Elena Tremolati

Impact of Human Bocavirus on Children and Their Families

ABSTRACT This study was planned to investigate the prevalence and clinical features of the illnesses associated with human bocavirus (hBoV) in children with acute disease. We prospectively enrolled all subjects aged less than 15 years attending an emergency room in Milan, Italy, on Wednesdays and Sundays between 1 November 2004 and 31 March 2005 for any acute medical reason, excluding surgical diseases and trauma. Nasopharyngeal swabs were collected at admission to detect hBoV; influenza A and B viruses; respiratory syncytial virus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; rhinovirus; adenovirus; and coronaviruses 229E, OC43, NL63, and HKU1 by real-time PCR. Among the 1,332 enrolled children, hBoV was the fifth most frequently detected virus (7.4%). The rate of hBoV coinfections with other viruses was significantly higher than for the other viruses (50.5% versus 27.5%; P < 0.0001). Eighty-nine of the 99 hBoV-positive children (89.9%) had a respiratory tract infection, and 10 (10.1%) had gastroenteritis. hBoV coinfections had a significantly greater clinical and socioeconomic impact on the infected children and their households than hBoV infection alone. In conclusion, these findings show that the role of hBoV infection alone seems marginal in children attending an emergency room for acute disease; its clinical and socioeconomic importance becomes relevant only when it is associated with other viruses.

Impact of human coronavirus infections in otherwise healthy children who attended an emergency department

This prospective clinical and virological study of 2,060 otherwise healthy children aged <15 years of age (1,112 males; mean age ± SD, 3.46 ± 3.30 years) who attended the Emergency Department of Milan Universitys Institute of Pediatrics because of an acute disease excluding trauma during the winter season 2003–2004 was designed to compare the prevalence and clinical importance of human coronaviruses (HCoVs) in children. Real‐time polymerase chain reaction (PCR) in nasopharyngeal aspirates revealed HCoV infection in 79 cases (3.8%): 33 HCoV‐229E (1.6%), 13 HCoV‐NL63 (0.6%), 11 HCoV‐OC43 (0.5%), none HCoV‐HKU1 genotype A, and 22 (1.1%) co‐detections of a HCoV and another respiratory virus. The HCoVs were identified mainly in children with upper respiratory tract infection; there was no significant difference in clinical presentation between single HCoV infections and HCoV co‐infections. Diagnostic methods were used in a limited number of patients, and the therapy prescribed and clinical outcomes were similar regardless of the viral strain. There were a few cases of other members of the households of HCoV‐positive children falling ill during the 5–7 days following enrollment. These findings suggest that HCoV‐229E and HCoV‐OC43 have a limited clinical and socioeconomic impact on otherwise healthy children and their household contacts, and the HCoV‐NL63 identified recently does not seem to be any different. The quantitative and qualitative role of HCoV‐HKU1 genotype A is apparently very marginal. J. Med. Virol. 78:1609–1615, 2006.

Role of atypical bacteria and azithromycin therapy for children with recurrent respiratory tract infections.

Background: The aim of this study of 352 patients, 1–14 years of age, with acute respiratory infections and a history of recurrent respiratory tract infections (RRTIs), and 208 healthy subjects was to evaluate whether Mycoplasma pneumoniae and Chlamydia pneumoniae played a role in causing acute respiratory episodes among children with RRTIs and whether specific antibiotic treatment for these bacteria could improve the acute episodes and reduce recurrences. Methods: The patients were blindly randomized to receive azithromycin (10 mg/kg/d for 3 days weekly, for 3 weeks) together with symptom-specific agents or symptom-specific agents alone. Acute M. pneumoniae and/or C. pneumoniae infection was diagnosed if the child had a significant antibody response in paired sera and/or if the DNA of the bacteria was detected in nasopharyngeal aspirates. Results: Atypical bacterial infections were identified for 190 patients (54.0%) and 8 healthy control subjects (3.8%; P < 0.0001). Short term (1-month) clinical success was significantly more frequent among the patients who had received azithromycin together with symptom-specific agents than among those who had received symptom-specific agents alone, but the difference was significant only for the group of patients with atypical bacteria. In contrast, long term (6-month) clinical success was significantly more frequent among the patients who had received azithromycin in addition to symptom-specific agents, regardless of whether they experienced infections with atypical bacteria or other pathogens, although positive outcomes were significantly more frequent among those with atypical bacteria. Conclusions: Atypical bacteria seem to play a role among children with RRTIs, and prolonged azithromycin therapy can significantly improve the acute episodes and reduce the risk of recurrences.

Association between high nasopharyngeal viral load and disease severity in children with human metapneumovirus infection

Abstract Background Previous studies have shown that viral genotype and viral load may play a significant role in the pathogenesis of viral infections. Objectives The aim of this study was to evaluate these aspects of hMPV infections in children and their household contacts. Study design Between 1 November 2003 and 31 March 2004, we prospectively studied 2060 children attending our Emergency Department for acute reasons. Nasopharyngeal swabs were collected upon enrolment and then tested with real-time PCR assays for the major viral causes of respiratory illness. Results Sixty children (2.9%) were infected by hMPV: 24 (1.2%) by hMPV A, 14 (0.7%) by hMPV B, 11 (0.5%) by untyped hMPV, and 11 (0.5%) by hMPV and an additional respiratory virus. There were no differences in disease presentation or in clinical or socioeconomic impact in relation to viral genotypes. HMPV viral load was significantly higher in children with lower respiratory tract involvement (p <0.05), hospitalised children (p <0.05), and the prevalence of secondary cases of a similar disease in the household of index cases (p <0.05). Conclusion A high hMPV viral load correlated with disease presentation, whereas the overall clinical and socioeconomic burden caused by the two hMPV genotypes was similar.

Safe administration of an inactivated virosomal adjuvanted influenza vaccine in asthmatic children with egg allergy

In order to evaluate whether the virosomal adjuvanted influenza vaccine that has been shown to have the lowest egg protein content (Inflexal V, Berna Biotech) could be administered to children with even severe egg allergy without any risk of allergic reactions, we used epicutaneous skin testing with the undiluted vaccine in 88 asthmatic children (44 with and 44 without egg allergy), none of whom had a positive response. They were then vaccinated with the whole dose of Inflexal V intramuscularly in a one-dose protocol, and the occurrence of any immediate or delayed adverse events were actively monitored for 28 days. The results showed the safety of the administration, and demonstrated that Inflexal V can be safely given without performing a vaccine skin test in children with any kind of egg allergy.

Evaluation of a rapid bedside test for the quantitative determination of C-reactive protein

Abstract Regardless of its origin, any condition associated with inflammation is accompanied by an increase in serum C-reactive protein levels. This study compared the results of a rapid test for the bedside assay of C-reactive protein (QuikRead CRP, Orion Corporation, Orion Diagnostica, Espoo, Finland) with those of a standard laboratory assay in samples taken from 231 children aged less than 14years (126 males; median age 4.7years) attending the Emergency Department of Milan Universitys Institute of Pediatrics because of acute respiratory infection. The two methods showed similar median C-reactive protein levels (standard laboratory assay: 34.7mg/L, range 4–199mg/L; QuikRead CRP: 33.3mg/L, range <8–196mg/L; p=0.779) and a similar distribution of children with C-reactive protein levels of <20mg/L, 20–70mg/L and >70mg/L. This study shows for the first time that the rapid QuikRead CRP test can be performed at the bedside or in an outpatient clinic and, in less than 5min, gives the same quantitative results as those obtained using a more complex routine laboratory method.

Acute Tonsillopharyngitis Associated with Atypical Bacterial Infection in Children: Natural History and Impact of Macrolide Therapy

This study evaluated the natural history of acute tonsillopharyngitis associated with atypical bacterial infections, showing that Mycoplasma pneumoniae and Chlamydia pneumoniae organisms are frequently found in children with acute tonsillopharyngitis. The study also demonstrated, for what we believe to be the first time, that, unless adequately treated, acute tonsillopharyngitis associated with infection with M. pneumoniae and C. pneumoniae may have a negative outcome with a high risk of recurrence of respiratory illness.

Altered cardiac rhythm in infants with bronchiolitis and respiratory syncytial virus infection

BackgroundAlthough the most frequent extra-pulmonary manifestations of respiratory syncytial virus (RSV) infection involve the cardiovascular system, no data regarding heart function in infants with bronchiolitis associated with RSV infection have yet been systematically collected. The aim of this study was to verify the real frequency of heart involvement in patients with bronchiolitis associated with RSV infection, and whether infants with mild or moderate disease also risk heart malfunction.MethodsA total of 69 otherwise healthy infants aged 1-12 months with bronchiolitis hospitalised in standard wards were enrolled. Pernasal flocked swabs were performed to collect specimens for the detection of RSV by real-time polymerase chain reaction, and a blood sample was drawn to assess troponin I concentrations. On the day of admission, all of the infants underwent 24-hour Holter ECG monitoring and a complete heart evaluation with echocardiography. Patients were re-evaluated by investigators blinded to the etiological and cardiac findings four weeks after enrolment.ResultsRegardless of their clinical presentation, sinoatrial blocks were identified in 26/34 RSV-positive patients (76.5%) and 1/35 RSV-negative patients (2.9%) (p < 0.0001). The blocks recurred more than three times over 24 hours in 25/26 RSV-positive patients (96.2%) and none of the RSV-negative infants. Mean and maximum heart rates were significantly higher in the RSV-positive infants (p < 0.05), as was low-frequency power and the low and high-frequency power ratio (p < 0.05). The blocks were significantly more frequent in the children with an RSV load of ≥100,000 copies/mL than in those with a lower viral load (p < 0.0001). Holter ECG after 28 ± 3 days showed the complete regression of the heart abnormalities.ConclusionsRSV seems associated with sinoatrial blocks and transient rhythm alterations even when the related respiratory problems are mild or moderate. Further studies are needed to clarify the mechanisms of these rhythm problems and whether they remain asymptomatic and transient even in presence of severe respiratory involvement or chronic underlying disease.

Coronavirus HKU1 in an Italian pre-term infant with bronchiolitis

Respiratory syncytial virus (RSV) is the major cause f bronchiolitis, a common disease in the first months of ife (Esposito et al., 2005; Lanari et al., 2002; Purcell and ergie, 2004). Bronchiolitis is also associated with influenza nd parainfluenza viruses, adenovirus, rhinoviruses, and nteroviruses (Bosis et al., 2005; Coiras et al., 2003; Legg et l., 2005). Although human metapneumovirus (hMPV) and uman coronavirus NL63 (HCoV-NL63) have been identified nd associated with a significant proportion of bronchiolitis ver the last 3 years, no pathogen is recovered in a substantial roportion of cases (Bastien et al., 2005; Chiu et al., 2005; sper et al., 2005; Principi et al., 2004, 2006). While studying the epidemiology of viral respiratory nfections in 2156 children (1190 males; mean age±S.D., .39± 3.40 years) who attended the Emergency Departent of Milan University’s Institute of Pediatrics because f acute disease (58.2% respiratory tract infections, 12.9% astrointestinal and intra-abdominal diseases, 5.1% fever of nknown origin, 4.5% seizures with or without fever, 4.7% xanthematious disease, 4.4% nephritic or nephrotic synrome, 3.7% skin and soft tissue infections, 2.3% bone or oint infections, 1.7% coagulation disorders, 1.0% meningiis/encephalitis, 0.9% sepsis, and 0.6% conjunctivitis) during