RESUMO
Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.
Assuntos
Doenças do Sistema Nervoso , Infecção por Zika virus , Zika virus , Animais , Feminino , Humanos , Camundongos , Placenta , Gravidez , Replicação Viral , Infecção por Zika virus/complicaçõesRESUMO
Multidrug-resistant tuberculosis (MDR-TB) represents a significant impact in transmission, outcome, and health costs. The World Health Organization recommends implementation of rapid diagnostic methods for multidrug-resistance detection. This study was performed to evaluate the frequency of pre- and extensively drug resistant tuberculosis (pre-XDR-TB and XDR-TB) among MDR-TB patients, the pattern of resistance mutations for fluoroquinolones and the clinical outcome. Adult patients followed at a Brazilian regional reference center for TB, from January 2013 to June 2019 were included. Stored Mycobacterium tuberculosis (Mtb) cultures were recovered, the DNA was extracted, and the susceptibility test was performed using the line probe assay for second line antimycobacterial drugs, Genotype MTBDRsl version 2.0 (Hain Lifescience, CmbH, Germany). Among 33 MDR-TB included patients, we diagnosed XDR-TB or pre-XDR in five (15%) cases. Of these, mutations related to fluoroquinolones resistance were observed in four Mtb isolates, including one who had no phenotypic resistance profile. In two other patients with phenotypic resistance to ofloxacin, genotypic resistance was not found. Case fatality rate was 60% in pre/XDR-TB group, compared to 3.6% in the remaining of patients. This study observed few cases of pre-XDR and XDR-TB among a MDR-TB cohort. Phenotypic and genotypic assays presented good agreement. Clinical outcome was more favorable for patients with susceptibility to fluoroquinolones and injectable drugs.
Assuntos
Mycobacterium tuberculosis , Preparações Farmacêuticas , Tuberculose Resistente a Múltiplos Medicamentos , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Brasil , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genéticaAssuntos
Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Hospedeiro Imunocomprometido , Adulto , Idoso , Técnicas Bacteriológicas , Brasil , Escherichia coli/classificação , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Feminino , Genótipo , Hospitais de Ensino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Sorogrupo , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Zika virus (ZIKV) is an emerging arthropod-borne flavivirus transmitted by Aedes mosquitoes. Recent commentaries regarding ZIKV routes of transmission describe a potential transmission by transfusion. Herein, we report a probable case of transfusion-transmitted ZIKV infection through a platelet transfusion that was detected from postdonation information. CASE REPORT: A blood donor made a voluntary telephone report to the blood donor facility 3 days after donation and informed the facility of a febrile illness (fever, malaise, and headaches). Due to the ongoing dengue epidemic, the initial clinical investigation included dengue among other possible diagnoses. The serology and molecular laboratory results excluded dengue infection. However, stored samples from the donation were positive for ZIKV on reverse transcription-polymerase chain reaction (RT-PCR) analysis. A retrospective investigation demonstrated that the platelet concentrate, which was part of a pool, had been transfused after a liver transplantation. A physician had evaluated the patient 4 days after surgery. Laboratory investigation showed enzyme-linked immunosorbent assay results that were negative for dengue immunoglobulin M antibodies; however, the results were positive for hemagglutination inhibition antibodies against flavivirus. ZIKV RT-PCR and virus isolation analyses in cell cultures from recipient serum were both positive. The sequencing confirmed ZIKV in the donor and patient samples. Ten partial nucleotide sequences from the ZIKV strain that were detected in the donor were aligned and compared with the ZIKV genome detected in the recipient, revealing a 99.8% homology between the two strains. CONCLUSIONS: This is a case of probable transmission of ZIKV through blood transfusion. The patient had been transfused with the blood product from an infected donor, most likely in the incubation period after ZIKV infection but prior to clinical disease onset. This report emphasizes the importance of postdonation information and recipient investigations during outbreaks of potentially blood-borne infections.
Assuntos
Transfusão de Plaquetas/efeitos adversos , Torque teno virus/isolamento & purificação , Infecção por Zika virus/transmissão , Zika virus/isolamento & purificação , Doadores de Sangue , Plaquetas/virologia , Patógenos Transmitidos pelo Sangue , Brasil , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de RNA , Torque teno virus/genética , Zika virus/genética , Infecção por Zika virus/diagnósticoRESUMO
BACKGROUND: Dengue is a mosquito-borne viral disease with an increasing incidence worldwide. Thrombocytopenia is a common finding in dengue virus (DV) infection; however, the underlying mechanisms remain unknown. CASE REPORT: Here we provide the first evidence of a case of antibody formation against ADAMTS13 (ADAMTS13 inhibitor) in the course of a severe acute DV infection resulting in thrombotic microangiopathy (TMA). The patient presented with classical dengue symptoms (positive epidemiology, high fever, myalgia, predominantly in the lower limbs and lumbar region for 1 week) and, after 11 days of initial symptoms, developed TMA. Clinical and laboratorial investigation of dengue and TMA was performed. RESULTS: The patient presented with ADAMTS13 inhibitor (IgG) during the acute phase of the disease, without anti-platelet antibodies detectable. Dengue infection had laboratorial confirmation. There were excellent clinical and laboratory responses to 11 serial plasma exchanges. Anti-ADAMTS13 inhibitor disappeared after remission of TMA and dengue resolution. No recurrence of TMA symptoms was observed after 2-year follow-up. CONCLUSIONS: Although the real incidence of dengue-related TMA is unknown, this case provides the basis for future epidemiologic studies on acquired ADAMTS13 deficiency in DV infection. The prompt clinical recognition of this complication and early installment of specific therapy with plasma exchange are likely to improve the outcome of severe cases of dengue.
Assuntos
Proteínas ADAM/imunologia , Autoanticorpos/sangue , Dengue/imunologia , Microangiopatias Trombóticas/imunologia , Proteína ADAMTS13 , Doença Aguda , Plaquetas/imunologia , Dengue/sangue , Dengue/complicações , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/terapiaRESUMO
Many aspects of the human asymptomatic visceral leishmaniasis (VL) remain not elucidated, and moreover, almost all the data come from highly endemic areas. The recent appearance of American VL (AVL) in the northeastern region of the state of São Paulo, Brazil, offered a good opportunity for further understanding. We present the preliminary results from a seroprevalence study on AVL in humans in Araçatuba, São Paulo. This was a cross-sectional survey on a random sample of the population (one-stage simple random sampling) in two areas, using rK39 dipstick tests. The sex ratios and age distributions in the two areas were comparable. Detectable antibodies were found in 23 subjects (20%) in area A1 and in 6 subjects (4.8%) in area A2. There was no significant difference in age distribution of seropositivity between the areas. We observed a difference in asymptomatic infection rates between the two areas, possibly associated with socioeconomic levels and transmission intensity.
Assuntos
Anticorpos Antiprotozoários/sangue , Leishmania infantum/imunologia , Leishmaniose Visceral/epidemiologia , População Urbana , Adolescente , Adulto , Idoso , Animais , Antígenos de Protozoários/imunologia , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Cães , Feminino , Humanos , Leishmaniose Visceral/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas de Protozoários/imunologia , Estudos SoroepidemiológicosRESUMO
Brazilian spotted fever (BSF) is the most important tick-borne disease in Brazil and is caused by Rickettsia rickettsii and transmitted by the Ixodid tick Amblyomma cajennense, its main vector. We present epidemiologic aspects of a case series of patients admitted to the Hospital das Clínicas da UNICAMP from 1985 to 2003 with a confirmed diagnosis of BSF either by a fourfold rise in indirect immunofluorescence (IFA) titers of IgG antibodies reactive with R. rickettsii or isolation of R. rickettsii from blood or skin specimens. Seasonal variation of case occurrence seems to be associated with the life cycle of the tick. The recent reemergence of cases seems to be associated with the growing numbers of the capybara (Hydrochaeris hydrochaeris) and their expansion into urban areas.
Assuntos
Infecções por Rickettsia/epidemiologia , Febre Maculosa das Montanhas Rochosas/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Brasil/epidemiologia , Criança , Pré-Escolar , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Incidência , Pessoa de Meia-Idade , Rickettsia rickettsii/isolamento & purificaçãoRESUMO
This case series study is based on a retrospective review of medical records and case notification files of patients admitted to The Hospital das Clínicas da UNICAMP from 1985 to 2003 with a confirmed diagnosis of BSF either by fourfold rise in indirect immunofluorescence assay (IFA) titers of IgG antibodies reactive with R. rickettsii or isolation of R. rickettsii from blood or skin specimens. A median lethality of 41.9 % was observed between 1985 and 2004. The case-fatality ratio of 30 % in our study, lower than the overall São Paulo state ratio, could be explained by a higher index of suspicion and a larger experience in our hospital, a regional referral center for BSF. The presence of the classical triad of fever, rash, and headache as described in RMSF was observed in fever than half (35.2%) of our patients.
Assuntos
Infecções por Rickettsia/epidemiologia , Brasil/epidemiologia , Humanos , Incidência , Prontuários Médicos , Estudos Retrospectivos , Infecções por Rickettsia/diagnóstico , Infecções por Rickettsia/mortalidade , Análise de SobrevidaRESUMO
This study evaluated the IS6110-RFLP patterns of 109 Mycobacterium tuberculosis isolates of patients with HIV cared for at a Brazilian university hospital. Thirteen clusters involving 35 (32.1%) individuals were identified. Nosocomial transmission was possible in 5 cases. Strategies to prevent M. tuberculosis transmission should be implemented in hospitals in developing countries.
Assuntos
Infecção Hospitalar , Países em Desenvolvimento , Infecções por HIV/complicações , Tuberculose Pulmonar/transmissão , Adulto , Brasil , DNA Bacteriano/análise , Feminino , Hospitais Universitários , Humanos , Controle de Infecções , Masculino , Polimorfismo de Fragmento de Restrição , Estudos Retrospectivos , Fatores de Risco , Tuberculose Pulmonar/genéticaRESUMO
O número de casos nodificados de tétano acidental no Estado de Säo Paulo sofreu reduçäo. O declínio do número de casos de qualquer doença sempre traz transformaçöes no seu perfil epidemiológico, que devem sempre ser analisadas para aprimorar as medidas preventivas. Assim, foi analisado o perfil clínico e epidemiológico dos casos de tétano internados em hospital universitário de Campinas de 1989 a 1996. Estudo descritivo e retrospectivo (série de casos). Todos os pacientes com diagnóstico de tétano de janeiro de 1989 a março de 1996, internados no hospital universitário, foram analisados. Catorze (28 por cento) eram da zona rural e 36 (72 por cento) da zona urbana. A idade média foi de 47,6 anos e a mediana de 49,5. Dos pacientes da zona rural, 42,8 por cento tinham até 30 anos e 21,42 por cento tinham mais de 50 anos, sendo a média 36,21 e a mediana 34,5: dos pacientes da zona urbana, 13,9 por cento tinham até 30 anos e 58,3 por cento mais de 50 anos, sendo a média de 52,2 a a mediana de 54,5. A letalidade foi de 20 por cento, mais elevada nos pacientes curarizados (60 por cento). Na regiäo estudada existem dois padröes epidemiológicos: o rural, com maior número de jovens, refletindo uma vacinaçäo inadequada, e o urbano, semelhante ao dos países desenvolvidos, com predomínio das faixas etárias mais altas