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Powassan virus is an emerging tick-borne virus of concern for public health, but very little is known about its transmission patterns and ecology. Here, we expanded the genomic dataset by sequencing 279 Powassan viruses isolated from Ixodes scapularis ticks from the northeastern United States. Our phylogeographic reconstructions revealed that Powassan virus lineage II was likely introduced or emerged from a relict population in the Northeast between 1940 and 1975. Sequences strongly clustered by sampling location, suggesting a highly focal geographical distribution. Our analyses further indicated that Powassan virus lineage II emerged in the northeastern United States mostly following a south-to-north pattern, with a weighted lineage dispersal velocity of ~3 km/y. Since the emergence in the Northeast, we found an overall increase in the effective population size of Powassan virus lineage II, but with growth stagnating during recent years. The cascading effect of population expansion of white-tailed deer and I. scapularis populations likely facilitated the emergence of Powassan virus in the northeastern United States.
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Cervos , Vírus da Encefalite Transmitidos por Carrapatos , Ixodes , Animais , New EnglandRESUMO
IMPORTANCE: Several coronaviruses (CoVs) have been detected in domesticated, farmed, and wild meso-carnivores, causing a wide range of diseases and infecting diverse species, highlighting their important but understudied role in the epidemiology of these viruses. Assessing the viral diversity hosted in wildlife species is essential to understand their significance in the cross-species transmission of CoVs. Our focus here was on CoV discovery in meso-carnivores in the Northeast United States as a potential "hotspot" area with high density of humans and urban wildlife. This study identifies novel alphacoronaviruses circulating in multiple free-ranging wild and domestic species in this area and explores their potential epidemiological importance based on regions of the Spike gene, which are relevant for virus-host interactions.
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Alphacoronavirus , Carnívoros , Fezes , Saliva , Animais , Humanos , Alphacoronavirus/classificação , Alphacoronavirus/genética , Alphacoronavirus/isolamento & purificação , Animais Domésticos/virologia , Animais Selvagens/virologia , Carnívoros/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/veterinária , Fezes/virologia , Interações entre Hospedeiro e Microrganismos , New England/epidemiologia , Saliva/virologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Zoonoses Virais/transmissão , Zoonoses Virais/virologiaRESUMO
Canine parvovirus (CPV) is a small nonenveloped single-stranded DNA virus that causes serious diseases in dogs worldwide. The original strain of the virus (CPV-2) emerged in dogs during the late 1970s due to a host range switch of a virus similar to the feline panleukopenia virus that infected another host. The virus that emerged in dogs had altered capsid receptor and antibody binding sites, with some changes affecting both functions. Further receptor and antibody binding changes arose when the virus became better adapted to dogs or to other hosts. Here, we used in vitro selection and deep sequencing to reveal how two antibodies with known interactions select for escape mutations in CPV. The antibodies bound two distinct epitopes, and one largely overlapped the host receptor binding site. We also generated mutated antibody variants with altered binding structures. Viruses were passaged with wild-type (WT) or mutated antibodies, and their genomes were deep sequenced during the selective process. A small number of mutations were detected only within the capsid protein gene during the first few passages of selection, and most sites remained polymorphic or were slow to go to fixation. Mutations arose both within and outside the antibody binding footprints on the capsids, and all avoided the transferrin receptor type 1 binding footprint. Many selected mutations matched those that have arisen in the natural evolution of the virus. The patterns observed reveal the mechanisms by which these variants have been selected in nature and provide a better understanding of the interactions between antibody and receptor selections. IMPORTANCE Antibodies protect animals against infection by many different viruses and other pathogens, and we are gaining new information about the epitopes that induce antibody responses against viruses and the structures of the bound antibodies. However, less is known about the processes of antibody selection and antigenic escape and the constraints that apply in this system. Here, we used an in vitro model system and deep genome sequencing to reveal the mutations that arose in the virus genome during selection by each of two monoclonal antibodies or their mutated variants. High-resolution structures of each of the Fab:capsid complexes revealed their binding interactions. The wild-type antibodies or their mutated variants allowed us to examine how changes in antibody structure influence the mutational selection patterns seen in the virus. The results shed light on the processes of antibody binding, neutralization escape, and receptor binding, and they likely have parallels for many other viruses.
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Anticorpos Antivirais , Sítios de Ligação de Anticorpos , Capsídeo , Parvovirus Canino , Animais , Cães , Capsídeo/metabolismo , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Epitopos/genética , Epitopos/análise , Parvovirus Canino/genética , Parvovirus Canino/metabolismo , Mutação , Anticorpos Antivirais/genética , Anticorpos Antivirais/metabolismo , Sítios de Ligação de Anticorpos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos Virais/metabolismo , Seleção GenéticaRESUMO
Infections caused by antimicrobial-resistant Escherichia coli are the leading cause of death attributed to antimicrobial resistance (AMR) worldwide, and the known AMR mechanisms involve a range of functional proteins. Here, we employed a pan-genome wide association study (GWAS) approach on over 1,000 E. coli isolates from sick dogs collected across the US and Canada and identified a strong statistical association (empirical P < 0.01) of AMR, involving a range of antibiotics to a group 1 capsular (CPS) gene cluster. This cluster included genes under relaxed selection pressure, had several loci missing, and had pseudogenes for other key loci. Furthermore, this cluster is widespread in E. coli and Klebsiella clinical isolates across multiple host species. Earlier studies demonstrated that the octameric CPS polysaccharide export protein Wza can transmit macrolide antibiotics into the E. coli periplasm. We suggest that the CPS in question, and its highly divergent Wza, functions as an antibiotic trap, preventing antimicrobial penetration. We also highlight the high diversity of lineages circulating in dogs across all regions studied, the overlap with human lineages, and regional prevalence of resistance to multiple antimicrobial classes. IMPORTANCE: Much of the human genomic epidemiology data available for E. coli mechanism discovery studies has been heavily biased toward shiga-toxin producing strains from humans and livestock. E. coli occupies many niches and produces a wide variety of other significant pathotypes, including some implicated in chronic disease. We hypothesized that since dogs tend to share similar strains with their owners and are treated with similar antibiotics, their pathogenic isolates will harbor unexplored AMR mechanisms of importance to humans as well as animals. By comparing over 1,000 genomes with in vitro antimicrobial susceptibility data from sick dogs across the US and Canada, we identified a strong multidrug resistance association with an operon that appears to have once conferred a type 1 capsule production system.
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Antibacterianos , Doenças do Cão , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli , Escherichia coli , Cães , Animais , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Doenças do Cão/microbiologia , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/microbiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Canadá , Estudo de Associação Genômica Ampla , Genoma Bacteriano , Estados Unidos , Cápsulas Bacterianas/genética , Família Multigênica , Evolução Molecular , Genômica , Proteínas de Escherichia coli/genéticaRESUMO
BACKGROUND AND OBJECTIVE: Congenital heart defects are known to be associated with increased odds of severe COVID-19. Congenital anomalies affecting other body systems may also be associated with poor outcomes. This study is an exhaustive assessment of congenital anomalies and odds of severe COVID-19 in pediatric patients. METHODS: Data were retrieved from the COVID-19 dataset of Cerner® Real-World Data for encounters from March 2020 to February 2022. Prior to matching, the data consisted of 664,523 patients less than 18 years old and 927,805 corresponding encounters with COVID-19 from 117 health systems across the United States. One-to-one propensity score matching was performed, and a cumulative link mixed-effects model with random intercepts for health system and patients was built to assess corresponding associations. RESULTS: All congenital anomalies were associated with worse COVID-19 outcomes, with the strongest association observed for cardiovascular anomalies (odds ratio [OR], 3.84; 95% CI, 3.63-4.06) and the weakest association observed for anomalies affecting the eye/ear/face/neck (OR, 1.16; 95% CI, 1.03-1.31). CONCLUSIONS AND RELEVANCE: Congenital anomalies are associated with greater odds of experiencing severe symptoms of COVID-19. In addition to congenital heart defects, all other birth defects may increase the odds for more severe COVID-19. IMPACT: All congenital anomalies are associated with increased odds of severe COVID-19. This study is the largest and among the first to investigate birth defects across all body systems. The multicenter large data and analysis demonstrate the increased odds of severe COVID19 in pediatric patients with congenital anomalies affecting any body system. These data demonstrate that all children with birth defects are at increased odds of more severe COVID-19, not only those with heart defects. This should be taken into consideration when optimizing prevention and intervention resources within a hospital.
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COVID-19 , Anormalidades Congênitas , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Estados Unidos/epidemiologia , Criança , Feminino , Masculino , Adolescente , Anormalidades Congênitas/epidemiologia , Pré-Escolar , Lactente , Índice de Gravidade de Doença , Recém-Nascido , Cardiopatias Congênitas/epidemiologia , Fatores de Risco , Pontuação de Propensão , Razão de ChancesRESUMO
PURPOSE: Pediatric surgical care in low- and middle-income countries is often hindered by systemic gaps in healthcare resources, infrastructure, training, and organization. This study aims to develop and validate the Global Assessment of Pediatric Surgery (GAPS) to appraise pediatric surgical capacity and discriminate between levels of care across diverse healthcare settings. METHODS: The GAPS Version 1 was constructed through a synthesis of existing assessment tools and expert panel consultation. The resultant GAPS Version 2 underwent international pilot testing. Construct validation categorized institutions into providing basic or advanced surgical care. GAPS was further refined to Version 3 to include only questions with a > 75% response rate and those that significantly discriminated between basic or advanced surgical settings. RESULTS: GAPS Version 1 included 139 items, which, after expert panel feedback, was expanded to 168 items in Version 2. Pilot testing, in 65 institutions, yielded a high response rate. Of the 168 questions in GAPS Version 2, 64 significantly discriminated between basic and advanced surgical care. The refined GAPS Version 3 tool comprises 64 questions on: human resources (9), material resources (39), outcomes (3), accessibility (3), and education (10). CONCLUSION: The GAPS Version 3 tool presents a validated instrument for evaluating pediatric surgical capabilities in low-resource settings.
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Países em Desenvolvimento , Recursos em Saúde , Pediatria , Humanos , Projetos Piloto , Pediatria/educação , Saúde Global , Criança , Procedimentos Cirúrgicos Operatórios , Especialidades Cirúrgicas/educaçãoRESUMO
Diarrhoeal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of paediatric diarrhoea, with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor an effective treatment. Here we establish a drug discovery process built on scalable phenotypic assays and mouse models that take advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity, we identify pyrazolopyridines as inhibitors of Cryptosporidium parvum and Cryptosporidium hominis. Oral treatment with the pyrazolopyridine KDU731 results in a potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhoea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection. Our results suggest that the Cryptosporidium lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) is a target for pyrazolopyridines and that KDU731 warrants further preclinical evaluation as a drug candidate for the treatment of cryptosporidiosis.
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1-Fosfatidilinositol 4-Quinase/antagonistas & inibidores , Criptosporidiose/tratamento farmacológico , Criptosporidiose/parasitologia , Cryptosporidium/efeitos dos fármacos , Cryptosporidium/enzimologia , Pirazóis/farmacologia , Piridinas/farmacologia , Animais , Animais Recém-Nascidos , Bovinos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Hospedeiro Imunocomprometido , Interferon gama/deficiência , Interferon gama/genética , Masculino , Camundongos , Camundongos Knockout , Pirazóis/química , Pirazóis/farmacocinética , Piridinas/química , Piridinas/farmacocinética , Ratos , Ratos WistarRESUMO
OBJECTIVES: Literature is emerging regarding the role of center volume as an independent variable contributing to improved outcomes. A higher volume of index procedures may be associated with decreased morbidity and mortality. This association has not been examined for the subgroup of infants with congenital diaphragmatic hernia (CDH) receiving extracorporeal life support (ECLS). Our study aims to examine the risk-adjusted association between center volume and outcomes in CDH-ECLS neonates, hypothesizing that higher center volume confers a survival advantage. DESIGN: Multicenter, retrospective comparative study using the Extracorporeal Life Support Organization database. SETTING: One hundred twenty international pediatric centers. PATIENTS: Neonates with CDH managed with ECLS from 2000 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort included 4,985 neonates with a mortality rate of 50.6%. For the 120 centers studied, mean center volume was 42.4 ± 34.6 CDH ECLS cases over the 20-year study period. In an adjusted model, higher ECLS volume was associated with lower odds of mortality: odds ratio (OR) 0.995 (95% CI, 0.992-0.999; p = 0.014). For an increase in one sd in volume, that is, 1.75 cases annually, the OR for mortality was lower by 16.7%. Volume was examined as a categorical exposure variable where low-volume centers (fewer than 2 cases/yr) were associated with 54% higher odds of mortality (OR, 1.54; 95% CI, 1.03-2.29) compared with high-volume centers. On-ECLS complications (mechanical, neurologic, cardiac, hematologic metabolic, and renal) were not associated with volume. The likelihood of infectious complications was higher for low- (OR, 1.90; 95% CI, 1.06-3.40) and medium-volume (OR, 1.87; 95% CI, 1.03-3.39) compared with high-volume centers. CONCLUSIONS: In this study, a survival advantage directly proportional to center volume was observed for CDH patients managed with ECLS. There was no significant difference in most complication rates. Future studies should aim to identify factors contributing to the higher mortality and morbidity observed at low-volume centers.
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Oxigenação por Membrana Extracorpórea , Hérnias Diafragmáticas Congênitas , Recém-Nascido , Lactente , Humanos , Criança , Hérnias Diafragmáticas Congênitas/terapia , Oxigenação por Membrana Extracorpórea/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Razão de ChancesRESUMO
BACKGROUND: Despite advancements in minimally invasive repair of pectus excavatum (MIRPE), Nuss procedure, postoperative pain control remains challenging. This report covers a multimodal regimen using bilateral single-shot paravertebral block (PVB) and bilateral thoracoscopic intercostal nerve (T3-T7) cryoablation, leading to significant reduction in length of stay (LOS) and high rate of same-day discharge. METHODS: This is a comparative study of pain management protocols for patients undergoing the Nuss procedure at a single center from 2016 through 2020. All patients underwent the the same surgical technique for the treatment of pectus excavatum at a single center. Patients received bilateral PVB with continuous infusion (Group 1, n = 12), bilateral PVB with infusion and right-side cryoablation (Group 2, n = 9), or bilateral single-shot PVB and bilateral cryoablation (Group 3, n = 17). The primary outcome was LOS with focus on same-day discharge, and the secondary outcome was decreased opioid usage. RESULTS: Eleven of 17 patients in Group 3 (65%) (bilateral single-shot PVB and bilateral cryoablation) were discharged the same day as surgery. The remaining Group 3 patients were discharged the following day with no complications or interventions. Compared to Group 1 (no cryoablation), Group 3 had shorter LOS (median 4.4 days vs. 0.7 days, respectively, p < 0.001) and significantly decreased median opioid use on the day of surgery (0.92 mg/kg vs. 0.47 mg/kg, p = 0.006). CONCLUSION: Findings demonstrate the feasibility of multimodal pain management for same-day discharge after the Nuss procedure. Future multisite studies are needed to investigate the superiority of this approach to established methods. LEVEL OF EVIDENCE: III.
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Tórax em Funil , Manejo da Dor , Humanos , Criança , Analgésicos Opioides , Projetos Piloto , Alta do Paciente , Tórax em Funil/cirurgia , Estudos Retrospectivos , Dor Pós-Operatória/tratamento farmacológico , Procedimentos Cirúrgicos Minimamente Invasivos/métodosRESUMO
This report describes the clinical, computed tomography, and magnetic resonance imaging findings for a Jacob sheep lamb diagnosed with meningoencephalocele and supernumerary ectopic limb. Key clinical message: This case demonstrates the utility of tomographic imaging in diagnosing congenital malformations in sheep and can be used to assess the extent of the lesion. This may help to determine any viable treatment, or, as in the case presented here, determine that the extent of the lesion precludes surgical intervention.
Méningoencéphalocèle et membre ectopique surnuméraire provenant de l'os occipital chez un agneau Jacob. Ce rapport décrit les résultats cliniques, de tomodensitométrie et d'imagerie par résonance magnétique d'un agneau de Jacob chez qui on a diagnostiqué une méningoencéphalocèle et un membre ectopique surnuméraire.Message clinique clé :Ce cas démontre l'utilité de l'imagerie tomographique dans le diagnostic des malformations congénitales chez le mouton et peut être utilisée pour évaluer l'étendue de la lésion. Cela peut aider à déterminer tout traitement viable ou, comme dans le cas présenté ici, à déterminer que l'étendue de la lésion exclut une intervention chirurgicale.(Traduit par Dr Serge Messier).
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Meningocele , Doenças dos Ovinos , Animais , Ovinos , Encefalocele/diagnóstico por imagem , Encefalocele/veterinária , Meningocele/diagnóstico , Meningocele/cirurgia , Meningocele/veterinária , Osso Occipital/anormalidades , Osso Occipital/patologia , Extremidades , Tomografia Computadorizada por Raios X/veterinária , Imageamento por Ressonância Magnética/veterinária , Doenças dos Ovinos/diagnósticoRESUMO
More than two thirds of the global population lack access to safe, affordable surgical and anesthesia care. This inequity disproportionately affects children in low- and middle-income countries (LMIC). In 2016, a group of pediatric surgical care providers founded the Global Initiative for Children's Surgery (GICS). Their goal was to assemble a multidisciplinary team of specialists and advocates to improve surgical care for children, with a particular emphasis on those in low-resource settings. This review details the history of GICS, the process of its inception, the values guiding its work, its past achievements, and its current initiatives. The experience of GICS may serve as an effective model for global collaboration on other areas of public and global health.
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Saúde Global , Criança , HumanosRESUMO
INTRODUCTION: The optimal laparoscopic appendectomy approach is not clear, comparing single site laparoscopic appendectomy (SILA) to conventional 3-port appendectomy (CLA). We investigated outcomes in pediatric patients comparing SILA to CLA: length of operation, length of stay, time to resumption of regular diet, follow up, rehospitalization, and cost. METHODS: Data was collected from children 1 to 18 years with appendectomy at Loma Linda University from 2018 to 2020, operated by two surgeons. Analysis utilized two-sample T, chi-squared, and Fisher's exact tests. RESULTS: Of 173 patients, 77 underwent SILA and 96 had CLA. There was no gender, age, or race difference between groups. Mean WBC was 17.5 × 103/mL in SILA group, compared to 15.3 × 103/mL in CLA group (P = 0.004). Operative time was 47.0 SILA compared to 49.5 minutes CLA (P = 0.269). Of SILA cases, 55.8% were simple appendicitis, while 53.3% of the CLA cases were simple (P = 0.857). Regular diet was resumed after 1.7 days in the SILA group, 1.1 days in CLA (P = 0.018). Length of stay was 2.9 days for SILA, 2.4 days for CLA (P = 0.144). Seven children required hospital readmission, 5 SILA and 2 CLA (P = 0.244). Five of the children who returned had intra-abdominal abscesses, of whom 4 had SILA. There was no difference in cost. CONCLUSIONS: The operative techniques had similar outcomes and operative times. There was a trend toward more intra-abdominal abscesses in the SILA group. Further study and longer follow up is needed to determine if there is an advantage to one laparoscopic approach over another.
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Abscesso Abdominal/epidemiologia , Apendicectomia/efeitos adversos , Apendicite/cirurgia , Laparoscopia/efeitos adversos , Dor Pós-Operatória/epidemiologia , Abscesso Abdominal/economia , Abscesso Abdominal/etiologia , Adolescente , Apendicectomia/economia , Apendicectomia/métodos , Apendicite/economia , Criança , Pré-Escolar , Análise Custo-Benefício , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Lactente , Laparoscopia/economia , Laparoscopia/métodos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Duração da Cirurgia , Medição da Dor/estatística & dados numéricos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/economia , Dor Pós-Operatória/etiologia , Readmissão do Paciente/economia , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Temperature is increasingly recognized as an important component of wildlife habitat. Temperature is particularly important for avian nest sites, where extreme temperatures can influence adult behavior, embryonic development, and survival. For species inhabiting arid and semiarid climates, such as the scaled quail (Callipepla squamata), frequent exposure to extreme temperatures may increase the importance of the nest microclimate. Limited data suggest that scaled quail respond to temperature when selecting nest sites, and they are also known to respond to the presence of surface water and shrub cover on the landscape, two resources which may mitigate thermal stress. To better understand the role of temperature in nest site selection and survival, and to evaluate how other landscape resources may benefit nesting quail, we investigated nest site characteristics of scaled quail in southeastern New Mexico, USA. During the breeding seasons of 2018 and 2019 we located nests, monitored nest fate, and recorded thermal and vegetation characteristics at three spatial scales: the nest bowl, the nest microsite (area within 10 m of the nest bowl), and the landscape. We found that nest bowls moderated temperature relative to both the surrounding microsite and the broader landscape, remaining almost 5 °C cooler on average than the surrounding microsite at mid-day. Nest bowls also had taller, greater cover of vegetation compared to both the surrounding microsites and the landscape. Despite apparent selection for cooler temperatures and taller vegetation, these characteristics demonstrated a weak relationship with nest survival. Rather, nest survival was positively influenced by proximity to surface water and honey mesquite (Prosopis glandulosa), with survival decreasing with increasing distance from these features. Although the mechanism for this relationship is unclear, our results support the importance of temperature for nest site selection of ground-nesting birds in semiarid landscapes, and suggest further exploration of landscape-level sources of thermal mitigation.
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Comportamento de Nidação , Codorniz/fisiologia , Termotolerância , Distribuição Animal , Animais , EcossistemaRESUMO
Canine parvovirus (CPV) is a highly successful pathogen that has sustained pandemic circulation in dogs for more than 40 years. Here, integrating full-genome and deep-sequencing analyses, structural information, and in vitro experimentation, we describe the macro- and microscale features that accompany CPV's evolutionary success. Despite 40 years of viral evolution, all CPV variants are more than â¼99% identical in nucleotide sequence, with only a limited number (<40) of substitutions becoming fixed or widespread during this time. Notably, most substitutions in the major capsid protein (VP2) gene are nonsynonymous, altering amino acid residues that fall within, or adjacent to, the overlapping receptor footprint or antigenic regions, suggesting that natural selection has channeled much of CPV evolution. Among the limited number of variable sites, CPV genomes exhibit complex patterns of variation that include parallel evolution, reversion, and recombination, compromising phylogenetic inference. At the intrahost level, deep sequencing of viral DNA in original clinical samples from dogs and other host species sampled between 1978 and 2018 revealed few subconsensus single nucleotide variants (SNVs) above â¼0.5%, and experimental passages demonstrate that substantial preexisting genetic variation is not necessarily required for rapid host receptor-driven adaptation. Together, these findings suggest that although CPV is capable of rapid host adaptation, a relatively low mutation rate, pleiotropy, and/or a lack of selective challenges since its initial emergence have inhibited the long-term accumulation of genetic diversity. Hence, continuously high levels of inter- and intrahost diversity are not necessarily required for virus host adaptation.IMPORTANCE Rapid mutation rates and correspondingly high levels of intra- and interhost diversity are often cited as key features of viruses with the capacity for emergence and sustained transmission in a new host species. However, most of this information comes from studies of RNA viruses, with relatively little known about evolutionary processes in viruses with single-stranded DNA (ssDNA) genomes. Here, we provide a unique model of virus evolution, integrating both long-term global-scale and short-term intrahost evolutionary processes of an ssDNA virus that emerged to cause a pandemic in a new host animal. Our analysis reveals that successful host jumping and sustained transmission does not necessarily depend on a high level of intrahost diversity nor result in the continued accumulation of high levels of long-term evolution change. These findings indicate that all aspects of the biology and ecology of a virus are relevant when considering their adaptability.
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Proteínas do Capsídeo/genética , DNA Viral/genética , Doenças do Cão/epidemiologia , Genoma Viral , Infecções por Parvoviridae/veterinária , Parvovirus Canino/genética , Proteínas não Estruturais Virais/genética , Adaptação Fisiológica/genética , Animais , Evolução Biológica , Proteínas do Capsídeo/classificação , Proteínas do Capsídeo/metabolismo , DNA Viral/metabolismo , Doenças do Cão/transmissão , Doenças do Cão/virologia , Cães , Raposas/virologia , Especificidade de Hospedeiro/genética , Modelos Moleculares , Mutação , Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/transmissão , Infecções por Parvoviridae/virologia , Parvovirus Canino/classificação , Parvovirus Canino/patogenicidade , Filogenia , Conformação Proteica , Cães Guaxinins/virologia , Guaxinins/virologia , Proteínas não Estruturais Virais/classificação , Proteínas não Estruturais Virais/metabolismo , Sequenciamento Completo do GenomaRESUMO
Avian-origin H3N2 canine influenza virus (CIV) transferred to dogs in Asia around 2005, becoming enzootic throughout China and South Korea before reaching the United States in early 2015. To understand the posttransfer evolution and epidemiology of this virus, particularly the cause of recent and ongoing increases in incidence in the United States, we performed an integrated analysis of whole-genome sequence data from 64 newly sequenced viruses and comprehensive surveillance data. This revealed that the circulation of H3N2 CIV within the United States is typified by recurrent epidemic burst-fade-out dynamics driven by multiple introductions of virus from Asia. Although all major viral lineages displayed similar rates of genomic sequence evolution, H3N2 CIV consistently exhibited proportionally more nonsynonymous substitutions per site than those in avian reservoir viruses, which is indicative of a large-scale change in selection pressures. Despite these genotypic differences, we found no evidence of adaptive evolution or increased viral transmission, with epidemiological models indicating a basic reproductive number, R0, of between 1 and 1.5 across nearly all U.S. outbreaks, consistent with maintained but heterogeneous circulation. We propose that CIV's mode of viral circulation may have resulted in evolutionary cul-de-sacs, in which there is little opportunity for the selection of the more transmissible H3N2 CIV phenotypes necessary to enable circulation through a general dog population characterized by widespread contact heterogeneity. CIV must therefore rely on metapopulations of high host density (such as animal shelters and kennels) within the greater dog population and reintroduction from other populations or face complete epidemic extinction.IMPORTANCE The relatively recent appearance of influenza A virus (IAV) epidemics in dogs expands our understanding of IAV host range and ecology, providing useful and relevant models for understanding critical factors involved in viral emergence. Here we integrate viral whole-genome sequence analysis and comprehensive surveillance data to examine the evolution of the emerging avian-origin H3N2 canine influenza virus (CIV), particularly the factors driving ongoing circulation and recent increases in incidence of the virus within the United States. Our results provide a detailed understanding of how H3N2 CIV achieves sustained circulation within the United States despite widespread host contact heterogeneity and recurrent epidemic fade-out. Moreover, our findings suggest that the types and intensities of selection pressures an emerging virus experiences are highly dependent on host population structure and ecology and may inhibit an emerging virus from acquiring sustained epidemic or pandemic circulation.
Assuntos
Doenças do Cão/epidemiologia , Doenças do Cão/virologia , Epidemias , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Infecções por Orthomyxoviridae/veterinária , Animais , Número Básico de Reprodução , Transmissão de Doença Infecciosa , Cães , Epidemiologia Molecular , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/virologia , Filogenia , Seleção Genética , Análise de Sequência de DNA , Estados Unidos/epidemiologia , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Antimicrobial resistance (AMR) of bacterial pathogens is an emerging public health threat. This threat extends to pets as it also compromises our ability to treat their infections. Surveillance programs in the United States have traditionally focused on collecting data from food animals, foods, and people. The Veterinary Laboratory Investigation and Response Network (Vet-LIRN), a national network of 45 veterinary diagnostic laboratories, tested the antimicrobial susceptibility of clinically relevant bacterial isolates from animals, with companion animal species represented for the first time in a monitoring program. During 2017, we systematically collected and tested 1968 isolates. To identify genetic determinants associated with AMR and the potential genetic relatedness of animal and human strains, whole genome sequencing (WGS) was performed on 192 isolates: 69 Salmonella enterica (all animal sources), 63 Escherichia coli (dogs), and 60 Staphylococcus pseudintermedius (dogs). RESULTS: We found that most Salmonella isolates (46/69, 67%) had no known resistance genes. Several isolates from both food and companion animals, however, showed genetic relatedness to isolates from humans. For pathogenic E. coli, no resistance genes were identified in 60% (38/63) of the isolates. Diverse resistance patterns were observed, and one of the isolates had predicted resistance to fluoroquinolones and cephalosporins, important antibiotics in human and veterinary medicine. For S. pseudintermedius, we observed a bimodal distribution of resistance genes, with some isolates having a diverse array of resistance mechanisms, including the mecA gene (19/60, 32%). CONCLUSION: The findings from this study highlight the critical importance of veterinary diagnostic laboratory data as part of any national antimicrobial resistance surveillance program. The finding of some highly resistant bacteria from companion animals, and the observation of isolates related to those isolated from humans demonstrates the public health significance of incorporating companion animal data into surveillance systems. Vet-LIRN will continue to build the infrastructure to collect the data necessary to perform surveillance of resistant bacteria as part of fulfilling its mission to advance human and animal health. A One Health approach to AMR surveillance programs is crucial and must include data from humans, animals, and environmental sources to be effective.
Assuntos
Bactérias/efeitos dos fármacos , Bactérias/genética , Laboratórios/normas , Saúde Única , Medicina Veterinária/organização & administração , Sequenciamento Completo do Genoma , Animais , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/veterinária , Canadá/epidemiologia , Estados Unidos/epidemiologiaRESUMO
Myocarditis can cause death or permanent heart damage. As epidemiologic and etiopathologic data for canine myocarditis are lacking, we performed a retrospective study using nucleic acid extracted from archived (2007 to 2015) tissues from myocarditis cases and control dogs without myocardial lesions. Heart tissue from pediatric/juvenile and adult dogs was tested with a comprehensive panel of conventional and real-time polymerase chain reaction (PCR) assays targeting recognized agents of canine myocarditis based on a literature review and informed by the comparative epidemiology of human myocarditis. The PCR screen, which included canine parvovirus 2 (CPV-2), canine distemper virus, canine herpesvirus, Borrelia spp, West Nile virus, adenovirus, parainfluenza virus, pneumovirus, respiratory coronavirus, influenza virus, Bartonella spp, Rickettsia spp, Mycoplasma spp, and Neospora caninum, did not detect agents in 35 of 66 cases (53%; 95% confidence interval [CI], 41%-65%) and was frequently negative in adults (21/26); by comparison, agents were not detected in 27 of 57 controls (47%; 95% CI, 35%-60%). Canine distemper virus, herpesvirus, adenovirus, coronavirus, parainfluenza virus, Mycoplasma haemocanis, and N. caninum were occasionally detected in both cases and controls; thus, PCR detection was not considered to indicate causation. We previously reported that CPV-2 continues to be associated with myocarditis in young dogs despite widespread vaccination; in adults, CPV-2 was detected in 2 of 26 cases and 4 of 22 controls. As several agents were similarly detected in cases and controls, it is unclear if these are cardiopathogenic, incidental, or latent. West Nile virus was detected at the analytic limit in 1 adult case. We did not detect Borrelia spp, Bartonella spp, Rickettsia spp, or influenza A virus in the myocarditis cases. These data demonstrate the limitations of current targeted diagnostic tests and the need for additional research to identify unknown agents and develop testing strategies for canine myocarditis.
Assuntos
Doenças do Cão/etiologia , Fibrose/veterinária , Miocardite/veterinária , Animais , Cães , Fibrose/etiologia , Fibrose/patologia , Humanos , Miocardite/etiologia , Miocardite/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Five billion people worldwide lack access to safe surgery. American College of Surgeons (ACS) members have a strong history of humanitarian and volunteer work. Since its founding in 2004, Operation Giving Back (OGB) has served as a volunteer resource portal. This study sought to understand current activities, needs, and barriers to ACS member volunteerism, and to re-assess the role of OGB. METHODS: A 25-question electronic survey was sent to ACS members in August 2015. Utilizing branching logic, those who were involved or interested in volunteerism completed the full survey. Data were assessed using univariable analysis methods. RESULTS: Three percent (n = 1764) of those e-mailed answered the survey. Respondents were mostly men (82%), ≥50 years of age (61%), and general surgeons (70%). Fifty-three percent (n = 937) reported current or past volunteer activities, and 76.5% (n = 1349) were interested in activities within three years. Approximately 84% were interested in international volunteerism and 55% in domestic volunteerism. Few (5.7%) had both training and experience in emergency and disaster response, and only 17% had institutional salary support. Eighty-two percent wished to work with OGB, and 418 indicated organizations with whom they are involved could benefit from OGB collaboration. CONCLUSIONS: Interest in surgical volunteerism among ACS member survey respondents is high. OGB has the opportunity to meet member needs by developing programmatic activities, identifying volunteer prospects, facilitating multi-institutional consortia, and leading pre-deployment training. By maximizing volunteer efforts, OGB has the potential to foster sustainable and scalable ethical practices to improve basic access to surgical care globally.
Assuntos
Saúde Global , Missões Médicas/estatística & dados numéricos , Cirurgiões/estatística & dados numéricos , Voluntários/estatística & dados numéricos , Adulto , Altruísmo , Feminino , Humanos , Masculino , Missões Médicas/organização & administração , Pessoa de Meia-Idade , Sociedades Médicas/organização & administração , Cirurgiões/organização & administração , Cirurgiões/psicologia , Inquéritos e Questionários , Estados Unidos , Voluntários/psicologiaRESUMO
BACKGROUND: Mongolia is a country characterized by its vast distances and extreme climate. An underdeveloped medical transport infrastructure makes patient transfer from outlying regions dangerous. Providing pediatric surgical care locally is crucial to improve the lives of children in the countryside. This is the first structured assessment of nationwide pediatric surgical capacity. METHODS: Operation rates were calculated using data from the Mongolian Center for Health Development and population data from the Mongolian Statistical Information Service. The Pediatric Personnel, Infrastructure, Procedures, Equipment, and Supplies (PediPIPES) survey tool was used to collect data at all survey sites. Descriptive data analyses were completed using Excel. Studies of association were completed using Stata. All reported percentages are of the hospitals outside of the capital (n = 21). RESULTS: All provincial hospitals have general surgeons; seven (33.3%) of them have pediatric surgeon(s). One facility has no anesthesiologist. All facilities perform basic procedures and provide anesthesia. Four (19%) can treat common congenital anomalies. All facilities have basic operating room equipment. Nine hospitals do not have pulse oximetry available. Twelve hospitals do not have pediatric surgical instruments always available. Pediatric supplies are lacking. CONCLUSIONS: Provincial hospitals in Mongolia can perform basic procedures. However, essential pediatric supplies are lacking. Consequently, certain life-saving procedures are not available to children outside of the capital. Only a few improvements would be amendable to low-cost process improvement adjustment, and the majority of needs require resource additions. Procedure, equipment, and supply availability should be further explored to develop a comprehensive nationwide pediatric surgical program.
Assuntos
Recursos em Saúde/provisão & distribuição , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Pediatria , Especialidades Cirúrgicas , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Mongólia , Serviços de Saúde Rural/provisão & distribuiçãoRESUMO
BACKGROUND: Over one million asylum seekers were registered in Germany in 2016, most from Syria and Afghanistan. The Refugee Convention guarantees access to healthcare, however delivery mechanisms remain heterogeneous. There is an urgent need for more data describing the health conditions of asylum seekers to guide best practices for healthcare delivery. In this study, we describe the state of health of asylum seekers presenting to a multi-specialty primary care refugee clinic. METHODS: Demographic and medical diagnosis data were extracted from the electronic medical records of patients seen at the ambulatory refugee clinic in Dresden, Germany between 15 September 2015 and 31 December 2016. Data were de-identified and analyzed using Stata version 14.0. RESULTS: Two-thousand-seven-hundred and fifty-three individual patients were seen in the clinic. Of these, 2232 (81.1%) were insured by the state indicating arrival within the last 3 months. The median age was 25, interquartile range 16-34. Only 786 (28.6%) were female, while 1967 (71.5%) were male. The most frequent diagnoses were respiratory (17.4%), followed by miscellaneous symptoms and otherwise not classified ailments (R series, 14.1%), infection (10.8%), musculoskeletal or connective tissue (9.3%), gastrointestinal (6.8%), injury (5.9%), and mental or behavioral (5.1%) categories. CONCLUSIONS: This study illustrates the diverse medical conditions that affect the asylum seeker population. Asylum seekers in our study group did not have a high burden of communicable diseases, however several warranted additional screening and treatment, including for tuberculosis and scabies. Respiratory illnesses were more common amongst newly arrived refugees. Trauma-related mental health disorders comprised half of mental health diagnoses.