Vírus Dengue tipo 4 no estado do Rio de Janeiro: aspectos epidemiológicos, laboratoriais, clínicos e virais desde a sua emergência à sua endemicidade

Made available in DSpace on 2018-07-10T19:07:47Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) manoela_heringer_ioc_dout_2017.pdf: 17349885 bytes, checksum: 32eb97a285202723bec4979925275a40 (MD5) Previous issue date: 2017Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.A dengue é hoje um dos principais problemas de saúde pública no Brasil, que tem sido marcada por epidemias extensas. Dadas as opções limitadas de prevenção e controle, tem sido demonstrado que o diagnóstico laboratorial desempenha um papel importante no Sistema de Vigilância Epidemiológica, por infecções de monitoramento contínuo e confirmando novos casos. O principal objetivo deste estudo foi descrever a introdução do sorotipo 4 do vírus da dengue no Estado do Rio de Janeiro. Após a epidemia causada pelo DENV-2, em 2010, e durante a epidemia com maioria de DENV-1 em 2011, vimos a detecção de DENV-4 pela primeira vez no Rio de Janeiro, caracterizando um período com a co-circulação dos diferentes sorotipos no estado. Após a introdução de DENV-4 observamos uma queda na sensibilidade do método de ELISA para detecção do antígeno NS1, para melhorar esta sensibilidade fizemos um estudo com dissociação térmica anterior ao teste de ELISA e observamos um aumento na sensibilidade Um estudo descritivo e retrospectivo foi feito pela análise de uma base de dados contendo informações de registros epidemiológicos recebidos, juntamente com as amostras biológicas enviadas para o Laboratório de Flavivirus (LABFLA) e os resultados do diagnóstico laboratorial. Um total de 703 casos de DENV-4 foram confirmados nos anos de 2011 a 2013. A RT-PCR foi negativa para apenas 1 caso, enquanto a inoculação em células C6/36 confirmou 41% dos casos. Apenas 10% foram considerados dengue grave, com 14 mortes. Análise filogenética indicou a circulação do Genótipo II de provável origem da Venezuela ou Colômbia. O perfil da epidemia de DENV-a foi diferente das epidemias ocorridas no RJ anteriormente, principalmente em relação ao quadro clinico da doença.Dengue is now one of the main public health problems in Brazil, which has been marked by extensive epidemics. Given as limited options for prevention and control, it has been demonstrated that the laboratory diagnosis plays an important role in the Epidemiological Surveillance System, due to continuous monitoring infections and confirming new cases. The main objective of this study was to describe the introduction of serotype 4 of the dengue virus in the State of Rio de Janeiro. After an epidemic caused by DENV-2 and during epidemics with DENV-1 majority in 2011, we detected the detection of DENV-4 for the first time in Rio de Janeiro, characterizing a period with the co-circulation of the different serotypes in the state. After the introduction of DENV-4 we observed a decrease in the detection rate of the NS1 antigen, to solve we did a study with these samples of thermal dissociation prior to the ELISA test and observed an increase in sensitivity A descriptive and retrospective study was done by analyzing a database containing information from epidemiological records received, together with the biological samples sent to LABFLA and the results of the laboratory diagnosis. A total of 703 cases of DENV-4 were confirmed in the years 2011 to 2013. RTPCR was negative for only 1 case whereas inoculation in C6 / 36 cells confirmed 41% of the cases. Only 10% were considered severe dengue, with 14 deaths. In a phylogenetic analysis of representative strains only Genotype II was identified with a probable origin of Venezuela and Colombia. The comparison of epidemics with most cases of DENV-4 infection with other serotypes showed differences between them in epidemiological and laboratory variables, especially in relation to the clinical picture of the disease

Increased sensitivity of NS1 ELISA by heat dissociation in acute dengue 4 cases

Submitted by Sandra Infurna ([email protected]) on 2018-02-20T11:13:46Z No. of bitstreams: 1 rita2_nogueira_etal_IOC_2017.pdf: 480869 bytes, checksum: ed894cf6a24c55fa721813803f9bcab4 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-02-20T11:23:49Z (GMT) No. of bitstreams: 1 rita2_nogueira_etal_IOC_2017.pdf: 480869 bytes, checksum: ed894cf6a24c55fa721813803f9bcab4 (MD5)Made available in DSpace on 2018-02-20T11:23:49Z (GMT). No. of bitstreams: 1 rita2_nogueira_etal_IOC_2017.pdf: 480869 bytes, checksum: ed894cf6a24c55fa721813803f9bcab4 (MD5) Previous issue date: 2017Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivirus. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Saúde Escola Germano Sinval Faria. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivirus. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivirus. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivirus. Rio de Janeiro, RJ. Brasil.Dengue is an acute febrile illness considered the major arboviral disease in terms of morbidity, mortality, economic impact and dissemination worldwide. Brazil accounts for the highest notification rate, with circulation of all four dengue serotypes. The NS1 antigen is a dengue highly conserved specific soluble glycoprotein essential for viral replication and viability that can be detected 0 to 18 days from the onset of fever (peak first 3 days). It induces a strong humoral response and is known as a complement-fixing antigen. Lower NS1 test sensitivity occurs in secondary dengue infections probably due to immune complex formation impairing antigen detection by ELISA

NS1 Antigenemia and Viraemia Load: Potential Markers of Progression to Dengue Fatal Outcome?

Submitted by Sandra Infurna ([email protected]) on 2018-09-18T15:40:27Z No. of bitstreams: 1 flaviaB_santos_etal_IOC_2018.pdf: 2392586 bytes, checksum: fb1781d3cf9eca6c46eaf0bf0538c74b (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-09-18T15:53:05Z (GMT) No. of bitstreams: 1 flaviaB_santos_etal_IOC_2018.pdf: 2392586 bytes, checksum: fb1781d3cf9eca6c46eaf0bf0538c74b (MD5)Made available in DSpace on 2018-09-18T15:53:05Z (GMT). No. of bitstreams: 1 flaviaB_santos_etal_IOC_2018.pdf: 2392586 bytes, checksum: fb1781d3cf9eca6c46eaf0bf0538c74b (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Transmissores de Hematozoários. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunologia Viral. Rio de Janeiro, RJ, Brasil.Dengue is a worldwide problem characterized by a multifactorial pathogenesis. Considering the viral components, it is known that high viremia or high levels of the secreted nonstructural protein 1 (NS1) may be associated with a more severe disease. We aimed to characterize the NS1 antigenemia and viremia in dengue fatal and non-fatal cases, as potential markers of progression to a fatal outcome. NS1 antigenemia and viremia were determined in Brazilian dengue fatal cases (n = 40) and non-fatal cases (n = 40), representative of the four dengue virus (DENV) serotypes. Overall, the fatal cases presented higher NS1 levels and viremia. Moreover, the fatal cases from secondary infections showed significantly higher NS1 levels than the non-fatal ones. Here, irrespective of the disease outcome, DENV-1 cases presented higher NS1 levels than the other serotypes. However, DENV-2 and DENV-4 fatal cases had higher NS1 antigenemia than the non-fatal cases with the same serotype. The viremia in the fatal cases was higher than in the non-fatal ones, with DENV-3 and DENV-4 presenting higher viral loads. Viral components, such as NS1 and viral RNA, may be factors influencing the disease outcome. However, the host immune status, comorbidities, and access to adequate medical support cannot be ruled out as interfering in the disease outcome

Dengue type 4 in Rio de Janeiro, Brazil: case characterization following its introduction in an endemic region

Abstract Background Due to the populations’ susceptibility, DENV-4 introduction in 2010 led to the occurrence of explosive epidemics in the following years in Brazil. In 2011, DENV-4 was identified in Rio de Janeiro (RJ) and it was prevalent in 2012 and 2013. Here, we aimed to characterize clinical, epidemiological and laboratorial aspects of DENV-4 cases after this serotype introduction in an endemic scenario. Methods Dengue suspected cases (n = 3727) were received and analyzed from January 2011 to December 2013, during outbreaks occurred in RJ, Brazil. Samples were submitted to virological, serological and molecular methods for case confirmation. DENV-4 cases (n = 705) were characterized according to the type of infection, disease severity and, viremia levels and NS1 antigenemia were accessed. Representative strains were partial sequenced for genotyping. Results DENV-4 was identified in 44.2% (705/1593) of dengue positive cases, virus isolated in 48.7% of the cases. Anti-DENV IgM was detected in 39.4% of the cases, however an increased detection was observed in cases with ≥4 days of symptoms (57.0%). NS1 antigen was identified in 41.5% of DENV-4 cases however, after immune complexes dissociation, the detection significantly increased (87.6%). Females were more affected than males, so did children aged 11–15 years old. Primary cases were more frequently observed than secondary ones and most of them were classified as dengue. No differences on NS1 antigenemia and viraemia within the groups were observed. Despite the higher frequency of severe disease on individuals >65 years old, no differences were observed among the groups and type of infection. However, DENV-4 fatal cases were more frequent on secondary infections (57.1%). DENV-4 Genotype II was identified with a probable origin from Venezuela and Colombia. Conclusions It has been shown that laboratorial diagnosis is still a reliable tool for the disease surveillance, detecting and confirming emerging epidemics. Despite the occurrence of secondary infections, most DENV-4 cases presented a mild disease. As RJ is endemic for dengue, high rates of secondary infections would be expected. Despite the existence of two genotypes, only Genotype II was identified in our study

Increased Indoleamine 2,3-Dioxygenase 1 (IDO-1) Activity and Inflammatory Responses during Chikungunya Virus Infection.

Chikungunya virus (CHIKV) infection causes intense cytokine/chemokine inflammatory responses and debilitating joint pain. Indoleamine2,3-dioxygenase 1 (IDO-1) is an enzyme that initiates the tryptophan degradation that is important in initial host innate immune defense against infectious pathogens. Besides that, IDO-1 activation acts as a regulatory mechanism to prevent overactive host immune responses. In this study, we evaluated IDO-1 activity and cytokine/chemokine patterns in CHIKV patients. Higher IDO-1 (Kyn/Trp ratio) activation was observed during the early acute phase of CHIKV infection and declined in the chronic phase. Importantly, increased concentrations of Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), Interferon γ (IFN-γ), C-C motif chemokine ligand 2/Monocyte Chemoattractant Protein-1 (CCL2/MCP-1) and C-X-C motif chemokine ligand 10/Interferon Protein-10 (CXCL10/IP-10) were found in the acute phase of infection, while C-C motif chemokine ligand 4/Macrophage Inflammatory Protein 1 β (CCL4/MIP-1β) was found at increased concentrations in the chronic phase. Likewise, CHIKV patients with arthritis had significantly higher concentrations of CCL4/MIP-1β compared to patients without arthritis. Taken together, these data demonstrated increased IDO-1 activity, possibly exerting both antiviral effects and regulating exacerbated inflammatory responses. CCL4/MIP-1β may have an important role in the persistent inflammation and arthritic symptoms following chikungunya infection

30 years of dengue fatal cases in Brazil: a laboratorial-based investigation of 1047 cases

Abstract Background Dengue viruses (DENV) have emerged and reemerged in Brazil in the past 30 years causing explosive epidemics. The disease may range from clinically asymptomatic infections to severe and fatal outcomes. We aimed to describe the epidemiological, clinical and laboratorial aspects of the dengue fatal cases received by a Regional Reference Laboratory, Brazil in 30 years. Methods A total of 1047 suspected fatal dengue cases were received from 1986 to 2015 and analyzed in the Laboratory of Flavivirus, FIOCRUZ. Suspected cases were submitted to viral detection, serological and molecular methods for cases confirmation. Influence of gender, age, serotype and type of infection (primary/secondary) on death outcome, as well the interactions between serotype and age or infection and age and type of infection were also studied. Results A total of 359 cases (34.2%) were confirmed and DENV-1 (11.1%), DENV-2 (43.9%), DENV-3 (32.8%) and DENV-4 (13.7%) were detected. Overall, fatal cases occurred more often in primary infections (59.3%, p = 0.001). However, in 2008, fatal cases were mainly associated to secondary infections (p = 0.003). In 2008 and 2011, deaths were more frequent on children and those infected by DENV-2 presented a higher risk for fatal outcome. Moreover, children with secondary infections had a 4-fold higher risk for death. Conclusions Dengue is a multifactorial disease and, factors such as viral strain/serotype, occurrence of secondary infections and co-morbidities may lead to a severe outcome. However, the high dengue incidence and transmission during epidemics, such as those observed in Brazil may overwhelm and collapse the public health services, potentially impacting on increased disease severity and mortality

Following in the Footsteps of the Chikungunya Virus in Brazil: The First Autochthonous Cases in Amapá in 2014 and Its Emergence in Rio de Janeiro during 2016

Currently, Brazil lives a triple arboviruses epidemic (DENV, ZIKV and CHIKV) making the differential diagnosis difficult for health professionals. Here, we aimed to investigate chikungunya cases and the possible occurrence of co-infections during the epidemic in Amapá (AP) that started in 2014 when the first autochthonous cases were reported and in Rio de Janeiro (RJ) in 2016. We further performed molecular characterization and genotyping of representative strains. In AP, 51.4% of the suspected cases were confirmed for CHIKV, 71.0% (76/107). Of those, 24 co-infections by CHIKV/DENV, two by CHIKV/DENV-1, and two by CHIKV/DENV-4 were observed. In RJ, 76.9% of the suspected cases were confirmed for CHIKV and co-infections by CHIKV/DENV (n = 8) and by CHIKV/ZIKV (n = 17) were observed. Overall, fever, arthralgia, myalgia, prostration, edema, exanthema, conjunctival hyperemia, lower back pain, dizziness, nausea, retroorbital pain, and anorexia were the predominating chikungunya clinical symptoms described. All strains analyzed from AP belonged to the Asian genotype and no amino acid changes were observed. In RJ, the East-Central-South-African genotype (ECSA) circulation was demonstrated and no E1-A226V mutation was observed. Despite this, an E1-V156A substitution was characterized in two samples and for the first time, the E1-K211T mutation was reported in all samples analyzed