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Human Bocavirus: Multisystem Detection Raises Questions about Infection
... 5,6 Although our understanding of the epidemiology and genetic characteristics of this novel virus has been enhanced with the increasing information, we are still unable to discern the role of this virus in respiratory infections. [8][9][10] Longtin et al. and Garcia-Garcia et al. have also identified the virus among asymptomatic children. 11 The virus has also been identified in fecal samples of Spanish and Brazilian children with diarrheal symptoms. ...
... 4,6,[20][21][22][23] The role of HBoV as a pathogen remains unclear. 8,9 In our study, we detected HBoV as the most common viral agent, i.e. 23AE2% of the total samples tested. However, we were unable to detect an agent in 49AE0% of the samples, and we did not test for some known respiratory viruses, such as human rhinovirus, coronavirus or for bacterial agents. ...
Globally, respiratory infections are the primary cause of illness in developing countries, specifically among children; however, an etiological agent for many of these illnesses is rarely identified.
Our study aimed to estimate the frequency of human bocavirus (HBoV) infection among pediatric populations in Argentina, Nicaragua and Peru.
We conducted a cross-sectional study using stored samples of an influenza-like illness surveillance program. Irrespective of previous diagnosis, nasopharyngeal or nasal swab specimens were randomly selected and tested using real-time PCR from three sites during 2007 from patients younger than 6 years old.
A total of 568 specimens from Argentina (185), Nicaragua (192) and Peru (191) were tested. The prevalence of HBoV was 10·8% (95% CI: 6·3; 15·3) in Argentina, 33·3% in Nicaragua (95% CI: 26·6; 40·1) and 25·1% in Peru (95% CI: 18·9; 31·3).
These findings demonstrate circulation of HBoV in Argentina, Nicaragua and Peru among children with influenza-like symptoms enrolled in a sentinel surveillance program.
... Indeed, in most studies, HBoV is second only to respiratory syncytial virus in frequency and severity of disease in infants and young children. Although most initial studies concentrated on the involvement of HBoV in respiratory disease, it has also become apparent that infections are systemic and may be associated with other pathologies, arising, for example, from infection of the gastrointestinal tract [4,5]. ...
... The inclusion of rhinoviruses, enteroviruses, and newly discovered coronavirus groups in the total of 16 viruses examined by PCR and serological testing makes this archive one of the best characterized sample collections available for etiological studies of new viral pathogens. Allander et al. [5] had established previously that detection of HBoV DNA sequences in respiratory samples coincided with an acute, resolving viremia, indicating the systemic nature of primary infections. Viremia was specifically associated with high viral loads in respiratory samples (110,000 copies/ mL) and was relatively infrequent in patients who had viral loads below this threshold. ...
... Alternatively, HBoV is occasionally a passenger virus, and there is the possibility that another cause exists, because of the absence of pathological changes. Mackay et al. reported that persistent virus shedding for over a month was observed in patients who died of SIDS who had significant underlying diseases 21) . However, the possible causes of the sudden death of our patient are thought to be upper airway obstruction, limitation of thoracic expansion, and insufficient temperature control owing to viral infection. ...
Background : Infants who die due to sudden infant death syndrome are known to have significantly more respiratory infection symptoms before the event than the control group, indicating the involvement of suffocation and cardiopulmonary arrest. Methods : We present a case of sudden death of a 5-month-old baby who was positive for human bocavirus in his airway secretions. He had respiratory infection symptoms with wheezing before the event. After feeding, the baby was carried on the father's back for 25 minutes. At their destination, the father found the baby showing abnormalities, and the baby died at hospital soon after. Results : Lung autopsy demonstrated bronchopneumonia and the sample was positive for human bocavirus by real-time multiplex polymerase chain reaction (PCR). Conclusions : These results suggest that human bocavirus might be a causative pathogen of sudden death with airway obstruction.
... HRV may be detected concurrently with other viruses such as RSV, HMPV, InfV, or HCoV (Richard et al., 2008;Fujitsuka et al., 2011). Considering their ubiquity, it is interesting that the number of respiratory viruses detected concurrently with HRV strains is relatively low Mackay, 2007), supporting the concept that HRVs have a direct role in the clinical outcome of infection (Miller et al., 2007). In fact, HRV strains are co-detected with other pathogens in reproducible, but clinically undefined, patterns (Brunstein et al., 2008). ...
Acute respiratory illness (ARI) due to various viruses is not only the most common cause of upper respiratory infection in humans but is also a major cause of morbidity and mortality, leading to diseases such as bronchiolitis and pneumonia. Previous studies have shown that respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (HMPV), human parainfluenza virus (HPIV), and human enterovirus infections may be associated with virus-induced asthma. For example, it has been suggested that HRV infection is detected in the acute exacerbation of asthma and infection is prolonged. Thus it is believed that the main etiological cause of asthma is ARI viruses. Furthermore, the number of asthma patients in most industrial countries has greatly increased, resulting in a morbidity rate of around 10-15% of the population. However, the relationships between viral infections, host immune response, and host factors in the pathophysiology of asthma remain unclear. To gain a better understanding of the epidemiology of virus-induced asthma, it is important to assess both the characteristics of the viruses and the host defense mechanisms. Molecular epidemiology enables us to understand the pathogenesis of microorganisms by identifying specific pathways, molecules, and genes that influence the risk of developing a disease. However, the epidemiology of various respiratory viruses associated with virus-induced asthma is not fully understood. Therefore, in this article, we review molecular epidemiological studies of RSV, HRV, HPIV, and HMPV infection associated with virus-induced asthma.
... Otros estudios reportan que varios de los niños con HBoV tuvieron diarrea, sugiriendo que la enfermedad se extiende más allá del tracto respiratorio 11 . La descripción de niños infectados con HBoV que presentaron diarrea, sumado a la relación cercana de este virus con parvovirus bovino y el virus minute canino que infectan animales y causan enfermedad intestinal manifestada por vómitos, anorexia, letargia y diarrea con rápida deshidratación, hicieron plantear que este virus podría tener también un rol en enfermedades gastrointestinales en el humano y que podría ser detectado en muestras fecales 12,13 . ...
Bocavirus humano (HBoV), virus de la familia Par-voviridae, descubierto por métodos moleculares el año 2005, ha sido reportado en muestras respiratorias, fecales, sanguíneas y urinarias, tanto en niños como en adultos. Se han reportado prevalencias que van desde 0,8%) en muestras fecales de individuos con diarrea aguda hasta 19%o en muestras respiratorias y sanguíneas. En niños asintomáticos se ha detectado hasta 43%o de HBoV en muestras nasofaríngeas. En Chile, se ha detectado HBoV en muestras de hisopado nasofaríngeo en niños bajo 5 años de edad, con síntomas respiratorios, en 24,2%o, existiendo co-infección con otros virus en 74%o, y en niños asintomáticos bajo 5 años años se ha encontrado 37,5%o de muestras positivas para HBoV. Se discute el rol de HBoV como agente causal de enfermedades respiratorias y/o digestivas, debido a co-infección con otros microorganismos, dificultando determinar si HBoV participa como único agente infeccioso.
... Owing to the lack of an animal model and the lack of proof of Koch's modified postulates , some open questions remain concerning HBoV. Surprisingly, an otherwise healthy control group tested positive for HBoV after elective surgery in the ear, nose and throat section (43%) [89]. Reasons for this phenomenon have not yet been deciphered, but several explanations may apply. ...
The human bocavirus was first detected in 2005 and since then has been found in both respiratory secretions from patients with airway infections and in stool samples from patients with gastroenteritis. Meanwhile, four different genotypes have been identified that most likely derive from recombination events. Although the modified Kochs postulates have not yet been fulfilled completely, owing to the lack of an animal model or a simple cell culture system, there is increasing evidence that the human bocaviruses are serious participants in infectious diseases of the respiratory and the GI tracts. This article reviews the current status of the clinical features of human bocaviruses and provides an overview of the latest findings concerning the biology, phylogeny, epidemiology and diagnostic tools related to human bocaviruses. Furthermore, it discusses the potential pathogenicity of human bocavirus, as well as its persistence and reactivation in hosts.
... HBoV3 and HBoV2 were recently found in stool samples from Australian children with diarrhea [9], and HBoV4 was first identified in stool samples of children from Nigeria and Tunisia [26]. Whether any of the four HBoV species causes human disease is still undetermined [3,27,28]. ...
Human bocaviruses (HBoV) are highly prevalent human infections whose pathogenic potential remains unknown. Recent identification of the first non-human primate bocavirus [1] in captive gorillas raised the possibility of the persistent nature of bocavirus infection. To characterize bocavirus infection in humans, we tested intestinal biopsies from 22 children with gastrointestinal disease for the presence of HBoV DNA. Four HBoV-positive tissue samples were analyzed to determine whether viral DNA was present in the linear genomic, the episomal closed circular or the host genome-integrated form. Whereas one tissue sample positive for HBoV3 contained the episomal form (HBoV3-E1), none had the genome-integrated form. The complete genome sequence of HBoV3-E1 contains 5319 nucleotides of which 513 represent the non-coding terminal sequence. The secondary structure of HBoV3-E1 termini suggests several conserved and variable features among human and animal bocaviruses. Our observation that HBoV genome exists as head-to-tail monomer in infected tissue either reflects the likely evolution of alternative replication mechanism in primate bocaviruses or a mechanism of viral persistence in their host. Moreover, we identified the HBoV genomic terminal sequences that will be helpful in developing reverse genetic systems for these widely prevalent parvoviruses.
Significance
HBoV have been found in healthy human controls as well as individuals with respiratory or gastrointestinal disease. Our findings suggest that HBoV DNA can exist as episomes in infected human tissues and therefore can likely establish persistent infection in the host. Previous efforts to grow HBoV in cell culture and to develop reverse genetic systems have been unsuccessful. Complete genomic sequence of the HBoV3 episome and its genomic termini will improve our understanding of HBoV replication mechanism and its pathogenesis.
... The potential of causing other nonrespiratory diseases has been under discussion. 12,13 Later publications reported the virus in the gastrointestinal tract and serum, referring to a systemic dissemination. 14,15 The detection of HBoV DNA in a patient with KD raised question about the coincidental or possible etiological association. ...
Kawasaki disease (KD) is an acute febrile multisystem vasculitic syndrome of unknown etiology, occurring mostly in infants and children younger than 5 years of age. We present a 13-month-old male with KD from whom was found human bocavirus DNA in nasopharyngeal secretions. Human bocavirus DNA in a patient with KD raised question about the coincidental or possible etiological association.
... The co-infected patient was not classified as having severe illness. The role of HBoV as a causative agent of respiratory tract disease remains contentious (Blessing et al., 2009; Chow and Esper, 2009; Mackay, 2007; Schildgen et al., 2008). A recent study by (Blessing et al., 2009) demonstrated that qualitative detection of HBoV DNA within a patient sample was not sufficient to establish HBoV as the sole cause of respiratory illness. ...
First identified in 2001, human metapneumovirus (HMPV) is a novel pathogen and causative agent of acute respiratory tract infection. Re-infection with HMPV is common, and currently there is no available vaccine against HMPV infection. Two genotypes of HMPV have been identified, A and B, both of which can be divided further into at least two distinct sub-genotypes. Here we report the results of the first study to investigate the genetic variability of HMPV strains circulating within Cambodia. The overall incidence of HMPV infection amongst an all-ages population of patients hospitalised with ALRI in Cambodia during 3 consecutive years, between 2007 and 2009, was 1.7%. The incidence of HMPV infection was highest amongst children less than 5 years of age, with pneumonia or bronchopneumonia the most frequent clinical diagnoses across all age groups. The incidence of HMPV infection varied annually. As anticipated, genetic diversity was low amongst the conserved F gene sequences but very high amongst G gene sequences, some strains sharing as little as 56.3% and 34.2% homology at the nucleotide and amino acid levels, respectively. Simultaneous co-circulation of strains belonging to the HMPV sub-genotypes B1, B2 and lineage A2b, amongst patients recruited at 2 geographically distinct provincial hospitals, was detected. Sub-genotype B2 strains were responsible for the majority of the infections detected, and a significant (p=0.013) association between infection with lineage A2b strains and disease severity was observed.
... Nasal swabs were also tested for bocavirus. During the course of the study evidence emerged that bocavirus does not appear to be an etiologic agent of viral URIs in children over 2 years of age.(17,18) Therefore, we did not include bocavirus in our analysis. ...
The objective of this study was to develop a symptom scoring system for use in clinical studies that differentiates children with cold symptoms who have an identifiable viral etiology for their upper respiratory tract infection (URI) from those in whom no virus is detected. Nasal swabs for PCR testing for identification of respiratory viruses were obtained on children aged 2-11 y at baseline and when parents thought their child was developing a cold. Parental-recorded severity of specific symptoms in children with and without a documented viral URI were compared. Nasal swabs were obtained on 108 children whose parents reported their child was developing a cold. A viral etiology was identified in 62 of 108 (57.4%) samples. Symptom measures that best differentiated children with a viral etiology from those without were significant runny nose and significant cough on days 1-4 of the illness. A URI symptom score was developed based on these symptoms, with a sensitivity of 81.4%, specificity of 61.9%, and accuracy of 73.3%. Parental impression is only a moderately accurate predictor of viral URI in children. Our URI symptom score provided a more accurate method for identifying children with viral URIs for clinical studies.
... The region of the p104 gene that was used is highly conserved among a wide range of isolates within the species and importantly, is also speciÞc for T. parva relative to other species that are known to co-infect R. appendiculatus (Iams et al. 1990, Skilton et al. 2002). Although both nested and real-time PCR are useful for the analysis of clinical specimens and can potentially achieve similar levels of speciÞcity and sensitivity, major advantages of the qPCR assay are the ability to quantify the level of infection and the reduced risk of detecting false positives through crosscontamination (Mackay 2007). In conclusion, although the Kiambu tick strain is much more susceptible to salivary gland infection compared with the Muguga tick strain, both were able to transmit T. parva to naõ¨venaõ¨ve susceptible animals. ...
Theileria parva is the etiologic agent of East Coast fever, an economically important disease of cattle in sub-Saharan Africa. This protozoan parasite is biologically transmitted by Rhipicephalus appendiculatus (Neumann) (Acari: Ixodidae). An understanding of the vector-parasite interaction may aid the development of improved methods for controlling transmission. We developed quantitative polymerase chain reaction (qPCR) and nested PCR (nPCR) assays targeting the T. parva-specific p104 gene to study T. parva pathogenesis in two strains of R. appendiculatus that had previously been selected to be relatively more (Kiambu) or less (Muguga) susceptible to infection. Nymphs from both strains were fed simultaneously to repletion on acutely infected calves. Nymphs from the Kiambu strain showed significantly higher engorgement weights compared with Muguga strain nymphs. Immediately after engorgement qPCR confirmed that nymphal Kiambu ticks had significantly higher parasite loads at repletion than Muguga nymphs. By 12 d postengorgement, parasites were below quantifiable levels but could be detected by nPCR in 83-87% (Muguga and Kiambu, respectively) of nymphs. After the molt, adult feeding on naïve cattle stimulated parasite replication in the salivary glands. PCR detected significantly more infected ticks than microscopy, and there was a significant difference between the two tick strains both in the proportion of ticks that develop salivary gland infections, and in the number of parasites within infected salivary glands. These data confirm that although both tick strains were competent vectors, Kiambu is both a significantly more susceptible and a more efficient host for T. parva than Muguga. The mechanisms that contribute to the levels of susceptibility and efficiency are unknown; however, this study lays the groundwork for a comparison of the transcriptome of these tick strains, the next step toward discovering the genes involved in the tick-parasite interaction.
... Several studies reported no or few cases of HBoV infections in asymptomatic populations or differently symptomatic control populations but often without age matching and using different types of specimens. 16 In the present study, children hospitalized for non-respiratory diseases were tested for HBoV, using the same type of specimen, taken by the same physicians, for several months during the study period. Human bocavirus was detected in 2 ⁄ 21 children; these patients had symptoms (gastroenteritis or exanthema) similar to those described previously in HBoV infections. ...
Human bocavirus (HBoV) was first discovered in Sweden in 2005 and has now been found worldwide; however its role in clinically relevant diseases has not yet been clearly defined.
To gain new insight into HBoV infection among children hospitalized with acute respiratory infections in Rome.
Between November 2004 and May 2007, 415 nasal washings were tested for the presence of an extensive range of respiratory viruses using molecular methods.
Viral pathogens were detected in 214 children (51.6%), 28.9% being respiratory syncytial virus (RSV) and 9.6% being rhinovirus positive. Of the 34 children (8.2%) who tested positive for HBoV, 21 (61.8%) were co-infected with another respiratory virus, mainly RSV. Human bocavirus was the only pathogen identified in four pneumonia and six bronchiolitis cases in March 2005 and January 2007, respectively. Human bocavirus was also detected in one child hospitalized with gastroenteritis and in another with erythema.
In the examined population, HBoV was the third most common virus detected but with a high rate of co-infection with other respiratory viruses. Human bocavirus appeared to be the etiological agent in some pneumonia and bronchiolitis cases in which tests for all likely respiratory pathogens were negative.
... Indeed, subsequent investigations of their epidemiologies, transmission routes and disease associations have often proven to be major challenges. There is an ongoing effort, for example, to determine precisely whether HBoV is a significant cause of childhood respiratory disease, why it is so often co-detected with other respiratory pathogens, and whether it exclusively a respiratory virus (reviewed in (MacIntosh, 2006;Mackay, 2007). Disease associations of PARV4 are even less well defined (Simmonds et al., 2007). ...
WU virus (WUV) and KI polyomavirus (KIPyV) are newly discovered related human polyomaviruses detected in respiratory samples. To investigate their potential role in respiratory disease, we determined their frequencies of detection, clinical presentations and epidemiological characteristics among samples referred for diagnostic respiratory virus testing.
Anonymised samples and accompanying study subject information were obtained from the Edinburgh respiratory specimen archive. Samples were screened by nested PCR using two sets of primers conserved between WUV and KIPyV, as well for other respiratory viruses (respiratory syncytial virus [RSV], adenoviruses [AdV], influenza A/B and parainfluenza viruses 1-3, human bocavirus, B19).
WUV and KIPyV were detected in 10 and 14 samples, respectively from 983 specimens (from 9 to 10 different individuals from 612 study subjects). Infections occurred in two types of study subject; those who were young (<2 years) with lower respiratory tract infections (n=8), and almost invariably co-infected with other respiratory viruses (RSV, AdV), and a second, generally older group either without respiratory disease (n=6) or with mild upper respiratory tract infections (n=5) but who were generally clinically severely immunosuppressed from leukaemia or transplant therapy. Findings from either group do not support an aetiological link between infection with WUV or KIPyV and respiratory disease.
... HBoV was first cloned from pooled human respiratory tract samples collected in Sweden and was classified provisionally into the genus Bocavirus based on sequence comparisons (Allander et al., 2005). However, similar to the bovine bocavirus BPV, HBoV was recently reported to be associated with acute gastroenteritis (Lau et al., 2007;Lee et al., 2007;Mackay, 2007). The HBoV genome has been detected in respiratory tract infections. ...
Human bocavirus (HBoV) has been identified worldwide in children with lower respiratory tract infections with an incidence of approximately 2-11%. The role of HBoV in pathogenesis, however, is largely unknown, and little is known about the epidemiology of the virus. To study the seroepidemiology of HBoV infection, the capsid protein was expressed in insect cells. Expression of the putative major capsid protein VP2 in insect cells led to the formation of virus-like particles exhibiting the typical icosahedral appearance of parvoviruses with a diameter of approximately 20 nm. The expressed particles were used to establish an enzyme-linked immunosorbent assay (ELISA) method, and serum samples from groups of children of various ages in China were tested for IgG antibodies against HBoV. HBoV antibodies were detected in as high as 36% of healthy children under 9 years. Of children hospitalized with lower respiratory tract infections, 31% were seropositive, and all age groups of these children showed a significantly higher level of HBoV IgG antibody than their healthy counterparts. When divided into age cohorts, results showed that more than 48% of healthy children had seroconverted by age of 4. Thus, HBoV appears to be a common infection in children. The potential pathogenesis of this virus, especially its role in lower respiratory tract infections in children warrants further investigation.
... Most HBoV-positive specimens are from children, but this may represent a sampling bias. HBoV DNA has also been detected in blood [6,16] and in stool [17][18][19], although the significance of these findings remains unclear [20]. ...
Human bocavirus (HBoV) is a newly identified human parvovirus for which seroepidemiology and antigenic properties remain undefined.
The HBoV VP2 gene, expressed from a baculovirus vector, produced virus-like particles (VLPs), which were used to raise rabbit anti-HBoV antisera and to develop an enzyme-linked immunosorbent assay (ELISA). The VLP-based ELISA was used to screen for HBoV-specific immunoglobulin G antibodies in a convenience sample of 270 serum specimens, mostly from children, obtained at Yale-New Haven Hospital; 208 specimens were also screened for erythrovirus B19-specific antibodies by a B19 VLP-based ELISA.
Immunofluorescence and ELISA showed that human parvoviruses HBoV and B19 are antigenically distinct. By the HBoV VLP-based ELISA, 91.8% and 63.6% of serum specimens from infants in the first and second months of life, respectively, were found to be seropositive, as were 45.4% from 3-month-old infants and 25.0% from 4-month-old infants. The percentages of HBoV-seropositive children increased to 40.7%-60.0% for children 5-47 months of age and to >85% for individuals >or=48 months old. However, the overall percentage of B19-seropositive individuals was <40.5% for all age groups screened.
HBoV infection is common during childhood, but a minority of children and young adults screened have evidence of B19 infection.
... Today, half of all HRV detections can be found concurrently with another virus, on the surface, a significant fraction, and yet 80% or more of human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), HEV and influenzavirus (IFV) detections and 71% of human coronavirus (HCoV)NL63 detections can be found in the company of another virus ( Richard et al., 2008). Considering their ubiquity, it is interesting that relatively low numbers of concurrent detections of other respiratory viruses occur with HRV strains (Mackay, 2007;Lambert et al., 2007), supporting the concept that HRVs have a direct role in the clinical outcome of their infection (Miller et al., 2007). In fact, HRV strains are co-detected with other pathogens in reproducible, but clinically undefined, patterns (Brunstein et al., 2008). ...
Human rhinoviruses (HRVs) are the most common cause of viral illness worldwide but today, less than half the strains have been sequenced and only a handful examined structurally. This viral super-group, known for decades, has still to face the full force of a molecular biology onslaught. However, newly identified viruses (NIVs) including human metapneumovirus and bocavirus and emergent viruses including SARS-CoV have already been exhaustively scrutinized. The clinical impact of most respiratory NIVs is attributable to one or two major strains but there are 100+ distinct HRVs and, because we have never sought them independently, we must arbitrarily divide the literature's clinical impact findings among them. Early findings from infection studies and use of inefficient detection methods have shaped the way we think of 'common cold' viruses today.
To review past HRV-related studies in order to put recent HRV discoveries into context.
HRV infections result in undue antibiotic prescriptions, sizable healthcare-related expenditure and exacerbation of expiratory wheezing associated with hospital admission.
The finding of many divergent and previously unrecognized HRV strains has drawn attention and resources back to the most widespread and frequent infectious agent of humans; providing us the chance to seize the advantage in a decades-long cold war.
Background: Hyperoxia is one of the risks to cause BPD or ROP in preterm infants. It has been known to suppress the angiogenesis of vascular endothelial cells. However, the effect of hyperoxia to the antoxienzyme activity of vascular endothelial cells is not very clear.
Human rhinovirus (HRV) infections cause 70% of virus‐related wheezing exacerbations and cold and flu‐like disease. They are associated with otitis media, sinusitis and pneumonia. Annually, the health and socioeconomic impact of HRV infections costs billions of dollars. Since 1987, 100 officially recognised HRV serotypes have resided in two genetically distinct species, HRV‐A and HRV‐B. Their genome sequences were deduced in 2009. Recently a new species, HRV‐C was recognised, containing 60 genotypes, of which only two have been isolated in primary tissue. Little is known about HRV‐Cs. The HRVs reside within the genus Enterovirus , family Picornaviridae . What drives the development and maintenance of so many distinct viruses is unknown. What role recombination plays in generating this diversity and whether there are species‐specific circulation patterns and clinical outcomes remains unclear. In short, much remains uncertain about the HRVs but the current key features and clinical outcomes from HRV infection are presented.
Key Concepts
The nonenveloped HRVs have a small RNA genome of approximately 7000 base pairs.
A third, new species of HRV, HRV‐C was described in 2007; all species reside within the genus Enterovirus , family Picornaviridae.
HRV prevalence peaks twice per year.
HRVs cause cold and flu‐like symptoms and trigger asthma and chronic obstructive pulmonary disease exacerbations.
HRVs are associated with diseases such as otitis media, sinusitis and pneumonia.
HRV infections are associated with considerable direct and indirect healthcare expenditure annually.
The common cold is the result of an upper respiratory tract infection causing an acute syndrome characterised by a combination of non-specific symptoms, including sore throat, cough, fever, rhinorrhoea, malaise, headache, and myalgia. Respiratory viruses. alone or in combination, are the most common cause. The course of illness can be complicated by bacterial agents, causing pharyngitis or sinusitis, but they are a rare cause of cold and flu-like illnesses (CFLIs). Our understanding of CFLI epidemiology has been enhanced by molecular detection methods, particularly polymerase chain reaction (PCR) testing. PCR has not only improved detection of previously known viruses, but within the last decade has resulted in the detection of many divergent novel respiratory virus species. Human rhinovirus (HRV) infections cause nearly all CFLIs and they can be responsible for asthma and chronic obstructive pulmonary disease exacerbations HRVs are co-detected with other respiratory viruses in statistically significant patterns with HRVs occurring in the lowest proportion of co-detections, compared to most other respiratory viruses. Some recently identified rhinoviruses may populate an entirely new putative HRV species; HRV C. Further work is required to confirm a causal role Ior these newly identified viruses in CFLIs. The burden of illness associated with CFLIs is poorly documented, but where data are available, the impact of CFLIs is considerable. Individual infections, although they do not commonly result in more severe respiratory tract illness are associated with substantial direct and indirect resource use. TIle product of frequency and burden for CFLIs is likely to be greater in magnitude than for any other respiratory syndrome, but further work is required to document this. Our understanding of the viral causes of CLFIs, although incomplete, has improved in recent years. Documenting burden is also an important step in progress towards improved control and management of these illnesses.
Little is known about human bocavirus (HBoV) persistence and shedding and the association between HBoV detection and the onset and resolution of respiratory symptoms.
We performed HBoV testing on nasal swab samples from a prospective, longitudinal study of respiratory illness in 119 children who attended daycare.
HBoV was detected in 70 children (59%) and in 106 (33%) of the 318 cases of illness. Another virus was detected in 76 (72%) of 106 HBoV-positive cases. Extended and intermittent shedding was observed, with consistent HBoV detection documented for up to 75 days. HBoV was detected in 20 (44%) of 45 asymptomatic enrollment samples, and HBoV prevalence and viral load did not differ significantly between children with and children without symptoms at enrollment. HBoV-positive illnesses were longer than HBoV-negative illnesses (odds ratio for duration of symptoms >7 days, 2.44; 95% confidence interval, 1.41-4.22), and illnesses with HBoV load 4 log(10) copies/mL required a visit to a health care provider more often than did HBoV-negative illnesses (odds ratio, 1.64; 95% confidence interval, 1.02-2.64).
HBoV was more common in illnesses with greater severity. However, detection of HBoV was not associated with the presence of respiratory illness or with specific respiratory symptoms in this prospective study of infants and toddlers attending daycare centers.
The human bocavirus (HBoV), virus of the Parvoviridae family, discovered by molecular methods in 2005, has been reported in respiratory samples, stool, urine and blood, both in children and adults. Prevalence rates range from 0.8% in fecal samples of individuals with acute diarrhea, up to 19% in respiratory samples and blood. HBoV has been detected in up to 43% of nasopharyngeal samples in asymptomatic children. In Chile, HBoV was detected in 24.2% of nasopharyngeal swabs in children under 5 years of age with respiratory symptoms of which 74% had coinfection with other viruses. In asymptomatic children under 5 years of age, 37.5% of NP samples were positive for HBoV. We discuss the role of HBoV as a causal agent of respiratory and/or enteric disease in light of the high rates of coinfection and asymptomatic infections.
Recently, molecular screening for pathogenic agents has identified a partial genome of a novel parvovirus, called human bocavirus (HBoV). The presence of this newly described parvovirus correlated with upper and lower respiratory tract infections in children. Lower respiratory tract infections are a leading cause of hospital admission in children, and the etiological agent has not been identified in up to 39% of these cases. Using baculovirus expression vectors (BEVs) and an insect cell system, we produced virus-like particles (VLPs) of HBoV. The engineered BEVs express the HBoV capsid proteins stoichiometrically from a single open reading frame. Three capsid proteins assemble into the VLP rather than two proteins predicted from the HBoV genome sequence. The denatured capsid proteins VP1, VP2, and VP3 resolve on silver-stained sodium dodecyl sulfate-polyacrylamide gels as three bands with apparent molecular masses of 72 kDa, 68 kDa, and 62 kDa, respectively. VP2 apparently initiates at a GCT codon (alanine) 273 nucleotides downstream from the VP1 start site and 114 nucleotides upstream from the VP3 initiation site. We characterized the stable capsids using physical, biochemical, and serological techniques. We found that the density of the VLP is 1.32 g/cm(3) and is consistent with an icosahedral symmetry with approximately a 25-nm diameter. Rabbit antiserum against the capsid of HBoV, which did not cross-react with adeno-associated virus type 2, was used to develop enzyme-linked immunosorbent assays (ELISAs) for anti-HBoV antibodies in human serum. Using ELISA, we tested 404 human serum samples and established a range of antibody titers in a large U.S. adult population sample.
Human Bocavirus is a newly discovered parvovirus. This virus is the fourth most frequently detected virus among symptomatic children with respiratory infection. Human Bocavirus is present worldwide and is a probable cause of symptomatic respiratory infection, although Koch's postulates are not all fulfilled. In this article, we propose an overview of the main clinical data about this virus, two years after its discovery. In addition, we discuss some hypotheses about its tropism for the lung in young children.
Parvovirus B19 is a nonenveloped single-stranded DNA virus that commonly causes a benign childhood infection typically manifesting as a ‘slapped-cheek’ rash. In immunodeficient hosts, this infection can cause persistent anemia and occasionally pancytopenia. Recently, direct renal involvement has been reported in renal transplant recipients leading to various forms of glomerulopathy and allograft dysfunction. Most cases are primary infections and are donor transmitted through the transplanted organ. Clinical and virological response to intravenous immunoglobulin (Ig) is usually excellent.
We describe a case of donor-transmitted parvovirus infection in a 23-year-old male who received his first cadaver renal transplant. The patient had an uncomplicated postoperative course with immediate graft function. Eight weeks after transplantation, he presented with fever, polyarthralgia, pancytopenia, and allograft dysfunction. Serological studies revealed elevated IgM titers against parvovirus B19. A renal biopsy was performed, which showed no evidence of acute rejection but with moderate degree of tubular damage. Parvovirus B19 viral DNA was detected in the renal tissue via polymerase chain reaction (PCR). The patient received a 10-day course of intravenous Ig (400 mg/kg/day) with excellent response. His blood count normalized and the allograft improved to baseline function.
The incidence of parvovirus infection in renal transplant patients is probably underestimated, because patients are not routinely screened for it and anemia and/or pancytopenia in these patients are often ascribed to immunosuppressive drugs. Because this infection is treatable, we conclude that parvovirus B19 infection should be actively considered in transplant patients presenting with pancytopenia and allograft dysfunction.
Over 100 years ago, Robert Koch introduced his ideas about how to prove a causal relationship between a microorganism and a disease. Koch's postulates created a scientific standard for causal evidence that established the credibility of microbes as pathogens and led to the development of modern microbiology. In more recent times, Koch's postulates have evolved to accommodate a broader understanding of the host-parasite relationship as well as experimental advances. Techniques such as in situ hybridization, PCR, and representational difference analysis reveal previously uncharacterized, fastidious or uncultivated, microbial pathogens that resist the application of Koch's original postulates, but they also provide new approaches for proving disease causation. In particular, the increasing reliance on sequence-based methods for microbial identification requires a reassessment of the original postulates and the rationale that guided Koch and later revisionists. Recent investigations of Whipple's disease, human ehrlichiosis, hepatitis C, hantavirus pulmonary syndrome, and Kaposi's sarcoma illustrate some of these issues. A set of molecular guidelines for establishing disease causation with sequence-based technology is proposed, and the importance of the scientific concordance of evidence in supporting causal associations is emphasized.
The association between severe bronchiolitis and dual infection by human metapneumovirus (hMPV) and human respiratory syncytial
virus (hRSV) was investigated in !2-year-old infants with bronchiolitis who were admitted to the hospital during the 2001–2002
winter season. hMPV in nasopharyngeal aspirate and/or cells and fluid collected by nonbronchoscopic bronchoalveolar lavage
was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). hRSV was detected in nasopharyngeal aspirate and/or
cells and fluid collected by nonbronchoscopic bronchoalveolar lavage by enzyme immunoassay, tissue culture, and RT-PCR. Dual
infection with hMPV and hRSV confers a 10-fold increase in relative risk (RR) of admission to a pediatric intensive-care unit
for mechanical ventilation (RR, 10.99 [95% confidence interval, 5.0–24.12]; P < .001, by Fisher exact test). Dual infection by hMPV and hRSV is associated with severe bronchiolitis.
Community-acquired pneumonia (CAP) remains an important cause of morbidity and mortality. Polymerase chain reaction (PCR) has been shown to be more sensitive than current standard microbiological methods and, therefore, may improve the accuracy of microbiological diagnosis for patients with CAP.
Conventional detection techniques and multiplex real-time PCR for atypical bacteria and respiratory viruses were performed on samples collected from 105 adults enrolled in a prospective study. An infiltrate was visible on each patient's chest radiograph, and a pneumonia severity index score was determined for each patient.
Microbiological diagnoses were determined for 52 (49.5%) of 105 patients by conventional techniques and for 80 (76%) of 105 patients by real-time PCR. The time to obtain the result of real-time PCR could be reduced to 6 h. PCR methodology was significantly more sensitive for the detection of atypical pathogens and viruses (P< or =.001). Respiratory viral infections and mixed infections were detected in 15 (14.2%) and 3 (2.8%) of 105 patients, respectively, by conventional methods, but were detected in 59 (56.2%) and 28 (26.5%) of 105, respectively, by real-time PCR. Presence of a mixed infection was significantly associated with severe pneumonia (P=.002). Human rhinoviruses and coronaviruses, OC43 and 229E, were frequently identified pathogens.
The combined real-time PCR assay is more sensitive for diagnosis of the main viruses and atypical bacteria that cause CAP compared with conventional methods, and obtains results in a clinically relevant time period.
The identification of new virus species is a key issue for the study of infectious disease but is technically very difficult. We developed a system for large-scale molecular virus screening of clinical samples based on host DNA depletion, random PCR amplification, large-scale sequencing, and bioinformatics. The technology was applied to pooled human respiratory tract samples. The first experiments detected seven human virus species without the use of any specific reagent. Among the detected viruses were one coronavirus and one parvovirus, both of which were at that time uncharacterized. The parvovirus, provisionally named human bocavirus, was in a retrospective clinical study detected in 17 additional patients and associated with lower respiratory tract infections in children. The molecular virus screening procedure provides a general culture-independent solution to the problem of detecting unknown virus species in single or pooled samples. We suggest that a systematic exploration of the viruses that infect humans, “the human virome,” can be initiated.
• bioinformatics
• nucleotide sequencing
• respiratory tract infection
• virus
Human bocavirus (HBoV), a newly cloned human virus of the genus Bocavirus, was detected by PCR from nasopharyngeal swab samples (8 of 318; 5.7%) collected from children with lower respiratory tract
infections. HBoV may be one of the causative agents of lower respiratory tract infections in young children.
Molecular methods of pathogen discovery have recently led to the description of several new respiratory viruses. Human bocavirus (HBoV), a proposed member of the family Parvoviridae, is one of the most recently described respiratory viruses. Initial reports indicate that HBoV is a common cause of respiratory tract infection in children.
A total of 1474 nasal scraping specimens collected over a 20-month period were screened by polymerase chain reaction for the presence of HBoV nucleic acid. Positive results were confirmed with a second polymerase chain reaction assay from a different genomic region. The medical records of patients with positive results were reviewed for demographic and clinical data.
HBoV DNA was identified in 82 samples (5.6%). The peak rate of HBoV infection occurred during the period of March through May in both 2004 and 2005. Sixty-three percent of infected patients were <12 months of age. The most common symptoms were cough, rhinorrhea, and fever. Other symptoms of interest included diarrhea and a "paroxysmal" cough that was clinically suspected to be caused by Bordetella pertussis.
HBoV DNA is commonly present in children with upper and lower respiratory tract infections. The presence of a pertussis-like cough and diarrhea in association with HBoV infection merits further investigation.
This study was performed to evaluate the associations of newly recognized viruses, namely, human metapneumovirus (hMPV), human coronavirus (HCoV)-NL63, and human bocavirus (HBoV) with lower respiratory tract infections (LRTIs) in previously healthy children.
To determine the prevalences of 11 viruses--respiratory syncytial virus (RSV), adenovirus, rhinovirus, parainfluenza viruses (PIVs) 1 and 3, influenza viruses A and B, hMPV, HCoV, HCoV-NL63, and HBoV--among infants or children with LRTIs, in association with their epidemiologic characteristics, we performed multiplex reverse-transcriptase polymerase chain reaction on nasopharyngeal aspirates obtained from 515 children < or =5 years old with LRTIs during the period 2000-2005.
Viruses were identified in 312 (60.6%) of the 515 patients. RSV was detected in 122 (23.7%), HBoV in 58 (11.3%), adenovirus in 35 (6.8%), PIV-3 in 32 (6.2%), rhinovirus in 30 (5.8%), hMPV in 24 (4.7%), influenza A in 24 (4.7%), PIV-1 in 9 (1.7%), influenza B in 9 (1.7%), and HCoV-NL63 in 8 (1.6%). Coinfections with > or =2 viruses were observed in 36 patients (11.5%). Twenty-two patients (37.9%) infected with HBoV had a coinfection. Bronchiolitis was frequently diagnosed in patients who tested positive for RSV, PIV-3, or rhinovirus, whereas influenza A, PIV-1, and HCoV-NL63 were commonly found in patients with croup. The age distributions of patients with viral infections differed; notably, RSV was responsible for 77% of LRTIs that occurred in infants < or =3 months old. The number of hMPV infections peaked between February and April, whereas the number of HCoV-NL63 infections peaked between April and May.
This study describes the features of LRTIs associated with newly identified viruses in children, compared with those associated with known viruses. Additional investigations are required to define the role of HBoV in LRTI.
The recently discovered human bocavirus (HBoV) is the first member of the family Parvoviridae, genus Bocavirus, to be potentially associated with human disease. Several studies have identified HBoV in respiratory specimens from children
with acute respiratory disease, but the full spectrum of clinical disease and the epidemiology of HBoV infection remain unclear.
The availability of rapid and reliable molecular diagnostics would therefore aid future studies of this novel virus. To address
this, we developed two sensitive and specific real-time TaqMan PCR assays that target the HBoV NS1 and NP-1 genes. Both assays
could reproducibly detect 10 copies of a recombinant DNA plasmid containing a partial region of the HBoV genome, with a dynamic
range of 8 log units (101 to 108 copies). Eight blinded clinical specimen extracts positive for HBoV by an independent PCR assay were positive by both real-time
assays. Among 1,178 NP swabs collected from hospitalized pneumonia patients in Sa Kaeo Province, Thailand, 53 (4.5%) were
reproducibly positive for HBoV by one or both targets. Our data confirm the possible association of HBoV infection with pneumonia
and demonstrate the utility of these real-time PCR assays for HBoV detection.
This study presents the first evidence of human bocavirus infection in South Korean children. The virus was detected in 27 (8.0%) of 336 tested specimens, including 17 (7.5%) of 225 virus-negative specimens, collected from children with acute lower respiratory tract infection.
Human bocavirus was detected in 57 (18.3%) of 312 children with acute respiratory infection (ARI) who required hospitalization in Jordan. It was also detected in 30 (21.7%) of 138 children with severe ARI, in 27 (15.5%) of 174 with mild or moderate disease, and in 41 (72%) of 57 with other pathogens.
Human bocavirus was detected by PCR in 65 (5.1%) of 1,265 respiratory specimens collected in 2002 and 2003 from the Stollery
Children's Hospital from children <17 years of age. The spectrum of illness included upper respiratory infection, croup, bronchiolitis,
and pneumonia with a prominence of cough and fever.
The human bocavirus (HBoV) was recently isolated from respiratory tract samples. Within a study collective of children with
severe lower respiratory tract disease, the patients testing positive for HBoV (12.8%) had a higher rate of underlying cardiopulmonary
disease. Viral loads in respiratory tract specimens varied from 102 to 1010 genome equivalents/ml.
A quantitative PCR method was established to quantify human bocavirus (HBoV) genomic copies in clinical specimens from children with lower respiratory tract infections (LRTI) in China. A total of 257 respiratory tract specimens were tested, and 7 (2.7%) of these (all sputum samples) were positive, with genomic copies that ranged from 8.0 x 10(3) to 8.0 x 10(9) in the samples. The main clinical symptom of patients who were positive for HBoV DNA was a pneumonia-like syndrome represented by high fever and cough. Our results suggest that HBoV may be an important etiological agent of LRTI in children in China.
We have previously reported on a system for large-scale molecular virus screening of clinical samples. As part of an effort
to systematically search for unrecognized human pathogens, the technology was applied for virus screening of human respiratory
tract samples. This resulted in the identification of a previously unknown polyomavirus provisionally named KI polyomavirus.
The virus is phylogenetically related to other primate polyomaviruses in the early region of the genome but has very little
homology (<30% amino acid identity) to known polyomaviruses in the late region. The virus was found by PCR in 6 (1%) of 637
nasopharyngeal aspirates and in 1 (0.5%) of 192 fecal samples but was not detected in sets of urine and blood samples. Since
polyomaviruses have oncogenic potential and may produce severe disease in immunosuppressed individuals, continued searching
for the virus in different medical contexts is important. This finding further illustrates how unbiased screening of respiratory
tract samples can be used for the discovery of diverse virus types.
A newly identified parvovirus, human bocavirus (HBoV), was found in 21 (8.3%) of 252 nasopharyngeal aspirates from hospitalized children with lower respiratory tract infection in Hunan Province, People's Republic of China. Viral loads were 10(4) to 10(10) copies/mL. Phylogenetic analysis of the VP1 gene showed a single genetic lineage of HBoV worldwide.
Current antiretroviral therapy is effective in suppressing but not eliminating HIV-1 infection. Understanding the source of viral persistence is essential for developing strategies to eradicate HIV-1 infection. We therefore investigated the level of plasma HIV-1 RNA in patients with viremia suppressed to less than 50-75 copies/ml on standard protease inhibitor- or non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy using a new, real-time PCR-based assay for HIV-1 RNA with a limit of detection of one copy of HIV-1 RNA. Single copy assay results revealed that >80% of patients on initial antiretroviral therapy for 60 wk had persistent viremia of one copy/ml or more with an overall median of 3.1 copies/ml. The level of viremia correlated with pretherapy plasma HIV-1 RNA but not with the specific treatment regimen. Longitudinal studies revealed no significant decline in the level of viremia between 60 and 110 wk of suppressive antiretroviral therapy. These data suggest that the persistent viremia on current antiretroviral therapy is derived, at least in part, from long-lived cells that are infected prior to initiation of therapy.
We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus-specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.
In Spain, human bocavirus (HBoV) was detected in 48 (9.1%) of 527 children with gastroenteritis at similar frequency as for children with respiratory illness (40/520, 7.7%). Fecal excretion adds new concern about the transmission of HBoV. To our knowledge, this report is the first to document HBoV in human feces.
Over 100 years ago, Robert Koch introduced his ideas about how to prove a causal relationship between a microorganism and a disease. Koch's postulates created a scientific standard for causal evidence that established the credibility of microbes as pathogens and led to the development of modern microbiology. In more recent times, Koch's postulates have evolved to accommodate a broader understanding of the host-parasite relationship as well as experimental advances. Techniques such as in situ hybridization, PCR, and representational difference analysis reveal previously uncharacterized, fastidious or uncultivated, microbial pathogens that resist the application of Koch's original postulates, but they also provide new approaches for proving disease causation. In particular, the increasing reliance on sequence-based methods for microbial identification requires a reassessment of the original postulates and the rationale that guided Koch and later revisionists. Recent investigations of Whipple's disease, human ehrlichiosis, hepatitis C, hantavirus pulmonary syndrome, and Kaposi's sarcoma illustrate some of these issues. A set of molecular guidelines for establishing disease causation with sequence-based technology is proposed, and the importance of the scientific concordance of evidence in supporting causal associations is emphasized.
Respiratory syncytial virus (RSV), originally recovered from a colony of chimpanzees with coryza and designated chimpanzee coryza agent,1,2 and human parainfluenza virus types 1, 2, 3, and 4 have been known primarily as respiratory pathogens in young children. They are now recognized as important pathogens in adults as well. Adults infected with these viruses tend to have more variable and less distinctive clinical findings than children, and the viral cause of the infection is often unsuspected. The consistency of the annual outbreaks of these agents and the frequency of reinfection suggest that they impose a considerable, but ill-defined, disease . . .
Koch's postulates were derived from Robert Koch's work on infectious diseases, such as anthrax and tuberculosis, which still engage us to this day. These guidelines were an attempt to establish a standard for identifying the specific causation of an infectious disease and to convince sceptics that microorganisms could cause disease. They were also established to encourage an increasing number of novice microbiologists to use more rigorous criteria before claiming a causal relationship between a microorganism and a disease.
Undiagnosed cases of respiratory tract disease suspected of an infectious aetiology peak during the winter months. Since studies applying molecular diagnostic assays usually report reductions in the number of undiagnosed cases of infectious disease compared to traditional techniques, we applied PCR assays to investigate the role of two recently described viruses, namely human coronavirus (HCoV) HKU1 and human bocavirus (HBoV), in a hospital-based paediatric population. Both viruses were found among Australia children with upper or lower respiratory tract disease during the autumn and winter of 2004, contributing to 21.1% of all microbial diagnoses, with individual incidences of 3.1% (HCoV-HKU1) and 5.6% (HBoV) among 324 specimens. HBoV was found to coincide with another virus in more than half of all instances and displayed a single genetic lineage, whilst HCoV-HKU1 was more likely to occur in the absence of another microbe and strains could be divided into two genetic lineages which we propose be termed HCoV-HKU1 type A and type B. Children under the age of 2 years were most at risk of infection by these viruses which contribute significantly to the microbial burden among patients with respiratory tract disease during the colder months.
Viruses are the major cause of pediatric acute respiratory tract infection (ARTI) and yet many suspected cases of infection remain uncharacterized. We employed 17 PCR assays and retrospectively screened 315 specimens selected by season from a predominantly pediatric hospital-based population. Before the Brisbane respiratory virus research study commenced, one or more predominantly viral pathogens had been detected in 15.2% (n = 48) of all specimens. The Brisbane study made an additional 206 viral detections, resulting in the identification of a microbe in 67.0% of specimens. After our study, the majority of microbes detected were RNA viruses (89.9%). Overall, human rhinoviruses (HRVs) were the most frequently identified target (n = 140) followed by human adenoviruses (HAdVs; n = 25), human metapneumovirus (HMPV; n = 18), human bocavirus (HBoV; n = 15), human respiratory syncytial virus (HRSV; n = 12), human coronaviruses (HCoVs; n = 11), and human herpesvirus-6 (n = 11). HRVs were the sole microbe detected in 37.8% (n = 31) of patients with suspected lower respiratory tract infection (LRTI). Genotyping of the HRV VP4/VP2 region resulted in a proposed subdivision of HRV type A into sublineages A1 and A2. Most of the genotyped HAdV strains were found to be type C. This study describes the high microbial burden imposed by HRVs, HMPV, HRSV, HCoVs, and the newly identified virus, HBoV on a predominantly paediatric hospital population with suspected acute respiratory tract infections and proposes a new formulation of viral targets for future diagnostic research studies.
We describe a case of bronchiolitis associated with the newly detected human bocavirus (hBoV) in a child with a suspected Noonan syndrome. This is the first report of a bronchiolitis probably linked to hBoV that required intensive care while being accompanied by a congenital heart disease and a history of several episodes of severe respiratory symptoms.
Human bocavirus (HBoV) and PARV4 are newly discovered human parvoviruses. HBoV, which was first detected in respiratory samples, has a potential role in the development of human respiratory disease. The present study compared the frequencies, epidemiological profiles, and clinical backgrounds of HBoV and PARV4 infections with those of other respiratory virus infections, by evaluating diagnostic samples referred to the Specialist Virology Laboratory (SVL) at the Royal Infirmary of Edinburgh (Edinburgh, United Kingdom).
Anonymized samples and study subject information were obtained from the respiratory sample archive of the SVL. Samples were screened for HBoV, PARV4, B19, respiratory syncytial virus (RSV), adenoviruses, influenza viruses, and parainfluenza viruses by use of nested polymerase chain reaction.
HBoV infection was detected in 47 (8.2%) of 574 study subjects, ranking third in prevalence behind RSV infection (15.7%) and adenovirus infection (10.3%). Peak incidences of HBoV were noted among infants and young children (age, 6-24 months) during the midwinter months (December and January) and were specifically associated with lower respiratory tract infections. HBoV infections were frequently accompanied by other respiratory viruses (frequency, 43%), and they were more prevalent among individuals infected with other respiratory viruses (17%), frequently adenovirus or RSV. All respiratory samples were negative for PARV4.
In the present study, HBoV was a frequently detected, potential respiratory pathogen, with a prevalence and an epidemiological profile comparable to those of RSV. Identification of HBoV infections may be clinically important in the future.
Human bocavirus (HBoV) is a newly identified human parvovirus that was originally identified in the respiratory secretions of children with respiratory tract disease. To further investigate the epidemiological profile and clinical characteristics of HBoV infection, we screened infants and children <2 years of age (hereafter referred to as "children") for HBoV.
Children for whom respiratory specimens submitted to a diagnostic laboratory tested negative for respiratory syncytial virus, parainfluenza viruses (types 1-3), influenza A and B viruses, and adenovirus, as well as asymptomatic children, underwent screening for HBoV by use of polymerase chain reaction (PCR). Respiratory specimens were obtained from the children from 1 January 2004 through 31 December 2004.
Twenty-two (5.2%) of the 425 children who had a respiratory specimen submitted to the diagnostic laboratory and 0 of the 96 asymptomatic children were found to be positive for HBoV by PCR (P=.02). Fever, rhinorrhea, cough, and wheezing were observed in > or =50% of the HBoV-positive children. Of the 17 children who had chest radiography performed, 12 (70.6%) had abnormal findings. HBoV appeared to have a seasonal distribution. Nucleotide polymorphisms were detected in the viral capsid protein (VP) 1/VP2 genes. Two distinct HBoV genotypes circulated during the study period.
HBoV is circulating in the United States and is associated with both upper and lower respiratory tract disease in infants and young children.
hBoV, a recently discovered parvovirus, can be present in the respiratory tract of patients with acute respiratory diseases (ARD), but its etiologic involvement in the underlying diseases is still uncertain.
To determine in a retrospective study, the prevalence of hBoV, compared with common respiratory viruses (RV), in respiratory specimens from patients with ARD.
A total of 335 specimens obtained over 7 years were examined. Two hundred were nasal swabs from infants hospitalized for ARD, 84 were nasal swabs or bronchoalveolar lavages from adults with pneumonia, bronchopneumonia or asthma, and 51 were nasal swabs from healthy children.
The overall rate of hBoV detection in specimens from infants with ARD, which was 4.5%, varied slightly from year to year, except for the period 2000-2002, when no specimen was positive. Unlike other RV, no seasonal variation in hBoV incidence was noted. Infants with hBoV infection suffered either from bronchiolitis or from bronchopneumonia and 5 out of 9 cases yielded no co-infecting viral pathogen. Only one sample from an adult was hBoV positive. None of the nasal swabs from healthy subjects tested hBoV-positive.
The findings indicate that hBoV can cause ARD in infants.
sis of discharge data to compare find- ings from the United States with data from Germany. We therefore deter- mined the absolute number of inpa- tient discharges from all hospitals in Germany with the number of dis- charge diagnoses of CDAD reported in the national Statistische Bundesamt for the years 2000-2004. We then cal- culated the incidence of CDAD as a discharge diagnosis for each year and stratified our results by age groups (Figure). Our results confirm the observa- tions from the United States. The effect of C. difficile on illness of patients in hospitals in Germany has escalated dramatically. This is true especially for patients >60 years of age. This trend indicates the need for increased awareness of this pathogen and a concerted effort to control CDAD by reducing unnecessary antimicrobial drug use and imple- menting currently recommended infection control measures. It also highlights the need to develop more rapid and accurate diagnostic tools and more effective prevention and treatment strategies.
Human bocavirus (HBoV), a virus discovered in Sweden in 2005, has been associated with acute respiratory infections in young children and subsequent reports suggest that HBoV may have a worldwide distribution. This report describes the frequency and clinical presentation of HBoV in 261 Iranian children<5 years old with acute respiratory infections attending two regional hospitals in Rasht, Iran in the winter of 2003-2004. Polymerase chain reaction (PCR) and reverse transcription PCR (RT-PCR) were used for the detection of HBoV and other respiratory pathogens from nasopharyngeal specimens. HBoV was detected in 21 (8%) children. Fifteen (12%) of these children were identified among 122 children admitted to hospital and 6 (4%) from 139 outpatients (P < 0.05). Most children with HBoV were less than 2 years (17/21, 81%) and 7 (33%) were less than 1 year old. Although HBoV was identified in all ages it affected slightly older children than the respiratory syncytial virus (RSV). The frequency of the virus varied from 1 (3%) in 40 patients in November to 7 (12%) of 61 in February, suggesting a seasonal pattern during the autumn and early winter. Seven children had co-infections with RSV, adenovirus or influenza A. The relatively high frequency of HBoV suggests that the virus may contribute substantially to acute respiratory infections in children.
Human rhinoviruses (HRVs) are some of the earliest identified and most commonly detected viruses associated with acute respiratory tract infections (ARTIs) and yet the molecular epidemiology and genomic variation of individual serotypes remains undefined.
To molecularly characterise a novel HRV and determine its prevalence and clinical impact on a predominantly paediatric population.
Nucleotide sequencing was employed to determine the complete HRV-QPM coding sequence. Two novel real-time RT-PCR diagnostic assays were designed and employed to retrospectively screen a well-defined population of 1244 specimen extracts to identify the prevalence of HRV-QPM during 2003.
Phylogenetic studies of complete coding sequences defined HRV-QPM as a novel member the genus Rhinovirus residing within the previously described HRV-A2 sub-lineage. Investigation of the relatively short VP1 sequence suggest that the virus is resistant to Pleconaril, setting it apart from the HRV A species. Sixteen additional HRV-QPM strains were detected (1.4% of specimens) often as the sole micro-organism present among infants with suspected bronchiolitis. HRV-QPM was also detected in Europe during 2006, and a closely related virus circulated in the United States during 2004.
We present the molecular characterisation and preliminary clinical impact of a newly identified HRV along with sequences representing additional new HRVs.
Human bocavirus (HBoV) is a recently discovered parvovirus associated with respiratory tract infections in children. We conducted the first systematic prospective clinical and molecular study using nasopharyngeal aspirates (NPAs) and fecal samples.
NPAs negative for influenza virus, parainfluenza virus, respiratory syncytial virus, adenovirus, and coronavirus and fecal samples from patients with acute gastroenteritis were included. On the basis of results from a pilot study using 400 NPAs from all age groups, a prospective 12-month study was conducted to detect HBoV in 1,200 NPAs and 1,435 fecal samples from patients <18 years old by polymerase chain reaction. The complete genome sequences of HBoVs from 12 NPAs and 12 fecal samples were determined.
Of the 400 NPAs collected in the pilot study, 20 (5.0%) were found to contain HBoV, all from children <5 years old. In the subsequent prospective study of pediatric patients, HBoV was detected in 83 (6.9%) of 1,200 NPAs. Upper and lower respiratory tract infections were equally common. HBoV was detected in 30 (2.1%) of 1,435 fecal samples. Fever and watery diarrhea were the most common symptoms. The seasonality of HBoV in NPAs and fecal samples was similar. Codetection with other pathogens occurred in 33% and 56% of NPAs and fecal samples, respectively, from patients with HBoV infection. Genomes of HBoVs from NPAs and fecal samples displayed minimal sequence variations.
HBoV was detected in fecal specimens in children with acute gastroenteritis. A single lineage of HBoV was associated with both respiratory tract and enteric infections.
Human bocavirus infection among children
- Nm Kaplan
- W Dove
- Af Bu-Zeid
Kaplan NM, Dove W, bu-Zeid AF. Human
bocavirus infection among children, Jordan.
Emerg Infect Dis 2006; 12:1418–20.