Programa de Pós-graduação em Medicina Tropical e Saúde Pública
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Item Impacto da vacinação com a PCV10 na morbidade hospitalar por pneumonia no Brasil: análise de série temporal interrompida(Universidade Federal de Goiás, 2015-08-19) Afonso, Eliane Terezinha; Bierrenbach, Ana Luiza; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4763149D7; Andrade, Ana Lúcia Sampaio Sgambatti de; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4783408H2; Andrade, Ana Lúcia Sampaio Sgambatti de; Nishioka, Sérgio; Weckx, Lly Yin; Siqueira Neto, João Bosco; Habahi, MarceloBACKGROUND: Pneumonia causes substantial morbidity and mortality in all age groups around the world. The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine infant immunization in Brazil, free of charge, in March 2010. The aim of this study was to evaluate the impact PCV10 vaccination on rates of all cause pneumonia hospitalizations one year and three years after its introduction in Brazil. METHODS: We conducted two interrupted time series analysis studies. The first evaluated only the direct effect of PCV10 vaccination, in five Brazilian cities (Belo Horizonte, Curitiba, Porto Alegre, São Paulo and Recife), and was conducted one year after starting the vaccination. The second study evaluated the direct and indirect impact (individuals not vaccinated) of PCV10 vaccination in Brazil, and was conducted three years after vaccination. We used data from the Brazilian Hospitalization System from 2005-2013. The main outcome was monthly rates of all-cause pneumonia hospitalizations identified by ICD-10 codes J12-J18. We used hospitalization rates for congenital malformations and non-respiratory causes as a comparison groups. The time-series analysis was based on a generalized linear model. Pneumonia rates observed in the pre-vaccination period were used to estimate the hospitalization rates in the post-vaccination period of each study, adjusting for seasonality and secular trends. To estimate the direct (2-23 months of age) and indirect (≥5 years of age) impact of PCV10 vaccination, we calculated the percentage change in hospitalization rates, as the observed divided by the predicted rates of hospitalization in the post-intervention period minus one, with respective 95% CI and p values. The number of all-cause pneumonia hospitalizations averted by vaccination was calculated taking into account the difference between the predicted and observed number in the PCV10 post vaccination period. RESULTS: One year after introduction of PCV10 in Brazil, significant declines in hospitalizations for pneumonia in children aged 2-23 months were noted in Belo Horizonte (28.7%), Curitiba (23.3%), and Recife (27.4%). After three years of the introduction of PCV10, 461,519 pneumonia hospitalizations were averted in Brazil, and a significant decrease in rates of pneumonia hospitalization was observed in unvaccinated individuals aged 5-39 years, ranging from 14.1-17.4% (p<0.05). In contrast, an increased trend in pneumonia hospitalizations (p=0·004) was observed for elderly (≥ 65 years). CONCLUSION: Vaccination with PCV10 in Brazil was associated with reduction of pneumonia hospitalizations in vaccinated individuals. Herd effect was observed in individuals aged 5-39 years after three years of vaccination. Potential reasons for the increased trend in pneumonia hospitalization rates in the elderly should be investigated.Item Impacto da vacina pneumocócica conjugada 10-valente (PCV10) na hospitalização de crianças por pneumonia em Goiânia: uso de dados primários e secundários(Universidade Federal de Goiás, 2015-07-17) Andrade, Sabrina Sgambatti de; Andrade, Ana Lúcia Sampaio Sgambatti de; http://lattes.cnpq.br/7770363683068899; Andrade, Ana Lúcia Sampaio Sgambatti de; Moraes, Jose Cássio de; Berezin, Eitan Naaman; Sucasas, Paulo; Siqueira Júnior, João BoscoBackground. Anticipating the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) on childhood National Immunization Program (NIP), an active population-based surveillance on pneumonia hospitalizations was conducted as a baseline, enabling a vaccination impact study. The objectives of the present research were: (i) to assess the reliability of the Hospital Information System of the Unified Health System (SIH-SUS) as a data source for assessing PCV10 impact on pneumonia; (ii) to measure the impact of vaccination with PCV10 in reducing the incidence of clinical and X-Ray confirmed pneumonia, in children residing in Goiânia municipality. Methods. In this study, we conducted an active prospective population-based surveillance on pneumonia in the post PCV10 vaccination period (2011-2013), in all 17 pediatric hospitals of Goiânia, with similar methodology used in the previous pneumonia surveillance during the pre vaccination period (2007-2009). Children aged 2-35 months of age, admitted to hospitalization with suspected diagnosis of pneumonia, were elegible for the survey. Clinical pneumonia and X-Ray confirmed pneumonia were the outcomes. The intervention was the PCV10, introduced in June 2010 in Goiania. Probabilistic linkage was performed between the SIH-SUS database (secondary data) and the active population surveillance (primary data) for the year 2012, to measure the agreement of case identification on pneumonia hospitalization rates between both data sources. To assess the impact of PCV10, annual incidence of clinical pneumonia and X-Ray confirmed pneumonia (per 100,000 population) and respective 95% confidence interval (95%CI) was estimated for the post vaccinations period and compared to the rates obtained for the pre vaccination period. The relative risk for pneumonia and respective 95%CI were calculated based on Poisson distribution. The percentage change in rates (1-relative risk) between pre and post vaccination periods was calculated. Results. Pneumonia incidence rates obtained by the SIH-SUS were statistically similar to those obtained by active population surveillance for children 2-23meses (p = 0.184). On the PCV10 impact evaluation study, the rates of hospitalization for clinical and RXT confirmed pneumonia in children under 24 months decreased 13.1% (from 5,728/100,000 to 4,976/100,000) and 25.4% (from 2,497/100,000 to 1,862/100,000), respectively, after routine immunization.Item Uso de técnicas moleculares para determinação de Streptococcus pneumoniae e sorotipos colonizadores da nasofaringe na era pós-vacinal(Universidade Federal de Goiás, 2013-01-23) Garcia, Weslley José Moreira; Andrade, Ana Lúcia Sampaio Sgambatti de; http://lattes.cnpq.br/7770363683068899; Andrade, Ana Lúcia Sampaio Sgambatti de; Kipnis, André; Minamisava, RuthBrazil was the first country to introduce the pneumococcal conjugate 10valent vaccine into the National Immunization Program for infants, in 2010. The nasopharyngeal colonization by Streptococcus pneumoniae occurs early in life. It is the first step for the development of invasive diseases. So far no study has evaluated the impact of vaccination on the reduction on pneumococcal carriage. The evaluation of the impact of vaccination should based on technologies with high accuracy. In this investigation we applied molecular technologies, recently developed, to ascertain pneumococcal nasopharyngeal colonization and serotypes. Objectives: (i) to compare the prevalence of S. pneumoniae nasopharyngeal colonization by using real-time PCR (RT-PCR) and multiplex PCR, and culture (“gold standard”) in children residing in Goiania municipality; (ii) to evaluate the simultaneous colonization by different serotypes by using the multiplex PCR technique. Methods: A household populationbased survey was carried out between October/2010 and March/2011 by using a systematic sampling, weighted by census tract. Based on previous studies, the sample size was calculated taking into account an estimated 50% of pneumocococcal carriage. A total of 1,437 nasopharyngeal swabs were collected from children less than 24 months of age. Broth-enriched culture of nasopharynx specimens followed by pneumococcal isolation by both, culture and RT-PCR targeting the lytA gene (S. pneumoniae) were performed. Pneumococcal carriage was defined for RT-PCR Cycle threshold (Ct) < 35.0, and therefore all samples were submitted to multiplex PCR to detect serotypes. ROC curve (Receiver Operating Characteristics) were built up to identify Ct values predicted of S. pneumoniae positive culture. Results: The prevalence of pneumococcal carriage by RT-PCR (56.9%) was statistically higher (p< 0,001), compared to that obtained by culture (39.3%), regardless of the vaccination status. Among the 818 positive children/samples by RT-PCR, in 54.2% of them it was possible to detect the serotype. Simultaneous colonization by different types was found in 6.9% of the children. Ct values Ct33.0 showed the best accuracy (91.4%) to predict positive pneumococcal culture (Sensitivity=88% and Specificity=81.2%). When using Ct values 32.0 we found the best accuracy of multiplex PCR in detecting serotypes (Sensitivity =90% and Specificity =84,7%). Conclusion: Our findings suggest that RT-PCR and multiplex PCR techniques showed great potential to be used in evaluating the vaccination impact. Further studies are needed to evaluate the cost-effectiveness of using these technologies on a large scale.Item Cobertura vacinal e adesão aos esquemas recomendados da vacina pneumocócica conjugada 10 valente logo após sua introdução no calendário básico em Goiânia, GO: estudo transversal.(Universidade Federal de Goiás, 2014-11-03) Saraiva, Fabricia Oliveira; Andrade, Ana Lúcia Sampaio Sgambatti de; http://lattes.cnpq.br/7770363683068899; Andrade, Ana Lúcia Sampaio Sgambatti de; Costa, Paulo Sérgio Sucasas da; Soares, Cristiana Maria ToscanoBackground: Pneumococcal 10-valent conjugate vaccine (PCV10) was introduced to the routine immunization in Brazil in 2010. During PCV10 introduction year three schedules were used: (i) children aged ≤6 months: 3 doses + 1 booster; (ii) children aged 7-11 months: 2 doses + 1 booster (2p + 1), and (iii) children 12-15 months: single dose. The aim of this study was to assess vaccination coverage and compliance with recommended schedules after the introduction of PCV10 and to identify the factors associated with greater coverage and compliance. Methods: A household survey was conducted between December 2010 and February 2011 in Goiania, GO, where the PCV10 vaccination started on June, 2010. Systematic sampling was used to recruit 1,237 children. A sociodemographic questionnaire was applied during the home visits; dates of vaccination were obtained from the vaccination card. The child's age at vaccine introduction was calculated for July 14th, 2010 (30 days after the introduction of the vaccine on routine immunization) and the child was retrospectively classified into one of three age groups: ≤6 months, 7-11 months; 12-15 months. Vaccination coverage (percentage of children who received the number of recommended doses) and compliance with schedules (percentage of children who received all valid doses at the recommended time interval) were calculated for all children and for each of the three age groups; prevalence ratios were compared by chi-square test. Log binomial regression (prevalence ratio / PR) was used to identify variables independently associated with vaccination coverage and compliance with recommended schedules. Results: The overall vaccination coverage was 53.4% (95% CI: 50.8-56.2%), varying from 88.3% (12-15 months / single dose) to 39.3% (7-11 months / 2 doses). Compliance to vaccination schedules was 16.6% (95% CI: 14.5 to 18.7%), ranging from 35.6% (≥12 months / single dose) to 6.0% (7-11 months / 2 doses). Having a private health insurance was independently associated with both vaccination coverage (PR = 1.22; 95% CI: 1.04-1.43, p=0.013) and compliance with the vaccination schedule (PR = 1.08; 95% CI: 1.01-1.15, p=0.019). Conclusions: Vaccination coverage achieved high percentages before the first year of introduction of PCV10 on routine immunization. Compliance with PCV10 recommended schedules was low, being important gap in the program. Having private health insurance was associated with compliance and vaccination coverage, which may reflect an attitude of seeking health care frequently and not only on emergencies. Initiatives to increase rates of vaccination coverage and compliance should be pursued targeting children aged 7-11 months, who are under the highest risk of acquiring pneumococcal disease.Item Efeito da vacina pneumocócica conjugada na redução de sorotipos vacinais colonizadores da nasofaringe de crianças residentes no município de Goiânia, GO(Universidade Federal de Goiás, 2014-04-28) Ternes, Yves Mauro Fernandes; Andrade, Ana Lúcia Sampaio Sgambatti de; http://lattes.cnpq.br/7770363683068899; Andrade, Ana Lúcia Sampaio Sgambatti de; Sucasas, Paulo Sérgio; Morais Neto, Otaliba Libânio de; Bierrenbach, Ana Luiza de Souza; Waldman, Eliseu Alves10-valent conjugate pneumococcal vaccine (PCV10) was introduced in the routine immunization at Goiania in June, 2010. The aims of this study were: (i) to evaluate the direct effect of PCV10 in preventing vaccine types nasopharyngeal/NP pneumococcal carriage in younger children according to different schedules; (ii) to investigate possible genetic changes that could interfere in the pneumococcal capsular typing. Methods: A cross-sectional population-based household survey was conducted in Goiania, Brazil, from December/2010-February/2011, targeting children aged 7-18 months. To evaluate PPCV10 effectiveness/VE, NP swabs, clinical and demographic data, and vaccination dates were collected from 1,287 children during home visits. Main outcome and exposure of interest were PCV10 vaccine-type (VT) carriage and dosing schedules (3p+0, 2p+0, and one catch-up dose), respectively. Pneumococcal carriage was defined by positivity in culture after of NP secretions in enrichment broth and isolates serotyping was performed by Quellung reaction. The nontypeable isolates were processed by conventional multiplex PCR (cmPCR). Rate ratio/RR was calculated as the ratio between the prevalence of VTs carriage in children vaccinated with different schedules (exposed) and not vaccinated to PCV10 (non-exposed). Adjusted RR was estimated using Poisson regression. VE on VT carriage was calculated as 1-RR*100. Results: The prevalence of pneumococcal carriage in a total of 1,287 children was 41.0% (95%CI: 38.4%-43.7%). Serotypes covered by PCV10 and PCV13 were 35.2% and 53.0%, respectively. Serotypes 6B (11.6%), 6A (9,8%), 23F (7.8%), 14 (6.8%), 19F (6.6%), and 19A (6,3%) were the most frequently observed. After adjusted for confounders, children who had received 2p+0 or 3p+0 dosing schedule presented a significant reduction on pneumococcal VT carriage, with PCV10 VE equal to 35.9% (95%CI: 4.2%-57.1%; p=0.030) and 44.0% (95%CI: 14.2%-63.5%; p=0.008), respectively, when compared with unvaccinated children. For children who received one catch-up dose, no significant VE was detected (p=0.905). We identified 13 samples with a genetic variation that underestimated the capsular typing for 19F by cmPCR. Conclusion: PCV10 was associated with high protection against vaccine-type carriage for children vaccinated before the second year of life, for 2p+0 and 3p+0 schedules. The identification of genetic variations (19Fv) allowed adapt the molecular technique (cmPCR) for capsular typing samples from Latin America. The continuous evaluation of carriage serotype is mandatory to evaluate the long-term effectiveness and impact of pneumococcal vaccine on serotypes reduction.Item Impacto da vacinação contra o meningococo C na morbidade da doença meningocócica(Universidade Federal de Goiás, 2016-08-15) Tomich , Lísia Gomes Martins de Moura; Andrade, Ana Lúcia Sampaio Sgambatti de; http://lattes.cnpq.br/7770363683068899; Morais Neto , Otaliba Libânio de; Afonso , Eliane Terezinha; Andrade, Ana Lúcia Sampaio Sgambatti deINTRODUCTION: Routine infant immunization with meningococcal C conjugate vaccine (MenC-V) started in Brazil in November 2010, administered at three, five and 12 months of age with no catch-up for older age-groups. However, by March 2010, a vaccination campaign with MenC-V was performed in Salvador in individuals under five years-old, and from 10 to 24 yearsold. In São Paulo state, the outbreaks occurred in teenagers and young adults prompting one-time vaccination campaign from 2010 to 2014 targeting these age-groups. OBJECTIVE: To assess the direct and indirect impact (herd effect) of vaccination on invasive meningococcal disease (MD) for capsular group C (MenC) four years after the introduction of MenC-V in three scenarios: i) Brazil as a whole (routine vaccination in childhood only); ii) Brazil except for Salvador (vaccination campaign with teenagers during the year of MenC-V introduction); and iii) São Paulo state (vaccination campaign for adolescents and young adults during 2010-2014 to control outbreaks). METHODS: We performed an ecological quasi-experimental design from 2008 to 2014 using data from the National Reference Laboratory for Meningitis, and data from the National Information System for Notifiable Diseases. A deterministic linkage was performed between the two databases to improve the accuracy of the detection of MD, especially in capsular groups. An interrupted time-series analysis was conducted using the Holt-Winters technique to control for pre-existing trends and seasonal variations. The MenC vaccination impact was evaluated as the percentage of reduction in the incidence rates of MenC in the post-vaccination period (2012 to 2014), using the pre-vaccination period (2008 to 2010) to estimate what would be expected on the post-vaccination period, whether the vaccination had not been introduced. For Salvador, we analyzed the effect of the vaccination on the number of MenC cases. RESULTS: A total of 18,136 invasive MD cases were analyzed. For Brazil as a whole, the vaccination reduced 67.4% (lower 95%CI 42.5%) the rates for MenC for infants under 12 months, 92.3% (lower 95%CI 77.7%) for the age-group 12-23 months, and 65.7% (lower 95%CI 28%) for children aged 2-4 years. Indirect impact (20-24.7%) was observed in the age-group 5-19 years. When excluding Salvador from the analysis of Brazil, the indirect impact was observed only for children in the age-group 5-9 years. In the scenario of São Paulo state, similarly to Brazil, significant impact was observed in the target age-groups, in addition to indirect impact in the age group 5-9 years. In Salvador, in addition to the effect on the vaccinated population a sharp and sustainable decline of MenC cases was observed in all age-groups not target for vaccination. Overall, 1,170 cases of MenC were averted in Brazil after the introduced of Men-C vaccination. CONCLUSION: The strategy of catch-up for adolescents and young adults, especially during the year of MenC-V introduction may lead to rapid and sustainable herd effect.