RESUMO
Saint Louis encephalitis virus (SLEV) infection is an arbovirosis associated with a broad spectrum of neurological complications. We present a case of a 55-year-old man hailing from Manaus, a city situated in the heart of the Amazon Rainforest, who exhibited symptoms of vertigo, tremors, urinary and fecal retention, compromised gait, and encephalopathy 3 weeks following SLEV infection. Neuroaxis MRI revealed diffuse, asymmetric, and poorly defined margins hyperintense lesions with peripheral and ring enhancement in subcortical white matter, as well as severe spinal cord involvement. Serology for SLEV was positive both on serum and cerebrospinal fluid. To the best of our knowledge, the present report is the first to show brain lesions along with myelitis as a post-infectious complication of SLEV infection.
Assuntos
Encefalite de St. Louis , Encefalomielite Aguda Disseminada , Masculino , Humanos , Pessoa de Meia-Idade , Vírus da Encefalite de St. Louis/fisiologia , Encefalomielite Aguda Disseminada/diagnóstico por imagem , Encefalomielite Aguda Disseminada/etiologia , Encefalite de St. Louis/complicações , Encefalite de St. Louis/diagnósticoRESUMO
St. Louis encephalitis virus (SLEV) is a neglected mosquito-borne Flavivirus that may cause severe neurological disease in humans and other animals. There are no specific treatments against SLEV infection or disease approved for human use, and drug repurposing may represent an opportunity to accelerate the development of treatments against SLEV. Here we present a scalable, medium-throughput phenotypic cell culture-based screening assay on Vero CCL81 cells to identify bioactive compounds that could be repurposed against SLEV infection. We screened eighty compounds from the Medicines for Malaria Venture (MMV) COVID Box library to identify nine (11%) compounds that protected cell cultures from SLEV-induced cytopathic effects, with low- to mid-micromolar potencies. We validated six hit compounds using viral plaque-forming assays to find that the compounds ABT-239, Amiodarone, Fluphenazine, Posaconazole, Triparanol, and Vidofludimus presented varied levels of antiviral activity and selectivity depending on the mammalian cell type used for testing. Importantly, we identified and validated the antiviral activity of the anti-flavivirus nucleoside analog 7DMA against SLEV. Triparanol and Fluphenazine reduced infectious viral loads in both Vero CCL81 and HBEC-5i cell cultures and, similar to the other validated compounds, are likely to exert antiviral activity through a molecular target in the host.
Assuntos
Encefalite de St. Louis , Flavivirus , Malária , Triparanol , Animais , Humanos , Vírus da Encefalite de St. Louis , Encefalite de St. Louis/diagnóstico , Flufenazina , Antivirais/farmacologia , MamíferosRESUMO
La encefalitis por el virus de Saint Louis es una enfermedad que se transmite a través de mosquitos de la especie Culex.En Argentina, se registran casos esporádicos, habitualmente asintomáticos en niños. Se presenta el caso de una paciente con manifestaciones clínicas inusuales en edad pediátrica y lesiones en el sistema nervioso central no descritas hasta el momento en la literatura. Se trata de una niña de 8 años, que consultó por síndrome febril, cambios conductuales, ataxia, clonus y rigidez de nuca. En el líquido cefalorraquídeo, se detectó pleocitosis predominantemente mononuclear. Se realizó una resonancia magnética, que evidenció imágenes de isquemia bitalámica. La infección por virus de Saint Louis se diagnosticó por IgM en el suero y el líquido cefalorraquídeo. La paciente evolucionó de manera favorable. Al momento del egreso hospitalario, persistía con bradipsiquia y alteraciones conductuales y se recuperó definitivamente 45 días después del alta.
Saint Louis encephalitis is transmitted by Culex mosquitoes. In Argentina sporadic cases are registered. Symptomatic illness is unusual in children. We present a case of meningoencephalitis caused by an uncommon viral infection. The clinical signs and symptoms are unusual for pediatric patients and the bilateral thalamic compromise showed on magnetic resonance has not been described previously. An 8-year-old girl consulted due to fever, behavior disorders and ataxia. Clonus and neck stiffness were detected at physical exam. Cerebrospinal fluid revealed mononuclear leukocytosis; bilateral ischemic compromise was observed in thalamus by magnetic resonance. Saint Louis virus was confirmed by serology: serum and cerebrospinal fluid IgM were positive during the acute phase of the disease and serum IgG was positive four weeks later. Most of the signs and symptoms of the disease were resolved, however mild behavior disorders were observed as acute sequelae up to 45 days after hospital discharge.
Assuntos
Humanos , Feminino , Criança , Encefalite de St. Louis/diagnóstico , CulexRESUMO
Introduction Arboviruses are an important public health problem in Brazil, in especially flaviviruses, including the Saint Louis encephalitis virus (SLEV) and the Rocio virus (ROCV), are especially problematic. These viruses are transmitted to humans or other vertebrates through arthropod bites and may cause diseases with clinical manifestations that range from asymptomatic infection, viral hemorrhagic fever to encephalitis. Methods A serological survey of horses from various regions of Brazil using an enzyme-linked immunosorbent assay (ELISA) with recombinant SLEV domain III peptides and ROCV E protein as antigens. Results Overall, 415 (55.1%) of the 753 horses that were screened were seropositive for flavivirus and, among them, monotypic reactions were observed to SLEV in 93 (12.3%) and to ROCV in 46 (6.1%). These results suggested that these viruses, or other closely related viruses, are infecting horses in Brazil. However, none of the studied horses presented central nervous system infection symptoms. Conclusions Our results suggest that SLEV and ROCV previously circulated among horses in northeast, west-central and southeast Brazil. .
Assuntos
Animais , Anticorpos Antivirais/sangue , Vírus da Encefalite de St. Louis/imunologia , Encefalite de St. Louis/veterinária , Infecções por Flavivirus/veterinária , Doenças dos Cavalos/epidemiologia , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Encefalite de St. Louis/diagnóstico , Encefalite de St. Louis/epidemiologia , Infecções por Flavivirus/diagnóstico , Infecções por Flavivirus/epidemiologia , Cavalos , Doenças dos Cavalos/diagnóstico , Estudos SoroepidemiológicosRESUMO
Introduction Saint Louis encephalitis virus (SLEV) primarily occurs in the Americas and produces disease predominantly in humans. This study investigated the serological presence of SLEV in nonhuman primates and horses from southern Brazil. Methods From June 2004 to December 2005, sera from 133 monkeys (Alouatta caraya, n=43; Sapajus nigritus, n=64; Sapajus cay, n=26) trap-captured at the Paraná River basin region and 23 blood samples from farm horses were obtained and used for the serological detection of a panel of 19 arboviruses. All samples were analyzed in a hemagglutination inhibition (HI) assay; positive monkey samples were confirmed in a mouse neutralization test (MNT). Additionally, all blood samples were inoculated into C6/36 cell culture for viral isolation. Results Positive seroreactivity was only observed for SLEV. A prevalence of SLEV antibodies in sera was detected in Alouatta caraya (11.6%; 5/43), Sapajus nigritus (12.5%; 8/64), and S. cay (30.8%; 8/26) monkeys with the HI assay. Of the monkeys, 2.3% (1/42) of A. caraya, 6.3% 94/64) of S. nigritus, and 15.4% (4/26) of S. cay were positive for SLEV in the MNT. Additionally, SLEV antibodies were detected by HI in 39.1% (9/23) of the horses evaluated in this study. Arboviruses were not isolated from any blood sample. Conclusions These results confirmed the presence of SLEV in nonhuman primates and horses from southern Brazil. These findings most likely represent the first detection of this virus in nonhuman primates beyond the Amazon region. The detection of SLEV in animals within a geographical region distant from the Amazon basin suggests that there may be widespread and undiagnosed dissemination of this disease in Brazil. .
Assuntos
Animais , Camundongos , Vírus da Encefalite de St. Louis/imunologia , Encefalite de St. Louis/veterinária , Doenças dos Cavalos/epidemiologia , Doenças dos Macacos/epidemiologia , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Encefalite de St. Louis/diagnóstico , Encefalite de St. Louis/epidemiologia , Cavalos , Testes de Inibição da Hemaglutinação/veterinária , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/virologia , Doenças dos Macacos/diagnóstico , Doenças dos Macacos/virologia , Platirrinos , PrevalênciaRESUMO
Se presenta un varón de 10 años procedente de una zona pobre de Montevideo, que ingresa a fines del verano por un cuadro de 6 días de evolución caracterizado al inicio por fiebre agregando, posteriormente, cefaleas muy intensas y elementos de irritación meníngea. En la evolución: confuso, fotofobia, incapacidad de responder órdenes simples, no reconoce a los familiares ni al personal. Hipertensión arterial. Luego de 6 días de evolución mejora espontáneamente. En la paraclínica el único elemento positivo en sangre fue IgM positiva para encefalitis de San Luis. Esta enfermedad es transmitida por picadura de mosquitos del género Culex. El virus pertenece a la familia Flaviviridae. No hay descripciones previas de esta enfermedad en el país.
Assuntos
Humanos , Masculino , Criança , Culex musca , Encefalite de St. Louis/diagnóstico , Insetos VetoresRESUMO
St. Louis encephalitis virus (SLEV) and West Nile virus (WNV) present ecological and antigenic similarities and are responsible for serious human diseases. In addition, WNV is a significant pathogen in terms of equine health. The purpose of our study was to analyse the seroprevalence of SLEV and WNV in equine sera collected in Santa Fe Province, Argentina. The seroprevalence determined using the plaque reduction neutralisation test was 12.2% for SLEV, 16.2% for WNV and 48.6% for a combination of both viruses. These results provide evidence of the co-circulation of SLEV and WNV in equines in Santa Fe.
Assuntos
Animais , Vírus da Encefalite de St. Louis/isolamento & purificação , Encefalite de St. Louis/veterinária , Doenças dos Cavalos/virologia , Cavalos/virologia , Febre do Nilo Ocidental/veterinária , Vírus do Nilo Ocidental/isolamento & purificação , Argentina/epidemiologia , Vírus da Encefalite de St. Louis/imunologia , Encefalite de St. Louis/diagnóstico , Encefalite de St. Louis/epidemiologia , Encefalite de St. Louis/virologia , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/epidemiologia , Estudos Soroepidemiológicos , Febre do Nilo Ocidental/diagnóstico , Febre do Nilo Ocidental/epidemiologia , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/imunologiaRESUMO
Saint Louis encephalitis virus (SLE) is a mosquito borne disease. Only a small proportion of cases progress to severe clinical forms. There have been few reports on HIV-infected patients and the relationship between immunodeficiency and the course of the disease remains unclear. Herein we describe two cases of SLE in HIV-1-infected patients in Buenos Aires city.
Assuntos
Adulto , Humanos , Masculino , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Encefalite de St. Louis/diagnóstico , Argentina , CidadesRESUMO
Se describen los hallazgos epidemiológicos y clínicos de 13 enfermos con diagnóstico de infección por virus de la encefalitis de San Luis, con transmisión entre enero y marzo de 2010, en el Area Metropolitana Buenos Aires (AMBA). Los 13 enfermos, promedio de edad 38 años, tuvieron un comienzo agudo caracterizado por hipertermia y cefalea. Entre los días dos y diez de iniciados los síntomas, 7/13 enfermos tuvieron signos y síntomas de compromiso neurológico caracterizado por meningitis sin signos encefálicos en 1/7. En 6/7 los hallazgos más frecuentes fueron: rigidez de nuca, desorientación temporoespacial, fotofobia, confusión y alteración del lenguaje. Dos resonancias magnéticas y un electroencefalograma presentaron signos de afectación de lóbulos temporales. El líquido cefalorraquídeo se caracterizó por pleocitosis con predominio de células mononucleadas, glucorraquia normal y discreto aumento de proteínas. No hubo casos fatales. En 6/13 pacientes la sospecha clínica inicial fue dengue. Por la agrupación espacial y temporal de los casos puede considerarse un brote epidémico, el primero conocido en el AMBA, ya que no se había notificado previamente la circulación epidémica del virus.
We describe the epidemiological and clinical findings of 13 patients with diagnosis of infection by St. Louis encephalitis virus, transmitted between January and March 2010 in Buenos Aires Metropolitan Area (AMBA). Thirteen patients, average age 38 years, had an acute onset with hyperthermia and headache. Between days two and ten of the onset of symptoms, 7/13 patients had signs and symptoms of neurological involvement. This was characterized by meningitis without encephalic sings in 1/7 and in 6/7 the most frequent findings were: stiff neck, disorientation, photophobia, confusion and language impairment. Two MR and one EEG revealed signs of involvement of temporal lobes. The cerebrospinal fluid showed pleocytosis with predominance of mononuclear cells, normal glucose and moderately elevated protein. There were no fatalities cases. In 6/13 patients the initial clinical suspicion was dengue. As epidemic virus circulation had not been previously reported in the AMBA it can be considered an outbreak of St. Luis encephalitis for the spatial and temporal clustering of cases.
Assuntos
Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Surtos de Doenças/estatística & dados numéricos , Encefalite de St. Louis/epidemiologia , População Urbana/estatística & dados numéricos , Argentina/epidemiologia , Encefalite de St. Louis/líquido cefalorraquidiano , Encefalite de St. Louis/diagnósticoRESUMO
Se presenta un paciente de 80 años de edad, residente en la Ciudad de Buenos Aires, con diagnóstico serológico para el virus de la encefalitis de San Luis (SLE) durante el brote de dengue ocurrido entre enero y mayo de 2009. Presentaba leucemia linfoide crónica en tratamiento con clorambucilo, cáncer de próstata tratado con hormonoterapia y radioterapia, e imágenes óseas compatibles con metástasis. El estudio del líquido cefalorraquídeo demostró pleocitosis con predominio de mononucleares y proteinorraquia elevada. El resultado de los cultivos para bacterias, hongos y micobacterias, así como el PCR en LCR para herpes virus, HSV, CMV y EBV, fue negativo. Se detectaron anticuerpos IgM para virus SLE tanto en LCR como en muestra de suero, con seroconversión IgG por neutralización en cultivos celulares y resultados negativos para los demás Flavivirus con circulación en Argentina. Se revisan evidencias sobre la presencia de virus de San Luis en nuestro país, y se señala la importancia de la confirmación diagnóstica y el estudio de otros Flavivirus en casos sospechosos de dengue con presentación grave o atípica. Este trabajo remarca la necesidad de fortalecer tanto la vigilancia epidemiológica del virus SLE, como el control vectorial para prevenir las diferentes infecciones transmitidas por mosquitos y conocer su efecto en Salud Pública en la Argentina.
We report the case of a male, 80-year-old resident in the City of Buenos Aires, with a diagnosis of St. Louis encephalitis (SLE) during a countrywide dengue outbreak, from January to May 2009. The patient had a chronic lymphocytic leukemia treated with chlorambucil, prostate cancer (hormone therapy and radiotherapy) and images consistent with bone metastases. Cerebrospinal fluid examination showed pleocytosis with a predominance of mononuclear cells and high protein concentration. Bacteria, fungi and mycobacteria cultures, as well as the PCR for herpes virus, HSV, CMV and EBV, were negative. We confirmed the diagnosis of SLE by detection of IgM antibodies in both CSF and serum sample with IgG seroconversion by neutralization in cell cultures and negative results for other flaviviruses with known circulation in Argentina. We review the evidence for the presence of the St. Louis virus in our country and point to the importance of the diagnosis and the search of other Flavivirus in suspected dengue cases with severe or atypical presentation. This work emphasizes the need to strengthen both the epidemiological surveillance of SLE, and vector control to prevent different infections transmitted by mosquitoes and to understand their true impact on public health in Argentina.
Assuntos
Idoso de 80 Anos ou mais , Humanos , Masculino , Surtos de Doenças , Dengue/epidemiologia , Encefalite de St. Louis/diagnóstico , Argentina/epidemiologia , Imunoglobulina M/sangue , Imunoglobulina M/líquido cefalorraquidianoRESUMO
We prospectively sampled flavivirus-naïve horses in northern Colombia to detect West Nile virus (WNV) and St. Louis encephalitis virus (SLEV) seroconversion events, which would indicate the current circulation of these viruses. Overall, 331 (34.1 percent) of the 971 horses screened were positive for past infection with flaviviruses upon initial sampling in July 2006. During the 12-month study from July 2006-June 2007, 33 WNV seroconversions and 14 SLEV seroconversions were detected, most of which occurred in the department of Bolivar. The seroconversion rates of horses in Bolivar for the period of March-June 2007 reached 12.4 percent for WNV and 6.7 percent for SLEV. These results comprise the first serologic evidence of SLEV circulation in Colombia. None of the horses sampled developed symptoms of encephalitis within three years of initial sampling. Using seroconversions in sentinel horses, we demonstrated an active circulation of WNV and SLEV in northern Colombia, particularly in the department of Bolivar. The absence of WNV-attributed equine or human disease in Colombia and elsewhere in the Caribbean Basin remains a topic of debate and speculation.
Assuntos
Animais , Anticorpos Antivirais/sangue , Vírus da Encefalite de St. Louis/imunologia , Encefalite de St. Louis/veterinária , Doenças dos Cavalos/virologia , Cavalos/virologia , Febre do Nilo Ocidental/veterinária , Vírus do Nilo Ocidental/imunologia , Colômbia/epidemiologia , Ensaio de Imunoadsorção Enzimática , Encefalite de St. Louis/diagnóstico , Encefalite de St. Louis/epidemiologia , Doenças dos Cavalos/imunologia , Cavalos/imunologia , Estudos Prospectivos , Vigilância da População/métodos , Febre do Nilo Ocidental/diagnóstico , Febre do Nilo Ocidental/epidemiologiaAssuntos
Humanos , Masculino , Criança , Encefalite de St. Louis/diagnóstico , Febre/complicações , Febre/diagnóstico , ArgentinaRESUMO
O presente estudo relata o isolamento do vírus da encefalite São Luis (SLEV) de um caso febril humano suspeito de dengue, em São Pedro, Estado de São Paulo. MAC-ELISA realizado com soros das fases aguda e convalescente foi inconclusivo e anticorpos IgG foram detectados por inibição da hemaglutinação para flavivirus. Imunofluorescência indireta com cultura de células C6/36 inoculadas com soro da fase aguda foi positivo para flavivirus mas negativo quando testado com anticorpos monoclonais para dengue. O RNA extraído de cultura de células infectadas foi amplificado na presença de primers universais para o gênero Flavivirus, deduzidos de uma região da proteína não estrutural 5 e diretamente sequenciado. Os resultados da pesquisa no BLAST indicaram que a seqüência apresenta 93% de similaridade de nucleotídeos com a seqüência de SLEV (cepa MS1.7), confirmado por RT-PCR, realizado com primers específicos para SLEV. O fato de SLEV ter sido identificado como a causa de doença humana indica a necessidade de aprimorar a vigilância a fim de detectar precocemente esse agente no Estado de São Paulo e no Brasil. Esse caso é também um alerta para os profissionais de saúde sobre a necessidade de investigações clínicas e epidemiológicas mais completas sobre doenças febris como no caso relatado. Infecções por SLEV podem não ser reconhecidas ou confundidas com outras causadas por arbovírus como a dengue.