Genomic epidemiology unveils the dynamics and spatial corridor behind the Yellow Fever virus outbreak in Southern Brazil.

Despite the considerable morbidity and mortality of yellow fever virus (YFV) infections in Brazil, our understanding of disease outbreaks is hampered by limited viral genomic data. Here, through a combination of phylogenetic and epidemiological models, we reconstructed the recent transmission history of YFV within different epidemic seasons in Brazil. A suitability index based on the highly domesticated Aedes aegypti was able to capture the seasonality of reported human infections. Spatial modeling revealed spatial hotspots with both past reporting and low vaccination coverage, which coincided with many of the largest urban centers in the Southeast. Phylodynamic analysis unraveled the circulation of three distinct lineages and provided proof of the directionality of a known spatial corridor that connects the endemic North with the extra-Amazonian basin. This study illustrates that genomics linked with eco-epidemiology can provide new insights into the landscape of YFV transmission, augmenting traditional approaches to infectious disease surveillance and control.

Emergence of Dengue Virus Serotype 2 Cosmopolitan Genotype, Brazil.

We used nanopore sequencing and phylogenetic analyses to identify a cosmopolitan genotype of dengue virus serotype 2 that was isolated from a 56-year-old male patient from the state of Goiás in Brazil. The emergence of a cosmopolitan genotype in Brazil will require risk assessment and surveillance to reduce epidemic potential.

A Retrospective Overview of Zika Virus Evolution in the Midwest of Brazil.

Since the introduction of the Zika virus (ZIKV) into Brazil in 2015, its transmission dynamics have been intensively studied in many parts of the country, although much is still unknown about its circulation in the midwestern states. Here, using nanopore technology, we obtained 23 novel partial and near-complete ZIKV genomes from the state of Goiás, located in the Midwest of Brazil. Genomic, phylogenetic, and epidemiological approaches were used to retrospectively explore the spatiotemporal evolution of the ZIKV-Asian genotype in this region. As a likely consequence of a gradual accumulation of herd immunity, epidemiological data revealed a decline in the number of reported cases over 2018 to 2021. Phylogenetic reconstructions revealed that multiple independent introductions of the Asian lineage have occurred in Goiás over time and revealed a complex transmission dynamic between epidemic seasons. Together, our results highlight the utility of genomic, epidemiological, and evolutionary methods to understand mosquito-borne epidemics. IMPORTANCE Despite the considerable morbidity and mortality of arboviral infections in Brazil, such as Zika, chikungunya, dengue fever, and yellow fever, our understanding of these outbreaks is hampered by the limited availability of genomic data to track and control the epidemic. In this study, we provide a retrospective reconstruction of the Zika virus transmission dynamics in the state of Goiás by analyzing genomic data from areas in Midwest Brazil not covered by other previous studies. Our study provides an understanding of how ZIKV initiates transmission in this region and reveals a complex transmission dynamic between epidemic seasons. Together, our results highlight the utility of genomic, epidemiological, and evolutionary methods to understand mosquito-borne epidemics, revealing how this toolkit can be used to help policymakers prioritize areas to be targeted, especially in the context of finite public health resources.

Aprendizados no enfrentamento à pandemia / Lessons learned in coping with the pandemic

O novo coronavírus (SARSCoV-2) instaurou inúmeros desafios no contexto da gestão pública, não só da saúde pública, mas também da economia e da educação; e ainda nos aspectos da vida social e individual, deixando centenas de milhões de casos e milhões de mortes, transformando a realidade conhecida. Diante deste contexto este e-book buscou agregar e compilar experiências da Secretaria de Estado da Saúde de Goiás (SES/GO) no enfrentamento à pandemia, nos mais diferentes aspectos da gestão em saúde (vigilância, regulação, assistência, transparência, gestão de pessoas, entre outros)

The new coronavirus (SARSCoV-2) has created numerous challenges in the context of public management, not only in public health, but also in the economy and education; and even in the aspects of social and individual life, leaving hundreds of millions of cases and millions of deaths, transforming the known reality. Given this context, this e-book sought to aggregate and compile experiences of the State Department of Health of Goiás (SES/GO) in facing the pandemic, in the most different aspects of health management (surveillance, regulation, assistance, transparency, people management , between others)

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.

Analysis of Paracoccidioides secreted proteins reveals fructose 1,6-bisphosphate aldolase as a plasminogen-binding protein.

BACKGROUND: Despite being important thermal dimorphic fungi causing Paracoccidioidomycosis, the pathogenic mechanisms that underlie the genus Paracoccidioides remain largely unknown. Microbial pathogens express molecules that can interact with human plasminogen, a protein from blood plasma, which presents fibrinolytic activity when activated into plasmin. Additionally, plasmin exhibits the ability of degrading extracellular matrix components, favoring the pathogen spread to deeper tissues. Previous work from our group demonstrated that Paracoccidioides presents enolase, as a protein able to bind and activate plasminogen, increasing the fibrinolytic activity of the pathogen, and the potential for adhesion and invasion of the fungus to host cells. By using proteomic analysis, we aimed to identify other proteins of Paracoccidioides with the ability of binding to plasminogen. RESULTS: In the present study, we employed proteomic analysis of the secretome, in order to identify plasminogen-binding proteins of Paracoccidioides, Pb01. Fifteen proteins were present in the fungal secretome, presenting the ability to bind to plasminogen. Those proteins are probable targets of the fungus interaction with the host; thus, they could contribute to the invasiveness of the fungus. For validation tests, we selected the protein fructose 1,6-bisphosphate aldolase (FBA), described in other pathogens as a plasminogen-binding protein. The protein FBA at the fungus surface and the recombinant FBA (rFBA) bound human plasminogen and promoted its conversion to plasmin, potentially increasing the fibrinolytic capacity of the fungus, as demonstrated in fibrin degradation assays. The addition of rFBA or anti-rFBA antibodies was capable of reducing the interaction between macrophages and Paracoccidioides, possibly by blocking the binding sites for FBA. These data reveal the possible participation of the FBA in the processes of cell adhesion and tissue invasion/dissemination of Paracoccidioides. CONCLUSIONS: These data indicate that Paracoccidioides is a pathogen that has several plasminogen-binding proteins that likely play important roles in pathogen-host interaction. In this context, FBA is a protein that might be involved somehow in the processes of invasion and spread of the fungus during infection.

Micro-Raman spectroscopic characterization of a CR-39 detector.

Characterization by micro-Raman spectroscopy of polymeric materials used as nuclear track detectors reveals physico-chemical and morphological information on the material's molecular structure. In this work, the nuclear track detector poly(allyl diglycol carbonate), or Columbia Resin 39 (CR-39), was characterized according to the fluence of alpha particles produced by a (226)Ra source and chemical etching time. Therefore, damage of the CR-39 chemical structure due to the alpha-particle interaction with the detector was analyzed at the molecular level. It was observed that the ionization and molecular excitation of the CR-39 after the irradiation process entail cleavage of chemical bonds and formation of latent track. In addition, after the chemical etching, there is also loss of polymer structure, leading to the decrease of the group density C-O-C (∼888 cm(-1)), CH=CH (∼960 cm(-1)), C-O (∼1110 cm(-1)), C-O-C (∼1240 cm(-1)), C-O (∼1290 cm(-1)), C=O (∼1741 cm(-1)), -CH2- (∼2910 cm(-1)), and the main band -CH2- (∼2950 cm(-1)). The analyses performed after irradiation and chemical etching led to a better understanding of the CR-39 molecular structure and better comprehension of the process of the formation of the track, which is related to chemical etching kinetics.

O sistema MELD e a mortalidade em lista de espera para transplante de fígado em países em desenvolvimento: lições aprendidas em São Paulo / The MELD system and liver transplant waiting-list mortality in developing countries: lessons learned from São Paulo, Brazil

OBJETIVO: Este estudo foi desenhado para avaliar os resultados da nova política de alocação em relação à mortalidade na lista de espera. MÉTODOS: O banco de dados de transplante hepático do Estado de São Paulo foi revisado de forma retrospectiva, de julho de 2003 até julho de 2009. Os pacientes foram divididos naqueles transplantados antes (Grupo Pré-MELD) e depois (Grupo Pós-MELD) da implementação do sistema MELD (Model for End-stage Liver Disease). Foram incluídos apenas os candidatos adultos para transplante de fígado. O desfecho primário foi a mortalidade na lista de espera. RESULTADOS: A taxa não ajustada de óbitos na lista de espera diminuiu significativamente após a implementação do sistema MELD (de 91,2 para 33,5/1.000 pacientes por ano; p<0,0001). A análise multivariada mostrou uma queda significativa no risco de morte na lista de espera para pacientes após o MELD (HR de 0,34; p<0,0001). Atualmente, 48% dos pacientes são transplantados no primeiro ano na lista (versus 23% na era pré-MELD; p<0,0001). A sobrevida dos pacientes e do enxerto não mudou com a implementação do MELD. CONCLUSÃO: Houve redução no tempo de espera e na mortalidade na lista após implementação do sistema MELD em São Paulo. Os pacientes na lista no período pós-MELD apresentaram uma redução significativa no risco de mortalidade na lista de espera. Não houve mudanças nos resultados após o transplante. O MELD pode ser utilizado com sucesso para alocação para transplante fígado em países em desenvolvimento.

OBJECTIVE: The MELD system has not yet been tested as an allocation tool for liver transplantation in the developing countries. In 2006, MELD (Model for End-stage Liver Disease) was launched as a new liver allocation system in São Paulo, Brazil. This study was designed to assess the results of the new allocation policy on waiting list mortality. METHODS: The State of São Paulo liver transplant database was retrospectively reviewed from July 2003 through July 2009. Patients were divided into those who were transplanted before (Pre-MELD Group) and those who were transplanted after (post-MELD Group) the implementation of the MELD system. Only adult liver transplant candidates were included. Waiting list mortality was the primary endpoint. RESULTS: The unadjusted death rate in waiting list decreased significantly after the implementation of the MELD system (from 91.2 to 33.5/1,000 patients per year; p<0.0001). Multivariate analysis showed a significant drop in risk of waiting list death for post-MELD patients (HR 0.34; p<0.0001). Currently, 48% of patients are transplanted within 1-year of listing (versus 23% in the pre-MELD era; p<0.0001). Patient and graft survival did not change with MELD implementation. CONCLUSION: There was a reduction in waiting time and list mortality after implementation of the MELD system in São Paulo. Patients listed in the post-MELD era had a significant reduction in risk for the waiting list mortality. There were no changes in post-transplant outcomes. MELD can be successfully utilized for liver transplant allocation in developing countries.

The MELD system and liver transplant waiting-list mortality in developing countries: lessons learned from São Paulo, Brazil.

OBJECTIVE: The MELD system has not yet been tested as an allocation tool for liver transplantation in the developing countries. In 2006, MELD (Model for End-stage Liver Disease) was launched as a new liver allocation system in São Paulo, Brazil. This study was designed to assess the results of the new allocation policy on waiting list mortality. METHODS: The State of São Paulo liver transplant database was retrospectively reviewed from July 2003 through July 2009. Patients were divided into those who were transplanted before (Pre-MELD Group) and those who were transplanted after (post-MELD Group) the implementation of the MELD system. Only adult liver transplant candidates were included. Waiting list mortality was the primary endpoint. RESULTS: The unadjusted death rate in waiting list decreased significantly after the implementation of the MELD system (from 91.2 to 33.5/1,000 patients per year; p<0.0001). Multivariate analysis showed a significant drop in risk of waiting list death for post-MELD patients (HR 0.34; p<0.0001). Currently, 48% of patients are transplanted within 1-year of listing (versus 23% in the pre-MELD era; p<0.0001). Patient and graft survival did not change with MELD implementation. CONCLUSION: There was a reduction in waiting time and list mortality after implementation of the MELD system in São Paulo. Patients listed in the post-MELD era had a significant reduction in risk for the waiting list mortality. There were no changes in post-transplant outcomes. MELD can be successfully utilized for liver transplant allocation in developing countries.

Molecular epidemiological analysis of bloodstream isolates of candida albicans

Candidemia está geralmente relacionada à microbiota endógena, porém infecções exógenas originadas do staff ou do meio ambiente podem ocorrer. O método de DNA polimórfico amplificado aleatoriamente (RAPD) pode revelar variações específicas do isolado. Neste estudo, foi utilizada a análise de RAPD para avaliar a diversidade genética entre isolados de C. albicans, buscando-se encontrar similaridade entre os padrões de DNA dos isolados obtidos de amostras clínicas e ambientais da unidade de terapia intensiva (UTI) no Hospital das Clínicas da Universidade Federal de Goiás. Os primers denominados Cnd3 (5-CCAGATGCAC-3) e Cnd4 (5-ACGGTACACT-3) foram usados como primer na PCR. Perfis de RAPD do sangue e da urina, provenientes dos mesmos pacientes, mostraram-se idênticos em quase todas as amostras estudadas, exceto na de um paciente. O isolado da cama deste paciente tinha o mesmo genótipo da amostra obtida de seu sangue. Embora a maioria dos isolados de C. albicans provavelmente tivesse origem endógena, o encontro de isolados de pacientes com o mesmo perfil dos isolados do meio ambiente sugere que a candidemia pode resultar de uma fonte exógena.

Analysis of the Paracoccidioides brasiliensis triosephosphate isomerase suggests the potential for adhesin function.

Paracoccidioides brasiliensis is an important fungal pathogen. The disease it causes, paracoccidioidomycosis (PCM), ranges from localized pulmonary infection to systemic processes that endanger the life of the patient. Paracoccidioides brasiliensis adhesion to host tissues contributes to its virulence, but we know relatively little about molecules and the molecular mechanisms governing fungal adhesion to mammalian cells. Triosephosphate isomerase (TPI: EC 5.3.1.1) of P. brasiliensis (PbTPI) is a fungal antigen characterized by microsequencing of peptides. The protein, which is predominantly expressed in the yeast parasitic phase, localizes at the cell wall and in the cytoplasmic compartment. TPI and the respective polyclonal antibody produced against this protein inhibited the interaction of P. brasiliensis to in vitro cultured epithelial cells. TPI binds preferentially to laminin, as determined by peptide inhibition assays. Collectively, these results suggest that TPI is required for interactions between P. brasiliensis and extracellular matrix molecules such as laminin and that this interaction may play an important role in the fungal adherence and invasion of host cells.

Sistema Estadual de Transplantes em São Paulo: histórico, resultados e perspectivas / Transplantation System in the State of São Paulo: history, results, and future prospects

Este artigo relata a experiência da Central de Notificação, Captação e Distribuição de Órgãos (CNCDO) do Estado de São Paulo, mais comumente chamada de Central de Transplantes, atualmente ligada à Coordenadoria de Planejamento de Saúde, no papel de regular e controlar os transplantes no Estado de São Paulo. Resgata ainda os aspectos históricos dos transplantes no Brasil e, em particular, no Estado de São Paulo. Apresenta ainda todo o processo de desenvolvimento e implantação do Sistema Estadual de Transplantes (SET), com suas dificuldades e suas conquistas.

Documentação médica: guarda e manuseio dos prontuários médicos / Medical documentation: keeping and handling medical files

Atualmente, realizam-se, no Brasil, mais de 360 milhões de consultas médicas por ano, que geram quantidade imensa de prontuários médicos. Pela legislação brasileira, médicos, clínicas e hospitais são obrigados a manter esses prontuários arquivados por pelo menosdez anos, podendo, a partir desse prazo, ser microfilmados e destruídos. A quantidade de espaço que esses arquivos em papel exigem está tornando os custos cada vez mais elevados. Alguns estabelecimentos tiveram que ampliar ou alugar dependências próprias para arquivo, ocasionando considerável aumento de custos com uma atividade que extrapola os objetivos de um hospital.A partir de agora, os prontuários médicos podem ser elaborados e arquivados com computador. E a guarda dos mesmos poderá ser permanente , sem ocupação de espaço físico. Para garantir a confidencialidade(segredo médico) e a integridade dos dados dos pacientes(uma vez inseridos um dado no sistema, ele não poderá ser alterado), o Conselho Federal de Medicina aprovou normas rígidas para a guarda e o manuseio desses documentos. O sistema de informação utilizado deverá garantir, entre outros requisitos, um rígido controle de acesso aos dados e plena capacidade de recuperação dos registros originais. Cuidados maiores são exigidos nos casos de transmissão de dados do prontuário via internet. Para que possam viabilizar tais transferências, os sistemas deverão incorporar a criptografia assimétrica por chaves(pública e privada), nos termos definidos pela ICP-Brasil(Infra-estrutura de Chaves Públicas Brasileira).A criptografia por chaves garante a autenticidade e a confidencialidade dos documentos eletrônicos, permitindo a transmissão segura pela rede. Certificado fornecido pelo Conselho Federal de Medicina garantirá o valor legal e probante dos prontuários eletrônicos. Os prontuários em suporte de papel que assim permanecem deverão ser armazenados por um período mínimo de vinte anos, contando a partir do último registro...