The ferret has been widely used to study both the pathogenicity and the transmissibility of respiratory viral infections, but little is known about how host-associated microbial communities alter disease susceptibility owing to the lack of a validated model. Here, we compared the safety of injectable versus oral broad-spectrum antibiotics and their efficacy in reducing culturable bacteria from the upper respiratory tract of ferrets before an influenza A virus challenge. Both injectable and oral antibiotic treatment led to drastic reductions in cultivable bacteria from nasal wash specimens when assessed after 7 days of ongoing treatment. Even when extended to 14 days, there were few adverse events noted and no clinically significant bloodwork changes. During challenge with either a high-dose or low-dose A(H1N1)pdm09 influenza A virus inoculum, all animals became productively infected and had generally similar viral titers and clinical measurements, regardless of antibiotic pretreatment. Collectively, these results support that both antibiotic regimens evaluated in laboratory ferrets can be utilized to further characterize host-microbial interactions in the context of respiratory viral infections and other pathogens, including a needle-free approach that may be suitable for studies of high-consequence pathogens in containment laboratory facilities.

Advancement of vaccine candidates that demonstrate protective efficacy in screening studies necessitates detailed safety and immunogenicity investigations in pre-clinical models. A non-spreading Crimean-Congo hemorrhagic fever virus (CCHFV) viral replicon particle (VRP) vaccine was developed for single-dose administration to protect against disease. To date, several studies have supported safety, immunogenicity, and efficacy of the CCHF VRP in multiple highly sensitive murine models of lethal disease, but the VRP had yet to be evaluated in large animals. Here, we performed studies in non-human primates to further evaluate clinical utility of the VRP vaccine. Twelve adult male and female rhesus macaques were vaccinated intramuscularly and followed daily for clinical monitoring. At 3, 7, 14, 21, and 28 days post vaccination, animals were sedated for more detailed clinical assessment; for quantification of vaccine presence in blood and mucosal samples; and for evaluation of hematology, plasma inflammatory markers, and immunity. Consistent with findings in mice, vaccination was well tolerated, with no clinical alterations nor indication of vaccine spread or shedding. In addition, vaccination induced both humoral and cell-mediated responses, with immune profile and kinetics also corroborating data from small animal models. These studies provide key data in non-human primates further supporting development of the VRP for human clinical use.

OBJECTIVES: Vitamin D deficiency is highly prevalent worldwide; however, few large population-based studies have examined occupational risk factors. We examined associations between shift work, work schedule, hours worked, outdoor work, occupation and serum 25-hydroxyvitamin D (25(OH)D) levels in the US working population. METHODS: This cross-sectional study included 8601 workers from the 2005-2010 National Health and Nutrition Examination Survey (NHANES) cycles. NHANES occupational data were supplemented with measures of outdoor work from the Occupational Information Network. Serum 25(OH)D concentration in nanomoles per litre (nmol/L) was categorised as sufficient (≥75), insufficient (50-<75), moderately deficient (30-<50) and severely deficient (<30). Age-adjusted weighted multinomial and binary logistic regression were used to examine associations between work-related factors and vitamin D status with sex-race/ethnicity stratification. RESULTS: Shift workers had higher odds of severe vitamin D deficiency compared with day workers (OR: 1.64, 95% CI 1.22 to 2.19). Compared with those in white-collar occupations, those in natural resources were less likely to be deficient (OR: 0.31, 95% CI 0.19 to 0.52), while those in production were more likely to be deficient (OR: 2.25, 95% CI 1.48 to 3.43). Women working ≥40 hours/week compared with <40 hours/week were more likely to be moderately deficient (OR: 1.30, 95% CI 1.06 to 1.59). Black women working in sales were more likely to be deficient than those in management (OR: 1.53, 95% CI 1.03 to 2.27). Mexican American men working nights had the highest odds of deficiency (OR: 2.64, 95% CI 1.38 to 5.06). CONCLUSIONS: Work-related factors were associated with vitamin D status and there were race/ethnicity and sex differences. Targeted vitamin D screening and supplementation interventions may reduce these disparities.

Timely case notifications following the introduction of an uncommon pathogen, such as mpox, are critical for understanding disease transmission and for developing and implementing effective mitigation strategies. When Massachusetts public health officials notified the Centers for Disease Control and Prevention (CDC) about a confirmed orthopoxvirus case on May 17, 2023, which was later confirmed as mpox at CDC, mpox was not a nationally notifiable disease. Because existing processes for new data collections through the National Notifiable Disease Surveillance System were not well suited for implementation during emergency responses at the time of the mpox outbreak, several interim notification approaches were established to capture case data. These interim approaches were successful in generating daily case counts, monitoring disease transmission, and identifying high-risk populations. However, the approaches also required several data collection approvals by the federal government and the Council for State and Territorial Epidemiologists, the use of four different case report forms, and the establishment of complex data management and validation processes involving data element mapping and record-level de-duplication steps. We summarize lessons learned from these interim approaches to inform and improve case notifications during future outbreaks. These lessons reinforce CDC's Data Modernization Initiative to work in close collaboration with state, territorial, and local public health departments to strengthen case-based surveillance prior to the next public health emergency.

Type of feed is an important consideration in herbivore colony management, yet limited studies report on the effects of diet on common conditions such as urolithiasis in guinea pigs. Urolithiasis is a well-documented cause of lower urinary tract disease in guinea pigs, with calcium carbonate uroliths reported as the predominant calculi formed in the guinea pig urinary tract. A calcium-rich diet has been suggested as a risk factor for of urolithiasis, with numerous commercially available guinea pig diets formulated for adults avoiding ingredients that are higher in calcium. Due to the high incidence of urolithiasis in our strain 13/N guinea pig colony, we conducted a prospective control study following the implementation of dietary changes aimed at improving overall urinary tract health and reducing risk factors for urolithiasis, thus improving colony welfare. A control group was kept on the original ad libitum alfalfa hay-based pellet diet with restricted loose timothy hay (control diet, 14 juveniles and 24 adults). An experimental group was placed on a portioned, 1 oz daily, timothy hay-based pellet diet with ad libitum loose timothy hay (experimental diet, 21 juveniles and 23 adults). Juveniles and adults were followed for a total of 14 and 26 wk, respectively. Longitudinal blood and urine samples were collected to evaluate blood chemistry and urinary parameters, along with weight and body condition scores to assess general health. Overall, dietary changes did not improve parameters associated with improved urinary tract health or reduced risk of urolithiasis; feeding strategy was not found to meaningfully affect calcium crystalluria, urine protein, urine specific gravity, or renal values. These data support alfalfa hay-based pellet or timothy hay-based pellet, when fed with loose timothy hay, as viable options and suggest that practices aimed at reducing dietary calcium by reducing pelleted diet portions are insufficient to mitigate risk factors for urolithiasis in guinea pigs.

OBJECTIVES: Work schedule demands contribute to circadian disruption and may influence health via an inflammatory response. We examined the impact of shiftwork and long work hours on inflammation in a national US sample. METHODS: Participants included 12 487 employed black and white men and women aged ≥45 years enrolled in the REasons for Geographic and Racial Differences in Stroke Study who completed an occupational questionnaire (2011-2013) and clinical examination (2013-2016). Cross-sectional associations between shiftwork and work hours with log-transformed high-sensitivity C reactive protein (CRP) and white blood cell (WBC) count were examined by multiple linear regression analysis, overall and by race-sex subgroups. RESULTS: Overall, rotating shift workers had higher log-CRP concentration compared with day workers (β=0.09, 95% CI:0.02 to 0.16) and findings for WBC were null. Black women had the highest geometric mean CRP (2.82 mg/L), while white men had the highest WBC (6.35×10(9)/L). White men who worked afternoons had higher log-CRP compared with those who worked days (β=0.20, 95% CI: 0.08 to 0.33). Black men engaged in shiftwork <10 years working ≥55 hours/week had higher log-CRP and log-WBC compared with those working days <55 hours/week (β=0.33, 95% CI: 0.02 to 0.64 and β=0.10, 95% CI: 0.003 to 0.19). Among shift workers, non-retired white women working forward and backward shift rotations had higher log-CRP compared with those working forward only (β=0.49, 95% CI: 0.02 to 0.96). CONCLUSIONS: Shift workers had higher inflammatory markers compared with day workers and race-sex disparities should be examined further. These findings highlight a potential biological pathway linking work schedule demands and chronic disease.

As of March 7, 2023, a total of 30,235 confirmed and probable monkeypox (mpox) cases were reported in the United States,(†) predominantly among cisgender men(§) who reported recent sexual contact with another man (1). Although most mpox cases during the current outbreak have been self-limited, cases of severe illness and death have been reported (2-4). During May 10, 2022-March 7, 2023, 38 deaths among persons with probable or confirmed mpox(¶) (1.3 per 1,000 mpox cases) were reported to CDC and classified as mpox-associated (i.e., mpox was listed as a contributing or causal factor). Among the 38 mpox-associated deaths, 94.7% occurred in cisgender men (median age = 34 years); 86.8% occurred in non-Hispanic Black or African American (Black) persons. The median interval from symptom onset to death was 68 days (IQR = 50-86 days). Among 33 decedents with available information, 93.9% were immunocompromised because of HIV. Public health actions to prevent mpox deaths include integrated testing, diagnosis, and early treatment for mpox and HIV, and ensuring equitable access to both mpox and HIV prevention and treatment, such as antiretroviral therapy (ART) (5).

One of the principal uncertainties when estimating population risk of late effects from epidemiological data is that few radiation-exposed cohorts have been followed up to extinction. Therefore, the relative risk model has often been used to estimate radiation-associated risk and to extrapolate risk to the end of life. Epidemiological studies provide evidence that children are generally at higher risk of cancer induction than adults for a given radiation dose. However, the strength of evidence varies by cancer site and questions remain about site-specific age at exposure patterns. For solid cancers, there is a large body of evidence that excess relative risk (ERR) diminishes with increasing age at exposure. This pattern of risk is observed in the Life Span Study (LSS) as well as in other radiation-exposed populations for overall solid cancer incidence and mortality and for most site-specific solid cancers. However, there are some disparities by endpoint in the degree of variation of ERR with exposure age, with some sites (e.g., colon, lung) in the LSS incidence data showing no variation, or even increasing ERR with increasing age at exposure. The pattern of variation of excess absolute risk (EAR) with age at exposure is often similar, with EAR for solid cancers or solid cancer mortality decreasing with increasing age at exposure in the LSS. We shall review the human data from the Japanese LSS cohort, and a variety of other epidemiological data sets, including a review of types of medical diagnostic exposures, also some radiobiological animal data, all bearing on the issue of variations of radiation late-effects risk with age at exposure and with attained age. The paper includes a summary of several oral presentations given in a Symposium on "Age effects on radiation response" as part of the 67th Annual Meeting of the Radiation Research Society, held virtually on 3-6 October 2021.

We examined the association between self-reported sleep quality, sleep duration, and dietary patterns among police officers in the Buffalo Cardio-Metabolic Occupational Stress (BCOPS) study.422 police officers aged 21-74 (2004-2009).We used a cross-sectional study design and obtained sleep quality and duration from responses to the 19-item Pittsburgh Sleep Quality Index. Using 46 energy-adjusted food groups derived from a 125-item food frequency questionnaire, we identified dietary patterns using exploratory factor analysis. Multiple linear regression analysis was used to examine the associations of sleep quality and duration with the derived dietary patterns.We identified major dietary patterns: fruits and vegetables (FV), dairy products, starches and fried foods, and meat and eggs. Individuals with poor sleep quality had a lower average FV score than those with optimal sleep (β [SE] = -0.32 [0.13]; p = .01). Significant interactions were observed between sex and the FV and dairy products dietary patterns, where women with poor sleep quality had a lower mean FV score compared to women with optimal sleep quality (β [SE] = -0.81 [0.29]; p = .01). Women with < 6 hours sleep duration had a lower mean dairy score compared to women with ≥ 7 hours sleep duration (β [SE] = -0.69 [0.29]; p = .02). We did not observe these associations among men.Among women, good sleep quality and long sleep duration were associated with a dietary pattern high in consumption of both fruits and vegetables and dairy products.Abbreviations: BCOPS: Buffalo Cardio-Metabolic Occupational Stress study; BMI: body mass index; FFQ: food frequency questionnaire; FV: fruits and vegetables; KMO: Kaiser-Meyer-Olkin test; MET: metabolic equivalent of task score; PSQI: Pittsburgh Sleep Quality Index questionnaire.

As national flour fortification standards are one of the policy documents developed to guide food fortification, the objective was to compare national, mandatory wheat and maize flour fortification standards to World Health Organization (WHO) fortification guidelines. For each nutrient in 72 countries’ standards, the type of compound was noted as ‘yes’ if it was included in international guidelines or ‘no’ if it was not. Nutrient levels in standards were classified as lower than, equal to, or higher than those suggested by WHO. If another food (i.e. rice, oil, milk) was mass fortified with a nutrient categorized as “lower than,” the classification was changed to “less than recommendation and included in other mass fortified food”. At least 61% of standards included one or more recommended compounds for all nutrients in standards for wheat flour alone (iron, folic acid, vitamin A, zinc, vitamin B12,), wheat and maize flour together (iron, folic acid, vitamin A, zinc, vitamin B12) and maize flour alone (thiamin, riboflavin, niacin, pyridoxine); no country included pantothenic acid in its maize flour standard. For folic acid, vitamin A, thiamin, riboflavin, niacin and pyridoxine, at least 50% of standards (1) met or exceeded WHO suggested levels, or (2) were lower than suggested levels and another food was mass fortified with the specific nutrient in the country. For iron, zinc and vitamin B12, less than 50% of standards met (1) or (2). In conclusion, iron, zinc and vitamin B12 may require the most attention in national fortification standards.

Objective: Methods for developing mobile health (mHealth) interventions are not well described. To guide the development of future mHealth interventions, we describe the application of the agile science framework to iteratively develop an mHealth intervention for adolescent and young adult (AYA) survivors of childhood cancer. Method: We created the AYA STEPS mobile app (AYA Self-management via Texting, Education, and Plans for Survivorship) by modifying and integrating 2 existing programs: an online survivorship care plan (SCP) generator and a text messaging self-management intervention for AYA off treatment. The iterative development process involved 3 stages of agile science: (1) formative work, (2) obtaining feedback about the first AYA STEPS prototype, and (3) pilot testing and finalization of a prototype. We determined preferences of AYA stakeholders as well as discovered and addressed technology problems prior to beginning a subsequent randomized controlled trial. Results: AYA survivors reported that the app and the embedded tailored messages related to their health and SCP were easy to use and generally satisfying and beneficial. Usage data supported that AYA were engaged in the app. Technology glitches were discovered in the pilot and addressed. Conclusion: The iterative development of AYA STEPS was essential for creating a consistent and acceptable end user experience. This study serves as one example of how behavioral scientists may apply agile science to their own mHealth research.

While substance use and sexual risk behaviors among Hispanic youth continue to be public health concerns, few evidence-based preventive interventions are developed for and implemented with Hispanic/Latino youth. The objective of this study was to evaluate the efficacy of eHealth Familias Unidas, an Internet adaptation of an evidence-based family intervention for Hispanics. A randomized controlled trial design (n = 230) was used to evaluate intervention effects on substance use and condomless sex among a sample of Hispanic eighth graders with behavioral problems. Participants were randomized to eHealth Familias Unidas (n = 113) or prevention as usual (n = 117) and assessed at baseline and 3 and 12 months post baseline. We trained mental health school personnel and community mental health professionals to recruit and deliver the Internet-based intervention with Hispanic families. It was hypothesized that, over time, eHealth Familias Unidas would be more efficacious than prevention as usual in reducing drug use (marijuana, cocaine, inhalants, and other drugs), prescription drug use, cigarette use, alcohol use, and condomless sex and that these changes would be mediated by family functioning. Significant intervention effects were found across time for drug use, prescription drug use, and cigarette use. While eHealth Familias Unidas positively affected family functioning, mediation effects were not found. This study demonstrated that family-based eHealth interventions can be efficacious among Hispanic populations when delivered in community settings.

On December 1, 2015, the Puerto Rico Department of Health (PRDH) was notified by a local hospital of a suspected human rabies case. The previous evening, a Puerto Rican man aged 54 years arrived at the emergency department with fever, difficulty swallowing, hand paresthesia, cough, and chest tightness. The next morning the patient left against medical advice but returned to the emergency department in the afternoon with worsening symptoms. The patient's wife reported that he had been bitten by a mongoose during the first week of October, but had not sought care for the bite. While being transferred to the intensive care unit, the patient went into cardiac arrest and died. On December 3, rabies was confirmed from specimens collected during autopsy. PRDH conducted an initial rapid risk assessment, and five family members were started on rabies postexposure prophylaxis (PEP).

On July 16 2015, the Puerto Rico Department of Health (PRDH) was notified of a case of malaria, diagnosed by a hospital parasitology laboratory in a student who had traveled to Punta Cana, Dominican Republic, during late June for a school-organized graduation trip. Malaria is a mosquito-borne parasitic infection, characterized by fever, shaking chills, headaches, muscle pains, nausea, general malaise, and vomiting. Malaria can be clinically difficult to distinguish from other acute febrile illnesses, and a definitive diagnosis requires demonstration of malaria parasites using microscopy or molecular diagnostic tests. The student's initial diagnosis on July 10 was suspected dengue virus infection. Puerto Rico eliminated local malaria transmission during the mid-1950s; however, reintroduction remains a risk because of the presence of a competent vector (Anopheles albimanus) and ease of travel to areas where the disease is endemic, including Hispaniola, the island shared by the Dominican Republic and Haiti, and the only island in the Caribbean with endemic malaria. During 2014, the Dominican Republic reported 496 confirmed malaria cases and four associated deaths; Haiti reported 17,662 confirmed cases and nine deaths. During 2000-2014, Puerto Rico reported a total of 35 imported malaria cases (range = 0-7 per year); three cases were imported from Hispaniola. During June-August 2015, eight confirmed malaria cases among travelers to the Dominican Republic were reported to CDC's National Malaria Surveillance System (CDC, unpublished data, 2015).

An international study was performed by 26 experienced PCR laboratories from 14 countries to assess the performance of duplex quantitative real-time PCR (qPCR) strategies on the basis of TaqMan probes for detection and quantification of parasitic loads in peripheral blood samples from Chagas disease patients. Two methods were studied: Satellite DNA (SatDNA) qPCR and kinetoplastid DNA (kDNA) qPCR. Both methods included an internal amplification control. Reportable range, analytical sensitivity, limits of detection and quantification, and precision were estimated according to international guidelines. In addition, inclusivity and exclusivity were estimated with DNA from stocks representing the different Trypanosoma cruzi discrete typing units and Trypanosoma rangeli and Leishmania spp. Both methods were challenged against 156 blood samples provided by the participant laboratories, including samples from acute and chronic patients with varied clinical findings, infected by oral route or vectorial transmission. kDNA qPCR showed better analytical sensitivity than SatDNA qPCR with limits of detection of 0.23 and 0.70 parasite equivalents/mL, respectively. Analyses of clinical samples revealed a high concordance in terms of sensitivity and parasitic loads determined by both SatDNA and kDNA qPCRs. This effort is a major step toward international validation of qPCR methods for the quantification of T. cruzi DNA in human blood samples, aiming to provide an accurate surrogate biomarker for diagnosis and treatment monitoring for patients with Chagas disease.

Noroviruses are the most common cause of diarrheal disease in the community for all ages [1] and the most common cause of foodborne disease outbreaks in the United States [2]. Despite this ubiquity and high disease burden, there remains substantial uncertainty about some basic features of norovirus infection, epidemiology, and immunity. This knowledge gap partly results from a lack of studies with appropriate designs to examine this rather complicated virus. | Birth cohort studies can be vital for understanding the acquisition of protective immunity against a pathogen. Such studies have led to fundamental improvements in understanding rotavirus, for example, and, in turn, have supported the development of vaccination strategies. In a classic study of a birth cohort in Mexico, Velazquez and colleagues showed that severe disease is restricted to the first 2 infections, that each infection reduces future disease risk, and that homotypic protection comes earlier than protection against other genogroups [3]. The implications for vaccines were clear. Fifteen years after the publication of the Velazquez et al study, rotavirus vaccines are in widespread use and have led to remarkable declines in diarrheal disease in the United States and elsewhere. This is not to say that the Velazquez study single-handedly brought about this chain of events, but rather that it provided insights that were indispensable for the course of subsequent developments.

BACKGROUND: A century after its discovery, Chagas disease still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The purpose of this study was to evaluate the performance of PCR methods in detection of Trypanosoma cruzi DNA by an external quality evaluation. METHODOLOGY/FINDINGS: An international collaborative study was launched by expert PCR laboratories from 16 countries. Currently used strategies were challenged against serial dilutions of purified DNA from stocks representing T. cruzi discrete typing units (DTU) I, IV and VI (set A), human blood spiked with parasite cells (set B) and Guanidine Hidrochloride-EDTA blood samples from 32 seropositive and 10 seronegative patients from Southern Cone countries (set C). Forty eight PCR tests were reported for set A and 44 for sets B and C; 28 targeted minicircle DNA (kDNA), 13 satellite DNA (Sat-DNA) and the remainder low copy number sequences. In set A, commercial master mixes and Sat-DNA Real Time PCR showed better specificity, but kDNA-PCR was more sensitive to detect DTU I DNA. In set B, commercial DNA extraction kits presented better specificity than solvent extraction protocols. Sat-DNA PCR tests had higher specificity, with sensitivities of 0.05-0.5 parasites/mL whereas specific kDNA tests detected 5.10(-3) par/mL. Sixteen specific and coherent methods had a Good Performance in both sets A and B (10 fg/microl of DNA from all stocks, 5 par/mL spiked blood). The median values of sensitivities, specificities and accuracies obtained in testing the Set C samples with the 16 tests determined to be good performing by analyzing Sets A and B samples varied considerably. Out of them, four methods depicted the best performing parameters in all three sets of samples, detecting at least 10 fg/microl for each DNA stock, 0.5 par/mL and a sensitivity between 83.3-94.4%, specificity of 85-95%, accuracy of 86.8-89.5% and kappa index of 0.7-0.8 compared to consensus PCR reports of the 16 good performing tests and 63-69%, 100%, 71.4-76.2% and 0.4-0.5, respectively compared to serodiagnosis. Method LbD2 used solvent extraction followed by Sybr-Green based Real time PCR targeted to Sat-DNA; method LbD3 used solvent DNA extraction followed by conventional PCR targeted to Sat-DNA. The third method (LbF1) used glass fiber column based DNA extraction followed by TaqMan Real Time PCR targeted to Sat-DNA (cruzi 1/cruzi 2 and cruzi 3 TaqMan probe) and the fourth method (LbQ) used solvent DNA extraction followed by conventional hot-start PCR targeted to kDNA (primer pairs 121/122). These four methods were further evaluated at the coordinating laboratory in a subset of human blood samples, confirming the performance obtained by the participating laboratories. CONCLUSION/SIGNIFICANCE: This study represents a first crucial step towards international validation of PCR procedures for detection of T. cruzi in human blood samples.

Infections with rare pathogens are being recognized with increasing frequency in severely immunocompromised patients. As a result of these patients' underlying compromised defenses and susceptibility to atypical organisms, tissue biopsies from patients within this population may demonstrate nonclassical histopathological findings. Here, we describe an unusual granulomatous reaction to gram-positive cocci in the skin of a 52-year-old man undergoing salvage chemotherapy for acute myeloid leukemia. The patient presented with a papular eruption on the arms, trunk, and face and fever; concomitant blood cultures were positive for Rothia mucilaginosa and Streptococcus salivarius. Histologic evaluation revealed a granulomatous dermatitis associated with numerous small, round, predominantly intracellular bacteria. Classically, cutaneous infiltrates associated with coccoid bacterial infections are suppurative and not granulomatous. The intracellular organisms stained positive for Gram, periodic acid-Schiff, and Grocott methenamine silver stains, suggestive of R. mucilaginosa. Rothia mucilaginosa, a component of the oral flora, was first reported as a human pathogen in 1978. Although the majority of cases in the literature have described R. mucilaginosa bacteremia, other reported manifestations include meningitis, endocarditis, pneumonia, osteomyelitis, and peritonitis. To our knowledge, however, only 1 prior report has described a cutaneous manifestation of R. mucilaginosa septicemia, which occurred in a patient with neutropenia. This is the second reported case of an infectious granulomatous dermatitis associated with R. mucilaginosa bacteremia and raises awareness of this unusual histopathological presentation in the setting of a bacterial infection affecting the skin.