Levels of Angiopoietin 2 Are Predictive for Mortality in Patients Infected With Yellow Fever Virus.

In 2018 there was a large yellow fever outbreak in São Paulo, Brazil, with a high fatality rate. Yellow fever virus can cause, among other symptoms, hemorrhage and disseminated intravascular coagulation, indicating a role for endothelial cells in disease pathogenesis. Here, we conducted a case-control study and measured markers related to endothelial damage in plasma and its association with mortality. We found that angiopoietin 2 is strongly associated with a fatal outcome and could serve as a predictive marker for mortality. This could be used to monitor severe cases and provide care to improve disease outcome.

First DFT-supported point of care and novel electrochemical biosensing: Determination of yellow fever NS1 antibody in human plasma.

In our study, we developed a point of care electrochemical biosensing platform based on the functionalized cysteine-positioned gold electrode to diagnose yellow fever disease from human plasma samples. The developed platform underwent characterization through diverse methods encompassing cyclic voltammetry, electrochemical impedance spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, and density-functional theory. The capacitive interaction between yellow fever virus non-structural antigen and antibody gave a cathodic signal at approximately -260 mV, and increased in proportion to the amount of non-structural antibody. The created electrochemical biosensor has an ability to detect 96 ag/mL of the yellow fever non-structural antibody with an extensive analytical range varied from 0.1 fg/mL to 1 µg/mL. The interference effects of various substances that could be found in human plasma, and the performance of the method were examined from the point of recovery and relative standard deviation for human plasma samples; hereby, the results confirmed the unprecedented selectivity and accuracy of the proposed method.

Circulation of yellow fever virus in Benin city, Edo state Nigeria.

Yellow fever (YF) is one of the most acute viral hemorrhagic diseases of the 18th and 19th centuries, which continues to cause severe morbidity and mortality in Africa. After 21 years of no reported cases of yellow fever in Nigeria, till 2017 where a case was confirmed in Kwara State, also in November 2018,WHO was informed of a cluster of suspected yellow fever cases and deaths in Edo state, Nigeria. The study was among all age group attending health centres in Benin City, Edo state. A total of 280 blood samples were collected from consented febrile patients and were screened for antibodies to Zika virus using rapid diagnostic test (RDT) kits. Blood samples positive to Zika virus (IgM/IgG RDT), were subjected to molecular characterization. Using the flavividae family primers, six (6) samples where confirmed positive by Hemi-nested reverse transcription PCR (hnRT-PCR) sequencing. Nucleotide sequence blast revealed the sequenceswere similar to Yellow fever virus strains. Phylogenetic analysis revealed that the yellow fever virus sequences are closely related to the African strains. Despite the safe and effective yellow fever vaccine, yellow fever virus is seen to be in circulation, hence the need for continues mass vaccination.

Yellow fever: profile of cases and factors associated with death in a hospital in the State of Rio de Janeiro, 2017-2018 / Febre amarela: perfil dos casos e fatores associados ao óbito em hospital referência no estado do Rio de Janeiro, 2017-2018

ABSTRACT OBJECTIVE Describe the clinical and epidemiological profile of confirmed cases of yellow fever whose patients were hospitalized in a general hospital for infectious diseases in the State of Rio de Janeiro, Brazil, from March 11, 2017 to June 15, 2018, during a recent outbreak and factors associated with death. METHODS This is a retrospective observational study with analysis of secondary databases of local epidemiological surveillance system, and complementary data collection from epidemiological investigation records and clinical records. Study variables included demographic, epidemiological, clinical, and laboratory data. A descriptive statistical analysis and a bivariate and multivariate analysis by logistic regression were performed to analyze factors associated with death. RESULTS Fifty-two patients diagnosed with yellow fever were hospitalized, 86.5% male patients, median age 49.5 years, 40.4% rural workers. The most frequent signs and symptoms were fever (90.4%), jaundice (86.5%), nausea and/or vomiting (69.2%), changes in renal excretion (53.8%), bleeding (50%), and abdominal pain (48.1%), with comorbidity in 38.5% of all cases. The lethality rate was 40.4%. Factors significantly associated with a higher chance of death in the bivariate analysis were: bleeding, changes in renal excretion, and maximum values of direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine. In the multivariate analysis by logistic regression, only changes in renal excretion and ALT remained significant predictors of higher chance of death. A threshold effect was also observed for AST. The cutoff points identified as high risk for death were ALT > 4,000 U/L and AST > 6,000 U/L. CONCLUSIONS This study contributed to the knowledge on the profile of confirmed cases of high severity yellow fever. The main factors associated with death were changes in renal excretion and elevated serum transaminases, especially ALT. High lethality emphasizes the need for early diagnosis and treatment, and the importance of increasing vaccination coverage.

RESUMO OBJETIVO Descrever o perfil clínico-epidemiológico dos casos confirmados de febre amarela internados em hospital geral de referência para doenças infecciosas no estado do Rio de Janeiro, Brasil, de 11 de março de 2017 a 15 de junho de 2018, durante recente surto e fatores associados ao óbito. MÉTODOS Estudo observacional retrospectivo, com análise de bases de dados secundários da vigilância epidemiológica local e coleta complementar de dados nas fichas de investigação epidemiológica e prontuários clínicos. As variáveis analisadas incluíram dados demográficos, epidemiológicos, clínicos e laboratoriais. Foi conduzida análise estatística descritiva bivariada e múltipla por regressão logística para estudo de fatores associados ao óbito. RESULTADOS Foram internados 52 casos confirmados, 86,5% deles homens, com mediana de idade de 49,5 anos e 40,4% trabalhadores rurais. Os sinais e sintomas mais frequentes foram: febre (90,4%), icterícia (86,5%), náuseas e/ou vômitos (69,2%), alterações de excreção renal (53,8%), hemorragias (50%) e dor abdominal (48,1%), com comorbidade em 38,5% dos casos. A letalidade foi de 40,4%. Os fatores associados significativamente à maior chance de óbito na análise bivariada foram: hemorragia, alterações de excreção renal e valores máximos de bilirrubina direta, aspartato aminotransferase (AST), alanina aminotransferase (ALT), ureia e creatinina. Na análise múltipla por regressão logística, apenas alterações de excreção renal e ALT permaneceram como preditores significativos de maior chance de óbito. Observou-se ainda efeito limítrofe para AST. Os pontos de corte identificados como de alto risco para óbito foram ALT > 4.000 U/L e AST > 6.000 U/L. CONCLUSÕES O estudo contribuiu para o conhecimento do perfil de casos confirmados de febre amarela com gravidade alta. Os principais fatores associados ao óbito foram a alteração da excreção renal e a elevação sérica de transaminases, sobretudo a ALT. A letalidade elevada reforça a necessidade de diagnóstico e tratamento precoces, e a importância do incremento da cobertura vacinal.

Diagnóstico sorológico de infecções por dengue e febre amarela em casos suspeitos no Estado do Pará, Brasil, 1999 / Serological diagnosis of dengue and yellow fever infections in suspected cases from Pará State, Brazil, 1999

De junho a dezembro de 1999, foram coletadas 785 amostras de soro de pacientes com suspeita clínica de dengue e/ou febre amarela. Os pacientes foram atendidos nas unidades de saúde distribuídas pelas seis mesorregiöes do Estado do Pará, Brasil. As amostras de soro foram testadas pelo método de inibiçäo da hemaglutinaçäo para detecçäo de anticorpos para Flavivirus e pelo ensaio imunoenzimático para detecçäo de imunoglobulina M para dengue e febre amarela. Das amostras coletadas, 563 (71,7 por cento) foram positivas pelo IH, e dentre estas 150 (26,6 por cento) foram positivas pelo ELISA-IgM. O vírus dengue foi responsável pela maioria das infecçöes recentes em todas as mesorregiöes e os casos de febre amarela detectados neste estudo foram restritos às mesorregiöes Marajó e Sudeste

Respuestas serologicas secundarias en la epidemia de dengue de 1998 em Salta, Argentina, donde co-circulan otros flavivirus / Secondary serologic responses to dengue epidemic in 1998 in Salta, Argentina, where other flavivirus co-circulate

En 1998, ocurrió una epidemia de dengue (serotipo 2) en la provincia de Salta, Norte de Argentina, después de la primera detección de dengue en esa zona en 1997. En este trabajo se clasificaron las respuestas serológicas de los casos ocurridos en 1998 como primarios o secundarios, dado que riesgo de la enfermadad severa es mayor en los casos secundarios. Se estudiaron 154 casos por las pruebas de neutralización (NT) e inhibición de la hemoaglutinación. Se clasificaron 38 casos ( 25 porciento) como respuestas primarias y 84 casos (54 porciento) como respuestas secundarias. Los restantes 32 casos (21 porciento) con títulos de IgG en el límite no pudieron ser clasificados. Se analizó la exposición previa a otros flavivirus (Encefalitis de San Luis [SLE] y Fiebre Amarilla [YF]) que pueden cruzar serológicamente, como posible causa de los patrones secundarios. Nuestros resultados indican que el 83 porciento de los casos clasificados como respuesta a dengue secundaria, podrían atribuirse a exposiciones previas a los virus SLE o YF, o a reacciones serológicas cruzadas. La vacunación contra YF fue un factor menor contribuyente al patrón de respuesta secundaria encontrado. El hallazgo de serología positiva para YF en personas que no reconocen vacunación previa debe alertar acerca de la posible circulación silenciosa del virus de la YF, en una área que puede soportar tantos ciclos urbanos como selváticos. Otros casos que mostraron respuesta secundarias permanecen sin explicación, surgirindo la ocurrencia de infecciones previas por otros serotipos de dengue o por otro flavivirus distintos a SLE o YF.

Jungle yellow fever: clinical and laboratorial studies emphasizing viremia on a human case

Os autores estudaram um caso humano de febre amarela silvestre, sob os aspectos clinico, laboratorial e epidemiologico. O paciente apresentava febre (39ºC), calafrios, sudorese, cefaleia, dor lombar, mialgia, dor abdominal em epigastrico, nauseas, vomitos, diarreia e prostracao. Realatava permanencia em areas onde foram constatados casos de febre amarela silvestre e nao havia historico de vacinacao anterior...