A Single-shot ChAd3 Vaccine Provides Protection from Intramuscular and Aerosol Sudan Virus Exposure.

Infection with Sudan virus (SUDV) is characterized by an aggressive disease course with case fatality rates between 40-100% and no approved vaccines or therapeutics. SUDV causes sporadic outbreaks in sub-Saharan Africa, including a recent outbreak in Uganda which has resulted in over 100 confirmed cases in one month. Prior vaccine and therapeutic efforts have historically prioritized Ebola virus (EBOV), leading to a significant gap in available treatments. Two vaccines, Erbevo ® and Zabdeno ® /Mvabea ® , are licensed for use against EBOV but are ineffective against SUDV. Recombinant adenovirus vector vaccines have been shown to be safe and effective against filoviruses, but efficacy depends on having low seroprevalence to the vector in the target human population. For this reason, and because of an excellent safety and immunogenicity profile, ChAd3 was selected as a superior vaccine vector. Here, a ChAd3 vaccine expressing the SUDV glycoprotein (GP) was evaluated for immunogenicity and efficacy in nonhuman primates. We demonstrate that a single dose of ChAd3-SUDV confers acute and durable protection against lethal SUDV challenge with a strong correlation between the SUDV GP-specific antibody titers and survival outcome. Additionally, we show that a bivalent ChAd3 vaccine encoding the GP from both EBOV and SUDV protects against both parenteral and aerosol lethal SUDV challenge. Our data indicate that the ChAd3-SUDV vaccine is a suitable candidate for a prophylactic vaccination strategy in regions at high risk of filovirus outbreaks. One Sentence Summary: A single-dose of ChAd3 vaccine protected macaques from lethal challenge with Sudan virus (SUDV) by parenteral and aerosol routes of exposure.

Priming with Japanese encephalitis virus or yellow fever virus vaccination led to the recognition of multiple flaviviruses without boosting antibody responses induced by an inactivated Zika virus vaccine.

BACKGROUND: Complex patterns of cross-reactivity exist between flaviviruses, yet there is no precise understanding of how sequential exposures due to flavivirus infections or vaccinations impact subsequent antibody responses. METHODS: We investigated whether B cell priming from Japanese encephalitis virus (JEV) or yellow fever virus (YFV) vaccination impacted binding and functional antibody responses to flaviviruses following vaccination with a Zika virus (ZIKV) purified inactivated virus (ZPIV) vaccine. Binding antibody responses and Fc gamma receptor engagement against 23 flavivirus antigens were characterized along with neutralization titres and Fc effector responses in 75 participants at six time points. FINDINGS: We found no evidence that priming with JEV or YFV vaccines improved the magnitude of ZPIV induced antibody responses to ZIKV. Binding antibodies and Fc gamma receptor engagement to ZIKV antigens did not differ significantly across groups, while antibody-dependent cellular phagocytosis (ADCP) and neutralizing responses were higher in the naïve group than in the JEV and YFV primed groups following the second ZPIV immunization (p ≤ 0.02). After a third dose of ZPIV, ADCP responses remained higher in the naïve group than in the primed groups. However, priming affected the quality of the response following ZPIV vaccination, as primed individuals recognized a broader array of flavivirus antigens than individuals in the naïve group. INTERPRETATION: While a priming vaccination to either JEV or YFV did not boost ZIKV-specific responses upon ZIKV vaccination, the qualitatively different responses elicited in the primed groups highlight the complexity in the cross-reactive antibody responses to flaviviruses. FUNDING: This work was supported by a cooperative agreement between The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of the Army [W81XWH-18-2-0040]. The work was also funded in part by the National Institute of Allergy and Infectious Diseases (NIAID) R01AI155983 to SJK and KM.

Coronavirus Antibody Responses before COVID-19 Pandemic, Africa and Thailand.

Prior immune responses to coronaviruses might affect human SARS-CoV-2 response. We screened 2,565 serum and plasma samples collected from 2013 through early 2020, before the COVID-19 pandemic began, from 2,250 persons in 4 countries in Africa (Kenya, Nigeria, Tanzania, and Uganda) and in Thailand, including persons living with HIV-1. We detected IgG responses to SARS-CoV-2 spike (S) subunit 2 protein in 1.8% of participants. Profiling against 23 coronavirus antigens revealed that responses to S, subunit 2, or subunit 1 proteins were significantly more frequent than responses to the receptor-binding domain, S-Trimer, or nucleocapsid proteins (p<0.0001). We observed similar responses in persons with or without HIV-1. Among all coronavirus antigens tested, SARS-CoV-2, SARS-CoV-1, and Middle East respiratory syndrome coronavirus antibody responses were much higher in participants from Africa than in participants from Thailand (p<0.01). We noted less pronounced differences for endemic coronaviruses. Serosurveys could affect vaccine and monoclonal antibody distribution across global populations.

Evaluation of Antibody-Dependent Fc-Mediated Viral Entry, as Compared With Neutralization, in SARS-CoV-2 Infection.

Fc-mediated virus entry has been observed for many viruses, but the characterization of this activity in convalescent plasma against SARS-CoV-2 Variants of Concern (VOC) is undefined. In this study, we evaluated Fc-mediated viral entry (FVE) on FcγRIIa-expressing HEK293 cells in the presence of SARS-CoV-2 convalescent plasma and compared it with SARS-CoV-2 pseudovirus neutralization using ACE2-expressing HEK293 cells. The plasma were collected early in the pandemic from 39 individuals. We observed both neutralization and FVE against the infecting Washington SARS-CoV-2 strain for 31% of plasmas, neutralization, but not FVE for 61% of plasmas, and no neutralization or FVE for 8% of plasmas. Neutralization titer correlated significantly with the plasma dilution at which maximum FVE was observed, indicating Fc-mediated uptake peaked as neutralization potency waned. While total Spike-specific plasma IgG levels were similar between plasma that mediated FVE and those that did not, Spike-specific plasma IgM levels were significantly higher in plasma that did not mediate FVE. Plasma neutralization titers against the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) VOC were significantly lower than titers against the Washington strain, while plasma FVE activity against the VOC was either higher or similar. This is the first report to demonstrate a functional shift in convalescent plasma antibodies from neutralizing and FVE-mediating against the earlier Washington strain, to an activity mediating only FVE and no neutralization activity against the emerging VOC, specifically the Beta (B.1.351) and Gamma (P.1) VOC. It will be important to determine the in vivo relevance of these findings.

Effect of focused protocol on reducing radiation dose for children who require computed tomography for suspected appendicitis.

BACKGROUND: Despite efforts to incorporate ultrasound into the evaluation of children for appendicitis, computed tomography (CT) is often used to aid in its diagnosis. CT scans, however, expose children to a considerable amount of radiation. In 2017, our institution began using a height-based Focused CT protocol for children with suspected appendicitis in need of CT. OBJECTIVE: To compare the radiation dose received by children with suspected appendicitis who underwent a Standard CT of the abdomen and pelvis (CTAP) with that of a Focused CT. METHODS: We conducted a retrospective study of children <18 years who underwent a CT scan for suspected appendicitis (2014-2020). We included all patients whose indication for CT was "appendicitis" or "right lower quadrant pain" and excluded those whose CT scan record lacked a radiation dose report. The effective radiation dose delivered was calculated using the dose-length product from the dose report. We compared the effective dose of those who received a Standard CTAP to those who received a Focused CT. To account for differences in radiation dose over time and by CT scanner, analyses were adjusted for CT dose index volume (CTDIvol) and size-specific dose estimate (SSDE) using quantile regression. RESULTS: A total of 474 patients who underwent CT were included. Prior to CT, 362(76%) had received an ultrasound. In total, 309(65%) patients underwent a Standard CTAP and 165(35%) underwent a Focused CT. The appendix was identified in 259(84%) Standard CTAPs compared to 151(92%) Focused CTs (p = 0.02). Compared to the Standard CTAP, children who received a Focused CT were exposed to a significantly lower effective dose (relative difference: CTDI-adjusted -13%[95% CI:-21,-5]; SSDE-adjusted -14%[95% CI:-24,-3]). CONCLUSIONS: Our height-based Focused CT protocol reduces radiation for children undergoing CT evaluation for suspected appendicitis without sacrificing diagnostic accuracy. Further study is needed to validate these findings at other institutions.

The utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.

Most alphaviruses are mosquito-borne and can cause severe disease in humans and domesticated animals. In North America, eastern equine encephalitis virus (EEEV) is an important human pathogen with case fatality rates of 30-90%. Currently, there are no therapeutics or vaccines to treat and/or prevent human infection. One critical impediment in countermeasure development is the lack of insight into clinically relevant parameters in a susceptible animal model. This study examined the disease course of EEEV in a cynomolgus macaque model utilizing advanced telemetry technology to continuously and simultaneously measure temperature, respiration, activity, heart rate, blood pressure, electrocardiogram (ECG), and electroencephalography (EEG) following an aerosol challenge at 7.0 log10 PFU. Following challenge, all parameters were rapidly and substantially altered with peak alterations from baseline ranged as follows: temperature (+3.0-4.2°C), respiration rate (+56-128%), activity (-15-76% daytime and +5-22% nighttime), heart rate (+67-190%), systolic (+44-67%) and diastolic blood pressure (+45-80%). Cardiac abnormalities comprised of alterations in QRS and PR duration, QTc Bazett, T wave morphology, amplitude of the QRS complex, and sinoatrial arrest. An unexpected finding of the study was the first documented evidence of a critical cardiac event as an immediate cause of euthanasia in one NHP. All brain waves were rapidly (~12-24 hpi) and profoundly altered with increases of up to 6,800% and severe diffuse slowing of all waves with decreases of ~99%. Lastly, all NHPs exhibited disruption of the circadian rhythm, sleep, and food/fluid intake. Accordingly, all NHPs met the euthanasia criteria by ~106-140 hpi. This is the first of its kind study utilizing state of the art telemetry to investigate multiple clinical parameters relevant to human EEEV infection in a susceptible cynomolgus macaque model. The study provides critical insights into EEEV pathogenesis and the parameters identified will improve animal model development to facilitate rapid evaluation of vaccines and therapeutics.

Evaluation of the Cancer Control P.L.A.N.E.T. Web Portal.

CONTEXT: The Cancer Control P.L.A.N.E.T. (P.L.A.N.E.T.) Web portal was designed to ease access to data and evidence-based resources for cancer control practitioners and researchers focused on developing, implementing, and evaluating cancer control programs. OBJECTIVES: To determine usability, applicability, and opportunities to improve the P.L.A.N.E.T. Web portal after significant changes to the portal over time. DESIGN: The National Cancer Institute surveyed and interviewed cancer control professionals to assess factors influencing utilization of P.L.A.N.E.T. Data were collected from May 2017 to June 2018 via partner agencies, electronic publications, and online links. OUTCOME MEASURES: Descriptive statistics with χ test were used to analyze the quantitative data and examine the relationship among variables. Qualitative interviews further informed the quantitative analysis. RESULTS: Of the 724 participants surveyed, 51% were users of P.L.A.N.E.T., with the majority accessing P.L.A.N.E.T. within the last 6 months. Most users felt that P.L.A.N.E.T. effectively met their needs for accessing specific cancer data, identifying evidenced-based programs, and ascertaining details on various cancer topics. There were statistically significant differences in demographic characteristics between users and nonusers of P.L.A.N.E.T., where users were more likely to have more experience in the cancer field, were older in age, and located in southern states. CONCLUSION: Results indicate that P.L.A.N.E.T. is seen as a viable and credible source for cancer control program planning and delivery. A reassessment of P.L.A.N.E.T.'s goals is warranted, which may support reaching out to new audiences, amplifying or removing underutilized resources, and adding additional resources and topics. Consideration for training and tutorials on P.L.A.N.E.T. would benefit partner agencies and build capacity for evidence-based program development.

A high-throughput multiplex assay to characterize flavivirus-specific immunoglobulins.

Genus Flavivirus, which includes 53 virus species, is the leading cause of arthropod-borne diseases in humans. Diagnosis of these viral diseases is complicated by their overlapping epidemiology and clinical manifestations, and the fact that cross-reactive antibody responses are frequently elicited by individuals in response to infection. We developed a bead-based immunoassay to concomitantly profile the isotype and subclass of antibody responses (five isotypes and four subclasses) in parallel with specificity against multiple antigens. Our panel included 22 envelope (E) and non-structural 1 (NS1) proteins of different flaviviruses (Zika (ZIKV), Dengue (DENV), Yellow Fever (YFV), West Nile (WNV), Japanese Encephalitis (JEV) and Tick-Borne Encephalitis (TBEV)) and the envelope protein of Chikungunya virus (CHIKV). Using 54 samples from 40 individuals with ZIKV infection that had been pre-characterized, we identified 1) stronger ZIKV responses in individuals previously exposed to flavivirus compared to flavivirus-naïve individuals; 2) different antibody isotypes depending on the stage of infection: acute, convalescent and late convalescent; 3) cross-reactive responses; and 4) a potential CHIKV infection. The assay had a broad dynamic range (>5 logs) and has the potential to distinguish antigen-specific responses induced by ZIKV infection from cross-reactive responses. The multidimensional data provided by this high-throughput antibody-profiling platform can advance our understanding of the human immune response to flaviviruses as they expand their global reach.

Racial/ethnic minority children recently placed in the child welfare system: the impact of sociodemographic, medical and mental health factors on overweight /obesity.

Children in the child welfare system have greater rates of obesity and are more prone to overweight/obesity as adults compared to other children. There is limited research on how ecological, biological and developmental factors impact the trajectory of overweight/obesity in this group. This retrospective study examined these factors among children entering the child welfare system. Overweight/obesity was highest among children 12-18 years. Children with diagnoses indicative of poor nutrition, and limiting exercise, were more likely to be overweight/obese. Ecological risks often were not disclosed. Barriers to obtaining information to address overweight/obesity reflect challenges to addressing chronic disease more broadly.

Modeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey.

Mosquito-borne and sexual transmission of Zika virus (ZIKV), a TORCH pathogen, recently initiated a series of large epidemics throughout the Tropics. Animal models are necessary to determine transmission risk and study pathogenesis, as well screen antivirals and vaccine candidates. In this study, we modeled mosquito and sexual transmission of ZIKV in the African green monkey (AGM). Following subcutaneous, intravaginal or intrarectal inoculation of AGMs with ZIKV, we determined the transmission potential and infection dynamics of the virus. AGMs inoculated by all three transmission routes exhibited viremia and viral shedding followed by strong virus neutralizing antibody responses, in the absence of clinical illness. All four of the subcutaneously inoculated AGMs became infected (mean peak viremia: 2.9 log10 PFU/mL, mean duration: 4.3 days) and vRNA was detected in their oral swabs, with infectious virus being detected in a subset of these specimens. Although all four of the intravaginally inoculated AGMs developed virus neutralizing antibody responses, only three had detectable viremia (mean peak viremia: 4.0 log10 PFU/mL, mean duration: 3.0 days). These three AGMs also had vRNA and infectious virus detected in both oral and vaginal swabs. Two of the four intrarectally inoculated AGMs became infected (mean peak viremia: 3.8 log10 PFU/mL, mean duration: 3.5 days). vRNA was detected in oral swabs collected from both of these infected AGMs, and infectious virus was detected in an oral swab from one of these AGMs. Notably, vRNA and infectious virus were detected in vaginal swabs collected from the infected female AGM (peak viral load: 7.5 log10 copies/mL, peak titer: 3.8 log10 PFU/mL, range of detection: 5-21 days post infection). Abnormal clinical chemistry and hematology results were detected and acute lymphadenopathy was observed in some AGMs. Infection dynamics in all three AGM ZIKV models are similar to those reported in the majority of human ZIKV infections. Our results indicate that the AGM can be used as a surrogate to model mosquito or sexual ZIKV transmission and infection. Furthermore, our results suggest that AGMs are likely involved in the enzootic maintenance and amplification cycle of ZIKV.

Altered Mental Status as the Primary Presentation of Intussusception in a 3-Month-Old Child Diagnosed by Point-Of-Care Ultrasonography.

BACKGROUND: Intussusception can lead to significant morbidity in affected children secondary to tissue ischemia and necrosis. When a child outside of the classic age range presents with symptoms other than intermittent abdominal pain, the diagnosis of intussusception can be difficult and is often delayed. CASE REPORT: We present the case of a three-month-old boy who presented to the emergency department with waxing and waning mental status and seizure-like activity who was ultimately diagnosed with intussusception. The effective use of bedside ultrasonography, by the attending pediatric radiologist, enabled an interdisciplinary team to explore abdominal etiologies in parallel with testing for more commonly seen causes of altered mental status. This led to an expedited diagnosis and successful definitive management. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Intussusception is a common pediatric emergency encountered by emergency physicians where a timely diagnosis can have a profound impact on patient outcomes. Previous case reports highlight how easily intussusception can be overlooked with this atypical neurologic presentation. Furthermore, because patients with profound altered mental status are often too ill to leave the emergency department for diagnostic testing, bedside abdominal ultrasonography may be helpful in these patients.

Safely surrendered infants in Los Angeles County: A medically vulnerable population.

BACKGROUND: As a means to provide safety for a population at great risk of harm through abandonment, every state in the United States now has laws and practices for the safe relinquishment of newborns and infants. However, there is no national database tracking the population of infants surrendered through such programmes, and few states monitor these numbers. The primary aim of this study was therefore to examine the descriptive characteristics of infants who have been safely surrendered in a large, socio-economically diverse urban area. The secondary aim was to compare them with local population norms to determine whether differences exist and to begin exploring what implications such differences may have for the treatment provided to these infants. METHODS: A retrospective cross-sectional study was conducted among safely surrendered infants. RESULTS: Over half of the infants had medical issues, and the majority of the infants were surrendered in communities characterized by low median income. CONCLUSIONS: Preliminary information highlights potential economic, social, and medical risk factors, suggesting that these infants may require increased monitoring and/or specialized care.

Association of Perceived Maternal Stress During the Perinatal Period With Electroencephalography Patterns in 2-Month-Old Infants.

Importance: Variation in child responses to adversity creates a clinical challenge to identify children most resilient or susceptible to later risk for disturbances in cognition and health. Advances in establishing scalable biomarkers can lead to early identification and mechanistic understanding of the association of early adversity with neurodevelopment. Objectives: To examine whether maternal reports of stress are associated with patterns in resting electroencephalography at 2 months of age and whether unique electroencephalographic profiles associated with risk and resiliency factors can be identified. Design, Setting, and Participants: For this cohort study, a population-based sample of 113 mother-infant dyads was recruited from January 1, 2016, to March 1, 2018, during regularly scheduled pediatric visits before infants were 2 months of age from 2 primary care clinics in Boston, Massachusetts, and Los Angeles, California, that predominantly serve families from low-income backgrounds. Data are reported from a single time point, when infants were aged 2 months, of an ongoing cohort study longitudinally following the mother-infant dyads. Exposures: Maternal reported exposure to stressful life events and perceived stress. Main Outcomes and Measures: Spectral power (absolute and relative) in different frequency bands (Δ, θ, low and high α, ß, and γ) from infant resting electroencephalography (EEG) and EEG profiles across frequency bands determined by latent profile analysis. Results: Of 113 enrolled infants, 70 (mean [SD] age, 2.42 [0.37] months; 35 girls [50%]) provided usable EEG data. In multivariable hierarchical linear regressions, maternal perceived stress was significantly and negatively associated with absolute ß (ß = -0.007; 95% CI, -0.01 to -0.001; semipartial r = -0.25) and γ power (ß = -0.008; 95% CI, -0.01 to -0.002; semipartial r = -0.28). Maternal educational level was significantly and positively associated with power in high α, ß, and γ bands after adjusting for covariates (high school: γ: ß = 0.108; 95% CI, 0.014-0.203; semipartial r = -0.236; associate's degree or higher: high α: ß = 0.133; 95% CI, 0.018-0.248; semipartial r = 0.241; ß: ß = 0.167; 95% CI, 0.055-0.279; semipartial r = 0.309; and γ: ß = 0.183; 95% CI, 0.066-0.299; semipartial r = 0.323). Latent profile analysis identified 2 unique profiles for absolute and relative power. Maternal perceived stress (ß = 0.13; 95% CI, 0.01-0.25; adjusted odds ratio [AOR], 1.14; 95% CI, 1.01-1.28) and maternal educational level (high school: ß = 3.00; 95% CI, 0.35-5.65; AOR, 20.09; 95% CI, 1.42-283.16; associate's degree or higher: ß = 4.12; 95% CI, 1.45-6.79; AOR, 61.56; 95% CI, 4.28-885.01) were each associated with unique profile membership. Conclusions and Relevance: These findings suggest that unique contributions of caregiver stress and maternal educational level on infant neurodevelopment are detectable at 2 months; EEG might be a promising tool to identify infants most susceptible to parental stress and to reveal mechanisms by which neurodevelopment is associated with adversity. Additional studies validating subgroups across larger cohorts with different stressors and at different ages are required before use at the individual level in clinical settings.

Intranasal monkeypox marmoset model: Prophylactic antibody treatment provides benefit against severe monkeypox virus disease.

Concerns regarding outbreaks of human monkeypox or the potential reintroduction of smallpox into an immunological naïve population have prompted the development of animal models and countermeasures. Here we present a marmoset model of monkeypox and smallpox disease utilizing a relevant poxvirus via a natural exposure route. We found that 1000 plaque forming units (PFU) of Monkeypox virus was sufficient to recapitulate smallpox disease, to include an incubation period of approximately 13 days, followed by the onset of rash, and death between 15 and 17 days. Temporally accurate manifestation of viremia and oral shedding were also features. The number of lesions ranged from no lesions to 299, the most reported in a marmoset exposed to a poxvirus. To both evaluate the efficacy of our antibodies and the applicability of the model system, marmosets were prophylactically treated with two monoclonal antibodies, c7D11 and c8A. Of three marmosets, two were completely free of disease and a single marmoset died 8 days after the mock (n = 1) or PBS control(s) (n = 2). Evaluation of the serum levels of the three animals provided a possible explanation to the animal succumbing to disease. Interestingly, more females had lesions (and a greater number of lesions) and lower viral burden (viremia and oral shedding) than males in our studies, suggesting a possible gender effect.

Virus-encoded miRNAs in Ebola virus disease.

Ebola virus (EBOV) is a negative-strand RNA virus that replicates in the cytoplasm and causes an often-fatal hemorrhagic fever. EBOV, like other viruses, can reportedly encode its own microRNAs (miRNAs) to subvert host immune defenses. miRNAs are short noncoding RNAs that can regulate gene expression by hybridizing to multiple mRNAs, and viral miRNAs can enhance viral replication and infectivity by regulating host or viral genes. To date, only one EBOV miRNA has been examined in human infection. Here, we assayed mouse, rhesus macaque, cynomolgus macaque, and human samples infected with three EBOV variants for twelve computationally predicted viral miRNAs using RT-qPCR. Ten miRNAs aligned to EBOV variants and were detectable in the four species during disease with several viral miRNAs showing presymptomatic amplification in animal models. miRNA abundances in both the mouse and nonhuman primate models mirrored the human cohort, with miR-1-5p, miR-1-3p, and miR-T3-3p consistently at the highest levels. These striking similarities in the most abundant miRNAs during infection with different EBOV variants and hosts indicate that these miRNAs are potential valuable diagnostic markers and key effectors of EBOV pathogenesis.

Zika Virus Infection in Syrian Golden Hamsters and Strain 13 Guinea Pigs.

To evaluate potential immunocompetent small animal models of Zika virus (ZIKV) infection, we inoculated Syrian golden hamsters (subcutaneously or intraperitoneally) and strain 13 guinea pigs (intraperitoneally) with Senegalese ZIKV strain ArD 41525 or Philippines ZIKV strain CPC-0740. We did not detect viremia in hamsters inoculated subcutaneously with either virus strain, although some hamsters developed virus neutralizing antibodies. However, we detected statistically significant higher viremias (P = 0.0285) and a higher median neutralization titer (P = 0.0163) in hamsters inoculated intraperitoneally with strain ArD 41525 compared with strain CPC-0740. Furthermore, some hamsters inoculated with strain ArD 41525 displayed mild signs of disease. By contrast, strain 13 guinea pigs inoculated intraperitoneally with either strain did not have detectable viremias and less than half developed virus neutralizing antibodies. Our results support the use of the Syrian golden hamster intraperitoneal model to explore phenotypic variation between ZIKV strains.

Behavioral and mental health risk factor profiles among diverse primary care patients.

Behavioral and mental health risk factors are prevalent among primary care patients and contribute substantially to premature morbidity and mortality and increased health care utilization and costs. Although prior studies have found most adults screen positive for multiple risk factors, limited research has attempted to identify factors that most commonly co-occur, which may guide future interventions. The purpose of this study was to identify subgroups of primary care patients with co-occurring risk factors and to examine sociodemographic characteristics associated with these subgroups. We assessed 12 behavioral health risk factors in a sample of adults (n=1628) receiving care from nine primary care practices across six U.S. states in 2013. Using latent class analysis, we identified four distinct patient subgroups: a 'Mental Health Risk' class (prevalence=14%; low physical activity, high stress, depressive symptoms, anxiety, and sleepiness), a 'Substance Use Risk' class (29%; highest tobacco, drug, alcohol use), a 'Dietary Risk' class (29%; high BMI, poor diet), and a 'Lower Risk' class (27%). Compared to the Lower Risk class, patients in the Mental Health Risk class were younger and less likely to be Latino/Hispanic, married, college educated, or employed. Patients in the Substance Use class tended to be younger, male, African American, unmarried, and less educated. African Americans were over 7 times more likely to be in the Dietary Risk versus Lower Risk class (OR 7.7, 95% CI 4.0-14.8). Given the heavy burden of behavioral health issues in primary care, efficiently addressing co-occurring risk factors in this setting is critical.

Low potential for mechanical transmission of Ebola virus via house flies (Musca domestica).

BACKGROUND: Ebola virus (EBOV) infection results in high morbidity and mortality and is primarily transmitted in communities by contact with infectious bodily fluids. While clinical and experimental evidence indicates that EBOV is transmitted via mucosal exposure, the ability of non-biting muscid flies to mechanically transmit EBOV following exposure to the face had not been assessed. RESULTS: To investigate this transmission route, house flies (Musca domestica Linnaeus) were used to deliver an EBOV/blood mixture to the ocular/nasal/oral facial mucosa of four cynomolgus macaques (Macaca fascicularis Raffles). Following exposure, macaques were monitored for evidence of infection through the conclusion of the study, days 57 and 58. We found no evidence of systemic infection in any of the exposed macaques. CONCLUSIONS: The results of this study indicate that there is a low potential for the mechanical transmission of EBOV via house flies - the conditions in this study were not sufficient to initiate infection.

Factors Related to Implementation and Reach of a Pragmatic Multisite Trial: The My Own Health Report (MOHR) Study.

BACKGROUND: Contextual factors relevant to translating healthcare improvement interventions to different settings are rarely collected systematically. This study articulates a prospective method for assessing and describing contextual factors related to implementation and patient reach of a pragmatic trial in primary care. METHODS: In a qualitative case-series, contextual factors were assessed from the My Own Health Report (MOHR) study, focused on systematic health risk assessments and goal setting for unhealthy behaviors and behavioral health in nine primary care practices. Practice staff interviews and observations, guided by a context template were conducted prospectively at three time points. Patient reach was calculated as percentage of patients completing MOHR of those who were offered MOHR and themes describing contextual factors were summarized through an iterative, data immersion process.These included practice members' motivations towards MOHR, practice staff capacity for implementation, practice information system capacity, external resources to support quality improvement, community linkages, and implementation strategy fit with patient populations. CONCLUSIONS: Systematically assessing contextual factors prospectively throughout implementation of quality improvement initiatives helps translation to other health care settings. Knowledge of contextual factors is essential for scaling up of effective interventions.

High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus.

Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present.