ABSTRACT
Severe neurological complications following arbovirus infections have been a major concern in seasonal outbreaks, as reported in the Northeast region of Brazil, where the same mosquito transmitted Zika (ZIKV), Dengue (DENV), and Chikungunya (CHIKV) viruses. In this study, we evaluated the levels of 36 soluble markers, including cytokines, chemokines, growth factors, and soluble HLA-G (Luminex and ELISA) in: i) serum and cerebrospinal fluid (CSF), during the acute phase and two years after the infection (recovery phase, only serum), ii) the relationship among all soluble molecules in serum and CSF, and iii) serum of infected patients without neurological complications, during the acute infection. Ten markers (sHLA-G, IL-10, IL-22, IL-8, MIP-1α, MIP-1ß, MCP-1, HGF, VEGF, and IL-1RA) exhibited differential levels between the acute and recovery phases, with pronounced increases in MIP-1α (P<0.0001), MCP-1 (P<0.0001), HGF (P= 0.0001), and VEGF (P<0.0001) in the acute phase. Fourteen molecules (IL-1ß, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-13, IL-15, IL-17A, IFN-α, TNF, and G-CSF) exhibited distinct levels between arbovirus patients presenting or not neurological complications. IL-8, EGF, IL-6, and MCP-1 levels were increased in CSF, while RANTES and Eotaxin levels were higher in serum. Soluble serum (IL-22, RANTES, Eotaxin) and CSF (IL-8, EGF, IL-3) mediators may discriminate putative risks for neurological complications following arbovirus infections. Neurological complications were associated with the presence of a predominant inflammatory profile, whereas in non-complicated patients an anti-inflammatory profile may predominate. Mediators associated with neuroregeneration (EGF and IL-3) may be induced in response to neurological damage. Broad spectrum immune checkpoint molecules (sHLA-G) interact with cytokines, chemokines, and growth factors. The identification of soluble markers may be useful to monitor neurological complications and may aid in the development of novel therapies against neuroinflammation.
Subject(s)
Biomarkers/analysis , Cytokines/analysis , HLA-G Antigens/analysis , Nervous System Diseases/diagnosis , Zika Virus Infection/diagnosis , Acute-Phase Proteins/analysis , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Brazil , Cytokines/blood , Cytokines/cerebrospinal fluid , Female , HLA-G Antigens/blood , HLA-G Antigens/cerebrospinal fluid , Host-Pathogen Interactions , Humans , Male , Middle Aged , Nervous System Diseases/complications , Recovery of Function , Solubility , Zika Virus/physiology , Zika Virus Infection/complications , Zika Virus Infection/virologyABSTRACT
A dengue é uma arbovirose causada pelo vírus Dengue (DENV), cujos principais vetores são os mosquitos Aedes aegypti e Aedes albopictus. A. aegypti é o único vetor de DENV em Cabo Verde, país que teve a sua primeira epidemia da dengue registrada em 2009. Contudo, pouco se sabe acerca da variação no nível de competência vetorial das populações do vetor aos diferentes sorotipos de DENV. O estudo teve como objetivo avaliar a competência vetorial de A. aegypti da ilha de Santiago, Cabo Verde, a quatro sorotipos de DENV. Para isso, os mosquitos foram alimentados artificialmente com sangue contendo diferentes sorotipos de DENV, e em seguida dissecados ao 7º, 14º e 21º dia após infecção (dpi) para verificar a presença do vírus no intestino, cabeça e glândulas salivares usando a técnica de RT-PCR. Adicionalmente, o número de cópias de RNA viral presente nas glândulas salivares foi determinado por qRT-PCR. Foram observadas altas taxas de infecção das glândulas salivares para DENV-2 e DENV-3 (65 e 75 por cento respectivamente), enquanto que para DENV-1, o RNA viral só foi detectado no intestino e cabeça, não chegando a infectar as glândulas salivares. DENV-4 não disseminou para cabeça e glândulas salivares, mantendo a infecção apenas no intestino (9 por cento). O número de cópias de RNA viral nas glândulas salivares não variou significativamente entre DENV-2 e DENV-3 e nem entre os diferentes períodos de incubação do vírus e títulos de DENV testados. Conclui-se, que a população de Aedes aegypti da ilha de Santiago, Cabo Verde, possui alta competência vetorial para as cepas de DENV-2 e DENV-3 e são pouco susceptíveis para as de DENV-1 e DENV-4. As cópias de RNA viral nas glândulas salivares mantêm-se relativamente constante por 21 dias após a infecção, o que pode potencializar a capacidade vetorial de mosquito A. aegypti e sugere alguma forma de modulação da replicação do vírus nesse órgão
Dengue is an arboviral diseasecaused by dengue virus (DENV), for which the main vectors are the mosquitoes Aedes aegypti andAedes albopictus. A. aegypti is the only DENV vector in Cape Verde, a country which suffered its first dengue outbreak in 2009. However, little is known about the variation in the level of vector competence of this mosquito population to the different DENV serotypes...
Subject(s)
Aedes , Dengue Virus , Insect Vectors/virology , Polymerase Chain Reaction , Africa, WesternABSTRACT
Objetivo Determinar la frecuencia y severidad del compromiso hepático en niños con Dengue. Métodos Estudio descriptivo que incluyó a 108 niños menores de 13 años con diagnóstico de infección por virus de Dengue, confirmada por detección plasmática de NS1 e IgM dengue-específica, que consultaron al Hospital Universitario de Neiva, en el período de junio de 2009 a mayo de 2010.El grado de daño hepático fue evaluado por criterios clínicos y bioquímicos que incluyeron transaminasas y albúmina. El diagnóstico de infección con Leptospira o Hepatitis A fue realizado por detección de IgM plasmática específica medida en fase aguda y convaleciente. Resultados De los casos incluidos, 98 y 10 casos fueron clasificados como dengue con signos de alarma y Dengue grave, respectivamente. Dos de cada tres pacientes con Dengue presentaron signos de alarma y todos los pacientes con Dengue grave presentaron algún grado de compromiso hapático evidenciado clínica y bioquímicamente. Independientemente de la clasificación clínica, la hepatomegalia fue el signo clínico cardinal del compromiso hepático y se presentó en el 85 % del total de niños incluidos. De resaltar, 5 de los pacientes presentaron probable coinfección de dengue y leptospira, siendo la primera descripción en Colombia. En ninguno de los casos analizados se presentó enfermedad aguda por Hepatitis A. Conclusión El compromiso hepático es muy frecuente en la infección por virus Dengue. Enfermedades como la leptospirosis deben ser tenidas en cuenta no sólo en el diagnóstico diferencial del paciente pediátrico febril con compromiso hepático, sino como causa de coinfección en el niño con Dengue en el sur de Colombia.
Objective Dengue is the most important arthropod-borne viral disease in the world; it can be life-threatening because of liver involvement. Aim Determining liver involvement frequency and severity in dengue-infected children. Methods This was a descriptive case series study which involved studying 108 dengue-infected children aged less than 13 years old whose infection had been confirmed by the detection of dengue-specific IgM and NS1 in plasma. Clinical and biochemical parameters were used for evaluating liver involvement, including transaminases and albumin. Hepatitis A and leptospira infection were also evaluated by using ELISA to detect pathogen-specific IgM in plasma during acute and convalescence phases. The study was carried out at a teaching hospital in Neiva from June 2009 to May 2010. Results Ninety-eight of the aforementioned cases were clinically classified as dengue with warning signs (DWS) and 10 as severe dengue (SD). Two out of three DWS patients and all SD patients had some degree of liver involvement, shown clinically and biochemically. Regardless of the clinical classification, hepatomegaly was the main clinical sign of liver involvement and was present in 85% of all the children in the study. It is worth noting that 5 patients had probable dengue and leptospirosis co-infection, this being the first instance of this in Colombia. None of the cases analyzed here had acute hepatitis A. Conclusions Liver compromise should be considered in confirmed cases of dengue as shown in this series of children. Leptospirosis must be considered as differential diagnosis and also as causing co-infection in a febrile child.