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Background: Pediatric allogeneic hematopoietic cell transplant (allo‐HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials. Methods: A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo‐HCT recipients with at least one HAdV‐positive PCR. Results: Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo‐HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events. Conclusions: Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease. [ABSTRACT FROM AUTHOR]

A 3-year-old male with X-linked lymphoproliferative syndrome type 1 underwent an unrelated umbilical cord blood transplant (UUCBT). The week prior to transplant the patient tested positive for adenovirus (HAdV) with a viral load of <190 copies/mL and was started on cidofovir. UUCBT proceeded as scheduled, and the patient engrafted on day +19. The patient's HAdV load in serum continued to rise with resulting hepatic dysfunction, despite ongoing therapy with cidofovir and HAdV specific T-cell infusions. The patient died 6 months after transplantation having never cleared the virus. Next generation whole genome sequencing and sequence data analyses identified an intertypic recombinant HAdV-C P1H2F2 closely related (99.6% similarity) to genotype C108 in the isolates from three blood specimens obtained during the last week of life. Incidentally, the de novo assembly strategy enabled the detection of an adeno-associated virus type 2 (AAV2) genome in the DNA purified from the plasma isolates. Proteotyping analysis revealed minor differences in the predicted amino acid sequences for E1A, E1B 19K, E1B 55K, DNA polymerase, penton base, and fiber. None of the mutations previously described for HAdV-C5 variants resistant to cidofovir were identified. In silico restriction enzyme analysis revealed a distinct Sac I profile for the identified virus, supporting its designation as a C108 variant. [ABSTRACT FROM AUTHOR]

Adenovirus (HAdV) F41 is a common cause of gastroenteritis and has rarely been reported associated with disseminated disease. In this report, an adult patient with a history of ulcerative colitis, cryptogenic cirrhosis, stage III adenocarcinoma, high-grade diffuse large B-cell lymphoma on chemotherapy was diagnosed with disseminated adenovirus infection. HAdV DNA was quantified in stool, plasma, and urine with viral loads of 7, 4, and 3 log10 copies/mL, respectively. The patient's course was rapidly progressive and he passed away 2 days after initiation of antiviral therapy. The patient's infecting virus was characterized as HAdV-F41 by whole genome sequencing. [ABSTRACT FROM AUTHOR]

Two novel genotypes of species human mastadenovirus D designated 109 and 110 were isolated from three epidemiologically unrelated cases of acute respiratory disease detected in January 2018 by surveillance efforts at the California/Mexico border. Both genotypes represent examples of intertypic recombination. Genotype D109 is most closely related to genotype D56 (97.68% genomic similarity) and features a type D22‐like penton base, a type D19‐like hexon gene, and a type D9‐like fiber [P22/H19/F9]. On the other hand, genotype D110 is most closely related to type D22 (96.94% genomic similarity) and features a type D67‐like penton base, a novel hexon gene, and a type D9‐like fiber [P67/H110/F9]. Importantly, the fibers of both novel genotypes are highly similar to those of genotypes D56 and D59, which have also been isolated from a few cases of respiratory infections. The present report shows data contributing to the understanding of the molecular determinants of the expanded tissue tropism of certain members of species HAdV‐D. [ABSTRACT FROM AUTHOR]

Heterogeneity of COVID-19 manifestations in human population is vast, for reasons unknown. Cotton rats are a clinically relevant small animal model of human respiratory viral infections. Here, we demonstrate for the first time that SARS-CoV-2 infection in cotton rats affects multiple organs and systems, targeting species- and age-specific biological processes. Infection of S. fulviventer, which developed a neutralizing antibody response and were more susceptible to SARS-CoV-2 replication in the upper respiratory tract, was accompanied by hyperplasia of lacrimal drainage-associated lymphoid tissue (LDALT), a first known report of mucosa-associated lymphoid tissue activation at the portal of SARS-CoV-2 entry. Although less permissive to viral replication, S. hispidus showed hyperplasia of bone marrow in the facial bones and increased pulmonary thrombosis in aged males. Augmentation of these features by SARS-CoV-2 infection suggests a virus-induced breach in regulatory mechanisms which could be devastating for people of all ages with underlying conditions and in particular for elderly with a multitude of ongoing disorders. [ABSTRACT FROM AUTHOR]

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Background: Vaccines that are shelf stable and easy to administer are crucial to improve vaccine access and reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission around the world.Methods: In this study, we demonstrate that an oral, adenovirus-based vaccine candidate protects against SARS-CoV-2 in a Syrian hamster challenge model.Results: Hamsters administered 2 doses of VXA-CoV2-1 showed a reduction in weight loss and lung pathology and had completely eliminated infectious virus 5 days postchallenge. Oral immunization induced antispike immunoglobulin G, and neutralizing antibodies were induced upon oral immunization with the sera, demonstrating neutralizing activity.Conclusions: Overall, these data demonstrate the ability of oral vaccine candidate VXA-CoV2-1 to provide protection against SARS-CoV-2 disease. [ABSTRACT FROM AUTHOR]

Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The vast majority of cases are self-limited. However, the clinical spectrum is broad and fatalities may occur. Dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 100 genotypes and 52 serotypes of AdV have been identified and classified into seven species designated HAdV-A through -G. Different types display different tissue tropisms that correlate with clinical manifestations of infection. The predominant types circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been done. Cidofovir has been the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States but currently are not available to civilians. [ABSTRACT FROM AUTHOR]

Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation. Children often suffer from primary genetic forms of HLH, which can be triggered by infection. Others suffer from secondary HLH as a complication of infection, malignancy, or rheumatologic disease. Identifying the exact cause of HLH is crucial, as definitive treatment for primary disease is hematopoietic stem cell transplant. Adenoviruses have been associated with HLH but molecular epidemiology data are lacking. Methods We describe the clinical and virologic characteristics of 5 children admitted with adenovirus infection during 2018–2019 who developed HLH or HLH-like illness. Detailed virologic studies, including virus isolation and comprehensive molecular typing were performed. Results All patients recovered; clinical management varied but included immunomodulating and antiviral therapies. A genetic predisposition for HLH was not identified in any patient. Adenovirus isolates were recovered from 4/5 cases; all were identified as genomic variant 7d. Adenovirus type 7 DNA was detected in the fifth case. Phylogenetic analysis of genome sequences identified 2 clusters—1 related to strains implicated in 2016–2017 outbreaks in Pennsylvania and New Jersey, the other related to a 2009 Chinese strain. Conclusions It can be challenging to determine whether HLH is the result of an infectious pathogen alone or genetic predisposition triggered by an infection. We describe 5 children from the same center presenting with an HLH-like illness after onset of adenovirus type 7 infection. None of the patients were found to have a genetic predisposition to HLH. These findings suggest that adenovirus 7 infection alone can result in HLH. [ABSTRACT FROM AUTHOR]

Human adenoviruses (HAdV) are one of the most frequent causes of respiratory infections around the world, causing mild to severe disease. In Argentina, many studies focused on the association of HAdV respiratory infection with severe disease and fatal outcomes leading to the discovery in 1984 of a genomic variant 7h associated with high fatality. Although several molecular studies reported the presence of at least 4 HAdV species (B, C, D and E) in Argentina, few sequences were available in the databases. In this study, sequences from the hexon gene region were obtained from 141 patients as a first approach to assess the genetic diversity of HAdVs circulating in Buenos Aires, Argentina. Phylogenetic analysis of these sequences and others recovered from public databases confirmed the circulation of the four above-mentioned species represented by 11 genotypes, with predominance in species B and C and shifts in their proportion in the studied period (2000 to 2018). The variants detected in Argentina, for most of the genotypes, were similar to those already described in other countries. However, uncommon lineages belonging to genotypes C2, C5 and E4 were detected, which might indicate the circulation of local variants and will deserve further studies of whole-genome sequences. [ABSTRACT FROM AUTHOR]

Although in a sense a follower of both Isaiah and Machiavelli, Rosenzweig did not share their perception of a conflict between idealism and realism in human experience. His Star of Redemption advances a theory of the redemption of the world inspired by both Isaiah and Machiavelli, and at the same time critical of both of them – a theory in which ethics and politics are strongly connected but where ethics renounces the opposition to history and historical laws, and politics renounces the opposition to ethical ideas. [ABSTRACT FROM AUTHOR]

Human adenovirus type 55 (HAdV-55) causes acute respiratory disease of variable severity and has become an emergent threat in both civilian and military populations. HAdV-55 infection is endemic to China and South Korea, but data from other regions and time periods are needed for comprehensive assessment of HAdV-55 prevalence from a global perspective. In this study, we subjected HAdV-55 isolates from various countries collected during 1969-2018 to whole-genome sequencing, genomic and proteomic comparison, and phylogenetic analyses. The results show worldwide distribution of HAdV-55; recent strains share a high degree of genomic homogeneity. Distinct strains circulated regionally for several years, suggesting persistent local transmission. Several cases of sporadic introduction of certain strains to other countries were documented. Among the identified amino acid mutations distinguishing HAdV-55 strains, some have potential impact on essential viral functions and may affect infectivity and transmission. [ABSTRACT FROM AUTHOR]

Background Human adenoviruses (HAdVs) are associated with significant morbidity and death after hematopoietic cell transplantation (HCT). In this study, we sought to determine the incidence of HAdV infection among pediatric HCT recipients in the polymerase chain reaction (PCR) testing era, identify risk factors for viremia among patients undergoing HAdV surveillance, and assess the effectiveness of preemptive cidofovir. Methods A single-center retrospective cohort of patients who underwent a transplant within a 10-year period was assembled. The incidence of and outcomes of patients with HAdV infection and disease were determined by PCR results and chart review. A Cox regression model was used for surveilled allogeneic HCT recipients to identify factors associated with viremia. We also used a discrete-time failure model with inverse probability treatment weights to assess the effectiveness of preemptive cidofovir for infection. Results Among 572 HCT recipients, 76 (13.3%) had ≥1 sample that was HAdV PCR positive (3.5% of autologous HCT recipients and 19.7% of allogeneic HCT recipients). Among 191 allogeneic HCT recipients under surveillance, 58 (30.4%) had HAdV detected from any source, and 50 (26.2%) specifically had viremia. The mortality rate was higher in allogeneic HCT recipients with HAdV infection versus those without infection (25.9% vs 11.3%; P =.01). Factors associated with infection included an age of 6 to 12 years, an absolute lymphocyte count of <200 cells/μL, recent prednisone exposure, and recent bacteremia. Preemptive cidofovir was not associated with a reduced risk of infection progression (odds ratio, 0.96 [95% confidence interval, 0.30–3.05]). Conclusions HAdV infection is common and associated with an increased rate of death after allogeneic HCT. Using prediction models that incorporate factors associated with HAdV might help target surveillance. Preemptive cidofovir therapy was not protective in a subset of HAdV-positive patients. Larger observational or randomized investigations are necessary, because the utility of surveillance requires effective preemptive therapies. [ABSTRACT FROM AUTHOR]

Human adenovirus 7d is a respiratory pathogen capable of causing acute respiratory disease of variable severity. Phylogenetic analysis of whole-genome sequences of 15 strains isolated from cases of influenza-like-illness during 2017-2019 demonstrated the circulation of 2 distinct clades of genomic variant 7d in colleges in New York, USA. [ABSTRACT FROM AUTHOR]

Ocular infections caused by human adenovirus (HAdV) are highly contagious. The most severe are usually caused by members of species HAdV-D (types HAdV8, 19, 37, 53, 54, and 56) and can manifest as epidemic keratoconjunctivitis (EKC), often resulting in prolonged impairment of vision. During the early months of 2012, EKC outbreaks occurred in neonatal intensive care units (NICUs) in 3 hospitals in New York State (New York and Suffolk Counties). A total of 32 neonates were affected. For 14 of them, HAdV8 was laboratory-confirmed as the causative agent. Nine healthcare workers were also affected with 3 laboratory-confirmed, HAdV-positive EKC. A fourth EKC outbreak was documented among patients attending a private ophthalmology practice in Ulster County involving a total of 35 cases. Epidemiological linkage between the neonatal intensive care unit outbreaks was demonstrated by molecular typing of virus isolates with restriction enzyme analysis and next generation whole genome sequencing. The strain isolated from the ophthalmology clinic was easily distinguishable from the others by restriction enzyme analysis. [ABSTRACT FROM AUTHOR]

Background Solid organ transplant (SOT) recipients are at risk for invasive fungal disease (IFD). Data on IFD burden in pediatric patients are limited. We aimed to determine the incidence and outcome of IFD in a large cohort of pediatric patients who underwent SOT. Methods A single-center cohort of pediatric patients who underwent SOT between 2000 and 2013 was assembled retrospectively. The patients were followed for 180 days after transplant or until death to determine the presence or absence of IFD. The 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group Consensus Group criteria were used to define IFD as proven or probable. The incidence of IFD, all-cause mortality rate, and case-fatality rate at 180 days were calculated. Results Among 584 pediatric patients who underwent SOT, 13 patients sustained 14 episodes of IFD (candidiasis, aspergillosis, and mucormycosis). The overall incidence was 2.2% (14.3 IFD events per 100000 patient-days). The IFD rates according to transplant type were 12.5% (1 of 8) (heart/lung), 11.4% (4 of 35) (lung), 4.7% (8 of 172) (liver), 0% (0 of 234) (kidney), and 0% (0 of 135) (heart). Three patients with IFD (2 lung and 1 heart/lung) died, and all these deaths were deemed likely attributable to the IFD; the case-fatality rate was 21.4% (3 of 14). Conclusions The overall incidence of IFD in these pediatric SOT recipients was low but varied across transplant type, with heart/lung and lung recipients having the highest IFD rate. Given the attributable case-fatality rate, the risk of death resulting from IFD is potentially high. More data on groups at higher risk, such as lung transplant recipients, are needed to guide targeted antifungal prophylaxis. [ABSTRACT FROM AUTHOR]

Human adenovirus type 4 (HAdV-4) is most commonly isolated in military settings. We conducted detailed molecular characterization on 36 HAdV-4 isolates recovered from civilian adults with acute respiratory disease (ARD) in the northeastern United States during 2011-2015. Specimens came from college students, residents of long-term care facilities or nursing homes, a cancer patient, and young adults without co-morbidities. HAdV-4 genome types 4a1 and 4a2, the variants most frequently detected among US military recruits in basic training before the restoration of vaccination protocols, were isolated in most cases. Two novel a-like variants were recovered from students enrolled at a college in Tompkins County, New York, USA, and a prototype-like variant distinguishable from the vaccine strain was isolated from an 18-year-old woman visiting a physician's office in Ulster County, New York, USA, with symptoms of influenza-like illness. Our data suggest that HAdV-4 might be an underestimated causative agent of ARD among civilian adults. [ABSTRACT FROM AUTHOR]

Human rhinoviruses (HRVs) are the main cause of cold-like illnesses, and currently no vaccine or antiviral therapies against HRVs are available to prevent or mitigate HRV infection. There are more than 150 antigenically heterogeneous HRV serotypes, with ~90 HRVs belonging to major group species A and B. Development of small animal models that are susceptible to infection with major group HRVs would be beneficial for vaccine research. Previously, we showed that the cotton rat (Sigmodon hispidus) is semi-permissive to HRV16 (major group, species HRV-A virus) infection, replicating in the upper and lower respiratory tracts with measurable pathology, mucus production, and expression of inflammatory mediators. Herein, we report that intranasal infection of cotton rats with HRV14 (major group, species HRV-B virus) results in isolation of infectious virus from the nose and lung. Similar to HRV16, intramuscular immunization with live HRV14 induces homologous protection that correlated with high levels of serum neutralizing antibodies. Vaccination and challenge experiments with HRV14 and HRV16 to evaluate the development of cross-protective immunity demonstrate that intramuscular immunization with live HRV16 significantly protects animals against HRV14 challenge. Determination of the immunological mechanisms involved in heterologous protection and further characterization of infection with other major HRV serotypes in the cotton rat could enhance the robustness of the model to define heterotypic relationships between this diverse group of viruses and thereby increase its potential for development of a multi-serotype HRV vaccine. [ABSTRACT FROM AUTHOR]

During the 2014-15 influenza season, 13/168 respiratory samples from students with influenza-like illness (ILI) at a college in New York, USA, were positive for human adenovirus (HAdV); 4/13 samples were positive for HAdV-B14p1. During influenza season, HAdV should be included in the differential diagnostic panel used to determine the etiology of ILI. [ABSTRACT FROM AUTHOR]

Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The disease is more severe and dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 50 serotypes of AdV have been identified. Different serotypes display different tissue tropisms that correlate with clinical manifestations of infection. The predominant serotypes circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been conducted. Cidofovir is the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States, but currently are not available to civilians. [ABSTRACT FROM AUTHOR]

Human adenovirus 7d, a genomic variant with no reported circulation in the United States, was isolated from 2 adults with severe respiratory infections in Illinois. Molecular typing identified a close relationship with strains of the same genome type isolated from cases of respiratory disease in several provinces of China since 2009. [ABSTRACT FROM AUTHOR]

The 31st annual meeting of the Pan American Society for Clinical Virology and Clinical Virology Symposium was held in Daytona Beach, FL, USA on 26-29 April 2015. This year the symposium was jointly cosponsored by the American Society for Microbiology, the France Foundation and the Pan American Society for Clinical Virology. The event was chaired by Steven Specter and Richard Hodinka. [ABSTRACT FROM AUTHOR]

Background: Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is associated with reduced bone mineral density (BMD) and increased fracture rates, particularly in women. The structural underpinnings for skeletal fragility in coinfected women have not been characterized. We used tibial peripheral quantitative computed tomography to evaluate skeletal parameters in women, by HIV/HCV status. Methods: We conducted a cross-sectional study among 50 HIV/HCV-coinfected, 51 HCV-monoinfected, and 50 HIV-monoinfected women. Tibial volumetric BMD and cortical dimensions were determined with peripheral quantitative computed tomography. Race-specific z scores for age were generated using 263 female reference participants without HIV infection or liver disease. Results: Coinfected participants had lower mean z scores for trabecular volumetric BMD (-0.85), cortical volumetric BMD (-0.67), cortical area (-0.61), and cortical thickness (-0.77) than reference participants (all P < .001). The smaller cortical dimensions were due to greater mean z scores for endosteal circumference (+0.67; P < .001) and comparable z scores for periosteal circumference (+0.04; P = .87). Trabecular volumetric BMD was lower in coinfected than in HCV- or HIV-monoinfected participants. HCV-infected women with stage 3-4 liver fibrosis had lower mean z scores for trabecular volumetric BMD, cortical thickness, and total hip BMD those with stage 0-2 fibrosis. Conclusions: Compared with healthy reference patients, HIV/HCV-coinfected women had decreased tibial trabecular volumetric BMD, diminished cortical dimensions, and significant endocortical bone loss. [ABSTRACT FROM AUTHOR]

To determine the distribution of major blood lymphocyte subsets we evaluated blood lymphocytes by flow cytometry in adenovirus-infected infants aged 30-730 d. In addition, interleukin-1-receptor antagonist, interleukin-10 and transforming growth factor-beta1 were measured in serum by enzyme-linked immunosorbent assay. According to clinical parameters, mechanical ventilation and outcome, infections were classified as moderate (n = 15), severe (n = 11) and fatal (n = 12). Controls were 13 healthy children. In severe and fatal infection, T cells (CD5+/CD19-), NK effectors (CD16+), CD4+ T subset and B1 subset of B lymphocytes (CD5+/CD19+) were all significantly decreased. CD8+ cells were decreased in severe but not fatal cases. There was no difference in serum values of interleukin-10; however, fatal cases had high interleukin 1-receptor antagonist values. Interestingly, patients with moderate infection showed significantly increased values of transforming growth factor-beta1. These results demonstrate that life-threatening adenoviral infection is associated with marked abnormalities in blood lymphocyte and cytokine profile. [ABSTRACT FROM AUTHOR]

Background Human adenoviruses of species B, C, and E (HAdV-B, -C, -E) are frequent causative agents of acute respiratory infections worldwide. As part of a surveillance program aimed at identifying the etiology of influenza-like illness (ILI) in Egypt, we characterized 99 adenovirus isolates from clinical samples collected between 2003 and 2010. Methods Identification of the isolates as HAdV was accomplished by an immunofluorescence assay (IFA) and confirmed by a set of species and type specific polymerase chain reactions (PCR). Results Of the 105 isolates, 42% were identified as belonging to HAdV-B, 60% as HAdV-C, and 1% as HAdV-E. We identified a total of six co-infections by PCR, of which five were HAdVB/ HAdV-C co-infections, and one was a co-infection of two HAdV-C types: HAdV- 5/HAdV-6. Molecular typing by PCR enabled the identification of eight genotypes of human adenoviruses; HAdV-3 (n = 22), HAdV-7 (n = 14), HAdV-11 (n = 8), HAdV-1 (n = 22), HAdV-2 (20), HAdV-5 (n = 15), HAdV-6 (n = 3) and HAdV-4 (n = 1). The most abundant species in the characterized collection of isolates was HAdV-C, which is concordant with existing data for worldwide epidemiology of HAdV respiratory infections. Conclusions We identified three species, HAdV-B, -C and -E, among patients with ILI over the course of 7 years in Egypt, with at least eight diverse types circulating. [ABSTRACT FROM AUTHOR]

In Kawasaki disease (KD), molecular-based detection of human adenovirus (HAdV) infection is not uncommon, may represent persistence of HAdV-C, and should be interpreted with caution. Together, quantitative polymerase chain reaction and HAdV typing may aid in distinguishing HAdV disease mimicking KD from KD with concomitant HAdV detection.Background. Human adenovirus (HAdV) infection mimics Kawasaki disease (KD) but can also be detected in KD patients. Evidence suggests that HAdV-C species can persist in pediatric adenoids and/or tonsils. We sought to determine (1) the frequency of HAdV detection by real-time polymerase chain reaction in KD patients, (2) the differences in HAdV semiquantitative nasopharyngeal viral loads between KD patients with detectable HAdV vs those with HAdV disease, and (3) whether nasopharyngeal HAdV-C shedding is occurring in KD.Methods. From August 2009 through April 2011, HAdV-positive patients were identified in 1 of the following groups: group I, complete or incomplete KD as defined by the American Heart Association (AHA); group II, treated for incomplete KD but not fulfilling AHA criteria; and group III, otherwise healthy children with some KD-like features ultimately diagnosed with HAdV disease.Results. Among 77 KD patients diagnosed, 8.8% (5/57) of group I and 25% (5/20) of group II KD patients had HAdV detected. Viral loads were significantly lower in group I (n = 5) vs group III (n = 26; P = .034). Of the 13 specimens available for HAdV typing, 7 of 7 group III and 1 of 3 group II specimens were determined to be HAdV-B using viral culture. The remaining 5 KD samples were unable to be cultured and molecular typing showed either HAdV-C (n = 3) or were nontypeable (n = 2).Conclusions. In KD, molecular-based HAdV detection is not uncommon, may represent persistence of HAdV-C, and should be interpreted with caution. Together, quantitative polymerase chain reaction and HAdV typing may aid in distinguishing HAdV disease mimicking KD from KD with concomitant HAdV detection. [ABSTRACT FROM AUTHOR]

Background: Although significant epidemiological evidence indicates that cigarette smoke exposure increases the incidence and severity of viral infection, the molecular mechanisms behind the increased susceptibility of the respiratory tract to viral pathogens are unclear. Adenoviruses are non-enveloped DNA viruses and important causative agents of acute respiratory disease. The Coxsackievirus and adenovirus receptor (CAR) is the primary receptor for many adenoviruses. We hypothesized that cigarette smoke exposure increases epithelial susceptibility to adenovirus infection by increasing the abundance of apical CAR. Methodology and Findings: Cultured human airway epithelial cells (CaLu-3) were used as a model to investigate the effect of sidestream cigarette smoke (SSS), mainstream cigarette smoke (MSS), or control air exposure on the susceptibility of polarized respiratory epithelia to adenoviral infection. Using a Cultex air-liquid interface exposure system, we have discovered novel differences in epithelial susceptibility between SSS and MSS exposures. SSS exposure upregulates an eight-exon isoform of CAR and increases adenoviral entry from the apical surface whilst MSS exposure is similar to control air exposure. Additionally, the level of cellular glycogen synthase kinase 3β (GSK3β) is downregulated by SSS exposure and treatment with a specific GSKβ inhibitor recapitulates the effects of SSS exposure on CAR expression and viral infection. Conclusions: This is the first time that SSS exposure has been shown to directly enhance the susceptibility of a polarized epithelium to infection by a common respiratory viral pathogen. This work provides a novel understanding of the impact of SSS on the burden of respiratory viral infections and may lead to new strategies to alter viral infections. Moreover, since GSK3b inhibitors are under intense clinical investigation as therapeutics for a diverse range of diseases, studies such as these might provide insight to extend the use of clinically relevant therapeutics and increase the understanding of potential side effects. [ABSTRACT FROM AUTHOR]

Background: Subspecies B1 human adenoviruses (HAdV-B1) are prevalent respiratory pathogens. Compared to their species C (HAdV-C) counterparts, relatively little work has been devoted to the characterization of their unique molecular biology. The early region 3 (E3) transcription unit is an interesting target for future efforts because of its species-specific diversity in genetic content among adenoviruses. This diversity is particularly significant for the subset of E3-encoded products that are membrane glycoproteins and may account for the distinct Pathobiology of the different human adenovirus species. In order to understand the role of HAdV-B-specific genes in viral pathogenesis, we initiated the characterization of unique E3 genes. As a continuation of our efforts to define the function encoded in the highly polymorphic ORF E3-10.9K and testing the hypothesis that the E3-10.9K protein orthologs with a hydrophobic domain contribute to the efficient release of viral progeny, we generated HAdV-3 mutant viruses unable to express E3-10.9K ortholog E3-9K and examined their ability to grow, disseminate, and egress in cell culture. Results: No differences were observed in the kinetics of infected cell death, and virus progeny release or in the plaque size and dissemination phenotypes between cells infected with HAdV-3 E3-9K mutants or the parental virus. The ectopic expression of E3-10.9K orthologs with a hydrophobic domain did not compromise cell viability. Conclusions: Our data show that despite the remarkable similarities with HAdV-C E3-11.6K, HAdV-B1 ORF E3-10.9K does not encode a product with a "death-like" biological activity. [ABSTRACT FROM AUTHOR]

Human adenovirus (HAdV) serotype 14 is rarely identified. However, an emerging variant, termed HAdV14p1, recently has been described in the United States in association with outbreaks of acute respiratory disease with high rates of illness and death. We retrospectively analyzed specimens confirmed positive for HAdV by immunofluorescence, virus culture, or real-time PCR during July 1, 2009-July 31, 2010, and describe 9 cases of HAdV14p1 infection with characteristic mutations in the fiber and E1A genes that are phylogenetically indistinguishable from the viruses previously detected in the United States. Three patients died; 2 were immunocompromised, and 1 was an immunocompetent adult. We propose that surveillance should be increased for HAdV-14p1 and recommend that this virus be considered in the differential diagnosis of sudden-onset acute respiratory disease, particularly fatal infections, for which an etiology is not clear. [ABSTRACT FROM AUTHOR]

Epidemiological studies demonstrated that the number of emergency-room visits for respiratory indications increases during periods of Florida Red Tides. The purpose of this study was to examine whether or not repeated brevetoxin inhalation, as may occur during a Florida Red Tide, affects pulmonary responses to influenza A. Male F344 rats were divided into four groups: (1) sham aerosol/no influenza; (2) sham aerosol/influenza; (3) brevetoxin/no influenza; and (4) brevetoxin/influenza. Animals were exposed by nose-only inhalation to vehicle or 50 μg brevetoxin-3/m3, 2 h/d for 12 d. On d 6 of aerosol exposure, groups 2 and 4 were administered 10,000 plaque-forming units of influenza A, strain HKX-31 (H3N2), by intratracheal instillation. Subgroups were euthanized at 2, 4, and 7 d post influenza treatment. Lungs were evaluated for viral load, cytokine content, and histopathologic changes. Influenza virus was cleared from the lungs over the 7-d period; however, there was significantly more virus remaining in the group 4 lungs compared to group 2. Influenza virus significantly increased interleukins-1α and -6 and monocyte chemotactic protein-1 in lung; brevetoxin exposure significantly enhanced the influenza-induced response. At 7 d, the severity of perivascular and peribronchiolar inflammatory cell infiltrates was greatest in group 4. Bronchiolitis persisted, with low incidence and severity, only in group 4 at d 7. These results suggest that repeated inhalation exposure to brevetoxin may delay virus particle clearance and recovery from influenza A infection in the rat lung. [ABSTRACT FROM AUTHOR]

Background. First isolated in the Netherlands in 1955 during an outbreak of acute respiratory disease (ARD) among military recruits, human adenovirus 14 (HAdV-14) has historically been considered rare. With no precedent of circulation in North America, HAdV-14 has been isolated from military and civilian cases of ARD of variable severity since 2003 in the United States. Methods. Ninety-nine isolates from military and civilian cases from different geographic locations and circulation periods were characterized by restriction enzyme analysis of viral DNA and select gene sequencing. Results. All examined viruses were found to be identical and to belong to a new genome type designated "HAdV-14p1" (formerly known as "14a"). Comparative alignments of E1A, hexon, and fiber gene sequences with other subspecies B2 HAdVs suggest that HAdV-14p1, like the closely related HAdV-11a, arose from recombination among similar HAdV-11 and HAdV-14 ancestral strains. A deletion of 2 amino acids in the knob region of the fiber protein is the only identified unique characteristic of HAdV-14p1. Conclusion. The current geographic distribution of HAdV-14p1 involves at least 15 states in the Unites States. The role of the fiber mutations in the recent emergence of HAdV-14p1 ARD in North America warrants further study. [ABSTRACT FROM AUTHOR]

Background: Human adenovirus 14 (HAdV-14) is a recognized causative agent of epidemic febrile respiratory illness (FRI). Last reported in Eurasia in 1963, this virus has since been conspicuously absent in broad surveys, and was never isolated in North America despite inclusion of specific tests for this serotype in surveillance methods. In 2006 and 2007, this virus suddenly emerged in North America, causing high attack rate epidemics of FRI and, in some cases, severe pneumonias and occasional fatalities. Some outbreaks have been relatively mild, with low rates of progression beyond uncomplicated FRI, while other outbreaks have involved high rates of more serious outcomes. Methodology and Findings: In this paper we present the complete genomic sequence of this emerging pathogen, and compare genomic sequences of isolates from both mild and severe outbreaks. We also compare the genome sequences of the recent isolates with those of the prototype HAdV-14 that circulated in Eurasia 30 years ago and the closely related sequence of HAdV-11a, which has been circulating in southeast Asia. Conclusions: The data suggest that the currently circulating strain of HAdV-14 is closely related to the historically recognized prototype throughout its genome, though it does display a couple of potentially functional mutations in the fiber knob and E1A genes. There are no polymorphisms that suggest an obvious explanation for the divergence in severity between outbreak events, suggesting that differences in outcome are more likely environmental or host determined rather than viral genetics. [ABSTRACT FROM AUTHOR]

According to Kant, Mendelssohn could not accept the idea of the moral progress of humankind, maintained by Lessing in Erziehung des Menschengeschlechts (1780), because he erroneously inferred from some historical events a pessimistic view of the whole of history: as a dogmatic metaphysician Mendelssohn did not consider judgements about intelligible objects as "regulative," i.e. pronounced by a faculty of judgement founded on practical reason, but as "constitutive," i.e. endowed with scientific value. This article argues that the deepest reason of Mendelssohn's criticism of Lessing's philosophy of history was rather his rejection of Sabbatian messianism. Mendelssohn was accused of being the author of the Fragmente eines Ungenannten (composed by Hermann Samuel Reimarus) that—according to some Christian readers—described Jesus as a Sabbatai Zevi ante litteram and were inspired by Sabbatianism; Lessing, who in 1777 presented the first part of Erziehung as "objections" to the fourth Fragment he edited, nevertheless shared the Ungenannte's critique of Jewish and Christian revelation and his eulogy of man's autonomy. Mendelssohn's denial of this authorship appears in his letter of September 24, 1781 to Herder, where he also mentions Moshe Hayym Luzzatto: while praising Luzzatto as author of the drama Layesharim Tehila and defending him against the persecution he suffered in Italy and Germany, Mendelssohn keeps him at a distance as writer of cabalistic texts and new Psalms which show a Sabbatian attitude. Mendelssohn was aware—as Karl Gotthelf Lessing wrote to his brother on October 26, 1769—of the Sabbatian Jacob Frank's contemporary preaching in Poland and of the similarity between Sabbatianism and Bonnet's and Lavater's chiliastic Christianity. This article also argues that the criticism of Sabbatian messianism is the background of Mendelssohn's unilateral interpretation of Judaism as centred on the synagogue. [ABSTRACT FROM AUTHOR]

The article focuses on the study conducted in determining the potential impact of exposure to WR1065, an aminothiol, on cytotoxic and mutagenic effects of AZT-ddI. Its goal is to make an observation on the ability of the WR1065 in protecting human cells from nucleoside reverse transcriptase inhibitors' (NRTI) cytotoxic and mutagenic effects in vitro. Results show that WR1065 has cytoprotective and antimutagenic activities against NRTI.

Background. Adenoviruses are associated with sporadic infection and community and institutional outbreaks; they can cause especially severe disease in infants, young children, immunocompromised persons, and transplant recipients. Fifty-two adenovirus serotypes have been recognized and classified within 7 subgroups or species (A- G), with limited data available on associated clinical syndromes and disease severity in more than one-half of the known serotypes. Methods. We describe the clinical presentation and virologic characterization of 1 adult and 2 pediatric patients admitted to 2 separate hospitals during April-May 2006 with severe acute respiratory tract infection. All patients had underlying chrdnic pulmonary disease; none were severely immunocompromised. All 3 experienced serious chronic sequelae or died. Results. Adenovirus was isolated from all 3 case patients. Adenovirus serotype 14, a subspecies B2 serotype not previously associated with severe clinical illness, was confirmed by neutralization assay and sequencing of the hexon gene. Restriction enzyme analysis with BarnHI, BglII, Hindlil, and Smal showed all 3 viruses to be identical and to belong to a new genome type that we have designated "Adl4a." Conclusions. Our identification of severe respiratory illness due to a previously rarely reported adenovirus serotype may signify the emergence in the United States of a new genomic variant that has the potential to spread globally and cause epidemics. These case reports highlight the need for rapid diagnosis and improved surveillance, with serotyping and molecular characterization, to identify emerging variants of adenovirus, which may assist with targeted development of antiviral agents or type-specific vaccines. [ABSTRACT FROM AUTHOR]

BACKGROUND: Adenoviruses (Ads) cause continuous outbreaks of acute respiratory disease (ARD) in US military training facilities. In 1996, the loss of vaccines targeting the dominant recruit-associated serotypes precipitated the reemergence of Ads in these populations. Between 1999 and 2002, serotype 4 accounted for >95% of Ads isolated from recruits and for >50% of ARD cases in training facilities (15,000 cases/year). METHODS: Ads (n=1867) collected between 2002 and 2006 from recruits with ARD at 8 military training facilities in the United States were serotyped by serum neutralization and polymerase chain reaction. RESULTS: The dominance of Ad4 continued through 2005, followed by a simultaneous emergence of diverse species B serotypes at the majority of sites. This included the subspecies B1 serotypes 3, 7, and 21 and the subspecies B2 serotype 14. Ad14 was the most prevalent species B serotype, appearing in high numbers at 3 sites and becoming dominant at 1. CONCLUSIONS: Subspecies B2 Ads have rarely been associated with ARD, and only in Eurasia. This survey represents the first report of AdB2-associated ARD in the Western Hemisphere. The simultaneous emergence of several species B Ads suggests a common external source (the civilian population) and a decrease in preexisting immunity to species B Ads. [ABSTRACT FROM AUTHOR]

Background. Adenoviruses (Ads) cause continuous outbreaks of acute respiratory disease (ARD) in US military training facilities. In 1996, the loss of vaccines targeting the dominant recruit-associated serotypes precipitated the reemergence of Ads in these populations. Between 1999 and 2002, serotype 4 accounted for >95% of Ads isolated from recruits and for >50% of ARD cases in training facilities (15,000 cases/year). Methods. Ads (n = 1867) collected between 2002 and 2006 from recruits with ARD at 8 military training facilities in the United States were serotyped by serum neutralization and polymerase chain reaction. Results. The dominance of Ad4 continued through 2005, followed by a simultaneous emergence of diverse species B serotypes at the majority of sites. This included the subspecies B1 serotypes 3, 7, and 21 and the subspecies B2 serotype 14. Ad14 was the most prevalent species B serotype, appearing in high numbers at 3 sites and becoming dominant at 1. Conclusions. Subspecies B2 Ads have rarely been associated with ARD, and only in Eurasia. This survey represents the first report of AdB2-associated ARD in the Western Hemisphere. The simultaneous emergence of several species B Ads suggests a common external source (the civilian population) and a decrease in preexisting immunity to species B Ads. [ABSTRACT FROM AUTHOR]

Background. Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus. Methods. In an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during 2004-2006. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method. Results. Among civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%). Conclusions. For both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age <7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease. [ABSTRACT FROM AUTHOR]

Background. Military recruits are at a higher risk of respiratory infection than their civilian counterparts. Continuous outbreaks of adenovirus (Ad)—associated acute respiratory disease were documented among US trainees before the implementation of serotype 4 (Ad4) and serotype 7 vaccines in 1971. The discontinuation of Ad vaccination programs in 1999 precipitated the reemergence of Ad in training sites, with Ad4 accounting for 98% of all diagnosed cases. Methods. A total of 724 Ad4 strains isolated from recruits presenting with febrile respiratory illness at 8 training sites nationwide between 1997 and 2003 were genome typed by restriction enzyme analysis. Results. Seven genome types were identified, all of which were distinct from the prototype Ad4p and the vaccine type 4p1. Results showed very different, and often stable, genome type distributions at different geographic sites, despite the homogeneity of the recruit source population. Conclusions. The data support the hypothesis that reservoirs for Ad outbreaks are within recruit training sites or in their immediate environments, not in the incoming recruit population. Molecular characterization beyond serotype is critical to understanding the transmission dynamics of Ad infection in these unique susceptible populations and to the implementation of effective prevention approaches. [ABSTRACT FROM AUTHOR]

Background. High levels of morbidity caused by adenovirus among US military recruits have returned since the loss of adenovirus vaccines in 1999. The transmission dynamics of adenovirus have never been well understood, which complicates prevention efforts. Methods. Enrollment and end-of-study samples were obtained and active surveillance for febrile respiratory illnesses (FRIs) was performed for 341 recruits and support personnel. Environmental samples were collected simultaneously. Classic and advanced diagnostic techniques were used. Results. Seventy-nine percent (213⁄271) of new recruits were seronegative for either adenovirus serotype 4 (Ad-4) or adenovirus serotype 7 (Ad-7). FRI caused by Ad-4 was observed in 25% (67⁄271) of enrolled recruits, with 100% of them occurring in individuals with enrollment titers <1:4. The percentage of recruits seropositive for Ad-4 increased from 34% at enrollment to 97% by the end of the study. Adenovirus was most commonly detected in the environment on pillows, lockers, and rifles. Conclusions. Potential sources of adenovirus transmission among US military recruits included the presence of adenovirus on surfaces in living quarters and extended pharyngeal viral shedding over the course of several days. The introduction of new recruits, who were still shedding adenovirus, into new training groups was documented. Serological screening could identify susceptible recruits for the optimal use of available vaccines. New high-throughput technologies show promise in providing valuable data for clinical and research applications. [ABSTRACT FROM AUTHOR]

Praditpornsilpa K, Avihingsanon Y, Nivatvong S, Kansanabuch T, Eiam-Ong S, Tiranathanagul K, Chusil S, Tungsanga K. Outcome of microemulsion cyclosporine C2 concentration monitoring in kidney transplantation.Clin Transplant 2005 DOI: 10.1111/j.1399-0012.2005.000343.x© Blackwell Munksgaard, 2005Profiling of absorption of cyclosporine (CsA) microemulsion is a concept in therapeutic drug monitoring (TDM) designed to optimize the clinical benefits of the drug in transplant recipients. A single blood concentration at 2 h (C2) after CsA microemulsion administration in kidney transplant recipients accurately predicts graft outcome. An international guidelines has recommended the target C2 over time-course post-transplantation. We determined whether this recommendation is appropriate for our patients who are Asian ethnic. The clinical data of these C2 monitoring kidney transplant recipients were compared with the historical cohort of microemulsion CsA trough (C0) level monitoring during the first 24-month post-transplantation. The inclusion and exclusion criteria were applied for both C2 and C0 cohorts. The mean target C2 concentrations at 1, 3, 6, and 12-month post-transplantation were achieved in the C2 cohort as the international guildlines. At 3-month post-transplantation, patients who had C2 concentrations over 1500 ng/mL had higher serum creatinine as compared with those who had C2 levels<1300 ng/mL (2.23 ± 0.8 vs. 1.44 ± 0.38 mg/dL: p = 0.01). Also, at 6-month post-transplantation, patients who had C2 concentrations over 1300 ng/mL had higher serum creatinine (1.96 ± 0.29 vs. 1.37 ± 0.34 mg/dL: p < 0.01) as compared with those who had C2 levels<1100 ng/mL. There was no statistical difference of acute rejection episodes between the two cohorts. The international consensus for C2 concentraion may be too high for Asian ethnic kidney transplant recipients. The data from this study indicated lower than recommended C2 concentraion as an appropriate C2 target concentraion. [ABSTRACT FROM AUTHOR]

Discusses the monitored ballistic tests on shockproof sandwich glasses in different conditions. Assessment of the applicability of piezoelectric accelerometers; Components of the impulsive elastic tests; Analysis of strain gage and acceleration signals of sandwich glass.

Presents a study which determined the genetic variation among isolates of human adenovirus 7 (Ad7) from 1966 to 2000 from the U.S. Identification of Ad7 genome types; Information on Ad7 hexon gene sequencing; Temporal distribution of Ad7 genome types; Geographic distribution of Ad7 genome types.