Factors associated with death from dengue in the state of Minas Gerais, Brazil: historical cohort study

Abstract objectives To analyse the clinical and epidemiological profiles of dengue haemorrhagic fever (DHF), dengue shock syndrome (DSS) and complicated dengue cases and deaths from 2008 to 2010 that occurred in the state of Minas Gerais, south-eastern Brazil, and to identify factors associated with death from dengue. methods Historical cohort study using data from the Brazilian Information System for Notifiable Diseases. A descriptive analysis of the DHF, DSS and complicated dengue cases and deaths was performed; the incidence, mortality and case-fatality rates were estimated. Logistic regression analysis was used to identify factors associated with death from dengue. Comorbidities were not included in the analysis because the information system does not contain such data. conclusions The results support the importance of plasma leakage as a warning sign associated with death from dengue as well as the signs and symptoms that allow the diagnosis of DHF. Moreover, our findings suggest that increased attention is necessary for individuals over 65 years of age and in municipalities with populations under 100 000 inhabitants to ensure a better quality of care during the management of severe patients of dengue in these locations. Differences in the interpretation of the DHF definition have hindered the comparison of data from different countries; it can improve from the WHO 2009 dengue classification. keywords dengue fever, dengue haemorrhagic fever, dengue shock syndrome, plasma leakage, factors associated with death, case-fatality rate, Brazi

Características clínico-epidemiológicas dos casos graves e óbitos por dengue, Minas Gerais, 2008 a 2010

Exportado OPUSMade available in DSpace on 2019-08-11T15:03:19Z (GMT). No. of bitstreams: 1 dissertacao_mestrado_kauara_campos_13_10_2012.pdf: 3148553 bytes, checksum: 3fcb4d6e9c347dca79e43666e21e786d (MD5) Previous issue date: 4Dengue é uma doença febril aguda, de curso benigno ou grave podendo levar ao óbito, a depender de sua forma de apresentação: inaparente, dengue clássico (DC), febre hemorrágica do dengue (FHD)ou dengue com complicações (DCC). A OMS estima que ocorram anualmente 80 a 100 milhões de infecções, 400.000casos de FHD e 22.000 mortes por dengue, principalmente em crianças. Com a ocorrência de epidemias explosivas de dengue em grandes centros urbanos, a rápida propagação viral e potencial gravidade dos casos de FHD, a doença caracteriza-se como reemergente, dealto impacto econômico eimportância para a saúde pública internacional.Objetivos: Analisar o perfil clínico e epidemiológico dos casos graves e óbitos por dengue em Minas Gerais no período de 2008 a 2010, descrever a ocorrência dos casos graves e óbitos e os fatores associados à ocorrência de óbitos por dengue. Métodos:Foi realizado um estudo epidemiológico descritivo dos casos e óbitos por denguee um estudo caso-controlepara identificar fatores associados ao óbito por dengue dos pacientes de dengue grave (DCC e FHD), a partir de dados secundários provenientes da Secretaria de Estado de Saúde de Minas Geraise dos sistemas de informação SINAN e SIM.As seguintes variáveis foram avaliadas: idade, sexo,população e mesorregião geográficado município de residência,hospitalização, evolução do paciente,classificação final,sinais e sintomas clínicos (manifestações hemorrágicas: prova do laço positiva,epistaxe, metrorragia, gengivorragia, hematúria, petéquias espontâneas, sangramento do trato gastro-intestinal, sinais de extravasamento plasmático: derrame cavitário, hemoconcentração, hipoproteinemia),critério de confirmação do caso (laboratorial ou clínico epidemiológico),resultados de exames específicos e inespecíficos realizados,datas de início dos sintomas, internação e óbito, comorbidades e complicações. Foram analisadas as frequências de casos graves eóbitos segundo variáveis demográficas e clínicas,indicadores de incidência e taxa de letalidade,medidas de tendência central e de dispersão para as variáveis contínuas.Análise de regressão logística univariada de acordo com a ocorrência de óbito ou cura permitiu a identificação de variáveis associadas ao óbito com um nível de significância de p 65 anos(OR 3,05; IC95% 1,99-4,68), extravasamento plasmático(OR 1,69; IC95% 1,16-2,46), confirmação por exame laboratorial específico(OR 2,34; IC95% 1,34-4,07)e classificação em FHD(OR3,0 IC95% 2,02-4,47).Conclusão:Os casos graves e óbitos por dengue se distribuíram em todo o território de Minas Gerais, com maior freqüência nas faixas etárias extremas,reforçando a recomendação dos manuais de tratamento para que esses pacientes recebam cuidados diferenciados desde os primeiros sintomas da doença.É necessário aumentar a sensibilidade do sistema de vigilância dos casos graves e óbitos, favorecendointervenções adequadaspara sua redução.Dengue is an acute benign or severe febrile disease and it can cause death, depending on its presentation: inapparent, classic dengue (CD), dengue hemorrhagic fever (DHF) or dengue with complications (DWC). The World Health Organization estimates that 80 to 100 million infections occur annually, 400,000 cases of DHF and 22,000 deaths from dengue, especially in children. Due to the dengue explosive epidemics in large urban centers, the rapid viral dispersion and potential severity of DHF cases, the disease is characterized as re-emerging, with high-impact and economic importance to international public health. Objectives: To analyze the clinical and epidemiological profile of severe cases and deaths from dengue in Minas Gerais in the period 2008 to 2010 and to describe the occurrence of severe cases, deaths and the factors associated with the occurrence of deaths due to dengue. Methods: We conducted a descriptive epidemiological study of deaths from dengue and a case-control to identify factors associated with death from dengue patients with severe dengue (DHF and DWC), based on secondary data from the Health Secretary of Minas Gerais State, Health Information System and Mortality Information System. The following variables were evaluated: age, gender, population, residence city, region, hospital, patient outcomes, final classification, clinical signs and symptoms (hemorrhagic manifestations: positive tourniquet test, epistaxis, menorrhagia, gingival bleeding, hematuria, spontaneous petechiae, gastrointestinal bleeding, signs of plasma leakage, cavity effusion, hemoconcentration, hypoproteinemia), criteria for case confirmation (epidemiological or clinical laboratory), tests results performed specific and unspecific, symptoms onset dates, hospitalization and death, and comorbidities complications. We analyzed the frequency of severe cases and deaths by demographic and clinical variables, incidence and mortality rates, central tendency and dispersion measures for continuous variables. Univariate logistic regression analysis according to the occurrence of death or cure permitted the identification of variables associated with death and with a significance level p 65 years (OR 3,05; IC95% 1,99-4,68), plasma extravasation (OR 1,69; IC95% 1,16-2,46), confirmed by specific laboratory tests (OR 2,34; IC95% 1,34-4,07) and classification in DHF (OR 3,0 IC95% 2,02-4,47). Conclusion: The severe cases and deaths from dengue were distributed throughout the state of Minas Gerais, more often in extreme age groups, reinforcing the recommendation of treatment manuals for these patients receive special care from the onset of the disease. It is necessary to increase the sensitivity of the surveillance system of severe cases and deaths by promoting appropriate interventions for its reductio

Suscetibilidade de Aedes aegypti aos inseticidas piriproxifeno e malathion e competência de infecção por zika vírus em populações resistentes ao análogo de hormônio juvenil

Tese (doutorado) — Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Medicina Tropical, 2023.Introdução: No Brasil, o controle químico de Aedes aegypti continua sendo a principal ferramenta para prevenção de surtos de arboviroses. Monitorar a suscetibilidade do vetor aos inseticidas é importante para substituição das substâncias, caso haja resistência confirmada. Ainda, a relação entre mosquitos resistentes e a capacidade de infecção por arbovírus é pouco explorada e não está clara, principalmente por Zika vírus (ZIKV). Objetivos: Analisar a suscetibilidade de populações de Ae. aegypti aos inseticidas piriproxifeno (PPF) e malathion entre 2017 e 2018 no Brasil, assim como reavaliar a evolução da resistência ao PPF, após dois anos de exposição a aplicações bimestrais do larvicida, e investigar a relação entre mosquitos resistentes ao PPF e a capacidade de infecção por ZIKV. Métodos: Foram realizadas coletas de ovos de Ae. aegypti em 132 cidades por meio de armadilhas de oviposição. Colônias foram submetidas a testes de suscetibilidade com larvas expostas à Dose Diagnóstica (DD) de PPF (0,3 µg/L) e adultos com a DD de malathion obtida no laboratório (20 µg), além da DD indicada pela Organização Mundial da Saúde (OMS) (50 µg) em ensaio com garrafa. Posteriormente, bioensaios DoseResposta (DR) com PPF foram realizados em populações com IE < 98% para estimar a RR. Em 2020, ovos foram coletados nas cidades onde registramos resistência ao PPF anteriormente, para novos bioensaios DR. Mosquitos de populações com diferentes níveis de resistência ao PPF e uma cepa suscetível a inseticidas (Rockefeller) foram experimentalmente infectadas oralmente com ZIKV para determinar sua competência vetorial relativa. Resultados: A alteração da suscetibilidade ao PPF foi registrada em 6 (4,5%) populações do vetor, nos estados Bahia e Ceará, com Razão de Resistência (RR) entre 1,51 a 3,58. Para malathion, 73 (55,3%) populações distribuídas no país foram resistentes quando expostas à DD local (20 µg/garrafa). Por outro lado, nenhuma população foi resistente e apenas 10 (7,6%) populações apresentaram suscetibilidade reduzida (taxa de mortalidade 90 a 98%) quando a DD da OMS (50 µg/garrafa) foi utilizada. Em 2020, mosquitos de Icó, Serrinha, e Brumado apresentaram baixos níveis de resistência ao PPF (RR50= 2,33, 4,52 e 4,83, respectivamente), níveis moderados foram detectados nas populações de Juazeiro do Norte (RR50=5,83) e Itabuna (RR50=7,88), e alto nível em Quixadá (RR50=11). Embora todas as populações fossem competentes para infectar-se com ZIKV, aquelas com níveis moderados a altos de resistência a inseticidas (RI) exibiram suscetibilidade semelhante ou menor à infecção por ZIKV, comparando-se a populações de baixa RI ou à cepa suscetível. Conclusões: Registrou-se resistência ao PPF, em populações de Ae. aegypti procedentes do nordeste brasileiro, assim como a DD local para malathion (20µg/garrafa) foi mais sensível que a da OMS (50 µg/garrafa) para detectar precocemente diminuição da suscetibilidade; a evolução desta resistência pode comprometer os esforços para seu controle e o monitoramento contínuo é essencial no manejo efetivo de inseticidas. O uso do PPF para controle do Ae. aegypti pode estar associado ao benefício indireto de suscetibilidade reduzida à infecção por ZIKV, sem alterações na infecção disseminada e transmissão deste arbovirus entre fenótipos resistentes ao PPF.Ministério da Saúde do Brasil (MS) e Laboratório de Entomologia Médica da Universidade da Flórida (FMEL/UF).Introduction: Aedes aegypti chemical control in Brazil remains the main tool for preventing arboviral outbreaks. Monitoring the vector's susceptibility to insecticides is essential for replacing substances in case of confirmed resistance. Still, the relationship between resistant mosquitoes and the ability to infect arboviruses is little explored and unclear, especially with the Zika virus (ZKV). Objectives: To analyze the susceptibility of Ae. aegypti populations to the insecticides pyriproxyfen (PPF) and malathion between 2017 and 2018 in Brazil, as well as to reassess the evolution of PPF resistance after two years of exposure to bimonthly applications of the larvicide; and to investigate the relationship betweenresistant mosquitoes to PPF and its ability to be infected by ZIKV. Methods: Ae. aegypti eggs were collected in 132 cities using oviposition traps. Colonies were subjected to susceptibility tests with larvae exposed to the Diagnostic Dose (DD) of PPF (0.3 µg/L) and adults with the DD of malathion obtained in the laboratory (20 µg), in addition to the DD indicated by the World Health Organization (WHO) (50 µg) in bottle assay. Subsequently, DoseResponse (DR) bioassays with PPF were performed in populations with EI < 98% to estimate the RR. In 2020, eggs were collected in cities where we previously recorded PPF resistance for new DR bioassays. Mosquitoes from populations with different resistance levels to PPF and an insecticide-susceptible strain (Rockefeller) were experimentally orally infected with ZIKV to determine their relative vector competence. Results: Changes in susceptibility to PPF were recorded in 6 (4.5%) populations, in Bahia and Ceará states, with a Resistance Ratio (RR) from 1.51 to 3.58. For malathion, 73 (55.3%) populations distributed in the country were resistant when exposed to local DD (20 µg/bottle). On the other hand, no population was resistant, and only 10 (7.6%) populations showed reduced susceptibility (mortality rate 90 to 98%) when the WHO DD (50 µg/bottle) was used. In 2020, mosquitoes from Icó, Serrinha, and Brumado showed low levels of PPF resistance (RR50= 2.33, 4.52, and 4.83, respectively); moderate levels were detected in populations from Juazeiro do Norte (RR50=5.83) and Itabuna (RR50=7.88), and high level in Quixadá (RR50=11). Although all populations were competent to become infected with ZIKV, those with moderate to high levels of insecticide resistance (IR) exhibited similar or lower susceptibility to ZIKV infection compared to populations with low IR or the strain susceptible. Conclusions: Resistance to PPF was registered in Ae. aegypti populations from northeastern Brazil; as well as the local DD for malathion (20 µg/bottle) was more sensitive than the WHO one (50 µg/bottle) for early detection of decreased susceptibility; the evolution of this resistance can compromise efforts to control it, and continuous monitoring is essential for effective insecticide management. The use of PPF to control Ae. aegypti may be associated with the indirect benefit of reduced susceptibility to ZIKV infection without changes in disseminated infection and transmission of this arbovirus among PPF-resistant phenotypes.Faculdade de Medicina (FMD)Programa de Pós-Graduação em Medicina Tropica

Brazilian Populations of <i>Aedes aegypti</i> Resistant to Pyriproxyfen Exhibit Lower Susceptibility to Infection with Zika Virus

Zika virus (ZIKV) infection has caused devastating consequences in Brazil as infections were associated with neurological complications in neonates. Aedes aegypti is the primary vector of ZIKV, and the evolution of insecticide resistance (IR) in this species can compromise control efforts. Although relative levels of phenotypic IR in mosquitoes can change considerably over time, its influence on vector competence for arboviruses is unclear. Pyriproxyfen (PPF)-resistant populations of Ae. aegypti were collected from five municipalities located in Northeast of Brazil, which demonstrated different resistance levels; low (Serrinha, Brumado), moderate (Juazeiro do Norte, Itabuna), and high (Quixadá). Experimental per os infection using ZIKV were performed with individuals from these populations and with an insecticide susceptible strain (Rockefeller) to determine their relative vector competence for ZIKV. Although all populations were competent to transmit ZIKV, mosquitoes derived from populations with moderate to high levels of IR exhibited similar or lower susceptibility to ZIKV infection than those from populations with low IR or the susceptible strain. These observations suggest an association between IR and arbovirus infection, which may be attributable to genetic hitchhiking. The use of PPF to control Brazilian Ae. aegypti may be associated with an indirect benefit of reduced susceptibility to infection, but no changes in disseminated infection and transmission of ZIKV among PPF-resistant phenotypes

Kdr genotyping in Aedes aegypti from Brazil on a nation-wide scale from 2017 to 2018

International audienceInsecticide resistance is currently a threat to the control of Aedes agypti, the main vector of arboviruses in urban centers. Mutations in the voltage gated sodium channel (NaV), known as kdr (knockdown resistance), constitute an important selection mechanism for resistance against pyrethroids. In the present study, we investigated the kdr distribution for the Val1016Ile and Phe1534Cys alterations in Ae. aegypti from 123 Brazilian municipalities, based on SNP genotyping assays in over 5,500 mosquitoes. The alleles NaVS (1016Val+ + 1534Phe+), NaVR1 (1016Val+ + 1534Cyskdr) and NaVR2 (1016Ilekdr + 1534Cyskdr) were consistently observed, whereas kdr alleles have rapidly spread and increased in frequency. NaVS was the less frequent allele, mostly found in Northeastern populations. The highest allelic frequencies were observed for NaVR1, especially in the North, which was fixed in one Amazonian population. The double kdr NaVR2 was more prevalent in the Central-west and South-eastern populations. We introduce the ‘kdr index’, which revealed significant spatial patterns highlighting two to three distinct Brazilian regions. The 410L kdr mutation was additionally evaluated in 25 localities, evidencing that it generally occurs in the NaVR2 allele. This nationwide screening of a genetic mechanism for insecticide resistance is an important indication on how pyrethroid resistance in Ae. aegypti is evolving in Brazil