Despite annual vaccination, influenza B viruses (IBV) continue to cause significant morbidity and mortality in humans. We have found that IBV infection resulted in a weaker innate and adaptive immune response than influenza A viruses (IAV) in ferrets. To understand and overcome the weak immune responses to IBV in ferrets, we administered type-I or type-III interferon (IFN) to ferrets following infection or vaccination and evaluated their effects on the immune response. IFN signaling following viral infection plays an important role in the initial innate immune response and affects subsequent adaptive immune responses. In the respiratory tract, IFN lambda (IFNL) has regulatory effects on adaptive immunity indirectly through thymic stromal lymphopoietin (TSLP), which then acts on immune cells to stimulate the adaptive response. Following IBV infection or vaccination, IFN treatment (IFN-Tx) upregulated gene expression of early inflammatory responses in the upper respiratory tract and robust IFN, TSLP, and inflammatory responses in peripheral blood cells. These responses were sustained following challenge or vaccination in IFN-Tx animals. Serum IFNL and TSLP levels were enhanced in IFN-Tx animals following challenge/rechallenge over mock-Tx; however, this difference was not observed following vaccination. Antibody responses in serum of IFN-Tx animals following IBV infection or vaccination increased more quickly and to higher titers and were sustained longer than mock-Tx animals over 3 months. Following rechallenge of infected animals 3 months post treatment, antibody levels remained higher than mock-Tx. However, IFN-Tx did not have an effect on antibody responses following challenge of vaccinated animals. A strong direct correlation was found between TSLP levels and antibody responses following challenge-rechallenge and vaccination-challenge indicating it as a useful tool for predicting adaptive immune responses following IBV infection or vaccination. The effects of IFN on strengthening both innate and adaptive responses to IBV may aid in development of more effective treatments following infection and improved influenza vaccines.

OBJECTIVE: Identify commercial tobacco cessation interventions for American Indian and Alaska Native (AI/AN) communities, focusing on strategies used to advance health equity, including strategies to address social determinants of health (SDOH), community engagement, and cultural tailoring. DATA SOURCE: We searched Medline, Embase, PsycINFO, Cochrane Library, CINAHL, Scopus, ProQuest Central, Academic Search Complete, JSTOR, and Indigenous/Tribal health-related journals and databases. STUDY INCLUSION AND EXCLUSION CRITERIA: We included peer-reviewed studies on commercial tobacco cessation for AI/AN persons published January 1998-April 2023 that reported quit rates/attempts. We excluded studies that only used pharmaceutical interventions. DATA EXTRACTION: Two reviewers independently assessed each study against our inclusion/exclusion criteria. A reviewer extracted data, and another checked for completeness. DATA SYNTHESIS: Synthesis focused on reported intervention effectiveness and strategies used for addressing SDOH, community engagement, and cultural tailoring. We used a synthesis matrix which allowed for comparison across studies. RESULTS: We screened 1116 articles and included 12 for synthesis. Of the 12, five engaged community health workers; four included SDOH elements; and six were reported effective. Of these six, five included early-stage community engagement and four were culturally tailored. CONCLUSIONS: There are few commercial tobacco cessation interventions for AI/AN populations. Building capacity, including tribal capacity, to develop and test multi-level, culturally grounded cessation interventions that address relevant SDOH may advance commercial tobacco cessation efforts in these populations.

The continued emergence of deadly human coronaviruses from animal reservoirs highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq), we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryoelectron microscopy (cryo-EM) structure of 54043-5 bound to the prefusion S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses in vitro, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.

OBJECTIVE: During the first year of the COVID-19 pandemic, most of the Centers for Disease Control and Prevention (CDC)'s National Breast and Cervical Cancer Early Detection Program (NBCCEDP) funded programs (recipients) experienced significant declines in breast and cervical cancer screening volume. However, 6 recipients maintained breast and/or cervical cancer screening volume during July-December 2020 despite their states' high COVID-19 test percent positivity. We led a qualitative multi-case study to explore these recipients' actions that may have contributed to screening volume maintenance. METHODS: We conducted 22 key informant interviews with recipients, screening provider sites, and partner organizations. Interviews explored organizational and operational changes; screening barriers; actions taken to help maintain screening volume; and support for provider sites to continue screening. We documented contextual factors that may have influenced these actions, including program structures; clinic capacity; and state COVID-19 policies. RESULTS: Thematic analysis revealed crosscutting themes at the recipient, provider site, and partner levels. Recipients made changes to administrative processes to reduce burden on provider sites and delivered tailored technical assistance to support safe screening. Provider sites modified clinic protocols to increase patient safety, enhanced patient reminders for upcoming appointments, and increased patient education on the importance of timely screening during the pandemic. Partners worked with provider sites to identify and reduce patients' structural barriers to screening. CONCLUSION: Study findings provide lessons learned to inform emergency preparedness-focused planning and operations, as well as routine operations for NBCCEDP recipient programs, other cancer screening initiatives, primary care clinics, and chronic disease prevention programs.

IMPORTANCE: The function-based eat, sleep, console (ESC) care approach substantially reduces the proportion of infants who receive pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). This reduction has led to concerns for increased postnatal opioid exposure in infants who receive pharmacologic treatment. However, the effect of the ESC care approach on hospital outcomes for infants pharmacologically treated for NOWS is currently unknown. OBJECTIVE: To evaluate differences in opioid exposure and total length of hospital stay (LOS) for pharmacologically treated infants managed with the ESC care approach vs usual care with the Finnegan tool. DESIGN, SETTING, AND PARTICIPANTS: This post hoc subgroup analysis involved infants pharmacologically treated in ESC-NOW, a stepped-wedge cluster randomized clinical trial conducted at 26 US hospitals. Hospitals maintained pretrial practices for pharmacologic treatment, including opioid type, scheduled opioid dosing, and use of adjuvant medications. Infants were born at 36 weeks' gestation or later, had evidence of antenatal opioid exposure, and received opioid treatment for NOWS between September 2020 and March 2022. Data were analyzed from November 2022 to January 2024. EXPOSURE: Opioid treatment for NOWS and the ESC care approach. MAIN OUTCOMES AND MEASURES: For each outcome (total opioid exposure, peak opioid dose, time from birth to initiation of first opioid dose, length of opioid treatment, and LOS), we used generalized linear mixed models to adjust for the stepped-wedge design and maternal and infant characteristics. RESULTS: In the ESC-NOW trial, 463 of 1305 infants were pharmacologically treated (143/603 [23.7%] in the ESC care approach group and 320/702 [45.6%] in the usual care group). Mean total opioid exposure was lower in the ESC care approach group with an absolute difference of 4.1 morphine milligram equivalents per kilogram (MME/kg) (95% CI, 1.3-7.0) when compared with usual care (4.8 MME/kg vs 8.9 MME/kg, respectively; P = .001). Mean time from birth to initiation of pharmacologic treatment was 22.4 hours (95% CI, 7.1-37.7) longer with the ESC care approach vs usual care (75.4 vs 53.0 hours, respectively; P = .002). No significant difference in mean peak opioid dose was observed between groups (ESC care approach, 0.147 MME/kg, vs usual care, 0.126 MME/kg). The mean length of treatment was 6.3 days shorter (95% CI, 3.0-9.6) in the ESC care approach group vs usual care group (11.8 vs 18.1 days, respectively; P < .001), and mean LOS was 6.2 days shorter (95% CI, 3.0-9.4) with the ESC care approach than with usual care (16.7 vs 22.9 days, respectively; P < .001). CONCLUSION AND RELEVANCE: When compared with usual care, the ESC care approach was associated with less opioid exposure and shorter LOS for infants pharmacologically treated for NOWS. The ESC care approach was not associated with a higher peak opioid dose, although pharmacologic treatment was typically initiated later. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04057820.

In a recent article, Gebre1 suggests that endemic countries should lead in deciding on disease eradication initiatives and asserts that ‘elimination as a public health problem’ is the preferred option because eradication occurs at the expense of other health programs and weakens fragile health systems. The author's primary example is dracunculiasis (Guinea worm) eradication, but he fails to take into account that vertical disease elimination and eradication programs also strengthen health systems overall. Eradication means permanent reduction to an incidence of zero of a disease worldwide, while elimination as a public health problem means minimal disease incidence but control measures are still necessary.

Influenza B viruses (IBV) cocirculate with influenza A viruses (IAV) and cause periodic epidemics of disease, yet antibody and cellular responses following IBV infection are less well understood. Using the ferret model for antisera generation for influenza surveillance purposes, IAV resulted in robust antibody responses following infection, whereas IBV required an additional booster dose, over 85% of the time, to generate equivalent antibody titers. In this study, we utilized primary differentiated ferret nasal epithelial cells (FNECs) which were inoculated with IAV and IBV to study differences in innate immune responses which may result in differences in adaptive immune responses in the host. FNECs were inoculated with IAV (H1N1pdm09 and H3N2 subtypes) or IBV (B/Victoria and B/Yamagata lineages) and assessed for 72 h. Cells were analyzed for gene expression by quantitative real-time PCR, and apical and basolateral supernatants were assessed for virus kinetics and interferon (IFN), respectively. Similar virus kinetics were observed with IAV and IBV in FNECs. A comparison of gene expression and protein secretion profiles demonstrated that IBV-inoculated FNEC expressed delayed type-I/II IFN responses and reduced type-III IFN secretion compared to IAV-inoculated cells. Concurrently, gene expression of Thymic Stromal Lymphopoietin (TSLP), a type-III IFN-induced gene that enhances adaptive immune responses, was significantly downregulated in IBV-inoculated FNECs. Significant differences in other proinflammatory and adaptive genes were suppressed and delayed following IBV inoculation. Following IBV infection, ex vivo cell cultures derived from the ferret upper respiratory tract exhibited reduced and delayed innate responses which may contribute to reduced antibody responses in vivo.IMPORTANCEInfluenza B viruses (IBV) represent nearly one-quarter of all human influenza cases and are responsible for significant clinical and socioeconomic impacts but do not pose the same pandemic risks as influenza A viruses (IAV) and have thus received much less attention. IBV accounts for greater severity and deaths in children, and vaccine efficacy remains low. The ferret can be readily infected with human clinical isolates and demonstrates a similar course of disease and immune responses. IBV, however, generates lower antibodies in ferrets than IAV following the challenge. To determine whether differences in initial innate responses following infection may affect the development of robust adaptive immune responses, ferret respiratory tract cells were isolated, infected with IAV/IBV, and compared. Understanding the differences in the initial innate immune responses to IAV and IBV may be important in the development of more effective vaccines and interventions to generate more robust protective immune responses.

BACKGROUND: Rabies expert on demand (REOD) telehealth service is provided by the U.S. Centers for Disease Control and Prevention (CDC) to assist public health practitioners, health providers, and the public to interpret national and international rabies prevention guidelines. REOD is staffed by subject matter experts of the CDC Poxvirus and Rabies Branch to assess each unique situation and provide evidence-based guidance to stakeholders. This study aims to describe the utilization of a rabies telehealth system and provide insight into common consultations. METHODS: A cross-sectional study of the nature of inquiries to REOD was done using the data collected from September 1, 2017 to September 30, 2021. An inquiry tracking form and Microsoft Access database were developed to document all inquiries received. Inquired ones were summarized to determine the frequency of inquiries by month, category, and location. RESULTS: Over a 49-month period, REOD received 5228 inquiries. Peak inquiries (n = 108) occurred during August 2019. The most frequent inquiries received pertained to risk assessment and management of rabies exposures (n = 1109), requests for testing assistance (n = 912), consultation for suspected human rabies (n = 746), rabies exposures and post-bite treatment occurring internationally (n = 310), and consultation for deviations in the recommended pre- and postexposure prophylaxis regimen (n = 300). CONCLUSION: REOD is a global resource for consultation related to managing rabies exposures, diagnostic issues, and rabies control strategies. REOD is a regularly utilized CDC service, as the demand for up-to-date rabies guidance remains high. REOD fulfills a critical role for the interpretation and consultation on rabies prevention guidelines to stakeholder.

OBJECTIVES: Since rabies is lethal once symptoms appear, its prevention including community awareness, mass dog vaccination and post-exposure prophylaxis (PEP) is crucial. Although safe and potent rabies vaccines have long been available, the global rabies burden is still high and access to adequately-delivered PEP remains challenging. Here we offer healthcare providers up-to-date, simple, exhaustive, visual guidance on how to perform PEP steps correctly. PROTOCOL: PEP consists of 1) washing the wound with water and soap for 15 min, 2) assessing the need for rabies biologicals based on specific criteria; 3) administering, if required, rabies immunoglobulin or monoclonal antibodies deep in and around all wounds; 4) starting, if necessary, the WHO-recommended intradermal 1-week vaccination regimen; 5) informing patients adequately throughout the PEP process to increase compliance and avoid dangerous misconceptions about animal bite treatment and rabies risk. DISCUSSION: The intradermal 1-week vaccination regimen recommended by WHO is as safe as other regimens but carries important cost-, dose- and time-sparing benefits. As fundamental as the correct administration of rabies biologicals is clear doctor-patient communication and sharing of up-to-date knowledge among healthcare professionals. CONCLUSIONS: This resource will help ensuring that no life is lost to rabies, an incurable yet preventable disease.

INTRODUCTION: A study was conducted to examine treatment patterns and outcomes among women with a primary ovarian cancer diagnosis in the Midwest region of the United States, an area that has relatively fewer gynecologic oncologists (GOs) and diverse geography with respect to urban and rural areas. In this paper, we examine the methodology of working with central cancer registries (CCRs) to collect additional data items, including those related to GO involvement and detailed treatment. METHODS: Westat recruited 3 state CCRs from the Midwest to participate in the study. Cases were randomly selected from 2010-2012 ovarian, fallopian tube, or primary peritoneal cancer diagnoses in participating registry databases that met the selection criteria. CCRs abstracted additional information for selected cases, including study-specific data items regarding surgery and chemotherapy, GO involvement, and recurrence, where applicable. RESULTS: Abstracts with study-specific data items were collected among a total of 1,003 incidence ovarian cancer cases, with 432 additional abstracts for those cases identified as having recurrence. Variables with the highest frequency of unknowns were mostly for patients who had chemotherapy. While data were available for whether the patient received chemotherapy, the specifics about that chemotherapy were not always available, with dosing and unit being unknown in 27% of cases. There were several challenges with initiating and completing this study associated with recruitment, the data collection timeline, and the collection of study-specific data items. CONCLUSION: This paper outlines the methodologic approach and experience of collecting additional surgical and chemotherapy treatment variables and data on GO involvement in care from medical records. Experiences from this study provide critical lessons that can be applied to future data collection in this area. Ultimately, the accurate collection of these elements enables researchers to identify groups of women who are not receiving the benefit of optimal surgery or GO care and provides critical data on interventions for improved outcomes and survival in ovarian cancer patients.

INTRODUCTION: Dog-mediated rabies is enzootic in Vietnam, resulting in at least 70 reported human deaths and 500,000 human rabies exposures annually. In 2016, an integrated bite cases management (IBCM) based surveillance program was developed to improve knowledge of the dog-mediated rabies burden in Phu Tho Province of Vietnam. METHODS: The Vietnam Animal Rabies Surveillance Program (VARSP) was established in four stages: (1) Laboratory development, (2) Training of community One Health workers, (3) Paper-based-reporting (VARSP 1.0), and (4) Electronic case reporting (VARSP 2.0). Investigation and diagnostic data collected from March 2016 to December 2019 were compared with historical records of animal rabies cases dating back to January 2012. A risk analysis was conducted to evaluate the probability of a rabies exposure resulting in death after a dog bite, based on data collected over the course of an IBCM investigation. RESULTS: Prior to the implementation of VARSP, between 2012 and 2015, there was an average of one rabies investigation per year, resulting in two confirmed and two probable animal rabies cases. During the 46 months that VARSP was operational (2016 - 2019), 1048 animal investigations were conducted, which identified 79 (8%) laboratory-confirmed rabies cases and 233 (22%) clinically-confirmed(probable) cases. VARSP produced a 78-fold increase in annual animal rabies case detection (one cases detected per year pre-VARSP vs 78 cases per year under VARSP). The risk of succumbing to rabies for bite victims of apparently healthy dogs available for home quarantine, was three deaths for every 10,000 untreated exposures. DISCUSSION: A pilot IBCM model used in Phu Tho Province showed promising results for improving rabies surveillance, with a 26-fold increase in annual case detection after implementation of a One Health model. The risk for a person bitten by an apparently healthy dog to develop rabies in the absence of rabies PEP was very low, which supports the WHO recommendations to delay PEP for this category of bite victims, when trained animal assessors are available and routinely communicate with the medical sector. Recent adoption of an electronic IBCM system is likely to expedite adoption of VARSP 2.0 to other Provinces and improve accuracy of field decisions and data collection.

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformation and a leading cause of developmental disabilities such as sensorineural hearing loss (SNHL), motor and cognitive deficits. The significant disease burden from congenital CMV infection (cCMV) led the US National Institute of Medicine to rank CMV vaccine development as the highest priority. An average of 6.7/1000 live births are affected by cCMV, but the prevalence varies across and within countries. In contrast to other congenital infections such as rubella and toxoplasmosis, the prevalence of cCMV increases with CMV seroprevalence rates in the population. The true global burden of cCMV disease is likely underestimated because most infected infants (85-90 %) have asymptomatic infection and are not identified. However, about 7-11 % of those with asymptomatic infection will develop SNHL throughout early childhood. Although no licensed CMV vaccine exists, several candidate vaccines are in development, including one currently in phase 3 trials. Licensure of one or more vaccine candidates is feasible within the next five years. Various models of CMV vaccine strategies employing different target populations have shown to provide substantial benefit in reducing cCMV. Although CMV can cause end-organ disease with significant morbidity and mortality in immunocompromised individuals, the focus of this vaccine value profile (VVP) is on preventing or reducing the cCMV disease burden. This CMV VVP provides a high-level, comprehensive assessment of the currently available data to inform the potential public health, economic, and societal value of CMV vaccines. The CMV VVP was developed by a working group of subject matter experts from academia, public health groups, policy organizations, and non-profit organizations. All contributors have extensive expertise on various elements of the CMV VVP and have described the state of knowledge and identified the current gaps. The VVP was developed using only existing and publicly available information.

BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown. METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days -17 years with invasive candidiasis (predominantly candidemia) from 2014-2017. Ophthalmologic examination, abdominal imaging, echocardiogram, neuroimaging, and lumbar puncture were performed per clinician discretion. aDS performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed effects logistic regression. RESULTS: In 662 pediatric candidemia episodes, 490 (74%) underwent abdominal imaging, 450 (68%) ophthalmologic examination, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) lumbar puncture; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing ophthalmologic examination, abdominal imaging, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing abdominal imaging (aOR 2.38; 95% CI 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive ophthalmologic examination was reported in 15 (3%), abdominal imaging in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%) and lumbar puncture in 3 (4%). CONCLUSIONS: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted.

The purpose of this study is to test, for the first time, the association between spatial social polarization and incarceration among people who inject drugs (PWID) in 19 large U.S. metropolitan statistical areas (MSAs) in 2015. PWID were recruited from MSAs for the Centers for Disease Control and Prevention's 2015 National HIV Behavioral Surveillance. Administrative data were used to describe the ZIP-code areas, counties, and MSAs where PWID lived. We operationalized spatial polarization using the Index of Concentration at the Extremes (ICE), a measure that reflects polarization in race and household income at the ZIP-code level. We tested the association between spatial polarization and odds of past-year arrest and detainment using multilevel multivariable models. We found 37% of the sample reported being incarcerated in the past year. Report of past-year incarceration varied by race/ethnicity: 45% of non-Hispanic white PWID reported past-year incarceration, as did 25% of non-Hispanic Black PWID, and 43% of Hispanic/Latino PWID (N = 9047). Adjusted odds ratios suggest that Black PWID living in ZIP-code areas with a higher ICE score, meaning more white and affluent, had higher odds of past-year incarceration, compared to white PWID. In previous research, incarceration has been found to be associated with HIV acquisition and can deter PWID from engaging in harm reduction activities. © 2023

INTRODUCTION: Most adults who currently use tobacco start before age 21. Comprehensive, cost-effective strategies and interventions to prevent initiation and encourage tobacco use cessation among youth are critical aspects of protecting youth from the harms of commercial tobacco. We describe changes in current tobacco product use among youth in 34 sites using data from the Global Youth Tobacco Survey (GYTS). METHODS: GYTS is a nationally representative school-based survey of students aged 13 to 15 years. The analysis included 34 sites that completed 2 survey waves during 2012-2020. Prevalence of current tobacco use was assessed for each country. Marginal effects in multivariable logistic regression models were used to estimate adjusted prevalence difference (aPD) between waves. RESULTS: The adjusted prevalence of current tobacco product use remained unchanged in more than 60% of the included sites. For any tobacco use, significant decreases were reported for Bhutan (aPD = -8.1; 95% CI, -12.9 to -3.4), Micronesia (aPD = -7.2; 95% CI, -9.7 to -4.7), San Marino (aPD = -7.0; 95% CI, -11.2 to -2.7), Togo (aPD = -2.7; 95% CI, -4.6 to -0.7), and Panama (aPD = -2.2; 95% CI, -4.1 to -0.4); significant increases were reported for Moldova, Albania, and Paraguay. Current e-cigarette use increased significantly in 7 of 10 sites. CONCLUSION: Data show that progress toward reducing tobacco use among youth stalled during 2012-2020, while e-cigarette use increased in a few sites with available data.

Individuals with type 2 diabetes mellitus experience high rates of influenza virus infection and complications. We compared the magnitude and duration of serologic response to trivalent influenza vaccine in adults aged 50-80 with and without type 2 diabetes mellitus. Serologic response to influenza vaccination was similar in both groups: greater fold-increases in antibody titer occurred among individuals with lower pre-vaccination antibody titers. Waning of antibody titers was not influenced by diabetes status.Competing Interest StatementKKM, MPN and RZ have received research funds from Merck &amp; Co., Inc and Pfizer, Inc. KKM and RZ have received research funds from Sanofi Pasteur, Inc. LC is currently employed by Novartis. The remaining authors report no conflicts of interest.Funding StatementThis study was supported by cooperative agreements U01 IP000471 and U01 IP000467 from the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of those authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.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:Institutional Review Boards at the University of Pittsburgh and Marshfield Clinic approved this study.All 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.YesData are not publicly available at this time.

Strongyloidiasis is caused by the human infective nematodes Strongyloides stercoralis, Strongyloides fuelleborni subsp. fuelleborni and Strongyloides fuelleborni subsp. kellyi. The zoonotic potential of S. stercoralis and the potential role of dogs in the maintenance of strongyloidiasis transmission has been a topic of interest and discussion for many years. In Australia, strongyloidiasis is prevalent in remote socioeconomically disadvantaged communities in the north of the continent. Being an isolated continent that has been separated from other regions for a long geological period, description of the diversity of Australian Strongyloides genotypes adds to our understanding of the genetic diversity within the genus. Using PCR enrichment combined with Illumina sequencing technology, we sequenced the Strongyloides SSU 18S rDNA hyper-variable I and hyper-variable IV regions using Strongyloides-specific primers, and a fragment of the mtDNA cox1 gene using primers that are broadly specific for Strongyloides sp. and hookworms. These loci were amplified from DNA extracted from Australian human and dog faeces, and one human sputum sample. Using this approach, we confirm for the first time that potentially zoonotic S. stercoralis genotypes are present in Australia, suggesting that dogs represent a potential reservoir of human strongyloidiasis in remote Australian communities.Author summary Strongyloides stercoralis is a soil-transmitted nematode that causes the disease strongyloidiasis. Due to the autoinfective nature of this parasite, it can re-infect a host causing chronic infection. If not diagnosed and treated it can be highly detrimental to human health and has a high mortality rate. Strongyloidiasis is common in remote communities in the north of Australia and has been an issue for decades. Despite various successful intervention programs to treat human strongyloidiasis, the disease remains endemic in those communities. Here for the first time we looked at the Australian dogs’ potential to infect humans and found that they carry two genetically distinct strains of Strongyloides spp., one of which also infects humans. This supports the hypothesis that dogs are a potential source for human strongyloidiasis. We also found that dogs in Australia might be carrying unique haplotypes. Whether these new haplotypes are also human infective is to be confirmed by further research.

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.

Background The extent to which vaccinated persons who become infected with SARS-CoV-2 contribute to transmission is unclear. During a SARS-CoV-2 Delta variant outbreak among incarcerated persons with high vaccination rates in a federal prison, we assessed markers of viral shedding in vaccinated and unvaccinated persons. Methods Consenting incarcerated persons with confirmed SARS-CoV-2 infection provided mid-turbinate nasal specimens daily for 10 consecutive days and reported symptom data via questionnaire. Real-time reverse transcription-polymerase chain reaction (RT-PCR), viral whole genome sequencing, and viral culture was performed on these nasal specimens. Duration of RT-PCR positivity and viral culture positivity was assessed using survival analysis. Results A total of 978 specimens were provided by 95 participants, of whom 78 (82%) were fully vaccinated and 17 (18%) were not fully vaccinated. No significant differences were detected in duration of RT-PCR positivity among fully vaccinated participants (median: 13 days) versus those not fully vaccinated (median: 13 days; p=0.50), or in duration of culture positivity (medians: 5 days and 5 days; p=0.29). Among fully vaccinated participants, overall duration of culture positivity was shorter among Moderna vaccine recipients versus Pfizer (p=0.048) or Janssen (p=0.003) vaccine recipients. Conclusions As this field continues to develop, clinicians and public health practitioners should consider vaccinated persons who become infected with SARS-CoV-2 to be no less infectious than unvaccinated persons. These findings are critically important, especially in congregate settings where viral transmission can lead to large outbreaks. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv 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.

INTRODUCTION: The first outbreak of dengue in American Samoa was reported in 1911. Sporadic outbreaks have been reported since, as were outbreaks of other pathogens transmitted by Aedes species mosquitoes including Ross River, chikungunya, and Zika viruses. During an outbreak of dengue virus-type 2 (DENV-2) in 2016-2018, we conducted household-based cluster investigations to identify population-specific risk factors associated with infection and performed entomologic surveillance to determine the relative abundance of Ae. aegypti and Ae. polynesiensis. METHODS AND FINDINGS: We contacted dengue patients who had tested positive for DENV infection and offered them as well as their household members participation in household-based cluster investigations. For those that accepted participation, we also offered participation to residents of households within a 50-meter radius of each case-patient's home. Questionnaires were administered and serum specimens collected for testing by RT-PCR and anti-DENV IgM ELISA. Adult female mosquitoes were aspirated from inside and outside participating households and tested by RT-PCR. We analyzed characteristics associated with DENV infection in bivariate analyses. A total of 226 participants was enrolled from 91 households in 20 clusters. Median age of participants was 34 years (range: <1-94), and 56.2% were female. In total, 7 (3.2%) participants had evidence of DENV infection by IgM ELISA (n = 5) or RT-PCR (n = 2). Factors significantly associated with DENV infection were reporting a febrile illness in the past three months (prevalence ratio: 7.5 [95% confidence interval: 1.9-29.8]) and having a household septic tank (Fisher's Exact Test, p = 0.004). Of 93 Ae. aegypti and 90 Ae. polynesiensis females collected, 90% of Ae. aegypti were collected inside homes whereas 83% of Ae. polynesiensis were collected outside homes. DENV nucleic acid was not detected in any mosquito pools. Sequencing of the DENV-2 from patient specimens identified the Cosmopolitan genotype of DENV-2 and was most closely related to virus detected in the Solomon Islands during 2016. CONCLUSIONS: This investigation demonstrated that dengue is a continuing risk in American Samoa. Increased frequency of infection among residents with a septic tank suggests a need to investigate whether septic tanks serve as larval habitats for mosquito vectors of DENV in American Samoa. Future efforts should also evaluate the role of Ae. polynesiensis in DENV transmission in the wild.

BACKGROUND: Novel oral poliovirus vaccine type 2 (nOPV2) was administered in Liberia in response to an outbreak of circulating vaccine-derived poliovirus type 2 (cVDPV2) in 2021. We conducted a serological survey of polio antibodies after two national campaigns with nOPV2. METHODS: This clustered, cross-sectional, population-based seroprevalence survey was conducted in children aged 0-59 months, more than 4 weeks after the second nOPV2 vaccination round. We used a clustered sampling method in four geographical regions of Liberia, followed by a simple random sampling of households. One eligible child was randomly selected per household. Dried blood spot specimens were taken and vaccination history was recorded. The antibody titres against all three poliovirus serotypes were assessed using standard microneutralisation assays done at the US Centers for Disease Control and Prevention in Atlanta, GA, USA. FINDINGS: Analysable data were obtained from 436 (87%) of 500 enrolled participants. Of these, 371 (85%) children were reported via parental recall to have received two nOPV2 doses, 43 (10%) received one dose, and 22 (5%) received no doses. The seroprevalence against type 2 poliovirus was 38·3% (95% CI 33·7-43·0; 167 of 436 participants). No significant difference was observed between type 2 seroprevalence in children aged 6 months or older who were reported to have received two doses of nOPV2 (42·1%, 95% CI 36·8-47·5; 144 of 342), one dose (28·0%, 12·1-49·4; seven of 25), or no doses (37·5%, 8·5-75·5; three of eight; p=0·39). The seroprevalence against type 1 was 59·6% (54·9-64·3; 260 of 436), and the seroprevalence against type 3 was 53·0% (48·2-57·7; 231 of 436). INTERPRETATION: Unexpectedly, the data showed low type 2 seroprevalence after two reported doses of nOPV2. This finding is probably affected by the lower oral poliovirus vaccine immunogenicity previously demonstrated in resource-limited settings, with high prevalence of chronic intestinal infections in children and other factors discussed herein. Our results provide the first assessment of nOPV2 performance in outbreak response in the African region. FUNDING: WHO and Rotary International.

Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high; the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020.

BACKGROUND: Integrated bite case management (IBCM) is a multi-sectoral response to animal-bites which reduces human and canine rabies mortality through animal quarantine, bite-victim counseling, and vaccination tracking. Haiti's national rabies surveillance program was established in 2013 using paper-based IBCM (pIBCM) with adoption of an electronic smartphone application (eIBCM) in 2018. METHODS: We evaluated the feasibility of implementing the electronic app in Haiti and compared pIBCM and eIBCM data quality collected January 2013-August 2019. Deaths prevented, cost-per-death averted, and cost-per-investigation during use of pIBCM and eIBCM were estimated using a previously validated rabies cost-effectiveness tool that accounted for bite-victim demographics; probability of acquiring rabies; post-exposure prophylaxis; and costs including training, supplies, and salaries. We compared pIBCM and eIBCM based on data comprehensiveness, completeness, and reporting efficiency. Surveys were administered to IBCM staff to evaluate the usefulness, simplicity, flexibility, and acceptability of eIBCM. RESULTS: Of 15,526 investigations, 79% were paper-based and 21% electronic. IBCM prevented 241 (estimated) human rabies deaths. Using pIBCM, cost-per-death averted was $2,692 and the cost-per-investigation was $21.02; up to 55 data variables were collected per investigation; data transmission took 26 days to reach national staff, and 180 days until analysis. Using eIBCM, the cost-per-death averted was $1,247 and the cost-per-investigation was $22.70; up to 174 data variables were collected per investigation; data transmission took 3 days to reach national staff, and 30 days until analysis. Among 12,194 pIBCM investigations, 55% were mappable by commune, compared to 100% of eIBCM investigations mappable by GPS. Animal case definitions were incorrectly ascribed by investigators in 5.5% of pIBCM investigations and zero for eIBCM; typically, errors were in determining probable vs. suspect case assignments. Overall, eIBCM was well-accepted by staff, who reported the app is easy-to-use, facilitates investigations, and compared to pIBCM hastens data reporting. DISCUSSION: In Haiti, eIBCM showed improved data completeness, data quality, and shorter notification times with minimal increase in operational cost. The electronic app is simple-to-use and facilitates IBCM investigations. Rabies endemic countries could refer to eIBCM in Haiti as a cost-effective means to reduce human rabies mortality and improve surveillance capacity.

BACKGROUND: We estimated the magnitude of the HIV epidemic among children and youth living with HIV (CYHIV) aged 0-25 years in Thailand, projecting forward from 2005 to 2025, and identified underreported input parameters that influence epidemic projections, in order to inform future public health and research priorities. METHODS: We developed a focused multi-state transition model incorporating perinatally-acquired HIV and non-perinatally-acquired HIV, stratified by population, including men who have sex with men (MSM), female sex workers (FSW), people who inject drugs (PWID), and the remainder of the population ("other"). We populated the model with published and programmatic data from the Thai national AIDS program when available. We projected the period from 2005-2025 and compared model results to programmatic data and projections from other models. In a scenario analysis, we projected the potential impact of pre-exposure prophylaxis (PrEP) for MSM from 2018-2025. RESULTS: The initial 2005 cohort was comprised of 66,900 CYHIV; 8% CYHIV were &lt;5 years, 21% were 5-14 years, and 71% were 15-25 years of age. By 2020, 94% were projected to be &gt;15 years and infections among MSM constituted 83% of all new HIV infections. The numbers of CYHIV decreased over time, projected to reach 30,760 by 2020 (-54%) and 22,640 by 2025 (-66%). The proportion of all CYHIV aged 0-25 who were diagnosed and on ART increased from 37 to 60% over the 2005-2025 period. Projections were sensitive to variations in assumptions about initial HIV prevalence and incidence among MSM, PWID, and "other" youth. CONCLUSIONS: More data on incidence rates among sexual and gender minority youth and PWID are needed to characterize the role of specific exposures and key populations in the adolescent HIV epidemic. More accurate estimates will project shifts in population and inform more targeted interventions to prevent and care for Thai CYHIV.

Monkeypox virus (MPXV), an Orthopoxvirus that can cause monkeypox (mpox) disease in humans, was rarely seen outside Africa before 2022. Since May 2022, mpox has been reported in multiple countries and regions without endemic transmission, including the United States (1). New York City (NYC) quickly became one of the major foci of the 2022 outbreak after the first case in a NYC resident was diagnosed on May 19.* Epidemiologic profiles and clinical characteristics of mpox cases in the United States during this outbreak have been described (2,3), but previous summaries were limited by incomplete data or inclusion of only a subset of cases (2,3). Most case investigation data from mpox cases reported to the NYC Department of Health and Mental Hygiene (DOHMH) surveillance system have a high degree of completeness for gender, race or ethnicity, sexual orientation, and clinical signs and symptoms. To describe the characteristics of mpox in NYC, case investigation data for NYC residents with mpox diagnosed during May 19–July 15, 2022, were analyzed. Using a standardized form, DOHMH staff members attempted to interview all NYC residents with probable (a positive non-variola Orthopoxvirus polymerase chain reaction [PCR] test result)† or confirmed (a positive MPXV–specific PCR test result) mpox reported to DOHMH through mandated laboratory reporting. For patients who declined an interview or were unreachable, information obtained from medical care providers during DOHMH consultation calls was used. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.§

BACKGROUND: Successful linkage to HIV services and initiation of antiretroviral treatment (ART) for children living with HIV (CLHIV) is critical to improve pediatric ART coverage. We aimed to assess confirmatory testing, linkage, and rapid ART initiation among newly diagnosed CLHIV in Ethiopia from the perspectives of caregivers and healthcare workers (HCWs). METHODS: We conducted standardized surveys with HCWs and caregivers of children 2-14 years who were diagnosed with HIV but not yet on ART who had been identified during a cross-sectional study in Ethiopia from May 2017-March 2018. Eight health facilities based on their HIV caseload and testing volume and 21 extension sites were included. Forty-one children, 34 care givers and 40 healthcare workers were included in this study. Three months after study enrollment, caregivers were surveyed about timing and experiences with HIV service enrollment, confirmatory testing, and ART initiation. Data collected from HCWs included perceptions of confirmatory testing in CLHIV before ART initiation. SPSS was used to conduct descriptive statistics. RESULTS: The majority of the 41 CLHIV were enrolled to HIV services (n = 34, 83%) and initiated ART by three months (n = 32, 94%). Median time from diagnosis to ART initiation was 12 days (interquartile range 5-18). Five children died before the follow-up interview. Confirmatory HIV testing was conducted in 34 children and found no discordant results; the majority (n = 23, 68%) received it within one week of HIV diagnosis. Almost all HCWs (n = 39/40, 98%) and caregivers (n = 31/34, 91%) felt better/the same about test results after conducting confirmatory testing. CONCLUSION: Opportunities remain to strengthen linkage for newly diagnosed CLHIV in Ethiopia through intensifying early follow-up to ensure prompt confirmatory testing and rapid ART initiation. Additional services could help caregivers with decision-making around treatment initiation for their children.

BACKGROUND: Type 2 circulating vaccine-derived polioviruses (cVDPV2) from Sabin oral poliovirus vaccines (OPVs) are the leading cause of poliomyelitis. A novel type 2 OPV (nOPV2) has been developed to be more genetically stable with similar tolerability and immunogenicity to that of Sabin type 2 vaccines to mitigate the risk of cVDPV2. We aimed to assess these aspects of nOPV2 in poliovirus vaccine-naive newborn infants. METHODS: In this randomised, double-blind, controlled, phase 2 trial we enrolled newborn infants at the Matlab Health Research Centre, Chandpur, Bangladesh. We included infants who were healthy and were a single birth after at least 37 weeks' gestation. Infants were randomly assigned (2:1) to receive either two doses of nOPV2 or placebo, administered at age 0-3 days and at 4 weeks. Exclusion criteria included receipt of rotavirus or any other poliovirus vaccine, any infection or illness at the time of enrolment (vomiting, diarrhoea, or intolerance to liquids), diagnosis or suspicion of any immunodeficiency disorder in the infant or a close family member, or any contraindication for venipuncture. The primary safety outcome was safety and tolerability after one and two doses of nOPV2, given 4 weeks apart in poliovirus vaccine-naive newborn infants and the primary immunogenicity outcome was the seroconversion rate for neutralising antibodies against type 2 poliovirus, measured 28 days after the first and second vaccinations with nOPV2. Study staff recorded solicited and unsolicited adverse events after each dose during daily home visits for 7 days. Poliovirus neutralising antibody responses were measured in sera drawn at birth and at age 4 weeks and 8 weeks. This study is registered on ClinicalTrials.gov, NCT04693286. FINDINGS: Between Sept 21, 2020, and Aug 16, 2021, we screened 334 newborn infants, of whom three (<1%) were found to be ineligible and one (<1%) was withdrawn by the parents; the remaining 330 (99%) infants were assigned to receive nOPV2 (n=220 [67%]) or placebo (n=110 [33%]). nOPV2 was well tolerated; 154 (70%) of 220 newborn infants in the nOPV2 group and 78 (71%) of 110 in the placebo group had solicited adverse events, which were all mild or moderate in severity. Severe unsolicited adverse events in 11 (5%) vaccine recipients and five (5%) placebo recipients were considered unrelated to vaccination. 306 (93%) of 330 infants had seroprotective maternal antibodies against type 2 poliovirus at birth, decreasing to 58 (56%) of 104 in the placebo group at 8 weeks. In the nOPV2 group 196 (90%) of 217 infants seroconverted by week 8 after two doses, when 214 (99%) had seroprotective antibodies. INTERPRETATION: nOPV2 was well tolerated and immunogenic in newborn infants, with two doses, at birth and 4 weeks, resulting in almost 99% of infants having protective neutralising antibodies. FUNDING: Bill & Melinda Gates Foundation.

The guinea pig was the original animal model developed for investigating spotted fever rickettsiosis (SFR). This model system has persisted on account of the guinea pig's conduciveness to tick transmission of SFR agents and ability to recapitulate SFR in humans through clinical signs that include fever, unthriftiness, and in some cases the development of an eschar. The guinea pig is the smallest animal model for SFR that allows the collection of multiple blood and skin samples antemortem for longitudinal studies. This unit provides the basic protocols necessary to establish, maintain, and utilize a guinea pig-tick-Rickettsia model for monitoring the course of infection and immune response to an infection by spotted fever group Rickettsia (SFGR) that can be studied at biosafety level 2 (BSL-2) and arthropod containment level 2 (ACL-2); adaptations must be made for BSL-3 agents. The protocols cover methods for tick feeding and colony development, laboratory infection of ticks, tick transmission of Rickettsia to guinea pigs, and monitoring of the course of infection through clinical signs, rickettsial burden, and immune response. It should be feasible to adapt these methods to study other tick-borne pathogens. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Tick transmission of SFGR to guinea pigs Support Protocol 1: Laboratory infection of ticks by injection Alternate Protocol 1: Needle inoculation of SFGR to guinea pigs Basic Protocol 2: Monitoring the course of guinea pig rickettsial infection: clinical signs Basic Protocol 3: Monitoring the course of guinea pig rickettsial infection: collection of biological specimens Support Protocol 2: Guinea pig anesthesia Basic Protocol 4: Monitoring rickettsial burden in guinea pigs by multiplex qPCR Basic Protocol 5: Monitoring guinea pig immune response to infection: blood leukocytes by flow cytometry Basic Protocol 6: Monitoring immune response to guinea pig rickettsial infection: leukocyte infiltration of skin at the tick bite site by flow cytometry Basic Protocol 7: Monitoring the immune response to guinea pig rickettsial infection: antibody titer by ELISA Support Protocol 4: Coating ELISA Plates Alternate Protocol 2: Monitoring immune response to guinea pig rickettsial infection: antibody titer by immunofluorescence assay.

Even with the COVID-19 pandemic, tuberculosis remains a leading cause of human death due to a single infectious agent. Until successfully treated, infected individuals may continue to transmit Mycobacterium tuberculosis bacilli to contacts. As with other respiratory pathogens, such as SARS-CoV-2, modeling the process of person-to-person transmission will inform efforts to develop vaccines and therapies that specifically impede disease transmission. The ferret (Mustela furo), a relatively inexpensive, small animal has been successfully employed to model transmissibility, pathogenicity, and tropism of influenza and other respiratory disease agents. Ferrets can become naturally infected with Mycobacterium bovis and are closely related to badgers, well known in Great Britain and elsewhere as a natural transmission vehicle for bovine tuberculosis. Herein, we report results of a study demonstrating that within 7 weeks of intratracheal infection with a high dose (>5 x 10(3) CFU) of M. tuberculosis bacilli, ferrets develop clinical signs and pathological features similar to acute disease reported in larger animals, and ferrets infected with very-high doses (>5 x 10(4) CFU) develop severe signs within two to four weeks, with loss of body weight as high as 30%. Natural transmission of this pathogen was also examined. Acutely-infected ferrets transmitted M. tuberculosis bacilli to co-housed naïve sentinels; most of the sentinels tested positive for M. tuberculosis in nasal washes, while several developed variable disease symptomologies similar to those reported for humans exposed to an active tuberculosis patient in a closed setting. Transmission was more efficient when the transmitting animal had a well-established acute infection. The findings support further assessment of this model system for tuberculosis transmission including the testing of prevention measures and vaccine efficacy.

Rabies is one of the most lethal infectious diseases, with those living in Asia and Africa having the highest risk of dying from rabies. We conducted a knowledge, attitudes and practices survey in urban and peri-urban areas of Bangladesh to describe canine bite rates, rabies knowledge, and healthcare seeking behaviors and barriers to human and dog vaccination. A bite risk assessment score (BRAS) and healthcare-seeking behavior score (HSBS) was calculated for each bite victim. Respondents were given two hypothetical situations to assess potential behaviors after a bite and willingness to pay for rabies vaccine and immunoglobulin. In total, 2,447 households participated in the survey and 85 bite victims were identified. The BRAS identified that 31% of bites posed no risk of rabies transmission. Multivariate analyses showed that living in Chittagong (β = 1.4; 95% CI: 0.1, 2.7) was associated with a higher HSBS. Findings presented here provide useful information regarding bite occurrences, healthcare-seeking behaviors, and a need for strategies to increase rabies awareness.