Deletion of an immune evasion gene, steD, from a live Salmonella enterica serovar Typhimurium vaccine improves vaccine responses in aged mice.

Introduction: Non-typhoidal Salmonella (NTS) generally causes self-limiting gastroenteritis. However, older adults (≥65 years) can experience more severe outcomes from NTS infection. We have previously shown that a live attenuated S. Typhimurium vaccine, CVD 1926 (I77 ΔguaBA ΔclpP ΔpipA ΔhtrA), was immunogenic in adult but not aged mice. Here we describe modification of CVD 1926 through deletion of steD, a Salmonella effector responsible for host immune escape, which we hypothesized would increase immunogenicity in aged mice. Methods: Mel Juso and/or mutuDC cells were infected with S. Typhimurium I77, CVD 1926, and their respective steD mutants, and the MHC-II levels were evaluated. Aged (18-month-old) C57BL/6 mice received two doses of PBS, CVD 1926, or CVD 1926 ΔsteD perorally (109 CFU) and the number of FliC-specific CD4+ T cells were determined. Lastly, aged C57BL/6 mice received three doses of PBS, CVD 1926, or CVD 1926 ΔsteD perorally (109 CFU) and then were challenged perorally with wild-type S. Typhimurium SL1344 (108 CFU). These animals were also evaluated for antibody responses. Results: MHC-II induction was higher in cells treated with steD mutants, compared to their respective parental strains. Compared to PBS-vaccinated mice, CVD 1926 ΔsteD elicited significantly more FliC-specific CD4+ T cells in the Peyer's Patches. There were no significant differences in FliC-specific CD4+ T cells in the Peyer's patches or spleen of CVD 1926- versus PBS-immunized mice. CVD 1926 and CVD 1926 ΔsteD induced similar serum and fecal anti-core and O polysaccharide antibody titers after three doses. After two immunizations, the proportion of seroconverters for CVD 1926 ΔsteD was 83% (10/12) compared to 42% (5/12) for CVD 1926. Compared to PBS-immunized mice, mice immunized with CVD 1926 ΔsteD had significantly lower S. Typhimurium counts in the spleen, cecum, and small intestine upon challenge. In contrast, there were no differences in bacterial loads in the tissues of PBS-vaccinated and CVD 1926-immunized animals. Conclusion: These data suggest that the steD deletion enhanced the immunogenicity of our live attenuated S. Typhimurium vaccine. Deletion of immune evasion genes could be a potential strategy to improve the immunogenicity of live attenuated vaccines in older adults.

Soil geochemistry and constraint of tree seedlings immediately after germination on Macrotermes termite mounds in the Kruger National Park, South Africa.

Macrotermes termite mounds in the Kruger National Park occupy a significant part of the savanna landscapes, occurring at densities of up to 70 km-2 and often exceeding 10 m in width and 4 m in height. The mounds are usually devoid of trees, but have dense grass cover in wet years. As a result, these mounds form large patches of grassland amongst the wooded savanna. To our knowledge, it is not known why trees are largely excluded from the mounds. We analysed soil surface nutrient concentrations on and off mounds (0-2 cm deep, n = 80) to ascertain whether the availability of nutrients could be influencing competition between grasses and tree seedlings. The results showed that potential deficiencies in P, Ca, Cu, Zn and B in soils off the mounds are likely to be constraining plant growth. Notably, only B, with an average concentration of 0.19 mg kg-1, was likely to be limiting plant growth on the mounds. Notwithstanding likely interactions with herbivory and fire, we hypothesise that because grasses are far less susceptible to deficiencies of B than dicotyledonous trees, it is likely that grass competition with tree seedlings is considerably greater on mounds than off mounds.

Social Justice, Community Engagement, and Undergraduate STEM Education: Participatory Science as a Teaching Tool.

Social justice is increasingly being seen as relevant to the science curriculum. We examine the intersection of participatory science, social justice, and higher education in the United States to investigate how instructors can teach about social justice and enhance collaborations to work toward enacting social justice. Participatory science approaches, like those that collect data over large geographic areas, can be particularly useful for teaching students about social justice. Conversely, local-scale approaches that integrate students into community efforts can create powerful collaborations to help facilitate social justice. We suggest a variety of large-scale databases, platforms, and portals that could be used as starting points to address a set of learning objectives about social justice. We also describe local-scale participatory science approaches with a social justice focus, developed through academic and community partnerships. Considerations for implementing participatory science with undergraduates are discussed, including cautions about the necessary time investment, cultural competence, and institutional support. These approaches are not always appropriate but can provide compelling learning experiences in the correct circumstances.

Chronic diarrhoea and ichthyosis vulgaris: a rare presentation of Hodgkin's lymphoma.

A man in his 30s presented with several months of non-bloody diarrhoea and nausea along with conjunctivitis, diffuse ichthyosis and cellulitis in the setting of progressive neck swelling. He was ultimately diagnosed with nodular sclerosing Hodgkin's lymphoma after undergoing a broad infectious, rheumatological and neoplastic workup. This represents a rare presentation of classic Hodgkin's lymphoma and demonstrates the known alteration of cellular immunity in Hodgkin's lymphoma alongside manifestations of the profound inflammatory state associated with the disease. The patient was initiated on chemotherapy and many of his symptoms resolved. Hodgkin's lymphoma may present as a multisystemic cascade of symptoms and should be high on the differential diagnosis for a patient with lymphadenopathy and associated infectious, gastrointestinal and cutaneous symptoms.

NSF DARE-transforming modeling in neurorehabilitation: a patient-in-the-loop framework.

In 2023, the National Science Foundation (NSF) and the National Institute of Health (NIH) brought together engineers, scientists, and clinicians by sponsoring a conference on computational modelling in neurorehabiilitation. To facilitate multidisciplinary collaborations and improve patient care, in this perspective piece we identify where and how computational modelling can support neurorehabilitation. To address the where, we developed a patient-in-the-loop framework that uses multiple and/or continual measurements to update diagnostic and treatment model parameters, treatment type, and treatment prescription, with the goal of maximizing clinically-relevant functional outcomes. This patient-in-the-loop framework has several key features: (i) it includes diagnostic and treatment models, (ii) it is clinically-grounded with the International Classification of Functioning, Disability and Health (ICF) and patient involvement, (iii) it uses multiple or continual data measurements over time, and (iv) it is applicable to a range of neurological and neurodevelopmental conditions. To address the how, we identify state-of-the-art and highlight promising avenues of future research across the realms of sensorimotor adaptation, neuroplasticity, musculoskeletal, and sensory & pain computational modelling. We also discuss both the importance of and how to perform model validation, as well as challenges to overcome when implementing computational models within a clinical setting. The patient-in-the-loop approach offers a unifying framework to guide multidisciplinary collaboration between computational and clinical stakeholders in the field of neurorehabilitation.

Exploring the impact of pediatric short bowel syndrome on parent well-being using a disease-specific pilot survey.

BACKGROUND: Children with short bowel syndrome (SBS) have complex care needs, most of which are met in the home by family caregivers who may experience a range of stressors unique to this experience. Prior research suggests that parents of children with SBS have poorer health-related quality of life than peers parenting children without health needs, but the mechanisms shaping parent outcomes are understudied. METHODS: A pilot survey was developed using a community-driven research design to measure the impact of disease-specific items on parent-perceived well-being. The cross-sectional survey, which included both closed-ended and open-ended items, was distributed to a convenience sample of parents of children with SBS. Quantitative and qualitative data were integrated for a mixed-methods analysis of how individual items impacted parent well-being. RESULTS: Twenty parents completed the survey. Sleep interruptions, lack of support and resources, and psychological stressors and their mental health implications were more frequently reported as stressors than logistics related to caregiving (e.g., managing therapies and preparing specialized meals). CONCLUSION: The impact of a child's SBS on parent well-being may stem mainly from three interconnected domains: poor sleep and its consequences, lack of access to support and resources, and a range of psychological stressors that affect parent mental health. Understanding the mechanisms through which SBS shapes parent well-being is a necessary first step for developing targeted interventions to support parents and provide family-centered care.

Does the effect of walking balance perturbations generalize across contexts?

Balance perturbations are used to study locomotor instability. However, these perturbations are designed to provoke a specific context of instability that may or may not generalize to a broader understanding of falls risk. The purpose of this study was to determine if the effect of balance perturbations on instability generalizes across contexts. 29 younger adults and 28 older adults completed four experimental trials, including unperturbed walking and walking while responding to three perturbation contexts: mediolateral optical flow, treadmill-induced slips, and lateral waist-pulls. We quantified the effect of perturbations as an absolute change in margin of stability from unperturbed walking. We found significant changes in mediolateral and anteroposterior margin of stability for all perturbations compared to unperturbed walking in both cohorts (p-values ≤ 0.042). In older adults, the mediolateral effects of lateral waist-pulls significantly correlated with those of optical flow perturbations and treadmill-induced slips (r ≥ 0.398, p-values ≤ 0.036). In younger adults but not in older adults, we found positive and significant correlations between the anteroposterior effect of waist-pull perturbations and optical flow perturbations, and the anteroposterior and mediolateral effect of treadmill-induced slips (r ≥ 0.428, p-values ≤ 0.021). We found no "goldilocks" perturbation paradigm to endorse that would support universal interpretations about locomotor instability. Building the most accurate patient profiles of instability likely requires a series of perturbation paradigms designed to emulate the variety of environmental contexts in which falls may occur.

Genomic Resources for the First Federally Endangered Lichen: The Florida Perforate Cladonia (Cladonia perforata).

Thirty years after its designation as a federally endangered species, the Florida Perforate Cladonia (FPC) remains imperiled in isolated populations in the Florida scrub in the southeastern USA. For threatened and endangered species, such as FPC, reference genomes provide critical insight into genomic diversity, local adaptations, landscape-level genetics, and phylogenomics. Using high-throughput sequencing, we assemble the first draft nuclear and mitochondrial genomes for the FPC mycobiont-Cladonia perforata. We also assess genetic diversity within and among populations in southeastern Florida using genome-scale data and investigate diversity across the entire nuclear ribosomal cistron, including the standard DNA barcoding marker for fungi. The draft nuclear genome spanned 33.6 Mb, and the complete, circular mitochondrial genome was 59 Kb. We also generated the first chloroplast genome, to our knowledge, for the photobiont genus associated with FPC, an undescribed Asterochloris species. We inferred the presence of multiple, distinct mycobiont parental genotypes (genets) occurring at local scales in southeastern Florida, and strikingly, no genets were shared among even the closest sample sites. All sampled thalli shared identical mitochondrial genomes, while the nuclear ribosomal cistron showed limited variability-highlighting the genetic resolution provided by nuclear genome-scale datasets. The genomic resources generated here provide critical resources for informed conservation efforts for the FPC.

Reduced immunogenicity of a live Salmonella enterica serovar Typhimurium vaccine in aged mice.

Introduction: Non-typhoidal Salmonella (NTS) is responsible for a high burden of foodborne infections and deaths worldwide. In the United States, NTS infections are the leading cause of hospitalizations and deaths due to foodborne illnesses, and older adults (≥65 years) are disproportionately affected by Salmonella infections. Due to this public health concern, we have developed a live attenuated vaccine, CVD 1926 (I77 ΔguaBA ΔclpP ΔpipA ΔhtrA), against Salmonella enterica serovar Typhimurium, a common serovar of NTS. Little is known about the effect of age on oral vaccine responses, and due to the decline in immune function with age, it is critical to evaluate vaccine candidates in older age groups during early product development. Methods: In this study, adult (six-to-eight-week-old) and aged (18-month-old) C57BL/6 mice received two doses of CVD 1926 (109 CFU/dose) or PBS perorally, and animals were evaluated for antibody and cell-mediated immune responses. A separate set of mice were immunized and then pre-treated with streptomycin and challenged orally with 108 CFU of wild-type S. Typhimurium SL1344 at 4 weeks postimmunization. Results: Compared to PBS-immunized mice, adult mice immunized with CVD 1926 had significantly lower S. Typhimurium counts in the spleen, liver, and small intestine upon challenge. In contrast, there were no differences in bacterial loads in the tissues of vaccinated versus PBS aged mice. Aged mice exhibited reduced Salmonella-specific antibody titers in the serum and feces following immunization with CVD 1926 compared to adult mice. In terms of T cell responses (T-CMI), immunized adult mice showed an increase in the frequency of IFN-γ- and IL-2-producing splenic CD4 T cells, IFN-γ- and TNF-α-producing Peyer's Patch (PP)-derived CD4 T cells, and IFN-γ- and TNF-α-producing splenic CD8 T cells compared to adult mice administered PBS. In contrast, in aged mice, T-CMI responses were similar in vaccinated versus PBS mice. CVD 1926 elicited significantly more PP-derived multifunctional T cells in adult compared to aged mice. Conclusion: These data suggest that our candidate live attenuated S. Typhimurium vaccine, CVD 1926, may not be sufficiently protective or immunogenic in older humans and that mucosal responses to live-attenuated vaccines decrease with increasing age.

Susceptibility to walking balance perturbations in young adults is largely unaffected by anticipation.

Despite progress in understanding the mechanisms governing walking balance control, the number of falls in our older adult population is projected to increase. Falls prevention systems and strategies may benefit from understanding how anticipation of a balance perturbation affects the planning and execution of biomechanical responses to mitigate instability. However, the extent to which anticipation affects the proactive and reactive adjustments to perturbations has yet to be fully investigated, even in young adults. Our purpose was to investigate the effects of anticipation on susceptibility to two different mechanical balance perturbations - namely, treadmill-induced perturbations and impulsive waist-pull perturbations. Twenty young adults (mean ± standard deviation age: 22.8 ± 3.3 years) walked on a treadmill without perturbations and while responding to treadmill belt (200 ms, 6 m/s2) and waist-pull (100 ms, 6% body weight) perturbations delivered in the anterior and posterior directions. We used 3D motion capture to calculate susceptibility to perturbations during the perturbed and preceding strides via whole-body angular momentum (WBAM) and anterior-posterior margin of stability (MoSAP). Contrary to our hypotheses, anticipation did not affect young adults' susceptibility to walking balance challenges. Conversely, perturbation direction significantly affected walking instability. We also found that susceptibility to different perturbation contexts is dependent on the outcome measure chosen. We suggest that the absence of an effect of anticipation on susceptibility to walking balance perturbations in healthy young adults is a consequence of their having high confidence in their reactive balance integrity. These data provide a pivotal benchmark for the future identification of how anticipation of a balance challenge affects proactive and reactive balance control in populations at risk of falls.

Young adults use whole-body feedback and ankle proprioception to perceive small locomotor disturbances.

To prevent a fall when a disturbance to walking is encountered requires sensory information about the disturbance to be sensed, integrated, and then used to generate an appropriate corrective motor response. Prior research has shown that feedback of whole-body motion (e.g., center-of-mass kinematics) drives this corrective response. Here, we hypothesized that young adults also use whole-body motion to perceive locomotor disturbances. 15 subjects performed a locomotor discrimination task in which the supporting leg was slowed during stance every 8-12 steps to emulate subtle slips. The perception threshold of these disturbances was determined using a psychometrics approach and found to be 0.08 ± 0.03 m/s. Whole-body feedback was examined through center-of-mass (CoM) kinematics and whole-body angular momentum (WBAM). Perturbation-induced deviations of CoM and WBAM were calculated in response to the two perturbation levels nearest each subject's perception threshold. Consistent with our hypothesis, we identified significantly higher perturbation induced deviations for perceived perturbations in sagittal-plane WBAM, anteroposterior CoM velocity, and vertical CoM velocity and acceleration. Because whole body motion is not sensed directly but instead arises from the integration of various sensory feedback signals, we also explored local sensory feedback contributions to the perception of locomotor disturbances. Local sensory feedback was estimated through kinematic analogues of vision (head angle), vestibular (head angular velocity), proprioception (i.e., sagittal hip, knee, and ankle angles), and somatosensation (i.e., anterior-posterior & mediolateral center-of-pressure, COP). We identified significantly higher perturbation induced deviations for perceived perturbations in sagittal-plane ankle angle. These results provide evidence for both whole-body feedback and ankle proprioception as important for the perception of subtle slip-like locomotor disturbances in young adults. Our interpretation is ankle proprioception is a dominant contributor to estimates of whole-body motion to perceive locomotor disturbances.

A novel method to quantify individual limb contributions to standing postural control.

BACKGROUND: Understanding individual limb contributions to standing postural control is valuable when evaluating populations with asymmetric function (e.g., stroke, amputations). We propose a method of quantifying three contributions to controlling the net anteroposterior center of pressure (CoP) during quiet standing: CoP moving under left and right limbs and weight shifting between the two limbs. RESEARCH QUESTION: Can these contributions to standing postural control be quantified from CoP trajectories in neurotypical adults? METHODS: Instantaneous contributions can be negative or larger than one, and integrated contributions sum to equal one. Proof-of-concept demonstrations validated these calculated contributions by restricting CoP motion under one or both feet. We evaluated these contributions in 30 neurotypical young adults who completed two (eyes opened; eyes closed) 30-s trials of bipedal standing. We evaluated the relationships between limb contributions, self-reported limb dominance, and between-limb weight distributions. RESULTS: All participants self-reported as right-limb dominant; however, a range of mean limb contributions were observed with eyes opened (Left: mean [range] = 0.52 [0.37-0.63]; Right: 0.48 [0.31-0.63]) and with eyes closed (Left: 0.51 [0.39-0.63]; Right: 0.49 [0.37-0.61]). Weight-shift contributions were small with eyes opened (0.00 [-0.01 to 0.01]) and eyes closed (0.00 [-0.01 to 0.02]). We did not identify any between-limb differences in contributions when grouped by self-reported limb dominance (p > 0.10, d < 0.31). Contributions did not significantly correlate with Waterloo Footedness scores (-0.22 < r < 0.21, p > 0.25) or between-limb weight distributions (0 < r < 0.24, p > 0.20). SIGNIFICANCE: Across neurotypical participants, we observed a notable range of limb contributions not related to self-reported limb dominance or between-limb weight distributions. With this tool, we can characterize differences in the amount of CoP motion and the underlying control strategies. Changes in limb contribution can be measured longitudinally (i.e., across rehabilitation programs, disease progression, aging) representative of limb function, which may be particularly useful in populations with asymmetric function.

The effect of pre-event instructions on eyewitness identification.

Research on eyewitness identification often involves exposing participants to a simulated crime and later testing memory using a lineup. We conducted a systematic review showing that pre-event instructions, instructions given before event exposure, are rarely reported and those that are reported vary in the extent to which they warn participants about the nature of the event or tasks. At odds with the experience of actual witnesses, some studies use pre-event instructions explicitly warning participants of the upcoming crime and lineup task. Both the basic and applied literature provide reason to believe that pre-event instructions may affect eyewitness identification performance. In the current experiment, we tested the impact of pre-event instructions on lineup identification decisions and confidence. Participants received non-specific pre-event instructions (i.e., "watch this video") or eyewitness pre-event instructions (i.e., "watch this crime video, you'll complete a lineup later") and completed a culprit-absent or -present lineup. We found no support for the hypothesis that participants who receive eyewitness pre-event instructions have higher discriminability than participants who receive non-specific pre-event instructions. Additionally, confidence-accuracy calibration was not significantly different between conditions. However, participants in the eyewitness condition were more likely to see the event as a crime and to make an identification than participants in the non-specific condition. Implications for conducting and interpreting eyewitness identification research and the basic research on instructions and attention are discussed.

Action on the social determinants for advancing health equity in the time of COVID-19: perspectives of actors engaged in a WHO Special Initiative.

Since the 2008 publication of the reports of the Commission on Social Determinants of Health and its nine knowledge networks, substantial research has been undertaken to document and describe health inequities. The COVID-19 pandemic has underscored the need for a deeper understanding of, and broader action on, the social determinants of health. Building on this unique and critical opportunity, the World Health Organization is steering a multi-country Initiative to reduce health inequities through an action-learning process in 'Pathfinder' countries. The Initiative aims to develop replicable and reliable models and practices that can be adopted by WHO offices and UN staff to address the social determinants of health to advance health equity. This paper provides an overview of the Initiative by describing its broad theory of change and work undertaken in three regions and six Pathfinder countries in its first year-and-a-half. Participants engaged in the Initiative describe results of early country dialogues and promising entry points for implementation that involve model, network and capacity building. The insights communicated through this note from the field will be of interest for others aiming to advance health equity through taking action on the social determinants of health, in particular as regards structural determinants.

Evaluation of the matrix metalloproteinase 9 (MMP9) inhibitor Andecaliximab as an Anti-invasive therapeutic in Head and neck squamous cell carcinoma.

OBJECTIVES: Locoregional and lymphovascular involvement of invasive head and neck squamous cell carcinoma (HNSCC) complicates curative treatment. Matrix metalloproteinase (MMP) 9 is a negative prognostic marker in HNSCC and targets multiple extracellular matrix (ECM) substrates, where it contributes to breaching basement membrane and stromal barriers enabling invasive spread. Andecaliximab (ADX) is a second-generation MMP9 inhibitor well tolerated in clinical trials of gastric and pancreatic adenocarcinoma. The impact of selective MMP9 targeting by ADX in HNSCC has not been evaluated. MATERIALS AND METHODS: Established and patient-derived xenograft (PDX) cell lines were utilized in HNSCC invasion assays to determine the inhibitory ability of MMP9-mediated invasion by ADX. MMP9 expression was confirmed using immunohistochemistry (IHC) and immunoblotting. ECM degradation was evaluated with confocal microscopy. Cell invasion from tumor spheroids was monitored by phase microscopy. Histological evaluation was used to determine ADX efficacy in three-dimensional organotypic cultures containing cancer associated fibroblasts (CAFs). RESULTS: MMP9 was expressed in all established and PDX-derived cell lines. While the broad spectrum clinical MMP inhibitor marimastat (BB2516) blocked HNSCC invadopodia function and tumor spheroid invasion, ADX treatment failed to inhibit invadopodia-based matrix degradation, tumor cell or fibroblast-driven ECM invasion in collagen I-based matrices. CONCLUSION: ADX monotherapy was ineffective at blocking initial MMP-dependent events of HNSCC invasion, likely due to redundant functions of additional non-targeted MMPs produced by tumor cells and microenvironment. Combination of ADX with existing and emerging therapies targeting additional MMP activation pathways may warrant future investigation.

Slowing down to preserve balance in the presence of optical flow perturbations.

BACKGROUND: The use of sensory and mechanical perturbations applied during walking has grown in popularity due to their ability to elicit instability relevant to falls. However, the vast majority of perturbation studies on walking balance are performed on a treadmill at a fixed speed. RESEARCH QUESTION: The aim of this study was to quantify the effects of mediolateral optical flow perturbations on walking speed and balance outcomes in young adults walking with fixed-speed and self-paced treadmill controllers. METHODS: Fifteen healthy young adults (8 female, age: 23.1 ± 4.6 yrs) completed four five-minute randomized walking trials in a speed-matched virtual reality hallway. In two of the trials, we added continuous mediolateral optical flow perturbations to the virtual hallway. Trials with and without optical flow perturbations were performed with either a fixed-speed or self-paced treadmill controller. We measured walking speed, balance outcomes (step width, margin of stability, local dynamic instability) and gait variability (step width variability and margin of stability variability). RESULTS: We found significant increases in step width (+20%, p = 0.004) and local dynamic instability (+11%, p = 0.008) of participants while responding to optical flow perturbations at a fixed treadmill speed. We found no significant differences in these outcome measures when perturbations were applied on a self-paced treadmill. Instead, participants walked 5.7% slower between the self-paced treadmill controller conditions when responding to optical flow perturbations (1.48 ± 0.13 m/s vs. 1.57 ± 0.16 m/s, p = 0.005). SIGNIFICANCE: Our findings suggest that during walking, when presented with a balance challenge, an individual will instinctively reduce their walking speed in order to better preserve stability. However, comparisons to prior literature suggest that this response may depend on environmental and/or perturbation context. Cumulatively, our results point to opportunities for leveraging self-paced treadmill controllers as a more ecologically-relevant option in balance research with potential clinical applications in diagnostics and rehabilitation.

A call to reconceptualize lichen symbioses.

Several decades of research across disciplines have overturned historical perspectives of symbioses dominated by binary characterizations of highly specific species-species interactions. This paradigm shift has unlocked the previously underappreciated and overlooked dynamism of fungal mutualisms such as mycorrhizae. Lichens are another example of important fungal mutualisms where reconceptualization is urgently needed to realize their potential as model systems. This reconceptualization requires both an objective synthesis of new data and envisioning a revised integrative approach that unifies the spectrum of ecology and evolution. We propose a ten-theme framework that if pursued would propel lichens to the vanguard of symbiotic theory.

A country classification system to inform rabies prevention guidelines and regulations.

BACKGROUND: Assessing the global risk of rabies exposure is a complicated task requiring individual risk assessments, knowledge of rabies epidemiology, surveillance capacity and accessibility of rabies biologics on a national and regional scale. In many parts of the world, availability of this information is limited and when available is often dispersed across multiple sources. This hinders the process of making evidence-based health and policy recommendations to prevent the introduction and spread of rabies. METHODS: CDC conducted a country-by-country qualitative assessment of risk and protective factors for rabies to develop an open-access database of core metrics consisting of the presence of lyssaviruses (specifically canine or wildlife rabies virus variants or other bat lyssaviruses), access to rabies immunoglobulins and vaccines, rabies surveillance capacity and canine rabies control capacity. Using these metrics, we developed separate risk scoring systems to inform rabies prevention guidance for travelers and regulations for the importation of dogs. Both scoring systems assigned higher risk to countries with enzootic rabies (particularly canine rabies), and the risk scoring system for travelers also considered protective factors such as the accessibility of rabies biologics for post-exposure prophylaxis. Cumulative scores were calculated across the assessed metrics to assign a risk value of low, moderate or high. RESULTS: A total of 240 countries, territories and dependencies were assessed, for travelers, 116 were identified as moderate to high risk and 124 were low or no risk; for canine rabies virus variant importation, 111 were identified as high-risk and 129 were low or no risk. CONCLUSIONS: We developed a comprehensive and easily accessible source of information for assessing the rabies risk for individual countries that included a database of rabies risk and protective factors based on enzootic status and availability of biologics, provided a resource that categorizes risk by country and provided guidance based on these risk categories for travelers and importers of dogs into the United States.