Seroprevalence of Human Papillomavirus 6, 11, 16, and 18 in Young Primiparous Women in Sao Paulo, Brazil

Introduction: Data on epidemiology of HPV infection are needed for the development of human papillomavirus (HPV) vaccine recommendations, especially in countries where HPV vaccination is not yet included in public vaccination programs. The aim of this study was to determine the prevalence of serum antibodies to HPV types 6, 11, 16, and 18 and associated factors among young women after birth of the first child. Methods: This cross-sectional study was carried out in a large public maternity hospital in Sao Paulo, Brazil. Three hundred one women aged 15 to 24 years who gave birth to their first child were recruited between 43 and 60 days after delivery. Seroprevalence was performed using a type-specific enzyme-linked immunosorbent assay based on HPV Late protein 1 viruslike particles. The association of seroreactivity with these 4 HPV types with selected demographic and behavioral factors was assessed by Generalized Linear Model analysis. Results: Fifty-eight (19.3%) women (95% confidence interval, 15.0%-24.2%) had antibodies to any of the 4 viruslike particles tested. The overall seroprevalence rates of the HPV types were: HPV16, 9.0%; HPV18, 7.0%; and HPV 6+11, 7.7%, which are targeted by the HPV prophylactic vaccines. In the multivariate analysis, only age (inversely, P = 0.044 for trend) and previous sexually transmitted disease (P = 0.008) were 2 factors independently associated with HPV seropositivity. Conclusions: These data offer additional information on the epidemiology of HPV in a group of young Brazilian women after first delivery and contribute to establish a baseline of HPV seroprevalence against which post-HPV vaccine era seroprevalence can be compared.

Diminished CD4+/CD25+T cell and increased IFN-gamma levels occur in dogs vaccinated with Leishmune (R) in an endemic area for visceral leishmaniasis

The Leishmune (R) vaccine has been used in endemic areas to prevent canine visceral leishmaniasis in Brazil, but cytokine production induced by vaccination has rarely been investigated in dogs. This study aimed to evaluate the immune response of dogs vaccinated with Leishmune FML vaccine (Fort Dodge) against total antigen of Leishmania (Leishmania) chagasi (TAg) and FML. Twenty healthy dogs from Aracatuba, Sao Paulo, Brazil, an endemic leishmaniasis area, received three consecutive subcutaneous injection of Leishmune vaccine at 21-day intervals. PBMC were isolated before and 10 days after completing vaccination and lymphoproliferative response and antibody production against FML or total promastigote antigen were tested. Cytokines IFN-gamma, IL-4 and TNF-alpha were measured in culture supernatant and CD4+/CD25+ and CD8+/CD25+ T cell presence was determined. Analysis of the data indicated that the vaccine conferred humoral responses (100%) against both antigens and cellular immunity to FML (85%) and total antigen (80%), the supernatant of cultured cells stimulated with TAg and FML showed an increase in IFN-gamma (P < 0.05), and the vaccine reduced CD4+/CD25+ T cell presence compared to that observed before vaccination. These responses may constitute part of the immune mechanism induced by Leishmune. (C) 2010 Elsevier B.V. All rights reserved.

Rotavirus morbidity and mortality in children in Brazil

Objective. To study the epidemiology of rotavirus and estimate rotavirus- associated morbidity and mortality in children <= 5 years of age in Brazil in 2004 before introducing the rotavirus vaccine in Brazil`s National Immunization Program ( Programa Nacional de Imunizacoes, PNI). Methods. To estimate rotavirus morbidity, published studies ( 1999 - 2006) addressing incidence of acute diarrhea among children <= 5 years of age and frequency of rotavirus infection among children with diarrhea in Brazil were reviewed. Diarrhea episodes were divided into three categories of severity by level of care: mild cases requiring only home- based care; moderate cases requiring a visit to an outpatient healthcare facility; and severe cases requiring hospitalization. To estimate rotavirus mortality, information on the number of registered deaths from diarrhea in children <= 5 years of age was obtained from the Mortality Information System ( Sistema de Informacao, sobre Mortalidade, SIM) of Brazil`s public healthcare system ( Sistema Unico de Sa de, SUS) and the proportion of deaths due to rotavirus was calculated. Results. Rotavirus infections were estimated to cause 3 525 053 episodes of diarrhea, 655 853 visits to outpatient healthcare facilities, 92 453 hospitalizations, and 850 deaths of children <= 5 years of age each year in Brazil. Conclusion. Rotavirus infections are an important cause of child morbidity and mortality in Brazil.

Exclusive Breastfeeding in Southern Brazil: Prevalence and Associated Factors

Background: Worldwide strategies have been conducted in order to guarantee longer periods of exclusive breastfeeding for most children, especially those from developing countries. The evaluation of infant feeding practices and the identification of weaning risk factors are essential for public health policy planning. Methods: This cross-sectional study was carried out in Joinville, the biggest city of Santa Catarina State in the southern Brazilian region. The caregivers of children under 1 year of age were systematically selected for interview in previously drawn immunization units during the 2005 National Vaccination Campaign. A structured questionnaire was applied for collection of infant, maternal, and healthcare variables. A 24-hour food recall survey was included in order to evaluate infant feeding practices. Descriptive statistic analysis on breastfeeding prevalence and Poisson regression analysis of risk factors for discontinuing exclusive breastfeeding for infants up to 6 months of age were performed. Results: Caregivers of 1,470 infants were interviewed. The feeding inquiry showed an overall rate of breastfeeding of 72.5% and a frequency of exclusive breastfeeding of 43.7% and 53.9% among infants younger than 6 and 4 months of age, respectively. The findings associated with the interruption of exclusive breastfeeding for infants up to 6 months were: higher infant age (P < 0.001), pacifier use (P < 0.001), and lower maternal educational level (P = 0.013). Conclusions: In developing countries, specific strategies must be created for the delivery of information about breastfeeding and the effect of pacifier use, especially for less educated women.

Immunogenicity of 23-valent pneumococcal polysaccharide vaccine in HIV-infected pregnant women and kinetics of passively acquired antibodies in young infants

Whether gestational immunization of HIV-infected mothers with the 23-valent pneumococcal polysaccharide vaccine (PPV) confers maternal and infant early life, passive protection is not known. We evaluated safety, immunogenicity and placental transfer of antibodies in 44 HIV-infected women. Pneumococcal IgG antibodies against serotypes 1, 3, 5, 613, 9V, and 14 were measured in mothers (pre-vaccination and at delivery), and infants (at birth, 1, 2, 3, and 6 months). PPV was safe and immunogenic in mothers. Newborns received 46-72% of maternal antibody titers. Overall, infants had antibody levels lower than protective by 2 months of age. Alternative pneumococcal vaccination of HIV-infected pregnant women should be explored with the aim of prolonging passive protection in their infants. (C) 2009 Elsevier Ltd. All rights reserved.

Evaluation of antibody response to the heptavalent pneumococcal conjugate vaccine in pediatric chronic kidney disease

Pneumococcal vaccination has been recommended for immunocompromised children, including patients with chronic kidney disease. We determined pneumococcal immunoglobulin (Ig) G antibodies to serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F before and after 48 pediatric patients with chronic renal failure were administered heptavalent conjugated pneumococcal vaccine. The patients were between 1 and 9 years of age and were separated into a conservative treatment group (Group 1) and a dialysis group Group 2). The antibody response to the vaccinal serotypes was evaluated by measuring antibody concentrations before the first dose and 60 days after the second one. Pre-vaccinal IgG concentrations >= 0.35 mu g/ml were detected for all serotypes in at least 50% of the patients in both groups. Patients from both groups showed a statistically indistinguishable behavior in terms of the medians of post-vaccination IgG levels. An ""adequate"" vaccine response was defined as a post-immunization level of specific pneumococcal serotype antibody >= 0.35 mu g/ml, based on the World Health Organization`s (WHO) protective antibody concentration definition for pneumococcal conjugate vaccines, or on a fourfold increase over baseline for at least five of the seven antigens of the vaccine. An ""adequate"" vaccinal response was obtained in 100% of the patients of both groups using WHO`s definition, or in 45.8% of Group 1 patients and 37.5% of Group 2 patients when the criterion was a fourfold antibody increase over baseline antibody concentrations.

Preterm and term neonates transplacentally acquire IgG antibodies specific to LPS from Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa

High incidences of Gram-negative bacteria are found in neonatal nosocomial infections. Our aim was to investigate placental transmission of immunoglobulin G (IgG) reactive with lipopolysaccharide from Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia colt O111, O6 and O26. The total and lipopolysaccharide-specific IgM and IgG were determined in 11 maternal/umbilical-cord sera aged <= 33 weeks (GI); 21 aged > 33 and < 37 weeks (GII); and 32 term newborns (GIII). The total and lipopolysaccharide-specific IgM concentrations were equivalent in maternal sera. The total IgG concentrations were equivalent in maternal and newborn sera, with the exception of GIII newborns as compared with their mothers (P < 0.0001) and with neonates from GI and GII (P < 0.05). Lipopolysaccharide-specific IgG concentrations were lower in GI neonates than in their mothers (P < 0.01) and lower in GII (P < 0.05). Lower lipopolysaccharide-specific IgG levels were observed among neonates only for O111 in GI (P < 0.05) and for 026 and Pseudomonas in GII, both as compared with GIII (P < 0.05). The anti-lipopolysaccharide IgG transfer ratios were lower in GI (except for 026) and in GII (except for Klebsiella and O111) as compared with GIII (P < 0.05). Our results suggest that the greater susceptibility to infections in preterm infants is influenced (besides the humoral response) by factors intrinsic and extrinsic to the condition of prematurity.

Characterization of leptospiral proteins that afford partial protection in hamsters against lethal challenge with Leptospira interrogans

Leptospirosis is a worldwide zoonosis caused by pathogenic Leptospira. The whole-genome sequence of Leptospira interrogans serovar Copenhageni together with bioinformatic tools allow us to search for novel antigen candidates suitable for improved vaccines against leptospirosis. This study focused on three genes encoding conserved hypothetical proteins predicted to be exported to the outer membrane. The genes were amplified by PCR from six predominant pathogenic serovars in Brazil. The genes were cloned and expressed in Escherichia coli strain BL21-SI using the expression vector pDEST17. The recombinant proteins tagged with N-terminal 6xHis were purified by metal-charged chromatography. The proteins were recognized by antibodies present in sera from hamsters that were experimentally infected. Immunization of hamsters followed by challenge with a lethal dose of a virulent strain of Leptospira showed that the recombinant protein rLIC12730 afforded statistically significant protection to animals (44 %), followed by rLIC10494 (40 %) and rLIC12922 (30 %). Immunization with these proteins produced an increase in antibody titres during subsequent boosters, suggesting the involvement of a T-helper 2 response. Although more studies are needed, these data suggest that rLIC12730 and rLIC10494 are promising candidates for a multivalent vaccine for the prevention of leptospirosis.

Humoral responses and immune protection in mice immunized with irradiated T. gondii tachyzoites and challenged with three genetically distinct strains of T. gondii

Toxoplasma gondii is an obligate intracellular parasite that infects a variety of mammals and birds. T. gondii also causes human toxoplasmosis; although toxoplasmosis is generally a benign disease, ocular, congenital or reactivated disease is associated with high numbers of disabled people. Infection occurs orally through the ingestion of meat containing cysts or by the intake of food or water contaminated with oocysts. Although the immune system responds to acute infection and mediates the clearance of tachyzoites, parasite cysts persist for the lifetime of the host in tissues such as the eye, muscle, and CNS. However, T. gondii RH strain tachyzoites irradiated with 255 Gy do not cause residual infection and induce the same immunity as a natural infection. To assess the humoral response in BALB/c and C57BL/6J mice immunized with irradiated tachyzoites either by oral gavage (p.o.) or intraperitoneal (i.p.) injection, we analyzed total and high-affinity IgG and IgA antibodies in the serum. High levels of antigen-specific IgG were detected in the serum of parenterally immunized mice, with lower levels in mice immunized via the oral route. However, most serum antibodies exhibited low affinity for antigen in both mice strain. We also found antigen specific IgA antibodies in the stools of the mice, especially in orally immunized BALB/c mice. Examination of bone marrow and spleen cells demonstrated that both groups of immunized mice clearly produced specific lgG, at levels comparable to chronic infection, suggesting the generation of IgG specific memory. Next, we challenged i.p. or p.o. immunized mice with cysts from ME49. VEG or P strains of T. gondii. Oral immunization resulted in partial protection as compared to challenged naive mice: these findings were more evident in highly pathogenic ME49 strain challenge. Additionally, we found that while mucosal IgA was important for protection against infection, antigen-specific IgG antibodies were involved with protection against disease and disease pathogenesis. Most antigen responsive cells in culture produced specific high-affinity IgG after immunization, diverse of the findings in serum IgG or from cells after infection, which produced low proportion of high-avidity IgG. (C) 2011 Elsevier B.V. All rights reserved.

CpG-Induced Th1-Type Response in the Downmodulation of Early Development of Allergy and Inhibition of B7 Expression on T Cells of Newborn Mice

Several differences have been described between neonatal and adult immune responses. The predisposition in early life to Th2-type response or tolerance makes it a susceptible period for infections and allergic sensitization. The aim of this work was to evaluate the effects of CpG-containing oligodeoxynucleotides on neonatal and adult immunization with ovalbumin and Blomia tropicalis extract and compare the CpG effects on B and T cells of neonatal and adult mice. Mice that received CpG showed reduced immunoglobulin E (IgE) antibody production in both neonatal and adult periods, in parallel to increased IgG2a antibody levels. We observed that spleen cells of mice that received CpG in early life produced increased amounts of interferon-gamma upon anti-CD3 stimulation. Negative regulation of IgE response was more pronounced in adult than neonate mice; further, CpG decreased anaphylactic antiovalbumin IgG1 only in adults. Also, an upregulation of toll-like receptor 9 expression was detected in adult B cells, but not in neonatal, upon CpG stimuli. Neonatal B cells showed enhanced interleukin (IL)-10 expression and decreased IL-6 levels than adult B cells in response to CpG. When we analyzed in vitro activation of CD4+ T cells, an increased expression of B7 molecules on T cells in neonates was suppressed by CpG. Altogether, we verified qualitative and quantitative evidences regarding CpG effect on neonatal and adult allergens immunizations, which points to the importance of understanding neonatal immune system to establish immunomodulatory strategies for prevention of allergic diseases.

Immunogenicity and tolerability of a virosome influenza vaccine compared to split influenza vaccine in patients with sickle cell anemia

The immunogenicity and tolerability of virosome and of split influenza vaccines in patients with sickle cell anemia (SS) were evaluated Ninety SS patients from 8 to 34 years old were randomly assigned to receive either virosome (n = 43) or split vaccine (n = 47) Two blood samples were collected, one before and one 4-6 weeks after vaccination Antibodies against viral strains (2006) A/New Caledonia (H1N1), A/California (H3N2), B/Malaysia were determined using the hemagglutinin inhibition test Post-vaccine reactions were recorded over 7 days Seroconversion rates for HI NI, H3N2 and B were 65 1%. 60 4% and 83 7% for virosome vaccine, and 68 0%, 61 7% and 68 0% for split vaccine Seroprotection rates for HI NI, H3N2 e B were 100%. 97 6% and 69.7% for virosome. and 97 8%, 97 8% and 76 6% for split vaccine No severe adverse reactions were recorded Virosome and split vaccines in patients with sickle cell anemia were equally Immunogenic. with high seroconversion and seroprotection rates Both vaccines were well tolerated (C) 2009 Elsevier Ltd All rights reserved

Balance between early life tolerance and sensitization in allergy: dependence on the timing and intensity of prenatal and postnatal allergen exposure of the mother

P>Allergens can be maternally transferred to the fetus or neonate, though it is uncertain how this initial allergen exposure may impact the development of allergy responses. To evaluate the roles of timing and level of maternal allergen exposure in the early life sensitization of progeny, female BALB/c mice were given ovalbumin (OVA) orally during pregnancy, lactation or weekly at each stage to investigate the immunoglobulin E (IgE) antibody production and cellular responsiveness of their offspring. Exposure to OVA during pregnancy was also evaluated in OVA-specific T-cell receptor (TCR) transgenic (DO11.10) mice. The effect of prenatal antigen exposure on offspring sensitization was dependent on antigen intake, with low-dose OVA inducing tolerance followed by neonatal immunization that was sustained even when pups were immunized when 3 weeks old. These offspring received high levels of transforming growth factor-beta via breastfeeding. High-dose exposure during the first week of pregnancy or perinatal period induced transient inhibition of IgE production following neonatal immunization; although for later immunization IgE production was enhanced in these offspring. Postnatal maternal antigen exposure provided OVA transference via breastfeeding, which consequently induced increased offspring susceptibility to IgE antibody production according to week post-birth. The effect of low-dose maternal exposure during pregnancy was further evaluated using OVA transgenic TCR dams as a model. These progeny presented pronounced entry of CD4(+) T cells into the S phase of the cell cycle with a skewed T helper type 2 response early in life, revealing the occurrence of allergen priming in utero. The balance between tolerance and sensitization depended on the amount and timing of maternal allergen intake during pregnancy.

Oral tolerance reduces Th17 cells as well as the overall inflammation in the central nervous system of EAE mice

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory immune response directed against myelin antigens of the central nervous system. In its murine model, EAE, Th17 cells play an important role in disease pathogenesis. These cells can induce blood-brain barrier disruption and CNS immune cells activation, due to the capacity to secrete high levels of IL-17 and IL-22 in an IL-6 + TGF-beta dependent manner. Thus, using the oral tolerance model, by which 200 mu g of MOG 35-55 is given orally to C57BL/6 mice prior to immunization, we showed that the percentage of Th17 cells as well as IL-17 secretion is reduced both in the periphery and also in the CNS of orally tolerated animals. Altogether, our data corroborates with the pathogenic role of IL-17 and IFN-gamma in EAE, as its reduction after oral tolerance, leads to an overall reduction of pro-inflammatory cytokines, such as IL-1 alpha, IL-6, IL-9, IL-12p70 and the chemokines MIP-1 beta, RANTES, Eotaxin and KC in the CNS. It is noteworthy that this was associated to an increase in IL-10 levels. Thus, our data clearly show that disease suppression after oral tolerance induction, correlates with reduction in target organ inflammation, that may be caused by a reduced Th1/Th17 response. Crown Copyright (c) 2010 Published by Elsevier B.V. All rights reserved.

Cost-effectiveness analysis of routine rotavirus vaccination in Brazil

Objective. The objective of this study was to conduct a cost-effectiveness analysis of a universal rotavirus vaccination program among children : 5 years of age in Brazil. Methods. Considering a hypothetical annual cohort of approximately 3 300 000 newborns followed over 5 years, a decision-tree model was constructed to examine the possible clinical and economic effects of rotavirus infection with and without routine vaccination of children. Probabilities and unit costs were derived from published research and national administrative data. The impact of different estimates for key parameters was studied using sensitivity analysis. The analysis was conducted from both healthcare system and societal perspectives. Results. The vaccination program was estimated to prevent approximately 1735 351 (54%) of the 3 210 361 cases of rotavirus gastroenteritis and 703 (75%) of 933 rotavirus-associated deaths during the 5-year period. At a vaccine price of 18.6 Brazilian reais (R$) per dose, this program would cost R$121 673 966 and would save R$38 536 514 in direct costs to the public healthcare system and R$71 778 377 in direct and indirect costs to society. The program was estimated to cost R$1 028 and R$1 713 per life-years saved (LYS)from the societal and healthcare system perspectives, respectively. Conclusions. Universal rotavirus vaccination was a cost-effective strategy for both perspectives. However, these findings are highly sensitive to diarrhea incidence rate, proportion of severe cases, vaccine coverage, and vaccine price.

A subunit vaccine based on biodegradable microspheres carrying rHsp65 protein and KLK protects BALB/c mice against tuberculosis infection

Of the hundreds of new tuberculosis ( TB) vaccine candidates some have therapeutic value in addition to their prophylactic properties. This is the case for the DNA vaccine encoding heat-shock protein 65 (DNAhsp65) from Mycobacterium leprae. However, there are concerns about the use of DNA vaccines in certain populations such as newborns and pregnant women. Thus, the optimization of vaccination strategies that circumvent this limitation is a priority. This study evaluated the efficacy of a single dose subunit vaccine based on recombinant Hsp65 protein against infection with M. tuberculosis H37Rv. The Hsp65 protein in this study was either associated or not with immunostimulants, and was encapsulated in biodegradable PLGA microspheres. Our results demonstrate that the protein was entrapped in microspheres of adequate diameter to be engulfed by phagocytes. Mice vaccinated with a single dose of Hsp65-microspheres or Hsp65 + CpG-microspheres developed both humoral and cellular-specific immune responses. However, they did not protect mice against challenge with M. tuberculosis. By contrast, Hsp65+KLK-microspheres induced specific immune responses that reduced bacilli loads and minimized lung parenchyma damage. These data suggest that a subunit vaccine based on recombinant protein Hsp65 is feasible.