Cerebral visual impairment: genetic diagnoses and phenotypic associations.

BACKGROUND: Cerebral visual impairment (CVI) is the most common form of paediatric visual impairment in developed countries. CVI can arise from a host of genetic or acquired causes, but there has been limited research to date on CVI in the context of genetic disorders. METHODS: We carried out a retrospective analysis of genotypic and phenotypic data for participants with CVI within the DECIPHER database and 100 000 Genomes Project (100KGP). RESULTS: 158 individuals with CVI were identified across both cohorts. Within this group, pathogenic or likely pathogenic sequence variants in 173 genes were identified. 25 of these genes already have known associations with CVI, while the remaining 148 are candidate genes for this phenotype. Gene ontology analysis of the CVI gene sets from both DECIPHER and 100KGP suggests that CVI has a similar degree of genetic heterogeneity to other neurodevelopmental phenotypes, and a strong association with genetic variants converging on ion channels and receptor functions. Individuals with a monogenic disorder and CVI have a higher frequency of epilepsies and severe neurodisability than individuals with a monogenic disorder but not CVI. CONCLUSION: This study supports the availability of genetic testing for individuals with CVI alongside other neurodevelopmental difficulties. It also supports the availability of ophthalmological screening for individuals with genetic diagnoses linked to CVI. Further studies could elaborate on the links between specific genetic disorders, visual maturation and broader neurodevelopmental characteristics.

Trends in shigellosis notifications in England, January 2016 to March 2023.

We reviewed all diagnoses of Shigella species notified to the UK Health Security Agency from January 2016 to March 2023. An overall increase in notifications of shigellosis was seen between 2016 (n = 415/quarter) and 2023 (n = 1 029/quarter). However, notifications dramatically declined between March 2020 and September 2021 during the COVID-19 pandemic (n = 208/quarter) highlighting the impact of travel and social distancing restrictions on transmission. S. sonnei diagnoses were more affected by lockdown restrictions than S. flexneri, most likely due to a combination of species-specific characteristics and host attributes. Azithromycin resistance continued to be associated with epidemics of sexually transmissible S. flexneri (adult males = 45.6% vs. adult females = 8.7%) and S. sonnei (adult males = 59.5% vs. adult females = 14.6%). We detected resistance to ciprofloxacin in S. sonnei from adult male cases not reporting travel at a higher frequency (79.4%) than in travel-associated cases (61.7%). Extensively drug-resistant Shigella species associated with sexual transmission among men almost exclusively had ESBL encoded by blaCTX-M-27, whereas those associated with returning travellers had blaCTX-M-15. Given the increasing incidence of infections and AMR, we recommend that enhanced surveillance is used to better understand the impact of travel and sexual transmission on the acquisition and spread of MDR and XDR Shigella species.

International travel as a risk factor for gastrointestinal infections in residents of North East England.

International travel is thought to be a major risk factor for developing gastrointestinal (GI) illness for UK residents. Here, we present an analysis of routine laboratory and exposure surveillance data from North East (NE) England, describing the destination-specific contribution that international travel makes to the regional burden of GI infection.Laboratory reports of common notifiable enteric infections were linked to exposure data for cases reported between 1 January 2013 and 31 December 2022. Demographic characteristics of cases were described, and rates per 100,000 visits were determined using published estimates of overseas visits from the Office for National Statistics (ONS) International Passenger Survey (IPS).About 34.9% of cases reported international travel during their incubation period between 2013 and 2022, although travel-associated cases were significantly reduced (>80%) during the COVID-19 pandemic. Between 2013 and 2019, half of Shigella spp. and non-typhoidal Salmonella infections and a third of Giardia sp., Cryptosporidium spp., and Shiga toxin-producing Escherichia coli (STEC) infections were reported following travel. Rates of illness were highest in travellers returning from Africa and Asia (107.8 and 61.1 per 100,000 visits), with high rates also associated with tourist resorts like Turkey, Egypt, and the Dominican Republic (386.4-147.9 per 100,000 visits).International travel is a major risk factor for the development of GI infections. High rates of illness were reported following travel to both destinations, which are typically regarded as high-risk and common tourist resorts. This work highlights the need to better understand risks while travelling to support the implementation of guidance and control measures to reduce the burden of illness in returning travellers.

Early mortality in STXBP1-related disorders.

INTRODUCTION: Pathogenic variants in STXBP1 cause a spectrum of disorders mainly consisting of developmental and epileptic encephalopathy (DEE), often featuring drug-resistant epilepsy. An increased mortality risk occurs in individuals with drug-resistant epilepsy and DEE, with sudden unexpected death in epilepsy (SUDEP) often the major cause of death. This study aimed to identify the rate and causes of mortality in STXBP1-related disorders. METHODS: Through an international call, we analyzed data on individuals with STXBP1 pathogenic variants, who passed away from causes related to their disease. RESULTS: We estimated a mortality rate of 3.2% (31/966), based on the STXBP1 Foundation and the STXBP1 Global Connect registry. In total, we analyzed data on 40 individuals (23 males) harboring pathogenic STXBP1 variants, collected from different centers worldwide. They died at a median age of 13 years (range: 11 months-46 years). The most common cause of death was SUDEP (36%), followed by pulmonary infections and respiratory complications (33%). The incidence of SUDEP peaked in mid-childhood, while non-SUDEP causes were more frequent in early childhood or adulthood (p = 0.006). In the most severe phenotypes, death was related to non-SUDEP causes (p = 0.018). CONCLUSION: We found a mortality rate in STXBP1-related disorders similar to other DEEs, with an early age at death and SUDEP as well as pulmonary infections as the main cause of death. These findings assist in prognostic evaluation and genetic counseling for the families. They help to define the mortality risk of STXBP1-related disorders and implement preventative strategies.

Shigella Serotypes Associated With Carriage in Humans Establish Persistent Infection in Zebrafish.

Shigella represents a paraphyletic group of enteroinvasive Escherichia coli. More than 40 Shigella serotypes have been reported. However, most cases within the men who have sex with men (MSM) community are attributed to 3 serotypes: Shigella sonnei unique serotype and Shigella flexneri 2a and 3a serotypes. Using the zebrafish model, we demonstrate that Shigella can establish persistent infection in vivo. Bacteria are not cleared by the immune system and become antibiotic tolerant. Establishment of persistent infection depends on the O-antigen, a key constituent of the bacterial surface and a serotype determinant. Representative isolates associated with MSM transmission persist in zebrafish, while representative isolates of a serotype not associated with MSM transmission do not. Isolates of a Shigella serotype establishing persistent infections elicited significantly less macrophage death in vivo than isolates of a serotype unable to persist. We conclude that zebrafish are a valuable platform to illuminate factors underlying establishment of Shigella persistent infection in humans.

A sensor histidine kinase from a plant-endosymbiont bacterium restores the virulence of a mammalian intracellular pathogen.

Alphaproteobacteria include organisms living in close association with plants or animals. This interaction relies partly on orthologous two-component regulatory systems (TCS), with sensor and regulator proteins modulating the expression of conserved genes related to symbiosis/virulence. We assessed the ability of the exoS+Sm gene, encoding a sensor protein from the plant endosymbiont Sinorhizobium meliloti to substitute its orthologous bvrS in the related animal/human pathogen Brucella abortus. ExoS phosphorylated the B. abortus regulator BvrR in vitro and in cultured bacteria, showing conserved biological function. Production of ExoS in a B. abortus bvrS mutant reestablished replication in host cells and the capacity to infect mice. Bacterial outer membrane properties, the production of the type IV secretion system VirB, and its transcriptional regulators VjbR and BvrR were restored as compared to parental B. abortus. These results indicate that conserved traits of orthologous TCS from bacteria living in and sensing different environments are sufficient to achieve phenotypic plasticity and support bacterial survival. The knowledge of bacterial genetic networks regulating host interactions allows for an understanding of the subtle differences between symbiosis and parasitism. Rewiring these networks could provide new alternatives to control and prevent bacterial infection.

Assessing the landscape of STXBP1-related disorders in 534 individuals.

Disease-causing variants in STXBP1 are among the most common genetic causes of neurodevelopmental disorders. However, the phenotypic spectrum in STXBP1-related disorders is wide and clear correlations between variant type and clinical features have not been observed so far. Here, we harmonized clinical data across 534 individuals with STXBP1-related disorders and analysed 19 973 derived phenotypic terms, including phenotypes of 253 individuals previously unreported in the scientific literature. The overall phenotypic landscape in STXBP1-related disorders is characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of individuals, including focal-onset seizures as the most common seizure type (47%). More than 88% of individuals with STXBP1-related disorders have seizure onset in the first year of life, including neonatal seizure onset in 47%. Individuals with protein-truncating variants and deletions in STXBP1 (n = 261) were almost twice as likely to present with West syndrome and were more phenotypically similar than expected by chance. Five genetic hotspots with recurrent variants were identified in more than 10 individuals, including p.Arg406Cys/His (n = 40), p.Arg292Cys/His/Leu/Pro (n = 30), p.Arg551Cys/Gly/His/Leu (n = 24), p.Pro139Leu (n = 12), and p.Arg190Trp (n = 11). None of the recurrent variants were significantly associated with distinct electroclinical syndromes, single phenotypic features, or showed overall clinical similarity, indicating that the baseline variability in STXBP1-related disorders is too high for discrete phenotypic subgroups to emerge. We then reconstructed the seizure history in 62 individuals with STXBP1-related disorders in detail, retrospectively assigning seizure type and seizure frequency monthly across 4433 time intervals, and retrieved 251 anti-seizure medication prescriptions from the electronic medical records. We demonstrate a dynamic pattern of seizure control and complex interplay with response to specific medications particularly in the first year of life when seizures in STXBP1-related disorders are the most prominent. Adrenocorticotropic hormone and phenobarbital were more likely to initially reduce seizure frequency in infantile spasms and focal seizures compared to other treatment options, while the ketogenic diet was most effective in maintaining seizure freedom. In summary, we demonstrate how the multidimensional spectrum of phenotypic features in STXBP1-related disorders can be assessed using a computational phenotype framework to facilitate the development of future precision-medicine approaches.

A tale of two plasmids: contributions of plasmid associated phenotypes to epidemiological success among Shigella.

Dissemination of antimicrobial resistance (AMR) genes by horizontal gene transfer (HGT) mediated through plasmids is a major global concern. Genomic epidemiology studies have shown varying success of different AMR plasmids during outbreaks, but the underlying reasons for these differences are unclear. Here, we investigated two Shigella plasmids (pKSR100 and pAPR100) that circulated in the same transmission network but had starkly contrasting epidemiological outcomes to identify plasmid features that may have contributed to the differences. We used plasmid comparative genomics to reveal divergence between the two plasmids in genes encoding AMR, SOS response alleviation and conjugation. Experimental analyses revealed that these genomic differences corresponded with reduced conjugation efficiencies for the epidemiologically successful pKSR100, but more extensive AMR, reduced fitness costs, and a reduced SOS response in the presence of antimicrobials, compared with the less successful pAPR100. The discrepant phenotypes between the two plasmids are consistent with the hypothesis that plasmid-associated phenotypes contribute to determining the epidemiological outcome of AMR HGT and suggest that phenotypes relevant in responding to antimicrobial pressure and fitness impact may be more important than those around conjugation in this setting. Plasmid phenotypes could thus be valuable tools in conjunction with genomic epidemiology for predicting AMR dissemination.

Expanding the genotype and phenotype spectrum of SYT1-associated neurodevelopmental disorder.

PURPOSE: Synaptotagmin-1 (SYT1) is a critical mediator of neurotransmitter release in the central nervous system. Previously reported missense SYT1 variants in the C2B domain are associated with severe intellectual disability, movement disorders, behavioral disturbances, and electroencephalogram abnormalities. In this study, we expand the genotypes and phenotypes and identify discriminating features of this disorder. METHODS: We describe 22 individuals with 15 de novo missense SYT1 variants. The evidence for pathogenicity is discussed, including the American College of Medical Genetics and Genomics/Association for Molecular Pathology criteria, known structure-function relationships, and molecular dynamics simulations. Quantitative behavioral data for 14 cases were compared with other monogenic neurodevelopmental disorders. RESULTS: Four variants were located in the C2A domain with the remainder in the C2B domain. We classified 6 variants as pathogenic, 4 as likely pathogenic, and 5 as variants of uncertain significance. Prevalent clinical phenotypes included delayed developmental milestones, abnormal eye physiology, movement disorders, and sleep disturbances. Discriminating behavioral characteristics were severity of motor and communication impairment, presence of motor stereotypies, and mood instability. CONCLUSION: Neurodevelopmental disorder-associated SYT1 variants extend beyond previously reported regions, and the phenotypic spectrum encompasses a broader range of severities than initially reported. This study guides the diagnosis and molecular understanding of this rare neurodevelopmental disorder and highlights a key role for SYT1 function in emotional regulation, motor control, and emergent cognitive function.

Biallelic CACNA1A variants: Review of literature and report of a child with drug-resistant epilepsy and developmental delay.

Biallelic variants in CACNA1A have previously been reported in nine individuals (four families) presenting with epilepsy and cognitive impairments of variable severity and age-of-onset. Here, we describe a child who presented at 6 months of age with drug-resistant epilepsy and developmental delay. At 10 years of age, she has profound impairments in motor function and communication. MRI was initially unremarkable, but progressed to severe cerebellar atrophy by age 3 years. Next Generation Sequencing and panel analysis identified a maternally inherited truncating variant c.2042_2043delAG, p.(Gln681ArgfsTer100) and paternally inherited missense variant c.1693G>A, p.(Glu565Lys). In contrast to previously reported biallelic cases, parents carrying these monoallelic variants did not display clear signs of a CACNA1A-associated syndrome. In conclusion, we provide further evidence that biallelic CACNA1A variants can cause a severe epileptic and developmental encephalopathy with progressive cerebellar atrophy, and highlight complexities of genetic counseling in such situations.

AccessLab: Workshops to broaden access to scientific research.

AccessLabs are workshops with two simultaneous motivations, achieved through direct citizen-scientist pairings: (1) to decentralise research skills so that a broader range of people are able to access/use scientific research, and (2) to expose science researchers to the difficulties of using their research as an outsider, creating new open access advocates. Five trial AccessLabs have taken place for policy makers, media/journalists, marine sector participants, community groups, and artists. The act of pairing science academics with local community members helps build understanding and trust between groups at a time when this relationship appears to be under increasing threat from different political and economic currents in society. Here, we outline the workshop motivations, format, and evaluation, with the aim that others can build on the methods developed.

The use of alkaline phosphatase and runx2 to distinguish osteosarcoma from other common malignant primary bone tumors in dogs.

In dogs, primary bone tumors can be difficult to distinguish with histopathology. Of those tumors, osteosarcoma (OSA) is the most common and aggressive. In this study, 4 immunohistochemistry markers-alkaline phosphatase (ALP), osteonectin (ON), osteopontin (OP), and runx2-were evaluated for their ability to distinguish OSA from other primary bone tumors. The 42 formalin-fixed, paraffin-embedded, primary canine bone tumors included 15 OSAs, 8 chondrosarcomas, 11 fibrosarcomas, and 8 histiocytic sarcomas. All 4 antibodies were highly sensitive for detection of osteosarcoma. ALP was the most sensitive at 100% and runx2 the most specific at 78%. Running ALP and runx2 in series resulted in a sensitivity of 87% and a specificity of 85%. This combination of immunomarkers resulted in a diagnostic panel for distinguishing osteosarcoma from other primary bone tumors.

Improving transparency-A call to include social housing information in biomedical research articles involving nonhuman primates.

The social setting of animal subjects in the research environment has known effects on a variety of dependent measures used in biomedical research. Proper evaluation of the robustness of published research is dependent upon transparent, detailed, and accurate reporting of research methods, including the animals' social housing conditions. However, to date, most research articles utilizing nonhuman primates (NHPs) provide only partial data on this topic, hampering transparency, and reproducibility. Therefore, we call for the inclusion of information pertaining to the social aspects of the animals' housing conditions in publications involving NHPs to improve transparency. We argue that including this information in scientific publications is crucial for the interpretation of research findings in the appropriate context and for understanding unexplained variability in study findings. Finally, the inclusion of this information in publications will additionally familiarize scientists with how other researchers conducting similar studies are housing their animals and will encourage them to consider the implications of various housing conditions on their research outcomes.

American Society for Veterinary Clinical Pathology-Recommended Clinical Pathology Competencies for Graduating Veterinarians.

Given the move toward competency-based veterinary education and the subsequent reevaluation of veterinary curricula, there is a need for specialties to provide guidance to veterinary college administrators and educators on the core knowledge and skills pertaining to their specialty to ensure their inclusion in revised or redesigned curricula. The American Society for Veterinary Clinical Pathology (ASVCP) Education Committee sought to create a list of competencies specific to clinical pathology expected of graduating veterinarians. The stimulus for this project was the American Veterinary Medical Association Council on Education Standards of Accreditation for Colleges of Veterinary Medicine, further driven by the 2018 publication of the Association of American Veterinary Medical Colleges Competency-Based Veterinary Education Working Group framework. The recommendations made in this document are the culmination of the 2016 ASVCP Education Forum for Discussion, multiple remote subcommittee communications, and feedback obtained from ASVCP membership. The final framework includes 8 clinical pathology-focused domains of competence with 20 clinical pathology competencies and 61 clinical pathology illustrative sub-competencies. The clinical pathology-focused domains of competence are: the pre-analytical phase of testing, laboratory medicine and instrumentation, principles of test selection and interpretation, hematology and hemostasis, chemistry, endocrinology, urinalysis, and cytology. These are not intended to replace the nine established AAVMC domains of competence with supportive competencies and illustrative sub-competencies but to guide institutions for how clinical pathology aligns within the competency-based veterinary education (CBVE) framework for the practice-ready veterinary graduate. This clinical pathology competency framework may prove useful and empowering during discussions of curriculum revisions and redesigns.

The neurodevelopmental spectrum of synaptic vesicle cycling disorders.

In this review, we describe and discuss neurodevelopmental phenotypes arising from rare, high penetrance genomic variants which directly influence synaptic vesicle cycling (SVC disorders). Pathogenic variants in each SVC disorder gene lead to disturbance of at least one SVC subprocess, namely vesicle trafficking (e.g. KIF1A and GDI1), clustering (e.g. TRIO, NRXN1 and SYN1), docking and priming (e.g. STXBP1), fusion (e.g. SYT1 and PRRT2) or re-uptake (e.g. DNM1, AP1S2 and TBC1D24). We observe that SVC disorders share a common set of neurological symptoms (movement disorders, epilepsies), cognitive impairments (developmental delay, intellectual disabilities, cerebral visual impairment) and mental health difficulties (autism, ADHD, psychiatric symptoms). On the other hand, there is notable phenotypic variation between and within disorders, which may reflect selective disruption to SVC subprocesses, spatiotemporal and cell-specific gene expression profiles, mutation-specific effects, or modifying factors. Understanding the common cellular and systems mechanisms underlying neurodevelopmental phenotypes in SVC disorders, and the factors responsible for variation in clinical presentations and outcomes, may translate to personalized clinical management and improved quality of life for patients and families.

Childhood intellectual disability and parents' mental health: integrating social, psychological and genetic influences.

BACKGROUND: Intellectual disability has a complex effect on the well-being of affected individuals and their families. Previous research has identified multiple risk and protective factors for parental mental health, including socioeconomic circumstances and child behaviour. AIMS: This study explored whether genetic cause of childhood intellectual disability contributes to parental well-being. METHOD: Children from across the UK with intellectual disability due to diverse genetic causes were recruited to the IMAGINE-ID study. Primary carers completed the Development and Well-being Assessment, including a measure of parental distress (Everyday Feeling Questionnaire). Genetic diagnoses were broadly categorised into aneuploidy, chromosomal rearrangements, copy number variants (CNVs) and single nucleotide variants. RESULTS: Compared with the UK general population, IMAGINE-ID parents (n = 888) reported significantly elevated emotional distress (Cohen's d = 0.546). Within-sample variation was related to recent life events and the perceived impact of children's difficulties. Impact was predicted by child age, physical disability, autistic characteristics and other behavioural difficulties. Genetic diagnosis also predicted impact, indirectly influencing parental well-being. Specifically, CNVs were associated with higher impact, not explained by CNV inheritance, neighbourhood deprivation or family structure. CONCLUSIONS: The mental health of parents caring for a child with intellectual disability is influenced by child and family factors, converging on parental appraisal of impact. We found that genetic aetiologies, broadly categorised, also influence impact and thereby family risks. Recognition of these risk factors could improve access to support for parents, reduce their long-term mental health needs and improve well-being of individuals with intellectual disability.

Functional network dynamics in a neurodevelopmental disorder of known genetic origin.

Dynamic connectivity in functional brain networks is a fundamental aspect of cognitive development, but we have little understanding of the mechanisms driving variability in these networks. Genes are likely to influence the emergence of fast network connectivity via their regulation of neuronal processes, but novel methods to capture these rapid dynamics have rarely been used in genetic populations. The current study redressed this by investigating brain network dynamics in a neurodevelopmental disorder of known genetic origin, by comparing individuals with a ZDHHC9-associated intellectual disability to individuals with no known impairment. We characterised transient network dynamics using a Hidden Markov Model (HMM) on magnetoencephalography (MEG) data, at rest and during auditory oddball stimulation. The HMM is a data-driven method that captures rapid patterns of coordinated brain activity recurring over time. Resting-state network dynamics distinguished the groups, with ZDHHC9 participants showing longer state activation and, crucially, ZDHHC9 gene expression levels predicted the group differences in dynamic connectivity across networks. In contrast, network dynamics during auditory oddball stimulation did not show this association. We demonstrate a link between regional gene expression and brain network dynamics, and present the new application of a powerful method for understanding the neural mechanisms linking genetic variation to cognitive difficulties.

Persistent Transmission of Shigellosis in England Is Associated with a Recently Emerged Multidrug-Resistant Strain of Shigella sonnei.

Whole-genome sequencing has enhanced surveillance and facilitated detailed monitoring of the transmission of Shigella species in England. We undertook an epidemiological and phylogenetic analysis of isolates from all cases of shigellosis referred to Public Health England between 2015 and 2018 to explore recent strain characteristics and the transmission dynamics of Shigella species. Of the 4,950 confirmed cases of shigellosis identified during this period, the highest proportion of isolates was Shigella sonnei (54.4%), followed by S. flexneri (39.2%), S. boydii (4.1%), and S. dysenteriae (2.2%). Most cases were adults (82.9%) and male (59.5%), and 34.9% cases reported recent travel outside the United Kingdom. Throughout the study period, diagnoses of S. flexneri and S. sonnei infections were most common in men with no history of recent travel abroad. The species prevalence was not static, with cases of S. flexneri infection in men decreasing between 2015 and 2016 and the number of cases of S. sonnei infection increasing from 2017. Phylogenetic analysis showed this recent increase in S. sonnei infections was attributed to a novel clade that emerged from a Central Asia sublineage exhibiting resistance to ciprofloxacin and azithromycin. Despite changes in species prevalence, diagnoses of Shigella infections in England are persistently most common in adult males without a reported travel history, consistent with sexual transmission among men who have sex with men. The trend toward increasing rates of ciprofloxacin resistance in S. sonnei, in addition to plasmid-mediated azithromycin resistance, is of significant public health concern with respect to the transmission of multidrug-resistant gastrointestinal pathogens and the risk of treatment failures.

Trio housing of adult male rhesus macaques (Macaca mulatta): Methodology and outcome predictors.

BACKGROUND: This study evaluated the feasibility of trio housing caged adult male rhesus macaques and attempted to identify outcome predictors for trio housing formation and its intermediary introduction steps. METHODS: Subjects were familiarized consecutively to each potential group member via protected contact prior to introduction into the trio. Seven trios were attempted, involving 18 males, with three males attempted in two different trios. RESULTS: One group was deemed successful, with a tenure of 51 days. Five were disbanded within minutes, and one was deemed unsuccessful the following morning. Two males sustained wounds requiring veterinary care over the course of the study. Outcome of the protected contact phase was predicted by age and temperament disparities as well as initial behavior. CONCLUSIONS: While outcomes were poor, it suggests that attempts can be made relatively safely, and alternative introduction strategies should be explored to increase the feasibility of trio housing for adult males.

Salmonella enterica Serovar Panama, an Understudied Serovar Responsible for Extraintestinal Salmonellosis Worldwide.

In recent years nontyphoidal Salmonella has emerged as one of the pathogens most frequently isolated from the bloodstream in humans. Only a small group of Salmonella serovars cause this systemic infection, known as invasive nontyphoidal salmonellosis. Here, we present a focused minireview on Salmonella enterica serovar Panama, a serovar responsible for invasive salmonellosis worldwide. S Panama has been linked with infection of extraintestinal sites in humans, causing septicemia, meningitis, and osteomyelitis. The clinical picture is often complicated by antimicrobial resistance and has been associated with a large repertoire of transmission vehicles, including human feces and breast milk. Nonhuman sources of S Panama involve reptiles and environmental reservoirs, as well as food animals, such as pigs. The tendency of S Panama to cause invasive disease may be linked to certain serovar-specific genetic factors.