Matti Waris

Etiology of community-acquired pneumonia in 254 hospitalized children.

Background. Childhood community‐acquired pneumonia is a common illness, but there have been relatively few comprehensive studies of the viral and bacterial etiology in developed countries. The aim of the present investigation was to determine the etiology of community‐acquired pneumonia in hospitalized children by several laboratory methods. Methods. In a 3‐year prospective study a nasopharyngeal aspirate for viral studies and acute and convalescent serum samples for viral and bacterial serology were taken from 254 children with symptoms of acute infection and infiltrates compatible with pneumonia in the chest radiograph. The role of 17 microbes was investigated. Results. A potential causative agent was detected in 215 (85%) of the 254 patients. Sixty‐two percent of the patients had viral infection, 53% had bacterial infection and 30% had evidence of concomitant viral‐bacterial infection. Streptococcus pneumoniae (37%), respiratory syncytial virus (29%) and rhinovirus (24%) were the most common agents associated with community‐acquired pneumonia. Only one patient had a positive blood culture (S. pneumoniae) of 125 cultured. A dual viral infection was detected in 35 patients, and a dual bacterial infection was detected in 19 patients. Conclusions. The possible causative agent of childhood community‐acquired pneumonia can be detected in most cases. Further studies are warranted to determine what etiologic investigations would aid in the management of pneumonia. With effective immunization for S. pneumoniae and respiratory syncytial virus infections, more than one‐half of the pneumonia cases in this study could have been prevented.

Human bocavirus and acute wheezing in children.

Abstract 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.

Rhinovirus-induced wheezing in infancy—the first sign of childhood asthma?

Abstract Background: Although known as common causes of upper respiratory infections, rhinoviruses, enteroviruses, and corona-viruses are poorly studied as inducers of wheezing in infants, and their possible role in the development of childhood asthma has not been investigated. Objective: The purposes of this study were to assess the occurrence of RV, enterovirus, and coronavirus infections in wheezing infants and to evaluate the association of these viral findings with early school-age asthma. Methods: In 1999, outcome in relation to asthma was studied in 82 of 100 initially recruited children who had been hospitalized for wheezing in infancy during the period 1992-1993. In 2000, etiologic viral studies regarding the index episode of wheezing were supplemented by rhinovirus, enterovirus, and coronavirus detection by RT-PCR from frozen nasopharyngeal aspirates in 81 of the children for whom adequate samples were available. Of these children, 66 had participated in the follow-up in 1999. Results: Rhinoviruses were identified in 27 (33%) of the 81 children, enteroviruses in 10 (12%), and coronaviruses in none. Rhinoviruses were present as single viral findings in 22 (81%) of the 27 rhinovirus-positive cases, and rhinovirus infections were associated with the presence of atopic dermatitis in infancy. Enteroviruses were commonly encountered in mixed infections and had no association with atopy. As single viral findings, rhinoviruses were associated with the development of asthma (P = .047; odds ratio, 4.14; 95% CI, 1.02-16.77 versus rhinovirus-negative cases [by logistic regression adjusted for age, sex, and atopic dermatitis on entry)]. Conclusion: Our results present rhinoviruses as important inducers of wheezing even in infancy. The association with atopy and subsequent asthma calls for reevaluation of the role of rhinoviruses in the development of asthma. (J Allergy Clin Immunol 2003;111:66-71.)

Coxsackievirus A6 and Hand, Foot, and Mouth Disease, Finland

During fall 2008, an outbreak of hand, foot, and mouth disease (HFMD) with onychomadesis (nail shedding) as a common feature occurred in Finland. We identified an unusual enterovirus type, coxsackievirus A6 (CVA6), as the causative agent. CVA6 infections may be emerging as a new and major cause of epidemic HFMD.

Rhinovirus Transmission within Families with Children: Incidence of Symptomatic and Asymptomatic Infections

BACKGROUND Rhinoviruses are the most common cause of respiratory tract infections, but the transmission in families has not been studied using sensitive and specific molecular detection methods. METHODS Children hospitalized for any infection were screened for rhinoviruses. Eight families with a rhinovirus-positive index child and 16 families with a rhinovirus-negative index child were monitored for 3 weeks for disease symptoms, and the presence and quantity of rhinoviruses in nasal swab samples were determined by quantitative reverse transcription-polymerase chain reaction. Rhinoviruses were further identified by melting temperature and partial sequence analysis. RESULTS The rates of rhinovirus infection were 1.00 cases per person among the 17 siblings and 0.50 cases per person among the 14 parents of rhinovirus-positive index patients; the rates were 0.54 cases per person among the 24 siblings and 0.23 cases per person among the 30 parents of rhinovirus-negative index patients. Symptomatic infections were associated with an age of <7 years but not with a high copy number of rhinovirus genomes. Virus typing revealed the transmission routes of the viruses and showed that several virus types could circulate in the families simultaneously. CONCLUSIONS Rhinoviruses are frequently transmitted from children to other family members. Most rhinovirus infections in young children are symptomatic, but secondary infections in adults are often asymptomatic. Multiple virus types circulate simultaneously in families.

Microbiology of Acute Otitis Media in Children with Tympanostomy Tubes: Prevalences of Bacteria and Viruses

Abstract Background. Bacteria are found in 50%–90% of cases of acute otitis media (AOM) with or without otorrhea, and viruses are found in 20%–49% of cases. However, for at least 15% of patients with AOM, the microbiological etiology is never determined. Our aim was to specify the full etiology of acute middle ear infection by using modern microbiological methods concomitantly for bacterial and viral detection. Methods. The subjects were 79 young children having AOM with new onset (<48 h) of otorrhea through a tympanostomy tube. Middle ear fluid samples were suctioned from the middle ear through the tympanostomy tube. Bacteria were sought by culture and polymerase chain reaction; viruses were analyzed by culture, antigen detection, and polymerase chain reaction. Results. At least 1 respiratory tract pathogen was noted in 76 children (96%). Bacteria were found in 73 cases (92%), and viruses were found in 55 (70%). In 52 patients (66%), both bacteria and viruses were found. Bacteria typical of AOM were detected in 86% of patients. Picornaviruses accounted for 60% of all viral findings. Conclusions. In the great majority of children, AOM is a coinfection with bacteria and viruses. The patent tympanostomy tube does not change the spectrum of causative agents in AOM. A microbiological etiology can be established in practically all cases.

Rhinovirus-associated wheezing in infancy: comparison with respiratory syncytial virus bronchiolitis.

Background: There is increasing evidence that rhinoviruses (RV) are able to cause lower airway infections and to induce wheezing in young children. There are few data on the clinical characteristics of RV infections in infants. Objective: The aim of the study was to compare clinical characteristics of infantile RV infection associated with wheezing and respiratory syncytial virus (RSV) bronchiolitis. Material and Methods: During a 22-month study period in 1992–1993, 100 children younger than 24 months old were hospitalized with respiratory tract infection-associated wheezing. Viral etiology was originally assessed by antibody and antigen assays. Etiologic studies were later supplemented by polymerase chain reaction for RVs (in 2000) and for RSV (in 2002), studied in frozen respiratory samples. There were 81 children with adequate determinations for both RVs and RSV. Twenty-six children had RV and 24 had RSV infection, and these 50 cases form the material of the present study. Atopic dermatitis, oxygen saturation, respiratory rates and clinical scores based on wheezing and retractions and total serum IgE concentrations and blood eosinophil counts were studied in all cases on admission. Results: The children with RV infection, compared with RSV patients, were older (median, 13 versus 5 months), presented more often with atopic dermatitis (odds ratio, 16.7; 95% confidence interval, 2.22–100) and blood eosinophilia (odds ratio, 2.22; 95% confidence interval, 1.04–50). The groups did not differ from each other with regard to total serum IgE. Oxygen saturation values were lower in children with RSV infection. There were no significant differences in respiratory rates or scores combining wheezing and retractions. Conclusion: RV-associated wheezing and RSV bronchiolitis, although having rather similar clinical characteristics, differ significantly with regard to age, presence of atopic dermatitis and eosinophilia during infection.

Identification of respiratory viruses in asymptomatic subjects: asymptomatic respiratory viral infections.

The medical literature of the past 4 decades was searched regarding respiratory virus detection by polymerase chain reaction and conventional methods (culture, antigen detection, serology) in asymptomatic subjects in an attempt to determine the prevalence and clinical significance of such viruses in normal persons.

Viruses and bacteria in sputum samples of children with community-acquired pneumonia

Abstract Few comprehensive studies have searched for viruses and bacteria in children with community-acquired pneumonia (CAP). We identified 76 children hospitalized for pneumonia. Induced sputum samples were analysed for 18 viruses by antigen detection and PCR, and for six bacteria by culture and PCR. Viruses were found in 72% of samples, bacteria in 91%, and both in 66%. Rhinovirus (30%), human bocavirus (18%) and human metapneumovirus (14%) were the most commonly detected viruses. Two viruses were found in 22% of samples and three in 8%. The most common bacteria found were Streptococcus pneumoniae (50%), Haemophilus influenzae (38%), and Moraxella catarrhalis (28%). Rhinovirus–S. pneumoniae was the most commonly found combination of virus and bacterium (16%). All six children with treatment failure had both viruses and bacteria detected in the sputum. Otherwise, we found no special clinical characteristics in those with mixed viral–bacterial detections. With modern molecular diagnostic techniques, there are high rates of both viral and bacterial identification in childhood CAP. The clinical significance of mixed viral–bacterial infections remains unclear, although we found a potential association between them and treatment failure.

Induced sputum in the diagnosis of childhood community-acquired pneumonia

Background: The usefulness of induced sputum in searching for causative agents of pneumonia in children has not been studied. Methods: The study involved 101 children, aged 6 months to 15 years, treated for community-acquired pneumonia at Turku University Hospital (Turku, Finland) from January 2006 to April 2007. Nasopharyngeal aspirate samples were first collected through both nostrils. Sputum production was then induced by inhalation of 5.0% hypertonic saline for 5–10 min and a sputum sample was either aspirated or expectorated. The presence and amount of bacteria and viruses in paired nasopharyngeal aspirate and sputum specimens was analysed and compared using semiquantitative bacterial culture and quantitative PCR techniques. Results: A good quality sputum specimen was obtained from 76 children. The possible causative agent was found in 90% of cases. Streptococcus pneumoniae (46%) and rhinovirus (29%) were the most common microbes detected. Newly discovered viruses human bocavirus and human metapneumovirus were detected in 18% and 13% of the children, respectively. One-quarter of all bacterial findings were only detected in sputum, and the amount of bacteria in the remainder of the sputum specimens compared with nasopharyngeal aspirate was higher in 14% and equal in 70%. The amount of rhinovirus in sputum was higher than in nasopharyngeal aspirate in 82%. Conclusions: Sputum induction provides good quality sputum specimens with high microbiological yield in children with community-acquired pneumonia. Induced sputum analysis can be useful in the microbiological diagnosis of childhood community-acquired pneumonia.