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Human adenoviruses (HAdVs) were previously detected at high prevalence by real‐time reverse transcription‐polymerase chain reaction (rRT‐PCR) in the upper respiratory tract of residents of two Kenyan refugee camps under surveillance for acute respiratory infection (ARI) between October 2006 and April 2008. We sought to confirm this finding and characterize the HAdVs detected. Of 2148 respiratory specimens originally tested, 511 (23.8%) screened positive for HAdV and 510 were available for retesting. Of these, 421 (82.4%) were confirmed positive by repeat rRT‐PCR or PCR and sequencing. Other respiratory viruses were codetected in 55.8% of confirmed HAdV‐positive specimens. Species B and C viruses predominated at 82.8%, and HAdV‐C1, ‐C2, and ‐B3 were the most commonly identified types. Species A, D, and F HAdVs, which are rarely associated with ARI, comprised the remainder. Viral loads were highest among species B HAdVs, particularly HAdV‐B3. Species C showed the widest range of viral loads, and species A, D, and F were most often present at low loads and more often with codetections. These findings suggest that many HAdV detections were incidental and not a primary cause of ARI among camp patients. Species/type, codetections, and viral load determinations may permit more accurate HAdV disease burden estimates in these populations. A high prevalence of human adenovirus (HAdV) detections were confirmed from the respiratory tract of refugees in Kenya presenting with acute respiratory infection (ARI).HAdV species B and C predominated, although other HAdV species not commonly associated with ARI were also detected.A high proportion of HAdV positive respiratory specimens had low virus loads and co-detections with other respiratory virus pathogens were common.Many HAdV detections in this refugee population were likely incidental and not associated with ARI. [ABSTRACT FROM AUTHOR]

Background: Human adenoviruses (HAdV) play a significant role in pediatric respiratory tract infections. To date, over 60 types of HAdV have been identified. Here, HAdV types are characterized in children in the Beijing area with acute lower respiratory tract infections (ALRTIs) and the clinical features and laboratory findings of hospitalized HAdV-infected cases are described.Methods: Respiratory specimens were collected from pediatric patients with ALRTIs in the emergency department or from those admitted to Beijing Children's Hospital between March 2007 and December 2012. Infections with common respiratory viruses were determined by PCR or RT-PCR. HAdV positive samples were further typed by PCR and sequencing.Results: Among 3356 patients with ALRTIs, 194 (5.8 %) were found to have HAdV infection. HAdV infection was primarily confined to children (88.35 %) less than 5 years of age. A total of 11 different types of HAdV were detected throughout the study period, with HAdV-B7 (49.0 %) and HAdV-B3 (26.3 %) as the most prevalent types, followed by HAdV-C2 (7.7 %) and HAdVC1 (4.6 %). Newly emerging and re-emergent types or variants, HAdV-B55 (n = 5), HAdV-C57 (n = 3), and HAdV-B14p1 (n = 1), were identified. Results also included the reported first case of co-infection with HAdV-C2 and HAdV-C57. Clinical entities of patients with single HAdV infection (n = 49) were similar to those with mixed HAdV/respiratory syncytial virus (RSV) infections (n = 41). Patients with HAdV-B7 infection had longer duration of fever and higher serum levels of muscle enzymes than HAdV-B3-infected patients.Conclusions: During the study period, HAdV-B7 and HAdV-B3 were the predominant types identified in pediatric ALRTIs. HAdV-B7 infection tends to have more severe clinical consequences. The presence of newly emerging types or variants and co-infection with different types of HAdV highlights the need for constant and close surveillance of HAdV infection. [ABSTRACT FROM AUTHOR]

Background: There is scarcity of data regarding epidemiology and clinical aspects of human adenovirus acute respiratory infection (ARI) among children in developing countries. Methods: Retrospective data on demographics, clinical presentation, outcomes and laboratory findings of 116 children admitted into Tuanku Jaafar Hospital in Seremban, Malaysia from 2012 to 2013 with documented diagnosis of community-acquired adenovirus ARI were collected and analyzed. Results: Male to female ratio was 1.70. Median age was 14 (1-107) months. The commonest symptoms were fever (94.8%; 110/116), cough (82.8%, 96), rhinorrhea (63.8%; 74), interrupted feeding (66.4%; 77), diarrhea (33.6%; 39) and conjunctivitis (21.6%; 25). Mean temperature on admission was 38.48°C±0.98°C. Among all 116 subjects, 20.7% (24) needed oxygen supplementation, 57.8% (67) required intravenous hydration, 11.2% (13) were admitted into the pediatric intensive care unit and 6.9% (8) required mechanical ventilation. Only 1% (1/87) had positive blood culture (Streptococcus pneumoniae) among 87 who received antibiotic treatment. Case fatality rate was 2.6% (3/116) and 1.7% (2/116) developed bronchiolitis obliterans. Median length of hospital stay was 4 (1-50) days. Conclusion: Adenovirus ARI caused significant morbidity and substantial resource utilization among hospitalized Malaysian children. It should be considered in the differential diagnosis of infants below two years presenting with ARI associated with high fever. Antibiotics should not be prescribed as secondary bacterial infections are uncommon. [ABSTRACT FROM AUTHOR]

Human adenoviruses (HADVs) comprise at least 54 types and cause a wide spectrum of respiratory tract infections; early diagnosis and epidemiological monitoring of HADV infections requires a rapid and sensitive assay. The use of a real-time polymerase chain reaction (PCR) assay was evaluated with one set of in-house designed primers for respiratory adenoviral infections. The assay was first validated by detecting successfully 6 representative types and 100 clinical isolates. A concomitant prospective surveillance of viral aetiology using conventional cultures and PCR assays in 160 febrile children with acute respiratory tract symptoms was conducted between May 2010 and July 2011. Viral aetiologies were confirmed in 72 (45%) cases using conventional cultures, including 51 adenoviral infections. The concordance between the real-time PCR and culture was good (Kappa = 0.94), and two additional culture-negative adenovirus infections were identified. During the study period (January 2011), an adenoviral community epidemic occurred. Adenovirus B3 was the predominant type in this epidemic (69.8%), followed by C2 (5.7%), C1 (5.7%), C5 (1.9%), E4 (1.9%), C6 (1.9%), F41 (1.9%), and 4 unclassified species C (7.5%). Significantly prolonged duration of fever (>5 days), higher leukocyte counts, higher neutrophil counts, and higher C-reactive protein levels were in the adenoviral infected group (n = 53, P < 0.001), compared with the non-adenoviral infected group (n = 107). In conclusion, this in-house real-time PCR is capable of detecting adenoviral respiratory infections of various types in children; and patients with adenoviral aetiology suffered from more severe clinical manifestations. J. Med. Virol. 86:2128-2133, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background and Objective: Respiratory tract infections (RTI) are the most common infectious disorders, worldwide. About 80%-90% of RTI are caused by four viruses such as Adenoviruses, 51 serotypes have been introduced so far. The aim of this survey was to evaluate the frequency of Adenovirus in respiratory infected patients by PCR method in Golestan province, Iran. Material and Methods: This descriptive cross-sectional study was conducted on 400 patients with clinical diagnosis of flu-like respiratory infection, 2010-2012. In addition to collecting demographic and clinical data, nasopharyngeal swabs were taken and transferred to the virology laboratory in viral transport medium (VTM), and evaluated by PCR method for Adenovirus after genomic extraction. Results: Thirty-seven (9.2%) were positive for Adenovirus. No significant correlation was found between being positive for Adenovirus and the variables such as age, gender and season. Clinical signs were coughing (27; 73%), body pain (25; 67.6%), and fever (24; 64.9%). Thirty-five of the patients (94.5%) had at least one symptom. Conclusion: Our findings are consistent with other research conducted in Iran and other countries. There is a significant correlation between Adenovirus infection and clinical symptoms. [ABSTRACT FROM AUTHOR]

To develop adenoviral cell- or tissue-specific gene delivery, understanding of the infection mechanisms of adenoviruses is crucial. Several adenoviral attachment proteins such as CD46, CAR and sialic acid have been identified and studied. However, most receptor studies were performed on non-human cells. Combining our reporter gene-tagged adenovirus library with an in vitro human gene knockout model, we performed a systematic analysis of receptor usage comparing different adenoviruses side-by-side. The CRISPR/Cas9 system was used to knockout CD46 and CAR in the human lung epithelial carcinoma cell line A549. Knockout cells were infected with 22 luciferase-expressing adenoviruses derived from adenovirus species B, C, D and E. HAdV-B16, -B21 and -B50 from species B1 as well as HAdV-B34 and -B35 were found to be CD46-dependent. HAdV-C5 and HAdV-E4 from species E were found to be CAR-dependent. Regarding cell entry of HAdV-B3 and -B14 and all species D viruses, both CAR and CD46 play a role, and here, other receptors or attachment structures may also be important since transductions were reduced but not completely inhibited. The established human knockout cell model enables the identification of the most applicable adenovirus types for gene therapy and to further understand adenovirus infection biology. [ABSTRACT FROM AUTHOR]

In immunocompromised patients, human adenovirus (HAdV) infections can cause life-threatening multiorgan disease. This review summarizes the incidence and risk factors of invasive human adenovirus infections in immunocompromised patients as well as the recently developed standards for diagnostic methods and strategies according to the predominant risk factors in adults and children. Recommendations for preemptive and therapeutic treatment strategies and the outcome in different risk groups are presented. Novel therapeutic approaches including CMX001, a new orally bioavailable lipid conjugate of cidofovir and the transfer of adenovirus-specific donor T cells in the context of allogeneic stem cell transplantation are discussed. [ABSTRACT FROM AUTHOR]

Compared to traditional testing strategies, nucleic acid amplification tests such as real-time PCR offer many advantages for the detection of human adenoviruses. However, commercial assays are expensive and cost prohibitive for many clinical laboratories. To overcome fiscal challenges, a cost effective strategy was developed using a combination of homogenization and heat treatment with an "in-house" real-time PCR. In 196 swabs submitted for adenovirus detection, this crude extraction method showed performance characteristics equivalent to viral DNA obtained from a commercial nucleic acid extraction. In addition, the in-house real-time PCR outperformed traditional testing strategies using virus culture, with sensitivities of 100% and 69.2%, respectively. Overall, the combination of homogenization and heat treatment with a sensitive in-house real-time PCR provides accurate results at a cost comparable to viral culture. [ABSTRACT FROM AUTHOR]

Human Adenoviruses (HAdV) are known to be potentially associated with strong inflammatory responses and morbidity in pediatric patients. Although most of the primary infections are self-limiting, the severity of clinical presentation, the elevation of the white blood cell count and inflammatory markers often mimic a bacterial infection and lead to an inappropriate use of antibiotics. In infections caused by HAdV, rapid antigen detection kits are advisable but not employed routinely; costs and feasibility of rapid syndromic molecular diagnosis may limit its use in the in-hospital setting; lymphocyte cultures and two-sampled serology are time consuming and impractical when considering the use of antibiotics. In this review, we aim to describe the principal diagnostic tools and the immune response in HAdV infections and evaluate whether markers based on the response of the host may help early recognition of HAdV and avoid inappropriate antimicrobial prescriptions in acute airway infections. [ABSTRACT FROM AUTHOR]

The recently discovered exchange protein directly activated by cAMP (EPAC), compared with protein kinase A (PKA), is a fairly new family of cAMP effectors. Soon after the discovery, EPAC has shown its significance in many diseases including its emerging role in infectious diseases. In a recent study, we demonstrated that EPAC, but not PKA, is a promising therapeutic target to regulate respiratory syncytial virus (RSV) replication and its associated inflammation. In mammals, there are two isoforms of EPAC—EPAC1 and EPAC2. Unlike other viruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) and Ebola virus, which use EPAC1 to regulate viral replication, RSV uses EPAC2 to control its replication and associated cytokine/chemokine responses. To determine whether EPAC2 protein has a broad impact on other respiratory viral infections, we used an EPAC2-specific inhibitor, MAY0132, to examine the functions of EPAC2 in human metapneumovirus (HMPV) and adenovirus (AdV) infections. HMPV is a negative-sense single-stranded RNA virus belonging to the family Pneumoviridae, which also includes RSV, while AdV is a double-stranded DNA virus. Treatment with an EPAC1-specific inhibitor was also included to investigate the impact of EPAC1 on these two viruses. We found that the replication of HMPV, AdV, and RSV and the viral-induced immune mediators are significantly impaired by MAY0132, while an EPAC1-specific inhibitor, CE3F4, does not impact or slightly impacts, demonstrating that EPAC2 could serve as a novel common therapeutic target to control these viruses, all of which do not have effective treatment and prevention strategies. [ABSTRACT FROM AUTHOR]