, respectively, a pattern consistent with the sizes of the traps. These results indicated that GAT traps and SGT traps captured 35.5% and 84.7% fewer females of Ae. aegypti, respectively, than AGO traps. Although Ae. aegypti was present in all 20 sites during the 8 wk of observations, AGO, GAT, and SGT traps did not catch specimens in 1, 9, and 58 out of 160 observations per trap type (trap-wk), respectively. Trap failures were 1, 6, and 1 for the AGO, GAT, and SGT traps, respectively. Despite the absence of females of Ae. aegypti at some sites and weeks in each of the traps, all 3 traps were able to detect the presence of this mosquito at each of the 20 sites during the 8 wk of observations and could be used for Ae. aegypti surveillance.

Background/Purpose: The burden and epidemiology of Mycoplasma pneumoniae (Mp) community-acquired pneumonia (CAP) among hospitalized U. S. adults (≥ 18 years) are poorly understood. Methods: In the Etiology of Pneumonia in the Community (EPIC) study, we prospectively enrolled 2272 adults hospitalized with radiographically-confirmed pneumonia between January 2010-June 2012 and tested nasopharyngeal/oropharyngeal swabs for Mp by real-time polymerase chain reaction (PCR). Clinical and epidemiological features of Mp-PCR-positive and -negative adults were compared using logistic regression. Macrolide susceptibility was assessed by genotyping isolates. Results: Among 2272 adults, 43 (1.8%) were Mp-PCR-positive (median age: 45 years); 52% were male, and 56% were non-Hispanic white. Only one patient had Mp macrolide resistance. Four (9%) were admitted to the intensive care unit (ICU). No in-hospital deaths were reported. Of the 9 (21%) who received an outpatient antibiotic ≤5 days pre-admission, 2 (22%) received an antibiotic with Mp activity. Variables significantly associated with higher odds of Mp detection included age {18-29 years [(adjusted odds ratio (aOR): 11.7 (95% confidence interval (CI): 5.1- 26.6) versus ≥50 years]} and radiographic lymphadenopathy [aOR: 3.5 (95% CI: 1.2- 9.3)]. Conclusions: M. pneumoniae, commonly known to cause "walking pneumonia", was detected among hospitalized adults, with the highest prevalence among young adults. Although associated with clinically non-specific symptoms, approximately one out of every ten patients were admitted to the ICU. Increasing access to M. pneumoniae point-of-care testing could facilitate targeted treatment and avoid hospitalization.

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.

Multiplex-based serological surveillance is a valuable but underutilized tool to understand gaps in population-level exposure, susceptibility, and immunity to infectious diseases. Assays for which blood samples can be tested for antibodies against several pathogens simultaneously, such as multiplex bead immunoassays, can more efficiently integrate public health surveillance in low- and middle-income countries. On March 7-8, 2023 a group of experts representing research institutions, multilateral organizations, private industry, and country partners met to discuss experiences, identify challenges and solutions, and create a community of practice for integrated, multi-pathogen serosurveillance using multiplex bead assay technologies. Participants were divided into six working groups: 1) supply chain; 2) laboratory assays; 3) seroepidemiology; 4) data analytics; 5) sustainable implementation; and 6) use case scenarios. These working groups discussed experiences, challenges, solutions, and research needs to facilitate integrated, multi-pathogen serosurveillance for public health. Several solutions were proposed to address challenges that cut across working groups.

OBJECTIVE: To estimate the national and regional population attributable fraction (PAF) and potential number of preventable anemia cases for three nutritional risk factors (iron, red blood cell folate [RBCF], and vitamin B12 deficiencies) among women of childbearing age in Belize. METHODS: A national probability-based household and micronutrient survey capturing sociodemographic and health information was conducted among 937 nonpregnant Belizean women aged 15-49 years. Blood samples were collected to determine hemoglobin, ferritin, alpha-1-glycoprotein (AGP), RBCF, and vitamin B12 status. All analyses used sample weights and design variables to reflect a complex sample survey. Logistic regression was used to determine adjusted prevalence risk (aPR) ratios, which were then used to estimate national and regional PAF for anemia. RESULTS: The overall prevalence of anemia (hemoglobin <12 g/dL) was 21.2% (95% CI [18.7, 25.3]). The prevalence of anemia was significantly greater among women with iron deficiency (59.5%, 95% CI [48.7, 69.5]) compared to women without iron deficiency (15.2%, 95% CI [12.2, 18.3]; aPR 3.9, 95% CI [2.9, 5.1]). The three nutritional deficiencies examined contributed to 34.6% (95% CI [22.1, 47.1]) of the anemia cases. If all these nutritional deficiencies could be eliminated, then an estimated 5 953 (95% CI [3 807, 8 114]) anemia cases could be prevented. CONCLUSIONS: This study suggests that among women of child-bearing age in Belize, anemia cases might be reduced by a third if three modifiable nutritional risk factors (iron, RBCF, and vitamin B12 deficiencies) could be eliminated. Fortification is one potential strategy to improve nutritional status and reduce the burden of anemia in this population.

BACKGROUND: Dengue is a leading cause of febrile illness among international travellers. We aimed to describe the epidemiology and clinical characteristics of imported dengue in returning travellers evaluated at GeoSentinel sites from 2007-2022. METHODS: We retrieved GeoSentinel records of dengue among travellers residing in non-endemic countries. We considered dengue confirmed when diagnosed by a positive DENV-specific RT-PCR, positive NS-1 antigen, and/or anti-DENV IgG seroconversion, and probable when diagnosed by single anti-DENV IgM or high titre anti-DENV IgG detection. Severe dengue was defined as evidence of clinically significant plasma leakage or bleeding, organ failure, or shock, according to the 2009 WHO guidance. Complicated dengue was defined as either severe dengue or dengue with presence of any warning sign. Analyses were descriptive. RESULTS: This analysis included 5958 travellers with confirmed (n = 4859; 81.6%) or probable (n = 1099; 18.4%) dengue. The median age was 33 years (range: < 1-91); 3007 (50.5%) travellers were female. The median travel duration was 21 days (interquartile range [IQR]: 15-32). The median time between illness onset and GeoSentinel site visit was 7 days (IQR: 4-15). The most frequent reasons for travel were tourism (67.3%), visiting friends or relatives (12.2%), and business (11.0%). The most frequent regions of acquisition were Southeast Asia (50.4%), South-Central Asia (14.9%), the Caribbean (10.9%), and South America (9.2%). Ninety-five (1.6%) travellers had complicated dengue, of whom 27 (0.5%) had severe dengue, and one died. Of 2710 travellers with data available, 724 (26.7%) were hospitalized. The largest number of cases (n = 835) was reported in 2019. CONCLUSIONS: A broad range of international travellers should be aware of the risk of acquiring dengue and receive appropriate pretravel counselling regarding preventive measures. Prospective cohort studies are needed to further elucidate dengue risk by destination and over time, as well as severe outcomes and prolonged morbidity (long-dengue) due to travel-related dengue.

Anopheles stephensi, an Asian malaria vector, continues to expand across Africa. The vector is now firmly established in urban settings in the Horn of Africa. Its presence in areas where malaria resurged suggested a possible role in causing malaria outbreaks. Here, using a prospective case-control design, we investigated the role of An. stephensi in transmission following a malaria outbreak in Dire Dawa, Ethiopia in April-July 2022. Screening contacts of patients with malaria and febrile controls revealed spatial clustering of Plasmodium falciparum infections around patients with malaria in strong association with the presence of An. stephensi in the household vicinity. Plasmodium sporozoites were detected in these mosquitoes. This outbreak involved clonal propagation of parasites with molecular signatures of artemisinin and diagnostic resistance. To our knowledge, this study provides the strongest evidence so far for a role of An. stephensi in driving an urban malaria outbreak in Africa, highlighting the major public health threat posed by this fast-spreading mosquito.

Fecal-orally transmitted gastroenteritis viruses, particularly human noroviruses (HuNoVs), are a public health concern. Viral transmission risk through contaminated water results underexplored as they have remained largely unculturable until recently and the robust measuring of gastroenteritis viruses infectivity in a single cell line is challenging. This study primarily aimed to test the feasibility of the human intestinal enteroids (HIE) model to demonstrate the infectivity of multiple gastroenteritis viruses in wastewater. Initially, key factors affecting viral replication in HIE model were assessed, and results demonstrated that the reagent-assisted disruption of 3D HIE represents an efficient alternative to syringe pass-through, and the filtering of HuNoV stool suspensions could be avoided. Moreover, comparable replication yields of clinical strains of HuNoV genogroup I (GI), HuNoV GII, rotavirus (RV), astrovirus (HAstV), and adenoviruses (HAdV) were obtained in single and multiple co-infections. Then, the optimized HIE model was used to demonstrate the infectivity of multiple naturally occurring gastroenteritis viruses from wastewater. Thus, a total of 28 wastewater samples were subjected to (RT)-qPCR for each virus, with subsequent testing on HIE. Among these, 16 samples (57 %) showed replication of HuNoVs (n = 3), RV (n = 5), HAstV (n = 8), and/or HAdV (n = 5). Three samples showed HuNoV replication, and sequences assigned to HuNoV GI.3[P13] and HuNoV GII.4[P16] genotypes. Concurrent replication of multiple gastroenteritis viruses occurred in 4 wastewater samples. By comparing wastewater concentrate and HIE supernatant sequences, diverse HAstV and HAdV genotypes were identified in 4 samples. In summary, we successfully employed HIE to demonstrate the presence of multiple infectious human gastroenteritis viruses, including HuNoV, in naturally contaminated wastewater samples.

BACKGROUND: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. METHODS: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. RESULTS: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. CONCLUSIONS: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen.

PURPOSE: Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. METHODS: Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. RESULTS: Between 29(th) February 2016 and 24(th) April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. CONCLUSION: This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets.

BACKGROUND: One of the three main targets of the World Health Organization (WHO) End TB Strategy (2015-2035) is that no tuberculosis (TB) patients or their households face catastrophic costs (defined as exceeding 20% of the annual household income) because of the disease. Our study seeks to determine, as a baseline, the magnitude and main drivers of the costs associated with TB disease for patients and their households and to monitor the proportion of households experiencing catastrophic costs in Brazil. METHODS: A national cross-sectional cluster-based survey was conducted in Brazil in 2019-2021 following WHO methodology. TB patients of all ages and types of TB were eligible for the survey. Adult TB patients and guardians of minors (<18 years old) were interviewed once about costs, time loss, coping measures, income, household expenses, and asset ownership. Total costs, including indirect costs measured as reported household income change, were expressed as a percentage of annual household income. We used descriptive statistics to analyze the cost drivers and multivariate logistic regression to determine factors associated with catastrophic costs. RESULTS: We interviewed 603 patients, including 538 (89%) with drug-sensitive (DS) and 65 (11%) with drug-resistant (DR) TB. Of 603 affected households, 48.1% (95%CI: 43-53.2) experienced costs above 20% of their annual household income during their TB episode. The proportion was 44.4% and 78.5% among patients with DS- and DR-TB, respectively. On average, patients incurred costs of US$1573 (95%CI: 1361.8-1785.0) per TB episode, including pre-diagnosis and post-diagnosis expenses. Key cost drivers were post-diagnosis nutritional supplements (US$317.6, 95%CI: 232.7-402.6) followed by medical costs (US$85.5, 95%CI: 54.3-116.5) and costs of travel for clinic visits during treatment (US$79.2, 95%CI: 61.9-96.5). In multivariate analysis, predictors of catastrophic costs included positive HIV status (aOR = 3.0, 95%CI:1.1-8.6) and self-employment (aOR = 2.7, 95%CI:1.1-6.5); high education was a protective factor (aOR = 0.1, 95%CI:0.0-0.9). CONCLUSIONS: Although the services offered to patients with TB are free of charge in the Brazilian public health sector, the availability of free diagnosis and treatment services does not alleviate patients' financial burden related to accessing TB care. The study allowed us to identify the costs incurred by patients and suggest actions to mitigate their suffering. In addition, this study established a baseline for monitoring catastrophic costs and fostering a national policy to reduce the costs to patients for TB care in Brazil.

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.

The term "dark citations," which has been previously used to refer to citations of information products outside of traditional peer-reviewed journal articles, is adapted here to refer to those that are not linked to a known indexed identifier and are effectively invisible to traditional bibliometric analysis. We investigate an unexplored source of citations in the biomedical and public health literature by surveying the extent of dark citations across the U.S. government. We systematically focus on public health, quantify their occurrences across the government, and provide a comprehensive dataset for all dark citations within PubMed.

BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]). | Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium’s analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps. | eng

Four Chlamydia psittaci isolates were recovered from clinical specimens from ill workers during a multistate outbreak at two chicken processing plants. Whole genome sequencing analyses revealed high similarity to C. psittaci genotype D. The isolates differed from each other by only two single nucleotide polymorphisms, indicating a common source.

Balancing the control of SARS-CoV-2 transmission with the resumption of travel is a global priority. Current recommendations include mitigation measures before, during, and after travel. Pre- and post-travel strategies including symptom monitoring, testing, and quarantine can be combined in multiple ways considering different trade-offs in feasibility, adherence, effectiveness, cost and adverse consequences. Here we use a mathematical model to analyze the expected effectiveness of symptom monitoring, testing, and quarantine under different estimates of the infectious period, test-positivity relative to time of infection, and test sensitivity to reduce the risk of transmission from infected travelers during and after travel. If infection occurs 0-7 days prior to travel, immediate isolation following symptom onset prior to or during travel reduces risk of transmission while traveling by 26-30%. Pre-departure testing can further reduce risk if testing is close to the time of departure. For example, testing on the day of departure can reduce risk while traveling by 37-61%. For transmission risk after travel with infection time up to 7 days prior to arrival at the destination, isolation based on symptom monitoring reduced introduction risk at the destination by 42-56%. A 14-day quarantine after arrival, without symptom monitoring or testing, can reduce risk by 97-100% on its own. However, a shorter quarantine of 7 days combined with symptom monitoring and a test on day 3-4 after arrival is also effective (95-99%) at reducing introduction risk and is less burdensome, which may improve adherence. To reduce the risk of introduction without quarantine, optimal test timing after arrival is close to the time of arrival; with effective quarantine after arrival, testing a few days later optimizes sensitivity to detect those infected immediately before or while traveling. These measures can complement recommendations such as social distancing, using masks, and hand hygiene, to further reduce risk during and after travel.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding supported this research.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Centers for Disease Control and PreventionAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesOnly publicly available data informed this research.

The term "dark citations", which has been previously used to refer to citations of information products outside of traditional peer-reviewed journal articles, is adapted here to refer to those that are not linked to a known indexed identifier and are effectively invisible to traditional bibliometric analysis. We investigate an unexplored source of citations in the biomedical and public health literature by surveying the extent of dark citations across the U.S. government. We systematically focus on public health, quantify their occurrences across the government, and provide a comprehensive dataset for all dark citations within PubMed. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Sosuga virus (SOSV) is a recently discovered paramyxovirus with a single known human case of disease. There has been little laboratory research on SOSV pathogenesis or immunity, and no approved therapeutics or vaccines are available. Here, we report the discovery of human monoclonal antibodies (mAbs) from the circulating memory B cells of the only known human case and survivor of SOSV infection. We isolated six mAbs recognizing the functional attachment protein (HN) and 18 mAbs against the fusion (F) protein. The anti-HN mAbs all target the globular head of the HN protein and can be organized into 4 competition-binding groups that exhibit epitope diversity. The anti-F mAbs can be divided into pre- or post-fusion conformation-specific categories and further into 8 competition-binding groups. Generally, pre-fusion conformation-specific anti-F mAbs showed higher potency in neutralization assays than did mAbs only recognizing the post-fusion conformation of F protein. Most of the anti-HN mAbs were more potently neutralizing than the anti-F mAbs, with mAbs in one of the HN competition-binding groups possessing ultra-potent (<1 ng/mL) half maximal inhibitory (IC50) virus neutralization values. These findings provide insight into the molecular basis for human antibody recognition of paramyxovirus surface proteins and the mechanisms of SOSV neutralization. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

The objective of this analysis was to describe patterns of prescription medication use during pregnancy, including secular trends, with consideration of indication, and distributions of use within demographic subgroups. We conducted a descriptive secondary analysis using data from 9,755 women whose infants served as controls in two large United States case-control studies from 1997-2011 and 2014-2018. After excluding vitamin, herbal, mineral, vaccine, IV fluid, and topical products and over-the-counter medications, the proportion of women that reported taking at least one prescription medication in the first trimester increased over the study years, from 37% to 50% of women. The corresponding proportions increased with increasing maternal age and years of education, were highest for non-Hispanic White women (47%) and lowest for Hispanic women (24%). The most common indication for first trimester use of a medication was infection (12-15%). Increases were observed across the years for medications used for indications related to nausea/vomiting, depression/anxiety, infertility, thyroid disease, diabetes, and epilepsy. The largest relative increase in use among women was observed for medications to treat nausea/vomiting, which increased from 3.8% in the earliest years of the study (1997-2001) to 14.8% in 2014-2018, driven in large part by ondansetron use. Prescription medication use in the first trimester of pregnancy is common and increasing. Many medical conditions require treatments among pregnant women, often involving pharmacotherapy, which necessitates consideration of the risk and safety profiles for both mother and fetus.

Wastewater-based epidemiology (WBE) emerged during the coronavirus disease 2019 (COVID-19) pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden. The lack of high-resolution fecal shedding data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) limits our ability to link WBE measurements to disease burden. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as for the commonly used fecal indicators pepper mild mottle virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2-infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding. Of the individuals that provided at least three stool samples spanning more than 14 days, 77% had one or more samples that tested positive for SARS-CoV-2 RNA. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall. CrAssphage DNA was detected in at least one sample from 80% (38/48) of individuals and was detected in 48% (179/371) of all samples. The geometric mean concentrations of PMMoV and crAssphage in stool across all individuals were 8.7 × 10(4) and 1.4 × 10(4) gene copies/milligram-dry weight, respectively, and crAssphage shedding was more consistent for individuals than PMMoV shedding. These results provide us with a missing link needed to connect laboratory WBE results with mechanistic models, and this will aid in more accurate estimates of COVID-19 burden in sewersheds. Additionally, the PMMoV and crAssphage data are critical for evaluating their utility as fecal strength normalizing measures and for source-tracking applications. IMPORTANCE This research represents a critical step in the advancement of wastewater monitoring for public health. To date, mechanistic materials balance modeling of wastewater-based epidemiology has relied on SARS-CoV-2 fecal shedding estimates from small-scale clinical reports or meta-analyses of research using a wide range of analytical methodologies. Additionally, previous SARS-CoV-2 fecal shedding data have not contained sufficient methodological information for building accurate materials balance models. Like SARS-CoV-2, fecal shedding of PMMoV and crAssphage has been understudied to date. The data presented here provide externally valid and longitudinal fecal shedding data for SARS-CoV-2, PMMoV, and crAssphage which can be directly applied to WBE models and ultimately increase the utility of WBE.

BACKGROUND: Dengue virus is a flavivirus transmitted by Aedes mosquitoes and is an important cause of illness worldwide. Data on the severity of travel-associated dengue illness are limited. OBJECTIVE: To describe the epidemiology, clinical characteristics, and outcomes among international travelers with severe dengue or dengue with warning signs as defined by the 2009 World Health Organization classification (that is, complicated dengue). DESIGN: Retrospective chart review and analysis of travelers with complicated dengue reported to GeoSentinel from January 2007 through July 2022. SETTING: 20 of 71 international GeoSentinel sites. PATIENTS: Returning travelers with complicated dengue. MEASUREMENTS: Routinely collected surveillance data plus chart review with abstraction of clinical information using predefined grading criteria to characterize the manifestations of complicated dengue. RESULTS: Of 5958 patients with dengue, 95 (2%) had complicated dengue. Eighty-six (91%) patients had a supplemental questionnaire completed. Eighty-five of 86 (99%) patients had warning signs, and 27 (31%) were classified as severe. Median age was 34 years (range, 8 to 91 years); 48 (56%) were female. Patients acquired dengue most frequently in the Caribbean (n = 27 [31%]) and Southeast Asia (n = 21 [24%]). Frequent reasons for travel were tourism (46%) and visiting friends and relatives (32%). Twenty-one of 84 (25%) patients had comorbidities. Seventy-eight (91%) patients were hospitalized. One patient died of nondengue-related illnesses. Common laboratory findings and signs were thrombocytopenia (78%), elevated aminotransferase (62%), bleeding (52%), and plasma leakage (20%). Among severe cases, ophthalmologic pathology (n = 3), severe liver disease (n = 3), myocarditis (n = 2), and neurologic symptoms (n = 2) were reported. Of 44 patients with serologic data, 32 confirmed cases were classified as primary dengue (IgM+/IgG-) and 12 as secondary (IgM-/IgG+) dengue. LIMITATIONS: Data for some variables could not be retrieved by chart review for some patients. The generalizability of our observations may be limited. CONCLUSION: Complicated dengue is relatively rare in travelers. Clinicians should monitor patients with dengue closely for warning signs that may indicate progression to severe disease. Risk factors for developing complications of dengue in travelers need further prospective study. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention, International Society of Travel Medicine, Public Health Agency of Canada, and GeoSentinel Foundation.

Mozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected in 2015 and 2018 in seven provinces of Mozambique to genotype antimalarial resistance markers and interrogate parasite population structure using genome-wide microhaplotyes. Here we show that the only resistance-associated markers observed at frequencies above 5% were pfmdr1-184F (59%), pfdhfr-51I/59 R/108 N (99%) and pfdhps-437G/540E (89%). The frequency of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine resistance increased from 80% in 2015 to 89% in 2018 (p < 0.001), with a lower expected heterozygosity and higher relatedness of microhaplotypes surrounding pfdhps mutants than wild-type parasites suggestive of recent selection. pfdhfr/pfdhps quintuple mutants also increased from 72% in the north to 95% in the south (2018; p < 0.001). This resistance gradient was accompanied by a concentration of mutations at pfdhps-436 (17%) in the north, a south-to-north increase in the genetic complexity of P. falciparum infections (p = 0.001) and a microhaplotype signature of regional differentiation. The parasite population structure identified here offers insights to guide antimalarial interventions and epidemiological surveys.

Diaz et al. highlight the potential for severe airway reactivity and perioperative challenges when performing bronchoscopy and BAL in patients with EVALI, and Russell and Cevik stress the importance of ruling out infectious causes in these patients. These two points reflect the complexities of evaluating patients with EVALI and managing their care. Recent Centers for Disease Control and Prevention clinical guidance emphasizes that the decision to perform a bronchoscopy and BAL should be made on a case-by-case basis and in consultation with pulmonary specialists.1 Many patients with EVALI have required intubation and mechanical ventilation, and consultation with critical care specialists is also recommended.

The authors reply: Weng et al. question the clinical benefit of remdesivir treatment. In our article, we noted that the decision to administer remdesivir for compassionate use was based on the patient’s worsening clinical status. No inferences are possible from the uncontrolled treatment of one patient, and we stated, “randomized, controlled trials are needed to determine the safety and efficacy of remdesivir and any other investigational agents for treatment of patients with 2019-nCoV infection.” | | Tsung notes that an increase in lymphocyte counts and subsequent clinical improvement are consistent with activation of the adaptive immune response and resolution of SARS-CoV-2 infection. IgM and IgA antibodies may be detectable early in the clinical course, and IgG antibodies can be detected a median of 14 days after the onset of illness.1 We agree that the adaptive immune response contributes to clinical recovery and clearance of SARS-CoV-2, although one study showed that seroconversion was not correlated with a rapid decline in the SARS-CoV-2 load.2 In another study that showed a good correlation between IgG and neutralizing antibody titers, an increase in IgG antibody levels was correlated with a decrease in the viral load between 1 and 3 weeks after the onset of illness, but SARS-CoV-2 RNA was still detectable for prolonged periods.3 | | Zhang inquires about detection of SARS-CoV-2 in stool and urine specimens after remdesivir treatment. In our patient, although a stool specimen collected on day 7 of illness was positive with high cycle threshold values (36 to 38) that were consistent with detection of viral RNA and probably not infectious virus, a stool specimen obtained from the patient on day 14 of illness was negative. SARS-CoV-2 RNA was not detected in urine specimens; these findings are consistent with those in a larger study.4 | | Wen et al. and Link and Hold raise the issue of fecal–oral transmission of SARS-CoV-2. Diarrhea has been reported to occur in patients with Covid-19, and it can precede the development of respiratory symptoms and progression to pneumonia. SARS-CoV-2 RNA has been detected in stool specimens, and recovery of live infectious virus from stool has been reported.4 Further studies are needed to understand the implications of SARS-CoV-2 detected in stool for transmission of the virus. | | Ren et al. argue that high-resolution low-dose chest CT should be performed instead of chest radiography in persons with fever and suspected Covid-19. The Centers for Disease Control and Prevention recommends collection of nasopharyngeal swab specimens and lower respiratory specimens, if available, for SARS-CoV-2 testing and prioritizes testing of hospitalized patients and symptomatic health care workers. Furthermore, the American College of Radiology has noted concerns regarding prevention and control of SARS-CoV-2 transmission in health care facilities, including transmission that may occur with the use of CT scanners, and has recommended that CT should not be used to screen for or diagnose Covid-19.5

OBJECTIVE: The impact of the COVID-19 pandemic goes beyond morbidity and mortality from that disease. Increases in maternal mortality have also been described but have not been extensively studied to date. This study aimed to examine changes in maternal mortality and identify correlates and predictors of excess maternal mortality in Colombia during the pandemic. SETTING: Analysis of data from the national epidemiological surveillance databases of Colombia (Sivigila). PARTICIPANTS: Deaths among 6342 Colombian pregnant women who experienced complications associated with pregnancy, childbirth or the perperium during 2008-2020 were included in this study. For inequalities analysis, a subsample of 1055 women from this group who died in 2019 or 2020 years were analysed. METHODS: We collected data from the national surveillance system (Sivigila) on maternal mortality. Analysis was carried out in two stages, starting with a time series modelling using the Box-Jenkins approach. Data from Sivigila for 2008-2019 were used to establish a baseline of expected mortality levels. Both simple and complex inequality metrics, with the maternal mortality ratios (MMRs), were then calculated using the Multidimensional Poverty Index as a socioeconomic proxy. RESULTS: Maternal deaths in 2020 were 12.6% (95% CI -21.4% to 95.7%) higher than expected. These excess deaths were statistically significant in elevation for the months of July (97.4%, 95% CI 35.1% to 250.0%) and August (87.8%, 95% CI 30.5% to 220.8%). The MMR was nearly three times higher in the poorest municipalities compared with the most affluent communities in 2020. CONCLUSIONS: The COVID-19 pandemic had considerable impact on maternal health, not only by leading to increased deaths, but also by increasing social health inequity. Barriers to access and usage of essential health services are a challenge to achieving health-related Sustainable Development Goals.

Each year, 2.4 million children die within their first month of life. Child Health and Mortality Prevention Surveillance (CHAMPS) established in 7 countries aims to generate accurate data on why such deaths occur and inform prevention strategies. Neonatal deaths that occurred between December 2016 and December 2021 were investigated with MITS within 24-72 hours of death. Testing included blood, cerebrospinal fluid and lung cultures, multi-pathogen PCR on blood, CSF, nasopharyngeal swabs and lung tissue, and histopathology examination of lung, liver and brain. Data collection included clinical record review and family interview using standardized verbal autopsy. The full set of data was reviewed by local experts using a standardized process (Determination of Cause of Death) to identify all relevant conditions leading to death (causal chain), per WHO recommendations. For analysis we stratified neonatal death into 24-hours of birth, early (1-<7 days) and late (7-<28 days) neonatal deaths. We analyzed 1458 deaths, 41% occurring within 24-hours, 41% early and 18% late neonatal deaths. Leading underlying causes of death were complications of intrapartum events (31%), complications of prematurity (28%), infections (17%), respiratory disorders (11%), and congenital malformations (8%). In addition to the underlying cause, 62% of deaths had additional conditions and 14% had ≥3 other conditions in the causal chain. The most common causes considering the whole causal chain were infection (40%), prematurity (32%) and respiratory distress syndrome (28%). Common maternal conditions linked to neonatal death were maternal hypertension (10%), labour and delivery complications (8%), multiple gestation (7%), placental complications (6%) obstructed labour and chorioamnionitis (5%, each). CHAMPS' findings showing the full causal chain of events that lead to death, in addition to maternal factors, highlights the complexities involved in each death along with the multiple opportunities for prevention. Highlighting improvements to prenatal and obstetric care and infection prevention are urgently needed in high-mortality settings.

OBJECTIVE: Systematize the experience and identify challenges and lessons learned in the implementation of an initiative for integrated serosurveillance of communicable diseases using a multiplex bead assay in countries of the Americas. METHODS: Documents produced in the initiative were compiled and reviewed. These included concept notes, internal working papers, regional meetings reports, and survey protocols from the three participating countries (Mexico, Paraguay, and Brazil) and two additional countries (Guyana and Guatemala) where serology for several communicable diseases was included in neglected tropical diseases surveys. Information was extracted and summarized to describe the experience and the most relevant challenges and lessons learned. RESULTS: Implementing integrated serosurveys requires interprogrammatic and interdisciplinary work teams for the design of survey protocols to respond to key programmatic questions aligned to the needs of the countries. Valid laboratory results are critical and rely on the standardized installment and roll-out of laboratory techniques. Field teams require adequate training and supervision to properly implement survey procedures. The analysis and interpretation of serosurveys results should be antigen-specific, contextualizing the responses for each disease, and triangulated with programmatic and epidemiological data for making decisions tailored to specific population socioeconomic and ecologic contexts. CONCLUSIONS: Integrated serosurveillance as a complementary tool for functional epidemiological surveillance systems is feasible to use and key components should be considered: political engagement, technical engagement, and integrated planning. Aspects such as designing the protocol, selecting target populations and diseases, laboratory capacities, anticipating the capacities to analyze and interpret complex data, and how to use it are key.

We developed and assessed the performance of a new multiplex real-time PCR assay for the detection of all Chlamydia species and simultaneous differentiation of Chlamydia psittaci and Chlamydia pneumoniae-two important human respiratory pathogens-in human clinical specimens. Next-generation sequencing was used to identify unique targets to design real-time PCR assays targeting all Chlamydia species, C. psittaci, and C. pneumoniae. To validate the assay, we used a panel of 49 culture isolates comprising seven C. psittaci genotypes, eight C. pneumoniae isolates, seven other Chlamydia species, and 22 near-neighbor bacterial and viral isolates, along with 22 specimens from external quality assessment (EQA) panels and 34 nasopharyngeal and oropharyngeal swabs and cerebrospinal fluid, stool, and sputum specimens previously identified as positive or negative for C. psittaci or C. pneumoniae. The assays were 100% specific, with limits of detection of 7.64- 9.02 fg/μL. The assay results matched with historical assay results for all specimens, except for one owing to the increased sensitivity of the new C. psittaci assay; the results of the EQA specimens were 100% accurate. This assay may improve the timely and accurate clinical diagnosis of Chlamydia infections and provide a greater understanding of the burden of disease caused by these agents.