Burden of Respiratory Syncytial Virus Infection During the First Year of Life.

BACKGROUND: Although many infants with respiratory syncytial virus (RSV) infection are hospitalized, most infants are treated as outpatients. Limited data are available on the burden of RSV in outpatient infants. METHODS: In a prospective study, we enrolled 431 newborn infants and followed them up for a 10-month period (September-June). During each respiratory illness, we examined the infants and obtained nasopharyngeal specimens for the detection of RSV. The parents completed daily symptom diaries throughout the study. RESULTS: Among 408 active participants, the seasonal incidence rate of RSV illness was 328.4 per 1000 (95% confidence interval [CI], 275.2-389.0). Infants with ≥1 sibling had a 1.9-fold higher incidence of RSV illness than those without siblings (95% CI, 1.3-2.8; P < .001). Acute otitis media developed in 103 (76.9%) of 134 infants with RSV infection, and 95 (70.9%) were treated with antibiotics. Nine infants with RSV (6.7%) were hospitalized, for a seasonal incidence rate of RSV hospitalization of 22.1 per 1000 (95% CI, 10.1-41.9). CONCLUSIONS: The outpatient burden of RSV is heavy on infants during the first year of life. Acute otitis media is a frequent complication of RSV, and it should be included in cost-effectiveness analyses of prevention or treatment of RSV infections in infants.

Efficacy of inhaled salbutamol with and without prednisolone for first acute rhinovirus-induced wheezing episode.

BACKGROUND: Acute rhinovirus-induced wheezing is common in young children and may respond to systemic corticosteroid. There are no trials on the efficacy of inhaled beta2 -agonist in this clinical scenario. OBJECTIVE: To study post hoc the short-term (up to 2 months) efficacy of inhaled beta2 -agonist with and without oral corticosteroid in the first acute rhinovirus-induced severe wheezing episode in young hospitalized children. METHODS: The study population came from two randomized controlled trials comparing oral prednisolone (2 mg/kg/d for 3 days) to placebo: Vinku (n = 35, NCT00494624) used high-dose regular nebulized salbutamol (0.15 mg/kg 2-4 h intervals) and Vinku2 (n = 60, NCT00731575, EudraCT 2006-007100-42) used inhaled salbutamol on-demand. Both studies used identical detailed follow-up assessments. The primary outcome of the former was the duration of hospitalization and of the latter the occurrence of and the time to a new physician-confirmed wheezing episode within 2 months after discharge. Treatment groups included salbutamol high-dose vs. salbutamol on-demand while adjusting for prednisolone status and acknowledging for interactions with exception of the duration of hospitalization in which prednisolone groups could not be fully used due to protocol differences. RESULTS: Median age of subjects was 13 months, 32% were sensitized and 22% had doctor-diagnosed eczema. In the duration of hospitalization, salbutamol high-dose/placebo versus salbutamol on-demand/placebo groups did not differ (p = .12). In the occurrence of and time to relapse within 2 months, a significant group × treatment interaction was observed (both p = .02), such that high-dose group had less and longer time to relapses than on-demand group in prednisolone arm (both p < .05), but no difference was detected in placebo arm (both p > .26). CONCLUSIONS: In young, hospitalized children with first episode of rhinovirus-induced wheezing, high-dose inhaled salbutamol may interact with oral prednisolone. However, further trials are warranted.

Rhinovirus-induced first wheezing episode predicts atopic but not nonatopic asthma at school age.

BACKGROUND: Persistent childhood asthma is mainly atopy driven. However, limited data exist on the risk factors for childhood asthma phenotypes. OBJECTIVE: We sought to identify risk factors at the first severe wheezing episode for current asthma 7 years later and separately for atopic and nonatopic asthma. METHODS: One hundred twenty-seven steroid-naive children with the first severe wheezing episode (90% hospitalized/10% emergency department treated) were followed for 7 years. The primary outcome was current asthma at age 8 years, which was also analyzed separately as atopic and nonatopic asthma. Risk factors, including sensitization, viral cause, and other main asthma risk factors, were analyzed. RESULTS: At study entry, median age was 11 months (interquartile range, 6-16 months); 17% were sensitized, and 98% were virus positive. Current asthma (n = 37) at 8 years was divided into atopic (n = 19) and nonatopic (n = 18) asthma. The risk factors for current atopic asthma at study entry were sensitization (adjusted odds ratio [OR], 12; P < .001), eczema (adjusted OR, 4.8; P = .014), and wheezing with rhinovirus (adjusted OR, 5.0; P = .035). The risk factors for nonatopic asthma were the first severe respiratory syncytial virus/rhinovirus-negative wheezing episode (adjusted OR, 8.0; P = .001), first wheezing episode at age less than 12 months (adjusted OR, 7.3; P = .007), and parental smoking (adjusted OR, 3.8; P = .028). CONCLUSIONS: The data suggest diverse asthma phenotypes and mechanisms that can be predicted by using simple clinical markers at the time of the first severe wheezing episode. These findings are important for designing early intervention strategies for secondary prevention of asthma.

Short- and long-term efficacy of prednisolone for first acute rhinovirus-induced wheezing episode.

BACKGROUND: Rhinovirus-induced wheezing is an important risk factor for recurrent wheezing. There are no randomized controlled trials on the effect of systemic corticosteroids in patients with this disease. OBJECTIVE: We sought to study the short- and long-term effects of prednisolone treatment of the first acute, moderate-to-severe, rhinovirus-induced wheezing episode in young children. METHODS: After confirming rhinovirus from nasopharyngeal aspirate by using PCR, 79 children with a first wheezing episode at age 3 to 23 months were randomized to receive oral prednisolone (first dose of 2 mg/kg, followed by 2 mg/kg/d in 2 divided doses for 3 days) or placebo. The trial was double blind throughout the 12-month follow-up. The primary outcomes were long term: new physician-confirmed wheezing episode within 2 months, number of physician-confirmed wheezing episodes within 12 months, and initiation of regular controller medication for asthma symptoms within 12 months. The primary interaction analysis examined rhinovirus load. RESULTS: Seventy-four patients completed the study (mean age, 13 months; 28% atopic). Long-term outcomes did not differ between groups (all P ≥ .30). For short-term outcomes, the prednisolone group had less cough, rhinitis, noisy breathing, severe breathing difficulties, and nocturnal respiratory symptoms at home within 2 weeks (all P < .05). The 25 children with greater than 7000 rhinovirus copies/mL (most sensitive cutoff) benefitted from prednisolone in terms of less risk of physician-confirmed recurrence within 2 and 12 months compared with placebo (both P < .05). CONCLUSIONS: Prednisolone cannot be routinely recommended for all young children experiencing their first acute, moderate-to-severe, rhinovirus-induced wheezing episode. Prednisolone might be beneficial in a subgroup of children with high viral loads.

Prednisolone reduces recurrent wheezing after first rhinovirus wheeze: a 7-year follow-up.

BACKGROUND: To better understand the role of human rhinovirus-associated wheeze as a risk factor for childhood recurrent wheezing, a cohort of young children experiencing their first wheezing episode was followed until school age. METHODS: All 111 hospitalized wheezing children (median age, 12 months) were initially participated in a randomized, double-blind, placebo-controlled, parallel trial on the efficacy of oral prednisolone. In this 7-yr follow-up, risk factors for recurrent wheezing were analysed, and then, the efficacy of prednisolone was evaluated overall and in pre-specified subgroups post-hoc. The main outcome was time to recurrent wheezing. RESULTS: The strongest independent risk factor for recurrent wheezing was rhinovirus detection (hazard ratio 3.54; 95% confidence interval 1.51-8.30) followed by sensitization (3.47; 1.55-8.30, respectively) age <1 yr (2.45; 1.29-4.65) and eczema (2.33; 1.11-4.90). Overall, prednisolone did not prevent recurrent wheezing. In subgroup analysis, prednisolone was associated with less recurrent wheezing in children affected by rhinovirus (0.32; 0.12-0.90, adjusted to sensitization, young age, viral aetiology and parental asthma) and/or with eczema (0.27; 0.08-0.87, adjusted respectively). CONCLUSIONS: Our data strengthen the role of rhinovirus-associated wheeze as an important risk factor for recurrent wheezing and asthma in young first-time wheezing children. Prospective randomized trials on the efficacy of corticosteroids in rhinovirus-associated early wheezing are warranted. (ClinicalTrials.gov number, NCT 00494624).

Burden of influenza during the first year of life.

BACKGROUND: Every year, influenza viruses infect millions of children and cause an enormous burden of disease. Young children are at the highest risk for influenza-attributable hospitalizations. Nevertheless, most young children are treated as outpatients, and limited data are available on the burden of influenza in these children. METHODS: We carried out a prospective cohort study and followed 431 infants born in June-August 2017 for 10 months from September 1, 2017, to June 30, 2018. The parents filled out daily symptom diaries and were instructed to bring their child for clinical examination at our study clinic each time the child had fever or any signs or symptoms of respiratory tract infection. During each visit, we obtained nasopharyngeal swab specimens for determination of the viral etiology of the illness. RESULTS: A total of 55 episodes of laboratory-confirmed influenza were diagnosed among the 408 actively participating children, which corresponds to an annual incidence rate of 135/1000 children (95% Cl, 102-175). Excluding five children with double viral infection, acute otitis media developed as a complication of influenza in 23 (46%) children. One (2%) child with influenza was hospitalized because of febrile convulsion. The effectiveness of influenza vaccination was 48% (95% CI, -29%-80%). CONCLUSIONS: The burden of influenza during the first year of life is heavy in the outpatient setting where most infants with influenza are managed. Effective strategies for the prevention of influenza particularly in infants under 6 months of age are needed to diminish the burden of disease in this age group.

Early oseltamivir treatment of influenza in children 1-3 years of age: a randomized controlled trial.

BACKGROUND: Oseltamivir provides modest clinical benefits to children with influenza when started within 48 hours of symptom onset. The effectiveness of oseltamivir could be substantially greater if the treatment were started earlier during the course of the illness. METHODS: We carried out a randomized, double-blind, placebo-controlled trial of the efficacy of oseltamivir started within 24 hours of symptom onset in children 1-3 years of age with laboratory-confirmed influenza during the seasons of 2007-2008 and 2008-2009. Eligible children received either orally administered oseltamivir suspension or a matching placebo twice daily for 5 days. The children received clinical examinations, and the parents filled out detailed symptom diaries for 21 days. RESULTS: Of 408 randomized children who received the study drug (oseltamivir, 203, and placebo, 205), 98 had laboratory-confirmed influenza (influenza A, 79, and influenza B, 19). When started within 12 hours of the onset of symptoms, oseltamivir decreased the incidence of acute otitis media by 85% (95% confidence interval, 25%-97%), but no significant reduction was observed with treatment started within 24 hours. Among children with influenza A, oseltamivir treatment started within 24 hours shortened the median time to resolution of illness by 3.5 days (3.0 vs 6.5 days; P = .006) in all children and by 4.0 days (3.4 vs 7.3; P = .006) in unvaccinated children and reduced parental work absenteeism by 3.0 days. No efficacy was demonstrated against influenza B infections. CONCLUSIONS: Oseltamivir treatment started within 24 hours of symptom onset provides substantial benefits to children with influenza A infection. Clinical trials registration. ClinicalTrials.gov identifier: NCT00593502.

Clinical assessment and improved diagnosis of bocavirus-induced wheezing in children, Finland.

Human bocavirus (HBoV) is a widespread respiratory virus. To improve diagnostic methods, we conducted immunoglobulin (Ig) G and IgM enzyme immunoassays with recombinant virus-like particles of HBoV as antigen. Acute-phase and follow-up serum samples from 258 wheezing children and single serum samples from 115 healthy adults in Finland were examined. Our assays had a sensitivity of 97% and a specificity of 99.5%. Of adults, 96% had immunity; none had an acute infection. Of 48 children with serologically diagnosed acute HBoV infections, 45 were viremic and 35 had virus in nasopharyngeal aspirates (NPAs). Of 39 HBoV NPA PCR-positive children co-infected with another virus, 64% had a serologically verified HBoV infection. HBoV caused illness of longer duration than rhinovirus and of equal severity to that of respiratory syncytial virus. Among children with bronchiolitis, >25% had acute HBoV infections. Accurate HBoV diagnosis requires serologic analysis or PCR of serum; PCR of NPAs alone is insufficient.

Bronchiolitis: age and previous wheezing episodes are linked to viral etiology and atopic characteristics.

BACKGROUND: : Diagnostic criteria for bronchiolitis are variable. OBJECTIVE: : To study how the risk factors for recurrent wheezing and asthma vary by different definitions of bronchiolitis. METHODS: : Viral etiology and atopic characteristics were studied in 259 hospitalized wheezing children (median age, 14 months; range, 0-36 months). The data were analyzed according to age (<6, <12, <24 and <36 months) and whether they had a history or no history of a previous wheezing episode. Sixteen viruses were detected by conventional and molecular methods. Atopic characteristics included the presence of eczema, specific and total IgE responses, blood eosinophil count, and modified asthma predictive index. RESULTS: : Evidence of respiratory virus infection was found in 93% of the cases and allergic sensitization in 26% of the cases. Rhinovirus infections and atopic characteristics (sensitization, blood eosinophil count, and modified asthma predictive index) increased by age and were significantly more common in children with recurrent wheezing episodes than in first-time wheezers in age categories of <24 and <36 months (P < 0.05 for all). CONCLUSIONS: : In children with bronchiolitis, 2 clinical factors, age and number of previous wheezing episodes, are linked to inflammatory (atopy-related factors) and virologic risk factors of asthma (rhinovirus-associated disease). According to current US and UK guidelines, bronchiolitis includes wheezing children <24 months of age. Our observations suggest that the clinical definition should include only children with their first episode of wheezing.

Clinical presentation of influenza in unselected children treated as outpatients.

BACKGROUND: Influenza causes a great disease burden on children especially in the outpatient setting. The signs and symptoms of influenza in unselected children treated as outpatients have not been previously published. METHODS: We assessed the clinical presentation of influenza in a prospective study of respiratory infections in preenrolled cohorts of children < or =13 years of age during 2 consecutive respiratory seasons (2231 child-seasons of follow-up). We examined the children and obtained a nasal swab for the detection of influenza during every episode of illness, regardless of the presence or absence of fever or the severity of the symptoms. RESULTS: Influenza was virologically confirmed in 372 children, of whom 353 (95%) providing complete data on the signs and symptoms were included in the analyses. A total of 95% of these children were febrile, and 50% had fever > or =39.0 degrees C. Among children <3 years of age, 20% had fever > or =40.0 degrees C. Seventy-seven percent of the children had cough and 78% had rhinitis. In children 7 to 13 years of age, only 39% had headache and 13% had myalgia. CONCLUSIONS: High fever is a prominent sign of influenza in children, and the clinical presentation of influenza is most severe in children <3 years of age. Headache and myalgia are not typical features of influenza in outpatient children. Most children with influenza have rhinitis during the early phase of the illness, which makes the clinical diagnosis of influenza difficult especially in the youngest children.

Systemic T-helper and T-regulatory cell type cytokine responses in rhinovirus vs. respiratory syncytial virus induced early wheezing: an observational study.

BACKGROUND: Rhinovirus (RV) associated early wheezing has been recognized as an independent risk factor for asthma. The risk is more important than that associated with respiratory syncytial virus (RSV) disease. No comparative data are available on the immune responses of these diseases. OBJECTIVE: To compare T-helper1 (Th1), Th2 and T-regulatory (Treg) cell type cytokine responses between RV and RSV induced early wheezing. METHODS: Systemic Th1-type (interferon [IFN] -gamma, interleukin [IL] -2, IL-12), Th2-type (IL-4, IL-5, IL-13) and Treg-type (IL-10) cytokine responses were studied from acute and convalescence phase serum samples of sole RV (n = 23) and RSV affected hospitalized wheezing children (n = 27). The pre-defined inclusion criteria were age of 3-35 months and first or second wheezing episode. Analysis was adjusted for baseline differences. Asymptomatic children with comparable demographics (n = 11) served as controls for RV-group. RESULTS: RV-group was older and had more atopic characteristics than RSV-group. At acute phase, RV-group had higher (fold change) IL-13 (39-fold), IL-12 (7.5-fold), IFN-gamma (6.0-fold) and IL-5 (2.8-fold) concentrations than RSV-group and higher IFN-gamma (27-fold), IL-2 (8.9-fold), IL-5 (5.6-fold) and IL-10 (2.6-fold) than the controls. 2-3 weeks later, RV-group had higher IFN-gamma (>100-fold), IL-13 (33-fold) and IL-10 (6.5-fold) concentrations than RSV-group and higher IFN-gamma (15-fold) and IL-2 (9.4-fold) than the controls. IL-10 levels were higher in acute phase compared to convalescence phase in both infections (p < 0.05 for all). CONCLUSION: Our results support a hypothesis that RV is likely to trigger wheezing mainly in children with a predisposition. IL-10 may have important regulatory function in acute viral wheeze.

Serodiagnosis of human bocavirus infection.

BACKGROUND: A new human-pathogenic parvovirus, human bocavirus (HBoV), has recently been discovered and associated with respiratory disease in small children. However, many patients have presented with low viral DNA loads, suggesting HBoV persistence and rendering polymerase chain reaction-based diagnosis problematic. Moreover, nothing is known of HBoV immunity. We examined HBoV-specific systemic B cell responses and assessed their diagnostic use in young children with respiratory disease. PATIENTS AND METHODS: Paired serum samples from 117 children with acute wheezing, previously studied for 16 respiratory viruses, were tested by immunoblot assays using 2 recombinant HBoV capsid antigens: the unique part of virus protein 1 and virus protein 2. RESULTS: Virus protein 2 was superior to the unique part of virus protein 1 with respect to immunoreactivity. According to the virus protein 2 assay, 24 (49%) of 49 children who were positive for HBoV according to polymerase chain reaction had immunoglobulin (Ig) M antibodies, 36 (73%) had IgG antibodies, and 29 (59%) exhibited IgM antibodies and/or an increase in IgG antibody level. Of 22 patients with an increase in antibody levels, 20 (91%) had a high load of HBoV DNA in the nasopharynx, supporting the hypothesis that a high HBoV DNA load indicates acute primary infection, whereas a low load seems to be of less clinical significance. In a subgroup of patients who were previously determined to have acute HBoV infection (defined as a high virus load in the nasopharynx, viremia, and absence of other viral infections), 9 (100%) of 9 patients had serological evidence of primary infection. In the control group of 68 children with wheezing who had polymerase chain reaction results negative for HBoV in the nasopharynx, 9 (13%) had IgM antibodies, including 5 who displayed an increase in IgG antibody levels and were viremic. No cross-reactivity with human parvovirus B19 was detected. CONCLUSIONS: Respiratory infections due to HBoV are systemic, elicit B cell immune responses, and can be diagnosed serologically. Serological diagnoses correlate with high virus loads in the nasopharynx and with viremia. Serological testing is an accurate tool for disclosing the association of HBoV infection with disease.

Human bocavirus and acute wheezing in children.

BACKGROUND: Human bocavirus is a newly discovered parvovirus. It has been detected primarily in children with acute lower respiratory tract infection, but its occurrence, clinical profile, and role as a causative agent of respiratory tract disease are not clear. METHODS: We investigated the presence of human bocavirus by quantitative polymerase chain reaction of nasopharyngeal aspirate specimens and selected serum samples obtained from 259 children (median age, 1.6 years) who had been hospitalized for acute expiratory wheezing. The samples were analyzed for 16 respiratory viruses by polymerase chain reaction, virus culture, antigen detection, and serological assays. RESULTS: At least 1 potential etiologic agent was detected in 95% of children, and >1 agent was detected in 34% of children. Human bocavirus was detected in 49 children (19%). A large proportion of the cases were mixed infections with other viruses, but human bocavirus was the only virus detected in 12 children (5%). High viral loads of human bocavirus were noted mainly in the absence of other viral agents, suggesting a causative role for acute wheezing. In addition, infections that had uncertain clinical relevance and low viral loads were prevalent. Human bocavirus DNA was frequently detected in serum specimens obtained from patients with acute wheezing, suggesting systemic infection. CONCLUSIONS: Human bocavirus is prevalent among children with acute wheezing and can cause systemic infection. Results suggest a model for bocavirus infection in which high viral loads are potentially associated with respiratory symptoms and low viral loads indicate asymptomatic shedding. Therefore, quantitative polymerase chain reaction analysis may be important for additional studies of human bocavirus.

Atopic characteristics of wheezing children and responses to prednisolone.

We wanted to test the hypothesis that the efficacy of systemic corticosteroid is associated with atopic characteristics in wheezing children. A randomized controlled trial comparing oral prednisolone (2 mg/kg/day in 3 divided doses for 3 days) with placebo in hospitalized wheezing children (n = 266, median 1.6 years, range 3 months to 15.2 years) was conducted. In this post-hoc analysis, we assessed the link between the efficacy of prednisolone and several atopic characteristics, such as atopy, aeroallergen sensitization, total IgE level, number of sensitizations, eczema, atopic eczema, blood or nasal eosinophils, exhaled nitric oxide, positive modified asthma predictive index/asthma, inhaled corticosteroid medication and parental asthma/allergy. Virology was studied comprehensively. Our primary endpoint was the time until ready for discharge, and the most important secondary endpoint was the occurrence of relapses during the following 2 months. For statistics, we used interaction analyses in uni- and multivariate regression models. Overall, prednisolone did not decrease any of our predefined clinical endpoints. Neither was the efficacy of prednisolone associated with atopy. However, prednisolone significantly decreased the time until ready for discharge in children with positive modified asthma predictive index/asthma, inhaled corticosteroids, or rhinovirus infection and/or in children without azithromycin treatment. Prednisolone significantly decreased relapses in children with eczema, nasal eosinophilia and rhinovirus infection. The multiple clinical, inflammatory and viral markers associating with the efficacy of prednisolone should be confirmed in prospective trials. It is important that corticosteroid intervention trials have strict design for these potentially confounding factors.

Evaluation of the efficacy of prednisolone in early wheezing induced by rhinovirus or respiratory syncytial virus.

BACKGROUND: The role of systemic corticosteroids in the treatment of early childhood wheezing in children is not clear. OBJECTIVE: We sought to determine whether prednisolone is effective in rhinovirus-induced early wheezing. METHODS: We conducted a controlled trial comparing oral prednisolone (2 mg/kg per day in three divided doses for 3 days) with placebo in 78 hospitalized children (mean age, 1.1 year; standard deviation, 0.7) experiencing their first or second episode of wheezing induced by rhinovirus or respiratory syncytial virus. Mixed viral infections were excluded. Our primary end point was the time until the patient was ready for discharge; secondary end points included oxygen saturation during hospitalization, duration of symptoms, occurrence of relapses during the next 2 months and blood eosinophil counts at discharge and 2 weeks later. RESULTS: In multivariate regression analysis, prednisolone did not influence the time until ready for discharge, but it decreased relapses during the subsequent 2-month period in rhinovirus-affected children (prednisolone versus placebo, 22% versus 56%; odds ratio, 19.06; 95% confidence interval, 2.52-144.03; P = 0.004) and in children with blood eosinophils > or = 0.2 x 10/L (respectively, 24% versus 71%; odds ratio, 10.57; 95% confidence interval, 1.99-56.22; P = 0.006). Rhinovirus-affected children had more blood eosinophils on admission (mean, 0.44 versus 0.086 x 10/L), had a higher prevalence of atopy (44% versus 8%) and were older (mean, 1.4 versus 0.9 years, P < 0.001 for all) than respiratory syncytial virus-infected children. CONCLUSION: Prednisolone reduced relapses during a 2-month period after first episodes of wheezing associated with rhinovirus infection or blood eosinophils > or = 0.2 x 10/L.

Absence of Bordetella pertussis Among Infants Hospitalized for Bronchiolitis in Finland, 2008-2010.

In 169 Finnish infants hospitalized for bronchiolitis at age <6 months in 2008-2010, nasopharyngeal aspirates were tested by polymerase chain reaction for Bordetella pertussis and 16 viruses. Respiratory viruses were detected in 89% (71% with respiratory syncytial virus), but no infant had B. pertussis. The latter finding may reflect a positive effect from the broadening of the Finnish pertussis vaccination program in 2005.

Incidence of influenza in Finnish children.

BACKGROUND: Influenza is an important cause of respiratory illness in children, but data on virologically confirmed influenza infections in children treated as outpatients are limited. METHODS: We carried out a prospective cohort study of normal children younger than 13 years (n = 1338) in the winter of 2000 to 2001. During the study period of 32 weeks, the children were examined at the study clinic whenever they had fever or signs of respiratory infection. Nasal swabs were obtained during each episode of infection for determination of the viral etiology of the illness. RESULTS: The overall attack rate of influenza in the cohort was 18.8%. Influenza viruses were isolated from the children from the beginning of November 2000 through May 2001. Virtually in each week between mid-November and the end of April (a period of 24 weeks), influenza viruses accounted for at least 5% of all respiratory infections in the children. During the peak of the epidemic, the percentage of influenza-positive children exceeded 20%. CONCLUSIONS: This study confirms the important role of influenza as a cause of acute respiratory infections in children, even in winters of mild or moderate influenza activity. The study also shows that influenza viruses may circulate in the community at substantial levels much longer than previously thought.

Effectiveness of inactivated influenza vaccine in children aged 9 months to 3 years: an observational cohort study.

BACKGROUND: Few prospectively collected data are available to support the effectiveness of inactivated influenza vaccines in children younger than 2 years. We aimed to establish the effectiveness of trivalent inactivated influenza vaccine against laboratory-confirmed influenza A and B infections in a cohort of children younger than 3 years. METHODS: In a prospective cohort study during the influenza season of 2007-08 in Turku, Finland, between Jan 14 and April 9, 2008, we assessed the effectiveness of trivalent inactivated influenza vaccine against laboratory-confirmed influenza A and B infections in children aged 9 months to 3 years. Our study was part of a clinical trial on antiviral treatment of influenza in children (ClinicalTrials.gov, number NCT00593502). The vaccine was given as part of the Finnish vaccination programme as a 0·5 mL injection. Children enrolled into our study through mailed announcements and local advertisements were examined every time they had fever or signs of respiratory infection. No exclusion criteria were used for enrolment. Influenza was diagnosed with viral culture, antigen detection, and RT-PCR assays of nasal swab specimens. Vaccination status of children was determined by parental report. We calculated the primary effectiveness of influenza vaccination by comparing the proportions of infections in fully vaccinated and unvaccinated children in the follow-up cohort. FINDINGS: We enrolled 631 children into our study with a mean age of 2·13 years (range 9-40 months). Seven (5%) of 154 fully vaccinated children and 61 (13%) of 456 unvaccinated children contracted influenza during the study (effectiveness 66%, 95% CI 29-84; p=0·003). In the subgroup of children younger than 2 years, four (4%) of 96 fully vaccinated children and 21 (12%) of 172 unvaccinated children contracted influenza (66%, 9-88, p=0·03). We were unable to record any adverse events associated with the vaccination of the children in our study. INTERPRETATION: Trivalent inactivated influenza vaccine was effective in preventing influenza in young children, including those younger than 2 years. Our findings suggest that influenza vaccine recommendations should be reassessed in most countries. FUNDING: F Hoffmann-La Roche Ltd.

Expression and serological characterization of polyomavirus WUPyV and KIPyV structural proteins.

The polyomaviruses WUPyV and KIPyV were recently discovered. We expressed their structural proteins VP1, VP2, and VP3, and the corresponding proteins of BKV and JCV, for immunoblotting of IgG antibodies from 115 wheezing young children and 25 asymptomatic adults. Furthermore, nasopharyngeal aspirates (NPA) and sera from the children were examined by PCR for viral DNA. The overlapping minor proteins VP2 and VP3 of WUPyV and KIPyV were more reactive in immunoblots than the major protein VP1; of 100 NPA PCR-negative wheezing children aged < or = 4 y, 31 (31%) and 31 (31%) were positive for WUPyV and KIPyV VP2/VP3, compared to only 3 (3%) and 5 (5%) for VP1, respectively. For comparison, the respective WUPyV and KIPyV IgG seroprevalences as determined by immunofluorescence assay (IFA) with nondenatured VP1 were 80% and 54%, respectively, among 50 NPA PCR-negative children aged < or = 2 y. This difference shows the importance of conformational VP1 antigenicity. Of the 25 adults, 52% and 68% were IgG-positive in immunoblots for VP2/VP3 of WUPyV and KIPyV, and 8% and 12% were for VP1, respectively. Of the 192 NPA samples studied by PCR, 7 (3.6%) were positive for WUPyV, and 3 (1.5%) were positive for KIPyV DNA. Unlike the NPA samples, none of the corresponding 443 sera contained WUPyV or KIPyV DNA. Together with the high VP2/VP3 IgG prevalence, this points to a paucity or brevity of KIPyV and WUPyV viremias among immunocompetent children. Our results indicate the significance of protein conformation in immunoreactivity of VP1, and show the antigenic importance of the WUPyV and KIPyV minor proteins VP2 and VP3. The high and rapidly increasing IgG prevalence rates observed in this study for WUPyV and KIPyV support the notion that these novel polyomaviruses are widespread and are acquired early in childhood.