Necrotizing Ventriculitis in Fledgling Chimney Swifts (Chaetura Pelagica) Associated With a Novel Adenovirus, Chimney Swift Adenovirus-1 (CsAdV-1).

Five chimney swift fledglings died following a progressive loss of appetite and condition while being cared for by an experienced wildlife rehabilitator. All animals had severe necrotizing and heterophilic ventriculitis, with myriad epithelial cells characterized by karyomegaly with intranuclear inclusion bodies. Transmission electron microscopy showed distention of epithelial cell nuclei and chromatin peripheralization by nonenveloped, icosahedral, 75- to 85-nm-diameter virions. Degenerate nested PCR for a highly conserved region of the adenovirus DNA polymerase gene was positive. BLAST analysis of the amplicon sequence indicated the presence of a novel adenovirus, with 74% homology to Antarctic penguin adenoviruses and 72% homology to a bat adenovirus, at low query coverages of only 65% and 63%, respectively. BLAST analysis of the predicted amino acid sequence generated the highest scores for squamate adenoviruses at 100% query coverage. Based on phylogenetic analysis of the partial amino acid sequence of the DNA polymerase, the chimney swift virus was a novel adenovirus most closely related to the Atadenovirus genus. Using a probe based on the novel viral sequence, DNA in situ hybridization identified viral nucleic acid in the nucleus. While the tentatively named chimney swift adenovirus-1 (CsAdV-1) is so far classified with the Atadenoviruses, it is relatively divergent from other members of that genus and may represent the first identified member of a new genus of Adenoviruses.

Thin-section computed tomography findings in 104 immunocompetent patients with adenovirus pneumonia.

Background To date, there has been no computed tomography (CT) evaluation of adenovirus pneumonia in a large number of immunocompetent patients. Purpose To describe the thin-section CT findings of immunocompetent patients with adenovirus pneumonia. Material and Methods We prospectively enrolled 104 patients with adenovirus pneumonia from a military hospital. CT scans of each patient were retrospectively and independently assessed by two radiologists for the presence of abnormalities, laterality and zonal predominance of the parenchymal abnormalities, and dominant imaging patterns and their anatomic distributions. Results CT findings included consolidation (n = 92), ground-glass opacity (GGO; n = 82), septal thickening (n = 34), nodules (n = 46), bronchial wall thickening (n = 32), pleural effusion (n = 16), and lymphadenopathy (n = 3). Eighty-four patients (81%) exhibited unilateral parenchymal abnormalities and 57 (57%) exhibited lower lung zone abnormalities. The most frequently dominant CT pattern was consolidation with surrounding GGO (n = 50), with subpleural (70%) and peribronchovascular (94%) distributions. Consolidation-the second-most common pattern (n = 33)-also exhibited subpleural (79%) and peribronchovascular (97%) distributions. The dominant nodule pattern (n = 14) exhibited mixed (64%) and peribronchovascular (100%) distributions. A dominant GGO pattern was only observed in four patients; none had central distribution. Conclusion Although the manifestations of adenovirus pneumonia on CT are varied, we found the most frequent pattern was consolidation with or without surrounding GGO, with subpleural and peribronchovascular distributions. Parenchymal abnormalities were predominantly unilateral and located in the lower lung zone. If dominant consolidation findings are present in immunocompetent patients during the early stages, adenovirus pneumonia should be considered.

Adenovirus cerebellitis in an immunocompetent 2-year-old girl.

Acute cerebellitis (AC) is a principal cause of acute cerebellar dysfunction in previously well children. Although the condition is usually benign, fatal complications include obstructive hydrocephalus and brainstem compression; therefore, prompt accurate diagnosis is vital. 1 There are various pathogens reported in the literature as aetiological agents of AC; however, adenovirus is very rarely mentioned, with only one previous case report in the literature to the best of our knowledge. 2 This case demonstrates the importance of recognising adenovirus as a cause of AC, particularly when preceded by a respiratory tract infection in the paediatric age group. Furthermore, we highlight the role of early neuroimaging in differentiating AC from other causes of acute cerebellar dysfunction, which require different management. Our patient made a full recovery with no long-term deficits demonstrating that comprehensive investigation and consideration of atypical pathogens in the context of AC is vital in securing a favourable outcome.

Chronic lung damage caused by adenovirus type 7: a ten-year follow-up study.

Twenty-seven children aged 0.6 to 7.0 (mean 2.1) years were admitted to the hospital in 1967 and 1968 with type 7 adenoviral pneumonia. All ran a prolonged course. Type 7 adenovirus was isolated from 14 children, and in the other 13, the rise in the titer of complement-fixing antibodies to adenovirus was fourfold or greater. The outcome of the disease in these 27 children was reassessed in 1979, 9.6 to 12.1 (mean 10.7) years after the adenovirus type 7 pneumonia. Twenty-two were examined clinically and roentgenographically and all had lung function tests. Twelve had abnormal chest roentgenograms, and of these, six had bronchiectasis. Six of the ten children with normal chest x-ray films and ten of the 12 with abnormal chest roentgenograms had abnormal pulmonary function tests. Of the six patients with bronchiectasis, four showed no discernible cause of bronchiectasis other than the antecedent type 7 adenoviral infection. The other two patients had bronchial asthma, which can be a risk factor for bronchiectasis.

Persistent adenoviral infection and chronic obstructive bronchitis in children: is there a link?

Chronic obstructive bronchitis with inadequate response to inhaled steroid and bronchodilator therapy is a rather rare disorder in children. Persistence of an adenoviral infection has been described as a possible cause of unremitting airway obstruction. We studied a group of 11 children with the clinical feature of chronic bronchial obstruction. A high-resolution computed tomography (HR-CT) scan was performed and typically showed hyperinflation and ground-glass-like opacities. All children underwent either bronchoscopic transbronchial or open lung biopsy. Biopsy specimens were stained with monoclonal antibodies detecting adenoviral antigen and analyzed by light-microscopy. Bronchoalveolar lavage (BAL) fluid was cultured for adenovirus, and antigen detection tests were performed. While some children had a history of proven adenoviral infection at the onset of their disease, in none of the cases could a persistence of adenovirus be shown. We conclude that adenoviral infection might act as a starter of chronic obstructive bronchitis in children, but that pathogenetic mechanisms other than persistent infection must be responsible for the chronicity of the disease.

Adenoviral bronchopneumonia in an immunocompetent adult: computed tomography and pathologic correlations.

Acute febrile lung disease associated with "patchy ground-glass pattern" on high-resolution computed tomography (HRCT) of the lung in an immunocompromised patient is suggestive of Pneumocystis carinii pneumonia; however, in an immunocompetent young person, it is suggestive of an atypical pneumonia, including viral bronchopneumonia. We studied a 31-year-old man who presented with fever, cough and hypoxemia. HRCT showed bilateral patchy ground-glass opacification. HIV test was negative and lung biopsy specimen grew adenovirus on viral culture. Histopathology of the lung was compatible with bronchopneumonia. In patients without HIV who present with acute lower respiratory infections and patchy ground-glass opacification on HRCT, adenoviral bronchopneumonia should be included in the differential diagnosis.

Adenovirus pneumonia presenting with nodular shadows on chest X-ray in two unrelated allogeneic bone marrow transplant recipients.

Adenoviruses are increasingly recognized as important pathogens following allogeneic stem cell transplantation. We herein report two cases of disseminated adenovirus infection that presented with nodular shadows on chest X-ray after allogeneic bone marrow transplantation from unrelated donors. Both patients died of respiratory failure. Autopsies revealed adenovirus infection of multiple organs. Adenovirus infection should be suspected when nodular lung lesions of unknown origin appear in allogeneic stem cell transplant recipients.

Outbreak of febrile respiratory illness caused by adenovirus at a South Korean military training facility: clinical and radiological characteristics of adenovirus pneumonia.

Adenovirus often causes respiratory disease outbreaks in military training soldiers. Compared with adenovirus pneumonia in young military adults, symptoms arising from febrile respiratory illness (FRI) caused by adenovirus have not been previously evaluated in Korean soldiers. We conducted an event-based outbreak investigation involving 712 male soldiers aged 19 to 21 years from March 14 to 30, 2012 to evaluate the epidemiological and clinical characteristics of patients with pneumonia and FRI caused by adenovirus. We described the laboratory and radiological characteristics of patients with adenovirus pneumonia. Among these, 407 cases of FRI and 15 cases of pneumonia were identified through active surveillance (attack rate of FRI, 57.16%; attack rate of pneumonia, 2.11%). Fire training and march training may present environmental risk factors for adenovirus-associated outbreaks. Most symptoms were mild. The most frequent symptom in patients with pneumonia and FRI was cough. Patients with pneumonia were associated with an increased incidence of dizziness (crude odds ratio [cOR], 9.65; 95% confidence interval [CI], 2.38-37.15) and a decreased incidence of rhinorrhea (cOR, 0.15; 95% CI, 0.04-0.53) during adenovirus-associated outbreaks. Differential leukocyte count revealed high monocytes, low lymphocytes, and low eosinophils, and chest computed tomography revealed a consolidation pattern and right lobar pneumonia. These findings warrant a high level of suspicion for adenovirus pneumonia.

Radiological findings in 210 paediatric patients with viral pneumonia: a retrospective case study.

OBJECTIVE: The objective of this study was to assess the radiological presentations of different types of viral pneumonia in children. METHODS: Nasopharyngeal swab specimens and bronchial aspirate samples from children with acute respiratory infections were obtained and tested for influenza B, adenovirus, respiratory syncytial virus and parainfluenza (Types 1, 2 and 3) by direct immunofluorescence assay, or for influenza A (Subtype H1N1) by quantitative real-time polymerase chain reaction. The chest radiographs of the 210 confirmed cases of viral pneumonia were analysed retrospectively by two independent radiologists for the identification, characterisation and description of the distribution of imaging abnormalities. The cases were divided into six groups on the basis of confirmed causative viral agent, and radiographic findings were compared, analysed and presented. RESULTS: The abnormal chest radiograph findings consisted of bilateral patchy areas of consolidation (n=133), interstitial lung disease (n=33), diffuse areas of air space consolidation (n=29) and lobar consolidation (n=15). The abnormalities were distributed bilaterally in 195 cases and observed more frequently in the lower zones than in other regions. The radiological findings varied significantly among the six groups (p=0.0050). Pairwise comparison showed significant difference between influenza A (H1N1) and adenovirus (p=0.0031) only. CONCLUSION: The predominant radiological finding in paediatric viral pneumonia was bilateral patchy areas of consolidation. The radiological findings differed significantly only between adenovirus and influenza A pneumonia. The diagnosis of the specific causative organism requires laboratory confirmation.

SPECT/CT imaging of oncolytic adenovirus propagation in tumours in vivo using the Na/I symporter as a reporter gene.

Oncolytic adenoviruses have shown some promise in cancer gene therapy. However, their efficacy in clinical trials is often limited, and additional therapeutic interventions have been proposed to increase their efficacies. In this context, molecular imaging of viral spread in tumours could provide unique information to rationalize the timing of these combinations. Here, we use the human sodium iodide symporter (hNIS) as a reporter gene in wild-type and replication-selective adenoviruses. By design, hNIS cDNA is positioned in the E3 region in a wild-type adenovirus type 5 (AdIP1) and in an adenovirus in which a promoter from the human telomerase gene (RNA component) drives E1 expression (AdAM6). Viruses show functional hNIS expression and replication in vitro and kinetics of spread of the different viruses in tumour xenografts are visualized in vivo using a small animal nano-SPECT/CT camera. The time required to reach maximal spread is 48 h for AdIP1 and 72 h for AdAM6 suggesting that genetic engineering of adenoviruses can affect their kinetics of spread in tumours. Considering that this methodology is potentially clinically applicable, we conclude that hNIS-mediated imaging of viral spread in tumours may be an important tool for combined anticancer therapies involving replicating adenoviruses

Neonatal adenoviral pneumonia--report of three autopsy cases.

Adenovirus pneumonia, while common in infancy and childhood, is rarely documented but may be fatal in the neonatal period. In regard to the serious outcome and no responsiveness to common anti-viral agents, adenovirus infection should be considered in the differential diagnosis of pneumonia in neonates. We report three cases of fatal neonatal adenovirus pneumonia, all of which were diagnosed by postmortem examination. Two patients were born by cesarean section at 35 or 36 weeks of gestation, and the other was a 5100 gm postmature baby born by vaginal delivery at 43 weeks of gestation. Respiratory insufficiency was detected just after birth or in the immediate postnatal period, and was associated with lethargy and chest X-ray findings of pneumonic infiltration. The postmortem findings of these patients were remarkably consistent and characterized by predominant lung involvement. The lungs showed diffuse massive consolidation with scattered patchy hemorrhage, and histologically revealed multifocal necrotizing alveolitis and/or bronchiolitis, often with hemorrhage. Alveolar lining cells and desquamated cells contained numerous smudge ells and many cells with characteristic inclusion bodies. Electron microscopy revealed that these inclusion bodies consisted of arrays of icosahedral particles of adenovirus. It is unusual that one of the patients, who was born by cesarean section without any evidence of prenatal infection, developed adenoviral pneumonia; this indicates that infection may occur in the immediate postnatal period as well as during passage of the birth canal.

Radiology of epidemic adenovirus 21 infection of the lower respiratory tract in infants and young children.

The radiologic features of 18 children admitted to Princess Mary Hospital, Auckland, New Zealand, in the winter and spring of 1977 with adenovirus 21 infection are reported. Attention is drawn to the severity of the disease in the respiratory tract, manifest radiologically as widespread patchy or confluent pulmonary opacification, extensive bronchial wall thickening, or peribronchial linear opacities. No hilar adenopathy was present. Prominent residual bronchopulmonary abnormalities were present in 13 of 15 patients 6--12 months after epidemic. High kilovoltage chester radiography or bronchography demonstrated bronchiectasis in five patients. These findings emphasize the role of adenovirus as a cause of chronic pulmonary disease and bronchiectasis in children.

[Severe viral pneumonia. A radiological classification with prognostic value]. / Bronchopneumopathies virales graves classification radiographique, interet pour le pronostic.

In one year eighteen children were admitted to an intensive care unit with severe viral pneumonia. Four groups were identified by the appearance of the chest X-ray. Bronchiolitis was seen in eight patients, alveolitis in four, interstitial pneumonia in two and combined bronchiolitis and alveolitis in four. Three of the four children with alveolitis died and six of the twelve with bronchiolitis, alone or with alveolitis, had residual bronchial obstruction.

An outbreak of adenovirus type 7 infection in children in Montreal.

Thirteen infants and children with adenovirus type 7 infection proved by virus isolation are described. High fever, cough and dyspnea were the most frequent findings; in infants under 1 year of age wheezing was common. Four patients required artificial ventilation. Lobar collapse, consolidation and hyperinflation were frequent radiologic findings. None of the symptoms responded to antibiotic therapy or bronchodilator drugs. Three patients died (mortality rate of 23%). Pathologic findings were compatible with adenovirus type 7 pneumonia, and were characterized by a necrotizing bronchitis and bronchiolitis, patchy alveolar fibrinopurulent exudate and hyaline membrane formation. Some intra-alveolar epithelial cells showed strikingly abnormal nuclei and rare typical halo-outlined intranuclear inclusions were seen. Only one of eight survivors had evidence of significant chronic chest disease.

Comparison of [18F]FHBG and [14C]FIAU for imaging of HSV1-tk reporter gene expression: adenoviral infection vs stable transfection.

Earlier studies involving comparison of different reporter probes have shown conflicting results between pyrimidine nucleosides [e.g., 2'-fluoro-2'-deoxy-1-beta- d-arabinofuranosyl-5-iodouracil (FIAU)] and acycloguanosine derivatives [e.g., penciclovir (PCV), 9-(4-fluoro-3-hydroxymethylbutyl)guanine (FHBG)]. We hypothesized that this reported discrepancy may be related to how the reporter gene is delivered to the cells-stably transfected vs adenoviral infection. We directly compared the uptake characteristics of [(18)F]FHBG, [(3)H]PCV, and [(14)C]FIAU in cell culture and in vivo using an adenoviral mediated gene transfer model and stably transfected cells. We further compared the uptake of three reporter probes using both HSV1-tk and a mutant HSV1-sr39tk expressing cells to assess the optimal reporter probe/reporter gene combination. [(14)C]FIAU accumulation was greater than that of [(3)H]PCV and [(18)F]FHBG in control cells and in HSV1-tk stably transfected cells ( P<0.001). After infection of C6 cells with AdCMV- HSV1-tk (1.5x10(8) pfu), [(18)F]FHBG and [(3)H]PCV accumulation was significantly greater than that of [(14)C]FIAU ( P<0.01). [(18)F]FHBG and [(3)H]PCV accumulated to a significantly greater extent than [(14)C]FIAU in C6-stb-sr39tk+ and AdCMV- HSV1-sr39tk infected C6 cells ( P<0.001). Results from the nude mice supported the results in cell culture. [(14)C]FIAU led to significantly higher %ID/g in C6-stb-tk+ xenografts than [(18)F]FHBG ( P<0.05); however, compared with [(14)C]FIAU, [(18)F]FHBG led to as high %ID/g in HSV1-tk expressing hepatocytes and to significantly greater %ID/g in C6-stb-sr39tk+ xenografts and HSV1-sr39tk expressing hepatocytes. Dynamic sequential images showed that [(18)F]FHBG was well retained in HSV1-sr39tk expressing cells (C6-stb-sr39tk+) for at least 4 h after injection, while it was rapidly cleared from HSV1-tk expressing cells (MH3924A-stb-tk+). [(14)C]FIAU accumulated in HSV1-tk stably expressing cells to a greater extent than either [(3)H]PCV or [(18)F]FHBG. However, the accumulation of [(3)H]PCV and [(18)F]FHBG in adenoviral infected C6 cells or hepatocytes was equivalent to or greater than that of [(14)C]FIAU. These results may be due to intracellular biochemical changes (e.g., thymidine) when cells are infected with adenovirus. For adenoviral studies, the [(18)F]FHBG/ HSV1-sr39tk combination was shown to be more sensitive than the [(14)C]FIAU/ HSV1-tk combination HSV1-tk.

Roentgenographic features of common pediatric viral respiratory tract infections.

Viral infections of the respiratory tract in infants and children are common. Little has been reported on roentgenographic findings associated with infection caused by common viruses other than with respiratory syncytial virus. We studied chest roentgenograms from 128 previously healthy infants and children who were infected with respiratory syncytial virus, parainfluenza virus, influenza virus, or adenovirus. Four common roentgenographic findings were detected: parahilar peribronchial infiltrates, hyperexpansion, segmental or lobar atelectasis, and hilar adenopathy. Diffuse interstitial infiltrates and significant pleural fluid accumulations rarely occurred in our series. We confirmed the popular but not well-documented belief that other common respiratory viruses can be associated with roentgenographic findings similar to those caused by respiratory syncytial virus. However, respiratory syncytial virus infection is associated with more abnormal chest roentgenograms than any of the other viruses regardless of the clinical syndrome. Hilar adenopathy was more common in adenovirus infection. Young infants had significantly more abnormal chest roentgenograms, with more hyperexpansion and parahilar peribronchial infiltration than older children. We also found a significant correlation between lobar atelectasis and severity of the illness. In infants and children with viral infection of the lower respiratory tract, roentgenographic information can be a useful adjunct to clinical viral diagnosis.

Adenovirus type 3 pneumonia causing lung damage in childhood.

An outbreak of adenovirus type 3 infection occurred in a hospital in 19 North American Indian infants and young children who were being treated for unrelated problems. Pneumonia occurred in 14 and was usually severe, with persistent signs of airway obstruction. Eleven of the 14 were followed periodically and complete medical reviews were conducted 8 to 10 years later. Ten had abnormal chest radiographs, and bronchography revealed bronchiectasis and minor airways changes in seven. In three cases there was clear evidence that these changes were directly related to the adenovirus type 3 infection. Pulmonary function studies showed a combination of restrictive and obstructive changes with minimal hypoxemia in most. Despite the presence of a persistent productive cough all were able to carry on a relatively normal life.