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Background No data are currently available on immunogenicity of higher-valent pneumococcal conjugate vaccines when co-administered with a 4-component meningococcal serogroup B vaccine (4CMenB). Methods Post-hoc analysis of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) immunogenicity when co-administered with 4CMenB (2 + 1 schedule) and/or a CRM-conjugated meningococcal serogroup C vaccine (MenC-CRM) in a trial assessing 4CMenB reduced schedules and co-administration with MenC-CRM (NCT01339923). Infants were randomized to receive 4CMenB and MenC-CRM (Group 1) or MenC-CRM (Group 2) at 3, 5, and 12 months (M) of age. Both groups received PHiD-CV (3 + 1 schedule) as part of the Brazilian national immunisation programme at 3 M, 5 M, 7 M, and 12 M of age. Antibody responses were assessed pre-vaccination, 1 M post-dose 2, pre-booster, and 1 M post-booster. Results Anti-pneumococcal antibody responses were in similar ranges in the two study groups. Conclusions 4CMenB co-administration did not seem to impact antibody responses to PHiD-CV in infants.

Several COVID-19 vaccines have shown good efficacy in clinical trials, but there remains uncertainty about the efficacy of vaccines against different variants. Here, we investigate the efficacy of ChAdOx1 nCoV-19 (AZD1222) against symptomatic COVID-19 in a post-hoc exploratory analysis of a Phase 3 randomised trial in Brazil (trial registration ISRCTN89951424). Nose and throat swabs were tested by PCR in symptomatic participants. Sequencing and genotyping of swabs were performed to determine the lineages of SARS-CoV-2 circulating during the study. Protection against any symptomatic COVID-19 caused by the Zeta (P.2) variant was assessed in 153 cases with vaccine efficacy (VE) of 69% (95% CI 55, 78). 49 cases of B.1.1.28 occurred and VE was 73% (46, 86). The Gamma (P.1) variant arose later in the trial and fewer cases (N = 18) were available for analysis. VE was 64% (−2, 87). ChAdOx1 nCoV-19 provided 95% protection (95% CI 61%, 99%) against hospitalisation due to COVID-19. In summary, we report that ChAdOx1 nCoV-19 protects against emerging variants in Brazil despite the presence of the spike protein mutation E484K., Emerging variants of SARS-CoV-2 raise concerns about vaccine efficiency. Here, the authors present a post-hoc analysis for the ChAdOx1 nCoV-19 (AZD1222) vaccine trial in Brazil and provide efficacy against symptomatic COVID-19 caused by the Zeta (P.2) and other variants.

Introduction Active pharmacovigilance studies are pivotal to better characterize vaccine safety. Methods These are multicenter prospective cohort studies to evaluate the safety of the 2017 and 2018 seasonal trivalent influenza vaccines (TIVs) manufactured by Instituto Butantan, by means of active pharmacovigilance practices. Elderly, children, healthcare workers, pregnant women, and women in the puerperium period were invited to participate in the study during the 2017 and 2018 Brazilian national seasonal influenza vaccination campaigns. Following immunization, participants were observed for 30 minutes and they received a participant card to register adverse events information. All safety information registered were checked at a clinical site visit 14 days after immunization and by a telephone contact 42 days after immunization for unsolicited Adverse Events (AE) and Guillain-Barré Syndrome (GBS). Results A total of 942 volunteers participated in the two studies: 305 elderly, 109 children, 108 pregnant women, 32 women in the postpartum period, and 388 health workers. Overall, the median number of AR per participant ranged from 1 to 4. The lowest median number of AR per participant was observed among healthcare workers (1 AR per participant) and the highest among pregnant women (4 AR per participant). Overall, local pain (46.6%) was the most frequent solicited local AR. The most frequent systemic ARs were: headache (22.5%) followed by fatigue (16.0%), and malaise (11.0%). The majority of solicited ARs (96%) were mild, Grades 1 or 2), only 3% were Grade 3, and 1% was Grade 4. No serious AEs, including Guillain-Barré Syndrome, were reported up to 42 days postvaccination. Conclusion The results from the two studies confirmed that the 2017 and 2018 seasonal trivalent influenza vaccines produced by Instituto Butantan were safe and that active pharmacovigilance studies should be considered, when it is feasible, as an important initiative to monitor vaccine safety in the post-marketing period.

Background The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials. Methods Participants (ZOE-50: ≥50; ZOE-70: ≥70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing ≥2 of 4 activation markers assessed (CD42+) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity. Results After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD42+ T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained ≥5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Conclusions Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination. Clinical Trials Registration NCT01165177; NCT01165229., The herpes zoster subunit vaccine, consisting of varicella-zoster virus glycoprotein E and the AS01B Adjuvant System, stimulated specific antibody and CD4 T-cell responses in >90% of recipients which, in most, persisted for the 36-month duration of the study.

Introduction: Immune response to vaccination in infants born prematurely may be lower than in infants born at full-term. Some clinical factors might be associated with humoral immune response. Objectives: The objectives of this study were to compare the immune response to measles and varicella vaccination in infants born prematurely with those born at full-term and to analyze factors associated with measles and varicella antibody levels. Methods: Prospective study including two groups of infants aged 12 months. One group of infants born prematurely with birth-weight

Meningococcal carriage is a prerequisite for invasive infection. This cross-sectional study assessed the pharyngeal carriage prevalence in healthy subjects aged 1–24 years in Embu das Artes city, São Paulo, Brazil. Pharyngeal swabs were examined for the presence of Neisseria meningitidis. The isolates were tested for different serogroups using agglutination and polymerase chain reaction. A logistic regression model assessed any independent association between Neisseria meningitidis carriage and various risk factors. A total of 87/967 subjects (9%, 95% Confidence Interval (CI): 7.3–11.0) tested positive for N. meningitidis: 6.2% (95% CI: 3.8–9.4) in 1–4 years, 8.5% (95% CI: 5.1–13.0) in 5–9 years, 12.5% (95% CI: 7.8–18.6) in 10–14 years, 12.6% (95% CI: 7.4–19.7) in 15–19 years and 9% (95% CI: 4.9–14.9) in 20–24 years age groups. Highest carriage prevalence was observed in adolescents 10–19 years old. Serogroup C was predominant (18.4%) followed by serogroup B (12.6%). The 15–19 years age group showed a significant association between number of household members and carriers of N. meningitidis. This cross-sectional study is the first in Brazil to evaluate meningococcal carriage prevalence and associated factors in a wide age range. Keywords: Carriage, Meningococcal disease, Neisseria meningitidis, Pharyngeal, Serogroup

Background This study evaluated the immunogenicity and safety of a licensed meningococcal serogroup B vaccine (4CMenB) administered alone according to reduced schedules in infants or catch-up series in children. Methods In this open-label, multicentre, phase 3b study (NCT01339923), infants randomised 1:1:1 received 4CMenB: 2 + 1 doses at 3½–5–11 months or 6–8–11 months of age, 3 + 1 doses at ages 2½–3½–5–11 months. Children aged 2–10 years received 2 catch-up doses administered 2 months apart. Immune responses were measured by hSBA assays against 4 strains specific for vaccine components fHbp, NadA, PorA and NHBA. Sufficiency of immune responses was defined in groups with 2 + 1 doses schedules as a lower limit ≥70% for the 97.5% confidence interval of the percentage of infants with hSBA titres ≥4, 1 month post-dose 2 for fHbp, NadA, PorA. Adverse events were collected for 7 days post-vaccination; serious adverse events (SAEs) throughout the study. Results 754 infants and 404 children were enrolled. Post-primary vaccination, 98–100% of infants across all groups developed hSBA titres ≥4 for fHbp, NadA, PorA, and 48–77% for NHBA. Sufficiency of immune responses in infants receiving 2 + 1 schedules was demonstrated for fHbp, NadA, PorA after 2 doses of 4CMenB, as pre-specified criteria were met. Following receipt of 2 catch-up doses, 95–99% of children developed hSBA titres ≥4 for 4CMenB components. Similar safety profiles were observed across groups. A total of 45 SAEs were reported, 3 of which were related to vaccination. Conclusion Reduced infant schedules and catch-up series in children were immunogenic and safe, having the potential to widen 4CMenB vaccine coverage. Funding GlaxoSmithKline Biologicals SA.

Summary Background Better population data on respiratory viruses in children in tropical and southern hemisphere countries is needed. Methods The epidemiology of respiratory viruses among healthy children (6 months to

Background Herpes zoster (HZ) risk appears to vary by sex and geographic ancestry/ethnicity. Methods In 2 randomized clinical trials, participants received 2 doses of adjuvanted recombinant zoster vaccine (RZV) or placebo intramuscularly, 2 months apart. In this post-hoc analysis, we investigate efficacy of RZV against HZ and postherpetic neuralgia (PHN) by sex, geographic region, and geographic ancestry/ethnicity in ≥50-year-olds (ZOE-50: NCT01165177) and ≥70-year-olds (pooled data from ZOE-50 and ZOE-70: NCT01165229). Results Vaccine efficacy against HZ or PHN was similar in women and men. Across geographic regions, efficacy against HZ ranged between 95.7 and 97.2% in ≥50-year-olds, and between 87.3% and 95.1% in ≥70-year-olds; efficacy against PHN ranged between 86.8 and 100% in ≥70-year-olds. Across ancestral/ethnic groups, efficacy ranged between 88.1 and 100% against HZ and between 65.9 and 100% against PHN in ≥70-year-olds. Conclusions While the ZOE-50/70 studies were not powered or pre-designed for these post-hoc analyses, RZV appears efficacious against HZ and PHN irrespective of sex, region, or geographic ancestry/ethnicity.

Background: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was >= 90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. Methods: Adults aged >= 50 (ZOE-50) and >= 70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. Results: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. Conclusions: No safety concerns arose, supporting the favorable benefit-risk profile of RZV. (C) 2019 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.

A decline of protective antibody titers after MCC vaccine has been demonstrated in healthy children, this may be an issue of concern for risk groups. The aim of this study was to evaluate the persistence of bactericidal antibodies after MCC vaccine in sickle cell disease (SCD) patients. The type of vaccine used and booster response were also analyzed.SCD patients (n=141) previously immunized with MCC vaccines had blood drawn 2-8 years after the last priming dose. They were distributed according to age at primary immunization into groups:2 years and 2-13 years and evaluated by years since vaccination (2-3, 4-5 and 6-8). Serum bactericidal antibodies with baby rabbit complement (rSBA) and serogroup C-specific IgG concentrations were measured. The correlate of protection was rSBA titer ⩾8. Subjects with rSBA8 received a booster dose and antibody levels re-evaluated after 4-6 weeks.For children primed under 2years of age rSBA titer ⩾8 was demonstrated in 53.3%, 21.7% and 35.0%, 2-3, 4-5, 6-8years, respectively, after vaccination, compared with 70.0%, 45.0% and 53.5%, respectively, for individuals primed at ages 2-13years. rSBA median titers and IgG median levels were higher in the older group. Six to eight years after vaccination the percentage of patients with rSBA titers ⩾8 was significantly higher in the group primed with MCC-TT (78.5%) compared with those primed with MCC-CRM197 [Menjugate® (33.3%) or Meningitec® (35.7%)] (p=0.033). After a booster, 98% achieved rSBA titer ⩾8.Immunity to meningococcal serogroup C in SCD children declines rapidly after vaccination and is dependent on the age at priming. Booster doses are needed to maintain protection in SCD patients. Persistence of antibodies seems to be longer in individuals primed with MCC-TT vaccine comparing to those immunized with MCC-CRM197.

Background Pertussis cases have increased worldwide and knowledge on immune response and cytokine profile after Tdap vaccine in immunodeficient adolescents is scarce. Objective To evaluate the immune response after Tdap in HIV-infected (HIV) and in healthy adolescents (CONTROL). Methodology Thirty HIV adolescents with CD4 cell counts >200 and 30 CONTROLs were immunized with Tdap, after a prior whole-cell DTP vaccine primary scheme. Blood samples were collected immediately before and after vaccine. Lymphocyte immunophenotyping was performed by flow cytometry; tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with tetanus toxoid and Bordetella pertussis and supernatants were assessed for cytokines by xMAP. Results Mean age of HIV and CONTROL groups were 17.9 e 17.1 years, respectively. Pain at injection site was more intense in CONTROL group. HIV group had similar increase in tetanus antibodies at 28 days (geometric mean concentration, GMC, 15.6; 95% CI, 7.52–32.4) than CONTROL group (GMC, 23.1; 95% CI, 15.0–35.5), but lower diphtheria antibodies at 28 days (GMC, 2.3; 95% CI, 0.88–6.19) than CONTROL group (GMC, 16.4; 95% CI, 10.3–26.2); for pertussis, the percentage of individuals who seroconverted was lower in HIV than CONTROL group (HIV, 62.1% versus CONTROL, 100%; p = .002). Both groups built a cellular immune response to tetanus, with a Th2 (IL-4, IL-5 and IL-13) and Th1 (IFN-γ) response, with lower cytokine levels in HIV than in CONTROL group. Especially for pertussis, cellular and humoral responses were less intense in HIV adolescents, with a lower Th1 and Th17 profile and higher IL-10 levels. HIV-infected adolescents on viral suppression showed an enhanced immune response to all the three vaccine antigens, although still at lower levels if compared to CONTROL group. Conclusions Both groups tolerated well and built an immune response after Tdap. However, HIV-infected adolescents would probably benefit from more frequent booster doses.

Summary An increased incidence of pertussis has been observed recently in adults, and healthcare workers (HCWs) are considered a risk group for transmission to infants. Prevalence of recent pertussis infection was assessed in HCWs from a paediatric department of a tertiary care hospital in Brazil. Serum pertussis toxin IgG antibodies were measured by enzyme-linked immunosorbent assay. Of 388 HCWs included in the analysis, 6.4% had serology suggestive of recent infection. Medical residents [odds ratio (OR): 4.15; 95% confidence interval (CI): 1.42–12.14; P = 0.009] and those working >40h a week (OR: 3.29; 95% CI: 1.17–9.26; P = 0.024) had increased risk of pertussis infection.

Rubella virus (RUBV) infection during pregnancy can lead to fetal infection and cause miscarriage, fetal death, or congenital rubella syndrome (CRS), which includes birth defects such as cataracts, sensorineural hearing loss, heart defects, and mental retardation [1]. Despite availability of safe, effective, and inexpensive vaccines, the World Health Organization (WHO) estimated that 103 000 infants with CRS were born in 2010, mainly in developing countries that have not introduced rubella vaccination [1]. In 1998, the Technical Advisory Group on Vaccine-Preventable Diseases of the Region of the Americas recommended that all countries in the region incorporate rubella virus (RUBV)–containing vaccine (RCV) into their childhood vaccination program [2, 3]. In 2011, the WHO recommended that all countries take the opportunity offered by accelerated measles control and elimination activities to introduce RCV [4]. By 2012, 132 (68%) of 194 WHO Member States included RCV in their routine immunization programs [5]. Determining the burden of CRS-related disabilities may inform decisions regarding vaccine introduction. The CRS incidence has been measured in follow-up studies of women infected with RUBV during pregnancy [6, 7], obtained through CRS surveillance targeting children 133 confirmed rubella cases in pregnant women were reported in 1999 and 2000 [23]. Brazil developed a vaccination effort, using measles-rubella vaccine (containing Edmonston-Zagreb measles and RA 27/3 RUBV strains), to accelerate CRS prevention during 2000 and 2001. A second national rubella vaccination campaign, conducted in 2008, interrupted endemic rubella transmission; the last endemic CRS case occurred in 2009. The goal of the current serologic study was to characterize the immune responses of school-aged children with CRS and compare these responses with those of their biological mothers and a group of similarly aged children without CRS. We hypothesized that specific immune responses, including the persistence of low-avidity IgG antibody, the level of the IgG anti-E1 signal, and the level of the IgG anti-C signal, would be associated with CRS.

GlaxoSmithKline Biologicals Background. the vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to

SUMMARY BCG adverse events (BCG-AE) are rare conditions with no well-established treatment. This study aims to describe clinical characteristics and outcome of localized BCG-AE. Children with BCG-AEs who were treated at the Reference Center for Special Immunobiologicals of the Federal University of São Paulo from 2009 to 2011 were included. Patients were followed monthly until 3 months after healing. One hundred and twenty-seven patients with localized BCG-AE were followed: 67 (52.7%) had suppurative lymphadenitis; 30 (23.6%) injection-site abscess; five (3.9%) had enlarged lymph node > 3 cm; four (3.1%) had ulcer > 1 cm; and one (0.8%) had a local bacterial infection. Five patients (3.9%) had more than one BCG-AE simultaneously. Fifteen patients (11.8%) had atypical manifestations: seven wart-like lesions; five BCG reactivations; two other dermatologic lesions and one with vasomotor phenomenon. Isoniazid was used in 96 patients with typical BCG-AE (85.7%) until lesion resolution which took place 3.1 months later (in median); the healing rate was 90.6%. Patients with atypical manifestations had an individual approach. Regarding the outcome, 105/112 patients with typical AE and 13/15 patients with atypical AE had resolution of BCG-AE. Localized BCG-AE caused by BCG Moreau RJ had positive outcome when treated with a short course of isoniazid. Atypical BCG-AE are not infrequent.

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil Tuberculosis (TB) infection was evaluated in Brazilian immunocompetent children and adolescents exposed and unexposed (control group) to adults with active pulmonary TB. Both groups were analysed by clinical and radiological assessment, TST, QFT-IT and T-SPOT. TB. The three tests were repeated after 8 weeks in the TB-exposed group if results were initially negative. Individuals with latent tuberculosis infection (LTBI) were treated and tests were repeated after treatment. Fifty-nine TB-exposed and 42 controls were evaluated. Rate of infection was 69.5% and 9.5% for the exposed and control groups, respectively. The exposed group infection rate was 61% assessed by TST, 57.6% by T-SPOT. TB, and 59.3%, by QFT-IT. No active TB was diagnosed. Agreement between the three tests was 83.1% and 92.8% in the exposed and control groups, respectively. In the exposed group, T-SPOT. TB added four TB diagnoses [16%, 95% confidence interval (CI) 1.6-30.4] and QFT-IT added three TB diagnoses (12%, 95% CI 0-24.7) in 25 individuals with negative tuberculin skin test (TST). Risk factors associated to TB infection were contact with an adult with active TB [0-60 days: odds ratio (OR) 6.9; >60 days: OR 27.0] and sleeping in the same room as an adult with active TB (OR 5.2). In Brazilian immunocompetent children and adolescents, TST had a similar performance to interferon-gamma release assays and detected a high rate of LTBI. Univ Fed Sao Paulo, Dept Pediat, Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Dept Diagnost Imaging, Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Dept Pediat, Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Dept Diagnost Imaging, Sao Paulo, SP, Brazil FAPESP: 2009/07603-7 Web of Science

Background The inclusion of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs in many countries has significantly decreased the incidence of disease caused by Streptococcus pneumoniae . However, a substantial portion of disease remained and, in some areas, there has been an increase in disease produced by serotypes not included in PCV7. A 13-valent pneumococcal conjugate vaccine (PCV13) was studied in healthy Brazilian infants in a phase 3, double-blind, randomized study. Methods Infants were randomized to receive either PCV7 or PCV13 at 2, 4, 6, (doses 1–3), and 12 (toddler dose) months of age, along with routine pediatric vaccinations (diphtheria, tetanus, whole-cell pertussis, and Haemophilus influenzae type b vaccine). Pneumococcal anticapsular polysaccharide-binding immunoglobulin G (IgG) responses and antibody responses to pertussis antigens were measured 1 month after both dose 3 of the infant series and the toddler dose. Safety and tolerability were also assessed. Results The proportion of subjects achieving a serotype-specific IgG concentration ≥0.35 μg/mL measured 1 month after the infant series was comparable in the PCV13 (≥94.2%) and PCV7 (≥93.0%) groups for the 7 serotypes common to both vaccines. The percentage of responders for the 6 additional serotypes ranged from 87.1 to 100% for PCV13. The percentage of responders varied across the pertussis antigens studied, but was not different in PCV13 and PCV7 recipients. Overall, the safety profile of PCV13 was comparable with that of PCV7. Conclusions PCV13 was comparable to PCV7 in safety and tolerability, elicited comparable immune responses to the common serotypes, and did not interfere with immune responses to concomitantly administered whole-cell pertussis vaccine. The robust immunogenicity exhibited by PCV13 for the additional serotypes suggests that it could provide significant protection against these serotypes.

Objective To evaluate whether the quadrivalent human papillomavirus (HPV) (types 6, 11, 16, and 18) vaccine influences the clinical course of juvenile-onset recurrent respiratory papillomatosis (RRP) when administered to a group of patients with this condition. Methods Uncontrolled intervention study of patients with juvenile-onset RRP examined at the Pediatric Otorhinolaryngology Clinic, Federal University of Sao Paulo, where nine patients between the ages of nine and 17 received three doses of the prophylactic quadrivalent HPV vaccine (Gardasil ® ) and were followed for one year. Disease staging, intervals between relapses, intervals between surgeries, and the number of surgeries during the year prior to vaccination and during the first year after vaccination were compared. Results Eight patients were infected with HPV-6 and one with HPV-11. There were no statistically significant differences in the clinical scores ( p = 0.083), anatomical scores ( p = 0.257), intervals between relapses ( p = 0.062), intervals between surgeries ( p = 0.357), or the numbers of surgeries ( p = 0.180) when the years before and after vaccination were compared. All patients had relapses following vaccination. Conclusion Patients with juvenile-onset RRP experienced a similar clinical course in the year after versus the year before vaccination with Gardasil ® .

Summary Thirty percent of acute pharyngotonsillitis is caused by Streptococcus pyogenes, which increased the risk of glomerulonephritis and rheumatic fever. Children attending daycare centers have a higher incidence of these infections. Aim to identify and compare the prevalence of Streptococcus pyogenes in the oropharynx of children who are enrolled and who are not enrolled in daycare centers in different regions of Brazil. Materials and Methods A prospective study of two hundred children from Sao Paulo/SP and Porto Velho/RO. Children from each city were divided into two groups: those attending, and those not attending daycare centers. Swabs of the oropharynx were taken for bacteriological culture and identification. Results The prevalence of Streptococcus pyogenes in the Sao Paulo groups were 8% and 2% for daycare and control groups, which was statistically significant (p=0.02). The prevalence in children from Porto Velho/RO was 24% and 16% for daycare and control groups, which was statistically significant (p=0.015). Statistical analysis also showed a significant difference between the corresponding groups in the two locations (p Conclusion These results show that daycare attendance is a risk factor for oropharyngeal streptococcal colonization; this was seen in different populations, but was statistically significance in only one of the two samples.

Background HIV infection can have important although sometimes unexpected consequences, such as contributing to enlargement of the pool of rubella-susceptible children. Methods At the Federal University of Sao Paulo, Brazil, we assessed response to rubella immunization at 15 months of age in 15 human immunodeficiency virus type 1 (HIV)-infected children, 20 seroreverted children (SR) and 18 healthy control children born to HIV-seronegative mothers (CON). Blood samples were collected before and 3 months after vaccination. All HIV-infected children had started highly active antiretroviral therapy during their first 6 months of life. Serum samples were tested with a rubella IgG enzyme-linked immunosorbent assay kit. Results HIV children in immunologic categories 2/3 had lower rubella antibody titers (geometric mean, 33 IU/mL) than those from CON (125 IU/mL) and SR group (236 IU/mL) (Tukey, P = 0.01). Antibody values after vaccination were positively associated with CD4 T cell numbers and negatively associated with HIV viral load assessed immediately before vaccination. The percentage of children with protective antibodies after vaccination (above 10.0 IU/mL) was also significantly different among groups (Fisher's exact test, P = 0.013): CON, 94%; SR, 100%; HIV category 1, 100%; HIV category 2/3, 62%. Conclusions HIV-infected children with a preserved immune system at measles-mumps-rubella immunization can have a good response to rubella vaccine. In contrast, those in more advanced categories for HIV infection respond poorly.

Although frequently reported in the literature, a staff varicella policy is not standard in many hospitals even in developed countries. In the present study, we assessed varicella zoster immunity in staff from two neonatal units from hospitals in São Paulo, Brazil. Ninety-seven percent of all staff working in both units agreed to participate. A simple and cost-effective varicella policy was subsequently set up, based on costs and data from serology and a history of previous varicella infection. Our results confirm that a varicella vaccination programme can be implemented in a healthcare facility, even in developing countries.

In children aged 6 months to, Background. The high burden of respiratory syncytial virus (RSV)-associated morbidity and mortality makes vaccine development a priority. Methods. As part of an efficacy trial of pandemic influenza vaccines (NCT01051661), RSV epidemiology in healthy children aged 6 months to

OBJETIVO:Identificar os vírus envolvidos nos quadros de infecções agudas de trato respiratório e analisar as taxas de internação e de óbito em crianças submetidas à profilaxia com palivizumabe.MÉTODOS:Coorte prospectiva com 198 crianças menores de um ano nascidas antes de 29 semanas de idade gestacional e crianças menores de dois anos com cardiopatia hemodinamicamente instável ou doença pulmonar crônica que receberam palivizumabe para profilaxia contra infecções graves pelo vírus sincicial respiratório, em 2008. No período do estudo, em cada episódio de infecção aguda do trato respiratório, coletou-se aspirado de nasofaringe para identificar vírus sincicial respiratório, adenovírus, parainfluenza 1, 2 e 3, influenza A e B por imunofluorescência direta, rinovírus e metapneumovírus por reação em cadeia de polimerase precedida de transcriptase reversa. Monitoraram-se internações e óbitos nesse grupo.RESULTADOS: Das 198 crianças acompanhadas, 117 (59,1%) apresentaram infecções agudas de trato respiratório, totalizando 175 episódios. De 76 aspirados de nasofaringe coletados na vigência de infecções do trato respiratório, 37 foram positivos, encontrando-se: rinovírus (75,7%), vírus sincicial respiratório (18,9%), parainfluenza (8,1%), adenovírus (2,7%), metapneumovírus (2,7%) e múltiplos agentes em três amostras. Das 198 crianças, 48 (24,4%) foram internadas, sendo 30 (15,2%) por etiologia não respiratória e 18 (9,1%) por problemas respiratórios; entre os 18 casos, um foi por vírus sincicial respiratório. Duas crianças evoluíram para óbito, não tendo sido identificado o vírus sincicial respiratório.CONCLUSÕES:Na vigência de profilaxia, observou-se frequência baixa de infecções pelo vírus sincicial respiratório e baixo índice de hospitalizações, sugerindo benefício da profilaxia com palivizumabe. OBJECTIVE: To identify the viruses involved in acute respiratory tract infections and to analyze the rates of hospitalization and death in children on palivizumab prophylaxis.METHODS:Prospective cohort of 198 infants up to one year old who were born before 29 weeks of gestational age and infants under two years old with hemodynamically unstable cardiopathy or chronic pulmonary disease who received prophylactic palivizumab against severe respiratory syncytial virus infections in 2008. During the study period, in each episode of acute respiratory tract infection, nasopharyngeal aspirate was collected to identify respiratory syncytial virus, adenovirus, parainfluenza 1, 2 and 3, influenza A and B by direct immunofluorescence, rhinovirus and metapneumovirus by polymerase chain reaction preceded by reverse transcription. Data regarding hospitalization and deaths were monitored.RESULTS:Among the 198 studied infants, 117 (59.1%) presented acute respiratory tract infections, with a total of 175 episodes. Of the 76 nasopharyngeal aspirates collected during respiratory tract infections, 37 were positive, as follow: rhinovirus (75.7%), respiratory syncytial virus (18.9%), parainfluenza (8.1%), adenovirus 2 (2.7%), metapneumovirus (2.7%) and three samples presented multiple agents. Of the 198 children, 48 (24.4%) were hospitalized: 30 (15.2%) for non-infectious etiology and 18 (9.1%) for respiratory causes. Among these 18 children, one case of respiratory syncytial virus was identified. Two deaths were reported, but respiratory syncytial virus was not identified.CONCLUSIONS:During the prophylaxis period, low frequency of respiratory syncytial virus infections and low rates of hospitalization were observed, suggesting the benefit of palivizumab prophylaxis. OBJETIVO:Identificar los virus implicados en los cuadros de infecciones agudas de trato respiratorio y analizar las tasas de internación y de óbito en niños sometidos a la profilaxis con palivizumabe.MÉTODOS:Cohorte prospectiva con 198 niños con menos de un año nacidas antes de 29 semanas de edad gestacional y niños con menos de dos años con cardiopatía hemodinámicamente inestable o enfermedad pulmonar crónica que recibieron palivizumabe para profilaxis contra infecciones graves por el virus sincitial respiratorio, en 2008. En el periodo de estudio, en cada episodio de infección aguda del trato respiratorio, se recogió aspirado de nasofaringe para identificar virus sincitial respiratorio, adenovirus, parainfluenza 1,2 y 3, influenza A y B por técnica del anticuerpo fluorescente directa, rinovirus y metapneumovirus por reacción en cadena de la polimerasa precedida por transcriptasa inversa. Se monitorean internaciones y óbitos en ese grupo.RESULTADOS:De los 198 niños seguidos, 117 (59,1%) presentaron infecciones agudas de trato respiratorio, totalizando 175 episodios. De 76 aspirados de nasofaringe recogidos en la vigencia de infecciones de trato respiratorio, 37 fueron positivos, encontrándose: rinovirus (75,7%), virus sincitial respiratorio (18,9%), parainfluenza (8,1%), adenovirus (2,7%), metapneumovirus (2,7%) y múltiples agentes en tres muestras. De los 198 niños, 48 (24,4%) fueron internados, siendo 30 (15,2%) por etiología no respiratoria y 18 (9,1%) por problemas respiratorios; entre los 18 casos, uno fue por virus sincitial respiratorio. Dos niños evolucionaron a óbito, no habiendo sido identificado el virus sincitial respiratorio.CONCLUSIONES:En la vigencia de profilaxis, se observó frecuencia baja de infecciones por el virus sincitial respiratorio y bajo índice de hospitalizaciones, sugiriendo beneficio de la profilaxis con palivizumabe. Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) UNIFESP, EPM SciELO

This study aims to assess the cellular and humoral immune response pre- and post-vaccine rechallenge in healthy adults with previous exposure to measles (virus or vaccine) and different time intervals since last tetanus vaccine. Humoral immunity was tested by ELISA, and cellular immunity was tested by intracellular interferon gamma detection after in vitro stimulation with antigens. While cellular immunity was comparable among vaccinated individuals and those who had measles, higher antibody levels were found in those who had the disease in the past. Both antibodies and CD4+ T cell tetanus immune responses depended on elapsed time since last immunization. Following a vaccine booster, an increase in cellular immunity and antibodies was observed to both tetanus and measles. Measles humoral response was much more intense among individuals previously exposed to a wild virus. In an era when natural boosters are less frequent, an immune surveillance might be necessary to investigate waning immunity as occurs for tetanus.

Palivizumab is currently recommended to high-risk children as a prophylaxis for respiratory syncytial virus (RSV) infection. However, it is still very expensive for developing countries like Brazil. Herein, we describe our strategy to minimize wastage of Palivizumab during the 2008 RSV season. Appointments were fixed for 304 children on 2 days of the week, so that a mean of 19.9 children received Palivizumab per day. That allowed remaining volumes of Palivizumab vials to be pooled and used for other children on the same day within the 6 h period after opening a vial. That strategy saved 26.3% of vials, which represents USD $749,143.75.

OBJECTIVE: To evaluate the prevalence of hepatitis A virus antibodies in HIV-exposed and/or HIV-infected children and adolescents. METHODS: Between September 1996 and August 2002, 352 patients (200 exposed, but not HIV-infected and 152 HIV exposed and infected) were included in this study. These children and adolescents (age ranged between 1 and 14 years) were all followed up at the Pediatric AIDS Clinic of the Federal University of Sao Paulo (UNIFESP) and had anti-HAV antibodies determined by a commercially available ELISA method (tests for total anti-HAV antibodies and specific IgM antibodies) (Dia Sorin and Radim). Statistical analyses were done with chi-squared and t test. RESULTS: The prevalence of hepatitis A virus antibodies in HIV-infected and HIV-exposed, but uninfected patients was 34% and 19.7%, respectively. We noticed that in the age range between 2 years and 10 years, the group of HIV-infected children presented a higher prevalence of hepatitis A virus antibodies (35.5%) than the group of uninfected children (16.7%) (p = 0.005). In the HIV infected group, children from B and C categories had a prevalence of hepatitis A virus antibodies (40.5%) higher than N and A categories (24.1%) (p = 0.042). Mean age did not differ when children from B and C categories were compared with N and A categories (5.18 and 5.66 years, respectively) (p = 0.617). CONCLUSIONS: The prevalence of hepatitis A virus antibodies in HIV exposed and/or infected children and adolescents between 1 and 14 years old was 26%. Considering the possibility of HIV infection aggravation when associated with hepatitis A virus infection, we suggest that hepatitis A virus inactivated vaccine should be administered to these patients.

The cellular immune response probably plays a pivotal role in determining the clinical outcome after exposure to Mycobacterium tuberculosis. We used multi-parameter flow-cytometry to evaluate the distribution of T-lymphocyte subsets during infection and disease caused by M. tuberculosis. Samples were obtained from 71 volunteers to identify the T CD4(+) and CD8(+) lymphocyte numbers, and the activation plus memory/naive phenotypes, as defined by CD38, HLA-DR, CD45RA and CD27 markers. Subjects were divided into 18 healthy volunteers without detectable reaction to purified protein derivative (PPD-), 18 health care workers with a recent conversion to PPD, 20 patients with active pulmonary tuberculosis (TBC) and 15 patients with treated TBC at 6 months of therapy. By multiple-comparison analyses, the T CD4(+) lymphocyte number of the TBC group was lower than the PPD- group (P < 0.05). Ibis difference was apparently lost after treatment. the higher and the lower number of naive T CD4(+) cells was observed in the PPD- and TB C group, respectively. CD8(+) T lymphocytes were also statistically different among the four groups (P = 0.0002), lower in the TBC group (P < 0.05). CD8(+) T lymphocyte activation was evaluated by the CD38 and HLA-DR surface expression. the percentage distribution of these markers was statistically different between the four groups (P = 0.0055). TBC patients had a higher percentage of CD38(+) cells and mean fluorescence index, suggesting an overall increase of cell activation. These results suggest that peripheral T lymphocytes reflect cellular activation during TBC, along with possible redistribution of naive, memory/effector and late differentiated memory/effector phenotypes in the peripheral blood after infection and disease caused by M. tuberculosis. Universidade Federal de São Paulo, LKab Imunol, Disciplina Doencas Infecc & Parasitarias, Escola Paulista Med,Infect Dis Discipline, BR-04039032 São Paulo, Brazil Univ Rochester, Infect Dis Unit, Rochester, NY 14627 USA Universidade Federal de São Paulo, LKab Imunol, Disciplina Doencas Infecc & Parasitarias, Escola Paulista Med,Infect Dis Discipline, BR-04039032 São Paulo, Brazil Web of Science

Epidemiological data regarding tetanus and diphtheria immunity in elderly people in Brazil are scarce. During the First National Immunization Campaign for the Elderly in Brazil in April 1999, 98 individuals (median age: 84 years) received one tetanus-dyphtheria (Td) vaccine dose (Butantan Institute, lot number 9808079/G). Inclusion criteria were elderly individuals without a history of severe immunosuppressive disease, acute infectious disease or use of immunomodulators. Blood samples were collected immediately before the vaccine and 30 days later. Serum was separated and stored at -20ºC until analysis. Tetanus and diphtheria antibodies were measured by the double-antigen ELISA test. Tetanus and diphtheria antibody concentrations lower than 0.01 IU/mL were considered to indicate the absence of protection, between 0.01 and 0.09 IU/mL were considered to indicate basic immunity, and values of 0.1 IU/mL or higher were considered to indicate full protection. Before vaccination, 18% of the individuals were susceptible to diphtheria and 94% were susceptible to tetanus. After one Td dose, 78% became fully immune to diphtheria, 13% attained basic immunity, and 9% were still susceptible to the disease. In contrast, 79% remained susceptible to tetanus, 4% had basic immunity and 17% were fully immune. Although one Td dose increases immunity to diphtheria in many elderly people who live in Brazil, a complete vaccination series appears to be necessary for the prevention of tetanus. Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de Infectologia Pediátrica Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de Infectologia UNIFESP, EPM, Disciplina de Infectologia Pediátrica UNIFESP, EPM, Disciplina de Infectologia SciELO