Human Bocavirus Infection In Children Research Articles

Clinical Course and Molecular Characterization of Human Bocavirus Associated with Acute Lower Respiratory Tract Infections in a Tertiary Care Hospital in Northern India.

Respiratory samples from 139 hospitalized children were screened for the human bocavirus (HBoV) genome. Positive samples were sequenced for the partial VP1/VP2 gene followed by molecular and phylogenetic analyses. HBoV positivity was noted in 7.2% (10/139) of patients. All HBoV-positive children presented with fever, cough, and respiratory distress (90%, 9/10). Three children developed multisystemic viral illness, with one fatality. Eight children required intensive care management and five required mechanical ventilation. The nucleotide percent identity of the partial VP1/VP2 gene in the HBoV study strains ranged from 97.52% to 99.67%. Non-synonymous mutations in the VP1 protein were T591S (n = 8) and Y517S (n = 1) in the HBoV St1 strain and N475S (n = 8) and S591T (n = 2) in the HBoV St2 strain. One strain showed A556P, H556P, I561S, and M562R non-synonymous mutations. All the study strains belonged to the HBoV1 type. Seven HBoV strains belonged to the same lineage, and three belonged to another lineage. For evolutionary dynamics, GTR+I substitution model with uncorrelated relaxed lognormal clock and Bayesian Skyline tree prior showed 9.0 × 10-4 (95% highest probability density interval: 3.1 × 10-6, 2.1 × 10-3) nucleotide substitutions per site per year. Clinical suspicion and virological screening are necessary to identify HBoV infections in children.

Research progress of human bocavirus infection in children

Human bocavirus is a novel pathogen first detected in respiratory tract samples in 2005. People of different ages can be infected by human bocavirus. Children are the susceptible population, especially the infants aged from 6-24 months old. The epidemic season varies in different regions due to the differences in climate and geographical location, and it mainly occurs in autumn and winter. It's demonstrated that human bocavirus-1 is closely related to respiratory system diseases and even causes life-threatening critical illness. Also, the severity of symptom is positively correlated with viral load. Co-infections between human bocavirus-1 and other viruses often present high frequency occurrence. Human bocavirus-1 interferes immune function of host by inhibiting interferon secrete pathway. Currently, it remains limited knowledge and understanding of the roles of human bocavirus 2-4 in diseases, but the gastrointestinal diseases should be paid more attention. Detection of human bocavirus DNA by traditional polymerase chain reaction (PCR) assay shouldn't be regarded as conclusive diagnostic basis. Instead, combined with mRNA and specific antigen detection, it is beneficial to improve the accuracy of diagnosis. Till now, the knowledge of human bocavirus remains poorly studied, which is deserved to further progress.

Epidemiologic and Clinical Characteristics of Human Bocavirus Infection in Children with or without Acute Gastroenteritis in Acre, Northern Brazil.

Human bocavirus (HBoV) is an emerging virus detected around the world that may be associated with cases of acute gastroenteritis (AGE). However, its contribution to AGE has not been elucidated. This study aimed to describe the frequency, clinical features, and HBoV species circulation in children up to 5 years with or without AGE symptoms in Acre, Northern Brazil. A total of 480 stool samples were collected between January and December 2012. Fecal samples were used for extraction, nested PCR amplification, and sequencing for genotyping. Statistical analysis was applied to verify the association between epidemiological and clinical characteristics. Overall, HBoV-positivity was 10% (48/480), with HBoV-positive rates of 8.4% (19/226) and 11.4% (29/254) recorded in diarrheic and non-diarrheic children, respectively. The most affected children were in the age group ranging between 7 and 24 months (50%). HBoV infection was more frequent in children who live in urban areas (85.4%), use water from public networks (56.2%), and live with adequate sewage facilities (50%). Co-detection with other enteric viruses was 16.7% (8/48) and the most prevalent coinfection was RVA+ HBoV (50%, 4/8). HBoV-1 was the most frequent species detected in diarrheic and non-diarrheic children, responsible for 43.8% (21/48) of cases, followed by HBoV-3 (29.2%, 14/48) and HBoV-2 (25%, 12/48). In this study, HBoV infection was not always associated with AGE, as most HBoV cases belonged to the non-diarrheal group. Future studies are warranted in order to determine the role of HBoV in causing acute diarrhea disease.

Epidemiologic and clinical characteristics of human bocavirus infection in children hospitalized for acute respiratory tract infection in Qingdao, China.

Persistent infection and prolonged shedding of human bocavirus 1 (HBoV1) in children have been reported, and the role of HBoV1 as a sole causative pathogen in acute respiratory infection (ARI) is yet to be established. While the reported prevalence of HBoV infection varies due to different detection methods and sampling criteria, determining the viral and bacterial etiology of HBoV infection using multiplex real-time PCR is yet to be reported. Herein, we aimed to further explore the pathogenicity of HBoV in patients with ARI by screening the viral and bacterial infections in children with ARI in Qingdao and comparing the epidemiological, clinical characteristics, and etiological results. Human bocavirus was identified in 28.1% of the samples, and further sequencing analysis of the detected HBoV confirmed 96.4% as HBoV1. The rate of HBoV as a single viral infection was 75%, and the rate of coinfection with bacteria was 66.1%, suggesting the need for continued monitoring of HBoV in children with ARIs. Clinical characterization suggested that HBoV infection may affect the function of organs, such as the liver, kidney, and heart, and the blood acid–base balance. Additionally, it is essential to promote awareness about the importance of disinfection and sterilization of the hospital environment and standardizing operations. The interactions between HBoV and other pathogens remain to be investigated in further detail in the future.

Human bocavirus infection in children hospitalized with lower respiratory tract infections: Does viral load affect disease course?

Human bocavirus infection in children hospitalized with lower respiratory tract infections: Does viral load affect disease course?

Predominance of Human Bocavirus Genotype 1 and 3 in Outpatient Children with Diarrhea from Rural Communities in South Africa, 2017-2018.

Human bocavirus (HBoV) is an emerging virus globally associated with diarrhea in young children. This study aims to investigate the prevalence of HBoV genotypes in children (≤5 years) from rural communities in South Africa (SA) suffering from acute gastroenteritis (AGE). A total of 141 fecal samples of children ≤5 years with acute gastroenteritis (AGE) were collected from rural primary health care facilities in the Vhembe district of SA between June 2017 and July 2018. Clinical symptoms and demographic data were also recorded. A total of 102 (72%) were outpatients, and 39 (28%) were hospitalized patients. Human bocavirus (HBoV) genotypes were determined using real-time multiplex PCR. DNA extracts of positive samples were confirmed by conventional PCR targeting the NS1 gene. Co-infection with other enteric viruses were determined in HBoV-positive samples using real-time PCR. HBoV was detected in eight (5.7%) children with AGE, of which three (37.5%) were HBoV1, three (37.5%) were HBoV3, and two (25%) were HBoV2. The majority of positive cases were identified in outpatients (62%) between the ages of 1 and 24 months. Co-infection in HBoV-positive samples with other enteric viruses included rotavirus (37.5%), adenovirus (37.5%), norovirus (25%), and astrovirus (12.5%). HBoV infections could be seen as a potential emerging diarrheal pathogen in South Africa. However, more studies are needed to understand the role of HBoV infections in children with AGE.

Detection of Human Bocavirus Infection in Children with Lower Respiratory

Detection of Human Bocavirus Infection in Children with Lower Respiratory

Clinical analysis of human bocavirus infection in children with severe lower respiratory tract infection

Objective To explore the clinical characteristics of human bocavirus(HBoV) infection in the children with severe lower respiratory tract infection. Methods The clinical data of the hospitalized children with sputum HBoV-positive were analyzed retrospectively, who were hospitalized at the Pediatric Intensive Care Unit of Children′s Hospital Affiliated to Capital Institute of Pediatrics from September 1, 2016 to March 31, 2017. Results A total of 17 children were included in the study.The ratio of male to female was 152.The diagnostic age ranged from 4 months to 4 years and 10 months old.82.4%(14/17 cases) of the patients were infants less than 2 years old.Autumn and winter were high-occurrence seasons.Pediatric Critical Illness Scores(PCIS) were 68-88 scores(median 82 scores). PCIS was less than 70 scores in 1 case, and between 70 scores and 80 scores in 7 cases, and more than 80 scores in 9 cases.The main clinical manifestations were respiratory system involvement, including dyspnea in 17 cases (100%), fever in 14 cases (82.4%), cough in 16 cases(94.1%), wheezing in 13 cases (76.5%), and moist rales in 13 cases (76.5%). The main abnormal chest radiological findings showed patchy shadows in 7 cases (41.2%) and consolidation in 6 cases (35.3%). The oxygenation index was 73.9-296.0 mmHg(1 mmHg=0.133 kPa), and median was 176 mmHg. The oxygenation index was between 100-200 mmHg in 7 cases(41.2%), and less than 100 mmHg in 2 cases(11.7%). Type Ⅰ respiratory failure occurred in 11 cases (64.7%), while type Ⅱ respiratory failure occurred in 6 cases (35.3%). All of the patients need respiratory support with mechanical ventilation.Among them, 6 patients (35.3%) were treated by non-invasive ventilation and their ventilation time were 25-128 h(median 65 h), while 11 patients (64.7%) were treated by invasive ventilation and their ventilation time was 42-178 h(median 70 h). Other organ or system dysfunction is mild.The length of hospital stay ranged from 3 days to 13 days.The cure rate was 100%. Conclusions HBoV infection in the children with severe lower respiratory tract infection is common in infants under 2 years old, with acute onset and rapid recovery.The obvious clinical symptoms are fever, cough, wheezing and dyspnea.Although respiratory failure is common, other organ or system dysfunction is mild, which may bring about a good prognosis. Key words: Child; Human bocavirus; Severe; Lower respiratory tract infection

Risk of acute gastroenteritis associated with human bocavirus infection in children: A systematic review and meta-analysis.

Human bocaviruses (HBoVs), which were first identified in 2005 and are composed of genotypes 1–4, have been increasingly detected worldwide in pediatric patients with acute gastroenteritis. To investigate if HBoV infection is a risk factor of acute gastroenteritis in children younger than 5 years old, we searched PubMed, Embase (via Ovid), the Chinese Biomedical Literature Database (CBM), and the Cochrane Library for studies assessing the prevalence of HBoVs in individuals from Oct 25, 2005 to Oct 31, 2016. We included studies using PCR-based diagnostics for HBoVs from stool specimens of patients with or without acute gastroenteritis that carried out research for over 1 year on pediatric patients aged younger than 5 years old. The primary outcome was the HBoV prevalence among all cases with acute gastroenteritis. Pooled estimates of the HBoV prevalence were then generated by fitting linear mixed effect meta-regression models. Of the 36 studies included, the pooled HBoV prevalence in 20,591 patients with acute gastroenteritis was 6.90% (95% confidence interval (95% CI): 5.80–8.10%). In the ten studies with a control group, HBoVs were detected in 12.40% of the 3,620 cases with acute gastroenteritis and in 12.22% of the 2,030 control children (odds ratio (OR): 1.44; 95% CI: 0.95–2.19, p = 0.09 between case and control groups). HBoV1 and HBoV2 were detected in 3.49% and 8.59% of acute gastroenteritis cases, respectively, and in 2.22% and 5.09% of control children, respectively (OR: 1.40; 95% CI: 0.61–3.25; p = 0.43 and OR: 1.68; 95% CI: 1.21–2.32; p = 0.002, respectively). Current evidence suggests that the overall HBoV prevalence in children younger than 5 years old is not significantly different between groups with or without acute gastroenteritis. However, when HBoV1 was excluded, the HBoV2 prevalence was significantly different between these two groups, which may imply that HBoV2 is a risk factor of acute gastroenteritis in children younger than 5 years old.

Atypical presentation of human bocavirus: Severe respiratory tract infection complicated with encephalopathy.

Human bocavirus (HBOV) has been reported as a worldwide distributed respiratory pathogen. It has also been associated with encephalitis recently by detection of the virus in cerebrospinal fluid (CSF) of patients presented with encephalitis. This retrospective study aimed to present clinical features of HBOV infections in children with respiratory symptoms and describe unexplained encephalopathy in a subgroup of these patients. Results of 1,143 pediatric nasal samples from mid‐December 2013 to July 2014 were reviewed for detection of HBOV. A multiplex real time polymerase chain reaction assay was used for viral detection. Medical records of the patients were retrospectively analyzed. HBOV was detected in 30 patients (2.6%). Median age was 14 months (5–80). Clinical diagnoses were upper respiratory tract infection (n = 10), bronchopneumonia (n = 9), acute bronchiolitis (n = 5), pneumonia (n = 4), acute bronchitis (n = 1), and asthma execarbation (n = 1). Hospitalization was required in 16 (53.3%) patients and 10 (62.5%) of them admitted to pediatric intensive care unit (PICU). Noninvasive mechanical ventilation modalities was applied to four patients and mechanical ventilation to four patients. Intractable seizures developed in four patients while mechanically ventilated on the 2nd–3rd days of PICU admission. No specific reason for encephalopathy was found after a thorough investigation. No mortality was observed, but two patients were discharged with neurological sequela. HBOV may lead to respiratory infections in a wide spectrum of severity. This report indicates its potential to cause severe respiratory infections requiring PICU admission and highlights possible clinical association of HBOV and encephalopathy, which developed during severe respiratory infection. J. Med. Virol. 87:1831–1838, 2015. © 2015 Wiley Periodicals, Inc.

Human Bocavirus Infection in Children with Acute Respiratory Infection in Nairobi, Kenya

Background: Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children under five years of age in developing countries with viruses contributing significantly to this problem. The recently identified parvovirus, Human Bocavirus (HBoV), has also been associated with ARI. Objective: To determine the frequency of HBoV in patients with ARI. Materials and Methods: Samples from 125 consenting patients with influenza like illness signs and symptoms were collected. DNA was extracted from these samples using the QIAamp DNA blood mini kit (Qiagen, Germany). Conventional PCR was carried out and the amplicons were examined in 2% agarose gels stained with ethidium bromide. This was followed by sequencing of the HBoV positive samples. Results: Twenty one (16.8%) patients were found to have HBoV infection. Males (n = 61.9%) were mainly infected with HBoV. Local HBoV strains had 98.9% - 100% similarities and were found to cluster together with other strains obtained elsewhere. Conclusion: These findings suggest that HBoV plays a role in respiratory tract infections in children in Kenya just like it has been found elsewhere. It also sheds light on multiple infections associated with HBoV infections in Kenya.

Human bocavirus infection in children with acute gastroenteritis in Japan and Thailand

A total of 329 fecal specimens, which had been known to be negative for rotavirus, adenovirus, norovirus, sapovirus, and astrovirus, and which were collected from infants and children with acute gastroenteritis in Japan and Thailand during 2005-2008 were screened for human bocavirus (HBoV). HBoV was detected by PCR with a primer pair that amplified the NP1 region of its genome and was genotyped by sequencing of the VP1/VP2 region. Of the 329 samples tested, 6 (1.8%) were positive for HBoV. Of these, five samples were collected from Japan and one sample was from Thailand, and the detection rates of HBoV in each country were 2% and 1.2%, respectively. For the detected HBoV, the capsid VP1/VP2 gene of all HBoV strains was successfully sequenced. Four Japanese HBoV strains studied were clustered into group 1, while the remaining Japanese strain and a unique Thai strain belonged to group 2. No severe acute gastroenteritis associated with HBoV was noted. This study provides better understanding on the epidemiology of HBoV infections in children with acute gastroenteritis in Japan and Thailand.

Prevalence and clinical aspects of human bocavirus infection in children

Human bocavirus (HBoV) was recently described as a new member of the Parvoviridae. In order to investigate the suggested association of HBoV with respiratory and gastric disease in infants and young children, sera of 357 paediatric patients hospitalized with infectious and non-infectious diseases were retrospectively analyzed for the presence of HBoV DNA and virus-specific antibodies using quantitative PCR and ELISA, respectively. HBoV seroprevalence was determined to range from 25% in infants younger than 1 year of age to 93% in children aged more than 3 years. Viral loads between 1 × 102 1.2 × 106 geq/mL were observed in 6.7% (20/297) of sera obtained preferentially from young children suffering from infectious diseases. HBoV genomes were furthermore detected in 5% (3/60) of sera collected from individuals with non-infectious illnesses. HBoV DNA was present most frequently in patients with respiratory disease (9.6%). Whereas only 5.2% of patients with upper respiratory tract disease were viraemic, HBoV DNA was found in 14.6% and 10.0% of patients with lower respiratory tract illness and pneumonia, respectively. Acute HBoV infections were also observed in 7.5% of patients with gastroenteritis and in one child with inflammatory bowel disease. None of 77 patients hospitalized for various other infectious diseases (e.g. rash, urinary tract infection, meningitis) displayed viraemia. In 60.9% and 47.8% of DNA–positive children, HBoV-specific IgM and IgG was observed, respectively. The present prospective study provides comprehensive data on the clinical association of acute HBoV infection with respiratory illness and on the seroprevalence of virus-specific antibodies in children.

Serologic Diagnosis of Human Bocavirus Infection in Children

To the Editors: Blessing et al published recently in the journal their interesting findings on prolonged human bocavirus (hBoV) DNA shedding by repeated nasopharyngeal aspirates (NPA) in 6 children.1 The interval between the samples varied from 29 to 142 days. In the latter case, the prolonged shedding was documented by 6 samples taken on days 0, 25, 53, 78, 135, and 142.1 The authors concluded that, in contrast to most other respiratory viruses, hBoV DNA detection in a single NPA sample is not sufficient to implicate hBoV as the causative agent of acute respiratory tract disease. The authors proposed that serologic assays, detection of hBoV viremia or high viral loads in NPA samples may be more useful approaches. We have recently introduced new IgM and IgG enzyme immunoassays (EIAs) for the diagnosis of acute respiratory tract hBoV infection.2 In 48 wheezing children with hBoV infection diagnosed by EIA in paired sera, 45 (94%) had viremia and 35 (73%) had hBoV in NPA by polymerase chain reaction (PCR). The EIA test was diagnostic in 27/28 (96%) of those with a high load hBoV DNA in NPA, and in 45/49 (92%) of those with hBoV DNA in serum. The respective figure in those with a low load of hBoV in NPA was 38%. About 12 children had a single hBoV infection, though an extensive test panel, including PCR, culture, antigen detection, and antibody assays, was in use for other viruses.2 In 101 children with pneumonia, serologic evidence of acute hBoV infection was found in 12 (12%) by EIA.3 Significant increases in IgG antibodies were seen in 7 cases, IgM antibodies were seen in 11 cases, and both IgG and IgM findings were documented in 6 cases. In IgG positive cases, the increases in IgG antibodies between paired sera varied from 9- to >100-fold. Thus, our findings by antibody assays verify the notion of Blessing et al, as well as other recent findings4 that hBoV is a true pathogen in respiratory tract infections in children. Qualitative PCR in NPA alone is not sufficient for a reliable hBoV diagnosis. Our results highlight the role of antibody assays. Matti Korppi, MD, PhD Pediatric Research Center University Hospital, Tampere University Tampere, Finland Tuomas Jartti, MD, PhD Department of Pediatrics University Central Hospital Turku University Turku, Finland Klaus Hedman, MD, PhD Department of Virology Maria Söderlund-Venermo, PhD Department of Virology Helsinki University Central Hospital Laboratory Division Helsinki, Finland

Human bocavirus infection in children with acute respiratory tract infection in India

Human bocavirus (HBoV) is a new human parvovirus identified in children with respiratory tract disease. Nasopharyngeal aspirates were collected from 305 children <5 years of age with acute respiratory tract infection from April 2005 to March 2007 and screened for the presence of HBoV by two separate sets of a polymerase chain reaction (PCR) described previously. Twenty-two (7.2%) children who had acute respiratory infection were found to be positive for HBoV by both sets of PCR. The main clinical symptoms were cough (95%), runny nose (64%), and fever (59%). In two samples, HBoV was identified together with respiratory syncytial virus in one sample and influenza A virus in another. HBoV appeared to have no seasonal distribution and is associated with both upper and lower respiratory tract disease in young children in India.

Human bocavirus infection in children with respiratory tract disease

Human bocavirus infection in children with respiratory tract disease

Human Bocavirus Infection in Children with Acute Gastroenteritis and Healthy Controls

Human bocavirus (HBoV) is a novel virus which can cause respiratory tract disease in infants and children. Recently, the prevalence of this virus was studied worldwide not only in the respiratory tract, but also in the gastrointestinal tract. The results of this study focusing on the HBoV detection in stool samples showed that HBoV could only be found in the stool of children with acute gastroenteritis (0.9%), not in the healthy control samples. Moreover, the complete coding sequences of these HBoV also showed very conserved sequences.

Human Bocavirus Infection in Children With Respiratory Tract Disease

Human bocavirus (HBoV) is a ubiquitous, newly described member of the Parvoviridae family frequently detected in the respiratory tract of children, but only few reports provide data proving the link between HBoV and respiratory tract disease (RTD). To evaluate the incidence of HBoV infection in children with RTD; to analyze the clinical features of HBoV infection; and to clinically compare HBoV, respiratory syncytial virus (RSV), and human metapneumovirus (HMPV) infections. A prospective 1-year study was conducted in children <5 years of age hospitalized with RTD and in asymptomatic control children. Human bocavirus was detected in 55 (10.8%) of the 507 children tested and in none of the 68 asymptomatic control children (P = 0.01). About 80% of these infections occurred between November and March. Coinfection with another virus was observed in 22 (40%) of the HBoV-positive children. HBoV viral load was significantly higher in samples from children with HBoV monoinfection than in those with coinfection. Subsequent detection of HBoV more than 2 months after the initial detection could be documented in 3 children. Clinical features associated with HBoV infection were similar to those observed with either RSV or HMPV infections, but HBoV infections were less severe than RSV infections. The difference observed in HBoV prevalence between children with RTD and controls provides support for a role of this virus in RTD. The frequent associations of HBoV with other respiratory viruses might be explained by the persistence of HBoV in the respiratory tract. The significance of HBoV viral load in nasopharyngeal secretions as a marker of pathogenicity merits further investigation.

Human bocavirus infection in children hospitalized with acute gastroenteritis in China

Background Human bocavirus (HBoV) was first identified in children with acute respiratory-tract infections, but recent studies have revealed that HBoV is also frequently detected in fecal specimens from children with gastroenteritis. Objectives To investigate the prevalence of HBoV in children hospitalized with gastroenteritis in different areas of China. Study design Employing ELISA, RT-PCR or PCR, we evaluated 1216 fecal samples for common diarrheal agents from children aged less than 5-year-old hospitalized with acute gastroenteritis. MEGA software was used to construct phylogenetic trees of the VP1/VP2 partial sequences of the HBoV genome. Results There were 67 HBoV-positive specimens, 52 (77.6%) were co-infected with rotavirus, norovirus, astrovirus, or enteric adenovirus. Statistical analysis of the clinical data indicated that children infected with both rotavirus and bocavirus did not have more severe clinical symptoms than children infected with rotavirus. The phylogenetic analysis of the VP1/VP2 partial sequences of the HBoV genome revealed a single genetic lineage. Conclusions Despite its high infection rate, there was no statistically significant a causual relationship between HBoV and gastroenteritis in children.

Steps towards Serological Diagnosis of Human Bocavirus Infections

The study by Kantola et al. [1] in the current issue of Clinical Infectious Diseases represents an important advance in the development of diagnostic assays for the newly discovered, potentially major respiratory pathogen human bocavirus (HBoV). It also provides a series of new insights into the nature and epidemiology of HBoV infection in children, its systemic spread, and the relationship between HBoV detected in respiratory samples and blood with antibody responses to infection. Although not a state of the art serological test, the Western blot assay developed for IgG and IgM antibodies elicited by HBoV infection provides the important first steps towards the establishment of serological diagnosis of HBoV infection. HBoV is one of several new viruses that have been identified and characterized as