Chikungunya Death Risk Factors in Brazil, in 2017: A case-control study.

BACKGROUND: In 2016/2017 we had a major epidemic of chikungunya (CHIK) in Brazil, with many deaths. We evaluated to factors associated with deaths from CHIK that occurred in the city of Fortaleza, Brazil. METHODS: A matched case-control study was conducted (1:2), by sex, age (± 5 years) and neighborhood. Cases were CHIK deaths that occurred between January 1 and December 31, 2017, in Fortaleza, Brazil, and which were laboratory confirmed. Controls were laboratory confirmed CHIK patients occurring in the same neighborhood and in the same period, but which did not progress to death. RESULTS: 82 cases of CHIK and 164 controls were included. Considering the clinical history, significant associations were found between other chronic heart diseases (OR 3.8; CI: 1.53-9.26) and chronic kidney disease (OR 12.77; CI: 2.75-59.4). In the multivariate analysis of the variables related to signs and symptoms, fever (OR: 19.23 CI: 1.73-213.78), abdominal pain (OR: 3; 74 CI: 1.06-13.16), apathy (OR: 11.62 CI: 2.95-45.82) and dyspnea (OR: 50.61; CI: 12.37-207.18) were identified with greater likelihood of death from CHIK. It also stood out that altered blood glucose was associated with cases with a worse prognosis (OR: 13.5; CI: 1.3-135.0). Among the laboratory findings, only lymphocytes and albumin were not associated with greater likelihood of death. CONCLUSION: The factors related with deaths were chronic kidney disease and previous heart disease, presence of fever, abdominal pain, apathy, dyspnea and arthritis and laboratory findings such as leukocytosis, leukopenia, thrombocytopenia, neutropenia and lymphopenia.

Neurological growth and development of children asymptomatic at birth whose mothers had Zika during pregnancy.

INTRODUCTION: Newborn who had Zika vírus but did not show microcephaly at birth may have neuropsychomotor development problems. We aimed to evaluate the developmental and anthropometric milestones of asymptomatic children whose mothers had Zika during pregnancy in Northeastern Brazil in 2015 and 2016. METHODS: We conducted a descriptive cross-sectional case series study of children in Fortaleza born without microcephaly whose mothers had Zika during pregnancy. Home visits were undertaken to evaluate the developmental milestones and gather anthropometric data of the children and to conduct semi-structured interviews with the mothers to identify their socioeconomic and gestational profiles and assess the newborns after birth. RESULTS: In total, 30 cases were identified. Of these, 17 children and their mothers participated in the study. The median age of the mothers at the time of delivery was 26 years. All were symptomatic, and TORCH was negative. At the time of the home visit, all had growth profiles suitable for their age. However, nearly all children (15/17, 88.2%) presented at least one developmental delay, considering their age group. CONCLUSIONS: There were late changes in the neuropsychomotor development of children born to mothers who had Zika during pregnancy, suggesting the need for specialized medical follow-ups.

Fatal Outcome of Chikungunya Virus Infection in Brazil.

BACKGROUND: Chikungunya virus (CHIKV) emerged in the Americas in 2013 and has caused approximately 2.1 million cases and >600 deaths. A retrospective investigation was undertaken to describe clinical, epidemiological, and viral genomic features associated with deaths caused by CHIKV in Ceará state, northeast Brazil. METHODS: Sera, cerebrospinal fluid (CSF), and tissue samples from 100 fatal cases with suspected arbovirus infection were tested for CHIKV, dengue virus (DENV), and Zika virus (ZIKV). Clinical, epidemiological, and death reports were obtained for patients with confirmed CHIKV infection. Logistic regression analysis was undertaken to identify independent factors associated with risk of death during CHIKV infection. Phylogenetic analysis was conducted using whole genomes from a subset of cases. RESULTS: Sixty-eight fatal cases had CHIKV infection confirmed by reverse-transcription quantitative polymerase chain reaction (52.9%), viral antigen (41.1%), and/or specific immunoglobulin M (63.2%). Co-detection of CHIKV with DENV was found in 22% of fatal cases, ZIKV in 2.9%, and DENV and ZIKV in 1.5%. A total of 39 CHIKV deaths presented with neurological signs and symptoms, and CHIKV-RNA was found in the CSF of 92.3% of these patients. Fatal outcomes were associated with irreversible multiple organ dysfunction syndrome. Patients with diabetes appear to die at a higher frequency during the subacute phase. Genetic analysis showed circulation of 2 CHIKV East-Central-South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome. CONCLUSIONS: The investigation of the largest cross-sectional cohort of CHIKV deaths to date reveals that CHIKV-ECSA strains can cause death in individuals from both risk and nonrisk groups, including young adults.

Neurological growth and development of children asymptomatic at birth whose mothers had Zika during pregnancy

Abstract INTRODUCTION: Newborn who had Zika vírus but did not show microcephaly at birth may have neuropsychomotor development problems. We aimed to evaluate the developmental and anthropometric milestones of asymptomatic children whose mothers had Zika during pregnancy in Northeastern Brazil in 2015 and 2016. METHODS: We conducted a descriptive cross-sectional case series study of children in Fortaleza born without microcephaly whose mothers had Zika during pregnancy. Home visits were undertaken to evaluate the developmental milestones and gather anthropometric data of the children and to conduct semi-structured interviews with the mothers to identify their socioeconomic and gestational profiles and assess the newborns after birth. RESULTS: In total, 30 cases were identified. Of these, 17 children and their mothers participated in the study. The median age of the mothers at the time of delivery was 26 years. All were symptomatic, and TORCH was negative. At the time of the home visit, all had growth profiles suitable for their age. However, nearly all children (15/17, 88.2%) presented at least one developmental delay, considering their age group. CONCLUSIONS: There were late changes in the neuropsychomotor development of children born to mothers who had Zika during pregnancy, suggesting the need for specialized medical follow-ups.

Seroprevalence, spatial dispersion and factors associated with flavivirus and chikungunha infection in a risk area: a population-based seroprevalence study in Brazil.

BACKGROUND: The State of Ceará, in Northeastern Brazil, suffers from a triple burden of arboviruses (dengue, Zika and chikungunya). We measured the seroprevalence of chikungunya, dengue and Zika and its associated factors in the population of Juazeiro do Norte, Southern Ceará State, Brazil. METHODS: A cross-sectional study of analytical and spatial analysis was performed to estimate the seroprevalence of dengue, Zika and chikungunya, in the year 2018. Participants were tested for IgM and IgG against these three viruses. Those with IgM and/or IgG positive tests results were considered positive. Poisson regression was used to analyze the factors associated with positive cases, in the same way that the spatial analysis of positive cases was performed to verify whether the cases were grouped. RESULTS: Of the 404 participants, 25.0% (103/404) were positive for CHIKV, 92.0% (373/404) for flavivirus (dengue or Zika) and of these, 37.9% (153/404) samples were classified as probable dengue infection. Of those who reported having had an arbovirus in the past, positive CHIKV cases had 58.7% arthralgia (PR = 4.31; 95% CI: 2.06-9.03; p = 0.000) mainly in the hands, ankles and feet. Age over 60 years had a positive association with cases of flavivirus (PR = 1.29; 95% CI: 1.09-1.54; p = 0.000). Fever, muscle pain, joint pain and skin rash were the most reported symptoms (46.1, 41.0, 38.3 and 28.41%, respectively). The positive cases of chikungunya and dengue or Zika were grouped in space and the city center was most affected area. CONCLUSIONS: Four years after the introduction of CHIKV, where DENV has been in circulation for over 30 years, 1/4 of the population has already been exposed, showing the extent of the epidemic. The measured prevalence was much higher than that reported by local epidemiological surveillance.

Experience of the Arbovirus Death Investigation Committee in Ceará, Brazil, in 2017: advances and challenges. / Experiência do Comitê de Investigação de Óbitos por Arboviroses no Ceará em 2017: avanços e desafios.

OBJECTIVE: to describe the experience and preliminary results of the Arbovirus Death Investigation Committee in Ceará, Brazil, in 2017. METHODS: the Committee investigates and discusses all suspected cases of arbovirus deaths reported by the epidemiological surveillance service. RESULTS: a total of 443 suspected arbovirus deaths were reported, 220 (49.7%) of which were confirmed; of these, 88.2% were from chikungunya and 11.8% from dengue; the median age of chikungunya deaths was higher when compared to dengue (77 versus 56 years) and the time until death was also longer when compared to dengue (38 versus 12 days); median time for case closure was 54.5 days; in 2017, Ceará confirmed 80.4% of Brazilian chikungunya deaths. CONCLUSION: the investigation of deaths showed that CHIK viruses were responsible for the majority of arboviral deaths in the state of Ceará, in 2017.

A major chikungunya epidemic with high mortality in northeastern Brazil.

INTRODUCTION: Chikungunya causes fever and severe and persistent joint pain. METHODS: We reported a chikungunya outbreak that occurred in Ceará State, Brazil between 2016 and 2017 with emphasis on epidemiological characterization of cases, high number of deaths, mortality-associated factors, and spatial and temporal spread of the epidemic among municipalities. RESULTS: In November 2015, the first autochthonous cases of chikungunya were confirmed in Ceará, Brazil. In 2016-2017, 195,993 cases were reported, with an incidence of 2,186.5/100,000 inhabitants and 244 confirmed deaths. CONCLUSIONS: Rapid transmission and high mortality rate are serious problems, especially in regions with co-circulating arboviruses.

A major chikungunya epidemic with high mortality in northeastern Brazil

Abstract INTRODUCTION Chikungunya causes fever and severe and persistent joint pain. METHODS We reported a chikungunya outbreak that occurred in Ceará State, Brazil between 2016 and 2017 with emphasis on epidemiological characterization of cases, high number of deaths, mortality-associated factors, and spatial and temporal spread of the epidemic among municipalities. RESULTS: In November 2015, the first autochthonous cases of chikungunya were confirmed in Ceará, Brazil. In 2016-2017, 195,993 cases were reported, with an incidence of 2,186.5/100,000 inhabitants and 244 confirmed deaths. CONCLUSIONS: Rapid transmission and high mortality rate are serious problems, especially in regions with co-circulating arboviruses.

Maternal and infant death after probable vertical transmission of chikungunya virus in Brazil - case report.

BACKGROUND: Chikungunya virus infection in neonates is relatively rare and can lead to death. CASE PRESENTATION: We report the occurrence of the first death of a mother and child after probable vertical transmission of chikungunya virus in Brazil. A 28-year-old pregnant woman with hypertension presented with symptoms compatible with an arboviral disease at 34 weeks' gestation. She developed preeclampsia with severe respiratory failure which resulted in the emergency cesarean section, and the patient died 12 days after the onset of symptoms. The pre-term newborn weighed 2535 g, with an Apgar score of 4/8. He was referred to the neonatal ICU with neutrophilia and thrombocytopenia, several seizure episodes, and hemorrhagic disorders, which resulted in death. Chikungunya IgM antibody was detected in the cerebrospinal fluid. CONCLUSIONS: We present the first documented maternal and neonatal death in Brazil after probable chikungunya infection during pregnancy.

Chikungunya and diabetes, what do we know?

BACKGROUND: Chikungunya (CHIK) is a viral disease transmitted by mosquitoes. The first cases in Brazil were confirmed in 2014. Between 2016 and 2017, over 300,000 cases were identified during this period, with nearly 300 deaths. The clinical manifestations, pathogenesis and risk factors for occurrence of severe cases are not yet well understood, although it is known that the severity of the cases is associated with the presence of comorbidities, especially diabetes mellitus (DM). OBJECTIVE: To review the medical literature for the associations between DM and CHIK and to understand the potential impact on metabolic state and its complications. METHODS: Literature review was carried out to search for articles (English, Portuguese and Spanish) in Medline and Virtual Health Library databases for the period between 1952 and 2017, with the following keywords: "Chikungunya fever", "Chikungunya virus", "diabetes mellitus", "diabetes", "diabetes complications "and "multi-morbidities (MeSH) "with interposition of the Boolean operator "AND". RESULTS: After removal of duplicities and following exclusion criteria, 11 articles were selected. Our results showed that the patients of CHIK with DM had more severe and prolonged symptoms of CHIK and more frequently required hospitalization. No study investigated the biological process to explain how hyperglycemic state worsened the clinical manifestations of Chikungunya in diabetic patients. CONCLUSION: An important association between DM and the severity of CHIK is observed. Prospective and more rigorous controlled studies are required to generate evidence that might y elucidate the causes of this relationship. Given the fast expanding viral infection of Chikungunya in Central and South America, Asia and Africa in recent years in the context of exponential increase in diabetes globally, the issue deserves global attention.

Entomological and epidemiological aspects of dengue epidemics in Fortaleza, Ceará, Brazil, 2001-2012. / Aspectos entomológicos e epidemiológicos das epidemias de dengue em Fortaleza, Ceará, 2001-2012.

OBJECTIVE: to characterize the entomological and epidemiological aspects of dengue epidemics occurred in Fortaleza, Ceará, Brazil, from 2001 to 2012. METHODS: descriptive study with data from the Information System for Notifiable Diseases (Sinan), Information System of Hospitalizations due to Yellow Fever and Dengue (2001-2009), National Program for Dengue Control (2010-2012), and Rapid Survey of Aedes aegypti Infestation Index, referring to the years in which the incidence of dengue was above 75%. RESULTS: from 2001 to 2012, 194,446 cases of suspected dengue were notified; the epidemic years were 2001, 2006, 2008, 2011 and 2012; there was a progressive increase in the incidence of the disease (587.0/100 thousand inhabitants in 2001 and 1,561.1/100 inhabitants in 2012); there was co-circulation of up to three serotypes and high vector infestation, especially in water tanks. CONCLUSION: after a long period of virus circulation in Fortaleza, dengue remains as an important health issue, with severe cases and high fatality rate.

Trinta anos de dengue no Ceará: história, contribuições para ciência e desafios no cenário atual com tripla circulação de arbovírus / Thirty years of dengue in Ceará: history, contributions to science and challenges in the current scenario with triple arbovirus circulation

Introdução: Embora os primeiros casos de dengue no estado do Ceará tenham ocorrido em 1986, há registros da presença do mosquito Aedes aegypti desde os anos de 1851/1852. Mesmo após 30 anos, a dengue permanece como um problema grave de saúde pública com epidemias cada vez mais frequentes. Objetivo: Resgatar, reunir e sintetizar a evidência científica produzida nos primeiros 30 anos de dengue no Ceará, contribuindo para melhorar sua compreensão e as intervenções de vigilância e controle. Métodos: Realizou-se uma revisão de literatura com busca de artigos (inglês, português e espanhol) nas bases de dados Pubmed, Scielo, Clinicalkey, Lilacs, Google Acadêmico e banco virtual de teses e dissertações da CAPES, além de livros. O período de 1986 a 2016 foi usado como limite de busca e a mesma foi realizada entre os meses de agosto a novembro de 2016. Utilizaram-se os descritores controlados: dengue, Ceará, Fortaleza e Aedes; com interposição do operador boleano "AND". Resultados: Foram identificadas 574 publicações potencialmente elegíveis, sendo 461 artigos e 113 dissertações ou teses. Foram retirados 272 artigos duplicados ou que não atenderam aos critérios de inclusão. Foram lidos 114 artigos publicados em 60 revistas diferentes, sendo 72,8% artigos completos, 75,2% em inglês, 42,2% experimentais e 81,5% com abordagem quantitativa. Foi publicado apenas um artigo na década de 1980, já na década seguinte foram sete, número que cresceu bastante nos anos 2000, com 38 artigos. No entanto, já há 69 artigos publicados apenas na primeira metade da década de 2010. No período, o Ceará confirmou quase um milhão de casos de dengue, com a circulação dos quatro sorotipos (DENV1 - 1986, DENV2 - 1994, DENV3 - 2002 e DENV4 - 2011) e registrou pelo menos 14 epidemias. A partir de 2015, o Ceará passou a apresentar um cenário diferenciado de tripla epidemia, com a cocirculação autóctone de dois outros arbovírus: Chikungunya e Zika. Conclusão: Nesse período de 30 anos (1986-2016), o Ceará vivenciou várias epidemias de dengue, e, de certa forma, isto vem impulsionando a busca por respostas para o controle desta doença. Há claramente um crescimento em número de artigos publicados a cada ano, revelando a pujança dos grupos locais, que contribuiu de forma importante para a produção científica em diversos fatores relacionados à compreensão da epidemiologia e controle da dengue. (AU)

Introduction: Although the first cases of dengue in the state of Ceará occurred in 1986, there are records of the presence of the Aedes aegypti mosquito since the years 1851/1852. Even after 30 years, dengue remains a serious public health problem with frequent epidemics. Objective: To rescue, gather and synthesize scientific evidence in the first 30 years of dengue in Ceará, contributing to improve its understanding, surveillance and control interventions. Methods: An integrative review was carried out with the search of articles (English, Portuguese and Spanish) in the databases Pubmed, Scielo, Clinicalkey, Lilacs, Google Scholar and virtual bank of thesis and dissertations of CAPES, as well as books. The period from 1986 to 2016 was used as a search limit and it was carried out between August and November 2016. The following descriptors were used: dengue, Ceará, Fortaleza and Aedes; with interposition of the Boolean operator "AND". Results: 574 potentially eligible publications were identified, 461 articles and 113 dissertations or thesis. 272 duplicate articles were removed or did not meet the inclusion criteria. We have read 114 articles published in 60 different journals, 72.8% were full articles, 75.2% were in English, 42.2% were experimental and 81.5% were quantitative. Only one article was published in the 1980s, and in the next decade there were seven, this number grew up considerably in the 2000s with 38 articles. However, there are already 69 articles published only in the first half of the decade of 2010. In this period, Ceará confirmed almost 1 million cases of dengue with the circulation of the four serotypes (DENV1 - 1986, DENV2 - 1994, DENV3 - 2002 and DENV4 - 2011) and recorded at least 14 epidemics. From 2015 on, Ceará started to present a differentiated scenario of a triple epidemic, with the autochthonous co-circulation of two other arboviruses: chikungunya and Zika. Conclusion: In this period of 30 years (1986-2016), Ceará experienced. (AU)

Aspectos entomológicos e epidemiológicos das epidemias de dengue em Fortaleza, Ceará, 2001-2012 / Aspectos entomológicos y epidemiológicos de las epidemias de dengue en Fortaleza, Ceará, Brasil, 2001-2012 / Entomological and epidemiological aspects of dengue epidemics in Fortaleza, Ceará, Brazil, 2001-2012

Objetivo: descrever os aspectos entomológicos e epidemiológicos das epidemias de dengue ocorridas em Fortaleza, Ceará, Brasil, de 2001 a 2012. Métodos: estudo descritivo com dados dos Sistemas de Informação de Agravos de Notificação (Sinan), de Informações Hospitalares (SIH), do Programa de Febre Amarela e Dengue (2001-2009), do Programa Nacional de Controle da Dengue (2010-2012) e Levantamento Rápido do Índice de Infestação de Aedes aegypti, referentes aos anos quando a incidência da doença superou o percentil 75%. Resultados: De 2001 a 2012 foram notificados 194.446 casos suspeitos de dengue. Os anos epidêmicos foram: 2001, 2006, 2008, 2011 e 2012. Houve aumento progressivo da incidência (587,0/100 mil hab. [2001] e 1.561,1/100 mil hab [2012]), com cocirculação de até três sorotipos e elevada infestação vetorial, principalmente em depósitos para armazenar água. Conclusão: após longo período de circulação do vírus em Fortaleza, a dengue permanece como importante problema de saúde, com casos graves e alta letalidade.

Objetivo: caracterizar los aspectos entomoepidemiológicos de epidemias de dengue ocurridas en Fortaleza, Ceará, Brasil, entre 2001 y 2012. Métodos: estudio descriptivo con datos del Sistema de Información de Agravios de Notificación (Sinan), de Hospitalizaciones, del Sistema de Información de Fiebre Amarilla y Dengue (2001-2009), SisPNCD (2010-2012) y del Levantamiento Rápido del Índice de Infestación de Aedes aegypti, referentes a los años cuando la incidencia de dengue fue superior al percentil 75%. Resultados: en 2001-2012, se notificaron 194.446 casos sospechosos de dengue; los años epidémicos fueron 2001, 2006, 2008, 2011 y 2012; hubo un aumento progresivo de incidencia de dengue (587,0/100 mil hab. en 2001 y 1.561,1/100 hab. en 2012), con co-circulación de hasta tres serotipos y elevada infestación vectorial, principalmente en depósitos utilizados para almacenar agua. Conclusión: tras un largo período de circulación del virus en Fortaleza, el dengue permanece como un importante problema de salud, con casos más graves y alta letalidad.

Objective: to characterize the entomological and epidemiological aspects of dengue epidemics occurred in Fortaleza, Ceará, Brazil, from 2001 to 2012. Methods: descriptive study with data from the Information System for Notifiable Diseases (Sinan), Information System of Hospitalizations due to Yellow Fever and Dengue (2001-2009), National Program for Dengue Control (2010-2012), and Rapid Survey of Aedes aegypti Infestation Index, referring to the years in which the incidence of dengue was above 75%. Results: from 2001 to 2012, 194,446 cases of suspected dengue were notified; the epidemic years were 2001, 2006, 2008, 2011 and 2012; there was a progressive increase in the incidence of the disease (587.0/100 thousand inhabitants in 2001 and 1,561.1/100 inhabitants in 2012); there was co-circulation of up to three serotypes and high vector infestation, especially in water tanks. Conclusion: after a long period of virus circulation in Fortaleza, dengue remains as an important health issue, with severe cases and high fatality rate.

Changes in infestation sites of female Aedes aegypti in Northeast Brazil.

INTRODUCTION: We report the behavioral changes in use of oviposition sites in Aedes aegypti in Fortaleza, Brazil. METHODS: We evaluated the relationship between different types of breeding sites and changes in use from 2001 to 2012. RESULTS: More than 40% of the infested breeding sites were used to store water. We observed a three-fold reduction in the infestation of water tanks (p = 0.038) and more than nine-fold in tires (p = 0.035). The proportion of infested plant pots increased six-fold (p < 0.001). CONCLUSIONS: Infested breeding sites changed over time from domestic water tanks to small-volume breeding sites.