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1.
Viruses ; 12(12)2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339324

RESUMO

Baculovirus expression vectors are successfully used for the commercial production of complex (glyco)proteins in eukaryotic cells. The genome engineering of single-copy baculovirus infectious clones (bacmids) in E. coli has been valuable in the study of baculovirus biology, but bacmids are not yet widely applied as expression vectors. An important limitation of first-generation bacmids for large-scale protein production is the rapid loss of gene of interest (GOI) expression. The instability is caused by the mini-F replicon in the bacmid backbone, which is non-essential for baculovirus replication in insect cells, and carries the adjacent GOI in between attTn7 transposition sites. In this paper, we test the hypothesis that relocation of the attTn7 transgene insertion site away from the mini-F replicon prevents deletion of the GOI, thereby resulting in higher and prolonged recombinant protein expression levels. We applied lambda red genome engineering combined with SacB counterselection to generate a series of bacmids with relocated attTn7 sites and tested their performance by comparing the relative expression levels of different GOIs. We conclude that GOI expression from the odv-e56 (pif-5) locus results in higher overall expression levels and is more stable over serial passages compared to the original bacmid. Finally, we evaluated this improved next-generation bacmid during a bioreactor scale-up of Sf9 insect cells in suspension to produce enveloped chikungunya virus-like particles as a model vaccine.


Assuntos
Baculoviridae/genética , Genoma Viral , Instabilidade Genômica , Recombinação Homóloga , Mutagênese Insercional , Proteínas Recombinantes/genética , Transgenes , Animais , Reatores Biológicos , Linhagem Celular , Vírus Chikungunya/imunologia , Engenharia Genética , Vetores Genéticos/genética , Insetos , Células Sf9 , Vacinas de Partículas Semelhantes a Vírus/imunologia
2.
PLoS Negl Trop Dis ; 14(12): e0008934, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33347450

RESUMO

BACKGROUND: Chikungunya virus (CHIKV) is an important emerging and re-emerging public health problem worldwide. In Indonesia, where the virus is endemic, epidemiological information from outside of the main islands of Java and Bali is limited. METHODOLOGY/PRINCIPAL FINDINGS: Four hundred and seventy nine acutely febrile patients presenting between September 2017-2019 were recruited from three city hospitals situated in Ambon, Maluku; Banjarmasin, Kalimantan; and Batam, Batam Island as part of a multi-site observational study. CHIKV RNA was detected in a single serum sample while a separate sample was IgM positive. IgG seroprevalence was also low across all three sites, ranging from 1.4-3.2%. The single RT-PCR positive sample from this study and 24 archived samples collected during other recent outbreaks throughout Indonesia were subjected to complete coding region sequencing to assess the genetic diversity of Indonesian strains. Phylogenetic analysis revealed all to be of a single clade, which was distinct from CHIKV strains recently reported from neighbouring regions including the Philippines and the Pacific Islands. CONCLUSIONS/SIGNIFICANCE: Chikungunya virus strains from recent outbreaks across Indonesia all belong to a single clade. However, low-level seroprevalence and molecular detection of CHIKV across the three study sites appears to contrast with the generally high seroprevalences that have been reported for non-outbreak settings in Java and Bali, and may account for the relative lack of CHIKV epidemiological data from other regions of Indonesia.


Assuntos
Febre de Chikungunya/epidemiologia , Vírus Chikungunya/imunologia , Surtos de Doenças , Adolescente , Adulto , Febre de Chikungunya/virologia , Vírus Chikungunya/genética , Criança , Pré-Escolar , Feminino , Humanos , Indonésia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Viral/genética , Estudos Soroepidemiológicos , Adulto Jovem
3.
PLoS Negl Trop Dis ; 14(9): e0008549, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32881913

RESUMO

BACKGROUND: Chikungunya (CHIK) and yellow fever (YF) are becoming major public health threats in East African countries including Ethiopia. In Ethiopia, there is no reliable information about the epidemiology of CHIK. This study aimed to assess a community-based sero-prevalence of CHIK and YF in the South Omo Valley, an endemic area for YF. METHODS: Between February and June 2018, blood samples were collected from study participants and screened for IgG antibody against CHIK virus (CHIKV) and YF virus (YFV) infections using ELISA. Data were computerized using Epi Data Software v.3.1 and analyzed using SPSS. RESULTS: A total of 360 participants (51.7% males, age range from 6 to 80, mean age ± SD = 31.95 ± 14.05 years) participated in this study. The overall sero-prevalence of IgG antibody was 43.6% (157/360) against CHIKV, while it was 49.5% (155/313) against YFV. Out of 155 samples which were positive for IgG antibody to YFV, 93 (60.0%) were positive for IgG antibody to CHIKV. Out of 158 samples which were negative for IgG antibody to YFV, 64(40.5%) were positive for IgG antibody to CHIKV. There was a significant positive correlation between IgG antibodies to CHIKV and YFV (sr = 0.82; P<0.01). Residency in the Debub Ari district (AOR = 8.47; 95% CI: 1.50, 47.74) and travel history to sylvatic areas (AOR = 2.21; 95% CI: 1.02, 4.81) were significantly and positively associated with high sero-prevalence of IgG antibody to CHIKV and YFV, respectively. CONCLUSION: High sero-prevalence of IgG antibody to CHIKV shows the circulation of the virus in the present study area. A low sero-prevalence of IgG antibody to YFV in YF vaccine received individuals is highly concerning from a public health point of view as waning of immune response to YFV infection could result in a periodic outbreaks of YF in endemic areas.Nevertheless, the present study has not investigated for possible cross-reactivity of antibody to CHIKV with other alphaviruses like O'nyong-nyong virus and antibody to YFV with other flaviviruses like Dengue fever virus and this warrants further studies in the present study area.


Assuntos
Anticorpos Antivirais/sangue , Febre de Chikungunya/sangue , Febre Amarela/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/imunologia , Vírus Chikungunya/isolamento & purificação , Criança , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Características de Residência , Estudos Soroepidemiológicos , Febre Amarela/epidemiologia , Febre Amarela/virologia , Vírus da Febre Amarela/imunologia , Vírus da Febre Amarela/isolamento & purificação , Adulto Jovem
6.
PLoS Pathog ; 16(8): e1008754, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32776975

RESUMO

Arbovirus infection of Aedes aegypti salivary glands (SGs) determines transmission. However, there is a dearth of knowledge on SG immunity. Here, we characterized SG immune response to dengue, Zika and chikungunya viruses using high-throughput transcriptomics. We also describe a transcriptomic response associated to apoptosis, blood-feeding and lipid metabolism. The three viruses differentially regulate components of Toll, Immune deficiency (IMD) and c-Jun N- terminal Kinase (JNK) pathways. However, silencing of the Toll and IMD pathway components showed variable effects on SG infection by each virus. In contrast, regulation of the JNK pathway produced consistent responses in both SGs and midgut. Infection by the three viruses increased with depletion of the activator Kayak and decreased with depletion of the negative regulator Puckered. Virus-induced JNK pathway regulates the complement factor, Thioester containing protein-20 (TEP20), and the apoptosis activator, Dronc, in SGs. Individual and co-silencing of these genes demonstrate their antiviral effects and that both may function together. Co-silencing either TEP20 or Dronc with Puckered annihilates JNK pathway antiviral effect. Upon infection in SGs, TEP20 induces antimicrobial peptides (AMPs), while Dronc is required for apoptosis independently of TEP20. In conclusion, we revealed the broad antiviral function of JNK pathway in SGs and showed that it is mediated by a TEP20 complement and Dronc-induced apoptosis response. These results expand our understanding of the immune arsenal that blocks arbovirus transmission.


Assuntos
Aedes/imunologia , Apoptose , Febre de Chikungunya/imunologia , Proteínas do Sistema Complemento/imunologia , Dengue/imunologia , Sistema de Sinalização das MAP Quinases , Glândulas Salivares/imunologia , Infecção por Zika virus/imunologia , Aedes/virologia , Animais , Febre de Chikungunya/metabolismo , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/virologia , Vírus Chikungunya/imunologia , Proteínas do Sistema Complemento/metabolismo , Dengue/metabolismo , Dengue/prevenção & controle , Dengue/virologia , Vírus da Dengue/imunologia , Feminino , Interações Hospedeiro-Patógeno , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Insetos Vetores/imunologia , Insetos Vetores/virologia , Glândulas Salivares/virologia , Transcriptoma , Replicação Viral , Zika virus/imunologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/virologia
7.
PLoS Negl Trop Dis ; 14(7): e0008061, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32687540

RESUMO

Tanzania has recently experienced outbreaks of dengue in two coastal regions of Dar es Salaam and Tanga. Chikungunya and Rift Valley Fever outbreaks have also been recorded in the past decade. Little is known on the burden of the arboviral disease causing viruses (Dengue, Rift Valley and Chikungunya) endemically in the inter-epidemic periods. We aimed at determining the prevalence of the dengue, rift valley and chikungunya among humans in two geo ecologically distinct sites. The community-based cross-sectional study was conducted in Magugu in Manyara region and Wami-Dakawa in Morogoro region in Tanzania. Venous blood was collected from participants of all age groups, serum prepared from samples and subjected to ELISA tests for RVFV IgG/IgM, DENV IgG/IgM, and CHIKV IgM/IgG. Samples that were positive for IgM ELISA tests were subjected to a quantitative RT PCR for each virus. A structured questionnaire was used to collect socio-demographic information. Data analysis was performed by using SPSSv22. A total of 191 individuals from both sites participated in the study. Only one individual was CHIKV seropositive in Magugu, but none was seropositive or positive for either RVFV or DENV. Of the 122 individuals from Wami-Dakawa site, 16.39% (n = 20) had recent exposure to RVFV while 9.83% (n = 12) were seropositive for CHIKV. All samples were negative by RVFV and CHIKV qPCR. Neither infection nor exposure to DENV was observed in participants from both sites. Being more than 5 in a household, having no formal education and having recently travelled to an urban area were risk factors associated with RVFV and CHIKV seropositivity. We report a considerable exposure to RVFV and CHIKV among Wami-Dakawa residents during the dry season and an absence of exposure of the viruses among humans in Magugu site. In both sites, neither DENV exposure nor infection was detected.


Assuntos
Anticorpos Antivirais/sangue , Febre de Chikungunya/sangue , Vírus Chikungunya/imunologia , Vírus da Dengue/imunologia , Dengue/sangue , Febre do Vale de Rift/sangue , Vírus da Febre do Vale do Rift/imunologia , Adulto , Animais , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/fisiologia , Estudos Transversais , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue/fisiologia , Feminino , Humanos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Febre do Vale de Rift/epidemiologia , Febre do Vale de Rift/virologia , Vírus da Febre do Vale do Rift/fisiologia , Estudos Soroepidemiológicos , Tanzânia/epidemiologia , Adulto Jovem
8.
Am J Trop Med Hyg ; 103(4): 1660-1669, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32700661

RESUMO

Chikungunya fever is a viral mosquito-borne, acute febrile illness associated with rash, joint pain, and occasionally prolonged polyarthritis. Chikungunya outbreaks have been reported worldwide including many provinces of Thailand. Although chikungunya virus (CHIKV) occurs in Thailand, details on its epidemiology are lacking compared with dengue, a common mosquito-borne disease in the country. Therefore, study on CHIKV and its epidemiology in both humans and mosquitoes is required to better understand its importance clinically and dynamics in community settings. So a prospective examination of virus circulation in human and mosquito populations in northeastern Thailand using serological and molecular methods, including the genetic characterization of the virus, was undertaken. The study was conducted among febrile patients in eight district hospitals in northeastern Thailand from June 2016 to October 2017. Using real-time PCR on the conserved region of nonstructural protein 1 gene, CHIKV was detected in eight (4.9%) of 161 plasma samples. Only one strain yielded a sequence of sufficient size allowing for phylogenetic analysis. In addition, anti-CHIKV IgM and IgG were detected in six (3.7%) and 17 (10.6%) patient plasma samples. The single sequenced sample belonged to the East/Central/South Africa (ECSA) genotype and was phylogenetically similar to the Indian Ocean sub-lineage. Adult Aedes mosquitoes were collected indoors and within a 100-m radius from the index case house and four neighboring houses. CHIKV was detected in two of 70 (2.9%) female Aedes aegypti mosquito pools. This study clearly demonstrated the presence and local transmission of the ECSA genotype of CHIKV in the northeastern region of Thailand.


Assuntos
Aedes/virologia , Anticorpos Antivirais/sangue , Febre de Chikungunya/epidemiologia , Vírus Chikungunya/imunologia , Surtos de Doenças , Mosquitos Vetores/virologia , Adolescente , Adulto , Idoso , Animais , Febre de Chikungunya/transmissão , Febre de Chikungunya/virologia , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Filogenia , Estudos Prospectivos , Tailândia/epidemiologia , Adulto Jovem
9.
Am J Trop Med Hyg ; 103(3): 1228-1233, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32588813

RESUMO

Zoonotic pathogens such as arboviruses have comprised a significant proportion of emerging infectious diseases in humans. The role of wildlife species as reservoirs for arboviruses is poorly understood, especially in endemic areas such as Southeast Asia. This study aims to determine the exposure history of different macaque species from national parks in Thailand to mosquito-borne flaviviruses and alphavirus by testing the serum samples collected from 25 northern pigtailed macaques, 33 stump-tailed macaques, and 4 long-tailed macaques for the presence of antibodies against dengue, Zika, and chikungunya viruses by plaque reduction neutralization assay. Specific neutralizing antibodies against Dengue virus (DENV1-4) and Zika virus (ZIKV) were mainly found in stump-tailed macaques, whereas neutralizing antibody titers were not detected in long-tailed macaques and pigtailed macaques as determined by 90% plaque reduction neutralization assay (PRNT90). One long-tailed macaque captured from the south of Thailand exhibited antibody titers against chikungunya virus (CHIKV), suggesting enzootic of this virus to nonhuman primates (NHPs) in Thailand. Encroachment of human settlements into the forest has increased the interface that exposes humans to zoonotic pathogens such as arboviruses found in monkeys. Nonhuman primates living in different regions of Thailand showed different patterns of arboviral infections. The presence of neutralizing antibodies among wild monkeys in Thailand strongly suggests the existence of sylvatic cycles for DENV, ZIKV, and CHIKV in Thailand. The transmission of dengue, Zika, and chikungunya viruses among wild macaques may have important public health implications.


Assuntos
Febre de Chikungunya/epidemiologia , Vírus Chikungunya/imunologia , Culicidae/virologia , Vírus da Dengue/imunologia , Dengue/epidemiologia , Infecção por Zika virus/epidemiologia , Zika virus/imunologia , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais/sangue , Febre de Chikungunya/virologia , Dengue/virologia , Feminino , Geografia , Humanos , Macaca , Masculino , Mosquitos Vetores/virologia , Estudos Soroepidemiológicos , Tailândia/epidemiologia , Infecção por Zika virus/virologia
10.
Nat Commun ; 11(1): 2842, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503971

RESUMO

Characterizing the circulation of Mayaro virus (MAYV), an emerging arbovirus threat, is essential for risk assessment but challenging due to cross-reactivity with other alphaviruses such as chikungunya virus (CHIKV). Here, we develop an analytical framework to jointly assess MAYV epidemiology and the extent of cross-reactivity with CHIKV from serological data collected throughout French Guiana (N = 2697). We find strong evidence of an important sylvatic cycle for MAYV with most infections occurring near the natural reservoir in rural areas and in individuals more likely to go to the forest (i.e., adult males) and with seroprevalences of up to 18% in some areas. These findings highlight the need to strengthen MAYV surveillance in the region and showcase how modeling can improve interpretation of cross-reacting assays.


Assuntos
Infecções por Alphavirus/epidemiologia , Arbovirus/isolamento & purificação , Vírus Chikungunya/imunologia , Doenças Transmissíveis Emergentes/epidemiologia , Monitoramento Epidemiológico , Adolescente , Adulto , Infecções por Alphavirus/sangue , Infecções por Alphavirus/imunologia , Infecções por Alphavirus/virologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Arbovirus/imunologia , Criança , Pré-Escolar , Doenças Transmissíveis Emergentes/sangue , Doenças Transmissíveis Emergentes/imunologia , Doenças Transmissíveis Emergentes/virologia , Reações Cruzadas/imunologia , Estudos Transversais , Feminino , Guiana Francesa/epidemiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Masculino , Pessoa de Meia-Idade , Saúde da População Rural/estatística & dados numéricos , Estudos Soroepidemiológicos , Adulto Jovem
12.
J Cell Mol Med ; 24(12): 6988-6999, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32374474

RESUMO

Outbreaks of infections with viruses like Sars-CoV-2, Ebola virus and Zika virus lead to major global health and economic problems because of limited treatment options. Therefore, new antiviral drug candidates are urgently needed. The promising new antiviral drug candidate silvestrol effectively inhibited replication of Corona-, Ebola-, Zika-, Picorna-, Hepatis E and Chikungunya viruses. Besides a direct impact on pathogens, modulation of the host immune system provides an additional facet to antiviral drug development because suitable immune modulation can boost innate defence mechanisms against the pathogens. In the present study, silvestrol down-regulated several pro- and anti-inflammatory cytokines (IL-6, IL-8, IL-10, CCL2, CCL18) and increased TNF-α during differentiation and activation of M1-macrophages, suggesting that the effects of silvestrol might cancel each other out. However, silvestrol amplified the anti-inflammatory potential of M2-macrophages by increasing expression of anti-inflammatory surface markers CD206, TREM2 and reducing release of pro-inflammatory IL-8 and CCL2. The differentiation of dendritic cells in the presence of silvestrol is characterized by down-regulation of several surface markers and cytokines indicating that differentiation is impaired by silvestrol. In conclusion, silvestrol influences the inflammatory status of immune cells depending on the cell type and activation status.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Citocinas/genética , Células Dendríticas/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Triterpenos/farmacologia , Betacoronavirus/crescimento & desenvolvimento , Betacoronavirus/imunologia , Diferenciação Celular/efeitos dos fármacos , Vírus Chikungunya/efeitos dos fármacos , Vírus Chikungunya/crescimento & desenvolvimento , Vírus Chikungunya/imunologia , Citocinas/classificação , Citocinas/imunologia , Células Dendríticas/imunologia , Células Dendríticas/virologia , Ebolavirus/efeitos dos fármacos , Ebolavirus/crescimento & desenvolvimento , Ebolavirus/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Vírus da Hepatite E/efeitos dos fármacos , Vírus da Hepatite E/crescimento & desenvolvimento , Vírus da Hepatite E/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/virologia , Especificidade de Órgãos , Picornaviridae/efeitos dos fármacos , Picornaviridae/crescimento & desenvolvimento , Picornaviridae/imunologia , Cultura Primária de Células , Transdução de Sinais , Zika virus/efeitos dos fármacos , Zika virus/crescimento & desenvolvimento , Zika virus/imunologia
13.
JAMA ; 323(14): 1369-1377, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286643

RESUMO

Importance: Chikungunya virus (CHIKV) is a mosquito-borne Alphavirus prevalent worldwide. There are currently no licensed vaccines or therapies. Objective: To evaluate the safety and tolerability of an investigational CHIKV virus-like particle (VLP) vaccine in endemic regions. Design, Setting, and Participants: This was a randomized, placebo-controlled, double-blind, phase 2 clinical trial to assess the vaccine VRC-CHKVLP059-00-VP (CHIKV VLP). The trial was conducted at 6 outpatient clinical research sites located in Haiti, Dominican Republic, Martinique, Guadeloupe, and Puerto Rico. A total of 400 healthy adults aged 18 through 60 years were enrolled after meeting eligibility criteria. The first study enrollment occurred on November 18, 2015; the final study visit, March 6, 2018. Interventions: Participants were randomized 1:1 to receive 2 intramuscular injections 28 days apart (20 µg, n = 201) or placebo (n = 199) and were followed up for 72 weeks. Main Outcomes and Measures: The primary outcome was the safety (laboratory parameters, adverse events, and CHIKV infection) and tolerability (local and systemic reactogenicity) of the vaccine, and the secondary outcome was immune response by neutralization assay 4 weeks after second vaccination. Results: Of the 400 randomized participants (mean age, 35 years; 199 [50%] women), 393 (98%) completed the primary safety analysis. All injections were well tolerated. Of the 16 serious adverse events unrelated to the study drugs, 4 (25%) occurred among 4 patients in the vaccine group and 12 (75%) occurred among 11 patients in the placebo group. Of the 16 mild to moderate unsolicited adverse events that were potentially related to the drug, 12 (75%) occurred among 8 patients in the vaccine group and 4 (25%) occurred among 3 patients in the placebo group. All potentially related adverse events resolved without clinical sequelae. At baseline, there was no significant difference between the effective concentration (EC50)-which is the dilution of sera that inhibits 50% infection in viral neutralization assay-geometric mean titers (GMTs) of neutralizing antibodies of the vaccine group (46; 95% CI, 34-63) and the placebo group (43; 95% CI, 32-57). Eight weeks following the first administration, the EC50 GMT in the vaccine group was 2005 (95% CI, 1680-2392) vs 43 (95% CI, 32-58; P < .001) in the placebo group. Durability of the immune response was demonstrated through 72 weeks after vaccination. Conclusions and Relevance: Among healthy adults in a chikungunya endemic population, a virus-like particle vaccine compared with placebo demonstrated safety and tolerability. Phase 3 trials are needed to assess clinical efficacy. Trial Registration: ClinicalTrials.gov Identifier: NCT02562482.


Assuntos
Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/imunologia , Vacinas de Partículas Semelhantes a Vírus/efeitos adversos , Vacinas Virais/efeitos adversos , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , Febre de Chikungunya/imunologia , Método Duplo-Cego , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Adulto Jovem
14.
Int J Infect Dis ; 95: 167-173, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32247051

RESUMO

BACKGROUND: A longitudinal cohort study performed in Cebu City, Philippines found that the presence of pre-existing chikungunya virus (CHIKV) neutralizing antibodies (NAb) was associated with a decreased risk of symptomatic CHIKV infection. However, the relationship between pre-existing NAb and the risk of subclinical seroconversion has not been well described. METHODS: Data were analyzed from a longitudinal cohort aged 6 months to 83 years who underwent active fever surveillance in Cebu City, Philippines from 2012 to 2014. Participants with a history of fever underwent acute and 3-week convalescent visits with blood collection, and annual visits at baseline, 12 months, and 24 months. Symptomatic CHIKV infections were detected by PCR of acute illness sera. Subclinical seroconversion was defined as a ≥8-fold rise in 80% plaque reduction neutralization test (PRNT80) titer between annual visits without intervening symptomatic infection. RESULTS: Among 854 participants who completed the 12-month visit (year 1) and 765 who completed the 24-month visit (year 2), 25 symptomatic CHIKV infections and 104 subclinical seroconversions occurred among 615 individuals with no detectable pre-year NAb in year 1 and 444 in year 2, while no symptomatic infections and one subclinical seroconversion occurred in those with a pre-year PRNT80 titer ≥1:10. Pre-year PRNT80 titer ≥1:10 was associated with zero relative risk of symptomatic CHIKV infection and 0.018 risk of subclinical seroconversion. CONCLUSIONS: The presence of detectable pre-existing CHIKV NAb correlated with a decreased risk of both symptomatic CHIKV infection and subclinical seroconversion. These findings support the potential use of CHIKV NAb titer as a surrogate endpoint of protection from infection for vaccine development.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Febre de Chikungunya/imunologia , Vírus Chikungunya/imunologia , Soroconversão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Assintomáticas , Febre de Chikungunya/diagnóstico , Criança , Pré-Escolar , Febre , Humanos , Lactente , Estudos Longitudinais , Pessoa de Meia-Idade , Testes de Neutralização , Filipinas , Reação em Cadeia da Polimerase
15.
Sci Rep ; 10(1): 4017, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32132648

RESUMO

Mosquito borne viral diseases are an emerging threat as evident from the recent outbreak of Zika virus (ZIKV) as well as repeated outbreaks of Chikungunya (CHIKV), Yellow fever (YFV) and Japanese encephalitis (JEV) virus in different geographical regions. These four arboviruses are endemic in overlapping regions due to the co-prevalence of the transmitting mosquito vector species Aedes and Culex. Thus, a multivalent vaccine that targets all four viruses would be of benefit to regions of the world where these diseases are endemic. We developed a potential Virus Like Particle (VLP) based multivalent vaccine candidate to target these diseases by using stable cell lines that continuously secrete VLPs in the culture supernatants. Moreover, inclusion of Capsid in the VLPs provides an additional viral protein leading to an enhanced immune response as evident from our previous studies with ZIKV. Immunization of Balb/c mice with different combinations of Capsid protein containing VLPs either as monovalent, bivalent or tetravalent formulation resulted in generation of high levels of neutralizing antibodies. Interestingly, the potential tetravalent VLP vaccine candidate provided strong neutralizing antibody titers against all four viruses. The 293 T stable cell lines secreting VLPs were adapted to grow in suspension cultures to facilitate vaccine scale up. Our stable cell lines secreting individual VLPs provide a flexible yet scalable platform conveniently adaptable to different geographical regions as per the need. Further studies in appropriate animal models will be needed to define the efficacy of the multivalent vaccine candidate to protect against lethal virus challenge.


Assuntos
Vírus Chikungunya , Vírus da Encefalite Japonesa (Espécie) , Vacinas de Partículas Semelhantes a Vírus , Vacinas Virais , Viroses/imunologia , Vírus da Febre Amarela , Zika virus , Animais , Vírus Chikungunya/genética , Vírus Chikungunya/imunologia , Chlorocebus aethiops , Vírus da Encefalite Japonesa (Espécie)/genética , Vírus da Encefalite Japonesa (Espécie)/imunologia , Humanos , Células K562 , Camundongos , Camundongos Endogâmicos BALB C , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas de Partículas Semelhantes a Vírus/imunologia , Células Vero , Vacinas Virais/genética , Vacinas Virais/imunologia , Viroses/genética , Viroses/prevenção & controle , Vírus da Febre Amarela/genética , Vírus da Febre Amarela/imunologia , Zika virus/genética , Zika virus/imunologia
16.
Infez Med ; 28(1): 98-103, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32172268

RESUMO

Dengue fever is a mosquito-borne infection that co-circulates with Chikungunya and Zika virus infection in many parts of the world. Dengue virus (DENV) is occasionally responsible for acute hepatitis and a few cases of acute hepatitis due to co-infection with DENV and hepatitis E virus have been described in India. A 37-year-old Cuban woman living in Italy was admitted to our hospital with a presumed arboviral infection upon her return to Italy short after a 15-day trip to her home-country to visit relatives. An acute infection due to DENV serotype 1 was initially diagnosed, following a clinical course characterized by signs of liver dysfunction that were possibly due to co-infection with hepatitis E virus.


Assuntos
Coinfecção , Dengue/complicações , Hepatite E/complicações , Doença Relacionada a Viagens , Doença Aguda , Adulto , Vírus Chikungunya/imunologia , Coinfecção/diagnóstico , Coinfecção/virologia , Doenças Transmissíveis Importadas/complicações , Doenças Transmissíveis Importadas/diagnóstico , Doenças Transmissíveis Importadas/imunologia , Doenças Transmissíveis Importadas/virologia , Reações Cruzadas , Cuba/etnologia , Dengue/diagnóstico , Dengue/virologia , Vírus da Dengue/imunologia , Feminino , Hepatite E/diagnóstico , Hepatite E/virologia , Humanos , Itália , Zika virus/imunologia
17.
Am J Trop Med Hyg ; 102(4): 857-868, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32067624

RESUMO

Chikungunya fever (CHIKF) is a major public health concern and is caused by chikungunya virus (CHIKV). In 2005, the virus was reintroduced into India, resulting in massive outbreaks in several parts of the country. During 2010 and 2016 outbreaks, we recruited 588 patients from a tertiary care hospital in New Delhi, India, during the acute phase of CHIKF; collected their blood and clinical data; and determined their arthralgic status 12 weeks post-onset of fever. We evaluated IgM/IgG CHIKV-binding antibodies and their neutralizing capacity, sequenced complete genomes of 21 CHIKV strains, and correlated mutations with patient sequelae status. We also performed infections in murine models using representative strains from each outbreak to evaluate differences in pathogenesis. Our screening and analysis revealed that patients of the 2016 outbreak developed earlier IgM and neutralizing antibody responses that were negatively correlated with sequelae, compared with 2010 patients. Mutations that correlated with human disease progression were also correlated with enhanced murine virulence and pathogenesis. Overall, our study suggests that the development of early neutralizing antibodies and sequence variation in clinical isolates are predictors of human sequelae.


Assuntos
Anticorpos Neutralizantes/imunologia , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/imunologia , Vírus Chikungunya/imunologia , Surtos de Doenças , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Afinidade de Anticorpos , Febre de Chikungunya/patologia , Criança , Feminino , Genoma Viral , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
18.
Braz J Infect Dis ; 24(1): 1-6, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32001210

RESUMO

Febrile illnesses in developing countries are often misdiagnosed as malaria or typhoid fever. Although arboviral infections have similar clinical symptoms, they are usually not screened because of limited resources and the fact that there are several viruses in this group. Chikungunya virus (CHIKV) has been isolated in parts of Nigeria, but there is no documented evidence of the infection in Kogi State. This study determined seroprevalence of active and past CHIKV infection among febrile patients who tested negative for malaria and typhoid fever. Sera from 243 febrile patients were screened for CHIKV IgG and IgM using an immunochromatographic test kit. Clinical and socio-demographic variables were collected using a structured questionnaire. Recent CHIKV infection was observed in 5.8% of the study participants while 25.1% had IgG antibodies demonstrating previous infection. Significant associations were observed between seropositivity and age of participants (p<0.001), sex (p=0.044), marital status (p=0.002), and occupation (p<0.001). Clinical symptoms such as fever, joint pain, and headache were significantly associated with seropositivity. This study identified recent CHIKV infection in Anyigba. Therefore, there is need for routine screening of febrile patients and molecular characterization to determine the nature of circulating strains.


Assuntos
Febre de Chikungunya/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Febre de Chikungunya/imunologia , Vírus Chikungunya/imunologia , Criança , Estudos Transversais , Feminino , Febre/epidemiologia , Humanos , Imunoensaio , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Prevalência , Valores de Referência , Estudos Soroepidemiológicos , Distribuição por Sexo , Fatores Socioeconômicos , Adulto Jovem
19.
Braz. j. infect. dis ; 24(1): 1-6, Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1089330

RESUMO

ABSTRACT Febrile illnesses in developing countries are often misdiagnosed as malaria or typhoid fever. Although arboviral infections have similar clinical symptoms, they are usually not screened because of limited resources and the fact that there are several viruses in this group. Chikungunya virus (CHIKV) has been isolated in parts of Nigeria, but there is no documented evidence of the infection in Kogi State. This study determined seroprevalence of active and past CHIKV infection among febrile patients who tested negative for malaria and typhoid fever. Sera from 243 febrile patients were screened for CHIKV IgG and IgM using an immunochromatographic test kit. Clinical and socio-demographic variables were collected using a structured questionnaire. Recent CHIKV infection was observed in 5.8% of the study participants while 25.1% had IgG antibodies demonstrating previous infection. Significant associations were observed between seropositivity and age of participants (p < 0.001), sex (p = 0.044), marital status (p = 0.002), and occupation (p < 0.001). Clinical symptoms such as fever, joint pain, and headache were significantly associated with seropositivity. This study identified recent CHIKV infection in Anyigba. Therefore, there is need for routine screening of febrile patients and molecular characterization to determine the nature of circulating strains.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Febre de Chikungunya/epidemiologia , Valores de Referência , Fatores Socioeconômicos , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Imunoensaio , Estudos Soroepidemiológicos , Vírus Chikungunya/imunologia , Prevalência , Estudos Transversais , Distribuição por Sexo , Distribuição por Idade , Febre/epidemiologia , Febre de Chikungunya/imunologia , Anticorpos Antivirais/sangue , Nigéria/epidemiologia
20.
Rev Soc Bras Med Trop ; 53: e20190160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31994659

RESUMO

Acute disseminated encephalomyelitis (ADEM) is a demyelinating autoimmune neuropathic condition characterized by extensive bilateral and confluent lesions in the cerebral white matter and cerebellum. The basal ganglia and gray matter may also be involved. In most cases, the symptoms are preceded by viral infection or vaccination. In this report, we present a case of ADEM associated with optic neuritis presenting alongside two potential triggering factors: chikungunya virus infection and yellow fever immunization.


Assuntos
Febre de Chikungunya/complicações , Vírus Chikungunya/imunologia , Encefalomielite Aguda Disseminada/diagnóstico por imagem , Encefalomielite Aguda Disseminada/virologia , Neurite Óptica/diagnóstico por imagem , Adulto , Febre de Chikungunya/diagnóstico , Encefalomielite Aguda Disseminada/complicações , Humanos , Imagem por Ressonância Magnética , Masculino
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