In silico-chemogenomic repurposing of new chemical scaffolds for histoplasmosis treatment.

BACKGROUND: Histoplasmosis is a systemic form of endemic mycosis to the American continent and may be lethal to people living with HIV/AIDS. The drugs available for treating histoplasmosis are limited, costly, and highly toxic. New drug development is time-consuming and costly; hence, drug repositioning is an advantageous strategy for discovering new therapeutic options. OBJECTIVE: This study was conducted to identify drugs that can be repositioned for treating histoplasmosis in immunocompromised patients. METHODS: Homologous proteins among Histoplasma capsulatum strains were selected and used to search for homologous targets in the DrugBank and Therapeutic Target Database. Essential genes were selected using Saccharomyces cerevisiae as a model, and functional regions of the therapeutic targets were analyzed. The antifungal activity of the selected drugs was verified, and homology modeling and molecular docking were performed to verify the interactions between the drugs with low inhibitory concentration values and their corresponding targets. RESULTS: We selected 149 approved drugs with potential activity against histoplasmosis, among which eight were selected for evaluating their in vitro activity. For drugs with low minimum inhibitory concentration values, such as mebendazole, everolimus, butenafine, and bifonazole, molecular docking studies were performed. A chemogenomic framework revealed lanosterol 14-α-demethylase, squalene monooxygenase, serine/threonine-protein kinase mTOR, and the ß-4B tubulin chain of H. capsulatum, respectively, as the protein targets of the drugs. CONCLUSIONS: Our strategy can be used to identify promising antifungal targets, and drugs with repositioning potential for treating H. capsulatum.

The cost of oral cancer: A systematic review.

Although clinical and epidemiological aspects of oral cancers (OC) are well-documented in the literature, there is a lack of evidence on the economic burden of OC. This study aims to provide a comprehensive systematic assessment on the economic burden of OC based on available evidence worldwide. A systematic review was conducted. The population was any individual, who were exposed to OC, considered here as lip (LC), oral cavity (OCC), or oropharynx (OPC) cancer. The outcome was information on direct (medical and non-medical) and indirect (productivity loss and early death) costs. The data sources included Scopus, Web of Science, Cochrane, BVS, and NHS EED. A search of grey literature (ISPOR and INAHTA proceedings) and a manual search in the reference lists of the included publications were performed (PROSPERO no. CRD42020172471). We identified 24 studies from 2001 to 2021, distributed by 15 countries, in 4 continents. In some developed western countries, the costs of LC, OCC, and OPC reached an average of Gross Domestic Product per capita of 18%, 75%, and 127%, respectively. Inpatient costs for OC and LC were 968% and 384% higher than those for outpatients, respectively. Advanced cancer staging was more costly (from ~22% to 373%) than the early cancer staging. The economic burden of oral cancer is substantial, though underestimated.

Potential kidney damage associated with the use of remdesivir for COVID-19: analysis of a pharmacovigilance database.

The U.S. Food and Drug Administration (FDA) has stated that the prescription of remdesivir should be cautious for patients with estimated glomerular filtration rate (eGFR) < 30 and some studies reported risk of adverse renal events. The available information on the renal safety profile for remdesivir is limited, thus we analyzed the renal and urinary adverse reactions attributed to remdesivir reported in a large open pharmacovigilance database. We obtained reports of remdesivir and other drugs used to treat COVID-19 (tocilizumab, hydroxychloroquine, lopinavir/ritonavir) registered by September 30 2020, from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed the reporting odds ratios (RORs) for reports of adverse renal and urinary events for remdesivir and other drugs. We found 2,922 reports with remdesivir registered in FAERS for COVID-19. Among these, 493 renal and urinary adverse effects (16.9%) were reported. The most frequent events were acute kidney injury (338; 11.6%), renal impairment (86; 2.9%), and renal failure (53; 1.8%). Versus hydroxychloroquine, lopinavir/ritonavir, or tocilizumab, the use of remdesivir was associated with an increased chance of reporting renal and urinary disorders regardless of gender and age of patients (2.53; 95%CI: 2.10-3.06). The ROR remained significant when we restricted the analysis to hydroxychloroquine (4.31; 95%CI: 3.25-5.71) or tocilizumab (3.92; 95%CI: 2.51-6.12). Our results reinforce this already reported signal, emphasizing that it could be extremely useful for health professionals who prescribe this new antiviral to treat COVID-19, mainly knowing its low efficacy.

Zika Brazilian Cohorts (ZBC) Consortium: Protocol for an Individual Participant Data Meta-Analysis of Congenital Zika Syndrome after Maternal Exposure during Pregnancy.

Despite great advances in our knowledge of the consequences of Zika virus to human health, many questions remain unanswered, and results are often inconsistent. The small sample size of individual studies has limited inference about the spectrum of congenital Zika manifestations and the prognosis of affected children. The Brazilian Zika Cohorts Consortium addresses these limitations by bringing together and harmonizing epidemiological data from a series of prospective cohort studies of pregnant women with rash and of children with microcephaly and/or other manifestations of congenital Zika. The objective is to estimate the absolute risk of congenital Zika manifestations and to characterize the full spectrum and natural history of the manifestations of congenital Zika in children with and without microcephaly. This protocol describes the assembly of the Consortium and protocol for the Individual Participant Data Meta-analyses (IPD Meta-analyses). The findings will address knowledge gaps and inform public policies related to Zika virus. The large harmonized dataset and joint analyses will facilitate more precise estimates of the absolute risk of congenital Zika manifestations among Zika virus-infected pregnancies and more complete descriptions of its full spectrum, including rare manifestations. It will enable sensitivity analyses using different definitions of exposure and outcomes, and the investigation of the sources of heterogeneity between studies and regions.

Three-Year Clinical Follow-Up of Children Intrauterine Exposed to Zika Virus.

Congenital Zika virus (ZIKV) infection may present with a broad spectrum of clinical manifestations. Some sequelae, particularly neurodevelopmental problems, may have a later onset. We conducted a prospective cohort study of 799 high-risk pregnant women who were followed up until delivery. Eighty-three women and/or newborns were considered ZIKV exposed and/or infected. Laboratory diagnosis was made by polymerase chain reaction in the pregnant mothers and their respective newborns, as well as Dengue virus, Chikungunya virus, and ZIKV serology. Serology for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and syphilis infections were also performed in microcephalic newborns. The newborns included in the study were followed up until their third birthday. Developmental delay was observed in nine patients (13.2%): mild cognitive delay in three patients, speech delay in three patients, autism spectrum disorder in two patients, and severe neurological abnormalities in one microcephalic patient; sensorineural hearing loss, three patients and dysphagia, six patients. Microcephaly due to ZIKV occurred in three patients (3.6%). Clinical manifestations can appear after the first year of life in children infected/exposed to ZIKV, emphasizing the need for long-term follow-up.

Direct healthcare costs of lip, oral cavity and oropharyngeal cancer in Brazil.

The efficiency of public policies includes the measurement of the health resources used and their associated costs. There is a lack of studies evaluating the economic impact of oral cancer (OC). This study aims to estimate the healthcare costs of OC in Brazil from 2008 to 2016. This is a partial economic evaluation using the gross costing top-down method, considering the direct healthcare costs related to outpatients, inpatients, intensive care units, and the number of procedures, from the perspective of the public health sector. The data were extracted from the Outpatient and Inpatient Information System of the National Health System, by diagnosis according to the 10th Revision of the International Classification of Diseases, according to sites of interest: C00 to C06, C09 and C10. The values were adjusted for annual accumulated inflation and expressed in 2018 I$ (1 I$ = R$2,044). Expenditure on OC healthcare in Brazil was I$495.6 million, which was composed of 50.8% (I$251.6 million) outpatient and 49.2% (I$244.0 million) inpatient healthcare. About 177,317 admissions and 6,224,236 outpatient procedures were registered. Chemotherapy and radiotherapy comprised the largest number of procedures (88.8%) and costs (94.9%). Most of the costs were spent on people over 50 years old (72.9%) and on males (75.6%). Direct healthcare costs in Brazil for OC are substantial. Outpatient procedures were responsible for the highest total cost; however, inpatient procedures had a higher cost per procedure. Men over 50 years old consumed most of the cost and procedures for OC. The oropharynx and tongue were the sites with the highest expenditure. Further studies are needed to investigate the cost per individual, as well as direct non-medical and indirect costs of OC.

Potential kidney damage associated with the use of remdesivir for COVID-19: analysis of a pharmacovigilance database / Potencial nefropatia associada ao uso do remdesivir para COVID-19: análise de uma base de dados de farmacovigilância / Potenciales lesiones renales asociadas con el uso de remdesivir para la COVID-19: análisis de una base de datos de farmacovigilancia

Abstract: The U.S. Food and Drug Administration (FDA) has stated that the prescription of remdesivir should be cautious for patients with estimated glomerular filtration rate (eGFR) < 30 and some studies reported risk of adverse renal events. The available information on the renal safety profile for remdesivir is limited, thus we analyzed the renal and urinary adverse reactions attributed to remdesivir reported in a large open pharmacovigilance database. We obtained reports of remdesivir and other drugs used to treat COVID-19 (tocilizumab, hydroxychloroquine, lopinavir/ritonavir) registered by September 30 2020, from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed the reporting odds ratios (RORs) for reports of adverse renal and urinary events for remdesivir and other drugs. We found 2,922 reports with remdesivir registered in FAERS for COVID-19. Among these, 493 renal and urinary adverse effects (16.9%) were reported. The most frequent events were acute kidney injury (338; 11.6%), renal impairment (86; 2.9%), and renal failure (53; 1.8%). Versus hydroxychloroquine, lopinavir/ritonavir, or tocilizumab, the use of remdesivir was associated with an increased chance of reporting renal and urinary disorders regardless of gender and age of patients (2.53; 95%CI: 2.10-3.06). The ROR remained significant when we restricted the analysis to hydroxychloroquine (4.31; 95%CI: 3.25-5.71) or tocilizumab (3.92; 95%CI: 2.51-6.12). Our results reinforce this already reported signal, emphasizing that it could be extremely useful for health professionals who prescribe this new antiviral to treat COVID-19, mainly knowing its low efficacy.

Resumo: De acordo com a Agência de Controle de Alimentos e Medicamentos dos Estados Unidos (FDA), a prescrição do remdesivir deve ser feita com cautela em pacientes com taxa de filtração glomerular estimada (TFGe) < 30, sendo que diversos estudos relatam risco de eventos adversos renais. São limitados os dados disponíveis sobre o perfil de segurança renal do remdesivir. Assim, analisamos as reações adversas renais e urinárias atribuídas ao remdesivir e notificadas em um grande base de dados abertos de farmacovigilância. Obtivemos notificações sobre remdesivir e outros medicamentos usados para tratar a COVID-19 (tocilizumabe, hidroxicloroquina, lopinavir/ritonavir) registradas até 30 de setembro de 2020 do Sistema de Notificação de Eventos Adversos da FDA (FAERS). Analisamos as razões de chances de notificação (RORs) para notificações de eventos adversos renais e urinários referentes ao remdesivir e outros medicamentos. Encontramos 2.922 notificações sobre remdesivir registradas no FAERS para COVID-19. Entre esses casos, foram notificados 493 efeitos adversos renais e urinários (16,9%). Os eventos mais frequentes foram lesão renal aguda (338; 11,6%), comprometimento renal (86; 2,9%) e insuficiência renal (53; 1,8%). Comparado com a hidroxicloroquina, lopinavir/ritonavir ou tocilizumabe, o uso do remdesivir esteve associado com um aumento das chances de notificação de transtornos renais e urinários, independentemente do sexo e idade dos pacientes (2,53; IC95%: 2,10-3,06). A ROR permaneceu significativo quando limitamos a análise à hidroxicloroquina (4,31; IC95%: 3,25-5,71) ou ao tocilizumabe (3,92; IC95%: 2,51-6,12). Nossos resultados corroboram outros estudos e destacam a utilidade para profissionais da saúde que usam esse novo antiviral para tratar a COVID-19, sobretudo em função de sua baixa eficácia.

Resumen: La Agencia Americana de Control de Alimentos y Medicamentos (FDA) ha destacado que la prescripción de remdesivir debe ser prudente con pacientes con tasa de filtración glomerular estimada (TGFe) < 30; además, algunos estudios informaron del riesgo de reacciones adversas renales. La información disponible sobre el perfil de seguridad renal, en el caso del remdesivir, es limitada. Por ello, analizamos las reacciones adversas renales y urinarias atribuidas al remdesivir e notificadas en una extensa base de datos abierta de farmacovigilancia. Obtuvimos las notificaciones de remdesivir y otros medicamentos usados para tratar la COVID-19 (tocilizumab, hidroxicloroquina, lopinavir/ritonavir) registrados el 30 de septiembre de 2020 por el Sistema de Notificación de Eventos Adversos de la FDA (FAERS). Analizamos las odds ratios informadas (RORs) en el caso de informes de eventos adversos renales y urinarios adversos relacionados con el remdesivir y otros medicamentos. En el FAERS, encontramos 2.922 notificaciones de remdesivir registradas como medicament sospechoso usado en COVID-19. De estos, habían 493 con efectos renales y urinarios adversos (16,9%). Los efectos adversos más frecuentes fueron lesiones renales agudas (338; 11,6%), insuficiencia renal (86; 2,9%), y fallo renal (53; 1,8%). Frente a hidroxicloroquina, lopinavir/ritonavir, o tocilizumab, el uso de remdesivir se asoció con un riesgo mayor de notificar alteraciones renales y urinarios, independientemente del género y edad de los pacientes (2,53; IC95%: 2,10-3,06). La ROR permaneció significativo al restringir el análisis a la hidroxicloroquina (4,31; IC95%: 3,25-5,71) o tocilizumab (3,92; IC95%: 2,51-6,12). Nuestros resultados corroboran datos previos, algo que podría ser extremadamente útil para los profesionales de la salud que decidan usar este nuevo antiviral para tratar la COVID-19, sobre todo conociendo su baja eficacia.

Risk Factors and Diagnosis of Diabetic Foot Ulceration in Users of the Brazilian Public Health System.

BACKGROUND: An individual with diabetes mellitus (DM) has an approximately 25% risk of developing ulcerations and/or destruction of the feet's soft tissues. These wounds represent approximately 20% of all causes of hospitalizations due to DM. OBJECTIVE: To identify the factors for the development of diabetic foot ulceration (DFU) among individuals treated by the Brazilian public health system. METHODS: This cross-sectional study was conducted on individuals with diabetes mellitus, aged above 18 years, of both sexes, and during July-October 2018 within a public healthcare unit in Brazil. All participants were assessed based on their socioeconomic, behavioral, and clinical characteristics, along with vascular and neurological evaluations. All participants were also classified according to the classification of risk of developing DFU, in accordance with the International Working Group on the Diabetic Foot (IWGDF). Statistical analyses were conducted using the chi-squared test, chi-squared test for trend, and Fisher's exact test, with a significance level of 5% (p < 0.05). RESULTS: The study consisted of 85 individuals. The DFU condition was prevalent in 10.6% of the participants. Adopting the classification proposed by IWGDF, observed risks for stratification categories 0, 1, 2, and 3 were 28.2%, 29.4%, 23.5%, and 8.2%, respectively. A statistically significant (p < 0.05) association was observed between the development of DFU and the following variables: time since the diagnosis of diabetes and the appearance of the nails, humidity, and deformations on the feet. CONCLUSION: The present study found an elevated predominance of DM patients in the Brazilian public health system (SUS) featuring cutaneous alterations that may lead to ulcers; these individuals had elevated risks of developing DFU. Furthermore, it was revealed that the feet of patients were not physically examined during treatment.

Syphilis in pregnancy and congenital syphilis and their relationship with Family Health Strategy coverage, Goiás, Brazil, 2007-2014: an ecological study. / Sífilis gestacional e congênita e sua relação com a cobertura da Estratégia Saúde da Família, Goiás, 2007-2014: um estudo ecológico.

OBJECTIVE: to analyze the incidence of syphilis in pregnant women (SPW) and congenital syphilis (CS) and the correlation of these indicators with Family Health Strategy (FHS) coverage in Goiás, Brazil, from 2007 to 2014. METHODS: this was an ecological study using Notifiable Diseases Information System (SINAN) data and data from the Health Ministry's Department of Primary Care; Spearman's correlation was used to evaluate the relationship between FHS coverage and syphilis incidence. RESULTS: SPW incidence increased from 2.8 to 9.5/1,000 live births, while CS incidence increased from 0.3 to 2.5/1,000 live births (p<0.05) in the period 2007-2014; there was a significant increase in CS cases in municipalities with percentage FHS coverage below 75% (p<0.001). CONCLUSION: the concomitant increase in SPW and CS incidence suggests failures in the prevention of vertical transmission of syphilis, especially in regions with lower FHS coverage.

Antifungal potential of punicalagin against Cryptococcus neoformans species complex.

This study evaluated the antifungal activity and cytotoxicity profile of the ellagitannin punicalagin, a compound extracted from the L. pacari A. St.-Hil (Lythraceae) leaf, against Cryptococcus neoformans species complex. Minimum inhibitory concentrations (MIC) were checked using the broth microdilution method. Minimum fungicidal concentrations (MFC) and time of death were used to confirm the antifungal activity of the compound. The in vitro cytotoxicity of punicalagin was tested in BALB/c3T3 fibroblasts and A549 human lung cancer cell line, while the hemolytic potential was tested on sheep erythrocytes. The morphological changes induced in yeast strains by the presence of punicalagin were also analyzed. Tested on eight isolates of the C. neoformans complex punicalagin showed MIC of 0.5 to 4.0 µg/mL and MFC> 256 µg/mL. Punicalagin also demonstrated a good growth inhibitory activity in time-kill curves, but it was not able to achieve a statistically significant reduction of fungal growth suggesting a fungistatic effect of the compound. In vitro cytotoxicity studies using the two cell lines showed that punicalagin has low activity on these cells and no activity on sheep erythrocytes. Morphological changes were seen in the yeasts strains studied when treated with punicalagin. Therefore, punicalagin is a potential antifungal for important pathogenic yeasts and presents a low cytotoxicity profile associated with no hemolytic effects.

Sífilis gestacional e congênita e sua relação com a cobertura da Estratégia Saúde da Família, Goiás, 2007-2014: um estudo ecológico / Sífilis gestacional y congénita y su relación con la cobertura de la Estrategia Salud de la Familia, Goiás, Brasil, 2007-2014: un estudio ecológico / Syphilis in pregnancy and congenital syphilis and their relationship with Family Health Strategy coverage, Goiás, Brazil, 2007-2014: an ecological study

Objetivo: analisar a incidência de sífilis em gestante (SG) e sífilis congênita (SC) e a correlação desses indicadores com a cobertura da Estratégia Saúde da Família (ESF) em Goiás, Brasil, de 2007 a 2014. Métodos: estudo ecológico utilizando dados do Sistema de Informação de Agravos de Notificação (Sinan) e do Departamento de Atenção Básica (DAB)/Ministério da Saúde; utilizou-se a correlação de Spearman para avaliar a relação entre cobertura da ESF e a incidência de sífilis. Resultados: a incidência de SG passou de 2,8 para 9,5/mil nascidos vivos, e a de SC, de 0,3 para 2,5/mil nascidos vivos (p<0,05), no período 2007-2014; houve aumento significativo de casos de SC nos municípios que apresentaram percentuais de cobertura da ESF inferiores a 75% (p<0,001). Conclusão: o aumento concomitante da incidência de SG e de SC sugere falhas na prevenção da transmissão vertical da sífilis, sobretudo nas regiões com menor cobertura da ESF.

Objetivo: analizar la incidencia de sífilis en gestante (SG) y sífilis congénita (SC) y la correlación de esos indicadores con la cobertura de la Estrategia Salud de la Familia (ESF) en Goiás, Brasil, de 2007 a 2014. Métodos: estudio ecológico utilizando datos del Sistema de Información de Agravamientos de Notificación (Sinan) y del Departamento de Atención Básica (DAB)/Ministerio de la Salud; se utilizó la correlación de Spearman para evaluar la relación entre la cobertura de la ESF y la incidencia de sífilis. Resultados: la incidencia de SG pasó de 2,8 a 9,5/1.000 nacidos vivos, y la de SC, de 0,3 a 2,5/1.000 nacidos vivos (p<0,05) en el período 2007-2014; hubo un aumento significativo de casos de SC en los municipios que presentaron un porcentaje de cobertura de la ESF inferior al 75% (p<0,001). Conclusión: el aumento concomitante de la incidencia de SG y de SC sugiere fallas en la prevención de la transmisión vertical de la sífilis, sobre todo en las regiones con menor porcentaje de cobertura de la ESF.

Objective: to analyze the incidence of syphilis in pregnant women (SPW) and congenital syphilis (CS) and the correlation of these indicators with Family Health Strategy (FHS) coverage in Goiás, Brazil, from 2007 to 2014. Methods: this was an ecological study using Notifiable Diseases Information System (SINAN) data and data from the Health Ministry's Department of Primary Care; Spearman's correlation was used to evaluate the relationship between FHS coverage and syphilis incidence. Results: SPW incidence increased from 2.8 to 9.5/1,000 live births, while CS incidence increased from 0.3 to 2.5/1,000 live births (p<0.05) in the period 2007-2014; there was a significant increase in CS cases in municipalities with percentage FHS coverage below 75% (p<0.001). Conclusion: the concomitant increase in SPW and CS incidence suggests failures in the prevention of vertical transmission of syphilis, especially in regions with lower FHS coverage.

[Aedes aegypti control strategies: a review]. / Estratégias de controle do Aedes aegypti: uma revisão.

OBJECTIVE: to describe the main strategies to control Aedes aegypti, with emphasis on promising technological innovations for use in Brazil. METHODS: this study is a non-systematic review of the literature. Results: several technologies have been developed as alternatives in the control of Ae. aegypti, using different mechanisms of action, such as selective monitoring of the infestation, social interventions, dispersing insecticides, new biological control agents and molecular techniques for population control of mosquitoes, also considering the combination between them. Evolving technologies require evaluation of the effectiveness, feasibility and costs of implementation strategies as complementary to the actions already recommended by the National Program for Dengue Control. CONCLUSION: the integration of different compatible and effective vector control strategies, considering the available technologies and regional characteristics, appears to be a viable method to try to reduce the infestation of mosquitoes and the incidence of arbovirus transmitted by them.

Estratégias de controle do Aedes aegypti: uma revisão / Aedes aegypti control strategies: a review / Estrategias de control del Aedes aegypti: una revisión

OBJETIVO: descrever as principais estratégias de controle do Aedes aegypti, com ênfase nas inovações tecnológicas promissoras para utilização no Brasil. MÉTODOS: trata-se de estudo de revisão não sistemática da literatura. RESULTADOS: diversas tecnologias têm sido desenvolvidas como alternativas no controle do Ae. aegypti, utilizando-se diferentes mecanismos de ação - como monitoramento seletivo da infestação, medidas sociais, dispersão de inseticidas, novos agentes de controle biológico e técnicas moleculares para controle populacional dos mosquitos -, considerando-se também a combinação entre elas. As tecnologias em desenvolvimento demandam avaliação da eficácia, viabilidade e custos para implementação como estratégias complementares às ações já preconizadas pelo Programa Nacional de Controle da Dengue. CONCLUSÃO: a integração de diferentes estratégias de controle vetorial compatíveis e eficazes, considerando as tecnologias disponíveis e as características regionais, parece ser um método viável para tentar reduzir a infestação dos mosquitos e a incidência das arboviroses transmitidas por eles.

OBJECTIVE: to describe the main strategies to control Aedes aegypti, with emphasis on promising technological innovations for use in Brazil. METHODS: this study is a non-systematic review of the literature. Results: several technologies have been developed as alternatives in the control of Ae. aegypti, using different mechanisms of action, such as selective monitoring of the infestation, social interventions, dispersing insecticides, new biological control agents and molecular techniques for population control of mosquitoes, also considering the combination between them. Evolving technologies require evaluation of the effectiveness, feasibility and costs of implementation strategies as complementary to the actions already recommended by the National Program for Dengue Control. CONCLUSION: the integration of different compatible and effective vector control strategies, considering the available technologies and regional characteristics, appears to be a viable method to try to reduce the infestation of mosquitoes and the incidence of arbovirus transmitted by them.

Economic Impact of Dengue: Multicenter Study across Four Brazilian Regions.

BACKGROUND: Dengue is an increasing public health concern in Brazil. There is a need for an updated evaluation of the economic impact of dengue within the country. We undertook this multicenter study to evaluate the economic burden of dengue in Brazil. METHODS: We estimated the economic burden of dengue in Brazil for the years 2009 to 2013 and for the epidemic season of August 2012- September 2013. We conducted a multicenter cohort study across four endemic regions: Midwest, Goiania; Southeast, Belo Horizonte and Rio de Janeiro; Northeast: Teresina and Recife; and the North, Belem. Ambulatory or hospitalized cases with suspected or laboratory-confirmed dengue treated in both the private and public sectors were recruited. Interviews were scheduled for the convalescent period to ascertain characteristics of the dengue episode, date of first symptoms/signs and recovery, use of medical services, work/school absence, household spending (out-of-pocket expense) and income lost using a questionnaire developed for a previous cost study. We also extracted data from the patients' medical records for hospitalized cases. Overall costs per case and cumulative costs were calculated from the public payer and societal perspectives. National cost estimations took into account cases reported in the official notification system (SINAN) with adjustment for underreporting of cases. We applied a probabilistic sensitivity analysis using Monte Carlo simulations with 90% certainty levels (CL). RESULTS: We screened 2,223 cases, of which 2,035 (91.5%) symptomatic dengue cases were included in our study. The estimated cost for dengue for the epidemic season (2012-2013) in the societal perspective was US$ 468 million (90% CL: 349-590) or US$ 1,212 million (90% CL: 904-1,526) after adjusting for under-reporting. Considering the time series of dengue (2009-2013) the estimated cost of dengue varied from US$ 371 million (2009) to US$ 1,228 million (2013). CONCLUSIONS: The economic burden associated with dengue in Brazil is substantial with large variations in reported cases and consequently costs reflecting the dynamic of dengue transmission.

Avaliação da qualidade dos dados, valor preditivo positivo, oportunidade e representatividade do sistema de vigilância epidemiológica da dengue no Brasil, 2005 a 2009* / Evaluation of the Dengue Epidemiological Surveillance System data quality, positive predictive value, timeliness and representativeness, Brazil, 2005-2009

Avaliar a qualidade dos dados, o valor preditivo positivo (VPP), a oportunidade e a representatividade do sistema de vigilância epidemiológica da dengue no Brasil entre 2005 e 2009. Métodos: estudo de avaliação, com análise dos dados de dengue do Sistema de Informação de Agravos de Notificação (Sinan) conforme atributos selecionados da metodologia do Centers for Disease Control and Prevention (Atlanta/GA, Estados Unidos da América). Resultados: houve melhora na qualidade dos dados quanto a sua consistência; o VPP dos casos de dengue variou de 34 a 65 por cento; o sistema apresentou uma mediana de oportunidade para notificação dos casos de 3 dias e revelou-se representativo, permitindo conhecer a situação da doença no país. Conclusão: o sistema de vigilância da dengue no Brasil mostrou-se consistente, com valor preditivo positivo expressivo, oportuno para notificação de casos e representativo, capaz de detectar tendência de mudança no perfil epidemiológico da doença...

To evaluate the dengue surveillance system data quality, positive predictive value (PPV), timeliness and representativeness in Brazil from 2005 to 2009. Methods: this was an observational, descriptive and cross-sectional study with analysis of data on dengue held on the Notifiable Diseases Information System (Sinan), based on the methodology proposed by the Centers for Disease Control and Prevention. Results: improvement in the quality of the data with regard to consistency; dengue case PPV ranged from 34 per cent to 65 per cent; the system showed a median time of three days for case notification and was found to be representative, providing knowledge of the disease’s status in the country. Conclusion: the dengue surveillance system in Brazil proved to be consistent, with significant positive predictive value, timely case reporting, as well as being representative and able to detect trends of change in the disease’s epidemiological profile...

Avaliação dos atributos de aceitabilidade e estabilidade do sistema de vigilância da dengue no estado de Goiás, 2011 / An evaluation of the acceptability and stability of the Dengue Surveillance System in Goiás state, Brazil, 2011

Objetivo: avaliar os atributos de aceitabilidade e estabilidade do sistema de vigilância da dengue no estado de Goiás, Brasil, em 2011. Métodos: estudo descritivo utilizando o método do Centers for Disease Control and Prevention (CDC/USA), com aplicação de questionário a profissionais envolvidos na vigilância da dengue. Resultados: 134 profissionais participaram do estudo, representando 41,5 por cento (102/246) dos municípios goianos; dificuldades para o encerramento dos casos graves foram referidas por 34,5 por cento dos coordenadores de vigilância; aproximadamente 70 por cento dos participantes informaram desconhecer a existência de um plano de contingência para o enfrentamento de epidemias de dengue e 59 por cento responderam que todos os casos suspeitos de dengue deveriam ser confirmados laboratorialmente, independentemente da ocorrência de epidemias; para 75 por cento dos entrevistados, a digitação das fichas de notificação/investigação foi realizada sem intercorrências. Conclusão: o sistema de vigilância da dengue apresentou funcionamento estável; porém, as limitações observadas remetem à necessidade de seu aprimoramento.

Objective: to evaluate the acceptability and stability of the dengue surveillance system in Goiás State, Brazil. Methods:descriptive study based on the Centers for Disease Control and Prevention (CDC) method using a questionnaire applied to professionals involved in dengue surveillance in 2011. Results: 134 professionals participated in the study, representing 41.5 per cent (102/246) of the municipalities in Goiás. Difficulties in closing severe cases were reported by 34.5 per cent of epidemiological surveillance coordinators, some 70 por cent of participants were unaware of the existence of a contingency plan for dengue outbreaks and 59 per cent responded that all suspected cases should be laboratory confirmed, regardless of the occurrence of epidemics. 75 per cent of respondents reported having no difficulty in inputting data on the Surveillance Information System. Conclusion: despite the stability of the dengue surveillance routines, the limitations observed indicate the need for system enhancement.