Human bocavirus respiratory infection: Tracing the path from viral replication and virus-cell interactions to diagnostic methods.

Human bocaviruses were first described between 2005 and 2010, identified in respiratory and enteric tract samples of children. Screening studies have shown worldwide distribution. Based on phylogenetic analysis, they were classified into four genotypes (HBoV1-4). From a clinical perspective, human bocavirus 1 (HBoV1) is considered the most relevant, since it can cause upper and lower acute respiratory tract infection, mainly in infants, including common cold, bronchiolitis, and pneumonia, as well as wheezing in susceptible patients. However, the specific processes leading to structural, biochemical, and functional changes resulting in the different clinical presentations have not been elucidated yet. This review surveys the interactions between the virus and target cells that can potentially explain disease-causing mechanisms. It also summarises the clinical phenotype of cases, stressing the role of HBoV1 as an aetiological agent of lower acute respiratory infection in infants, together with laboratory tests for detection and diagnosis. By exploring the current knowledge on the epidemiology of HBoV1, insights into the complex scenario of paediatric respiratory infections are presented, as well as the potential effects that changes in the circulation can have on the dynamics of respiratory agents, spotlighting the benefits of comprehensively increase insights into incidence, interrelationships with co-circulating agents and potential control of HBoV1.

Circulation of human coronaviruses OC43 and 229E in Córdoba, Argentina.

This is the first study of respiratory infections in Córdoba, Argentina, caused by endemic human coronavirus (HCoV)-OC43 and HCOV-229E, which circulated during 2011-2012 at a 3% rate, either as single or multiple infections. They were detected mainly in children, but HCoV-229E was also found in adults. HCoV-229E was detected in five out of 631 samples (0.8%), and HCoV-OC43 was found in 14 out of 631 (2.2%) samples. Clinical manifestations ranged from fever to respiratory distress, and a significant association of HCoV-229E with asthma was observed. Further studies and surveillance are needed to provide better clinical insights, early diagnosis, and medical care of patients, as well as to contribute to epidemiology modeling and prevention.

Comorbidity and high viral load linked to clinical presentation of respiratory human bocavirus infection.

Human bocavirus (HBoV) is a new parvovirus associated with acute respiratory tract infection (ARTI). In order to evaluate HBoV significance as an agent of acute respiratory disease, we screened 1,135 respiratory samples from children and adults with and without symptoms during two complete calendar years. HBoV1 prevalence in patients with ARTI was 6.33 % in 2011 and 11.64 % in 2012, including neonatal and adult patients. HBoV1 was also detected in 3.77 % of asymptomatic individuals. The co-detection rate was 78.1 %. Among children, 87 % were clinically diagnosed with lower respiratory infection (no significant differences between patients with and without coinfection), and 31 % exhibited comorbidities. Pediatric patients with comorbidities were significantly older than patients without comorbidities. Patients with ARTI had either high or low viral load, while controls had only low viral load, but there were no clinical differences between patients with high or low viral load. In conclusion, we present evidence of the pathogenic potential of HBoV1 in young children with ARTI. Since patients with HBoV1-single infection are not significantly different from those with coinfection with respect to clinical features, the virus can be as pathogenic by itself as other respiratory agents are. Furthermore, an association between high HBoV1 load and disease could not be demonstrated in this study, but all asymptomatic individuals had low viral loads. Also, children with comorbidities are susceptible to HBoV1 infection at older ages than previously healthy children. Thus, the clinical presentation of infection may occur depending on both viral load and the particular interaction between the HBoV1 and the host.

Clinical characterization of human bocavirus 1 infection in infants hospitalized in an intensive care unit for severe acute respiratory tract disease.

Acute respiratory infections represent the leading cause of morbimortality in children and viruses are the main etiological agents. Here we describe the clinical characteristics and evolution of infants admitted to intensive care unit with severe acute respiratory infection (SARI) due to Human Bocavirus 1 mono-infection in patients without previous comorbidity. We also compared them with respiratory syncytial virus (RSV) cases. Of 141 cases included (age 5.43 ± 4.54 months, 52% male), 80% had at least 1 virus detected. RSV was the most frequent in the series (71.6%) followed by HBoV1 (28%). Five cases of HBoV1 mono-detection were identified. Pediatric acute respiratory distress syndrome was present in both groups, HBoV1 and RSV. The clinical presentation and evolution of HBoV1 single infection was similar to RSV. HBoV1 should be included among the agents investigated in cases of SARI in infants.

Measles and Rubella Seroprevalence Among Children and Adolescents of Córdoba, Argentina: A Cross-Section Study in the Context of the Elimination Program.

We determined anti-rubella and anti-measles immunoglobulin G (IgG) in 7- to 19-year-old children and adolescents with vaccine only-induced immunity of Córdoba, Argentina, during a 6-month period over 2021-2022. Of the 180 individuals studied, 92.2% and 88.3% were positive for anti-measles and anti-rubella IgG, respectively. No significant differences were found comparing anti-rubella IgG concentrations (p = 0.144) and anti-measles IgG concentrations (p = 0.105) of individuals classified by age, but anti-measles IgG and anti-rubella IgG levels were significantly higher among female individuals compared with males (p = 0.031 and p = 0.036, respectively). Female subjects in the younger age group had higher concentrations of anti-rubella IgG as well (p = 0.020), even when anti-measles IgG concentrations did not differ among female age-subgroups (p = 0.187). In contrast, age subgroups of male individuals did not have significantly different IgG concentrations for rubella (p = 0.745) or measles (p = 0.124). Among samples with discordant results (22/180, 12.6%), 9.1% were negative for rubella but positive for measles; 13.6% were equivocal for rubella and positive for measles; 22.7% were equivocal for rubella and negative for measles, while 54.5% were positive for rubella but negative for measles. The findings indicate a seroprevalence below recommended for preventing measles in the population studied, while they evidence the need for standardization of serological tests for rubella IgG.

Human parvovirus B19 infection in a pregnant patient resulting in severe hydrops, foetal death and persistent infection.

Human parvovirus B19 (B19V) is the aetiological agent of erythema infectiosum. Primary infection during pregnancy can be transmitted to the foetus and cause foetal abnormalities related to depletion of erythrocyte progenitor cells, including congenital anaemia, hydrops, and foetal death. In this paper we report the detection of B19V infection in a pregnant patient, which onset occurred without appreciable signs and symptoms until she developed inappropriate contractions for gestational age and fluid loss. B19V infection resulted in severe hydrops fetalis with a fatal course for the foetus, while persisted in the mother at least 12 months after foetal death. The objective of this report is to highlight the importance of optimizing B19V diagnosis through early suspicion and testing during pregnancy. Knowing the mother's immune status before or at the beginning of gestation can contribute, together with early diagnosis, to improve the management of patients at risk.

Diagnosis and clinical significance of Human bocavirus 1 in children hospitalized for lower acute respiratory infection: molecular detection in respiratory secretions and serum.

Introduction. Human bocavirus 1 (HBoV1) infection occurs with viral genome presence in respiratory secretions (RS) and serum, and therefore both samples can be used for diagnosis.Gap statement. The diagnostic sensitivity of HBoV1 DNA detection in serum and the duration of DNAaemia in severe clinical cases have not been elucidated.Aim. To determine HBoV1 DNA in serum and RS of paediatric patients hospitalized for lower acute respiratory infection (LARI) and to analyse the clinical-epidemiological features of positive cases.Methodology. This was a prospective, transverse study. Physicians selected the clinical situations and obtained paired clinical samples (RS and serum) that were tested by PCR/qPCR for HBoV1. Positive cases were analysed considering time of specimen collection, co-detection, clinical manifestations and viral load; statistical significant level was set at α=0.05.Results. HBoV1 was detected in 98 of 402 cases included (24 %); 18/98 (18 %) patients had the virus detectable in serum and 91/98 (93 %) in RS (P<0.001). Positivity rates were not significantly different in patients with RS and serum collected within or beyond 24 h of admission. Single HBoV1 infection was identified in 39/98 patients (40 %), three patients had HBoV1 in both clinical samples (3/39, 8 %) and 32 (32/39, 82 %) only in RS, 22 of them (69 %) with both clinical samples within 24 h of admission. Cough (P=0.001) and rhinitis (P=0.003) were significantly frequent among them and most patients were diagnosed with bronchiolitis (22/39, 56 %) and pneumonia (9/39, 23 %), which was more frequent compared to cases with co-infection (P=0.04). No significant differences were identified among patients with high, medium or low viral load of HBoV1 regarding rate of positivity in both clinical samples, the time of collection of RS and serum, co-detection, first episode of LARI, clinical manifestations, comorbidity or requirement for assisted ventilation. Intensive care unit (ICU) patients had a significantly higher frequency of detection (P<0.001) and co-detection (P=0.001) compared to patients on standard care.Conclusions. HBoV1 is prevalent among infant patients hospitalized for LARI and including it in the standard testing can add to the aetiological diagnosis in these cases, especially for patients admitted to the ICU. HBoV1 detection in serum did not contribute significantly to the diagnosis as compared to detection in respiratory secretions.

Human Metapneumovirus: Epidemiology and genotype diversity in children and adult patients with respiratory infection in Córdoba, Argentina.

Human Metapneumovirus (hMPV) is responsible for acute respiratory infections in humans, with clinical and epidemiological relevance in pediatric, elderly, and immunocompromised populations. These features are largely unknown in Córdoba, Argentina and in adults in general. Hence, our goal was to broadly characterize hMPV infection in patients of all ages hospitalized with acute respiratory infections in Córdoba, Argentina, including epidemiology, clinical features and genetic diversity. Nasopharyngeal secretions were obtained from 795 patients during 2011-2013, 621 patients were 0-25 years old and 174 were 26-85 years old. HMPV was assayed by RT-PCR and other respiratory viruses by indirect immunofluorescence. Local strains were identified by sequence analysis. Human Metapneumovirus was detected in 20.3% (161/795) patients, 13.1% as single infections and 7.2% in co-infections, more frequently with Respiratory Syncytial Virus. HMPV circulated during late winter and spring in all age patients, but mainly in children under 4 years old in 71.4% (115/161) and adults between 26 and 59 years old in 12.4% (20/161). The most prevalent diagnosis was mild acute respiratory infection in 59.6% (96/161) and bronchiolitis in 9.3% (15/161). Local strains were clustered within A2 subtype; they presented 73-100% identities among them, showing a high degree of homology compared to isolations from neighboring countries. We demonstrate that hMPV circulated among all age patients with respiratory infection during 2011-2013 in Córdoba, contributing to the understanding of this virus, its diagnosis and patient handling in local health-care centers.

Human parvovirus B19 frequency among blood donors after an epidemic outbreak: relevance of the epidemiological scenario for transfusion medicine.

A retrospective, cross-sectional study was conducted to determine the frequency of human parvovirus B19 (B19V) infected individuals, viral loads and immunity among blood donors from Argentina, in a post-epidemic outbreak period. B19V DNA and specific IgG were tested in minimum study samples of donors attending a blood bank at Córdoba, Argentina, in 2014. Anti-B19V IgM and viral loads were determined in B19V-positive plasma samples. Seven of 731 samples (0.96%) resulted positive, corresponding to individuals aged 32-53 years, four of them repeat donnors and three first-time donors. Viral loads were <103 IU/mL. None had IgM and 6/7 had IgG, one of them at a high level (in the range of 100-200 IU/ml, and the remaining 5 at low to medium level, 5-50 IU/ml). Thus one case was classified as acute infection (DNA+/IgM-/IgG-) and six as potentially persistent infections (DNA+/IgM-/IgG+). No coinfections with other pathogens of mandatory control in the pre-transfusion screening were detected. Prevalence of IgG was 77.9% (279/358). This study provides the first data of B19V prevalence in blood donors in Argentina, demonstrating high rates of acute and persistent B19V infections and high prevalence of anti-B19V IgG in a post-epidemic period. Further research is needed to elucidate mechanisms/factors for B19V persistence as well as follow-up of recipients in the context of haemo-surveillance programs, contributing to the knowledge of B19V and blood transfusion safety.

Molecular screening of the human parvoviruses B19 and bocavirus 1 in the study of congenital diseases as applied to symptomatic pregnant women and children.

INTRODUCTION: B19 virus (B19V) and bocavirus 1 (HBoV1) are human pathogenic parvoviruses that are prevalent worldwide and are responsible for a diverse and not yet fully established spectrum of clinical manifestations. OBJECTIVE: To screen B19V and HBoV1 in patients with clinical manifestations associated with acquisition of the infection during gestation. METHODS: A retrospective, observational study was performed that included serum samples from patients without a previous known aetiology. B19V and HBoV1 were determined by end-point PCR. Positive samples were genotyped. RESULTS: A total of 106 serum samples were analysed, 61 from pregnant women and 45 from neonates and paediatric patients. None were positive for HBoV1, while B19V was detected in 37/106 [34.9 %, 95 % confidence interval (CI): 26.5-44.4] of the samples studied. In the group of pregnant women, 28/61 (45.9 %, 95 % CI: 34.0-58.3) were B19V-positive, and 2 of them had foetal anaemia followed by hydrops and foetal death, 3 were associated with a history of recurrent pregnancy loss and there was 1 case of spontaneous abortion. B19V was also detected in cases of maternal febrile exanthema, polyhydramnios, oligohydramnios and foetal ascites. In the group of children, 9/45 (20.0 %, 95 % CI: 10.9-33.8) neonatal patients were B19V-positive, and this was associated with foetal hydrops, TORCH syndrome and cardiac alterations. The nucleotide sequences analysed confirmed the identity of B19V genotype 1. CONCLUSIONS: We found no evidence to indicate the presence of HBoV1 in maternal blood or in the newborns/paediatric patients (hence providing no support for the supposed vertical transmission). On the other hand, the high frequency of B19V in the pathologies studied indicates the importance of molecular diagnosis in both the mother and the child. Future efforts should contribute to early detection and characterization of infections.

[Human Bocavirus 1: role in the acute respiratory infection and epidemiology in Cordoba, Argentina]. / Bocavirus Humano 1: su participación en la infección respiratoria aguda y epidemiología en Argentina.

Human bocavirus 1 (HBoV1) is an agent of acute respiratory infection frequent in children. It can cause pneumonia in infants, in the absence of epidemiological risk factors and comorbidities. Well-controlled studies of clinical cases and case series are still useful for the characterization of the clinicoepideiological features of the infection, while research dives on the molecular biology of the virus and the virus-cell relationship allowing to unveil tha natural history of the infection. This article reviews the state of the art and future perspectives on this new human parvovirus and its etiological role in the respiratory pathology.

Human bocavirus 1 infection of CACO-2 cell line cultures.

Human bocavirus 1 (HBoV1) is a parvovirus associated with pneumonia in infants. It has been detected in different tissues, including colorectal tumors. In this study, we investigated whether Caco-2 cell line, derived from human colon cancer, can be utilized as a model for HBoV1 replication. We demonstrate HBoV1 replication in Caco-2 cultures supplemented with DEAE-dextran after inoculation with respiratory material from infected patients presenting with acute respiratory infection. A viral cycle of rapid development is displayed. However, in spite of HBoV1 DNA 4-fold increment in the supernatants and monolayers by day 1, evidencing that the system allows the virus genome replication after the entry occurred, infectious progeny particles were not produced. These results are consistent with an infection that is limited to a single growth cycle, which can be associated to mutations in the NS1 and VP1/VP2 regions of HBoV1 genome. Further research will contribute to fully elucidate these observations.

Parvovirus B19 in HIV+ adult patients with different CD4+ lymphocyte counts.

PURPOSE: Human parvovirus B19 (B19V) can cause anemia in immunocompromised patients. We aimed to investigate the presence of B19V in HIV+ adults with different CD4+ T cell counts, to recognise the frequency of B19V in these different conditions and its possible association with anemia. METHODOLOGY: We studied B19V specific IgM, IgG and DNA in 98 HIV+ patients and in 52 healthy individuals. HIV load, CD4+ counts and haemoglobin level were also determined in the patients. RESULTS: No individual in the control group had detectable IgM, 41/52 (78.8 %) had IgG and 5/52 (9.6 %) had B19V DNA. Among HIV+ patients, we found 5/98 (5.1 %) IgM+, 66/98 (67.3 %) IgG+ and 15/98 (15.3 %) had B19V DNA (no significant differences between the two groups compared). Considering the CD4+ cell range in HIV patients, 37 had <200 CD4+ cells ml-1, 31 had 200-500, and 30 had >500. Anti-B19V IgG prevalence in patients with >500 CD4+ cells ml-1 was significantly higher than in the rest (P=0.004) and compared to the control (P=0.046). B19V DNA concentration was always <103 IU ml-1, including 5 healthy individuals and 15 HIV+ patients. There was no significant association between B19V IgM or DNA and anemia nor between B19V DNA and HIV load. CONCLUSIONS: The results indicate that B19V is not a high-risk factor for anemia in adult HIV+ patients under HAART treatment. Further studies will contribute to elucidate the mechanisms and significance of B19V DNA prevalence/persistence in adults, independently of the CD4+ cell status.

[Monoinfection of human Metapneumovirus in Cordoba: first clinical and epidemiological research in children with respiratory infection in 2011]. / Monoinfección de Metapneumovirus humano en Córdoba: primeras investigaciones clínico-epidemiológicas en niños con infección respiratoria en 2011.

Human metapneumovirus (hMPV) RNA virus discovered in 2001, is a pathogen associated with acute respiratory infection (ARI) in children under 5 years; its prevalence ranges from 5-15%. In Córdoba, it is not integrated into the viral research in patients with low IRA (LARI). OBJECTIVE: Detect hMPV in children under 5 years hospitalized for LARI in the Children's Hospital "Santísima Trinidad" of Cordoba (HNC) in 2011 and describe the clinical and epidemiological characteristics of monoinfecciones without comorbidity. POPULATION AND METHOD: Prospective, observational study. It includes (informed consent) children under 5 years with LARI of HNC from January to December 2011. The viral detection was performed using immunofluorescence of nasopharyngeal aspirate secretions. Demographic, epidemiological and clinical data of positive cases were recorded. RESULTS: Of 223 patients enrolled, respiratory viruses were detected in 74 (33.2%). HMPV prevalence was 4.04% (9/223), representing the 2nd place with Parainfluenza 3 (4.04%) after RSV (19.73%). Season from July to December. The average age for hMPV was 7.4 ± 6.8 months (0-60 months), 4/9 males. The average hospital stay in days was 5.6 ± 0.5 and prodrome days: 1.9 days ± 0.6. All patients require oxygen therapy (3.9 ± 1.3 days) without mechanical ventilation. Diagnosis of bronchiolitis cases occurred in 5/9 and 4/9 pneumonia. No complications at discharge. CONCLUSIONS: First report to document the presence of hMPV in child population of Cordoba. Its prevalence in 2011 was 4, 04%. Among monoinfecciones no fatalities or complications at discharge were recorded.

Metapneumovirus humano (MPVh), virus ARN descubierto en 2001, es un patógeno relacionado con infección respiratoria aguda (IRA) en menores de 5 años; su prevalencia oscila entre el 5-15%. En Córdoba no está integrado a la pesquisa viral en pacientes con IRA baja (IRAB). Objetivo. Detectar MPVh en menores de 5 años hospitalizados por IRAB en el Hospital de Niños de la Santísima Trinidad de Córdoba (HNC) durante el 2011 y describir características clínico-epidemiológicas de las monoinfecciones sin comorbilidad previa. Población y método. Estudio prospectivo, observacional. Participaron (consentimiento informado) menores de 5 años con IRAB del HNC desde enero a diciembre de 2011. La detección viral se realizó con Inmunofluorescencia de aspirado de secreciones nasofaríngeas. Se registraron datos demográficos, epidemiológicos y clínicos de los casos positivos. Resultados. De 223 pacientes incluidos, se detectó algún virus respiratorio en 74 (33,2%). La prevalencia de MPVh fue de 4,04% (9/223), representando el 2° lugar con Parainfluenza 3 (4,04 %), luego de VRS (19,73%). Estacionalidad julio-diciembre. La edad media para MPVh fue de 7,4±6,8 meses (0 a 60 meses), 4/9 varones. La media de hospitalización fue de 5,6±0,5 días, y de pródromo 1,9±0,6 días. Todos requirieron oxigenoterapia (3,9±1,3 días) sin asistencia respiratoria mecánica. Diagnóstico de bronquiolitis en 5/9 casos y neumonía en 4/9. Sin complicaciones al alta. Conclusiones. Primer trabajo en documentar la presencia de MPVh en población infantil de Córdoba. Su prevalencia durante el 2011 fue del 4, 04 %. Entre las monoinfecciones no se registraron casos fatales ni complicaciones al momento del alta.

[First report of complete genome sequence and phylogenetic analysis of Human Bocavirus 1 isolated in Argentina]. / Primer reporte de secuencia genómica completa y análisis filogenético de Bocavirus Humano 1 aislado en Argentina.

ANTECEDENTS: Human bocavirus (HBoV) is a parvovirus identified for the first time in 2005 associated to upper- and lower- acute respiratory tract infection (ARI), which is one of the main causes of morbimortality in infant population worldwide. Currently four genotypes have been described named HBoV1-4, of which HBoV1 is the one predominantly related to ARI. OBJECTIVE: To obtain the complete genome of respiratory HBoV locally isolated. METHODS: By means of bioinformatics tools such as ClustalW and NCBI Primer-Blast, primers were designed to amplify overlapping DNA fragments altogether spanning the complete genome of HBoV. Fragments were amplified by PCR and sequenced by BigDye Terminator capillary technology. Sequence editing and phylogenetic analysis were accomplished using MEGA v6 software. RESULTS: Complete genome sequence of HBoV1 strain 307AR09 was obtained after isolation from respiratory secretion of a pediatric patient with bronchiolitis. The sequence was deposited in the GenBank public database (accession number KJ634207). The phylogenetic analysis including complete genome sequences of all four genotypes from around the world shows similarity close to 100% between the local strain and the virus originally discovered in Sweden (DQ000495). The four genotypes clustered in 2 groups of high internal homology: HBoV1-HBoV3 and HBoV2-HBoV4. CONCLUSIONS: We provide local molecular data that can be used in future technological developments for research and diagnostic tests intended for medical practice. Our results add support to the proposed redistribution of the four genotypes into 2 species.

Antecedentes. El Bocavirus humano (HBoV) es un parvovirus descripto por primera vez en 2005, asociado a cuadros leves y graves de infección respiratoria aguda (IRA), una de las principales causas de morbimortalidad en la población infantil en todo el mundo. Al presente se han identificado 4 genotipos, nombradas HBoV1 a 4, de los cuales el primero es el que se asocia a IRA con predominancia. Objetivo. Obtener el genoma completo de HBoV respiratorio aislado localmente. Métodos. Se diseñaron primers para fragmentos superpuestos del genoma completo de HBoV, empleando las herramientas informáticas ClustalW y NCBI Primer-Blast. Los fragmentos se amplificaron por PCR convencional y se secuenciaron mediante tecnología capilar BigDye Terminator. La edición de las secuencias y análisis filogenético se realizó con el programa MEGA v6. Resultados. Se obtuvo la secuencia genómica completa de HBoV1 cepa 307AR09, aislada de secreción respiratoria de paciente pediátrico con bronquiolitis. La misma fue depositada en la base de datos GenBank con número de acceso KJ634207. El análisis filogenético con secuencias genómicas completas de los 4 genotipos obtenidas en distintas regiones del mundo muestra similitud cercana al 100% con la secuencia original descubierta en Suecia (DQ000495), así como el agrupamiento de los 4 genotipos en 2 clusters de alta homología interna: HBoV1-HBoV3 y HBoV2-HBoV4. Conclusiones. Se aportan datos locales para futuros desarrollos tecnológicos destinados tanto a la investigación como al diseño de métodos diagnósticos para la práctica médica. Por otra parte, los resultados sustentan la propuesta de redistribución taxonómica de los 4 genotipos en 2 especies.

Human bocavirus respiratory infection in infants in Córdoba, Argentina.

UNLABELLED: It has been suggested that human bocavirus (HBoV) is related to acute respiratory infection (ARI) in children (prevalence: 0.9% to 33%) although clinical characteristics have not been clearly established yet. OBJECTIVES: To identify the presence of HBoV in patients with ARI hospitalized in Hospital de Niños de Córdoba and describe cases without co-infection. METHOD: HBoV screening was done by traditional PCR. Specimens to be screened were obtained from nasal secretions of 222 children under 2 years of age hospitalized due to an ARI during 2011. Demographic, clinical and radiological data were recorded. RESULTS: Fifteen HBoV+ patients (6.8%) were identified. Their median age was 3.5 months (range: 1-22), 7/15 in co-infection (5 respiratory syncytial virus, 1 parainfuenza-3, 1 Bordetella pertussis). Cases without co-infection: pneumonia 5/8, bronchiolitis 3/8; two required intermediate care, 7/8 oxygen therapy, 7/8 bronchodilators, 6/8 antibiotics; associated disease 1/8 (microcephalus/heart disease). CONCLUSIONS: HBoV was identified in 15 out of 222 children (6.8%); the diagnosis of pneumonia was predominant without severe cases nor complications upon discharge.

High frequency of human bocavirus 1 DNA in infants and adults with lower acute respiratory infection.

Human bocavirus (HBoV) is a parvovirus with a possible aetiological role in respiratory disease that is currently under investigation. We detected HBoV1 in children and adults hospitalized with acute disease of the lower respiratory tract. HBoV genome was detected by PCR in nasopharyngeal swabs collected from 75 patients aged 0-89 years during 2010. HBoV was found in 17/75 (22.7 %) patients, 64.7 % of them infants younger than 1 year old and 29.4 % adults older than 30 years [the bimodal age distribution among HBoV-positive (HBoV(+)) patients was statistically significant, P<0.001]. Of all HBoV(+) cases, 35.3 % were co-infected; all co-infections occurred in children (≤13 years old) and 83.3 % of them were HBoV-respiratory syncytial virus (RSV) co-infections. Among infants younger than 1 year, 50 % HBoV(+) specimens were co-infected, all of them with RSV. The rate of co-infection in infants was significantly higher compared to the frequency of co-infection in the whole cohort (P = 0.003). The results suggest that HBoV1 is involved in acute respiratory disease. Interplay between HBoV1 and RSV cannot be discarded as a cause of elevated percentages of co-detections in infants.

High prevalence of human bocavirus 1 in infants with lower acute respiratory tract disease in Argentina, 2007-2009.

UNLABELLED: Human bocavirus (HBoV) is a parvovirus whose association with respiratory disease is currently under investigation. OBJECTIVE: To determine HBoV prevalence in children with lower acute respiratory infection. METHODS: We investigated HBoV in 433 nasopharyngeal aspirates collected in 2007-2009 from children 0 to 5 years old hospitalized with bronchiolitis or pneumonia in Córdoba, Argentina. RESULTS: The general prevalence of HBoV was 21.5% and the positive cases (HBoV+) were more frequent during winter and spring. The mean age of HBoV+ patients was 6.9 months, with 87.1% of the detections corresponding to infants less than 1 year old (among which the prevalence of HBoV was 26.3% in patients < 3 months of age, 22.1% in 3 to 6 months, 25.3% in 6 to 9 months, and 18.8% in 9 to 12 months). The sequence analysis of the NP1 coding region of 15 isolates showed that all isolates from Cordoba were HBoV1 which exhibited a homology of nearly 100% both among themselves and with the originally discovered virus from 2005. CONCLUSION: Overall, our results indicate that HBoV is a significant pathogen that contributes to acute respiratory infection both on its own and during coinfection with other viruses.

Infección respiratoria por bocavirus humano en lactantes de Córdoba, Argentina / Human bocavirus respiratory infection in infants in Córdoba, Argentina

Bocavirus humano (BoVh) ha sido relacionado con la infección respiratoria aguda (IRA) en los niños (prevalencia 0,9% a 33%), aunque las características clínicas aún no han sido claramente establecidas. Objetivos. Identificar la presencia de BoVh en pacientes con IRA internados en el Hospital de Niños de Córdoba y describir los casos sin coinfección detectada. Método. Se realizó la pesquisa de BoVh por PCR convencional a partir de secreciones nasales de 222 niños menores de 2 años hospitalizados por IRA durante 2011 y se registraron los datos demográficos, clínicos y radiológicos. Resultados. Se identificaron 15 pacientes BoVh+ (6,8%), con una mediana de edad de 3,5 meses (rango 1 a 22), 7/15 en coinfección (5 virus respiratorio sincicial, 1 parainfluenza-3, 1 Bordetella pertussis). Casos sin coinfección: neumonía 5/8, bronquiolitis 3/8; dos requirieron cuidados intermedios, 7/8 oxigenoterapia, 7/8 broncodilatadores, 6/8 antibióticos; enfermedad asociada 1/8 (microcefalia/cardiopatía). Conclusiones. Se identificó BoVh en 15 de 222 niños (6,8%); predominó el diagnóstico de neumonía sin casos graves ni complicaciones al alta.

It has been suggested that human bocavirus (HBoV) is related to acute respiratory infection (ARI) in children (prevalence: 0.9% to 33%) although clinical characteristics have not been clearly established yet. Objectives. To identify the presence of HBoV in patients with ARI hospitalized in Hospital de Niños de Córdoba and describe cases without co-infection. Method. HBoV screening was done by traditional PCR. Specimens to be screened were obtained from nasal secretions of 222 children under 2 years of age hospitalized due to an ARI during 2011. Demographic, clinical and radiological data were recorded. Results. Fifteen HBoV+ patients (6.8%) were identified. Their median age was 3.5 months (range: 1-22), 7/15 in co-infection (5 respiratory syncytial virus, 1 parainfluenza-3, 1 Bordetella pertussis). Cases without co-infection: pneumonia 5/8, bronchiolitis 3/8; two required intermediate care, 7/8 oxygen therapy, 7/8 bronchodilators, 6/8 antibiotics; associated disease 1/8 (microcephalus/heart disease). Conclusions. HBoV was identified in 15 out of 222 children (6.8%); the diagnosis of pneumonia was predominant without severe cases nor complications upon discharge.

Analysis of gene expression in fetal and adult cells infected with rubella virus.

Congenital infection with rubella virus (RUB) leads to persistent infection and congenital defects and we showed previously that primary human fetal fibroblasts did not undergo apoptosis when infected with RUB, which could promote fetal virus persistence [Adamo, P., Asís, L., Silveyra, P., Cuffini, C., Pedranti, M., Zapata, M., 2004. Rubella virus does not induce apoptosis in primary human embryo fibroblasts cultures: a possible way of viral persistence in congenital infection. Viral Immunol. 17, 87-100]. To extend this observation, gene chip analysis was performed on a line of primary human fetal fibroblasts (10 weeks gestation) and a line of human adult lung fibroblasts (which underwent apoptosis in response to RUB infection) to compare gene expression in infected and uninfected cells. A total of 632 and 516 genes were upregulated or downregulated in the infected fetal and adult cells respectively in comparison to uninfected cells, however only 52 genes were regulated in both cell types. Although the regulated genes were different, across functional gene categories the patterns of gene regulation were similar. In general, regulation of pro- and anti-apoptotic genes following infection appeared to favor apoptosis in the adult cells and lack of apoptosis in the fetal cells, however there was a greater relative expression of anti-apoptotic genes and reduced expression of pro-apoptotic genes in uninfected fetal cells versus uninfected adult cells and thus the lack of apoptosis in fetal cells following RUB infection was also due to the prevailing background of gene expression that is antagonistic to apoptosis. In support of this hypothesis, it was found that of a battery of five chemicals known to induce apoptosis, two induced apoptosis in the adult cells, but not in fetal cells, and two induced apoptosis more rapidly in the adult cells than in fetal cells (the fifth did not induce apoptosis in either). A robust interferon-stimulated gene response was induced following infection of both fetal and adult cells and many of the genes upregulated in both cell types were those involved in establishment of an antiviral state; this is the first demonstration of an interferon response at this early stage of human embryonic development. In both fetal and adult cells, interferon controlled but did not eliminate virus spread and apoptosis was not induced in infected fetal cells in the absence of interferon. In addition to the interferon response, chemokines were induced in both infected fetal and adult cells. Thus, it is possible that fetal damage following congenital RUB infection, which involves cell proliferation and differentiation, could be due to induction of the innate immune response as well as frank virus infection.