Detection of Ebola Virus RNA Through Aerosol Sampling of Animal Biosafety Level 4 Rooms Housing Challenged Nonhuman Primates.

Ebola virus disease is a serious illness of humans and nonhuman primates (NHPs). Direct contact has been shown to be the primary source of Ebola (EBOV) transmission. We used a high-volume air sampler to determine whether EBOV could be detected during 3 independent studies with EBOV-challenged NHPs. Viral RNA was recovered during days 9 and 10 of Study I and days 7 and 8 of Study III. Viral RNA levels were below limits of detection during all other collections. The results demonstrate that the biosafety level 4 (BSL-4) suit protects workers from aerosols in a BSL-4 environment using proper engineering and administrative controls.

Genomic variability of monkeypox virus among humans, Democratic Republic of the Congo.

Monkeypox virus is a zoonotic virus endemic to Central Africa. Although active disease surveillance has assessed monkeypox disease prevalence and geographic range, information about virus diversity is lacking. We therefore assessed genome diversity of viruses in 60 samples obtained from humans with primary and secondary cases of infection from 2005 through 2007. We detected 4 distinct lineages and a deletion that resulted in gene loss in 10 (16.7%) samples and that seemed to correlate with human-to-human transmission (p = 0.0544). The data suggest a high frequency of spillover events from the pool of viruses in nonhuman animals, active selection through genomic destabilization and gene loss, and increased disease transmissibility and severity. The potential for accelerated adaptation to humans should be monitored through improved surveillance.

The COVID-19 experience through the lens of disability Twitter: A qualitative analysis.

PURPOSE: The societal response and constraints of the COVID-19 pandemic reinforced ableism for disabled people who were yet again treated as an afterthought in society. Systemic ableism impacted their well-being, access, and ability to be active members of their community. Disabled experiences and voices must be heard and amplified to improve preparedness and address ableism. Disability Twitter is one avenue where the disability community can collectively listen and support one another. These voices can and should be used to influence policy and practice. This study used Disability Twitter to represent and honor the experiences of the disability community, using the COVID-19 pandemic as a moment in time. RESEARCH METHOD/DESIGN: Qualitative thematic analysis of U.S.-based Twitter posts was conducted using retrospective social media posts. A total of 238 initial tweets from January 1, 2020 and September 30, 2022 were analyzed by the research team. RESULTS: Five themes were observed including ableism, devaluation, worthiness, act of reclaiming, and emotion. Disabled people reported instances of ableism, devaluation, and victimization by individuals, systems, and government entities throughout the pandemic. Disabled individuals utilized Twitter to share their collective experiences, urging society to address and respond to the needs of the disability community. CONCLUSIONS: Using social media to center the perspectives of the disability community can invoke system-wide change and inform policies. Implications for combating systemic ableism and promoting allyship for clinical professionals, research scholars, and educators are provided. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Development of a novel nonhuman primate model for Rift Valley fever.

Rift Valley fever (RVF) virus (RVFV) can cause severe human disease characterized by either acute-onset hepatitis, delayed-onset encephalitis, retinitis and blindness, or a hemorrhagic syndrome. The existing nonhuman primate (NHP) model for RVF utilizes an intravenous (i.v.) exposure route in rhesus macaques (Macaca mulatta). Severe disease in these animals is infrequent, and large cohorts are needed to observe significant morbidity and mortality. To overcome these drawbacks, we evaluated the infectivity and pathogenicity of RVFV in the common marmoset (Callithrix jacchus) by i.v., subcutaneous (s.c.), and intranasal exposure routes to more closely mimic natural exposure. Marmosets were more susceptible to RVFV than rhesus macaques and experienced higher rates of morbidity, mortality, and viremia and marked aberrations in hematological and chemistry values. An overwhelming infection of hepatocytes was a major consequence of infection of marmosets by the i.v. and s.c. exposure routes. Additionally, these animals displayed signs of hemorrhagic manifestations and neurological impairment. Based on our results, the common marmoset model more closely resembles severe human RVF disease and is therefore an ideal model for the evaluation of potential vaccines and therapeutics.

Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo.

Studies on the burden of human monkeypox in the Democratic Republic of the Congo (DRC) were last conducted from 1981 to 1986. Since then, the population that is immunologically naïve to orthopoxviruses has increased significantly due to cessation of mass smallpox vaccination campaigns. To assess the current risk of infection, we analyzed human monkeypox incidence trends in a monkeypox-enzootic region. Active, population-based surveillance was conducted in nine health zones in central DRC. Epidemiologic data and biological samples were obtained from suspected cases. Cumulative incidence (per 10,000 population) and major determinants of infection were compared with data from active surveillance in similar regions from 1981 to 1986. Between November 2005 and November 2007, 760 laboratory-confirmed human monkeypox cases were identified in participating health zones. The average annual cumulative incidence across zones was 5.53 per 10,000 (2.18-14.42). Factors associated with increased risk of infection included: living in forested areas, male gender, age < 15, and no prior smallpox vaccination. Vaccinated persons had a 5.2-fold lower risk of monkeypox than unvaccinated persons (0.78 vs. 4.05 per 10,000). Comparison of active surveillance data in the same health zone from the 1980s (0.72 per 10,000) and 2006-07 (14.42 per 10,000) suggests a 20-fold increase in human monkeypox incidence. Thirty years after mass smallpox vaccination campaigns ceased, human monkeypox incidence has dramatically increased in rural DRC. Improved surveillance and epidemiological analysis is needed to better assess the public health burden and develop strategies for reducing the risk of wider spread of infection.

In vitro inhibition of monkeypox virus production and spread by Interferon-ß.

BACKGROUND: The Orthopoxvirus genus contains numerous virus species that are capable of causing disease in humans, including variola virus (the etiological agent of smallpox), monkeypox virus, cowpox virus, and vaccinia virus (the prototypical member of the genus). Monkeypox is a zoonotic disease that is endemic in the Democratic Republic of the Congo and is characterized by systemic lesion development and prominent lymphadenopathy. Like variola virus, monkeypox virus is a high priority pathogen for therapeutic development due to its potential to cause serious disease with significant health impacts after zoonotic, accidental, or deliberate introduction into a naïve population. RESULTS: The purpose of this study was to investigate the prophylactic and therapeutic potential of interferon-ß (IFN-ß) for use against monkeypox virus. We found that treatment with human IFN-ß results in a significant decrease in monkeypox virus production and spread in vitro. IFN-ß substantially inhibited monkeypox virus when introduced 6-8 h post infection, revealing its potential for use as a therapeutic. IFN-ß induced the expression of the antiviral protein MxA in infected cells, and constitutive expression of MxA was shown to inhibit monkeypox virus infection. CONCLUSIONS: Our results demonstrate the successful inhibition of monkeypox virus using human IFN-ß and suggest that IFN-ß could potentially serve as a novel safe therapeutic for human monkeypox disease.

Mobile Cricothyrotomy Simulation Cart Improves Anesthesia Providers' Confidence, Technical Skills, and Procedure Time.

Cricothyrotomy is an invasive airway used in "cannot intubate, cannot ventilate" events and can be taught using simulation. A mobile cricothyrotomy simulation for 66 anesthesia providers included an initial cricothyrotomy attempt (pretest), education, practice and feedback, and a second cricothyrotomy attempt (posttest). Provider confidence, skills, and procedure time were measured. Comparison of the posttest to the pretest showed significant improvement in: (a) provider confidence scores (Z = 7.01, P < .001), (b) technical skills (Global Rating Scale for Cricothyrotomy: Z = 7.05, P <.001; Checklist for Cricothyrotomy Performance: Z = 7.07, P < .001), and (c) procedure time (Z = 2.68, P = .007). The mobile cricothyrotomy simulation significantly improved anesthesia providers' confidence, cricothyrotomy skills, and procedure time.

Effects of a blend of essential oils, medium-chain fatty acids, and a toxin-adsorbing mineral on diarrhea and gut microbiome of weanling pigs experimentally infected with a pathogenic Escherichia coli.

A proprietary antimicrobial feed additive comprised of essential oils, medium-chain fatty acids, and a toxin-adsorbing mineral showed promising bacteriostatic and bactericidal effects in vitro. This study investigated the impacts of supplementing this blend on growth, gut microbiome, and enteric disease resilience in weaned pigs experimentally challenged with an enterotoxigenic Escherichia coli (ETEC). Thirty-six weanling pigs (6.88 ±â€…0.30 kg body weight) blocked by weight and gender were assigned to one of three dietary treatments: control or dietary supplementation with 0.25% or 0.50% of the antimicrobial blend. This study lasted 28 d with 7 d before and 21 d after the first ETEC inoculation (day 0). All pigs were orally inoculated with 1010 CFU F18 + ETEC/3-mL dose for 3 consecutive days. Growth performance data and diarrhea scores were recorded throughout the experiment. Fecal samples collected on days -7, 0, 7, and 21 post first inoculation (PI), and ileal digesta and mucosal tissue collected on day 21 PI were further analyzed for gut microbiome using 16S rRNA sequencing. All data, except for frequency of diarrhea and gut microbiome, were analyzed by ANOVA using the PROC MIXED of SAS. The chi-square test was used for analyzing frequency of diarrhea. Gut microbiome data were analyzed using QIIME2 and visualized using the R program. Dietary supplementation of 0.25% or 0.5% of the antimicrobial blend increased (P < 0.05) feed efficiency on days 14 to 21 PI of ETEC and reduced (P < 0.05) frequency of diarrhea during the study. Compared with the control group, adding 0.5% dietary antimicrobial blend increased (P < 0.05) relative abundance of Firmicutes but reduced (P < 0.05) Bacteroidetes and Proteobacteria in feces on day 7 PI. Pigs that received the antimicrobial blend also had higher (P < 0.05) relative abundance of Lactobacillaceae, but lower (P < 0.05) relative abundance of Enterobacteriaceae in feces on day 7 PI than pigs in control. In conclusion, supplementation of this antimicrobial blend at 0.5% reduced incidence of severe diarrhea in weaned pigs challenged with F18 ETEC and enhanced feed efficiency of weaned pigs at the last week of the experiment. Supplementation of this antimicrobial blend also modified the microbiota diversity in feces and ileal mucosa of weaned pigs.

This experiment aims to investigate an antimicrobial blend consisting of essential oils, medium-chain fatty acids, and a toxin-adsorbing mineral on diarrhea, growth performance, and gut microbiome of newly weaned pigs experimentally infected with a pathogenic Escherichia coli (F18 E. coli). A total of 36 weaned pigs were randomly allotted to one of three dietary treatments: (1) a complex control diet that met the nutrient requirement of weaned pigs; (2) supplementing 0.25% of the antimicrobial blend; and (3) 0.50% of the antimicrobial blend. The experiment lasted 28 d with 7 d adaptation and 21 d after the first F18 E. coli inoculation. Results of this experiment demonstrate that supplementation of this antimicrobial blend enhanced disease resistance of weaned pigs, as indicated by reduced frequency of diarrhea during the entire experimental period. An improved feed efficiency was also observed in pigs supplemented with antimicrobial blend at the last week of the experiment. In addition, feces collected on day 7 post-E. coli inoculation contained relatively more Lactobacillaceae but less Enterobacteriaceae when pigs were supplemented with this antimicrobial blend. In conclusion, supplementation of antimicrobial blend could reduce diarrhea of E. coli-infected pigs and modify fecal microbiome of weaned pigs during the peak of E. coli infection.

Detailed analysis of the pathologic hallmarks of Nipah virus (Malaysia) disease in the African green monkey infected by the intratracheal route.

Disease associated with Nipah virus infection causes a devastating and often fatal spectrum of syndromes predominated by both respiratory and neurologic conditions. Additionally, neurologic sequelae may manifest months to years later after virus exposure or apparent recovery. In the two decades since this disease emerged, much work has been completed in an attempt to understand the pathogenesis and facilitate development of medical countermeasures. Here we provide detailed organ system-specific pathologic findings following exposure of four African green monkeys to 2.41×105 pfu of the Malaysian strain of Nipah virus. Our results further substantiate the African green monkey as a model of human Nipah virus disease, by demonstrating both the respiratory and neurologic components of disease. Additionally, we demonstrate that a chronic phase of disease exists in this model, that may provide an important opportunity to study the enigmatic late onset and relapse encephalitis as it is described in human disease.

A SARS-CoV-2 Spike Ferritin Nanoparticle Vaccine Is Protective and Promotes a Strong Immunological Response in the Cynomolgus Macaque Coronavirus Disease 2019 (COVID-19) Model.

The COVID-19 pandemic has had a staggering impact on social, economic, and public health systems worldwide. Vaccine development and mobilization against SARS-CoV-2 (the etiologic agent of COVID-19) has been rapid. However, novel strategies are still necessary to slow the pandemic, and this includes new approaches to vaccine development and/or delivery that will improve vaccination compliance and demonstrate efficacy against emerging variants. Here, we report on the immunogenicity and efficacy of a SARS-CoV-2 vaccine comprising stabilized, pre-fusion spike protein trimers displayed on a ferritin nanoparticle (SpFN) adjuvanted with either conventional aluminum hydroxide or the Army Liposomal Formulation QS-21 (ALFQ) in a cynomolgus macaque COVID-19 model. Vaccination resulted in robust cell-mediated and humoral responses and a significant reduction in lung lesions following SARS-CoV-2 infection. The strength of the immune response suggests that dose sparing through reduced or single dosing in primates may be possible with this vaccine. Overall, the data support further evaluation of SpFN as a SARS-CoV-2 protein-based vaccine candidate with attention to fractional dosing and schedule optimization.

Effects of team sports on anxiety, depression, perceived stress, and sleep quality in college students.

OBJECTIVE: This study aimed to assess the effectiveness of team sports on alleviating depression, anxiety, perceived stress, and poor sleep quality in college students. Participants: Undergraduates (n = 291) from a major public university in China. Methods: A 12-week quasi-experimental study was conducted. Students were enrolled in team sports classes (n = 138, experimental group) and aerobic dance classes (n = 153, comparison group). Data was collected via questionnaires at pre and post-test. Results: Results indicated significant improvement in depression and sleep quality for college students over time (p < .05). Depression levels decreased significantly more for team sports group (p < .05) compared to aerobic dance group. Results showed no significant differences in anxiety or perceived stress between the two groups over time (p > .05). Conclusions: Team sports may help reduce depression and poor sleep quality in college students. However, physical activity alone may not help improve anxiety and perceived stress.

Delayed Disease in Cynomolgus Macaques Exposed to Ebola Virus by an Intranasal Route.

Ebola virus remains a significant public health concern due to high morbidity and mortality rates during recurrent outbreaks in endemic areas. Therefore, the development of countermeasures against Ebola virus remains a high priority, and requires the availability of appropriate animal models for efficacy evaluations. The most commonly used nonhuman primate models for efficacy evaluations against Ebola virus utilize the intramuscular or aerosol route of exposure. Although clinical disease signs are similar to human cases, disease progression in these models is much more rapid, and this can pose significant hurdles for countermeasure evaluations. The objective of the present study was to evaluate the Ebola virus disease course that arises after cynomolgus macaques are exposed to Ebola virus by a mucosal route (the intranasal route). Two different doses (10 pfu and 100 pfu) and delivery methodologies (drop-wise and mucosal atomization device) were evaluated on this study. Differences in clinical disease between dose and delivery groups were not noted. However, a delayed disease course was identified for approximately half of the animals on study, and this delayed disease was dose and administration method independent. Therefore, it appears that mucosal exposure with Ebola virus results in a disease course in cynomolgus macaques that more accurately replicates that which is documented for human cases. In summary, the data presented support the need for further development of this model as a possible alternative to parenteral and small-particle aerosol models for the study of human Ebola virus disease and for countermeasure evaluations.

Detecting Pathogen Exposure During the Non-symptomatic Incubation Period Using Physiological Data: Proof of Concept in Non-human Primates.

Background and Objectives: Early warning of bacterial and viral infection, prior to the development of overt clinical symptoms, allows not only for improved patient care and outcomes but also enables faster implementation of public health measures (patient isolation and contact tracing). Our primary objectives in this effort are 3-fold. First, we seek to determine the upper limits of early warning detection through physiological measurements. Second, we investigate whether the detected physiological response is specific to the pathogen. Third, we explore the feasibility of extending early warning detection with wearable devices. Research Methods: For the first objective, we developed a supervised random forest algorithm to detect pathogen exposure in the asymptomatic period prior to overt symptoms (fever). We used high-resolution physiological telemetry data (aortic blood pressure, intrathoracic pressure, electrocardiograms, and core temperature) from non-human primate animal models exposed to two viral pathogens: Ebola and Marburg (N = 20). Second, to determine reusability across different pathogens, we evaluated our algorithm against three independent physiological datasets from non-human primate models (N = 13) exposed to three different pathogens: Lassa and Nipah viruses and Y. pestis. For the third objective, we evaluated performance degradation when the algorithm was restricted to features derived from electrocardiogram (ECG) waveforms to emulate data from a non-invasive wearable device. Results: First, our cross-validated random forest classifier provides a mean early warning of 51 ± 12 h, with an area under the receiver-operating characteristic curve (AUC) of 0.93 ± 0.01. Second, our algorithm achieved comparable performance when applied to datasets from different pathogen exposures - a mean early warning of 51 ± 14 h and AUC of 0.95 ± 0.01. Last, with a degraded feature set derived solely from ECG, we observed minimal degradation - a mean early warning of 46 ± 14 h and AUC of 0.91 ± 0.001. Conclusion: Under controlled experimental conditions, physiological measurements can provide over 2 days of early warning with high AUC. Deviations in physiological signals following exposure to a pathogen are due to the underlying host's immunological response and are not specific to the pathogen. Pre-symptomatic detection is strong even when features are limited to ECG-derivatives, suggesting that this approach may translate to non-invasive wearable devices.

Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques.

Ebola virus disease (EVD) is a serious global health concern because case fatality rates are approximately 50% due to recent widespread outbreaks in Africa. Well-defined nonhuman primate (NHP) models for different routes of Ebola virus exposure are needed to test the efficacy of candidate countermeasures. In this natural history study, four rhesus macaques were challenged via aerosol with a target titer of 1000 plaque-forming units per milliliter of Ebola virus. The course of disease was split into the following stages for descriptive purposes: subclinical, clinical, and decompensated. During the subclinical stage, high levels of venous partial pressure of carbon dioxide led to respiratory acidemia in three of four of the NHPs, and all developed lymphopenia. During the clinical stage, all animals had fever, viremia, and respiratory alkalosis. The decompensatory stage involved coagulopathy, cytokine storm, and liver and renal injury. These events were followed by hypotension, elevated lactate, metabolic acidemia, shock and mortality similar to historic intramuscular challenge studies. Viral loads in the lungs of aerosol-exposed animals were not distinctly different compared to previous intramuscularly challenged studies. Differences in the aerosol model, compared to intramuscular model, include an extended subclinical stage, shortened clinical stage, and general decompensated stage. Therefore, the shortened timeframe for clinical detection of the aerosol-induced disease can impair timely therapeutic administration. In summary, this nonhuman primate model of aerosol-induced EVD characterizes early disease markers and additional details to enable countermeasure development.

Natural history of disease in cynomolgus monkeys exposed to Ebola virus Kikwit strain demonstrates the reliability of this non-human primate model for Ebola virus disease.

Filoviruses (Family Filoviridae genera Ebolavirus and Marburgvirus) are negative-stranded RNA viruses that cause severe health effects in humans and non-human primates, including death. Except in outbreak settings, vaccines and other medical countermeasures against Ebola virus (EBOV) will require testing under the FDA Animal Rule. Multiple vaccine candidates have been evaluated using cynomolgus monkeys (CM) exposed to EBOV Kikwit strain. To the best of our knowledge, however, animal model development data supporting the use of CM in vaccine research have not been submitted to the FDA. This study describes a large CM database (122 CM, 62 female and 60 male, age 2 to 9 years) and demonstrates the consistency of the CM model through time to death models and descriptive statistics. CMs were exposed to EBOV doses of 0.1 to 100,000 PFU in 33 studies conducted at three Animal Biosafety Level 4 facilities, by three exposure routes. Time to death was modeled using Cox proportional hazards models with a frailty term that incorporated study-to-study variability. Despite significant differences attributed to exposure variables, all CMs exposed to the 100 to 1,000 pfu doses commonly used in vaccine studies died or met euthanasia criteria within 21 days of exposure, median 7 days, 93% between 5 and 12 days of exposure. Moderate clinical signs were observed 4 to 5 days after exposure and preceded death or euthanasia by approximately one day. Viremia was detected within a few days of infection. Hematology indices were indicative of viremia and the propensity for hemorrhage with progression of Ebola viremia. Changes associated with coagulation parameters and platelets were consistent with coagulation disruption. Changes in leukocyte profiles were indicative of an acute inflammatory response. Increased liver enzymes were observed shortly after exposure. Taken together, these factors suggest that the cynomolgus monkey is a reliable animal model for human disease.

Development of a coronavirus disease 2019 nonhuman primate model using airborne exposure.

Airborne transmission is predicted to be a prevalent route of human exposure with SARS-CoV-2. Aside from African green monkeys, nonhuman primate models that replicate airborne transmission of SARS-CoV-2 have not been investigated. A comparative evaluation of COVID-19 in African green monkeys, rhesus macaques, and cynomolgus macaques following airborne exposure to SARS-CoV-2 was performed to determine critical disease parameters associated with disease progression, and establish correlations between primate and human COVID-19. Respiratory abnormalities and viral shedding were noted for all animals, indicating successful infection. Cynomolgus macaques developed fever, and thrombocytopenia was measured for African green monkeys and rhesus macaques. Type II pneumocyte hyperplasia and alveolar fibrosis were more frequently observed in lung tissue from cynomolgus macaques and African green monkeys. The data indicate that, in addition to African green monkeys, macaques can be successfully infected by airborne SARS-CoV-2, providing viable macaque natural transmission models for medical countermeasure evaluation.

Vaccinia virus protein F12 associates with intracellular enveloped virions through an interaction with A36.

Vaccinia virus is the prototypical member of the family Poxviridae. Three morphologically distinct forms are produced during infection: intracellular mature virions (IMV), intracellular enveloped virions (IEV), and extracellular enveloped virions (EEV). Two viral proteins, F12 and A36, are found exclusively on IEV but not on IMV and EEV. Analysis of membranes from infected cells showed that F12 was only associated with membranes and is not an integral membrane protein. A yeast two-hybrid assay revealed an interaction between amino acids 351 to 458 of F12 and amino acids 91 to 111 of A36. We generated a recombinant vaccinia virus that expresses an F12, which lacks residues 351 to 458. Characterization of this recombinant revealed a small-plaque phenotype and a subsequent defect in virus release similar to a recombinant virus that had F12L deleted. In addition, F12 lacking residues 351 to 458 was unable to associate with membranes in infected cells. These results suggest that F12 associates with IEV through an interaction with A36 and that this interaction is critical for the function of F12 during viral egress.

Nipah virus persists in the brains of nonhuman primate survivors.

Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes highly lethal henipavirus encephalitis in humans. Survivors develop various neurologic sequelae, including late-onset and relapsing encephalitis, several months up to several years following initial infection. However, the underlying pathology and disease mechanisms of persistent neurologic complications remain unknown. Here, we demonstrate persistent NiV infection in the brains of grivets that survived experimental exposure to NiV. Encephalitis affected the entire brains, with the majority of NiV detected in the neurons and microglia of the brainstems, cerebral cortices, and cerebella. We identified the vascular endothelium in the brain as an initial target of NiV infection during the acute phase of disease, indicating a primary path of entry for NiV into the brain. Notably, we were unable to detect NiV anywhere else except the brains in the examined survivors. Our findings indicate that late-onset and relapsing encephalitis of NiV in human survivors may be due to viral persistence in the brain and shed light on the pathogenesis of chronic henipavirus encephalitis.

Comparison of methods to measure heart size using noncontrast-enhanced computed tomography: correlation with left ventricular mass.

OBJECTIVE: Left ventricular (LV) mass is a useful independent predictor of cardiovascular events. We sought to develop a new correlate of LV mass using noncontrast-enhanced cardiac computed tomography (NCE-CCT). METHODS: We assessed 22 different ventricular measurements made with NCE-CCT in 60 participants in the Multi-Ethnic Study of Atherosclerosis. The primary outcome was the correlation between the NCE-CCT measurements and magnetic resonance imaging (MRI)-derived LV mass. RESULTS: Correlation coefficients (r) for the 22 NCE-CCT techniques in comparison to MRI-derived LV mass ranged from 0.12 to 0.80, with 14 of the 22 techniques having r > 0.7. The highest correlation was achieved using the modified Simpson Rule method to determine the biventricular volume (r = 0.80; P < 0.001). Interrater reliability was good, with intraclass correlation coefficients of 0.84 to 0.90 for the best (r > 0.75) NCE-CCT methods. CONCLUSIONS: Noncontrast-enhanced cardiac computed tomography measurements of both biventricular volume and LV volume correlated well with MRI-derived LV mass in a population free of clinical cardiovascular disease.

Attenuation and efficacy of live-attenuated Rift Valley fever virus vaccine candidates in non-human primates.

Rift Valley fever virus (RVFV) is an important mosquito-borne veterinary and human pathogen that has caused large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Currently, no licensed vaccine or therapeutics exists to treat this potentially deadly disease. The explosive nature of RVFV outbreaks and the severe consequences of its accidental or intentional introduction into RVFV-free areas provide the impetus for the development of novel vaccine candidates for use in both livestock and humans. Rationally designed vaccine candidates using reverse genetics have been used to develop deletion mutants of two known RVFV virulence factors, the NSs and NSm genes. These recombinant viruses were demonstrated to be protective and immunogenic in rats, mice, and sheep, without producing clinical illness in these animals. Here, we expand upon those findings and evaluate the single deletion mutant (ΔNSs rRVFV) and double deletion mutant (ΔNSs-ΔNSm rRVFV) vaccine candidates in the common marmoset (Callithrix jacchus), a non-human primate (NHP) model resembling severe human RVF disease. We demonstrate that both the ΔNSs and ΔNSs-ΔNSm rRVFV vaccine candidates were found to be safe and immunogenic in the current study. The vaccinated animals received a single dose of vaccine that led to the development of a robust antibody response. No vaccine-induced adverse reactions, signs of clinical illness or infectious virus were detected in the vaccinated marmosets. All vaccinated animals that were subsequently challenged with RVFV were protected against viremia and liver disease. In summary, our results provide the basis for further development of the ΔNSs and ΔNSs-ΔNSm rRVFV as safe and effective human RVFV vaccines for this significant public health threat.