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

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.

Pediatrician knowledge and attitudes regarding human papillomavirus disease and its prevention.

Between 1 September and 8 October 2006, we used a self-administered, anonymous questionnaire in order to evaluate knowledge and attitudes regarding HPV disease and its prevention in a nationally representative sample of Italian pediatricians. Three hundred and eleven of the 400 enrolled physicians (175 primary care pediatricians, 160 hospital pediatricians and 65 residents in pediatrics) returned completed surveys (227 females; mean age+/-standard deviation, 45.3+/-11.61 years). The results showed a lack of knowledge concerning HPV disease and its prevention, with marginal differences between the subgroups, even though the majority would recommend HPV vaccination. These findings highlight an urgent need to improve pediatrician information in order to ensure the optimal implementation of HPV vaccination, and the adequate acceptability of HPV vaccines to adolescents and their parents.

Impact on respiratory tract infections of heptavalent pneumococcal conjugate vaccine administered at 3, 5 and 11 months of age.

BACKGROUND: Medical and public health importance of pneumococcal infections justifies the implementation of measures capable of reducing their incidence and severity, and explains why the recently marketed heptavalent pneumococcal conjugate vaccine (PCV-7) has been widely studied by pediatricians. This study was designed to evaluate the impact of PCV-7 administered at 3, 5 and 11 months of age on respiratory tract infections in very young children. METHODS: A total of 1,571 healthy infants (910 males) aged 75-105 days (median 82 days) were enrolled in this prospective cohort trial to receive a hexavalent vaccine (DTaP/IPV/HBV/Hib) and PCV-7 (n = 819) or the hexavalent vaccine alone (n = 752) at 3, 5 and 11 months of age. Morbidity was recorded for the 24 months following the second dose by monthly telephone interviews conducted by investigators blinded to the study treatment assignment using standardised questionnaires. During these interviews, the caregivers and the children's pediatricians were questioned about illnesses and the use of antibiotics since the previous telephone call. All of the data were analysed using SAS Windows v.12. RESULTS: Among the 1,555 subjects (98.9%) who completed the study, analysis of the data by the periods of follow-up demonstrated that radiologically confirmed community-acquired pneumonia (CAP) was significantly less frequent in the PCV-7 group during the follow-up as a whole and during the last period of follow-up. Moreover, there were statistically significant between-group differences in the incidence of acute otitis media (AOM) in each half-year period of follow-up except the first, with significantly lower number of episodes in children receiving PCV-7 than in controls. Furthermore, the antibiotic prescription data showed that the probability of receiving an antibiotic course was significantly lower in the PCV-7 group than in the control group. CONCLUSION: Our findings show the effectiveness of the simplified PCV-7 schedule (three doses administered at 3, 5 and 11-12 months of age) in the prevention of CAP and AOM, diseases in which Streptococcus pneumoniae plays a major etiological role. A further benefit is that the use of PCV-7 reduces the number of antibiotic prescriptions. All of these advantages may also be important from an economic point of view.

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 University's 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.

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.

Influenza vaccination coverage among children with high-risk medical conditions.

We evaluated influenza vaccination coverage in children with chronic disease at high risk of influenza complications, and the need for methods to increase parents' and pediatricians' knowledge of influenza and its prevention. The 5286 children aged less than 14 years attending our Emergency Department on Wednesdays and Sundays between 1 January and 30 April 2003 included 274 (5.2%) high-risk patients. The use of influenza vaccine during the previous three seasons had been very low, but significantly increased in the last season (2000-2001, 5.1%; 2001-2002, 12.9%; 2002-2003, 26.3%; p<0.001). The children with asthma or cardiac disease showed the lowest vaccination rates; their parents and primary care pediatricians had only a marginal knowledge of influenza and the benefits of its prevention. In conclusion, the delivery of influenza vaccine to children with chronic disease at high risk of influenza complications is completely inadequate, and major efforts are urgently needed to increase parents' and pediatricians' knowledge of its importance.

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.

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

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 14 years (126 males; median age 4.7 years) attending the Emergency Department of Milan University's Institute of Pediatrics because of acute respiratory infection. The two methods showed similar median C-reactive protein levels (standard laboratory assay: 34.7 mg/L, range 4-199 mg/L; QuikRead CRP: 33.3 mg/L, range <8-196 mg/L; p = 0.779) and a similar distribution of children with C-reactive protein levels of <20 mg/L, 20-70 mg/L and >70 mg/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 5 min, gives the same quantitative results as those obtained using a more complex routine laboratory method.

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.