RESUMO
Despite being the most significant arboviral disease worldwide, dengue has no antiviral treatment or reliable severity predictors. It has been shown that apoptotic cells from blood and tissues may be involved in the complex pathogenesis of dengue. However, very little is known about the interplay between proapoptotic and antiapoptotic mediators in this disease. Therefore, plasma levels of the three proapoptotic mediators Fas ligand (FasL), tumor necrosis factor-α (TNF-α), and TNF-related apoptosis-inducing ligand (TRAIL) were measured in dengue patients. Patients were classified according to the World Health Organization classification of dengue revised in 2009. Additionally, inhibitors of apoptosis protein (IAPs) were determined in plasma (Survivin) and peripheral blood mononuclear cells (PBMCs) lysates (cIAP-1, cIAP-2, XIAP). Levels of apoptotic proteins in plasma were correlated with counts of blood cells. FasL and TRAIL levels were elevated in dengue patients without warning signs when compared to patients with severe dengue and controls. Dengue patients with warning signs showed decreased levels of Survivin compared to patients with severe dengue and controls. TRAIL was inversely correlated with counts of lymphocyte subsets. In contrast, Survivin was positively correlated with leukocyte counts. There was a trend of elevated IAPs levels in PBMCs of patients with severe dengue. The results suggest a likely antiviral effect of TRAIL in dengue. It appears that TRAIL might be involved with apoptosis induction of lymphocytes, whereas IAPs might participate in protecting leukocytes from apoptosis. Further research is needed to explore the interactions between pro and antiapoptotic molecules and their implications in dengue pathogenesis.
Assuntos
Proteínas Reguladoras de Apoptose/sangue , Apoptose , Dengue/imunologia , Dengue/patologia , Leucócitos Mononucleares/química , Plasma/química , Adulto , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Microsporidiosis is a life threatening opportunistic infection of AIDS patients. The infection is usually restricted to specific anatomical areas, but could become systemic depending on the involved species. Genital microsporidiosis in female patients is rare. OBJECTIVE: To report genital microsporidiosis in female AIDS patients. METHODS: Tissues samples from the genital tract (ovary, fallopian tubes and uterus) of eight deceased women who died of wasting syndrome associated to AIDS and disseminated microsporidiosis at the Institute of Tropical Medicine Pedro Kourí were collected between 1997 and 2005. Using an indirect immunohistochemistry assay the microsporidia species involved in those cases were identified. RESULTS: We report several cases of microsporidial infection of the female genital tract. Six out of eight women with the disseminated form of the disease showed the presence of microsporidia in the genital tract. Encephalitozoon cuniculi and Encephalitozoon hellem were identified in the internal lining epithelium of the fallopian tubes and endometrium. CONCLUSIONS: Microsporidia species could disseminate to other organs and become systemic in severe immunocompromised cases. To our knowledge this is the greatest number of female genital tract microsporidiosis cases so far reported in humans.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/patologia , Encefalitozoonose/patologia , Doenças dos Genitais Femininos/patologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Autopsia , Vasos Sanguíneos/microbiologia , Colo do Útero/microbiologia , Progressão da Doença , Encephalitozoon/isolamento & purificação , Encephalitozoon cuniculi/isolamento & purificação , Encefalitozoonose/microbiologia , Endométrio/microbiologia , Células Epiteliais/microbiologia , Tubas Uterinas/microbiologia , Feminino , Doenças dos Genitais Femininos/microbiologia , Síndrome de Emaciação por Infecção pelo HIV/patologia , Humanos , Macrófagos/microbiologia , Especificidade de Órgãos , Esporos Fúngicos/isolamento & purificaçãoRESUMO
BACKGROUND: An outbreak of acute hemorrhagic conjunctivitis occurred in Cuba in 2008 and 2009. OBJECTIVE: To determinate the etiological agent associated with the Cuban outbreaks of acute hemorrhagic conjunctivitis during 2008 and 2009. STUDY DESIGN: Conjunctival swabs and/or faecal samples from 382 patients with clinical diagnosis suggestive of acute hemorrhagic conjunctivitis were subject to viral culture in HEp-2 human laryngeal epidermoid carcinoma cells. Positive samples were identified by a specific Coxsackievirus A24 variant PCR and the 3C protease region of 16 isolates was sequenced for phylogenetic analysis. RESULTS: Enterovirus cytopathic effect was observed in 138 cases (36%). A higher percent of CA24v was recovered from faecal samples, 19 out of 45 cases (42.2%), than from conjunctival swabs, 127 out of 355 samples (35.8%). All isolates were identified as Coxsackievirus A24 variant. Phylogenetic analysis revealed that 2008 and 2009 Cuban outbreaks were caused by the same virus strains and that isolates were closely related to those from Taiwan (2006-2007), China (2007-2008) and Singapore (2005) with a bootstrap value of 71%. CONCLUSIONS: Outbreaks of acute hemorrhagic conjunctivitis occurred in Cuba in 2008 and 2009 were caused by Coxsackievirus A24 variant. The faecal-oral route is another mode of transmission of CA24v in the acute hemorrhagic conjunctivitis outbreaks. Phylogenetic analysis of Cuban CA24v strains involved in an acute hemorrhagic conjunctivitis outbreak in 2008 and 2009 confirms a new introduction of the CA24 variant into the Americas from South-east Asia.
Assuntos
Conjuntivite Hemorrágica Aguda/virologia , Infecções por Coxsackievirus/virologia , Enterovirus Humano C/isolamento & purificação , Sequência de Bases , Linhagem Celular Tumoral , Conjuntivite Hemorrágica Aguda/diagnóstico , Conjuntivite Hemorrágica Aguda/epidemiologia , Conjuntivite Hemorrágica Aguda/transmissão , Infecções por Coxsackievirus/epidemiologia , Infecções por Coxsackievirus/transmissão , Cuba/epidemiologia , Enterovirus Humano C/classificação , Enterovirus Humano C/patogenicidade , Fezes/virologia , Genótipo , Humanos , Filogenia , RNA Viral/genéticaRESUMO
UNLABELLED: / BACKGROUND: Dengue is the most important arthropod borne viral disease worldwide in terms of morbidity and mortality and is caused by any of the four serotypes of dengue virus (DENV-1 to 4). Brazil is responsible for approximately 80% of dengue cases in the Americas, and since the introduction of dengue in 1986, a total of 5,944,270 cases have been reported including 21,596 dengue hemorrhagic fever and 874 fatal cases. DENV can infect many cell types and cause diverse clinical and pathological effects. The goal of the study was to investigate the usefulness of NS1 capture tests as an alternative tool to detect DENV in tissue specimens from previously confirmed dengue fatal cases (n = 23) that occurred in 2002 in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: A total of 74 tissue specimens were available: liver (n = 23), lung (n = 14), kidney (n = 04), brain (n = 10), heart (n = 02), skin (n = 01), spleen (n = 15), thymus (n = 03) and lymph nodes (n = 02). We evaluated three tests for NS1 antigen capture: first generation Dengue Early ELISA (PanBio Diagnostics), Platelia NS1 (BioRad Laboratories) and the rapid test NS1 Ag Strip (BioRad Laboratories). The overall dengue fatal case diagnosis based on the tissues analyzed by Dengue Early ELISA, Platelia NS1 and the NS1 Ag Strip was 34.7% (08/23), 60.8% (14/23) and 91.3% (21/23), respectively. The Dengue Early ELISA detected NS1 in 22.9% (17/74) of the specimens analyzed and the Platelia NS1 in 45.9% (34/74). The highest sensitivity (78.3%; 58/74) was achieved by the NS1 Ag Strip, and the differences in the sensitivities were statistically significant (p<0.05). The NS1 Ag Strip was the most sensitive in liver (91.3%; 21/23), lung (71.4%; 10/14), kidney (100%; 4/4), brain (80%; 8/10), spleen (66.6%, 10/15) and thymus (100%, 3/3) when compared to the other two ELISA assays. CONCLUSIONS/SIGNIFICANCE: This study shows the DENV NS1 capture assay as a rapid and valuable approach to postmortem dengue confirmation. With an increasing number of DHF and fatal cases, the availability of new approaches useful for cases confirmation plays an important tool for the disease surveillance.
Assuntos
Antígenos Virais/isolamento & purificação , Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Patologia/métodos , Proteínas não Estruturais Virais/isolamento & purificação , Adulto , Antígenos Virais/imunologia , Brasil , Vírus da Dengue/imunologia , Diagnóstico , Feminino , Humanos , Imunoensaio/métodos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Proteínas não Estruturais Virais/imunologiaRESUMO
Although dengue virus (DEN) endemic regions overlap with human immunodeficiency virus 1 (HIV) high incidence areas, little has been documented on HIV and DEN mixed infection. Here we report DEN/HIV concurrent infections recorded during the DEN-3 epidemic in 2001-2002 in Havana. Serologic-confirmed DEN is described in two HIV-infected subjects with dengue fever symptoms. Although patients had dengue disease, the CD4+ cells remained within normal levels and no accelerated progression of HIV disease was observed. To our knowledge, DEN cases caused by DEN-3 in HIV-infected individuals have not been reported previously. Further research is needed to diagnose this likely underreported mixed viral infection in DEN endemic areas.
Assuntos
Dengue/complicações , Dengue/diagnóstico , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Adulto , Contagem de Linfócito CD4 , Cuba , Dengue/epidemiologia , Vírus da Dengue/isolamento & purificação , HIV-1/isolamento & purificação , Humanos , Masculino , Adulto JovemAssuntos
Anemia Falciforme , Apoptose , Vírus da Dengue/isolamento & purificação , Dengue , Surtos de Doenças , Neurônios/patologia , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Animais , Células Cultivadas , Cuba/epidemiologia , Culicidae , Dengue/complicações , Dengue/epidemiologia , Dengue/virologia , Evolução Fatal , HumanosRESUMO
BACKGROUND: Apoptosis, or programmed cell death, has been implicated in dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) pathogenesis. OBJECTIVES: To determine the in vivo apoptosis contribution to the pathogenesis of fatal DHF/DSS during a Cuban dengue epidemic. STUDY DESIGN: We detected apoptosis by the TdT-mediated dUTP Nick-End Labeling (TUNEL) technique and dengue virus (DENV) antigens by an immunohistochemical assay in different tissues from six individuals who died of DHF/DSS during the Santiago de Cuba DENV-2 epidemic in 1997. RESULTS: DENV antigens were immunolocalized mainly in hepatocytes. Apoptotic cells were found in five of the six cases studied. Apoptosis was demonstrated in liver, brain, intestinal and lung tissues. Severe brain hypoxia and ischemia in the studied subjects during DHF/DSS probably might induce apoptosis in cerebral cells. Apoptotic microvascular endothelial cells (ECs) in pulmonary and intestinal tissues, a finding only previously reported in vitro, are likely related to vascular plasma leakage manifested by the individuals. CONCLUSIONS: Apoptosis was demonstrated in cerebral cells, white blood cells, intestinal and pulmonary microvascular ECs from Cuban fatal cases of DHF/DSS. As far as we know, these findings have not been previously reported in DHF/DSS. Our results indicate there is very likely an in vivo contribution of apoptosis to the pathophysiological mechanisms of DHF/DSS.