Nicola Principi

Mother-to-infant transmission of hepatitis C virus

The rate of mother-to-infant transmission of hepatitis C virus (HCV) is approximately 5%, but is higher when the mother is co-infected with HIV Vertical transmission is restricted to infants whose mothers are viraemic. The risk of transmission increases with increasing maternal viral load but a specific cut-off value predicting infection cannot be defined. There is no specific HCV genotype which is preferentially transmitted. The mode of delivery (caesarean versus vaginal) does not appear to influence the rate of transmission, but firm evidence is lacking. There is no evidence to suggest an increased risk of HCV transmission through breast feeding. Pregnancy is not contra-indicated in HCV-infected women. Without drugs to treat established infections in mothers and infants and interventions to prevent vertical transmission, routine HCV screening is not recommended in pregnant women.

Immunogenicity and Tolerability of Recombinant Serogroup B Meningococcal Vaccine Administered With or Without Routine Infant Vaccinations According to Different Immunization Schedules: A Randomized Controlled Trial

CONTEXT In the absence of an effective vaccine, serogroup B Neisseria meningitidis (MenB) remains a major cause of invasive disease in early childhood in developed countries. OBJECTIVE To determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately. DESIGN, SETTING, AND PARTICIPANTS Phase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe. INTERVENTION Participants were randomized 2:2:1:1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months. MAIN OUTCOME MEASURES Percentage of participants with human complement serum bactericidal activity (hSBA) titer of 1:5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99). RESULTS After three 4CMenB vaccinations, 99% or more of infants developed hSBA titers of 1:5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79% (95% CI, 75.2%-82.4%) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1% (95% CI, 82.9%-89.0%) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7% (95% CI, 76.6%-86.2%) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26% (158/602) to 41% (247/607) of 4CMenB doses when administered alone, compared with 23% (69/304) to 36% (109/306) after routine vaccines given alone and 51% (306/605) to 61% (380/624) after 4CMenB and routine vaccines administered together. CONCLUSION A 4CMenB vaccine is immunogenic against reference strains when administered with routine vaccines at 2, 4, and 6 or at 2, 3, and 4 months of age, producing minimal interference with the response to routine infant vaccinations. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00721396.

Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in Children with Community-Acquired Lower Respiratory Tract Infections

In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs). The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999. Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M. pneumoniae and C. pneumoniae antibodies. Nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae were obtained on admission. Acute M. pneumoniae infections in 210 patients (34.3%) and acute C. pneumoniae infections in 87 (14.1%) were diagnosed. Fifteen of the 18 children with M. pneumoniae and/or C. pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides. Our study confirms that M. pneumoniae and/or C. pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents.

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.

Perinatal transmission and manifestation of hepatitis C virus infection in a high risk population.

We studied the perinatal transmission of hepatitis C virus (HCV) in 70 high risk mother/infant pairs. Seventy-six percent of the mothers (53 of 70) were coinfected with human immunodeficiency virus (HIV) and 79% (55 of 70) had a history of drug addiction. During the follow-up HCV RNA was detected in 14 of 70 (20%) infants: 12% (2 of 17) in infants born to HIV-negative mothers; and 23% (12 of 53) in infants to HIV-positive mothers. The rate of vertical transmission was significantly higher in vaginally delivered infants than in those delivered by cesarean section (32% vs. 6%; P < 0.05). All 56 uninfected infants lost passively acquired anti-HCV by age 9 \pm 4 months and only 2 of 56 infants (4%) had evidence of HIV infection. Four of 14 HCV RNA-positive infants (29%) had evidence of HTV coinfection. We observed 3 clinical patterns of HCV infection: a transient viremia in 2 infants; an acute pattern in 2 infants; and a chronic pattern in 10 infants. All 4 HIV-coinfected infants had chronic HCV infection. All infants with a chronic pattern, had increased alanine aminotransferase values for more than 6 months and 5 had a liver biopsy that showed signs of chronic persistent hepatitis. HCV perinatal transmission was more frequent in infants born to HIV-coinfected mothers than in infants born to HIV-noninfected women, particularly when delivered vaginally.

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.

Increased Risk of Maternal-Infant Hepatitis C Virus Transmission for Women Coinfected with Human Immunodeficiency Virus Type 1

To estimate the risk of mother-to-child transmission of hepatitis C virus (HCV) and identify correlates of transmission, 245 perinatally exposed singleton children followed prospectively beyond 18 months of age were studied. Overall, 28 (11.4%) of the 245 children acquired HCV infection. Transmission occurred in 3 of 80 children (3.7%) whose mothers had HCV infection alone and in 25 of 165 (15.1%; P < .01) whose mothers had concurrent infection with human immunodeficiency virus type 1 (HIV-1). The percentage of HIV-1-infected children was similar (22 of 165, 13.3%), but each virus was transmitted independently; only six infants (3.6%) were coinfected with HCV and HIV-1. The risk of HCV transmission was not associated with maternal HIV-1-related symptoms, intravenous drug use, prematurity, low birth weight, or breast-feeding, whereas it was lower with cesarean section than with vaginal delivery (5.6% vs. 13.9%, P = .06). This suggests that transmission occurs mainly around the time of delivery.

Safety and Immunogenicity of a 13-Valent Pneumococcal Conjugate Vaccine Compared to Those of a 7-Valent Pneumococcal Conjugate Vaccine Given as a Three-Dose Series with Routine Vaccines in Healthy Infants and Toddlers

ABSTRACT A 13-valent pneumococcal conjugate vaccine (PCV13) has been developed to improve protection against pneumococcal disease beyond that possible with the licensed 7-valent vaccine (PCV7). This study compared the safety and immunogenicity of PCV13 with those of PCV7 when given as part of the pediatric vaccination schedule recommended in Italy. A total of 606 subjects were randomly assigned to receive either PCV13 or PCV7 at 3, 5, and 11 months of age; all subjects concomitantly received diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type B (DTaP-HBV-IPV/Hib) vaccine. Vaccine reactions were monitored. Antibody responses to DTaP-HBV-IPV/Hib antigens, serotype-specific anticapsular polysaccharide IgG responses, and antipneumococcal opsonophagocytic assay (OPA) activity were measured 1 month after the two-dose primary series and 1 month after the toddler dose. Overall, the safety profile of PCV13 was similar to that of PCV7. The response to DTaP-HBV-IPV/Hib antigens was substantially the same with both PCV13 and PCV7. PCV13 elicited antipneumococcal capsular IgG antibodies to all 13 vaccine serotypes, with notable increases in concentrations seen after the toddler dose. Despite a lower immunogenicity for serotypes 6B and 23F after the primary series of PCV13, responses to the seven common serotypes were comparable between the PCV13 and PCV7 groups when measured after the toddler dose. PCV13 also elicited substantial levels of OPA activity against all 13 serotypes following both the infant series and the toddler dose. In conclusion, PCV13 appeared comparable to PCV7 in safety profile and immunogenicity for common serotypes, demonstrated functional OPA responses for all 13 serotypes, and did not interfere with immune responses to concomitantly administered DTaP-HBV-IPV/Hib vaccine.

Emerging role of Mycoplasma pneumoniae and Chlamydia pneumoniae in paediatric respiratory- tract infections

Increased use of specialised diagnostic techniques over the past 10 years has allowed considerable new information to be obtained concerning Mycoplasma pneumoniae and Chlamydia pneumoniae infections. In children, these pathogens seem to have a more important role in causing respiratory-tract infections than previously thought; they have been associated with wheezing, and they are also frequent in children aged under 5 years. Contrary to original belief, no clinical, laboratory, or radiological findings seem to be unique to M. pneumoniae or C. pneumoniae; furthermore, there is no rapid and cost-effective diagnostic test capable of identifying these pathogens. Appropriate antimicrobial treatment of the infections they cause is needed to reduce the recurrent episodes of wheezing and other respiratory symptoms, to decrease morbidity, and to avoid the spread of the pathogens. However, a number of therapeutic issues remain unsolved.

Early immune reconstitution after potent antiretroviral therapy in HIV-infected children correlates with the increase in thymus volume

DesignDespite significant rises in total CD4 T cells, the process of immune reconstitution in adults with HIV infection treated with potent antiretroviral treatment results in a rather slow increase in phenotypically naive lymphocytes. In children more than in adults, thymic function may be at least partly restored when disease-induced immunosuppression is attenuated by pharmacological means. MethodsTwenty-five vertically infected and antiretroviral-experienced [zidovudine (ZDV)/ZDV plus didanosine (ddI)] children were prospectively followed during 12 months of treatment with lamivudine (3TC), stavudine (d4T) and indinavir (IDV). The plasma HIV viral load and phenotypic and functional cellular immunity-defining parameters were examined. The relationship between the degree of immune reconstitution and thymus volume assessed by nuclear magnetic resonance was also examined. ResultsAn early and steep increase in CD45RA+62L+ T cells was observed in parallel with a sustained decrease in plasma HIV RNA levels and a significant rise in total CD4 T cells. This increase was significantly greater than that observed in CD4+CD45RO+ T cells. Analysis of the CD4 T cell receptor (TCR) beta repertoire and T helper function showed the ability to reconstitute families almost completely absent at baseline, and a substantial improvement of antigen-specific responses by peripheral blood lymphocytes. The rise in CD4 cells and in CD4+CD45RA+62L+ T cells was statistically associated with changes in thymus size observed over time. ConclusionThese data suggest a relevant contribution of the thymus to reconstitution of the peripheral pool of T cells in vertically HIV-infected children treated with potent antiretroviral regimens.