Diagnostic approaches that combine the high sensitivity and specificity of laboratory-based digital detection with the ease of use and affordability of point-of-care (POC) technologies could revolutionize disease diagnostics. This is especially true in infectious disease diagnostics, where rapid and accurate pathogen detection is critical to curbing the spread of disease. We have pioneered an innovative label-free digital detection platform that utilizes Interferometric Reflectance Imaging Sensor (IRIS) technology. IRIS leverages light interference from an optically transparent thin film, eliminating the need for complex optical resonances to enhance the signal by harnessing light interference and the power of signal averaging in shot-noise-limited operation In our latest work, we have further improved our previous 'Single-Particle' IRIS (SP-IRIS) technology by allowing the construction of the optical signature of target nanoparticles (whole virus) from a single image. This new platform, 'Pixel-Diversity' IRIS (PD-IRIS), eliminated the need for z-scan acquisition, required in SP-IRIS, a time-consuming and expensive process, and made our technology more applicable to POC settings. Using PD-IRIS, we quantitatively detected the Monkeypox virus (MPXV), the etiological agent for Monkeypox (Mpox) infection. MPXV was captured by anti-A29 monoclonal antibody (mAb 69-126-3) on Protein G spots on the sensor chips and were detected at a limit-of-detection (LOD) - of 200 PFU/mL (∼3.3 aM). PD-IRIS was superior to the laboratory-based ELISA (LOD - 1800 PFU/mL) used as a comparator. The specificity of PD-IRIS in MPXV detection was demonstrated using Herpes simplex virus, type 1 (HSV-1), and Cowpox virus (CPXV). This work establishes the effectiveness of PD-IRIS and opens possibilities for its advancement in clinical diagnostics of Mpox at POC. Moreover, PD-IRIS is a modular technology that can be adapted for the multiplex detection of pathogens for which high-affinity ligands are available that can bind their surface antigens to capture them on the sensor surface.

BACKGROUND: Borealpox virus (BRPV, formerly known as Alaskapox virus) is a zoonotic member of the Orthopoxvirus genus first identified in a person in 2015. In the six patients with infection previously observed BRPV involved mild, self-limiting illness. We report the first fatal BRPV infection in an immunosuppressed patient. METHODS: A man aged 69 years from Alaska's Kenai Peninsula was receiving anti-CD20 therapy for chronic lymphocytic leukemia. He presented to care for a tender, red papule in his right axilla with increasing induration and pain. The patient failed to respond to multiple prescribed antibiotic regimens and was hospitalized 65 days postsymptom onset for progression of presumed infectious cellulitis. BRPV was eventually detected through orthopoxvirus real-time polymerase chain reaction testing of mucosal swabs. He received combination antiviral therapy, including 21 days of intravenous tecovirimat, intravenous vaccinia immunoglobulin, and oral brincidofovir. Serial serology was conducted on specimens obtained posttreatment initiation. FINDINGS: The patient's condition initially improved with plaque recession, reduced erythema, and epithelization around the axillary lesion beginning one-week post-therapy. He later exhibited delayed wound healing, malnutrition, acute renal failure, and respiratory failure. He died 138 days postsymptom onset. Serologic testing revealed no evidence the patient generated a humoral immune response. No secondary cases were detected. CONCLUSION: This report demonstrates that BRPV can cause overwhelming disseminated infection in certain immunocompromised patients. Based on the patient's initial response, early BRPV identification and antiviral therapies might have been beneficial. These therapies, in combination with optimized immune function, should be considered for patients at risk for manifestations of BRPV.

BACKGROUND: After months of few mpox cases, an increase in cases was reported in Chicago during May 2023, predominantly among fully vaccinated (FV) patients. We investigated the outbreak scope, differences between vaccinated and unvaccinated patients, and hypotheses for monkeypox virus (MPXV) infection after vaccination. METHODS: We interviewed patients and reviewed medical records to assess demographic, behavioral, and clinical characteristics; mpox vaccine status; and vaccine administration routes. We evaluated serum antibody levels after infection and compared patient viral genomes with MPXV sequences in available databases. We discussed potential vaccine compromise with partners who manufactured, handled, and administered the vaccine associated with breakthrough infections. RESULTS: During 18 March-27 June 2023, we identified 49 mpox cases; 57% of these mpox patients were FV. FV patients received both JYNNEOS doses subcutaneously (57%), intradermally (7%), or via heterologous administration (36%). FV patients had more median sex partners (3; interquartile range [IQR] = 1-4) versus not fully vaccinated patients (1; IQR = 1-2). Thirty-six of 37 sequenced specimens belonged to lineage B.1.20 of clade IIb MPXV, which did not demonstrate any amino acid changes relative to B.1, the predominant lineage from May 2022. Vaccinated patients demonstrated expected humoral antibody responses; none were hospitalized. No vaccine storage excursions were identified. Approximately 63% of people at risk for mpox in Chicago were FV during this period. CONCLUSIONS: Our investigation indicated that cases were likely due to frequent behaviors associated with mpox transmission, even with relatively high vaccine effectiveness and vaccine coverage. Cases after vaccination might occur in similar populations.

Background: Bilateral oophorectomy has been linked to numerous health outcomes, some of which can have a long latency period. Limited data are available on bilateral oophorectomy prevalence among U.S. women. Methods: The National Health Interview Survey fielded measures of bilateral oophorectomy most recently in 2010 and 2015. We pooled these 2 data years to present bilateral oophorectomy prevalence estimates by age-group, race, ethnicity, geographic region, and hysterectomy status. Results: Our study found bilateral oophorectomy was common among older women. Among women aged 70-79 years, 29% reported a bilateral oophorectomy, compared with <1% for women aged 20-29 years. By geographic region, bilateral oophorectomy prevalence among women 20-84 years was 12.3% in the South, 10.8% in the Midwest, 9.4% in the West, and 8.0% in the Northeast. Small numbers limited our ability to generate age-specific estimates for American Indian and Alaska Native women and subgroups of Asian and Hispanic women. Nearly half of women who had a bilateral oophorectomy reported their procedure occurred more than 20 years ago. Among women aged 20-84 years who reported a hysterectomy, 57% reported they also had both of their ovaries removed. Conclusion: Standard measures of incidence rates for ovarian cancer are not adjusted for oophorectomy status. These findings suggest that ovarian cancer incidence rates may be underestimated among older women. Continued monitoring of bilateral oophorectomy prevalence will be needed to track its potential impact on ovarian cancer incidence and numerous other chronic health outcomes.

A healthcare provider unknowingly treated a patient with mpox and subsequently developed ocular mpox without rash. She breastfed during illness; her infant was not infected. This report addresses 3 challenges in mpox management and control: diagnosis in the absence of rash, exposures in healthcare settings, and management of lactating patients.

BACKGROUND: People experiencing homelessness (PEH) are underrepresented in public health and clinical research. Study methods that can improve participation by this group are needed. METHODS: In late 2022, the Centers for Disease Control and Prevention conducted an mpox serological survey using venipuncture among PEH in San Francisco, California. Blood collection by a minimally invasive device was offered if venipuncture was not possible or preferred. Participants who had a successful blood draw using the device were asked about device acceptability. RESULTS: Of the 209 successful blood collections, 137 (66%) were among participants who underwent venipuncture and 72 (34%) were among participants who used the device. Use of the device increased overall blood collection participation by 53%. Participants reported high acceptability and preference for the device over venipuncture. CONCLUSIONS: Minimally invasive blood collection devices may increase participation and representation of PEH in serosurveys.

Community health workers (CHWs) are increasingly addressing health disparities in primary care settings; however, there is little information about how primary care practitioners (PCPs) interact with CHWs or perceive CHW roles. We examined PCP engagement with CHWs in adult primary care settings. Overall, 55% of 1504 PCPs reported working with CHWs; involvement with CHWs differed by some PCP demographic and practice-related factors. While PCPs perceived CHWs as engaging in most nationally endorsed CHW roles, they identified several barriers to integrating CHWs into care teams. Findings can inform ongoing efforts to advance health equity through integrating CHWs into primary care practices.

We assessed early antibody responses after two doses of JYNNEOS (IMVANEX) mpox vaccine in the District of Columbia (D.C.) in persons at high risk for mpox without characteristic lesions or rash. Participants with PCR mpox negative specimens (oral swab, blood, and/or rectal swab) on the day of receipt of the first vaccine dose and who provided a baseline (day 0) serum sample and at least one serum sample at ∼28, ∼42-56 days, or 180 days post vaccination were included in this analysis. Orthopoxvirus (OPXV)-specific IgG and IgM ELISAs and neutralizing antibody titers were performed, and longitudinal serologic responses were examined. Based on participants' IgG and IgM antibody levels at baseline, they were categorized as naïve or non-naïve. Linear mixed effects regression models were conducted to determine if IgG antibody response over time varied by age, sex, HIV status, and route of administration for both naïve and non-naïve participants. Among both naïve and non-naïve participants IgG seropositivity rates increased until day 42-56, with 89.4 % of naïve and 92.1 % of non-naïve participants having detectable IgG antibodies. The proportion of naive participants with detectable IgG antibodies declined by day 180 (67.7 %) but remained high among non-naïve participants (94.4 %). Neutralizing antibody titers displayed a similar pattern, increasing initially post vaccination but declining by day 180 among naïve participants. There were no significant serologic response differences by age, sex, or HIV status. Serologic response did vary by route of vaccine administration, with those receiving a combination of intradermal and subcutaneous doses displaying significantly higher IgG values than those receiving both doses intradermally. These analyses provide initial insights into the immunogenicity of a two-dose JYNNEOS PEP regimen in individuals at high risk of mpox exposure in the United States.

BACKGROUND: The extent to which infections may have been undetected in an epicenter of the 2022 mpox outbreak is unknown. METHODS: A serosurvey (July and August 2022) assessed the seroprevalence and correlates of mpox infection among a diverse sample of asymptomatic patients with no prior mpox diagnoses and no known histories of smallpox or mpox vaccination. We present seropositivity stratified by participant characteristics collected via survey. RESULTS: Two-thirds of 419 participants were cismen (281 of 419), of whom 59.1% (166 of 281) reported sex with men (MSM). The sample also included 109 ciswomen and 28 transgender/gender nonconforming/nonbinary individuals. Overall seroprevalence was 6.4% (95% confidence interval [CI], 4.1%-8.8%); 3.7% among ciswomen (95% CI, 1.0%-9.1%), 7.0% among cismen with only ciswomen partners (95% CI, 2.0%-11.9%), and 7.8% among MSM (95% CI, 3.7%-11.9%). There was little variation in seroprevalence by race/ethnicity, age group, HIV status, or number of recent sex partners. No participants who reported close contact with mpox cases were seropositive. Among participants without recent mpox-like symptoms, 6.3% were seropositive (95% CI, 3.6%-9.0%). CONCLUSIONS: Approximately 1 in 15 vaccine-naive people in our study had antibodies to mpox during the height of the NYC outbreak, indicating the presence of asymptomatic infections that could contribute to ongoing transmission.

INTRODUCTION: Cardiometabolic diseases are associated with greater COVID-19 severity; however, the influences of cardiometabolic health on SARS-CoV-2 infections after vaccination remain unclear. Our objective was to investigate the associations between temporal blood pressure and total cholesterol patterns and incident SARS-CoV-2 infections among those with serologic evidence of vaccination. METHODS: In this prospective cohort of blood donors, blood samples were collected in 2020-2021 and assayed for binding antibodies of SARS-CoV-2 nucleocapsid protein antibody seropositivity. We categorized participants into intraindividual pattern subgroups of blood pressure and total cholesterol (persistently, intermittently, or not elevated [systolic blood pressure <130 mmHg, diastolic blood pressure <80 mmHg, total cholesterol <200 mg/dL]) across the study time points. RESULTS: Among 13,930 donors with 39,736 donations representing 1,127,071 person-days, there were 221 incident SARS-CoV-2 infections among those with serologic evidence of vaccination (1.6%). Intermittent hypertension was associated with greater SARS-CoV-2 infections among those with serologic evidence of vaccination risk (adjusted incidence rate ratio=2.07; 95% CI=1.44, 2.96; p<0.01) than among participants with consistent normotension on the basis of a multivariable Poisson regression. Among men, intermittently elevated total cholesterol (adjusted incidence rate ratio=1.90; 95% CI=1.32, 2.74; p<0.01) and higher BMI at baseline (adjusted hazard ratio=1.44; 95% CI=1.07, 1.93; p=0.01; per 10 units) were associated with greater SARS-CoV-2 infections among those with serologic evidence of vaccination probability; these associations were null among women (both p>0.05). CONCLUSIONS: Our findings underscore that the benefits of cardiometabolic health, particularly blood pressure, include a lower risk of SARS-CoV-2 infection after vaccination.

IMPORTANCE: Non-Hispanic American Indian/Alaska Native people have the second highest incidence rate of invasive cutaneous melanoma in the US after non-Hispanic White people. OBJECTIVE: To examine invasive cutaneous melanoma incidence rates and trends over time among non-Hispanic American Indian/Alaska Native people. DESIGN, SETTING, AND PARTICIPANTS: This descriptive, observational cross-sectional study used population-based cancer registry data (US Cancer Statistics AI/AN Incidence Analytic Database) linked to the Indian Health Service administrative database to examine incidence rates by age, sex, region, histology, tumor site, stage, and other demographic and clinical characteristics. The study examined trends from 1999 to 2019 time period by age, sex, stage at diagnosis, and region. Non-Hispanic American Indian/Alaska Native people 15 years and older who received a diagnosis of invasive cutaneous melanoma from 1999 to 2019 who were members of federally recognized tribes and resided in Indian Health Service purchased/referred care delivery areas were included in this study to reduce racial misclassification and provide more accurate rates. The data were analyzed in 2022. EXPOSURES: Demographic and clinical characteristics, such as age, sex, geographic region, histology, stage, and tumor site. MAIN OUTCOMES AND MEASURES: Invasive cutaneous melanoma incidence rates by age group, sex, region, resident county characteristics (poverty level, rurality, education level, and socioeconomic status), stage at diagnosis, tumor site, and histology. Trends over time by age, sex, region, and stage. RESULTS: From 1999 to 2019, 2151 non-Hispanic American Indian/Alaska Native people (1021 female individuals [47.5%]) received a diagnosis of incident cutaneous melanoma (rate, 10.7 per 100 000; 95% CI, 10.3-11.2). Rates were higher among male than female individuals (13.0 [95% CI, 12.2-13.8] vs 9.2 [95% CI, 8.6-9.8]) and for people 55 years and older (24.2; 95% CI, 22.8-25.7) compared with those aged 15 to 39 years (3.5; 95% CI, 3.2-3.9). Rates were highest for male individuals 55 years and older (34.5; 95% CI, 31.8-37.3) and people living in the Southern Plains (male individuals: 23.8; 95% CI, 21.5-26.2; female individuals: 15.5; 95% CI, 14.0-17.2) and Pacific Coast region (male individuals: 16.5; 95% CI, 14.5-18.7; female individuals: 12.3; 95% CI, 10.9-13.9). Rates increased among female individuals from 1999 to 2019 (average annual percent change [AAPC], 2.5; P < .001); among regional/distant stage tumors (AAPC, 2.5; P = .01) and people 55 years and older (AAPC, 2.8; P = .001). CONCLUSIONS AND RELEVANCE: The results of this study suggest that additional studies could potentially identify risk factors among non-Hispanic American Indian/Alaska Native people.

CONTEXT: Opportunities to reduce the risk of cancer, including cervical, liver, and skin cancer, start early in life. To encourage adoption of primary prevention activities in childhood to reduce cancer risk later in life, Centers for Disease Control and Prevention conducted a demonstration project with 3 National Comprehensive Cancer Control Program (NCCCP) recipients. PROGRAM: Iowa, Northwest Portland Area Indian Health Board (NPAIHB), and Pennsylvania NCCCP recipients implemented evidence-based primary prevention activities for cervical, liver, and skin cancer among children using health care provider education, patient education, and policy development. IMPLEMENTATION: Iowa implemented an announcement approach to improve provider education on human papillomavirus (HPV) vaccination. Pennsylvania focused on patient education for reducing skin cancer risk and both provider and patient education for liver cancer prevention. NPAIHB created a sun safety intervention for tribal organizations, including a policy guide, media materials, and patient education. RESULTS: In Iowa, health care providers taking the announcement approach reported significantly higher mean scores on a posttest compared with a pretest regarding perceptions about HPV vaccination, self-efficacy, and behavioral intentions related to vaccination. Pennsylvania integrated sun safety education and sunscreen dispenser programs as a health and wellness initiative in 8 state parks and the Pennsylvania Department of Conservation and Natural Resources incorporated the program in its Pennsylvania Outdoor Recreation Plan. Pennsylvania also implemented health care provider education on the primary prevention of liver cancer through hepatitis B and hepatitis C screening and hepatitis B vaccination. The NPAIHB skin cancer policy guide was created and distributed for use to all 43 federally recognized tribes of Oregon, Washington, and Idaho served by NPAIHB. DISCUSSION: The identification, dissemination, and implementation of these efforts can serve as best practices for future childhood primary prevention programs. NCCCP recipients and public health professionals can use health care provider education, patient education, and policy development to reduce future risk for cervical, liver, and skin cancer among children.

Since May 2022, mpox has been identified in 108 countries without endemic disease; most cases have been in gay, bisexual, or other men who have sex with men. To determine number of missed cases, we conducted 2 studies during June-September 2022: a prospective serologic survey detecting orthopoxvirus antibodies among men who have sex with men in San Francisco, California, and a retrospective monkeypox virus PCR testing of swab specimens submitted for other infectious disease testing among all patients across the United States. The serosurvey of 225 participants (median age 34 years) detected 18 (8.0%) who were orthopoxvirus IgG positive and 3 (1.3%) who were also orthopoxvirus IgM positive. The retrospective PCR study of 1,196 patients (median age 30 years; 54.8% male) detected 67 (5.6%) specimens positive for monkeypox virus. There are likely few undiagnosed cases of mpox in regions where sexual healthcare is accessible and patient and clinician awareness about mpox is increased.

Orthopoxviruses are complex, large-genome DNA viruses that have repeatedly confounded expectations in terms of the clinical illness they cause and their patterns of spread. Monkeypox virus (MPXV) was originally characterized during outbreaks among captive primates in the late 1950's. Human disease (mpox) has been observed since the 1970's and inter-human spread has largely been associated with non-sexual, close physical contact in endemic areas of west and central Africa. In May 2022, a focus of Clade IIb MPXV transmission was detected, spreading largely by sexual contact through international networks of gay, bisexual, and other men who have sex with men. Despite decades of preparedness for the potential biothreat risk posed by smallpox, the outbreak grew in both size and geographic scope, testing the strength of smallpox preparedness tools and public health science alike. In this article we consider what was known about mpox prior to the 2022 outbreak, what we have learned about mpox and Clade IIb virus during the outbreak, and what outbreak response actions and continued research are needed to ensure the global public health community is equipped to detect and halt the further spread of this disease threat. We focus on how epidemiologic characterization and investigation together with laboratory studies have advanced our understanding of the transmission and pathogenesis of mpox, and describe what work remains to be done to optimize diagnostics, therapeutics, and vaccines. Persistent health inequities challenge our capacity to fully eliminate circulation of the 2022 outbreak strain of MPXV currently in the United States.

BACKGROUND: National organizations have issued comprehensive cancer survivorship care guidelines to improve care of cancer survivors, many of whom receive care from primary care providers (PCPs). METHODS: We analyzed Porter Novelli's 2019 fall DocStyles survey to assess use of cancer survivorship care guidelines, receipt of survivorship training, types of survivorship services provided, and confidence providing care among PCPs in the United States. We grouped PCPs by use of any guideline ("users") versus no guideline use ("nonusers"). We calculated descriptive statistics and conducted multivariable logistic regression analyses to examine guideline use, having received training on providing survivorship care services, and confidence in providing care. Within the panel, sampling quotas were set so that 1000 primary care physicians, 250 OB/GYNs, 250 pediatricians, and 250 nurse practitioners/physician assistants were recruited. RESULTS: To reach selected quotas, 2696 health professionals were initially contacted to participate, resulting in a response rate of 64.9%. Sixty-two percent of PCPs reported using guidelines and 17% reported receiving survivorship care training. Use of any guidelines or receiving training was associated with reporting providing a range of survivorship services and confidence in providing care. After adjusting for demographic characteristics, guideline users were more likely than nonusers to report assessing genetic cancer risk (OR = 2.65 95% confidence interval (CI) (1.68, 4.17)), screening for cancer recurrence (OR = 2.32 95% CI (1.70, 3.18)) or a new cancer (OR = 1.63, 95% CI (1.20, 2.22)), and treating depression (OR = 1.64, 95% CI (1.20, 2.25)). Receipt of training was also positively associated with providing genetic risk assessment, surveillance for recurrence, as well as assessing late/long-term effects, and treating pain, fatigue, and sexual side effects. CONCLUSION: Survivorship care guidelines and training support PCPs in providing a range of survivorship care services.

In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISAs to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with differing Smallpox-vaccine doses and those with prior MPXV infection were tested on these assays, where we observed that one dose of Smallpox vaccination induces a low number of antibodies to a limited number of MPXV antigens but increasing with further vaccination doses. MPXV infection induced similar antibody responses to diverse poxvirus antigens observed in Smallpox-vaccinated individuals. We identify MPXV A27 as a serological marker of MPXV-infection, whilst MPXV M1 (VACV L1) is likely IMVANEX-specific. Here, we demonstrate analogous humoral antigen recognition between both MPXV-infected or Smallpox-vaccinated individuals, with binding to diverse yet core set of poxvirus antigens, providing opportunities for future vaccine (e.g., mRNA) and therapeutic (e.g., mAbs) design.

Routine screening for breast, cervical, and colorectal cancers decreased substantially after the COVID-19 public health emergency was declared in early 2020.1, 2 This decrease was largely due to facility closures, local policies to limit viral spread, and cancelation of non-emergency procedures.1, 2 Screening generally rebounded later in 2020, but not uniformly across all areas of the USA or segments of the population.1, 2 Some people might have also delayed seeking medical care during the height of the pandemic for symptoms suggestive of cancer because of concerns regarding contact with SARS-CoV-2.3 | | 3 years after the start of the pandemic, US nationwide cancer incidence data are starting to reveal its impact on cancer diagnoses. In The Lancet Oncology, a study by Xuesong Han and colleagues assessed data from the US Commission on Cancer's National Cancer Database, including the recently released 2020 dataset.4 The authors found a 17·2% reduction in stage I cancers diagnosed in 2020 compared with 2019 (278 400 cases in 2020 vs 336 136 in 2019). Diagnoses of stage IV cancers decreased by 9·8% (148 339 in 2020 vs 164 545 in 2019). However, the odds of having a cancer diagnosed as stage IV in 2020 increased by about 7% compared with 2019 (adjusted odds ratio [aOR] 1·074 [1·066–1·083] for stage IV vs stage I–III).

The emergence and rapid worldwide spread of SARS-CoV-2 has accelerated research and development for controlling the pandemic. A multi-coronavirus protein microarray was created containing full-length proteins, overlapping protein fragments of varying lengths and peptide libraries from SARS-CoV-2 and four other human coronaviruses. Sera from confirmed COVID-19 patients as well as unexposed individuals were applied to multi-coronavirus arrays to identify specific antibody reactivity. High level IgG, IgM and IgA reactivity to structural proteins S, M and N, as well as accessory proteins, of SARS-CoV-2 were observed that was specific to COVID-19 patients. Overlapping 100, 50 and 30 amino acid fragments of SARS-CoV-2 proteins identified antigenic regions. Numerous proteins of SARS-CoV, MERS-CoV and the endemic human coronaviruses, HCoV-NL63 and HCoV-OC43 were also more reactive with IgG, IgM and IgA in COVID-19 patient sera than in unexposed control sera, providing further evidence of immunologic cross-reactivity between these viruses. The multi-coronavirus protein microarray is a useful tool for mapping antibody reactivity in COVID-19 patients.Competing Interest StatementDavid Camerini, Arlo Z. Randall, Amit Oberai, Christopher Hung, Joshua Edgar, Adam Shandling, Vu Huynh, Andy A. Teng, Gary Hermanson, Jozelyn V. Pablo, Xiaowu Liang, Angela Yee and Joseph J. Campo are employees of Antigen Discovery Inc. In addition, Xiaowu Liang and Angela Yee have an equity interest in Antigen Discovery Inc. The other authors declare non competing interests.Funding StatementNo external funding was used in this study.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:This study was approved by the Mayo Clinic Human Subjects Institutional Review Board and the Centers for Disease Control and Prevention Human Subjects Office.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.YesAll data are freely available.

Orthopoxviruses (OPXVs) have a broad host range in mammalian cells, but Chinese hamster ovary (CHO) cells are non-permissive for vaccinia virus (VACV). Here, we revealed a species-specific difference in host restriction factor SAMD9L as the cause for the restriction and identified orthopoxvirus CP77 as a unique inhibitor capable of antagonizing Chinese hamster SAMD9L (chSAMD9L). Two known VACV inhibitors of SAMD9 and SAMD9L (SAMD9&amp;L), K1 and C7, can bind human and mouse SAMD9&amp;L, but neither can bind chSAMD9L. CRISPR-Cas9 knockout of chSAMD9L from CHO cells removed the restriction for VACV, while ectopic expression of chSAMD9L imposed the restriction for VACV in a human cell line, demonstrating that chSAMD9L is a potent restriction factor for VACV. Contrary to K1 and C7, cowpox virus CP77 can bind chSAMD9L and rescue VACV replication in cells expressing chSAMD9L, indicating that CP77 is yet another SAMD9L inhibitor but has a unique specificity for chSAMD9L. Binding studies showed that the N-terminal 382 amino acids of CP77 were sufficient for binding chSAMD9L and that both K1 and CP77 target a common internal region of SAMD9L. Growth studies with nearly all OPXV species showed that the ability of OPXVs in antagonizing chSAMD9L correlates with CP77 gene status and that a functional CP77 ortholog was maintained in many OPXVs, including monkeypox virus. Our data suggest that species-specific difference in rodent SAMD9L poses a barrier for cross-species OPXV infection and that OPXVs have evolved three SAMD9L inhibitors with different specificities to overcome this barrier.IMPORTANCE Several OPXV species, including monkeypox virus and cowpox virus, cause zoonotic infection in humans. They are believed to use wild rodents as the reservoir or intermediate hosts, but the host or viral factors that are important for OPXV host range in rodents are unknown. Here, we showed that the abortive replication of several OPXV species in a Chinese hamster cell line was caused by a species-specific difference in the host antiviral factor SAMD9L, indicating that SAMD9L divergence in different rodent species poses a barrier for cross-species OPXV infection. While the Chinese hamster SAMD9L could not be inhibited by two previously identified OPXV inhibitors of human and mouse SAMD9L, it can be inhibited by cowpox virus CP77, indicating that OPXVs encode three SAMD9L inhibitors with different specificity. Our data suggest that OPXV host range in broad rodent species depends on three SAMD9L inhibitors with different specificities.

Mosquito-borne diseases are a major global public health concern and mosquito surveillance systems are essential for the implementation of effective mosquito control strategies. The objective of our study is to determine the spatiotemporal distribution of vector mosquito species in Maricopa County, AZ from 2011 to 2021, and to identify the hotspot areas for West Nile virus (WNV) and St. Louis Encephalitis virus (SLEV) transmission in 2021. The Maricopa County Mosquito Control surveillance system utilizes BG-Sentinel and EVS-CDC traps throughout the entire urban and suburban areas of the county. We estimated specific mosquito species relative abundance per unit area using the Kernel density estimator in ArcGIS 10.2. We calculated the distance between all traps in the surveillance system and created a 4 km buffer radius around each trap to calculate the extent to which each trap deviated from the mean number of Cx. quinquefasciatus and Cx. tarsalis collected in 2021. Our results show that vector mosquito species are widely distributed and abundant in the urban areas of Maricopa County. A total of 691,170 Culex quinquefasciatus, 542,733 Culex tarsalis, and 292,305 Aedes aegypti were collected from 2011 to 2022. The relative abundance of Ae. aegypti was highly seasonal peaking in the third and fourth quarters of the year. Culex quinquefasciatus, on the other hand, was abundant throughout the year with several regions consistently yielding high numbers of mosquitoes. Culex tarsalis was abundant but it only reached high numbers in well-defined areas bordering natural and rural areas. We also detected high levels of heterogeneity in the risk of WNV and SLEV transmission to humans disregarding traps geographical proximity. The well-defined species-specific spatiotemporal and geographical patterns found in this study can be used to inform vector control operations. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.

Electronic health records (EHRs) are increasingly being used to support public health surveillance, including in cancer, where many population-based registries can now accept electronic case reporting. Using EHRs to supplement cancer registry data provides the opportunity to examine in more detail emerging issues in cancer control, such as the increasing incidence rates of early onset colorectal cancer (CRC). The purpose of this study was to evaluate the feasibility of a public health organization partnering with a health system to examine risk factors for early-onset CRC in a community cancer setting, and to further understand challenges with using EHRs to address emerging topics in cancer control. We conducted a mixed-methods evaluation using key informant interviews with public health practitioners, researchers, and registry staff to generate insights on how using EHRs and partnering with health systems can improve chronic disease surveillance and cancer control. A data quality assessment of variables representing risk factors for CRC and other clinical characteristics was conducted on all CRC patients diagnosed in 2016 at the participating cancer center. The quantitative assessment of the EHR data revealed that, while most chronic health conditions were well documented, around 25% of CRC patients were missing information on body mass index, alcohol, and tobacco use. Key informants offered ideas and ways to overcome challenges with using EHR data to support chronic disease surveillance. Their recommendations included the following activities: engaging EHR vendors in the development of standards, taking leadership roles on workgroups to address emerging technological issues, participating in pilot studies and task forces, and negotiating with EHR vendors so that clinical decision support tools built to support public health initiatives are freely available to all users of those EHRs. Although using EHR data to support public health efforts is not without its challenges, it soon could be an important part of chronic disease surveillance and cancer control.

We describe the results of a prospective observational study of the clinical natural history of human monkeypox (mpox) virus (MPXV) infections at the remote L'Hopital General de Reference de Kole (Kole hospital), the rainforest of the Congo River basin of the Democratic Republic of the Congo (DRC) from March 2007 until August 2011. The research was conducted jointly by the Institute National de Recherche Biomedical (INRB) and the US Army Medical Research Institute of Infectious Diseases (USAMRIID). The Kole hospital was one of the two previous WHO Mpox study sites (1981-1986). The hospital is staffed by a Spanish Order of Catholic Nuns from La Congregation Des Seours Missionnaires Du Christ Jesus including two Spanish physicians, who were members of the Order as well, were part of the WHO study on human mpox. Of 244 patients admitted with a clinical diagnosis of MPXV infection, 216 were positive in both the Pan-Orthopox and MPXV specific PCR. The cardinal observations of these 216 patients are summarized in this report. There were three deaths (3/216) among these hospitalized patients; fetal death occurred in 3 of 4 patients who were pregnant at admission, with the placenta of one fetus demonstrating prominent MPXV infection of the chorionic villi. The most common complaints were rash (96.8%), malaise (85.2%), sore throat (78.2%), and lymphadenopathy/adenopathy (57.4%). The most common physical exam findings were mpox rash (99.5%) and lymphadenopathy (98.6%). The single patient without the classic mpox rash had been previously vaccinated against smallpox. Age group of less than 5 years had the highest lesion count. Primary household cases tended to have higher lesion counts than secondary or later same household cases. Of the 216 patients, 200 were tested for IgM & IgG antibodies (Abs) to Orthopoxviruses. All 200 patients had anti-orthopoxvirus IgG Abs; whereas 189/200 were positive for IgM. Patients with hypoalbuminemia had a high risk of severe disease. Patients with fatal disease had higher maximum geometric mean values than survivors for the following variables, respectively: viral DNA in blood (DNAemia); maximum lesion count; day of admission mean AST and ALT.

Monkeypox virus (MPXV), a member of the Orthopoxvirus (OPXV) genus, is a zoonotic virus, endemic to central and western Africa that can cause smallpox-like symptoms in humans with fatal outcomes in up to 15% of patients. The incidence of MPXV infections in the Democratic Republic of the Congo, where the majority of cases have occurred historically, has been estimated to have increased as much as 20-fold since the end of smallpox vaccination in 1980. Considering the risk global travel carries for future disease outbreaks, accurate epidemiological surveillance of MPXV is warranted as demonstrated by the recent Mpox outbreak, where the majority of cases were occurring in non-endemic areas. Serological differentiation between childhood vaccination and recent infection with MPXV or other OPXVs is difficult due to the high level of conservation within OPXV proteins. Here, a peptide-based serological assay was developed to specifically detect exposure to MPXV. A comparative analysis of immunogenic proteins across human OPXVs identified a large subset of proteins that could potentially be specifically recognized in response to a MPXV infection. Peptides were chosen based upon MPXV sequence specificity and predicted immunogenicity. Peptides individually and combined were screened in an ELISA against serum from well-characterized Mpox outbreaks, vaccinee sera, and smallpox sera collected prior to eradication. One peptide combination was successful with ~86% sensitivity and ~90% specificity. The performance of the assay was assessed against the OPXV IgG ELISA in the context of a serosurvey by retrospectively screening a set of serum specimens from the region in Ghana believed to have harbored the MPXV-infected rodents involved in the 2003 United States outbreak.

On November 7, 2022, dengue virus (DENV), which is not endemic in the continental United States (1), was identified in a Maricopa County, Arizona resident by reverse transcription–polymerase chain reaction (RT-PCR) testing at Arizona State Public Health Laboratory (ASPHL). The patient (patient A) was admitted to a hospital on October 19 for a dengue-like illness, 7 days after traveling to and remaining in Mexicali, Mexico for <4 hours. Patient A was hospitalized for 3 days and subsequently recovered. Maricopa County Environmental Services Department (MCESD) conducted retrospective testing for DENV in samples collected from 21 mosquito pools located within 5 miles (8 km) of patient A’s residence during October 1–November 3. A sample collected from one mosquito pool (pool A) on October 5 was positive for DENV. Whole genome sequencing by CDC’s Dengue Branch later revealed that closely related DENV-3 strains not known to be circulating in the patient’s travel region were identified in both patient A and pool A, suggesting local DENV transmission.

We assessed mpox virus prevalence in blood, pharyngeal, and rectal specimens among persons without characteristic rash presenting for JYNNEOS vaccine. Our data indicate that the utility of risk-based screening for mpox in persons without skin lesions or rash via pharyngeal swabs, rectal swabs, and/or blood is likely limited.

Generations of medical educators have recommended including public and population health (PPH) content in the training of U.S. physicians. The COVID-19 pandemic, structural racism, epidemic gun violence, and the existential threats caused by climate change are currently unsubtle reminders of the essential nature of PPH in medical education and practice. To assess the state of PPH content in medical education, the authors reviewed relevant guidance, including policies, standards, and recommendations from national bodies that represent and oversee medical education for physicians with MD degrees. Findings confirm that guidance across the medical education continuum, from premedical education to continuing professional development, increasingly includes PPH elements that vary in specificity and breadth. Graduate medical education policies present the most comprehensive approach in both primary care and subspecialty fields. Behavioral, quantitative, social, and systems sciences are represented, although not uniformly, in guidance for every phase of training. Quantitative PPH skills are frequently presented in the context of research, but not in relation to the development of population health perspectives (e.g., evidence-based medicine, quality improvement, policy development). The interdependence between governmental public health and medical practice, environmental health, and the impact of structural racism and other systems of oppression on health are urgent concerns, yet are not consistently or explicitly included in curricular guidance. To prepare physicians to meet the health needs of patients and communities, educators should identify and address gaps and inconsistencies in PPH curricula and related guidance. Re-examinations of public health and health care systems in the wake of the COVID-19 pandemic support the importance of PPH in physician training and practice, as physicians can help to bridge clinical and public health systems. This review provides an inventory of existing guidance (presented in the appendices) to assist educators in establishing PPH as an essential foundation of physician training and practice.

Monkeypox (mpox) is a disease caused by an Orthopoxvirus. The 2022 multinational outbreak, which began in May 2022, has spread primarily by close skin-to-skin contact, including through sexual contact. Persons experiencing homelessness have been disproportionately affected by severe mpox (1). However, mpox prevalence and transmission pathways among persons experiencing homelessness are not known, and persons experiencing homelessness have not been specifically recommended to receive mpox vaccine during the 2022 outbreak (2,3). During October 25-November 3, 2022, a CDC field team conducted an orthopoxvirus seroprevalence survey among persons accessing homeless services or staying in encampments, shelters, or permanent supportive housing in San Francisco, California that had noted at least one case of mpox or served populations at risk. During field team visits to 16 unique sites, 209 participants completed a 15-minute survey and provided a blood specimen. Among 80 participants aged <50 years who did not report smallpox or mpox vaccination or previous mpox infection, two (2.5%) had detectable antiorthopoxvirus immunoglobulin (Ig) G antibody. Among 73 participants who did not report mpox vaccination or previous mpox infection and who were tested for IgM, one (1.4%) had detectable antiorthopoxvirus IgM. Together, these results suggest that three possible undetected mpox infections occurred among a sample of persons experiencing homelessness, highlighting the need to ensure that community outreach and prevention interventions, such as vaccination, are accessible to this population.

Background. The complexity of decision science models may prevent their use to assist in decision making. User-centered design (UCD) principles provide an opportunity to engage end users in model development and refinement, potentially reducing complexity and increasing model utilization in a practical setting. We report our experiences with UCD to develop a modeling tool for cancer control planners evaluating cancer survivorship interventions. Design. Using UCD principles (described in the article), we developed a dynamic cohort model of cancer survivorship for individuals with female breast, colorectal, lung, and prostate cancer over 10 y. Parameters were obtained from the National Program of Cancer Registries and peer-reviewed literature, with model outcomes captured in quality-adjusted life-years and net monetary benefit. Prototyping and iteration were conducted with structured focus groups involving state cancer control planners and staff from the Centers for Disease Control and Prevention and the American Public Health Association. Results. Initial feedback highlighted model complexity and unclear purpose as barriers to end user uptake. Revisions addressed complexity by simplifying model input requirements, providing clear examples of input types, and reducing complex language. Wording was added to the results page to explain the interpretation of results. After these updates, feedback demonstrated that end users more clearly understood how to use and apply the model for cancer survivorship resource allocation tasks. Conclusions. A UCD approach identified challenges faced by end users in integrating a decision aid into their workflow. This approach created collaboration between modelers and end users, tailoring revisions to meet the needs of the users. Future models developed for individuals without a decision science background could leverage UCD to ensure the model meets the needs of the intended audience. HIGHLIGHTS: Model complexity and unclear purpose are 2 barriers that prevent lay users from integrating decision science tools into their workflow.Modelers could integrate the user-centered design framework when developing a model for lay users to reduce complexity and ensure the model meets the needs of the users.

Mosquito-borne diseases are a major global public health concern and mosquito surveillance systems are essential for the implementation of effective mosquito control strategies. The objective of our study is to determine the spatiotemporal distribution of vector mosquito species in Maricopa County, AZ from 2011 to 2021, and to identify the hotspot areas for West Nile virus (WNV) and St. Louis Encephalitis virus (SLEV) transmission in 2021. The Maricopa County Mosquito Control surveillance system utilizes BG-Sentinel and EVS-CDC traps throughout the entire urban and suburban areas of the county. We estimated specific mosquito species relative abundance per unit area using the Kernel density estimator in ArcGIS 10.2. We calculated the distance between all traps in the surveillance system and created a 4 km buffer radius around each trap to calculate the extent to which each trap deviated from the mean number of Cx. quinquefasciatus and Cx. tarsalis collected in 2021. Our results show that vector mosquito species are widely distributed and abundant in the urban areas of Maricopa County. A total of 691,170 Culex quinquefasciatus, 542,733 Culex tarsalis, and 292,305 Aedes aegypti were collected from 2011 to 2022. The relative abundance of Ae. aegypti was highly seasonal peaking in the third and fourth quarters of the year. Culex quinquefasciatus, on the other hand, was abundant throughout the year with several regions consistently yielding high numbers of mosquitoes. Culex tarsalis was abundant but it only reached high numbers in well-defined areas near irrigated landscapes. We also detected high levels of heterogeneity in the risk of WNV and SLEV transmission to humans disregarding traps geographical proximity. The well-defined species-specific spatiotemporal and geographical patterns found in this study can be used to inform vector control operations.

OBJECTIVES: Early in the COVID-19 pandemic, several outbreaks were linked with facilities employing essential workers, such as long-term care facilities and meat and poultry processing facilities. However, timely national data on which workplace settings were experiencing COVID-19 outbreaks were unavailable through routine surveillance systems. We estimated the number of US workplace outbreaks of COVID-19 and identified the types of workplace settings in which they occurred during August-October 2021. METHODS: The Centers for Disease Control and Prevention collected data from health departments on workplace COVID-19 outbreaks from August through October 2021: the number of workplace outbreaks, by workplace setting, and the total number of cases among workers linked to these outbreaks. Health departments also reported the number of workplaces they assisted for outbreak response, COVID-19 testing, vaccine distribution, or consultation on mitigation strategies. RESULTS: Twenty-three health departments reported a total of 12 660 workplace COVID-19 outbreaks. Among the 12 470 workplace types that were documented, 35.9% (n = 4474) of outbreaks occurred in health care settings, 33.4% (n = 4170) in educational settings, and 30.7% (n = 3826) in other work settings, including non-food manufacturing, correctional facilities, social services, retail trade, and food and beverage stores. Eleven health departments that reported 3859 workplace outbreaks provided information about workplace assistance: 3090 (80.1%) instances of assistance involved consultation on COVID-19 mitigation strategies, 1912 (49.5%) involved outbreak response, 436 (11.3%) involved COVID-19 testing, and 185 (4.8%) involved COVID-19 vaccine distribution. CONCLUSIONS: These findings underscore the continued impact of COVID-19 among workers, the potential for work-related transmission, and the need to apply layered prevention strategies recommended by public health officials.