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The present study was done to identify the viral diversity, seasonality and burden associated with childhood acute respiratory tract infection (ARTI) in Sri Lanka. Nasopharyngeal aspirates (NPA) of hospitalized children (1 month-5 years) with ARTI were collected in 2 centers (wet and dry zones) from March 2013 to August 2014. Respiratory viral antigen detection by immunofluorescence assay (IFA) was used to identify the infecting viruses. IFA negative 100 NPA samples were tested for human metapeumovirus (hMPV), human bocavirus and corona viruses by polymerase chain reaction. Of the 443 and 418 NPAs, 37.2% and 39.4% were positive for any of the 8 different respiratory viruses tested from two centers studied. Viral co-infection was detected with respiratory syncytial virus (RSV) in both centers. Peak viral detection was noted in the wet zone from May-July 2013 and 2014 and in the dry zone from December-January 2014 suggesting a local seasonality for viral ARTI. RSV showed a clear seasonality with a direct correlation of monthly RSV infections with rainy days in the wet zone and an inverse correlation with temperature in both centers. The case fatality rate was 2.7% for RSV associated ARTI. The overall disability adjusted life years was 335.9 and for RSV associated ARTI it was 241.8. RSV was the commonly detected respiratory virus with an annual seasonality and distribution in rainy seasons in the dry and wet zones of Sri Lanka. Identifying the virus and seasonality will contribute to employ preventive measures and reduce the empirical use of antibiotics in resource limited settings., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Human bocavirus (HBoV) is a linear single-stranded DNA virus belonging to the Parvoviridae family. This study aimed to investigate the incidence of HBoV and co-infections in pediatric patients with symptoms of viral respiratory tract infection., Methodology: This study included 2,310 patients between the ages of 0-18 in whom HBoV and other respiratory tract viral pathogens were analyzed in nasopharyngeal swab specimens., Results: In the pediatric age group, HBoV was found in 4.5% (105/2310) of the patients and higher in children between the ages of 1 and 5. Mixed infection was detected in 43.8% (46/105) of HBoV positive patients (p = 0.10). Mono and mixed infection rates were higher in outpatients than in inpatients (p < 0.05). Respiratory syncytial virus was significantly higher than the other respiratory viral pathogens (p < 0.001)., Conclusions: This study is important as it is one of the rare studies performed on the incidence of HBoV in the Marmara region. In pediatric age group, the incidence of HBoV was found 4.5%. The incidence rate of HBoV in this study was similar to those in studies around the world, but close to low rates. The incidence of HBoV was found higher especially among children between the ages of 1-5 in this study. In addition to the incidence of HBoV, accompanying co-infections in the pediatric age group were also investigated in this study. Since concurrence of RSV, HRV and hMPV with HBoV was the most common it must be considered that there may be more than one agents in patients with symptoms of respiratory tract infection., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2020 Ayfer Bakir, Nuran Karabulut, Sema Alacam, Sevim Mese, Ayper Somer, Ali Agacfidan.)

Introduction. Globally, human bocavirus (HBoV) has been detected in respiratory samples from patients suffering from upper and lower respiratory diseases. In Kuwait, little is known about the epidemiological and clinical characterization of the virus and genetic characterization of the virus as a respiratory pathogen is unknown. Aim. This study aims to explore the molecular epidemiology and clinical features of HBoV isolates in patients with respiratory diseases. Methodology. Retrospectively, between 2018 and 2020, 5941 respiratory samples from patients with respiratory diseases were screened for respiratory viruses using multiplex real-time PCR. Samples that were positive for HBoV were then subjected to NP1 and VP1/PV2 phylogenetic analysis. Results. HBoV was detected in 1.9 % of the patients, with a peak incidence of infection among children <1 year old. Co-infection with other respiratory viruses was observed in 56.8 % of HBoV-positive patients. Fever, cough and respiratory distress were the most common clinical features of HBoV infection. Phylogenetic analysis of the Kuwaiti HBoV isolates revealed that all the isolates were of the HBoV-1 genotype, with slight sequence variations among the isolates. Conclusion. This study illustrated the predominance of the HBoV-1 genotype in patients with respiratory diseases in Kuwait with minimal genetic variability. It also highlighted the clinical features of HBoV-1 infection, verifying its role in respiratory diseases.

The objective of this study was to determine the frequency and seasonal distributions of HBoV detections among Iranian children presenting with acute respiratory or gastrointestinal symptoms and to compare infections among children with concomitant respiratory syncytial virus (RSV) and rotavirus (RV) infections. A cross-sectional study at Mofid Children's Hospital in Tehran, Iran, enrolled children < 3 years old presenting with either acute respiratory or gastrointestinal symptoms during the period of 2017-2018. Respiratory or stool specimens collected from each group were initially tested by RT-PCR assays for RSV and RV, respectively, and all specimens were tested for HBoV by PCR assay. Clinical and demographic data were collected and statistically compared. Five hundred respiratory and stool specimens each were tested and 67 (13.4%) and 72 (14.4%) were PCR positive for HBoV, respectively. Of 128 (25.6%) respiratory specimens positive for RSV, 65% were also positive for HBoV (p = 0.019); of 169 (33.8%) stool specimens positive for RV, 62.5% were also positive for HBoV (p = 0.023). Peak circulation of all viruses was during late winter and early spring months (Jan-Mar) in gastrointestinal infections and during winter (Feb-Jan) in respiratory infections. HBoV is commonly detected among Iranian children presenting with acute respiratory or gastrointestinal symptoms and is often present as co-infections with RSV and RV, respectively.

We report a case of lower respiratory tract infection with human bocavirus 1 (HboV1) in an immunodeficient 6-month-old boy leading to respiratory failure with fatal outcome. Polymerase chain reaction of serum/tracheal secretions revealed exceptionally high HboV1-DNA levels and immunoassays showed seroconversion indicating an acute primary HboV1 infection. All assays for other pathogens were negative, strongly suggesting that HboV1 was the causative agent in this case.

Objective: Human bocavirus (HBoV) is a newly identified pathogen that can cause upper and lower respiratory infections usually in children; however, its clinical characteristics and significance in respiratory infections in adults have not been well known. Our objective was to evaluate the clinical features of respiratory HBoV infection and to describe the CT findings of HBoV pneumonia in adults., Materials and Methods: A total of 185 adult patients diagnosed with HBoV infection at a tertiary referral center between January 2010 and December 2017 were retrospectively evaluated with respect to the clinical characteristics of HBoV infection and its risk factors for pneumonia. Chest CT findings for 34 patients with HBoV pneumonia without co-infection were analyzed and compared between immunocompetent (n = 18) and immunocompromised (n = 16) patients., Results: HBoV infections were predominantly noted between February and June. Among the 185 patients with HBoV infection, 119 (64.3%) had community-acquired infections and 110 (59.5%) had pneumonia. In multivariable analysis, older age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.00-1.04; p = 0.045) and nosocomial infection (OR, 2.07; 95% CI, 1.05-4.10; p = 0.037) were associated with HBoV pneumonia. The main CT findings were bilateral consolidation (70.6%) and/or ground-glass opacities (64.7%); centrilobular nodules (14.7%) were found less frequently. The pattern of CT findings were not significantly different between immunocompetent and immunocompromised patients (all, p > 0.05)., Conclusion: HBoV infection can be a potential respiratory tract infection in adults. The most frequent CT findings of HBoV pneumonia were bilateral consolidation and/or ground-glass opacities., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2019 The Korean Society of Radiology.)

Human bocavirus 1 (HBoV1), belonging to the Parvoviridae family, was discovered in 2005, in nasopharyngeal samples from children with respiratory tract infections. Three additional bocaviruses, HBoV2-4, were discovered in 2009-10. These viruses have mainly been found in faecal samples and their role in human diseases is still uncertain. HBoV1 causes a wide spectrum of respiratory diseases in children, including common cold, acute otitis media, pneumonia, bronchiolitis, and asthma exacerbations. HBoV1 DNA can persist in airway secretions for months after an acute infection. Consequently, acute HBoV1 infection cannot be diagnosed with standard DNA PCR; quantitative PCR and serology are better diagnostic approaches. Because of their high clinical specificity, diagnostic developments such as HBoV1 mRNA and antigen detection have shown promising results. This Review summarises the knowledge on human bocaviruses, with a special focus on HBoV1., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To investigate the relationship between human bocavirus 2 (HBoV2) infection and acute diarrhea in children younger than 5 years of age in a case-control study. Methods: This was a prospective case-control study. During May 2016 to December 2016, fecal specimens were collected from children ≤5 years of age with acute diarrhea who visited the Affiliated Children's Hospital of Capital Institute of Pediatrics (case group), or from children ≤5 years of age without diarrhea from Longtan Community Medical Service Center, Beijing (control group). The case group ( n= 240) and the control group ( n= 240) were divided into 8 age subgroups: ≤1 month old, >1-3 months old, >3-6 months old, >6-12 months old,>1-2 years old,>2-3 years old,>3-4 years old and >4-5 years old, and there were 30 cases in each age subgroup. The specimens were tested for 7 types of diarrhea-associated viruses, especially for HBoV2 by real-time PCR method. The HBoV2 viral load was predicted according to the cycle threshold (Ct). Finally, t -test was used to compare the differences between groups. Results: In the case group ( n =240), the positive rate of norovirus was 16.7% (40 cases); rotavirus, 10.8% (26 cases); HBoV2, 7.5% (18 cases); adenovirus, 7.1% (17 cases); astrovirus, 6.3% (15 cases); parachovirus, 3.8% (9 cases); and Aich virus, 0.4% (1 case). The positive rates of HBoV2 in case group (7.5%, 18 cases) and control group (5.0%, 12 cases) showed no significant difference (χ(2)=1.280, P= 0.258), as well as in different age groups (all P> 0.05) . However, the mean viral load of the HBoV2 in the case group (1×10(9)copies/L with cycle threshold (Ct) 25.8) was higher than that of control group (1×10(5)copies/L with Ct 33.8), showing a significant difference ( t= 0.597, P= 0.000). Conclusions: Norovirus and rotavirus are still the important viral pathogens in children with acute diarrhea. A higher load of HBoV2 may indicate a higher risk of acute diarrhea in children ≤5 years of age in Beijing.

Despite increased understanding of how viral infection is involved in asthma exacerbations, it is less clear which viruses are involved and to what extent they contribute to asthma exacerbations. Here, we sought to determine the prevalence of different respiratory viruses during asthma exacerbations. Systematic computerized searches of the literature up to June 2017 without language limitation were performed. The primary focus was on the prevalence of respiratory viruses, including AdV (adenovirus), BoV (bocavirus), CoV (coronavirus), CMV (cytomegalovirus), EnV (enterovirus), HSV (herpes simplex virus), IfV (influenza virus), MpV (metapneumovirus), PiV (parainfluenzavirus), RV (rhinovirus) and RSV (respiratory syncytial virus) during asthma exacerbations. We also examined the prevalence of viral infection stratified by age, geographic region, type of respiratory secretion, and detection method. Sixty articles were included in the final analysis. During asthma exacerbations, the mean prevalence of AdV, BoV, CoV, CMV, EnV, HSV, IfV, MpV, PiV, RV and RSV was 3.8%, 6.9%, 8.4%, 7.2%, 10.1%, 12.3%, 10.0%, 5.3%, 5.6%, 42.1% and 13.6%, respectively. EnV, MPV, RV and RSV were more prevalent in children, whereas AdV, BoV, CoV, IfV and PiV were more frequently present in adults. RV was the major virus detected globally, except in Africa. RV could be detected in both the upper and lower airway. Polymerase chain reaction was the most sensitive method for detecting viral infection. Our findings indicate the need to develop prophylactic polyvalent or polyvirus (including RV, EnV, IfV and RSV) vaccines that produce herd immunity and reduce the healthcare burden associated with virus-induced asthma exacerbations.

Background: The etiology of acute childhood diarrhea often eludes identification. We used a case-control study-stool archive to determine if nucleic acid tests for established and newly identified viruses diminish our previously published 32% rate of microbiologically unexplained episodes., Methods: Using polymerase chain reaction, we sought to detect noroviruses GI and GII, classic and novel astroviruses, and human bocaviruses (HBoVs) 2, 3, and 4 among 178 case and 178 matched control stool samples and St. Louis and Malawi polyomaviruses among a subset of 98 case and control stool samples. We calculated adjusted odds ratios and 95% confidence intervals using conditional logistic regression., Results: Noroviruses were more common in cases (GI, 2.2%; GII, 16.9%) than in controls (GI, 0%; GII, 4.5%) (adjusted odds ratio, 5.2 [95% confidence interval, 2.5-11.3]). Astroviruses and HBoVs 2, 3, and 4 were overrepresented among the cases, although this difference was not statistically significant. Malawi polyomavirus was not associated with case status, and St. Louis polyomavirus was identified in only 1 subject (a control). When identified in cases, HBoVs 2, 3, and 4 were frequently (77%) found in conjunction with a bona fide diarrheagenic pathogen. Thirty-five (20%) case and 3 (2%) control stool samples contained more than 1 organism of interest. Overall, a bona fide or plausible pathogen was identified in 79% of the case stool samples. Preceding antibiotic use was more common among cases (adjusted odds ratio, 4.5 [95% confidence interval, 2.3-8.5])., Conclusion: Noroviruses were found to cause one-third of the diarrhea cases that previously had no identified etiology. Future work should attempt to ascertain etiologic agents in the approximately one-fifth of cases without a plausible microbial cause, understand the significance of multiple agents in stools, and guide interpretation of nonculture diagnostics., (© The Author 2017. Published by the Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Human Bocavirus (HBoV) was first identified in 2005 and has been shown to be a common cause of respiratory infections and gastroenteritis in children. In a recent study, we found that 10.7% of children with acute respiratory infections (ARI) were infected by HBoV. Genetic characterization of this virus remains unknown in Central Africa, particularly in Cameroon Leeding us to evaluate the molecular characteristics of HBoV strains in Cameroonian children with ARI., Results: Phylogenetic analysis of partial HBoV VP1/2 sequences showed a low level of nucleotide variation and the circulation of HBoV genotype 1 (HBoV-1) only. Three clades were obtained, two clustering with each of the reference strains ST1 and ST2, and a third group consisting of only Cameroon strains. By comparing with the Swedish reference sequences, ST1 and ST2, Cameroon sequences showed nucleotide and amino acid similarities of respectively 97.36-100% and 98.35-100%. These results could help improve strategies for monitoring and control of respiratory infections in Cameroon.

Background: So far, many studies have shown that Human Bocavirus ( HBoV) is the main pathogen of the respiratory tract. Until now, there is no study that proves the association between HBoV and hepatitis. HBoV viremia/DNAemia has been associated closely with acute primary infection and moderate-to-severe illness but, more detailed clinical data about HBoV dissemination are still unavailable., Case Report: Here we report a 2-years-5-months-old girl suffering from respiratory distress and heptitis followed in our intensive care unit. HBoV was detected in our patients nose and throat swabs concurrent with whole blood sample by positive polymerase chain reactions. After a through investigation no causative agent other than HBoV viremia was found., Conclusion: Human Bocavirus viremia with high viral loads may be associated with hepatitis.

Acute necrotizing encephalopathy is characterized by multiple, symmetrical lesions involving the thalamus, brainstem, cerebellum, and white matter and develops secondarily to viral infections. Influenza viruses are the most common etiological agents. Here, we present the first case of acute necrotizing encephalopathy to develop secondarily to human bocavirus. A 3-year-old girl presented with fever and altered mental status. She had had a fever, cough, and rhinorrhea for five days. The patient was admitted to the intensive care unit with an initial diagnosis of encephalitis when vomiting, convulsions, and loss of consciousness developed. Signs of meningeal irritation were detected upon physical examination. There was a mild increase in proteins, but no cells, in the cerebrospinal fluid (CSF). Brain magnetic resonance imaging showed symmetrical, heterogeneous hyperintensities bilaterally in the caudate nuclei and putamen. Ammonium, lactate, tandem mass spectroscopy, and urine organic acid were normal. No bacteria were detected in the CSF cultures. Human bocavirus was detected in a nasopharyngeal aspirate using real-time PCR, while no influenza was detected. Oseltamivir, acyclovir, 3% hypertonic saline solution, and supportive care were used to treat the patient, who was discharged after two weeks. She began to walk and talk after one month of physical therapy and complete recovery was observed after six months. Human bocavirus is a recently identified virus that is mainly reported as a causative agent in respiratory tract infections. Here, we present a case of influenza-like acute necrotizing encephalopathy secondary to human bocavirus infection.

The human bocavirus (hBoV) has been identified in respiratory infections in children in a large number of studies. Despite this, the pathogenic role of the HBoV is under discussion. The main objectives of the study were: to determine the incidence of HBoV in hospitalized children; to describe the main clinical features of the positive children; and to compare the data with those from other viral infections in the same population. A prospective study was performed between 2005 and 2013 including children up to 14-year old with respiratory infection admitted to the Severo Ochoa Hospital (Spain). Nasopharyngeal aspirates were taken from 3,275 patients and were tested for HBoV and other 15 respiratory viruses by RT-nested PCR. HBoV was detected in 319 patients (9.9%); 80 cases as a single pathogen, and 239 cases (75%) as coinfections with other viruses. The HBoV was the fourth most common virus detected, behind respiratory syncytial virus (39.8%), rhinovirus (30.6%), and adenovirus (15%). The most common clinical diagnosis, in cases that HBoV was detected as a single pathogen was asthma exacerbation followed by pneumonia. A seasonal distribution was shown, with higher positivity rates in December and January. Children affected by HBoV were older than children infected by other viruses. Differences in terms of clinical diagnosis were found, bronchiolitis diagnosis was lower compared with the other viruses, and HBoV was associated with diagnosis of pneumonia, with increased use of antibiotics (41.8%), and radiographic infiltrates (47%). These findings could suggest a pathogenic role of HBoV in respiratory infections in children under 14 years of age. J. Med. Virol. 88:2052-2058, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA.)

Acute respiratory tract viral infections occur worldwide and are one of the major global burdens of diseases in children. The aim of this study was to determine the viral etiology of respiratory infections in hospitalized children, to understand the viral seasonality in a major Lebanese hospital, and to correlate disease severity and the presence of virus. Over a 1-year period, nasal and throat swabs were collected from 236 pediatric patients, aged 16-year old or less and hospitalized for acute respiratory illness. Samples collected were tested for the presence of 17 respiratory viruses using multiplex real-time RT-PCR. Pathogens were identified in 165 children (70%) and were frequently observed during fall and winter seasons. Co-infection was found in 37% of positive samples. The most frequently detected pathogens were human Rhinovirus (hRV, 23%), Respiratory Syncytial Virus (RSV, 19%), human Bocavirus (hBov, 15%), human Metapneumovirus (hMPV, 10%), and human Adenovirus (hAdV, 10%). A total of 48% of children were diagnosed with bronchiolitis and 25% with pneumonia. While bronchiolitis was often caused by RSV single virus infection and hAdV/hBoV coinfection, pneumonia was significantly associated with hBoV and HP1V1 infections. No significant correlation was observed between a single viral etiology infection and a specific clinical symptom. This study provides relevant facts on the circulatory pattern of respiratory viruses in Lebanon and the importance of using PCR as a useful tool for virus detection. Early diagnosis at the initial time of hospitalization may reduce the spread of the viruses in pediatric units. J. Med. Virol. 88:1874-1881, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Limited information is available on the non-influenza etiology and epidemiology of influenza-like illness (ILI) in China. From April 2011 to March 2014, we collected oropharyngeal swabs from children less than 5 years of age with symptoms of ILI who presented to the outpatient departments of Suzhou University Affiliated Children's Hospital (SCH). We used reverse transcription polymerase chain reaction (rt-PCR) or PCR to detect 11 respiratory viruses. Among 3,662 enrolled ILI patients, 1,292 (35.3%) tested positive for at least one virus. Influenza virus (16.9%) was detected most frequently (influenza A 7.4%, influenza B 9.5%), followed by respiratory syncytial virus (RSV) (5.6%), parainfluenza virus (PIV) types 1-4 (4.8%), human bocavirus (HBoV) (3.8%), human metapneumovirus (HMPV) (3.5%), and adenovirus (ADV) (3.0%). Co-infections were identified in 108 (2.9%) patients. Influenza virus predominantly circulated in January-March and June-July. The 2013-2014 winter peaks of RSV and influenza overlapped. Compared with other virus positive cases, influenza positive cases were more likely to present with febrile seizure, and RSV positive cases were more likely to present with cough and wheezing, and were most frequently diagnosed with pneumonia. These data provide a better understanding of the viral etiology of ILI among children less than 5 years of age in Suzhou, China. Influenza is not only the most frequently identified pathogen but it is also the only vaccine preventable illness among the 11 pathogens tested. Such findings suggest the potential value of exploring value of influenza vaccination among this influenza vaccination target group. J. Med. Virol. 88:1334-1340, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Human bocavirus (HBoV), a parvovirus, is a single-stranded DNA etiologic agent causing lower respiratory tract infections in young children worldwide. Nuclear factor kappa B (NF-κB) transcription factors play crucial roles in clearance of invading viruses through activation of many physiological processes. Previous investigation showed that HBoV infection could significantly upregulate the level of TNF-α which is a strong NF-κB stimulator. Here we investigated whether HBoV proteins modulate TNF-α-mediated activation of the NF-κB signaling pathway. We showed that HBoV NS1 and NS1-70 proteins blocked NF-κB activation in response to TNF-α. Overexpression of TNF receptor-associated factor 2 (TRAF2)-, IκB kinase alpha (IKKα)-, IκB kinase beta (IKKβ)-, constitutively active mutant of IKKβ (IKKβ SS/EE)-, or p65-induced NF-κB activation was inhibited by NS1 and NS1-70. Furthermore, NS1 and NS1-70 didn't interfere with TNF-α-mediated IκBα phosphorylation and degradation, nor p65 nuclear translocation. Coimmunoprecipitation assays confirmed the interaction of both NS1 and NS1-70 with p65. Of note, NS1 but not NS1-70 inhibited TNF-α-mediated p65 phosphorylation at ser536. Our findings together indicate that HBoV NS1 and NS1-70 inhibit NF-κB activation. This is the first time that HBoV has been shown to inhibit NF-κB activation, revealing a potential immune-evasion mechanism that is likely important for HBoV pathogenesis.

The human bocavirus (HBoV) was added as a new member of the Parvoviridae family in 2005 upon its discovery in nasopharyngeal aspirates from children with respiratory infection. Recently, there has been increasing evidence of worldwide circulation of HBoV; however, in Latin America few studies have been conducted. In order to detect the circulation of HBoV in Panama, based on the National Flu Surveillance System, we developed this retrospective, cross-sectional study, from January 2011 to January 2012. Children younger than 6 years old who presented with respiratory disease were enrolled in this study. Nasopharyngeal swabs were taken in sentinel surveillance sites. Samples were tested to detect mRNA from HBoV, as well as viral RNA and DNA from others respiratory viruses. A total of 1078 patients were enrolled in this study. Overall, 44 (4.1%) of the patients presented HBoV. The most common symptoms were cough (84.6%), fever (82.1%), rhinorrhea (74.4%), and sore throat (38.5%). Less than half (45.5%) of HBoV infected patients presented with monoinfection while 54.5% of cases presented with coinfection with others respiratory viruses. Both, outpatients and inpatients were included in this study. Outpatients corresponded to 52.3% of the cases and 47.7% were inpatients. Coinfection was observed in the 50% of the inpatient cases. Phylogenetic analyses indicated that the circulating strains belonged to different clades of HBoV genotype 1. Taken together, our results support the pathogenic nature of this viral agent, especially in younger children., (© 2015 Wiley Periodicals, Inc.)

Human bocavirus (HBoV), that was first identified in 2005 and classified in Parvoviridae family, is a small, non-enveloped, single-stranded DNA virus, responsible for upper and lower respiratory tract infections, especially in young children. Although HBoV generally causes self-limited influenza-like illness, it may also lead to pneumonia, bronchiolitis, croup and asthma attacks. In this report, a case of acute bronchiolitis complicated with pneumomediastinum and bilateral pneumothorax caused by HBoV has been presented. A three-year-old boy was referred to our pediatric intensive care unit with a two day history of fever, tachypnea, hypoxia and respiratory failure. On auscultation, there were widespread expiratory wheezing and inspiratory crackles. The chest radiography yielded paracardiac infiltration and air trapping on the right lung and infiltration on the left lung. The patient had leukocytosis and elevated C-reactive protein level. On the second day of admission, respiratory distress worsened and chest radiography revealed right pneumothorax and subcutaneous emphysema in bilateral cervical region and left chest wall. He was intubated because of respiratory failure. In the thorax computed tomography, pneumomediastinum and bilateral pneumothorax were detected and right chest tube was inserted. Repetitive blood and tracheal aspirate cultures were negative. A nasopharyngeal swab sample was analyzed by multiplex real-time polymerase chain reaction method with the use of viral respiratory panel (FTD(®) Respiratory Pathogens 21 Kit, Fast-Track Diagnostics), and positive result was detected for only HBoV. On the ninth day of admission, pneumomediastinum and bilateral pneumothorax improved completely and he was discharged with cure. In conclusion, HBoV bronchiolitis may progress rare but severe complications, it should be kept in mind as an etiological agent of the respiratory tract infections especially children younger than five years old.

Unlabelled: Human bocavirus 1 (HBoV1) is a single-stranded DNA parvovirus that causes lower respiratory tract infections in young children worldwide. In this study, we identified novel splice acceptor and donor sites, namely, A1' and D1', in the large nonstructural protein (NS1)-encoding region of the HBoV1 precursor mRNA. The novel small NS proteins (NS2, NS3, and NS4) were confirmed to be expressed following transfection of an HBoV1 infectious proviral plasmid and viral infection of polarized human airway epithelium cultured at an air-liquid interface (HAE-ALI). We constructed mutant pIHBoV1 infectious plasmids which harbor silent mutations (sm) smA1' and smD1' at the A1' and D1' splice sites, respectively. The mutant infectious plasmids maintained production of HBoV1 progeny virions at levels less than five times lower than that of the wild-type plasmid. Importantly, the smA1' mutant virus that does not express NS3 and NS4 replicated in HAE-ALI as effectively as the wild-type virus; however, the smD1' mutant virus that does not express NS2 and NS4 underwent an abortive infection in HAE-ALI. Thus, our study identified three novel NS proteins, NS2, NS3, and NS4, and suggests an important function of the NS2 protein in HBoV1 replication in HAE-ALI., Importance: Human bocavirus 1 infection causes respiratory diseases, including acute wheezing in infants, of which life-threatening cases have been reported. In vitro, human bocavirus 1 infects polarized human bronchial airway epithelium cultured at an air-liquid interface that mimics the environment of human lower respiratory airways. Viral nonstructural proteins are often important for virus replication and pathogenesis in infected tissues or cells. In this report, we identified three new nonstructural proteins of human bocavirus 1 that are expressed during infection of polarized human bronchial airway epithelium. Among them, we proved that one nonstructural protein is critical to the replication of the virus in polarized human bronchial airway epithelium. The creation of nonreplicating infectious HBoV1 mutants may have particular utility in vaccine development for this virus., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Human bocavirus (HBoV) 1-4 have been detected both in respiratory and stool samples since the first HBoV was discovered in 2005. HBoV-1 is mostly associated with respiratory infection, while HBoV 2-4 are usually associated with intestinal tract infection. A variety of signs and symptoms have been described in patients with HBoV infection, including cough, wheezing, pneumonia, and diarrhea, but the research on pathogenic mechanism of HBoV is limited because HBoV cannot be cultured in vitro due to the lack of appropriate host cells. Three-dimensional epithelial cell culture, reverse genetics, and viral metagenomics are identified as novel tools that may promote the research on pathogenic mechanism of HBoV and the discovery of new viruses. This review summaries currently available diagnostic approaches such as electron microscopy, cell culture, PCR, and immunoassay in order to provide a method reference for indepth research on HBoV.

Asthma is a multifactorial disease in which many factors play a role in its development and exacerbations. Viral infections are known to be the main cause of asthmatic exacerbations and are often the first manifestation of asthma in preschool age. However, there is much evidence suggesting a role of viral infections even in asthma development. Respiratory Syncytial Virus (RSV). has been first associated with an increased risk to develop asthma, but recently new viruses have been proposed to be involved in asthma pathogenesis. Further studies will be needed to demonstrate a causative role of viral infections in asthma development, in order to implement preventive strategies in high-risk children.

Background: Acute respiratory tract infections (ARTIs) are one of the major causes of morbidity and mortality among young children in developing countries. Information on the incidence of human metapneumovirus (hMPV) and human bocavirus (HBoV) infections in developing countries, especially among rural children, is very limited., Objectives: This study was conducted to identify whether these viruses were associated with ARTI among children ≤5 years of age in rural and peri-urban populations in South India., Methods: The study was cross-sectional with prospective sample collection. Oropharyngeal swabs were collected from children ≤5 years of age presenting with ARTI. None of the children in this study were known to have any immunosuppressive conditions. The two viruses, hMPV and HBoV, were identified using semi-nested polymerase chain reaction (PCR) assays and one-step PCR assays, respectively. The lower limits of detection of hMPV and HBoV were 6.69 × 10(5) plasmid copies and 5.77 × 10(3) plasmid copies, respectively, per 5 μL PCR reaction input., Results: The frequency of hMPV infection in children was higher than that of HBoV infection. The different frequencies of hMPV in patients in various age groups with upper and lower respiratory tract infections were compared, and the variance was found to be insignificant. In the 38 children who were hMPV positive, the majority (73.7%) were from rural communities. The overall hMPV-positive rate was higher in the rural population than in the peri-urban population, but the difference was statistically insignificant. The youngest age at which hMPV-positive status was recorded was 5 months., Conclusion: This study demonstrated that hMPV was associated with a significant number (i.e. >10%) of ARTIs in children in South India, whereas a relatively smaller number of HBoV infections was observed.

To investigate the prevalence of HBoV2 in pediatric patients with acute diarrhea in Beijing and the characteristic of the genome of the virus, 553 stool specimens were collected from pediatric outpatients with acute diarrhea in Affiliated Children's Hospital of Capital Institute of Pediatrics during Nov. 2010 to Oct. 2011. TaqMan-based Real-time polymerase chain reaction was performed to detect HBoV2 DNA from these specimens. Two positive specimens with high viral loads were selected for segmented amplification and then the amplified fragments were cloned into the plasmid vector pGEM-T, transformed into Escherichia coli DH5alpha and sequenced. Then genomic sequences assembled from those DNA fragments were compared with other parvovirus genomic sequences in the GenBank. Among these 553 specimens tested, 15 (2.7%) were HBoV2 DNA positive. The highest positive rate was shown in July (7.0%) through the whole year and in 3-6 month age group (4.1%) among different age groups. All these 15 specimens positive for HBoV2 DNA were collected from patients younger than 2 years old, including 4 simultaneously positive for norovirus, 3 positive for rotavirus and 1 positive for adenovirus. By sequence analysis, 2 almost complete HBoV2 genomic sequences assembled from gene fragments amplified from specimens BJQ19 and BJQ390 were typical HBoV2. And they shared high homology with each other (99.2%), while they shared the highest homology with FJ375129 from Shanghai China (99.1% and 99.2%) among other parvoviruses. These data suggest that some of acute diarrhea in pediatric patients in Beijing were associated with HBoV2, and infants and young children aged from 3 months to 2 years, are more likely to be infected by HBoV2.

Human bocavirus (HBoV) is a newly identified human parvovirus that associated with respiratory and gastrointestinal diseases. Epidemiological surveillance of HBoV was conducted on fecal specimens collected from hospitalized children with diarrhea in Chiang Mai, Thailand in 2011. Among a total of 222 fecal specimens tested, 17 (7.7%) were positive for HBoV by PCR. Of the 17 HBoV positive samples, double- or triple-infections together with other enteric viruses were found in 10 (58.8%) pediatric patients, while monoinfection with HBoV alone was detected in seven (41.2%) cases. Mixed infection among HBoV with norovirus GII was frequently observed in this population. The partial VP1 nucleotide sequences of all 17 HBoV strains demonstrated that all four species of HBoV were found in the specimens tested. Eleven strains were HBoV1. Other three strains showed the sequence identity with HBoV2, which were most closely related to the HBoV2A. In addition, other two HBoV strains showed the highest level of nucleotide sequence identity with the HBoV3. It was surprisingly to observe that one Thai HBoV strain showed a unique characteristic similar to the HBoV4, a rare species of HBoV found in acute gastroenteritis patients. In summary, this study presents the genetic background information of HBoV circulated in acute gastroenteritis children in Chiang Mai, Thailand and it was clearly demonstrated that HBoVs circulated in this area were genetically diverse as all four species of HBoVs (HBoV1-4) were detected in the fecal specimens collected from pediatric patients admitted to the hospitals in this area., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A serological survey was performed to determine the prevalence of antibodies against human bocavirus in an Apulian population. Anti-hBoV IgG antibodies were analysed in 1206 inhabitants (age range, 1month-84years) using a standardized ELISA test based on the use of recombinant hBoV VP2 virus-like particles. In total, 1075 (89.1%) of 1206 participants (mean age 32±24.8years) displayed anti-hBoV-IgG. The seroprevalence increased significantly (p<0.0001) in children from 2-4years (64.2%) to 5-9years (96.4%). A similar trend was observed in both male and female subjects. In conclusion, our results show that hBoV infection is common in this population, especially in children., (© 2011 University of Salento. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.)

Four species of human bocavirus (HBoV) have been recently discovered and classified in the Bocavirus genus (family Parvoviridae, subfamily Parvovirinae). Although detected both in respiratory and stool samples worldwide, HBoV1 is predominantly a respiratory pathogen, whereas HBoV2, HBoV3, and HBoV4 have been found mainly in stool. A variety of signs and symptoms have been described in patients with HBoV infection including rhinitis, pharyngitis, cough, dyspnea, wheezing, pneumonia, acute otitis media, fever, nausea, vomiting, and diarrhea. Many of these potential manifestations have not been systematically explored, and they have been questioned because of high HBoV co-infection rates in symptomatic subjects and high HBoV detection rates in asymptomatic subjects. However, evidence is mounting to show that HBoV1 is an important cause of lower respiratory tract illness. The best currently available diagnostic approaches are quantitative PCR and serology. This concise review summarizes the current clinical knowledge on HBoV species., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: Human bocavirus (HBoV) is a newly identified human parvovirus. HBoV is associated with upper and lower respiratory tract infections and gastroenteritis in children. Little is known about the seroepidemiology of HBoV in populations in the Caribbean., Methods: In a cross-sectional study conducted at the University Hospital of the West Indies in Kingston, Jamaica, 287 blood samples were collected from pediatric patients and tested for the presence of HBoV-specific antibody using a virus-like-particle based enzyme-linked immunosorbent assay (ELISA)., Results: HBoV-specific antibodies were found to be present in 220/287 (76.7%) of samples collected from the pediatric population. Seroprevalence of HBoV was highest in those ≥2 years old. The seroepidemiological profile suggests that most children are exposed to HBoV during the first two years of life in Jamaica., Conclusion: HBoV infection is common in children in Jamaica. HBoV seroprevalence rates in the Caribbean are similar to those previously reported in other areas of the world.

Human bocavirus (HBoV), discovered in 2005, can cause respiratory disease or no symptoms at all. We confirmed HBoV infection in an 8-month-old girl with hypoxia, respiratory distress, wheezing, cough, and fever. This case demonstrates that lower respiratory tract infection caused by HBoV can lead to severe and life-threatening disease.

Background: Acute gastroenteritis (AGE) is one of the leading causes of death in children worldwide. Human bocavirus 2 (HBoV2) was recently identified in stool samples and is involved in the pathogenesis of AGE, but the current data were too limited to clarify this issue., Objective: We conducted a case-control study on 632 children with diarrhea and 162 healthy controls in Lanzhou, China, to assess the role of HBoV2 in gastroenteritis., Study Design: Viruses known or suspected to be agents of AGE, including RV, HucV, AdV, AstV, and HBoVs, were detected. Viral loads of HBoV2 were quantified by Real-time PCR., Results: HBoV2 was detected in 129 (20.4%) and 20 (12.3%) of the gastroenteritis and control samples, respectively. The association between HBoV2 and gastroenteritis was weaker (OR = 1.269, CI= 0.704-2.288) than that between gastroenteritis and RV, HucV, AdV, or AstV, as determined by multivariate logistic regression analysis. The data also suggested that infection with HBoV2 did not exacerbate the clinical symptoms of gastroenteritis. Mean HBoV2 viral load in the case and control groups was fewer than 55 copies/ml extract., Conclusions: HBoV2 exhibit different epidemiological features from HBoV1 and HBoV3. The data presented herein do not support a causative role for HBoV2 in AGE, despite its high prevalence in stool samples., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The efficacy of prednisolone in acute wheezing associated with human bocavirus infection was investigated in 232 hospitalized children (median age, 1.6 years). Clinical history, atopy status, and viral etiology were carefully studied. Outcomes included hospitalization time, duration of symptoms, and occurrence of relapses. No efficacy of prednisolone was found in children with serologically confirmed acute human bocavirus infection.

Respiratory tract infections are a leading cause of morbidity and mortality worldwide. The human bocavirus (HBoV) is a newly recognized human parvovirus first reported in 2005. Since its discovery, this virus has been associated with upper and lower respiratory tract disease and gastroenteritis worldwide. This article is a comprehensive review of what is known about HBoV. It includes an evaluation of diagnostic modalities, symptoms occurring in affected patients, and a discussion as to whether HBoV is responsible for identified clinical manifestations. The article reviews the incidence and effect of coinfection and updates on related members (HBoV-2 and HBoV-3) recently reported. Understanding of respiratory viruses such as HBoV remains vitally important to the health of adult and pediatric patients.

Objective: The impact of human bocavirus (HBoV), a newly identified human parvovirus, on childhood persistent wheezing has not been identified. In this study, the clinical features of infantile persistent wheezing induced by HBoV was analyzed., Methods: Tracheal aspirates were collected by bronchofibroscope or nasopharyngeal (NP) aspirates from April, 2006 to January, 2007. HBoV DNA in the tracheal aspirates of 33 children with persistent wheezing and in NP aspirates of 6 children with persistent wheezing, who had at least or more than four weeks wheezing. RSV was identified by virus isolation in Hep-2 cells and antigen detetion by direct immunofluorescence assay (DIFA) which was also used for diagnosis of adenovirus, influenza A and B, parainfluenza 1, 2, 3 infection., Results: Of the 39 children with persistent wheezing, 12 cases (31%) were positive for HBoV DNA. Age of HBoV-positive patients ranged from 2 month to 1 year. The results of sequencing of PCR products proved that sequences of HBoV DNA from these 12 samples were exactly identical to the those of HBoV stored in GeneBank (accession numbers DQ000495 and DQ000496). Two cases with HBoV infection were found to be co-infected with RSV. Ten of the 12 HBoV-positive samples were collected during the period from winter to spring (1 in November, 4 in December, 2 in January and 3 in April), the other two HBoV-positive samples were collected during the period from summer to autumn (1 in May and the other in July). Seven of the 12 HBoV DNA-positive patients had fever, 5 of them had high fever. Significantly more patients with HBoV infection had fever as compared to patients with RSV infection. All the HBoV positive patients showed abnormal findings on chest X ray such as interstitial infiltrates, lung infiltration and hyperinflation. Abnormal findings on chest X ray were found in higher proportion of HBoV positive patients as compared with RSV positive patients. And other manifestations such as wheezing, cough and respiratory distress had no significant difference between HBoV and RSV infected patients., Conclusions: This study further demonstrated that HBoV probably is a common pathogen of lower respiratory infection in children and might particularly be associated with persistent wheezing.