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.

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.

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.

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.

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.

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.

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.

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.

Focused CT using a height-adjusted metric and the umbilicus as a landmark for children undergoing evaluation for appendicitis.

BACKGROUND: Confirmation of appendicitis in children often requires CT. A focused CT scan that is limited to the lower abdomen/pelvis might help to reduce radiation exposure. OBJECTIVE: To determine the position of the appendix relative to the umbilicus and derive a height-adjusted threshold for a focused CT that would identify most appendices. MATERIALS AND METHODS: We conducted a retrospective study of children younger than 18 years who underwent a CT scan for suspected appendicitis. A pediatric radiologist determined the distance from the most cephalad portion of the appendix to the center of the umbilicus. This distance was divided by the child's height to create a ratio for each child. We then assessed the largest of these distance/height ratios ("height constants") as potential height-adjusted thresholds that, when multiplied by any patient's height, would yield the superior threshold for the focused CT scan. Radiation reduction was calculated as percentage decrease in scan length compared to a complete abdominopelvic CT. RESULTS: Of 270 patients whose entire appendix was identified on CT, all were identified within 10.5 cm above the umbilicus. A focused CT using a height constant of 0.07 identified 100% of the appendices visualized on the complete CT scan and resulted in an estimated mean percentage radiation reduction of 27% (standard deviation [SD] +/-4.7). If a height constant of 0.03 was used, 97% of appendices were identified and the estimated radiation reduction was 43% (SD +/-4.3). CONCLUSION: A height-adjusted focused abdominopelvic CT scan might reduce radiation exposure without sacrificing the diagnostic accuracy of the complete CT scan.

Frequency and prioritization of patient health risks from a structured health risk assessment.

PURPOSE: To describe the frequency and patient-reported readiness to change, desire to discuss, and perceived importance of 13 health risk factors in a diverse range of primary care practices. METHODS: Patients (n = 1,707) in 9 primary care practices in the My Own Health Report (MOHR) trial reported general, behavioral, and psychosocial risk factors (body mass index [BMI], health status, diet, physical activity, sleep, drug use, stress, anxiety or worry, and depression). We classified responses as "at risk" or "healthy" for each factor, and patients indicated their readiness to change and/or desire to discuss identified risk factors with providers. Patients also selected 1 of the factors they were ready to change as most important. We then calculated frequencies within and across these factors and examined variation by patient characteristics and across practices. RESULTS: On average, patients had 5.8 (SD = 2.12; range, 0-13) unhealthy behaviors and mental health risk factors. About 55% of patients had more than 6 risk factors. On average, patients wanted to change 1.2 and discuss 0.7 risks. The most common risks were inadequate fruit/vegetable consumption (84.5%) and overweight/obesity (79.6%). Patients were most ready to change BMI (33.3%) and depression (30.7%), and most wanted to discuss depression (41.9%) and anxiety or worry (35.2%). Overall, patients rated health status as most important. CONCLUSIONS: Implementing routine comprehensive health risk assessments in primary care will likely identify a high number of behavioral and psychosocial health risks. By soliciting patient priorities, providers and patients can better manage counseling and behavior change.

Adoption, reach, implementation, and maintenance of a behavioral and mental health assessment in primary care.

PURPOSE: Guidelines recommend screening patients for unhealthy behaviors and mental health concerns. Health risk assessments can systematically identify patient needs and trigger care. This study seeks to evaluate whether primary care practices can routinely implement such assessments into routine care. METHODS: As part of a cluster-randomized pragmatic trial, 9 diverse primary care practices implemented My Own Health Report (MOHR)-an electronic or paper-based health behavior and mental health assessment and feedback system paired with counseling and goal setting. We observed how practices integrated MOHR into their workflows, what additional practice staff time it required, and what percentage of patients completed a MOHR assessment (Reach). RESULTS: Most practices approached (60%) agreed to adopt MOHR. How they implemented MOHR depended on practice resources, informatics capacity, and patient characteristics. Three practices mailed patients invitations to complete MOHR on the Web, 1 called patients and completed MOHR over the telephone, 1 had patients complete MOHR on paper in the office, and 4 had staff help patients complete MOHR on the Web in the office. Overall, 3,591 patients were approached and 1,782 completed MOHR (Reach = 49.6%). Reach varied by implementation strategy with higher reach when MOHR was completed by staff than by patients (71.2% vs 30.2%, P <.001). No practices were able to sustain the complete MOHR assessment without adaptations after study completion. Fielding MOHR increased staff and clinician time an average of 28 minutes per visit. CONCLUSIONS: Primary care practices can implement health behavior and mental health assessments, but counseling patients effectively requires effort. Practices will need more support to implement and sustain assessments.

Understanding the context of health for persons with multiple chronic conditions: moving from what is the matter to what matters.

PURPOSE: An isolated focus on 1 disease at a time is insufficient to generate the scientific evidence needed to improve the health of persons living with more than 1 chronic condition. This article explores how to bring context into research efforts to improve the health of persons living with multiple chronic conditions (MCC). METHODS: Forty-five experts, including persons with MCC, family and friend caregivers, researchers, policy makers, funders, and clinicians met to critically consider 4 aspects of incorporating context into research on MCC: key contextual factors, needed research, essential research methods for understanding important contextual factors, and necessary partnerships for catalyzing collaborative action in conducting and applying research. RESULTS: Key contextual factors involve complementary perspectives across multiple levels: public policy, community, health care systems, family, and person, as well as the cellular and molecular levels where most research currently is focused. Needed research involves moving from a disease focus toward a person-driven, goal-directed research agenda. Relevant research methods are participatory, flexible, multilevel, quantitative and qualitative, conducive to longitudinal dynamic measurement from diverse data sources, sufficiently detailed to consider what works for whom in which situation, and generative of ongoing communities of learning, living and practice. Important partnerships for collaborative action include cooperation among members of the research enterprise, health care providers, community-based support, persons with MCC and their family and friend caregivers, policy makers, and payers, including government, public health, philanthropic organizations, and the business community. CONCLUSION: Consistent attention to contextual factors is needed to enhance health research for persons with MCC. Rigorous, integrated, participatory, multimethod approaches to generate new knowledge and diverse partnerships can be used to increase the relevance of research to make health care more sustainable, safe, equitable and effective, to reduce suffering, and to improve quality of life.

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.

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.

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.

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.

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.

Eliminating health disparities through transdisciplinary research, cross-agency collaboration, and public participation.

Despite efforts to the contrary, disparities in health and health care persist in the United States. To solve this problem, federal agencies representing different disciplines and perspectives are collaborating on a variety of transdisciplinary research initiatives. The most recent of these initiatives was launched in 2006 when the Centers for Disease Control and Prevention's Office of Public Health Research and the Department of Health and Human Services' Office of Minority Health brought together federal partners representing a variety of disciplines to form the Federal Collaboration on Health Disparities Research (FCHDR). FCHDR collaborates with a wide variety of federal and nonfederal partners to support and disseminate research that aims to reduce or eliminate disparities in health and health care. Given the complexity involved in eliminating health disparities, there is a need for more transdisciplinary, collaborative research, and facilitating that research is FCHDR's mission.

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.