Valentina Ierardi

Association between peripheral T-Lymphocyte activation and impaired bone mineral density in HIV-infected patients

BackgroundHIV-infected patients display an increased and early incidence of osteopenia/osteoporosis. We investigated whether bone metabolism disorders in HIV-infected patients are related to immune hyperactivation and premature immune senescence.MethodsBone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA): low BMD (LBMD) was defined as T-score or z-scoreu2009<u2009-1. CD4+/CD8+ phenotype (CD38/HLA-DR, CD127, CD28/CD57), and circulating IL-7, TNF-α, RANKL, OPG were measured. The variables with pu2009<u2009.05 were evaluated by multivariate logistic regression.Results78 patients were enrolled: 55 were LBMD. LBMD patients showed increased activated HDLADRu2009+u2009CD4+ and CD8+ (pu2009=u2009.03 and pu2009=u2009.002, respectively). Interestingly, no differences in senescent CD28-CD57u2009+u2009CD4+/CD8+ T-cells were observed between groups. However, LBMD patients displayed a decreased CD4u2009+u2009CD28- phenotype (pu2009=u2009.04) at the advantage of the CD28+ pool (pu2009=u2009.03), possibly reflecting heightened apoptosis of highly differentiated CD28-negative cells.Activated HLADRu2009+u2009CD4+/CD8+ and CD28u2009+u2009CD4+ cells were independently associated with impaired BMD (AORu2009=u20091.08 for each additional HLADRu2009+u2009CD4+ percentage higher; CI 95%,1.01-1.15; pu2009=u2009.02; AORu2009=u20091.07 for each additional HLADRu2009+u2009CD8+ percentage higher; CI 95%,1.01-1.11; pu2009=u2009.01; AORu2009=u20091.06 for each additional CD28u2009+u2009CD4+ percentage higher; CI 95%,1.0-1.13; pu2009=u2009.05).ConclusionsHeightened T-cell activation in HIV-infected patients independently predicts BMD disorders, suggesting a critical role of immune activation in the pathogenesis of osteopenia/osteoporosis, even in patients achieving full viral suppression with HAART.

Pneumococcal bacterial load colonization as a marker of mixed infection in children with alveolar community-acquired pneumonia and respiratory syncytial virus or rhinovirus infection.

Background: The main aim of this study was to evaluate whether nasopharyngeal Streptococcus pneumoniae colonization in children with alveolar community-acquired pneumonia (CAP) and respiratory syncytial virus (RSV) or rhinovirus (RV) infection indicates a mixed lung infection. Methods: The nasopharyngeal secretions of 530 children with radiographically confirmed CAP were tested using the Luminex x TAG respiratory virus panel fast assay. Real-time polymerase chain reaction for the autolysin-A (LytA) and wzg (cpsA) genes of S. pneumoniae was performed on the RSV- and RV-positive samples. Results: Sixty-five of the 126 RSV-positive children (51.6%) were colonized with S. pneumoniae. Mean bacterial load was significantly higher in the patients with alveolar involvement (4.54 ± 1.47 log10 DNA copies/mL vs. 3.75 ± 1.62 log10 DNA copies/mL; P = 0.04). Serotypes 5 and 19A were almost exclusively identified in the children with RSV and alveolar CAP, although the difference was statistically significant only for serotype 19A (P = 0.03). Eighty-three of the 134 RV-positive children (61.9%) were colonized with S. pneumoniae and again mean bacterial load was significantly higher in the patients with alveolar involvement (4.21 ± 1.37 log10 DNA copies/mL vs. 3.41 ± 1.47 log10 DNA copies/mL; P = 0.03). Serotypes 1, 5 and 19A were more frequently identified in the children with RV and alveolar CAP, although the difference was statistically significant only for serotype 5 (P = 0.04). Conclusions: In children with alveolar CAP and RSV or RV infection, the determination of nasopharyngeal pneumococcal bacterial load and identification of the serotypes can contribute to the diagnosis of mixed lung infection.

Genetic polymorphisms and risk of recurrent wheezing in pediatric age

BackgroundWheezing during early life is a very common disorder, but the reasons underlying the different wheezing phenotypes are still unclear. The aims of this study were to analyse the potential correlations between the risk of developing recurrent wheezing and the presence of specific polymorphisms of some genes regulating immune system function, and to study the relative importance of the associations of different viruses and genetic polymorphisms in causing recurrent episodes.MethodsThe study involved 119 otherwise healthy infants admitted to hospital for a first episode of wheezing (74 of whom subsequently experienced recurrent episodes) and 119 age- and sex-matched subjects without any history of respiratory problem randomly selected from those attending our outpatient clinic during the study period. All of the study subjects were followed up for two years, and 47 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped on whole blood using an ABI PRISM 7900 HT Fast Real-time instrument.ResultsIL8-rs4073AT, VEGFA-rs833058CT, MBL2-rs1800450CT and IKBKB-rs3747811AT were associated with a significantly increased risk of developing wheezing (pu2009=u20090.02, pu2009=u20090.03, pu2009=u20090.05 and pu2009=u20090.0018), whereas CTLA4-rs3087243AG and NFKBIB-rs3136641TT were associated with a significantly reduced risk (pu2009=u20090.05 and pu2009=u20090.04). IL8-rs4073AT, VEGFA-rs2146323AA and NFKBIA-rs2233419AG were associated with a significantly increased risk of developing recurrent wheezing (pu2009=u20090.04, pu2009=u20090.04 and pu2009=u20090.03), whereas TLR3-rs3775291TC was associated with a significantly reduced risk (pu2009=u20090.03). Interestingly, the study of gene-environment interactions showed that rhinovirus was significantly associated with recurrent wheezing in the presence of IL4Ra-rs1801275GG and G (odds ratio [OR] 6.03, 95% confidence interval [CI]: 1.21-30.10, pu2009=u20090.03) and MAP3K1-rs702689AA (OR 4.09, 95% CI: 1.14-14.61, pu2009=u20090.03).ConclusionsThis study shows a clear relationship between the risk of wheezing and polymorphisms of some genes involved in the immune response. Although further studies are needed to confirm the results, these findings may be useful for the early identification of children at the highest risk of developing recurrent episodes and possibly subsequent asthma.

Hexavalent vaccines for immunization in paediatric age

Despite the potential for protection against a broad spectrum of pathogens, the availability of an increased number of effective vaccines could lead to a significant reduction in vaccination coverage as the result of issues with implementation of new vaccines within existing protocols. To overcome these problems, the development of combined vaccines has been promoted. The use of combined vaccines offers a number of potential benefits, including a reduction in the number of patient visits, reduced complications associated with multiple intramuscular injections, decreased costs of stocking and administering separate vaccines, and a lowering of the risk of delayed or missed vaccinations. The hexavalent vaccine includes antigens against diphtheria, tetanus, acellular pertussis (DTaP), hepatitis B (HBsAg), poliomyelitis (P1, P2, P3) and Haemophilus influenzae type B (Hib) infections. The primary goal of this review is to discuss the immunogenicity, efficacy, safety and tolerability of several hexavalent preparations that are either commercially available or still under development.

Pharyngeal colonization by Streptococcus pneumoniae in older children and adolescents in a geographical area characterized by relatively limited pneumococcal vaccination coverage.

Background: The aim of this study was to evaluate the relation between colonization and vaccination status with pneumococcal conjugate vaccine (PCV) in older children and adolescents living in an area characterized by relatively limited vaccination coverage. Methods: Oropharyngeal swabs were obtained from 2076 randomly selected healthy school-age children and adolescents, and the extracted genomic DNA was tested for Streptococcus pneumoniae by means of real-time polymerase chain reaction. All of the positive cases were subsequently serotyped, and the association between vaccination status with the heptavalent PCV (PCV7) and pneumococcal colonization was determined. Results: S. pneumoniae was identified in the oropharyngeal swabs of 1201 subjects (57.9%), and its prevalence declined with age (74.9% in subjects aged <10 years, 51.8% in those aged 10–14 years and 32.7% in those aged ≥15 years; P < 0.001). There were more carriers of any pneumococcal serotype, any of the serotypes in PCV7, or any of the 6 additional serotypes in 13-valent PCV (PCV13) among the vaccinated than the unvaccinated subjects, but no association emerged after adjustment for age and other selected covariates. Sub-analyses by serotype and age groups revealed significant differences in the case of serotypes 3 and 19A among children aged <10 years (odds ratios of 2.03 and 2.18, respectively). Conclusions: These results show the absence of any long-term effect of PCV7 on colonization, and raise doubts concerning the recent suggestion to use carriage to evaluate the efficacy of PCVs. The high prevalence of carriers in all of the age groups independent of previous pneumococcal vaccination indicates that further studies are needed to evaluate whether the extensive use of PCVs in healthy older children and adolescents might reduce pharyngeal colonization of these subjects thereby increasing herd immunity.

Impact of a mixed bacterial lysate (OM-85 BV) on the immunogenicity, safety and tolerability of inactivated influenza vaccine in children with recurrent respiratory tract infection

It is known that the immunogenicity and efficacy of conventional inactivated influenza vaccines (IIVs) are not completely satisfactory in children. The aim of this prospective, randomised, single-blind study was to compare the immune response to, and the effectiveness and safety of, an IIV (Fluarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) administered to 68 children aged 36-59 months affected by recurrent respiratory tract infections (RRTIs) who were vaccinated with (n=33) or without (n=35) the mixed bacterial lysate OM-85 BV (Broncho-vaxom, Vifor Pharma, Geneva, Switzerland). OM-85 BV had no effect on seroconversion or seroprotection rates, geometric mean titres, or dendritic cells, which were not significantly different between the two groups. Moreover, OM-85 BV did not significantly increase the pool of the memory B cells that produce IgG and IgM antibodies against the influenza antigens. However, respiratory morbidity was significantly lower in the children treated with OM-85 BV (p<0.05), thus confirming its positive effect on the incidence of RRTIs. There was no difference in the incidence of adverse events between the two groups. These findings show that the immune response of children to influenza vaccine is not significantly influenced by the administration of OM-85 BV. However, the use of OM-85 before and at the same time as IIV seems to reduce respiratory morbidity, and seems to be safe and well tolerated.

Pneumococcal colonization in older adults

BackgroundLittle is known about pneumococcal carrier states in older adults. The main aim of this study was to evaluate pneumococcal colonization patterns among older adults in two centres in Milan, Italy, before the widespread use of the 13-valent pneumococcal vaccine (PCV13) in this age group, to investigate demographic and clinical features that are associated with pneumococcal colonization and to estimate the potential coverage offered by PCV13.ResultsAmong 417 adults ≥65xa0years old (171, 41.1xa0%, ≥75xa0years), 41 (9.8xa0%) were pneumococcal carriers. Univariate and multivariate analyses revealed that pneumococcal colonization was significantly less common among individuals with underlying co-morbidities than among those without (odds ratio [OR] 0.453, 95xa0% confidence interval [CI] 0.235–0.875, pu2009=u20090.018; adjusted OR 0.503, 95xa0% CI 0.255–0.992, pu2009=u20090.047). Moreover, among these patients, those with cardiac disease had a significantly lower risk of colonization (OR 0.308, 95xa0% CI 0.119–0.795, pu2009=u20090.015; adjusted OR 0.341, 95xa0% CI 0.13–0.894, pu2009=u20090.029). Only one vaccinated subject who received 23-valent polysaccharide pneumococcal vaccine (PPV23) was colonized. Twenty-five (89.3xa0%) of the subjects who were <75xa0years old and 9 (75.0xa0%) of those who were ≥75xa0years old were colonized by at least one of the serotypes that is included in PCV13, with serotype 19xa0F being the most common. Respiratory allergies as well as overall co-morbidities were more common in subjects who were positive for only non-PCV13 serotypes compared with negative subjects and those who were carriers of only PCV13 serotypes.ConclusionsAlthough this study included a relatively small number of subjects and has been performed in a limited geographic setting, results showed that pneumococcal colonization in older people is common, and the monitoring of carriers can offer useful information about the circulation of this pathogen among older people and the potential protective effect of pneumococcal vaccines. Because the colonization in most cases involves the strains that are included in PCV13, this vaccine could be useful in the prevention of pneumococcal infections in the overall population of older people. In subjects with respiratory allergies and in those with co-morbidities, the addition of the PPV23 to PCV13 should be recommended. Due to the low vaccination coverage, urgent educational programmes are required to inform older adults and their medical doctors of the risks of pneumococcal infection and the efficacy and safety of the available pneumococcal vaccines.

Streptococcus pneumoniae colonisation in children and adolescents with asthma: impact of the heptavalent pneumococcal conjugate vaccine and evaluation of potential effect of thirteen-valent pneumococcal conjugate vaccine

BackgroundThe main aim of this study was to evaluate Streptococcus pneumoniae carriage in a group of school-aged children and adolescents with asthma because these results might indicate the theoretical risk of invasive pneumococcal disease (IPD) of such patients and the potential protective efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13).MethodsOropharyngeal samples were obtained from 423 children with documented asthma (300 males, 70.9xa0%), and tested for the autolysin-A-encoding (lytA) and the wzg (cpsA) gene of S. pneumoniae by means of real-time polymerase chain reaction.ResultsS. pneumoniae was identified in the swabs of 192 subjects (45.4xa0%): 48.4xa0% of whom were aged <10xa0years, 46.9xa0% aged 10–14 years, and 4.7xa0% aged ≥15xa0years (pu2009<u20090.001). Carriage was significantly less frequent among the children who had received recent antibiotic therapy (odds ratio [OR 0.41]; 95xa0% confidence interval [95xa0% CI] 0.22–0.76). Multivariate analyses showed no association between carriage and vaccination status, with ORs of 1.05 (95xa0% CI 0.70–1.58) for carriers of any pneumococcal serotype, 1.08 (95xa0% CI 0.72–1.62) for carriers of any of the serotypes included in 7-valent pneumococcal conjugate vaccine (PCV7), and 0.76 (95xa0% CI 0.45–1.28) for carriers of any of the six additional serotypes of PCV13. Serotypes 19xa0F, 4 and 9xa0V were the most frequently identified serotypes in vaccinated subjects.ConclusionsThese results showed that carriage of S. pneumoniae is relatively common in all school-aged children and adolescents with asthma, regardless of the severity of disease and the administration of PCV7 in the first years of life. This highlights the problem of the duration of the protection against colonisation provided by pneumococcal conjugate vaccine, and the importance of re-colonization by the same pneumococcal serotypes included in the previously used vaccine.

Oropharyngeal and nasal Staphylococcus aureus carriage by healthy children

BackgroundAs healthy children are the main reservoir of respiratory pathogens and the main cause of bacterial diffusion in the community, it could be interesting to investigate the type of screening that should be used during the early years of life in order to obtain a more precise estimate of Staphylococcus aureus circulation. The aim of this study was to evaluate oropharyngeal and nasal S. aureus carriage in otherwise healthy children and adolescents aged 6–17 years.MethodsThe oropharyngeal and nasal samples were collected in December 2013 from 497 healthy students attending five randomly selected schools in Milan, Italy, using an ESwab kit, and S. aureus was identified using the RIDA®GENE methicillin-resistant S. aureus (MRSA) system.ResultsTwo hundred and sixty-four subjects (53.1%) were identified as S. aureus carriers: 129 (25.9%) oropharyngeal carriers and 195 (39.2%) nasal carriers, of whom 60 (12.1%) were both oropharyngeal and nasal carriers. Oropharyngeal carriage increased with age (p <u20090.001), whereas nasal carriage decreased. There was little or no agreement between oropharyngeal and nasal carriage in any of the age groups. MRSA was identified in only three cases (0.6%), always in nasal samples. There were no differences between the carriers and non-carriers in terms of the distribution of age, gender, ethnicity, the number of siblings in the household, exposure to passive smoking, previous clinical history, allergic sensitisation, or previous influenza, pneumococcal and meningococcal vaccinations. The frequency of male children was higher among the subjects with positive nasal and oropharyngeal swabs (66.7%) than among those with positive oropharyngeal swabs alone (46.4%; p =u20090.02).ConclusionsThe oropharyngeal carriage of mainly methicillin-sensitive S. aureus is frequent in otherwise healthy children, including a relatively high proportion of those without nasal colonisation. These findings highlight the importance of adding throat to nasal screening when monitoring the circulation of S. aureus in the community.

Interaction between Streptococcus pneumoniae and Staphylococcus aureus in paediatric patients suffering from an underlying chronic disease

Little is known about the interaction between Streptococcus pneumoniae and Staphylococcus aureus in school-age children and adolescents suffering from an underlying chronic disease. To increase our knowledge in this regard, an oropharyngeal swab was obtained from school-age children and adolescents suffering from asthma (n = 423), cystic fibrosis (CF) (n = 212) and type 1 diabetes mellitus (DM1) (n = 296). S. pneumoniae detection and serotyping were performed using a real-time polymerase chain reaction, and S. aureus detection was performed using the RIDAGENE MRSA system. Among asthmatic, CF and DM1 patients, both pathogens were identified in 65/423 (15.4%), 21/212 (9.9%) and 62/296 (20.9%) children, respectively; S. pneumoniae alone was identified in 127/434 (30.0%), 21/212 (9.9%) and 86/296 (29.1%), respectively; S. aureus alone was identified in 58/434 (13.7%), 78/212 (36.8%) and 49/296 (16.6%), respectively. S. pneumoniae colonisation rates were higher in younger children and declined with age, whereas the frequency of S. aureus colonisation was quite similar in the different age groups. Among asthmatic and CF patients aged 6–9 years, S. aureus carriage was significantly higher in children who were positive for S. pneumoniae (P <0.05). No significant association emerged between S. aureus carriage and carriage of S. pneumoniae serotypes included in the pneumococcal conjugate vaccines (PCVs). This study shows for the first time that school-age children and adolescents with asthma, CF and DM1 are frequently colonised by S. pneumoniae and S. aureus and that no negative relationship seems to exist between these pathogens. Moreover, the supposed protection offered by PCV administration against S. aureus colonisation was not demonstrated.