Samantha Bosis

Characteristics of Streptococcus pneumoniae and Atypical Bacterial Infections in Children 2–5 Years of Age with Community-Acquired Pneumonia

The characteristics of community-acquired pneumonia associated with Streptococcus pneumoniae infection were compared with those associated with atypical bacterial infection and with mixed S. pneumoniae-atypical bacterial infection in 196 children aged 2-5 years. S. pneumoniae infections were diagnosed in 48 patients (24.5%); atypical bacterial infections, in 46 (23.5%); and mixed infections, in 16 (8.2%). Although white blood cell counts and C-reactive protein levels were higher in patients with pneumococcal infections, no other clinical, laboratory, or radiographic characteristic was significantly correlated with the different etiologic diagnoses. There was no significant difference in the efficacy of the different treatment regimens followed by children with S. pneumoniae infection, whereas clinical failure occurred significantly more frequently among children with atypical bacterial or mixed infection who were not treated with a macrolide. This study shows the major role of both S. pneumoniae and atypical bacteria in the development of community-acquired pneumonia in young children, the limited role of clinical, laboratory, and radiological features in predicting etiology, and the importance of the use of adequate antimicrobial agents for treatment.

Effectiveness of influenza vaccination of children with recurrent respiratory tract infections in reducing respiratory-related morbidity within the households

To evaluate the effectiveness of influenza vaccination in reducing respiratory-related morbidity among children with recurrent respiratory tract infections (RRTIs) and their household contacts, 127 children aged 6 months-9 years (78 males; median age, 3.7 years) with a history of RRTIs (>/=6 episodes per year if aged >/=3 years; >/=8 episodes per year if aged <3 years) were randomized to receive the intranasal virosomal influenza vaccine (n=64 with 176 household contacts) or a control placebo (n=63 with 173 household contacts). During influenza season, the vaccinated children had fewer respiratory infections, febrile respiratory illnesses, prescribed antibiotics and antipyretics, and missed school days than the controls, and similar benefits and a reduction in the loss of parental work were observed among their household contacts. This study shows that the benefits of influenza vaccination extend to children with RRTIs and their family members and encourages to recommend its use in such children.

Procalcitonin measurements for guiding antibiotic treatment in pediatric pneumonia

In order to evaluate the use of an algorithm based on a procalcitonin (PCT) cut-off value as a means of guiding antibiotic therapy, 319 hospitalised children with uncomplicated community-acquired pneumonia (CAP) were randomised 1:1 to be treated on the basis of the algorithm or in accordance with standard guidelines. The children in the PCT group did not receive antibiotics if their PCT level upon admission was <0.25 ng/mL, and those receiving antibiotics from the time of admission were treated until their PCT level was ≥ 0.25 ng/mL. The final analysis was based on 155 patients in the PCT group and 155 in the control group. In comparison with the controls, the PCT group received significantly fewer antibiotic prescriptions (85.8% vs 100%; p < 0.05), were exposed to antibiotics for a shorter time (5.37 vs 10.96 days; p < 0.05), and experienced fewer antibiotic-related adverse events (3.9% vs 25.2%; p < 0.05), regardless of CAP severity. There was no significant between-group difference in recurrence of respiratory symptoms and new antibiotic prescription in the month following enrollment. The results of this first prospective study using a PCT cut-off value to guide antibiotic therapy for pediatric CAP showed that this approach can significantly reduce antibiotic use and antibiotic-related adverse events in children with uncomplicated disease. However, because the study included mainly children with mild to moderate CAP and the risk of the use of the algorithm-based approach was not validated in a relevant number of severe cases, further studies are needed before it can be used in routine clinical practice.

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 respiratory pathogens in infants hospitalized for a first episode of wheezing and their impact on recurrences

ABSTRACT In order to evaluate the infectious agents associated with the first episode of severe acute wheezing in otherwise healthy infants and to define the role of each of them in recurrences, 85 patients in Italy, aged <12 months, hospitalized because of a first acute episode of wheezing, were prospectively enrolled between 1 October 2005 and 31 March 2006. Upon enrolment, nasopharyngeal swabs were collected for the real-time PCR detection of respiratory syncytial virus (RSV) types A and B, influenza virus types A and B, adenovirus, parainfluenza viruses types 1, 2, 3 and 4, rhinovirus, human metapneumovirus, human coronavirus types 229E, OC43, NL63, and HKU1, bocavirus, enterovirus, and paraechovirus; nasopharyngeal aspirates were also obtained to detect atypical bacteria. At least one infectious agent was identified in 76 children (89.4%). RSV was the most frequently detected pathogen and its prevalence was significantly higher than that of the other pathogens in both age groups, and significantly higher in the children aged 3–12 months than in those aged <3 months. Only the children with RSV infection experienced recurrent wheezing. Viral load was significantly higher in children with than in those without recurrent wheezing. This study shows that RSV is the main reason for hospitalization during the first wheezing episode in infants, and that it appears to be the only pathogen associated with a high frequency of recurrences. A high viral load seems to be strictly related to the likelihood of recurrence.

Long-Term Pertussis-Specific Immunity after Primary Vaccination with a Combined Diphtheria, Tetanus, Tricomponent Acellular Pertussis, and Hepatitis B Vaccine in Comparison with That after Natural Infection

ABSTRACT The aim of this study was to compare pertussis-specific humoral and cellular immunity in children 5 years after a primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis B vaccine (DTaP-HBV; InfanrixHepB; SmithKline Beecham) with immunity after natural infection. The subjects were 38 children aged 5 to 6 years who received DTaP-HBV at 3, 5, and 11 months of life and 21 subjects of similar ages and sex who acquired pertussis in the first year of life. Immunoglobulin G (IgG) antibody titers againstBordetella pertussis antigens, peripheral blood mononuclear cell-specific proliferation, and the secretion of cytokines were evaluated. After 5 years, only a small proportion of vaccinated and infected children had significant specific concentrations of IgG in serum against all three B. pertussis antigens, and T-cell responses persisted in a minority of subjects. A preferential type 1 cytokine response with the secretion of gamma interferon was observed in the pertussis group, whereas a type 2 skewed response was observed in the vaccinated children; however, the quantitative differences in the cytokines produced by DTaP-HBV and natural infection were minimal. In conclusion, our results show that the immune responses induced by primary pertussis vaccination are qualitatively and quantitatively similar to those seen in children who recovered from natural infection and highlight the need for booster immunization with pertussis vaccines in order to maintain adequate levels of a specific immune response to B. pertussis.

Human metapneumovirus in paediatric patients

ABSTRACT Acute respiratory tract infections (ARTIs) are a leading cause of morbidity and mortality in children worldwide, but the aetiology of many ARTIs is still unknown. In 2001, researchers in The Netherlands reported the discovery of a previously unidentified pathogen called human metapneumovirus (hMPV). Since its initial description, hMPV has been associated with ARTI in Europe (Italy, France, Spain, the UK, Germany, Denmark, Finland and Norway), America (the USA, Canada, Argentina and Brazil), Asia (India, Japan, China and Singapore), Australia and South Africa in individuals of all ages. The incidence of infection varies from 1.5% to 25%, indicating that hMPV is a ubiquitous virus with a worldwide distribution. hMPV seems to play an important role as a cause of paediatric upper and lower respiratory tract infection, with similar, but not identical, epidemiological and clinical features to those of respiratory syncytial virus and influenza virus. Moreover, the socio-economic impact of hMPV-infected children on their families seems to be considerable, which suggests that, like influenza virus, hMPV infection may be a substantial public health problem for the community. It may be associated with significant morbidity and mortality in pre-term infants and children with underlying clinical conditions, although more adequately controlled studies are needed to confirm its importance in such patients. Many fundamental questions concerning the pathogenesis of hMPV disease and the hosts specific immune response remain to be answered. Further studies are also required to properly define hMPV diagnosis, treatment and prevention strategies.

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.