Paola Marchisio

Risk factors for carriage of respiratory pathogens in the nasopharynx of healthy children

OBJECTIVES To assess risk factors for nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in a large sample of healthy children. METHODS In this point prevalence survey nasopharyngeal specimens were obtained from 1723 healthy children, ages 1 to 7 years, attending day-care centers or schools in 18 Italian cities. Written questionnaires for obtaining information about the demographics and medical history of the children were completed by the parents in the presence of a pediatrician. RESULTS The overall carrier rate of respiratory pathogens was 17.9% (S. pneumoniae, 3.5%; H. influenzae, 11.9%; M. catarrhalis, 4.1%). Only 5% of S. pneumoniae strains were penicillin-resistant whereas approximately 40% were erythromycin-resistant. Beta-lactamase production was found in 5.8% of H. influenzae and 88.7% of M. catarrhalis isolates. By multivariate analysis age (< or = 3 years), having older siblings, a history of prolonged full-time day-care attendance and living in a rural area significantly influenced the odds of carrying nasopharyngeal respiratory pathogens, particularly in children ages 1 to 5 years. Sex, breastfeeding, passive smoking and recent upper respiratory tract infections were not significant variables. Antibiotic treatment in the previous 3 months did not affect nasopharyngeal carriage, whereas repeated treatments with a macrolide were associated with carriage of S. pneumoniae. CONCLUSIONS Our results suggest that there is a strong and long term relationship between exposure to large numbers of children in the first years of life and nasopharyngeal carriage of all respiratory pathogens. In addition antimicrobial restrictive guidelines should be tailored to local microbiologic sceneries.

Socioeconomic impact of influenza on healthy children and their families

Background. Recent studies indicate that influenza can be clinically important in otherwise healthy children. However, the interpretation of many studies is limited because of lack of laboratory confirmation of influenza-like illnesses. Therefore it is difficult to conclude whether the socioeconomic impact of influenza justifies vaccinating all children regardless of age or underlying chronic disorders. Methods. We prospectively collected data from 3771 children younger than 14 years of age presenting to emergency departments or primary care pediatricians with symptoms of respiratory tract infection during the influenza season of 2001 to 2002. Influenza infections were verified by virus culture or polymerase chain reaction. We additionally randomized 303 children age 6 months to 5 years to receive either influenza vaccine (n = 202) or no vaccination (n = 101) before the influenza season. The socioeconomic impact of influenza was assessed for both the participating children and their household contacts. Results. Influenza was documented in 352 (9.3%) of the 3771 children. Compared with influenza-negative children, children with influenza had longer durations of fever and absenteeism from day care or school (P < 0.0001). Further the numbers of medical visits, missed work or school days and the need for help at home to care for the sick children were higher among the household contacts of influenza-positive children (P < 0.0001). Influenza vaccination reduced significantly the direct and indirect influenza-related costs in healthy children and their unvaccinated family members. Conclusions. The findings of this study support a wider use of influenza vaccine in healthy children of all ages to reduce the socioeconomic burden of influenza on the community.

Features of children perinatally infected with HIV-1 surviving longer than 5 years. Italian Register for HIV Infection in Children

Children infected with HIV do not necessarily develop AIDS to a set pattern but can be divided into long-term and short-term survivors. We examined long-term survival in children perinatally infected with HIV-1. Out of a total of 624, we studied 182 children who survived longer than 5 years (long-term survivors [LTS]) and 120 children who died of HIV-1-related disease before 5 years (defined as short-term survivors [STS]). 28 (15%) LTS were symptomless (Centers for Disease Control [CDC] P-1 children). 154 (85%) had symptoms (CDC P-2). The proportion of LTS with less than 0.2 x 10(9)/CD4 cells per L was 24/116 (21%) at 61-72 months, rising to 11/26 (41%) at more than 96 months. On at least one occasion, p24 antigenaemia was observed in 112 (62%) LTS. Annual rate of CD4 cell loss was lower in LTS (25% [95% CI: 21-29]) than in STS (53% [45-60]) and in LTS symptomless or with solitary P-2A signs (17%; [13-21]) than in LTS with severe manifestations (30% [25-35]). A new outlook emerges. A substantial number of children do survive after early childhood; severe diseases; low CD4 cell numbers, and p24 antigenaemia do not necessarily preclude long-term survival. The study shows that a CD4 cell decrease early in life can be predictive of outcome.

Impact of Pneumococcal Conjugate Vaccination on Otitis Media: A Systematic Review

Reduced rates of consultations for otitis media after introduction of pneumococcal conjugate vaccines (PCVs) have been overinterpreted. This systematic review suggests that PCV is only somewhat modestly effective against all-cause otitis media.

Burden of influenza in healthy children and their households

Objective: A prospective, multicentre study was conducted to evaluate the burden of laboratory confirmed influenza in healthy children and their household contacts. Methods: The patients were enrolled in four emergency departments (EDs) and by five primary care paediatricians (PCPs) in different Italian municipalities 2 days a week between November 1, 2001 and April 30, 2002. The study involved 3771 children less than 14 years of age with no chronic medical conditions who presented with a respiratory tract infection in EDs or PCP outpatient clinics during the study period. Nasopharyngeal swabs were collected for the isolation of influenza viruses and RNA detection. Information was also collected concerning respiratory illnesses and related morbidities among the study children and their household contacts. Results: Influenza virus was demonstrated in 352 cases (9.3%). In comparison with the influenza negative children, those who were influenza positive had an older mean age, were more often attending day care centres or schools, more frequently experienced fever and croup, received more antipyretics, and had a longer duration of fever and school absence. Furthermore, their parents and siblings had more respiratory illnesses, received more antipyretics and antibiotics, needed more medical visits, missed more work or school days, and needed help at home to care for the ill children for a longer period of time. Conclusions: Influenza has a significant clinical and socioeconomic impact on healthy children and their families. Prevention strategies should also focus on healthy children regardless of their age because of their role in disease transmission.

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.

Onset of clinical signs in children with HIV-1 perinatal infection

Objective: To investigate the timing of onset of each clinical sign in infants and children with HIV‐1 perinatal infection. Design and methods: A total of 200 HIV‐1‐infected children followed‐up from birth were studied. Failure and conditional probabilities were estimated by the Kaplan‐Meier product‐limit method. Cox proportional hazard analysis was used to evaluate independently associated factors. Results of 934 seroreverters were used to calculate reference values of CD4+ cell counts and predictivity of early signs. Results: Median age at the onset of any sign was 5.2 months (range, 0.03‐56 months). The probability of remaining asymptomatic was 19% [95% confidence interval (CI), 14‐25.1] at 12 months and 6.1% (95% Cl, 2.6‐11.7) at 5 years. Lymphadenopathy (69.5%), splenomegaly (62.4%) and hepatomegaly (58.4%) were the most common signs in the first year of life. Peculiar to the first year of life (compared with subsequent ages) was the onset of primary HIV‐1 hepatitis and diarrhoea (rate ratios, 23.3 and 15.2, respectively). When CD4+ cell counts in the asymptomatic stage (age, 2 months; range, 0.03‐5.9 months) were below rather than above the fifth percentile in seroreverters, onset of signs was earlier [3 (range, 0.03‐19) versus 5 (range, 0.03‐56) months]. Children manifesting signs before the 5.2‐month breakpoint had a lower survival rate [74% (range, 65.9‐82%) at 12 months and 45% (range, 32.9‐57%) at 5 years] than children manifesting signs later 198% (range, 92.2‐100%) at 12 months and 74% (range, 60.3‐87.7%) at 5 years]. Children whose birthweight was ≤2400g had an earlier onset (24 months; range, 1‐57 months) of severe conditions than children with higher birthweight (71 months; range, 1‐71 months). Development of lymphadenopathy or hepatosplenomegaly within 3 months of life were reliable indicators of infection. Conclusions: This study describes the sequence of onset of signs in perinatal HIV‐1 infection. Infection is shown to progress faster than in adults and in a different manner. Low birthweight, early decreased CD4+ cell counts, and early onset of signs are predictive of rapid progression. AIDS 1995, 9:455‐461

Comparison of immunogenicity and tolerability of a virosome-adjuvanted and a split influenza vaccine in children.

Objective. To compare the immunogenicity and safety of a virosome-adjuvanted influenza vaccine (Inflexal V; Berna Biotech, Berne, Switzerland) and a split influenza vaccine (Fluarix; GlaxoSmithKline Biologicals, Rixensart, Belgium) in children. Subjects and methods. The subjects, 453 children ages 6 to 71 months, were stratified into primed and unprimed and age groups (6 to 35 and 36 to 71 months) and then randomized 1:1 to receive virosome-adjuvanted (n = 224) or split influenza vaccine (n = 229), a half or full dose was given intramuscularly according to age. Unprimed children received a second dose after 4 weeks. Blood samples (n = 326) collected pre-and 28 days postvaccination were analyzed by hemagglutination inhibition test. Safety assessments were made at baseline and follow-up visits by the investigators and by parents for the 4 days after vaccinations. Results. Both vaccines induced an effective immune response. Seroconversion rates (>4-fold titer rise) against the WHO recommended strains A/New Caledonia (H3N2), A/Moscow (H1N1) and B/Hongkong (B) were 80.1, 66.0 and 90.4% for the virosome-adjuvanted and 75.9, 62.9 and 89.4% for the split influenza vaccine, respectively. Unprimed children’s seroconversion rates for H3N2 were significantly higher (P = 0.02) for the virosome-adjuvanted (88.8%) than for split influenza vaccine (77.5%). Seroprotection rates (titer of > 40) for H3N2, H1N1 and B, respectively, were 87.8, 80.1 and 90.4% after vaccination with the virosome-adjuvanted vaccine and 82.9, 78.2 and 89.4% after the split influenza vaccine. Unprimed children’s seroprotection rate was significantly higher (P = 0.03) for H3N2 after the virosome-adjuvanted (88.8%) than those for the split influenza vaccine (78.3%). Equivalent geometric mean titer fold increases were evident for both vaccines. No serious adverse events were seen. Pain/ tenderness, redness and swelling/induration was found in 25.4, 11.2 and 8.9% for the virosome-adjuvanted vaccine and in 24.0, 9.2 and 6.1% for the split influenza vaccine, respectively. The rates of fever, malaise/irritability and shivering was 6.3, 11.6 and 2.7% for the virosome-adjuvanted vaccine and 8.3, 11.8 and 2.6% for the split influenza vaccine, respectively. Conclusions. The virosome-adjuvanted influenza vaccine showed greater immunogenicity over the split influenza vaccine in unprimed children and showed a trend toward better immunogenicity in the rest of the study population. Both vaccines were well-tolerated.

Nasopharyngeal carriage of Streptococcus pneumoniae in healthy children: Implications for the use of heptavalent pneumococcal conjugate vaccine

We assessed the prevalence of Streptococcus pneumoniae serotypes in the nasopharynx of healthy children, antimicrobial susceptibility patterns, risk factors for carriage, and the coverage of heptavalent pneumococcal conjugate vaccine. In 2,799 healthy infants and children, the S. pneumoniae carrier rate was 8.6% (serotypes 3, 19F, 23F, 19A, 6B, and 14 were most common). Most pneumococci (69.4%) were resistant to one or more antimicrobial classes. The rate of penicillin resistance was low (9.1%); macrolide resistance was high (52.1%). Overall, 63.2% of the isolates belonged to strains covered by the heptavalent pneumococcal vaccine. This percentage was higher in children <2 years old (73.1%) and in those >2-5 years old(68.9%). Sinusitis in the previous 3 months was the only risk factor for carrier status; acute otitis media was the only risk factor for the carriage of penicillin-resistant S. pneumoniae. Most the isolated strains are covered by the heptavalent conjugate vaccine, especially in the first years of life, suggesting that its use could reduce the incidence of pneumococcal disease.