VIRAL INFECTIONS OF THE RESPIRATORY TRACT IN HOSPITALIZED CHILDREN A Study from Oslo during a 90 Months'Period

ABSTRACT. A diagnosis of 979 respiratory viral infections was made in hospitalized children. Respiratory syncytial virus greatly outnumbered the other viruses: it caused 58% of the total virus infections and occurred in winter epidemics. Influenza A and B virus occurred during late winter and spring, rhinovirus had a seasonal distribution towards spring and autumn, whereas adenovirus types 1, 2 and 5 had no distinct seasonal distribution. Whereas respiratory syncytial virus were mainly associated with bronchiolitis and adenovirus type 7 with pneumonia, rhinovirus infections were most often found in children with episodes of acute bronchial asthma. The influenza A and B and adenovirus types 1, 2 and 5 infections often occurred with extrarespiratory symptoms, especially febrile convulsions.     

Acute lower respiratory infections in hospitalized children over a 6 year period in Tokyo

BACKGROUND: Acute lower respiratory infections are major causes of hospitalization in children and are mainly caused by respiratory viruses. In the present study, we investigated the etiologic agents responsible for acute lower respiratory infections from the period November 1986 to October 1992 in order to determine the seasonal pattern and different characteristics of age distribution of respiratory infectious agents, mainly virus infections. METHODS: A total of 1521 patients with lower respiratory infections was hospitalized in Saiseikai Central Hospital, Tokyo, Japan. Nasopharyngeal secretions were obtained for virus isolation and paired sera in the acute and convalescent phases were obtained for serological examination. RESULTS: Etiological agents were identified in 668 of 1521 patients (43.9%) by serological antibody responses, virus isolation and/or detection of virus antigen: 240 (15.8%) with respiratory syncytial (RS) virus; 62 (4.1%) with influenza virus type A; 26 (1.7%) with influenza virus type B; 86 (5.7%) with adenovirus; 81 (5.3%) with parainfluenza virus; 32 (2.1%) with measles virus; 20 (1.3%) with enteroviruses or Herpes virus other than respiratory viruses; 75 (4.9%) with Mycoplasma pneumoniae; 10 (0.7%) with pertussis; and 36 (2.4%) with mixed infections. In the remaining 853 patients (56.1%), etiologic agents were not identified. Respiratory syncytial (RS) virus was a main causative agent of respiratory infections in patients younger than 3 years of age. Influenza virus and M. pneumoniae were two main causative agents in patients with acute respiratory illness over 5 years of age. Parainfluenza virus type 3 was frequently observed in infants from 9 to 12 months of age. A distinct seasonal pattern of viral infections was consistently observed in each year during the study period; RS and influenza viruses were prevalent in winter, parainfluenza virus was prevalent in spring and M. pneumoniae was prevalent in summer and autumn. However, adenovirus infections were observed in all seasons. Serological responses were poor in patients younger than 1 year of age and they were mainly diagnosed by virus isolation or detection of virus antigen. CONCLUSIONS: Virological epidemiology provides useful information in daily clinical practice for the prediction of etiological agents based on patient age and the seasonal distribution of agents. We should examine virus isolation and the detection of virus antigen, along with serological examinations in patients with respiratory infections, especially in infants younger than 1 year of age because of poor serological responses.     

Epidemiology and laboratory diagnosis of infection with viral and bacterial pathogens in infants hospitalized for suspected sepsis

A prospective study was conducted to determine the frequency and distribution of bacterial and viral pathogens in infants hospitalized with suspected sepsis and to evaluate the potential of virus detection for improving patient management. A causative organism was detected in 157 (67%) of 233 previously healthy infants less than 3 months of age, who had been hospitalized for suspected sepsis: 19 (8%) had bacterial infections, 135 (58%) had viral infections, and 3 (1%) had mixed viral-bacterial infections. Viral infections occurred in a seasonal pattern: enteroviruses were responsible for most of the hospitalizations during summer and fall (65/110; 63%) and respiratory syncytial and influenza A viruses were responsible for most of the infections during winter (44/81; 55%). In contrast, bacterial infections were not seasonally distributed. Virus was detected in 33% of the 138 infected infants within 24 hours, and in 64% within 3 days. We conclude that viral infections are prevalent among infants hospitalized for suspected sepsis, and most can be detected early enough to influence patient management.     

��ͯ������������Ⱦ�����ƽ�չ

??Respiratory infections??especially respiratory viral infections??are common diseases in children. Although most respiratory viral infection diseases are self-limiting??some children may be hospitalized or even life-threatened due to severe viral lower respiratory tract infection. With the progress of virology research??new and effective antiviral drugs have been developed. Thus??the study focuses on the therapeutic progress of respiratory viral infections so as to improve the treatment for common respiratory viral infections in children.     

Viruses and sudden infant death

Viral respiratory infections are the most likely trigger for sudden infant death syndrome (SIDS). SIDS cases commonly have evidence of respiratory tract inflammation, a preceding history of symptoms of minor illness and occur in winter peaks coinciding with respiratory viral epidemics. Respiratory infections are a common cause for infants presenting with sudden events, involving apnoea and hypoxaemia and there are physiological mechanisms by which infants may develop sudden and severe, potentially life-threatening hypoxaemia. The rate of SIDS has fallen in the last 15 years. This is probably more to do with the reasons for the fall in deaths from respiratory causes rather than changes in sleeping position. Further falls in SIDS death rates may occur with reductions in cigarette smoking, encouragement of breastfeeding and minimising the potential for young infants to acquire respiratory infections. Early identification and recognition of life-threatening features of infections may further minimise the risks of sudden death.     

The impact of dual viral infection in infants admitted to a pediatric intensive care unit associated with severe bronchiolitis

INTRODUCTION: Bronchiolitis is a major cause of morbidity and mortality in early childhood worldwide. The presence of more than one pathogen may influence the natural history of acute bronchiolitis in infants. OBJECTIVE: To investigate the relevance of dual viral infection in infants with severe bronchiolitis hospitalized in a short-term unit compared with those in a pediatric intensive care unit (PICU). STUDY DESIGN: One hundred eighty infants <1 year old hospitalized with bronchiolitis in a short-term unit (n = 92) or admitted to the PICU (n = 88) during 2 consecutive winter seasons 2003/2004 and 2004/2005 were evaluated. Molecular biology and standard methods were used to diagnose human respiratory viruses in nasal/throat swabs and nasal aspirates. Clinical data related to host factors and viral prevalence were compared among infants requiring or not PICU support. RESULTS: A viral agent was identified in 96.1% of infants with bronchiolitis. Respiratory syncytial virus (70.6% and 73.6%, respectively in the short-term unit and PICU) and rhinovirus (18.5% and 25.3%, respectively in the short-term unit and PICU) were the main detected respiratory viruses in infants hospitalized in both units. No significant difference in viral prevalence was observed between the populations studied. From multivariate analysis, infants with coinfections were 2.7 times (95% CI: 1.2-6.2) more at risk for PICU admission than those with a single infection. Respiratory syncytial virus and rhinovirus were the viruses most frequently identified in mixed infections in infants hospitalized with bronchiolitis. CONCLUSIONS: Dual viral infection is a relevant risk factor for the admission of infants with severe bronchiolitis to the PICU.     

Subtelomeric FISH analysis in 76 patients with syndromic developmental delay/intellectual disability

Background

Childhood asthma in the Caribbean is advancing in prevalence and morbidity. Though viral respiratory tract infections are reported triggers for exacerbations, information on these infections with asthma is sparse in Caribbean territories. We examined the distribution of respiratory viruses and their association with seasons in acute and stable asthmatic children in Trinidad.

Methods

In a cross-sectional study of 70 wheezing children attending the emergency department for nebulisation and 80 stable control subjects (2 to 16 yr of age) in the asthma clinic, nasal specimens were collected during the dry (n = 38, January to May) and rainy (n = 112, June to December) seasons. A multitarget, sensitive, specific high-throughput Respiratory MultiCode assay tested for respiratory-virus sequences for eight distinct groups: human rhinovirus, respiratory syncytial virus, parainfluenza virus, influenza virus, metapneumovirus, adenovirus, coronavirus, and enterovirus.

Results

Wheezing children had a higher [χ² = 5.561, p = 0.018] prevalence of respiratory viruses compared with stabilized asthmatics (34.3% (24) versus (vs.) 17.5% (14)). Acute asthmatics were thrice as likely to be infected with a respiratory virus (OR = 2.5, 95% CI = 1.2 – 5.3). The predominant pathogens detected in acute versus stable asthmatics were the rhinovirus (RV) (n = 18, 25.7% vs. n = 7, 8.8%; p = 0.005), respiratory syncytial virus B (RSV B) (n = 2, 2.9% vs. n = 4, 5.0%), and enterovirus (n = 1, 1.4% vs. n = 2, 2.5%). Strong odds for rhinoviral infection were observed among nebulised children compared with stable asthmatics (p = 0.005, OR = 3.6, 95% CI = 1.4 – 9.3,). RV was prevalent throughout the year (Dry, n = 6, 15.8%; Rainy, n = 19, 17.0%) and without seasonal association [χ² = 0.028, p = 0.867]. However it was the most frequently detected virus [Dry = 6/10, (60.0%); Rainy = 19/28, (67.9%)] in both seasons.

Conclusion

Emergent wheezing illnesses during childhood can be linked to infection with rhinovirus in Trinidad's tropical environment. Viral-induced exacerbations of asthma are independent of seasons in this tropical climate. Further clinical and virology investigations are recommended on the role of infections with the rhinovirus in Caribbean childhood wheeze.     

The clinical features of respiratory syncytial virus: Lower respiratory tract infection after upper respiratory tract infection due to influenza virus

BACKGROUND: Respiratory syncytial virus (RSV) and influenza virus are the primary pathogens of respiratory tract infection. However, epidemics of influenza virus infection have been observed to interrupt RSV epidemics (termed an epidemiological interference effect). METHODS: At a clinic in Tsuna county, Hyogo prefecture, Japan, a total of 1262 outpatients under 6 years of age with lower respiratory tract infection due to RSV (RSV-LRTI) and upper respiratory tract infection due to influenza virus (FLU-URTI) in three successive winter seasons (1999-2000, 2000-2001 and 2001-2002) were analyzed. RESULTS: The RSV-LRTI epidemic and FLU-URTI epidemic overlapped in each season, but the RSV-LRTI epidemic peak preceded that of the FLU-URTI epidemic. Epidemiological interference between RSV and influenza virus was observed in the second and third season; the number of patients with RSV-LRTI began to decrease after the start of the FLU-URTI epidemic and recovered to some extent after the FLU-URTI epidemic passed its peak. There were no differences in onset age, male-to-female ratio and severity of RSV-LRTI in outpatients before and after the start of the FLU-URTI epidemic in all the three seasons. CONCLUSION: An epidemiological interference between RSV and influenza virus was observed in Tsuna county in two of the three winter seasons. However, there was no difference between the clinical features of the patients with RSV-LRTI before and after the start of the influenza virus infection epidemic. The data suggest that the clinical severity of RSV infection is not changed by the epidemiological interference effect of influenza virus infection epidemics.     

CHILDHOOD ASTHMA IN BRISBANE: EPIDEMIOLOGICAL OBSERVATIONS

Analysis of hospital admissions for 20 years suggests that there has been an increase in childhood asthma in Brisbane. The characteristic seasonal pattern of asthma with waves in autumn and spring is evident from the second year of age and continues into adult life. It has not been explained, although respiratory infections, allergens and cold changes probably contribute to it. Unlike adults, children shown an increase in asthma in February-March, ascribed to infections spread at school. Maximal asthma is associated with a mean temperature of 20–21°C. This may be optimal for the production of allergens. Further viral studies of asthmatic attacks are desirable.     

Seasonal variation in childhood asthma hospitalisations in Finland, 1972–1992

All hospital treatment periods caused by asthma in children under 15 years in Finland during 1972–1992 were examined. The data were obtained from the Hospital Discharge Register, covering all hospitalisations in Finland. A total of 59,624 asthma related treatment periods were recorded. The monthly variation in hospitalisations peaked in May (35.6% above the trend) and in autumn and early winter (41.3% above the trend in October), whereas the monthly variations were low in late winter and in summer. The overall profile of seasonal variation was similar in both sexes, although admissions were lower for boys than for girls in winter and higher in autumn. The average monthly deviation was highest in the age group 0–4 years in May, 42.8% above the trend, and highest in the age group 5–9 years in October, 53.9% above the trend. Closer examination of the seasonal variation gives indirect information on possible trigger factors for acute asthma. Conclusion A clear seasonal variation could be obser ved in childhood asthma hospital admissions, together with age and sex-related differences in this seasonality. Preventive treatment for asthma should be used effectively in order to avoid acute attacks leading to hospitalisation in children who are allergic to birch pollen and also at times of viral respiratory infections. Received: 14 May 1996 / Accepted: 26 September 1996     

Frequency of Chlamydia pneumoniae and Mycoplasma pneumoniae infections in children

OBJECTIVE: Chlamydia pneumoniae and Mycoplasma pneumoniae are among the most important pathogens of acute respiratory infections in children between the ages of 5 and 15 years. We aimed to investigate seasonal frequency of respiratory infections caused by C. pneumoniae and M. pneumoniae, frequency of coinfection, clinical findings and to determine relationship between clinical findings and laboratory results. MATERIAL AND METHODS: Total of 284 patients (ranging 5-15 years of age), admitted to out-patient clinic with symptoms of respiratory tract infections between January 2004 and June 2005, were enrolled in the study. IgA, IgG and IgM antibodies against C. pneumoniae were quantitatively detected in all serum samples by using microimmunofluorescence (MIF). For the M. pneumoniae infection an IgM titer in the ELISA test were analyzed. Nasopharyngeal smear samples were collected for PCR detection. RESULTS: Mean age was 8 +/- 2.2 (range 5-14) years. Mycoplasma pneumoniae IgM in 86 (30.2%) cases, C. pneumoniae IgM in one (0.3%) case, IgA in six (2.1%) cases and IgG in 10 (3.5%) cases were found positive. In 10 (3.5%) cases, both C. pneumoniae IgG (a titer of >1/216) and M. pneumoniae IgM were found positive concomitantly. The M. pneumoniae IgM in winter was found significantly higher compared to other seasons. Mycoplasma pneumoniae PCR method was performed on a total of 203 samples in 33 (16.2%) of which M. pneumoniae was found positive. The false positive ratio of PCR technique was found 16.2%. In a total of 217 examined samples by PCR method, the DNA of C. pneumoniae was found positive in two patients. CONCLUSION: Mycoplasma pneumoniae was a common pathogen in respiratory infections. The otherwise C. pneumoniae infections were rarely seen in children. A Comparison of serology diagnostic tests for M. pneumoniae infections was found more sensitive and specific than PCR.     

Community- and hospital-acquired respiratory syncytial virus infections in Chile

Nasopharyngeal aspirates were obtained on admission from 614 patients younger than 2 years of age who were hospitalized in a ward for acute respiratory infections from June 1988 through October, 1989, in Santiago, Chile. Patients in two rooms were followed during the cold seasons by sampling aspirates every other day during the child's entire hospital stay. Clinical features were recorded daily. Indirect monoclonal immunofluorescent assay and isolation in HEp-2 were used for respiratory syncytial virus (RSV) diagnosis. The mean RSV detection rate was 39% at the time of admission, ranging from 8% in April, 1989, to 62% in July, 1988. During the cold months 43 of 288 (15%) nosocomial RSV cases were detected. Pneumonia and wheezing bronchitis were the principal diagnoses of both groups admitted, whether they were shedding RSV or not. It is concluded that RSV plays a major role in admissions for acute respiratory infections, as well as in nosocomial infections, in Santiago. Because clinical features do not allow one to differentiate viral from bacterial acute respiratory infections, the importance of rapid viral diagnosis is emphasized.     

Diagnosis of viral respiratory infections]

More than 80% of the cases of respiratory infections in children are of viral origin. Viral culture has been the reference method for the diagnosis of viral respiratory infections for years, but there is now a tendency to replace viral culture by molecular biology techniques, notably real-time PCR-based assay, because of its excellent sensitivity and good feasibility. Currently in most laboratories, however, diagnosis of viral respiratory infections is still done using techniques based on detection of viral antigens, especially immunofluorescence assays. Rapid diagnostic tests for use outside of laboratories are now available on the open market, and even if their sensitivity remains lower than that of other techniques, it is likely that they will become widely used, especially in doctors' offices, in the near future. New methods for the diagnosis of viral infections based on DNA microarray technologies are currently under investigation and appear to be very promising.     

Human metapneumovirus infections—biannual epidemics and clinical findings in children in the region of Basel,Switzerland

Human metapneumovirus (hMPV) epidemics vary in time and severity. We report findings for PCR for hMPV and respiratory syncytial virus (RSV) performed on nasopharyngeal aspirates (NPA) of hospitalized and outpatient children with respiratory tract infections between October 2004 and April 2008. A total of 3,934 NPAs were tested for hMPV and 3,859 for RSV. Of these, 198 (5%) were hMPV positive and 869 (23%) were RSV-positive. Median age was 17 months and 9 months for hMPV and RSV, respectively. Fifty-nine percent of hMPV and 58% of RSV patients were hospitalized. Proportions of hMPV positive samples for the four winter seasons were 0.4%, 11%, 0.2%, and 14%. For RSV, they were 28%, 15%, 28%, and 28%. HMPV epidemics follow a biannual variation in our area. Major epidemics were observed in winter seasons starting in odd years (2005/06 and 2007/08), minor epidemics in those starting in even years (2004/05 and 2006/07). RSV epidemics usually follow a reciprocal biannual pattern, leading to annually alternating major RSV and hMPV epidemics.     

Hospital-acquired viral respiratory illness on a pediatric ward.

All 171 patients admitted to four study rooms containing cribs were under surveillance during the winter and spring for development of nosocomial respiratory and infection. One sixth of the 90 children at risk acquired respiratory illness while in the hospital. Viruses were isolated from two thirds of the patients with nosocomial infections: rhinovirus, respiratory syncytial virus, parainfluenza, and influenza A and B. Serial viral cultures of the children under surveillance suggested that nine of 11 virus-positive nosocomial infections were not acquired from a roommate. Furthermore, the risk to a patient of becoming infected with a virus being shed by a roommate was only 3%. The need for isolation of all children with respiratory illness in a single room with a separate air exhaust system is not suggested by these data.     

One-Year Prospective Study of Community Acquired Influenza and Parainfluenza Viral Infections in Hospitalized Egyptian Children with Malignancy: Single Center Experience

Background: Respiratory viruses are widespread in the community and easily transmitted to immunocompromised patients. Aims: Assess the prevalence of community-acquired respiratory viral infections among children with cancer presenting with clinical picture suggestive of lower respiratory tract infections (LRTIs), and evaluate its risk factors and prognosis. Methods: Over a year, 90 hospitalized children with malignancy and LRTIs recruited, subjected to clinical assessment, investigated through hematology panel, blood culture, chest x-ray, CT chest and PCR for influenza A and B, parainfluenza (PIV) types 1 and 3 viruses, and respiratory syncytial virus (RSV), and prospectively followed up for the clinical outcome. Results: Viral pathogens were identified in 34 patients (37.7%), with a seasonal peak from April to May. The most frequently detected virus was influenza virus [type A (16 cases; 47%), type B (4 cases; 12%)] followed by parainfluenza virus [PIV1 (9 cases; 26%), PIV3 (3 cases; 15%)], and none had RSV. Bacteria were identified in 26 patients, fungi in four, mixed infections [bacterial/viral and bacterial/fungal] in 13, and 36 cases had unidentified etiology. The majority of patients with influenza and parainfluenza infections had hematological malignancy, presented with fever, and had mild self-limited respiratory illness. Five patients with mixed viral and bacterial infection had severe symptoms necessitating ICU admission. Six patients died from infection-related sequelae; two had mixed PIV and Staphylococcal infections. Conclusions: Community acquired influenza and parainfluenza infections are common in pediatrics patients with malignancy, either as isolated or mixed viral/bacterial infections. Clinical suspicion is essential as hematological and radiological manifestations are nonspecific. Rapid diagnosis and management are mandatory to improve patients’ outcome.     

Respiratory viral infections in children with asthma: do they matter and can we prevent them?

ABSTRACT: BACKGROUND: Asthma is a major public health problem with a huge social and economic burden affecting 300 million people worldwide. Viral respiratory infections are the major cause of acute asthma exacerbations and may contribute to asthma inception in high risk young children with susceptible genetic background. Acute exacerbations are associated with decreased lung growth or accelerated loss of lung function and, as such, add substantially to both the cost and morbidity associated with asthma. DISCUSSION: While the importance of preventing viral infection is well established, preventive strategies have not been well explored. Good personal hygiene, hand-washing and avoidance of cigarette smoke are likely to reduce respiratory viral infections. Eating a healthy balanced diet, active probiotic supplements and bacterial-derived products, such as OM-85, may reduce recurrent infections in susceptible children. There are no practical anti-viral therapies currently available that are suitable for widespread use.     

Comparison of clinical characteristics of influenza and respiratory syncytial virus infection in hospitalised children and adolescents

While significant morbidity due to respiratory syncytial virus (RSV) infection in the paediatric population has been well acknowledged, little is known about the burden of influenza in primarily healthy children in Europe. In our institution, a University Childrens Hospital in Switzerland, medical staff were encouraged to take nasopharyngeal specimens for multiplex polymerase chain reaction assays for influenza A and B, RSV and several other pathogens from patients hospitalised with respiratory symptoms. We took advantage of this strategy and performed a retrospective study to compare specific characteristics of influenza virus infections with those of RSV during two consecutive winter seasons. Overall, 126 patients were positive for RSV and 60 patients were positive for influenza (type A: 45; type B: 15). The median age of children with RSV, influenza A, and influenza B infection was 4 months; 2 years and 4 months; and 6 years and 2 months, respectively (P<0.001). Fever and cough predominated in children with influenza infection whereas cough, rhinorrhoea, feeding difficulties and dyspnoea were the major symptoms in children with RSV infection. Of patients with influenza, 41% suffered from lower respiratory tract infection compared to 91% of those with RSV infection (P<0.001). Of 60 patients hospitalised with influenza, 12 (20%) experienced febrile convulsions. None of the patients with influenza had been immunised in the respective winter season, although 27% of them had at least one underlying medical condition that would have counted as an indication for immunisation in Switzerland. Conclusion: influenza virus infections, like respiratory syncytial virus infections, are a major cause of hospitalisation in children with respiratory illness during the winter season. Since it is impossible to make an aetiological diagnosis on clinical grounds, it is important to apply specific diagnostic tools in children hospitalised with respiratory illness in order to better characterise the relative burden of disease caused by the respective agents.Abbreviations LRTI lower respiratory tract infection - NPS nasopharyngeal specimens - RAT rapid antigen test - RSV respiratory syncytial virusThis work forms the medical thesis of Susanne Meury at the Medical Faculty, University of Basel, Switzerland.