Homologous equivalence study of immunogenicity after third dose of Covid-19 vaccine (recombinant) with an interval of six months after the second dose, comparing the interval of eight and 12 weeks between the first two doses.

BACKGROUND: In response to the coronavirus disease 2019 (Covid-19) pandemic, Brazil authorised the Astra Zeneca/Fiocruz vaccine in January 2021. As the Delta variant emerged in May 2021, interval between vaccine doses was adjusted. By September 2021, the Brazilian National Immunisation Program recommended a booster dose for individuals over 70, and later expanded the recommendation to all adults. OBJECTIVES: Assess the equivalence of IgG antibody response against the Covid-19 S protein before and approximately 28 days after the third dose of a Covid-19 recombinant vaccine. Two groups received initial two doses with intervals of eight and 12 weeks. METHODS: This is a phase IV clinical study, uncontrolled, non-randomised. The study proposes calculating the ratio of geometric means titres (GMT) 28 days after the third dose, with a target ratio of confidence interval (CI) between 0.77 and 1.3. FINDINGS: In the primary endpoint, there was no equivalence between the eight- and 12-week intervals with a slight variation favouring the eight-week group. Post-third dose, both groups showed increases titres at 28 days, three months, six months and 12 months. Both groups responded similarly to Delta and Omicron BA.1, with a more significant increase for Delta. MAIN CONCLUSIONS: The study showed strong and consistent immune response in all age groups receiving the Covid-19 recombinant vaccine. Third dose elicited an increase in GMT by at least three times aligned with Ministry of Health strategies emphasising Bio-Manguinhos crucial role in pandemic control in the country.

Duration of post-vaccination immunity to yellow fever in volunteers ten years after a dose-response study - A complementary study.

A single dose of standard yellow fever (YF) vaccine is considered to provide life-long protection. In this study, we evaluate the seropositivity conferred by lower doses 10 years post-vaccination. In 2009, Bio-Manguinhos/Fiocruz performed a dose-response study with the 17DD yellow fever vaccine, administering the vaccine in the usual mean dose of 27.476 IU and in decreasing doses (10.447 IU, 3.013 IU, 587 IU, 158 IU and 31 IU), with the usual volume and route (0,5 ml subcutaneous). The decreasing doses were obtained by dilution in the laboratory of the manufacturer and the lots in test had standard quality control and were produced by good manufacturing practices (GMP). Around 30 days after the vaccination, doses down to 587 IU had similar immunogenicity and the 158 IU and 31 IU were inferior to the full dose. The seropositivity was maintained for 10 months, except on the 31 IU group. Eight years after, 85 % of 318 participants evaluated in a follow-up, maintained seropositivity that was similar across groups. Consistently, antibody titers in the reduced-dose groups were also comparable to those of the full-dose group. The current study, 10 years later, showed similarity between the vaccine groups (six arms who received the YF vaccine in decreasing doses: 27.476 IU, 10.447 IU, 3.013 IU, 587 IU, 158 IU, 31 IU) both in relation of seropositivity and in the evaluation of the geometric mean titers. The seropositivity rates across subgroups were 83,1%, 90 %, 87 %, 93 %, 83,8% and 85 %, correspondingly. These findings provides further support to the long-term immunogenicity of lower doses. Clinical trial registry: NCT04416477.

Comprehensive landscape of neutralizing antibody and cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF primary vaccination in adults.

The present study aimed at evaluating the YF-specific neutralizing antibody profile besides a multiparametric analysis of phenotypic/functional features of cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF vaccine, administered as a single subcutaneous injection. The immunological parameters of each volunteer was monitored at two time points, referred as: before (Day 0) [Non-Vaccinated, NV(D0)] and after vaccination (Day 30-45) [Primary Vaccinees, PV(D30-45)]. Data demonstrated high levels of neutralizing antibodies for PV(D30-45) leading to a seropositivity rate of 93%. A broad increase of systemic soluble mediators with a mixed profile was also observed for PV(D30-45), with IFN-γ and TNF-α presenting the highest baseline fold changes. Integrative network mapping of soluble mediators showed increased correlation numbers in PV(D30-45) as compared to NV(D0) (532vs398). Moreover, PV(D30-45) exhibited increased levels of Terminal Effector (CD45RA+CCR7-) CD4+ and CD8+ T-cells and Non-Classical memory B-cells (IgD+CD27+). Dimensionality reduction of Mass Cytometry data further support these findings. A polyfunctional cytokine profile (TNF-α/IFN-γ/IL-10/IL-17/IL-2) of T and B-cells was observed upon in vitro antigen recall. Mapping and kinetics timeline of soluble mediator signatures for PV(D30-45) further confirmed the polyfunctional profile upon long-term in vitro culture, mediated by increased levels of IFN-γ and TNF-α along with decreased production of IL-10. These findings suggest novel insights of correlates of protection elicited by the 1/5 fractional dose of 17DD-YF vaccine.

Immune response induced by standard and fractional doses of 17DD yellow fever vaccine.

The re-emergence of yellow fever (YF) urged new mass vaccination campaigns and, in 2017, the World Health Organization approved the use of the fractional dose (FD) of the YF vaccine due to stock shortage. In an observational cross-sectional investigation, we have assessed viremia, antibodies, soluble mediators and effector and memory T and B-cells induced by primary vaccination of volunteers with FD and standard dose (SD). Similar viremia and levels of antibodies and soluble markers were induced early after immunization. However, a faster decrease in the latter was observed after SD. The FD led to a sustained expansion of helper T-cells and an increased expression of activation markers on T-cells early after vaccination. Although with different kinetics, expansion of plasma cells was induced upon SD and FD immunization. Integrative analysis reveals that FD induces a more complex network involving follicular helper T cells and B-cells than SD. Our findings substantiate that FD can replace SD inducing robust correlates of protective immune response against YF.

Homologous equivalence study of immunogenicity after third dose of Covid-19 vaccine (recombinant) with an interval of six months after the second dose, comparing the interval of eight and 12 weeks between the first two doses

BACKGROUND In response to the coronavirus disease 2019 (Covid-19) pandemic, Brazil authorised the Astra Zeneca/Fiocruz vaccine in January 2021. As the Delta variant emerged in May 2021, interval between vaccine doses was adjusted. By September 2021, the Brazilian National Immunisation Program recommended a booster dose for individuals over 70, and later expanded the recommendation to all adults. OBJECTIVES Assess the equivalence of IgG antibody response against the Covid-19 S protein before and approximately 28 days after the third dose of a Covid-19 recombinant vaccine. Two groups received initial two doses with intervals of eight and 12 weeks. METHODS This is a phase IV clinical study, uncontrolled, non-randomised. The study proposes calculating the ratio of geometric means titres (GMT) 28 days after the third dose, with a target ratio of confidence interval (CI) between 0.77 and 1.3. FINDINGS In the primary endpoint, there was no equivalence between the eight- and 12-week intervals with a slight variation favouring the eight-week group. Post-third dose, both groups showed increases titres at 28 days, three months, six months and 12 months. Both groups responded similarly to Delta and Omicron BA.1, with a more significant increase for Delta. MAIN CONCLUSIONS The study showed strong and consistent immune response in all age groups receiving the Covid-19 recombinant vaccine. Third dose elicited an increase in GMT by at least three times aligned with Ministry of Health strategies emphasising Bio-Manguinhos crucial role in pandemic control in the country.

Seroprevalence of Hantavirus among Manual Cane Cutters and Epidemiological Aspects of HPS in Central Brazil.

Hantavirus pulmonary syndrome (HPS) is a rodent-borne zoonotic disease that is endemic throughout the Americas. Agricultural activities increase exposure to wild rodents, especially for sugarcane cutters. We carried out a survey of the epidemiological aspects of HPS and investigated the prevalence of hantavirus infection in the sugarcane cutter population from different localities in the Brazilian Midwest region. We conducted a retrospective study of all confirmed HPS cases in the state of Goiás reported to the National HPS surveillance system between 2007 and 2017, along with a seroepidemiological study in a population of sugarcane cutters working in Goiás state in 2016, using the anti-hantavirus (Andes) ELISA IgG. A total of 634 serum samples from cane cutters were tested for hantavirus antibodies, with 44 (6.9%) being IgG-reactive according to ELISA. The destination of garbage was the only statistically significant variable (p = 0.03) related to the detection of hantavirus IgG (p < 0.05). We described the epidemiological profile of reported hantavirus cases in Goiás-a highly endemic area for HPS, and where the seroepidemiological study was conducted. Our results increase our knowledge about hantavirus infections in Brazil and highlight the vulnerability of sugarcane cutters to a highly lethal disease that, to date, has no specific treatment or vaccination.

Standardization, validation, and comparative evaluation of a faster and high-performance test for quantification of yellow fever neutralizing antibodies.

Although it is considered the reference for quantification of neutralizing antibodies, classical method of the plaque reduction neutralization test (PRNT) is labor intensive, requires specific equipment and inputs, besides a long time for its finalization, even in the micro-PRNT version (in 96-well plates). It has a higher sample throughput, however the smaller wells make the reading of plaques more difficult. With an immunoenzymatic revelation step and a semi-automated reading, the µFRN-HRP (micro Focus Reduction Neutralization - Horseradish Peroxidase) is a faster and more efficient test for the quantification of YF neutralizing antibodies. This study aimed to standardize, validate, and compare it with the reference method in 6-well plates (PRNT). Once the execution protocol was standardized, precision, accuracy, selectivity, and robustness were evaluated to validate the µFRN-HRP. In addition, 200 sera of vaccinees were processed by the µFRN-HRP and by the micro-PRNT to compare with the reference test, estimating agreement by Intraclass Correlation Coefficient (ICC). The standardization and validation of the µFRN-HRP was carried out successfully. Weak to moderate agreement was observed between µFRN-HRP and PRNT for titers in reciprocal dilution, while the same comparison between the classical tests resulted in a better ICC. However, titers in milli-international units obtained by µFRN-HRP showed a substantial agreement with PRNT, while the agreement between micro-PRNT and PRNT was inferior. Therefore, µFRN-HRP can be used in the confirmation of natural YF infection and immune response to vaccination, replacing the micro-PRNT, gaining agility, while preserving the specificity of the result.

Timeline kinetics of protective immunity to SARS-CoV-2 upon primary vaccination and humoral response to variants after booster dose.

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, imposing the need for periodic booster doses. However, whether booster doses should be applied to the entire population or groups, and the booster doses interval, remains unclear. In this study, we evaluated humoral reactivity kinetics from before the first dose to 180 days after the third booster dose in different schedules in a well-controlled health worker cohort. Among the 2,506 employees, the first 500 vaccinated health workers were invited to participate. The third booster dose was administered 8 months after the first dose. Among the invited participants, 470 were included in the study; 258 received inactivated vaccine CoronaVac (VAC group) and 212 received viral vector vaccine ChAdOx1 (AZV group). The groups were homogeneous in terms of age and sex. 347 participants were followed up after the booster dose with AZV or BNT162b2 (Pfizer, BNT group): 63 with VAC/AZV, 117 with VAC/BNT, 72 with the AZV/AZV and 95 with AZV/BNT schedules. Blood samples were collected immediately before, 28 days after each dose and 180 days after the primary vaccination and booster dose. Anti-SARS-CoV-2 antibodies were measured by chemiluminescence and plaque reduction neutralization test (PRNT). Plasma immune mediators were quantified using a multiplex immunoassay. Geometric mean of antibodies increased 28 days after the second dose with 100 % seroconversion rate in both groups and decreased 180 days after the first dose. In the baseline-seropositive VAC group, the levels of plasma immune mediators increased after the second dose. Booster dose was applied at 4-6 months after the primary vaccination. Heterologous booster in VAC or AZV primary vaccinees were effective maintaining the titers of anti-SARS-CoV-2 antibodies even after 6 months of follow-up. The heterologous schedule induced higher and stable antibody reactivity, even after 180 days, protecting to ancestral (Wuhan), Delta, and Omicron variants.

'If I hadn't seen this picture, I'd be smoking'-perceptions about innovations in health warnings for cigarette packages in Brazil: a focus group study.

OBJECTIVE: To investigate the perceptions of young people and adults, smokers and non-smokers about the current set of innovations introduced in 2018 into the Brazilian tobacco products' health warnings. METHODS: Twenty focus groups were conducted in five state capitals in Brazil. The participants (n=163) were segmented by smoking status, age (15-17 years, 18-55 years) and social grade (C, D-E classes) to examine cigarette packaging and explore the participants' perceptions of health warnings. RESULTS: Health warnings capture attention, eliciting apprehension, fear, disgust and concern about the negative consequences of cigarette consumption. The 2018 Brazil health warnings are spontaneously recalled by participants, even without the presence of cigarette packages. However, the analysis also reveals the challenges of overcoming communication barriers and distorted interpretations, especially among smokers. The inclusion of direct and provocative stimuli, such as the use of the word 'you', attracts attention and creates more proximity to the recipient of the message. The results also highlight the interest and fear elicited by warnings on toxic constituents and the importance of using contrasting colours in warnings, which differentiate them from the colours of cigarette packs. CONCLUSION: Introducing innovative components in health warnings can catch consumers' attention but considering that the interviewees encountered difficulties interpreting textual warnings about toxic constituents in cigarettes, the study reinforces the importance of adopting direct language and pictures, instead of text, which can visually transmit the warning messages and the use of specific wording that generates proximity between the emitter and receiver.

Perfil epidemiológico dos casos suspeitos de sarampo e rubéola notificados no SINAN, Brasil, 2007 a 2016 / Epidemiological profile of suspected cases of measles and rubella notified on SINAN, Brazil, 2007 to 2016

Descrever os casos suspeitos de sarampo e rubéola notificados no Sistema de Informação de Agravos de Notificação (Sinan), Brasil, 2007 a 2016. Métodos: Os dados foram extraídos do Sinan, referentes aos anos de 2007 a 2016. As variáveis utilizadas foram os números de notificações de casos de sarampo e rubéola por regiões e ano, idade, sexo, hospitalização, estado gestacional, histórico vacinal, realização de bloqueio vacinal, coletas sorológicas (S1 e S2), sinais e sintomas, investigação adequada, critério de confirmação ou descarte e classificação final do caso. Resultados: Entre 2007 e 2016 houve 127.802 casos suspeitos de sarampo e rubéola notificados. Aproximadamente 92% dos casos foram investigados, a maioria em menores de cinco anos. Os sintomas mais frequentes foram tosse (40%) e coriza (38%). Como instrumento de vigilância foi coletado sangue para confirmação laboratorial em 87% das notificações. A maioria dos casos de sarampo ocorreu entre os anos de 2011 e 2015, relacionados a casos importados, totalizando 1.443 casos; para rubéola, 10.125 casos foram confirmados. Foram descartados 1,3% (1.698/127.802) e 5,1% (6.555/127.802) das notificações de sarampo e rubéola, respectivamente. Foram ignorados 9% (11.523/127.802) para sarampo e 49% (62.978/127.802) para rubéola. Conclusão: A vigilância dos casos de doenças exantemáticas permitiu demonstrar a situação dos casos de doenças exantemáticas circulantes no país como importante ferramenta de saúde pública. O grande número de casos descartados classificados como ignorados merece atenção, no sentido de melhorar o encerramento dos casos suspeitos notificados

To describe the suspected cases of measles and rubella notified in the Notifiable Diseases Information System (Sinan), Brazil, from 2007 to 2016. Methods: Data were extracted from Sinan referring to the years 2007 to 2016. The variables used were the number of notifications of measles and rubella cases by region and year, age, gender, hospitalization, gestational status, vaccination history, vaccination blockade, serological collections (S1 and S2), signs and symptoms, adequate investigation, confirmation criteria or disposal and final case classification. Results: Between 2007 and 2016, there were 127,802 suspected cases of measles and rubella reported. Approximately 92% of cases were investigated, mostly in children under five years of age. The most frequent symptoms were cough (40%) and runny nose (38%). As a surveillance tool, blood was collected for laboratory confirmation in 87% of notifications. Most Measles cases occurred between 2011 and 2015, related to imported cases, totaling 1,443 cases; for Rubella 10,125 cases were confirmed. 1.3% (1,698/127,802) and 5.1% (6,555/127,802) of measles and rubella notifications, respectively, were discarded. 9% (11,523/127,802) for measles and 49% (62,978/127,802) for rubella were ignored. Conclusion: Surveillance of cases of exanthematous diseases allowed demonstrating the situation of cases of exanthematous diseases circulating in the country as an important public health tool. The large number of discarded cases classified as ignored deserves attention, in order to improve the closing of notified suspected cases

Impacto da epidemia de COVID-19 na mortalidade em prisões / Impact of the COVID-19 epidemic on mortality in prisons

Resumo O objetivo deste artigo é avaliar o impacto da COVID-19 na mortalidade das pessoas privadas de liberdade (PPL) no estado do Rio de Janeiro e comparar as taxas observadas com as da população geral. Estudo quantitativo, retrospectivo, que associa análise de série histórica 2016-2021 de taxa anual de mortalidade, seccional, comparando 2016-2017 vs. 2020-2021 e análise de dados individuais obtidos a partir de fontes primárias e secundárias de informação. A razão de mortalidade padronizada entre PPL e população geral foi estimada para os grupos de causa. Série histórica mostrou queda anual (13%) da mortalidade de 2016 a 2019, tendência que se inverteu em 2020 devido à COVID-19, responsável por 20% do total de mortes. Das PPL que morreram por COVID-19, 54,8% eram idosas e/ou portadoras de comorbidade. A mortalidade por COVID-19 foi semelhante entre a PPL e a população geral, mas a mortalidade por tuberculose e HIV permaneceu muito mais elevada entre as PPL. A pandemia foi provavelmente determinante para a reversão da tendência de queda na mortalidade observada entre 2016 e 2019. A utilização da mortalidade como indicador de saúde e direitos humanos nas prisões por órgãos de saúde, justiça e organizações da sociedade civil implica o aprimoramento da informação sobre PPL no SIM.

Abstract Purpose: to assess the impact of COVID-19 on the mortality of people deprived of their liberty (PDL) in the state of Rio de Janeiro and compare the rates observed with those of the general population. Method: quantitative, retrospective study combining the analysis of the 2016-2021 time series of annual mortality rates, cross-sectional study comparing 2016-2017 vs. 2020-2021 and analysis of individual data obtained from primary and secondary sources of information. The standardized mortality ratio between PDL and the general population was estimated for the cause of death categories. Results: historical series showed an annual drop (13%) in mortality from 2016 to 2019, a trend that was inverted in 2020 due to COVID-19, which was responsible for 20% of all deaths. Of the COVID-19 deaths, 54.8% were elderly and/or had co-morbidities. Mortality from COVID-19 was similar between PDL and the general population, but mortality from tuberculosis and HIV remained much higher among PDL. Conclusion: the pandemic was probably a determinant of the downward trend reversal in mortality between 2016 and 2019. Using mortality as an indicator of health and human rights in prisons by health, justice and civil society organizations implies the improvement of information about PDL in the SIM.

Seroepidemiology of SARS-CoV-2 on a partially vaccinated island in Brazil: Determinants of infection and vaccine response.

Background: A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro. Objective: We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents. Methods: We performed a seroepidemiologic survey in all residents of Paquetá Island, a neighborhood of Rio de Janeiro city, during the COVID-19 vaccine roll-out. Serological tests were performed from June 16 to June 19, 2021, and adjusted seropositivity rates were estimated by age and epidemiological variables. Logistic regression models were used to estimate adjusted ORs for risk factors to SARS-CoV-2 seropositivity in non-vaccinated individuals, and potential determinants of the magnitude of antibody responses in the seropositive population. Results: We included in the study 3,016 residents of Paquetá (83.5% of the island population). The crude seroprevalence of COVID-19 antibodies in our sample was 53.6% (95% CI = 51.0, 56.3). The risk factors for SARS-CoV-2 seropositivity in non-vaccinated individuals were history of confirmed previous COVID-19 infection (OR = 4.74; 95% CI = 3.3, 7.0), being a household contact of a case (OR = 1.93; 95% CI = 1.5, 2.6) and in-person learning (OR = 2.01; 95% CI = 1.4, 3.0). Potential determinants of the magnitude of antibody responses among the seropositive were hybrid immunity, the type of vaccine received, and time since the last vaccine dose. Being vaccinated with Pfizer or AstraZeneca (Beta = 2.2; 95% CI = 1.8, 2.6) determined higher antibody titers than those observed with CoronaVac (Beta = 1.2; 95% CI = 0.9, 1.5). Conclusions: Our study highlights the impact of vaccination on COVID-19 collective immunity even in a highly affected population, showing the difference in antibody titers achieved with different vaccines and how they wane with time, reinforcing how these factors should be considered when estimating effectiveness of a vaccination program at any given time. We also found that hybrid immunity was superior to both infection-induced and vaccine-induced immunity alone, and online learning protected students from COVID-19 exposure.

Effectiveness, safety, and immunogenicity of half dose ChAdOx1 nCoV-19 COVID-19 Vaccine: Viana project.

Fractional dose is an important strategy to increase access to vaccines. This study evaluated the effectiveness, safety, and immunogenicity of half dose of ChAdOx1 nCoV-19 vaccine. A non-inferiority non-randomized controlled trial compared a half dose of ChAdOx1 nCoV-19 with the full dose, with an interval of 8 to 10 weeks, in individuals aged 18-49 years. The primary endpoints were the incidence rate of new cases/1,000 person-year at 90 days after 14 days of the second dose, confirmed by RT-PCR and new cases registered at SUS National Health Surveillance Database (e-SUS VS). The anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) by chemiluminescence and the neutralizing antibodies by plaque reduction neutralization test (PRNT) were titrated. The soluble biomarkers were quantified with a multiplex immunoassay. Follow-up was 90 days after 14 days of the second dose. A total of 29,598 individuals were vaccinated. After exclusion, 16,570 individuals who received half a dose and 6,402 who received full doses were analyzed. The incidence of new cases confirmed by RT-PCR of half dose was non-inferior to full dose (23.7 vs. 25.7 cases per 1,000 persons-year [coefficient group -0.09 CI95%(-0.49 to 0.31)], even after adjusting for age and sex. There were no deaths or hospitalization after immunization of either group. Immunogenicity was evaluated in a subsample (N=558) compared to 154 healthcare workers who received a full dose. The seroconversion rate in seronegative individuals at baseline half dose was 99.8%, similar to that of the full dose (100%). Geometric mean concentration (95% CI; BAU/mL) were half dose = 188 (163-217) and full dose = 529 (423-663) (p < 0.001). In seropositive subjects at baseline (pre-immune individuals), the first dose induced very high and similar IgG-S in half dose 1,359 (1,245-1,483) and full dose 1,354 (1,048-1,749) BAU/mL. A half dose induced a high increase in plasma chemokines, pro-inflammatory/regulatory cytokines, and growth factors. The frequency of adverse events was similar. No serious adverse events or deaths were reported. A half dose of ChAdOx1 nCoV-19 is as effective, safe, and immunogenic as the full dose. The immune response in pre-immune (seropositive in the baseline) individuals indicates that the half dose may be a booster dose schedule.

[Yellow fever prevention and control: assessment of surveillance activities in a previously unaffected area in Brazil]. / Prevenção e controle da febre amarela: avaliação de ações de vigilância em área indene no Brasil.

Following the reemergence of yellow fever in 2014/2015, Brazil recorded its largest yellow fever epidemic in recent decades, mainly affecting the country's Southeast region. Yellow fever is a hemorrhagic viral disease caused by a flavivirus transmitted by sylvatic mosquitos (Haemagogus; Sabethes). In the urban cycle, eradicated in Brazil since 1942, the virus is transmitted by Aedes aegypti. Nonhuman primates are the principal hosts of the virus and constitute "sentinels" in yellow fever surveillance. This article describes the control and prevention activities launched during the yellow fever epidemic in the State of Espírito Santo, Brazil, and the implementation of vaccination, through an ecological study with a spatial approach. The study revealed the lack of detection of epizootics in nonhuman primates by surveillance services in Espírito Santo, with simultaneous detection in humans. The study presented the evolution of vaccination activities, reaching 85% overall coverage for the state in six months, varying widely, from 59% to 122%, between municipalities (counties). Importantly, 55% of the municipalities with timely immunization, considering the interval adopted for this study, did not present human cases. The intensification of surveillance activities, communication between areas, and multidisciplinary teams in managing the epidemic optimized the detection and diagnosis of human cases and allowed control of the epidemic. The study identifies progress and points to some late measures and gaps in surveillance that require improvements.

A partir da reemergência da febre amarela em 2014/2015, o Brasil registrou nos anos sequentes sua maior epidemia de febre amarela das últimas décadas, atingindo principalmente a região sudeste. A febre amarela, doença viral hemorrágica, é causada por um flavivírus, transmitido por mosquitos silvestres (Haemagogus; Sabethes). Na ocorrência do ciclo urbano, erradicado no Brasil desde 1942, a transmissão se dá pelo Aedes aegypti. Primatas não humanos são os principais hospedeiros do vírus e constituem "sentinelas" na vigilância da febre amarela. Este artigo descreve as ações de controle e prevenção desencadeadas durante a epidemia de febre amarela no Estado do Espírito Santo, Brasil, e a implementação da vacinação por meio de um estudo ecológico com abordagem espacial. O estudo evidenciou a falha na detecção de epizootias em primatas não humanos pelos serviços de vigilância do Espírito Santo, sendo simultânea à detecção em humanos. Apresentou a evolução das ações de vacinação, com alcance de 85% de cobertura vacinal geral para o estado em seis meses, sendo heterogênea entre os municípios (de 59% a 122%). Destaca-se que 55% dos municípios com ações de imunização em tempo oportuno, considerando o intervalo adotado para este estudo, não apresentaram casos em humanos. A intensificação das ações de vigilância, interlocução entre as áreas e equipes multidisciplinares na condução da epidemia otimizou a detecção e o diagnóstico dos casos em humanos e viabilizou o controle da epidemia. Foi possível reconhecer avanços, apontar algumas medidas tardias e lacunas na vigilância que necessitam melhorias.

A partir del resurgimiento de la fiebre amarilla en 2014/2015, Brasil registró los años siguientes su mayor epidemia de fiebre amarilla de las últimas décadas, alcanzando principalmente la región sudeste. La fiebre amarilla, enfermedad viral hemorrágica, es causada por un flavivirus, transmitido por mosquitos silvestres (Haemagogus; Sabethes). Respecto a la ocurrencia del ciclo urbano, erradicado en Brasil desde 1942, la transmisión se produce por el Aedes aegypti. Primates no humanos son los principales huéspedes del virus, y constituyen "centinelas" en la vigilancia de la fiebre amarilla. Este artículo describe las acciones de control y prevención desencadenadas durante la epidemia de fiebre amarilla en el Estado de Espírito Santo, Brasil, y la implementación de la vacunación mediante un estudio ecológico con abordaje espacial. El estudio evidenció el fallo en la detección de epizootias en primates no humanos por los servicios de vigilancia de Espírito Santo, siendo simultánea a la detección en humanos. Presentó la evolución de las acciones de vacunación, con alcance de un 85% de cobertura en la vacunación general para el estado en seis meses, siendo heterogénea entre los municipios (de 59% a 122%). Se destaca que un 55% de los municipios con acciones de inmunización en tiempo oportuno, considerando el intervalo adoptado para este estudio, no presentaron casos humanos. La intensificación de las acciones de vigilancia, interlocución entre las áreas y equipos multidisciplinarios en la gestión de la epidemia optimizó la detección y diagnóstico de los casos humanos y viabilizó el control de la epidemia. Fue posible reconocer avances, apuntar algunas medidas tardías y lagunas en la vigilancia que necesitan mejorías.

Exploratory study of humoral and cellular immunity to 17DD Yellow Fever vaccination in children and adults residents of areas without circulation of Yellow Fever Virus.

The present investigation comprised two independent observational arms to evaluate the influence of pre-existing flavivirus humoral immunity and the age-impact on 17DD-YF vaccination immunity. Flavivirus (YFV; DENV; ZIKV) serology and YF-specific cellular immunity was evaluated in 288 children/9Mths-4Yrs and 288 adults/18-49Yrs residents of areas without YFV circulation. Data demonstrated that flavivirus seropositivity at baseline was higher in Adults as compared to Children (26%;87%;67% vs 6%;13%;15%, respectively). The heterologous flavivirus seropositivity (DENV; ZIKV) did not impact the YF-specific cellular immune response at baseline. However, higher levels of NCD4, EMCD8, IFN-MCD8, NCD19 and nCMCD19 were observed in subjects with pre-existing YFV seropositivity. Primary vaccination of YFV-seronegative volunteers led to higher levels of YF-neutralizing antibodies in Adults as compared to Younger Children (9Mths-2Yrs). Although similar seropositivity rates observed amongst Children and Adults at D30-45, lower rates were observed in Younger Children (9Mths-2Yrs) at D365 (94%;95%;100% vs 87%;96%;99%, respectively). A progressive decline in antibody levels were reported at D365, being more expressive in Children as compared to Adults. All age-subgroups exhibited at D30-45 increased levels of eEfCD4, EMCD4, IFN-MCD8 and nCMCD19 together with a decrease of eEfCD8 and CMCD8. While an increase of EMCD8 were observed in all subgroups at D30-45, a declined duration at D365 was reported only in Younger Children (9Mths-2Yrs). Biomarker signatures further support that only Younger Children (9Mths-2Yrs) presented a progressive decline of EMCD8 at D365. Together, these findings demonstrated that regardless the similarities observed in YF-neutralizing antibodies, the age impacts the duration of cellular immune response to primary 17DD-YF vaccination.

Homeopathic Treatment of Subclinical Hypothyroidism-A Series of 19 Cases.

BACKGROUND: Subclinical hypothyroidism (SCH) is a common clinical problem. Controversy surrounds the definition, clinical importance, and need for prompt diagnosis and treatment of the mild form of SCH. AIM: The aim of the study was to analyze the evolution of serum thyroid stimulating hormone (TSH) levels after a therapeutic homeopathic intervention in women older than 40 years with SCH. METHODS: This study is a retrospective series of 19 cases of SCH, with serum TSH levels between 5 and 10 mIU/L, treated exclusively with homeopathic medicines prescribed on an individualized basis. RESULTS: Nineteen patients were included according to the inclusion and exclusion criteria. Their mean age was 56 years, they were followed for a mean duration of 69 months, the mean number of serum TSH level measurements was 18, and the intervention was successful for 13 patients. CONCLUSION: The homeopathic therapeutic intervention was successful in 68% of the patients, with serum TSH levels back within the normal range (0.5-5.0 mIU/L).

Prevenção e controle da febre amarela: avaliação de ações de vigilância em área indene no Brasil / Yellow fever prevention and control: assessment of surveillance activities in a previously unaffected area in Brazil / Prevención y control de la fiebre amarilla: evaluación de acciones de vigilancia en un área indemne de Brasil

A partir da reemergência da febre amarela em 2014/2015, o Brasil registrou nos anos sequentes sua maior epidemia de febre amarela das últimas décadas, atingindo principalmente a região sudeste. A febre amarela, doença viral hemorrágica, é causada por um flavivírus, transmitido por mosquitos silvestres (Haemagogus; Sabethes). Na ocorrência do ciclo urbano, erradicado no Brasil desde 1942, a transmissão se dá pelo Aedes aegypti. Primatas não humanos são os principais hospedeiros do vírus e constituem "sentinelas" na vigilância da febre amarela. Este artigo descreve as ações de controle e prevenção desencadeadas durante a epidemia de febre amarela no Estado do Espírito Santo, Brasil, e a implementação da vacinação por meio de um estudo ecológico com abordagem espacial. O estudo evidenciou a falha na detecção de epizootias em primatas não humanos pelos serviços de vigilância do Espírito Santo, sendo simultânea à detecção em humanos. Apresentou a evolução das ações de vacinação, com alcance de 85% de cobertura vacinal geral para o estado em seis meses, sendo heterogênea entre os municípios (de 59% a 122%). Destaca-se que 55% dos municípios com ações de imunização em tempo oportuno, considerando o intervalo adotado para este estudo, não apresentaram casos em humanos. A intensificação das ações de vigilância, interlocução entre as áreas e equipes multidisciplinares na condução da epidemia otimizou a detecção e o diagnóstico dos casos em humanos e viabilizou o controle da epidemia. Foi possível reconhecer avanços, apontar algumas medidas tardias e lacunas na vigilância que necessitam melhorias.

Following the reemergence of yellow fever in 2014/2015, Brazil recorded its largest yellow fever epidemic in recent decades, mainly affecting the country's Southeast region. Yellow fever is a hemorrhagic viral disease caused by a flavivirus transmitted by sylvatic mosquitos (Haemagogus; Sabethes). In the urban cycle, eradicated in Brazil since 1942, the virus is transmitted by Aedes aegypti. Nonhuman primates are the principal hosts of the virus and constitute "sentinels" in yellow fever surveillance. This article describes the control and prevention activities launched during the yellow fever epidemic in the State of Espírito Santo, Brazil, and the implementation of vaccination, through an ecological study with a spatial approach. The study revealed the lack of detection of epizootics in nonhuman primates by surveillance services in Espírito Santo, with simultaneous detection in humans. The study presented the evolution of vaccination activities, reaching 85% overall coverage for the state in six months, varying widely, from 59% to 122%, between municipalities (counties). Importantly, 55% of the municipalities with timely immunization, considering the interval adopted for this study, did not present human cases. The intensification of surveillance activities, communication between areas, and multidisciplinary teams in managing the epidemic optimized the detection and diagnosis of human cases and allowed control of the epidemic. The study identifies progress and points to some late measures and gaps in surveillance that require improvements.

A partir del resurgimiento de la fiebre amarilla en 2014/2015, Brasil registró los años siguientes su mayor epidemia de fiebre amarilla de las últimas décadas, alcanzando principalmente la región sudeste. La fiebre amarilla, enfermedad viral hemorrágica, es causada por un flavivirus, transmitido por mosquitos silvestres (Haemagogus; Sabethes). Respecto a la ocurrencia del ciclo urbano, erradicado en Brasil desde 1942, la transmisión se produce por el Aedes aegypti. Primates no humanos son los principales huéspedes del virus, y constituyen "centinelas" en la vigilancia de la fiebre amarilla. Este artículo describe las acciones de control y prevención desencadenadas durante la epidemia de fiebre amarilla en el Estado de Espírito Santo, Brasil, y la implementación de la vacunación mediante un estudio ecológico con abordaje espacial. El estudio evidenció el fallo en la detección de epizootias en primates no humanos por los servicios de vigilancia de Espírito Santo, siendo simultánea a la detección en humanos. Presentó la evolución de las acciones de vacunación, con alcance de un 85% de cobertura en la vacunación general para el estado en seis meses, siendo heterogénea entre los municipios (de 59% a 122%). Se destaca que un 55% de los municipios con acciones de inmunización en tiempo oportuno, considerando el intervalo adoptado para este estudio, no presentaron casos humanos. La intensificación de las acciones de vigilancia, interlocución entre las áreas y equipos multidisciplinarios en la gestión de la epidemia optimizó la detección y diagnóstico de los casos humanos y viabilizó el control de la epidemia. Fue posible reconocer avances, apuntar algunas medidas tardías y lagunas en la vigilancia que necesitan mejorías.

[Mortality and causes of deaths in prisons in Rio de Janeiro, Brazil]. / Mortalidade e causas de óbitos nas prisões do Rio de Janeiro, Brasil.

Mortality in prisons, a basic indicator of the right to health for incarcerated persons, has never been studied extensively in Brazil. An assessment of all-cause and cause-specific mortality in prison inmates was conducted in 2016-2017 in the state of Rio de Janeiro, based on data from the Mortality Information System and Prison Administration. Mortality rates were compared between prison population and general population after standardization. The leading causes of death in inmates were infectious diseases (30%), cardiovascular diseases (22%), and external causes (12%). Infectious causes featured HIV/AIDS (43%) and TB (52%, considering all deaths with mention of TB). Only 0.7% of inmates who died had access to extramural health services. All-cause mortality rate was higher among prison inmates than in the state's general population. Among inmates, mortality from infectious diseases was 5 times higher, from TB 15 times higher, and from endocrine diseases (especially diabetes) and cardiovascular diseases 1.5 and 1.3 times higher, respectively, while deaths from external causes were less frequent in prison inmates. The study revealed important potentially avoidable excess deaths in prisons, reflecting lack of care and exclusion of this population from the Brazilian Unified National Health System. This further highlights the need for a precise and sustainable real-time monitoring system for deaths, in addition to restructuring of the prison staff through implementation of the Brazilian National Policy for Comprehensive Healthcare for Persons Deprived of Freedom in the Prison System in order for inmates to fully access their constitutional right to health with the same quality and timeliness as the general population.

A mortalidade nas prisões, indicador fundamental do direito à saúde das pessoas privadas de liberdade (PPL), nunca foi estudada de maneira aprofundada no Brasil. A avaliação da mortalidade global e por causas entre PPL encarceradas em 2016-2017 no Estado do Rio de Janeiro, foi realizada a partir de dados do Sistema de Informações sobre Mortalidade e da Administração Penitenciária. Taxas de mortalidade entre PPL e população geral do estado foram comparadas após padronização. As principais causas de morte entre PPL foram doenças infecciosas (30%), doenças do aparelho circulatório (22%) e causas externas (12%). Dentre as causas infecciosas, destacam-se HIV/aids (43%) e tuberculose (TB) (52% se considerados todos os óbitos com menção de TB). Somente 0,7% das PPL que faleceram tiveram acesso a serviço de saúde extramuros. A taxa global de mortalidade foi maior entre as PPL comparadas à população geral do estado, com mortalidade por doenças infecciosas 5 vezes superior, por TB 15 vezes e por doenças endócrinas, especialmente diabetes, e doenças circulatórias (1,5 e 1,3 vez, respectivamente), enquanto mortes por causa externa foram menos frequentes entre PPL. Este estudo mostra um expressivo excesso de mortes potencialmente evitáveis nas prisões, o que traduz importante desassistência e exclusão dessa população do Sistema Único de Saúde. Evidencia a necessidade de um sistema de monitoramento, em tempo real, dos óbitos, preciso e sustentável, além da reestruturação da saúde prisional por meio da efetivação da Política Nacional de Atenção Integral à Saúde das Pessoas Privadas de Liberdade no Sistema Prisional para que as PPL usufruam do direito constitucional à saúde em sua integralidade, com a mesma qualidade e tempestividade oferecida à população geral.

La mortalidad en las prisiones, indicador fundamental del derecho a la salud de personas privadas de libertad (PPL), nunca se estudió profundamente en Brasil. La evaluación de la mortalidad global y por causas entre PPL, encarceladas en 2016-2017 en el estado de Rio de Janeiro, se realizó a partir de datos del Sistema de Información de Mortalidad y la Administración Penitenciaria. Se compararon las tasas de mortalidad entre PPL y población general del estado tras la estandarización. Las principales causas de muerte entre PPL fueron: enfermedades infecciosas (30%), enfermedades del aparato circulatorio (22%) y causas externas (12%). Entre las causas infecciosas, se destacan VIH/sida (43%) y tuberculosis (TB) (52%, si se consideran todos los óbitos con mención TB). Solamente un 0,7% de las PPL que fallecieron tuvieron acceso a un servicio de salud extramuros. La tasa global de mortalidad fue mayor entre las PPL, comparada con la población general del estado. Entre las PPL, la mortalidad por enfermedades infecciosas fue 5 veces superior, por TB 15 veces, y por enfermedades endocrinas, especialmente diabetes, y enfermedades circulatorias (1,5 y 1,3 veces respectivamente), mientras que las muertes por causa externa fueron menos frecuentes entre PPLs. Este estudio muestra un expresivo exceso de muertes potencialmente evitables en las prisiones, lo que se traduce en una importante desasistencia y la exclusión de esta población del Sistema Único de Salud. Pone en evidencia la necesidad de un sistema de supervisión en tiempo real de los óbitos, preciso y sostenible, además de la reestructuración de la salud en las prisiones, mediante la efectivización de la Política Nacional de Atención Integral a la Salud de las Personas Privadas de Libertad en el Sistema Penitenciario para que las PPLs disfruten del derecho constitucional a la salud en su integridad, con la misma calidad y oportunidad ofrecida a la población general.

[Impact of calendar effect on morbidity and mortality from external causes in tourist towns in the State of São Paulo, Brazil, from 2004 to 2014]. / Impacto do efeito calendário na morbimortalidade por causas externas em municípios turísticos no Estado de São Paulo, Brasil, no período de 2004 a 2014.

This study aims to analyze the association between temporal variations in injuries and deaths from external causes and periods of greater flow of visitors in tourist municipalities (counties) on the coastline of the state of São Paulo, Brazil, from 2004 to 2014. This is an ecological study of daily and monthly time series based on data from the Brazilian Mortality Information System (SIM) and Brazilian Hospital Information System of the Brazilian Unified National Health System (SIH/SUS) from January 1, 2004, to December 31, 2014, using as the analytical units the four municipalities on the northern coast of the State of São Paulo. Negative binomial regression models were adjusted for the outcome that represented the number of hospital admissions and/or deaths from external causes, with calendar variables as predictors (days of the week, holidays, month, and year of occurrence). The Brazilian holidays New Year's Day, Carnival, Tiradentes, and Proclamation of the Republic stood out with mean numbers greater than or equal to 5 outcomes per day. Among the days of the week, Monday and Sunday had the highest mean numbers. Considering all the predictors, there was a higher tendency to the occurrence of outcomes on Monday (OR = 1.11; 95%CI: 1.05-1.18), New Year's Day (OR = 1.44; 95%CI: 1.19-1.74), and Proclamation of the Republic Day (OR = 1.49; 95%CI: 1.13-1.94) and in the months of January (OR = 1.11; 95%CI: 1.02-1.20) and February (OR = 1.13; 95%CI: 1.04-1.23). Morbidity and mortality from external causes in these tourist towns were higher in the period with the greatest flow of tourists, emphasizing the need to organize care for these injuries, alongside measures for prevention and health promotion targeted to this group of causes.

O objetivo desta pesquisa é analisar a associação de variações temporais dos agravos e das mortes por causas externas com períodos de maior fluxo de visitantes em municípios turísticos do litoral de São Paulo, Brasil, no período de 2004 a 2014. Trata-se de um estudo ecológico, de séries temporais diárias e mensais, baseado nos dados do Sistema de Informações sobre Mortalidade (SIM) e Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS) no período de 1º de janeiro de 2004 a 31 de dezembro de 2014, tendo como unidades de análise os quatro municípios do litoral norte do Estado de São Paulo. Modelos de regressão binomial negativa foram ajustados para o desfecho que representou o número de ocorrências de internações hospitalares e/ou óbitos por causas externas, tendo como preditores as variáveis de calendário (dias da semana, feriados, mês e ano de ocorrência). Os feriados de Ano Novo, Carnaval, Tiradentes e Proclamação da República destacaram-se com médias iguais ou superiores a 5 desfechos por dia. Dentre os dias da semana, a segunda-feira e o domingo apresentaram as maiores médias. Levando em consideração todos os preditores, verifica-se maior tendência de ocorrência dos desfechos na segunda-feira (OR = 1,11; IC95%: 1,05-1,18), nos feriados de Ano Novo (OR = 1,44; IC95%: 1,19-1,74) e Proclamação da República (OR = 1,49; IC95%: 1,13-1,94) e nos meses de janeiro (OR = 1,11; IC95%: 1,02-1,20) e fevereiro (OR = 1,13; IC95%: 1,04-1,23). A morbidade e a mortalidade por causas externas nos municípios estudados foram maiores no período de maior movimentação de turistas, subsidiando a estruturação do atendimento destas lesões e as ações de prevenção e de promoção de saúde direcionadas para este grupo de causas.

El objetivo de esta investigación es analizar la asociación de variaciones temporales en enfermedades y muertes por causas externas, durante períodos de mayor flujo de visitantes en municipios turísticos del litoral de São Paulo, Brasil, durante el período de 2004 a 2014. Se trata de un estudio ecológico, de series temporales diarias y mensuales, basado en los datos del Sistema de Información sobre Mortalidad (SIM) y Sistema de Informaciones Hospitalarias del Sistema Único de Salud (SIH/SUS), durante el período del 1º de enero de 2004 al 31 de diciembre de 2014, teniendo como unidades de análisis los cuatro municipios del litoral norte del Estado de São Paulo. Modelos de regresión binomial negativa se ajustaron al resultado que representó el número de ocurrencias de internamientos hospitalarios y/u óbitos por causas externas, teniendo como predictores variables de calendario (días de la semana, festivos, mes y año de ocurrencia). Los festivos de Año Nuevo, Carnaval, Tiradentes y Proclamación de la República se destacaron con medias iguales o superiores a 5 resultados por día. Entre los días de la semana, el lunes y el domingo presentaron las mayores medias. Teniendo en consideración todos los predictores, se verifica una mayor tendencia de ocurrencia de los resultados: los lunes (OR = 1,11; IC95%: 1,05-1,18), festivo de Año Nuevo (OR = 1,44; IC95%: 1,19-1,74) y Proclamación de la República (OR = 1,49; IC95%: 1,13-1,94) y, en los meses de enero (OR = 1,11; IC95%: 1,02-1,20) y de febrero (OR = 1,13; IC95%: 1,04-1,23). La morbilidad y mortalidad por causas externas en los municipios estudiados fueron mayores en el período de mayor movimiento de turistas, apoyando la organización de la atención a esas lesiones, así como acciones de prevención y promoción de salud dirigidas hacia este grupo de causas.

Impacto do efeito calendário na morbimortalidade por causas externas em municípios turísticos no Estado de São Paulo, Brasil, no período de 2004 a 2014 / Impact of calendar effect on morbidity and mortality from external causes in tourist towns in the State of São Paulo, Brazil, from 2004 to 2014 / Impacto del efecto calendario en la morbimortalidad por causas externas en municipios turísticos en el Estado de São Paulo, Brasil, durante el período de 2004 a 2014

O objetivo desta pesquisa é analisar a associação de variações temporais dos agravos e das mortes por causas externas com períodos de maior fluxo de visitantes em municípios turísticos do litoral de São Paulo, Brasil, no período de 2004 a 2014. Trata-se de um estudo ecológico, de séries temporais diárias e mensais, baseado nos dados do Sistema de Informações sobre Mortalidade (SIM) e Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS) no período de 1º de janeiro de 2004 a 31 de dezembro de 2014, tendo como unidades de análise os quatro municípios do litoral norte do Estado de São Paulo. Modelos de regressão binomial negativa foram ajustados para o desfecho que representou o número de ocorrências de internações hospitalares e/ou óbitos por causas externas, tendo como preditores as variáveis de calendário (dias da semana, feriados, mês e ano de ocorrência). Os feriados de Ano Novo, Carnaval, Tiradentes e Proclamação da República destacaram-se com médias iguais ou superiores a 5 desfechos por dia. Dentre os dias da semana, a segunda-feira e o domingo apresentaram as maiores médias. Levando em consideração todos os preditores, verifica-se maior tendência de ocorrência dos desfechos na segunda-feira (OR = 1,11; IC95%: 1,05-1,18), nos feriados de Ano Novo (OR = 1,44; IC95%: 1,19-1,74) e Proclamação da República (OR = 1,49; IC95%: 1,13-1,94) e nos meses de janeiro (OR = 1,11; IC95%: 1,02-1,20) e fevereiro (OR = 1,13; IC95%: 1,04-1,23). A morbidade e a mortalidade por causas externas nos municípios estudados foram maiores no período de maior movimentação de turistas, subsidiando a estruturação do atendimento destas lesões e as ações de prevenção e de promoção de saúde direcionadas para este grupo de causas.

This study aims to analyze the association between temporal variations in injuries and deaths from external causes and periods of greater flow of visitors in tourist municipalities (counties) on the coastline of the state of São Paulo, Brazil, from 2004 to 2014. This is an ecological study of daily and monthly time series based on data from the Brazilian Mortality Information System (SIM) and Brazilian Hospital Information System of the Brazilian Unified National Health System (SIH/SUS) from January 1, 2004, to December 31, 2014, using as the analytical units the four municipalities on the northern coast of the State of São Paulo. Negative binomial regression models were adjusted for the outcome that represented the number of hospital admissions and/or deaths from external causes, with calendar variables as predictors (days of the week, holidays, month, and year of occurrence). The Brazilian holidays New Year's Day, Carnival, Tiradentes, and Proclamation of the Republic stood out with mean numbers greater than or equal to 5 outcomes per day. Among the days of the week, Monday and Sunday had the highest mean numbers. Considering all the predictors, there was a higher tendency to the occurrence of outcomes on Monday (OR = 1.11; 95%CI: 1.05-1.18), New Year's Day (OR = 1.44; 95%CI: 1.19-1.74), and Proclamation of the Republic Day (OR = 1.49; 95%CI: 1.13-1.94) and in the months of January (OR = 1.11; 95%CI: 1.02-1.20) and February (OR = 1.13; 95%CI: 1.04-1.23). Morbidity and mortality from external causes in these tourist towns were higher in the period with the greatest flow of tourists, emphasizing the need to organize care for these injuries, alongside measures for prevention and health promotion targeted to this group of causes.

El objetivo de esta investigación es analizar la asociación de variaciones temporales en enfermedades y muertes por causas externas, durante períodos de mayor flujo de visitantes en municipios turísticos del litoral de São Paulo, Brasil, durante el período de 2004 a 2014. Se trata de un estudio ecológico, de series temporales diarias y mensuales, basado en los datos del Sistema de Información sobre Mortalidad (SIM) y Sistema de Informaciones Hospitalarias del Sistema Único de Salud (SIH/SUS), durante el período del 1º de enero de 2004 al 31 de diciembre de 2014, teniendo como unidades de análisis los cuatro municipios del litoral norte del Estado de São Paulo. Modelos de regresión binomial negativa se ajustaron al resultado que representó el número de ocurrencias de internamientos hospitalarios y/u óbitos por causas externas, teniendo como predictores variables de calendario (días de la semana, festivos, mes y año de ocurrencia). Los festivos de Año Nuevo, Carnaval, Tiradentes y Proclamación de la República se destacaron con medias iguales o superiores a 5 resultados por día. Entre los días de la semana, el lunes y el domingo presentaron las mayores medias. Teniendo en consideración todos los predictores, se verifica una mayor tendencia de ocurrencia de los resultados: los lunes (OR = 1,11; IC95%: 1,05-1,18), festivo de Año Nuevo (OR = 1,44; IC95%: 1,19-1,74) y Proclamación de la República (OR = 1,49; IC95%: 1,13-1,94) y, en los meses de enero (OR = 1,11; IC95%: 1,02-1,20) y de febrero (OR = 1,13; IC95%: 1,04-1,23). La morbilidad y mortalidad por causas externas en los municipios estudiados fueron mayores en el período de mayor movimiento de turistas, apoyando la organización de la atención a esas lesiones, así como acciones de prevención y promoción de salud dirigidas hacia este grupo de causas.