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Upper respiratory tract infections (“common cold”) are the most common acute illnesses in elite athletes. Numerous studies on exercise immunology have proposed that intense exercise may increase susceptibility to respiratory infections. Virological data to support that view are sparse, and several fundamental questions remain. Immunity to respiratory viral infections is highly complex, and there is a lack of evidence that minor short- or long-term alterations in immunity in elite athletes have clinical implications. The degree to which athletes are infected by respiratory viruses is unclear. During major sport events, athletes are at an increased risk of symptomatic infections caused by the same viruses as those in the general population. The symptoms are usually mild and self-limiting. It is anecdotally known that athletes commonly exercise and compete while having a respiratory viral infection; there are no virological studies to suggest that such activity would affect either the illness or the performance. The risk of myocarditis exists. Which simple mitigation procedures are crucial for effective control of seasonal respiratory viral infections is not known.

Influenza A outbreaks occurred in two professional hockey teams just after two games they played against each other. Thirteen players and two staff members fell ill during 17–20 April 2022, while COVID-19 was prevalent. Altogether, seven players missed an important game due to influenza. The rapid diagnosis permitted effective pharmaceutical and nonpharmaceutical control of the outbreaks.

We performed prospective studies on respiratory viral infections among Team Finland participants during the 2021 Oberstdorf World Ski Championships and the 2022 Beijing Olympic Games. We enrolled 73 athletes and 110 staff members. Compared with similar studies we conducted before the COVID-19 pandemic, illnesses and virus detections dropped by 10-fold.

Exercise has been shown to affect gut the microbiome and metabolic health, with athletes typically displaying a higher microbial diversity. However, research on the gut microbiota and systemic metabolism in elite athletes remains scarce. In this study, we compared the gut microbiota profiles and serum metabolome of national team cross-country skiers at the end of an exhausting training and competitive season to those of normally physically-active controls. The gut microbiota were analyzed using 16S rRNA amplicon sequencing. Serum metabolites were analyzed using nuclear magnetic resonance. Phylogenetic diversity and the abundance of several mucin-degrading gut microbial taxa, including

AIM To assess whether there was a difference in the frequency of symptoms and signs among children with community-acquired pneumonia (CAP) with viral or bacterial infection. METHODS A prospective cross-sectional study was conducted in Salvador, Brazil. Children less than 5-years-old hospitalized with CAP were recruited. Viral or only bacterial infection was diagnosed by an investigation of 11 viruses and 8 bacteria. Bacterial infection was diagnosed by blood culture, detection of pneumococcal DNA in acute buffy coat, and serological tests. Viral infection was diagnosed by detection of respiratory virus in nasopharyngeal aspirate and serological tests. Viral infection comprised only viral or mixed viral-bacterial infection subgroups. RESULTS One hundred and eighty-eight patients had a probable etiology established as only viral (51.6%), mixed viral-bacterial (30.9%), and only bacterial infection (17.5%). Asthma was registered for 21.4%. Report of wheezing (47.4% vs 21.2%; P = 0.006), rhonchi (38.0% vs 15.2%; P = 0.01), and wheezing detected on physical examination (51.0% vs 9.1%; P

We studied Immunoglobulin G (IgG) antibody responses against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in young children with acute viral type respiratory infection and analyzed the findings in a multivariate model including age, nasopharyngeal carriage of the tested bacteria and pneumococcal vaccination.We included 227 children aged 6-23 months with acute respiratory infection. Nasopharyngeal aspirates were tested for bacterial carriage through detection of messenger RNA (mRNA) transcript with nCounter analysis. Acute and convalescent serum samples were tested for IgG antibody response against eight pneumococcal proteins, three proteins from H. influenzae and five proteins from M. catarrhalis in a fluorescent multiplex immunoassay.A two-fold or greater increase in antibodies to S. pneumoniae, H. influenzae and M. catarrhalis was detected in 27.8, 9.7 and 14.1%, respectively. Nasopharyngeal carriage of each of the studied bacteria was not associated with antibody response detection against each respective bacterium. Furthermore, neither age nor pneumococcal vaccination were independently associated to detection of antibody response against the studied bacteria. Children who carried H. influenzae had higher frequency of colonization by M. catarrhalis (175 [80.3%] vs. 2 [22.2%]; p .001) than those without H. influenzae. Also, children with acute otitis media tended to have higher frequency of antibody response to S. pneumoniae.Nasopharyngeal colonization by S. pneumoniae, H. influenzae and M. catarrhalis did not induce significant increases in antibody levels to these bacteria. Carriage of pathogenic bacteria in the nasopharynx is not able to elicit antibody responses to protein antigens similar to those caused by symptomatic infections.

The measurement of antibody levels is a common test for the diagnosis of Streptococcus pneumoniae infection in research. However, the quality of antibody response, reflected by avidity, has not been adequately evaluated. We aimed to evaluate the role of avidity of IgG against eight pneumococcal proteins in etiologic diagnosis. Eight pneumococcal proteins (Ply, CbpA, PspA1 and 2, PcpA, PhtD, StkP-C, and PcsB-N) were used to develop a multiplex bead-based avidity immunoassay. The assay was tested for effects of the chaotropic agent, multiplexing, and repeatability. The developed assay was applied to paired samples from children with or without pneumococcal disease (n = 38 for each group), determined by either serology, polymerase chain reaction (PCR), or blood culture. We found a good correlation between singleplex and multiplex assays, with r ≥ 0.94.The assay was reproducible, with mean inter-assay variation ≤ 9% and intra-assay variation

Background Previous findings show that corticosteroid treatment during the first acute wheezing episode may reduce recurrent wheezing in children with high rhinovirus genome load at 12-month follow-up. Longer-term effects have not been investigated prospectively. Methods After PCR-confirmation of rhinovirus from nasopharyngeal aspirate, 79 children with the first acute wheezing episode were randomized to receive orally prednisolone or placebo for three days. The initiation of asthma control medication before the age of 5 years was confirmed from medical record and/or from parental interview. The outcome was the time to initiation of regular asthma control medication. Interaction analysis examined rhinovirus genome load. Results Fifty-nine (75%) children completed the follow-up. Asthma control medication was initiated in 40 (68%) children at the median age of 20 months. Overall, prednisolone did not affect the time to initiation of asthma control medication when compared to placebo (p=0.99). Rhinovirus load modified the effect of prednisolone regarding the time to initiation of asthma control medication (p-value for interaction=0.04). In children with high rhinovirus load (>7000 copies/mL)(n=23), the risk for initiation of medication was lower in the prednisolone group compared to the placebo group (p=0.05). In the placebo group asthma medication was initiated to all children with high rhinovirus load (n=9) during the 14 months after the first wheezing episode. Conclusions Overall, prednisolone did not affect the time to initiation of asthma control medication when compared to placebo. However, prednisolone may be beneficial in first-time wheezing children whose episode was severe and associated with high rhinovirus load. (ClinicalTrials. gov, NCT00731575). This article is protected by copyright. All rights reserved.

Background Atypical bacteria are treatable causative agents of community-acquired pneumonia (CAP). However, there is no conclusive evidence that a child with CAP should receive empirical treatment against such agents. Objectives We assessed the possibility of association between clinical failure and acute infection by these bacteria among children with CAP treated with amoxicillin. Patients and methods Patients aged 2-59 months with non-severe CAP received amoxicillin during prospective follow-up. Acute and convalescent blood samples were collected. Probable acute infection by Mycoplasma pneumoniae (specific IgM antibodies), by Chlamydia pneumoniae or Chlamydia trachomatis (specific IgM antibodies and/or IgG/IgA titre change) was investigated. Outcomes were assessed during follow-up at 2, 5 and 14-28 days. Treatment failure included development of danger signs, persistent fever, tachypnoea or death. ClinicalTrials.gov: NCT01200706. Results Of 787 children, 86 (10.9%; 95% CI = 8.9%-13.3%) had acute M. pneumoniae infection. C. pneumoniae acute infection was found in 79 of 733 (10.8%; 95% CI = 8.7%-13.2%) and C. trachomatis was found in 3 of 28 (10.7%; 95% CI = 2.8%-26.5%)

Background: Rhinovirus (RV) is the most common cause of respiratory tract infections in children but, still, the clinical characteristics of RV-associated pneumonia have not been sufficiently investigated. Methods: We identified children and adolescents younger than 18 years of age treated for community-acquired pneumonia as inpatients at the Turku University Hospital from 2003 to 2014 and analyzed for RV by PCR of a respiratory tract specimen. We collected the data from medical records and compared RV-positive children with RV-negative children. Results: Of the study population of 313 children with pneumonia who were studied for RV, it was detected in 82 (26%). RV-positive children were younger (median age 2.6 years, interquartile range [IQR] 1.1–4.6 vs. 3.5 years, IQR 1.7–8.3, p = 0.002) and they had more often a history of preterm birth (16% vs. 5%, adjusted odds ratio 2.89, 95% confidence interval 1.21–6.92, p = 0.017) than RV-negative children. RV-positive children had a higher median white blood cell count than RV-negative children at presentation with pneumonia. The signs, symptoms, and severity of pneumonia were mostly similar in RV-positive and RV-negative children. Conclusions: RV was frequently detected in young children hospitalized with community-acquired pneumonia. We identified premature birth as a factor associated with RV-positive pneumonia. The clinical features of pneumonia did not clearly differ between RV-positive and RV-negative children. Further studies are needed to clarify the clinical significance of detection of RV in children with pneumonia.

Conserved protein antigens have been investigated as vaccine candidates against respiratory pathogens. We evaluated the natural development of antibodies against Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis proteins during childhood. Serum samples were collected from 50 healthy children from their first months to age 13 years (median sampling interval, 6 months). We also analyzed serum samples from 24 adults. Serum IgG antibodies against eight pneumococcal proteins (Ply, CbpA, PspA 1 and 2, PcpA, PhtD, StkP-C, and PcsB-N), three H. influenzae proteins, and five M. catarrhalis proteins were measured using a multiplexed bead-based immunoassay. Antibody levels were analyzed using multilevel mixed-effects regression and Spearman's correlation. Antibody levels against pneumococcal proteins peaked at 3 to 5 years of age and then reached a plateau. Antibody levels against H. influenzae proteins peaked during the second year and then stabilized. Antibody levels against M. catarrhalis proteins peaked during the first year and then slowly decreased. Peak antibody levels during childhood were higher than those of adults. Correlations among pneumococcal antibody levels were highest among anti-CbpA, anti-PcpA, and anti-PhtD antibodies ( r = 0.71 to 0.75; P < 0.001). The children presented 854 symptomatic respiratory infections on 586 occasions. Symptomatic respiratory infections did not improve prediction of antibody levels in the regression model. The maturation of immune responses against the investigated pneumococcal proteins shares similarities, especially among CbpA, PcpA, and PhtD. Antibody production against H. influenzae and M. catarrhalis proteins starts early in life and reaches peak levels earlier than antibody production against the pneumococcal proteins. Basal antibody levels are not related to the occurrence of symptomatic respiratory infections.

Rationale: Rhinoviruses (RVs) are a major cause of symptomatic respiratory tract infection in all age groups. However, RVs can frequently be detected in asymptomatic individuals. Objectives: To evaluate the ability of host transcriptional profiling to differentiate between symptomatic RV infection and incidental detection in children. Methods: Previously healthy children younger than 2 years old (n = 151) were enrolled at four study sites and classified into four clinical groups: RV2 healthy control subjects (n = 37), RV1 asymptomatic subjects (n = 14),RV1 outpatients (n = 30), and RV1 inpatients (n = 70). Host responses were analyzed using whole-blood RNA transcriptional profiles. Measurements and Main Results: RV infection induced a robust transcriptional signature, which was validated in three independent cohorts and by quantitative real-time polymerase chain reaction with high prediction accuracy. The immune profile of symptomatic RV infection was characterized by overexpression of innate immunity and underexpression of adaptive immunity genes, whereas negligible changes were observed in asymptomatic RV1 subjects. Unsupervised hierarchical clustering identified two main clusters of subjects. The first included 93% of healthy control subjects and 100%ofasymptomatic RV1subjects, andthesecond comprised98% of RV1 inpatients and 88% of RV1 outpatients. Genomic scores of healthy control subjects and asymptomatic RV1 children were similar and significantly lower than those of RV1 inpatients and outpatients (P

Timely and reliable detection of viruses is of key importance in early diagnosis of infection(s) following allogeneic HSCT. Among the immunocompetent, infections with BKPyV and JCPyV are mostly subclinical, while post-HSCT, the former may cause HC and the latter PML. The epidemiology and clinical impact of the newly identified KIPyV, WUPyV, MCPyV, and TSPyV in this context remain to be defined. To assess the incidence and clinical impact of BKPyV, JCPyV, KIPyV, WUPyV, MCPyV, and TSPyV infections, we performed longitudinal molecular surveillance for DNAemias of these HPyVs among 53 pediatric HSCT recipients. Surveillance pre-HSCT and for three months post-HSCT revealed BKPyV DNAemia in 20 (38%) patients. Our data demonstrate frequent BKPyV DNAemia among pediatric patients with HSCT and the confinement of clinical symptoms to high copy numbers alone. MCPyV and JCPyV viremias occurred at low and TSPyV viremia at very low prevalences. KIPyV or WUPyV viremias were not demonstrable in this group of immunocompromised patients.

The aim of this study was to compare the results of serological assays using pneumococcal proteins or polysaccharides for the detection of pneumococcal infection in childhood pneumonia. Serological assays measured IgG against eight pneumococcal proteins (Ply,CbpA,PspA1,PspA2,PcpA,PhtD,StkP-C,PcsB-N), C-polysaccharide [in the whole study population, n = 183], or 19 pneumococcal capsular polysaccharides (1,2,4,5,6B,7F,8,9 V,10A,11A,12F,14,15B,17F,18C,19F,20,23F,33F) [only in a subgroup of patients, n = 53] in paired serum samples of children aged5 years-old hospitalized with clinical and radiological diagnosis of community-acquired pneumonia. We also performed an inhibition of binding test with the anti-capsular polysaccharide assay in order to confirm the specificity of the antibody responses detected. Invasive pneumococcal pneumonia was investigated by blood culture and PCR (ply-primer). Among 183 children, the anti-protein assay detected antibody response in 77/183(42.1%) patients and the anti-C-polysaccharide assay in 28/183(15.3%) patients. In a subgroup of 53 children, the anti-protein assay detected response in 32/53(60.4%) patients, the anti-C-polysaccharide assay in 11/53(20.8%) patients, and the anti-capsular polysaccharide in 25/53(47.2%) patients. Simultaneous antibody responses against ≥2 different capsular polysaccharides were detected in 11/53(20.8%) patients and this finding could not be explained by cross-reactivity between different serotypes. Among 13 patients with invasive pneumococcal pneumonia, the sensitivity of the anti-protein assay was 92.3%(12/13), of the anti-C-polysaccharide assay 30.8%(4/13), and of the anti-capsular polysaccharide assay 46.2%(6/13). The serological assay using pneumococcal proteins is more sensitive for the detection of pneumococcal infection in children with pneumonia than the assay using pneumococcal polysaccharides. Future studies on childhood pneumonia aetiology should consider applying serological assays using pneumococcal proteins.

Childhood community-acquired pneumonia is a common and potentially life-threatening illness in developing countries. We assessed the prognostic value of serum procalcitonin level upon admission on clinical response to antibiotic treatment.Out of 89 patients, the median (IQR) age was 19(12-29) months and 60% were boys. Viral (49.5%), typical bacterial (38%) and atypical bacterial (12.5%) infections as well as probable pneumococcal infections (26%) were diagnosed.Seventy-five (84%) children became afebrile ≤48h after treatment. In 14 children who remained febrile after 48h of treatment, median[IQR] serum procalcitonin (ng/ml) level on admission was higher than in those with rapid recovery (2.1[0.8-3.7] vs 0.6[0.1-2.2]; P=0.025). In the slow-responding children, pneumococcal infections were more common (71% vs 17%; P0.001). Procalcitonin concentrations on admission were higher in children with pneumococcal pneumonia compared to children with non-pneumococcal pneumonia (2[0.7-4.2] vs 0.5[0.08-2.1]; P=0.002). The ROC curve found that0.25ng/ml of serum procalcitonin had a high negative predictive value (93%[95%CI:80%-99%]) for pneumococcal infection. All children that remained febrile after 48h of treatment had procalcitonin0.25ng/ml on admission. The majority of children with pneumonia in a developing country become afebrile within 48h after onset of antibiotic treatment.Serum procalcitonin0.25ng/ml predicted rapid clinical response and non-pneumococcal etiology.

Objective Since acute otitis media (AOM) is the most prevalent bacterial infection in young children, the reliable exclusion of AOM by nurses might save physicians’ time for other duties. The study aim was to determine whether nurses without otoscopic experience can reliably use tympanometry or spectral gradient acoustic reflectometry (SG-AR) to exclude AOM. Design Three nurses were trained, who performed examinations with tympanometry and SG-AR. Pneumatic otoscopy by the study physician served as the diagnostic standard. Setting Study clinic at primary health care level. Patients. 281 children 6–35 months of age. Main outcome measures Predictive values (with 95% confidence interval) for tympanometry and SG-AR, and the clinical usefulness, i.e. the proportion of visits where nurses obtained the exclusive test result from both ears of the child. Results At 459 visits, the negative predictive value of type A and C1 tympanograms (tympanometric peak pressure >–200 daPa) was 94% (91–97%). Based on type A and C1 tympanograms, the nurse could exclude AOM at 94/459 (20%) of visits. The negative predictive value of SG-AR level 1 result (>95°) was 94% (89–97%). Based on the SG-AR level 1 result, the nurse could exclude AOM at 36/459 (8%) of visits. Conclusion Type A and C1 tympanograms and SG-AR level 1 results obtained by nurses are reliable test results in excluding AOM. However, the clinical usefulness of these test results is limited by their rarity. Type A and C1 tympanograms were obtained by nurses from both ears of the child only at one-fifth of the symptomatic visits.Key PointsAcute otitis media (AOM) is the most prevalent bacterial infection in young children. Nurses’ role in excluding AOM is unknown.Type A and C1 tympanograms (tympanometric peak pressure >–200 daPa) obtained by nurses are reliable test results in excluding AOM.With type A and C1 tympanograms, nurses could exclude AOM only at one-fifth of the symptomatic visits.The clinical usefulness of the exclusion of AOM performed by nurses seems to be limited.

The spectrum of acute symptoms in young outpatient children with respiratory tract infection (RTI) is variable, and it cannot be explained by the diagnosis of acute otitis media (AOM) versus uncomplicated RTI. We studied that the variation of symptoms is explained by the nasopharyngeal bacteria and/or respiratory viruses.Children aged 6-35 months with acute symptoms with AOM (n = 201) or without AOM (n = 225) were eligible in this cross-sectional study. We analyzed their nasopharyngeal samples for pathogenic bacteria by culture and for respiratory viruses by polymerase chain reaction. We surveyed 17 symptoms (fever, respiratory, ear related, nonspecific, gastrointestinal) with a structured questionnaire.Fever had a positive association with influenza viruses [odds ratio (OR): 6.61; 95% confidence interval (CI): 1.66-26.27], human metapneumovirus (OR: 3.84; 95% CI: 1.25-11.77), coronaviruses (OR: 3.45; 95% CI: 1.53-7.75) and parainfluenza viruses (OR: 2.18; 95% CI: 1.07-4.47). Rhinitis (OR: 5.07; 95% CI: 1.93-13.36), nasal congestion (OR: 2.03; 95% CI: 1.25-3.31) and cough (OR: 1.91; 95% CI: 1.15-3.17) had positive associations with Moraxella catarrhalis. Furthermore, cough had a positive association with respiratory syncytial virus (OR: 7.20; 95% CI: 1.59-32.71) and parainfluenza viruses (OR: 2.79; 95% CI: 1.02-7.69).The variation of acute symptoms in young children may be influenced by both nasopharyngeal bacteria and respiratory viruses. Our results showed a strong association between fever and respiratory viruses; rhinitis, nasal congestion and cough were associated with M. catarrhalis in the presence of viruses. Further studies are required to determine the possible synergistic role of M. catarrhalis in symptoms of RTI.

The role of chest radiograph (CXR) among children with community-acquired pneumonia is controversial. We aimed to assess if there is association between a specific etiology and radiologically confirmed pneumonia.This was a prospective cross-sectional study. Based on report of respiratory complaints and fever/difficulty breathing plus the detection of pulmonary infiltrate/pleural effusion on the CXR taken upon admission read by the pediatrician on duty, children5-year-old hospitalized with community-acquired pneumonia were enrolled. On admission, clinical data and biological samples were collected to investigate 19 etiological agents (11 viruses and 8 bacteria). CXR taken upon admission was independently read by a pediatric radiologist blinded to clinical data.The study group comprised 209 cases with evaluated CXR and establishment of a probable etiology. Radiologically confirmed pneumonia, normal CXR and other radiographic diagnoses were described for 165 (79.0%), 36 (17.2%) and 8 (3.8%) patients, respectively. Viral infection was significantly more common among patients without radiologically confirmed pneumonia (68.2% vs. 47.9%; P = 0.02), particularly among those with normal CXR (66.7% vs. 47.9%; P = 0.04) when compared with patients with radiologically confirmed pneumonia. Bacterial infection was more frequent among cases with radiologically confirmed pneumonia (52.1% vs. 31.8%; P = 0.02). Likewise, pneumococcal infection was more frequently detected among children with radiologically confirmed pneumonia in regard to children with normal CXR (24.2% vs. 8.3%; P = 0.04). Sensitivity (95% confidence interval) of radiologically confirmed pneumonia for pneumococcal infection was 93% (80-98%), and negative predictive value (95% confidence interval) of normal CXR for pneumococcal infection was 92% (77-98%).Bacterial infection, especially pneumococcal one, is associated with radiologically confirmed pneumonia.

To study the changes in the immunological status in 2 children with cartilage hair hypoplasia (CHH).A 4-6 year immunological follow-up from infancy.In infancy the children presented a combined T cell and B cell immunodeficiency which partly resolved in time. Mitogen-induced T cell proliferation values fluctuated but lymphopenia has remained constant. Both patients had no recent thymic emigrants (TREC). Both children have suffered from a prolonged viral infection. Hypogammaglobulinemia normalized during the first years of life but both children have a specific antibody deficiency (SAD).The changes in the immunological status in CHH patients emphasize the importance of a regular follow-up. SAD should be searched for in CHH. The absence of TRECs supports combined immunodeficiency and possible need of hematopoietic stem cell transplantation.

SummaryBackground The incidence of parapneumonic empyema in children has increased worldwide, but the long-term anatomical and functional consequences in the lungs after empyema are not known. Methods We investigated the long-term outcome of childhood empyema in 26 patients by physical examination, chest radiograph and magnetic resonance image (MRI) of the lungs, and pulmonary function tests. Results At follow-up 3–19 years (mean 8 years) after empyema, all patients had normal findings in the physical examination. Spirometry was normal in 80% of patients, and evidence of obstructive airway disease was detected in 16%. Thirty-six percent of patients had abnormal findings in the chest radiograph and 92% in the MRI of the lungs. In six patients, the MRI revealed significant pleural scarring (extension longer than 1 cm). Thirteen patients (50%) reported persistent respiratory symptoms, such as impaired tolerance of physical activity or prolonged cough after a common cold. During the follow-up four patients suffered a second pneumonia. Conclusions The long-term recovery of children with parapneumonic empyema is good, since most patients subsequently have normal lung function, chest radiograph, and clinical recovery. Half of the patients reported subjective respiratory symptoms and most patients had minor lung abnormalities, mostly pleural scars, detected in the MRI many years after empyema. However, as long-term impairment of lung function was rarely found, the clinical significance of the anatomical residues seen in the lung MRI seems to be minor. Pediatr Pulmonol. 2014; 49:1020–1027. © 2013 Wiley Periodicals, Inc.

Background Obtaining a nasal swab (NS) from a child for human rhinovirus (HRV) RNA detection is simple and well tolerated even for repeated sampling, but only few studies have compared them qualitatively and quantitatively with other sampling methods. Objectives Real-time PCR was used to study the stability of HRV genomes in swabs, and to compare different swabs and induced sputum specimens with nasopharyngeal aspirates (NPAs). Study design Replicate swabs in a dry test tube were stored at room temperature or mailed to the laboratory before freezing, and compared to freshly frozen specimens. To compare sampling methods, paediatric patients had NPA, NS and throat swab collected. In paired sputum and NPA specimens, viral load was correlated to the amount of β-actin mRNA. Results Specimens were stable at room temperature for at least 4 days and survived mailing without loss of HRV detectability. As compared to NPA, NS had an equal diagnostic sensitivity, with no significant quantitative difference using flocked nylon swabs and a 2.2-fold drop in the average copy number using cotton swabs. The diagnostic sensitivity of cotton swab-collected throat specimens was 97%, with a 26-fold lower mean copy number. Sputum specimens had higher HRV RNA (2.3-fold) and β-actin mRNA (1.6-fold) copy numbers than NPAs, but there was a poor correlation between HRV RNA and β-actin mRNA. Conclusion HRV remains well detectable by PCR in specimens mailed to the laboratory. The diagnostic efficacy of NPA can be obtained with NS, quantitative comparison and patient comfort favouring flocked nylon-tipped over cotton-tipped swabs.

Human bocavirus 1 (HBoV1) was detected in a young child hospitalized for pneumonia and subsequently in his twin brother and other family members. The mother’s nasopharyngeal samples intermittently showed HBoV1 DNA; the grandmother had HBoV1 reinfection. Findings in this family lead to consideration of HBoV virulence, latency, and reactivation.

Summary During the past decade, several new respiratory viruses and their subgroups have been discovered. All these new viruses, as well as previously known respiratory viruses, can be detected by sensitive PCR methods, which have become popular in the diagnostic workup of respiratory viral infections. Currently, respiratory viruses can be detected in up to 95% of children with lower respiratory tract illness. On the other hand, virus detection rates in asymptomatic children are also high (up to 68%), as are coinfection rates in symptomatic children (up to 43%) and justified concerns of causality have been raised. Imposing progress has been made in developing multiplex quantitative PCR assays; here, several primer sets are run within a single PCR mixture. These PCR assays give a better understanding of the dominant viral infection, of viral infections that may be incipient and of any waning infections than does a single-target PCR. Multiplex PCR assays are also gaining popularity due to their cost-effectiveness and short throughput time compared to multiple single-target PCRs. Our understanding of the indications of virus PCRs and our ability to interpret the results from a clinical point of view have improved. This paper reviews the progress in PCR assays and discusses their role in the diagnosis of lower respiratory tract infections in children.

OBJECTIVE:Bilateral acute otitis media (AOM) is considered more severe than unilateral AOM, and several guidelines recommend more active treatment and/or follow-up of bilateral AOM. We studied whether bilateral AOM is a clinically more severe illness than unilateral AOM by comparing symptoms and otoscopic signs between bilateral and unilateral AOM.METHODS:Two hundred thirty-two children aged 6 to 35 months diagnosed with AOM were eligible. We surveyed the symptoms with a structured questionnaire and recorded the otoscopic signs systematically.RESULTS:Ninety-eight children had bilateral and 134 children unilateral AOM. Children with bilateral AOM were more often CONCLUSIONS:Bilateral AOM seems to be a clinically only slightly more severe illness than unilateral AOM. Therefore, when assessing AOM severity, bilaterality should not be used as a determining criterion; instead, the child’s symptomatic condition together with otoscopic signs should also be taken into consideration.

Among the immunocompetent, infections with parvovirus B19 (B19V) and human bocavirus (HBoV) 1 range clinically from asymptomatic to severe, while following allogeneic hematopoietic SCT (HSCT) B19V can cause a persistent severe illness. The epidemiology and clinical impact of HBoV1 and the other emerging parvovirus 4 (PARV4) among immunocompromised patients have not been established. To determine the occurrence and clinical spectrum of B19V, PARV4 and HBoV1 infections, we performed a longitudinal molecular surveillance among 53 allogeneic HSCT recipients for pre- and post-HSCT DNAemias of these parvoviruses. Quantitative real-time PCR showed B19V DNA in sera of 16 (30%) patients, at mean levels of 4.6 × 10(3), 9.9 × 10(7), 1.1 × 10(10) and 1.6 × 10(2) B19V DNA copies/mL pre-HSCT (9/53), and at 1 (6/53), 2 (4/53) and 3 months (1/25) post HSCT, respectively. However, no clinical manifestation correlated with the presence of B19V viremia. All B19V sequences were of genotype 1. None of the sera investigated contained PARV4 or HBoV1 DNAs. Our data demonstrate B19V viremia to be frequent among pediatric allogeneic HSCT recipients, yet without apparent clinical correlates. PARV4 or HBoV1 viremias were not seen in these immunocompromised patients.

Summary Objectives To understand relationships between microbes in pathogenesis of acute otitis media during respiratory tract infections, we compared nasopharyngeal bacteria and respiratory viruses in symptomatic children with and without AOM. Methods We enrolled children (6–35 months) with acute symptoms suggestive of AOM and analyzed their nasopharyngeal samples for bacteria by culture and for 15 respiratory viruses by PCR. Non-AOM group had no abnormal otoscopic signs or only middle ear effusion, while AOM group showed middle ear effusion and acute inflammatory signs in pneumatic otoscopy along with acute symptoms. Results Of 505 children, the non-AOM group included 187 and the AOM group 318. One or more bacterial AOM pathogen ( Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis ) was detected in 78% and 96% of the non-AOM and AOM group, respectively ( P S. pneumoniae and H. influenzae , each alone, increased risk of AOM (odds ratio (OR) 2.92; 95% confidence interval (CI), .91–9.38, and 5.13; 1.36–19.50, respectively) and co-colonization with M. catarrhalis further increased risk (OR 4.36; 1.46–12.97, and 9.00; 2.05–39.49, respectively). Respiratory viruses were detected in 90% and 87% of the non-AOM and AOM group, respectively. RSV was significantly associated with risk of AOM without colonization by bacterial AOM pathogens (OR 6.50; 1.21–34.85). Conclusions Co-colonization by M. catarrhalis seems to increase risk of AOM and RSV may contribute to AOM pathogenesis even without nasopharyngeal bacterial colonization.

Objective: Community-acquired pneumonia is an important cause of morbidity in childhood, but the detection of its causative agent remains a diagnostic challenge. The authors aimed to evaluate the role of the chest radiograph to identify cases of community-aquired pneumonia caused by typical bacteria. Methods: The frequency of infection by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis was compared in non-hospitalized children with clinical diagnosis of community acquired pneumonia aged 2–59 months with or without radiological confirmation (n = 249 and 366, respectively). Infection by S. pneumoniae was diagnosed by the detection of a serological response against at least one of eight pneumococcal proteins (defined as an increase ≥2-fold in the IgG levels against Ply, CbpA, PspA1 and PspA2, PhtD, StkP-C, and PcsB-N, or an increase ≥1.5-fold against PcpA). Infection by H. influenzae and M. catarrhalis was defined as an increase ≥2-fold on the levels of microbe-specific IgG. Results: Children with radiologically confirmed pneumonia had higher rates of infection by S. pneumoniae. The presence of pneumococcal infection increased the odds of having radiologically confirmed pneumonia by 2.8 times (95% CI: 1.8–4.3). The negative predictive value of the normal chest radiograph for infection by S. pneumoniae was 86.3% (95% CI: 82.4–89.7%). There was no difference on the rates of infection by H. influenzae and M. catarrhalis between children with community-acquired pneumonia with and without radiological confirmation. Conclusions: Among children with clinical diagnosis of community-acquired pneumonia submitted to chest radiograph, those with radiologically confirmed pneumonia present a higher rate of infection by S. pneumoniae when compared with those with a normal chest radiograph. Resumo: Objetivos: O objetivo deste estudo foi avaliar o papel do raio-X de tórax na identificação de casos de pneumonia adquirida na comunidade (PAC) causada por agentes bacterianos. Métodos: A frequência de infecção por Streptococcus pneumoniae, Haemophilus influenzae e Moraxella catarrhalis em crianças com PAC não hospitalizadas foi comparada com a presença de confirmação radiológica da pneumonia (n = 249 crianças com pneumonia radiologicamente confirmada e 366 crianças com raio X de tórax normal). Infecção por S. pneumoniae foi diagnosticada com base na resposta sorológica a pelo menos uma dentre oito proteínas pneumocócicas investigadas (aumento ≥2 vezes nos níveis de IgG em relação a Ply, CbpA, PspA1 e 2, PhtD, StkP-C e PcsB-N ou aumento≥1,5 vezes em relação aPcpA). Infecção por H. influenzae e M. catarrhalis foi definida por aumento≥2 vezes nos níveis de IgG específica a antígenos de cada agente. Resultados: Crianças com pneumonia radiologicamente confirmada apresentaram maior taxa de infecção pelo pneumococo. Além disso, a presença de infecção pneumocócica foi um fator preditor de pneumonia radiologicamente confirmada, aumentando sua chance de detecção em 2,8 vezes (IC 95%: 1,8-4,3). O valor preditivo negative do raio X normal para a infecção por S. pneumoniae foi 86,3% (IC95%: 82,4%-89,7%). Não houve diferença nas frequências de infecção por H. influenzae e M. catarrhalis entre crianças com PAC com ou sem confirmação radiológica. Conclusões: Crianças com diagnóstico clínico de PAC submetidas a um raio X de tórax que apresentam confirmação radiológica tem maior taxa de infecção por S. pneumoniae, comparado às crianças com raio X normal. Keywords: Bacterial infection, Etiology, Lower respiratory tract infection, Radiological study, Serological tests, Palavras-chave: Infecção bacteriana, Etiologia, Infecção do trato respiratório inferior, Estudo radiológico, Testes sorológicos

Bahia State Agency for Research Funding (FAPESB), Brazil; Brazilian Council for Scientific and Technological Development (CNPq), Brazil; and in part by National Institute for Health

Since its discovery in 2005, human bocavirus type 1 has often been found in the upper airways of young children with respiratory disease. But is this virus the cause of the respiratory disease or just an innocent bystander? A unique study in Finland, which examined follow-up blood samples of 109 healthy children with no underlying illness starting at birth and until they were 13 years of age, found that acute bocavirus infection resulted in respiratory disease. All children had been infected by age 6. Most retained their antibodies to this virus; some lost them. Children who were later re-exposed to bocavirus did not get sick from this virus. Thus, human bocavirus type 1 is a major cause of respiratory disease in childhood., Human bocavirus 1 (HBoV1) DNA is frequently detected in the upper airways of young children with respiratory symptoms. Because of its persistence and frequent co-detection with other viruses, however, its etiologic role has remained controversial. During 2009–2011, using HBoV1 IgM, IgG, and IgG-avidity enzyme immunoassays and quantitative PCR, we examined 1,952 serum samples collected consecutively at 3- to 6-month intervals from 109 constitutionally healthy children from infancy to early adolescence. Primary HBoV1 infection, as indicated by seroconversion, appeared in 102 (94%) of 109 children at a mean age of 2.3 years; the remaining 7 children were IgG antibody positive from birth. Subsequent secondary infections or IgG antibody increases were evident in 38 children and IgG reversions in 10. Comparison of the seroconversion interval with the next sampling interval for clinical events indicated that HBoV1 primary infection, but not secondary immune response, was significantly associated with acute otitis media and respiratory illness.

Watchful waiting with the option of delayed antimicrobial treatment for acute otitis media is recommended in several guidelines. Our aim was to study whether delayed, as compared with immediate, initiation of antimicrobial treatment worsens the recovery from acute otitis media in young children.Children (6-35 months) with acute otitis media received either delayed or immediate antimicrobial treatment with amoxicillin-clavulanate for 7 days. The delayed antimicrobial treatment group (n = 53) consisted of placebo recipients from a randomized-controlled trial to whom antimicrobial treatment was initiated after a watchful waiting period. The immediate antimicrobial treatment group (n = 161) consisted of children allocated to receive antimicrobial treatment immediately.Improvement during antimicrobial treatment (which includes both symptoms and otoscopic signs) was observed in 91% and 96% of children in the delayed and immediate antimicrobial treatment groups, respectively (P = 0.15). Median watchful waiting period was 48 hours. Delayed initiation of antimicrobial treatment was associated with prolonged resolution of fever, ear pain, poor appetite and decreased activity, but not ear rubbing, irritability, restless sleep or excessive crying. Parents of children in the delayed antimicrobial treatment group missed more work days (mean 2.1 versus 1.2 days, P = 0.03). Diarrhea, vomiting and rash were equally common in both groups.Our results indicate that delayed initiation of antimicrobial treatment does not worsen the recovery from acute otitis media, as measured by improvement during treatment. However, watchful waiting before the initiation of delayed antimicrobial treatment might be associated with transient worsening of a child's condition, prolongation of symptoms and economic losses.

Neuroendocrine cell hyperplasia of infancy (NEHI) has recently been described as an obstructive airway disease that affects infants aged 1-24 months, and presents typically with tachypnoea, crackles and hypoxia. The pathogenesis of the disease is unknown. We describe the clinical course of nine infants with radiologically and histologically confirmed NEHI. Host or environmental factors were not associated with the disease development. All infants with lung function tests demonstrated findings consistent with severe irreversible peripheral airway obstruction, assessed with whole body plethysmography (6/6) or the rapid thoracoabdominal compression technique (5/5). While the symptoms abated in all infants, six infants developed a non-atopic asthma during the follow-up. Systemic or inhaled corticosteroid treatment did not affect the duration of the symptoms. NEHI may mimic severe asthma and thus this entity should be taken into account when evaluating infants with chronic respiratory symptoms.

Aims: To clarify the status of the coagulation system in children with community-acquired pneumonia. Methods: Coagulation activation markers (prothrombin fragment F1 + 2, thrombin–antithrombin complexes, D-dimer), the natural anticoagulants (antithrombin, protein C and S) and tissue factor were measured in 28 consecutive children with pneumonia on admission to the hospital. Patients were divided into those with either bacterial-type pneumonia (at least two of the following three criteria: plasma C-reactive protein (CRP) >80 mg/L, white blood cell count >15 × 109/L and alveolar infiltrates on the chest radiograph) or viral-type pneumonia. Results: The majority of the patients (79%) showed elevation of at least one of the three coagulation activation markers. Plasma CRP concentration correlated with F1 + 2 (R = 0.44, p

Human bocavirus (HBoV) is a human virus associated with respiratory disease in children. Limited information is available on acute infection with HBoV among children admitted to hospital with community-acquired pneumonia in tropical regions and the current diagnosis is inadequate. The aims were to diagnose and describe acute HBoV infections among children hospitalized for community-acquired pneumonia. In Salvador, Brazil, 277 children with community-acquired pneumonia were prospectively enrolled. Paired serum samples were tested by IgG, IgM, and IgG-avidity enzyme immunoassays (EIAs) using recombinant HBoV VP2. HBoV DNA was detected in nasopharyngeal aspirates and serum by a quantitative polymerase-chain reaction (PCR). HBoV DNA was detected in nasopharyngeal aspirates of 62/268 (23%) children and 156/273 (57%) were seropositive. Acute primary HBoV infection was reliably diagnosed (bearing at least two acute markers: Positive IgM, a fourfold increase/conversion of IgG, low IgG avidity or viremia) in 21 (8%) of 273 patients, 90% of 20 had HBoV DNA in nasopharyngeal aspirates, 83% with a high DNA load. The median age of infection with HBoV was 16 months, range 5–36. Community-acquired pneumonia was confirmed radiographically in 85% of 20 patients with acute HBoV infection diagnosed serologically. HBoV DNA was found in nasopharyngeal aspirates of 42/246(17%) children without an acute primary HBoV infection and available nasopharyngeal aspirate. Four children with HBoV secondary immune responses were detected, lacking both IgM and viremia. HBoV infection was diagnosed accurately in children aged 5–36 months with community-acquired pneumonia confirmed radiographically. PCR of nasopharyngeal aspirates is not a reliable marker of acute HBoV infection. J. Med. Virol. 84:253–258, 2012. © 2011 Wiley Periodicals, Inc.

Human bocavirus 1 (HBoV1) was discovered in 2005 [1] and has since been shown to circulate globally [2–5] and to be associated with acute respiratory disease in young children (reviewed in [6]). HBoV1 DNA is commonly found in feces [7, 8] and serum [2, 9], in addition to respiratory secretions. In 2009–2010, 3 more human bocaviruses, HBoV2–4, were identified in feces [8, 10, 11]. In the HBoV1–4 strains used here, the amino acid sequences of the major structural virus protein 2 (VP2) of HBoV2–4 are 22%–23% divergent relative to HBoV1 and ∼11% divergent relative to each other. HBoV2 and HBoV4 diverge from each other the most the most (11.3%) and HBoV2 and HBoV3 diverge from each other the least (10.6%). HBoV2 has been encountered more widely than HBoV3–4 and is likely to circulate globally [10–17]. Contrary to that of HBoV1, the tropism of HBoV2–4 seems to favor the intestines over the respiratory tract [8, 12, 13], although HBoV2 DNA has been detected also in the latter [14]. A case control study indicated a correlation of HBoV2 DNA detection in stool and acute gastroenteritis [10]. The persistent or intermittent presence of HBoV1 in the nasopharynx emphasizes the possibility that the detection of HBoV2–4 DNA in stool may not always be a sign of acute infection but may be due to prolonged shedding [18–20]. The relatively frequent detection of HBoV2 in the stool of asymptomatic participants [8, 10] also supports persistent shedding or reinfections. This would render qualitative polymerase chain reaction (PCR)–based diagnostics problematic, impede the assessment of the clinical role of these viruses, and underline the need for antibody assays for the dating of acute HBoV2–4 infections. On the other hand, the cocirculation of HBoV2–4 may influence serological tests for HBoV1. To address these issues, we expressed recombinant VP2s of all 4 currently known human bocaviruses for immunoenzymatic examination of adult and child sera for immunoglobulin G (IgG) antibodies. The pediatric sera were also tested for HBoV1-4 DNA by quantitative PCR (qPCR), and some also for immunoglobulin M (IgM). Polyclonal rabbit antisera generated toward HBoV1 and HBoV2 viruslike particles (VLPs) and competition assays for human sera were used to assess the antigenic relatedness and to compensate for serological cross-reactivities.

Trichodysplasia spinulosa (TS)-associated polyomavirus (TSV) was recently (in 2010) discovered in TS lesions. To investigate the seroprevalence and primary exposure time of this virus, we set up a virus protein (VP1) viruslike particle (VLP)-based immunoglobulin G enzyme immunoassay. The seroprevalence of TSV was 5%, among children aged 1-4 years, rising to 48% at 6-10 years, and 70% among 149 adults. The TSV antibodies did not cross-react with corresponding Merkel cell polyomavirus VLPs, and their reactivity appeared conformational. TSV circulates widely in the human population and primary exposure is extensive in childhood, beginning at age 1-2 years.

The diagnostics of respiratory viral infections has improved markedly during the last 15 years with the development of PCR techniques. Since 1997, several new respiratory viruses and their subgroups have been discovered: influenza A viruses H5N1 and H1N1, human metapneumovirus, coronaviruses SARS, NL63 and HKU1, human bocavirus, human rhinoviruses C and D and potential respiratory pathogens, the KI and WU polyomaviruses and the torque teno virus. The detection of previously known viruses has also improved. Currently, a viral cause of respiratory illness is almost exclusively identifiable in children, but in the elderly, the detection rates of a viral etiology are below 40%, and this holds also true for exacerbations of chronic respiratory illnesses. The new viruses cause respiratory symptoms like the common cold, cough, bronchitis, bronchiolitis, exacerbations of asthma and chronic obstructive pulmonary disease and pneumonia. Acute respiratory failure may occur. These viruses are distributed throughout the globe and affect people of all ages. Data regarding these viruses and the elderly are scarce. This review introduces these new viruses and reviews their clinical significance, especially with regard to the elderly population.

The prompt diagnosis of influenza enables the institution of antiviral therapy and adequate cohorting of patients, but scarce data are available to help clinicians correctly suspect influenza in children at the time of admission. This 16-year retrospective study assessed the main admission diagnoses of 401 children aged ≤16 years hospitalized with virologically confirmed influenza. The clinical data were derived from a systematic review of the medical records of the children. Sepsis-like illness was the main reason for admission in 52% of infants aged

Mucosal coinfections with respiratory viruses and Streptococcus pneumoniae are common, but the role of rhinovirus infections in the development of invasive pneumococcal disease (IPD) in children has not been studied.During 1995 and 2007, we analyzed the association of IPD in children less than 5 years of age with respiratory virus epidemics by combining data from the National Infectious Disease Register, 3 prospective epidemiologic studies, and the database of the Department of Virology, University of Turku, Finland.The mean IPD rate in children younger than 5 years of age in Finland was 2.9 cases per week (95% confidence interval [CI], 2.5-3.3) during periods of high rhinovirus activity, and 1.4 (95% CI, 1.2-1.6) during periods of low rhinovirus activity (P0.001). The IPD rate correlated with the rhinovirus activity recorded at the Department of Virology (correlation coefficient, 0.23; P = 0.001) and in the epidemiologic studies (correlation coefficients, 0.28, 0.25, and 0.31). The IPD rate was moderately increased during periods of high respiratory syncytial virus activity (mean, 2.1 cases per week; 95% CI, 1.8-2.3) compared with periods of low respiratory syncytial virus activity (mean, 1.7; 95% CI, 1.6-1.9; P = 0.008). There were no differences in the IPD rate between the periods of high and low influenza activity.Rhinovirus circulation in the community had an association with IPD in children younger than 5 years of age. This study suggests that rhinovirus infection may be a contributor in the development of IPD in the population of young children.

The efficacy of antimicrobial treatment in children with acute otitis media remains controversial.In this randomized, double-blind trial, children 6 to 35 months of age with acute otitis media, diagnosed with the use of strict criteria, received amoxicillin-clavulanate (161 children) or placebo (158 children) for 7 days. The primary outcome was the time to treatment failure from the first dose until the end-of-treatment visit on day 8. The definition of treatment failure was based on the overall condition of the child (including adverse events) and otoscopic signs of acute otitis media.Treatment failure occurred in 18.6% of the children who received amoxicillin-clavulanate, as compared with 44.9% of the children who received placebo (P0.001). The difference between the groups was already apparent at the first scheduled visit (day 3), at which time 13.7% of the children who received amoxicillin-clavulanate, as compared with 25.3% of those who received placebo, had treatment failure. Overall, amoxicillin-clavulanate reduced the progression to treatment failure by 62% (hazard ratio, 0.38; 95% confidence interval [CI], 0.25 to 0.59; P0.001) and the need for rescue treatment by 81% (6.8% vs. 33.5%; hazard ratio, 0.19; 95% CI, 0.10 to 0.36; P0.001). Analgesic or antipyretic agents were given to 84.2% and 85.9% of the children in the amoxicillin-clavulanate and placebo groups, respectively. Adverse events were significantly more common in the amoxicillin-clavulanate group than in the placebo group. A total of 47.8% of the children in the amoxicillin-clavulanate group had diarrhea, as compared with 26.6% in the placebo group (P0.001); 8.7% and 3.2% of the children in the respective groups had eczema (P=0.04).Children with acute otitis media benefit from antimicrobial treatment as compared with placebo, although they have more side effects. Future studies should identify patients who may derive the greatest benefit, in order to minimize unnecessary antimicrobial treatment and the development of bacterial resistance. (Funded by the Foundation for Paediatric Research and others; ClinicalTrials.gov number, NCT00299455.).

The role of viral infections in the etiology of severe community-acquired pneumonia (SCAP) was prospectively evaluated from 2008 to 2012 at a university-level intensive care unit.Clinical data and microbiological tests were assessed: blood cultures, urine pneumococcal and legionella antigens, Mycoplasma pneumoniae and Chlamydia pneumoniae antibodies from paired serums, and respiratory virus detection by multiplex, real-time polymerase chain reaction (PCR) from nasopharyngeal swabs and lower tracheal specimens via intubation tube.Of 49 mechanically ventilated SCAP patients (21 men and 28 women; median age, 54 years), the etiology was identified in 45 cases (92%). There were 21 pure bacterial infections (43%), 5 probably pure viral infections (10%), and 19 mixed bacterial-viral infections (39%), resulting in viral etiology in 24 patients (49%). Of 26 viruses, 21 (81%) were detected from bronchial specimens and 5 (19%) from nasopharyngeal swabs. Rhinovirus (15 cases, 58%) and adenovirus (4 cases, 15%) were the most common viral findings. The bacterial-viral etiology group had the highest peak C-reactive protein levels (median, 356 [25th-75th percentiles, 294-416], P = .05), whereas patients with probably viral etiology had the lowest peak procalcitonin levels (1.7 [25th-75th percentiles, 1.6-1.7]). The clinical characteristics of pure bacterial and mixed bacterial-viral etiologies were comparable. Hospital stay was longest among the bacterial group (17 vs 14 days; P = .02).Viral findings were demonstrated in almost half of the SCAP patients. Clinical characteristics were similar between the pure bacterial and mixed bacterial-viral infections groups. The frequency of viral detection depends on the availability of PCR techniques and lower respiratory specimens.

Jartti T, Kuusipalo H, Vuorinen T, Soderlund-Venermo M, Allander T, Waris M, Hartiala J, Ruuskanen O. Allergic sensitization is associated with rhinovirus-, but not other virus-, induced wheezing in children. Pediatr Allergy Immunol 2010: 21: 1008–1014. © 2010 John Wiley & Sons A/S Background: Data on the link between atopy and viral wheeze are limited. Aim: To evaluate the association between IgE sensitization and viral infection in wheezing children. Methods: This is an observational study in hospitalized wheezing children (n = 247; median age 1.6 ; interquartile range 1.1, 2.9). Eighteen respiratory viral infections were studied using all available methods. A specific immunoglobulin E (IgE) sensitization for common food and aeroallergens and other atopy-related variables including total IgE, blood and nasal eosinophils, exhaled nitric oxide, eczema and atopic eczema, parental allergy and asthma, number of wheezing episodes, positive asthma predictive index or asthma and use of inhaled corticosteroid were correlated with specific viral etiology. Results: Atopy was closely associated with sole rhinovirus etiology (n = 58) but not with sole respiratory syncytial virus, sole enterovirus, sole human bocavirus, sole other virus, mixed viral, or virus negative etiology. The number of sensitizations was particularly associated with sole rhinovirus etiology (odds ratio 4.59; 95% confidence interval 1.78, 11.8; adjusted to age and sex), followed by aeroallergen sensitization (respectively; 4.18; 2.00, 8.72), total IgE level (2.06; 1.32, 3.21), food allergen sensitization (2.02; 1.08, 3.78), and nasal eosinophil count (1.52; 1.08, 2.13). Conclusions: According to our data, allergic sensitization is positively linked to rhinovirus-, but not other virus-, associated wheezing and calls attention for studies to test rhinovirus-associated wheezing as a part of asthma risk indices.

The purpose of this study was to examine the association between bacterial colonization/infection and respiratory outcomes in children younger than 3 years old who were hospitalized for their first wheezing episode. This was an observational study. The primary outcome was hospitalization time and the secondary outcomes included relapses within 2 months and time to recurrent wheezing (i.e. three physician confirmed wheezing episodes) within 12 months. Bacterial antibody assays for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae and Chlamydia pneumoniae were studied as well as nasopharyngeal bacterial culture for the three former and urine pneumococcal antigen. Nasopharyngeal bacterial culture was positive in 31/52 (60%) children, serologic evidence of bacterial infection was found in 17/96 (18%) children, urine pneumococcal antigen was positive in 24/101 (24%), and any bacterial detection method was positive in 53/106 (50%) children. The children with positive nasopharyngeal bacterial culture had longer duration of hospitalization (hazard ratio 2.4) and more often relapsed within two months than those with negative culture (odds ratio 7.3). In this study, half of the first time wheezing children had bacterial colonization or symptomatic or asymptomatic bacterial infection. The bacterial colonization (i.e. positive nasopharyngeal bacterial culture) was associated with longer duration of hospitalization and higher risk of recurrent wheezing.

Background Human bocavirus (HBoV) is a widespread human parvovirus causing acute respiratory illness in young children. The HBoV primary infections are viremic and can be diagnosed serologically. Objectives To set up HBoV-IgG-avidity enzyme immuno assays (EIAs) using as antigen recombinant VP2 virus-like particles (VLPs), for diagnosis and timing of primary infections and their distinction from secondary infections or immunoactivations by this recently found virus. Study design The VLPs were utilized in setting up HBoV-IgG-avidity-EIAs of two different types. Paired sera were available from 36 wheezing children with acute primary HBoV infection, single sera from 108 nonsymptomatic university students, and 84 single or follow-up sera from 38 adults with pre-existing HBoV immunity. Results HBoV-IgG avidity for the VP2-VLPs was measured successfully by protein-denaturing EIAs of two types, employing low concentrations of urea (4.7 M and 2.5 M). The diagnostic specificities were 99.1% and 90.7%, and diagnostic sensitivities, 94.4% and 91.7%, respectively. Interestingly, of the adults followed up 44% (4/9) exhibited significant titre increases of past-immunity HBoV-IgG. Conclusions Diagnosis of HBoV primary infection can be strengthened by measurement of IgG avidity. HBoV secondary infections or anamnestic antibody responses occur ubiquitously in immunocompetent adults.

To analyze clinical characteristics and prevalence of rhinovirus infections in children in the hospital, we reviewed a retrospective dataset from a 20‐year period, and conducted a short‐term prospective study. Records of children and adolescents treated at our hospital during 1987–2006 with a documented rhinovirus infection were reviewed and compared with patients with other respiratory virus infections. Prospective study included all children ≥1 month of age admitted to pediatric infectious disease ward during an autumn period. Rhinoviruses were detected by reverse transcription‐PCR and/or culture, and sequence analysis was used for virus typing. In the retrospective study, the median age of 580 children with rhinovirus infection was 1.9 years (interquartile range, 1.0–4.3 years), and 27% had an underlying medical condition. Eighty‐four children (16% of in‐patients) were treated at pediatric intensive care unit. Twenty‐one children (4%) had a hospital‐acquired rhinovirus infection. In the prospective study, rhinoviruses were detected in 28% of 163 hospital episodes. Acute wheezing illness was diagnosed in 61% of children with rhinovirus and in 31% of children with respiratory syncytial virus, enterovirus, or no study virus (P