Prevalence of Human Bocavirus in Children Under 5 Years with Upper and Lower Respiratory Infections in Southeastern Iran

Background: Human Bocavirus (HBoV) is a parvovirus associated with mild to severe upper and lower respiratory tract infections in children. Objectives: This study aimed to detect the virus in the nasopharynx of children under 5-year-old with respiratory infection by polymerase chain reaction (PCR). Methods: Two hundred samples were taken from children referred to pediatric clinics in Kerman, southeastern Iran, with respiratory infections and were positive for virus by PCR. Next, the positive samples were genotyped by real-time PCR. Results: Out of 200 samples, 13 (6.5%) were positive for the Bocavirus gene, and all positive samples were infected by HBoV-1. We observed that 116 patients were male, and there was no difference in the prevalence of the virus based on gender (P = 0.345). The prevalence was significantly higher in infants under 10 months old (P = 0.049). Infection by Bucavirus virus was significantly correlated with symptoms, such as fever (P = 0.035, r = 0.7), otitis media (P = 0.013, r = 0.8), diarrhea, nausea, and vomiting (P = 0.001, r = 0.4). Conclusions: According to our findings, HBoV could be one of the causes of infections in the respiratory system of children, and the only type in the studied region is HBoV-1.

Spontaneous pneumomediastinum – a rare cause of chest pain and dyspnoe in children

Introduction. Spontaneous pneumomediastinum is a very rare condition in children. Nevertheless it should be considered in the differential diagnosis in patients who present with chest pain and dyspnoe.Aim. The aim of our study was to describe clinical presentation, management and outcomes of the paediatric patients with spontaneous pneumomediastinumMaterial and Methods. This was a retrospective analysis of the charts of all the patients who were admitted to the Department of Pneumonology, Paediatric Allergy and Clinical Immunology in a ten year period from 01.01.2011 till 31.12.2020 in whom spontaneous pneumomediastinum was diagnosed.Results. There were 11 children (7 females) with spontaneous pneumomediastinum. The median age of the children was 11 years (range 3 to 17.5 years). Most of the children presented to the hospital with chest pain, three children complained of the neck swelling and four children developed dyspnoe. Three children with the primary spontaneous pneumomediastinum had a history of physical exercise prior to the onset of symptoms. The secondary spontaneous pneumomediastinum occurred in two children with asthma and 4 children with pneumonia. Genetic material of human Bocavirus was identified in 3 cases. In 81.8% of children pneumomediastinum was accompanied by subcutaneous emphysema and in one case, in a child with severe pneumonia and respiratory insufficiency caused by Bocavirus with pneumorrhachis. In 10 children computed tomography was performed, bronchoscopy in 4 and esophagoscopy in two children. There was no evidence of esophageal rupture or bronchial tree rupture in any of our patients. Three children with pneumonia and pneumomediastinum developed respiratory insufficiency, two of these were treated with mechanical ventilation and one with High Flow Nasal Cannula oxygen therapy. All the children received oxygen. In one child surgical procedure was performed and the drain was inserted into mediastinal space in order to decompress it. Outcome was favourable in all children. Mean time to recovery was 10.6 ± 1.2 days. There was no recurrence of symptoms in any of our patients.Conclusions. Spontaneous pneumomediastinum in most cases is a benign condition, sporadically however it may progress rapidly, leading to respiratory insufficiency and warrant invasive management.

Contamination of Human Bocavirus Genotypes 1, 2, 3, and 4 in Environmental Waters in Thailand

Recently, we reported the detection of HBoV genotypes 1, 2, and 3 in pediatric patients with acute gastroenteritis, and the detection of HBoV1 and 2 in oysters in Thailand. In this study, we report the detection of HBoV1, 2, 3, and 4 contamination in environmental waters within the same geographic area.

Viral burden and diversity in acute respiratory tract infections in hospitalized children in wet and dry zones of Sri Lanka

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.

The large nonstructural protein (NS1) of the human bocavirus 1 (HBoV1) directly interacts with Ku70, which plays an important role in virus replication in human airway epithelia

Human bocavirus 1 (HBoV1), an autonomous human parvovirus, causes acute respiratory tract infections in young children. HBoV1 infects well-differentiated (polarized) human airway epithelium cultured at an air-liquid interface (HAE-ALI). HBoV1 expresses a large nonstructural protein, NS1, that is essential for viral DNA replication. HBoV1 infection of polarized human airway epithelial cells induces a DNA damage response (DDR) that is critical to viral DNA replication involving DNA repair with error-free Y-family DNA polymerases. HBoV1 NS1 or the isoform NS1-70 per se induces a DDR. In this study, using the second-generation proximity-dependent biotin identification (BioID2) approach, we identified that Ku70 is associated with the NS1-BioID2 pulldown complex through a direct interaction with NS1. Bio-layer Interferometry (BLI) assay determined a high binding affinity of the NS1 with Ku70, which has an equilibrium dissociation constant (K D ) value of 0.16 μM and processes the strongest interaction at the C-terminal domain. The association of Ku70 with NS1 was also revealed during HBoV1 infection of HAE-ALI. Knockdown of Ku70 and overexpression of the C-terminal domain of Ku70 significantly decreased HBoV1 replication in HAE-ALI. Thus, our study provides for the first time a direct interaction of a parvovirus large nonstructural protein NS1 with Ku70. IMPORTANCE Parvovirus infection induces a DNA damage response (DDR) that plays a pivotal role in viral DNA replication. The DDR includes activation of ATM (Ataxia telangiectasia mutated), ATR (ATM- and RAD3-related), and DNA-PKcs (DNA-dependent protein kinase catalytic subunit). The large nonstructural protein (NS1) often plays a role in the induction of DDR; however, how the DDR is induced during parvovirus infection or simply by the NS1 is not well studied. Activation of DNA-PKcs has been shown as one of the key DDR pathways in DNA replication of HBoV1. We identified that HBoV1 NS1 directly interacts with Ku70, but not Ku80, of the Ku70/Ku80 heterodimer at a high affinity. This interaction is also important for HBoV1 replication in HAE-ALI. We propose that the interaction of the NS1 with Ku70 recruits the Ku70/Ku80 complex to the viral DNA replication center, which activates DNA-PKcs and facilitates viral DNA replication.

Epidemiology of Human Bocavirus in the Middle East and North Africa: Systematic Review

The emergence of the COVID-19 pandemic highlighted the importance of studying newly emerging viruses that cause respiratory illnesses. Human bocavirus (HBoV) is one of the relatively newly discovered viruses that has been detected worldwide and causes respiratory and gastrointestinal infections, mainly in pediatric patients. However, little is known about the pathogenicity and evolution of HBoV. This systematic review was initiated to clarify the prevalence and circulating genotypes of HBoV in both respiratory and stool samples from patients of all age groups in the Middle East and North Africa (MENA) from 2005 to February 2021. We performed an electronic search through Science Direct, Scopus, PubMed, Mendeley and Cochrane Library databases. We included all studies reporting the detection rate of HBoV in the MENA region. Data were extracted, and the quality of the included articles was assessed. We included articles containing data on HBoV only or with other respiratory or gastrointestinal viral infections. Review articles, case studies, and animal and environmental studies were excluded. The final number of articles included in this study was 65 articles. The results showed that the HBoV prevalence in children was the lowest in Iran (0%) and the highest in Egypt (56.8%). In adults, the lowest and the highest prevalence were reported in Iran, with values of 0% and 6.6%, respectively. Regarding the respiratory cases, our findings revealed no significant difference between HBoV prevalence among the tested categories (p-value = 0.998). The present study has shown that HBoV is common in children and adults in the MENA region. This systematic review highlights the need for more data on the role of coinfection of HBoV and other viruses, for instance, SARS-CoV-2 in children with acute bronchiolitis.

Epidemiologic and clinical characteristics of human bocavirus infection in infants and young children suffering with community acquired pneumonia in Ningxia, China

Background Pneumonia has a high incidence rate and is a major cause of mortality in children, mostly community-acquired pneumonia (CAP). Human bocavirus (HBoV), since it first identified in 2005, has been repeatedly associated with respiratory tract infections. Nevertheless, the role and related information of HBoV as a pathogen of CAP has not been fulfilled. Here our study is to assess the epidemiological and clinical features in HBoV-positive children with CAP. Methods A total of 878 secretions of lower respiratory samples were obtained, multiplex PCR was used to detect HBoV and other respiratory viruses. Results Of all cases, HBoV was detected in 10.0%, with a peak incidence of infection among children < 2 year old, and predominantly noted in autumn and winter. Only 8 patients were HBoV single infection. Co-infection with other respiratory viruses was observed in 86.4%. Moreover, co-infection with bacteria occurred in 27.3% and with Mycoplasma pneumoniae (MP) in 33.0% of HBoV-positive patients. Among all HBoV-positive samples co-infected with bacteria, 87.5% are gram negative bacteria. Compared with HBoV-negative group, age (P = 0.048), wheezing (P = 0.015), tachypnea (P = 0.016), lactate dehydrogenase (P = 0.026) and severe pneumonia (P = 0.023) were statistically significant in HBoV-positive patients. Furthermore, HBoV-positive patients less than 1 year old were more likely to have co-infection with bacteria (P = 0.007). Conclusions HBoV can be detected alone in respiratory samples of children with CAP, maybe it is one of the causes of CAP in infants. The high incidence of severe pneumonia was found in HBoV-positive patients compared with HBoV-negative cases may indicate a relationship between severe pneumonia and HBoV.

Is Human Bocavirus Infection Associated with Gastroenteritis in Children? An Updated Systematic Review and Meta-analysis

Background: Human bocavirus (HBoV) figures as an increased risk factor of respiratory and gastrointestinal tract infections among children. A great deal of data is available to support the pathogenic role of HBoV in acute respiratory diseases. However, the association between HBoV infection and gastroenteritis remains controversial due to the ambiguous results. The present work aims to clarify the role of HBoV as a cause of gastroenteritis in children. Methodology/Principal findings: A systematic search of the literature was carried out from 1 January 2016 to 29 August 2021 in Embase, PubMed, Scopus, Web of Science, and the Chinese bibliographic database of biomedicine (CBM). Data from included studies were analyzed by use of a random-effects model. The pooled estimates of HBoV prevalence among all cases of gastroenteritis were generated and stratified by potential confounders. The pooled odds ratio (OR) and 95% confidence interval (CI) were computed for HBoV infection in relation to the risk of gastroenteritis. The overall prevalence of HBoV in children with gastroenteritis (9.1%, 95% CI: 6.7-11.8%) was considerably higher than that detected in children without gastroenteritis (4.0%, 95% CI: 1.1-8.5%). HBoV prevalence tended to be higher in cases of gastroenteritis under five years of age (12.1%, 95% CI: 6.8-18.7%). The highest frequency of HBoV was found in Egypt (57.8%, 95% CI: 47.7-67.6%). The predominant genotypes of HBoV circulating in children with gastroenteritis were genotype 1 (HBoV1, 3.8%, 95% CI: 2.7-5.2%) and genotype 2 (HBoV2, 2.4%, 95% CI: 1.3-3.7%). HBoV infection was significantly associated with an increased risk of gastroenteritis in children (OR 1.620, 95% CI: 1.023-2.566). Conclusion: The HBoV prevalence in pediatric cases of gastroenteritis is higher than that in children without gastroenteritis, demonstrating an increasing global burden of gastroenteritis in children caused by HBoV infection. Targeted intervention to reduce the HBoV burden should be established.

The contemporary study of acute myocarditis in South Africa – CAMISA

Introduction The aetiology and estimated incidence of acute myocarditis (AM) remains undefined in Africa. Whilst cardiac magnetic resonance (CMR) provides for a provisional non-invasive diagnosis, endomyocardial biopsy (EMB), which is infrequently clinically sought, remains the gold standard. The developed world has experienced a shift in the viral epidemiology of AM and the ESC's most recent position statement on myocarditis recommends both CMR and EMB as the standard of care in suspected cases. We report on the interim results of the study. Purpose To determine the nature of presentation, underlying aetiology, and outcomes of patients presenting with AM to a single tertiary centre in South Africa. Methods A cohort of patients from a single tertiary centre in South Africa will be recruited from January 2018 to December 2022. All patients presenting or referred to the centre with clinically suspected AM that are investigated according to the ESC recommendations on myocarditis, which includes blood tests (CRP, hsTNT, HIV and Hepatitis C serology, ANA), a standard twelve-lead ECG, TTE, coronary angiography, CMR and EMB, will be included. Enrolment is ongoing. Results A total of 102 (mean age 42.2±13 years, 64.7% male) cases of clinically suspected AM were identified between January 2018 and January 2021. AM was confirmed in 41 (40.2%) cases on CMR only, while 41 (40.2%) were also confirmed on EMB. 4 cases of sarcoidosis, 1 case each of eosinophilic myocarditis, amyloidosis and primary cardiac lymphoma were diagnosed. Viral genome was isolated by PCR in 60 (59.8%) patients. PVB19 (73.5%) was the most commonly identified virus in those with confirmed AM followed by EBV (12.2%), HHV6 (4.1%) and Human Bocavirus (2%). 3 were coinfected with PVB19/EBV, and 1 with PVB19/EBV/HHV6. PVB19 was also isolated in 9 patients with no evidence of AM on CMR or EMB, but with lower median viral load compared to those with AM (198copies/ml IQR 113 – 282 vs 483copies/ml IQR 366 – 1460, p=0.005). The virus-positive patients with confirmed AM tended to be older (43.1±13.4 years vs 37.6±12.2 years, p=n/s), had higher median CRP (24mg/L vs 16mg/L, p=n/s) but lower median hsTnT (326.5ng/L vs 434.5ng/L, p=n/s) at presentation, and were more likely to be EMB positive (60% vs 37.5%, p=0.04) when compared to the virus-negative group. To date 6 patients have demised, of which 4 were related to AM. Conclusion To our knowledge, this is the first study to evaluate AM in Africa, and the biggest cohort of AM patients outside of the developed world. It demonstrates the heterogeneity in presentations and provides insight into the viral pathogens within our local setting, which appears similar to those reported in the developed world. We were also able to highlight some differences in demographic and clinical characteristics between those with virus-positive and virus-negative AM. The background prevalence and causal role of PVB19 in our setting will also need to be further explored. FUNDunding Acknowledgement Type of funding sources: None.