Hand, foot and mouth disease: current knowledge on clinical manifestations, epidemiology, aetiology and prevention.

For a long time, hand, foot and mouth disease (HFMD) was seen as a mild viral infection characterized by typical clinical manifestations that spontaneously resolved in a few days without complications. In the past two decades, HFMD has received new attention because of evidence that this disease could have clinical, epidemiological and aetiological characteristics quite different from those initially thought. In contrast to previous beliefs, it has been clarified that HFMD can be associated with complications, leading to severe neurological sequelae and, rarely, to death. This finding has led to an enormous number of studies that have indicated that several viruses in addition to those known to be causes of HFMD could be associated with the development of disease. Moreover, it was found that if some viruses were more common in some geographic areas, frequent modification of the molecular epidemiology of the infecting strains could lead to outbreaks caused by infectious agents significantly different from those previously circulating. Vaccines able to confer protection against the most common aetiologic agents in a given country have been developed. However, simultaneous circulation of more than one causative virus and modification of the molecular epidemiology of infectious agents make preparations based on a single agent relatively inadequate. Vaccines with multiple components are a possible solution. However, several problems concerning their development must be solved before adequate prevention of severe cases of HFMD can be achieved.

Antimicrobial Prophylaxis in Neonates and Children Undergoing Dental, Maxillo-Facial or Ear-Nose-Throat (ENT) Surgery: A RAND/UCLA Appropriateness Method Consensus Study.

Surgical site infections (SSIs) represent a potential complication in surgical procedures, mainly because clean/contaminated surgery involves organs that are normally colonized by bacteria. Dental, maxillo-facial and ear-nose-throat (ENT) surgeries are among those that carry a risk of SSIs because the mouth and the first respiratory tracts are normally colonized by a bacterial flora. The aim of this consensus document was to provide clinicians with recommendations on surgical antimicrobial prophylaxis in neonates (<28 days of chronological age) and pediatric patients (within the age range of 29 days−18 years) undergoing dental, maxillo-facial or ENT surgical procedures. These included: (1) dental surgery; (2) maxilla-facial surgery following trauma with fracture; (3) temporo-mandibular surgery; (4) cleft palate and cleft lip repair; (5) ear surgery; (6) endoscopic paranasal cavity surgery and septoplasty; (7) clean head and neck surgery; (8) clean/contaminated head and neck surgery and (9) tonsillectomy and adenoidectomy. Due to the lack of pediatric data for the majority of dental, maxillo-facial and ENT surgeries and the fact that the recommendations for adults are currently used, there is a need for ad hoc studies to be rapidly planned for the most deficient areas. This seems even more urgent for interventions such as those involving the first airways since the different composition of the respiratory microbiota in children compared to adults implies the possibility that surgical antibiotic prophylaxis schemes that are ideal for adults may not be equally effective in children.

An open-label, randomized clinical trial assessing immunogenicity, safety and tolerability of pandemic influenza A/H1N1 MF59-adjuvanted vaccine administered sequentially or simultaneously with seasonal virosomal-adjuvanted influenza vaccine to paediatric kidney transplant recipients.

BACKGROUND: The aim of this study was to investigate the immunogenicity, safety and tolerability of the 2009 A/H1N1 MF59-adjuvanted influenza vaccine, administered sequentially or simultaneously with the seasonal 2009-10 virosomal-adjuvanted influenza vaccine, to paediatric kidney transplant recipients. METHODS: Thirty-two children and adolescents with transplanted kidneys and 32 age- and gender-matched healthy controls were randomized 1:1 to receive the pandemic vaccine upon enrolment and the seasonal vaccine 1 month later (16 transplant recipients and 16 healthy controls), or to receive the two vaccines simultaneously upon enrolment (16 transplant recipients and 16 healthy controls). RESULTS: When the pandemic vaccine was administered sequentially to the seasonal vaccine, it was significantly less immunogenic in the patients than in the controls (P < 0.05); when it was administered together with the seasonal vaccine, the immune response of both patients (P < 0.05) and controls (P < 0.05) was significantly greater than when it was administered sequentially. Seroconversion rates and the geometric mean titres of all of the seasonal antigens were significantly lower in the patients, regardless of the type of vaccine administration (P < 0.05). Simultaneous administration was associated with a better immune response against A/H1N1 and A/H3N2 antigens in both patients and controls, and did not increase the mild local and systemic reactions. No impact on renal function was observed. CONCLUSIONS: Paediatric kidney transplant recipients have a lower immune response to the pandemic influenza A/H1N1 MF59-adjuvanted and seasonal virosomal-adjuvanted influenza vaccines than healthy controls. The simultaneous administration of the two vaccines seems to increase immune response to both pandemic and seasonal A/H1N1 and A/H3N2 antigens, and has the same safety profile as that of the pandemic vaccine administered sequentially to the seasonal vaccine.

Immunogenicity, safety and tolerability of monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children and adolescents with Williams or Cornelia De Lange syndrome.

In some subjects with severe neurological diseases, a reduced immune response to seasonal influenza vaccine has been demonstrated. Patients with Williams or Cornelia de Lange syndrome frequently have abnormalities in neurodevelopment. This study has evaluated the immunogenicity, safety and tolerability of a monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in these subjects. Eighteen patients with Williams syndrome (ten males; mean age ± standard deviation [SD] 12.74 ± 4.49 years), 11 with Cornelia de Lange syndrome (six males; mean age 12.90 ± 4.85 years) and 30 age- and gender-matched healthy controls (16 males; mean age 12.49 ± 4.55 years), never vaccinated against influenza, received a dose of the vaccine between 1 and 30 November 2009. Four weeks later, the seroconversion rates in the three groups were between 72% and 80% and the seroprotection rates were 100%, with a similar increase in antibody levels. Two months later, most of the subjects remained seroconverted with no statistically significant difference between the groups, and about 94% of the patients with Williams syndrome, all of those with Cornelia de Lange syndrome and all of the healthy controls were still seroprotected. Safety and tolerability were very good, with no difference between the groups. None of the patients developed documented influenza during the study period. These results show that the immunogenicity, safety, and tolerability of a single dose of the monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children and adolescents with Williams or Cornelia de Lange syndrome and moderate to severe mental disabilities is very good, and similar to that of healthy subjects.

Immunogenicity and Safety of an MF59-adjuvanted Quadrivalent Seasonal Influenza Vaccine in Young Children at High Risk of Influenza-associated Complications: A Phase III, Randomized, Observer-blind, Multicenter Clinical Trial.

BACKGROUND: Vaccination against seasonal influenza is recommended for all children with a history of medical conditions placing them at increased risk of influenza-associated complications. The immunogenicity and efficacy of conventional influenza vaccines among young children are suboptimal; one strategy to enhance these is adjuvantation. We present immunogenicity and safety data for an MF59-adjuvanted quadrivalent influenza vaccine (aIIV4) in healthy children and those at a high risk of influenza-associated complications, based on the results of a recently completed phase III study. METHODS: Children 6 months to 5 years of age (N = 10,644) were enrolled. The study was conducted across northern hemisphere seasons 2013-2014 and 2014-2015. Subjects received either aIIV4 or a nonadjuvanted comparator influenza vaccine. Antibody responses were assessed by hemagglutination inhibition assay against vaccine and heterologous strains. Long-term antibody persistence was assessed (ClinicalTrials.gov: NCT01964989). RESULTS: aIIV4 induced significantly higher antibody titers than nonadjuvanted vaccine in high-risk subjects. aIIV4 antibody responses were of similar magnitude in high-risk and healthy subjects. Incidence of solicited local and systemic adverse events (AEs) was slightly higher in aIIV4 than nonadjuvanted vaccinees, in both the healthy and high-risk groups. Incidence of unsolicited AEs, serious AEs and AEs of special interest were similar for adjuvanted and nonadjuvanted vaccinees in the healthy and high-risk groups. CONCLUSION: aIIV4 was more immunogenic than nonadjuvanted vaccine in both the healthy and high-risk study groups. The reactogenicity and safety profiles of aIIV4 and the nonadjuvanted vaccine were acceptable and similar in 6-month- to 5-year-old high-risk and healthy children.

48, XXXY/49, XXXXY mosaic: new neuroradiological features in an ultra-rare syndrome.

BACKGROUND: Sex chromosomal aneuploidies in males are rare diseases with an overwhelming involvement of endocrinological and auxological issues; less frequently, other anomalies are observed. Neuroradiological issues are often not taken into account in single patients, and neuroradiological examinations are rarely performed. CASE PRESENTATION: Here, we report a boy with 48,XXXY/49,XXXXY mosaicism, phenotypically characterized by hypotonia, intellectual disability, ventricular septal defect, micropenis, and with mild hypertelorism, inverted nipples, a congenital hip dysplasia, and some neuroradiological features so far not described. The Magnetic Resonance Imaging showed white matter abnormalities and enlargement of lateral ventricles with never described dysmorphisms of cranio-cervical junction and posterior fossa. A cranio-cervical Computerized Tomography confirmed a dysmorphic aspect of the posterior fossa and occipital condyles, slight morphological asymmetry of C1 and slight lateralization to the right of the odontoid's apex. CONCLUSIONS: Considering the possible relevant clinical impact of these findings, the neuroradiological assessment seems potentially useful to the diagnostic approach of these patients.

Nasal resistances are useful in identifying children with severe obstructive sleep apnea before polysomnography.

OBJECTIVE: In this study, we would like to show that anterior rhinometry measurement of nasal resistance would be a simple and useful test to identify severe obstructive sleep apnea (OSA) in a population of children affected by adenotonsillar hypertrophy. METHODS: Seventy-three consecutive children (44 males; mean age 5.4+/-1.2 years) with adenotonsillar hypertrophy, who complained sleep-disordered breathing, were studied. All the parents completed a questionnaire concerning the children's sleeping habits and sleep complaints before consultation; each child underwent a general paediatric examination and an evaluation of craniofacial features and upper airway patency. In all 73 children polysomnography was performed and anterior rhinometry nasal patency was measured. RESULTS: The diagnosis of OSA was confirmed in 44/73 patients (60%). Total nasal resistance showed a significant direct correlation with apnea hypopnea index, arousal index, snoring time, percentage of sleep time spent at SaO(2)<90% and a significant inverse correlation with total sleep time, sleep efficiency and the mean of SaO(2)% during sleep. Total nasal resistance was significantly related to snoring, mouth breathing and daytime sleepiness. The receiver operator characteristics (ROC) curve indicates that in the range of age of our sample a nasal resistance value of 0.59 Pa/cm(3)/s has a sensitivity of 91% and specificity of 96% for identifying the children with adenotonsillar hypertrophy affected by OSA. CONCLUSIONS: Our study shows that in children with adenotonsillar hypertrophy nasal resistance seems to be risk factor for OSA. The anterior rhinometry appears as a useful tool in routine evaluation of sleep-disordered breathing in these patients.

Oropharyngeal and nasopharyngeal sampling for the detection of adolescent Streptococcus pneumoniae carriers.

Monitoring the dynamics of pneumococcal carriage makes it possible to evaluate the epidemiological characteristics of Streptococcus pneumoniae disease and the theoretical coverage offered by pneumococcal vaccines. It has been demonstrated that the nasopharyngeal (NP) sampling of respiratory secretions is superior to oropharyngeal (OP) sampling for identifying pneumococci carried by younger children, but adult data are conflicting and there are no published studies of adolescents. In order to compare the efficiency of OP and NP sampling in identifying and quantifying S. pneumoniae carriage in healthy adolescents, 2 swab samples were obtained from 530 adolescents aged 15-19 years, the first taken from the posterior pharyngeal wall through the mouth (OP) and the second through the nose (NP). Bacterial genomic DNA was tested for the autolysin-A-encoding gene (lytA) and wzg (cpsA) gene of S. pneumoniae in order to evaluate pneumococcal carrier status. All of the positive cases were serotyped. S. pneumoniae was identified in 35.8% of the OP swabs and 3.5% of the NP swabs (P<0.0001). The serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13) were found in all but two OP samples (98.9%) and only 64.7% of the NP samples (P<0.0001). The most frequently identified PCV13 serotype in both groups was 19F, followed by serotypes 5 and 9V. In conclusion, OP sampling appeared significantly more effective than NP sampling in identifying and characterizing pneumococcal carrier status in adolescents. This suggests that OP sampling should be used when evaluating the dynamics of pneumococcal carriage among adolescents and the theoretical coverage offered by PCV13.

Impact of vitamin D administration on immunogenicity of trivalent inactivated influenza vaccine in previously unvaccinated children.

As vitamin D (VD) has a significant regulatory effect on innate and adaptive immunity, the aim of this prospective, randomized, single-blinded, placebo-controlled study was to measure the impact of VD administration on the immune response to trivalent influenza vaccination (TIV). A total of 116 children (61 males, 52.6%; mean age 3.0 ± 1.0 y) with a history of recurrent acute otitis media (AOM), who had not been previously vaccinated against influenza, were randomized to receive daily VD 1,000 IU or placebo by mouth for four months. All of them received two doses of TIV (Fluarix, GlaxoSmithKline Biologicals) one month apart, with the first dose administered when VD supplementation was started. There was no difference in seroconversion or seroprotection rates, or antibody titers, in relation to any of the three influenza vaccine antigens between the VD and placebo groups, independently of baseline and post-treatment VD levels. The safety profile was also similar in the two groups. These data indicate that the daily administration of VD 1,000 IU for four months from the time of the injection of the first dose of TIV does not significantly modify the antibody response evoked by influenza vaccine.

Adjuvanted influenza vaccines.

The search for adjuvants has been stimulated by the need to ensure greater protection against influenza among subjects who show a reduced immune response to conventional influenza vaccines. Aluminum salts have long been used but are not considered satisfactory. This has led to the development of other possible compounds, sometimes on the basis of new knowledge concerning the mechanisms regulating the immune response to infections. Some of the new adjuvants (emulsions and virosomes) have been widely evaluated, and the apparently good results have led to the registration of adjuvanted influenza vaccines for use in humans, at least in some countries and in some subjects. In other cases, the adjuvants have been mainly or exclusively studied in experimental animals, and are unlikely to be used in humans in the near future. However, even in the case of those for which a considerable amount of data are available, assessments of their superiority over conventional influenza vaccines have mainly been based on immunogenicity studies, and have not been confirmed by comparative, randomized, double-blind clinical trials. Moreover, the very few human data comparing different adjuvants are frequently conflicting. The aim of this review is to discuss the characteristics and advantages of the adjuvants that have so far been used and to describe some of the new adjuvants that are still in the development phase.

Immunogenicity, safety and tolerability of MF59-adjuvanted seasonal influenza vaccine in children with juvenile idiopathic arthritis.

In order to evaluate the immunogenicity, safety, and tolerability of the MF-59 adjuvanted seasonal influenza vaccine in children and adolescents with juvenile idiopathic arthritis (JIA) treated with different anti-rheumatic drugs, 60 pediatric patients with JIA (30 treated with disease-modifying anti-rheumatic drugs [DMARDs] and 30 with etanercept) were compared with 30 healthy controls of similar gender and age. All of the patients received a single dose of the MF59-adjuvanted seasonal influenza vaccine (Fluad, Siena, Italy). Immunogenicity was assessed at baseline, and 1 and 3 months post-vaccination; safety and tolerability were also evaluated during the study period. The JIA patients treated with etanercept showed significantly lower geometric mean titres (GMTs) against the A/H1N1 strain than those treated with DMARDs (p<0.05) and the healthy controls (p<0.05), who had similar GMTs. The etanercept-treated JIA patients also showed a significant reduction in GMTs against the A/H1N1 and A/H3N2 strains from 1 to 3 months after vaccination (p<0.05). Furthermore, their seroconversion and seroprotection rates, and B antigen GMTs, were all significantly lower than those of the subjects in the other two groups (p<0.05). The safety and tolerability of the vaccine were good and similar between the groups. The results of this study indicate a reduced immune response to MF59-adjuvanted seasonal influenza vaccine in JIA children and adolescents treated with etanercept in comparison with those treated with DMARDs and healthy controls. The safety and tolerability of the vaccine appeared to be good in all of the study population.

Influenza A/H1N1 MF59-adjuvanted vaccine in preterm and term children aged 6 to 23 months.

OBJECTIVE: This study was designed to evaluate the immunogenicity, safety, and tolerability of a monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children aged 6 to 23 months who had different gestational ages (GAs) at birth. METHODS: The study involved 105 children: 35 preterm subjects with a GA of <32 weeks; 35 preterm subjects with a GA of 32 to 36 weeks; and 35 term subjects with a GA of 37 to 42 weeks. Each child received 2 intramuscular vaccine doses (Focetria [Novartis, Siena, Italy]): dose 1 at enrollment and dose 2 after 4 weeks (28 ± 2 days). Serum samples for antibody measurements were collected immediately before administration of dose 1, before administration of dose 2 (28 ± 2 days after baseline), and 4 weeks later (56 ± 2 days after baseline). Local and systemic reactions were assessed during the 14 days after each vaccination. RESULTS: Of the 101 children who completed the study 32 out of 34 preterm subjects with a GA of <32 weeks, all of the preterm subjects with a GA of 32 to 36 weeks, and all of the term subjects seroconverted and were seroprotected after the first vaccine dose. Local and systemic tolerability was good in all of the groups, but fever was significantly more common after the first dose than after the second dose (P < .05), and there were no between-group differences. CONCLUSIONS: A single dose of 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine evoked a significant immune response against pandemic influenza A/H1N1 virus in children aged 6 to 23 months even if their GA was <32 weeks. The vaccine had a good safety and tolerability profile.

Pandemic influenza A/H1N1 vaccine administered sequentially or simultaneously with seasonal influenza vaccine to HIV-infected children and adolescents.

In order to evaluate the immunogenicity, safety and tolerability of the 2009 A/H1N1 MF59-adjuvanted influenza vaccine administered sequentially or simultaneously with seasonal virosomal-adjuvanted influenza vaccine to HIV-infected children and adolescents, 36 HIV-infected children and adolescents, and 36 age- and gender-matched healthy controls were randomised 1:1 to receive the pandemic vaccine upon enrollment and the seasonal vaccine one month later, or to receive the pandemic and seasonal vaccines simultaneously upon enrollment. Seroconversion and seroprotection rates against the pandemic influenza A/H1N1 virus were 100% two months after vaccine administration in both groups, regardless of the sequence of administration. Geometric mean titres against pandemic and seasonal antigens were significantly higher when the seasonal and pandemic vaccines were administered simultaneously than when the seasonal vaccine was administered alone. Local and systemic reactions were mild and not increased by simultaneous administration. In conclusion, the 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine is as immunogenic, safe and well tolerated in HIV-infected children and adolescents as in healthy controls. Its simultaneous administration with virosomal-adjuvanted seasonal antigens seems to increase immune response to both pandemic and seasonal viruses with the same safety profile as that of the pandemic vaccine alone. However, because this finding cannot be clearly explained by an immunological viewpoint, further studies are needed to clarify the reasons of its occurrence.

Clinical assessment of adenoidal obstruction based on the nasal obstruction index is no longer useful in children.

OBJECTIVE: To evaluate the accuracy of clinical assessment of adenoidal obstruction based on a standardized score of the degree of mouth breathing and speech hyponasality (nasal obstruction index [NOI]) in comparison to nasal fiberoptic endoscopy. STUDY DESIGN: Cross-sectional study with planned data collection. SETTING: Outpatient clinics of the Departments of Maternal and Pediatric Sciences and Specialized Surgical Sciences, University of Milan, Italy. SUBJECTS AND METHODS: Children aged three to 12 years with adenoidal obstruction suspected on the grounds of persistent/recurrent otitis media or perceived obstructive nasal breathing were eligible. Ear, nose, and throat examination, allergy testing, NOI measurement, and nasal fiberoptic endoscopy to assess the degree of adenoidal hypertrophy were performed. Agreement between the NOI and adenoidal hypertrophy grade was assessed in the patients as a whole and by clinical subgroups. RESULTS: A total of 202 children were enrolled: 54.9 percent had otological diseases and 45.1 percent had perceived obstructive nasal breathing. Most of the children (79.2%) showed mild or moderate clinical nasal obstruction. Adenoidal hypertrophy ranged from no obstruction (18%) to severe obstruction (38%). There was no substantial agreement between the NOI and the degree of adenoidal obstruction in the population as a whole and in all the clinical subgroups. False positive findings were significantly more frequent among allergic children (50%) than non-allergic children (22.4%, P = 0.009). CONCLUSION: Clinical assessment based on the NOI is incapable of accurately predicting the degree of adenoidal obstruction. In children with clinical nasal obstruction not explainable by adenoidal size, the clinician should consider, among causes of more anterior obstruction, nasal allergy.

Immunogenicity, safety and tolerability of monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in patients with ß-thalassemia major.

In order to evaluate the immunogenicity, safety, and tolerability of monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in patients with ß-thalassemia major, 31 subjects (19 males; mean age 17.8±8.7 years) with ß-thalassemia major and 28 age- and gender-matched healthy controls were enrolled. Four weeks after vaccination, seroconversion rates were about 80% and seroprotection rates 100% in both groups. Three months after vaccination, most of the subjects remained seroconverted and the seroprotection rates were 93.5% among the patients and 100% among the controls. Safety and tolerability were also very good, with no differences between the groups.

Efficacy of injectable trivalent virosomal-adjuvanted inactivated influenza vaccine in preventing acute otitis media in children with recurrent complicated or noncomplicated acute otitis media.

BACKGROUND: Most cases of acute otitis media (AOM) follow an upper respiratory infection due to viruses, including influenza viruses. As effective and safe influenza vaccines are available, their use has been considered among the possible measures of AOM prophylaxis. OBJECTIVES: To evaluate the efficacy of an inactivated virosomal-adjuvanted influenza vaccine in preventing AOM in children with a history of noncomplicated recurrent AOM (rAOM) or rAOM complicated by spontaneous perforation. METHODS: In this prospective, randomized, single-blinded, placebo-controlled study, 180 children aged 1 to 5 years with a history of rAOM and previously unvaccinated against influenza were randomized to receive the inactivated virosomal-adjuvanted subunit influenza vaccine (n = 90) or no treatment (n = 90), and AOM-related morbidity was monitored every 4 to 6 weeks for 6 months. RESULTS: The number of children experiencing at least 1 AOM episode was significantly smaller in the vaccinated group (P < 0.001), as was the mean number of AOM episodes (P = 0.03), the mean number of AOM episodes without perforation (P < 0.001), and the mean number of antibiotic courses (P < 0.001); the mean duration of bilateral OME was significantly shorter (P = 0.03). The only factor that seemed to be associated with the significantly greater efficacy of influenza vaccine in preventing AOM was the absence of a history of recurrent perforation (crude odds ratio, P = 0.01; adjusted odds ratio, P = 0.006). CONCLUSIONS: The intramuscular administration of injectable trivalent inactivated virosomal-adjuvanted influenza vaccine in children with a history of rAOM significantly reduces AOM-related morbidity. However, the efficacy of this preventive measure seems to be reduced in children with rAOM associated with repeated tympanic membrane perforation.

Immunogenicity and effect of a virosomal influenza vaccine on viral replication and T-cell activation in HIV-infected children receiving highly active antiretroviral therapy.

In order to evaluate the immunogenicity and the effect of a virosomal influenza vaccine on viral replication and T-cell activation in HIV-infected children receiving highly active antiretroviral therapy (HAART), 29 children infected with HIV-1 vertically (19 primed with a previous influenza vaccination and 10 who were not been immunized against influenza) were immunized with an intramuscular virosome-adjuvanted influenza vaccine. According to the European Agency for Evaluation of Medical Products (EMEA) criteria, the immunogenicity of the vaccine was adequate against all three influenza strains (A H1N1, A H3N2, and B) in the primed children, and against A H1N1 and A H3N2 in the unprimed children. After in vitro stimulation with vaccine antigens, the IFN-gamma levels in the peripheral blood mononuclear cells cultures increased significantly from a baseline level of 103.0 +/- 229.8 pg/ml to a 30-day level of 390.7 +/- 606.3 pg/ml (P < 0.05), with concentrations significantly higher (P < 0.05) in the primed children than in the unprimed children. No increase in plasma HIV-1 RNA or HIV-1 proviral DNA was observed in either subgroup, and the immunophenotype analyses demonstrated that the CD4+ cell counts and percentages, the CD4/CD8 ratio and activated lymphocytes remained stable in either group from baseline to 1 month after each vaccine dose. This study showed that the virosomal influenza vaccine does seem to be immunogenic in the majority of HIV-infected children receiving HAART and does not induce viral replication or T-cell activation. Given the possible influenza-related complications in children infected with HIV, these results support the use of this influenza vaccine in such patients.