Dengue Fever Surveillance in Mato Grosso do Sul: Insights from Genomic Analysis and Implications for Public Health Strategies.

Since its discovery in early 1916, dengue fever, a common vector-borne illness in Brazil, has resulted in extensive urban outbreaks and poses a serious threat to the public's health. Understanding the dynamics of Dengue Virus (DENV) serotypes circulating in different regions of Brazil is essential for implementing effective disease control and prevention measures. In response to this urgent need, we conducted an on-site training program in genomic surveillance in collaboration with the Central Laboratory of Health and the Secretary of Health of the Mato Grosso do Sul state. This initiative resulted in the generation of 177 DENV genome sequences collected between May 2021 and May 2022, a period during which over 11,391 dengue fever cases were reported in the state. Through this approach, we were able to identify the co-circulation of two different dengue serotypes (DENV1 and DENV2) as well as the existence of diverse viral lineages within each genotype, suggesting that multiple introduction events of different viral strains occurred in the region. By integrating epidemiological data, our findings unveiled temporal fluctuations in the relative abundance of different serotypes throughout various epidemic seasons, highlighting the complex and changing dynamics of DENV transmission throughout time. These findings demonstrate the value of ongoing surveillance activities in tracking viral transmission patterns, monitoring viral evolution, and informing public health actions.

Unveiling the Impact of the Omicron Variant: Insights from Genomic Surveillance in Mato Grosso do Sul, Midwest Brazil.

Genomic surveillance has emerged as a crucial tool in monitoring and understanding the dynamics of viral variants during the COVID-19 pandemic. In the Midwest region of Brazil, Mato Grosso do Sul has faced a significant burden from the SARS-CoV-2 epidemic, with a total of 613,000 confirmed cases as of June 2023. In collaboration with the Central Public Health Laboratory in the capital city of Campo Grande, we conducted a portable whole-genome sequencing and phylodynamic analysis to investigate the circulation of the Omicron variant in the region. The study aimed to uncover the genomic landscape and provide valuable insights into the prevalence and transmission patterns of this highly transmissible variant. Our findings revealed an increase in the number of cases within the region during 2022, followed by a gradual decline as a result of the successful impact of the vaccination program together with the capacity of this unpredictable and very transmissible variant to quickly affect the proportion of susceptible population. Genomic data indicated multiple introduction events, suggesting that human mobility played a differential role in the variant's dispersion dynamics throughout the state. These findings emphasize the significance of implementing public health interventions to mitigate further spread and highlight the powerful role of genomic monitoring in promptly tracking and uncovering the circulation of viral strains. Together those results underscore the importance of proactive surveillance, rapid genomic sequencing, and data sharing to facilitate timely public health responses.

Serum soluble mediators as prognostic biomarkers for morbidity, disease outcome, and late-relapsing hepatitis in yellow fever patients.

This study described a soluble mediator storm in acute Yellow Fever/YF infection along the kinetics timeline towards convalescent disease. The analyses of the YF Viral RNAnemia, chemokines, cytokines, and growth factors were performed in YF patients at acute/(D1-15) and convalescent/(D16-315) phases. Patients with acute YF infection displayed a trimodal viremia profile spreading along D3, D6, and D8-14. A massive storm of mediators was observed in acute YF. Higher levels of mediators were observed in YF with higher morbidity scores, patients under intensive care, and those progressing to death than in YF patients who progress to late-relapsing hepatitis/L-Hep. A unimodal peak of biomarkers around D4-6 with a progressive decrease towards D181-315 was observed in non-L-Hep patients, while a bimodal pattern with a second peak around D61-90 was associated with L-Hep. This study provided a comprehensive landscape of evidence that distinct immune responses drive pathogenesis, disease progression, and L-Hep in YF patients.

Retrospective Investigation in Horses with Encephalitis Reveals Unnoticed Circulation of West Nile Virus in Brazil.

During these past years, several studies have provided serological evidence regarding the circulation of West Nile virus (WNV) in Brazil. Despite some reports, much is still unknown regarding the genomic diversity and transmission dynamics of this virus in the country. Recently, genomic monitoring activities in horses revealed the circulation of WNV in several Brazilian regions. These findings on the paucity of genomic data reinforce the need for prompt investigation of WNV infection in horses, which may precede human cases of encephalitis in Brazil. Thus, in this study, we retrospectively screened 54 suspicious WNV samples collected between 2017 and 2020 from the spinal cord and brain of horses with encephalitis and generated three new WNV genomes from the Ceará and Bahia states, located in the northeastern region of Brazil. The Bayesian reconstruction revealed that at least two independent introduction events occurred in Brazil. The first introduction event appears to be likely related to the North American outbreak, and was estimated to have occurred in March 2013.The second introduction event appears to have occurred in September 2017 and appears to be likely related to the South American outbreak. Together, our results reinforce the importance of increasing the priority of WNV genomic monitoring in equines with encephalitis in order to track the dispersion of this emerging pathogen through the country.

Replacement of the Gamma by the Delta variant in Brazil: Impact of lineage displacement on the ongoing pandemic.

The coronavirus disease 2019 (COVID-19) epidemic in Brazil was driven mainly by the spread of Gamma (P.1), a locally emerged variant of concern (VOC) that was first detected in early January 2021. This variant was estimated to be responsible for more than 96 per cent of cases reported between January and June 2021, being associated with increased transmissibility and disease severity, a reduction in neutralization antibodies and effectiveness of treatments or vaccines, and diagnostic detection failure. Here we show that, following several importations predominantly from the USA, the Delta variant rapidly replaced Gamma after July 2021. However, in contrast to what was seen in other countries, the rapid spread of Delta did not lead to a large increase in the number of cases and deaths reported in Brazil. We suggest that this was likely due to the relatively successful early vaccination campaign coupled with natural immunity acquired following prior infection with Gamma. Our data reinforce reports of the increased transmissibility of the Delta variant and, considering the increasing concern due to the recently identified Omicron variant, argues for the necessity to strengthen genomic monitoring on a national level to quickly detect the emergence and spread of other VOCs that might threaten global health.

Genomic epidemiology of the SARS-CoV-2 epidemic in Brazil

The high numbers of COVID-19 cases and deaths in Brazil have made Latin America an epicentre of the pandemic. SARS-CoV-2 established sustained transmission in Brazil early in the pandemic, but important gaps remain in our understanding of virus transmission dynamics at a national scale. We use 17,135 near-complete genomes sampled from 27 Brazilian states and bordering country Paraguay. From March to November 2020, we detected co-circulation of multiple viral lineages that were linked to multiple importations (predominantly from Europe). After November 2020, we detected large, local transmission clusters within the country. In the absence of effective restriction measures, the epidemic progressed, and in January 2021 there was emergence and onward spread, both within and abroad, of variants of concern and variants under monitoring, including Gamma (P.1) and Zeta (P.2). We also characterized a genomic overview of the epidemic in Paraguay and detected evidence of importation of SARS-CoV-2 ancestor lineages and variants of concern from Brazil. Our findings show that genomic surveillance in Brazil enabled assessment of the real-time spread of emerging SARS-CoV-2 variants.

CCL3, CCL5, IL-15, IL-1Ra and VEGF compose a reliable algorithm to discriminate classes of adverse events following 17DD-YF primary vaccination according to cause-specific definitions.

In the present study, a range of serum biomarkers were quantified in suspected cases of adverse events following YF immunization (YEL-AEFI) to propose a reliable laboratorial algorithm to discriminate confirmed YEL-AEFI ("A1" class) from cases with other illnesses ("C" class). Our findings demonstrated that increased levels of CXCL8, CCL2, CXCL10, IL-1ß, IL-6 and TNF-α were observed in YEL-AEFI ("A1" and "C" classes) as compared to primary vaccines without YEL-AEFI [PV(day 3-28)] and reference range (RR) controls. Notably, increased levels of CCL3, CCL4, CCL2, CCL5, IL-1ß, IL-15, IL-1Ra and G-CSF were found in "A1" as compared to "C" class. Venn diagrams analysis allowed the pre-selection of biomarkers for further analysis of performance indices. Data demonstrated that CCL3, CCL5, IL-15 and IL-1Ra presented high global accuracy (AUC = 1.00) to discriminate "A1" from "C". Decision tree was proposed with a reliable algorithm to discriminate YEL-AEFI cases according to cause-specific definitions with outstanding overall accuracy (91%). CCL3, CCL5, IL-15 and IL-1Ra appears as root attributes to identify "A1" followed by VEGF as branch nodes to discriminate Wild Type YFV infection ("C(WT-YFV)") from cases with other illnesses ("C*"). Together, these results demonstrated the applicability of serum biomarker measurements as putative parameters towards the establishment of accurate laboratorial tools for complementary differential diagnosis of YEL-AEFI cases.

Field and classroom initiatives for portable sequence-based monitoring of dengue virus in Brazil.

Brazil experienced a large dengue virus (DENV) epidemic in 2019, highlighting a continuous struggle with effective control and public health preparedness. Using Oxford Nanopore sequencing, we led field and classroom initiatives for the monitoring of DENV in Brazil, generating 227 novel genome sequences of DENV1-2 from 85 municipalities (2015-2019). This equated to an over 50% increase in the number of DENV genomes from Brazil available in public databases. Using both phylogenetic and epidemiological models we retrospectively reconstructed the recent transmission history of DENV1-2. Phylogenetic analysis revealed complex patterns of transmission, with both lineage co-circulation and replacement. We identified two lineages within the DENV2 BR-4 clade, for which we estimated the effective reproduction number and pattern of seasonality. Overall, the surveillance outputs and training initiative described here serve as a proof-of-concept for the utility of real-time portable sequencing for research and local capacity building in the genomic surveillance of emerging viruses.

Chikungunya virus ECSA lineage reintroduction in the northeasternmost region of Brazil.

The Northeast region of Brazil registered the second-highest incidence proportion of Chikungunya fever in 2019. In that year, an outbreak consisting of patients presenting with febrile disease associated with joint pain was reported by the public primary health care service in the city of Natal, in the state of Rio Grande do Norte, in March 2019. At first, the aetiological agent of the disease was undetermined. Since much is still unknown about chikungunya virus' (CHIKV) genomic diversity and evolutionary history in this northeasternmost state, we used a combination of portable whole-genome sequencing, molecular clock, and epidemiological analyses that revealed the reintroduction of the CHIKV East-Central-South-African (ECSA) lineage into Rio Grande do Norte. We estimated that the CHIKV ECSA lineage was first introduced into Rio Grande do Norte in early June 2014, while the 2019 outbreak clade diverged around April 2018, during a period of increased Chikungunya incidence in the Southeast region, which might have acted as a source of virus dispersion towards the Northeast region. Together, these results confirm that the ECSA lineage continues to spread across the country through interregional importation events, likely mediated by human mobility.

Yellow fever transmission in non-human primates, Bahia, Northeastern Brazil.

Yellow fever virus (YFV) causes a clinical syndrome of acute hemorrhagic hepatitis. YFV transmission involves non-human primates (NHP), mosquitoes and humans. By late 2016, Brazil experienced the largest YFV outbreak of the last 100 years, with 2050 human confirmed cases, with 681 cases ending in death and 764 confirmed epizootic cases in NHP. Among affected areas, Bahia state in Northeastern was the only region with no autochthonous human cases. By using next generation sequence approach, we investigated the molecular epidemiology of YFV in NHP in Bahia and discuss what factors might have prevented human cases. We investigated 47 YFV positive tissue samples from NHP cases to generate 8 novel YFV genomes. ML phylogenetic tree reconstructions and automated subtyping tools placed the newly generated genomes within the South American genotype I (SA I). Our analysis revealed that the YFV genomes from Bahia formed two distinct well-supported phylogenetic clusters that emerged most likely of an introduction from Minas Gerais and Espírito Santo states. Vegetation coverage analysis performed shows predominantly low to medium vegetation coverage in Bahia state. Together, our findings support the hypothesis of two independent YFV SA-I introductions. We also highlighted the effectiveness of the actions taken by epidemiological surveillance team of the state to prevented human cases.

Febre maculosa na Região Metropolitana de Belo Horizonte, Minas Gerais - Brasil: Descrição dos casos e dos ambientes prováveis de infecção, 2017 / Spotted fever in the Metropolitan Region of Belo Horizonte, Minas Gerais - Brazil: Description of cases and probable environments of infection, 2017

Objetivo: investigar os casos de febre maculosa, verificar os aspectos relacionados à assistência à saúde e caracterizar o perfil epidemiológico desses e do ambiente de infecção. Métodos: estudo descritivo dos casos confirmados de FM entre janeiro e novembro de 2017. Foi elaborado um formulário semiestruturado para coleta dos dados. Para as análises epidemiológicas, foram utilizados os programas EpiInfoTM 7 e Qgis® 2.18.1. Foram calculadas frequências, medidas de tendência central, dispersão e indicadores de oportunidade de assistência. Nos ambientes prováveis de infecção, foram realizadas coletas de carrapatos que foram identificados e submetidos à pesquisa de Rickettsia do grupo da FM. Resultados: foram confirmados 15 casos de FM; desses, a maioria foi do sexo masculino (93%) com média de 42 anos de idade; 10 evoluíram para óbito. Todos apresentaram febre, 13(87%) cefaleia e 12(80%) mialgia. Apresentaram mediana e média de evolução para óbito pela doença de 6 dias (1 a 9), oportunidades de hospitalização, tratamento, diagnóstico e notificação de 4,5(0 a 8); 7(0 a 26); 9(DP±6) e 33(DP±45) dias, respectivamente. Para assistência à saúde, 14(93%) casos procuraram atendimento mais de duas vezes, com tempo de internação de 4,5 dias (0 a 8 dias). O hospital foi o serviço procurado, exclusivamente, no quarto atendimento. Dengue e FM foram as hipóteses diagnósticas mais frequentes. Foram coletados 250 espécimes de carrapatos em quatro municípios, sendo em um município identificado Amblyomma sculptum naturalmente infectados. Conclusões: foram assinaladas condições assistenciais pouco sensíveis à ocorrência da FM, o que, provavelmente, colaborou para ocorrência de óbitos, além da necessidade de sensibilização de equipes de saúde e vigilância quanto à ocorrência da FM na região.

Objective: investigate the cases of spotted fever, verify aspects related to health care and characterize the epidemiological profile of these and of the environment of infection. Methods: A descriptive study of confirmed cases of SF between January and November 2017. A semi-structured form for data collection was developed. EpiInfoTM 7 and Qgis® 2.18.1. Frequencies, measures of central tendency, dispersion and indicators of opportunity of assistance were calculated. In the probable environments of infection ticks were collected, identified and submitted to Rickettsia research of the SF group. Results: Fifteen SF cases were confirmed; of these, the majority was male (93%) and averaged 42 years old; 10 evolved to death. All presented fever, 13 (87%) headache and 12 (80%) myalgia. They presented an average of evolution to death by SF of 6 days (1 to 9), opportunities for hospitalization, treatment, diagnosis and notification of 4.5(0 to 8); 7(0 to 26); 9(DP± 6) and 33(DP± 45) days respectively. For health care, 14(93%) cases sought care more than twice and were hospitalized for 4.5-days (0 to 8 days). The hospital was the only service exclusively sought in the fourth service. Dengue and SF were the most frequent diagnostic hypotheses. A total of 250 specimens of ticks were collected in four counties, and in one municipality Amblyomma sculptum was identified as naturally infected. Conclusions: It was pointed out that assistance conditions were not very sensitive to the occurrence of SF which probably contributed to the instance of deaths as well as the need for sensitization of health and surveillance teams regarding the appearance of SF in the region.

Return of the founder Chikungunya virus to its place of introduction into Brazil is revealed by genomic characterization of exanthematic disease cases.

Between June 2017 and August 2018, several municipalities located in Bahia state (Brazil) reported a large increase in the number of patients presenting with febrile illness similar to that of arboviral infections. Using a combination of portable whole genome sequencing, molecular clock and epidemiological analyses, we revealed the return of the CHIKV-ECSA genotype into Bahia. Our results show local persistence of lineages in some municipalities and the re-introduction of new epidemiological strains from different Brazilian regions, highlighting a complex dynamic of transmission between epidemic seasons and sampled locations. Estimated climate-driven transmission potential of CHIKV remained at similar levels throughout the years, such that large reductions in the total number of confirmed cases suggests a slow, but gradual accumulation of herd-immunity over the 4 years of the epidemic in Bahia after its introduction in 2014. Bahia remains a reservoir of the genetic diversity of CHIKV in the Americas, and genomic surveillance strategies are essential to assist in monitoring and understanding arboviral transmission and persistence both locally and over large distances.

Yellow Fever Virus Genotyping Tool and Investigation of Suspected Adverse Events Following Yellow Fever Vaccination.

The yellow fever (YF) vaccine consists of an attenuated virus, and despite its relative safety, some adverse events following YF vaccination have been described. At the end of 2016, Brazil experienced the most massive sylvatic yellow fever outbreak over the last 70 years and an intense campaign of YF vaccination occurred in Minas Gerais state in Southeast Brazil from 2016 to 2018. The present study aimed to develop a genotyping tool and investigate 21 cases of suspected adverse events following YF vaccination. Initial in silico analyses were performed using partial NS5 nucleotide sequences to verify the discriminatory potential between wild-type and vaccine viruses. Samples from patients were screened for the presence of the YFV RNA, using 5'UTR as the target, and then used for amplification of partial NS5 gene amplification, sequencing, and phylogenetic analysis. Genotyping indicated that 17 suspected cases were infected by the wild-type yellow fever virus, but four cases remained inconclusive. The genotyping tool was efficient in distinguishing the vaccine from wild-type virus, and it has the potential to be used for the differentiation of all yellow fever virus genotypes.

Yellow Fever Virus Reemergence and Spread in Southeast Brazil, 2016-2019.

The recent reemergence of yellow fever virus (YFV) in Brazil has raised serious concerns due to the rapid dissemination of the virus in the southeastern region. To better understand YFV genetic diversity and dynamics during the recent outbreak in southeastern Brazil, we generated 18 complete and nearly complete genomes from the peak of the epidemic curve from nonhuman primates (NHPs) and human infected cases across the Espírito Santo and Rio de Janeiro states. Genomic sequencing of 18 YFV genomes revealed the estimated timing, source, and likely routes of yellow fever virus transmission and dispersion during one of the largest outbreaks ever registered in Brazil. We showed that during the recent epidemic, YFV was reintroduced from Minas Gerais to the Espírito Santo and Rio de Janeiro states multiple times between 2016 and 2019. The analysis of data from portable sequencing could identify the corridor of spread of YFV. These findings reinforce the idea that continued genomic surveillance strategies can provide information on virus genetic diversity and transmission dynamics that might assist in understanding arbovirus epidemics.IMPORTANCE Arbovirus infections in Brazil, including yellow fever, dengue, zika, and chikungunya, result in considerable morbidity and mortality and are pressing public health concerns. However, our understanding of these outbreaks is hampered by the limited availability of genomic data. In this study, we investigated the genetic diversity and spatial distribution of YFV during the current outbreak by analyzing genomic data from areas in southeastern Brazil not covered by other previous studies. To gain insights into the routes of YFV introduction and dispersion, we tracked the virus by sequencing YFV genomes sampled from nonhuman primates and infected patients from the southeastern region. Our study provides an understanding of how YFV initiates transmission in new Brazilian regions and illustrates that genomics in the field can augment traditional approaches to infectious disease surveillance and control.

Haemagogus leucocelaenus and Haemagogus janthinomys are the primary vectors in the major yellow fever outbreak in Brazil, 2016-2018.

The yellow fever virus (YFV) caused a severe outbreak in Brazil in 2016-2018 that rapidly spread across the Atlantic Forest in its most populated region without viral circulation for almost 80 years. A comprehensive entomological survey combining analysis of distribution, abundance and YFV natural infection in mosquitoes captured before and during the outbreak was conducted in 44 municipalities of five Brazilian states. In total, 17,662 mosquitoes of 89 species were collected. Before evidence of virus circulation, mosquitoes were tested negative but traditional vectors were alarmingly detected in 82% of municipalities, revealing high receptivity to sylvatic transmission. During the outbreak, five species were found positive in 42% of municipalities. Haemagogus janthinomys and Hg. leucocelaenus are considered the primary vectors due to their large distribution combined with high abundance and natural infection rates, concurring together for the rapid spread and severity of this outbreak. Aedes taeniorhynchus was found infected for the first time, but like Sabethes chloropterus and Aedes scapularis, it appears to have a potential local or secondary role because of their low abundance, distribution and infection rates. There was no evidence of YFV transmission by Aedes albopictus and Aedes aegypti, although the former was the most widespread species across affected municipalities, presenting an important overlap between the niches of the sylvatic vectors and the anthropic ones. The definition of receptive areas, expansion of vaccination in the most affected age group and exposed populations and the adoption of universal vaccination to the entire Brazilian population need to be urgently implemented.

Emergence of chikungunya and Zika in a municipality endemic to dengue, Santa Luzia, MG, Brazil, 2015-2017.

INTRODUCTION: The recent circulation of arboviruses transmitted by vectors, such as dengue, chikungunya, and Zika, is concerning due to the high morbidity rates, clinical complications, and increased demand on health services. The objective of this study was to analyze the clinical and epidemiological aspects of an epidemic caused by arboviruses in the municipality of Santa Luzia, Minas Gerais, Brazil. METHODS: Longitudinal study of patients with acute febrile disease and suspected arbovirus infection reported to Brazilian Notifiable Disease Information System (Sistema de Informação de Agravos de Notificação) from the epidemiological week 44 of 2015 to epidemiological week 52 of 2016. Patients with confirmed chikungunya were followed-up for 18 months and those with Zika for 15 months. Additionally, we analyzed and described the temporal distribution of confirmed cases of these arboviruses in this municipality. RESULTS: Overall 3,531 arboviruses cases, including 3,481 (98.7%) cases of dengue, 38 (1.0%) cases of chikungunya, and 12 (0.3%) cases of Zika were confirmed. The highest incidence of arbovirus infection occurred in the first quarter of 2016 (epidemiological week 7 to 14). The most frequent symptoms were for dengue, which included fever, headache, retro-orbital pain, and exanthema. Chikungunya infection was associated with fever, myalgia, arthralgia, and rash while Zika infection with pruritus and rash. CONCLUSIONS: Given the similarities in the initial clinical profiles of these arboviruses, it is important to perform a detailed clinical analysis, laboratory diagnosis, and patient follow-up.

Emergence of chikungunya and Zika in a municipality endemic to dengue, Santa Luzia, MG, Brazil, 2015-2017

Abstract INTRODUCTION: The recent circulation of arboviruses transmitted by vectors, such as dengue, chikungunya, and Zika, is concerning due to the high morbidity rates, clinical complications, and increased demand on health services. The objective of this study was to analyze the clinical and epidemiological aspects of an epidemic caused by arboviruses in the municipality of Santa Luzia, Minas Gerais, Brazil. METHODS: Longitudinal study of patients with acute febrile disease and suspected arbovirus infection reported to Brazilian Notifiable Disease Information System (Sistema de Informação de Agravos de Notificação) from the epidemiological week 44 of 2015 to epidemiological week 52 of 2016. Patients with confirmed chikungunya were followed-up for 18 months and those with Zika for 15 months. Additionally, we analyzed and described the temporal distribution of confirmed cases of these arboviruses in this municipality. RESULTS: Overall 3,531 arboviruses cases, including 3,481 (98.7%) cases of dengue, 38 (1.0%) cases of chikungunya, and 12 (0.3%) cases of Zika were confirmed. The highest incidence of arbovirus infection occurred in the first quarter of 2016 (epidemiological week 7 to 14). The most frequent symptoms were for dengue, which included fever, headache, retro-orbital pain, and exanthema. Chikungunya infection was associated with fever, myalgia, arthralgia, and rash while Zika infection with pruritus and rash. CONCLUSIONS: Given the similarities in the initial clinical profiles of these arboviruses, it is important to perform a detailed clinical analysis, laboratory diagnosis, and patient follow-up.

Integralidade e integração dos serviços de saúde: desafios para redução dos óbitos por dengue / Integrality and integration of health services: challenges to reduce

A integralidade é um dos princípios doutrinários do SUS que se destina a conjugar as ações direcionadas à materialização da saúde, como direito e como serviço. Para qualificara atenção à saúde a partir da integralidade, é fundamental que os processos de trabalho sejam organizados com vistas ao enfrentamento dos principais problemas de saúde. O objetivo deste trabalho é relatar as atividades desenvolvidas pelo Ministério da Saúde, a partir de 2011,para promover a construção de um modelo de atenção integral à saúde, visando à redução do número de óbitos por dengue. Foram realizadas revisões das normas técnicas, estratégias diferenciadas de capacitação e integração das ações de vigilância e atenção à saúde no controle da dengue.

The integrality is one of the doctrinal principles of the SUS that intend to combine different actions for quality health care. It is essential that the work processes been organized with a view to addressing the major health problems for qualifying health care through integrality. The objective of this study is to report the activities of Ministry of Health, since 2011, to promotethe construction of model of integrate health care, aiming to reduce the number of dengue deaths. Review of technical standard, different training strategies and integration of surveillance and health care were conducted in dengue control.