A vaccination game based on public health actions and personal decisions

Susceptible-infective-removed (SIR) models are commonly used for representing the spread of contagious diseases. A SIR model can be described in terms of a probabilistic cellular automaton (PCA), where each individual (corresponding to a cell of the PCA lattice) is connected to others by a random network favoring local contacts. Here, this framework is employed for investigating the consequences of applying vaccine against the propagation of a contagious infection, by considering vaccination as a game, in the sense of game theory. In this game, the players are the government and the susceptible newborns. In order to maximize their own payoffs, the government attempts to reduce the costs for combating the epidemic, and the newborns may be vaccinated only when infective individuals are found in their neighborhoods and/or the government promotes an immunization program. As a consequence of these strategies supported by cost-benefit analysis and perceived risk, numerical simulations show that the disease is not fully eliminated and the government implements quasi-periodic vaccination campaigns. (C) 2011 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.

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.

Evaluation of the vaccination status in pediatric renal transplant recipients

To assess the immunization status of pediatric renal transplant patients followed at a single center in Brazil, vaccination charts of all patients aged between one and 18 yr were analyzed both pre- and post-transplantation. Appropriate immunization was defined according to the National Immunization Program (routine vaccines) - for all Brazilian children - and the Special Immunobiological Agents Program that also includes special vaccines for immunodeficient or other high-risk children. A total of 46 patients was evaluated (mean age 13.7 yr; range 4-17 yr). Vaccination charts were found to be up to date in only two patients (4.3%) pretransplant and in two (4.3%) post-transplant. Although 36 patients (62.2%) in the pretransplant phase and 24 (52.1%) in the post-transplant phase had been vaccinated according to the National Immunization Program, they had not received the special vaccines indicated for their immunocompromised condition. Therefore, despite being followed at a referral center, almost all patients presented an incomplete immunization status pre- and post-transplant. This probably reflects missed opportunities and medical/parental apprehension related to vaccination of patients with chronic renal insufficiency, dialysis or kidney transplantation. Efforts should be made to ensure adequate vaccination in children with kidney diseases, especially before kidney transplantation.

Epidemiology of bacterial meningitis among children in Brazil, 1997-1998

OBJECTIVE: To document the incidence and the descriptive epidemiology of bacterial meningitis among individuals under age 20 in a geographically defined region in Brazil during the two-year period immediately preceding the introduction of Haemophilus influenzae type b (Hib) vaccines into the national immunization program of Brazil. METHODS: Population-based epidemiological study of all cases of bacterial meningitis reported among residents of Campinas, Brazil, under age 20 (n=316,570) during the period of 1997-98, using comprehensive surveillance records compiled by the Campinas Health Department from cases reported among hospital inpatients, outpatients, emergency room visits, death certificates, and autopsy reports. RESULTS: The incidence of bacterial meningitis (n=274) was 334.9, 115 and 43.5 cases/10(5) person-years (pys) for residents of Campinas under age 1, 5 and 20, respectively. All cases were hospitalized, with an average length of stay of 12 days. Documented prior antibiotic use was 4.0%. The case-fatality rate of bacterial meningitis in individuals under age 20 was 9% (24/274) with 75% of deaths occurring in children under the age of five. The incidence of Hib meningitis (n=26) was 62.8 and 17 cases/10(5) pys in children age <1 and <5, respectively. CONCLUSIONS: The incidence of Hib meningitis in children under the age of 5 in Campinas during 1997-98 was similar to that reported in the US, Western Europe, and Israel prior to widespread Hib vaccine use in those regions. This study provides a baseline for later studies to evaluate changes in the etiology and incidence of bacterial meningitis in children after introduction of routine Hib vaccination in Brazil.

Safety and immunogenicity of hepatitis B vaccine ButaNG in adults

Recombinant yeast-derived hepatitis B vaccine manufactured by Instituto Butantan was administered in two groups of adult volunteers (I, II) following two different schedules of immunization. In the first trial (10 mg doses and 0, 1, 3 months vaccination schedule) 106 individuals completed the full immunization program. The results of seroconversion by age group varied from 70 to 100% and the GMT from 46.5 to 124.9 mIU mL-1. In the second trial with 68 individuals (for dosage comparison and 0, 1, 6 months vaccination schedule) indicated that the vaccine formulated in 20 mg was more effective than in 10 mg. The adverse reactions observed in the vaccinees were less frequent than the ones previously found since the introduction of similar vaccines.

Pandemic influenza A/H1N1 vaccination coverage, adverse reactions, and reasons for vaccine refusal among medical students in Brazil

The aim of this cross-sectional study was to determine, among medical students at a public university in Rio de Janeiro, Brazil, the acceptance of the pandemic influenza A/H1N1 vaccine during the 2010 mass immunization campaign and the vaccine safety in this group and, among unvaccinated students, the reasons for refusing vaccination. Of a total of 858 students, 678 (79%) participated in the study. Vaccination coverage was 60.4% among students aged 20 to 39 years (an age group targeted for vaccination) and 43.8% among those who did not belong to this age group. The most frequent adverse reactions to the vaccine were pain at the injection site (8.7%) and fever (7.9%). There were no serious adverse reactions. Among students aged 20 to 39 years, the most common reasons for refusing the vaccine were "lack of time" (42.4%), "fear of adverse reactions" (41.9%), and "difficult access to the vaccine" (11.5%). Other reasons for vaccine refusal were "uncertainties about vaccine safety and efficacy" and "vaccination was not needed". To increase the acceptance of the influenza vaccine, a comprehensive immunization program should be offered to these students.

HEPATITIS B VACCINATION COVERAGE AND POSTVACCINATION SEROLOGIC TESTING AMONG MEDICAL STUDENTS AT A PUBLIC UNIVERSITY IN BRAZIL

The aim of this cross-sectional study was to determine the hepatitis B vaccination coverage among medical students at a public university in Rio de Janeiro, Brazil, and their compliance with the postvaccination serologic testing recommendations. Of the total of 858 students, 675 (78.7%) participated in the study. Among the participants, 48.9% (95% CI: 45.1% to 52.7%) were vaccinated against hepatitis B (received ≥ 3 doses of the vaccine), 31.6% were not (received 0, 1 or 2 doses), and 19.6% did not know their vaccination status. Hepatitis B vaccination coverage increased from 26.0% among first-year students to 70.6% among sixth-year students while the prevalence of unknown vaccination status decreased from 39.7% among first-year students to 2.4% among sixth-year students. The frequency of unvaccinated students ranged from 23.7% among fifth-year students to 34.4% among first-year students. Only 34.8% of the vaccinated students performed the anti-HBs testing after vaccination. Among these medical students, we found a low adherence to the hepatitis B vaccination and to the postvaccination serologic testing. A comprehensive hepatitis B immunization program should be offered to students at this medical school.

Vaccines in pregnancy: a review of their importance in Brazil

Neonates and young children remain susceptible to many serious infectious diseases preventable through vaccination. In general, current vaccines strategies to prevent infectious diseases are unable to induce protective levels of antibodies in the first 6 months of life. Women vaccinated during pregnancy are capable of producing immunoglobulin antibodies that are transported actively to the fetus, and maternal immunization can benefit both the mother and the child. With few exceptions, maternal immunization is not a routine, because of the concerns related to the safety of this intervention. Ethical and cultural issues make the studies on maternal immunization difficult; however, in the last decade, the development of new vaccines, which are very immunogenic and safe has reactivated the discussions on maternal immunization. In this paper we present a review of the literature about maternal immunization based on MEDLINE data (1990 to 2002). The most important conclusions are: 1) there is no evidence of risk to the fetus by immunizing pregnant women with toxoids, polysaccharide, polysaccharide conjugated and inactive viral vaccines; 2) most viral attenuated vaccines are probably safe too, but data is still insufficient to demonstrate their safety; therefore these vaccines should be avoided in pregnant women; 3) in Brazil, there is a need for a maternal immunization program against tetanus. Many new candidate vaccines for maternal immunization are available, but studies should be conducted to evaluate their safety and efficacy, as well as regional priorities based on epidemiological data.

Protection against hepatitis B by the Butang® recombinant vaccine in newborn children in South Brazil

The prevention of hepatitis B by vaccination is one of the most efficient tools to avoid the transmission of the virus. This study evaluated the immunogenicity of the national vaccine Butang® in children born in Campo Mourão City, state of Paraná, Brazil, aged 7 to 12 months, by determining the anti-HBsAg antibodies levels after completion of the National Immunization Program Protocol for hepatitis B. All 70 children evaluated by the MEIA method (immune-enzymatic micro particles) showed seroconversion to the Butang® vaccine. Nine children (12.9%) presented a low response, with anti-HBs titers between 11 and 100 mUI/ml; 39 children (55.7%) showed a good response to the vaccine, with titers between 101 and 1000 mUI/ml; and 22 children (31.4%) showed antibodies titers higher than 1000 mUI/ml. The mean titer of the anti-HBs antibody titers was 1408.1 ± 2870.26 mUI/ml (15.7 to 19560.0 mUI/ml). The levels of antibodies produced by the prematurely-born children were not statistically different from those found in the newborns. Fifty-five children were also evaluated through the ELFA method (ELISA with a final detection in fluorescence), which presented similar results. The results obtained in our study corroborated the effectiveness of the national vaccine Butang® in newborn children of Campo Mourão City, Paraná, even if they were premature.

Immunogenicity, reactogenicity and consistency of production of a Brazilian combined vaccine against diphtheria, tetanus, pertussis and Haemophilus influenzae type b

A randomized, double-blinded study evaluating the immunogenicity, safety and consistency of production of a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine entirely produced in Brazil by Bio-Manguinhos and Instituto Butantan (DTP/Hib-BM) was undertaken. The reference vaccine had the same DTP vaccine but the Hib component was produced using purified materials supplied by GlaxoSmithKline (DTP/Hib-GSK), which is registered and has supplied the Brazilian National Immunization Program for over more than five years. One thousand infants were recruited for the study and received vaccinations at two, four and six months of age. With respect to immunogenicity, the vaccination protocol was followed in 95.6% and 98.4% of infants in the DTP/Hib-BM and DTP/Hib-GSK groups, respectively. For the Hib component of the study, there was 100% seroprotection (>0.15 µg/mL) with all three lots of DTP/Hib-BM and DTP/Hib-GSK. The geometric mean titer (GMT) was 9.3 µg/mL, 10.3 µg/mL and 10.3 µg/mL for lots 1, 2 and 3 of DTP/Hib-BM, respectively, and the GMT was 11.3 g/mL for DTP/Hib-GSK. For diphtheria, tetanus and pertussis, seroprotection was 99.7%, 100% and 99.9%, respectively, for DTP/Hib-BM, three lots altogether and 99.2%, 100% and 100% for DTP/Hib-GSK. GMTs were similar across all lots and vaccines. Adverse events rates were comparable among the vaccine groups. The Brazilian DTP/Hib vaccine demonstrated an immunogenicity and reactogenicity profile similar to that of the reference vaccine.

Acute diarrhoea in a community cohort of children who received an oral rotavirus vaccine in Northeast Brazil

Rotavirus is an important cause of childhood diarrhoea. A monovalent rotavirus vaccine (Rotarix®) was introduced into the Immunization Program of Brazil in 2006. In this study, we describe the incidence and burden of disease of rotavirus diarrhoea in two cohorts of children (vaccinated and unvaccinated). We followed two groups of 250 children under one year old, who were enrolled in December 2006 from a low-income residential area in Northeast Brazil. The children were monitored every two weeks for two years. Stool samples from children with diarrhoea were examined for the presence of rotavirus. Rotaviruses were genotyped using real time-polymerase chain reaction. The mean numbers of all-cause diarrhoea episodes/child (adjusted for age) in the first year were 0.87 and 0.84, in vaccinated and unvaccinated children, respectively. During the second year, the number of episodes/child decreased to 0.52 and 0.42. Only 16 (4.9%) of 330 stool samples were rotavirus-positive (10 vaccinated and 6 unvaccinated children) and only P[4]G2 rotaviruses were identified. All-cause diarrhoea episodes were more severe in unvaccinated children in the first year of age (p < 0.05), while vaccinated children had more severe episodes 18 months after vaccination. Rotavirus diarrhoea incidence was very low in both groups.

Occurrence of Haemophilus influenzae strains in three Brazilian states since the introduction of a conjugate Haemophilus influenzae type b vaccine

Few vaccines in history have induced such a dramatic decline in incidence over such a short period of time as the Haemophilus influenzae type b (Hib) conjugate. This vaccine was introduced in 1988 in the United States, but only in 1999 was Hib immunization introduced by the Brazilian Ministry of Health as part of the routine infant National Immunization Program. The authors analyzed 229 H. influenzae (Hi) isolates from Public Health Laboratories in three Brazilian states: Pernambuco (Northeast, N = 54), Santa Catarina (South, N = 19), and Rio de Janeiro (Southeast, N = 156). The isolates were collected from Brazilian children 0-10 years of age with meningitis and other infections from 1990 to 2003 and were part of the research collection of the National Institute of Quality Control in Health, FIOCRUZ. Bacterial strains were characterized by serotyping and biotyping. During the pre-vaccination period the prevalence infection due to Hib was of 165 isolates and only 2 non-b Hi among all the notified meningitis infections caused by Hi. Our results showed a significant decrease in the prevalence of Hib meningitis from 165 to 33 isolates after 1999. However, during the post-vaccination period of 2001-2003 we observed an increase in the number of non-b Hi isolates: only 2 non-b strains isolated from 1990 to 1999 and 29 from 1999 to 2003. Based on the present data, the authors emphasize the need for more sensitive epidemiological and bacteriological studies aiming the improvement of the available Hib vaccine, in order to protect the susceptible population to infections due to other serological types of Hi and the reevaluation of immunization schedules used by the National Immunization Program.

Tetanus and diphtheria immunity in adolescents from São Paulo, Brazil

Tetanus and diphtheria vaccines are of special concern in adolescents because boosters are necessary for adequate maintenance of protection and are often omitted. We assessed serum levels of tetanus and diphtheria antibodies in adolescents and their association with vaccination status. From May to October 2001, we evaluated the vaccination records of 208 adolescents aged 10 to 20 years in São Paulo, Brazil. Antibodies to tetanus and diphtheria were detected using double-antigen ELISA and vaccination records were analyzed according to the guidelines of the Brazilian National Immunization Program. All adolescents had received complete primary vaccinations against tetanus and diphtheria, but 23.1% of them had not received a booster dose in the last 10 years. All adolescents were immune to tetanus and 88.9% were fully protected (antibodies ³0.1 IU/mL). One individual (0.5%) was non-immune to diphtheria and 86% were fully protected against the disease. Adolescents with up-to-date vaccination records had higher antibody levels than those with not up-to-date records for tetanus (0.763 vs 0.239 IU/mL, t-test: P < 0.0001) and diphtheria (0.366 vs 0.233 IU/mL, t-test: P = 0.014). Full immunity against tetanus (antibodies ³0.1 IU/mL) was higher among individuals with up-to-date vaccination (93.1%) when compared to those with not up-to-date records (75%, Fisher's exact test: P = 0.001). All adolescents had received basic immunization in childhood and were protected against tetanus and diphtheria. However, these data indicate that more emphasis should be placed on the tetanus-diphtheria booster in order to avoid a decay in antibody levels.

Changes in epidemiology of rotavirus in the Triângulo Mineiro region of Brazil: lack of two consecutive rotavirus seasons

Rotaviruses are the main cause of infantile acute diarrhea, and a monovalent (G1P[8]) vaccine against the virus was introduced into the Brazilian National Immunization Program for all infants in March 2006. The objectives of this study were to determine the rate and genotype distribution of rotavirus causing infantile diarrhea in the Triângulo Mineiro region of Brazil during 2011-2012 and to assess the impact of local vaccination. Fecal specimens were analyzed for detection and characterization of rotavirus using polyacrylamide gel electrophoresis, reverse transcription followed by polymerase chain reaction (PCR), and PCR-genotyping assays. Overall, rotavirus was diagnosed in 1.7% (6/348) of cases. Rotavirus positivity rates decreased 88% [95% confidence intervals (CI)=15.2, 98.3%; P=0.026] in 2011 and 78% (95%CI=30.6, 93.0%; P=0.007) in 2012 when compared with available data for baseline years (2005/2006) in Uberaba. In Uberlândia, reductions of 95.3% (95%CI=66.0, 99.4%; P=0.002) in 2011, and 94.2% (95%CI=56.4, 99.2%; P=0.004) in 2012 were also observed compared with data for 2008. The circulation of rotavirus G2P[4] strains decreased during the period under study, and strains related to the P[8] genotype reemerged in the region. This study showed a marked and sustained reduction of rotavirus-related cases, with a lack of rotavirus in the 2011 and 2012 seasons, suggesting a positive impact of the vaccination program.