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Adenovirus infections [keywords]
- [Fever of unknown origin: a challenge for the pediatric infectious diseases specialist]. [English Abstract, Journal Article]
- Rev Chilena Infectol 2014 Feb; 31(1):87-91.
Introduction: Prolonged febrile syndrome (PFS) is defined as fever 7-10 days, with initial study does not allow etiologic diagnosis.
Objective:To describe the main causes of the PFS and its temporal behavior in Pediatric Infectious Diseases Unit Outpatient Care of Complejo Asistencial Dr. Sótero del Río (CASR). Patients and
Methods:A descriptive, prospective study between january 2007-december 2012, about 153 patients from 6 weeks to 14 years 11 months old, diagnosed with PFS, tab completing clinical and laboratory monitoring.
Results:etiology was obtained in 67.9%, the causes were infection (88.4%), neoplasms (4.8%), rheumatological (4.8%) and Kawasaki disease (2.8%). The most important infectious causes were enteric fevers (typhoid and paratyphoid) (18.4%), urinary tract infection (11.9%), Bartonella henselae infections and adenovirus (8.7%) each one and Epstein Barr virus (7.6%). Ninety eight percent of patients had complete resolution, 60.7% did not require hospitalization and mortality was 0%. Discussion: As in previous pediatric clinical series the infections were the most frequent causes. Enteric fever persists as principal cause, however, the epidemiological evidence is oscillating in time endorsing the local statistics can count over the years to improve the diagnostic and therapeutic approach.
- Association of serum Clara cell protein CC16 with respiratory infections and immune response to respiratory pathogens in elite athletes. [JOURNAL ARTICLE]
- Respir Res 2014 Apr 15; 15(1):45.
Respiratory epithelium integrity impairment caused by intensive exercise may lead to exercise-induced bronchoconstriction. Clara cell protein (CC16) has anti-inflammatory properties and its serum level reflects changes in epithelium integrity and airway inflammation. This study aimed to investigate serum CC16 in elite athletes and to seek associations of CC16 with asthma or allergy, respiratory tract infections (RTIs) and immune response to respiratory pathogens.The study was performed in 203 Olympic athletes. Control groups comprised 53 healthy subjects and 49 mild allergic asthmatics. Serum levels of CC16 and IgG against respiratory viruses and Mycoplasma pneumoniae were assessed. Allergy questionnaire for athletes was used to determine symptoms and exercise pattern. Current versions of ARIA and GINA guidelines were used when diagnosing allergic rhinitis and asthma, respectively.Asthma was diagnosed in 13.3% athletes, of whom 55.6% had concomitant allergic rhinitis. Allergic rhinitis without asthma was diagnosed in 14.8% of athletes. Mean CC16 concentration was significantly lower in athletes versus healthy controls and mild asthmatics. Athletes reporting frequent RTIs had significantly lower serum CC16 and the risk of frequent RTIs was more than 2-fold higher in athletes with low serum CC16 (defined as equal to or less than 4.99 ng/ml) . Athletes had significantly higher anti-adenovirus IgG than healthy controls while only non-atopic athletes had anti-parainfluenza virus IgG significantly lower than controls. In all athletes weak correlation of serum CC16 and anti-parainfluenza virus IgG was present (R = 0.20, p < 0.01). In atopic athletes a weak positive correlations of CC16 with IgG specific for respiratory syncytial virus (R = 0.29, p = 0.009), parainfluenza virus (R = 0.31, p = 0.01) and adenovirus (R = 0.27, p = 0.02) were seen as well.Regular high-load exercise is associated with decrease in serum CC16 levels. Athletes with decreased CC16 are more susceptible to respiratory infections. Atopy may be an additional factor modifying susceptibility to infections in subjects performing regular high-load exercise.
- Respiratory viral pathogens among Singapore military servicemen 2009 - 2012: epidemiology and clinical characteristics. [JOURNAL ARTICLE]
- BMC Infect Dis 2014 Apr 15; 14(1):204.
Few studies have comprehensively described tropical respiratory disease surveillance in military populations. There is also a lack of studies comparing clinical characteristics of the non-influenza pathogens with influenza and amongst themselves.From May 2009 through October 2012, 7733 consenting cases of febrile respiratory illness (FRI) (temperature [greater than or equal to]37.5degreesC with cough or sorethroat) and controls in the Singapore military had clinical data and nasal washes collected prospectively. Nasal washes underwent multiplex PCR, and the analysis was limited to viral mono-infections.49% of cases tested positive for at least one virus, of whom 10% had multiple infections. 53% of the FRI cases fulfilled the definition of influenza-like illness (ILI), of whom 52% were positive for at least one virus. The most frequent etiologies for mono-infections among FRI cases were Influenza A(H1N1)pdm09 (13%), Influenza B (13%) and coxsackevirus (9%). The sensitivity, specificity, positive predictive value and negative predictive value of ILI for influenza among FRI cases were 72%, 48%, 40% and 69% respectively. On logistic regression, there were marked differences in the prevalence of different symptoms and signs between viruses with fever more prevalent amongst influenza and adenovirus infections than other viruses.There are multiple viral etiologies for FRI and ILI with differing clinical symptoms in the Singapore military. Influenza and coxsackevirus were the most common etiology for FRI, while influenza and adenoviruses displayed the most febrile symptoms. Further studies should explore these differences and possible interventions.
- Viral Respiratory Infections (VRI) diagnosed by Multiplex PCR After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): long-term incidence and Outcome. [JOURNAL ARTICLE]
- Biol Blood Marrow Transplant 2014 Apr 11.
VRI are frequent after HSCT and constitute a potential cause of mortality. We analyzed the incidence, risk factors and prognosis of VRI in a cohort of transplanted patients. More frequent viruses were HCoV and HRV followed by flu-like viruses and adenovirus. Risk factors for death were lymphocytopenia and high steroid dosage.
- Lower Respiratory Tract Virus Findings in Mechanically Ventilated Patients with Severe Community-Acquired Pneumonia. [JOURNAL ARTICLE]
- Clin Infect Dis 2014 Apr 11.
Background. The role of viral infections in the etiology of severe community-acquired pneumonia (SCAP) was prospectively evaluated from 2008-2012 at university-level intensive care unit. Methods. Clinical data and microbiological tests were assessed: blood cultures, urine pneumococcal and legionella antigens, Mycoplasma pneumoniae and Chlamydia pneumoniae antibodies from paired serums and respiratory virus detections by multiplex, real-time polymerase chain reaction (PCR) from nasopharyngeal swabs and lower tracheal specimens via intubation tube. Results. Of 49 mechanically ventilated SCAP patients (21 males and 28 females; median age, 54 years), the etiology was identified in 45 cases (92%). There were 21 pure bacterial infections (43%), 5 probably pure viral infections (10%), and 19 mixed bacterial-viral infections (39%), resulting in viral etiology in 24 patients (49%). Out of 26 viruses, 21 (81%) were detected from bronchial specimens and five (19%) from nasopharyngeal swabs. Rhinovirus (15 cases, 58%) and adenovirus (4 cases, 15%) were most common viral findings. The bacterial-viral etiology group had the highest peak CRP levels (median 356 [25th-75th percentiles 294-416], p=0.05), while patients with probably viral etiology had the lowest peak PCT levels (1.7 [1.6-1.7]. The clinical characteristics of pure bacterial and mixed bacterial-viral etiologies were comparable. Hospital stay was longest among bacterial group (17 vs. 14 days, p=0.02). Conclusion. Viral findings were demonstrated in almost half of the SCAP patients. Clinical characteristics were similar between the pure bacterial and mixed bacterial-viral infections groups. The frequency of viral detection depends on the availability of PCR techniques and lower respiratory specimens.
- Profiling the approach to the investigation of viral infections in cases of sudden unexpected death in infancy in the Western Cape Province, South Africa. [JOURNAL ARTICLE]
- Forensic Sci Int 2014 Mar 18.:27-30.
Sudden unexpected death in infancy is one of the main contributory factors to high infant mortality rates world-wide. Several risk factors, including viral infection, have been implicated in SUDI cases, but no single factor has been confirmed as the main cause of death. At the Tygerberg Medico-legal Laboratory, Cape Town, South Africa, investigation of lung tissue for viral infection forms part of an institutional protocol for the examination of cases of sudden unexpected death in infancy.Lung tissue from 82 cases of sudden unexpected death in infancy was collected over a 10 month period. Routine shell vial cultures and histological examination of the tissue were performed according to the standard institutional protocol on fresh and formalin-fixed tissue, respectively. In addition, real-time polymerase chain reactions and immunohistochemical staining for adenovirus, cytomegalovirus and respiratory syncytial virus were done on fresh and formalin-fixed lung tissue, respectively.Huge variation was found in the number of positive cases confirmed by shell vial culture, real-time polymerase chain reaction and immunohistochemistry (0, 2 and 0 for adenovirus; 3, 29 and 2 for cytomegalovirus; and 0, 0 and 4 for respiratory syncytial virus, respectively).In the absence of a National Protocol for investigation of sudden unexpected death in infancy, we conclude that the selection of viruses and routine diagnostic technique included in the institutional investigation protocol might be suboptimal and should be re-evaluated.
- First-in-Man Clinical Results With Good Manufacturing Practice (GMP)-compliant Polypeptide-expanded Adenovirus-specific T Cells After Haploidentical Hematopoietic Stem Cell Transplantation. [Journal Article]
- J Immunother 2014 May; 37(4):245-9.
Adoptive immunotherapy against viral infections is a promising treatment option for patients after hematopoietic stem cell transplantation. However, the generation of virus-specific T cells is either cost-intensive or time-consuming. We developed the first GMP-compliant protocol to generate donor-derived adenovirus (HAdV), cytomegalovirus, and Epstein-Barr virus-specific T-cell lines (TCLs) within 12 days by the use of overlapping polypeptides derived from different viruses in combination with IL-15. Two patients after undergoing haploidentical hematopoietic stem cell transplantation with HAdV viremia displaying rising viral loads despite treatment with cidofovir received 1×10 donor-derived short-term expanded HAdV-specific TCLs per kg body weight. In both patients, HAdV-specific T cells could be detected by IFN-γ-ELISpot 30 and 22 days postinfusion, and resulted in complete clearance or >1.5 log reduction of viral load within 15 and 18 days, respectively. This protocol facilitates rapid and cost-effective generation of virus-specific TCLs, which appear to provide an effective treatment option.
- Clinical Characteristics and Outcome in Norovirus Gastroenteritis. [JOURNAL ARTICLE]
- Indian J Pediatr 2014 Apr 6.
To examine differences in clinical characteristics among children with norovirus, rotavirus, and bacterial gastroenteritis and investigate the outcomes in children with sporadic norovirus gastroenteritis.The study included patients aged 4 mo to 14 y who had acute gastroenteritis and were admitted to a tertiary care center between April 2008 and July 2009. The clinical features and laboratory findings of acute gastroenteritis were recorded. Fecal specimens were collected and tested for viruses, bacteria, and parasites.A total of 198 children (median age, 2.1 y) with acute gastroenteritis were studied. The pathogens identified included norovirus (n = 38), rotavirus (n = 47), adenovirus (n = 5), astrovirus (n = 1), bacteria (n = 43), and mixed infections (n = 7). No causative organisms were identified in 57 patients. The norovirus-infected group had a significantly higher proportion of those still vomiting 1 d after the onset of vomiting (p < 0.001, OR 5.0, 95 % CI 1.9-12.8), cessation of diarrhea 4 d after the onset of diarrhea (p < 0.001, OR 15.5, 95 % CI 5.1-47.0) and no fever 3 d after the onset of fever (p < 0.001, OR 27.5, 95 % CI 5.8-129.7) compared with the bacteria-infected group. The length of hospital stay of the norovirus-infected patients was positively correlated with the number of diarrhea episodes, duration of diarrhea, and severity score.The clinical manifestations on the day after onset of diarrhea, vomiting and fever reflected the occurrence of norovirus infection in children with sporadic gastroenteritis.
- Acute respiratory viral infections in pediatric cancer patients undergoing chemotherapy. [JOURNAL ARTICLE]
- J Pediatr (Rio J) 2014 Apr 1.
to estimate the prevalence of infection by respiratory viruses in pediatric patients with cancer and acute respiratory infection (ARI) and/or fever.cross-sectional study, from January 2011 to December 2012. The secretions of nasopharyngeal aspirates were analyzed in children younger than 21 years with acute respiratory infections. Patients were treated at the Grupo em Defesa da Criança Com Câncer (Grendacc) and University Hospital (HU), Jundiaí, SP. The rapid test was used for detection of influenza virus (Kit Biotrin, Inc. Ireland), and real-time multiplex polymerase chain reaction (FTD, Respiratory pathogens, multiplex Fast Trade Kit, Malta) for detection of influenza virus (H1N1, B), rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus, human parechovirus, bocavirus, metapneumovirus, and human coronavirus. The prevalence of viral infection was estimated and association tests were used (χ(2) or Fisher's exact test).104 samples of nasopharyngeal aspirate and blood were analyzed. The median age was 12 ± 5.2 years, 51% males, 68% whites, 32% had repeated ARIs, 32% prior antibiotic use, 19.8% cough, and 8% contact with ARIs. A total of 94.3% were in good general status. Acute lymphocytic leukemia (42.3%) was the most prevalent neoplasia. Respiratory viruses were detected in 50 samples: rhinoviruses (23.1%), respiratory syncytial virus AB (8.7%), and coronavirus (6.8%). Co-detection occurred in 19% of cases with 2 viruses and in 3% of those with 3 viruses, and was more frequent between rhinovirus and coronavirus 43. Fever in neutropenic patients was observed in 13%, of which four (30.7) were positive for viruses. There were no deaths.the prevalence of respiratory viruses was relevant in the infectious episode, with no increase in morbidity and mortality. Viral co-detection was frequent in patients with cancer and ARIs.
- Adenovirus E4ORF1-Induced MYC Activation Promotes Host Cell Anabolic Glucose Metabolism and Virus Replication. [Journal Article]
- Cell Metab 2014 Apr 1; 19(4):694-701.
Virus infections trigger metabolic changes in host cells that support the bioenergetic and biosynthetic demands of viral replication. Although recent studies have characterized virus-induced changes in host cell metabolism (Munger et al., 2008; Terry et al., 2012), the molecular mechanisms by which viruses reprogram cellular metabolism have remained elusive. Here, we show that the gene product of adenovirus E4ORF1 is necessary for adenovirus-induced upregulation of host cell glucose metabolism and sufficient to promote enhanced glycolysis in cultured epithelial cells by activation of MYC. E4ORF1 localizes to the nucleus, binds to MYC, and enhances MYC binding to glycolytic target genes, resulting in elevated expression of specific glycolytic enzymes. E4ORF1 activation of MYC promotes increased nucleotide biosynthesis from glucose intermediates and enables optimal adenovirus replication in primary lung epithelial cells. Our findings show how a viral protein exploits host cell machinery to reprogram cellular metabolism and promote optimal progeny virion generation.