Child and adolescent COVID-19 vaccination status and reasons for non-vaccination by parental vaccination status.

OBJECTIVES: COVID-19 vaccines are recommended for children ages ≥5 years. To develop effective interventions to increase uptake, this study explores reasons for parental hesitancy of child and adolescent COVID-19 vaccination. STUDY DESIGN: The Household Pulse Survey (HPS) is a nationally representative cross-sectional online household survey of adults aged ≥18 years that began data collection in April 2020 to help understand household experiences during the COVID-19 pandemic. METHODS: Using data from December 29, 2021, to January 10, 2022 (n = 11,478), we assessed child and adolescent COVID-19 vaccination coverage and parental intent to vaccinate their children and adolescents. Factors associated with child and adolescent vaccination coverage were examined using multivariable regression models. Reasons for not having had their child or adolescent vaccinated, stratified by parental vaccination status, were compared using tests of differences in proportions. RESULTS: Less than one-half (42.3%) of children and three-quarters (74.8%) of adolescents are vaccinated. Vaccination coverage was lower among households with lower education, as well as among children who had not had a preventive check-up in the past year. Parents of unvaccinated children were more likely to report that they do not trust COVID-19 vaccines, do not trust the government, and do not believe children need a COVID-19 vaccine compared to parents of vaccinated children. CONCLUSION: Efforts to increase uptake of vaccines by children and adolescents should target those with lower education, reassure parents of the vaccine safety and efficacy for themselves and their children/adolescents, and support yearly preventive care visits for their children.

Autocrine regulation of wound healing by ATP release and P2Y2 receptor activation.

AIMS: Application of exogenous nucleotides can modulate wound healing via the activation of purinergic receptors. However, evidence for the release of endogenous nucleotides and the subsequent activation of purinergic receptors in this process has not been well defined. Therefore, the current study aimed to investigate wound-mediated nucleotide release and autocrine purinergic signalling during HaCaT keratinocyte wound closure following scratch injury. MAIN METHODS: An in vitro scratch wound apparatus was employed to study wound healing over 24-h in the presence of modulators of ATP release, P2 receptors and pathways downstream of P2 receptor activation. KEY FINDINGS: Adenosine 5'-triphosphate (ATP) was released from scratched cells. The ectonucleotidase apyrase and pharmacological inhibition of the nucleotide release hemichannel, pannexin-1, decreased wound closure over time. The non-selective P2Y receptor antagonist suramin and the selective P2Y2 receptor antagonist AR-C118925XX, but not other P2 antagonists, decreased wound closure. AR-C118925XX decreased wound closure in a concentration-dependent fashion. However, exogenous P2Y2 receptor agonists, ATP or uridine 5'-triphosphate, did not enhance wound closure. PCR and immunoblotting confirmed P2Y2 receptor expression in HaCaT cells. U73122, a phospholipase C antagonist, and 2-aminoethoxydiphenylborate, an inositol 1,4,5-trisphosphate receptor-sensitive Ca2+-release channel antagonist, decreased wound closure consistent with P2Y2 receptor activation. Absence of extracellular or intracellular Ca2+ or inhibition of intracellular Ca2+-release also impaired wound closure. SIGNIFICANCE: These data describe a novel autocrine signalling mechanism in which wound-mediated release of endogenous ATP in response to mechanical scratching of HaCaT cells activates P2Y2 receptors to facilitate wound closure.

Bacterial colonization of bladder urothelial cells in women with refractory Detrusor Overactivity: the effects of antibiotic therapy.

Bacterial infection may have a pathophysiological role in refractory Detrusor Overactivity (DO). The aim of this study was to observe any impact of antibiotic therapy upon bacterial colonization of urothelial cells, and to determine whether a relationship existed between colonization and symptom severity. Mid-stream urine samples were collected as part of a clinical trial of antibiotics in women with refractory DO. Wright stained urothelial cells were categorized according to the degree of bacterial colonization as; 'clear' (free of bacteria), or as associated with bacteria that were 'adjacent' to the cell or 'intracellular' at low or high density. The average percentages were compared with routine microbiology cultures, over the 26 week trial, and with patient clinical outcome measures of DO severity. In patients receiving placebo, 'high-density intracellular bacteria' significantly increased during urinary tract infection (P = 0.0008). In antibiotic patients, 'clear' cells were more prevalent. Amoxicillin & Clavulanic Acid significantly decreased bacterial colonization within urothelial cells, suggesting that these antibiotics possess the greatest intracellular efficacy. 'High-density intracellular bacteria' positively correlated with symptom severity, measured by leakage on pad test (P = 0.014), leaks per day (P = 0.004), and voids per day (P = 0.005). Thus, by decreasing high density intracellular bacteria, antibiotic treatment may improve the refractory DO condition.

Inflammatory skin diseases and the risk of chronic kidney disease: population-based case-control and cohort analyses.

BACKGROUND: Emerging evidence suggests an association between common inflammatory skin diseases and chronic kidney disease (CKD). OBJECTIVES: To explore the association between CKD stages 3-5 (CKD3-5) and atopic eczema, psoriasis, rosacea and hidradenitis suppurativa. METHODS: We undertook two complementary analyses; a prevalent case-control study and a cohort study using routinely collected primary care data [UK Clinical Practice Research Datalink (CPRD)]. We matched individuals with CKD3-5 in CPRD in March 2018 with up to five individuals without CKD for general practitioner practice, age and sex. We compared the prevalence of CKD3-5 among individuals with and without each inflammatory skin disease. We included individuals in CPRD with diabetes mellitus (2004-2018) in a cohort analysis to compare the incidence of CKD3-5 among people with and without atopic eczema and psoriasis. RESULTS: Our study included 56 602 cases with CKD3-5 and 268 305 controls. Cases were more likely than controls to have a history of atopic eczema [odds ratio (OR) 1·14, 99% confidence interval (CI) 1·11-1·17], psoriasis (OR 1·13, 99% CI 1·08-1·19) or hidradenitis suppurativa (OR 1·49, 99% CI 1·19-1·85), but were slightly less likely to have been diagnosed with rosacea (OR 0·92, 99% CI 0·87-0·97), after adjusting for age, sex, practice (matching factors), index of multiple deprivation, diabetes, smoking, harmful alcohol use and obesity. Results remained similar after adjusting for hypertension and cardiovascular disease. In the cohort with diabetes (N = 335 827), there was no evidence that CKD3-5 incidence was associated with atopic eczema or psoriasis. CONCLUSIONS: Atopic eczema, psoriasis and hidradenitis suppurativa are weakly associated with CKD3-5. Future research is needed to elucidate potential mechanisms and the clinical significance of our findings.

Four childhood atopic dermatitis subtypes identified from trajectory and severity of disease and internally validated in a large UK birth cohort.

BACKGROUND: Atopic dermatitis (AD) disease activity and severity is highly variable during childhood. Early attempts to identify subtypes based on disease trajectory have assessed AD presence over time without incorporating severity. OBJECTIVES: To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables. METHODS: We split data from children in the Avon Longitudinal Study of Parents and Children birth cohort into development and validation sets. To identify subtypes, we ran latent class analyses in the development set on AD symptom reports up to age 14 years. We regressed identified subtypes on nongenetic variables in mutually adjusted, multiply imputed (genetic: unadjusted, complete case) multinomial regression analyses. We repeated analyses in the validation set and report confirmed results. RESULTS: There were 11 866 children who contributed to analyses. We identified one Unaffected/Rare class (66% of children) and four AD subtypes: Severe-Frequent (4%), Moderate-Frequent (7%), Moderate-Declining (11%) and Mild-Intermittent (12%). Symptom patterns within the first two subtypes appeared more homogeneous than the last two. Filaggrin (FLG) null mutations, an AD polygenic risk score (PRS), being female, parental AD and comorbid asthma were associated with higher risk for some or all subtypes; FLG, AD-PRS and asthma associations were stronger along a subtype gradient arranged by increasing severity and frequency; FLG and AD-PRS further differentiated some phenotypes from each other. CONCLUSIONS: Considering severity and AD trajectories leads to four well-defined and recognizable subtypes. The differential associations of risk factors among and between subtypes is novel and requires further research.

Atopic eczema and obesity: a population-based study.

BACKGROUND: Atopic eczema is a common chronic inflammatory skin disease. Research suggests an association between atopic eczema and obesity, with inconsistent evidence from European populations. OBJECTIVES: To explore the association between diagnosed atopic eczema and being overweight or obese, and whether increased atopic eczema severity was associated with higher body mass index. METHODS: We undertook a cross-sectional analysis within a cohort of adults (matched by age, sex and general practice) with and without a diagnosis of atopic eczema. We used primary care (Clinical Practice Research Datalink Gold) and linked hospital admissions data (1998-2016). We used conditional logistic regression to compare the odds of being overweight or obese (adjusting for confounders and potential mediators) in those with atopic eczema (mild, moderate and severe, and all eczema) vs. those without. RESULTS: We identified 441 746 people with atopic eczema, matched to 1 849 722 without. People with atopic eczema had slightly higher odds of being overweight or obese vs. those without [odds ratio (OR) 1·08, 95% confidence interval (CI) 1·07-1·09] after adjusting for age, asthma and socioeconomic deprivation. Adjusting for potential mediators (high-dose glucocorticoids, harmful alcohol use, anxiety, depression, smoking) had a minimal impact on effect estimates (OR 1·07, 95% CI 1·06-1·08). We saw no evidence that odds of being overweight or obese increased with increasing atopic eczema severity, and there was no association in people with severe eczema. CONCLUSIONS: We found evidence of a small overall association between atopic eczema and being overweight or obese. However, there was no association with obesity among those with the most severe eczema. Our findings are largely reassuring for this prevalent patient group who may already have an increased risk of cardiovascular disease.

The association between partner bereavement and melanoma: cohort studies in the U.K. and Denmark.

BACKGROUND: Psychological stress is commonly cited as a risk factor for melanoma, but clinical evidence is limited. OBJECTIVES: This study aimed to evaluate the association between partner bereavement and (i) first-time melanoma diagnosis and (ii) mortality in patients with melanoma. METHODS: We conducted two cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). In study 1, we compared the risk of first melanoma diagnosis in bereaved vs. matched nonbereaved people using stratified Cox regression. In study 2 we estimated hazard ratios (HRs) for death from melanoma in bereaved compared with nonbereaved individuals with melanoma using Cox regression. We estimated HRs separately for the U.K. and for Denmark, and then pooled the data to perform a random-effects meta-analysis. RESULTS: In study 1, the pooled adjusted HR for the association between partner bereavement and melanoma diagnosis was 0·88 [95% confidence interval (CI) 0·84-0·92] across the entire follow-up period. In study 2, we observed increased melanoma-specific mortality in people experiencing partner bereavement across the entire follow-up period (HR 1·17, 95% CI 1·06-1·30), with the peak occurring during the first year of follow-up (HR 1·31, 95% CI 1·07-1·60). CONCLUSIONS: We found decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. These findings may be partly explained by delayed detection resulting from the loss of a partner who could notice skin changes. Stress may play a role in melanoma progression. Our findings indicate the need for a low threshold for skin examination in individuals whose partners have died. What is already known about this topic? Psychological stress has been proposed as a risk factor for the development and progression of cancer, including melanoma, but evidence is conflicting. Clinical evidence is limited by small sample sizes, potential recall bias associated with self-report, and heterogeneous stress definitions. What does this study add? We found a decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. While stress might play a role in the progression of melanoma, an alternative explanation is that bereaved people no longer have a close person to help notice skin changes, leading to delayed melanoma detection. Linked Comment: Talaganis et al. Br J Dermatol 2020; 183:607-608.

Partner bereavement and risk of psoriasis and atopic eczema: cohort studies in the U.K. and Denmark.

BACKGROUND: Stress is commonly cited as a risk factor for psoriasis and atopic eczema, but such evidence is limited. OBJECTIVES: To investigate the association between partner bereavement (an extreme life stressor) and psoriasis or atopic eczema. METHODS: We conducted cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). The exposed cohort was partners who experienced partner bereavement. The comparison cohort was up to 10 nonbereaved partners, matched to each bereaved partner by age, sex, county of residence (Denmark) and general practice (U.K.). Outcomes were the first recorded diagnosis of psoriasis or atopic eczema. We estimated hazard ratios (HRs) and confidence intervals (CIs) using a stratified Cox proportional hazards model in both settings, which were then pooled in a meta-analysis. RESULTS: The pooled adjusted HR for the association between bereavement and psoriasis was 1·01 (95% CI 0·98-1·04) across the entire follow-up. Similar results were found in other shorter follow-up periods. Pooled adjusted HRs for the association between bereavement and atopic eczema were 0·97 (95% CI 0·84-1·12) across the entire follow-up, 1·09 (95% CI 0·86-1·38) within 0-30 days, 1·18 (95% CI 1·04-1·35) within 0-90 days, 1·14 (95% CI 1·06-1·22) within 0-365 days and 1·07 (95% CI 1·02-1·12) within 0-1095 days. CONCLUSIONS: We found a modest increase in the risk of atopic eczema within 3 years following bereavement, which peaked in the first 3 months. Acute stress may play a role in triggering onset of new atopic eczema or relapse of atopic eczema previously in remission. We observed no evidence for increased long-term risk of psoriasis and atopic eczema following bereavement.

Evaluation of the quality and health literacy demand of online renal diet information.

BACKGROUND: Dietary modification is critical in the self-management of chronic kidney disease. The present study describes the accuracy, quality and health literacy demand of renal diet information for adults with kidney disease obtained from the Internet and YouTube (www.youtube.com). METHODS: A comprehensive content analysis was undertaken in April and July 2015 of 254 eligible websites and 161 YouTube videos. The accuracy of the renal diet information was evaluated by comparing the key messages with relevant evidence-based guidelines for the dietary management of people with kidney disease. The DISCERN tool (www.discern.org.uk) was used to evaluate the quality of the material. Health literacy demand was evaluated using the Patient Education Material Assessment Tool (www.ahrq.gov/professionals/prevention-chronic-care/improve/self-mgmt/pemat/index.html) and seven validated readability calculators. RESULTS: The most frequent renal diet topic found online was generic dietary information for people with chronic kidney disease. The proportion of renal diet information obtained from websites that was accurate was 73%. However, this information was mostly of poor quality with extensive shortcomings, difficult to action and written with a high health literacy demand. By contrast, renal diet information available from YouTube was highly understandable and actionable, although only 18% of the videos were accurate, and a large proportion were of poor quality with extensive shortcomings. The most frequent authors of accurate, good quality, understandable, material were government bodies, dietitians, academic institutions and medical organisations. CONCLUSIONS: Renal diet information found online that is written by government bodies, dietitians, academic institutions and medical organisations is recommended. Further work is required to improve the quality and, most importantly, the actionability of renal diet information found online.

Widespread detection of highly pathogenic H5 influenza viruses in wild birds from the Pacific Flyway of the United States.

A novel highly pathogenic avian influenza virus belonging to the H5 clade 2.3.4.4 variant viruses was detected in North America in late 2014. Motivated by the identification of these viruses in domestic poultry in Canada, an intensive study was initiated to conduct highly pathogenic avian influenza surveillance in wild birds in the Pacific Flyway of the United States. A total of 4,729 hunter-harvested wild birds were sampled and highly pathogenic avian influenza virus was detected in 1.3% (n = 63). Three H5 clade 2.3.4.4 subtypes were isolated from wild birds, H5N2, H5N8, and H5N1, representing the wholly Eurasian lineage H5N8 and two novel reassortant viruses. Testing of 150 additional wild birds during avian morbidity and mortality investigations in Washington yielded 10 (6.7%) additional highly pathogenic avian influenza isolates (H5N8 = 3 and H5N2 = 7). The geographically widespread detection of these viruses in apparently healthy wild waterfowl suggest that the H5 clade 2.3.4.4 variant viruses may behave similarly in this taxonomic group whereby many waterfowl species are susceptible to infection but do not demonstrate obvious clinical disease. Despite these findings in wild waterfowl, mortality has been documented for some wild bird species and losses in US domestic poultry during the first half of 2015 were unprecedented.

The common marmoset as a model for the study of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. The more clinically concerning form of the disease, nonalcoholic steatohepatitis (NASH), is characterized by steatosis, lobular inflammation, and ballooning degeneration. Here we describe a naturally occurring syndrome in the common marmoset that recapitulates the pathologic findings associated with NAFLD/NASH in humans. Hepatomegaly determined to result from NAFLD was observed in 33 of 183 marmosets. A comprehensive histopathologic assessment performed in 31 marmosets demonstrated that NAFLD was characterized by variably sized, Oil Red O staining cytoplasmic vacuoles and observed primarily in animals with evidence of obesity and insulin resistance. A subset of marmosets (16 of 31) also demonstrated evidence of NASH characterized by multifocal inflammation combined with ballooning hepatocellular degeneration. Marmosets with NASH demonstrated an increase in immunostaining with an antibody targeted against the human leukocyte antigens (HLA)-DP, HLA-DQ, and HLA-DR compared with marmosets without NASH (38.89 cells/10× field vs 12.05 cells/10× field, P = .05). In addition, marmosets with NASH demonstrated increased Ki-67 immunopositive cellular proliferation compared with those without (5.95 cells/10× field vs 1.53 cells/10× field, P = .0002). Finally, animals with NASH demonstrated significantly increased mean circulating serum iron levels (160.47 µg/dl, P = .008) and an increase in numbers of Prussian blue-positive Kupffer cells (9.28 cells/40× field, P = .005) relative to marmosets without NASH (97.75 µg/dl and 1.87 cells/40×, respectively). This study further characterizes the histopathology of NAFLD/NASH and suggests that the marmoset may be a valuable animal model with which to investigate the host and environmental factors contributing to the progression of NAFLD/ NASH.

Isolation of digital dermatitis treponemes from hoof lesions in Wild North American Elk (Cervus elaphus) in Washington State, USA.

Since 2008, a large increase in the numbers of cases of lameness have been seen in wild North American elk (Cervus elaphus) from Washington State, USA. The most recent cases manifested as foot lesions similar both clinically and pathologically to those seen in digital dermatitis (DD) in cattle and sheep, a disease with a bacterial etiopathogenesis. To determine whether the same bacteria considered responsible for DD are associated with elk lameness, lesion samples were subjected to bacterial isolation studies and PCR assays for three phylogroups of relevant DD treponemes. The DD treponemes were isolated from lesional tissues but not from control feet or other areas of the diseased foot (including the coronary band or interdigital space), suggesting that the bacteria are strongly associated with DD lesions and may therefore be causal. In addition, PCR analysis revealed that all three unique DD treponeme phylotypes were found in elk hoof disease, and in 23% of samples, all 3 DD-associated treponemes were present in lesions. Sequence analysis of the 16S rRNA gene showed that the elk lesion treponemes were phylogenetically almost identical to those isolated from cattle and sheep DD lesions. The isolates were particularly similar to two of the three culturable DD treponeme phylotypes: specifically, the Treponema medium/Treponema vincentii-like and Treponema phagedenis-like DD spirochetes. The third treponeme culturable phylogroup (Treponema pedis), although detected by PCR, was not isolated. This is the first report describing isolation of DD treponemes from a wildlife host, suggesting that the disease may be evolving to include a wider spectrum of cloven-hoofed animals.

ATP during early bladder stretch is important for urgency in detrusor overactivity patients.

ATP is an important mediator of urgency in women with detrusor overactivity (DO). In order to understand how different degrees of bladder stretch elicited ATP release in DO patients compared with controls, sequential aliquots were collected during cystometry and ATP release was measured at each degree of bladder filling, in female patients with DO and controls. In both DO and control groups, ATP release was induced during bladder filling, suggesting that stretch stimulated further ATP release. However, the luminal ATP concentrations were already high at early filling stage (200 mL), which was even greater than those at the later filling stages (400 mL and maximum cystometric capacity, MCC), indicating that a substantial ATP release has been induced during early filling (200 mL) in both DO and controls. In DO, ATP release at 200 mL was significantly higher in those with low first desire to void (FDV) (≤ 200 mL) than in those with higher FDV (> 200 mL); this may suggest that ATP release at early stretch may play an important role in urgency (early sensation) in DO. ATP concentrations remained unchanged after voiding, suggesting that voiding did not further induce ATP release into intraluminal fluid.

Louping ill virus: an endemic tick-borne disease of Great Britain.

In Europe and Asia, Ixodid ticks transmit tick-borne encephalitis virus (TBEV), a flavivirus that causes severe encephalitis in humans but appears to show no virulence for livestock and wildlife. In the British Isles, where TBEV is absent, a closely related tick-borne flavivirus, named louping ill virus (LIV), is present. However, unlike TBEV, LIV causes a febrile illness in sheep, cattle, grouse and some other species, that can progress to fatal encephalitis. The disease is detected predominantly in animals from upland areas of the UK and Ireland. This distribution is closely associated with the presence of its arthropod vector, the hard tick Ixodes ricinus. The virus is a positive-strand RNA virus belonging to the genus Flavivirus, exhibiting a high degree of genetic homology to TBEV and other mammalian tick-borne viruses. In addition to causing acute encephalomyelitis in sheep, other mammals and some avian species, the virus is recognized as a zoonotic agent with occasional reports of seropositive individuals, particularly those whose occupation involves contact with sheep. Preventative vaccination in sheep is effective although there is no treatment for disease. Surveillance for LIV in Great Britain is limited despite an increased awareness of emerging arthropod-borne diseases and potential changes in distribution and epidemiology. This review provides an overview of LIV and highlights areas where further effort is needed to control this disease.

Safety biomarkers in preclinical development: translational potential.

The identification, application, and qualification of safety biomarkers are becoming increasingly critical to successful drug discovery and development as companies are striving to develop drugs for difficult targets and for novel disease indications in a risk-adverse environment. Translational safety biomarkers that are minimally invasive and monitor drug-induced toxicity during human clinical trials are urgently needed to assess whether toxicities observed in preclinical toxicology studies are relevant to humans at therapeutic doses. The interpretation of data during the biomarker qualification phase should include careful consideration of the analytic method used, the biology, pharmacokinetic and pharmacodynamic properties of the biomarker, and the pathophysiology of the process studied. The purpose of this review is to summarize commonly employed technologies in the development of fluid- and tissue-based safety biomarkers in drug discovery and development and to highlight areas of ongoing novel assay development.

Molecular localization techniques in the diagnosis and characterization of nonhuman primate infectious diseases.

Molecular localization techniques remain important diagnostic and research tools for the pathologist evaluating nonhuman primate tissues. In situ hybridization and immunohistochemistry protocols have been developed for many important pathogens of nonhuman primates, including RNA and DNA viruses, prions, and bacterial, protozoal, and fungal pathogens. Such techniques will remain critical in defining the impact and relevance of novel agents on animal health and disease. A comparative pathology perspective often provides valuable insight to the best strategy for reagent development and can also facilitate interpretation of molecular localization patterns. Such a perspective is grounded in a firm understanding of microbe-host pathobiology. This review summarizes current molecular localization protocols used in the diagnosis of selected primate infectious diseases.

Meeting report: Spontaneous lesions and diseases in wild, captive-bred, and zoo-housed nonhuman primates and in nonhuman primate species used in drug safety studies.

The combination of loss of habitat, human population encroachment, and increased demand of select nonhuman primates for biomedical research has significantly affected populations. There remains a need for knowledge and expertise in understanding background findings as related to the age, source, strain, and disease status of nonhuman primates. In particular, for safety/biomedical studies, a broader understanding and documentation of lesions would help clarify background from drug-related findings. A workshop and a minisymposium on spontaneous lesions and diseases in nonhuman primates were sponsored by the concurrent Annual Meetings of the American College of Veterinary Pathologists and the American Society for Veterinary Clinical Pathology held December 3-4, 2011, in Nashville, Tennessee. The first session had presentations from Drs Lowenstine and Montali, pathologists with extensive experience in wild and zoo populations of nonhuman primates, which was followed by presentations of 20 unique case reports of rare or newly observed spontaneous lesions in nonhuman primates (see online files for access to digital whole-slide images corresponding to each case report at http://www.scanscope.com/ACVP%20Slide%20Seminars/2011/Primate%20Pathology/view.apml). The minisymposium was composed of 5 nonhuman-primate researchers (Drs Bradley, Cline, Sasseville, Miller, Hutto) who concentrated on background and spontaneous lesions in nonhuman primates used in drug safety studies. Cynomolgus and rhesus macaques were emphasized, with some material presented on common marmosets. Congenital, acquired, inflammatory, and neoplastic changes were highlighed with a focus on clinical, macroscopic, and histopathologic findings that could confound the interpretation of drug safety studies.

Epizootic myocarditis associated with encephalomyocarditis virus in a group of rhesus macaques (Macaca mulatta).

Six cases of fatal myocarditis associated with encephalomyocarditis virus occurred over a 14-month period in a group of outdoor-housed juvenile rhesus macaques. All animals were younger than 3 years of age and died or were euthanized following acute onset of dyspnea or pulmonary effusion (3 of 6) or were found dead without premonitory signs (3 of 6). Gross findings included pulmonary congestion (6 of 6), variable degrees of pleural effusion (4 of 6), multifocal pale tan foci throughout the myocardium (3 of 6), hepatomegaly and hepatic congestion (3 of 6), and pericardial effusion (1 of 6). Histologically, affected myocardium was infiltrated multifocally by lymphoplasmacytic and histiocytic inflammation admixed with necrotic and degenerate myofibers and infrequent mineralization (6 of 6). Pulmonary edema was present in all animals. Encephalomyocarditis virus was confirmed in 6 of 6 hearts by immunohistochemistry, and virus was isolated from one case by polymerase chain reaction. Sequencing of virus isolated from 1 affected animal indicated infection with a novel encephalomyocarditis virus. Encephalomyocarditis virus should be considered as a differential etiology in outbreaks of myocarditis and pulmonary edema in juvenile primates.

Antibody response in horses following experimental infection with West Nile Virus lineages 1 and 2.

West Nile virus (WNV) has re-emerged as an important pathogen for humans and horses, which are considered to be incidental 'dead-end' hosts. We have demonstrated that horses are susceptible to experimental infection with WNV and that horses infected with either WNV lineage 1 or lineage 2 elicit a similar antibody profile in serum samples. These data suggest that virus-neutralizing antibody responses persist for longer than WNV-specific IgM levels in serum and that there are not any notable differences in the antibody profile following experimental infection of horses with either WNV lineage 1 and lineage 2 viruses. Furthermore, the duration of IgM appears to be short-lived in horses and may be useful for identifying and differentiating recent infections from previously exposed animals.