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1.
Euro Surveill ; 25(3)2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31992389

RESUMO

Recognition of measles is crucial to prevent transmissions in the hospital settings. Little is known about the level of recognition of measles and possible causes of not recognising the disease by physicians in the post-vaccine era. We report on a measles outbreak in a paediatric hospital in Austria in January to February 2017 with strikingly high numbers of not recognised cases. The extent and course of the outbreak were assessed via retrospective case finding. Thirteen confirmed measles cases were identified, two with atypical clinical picture. Of eight cases with no known epidemiological link, only one was diagnosed immediately; four were recognised with delay and three only retrospectively. Eleven typical measles cases had four 'unrecognised visits' to the outpatient clinic and 28 on the ward. Two atypical cases had two 'unrecognised visits' to the outpatient clinic and 19 on the ward.Thirteen clinicians did not recognise typical measles (atypical cases not included). Twelve of 23 physicians involved had never encountered a patient with measles before. The direct and indirect costs related to the outbreak were calculated to be over EUR 80,000. Our findings suggest the need to establish regular training programmes about measles, including diagnostic pitfalls in paediatric hospitals.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Vírus do Sarampo/genética , Vírus do Sarampo/imunologia , Sarampo/epidemiologia , Adolescente , Adulto , Áustria/epidemiologia , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Hospitais Pediátricos , Hospitais Universitários , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Masculino , Vírus do Sarampo/isolamento & purificação , RNA Viral/análise , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
2.
Am J Trop Med Hyg ; 102(3): 634-636, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31971157

RESUMO

In posterior reversible encephalopathy syndrome, brain magnetic resonance imaging (MRI) reveals bilateral occipital, parietal, and subcortical white matter hyperintensities on T2/fluid-attenuated inversion recovery (FLAIR) sequences. After treatment, imaging abnormalities are usually reversible. Eclampsia is the most frequent cause of posterior reversible encephalopathy syndrome in pregnancy. We report a 24-year-old woman, who presented to our clinic 4 weeks after normal vaginal delivery with bilateral vision loss. Loss of vision was first noticed in the 20th week of pregnancy. Even after delivery, her vision did not improve. In the postpartum period, she started having periodic myoclonic jerks. Electroencephalography demonstrated periodic generalized discharges. A brain MRI performed in the 20th week of the antepartum period showed bilateral parieto-occipital cortical white matter T2/FLAIR hyperintensities. A follow-up brain MRI, 5 months later, revealed marked reversal of white matter signal changes. Cerebrospinal fluid examination revealed raised anti-measles antibody titer, confirming the diagnosis of subacute sclerosing panencephalitis. In conclusion, in a patient with subacute sclerosing panencephalitis (SSPE) during the postpartum period, cortical vision loss and parieto-occipital white matter T2/FLAIR hyperintensities can simulate eclampsia. Inadvertent treatment with magnesium sulfate is likely if the diagnosis is missed.


Assuntos
Cegueira/etiologia , Complicações Infecciosas na Gravidez/patologia , Panencefalite Esclerosante Subaguda/patologia , Anticorpos Antivirais/sangue , Cegueira/patologia , Diagnóstico Diferencial , Feminino , Humanos , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Vírus do Sarampo/imunologia , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Período Pós-Parto , Gravidez , Panencefalite Esclerosante Subaguda/diagnóstico , Panencefalite Esclerosante Subaguda/tratamento farmacológico , Falha de Tratamento , Adulto Jovem
3.
BMC Med ; 17(1): 180, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31551070

RESUMO

BACKGROUND: Vaccination has reduced the global incidence of measles to the lowest rates in history. However, local interruption of measles virus transmission requires sustained high levels of population immunity that can be challenging to achieve and maintain. The herd immunity threshold for measles is typically stipulated at 90-95%. This figure does not easily translate into age-specific immunity levels required to interrupt transmission. Previous estimates of such levels were based on speculative contact patterns based on historical data from high-income countries. The aim of this study was to determine age-specific immunity levels that would ensure elimination of measles when taking into account empirically observed contact patterns. METHODS: We combined estimated immunity levels from serological data in 17 countries with studies of age-specific mixing patterns to derive contact-adjusted immunity levels. We then compared these to case data from the 10 years following the seroprevalence studies to establish a contact-adjusted immunity threshold for elimination. We lastly combined a range of hypothetical immunity profiles with contact data from a wide range of socioeconomic and demographic settings to determine whether they would be sufficient for elimination. RESULTS: We found that contact-adjusted immunity levels were able to predict whether countries would experience outbreaks in the decade following the serological studies in about 70% of countries. The corresponding threshold level of contact-adjusted immunity was found to be 93%, corresponding to an average basic reproduction number of approximately 14. Testing different scenarios of immunity with this threshold level using contact studies from around the world, we found that 95% immunity would have to be achieved by the age of five and maintained across older age groups to guarantee elimination. This reflects a greater level of immunity required in 5-9-year-olds than established previously. CONCLUSIONS: The immunity levels we found necessary for measles elimination are higher than previous guidance. The importance of achieving high immunity levels in 5-9-year-olds presents both a challenge and an opportunity. While such high levels can be difficult to achieve, school entry provides an opportunity to ensure sufficient vaccination coverage. Combined with observations of contact patterns, further national and sub-national serological studies could serve to highlight key gaps in immunity that need to be filled in order to achieve national and regional measles elimination.


Assuntos
Busca de Comunicante/estatística & dados numéricos , Erradicação de Doenças/métodos , Imunidade Coletiva , Vírus do Sarampo/imunologia , Sarampo/epidemiologia , Sarampo/imunologia , Sarampo/prevenção & controle , Adolescente , Adulto , Criança , Pré-Escolar , Erradicação de Doenças/organização & administração , Surtos de Doenças/prevenção & controle , Surtos de Doenças/estatística & dados numéricos , Feminino , Geografia , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Humanos , Imunidade Coletiva/fisiologia , Incidência , Lactente , Recém-Nascido , Masculino , Sarampo/transmissão , Vacina contra Sarampo/uso terapêutico , Modelos Estatísticos , Estudos Soroepidemiológicos , Vacinação/estatística & dados numéricos , Adulto Jovem
4.
PLoS One ; 14(6): e0218782, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31220172

RESUMO

Due to the Expanded Program on Immunization (EPI) and supplementary immunization activities (SIAs) in China, the incidence of measles in China has decreased extensively. The incidence reached its lowest levels in contemporary history in 2012 and 2017, with incidence rates of 4.6 and 4.3 per million population, respectively. However, more than 147,000 measles cases were reported from 2013 to 2016. Furthermore, the proportions of cases in infants < 8 months and adults have been increasing since 2013, representing a considerable challenge for measles elimination in China. A total of 14,868 measles viruses were isolated from confirmed measles cases from 2011 to 2017, of which 14,631 were identified as the predominant endemic genotype, H1; 87 were identified as genotype A viruses that were vaccine associated strains; and 150 were identified as non-H1 genotype viruses. The non-H1 genotype viruses included 62 D8 viruses, 70 D9 viruses, 3 D11 viruses, 14 B3 viruses, and 1 G3 virus, which were identified as imported or import-related viruses that caused sporadic cases or small outbreaks. Most of the transmission chains detected during the period 2011-2012 were interrupted and were followed by many new transmission chains of unknown origin that spread, causing a large measles resurgence in China during 2013-2016. After 4 years of measles resurgence and continuous implementation of the routine immunization program and SIAs, the population immunity reached a sufficiently high level to interrupt most of the transmission chains; only a few strains survived, which continued to be sporadically detected in China in 2017. In the present study, the results from the combined epidemiological and molecular virological data demonstrated the great progress towards measles elimination in China by the further analysis of circulation dynamics for the endemic H1 genotype measles virus from 2011 to 2017. And this study accumulated critical baseline data on circulating wild-type measles viruses in China and provides comprehensive information to the world. These comprehensive baseline data provide evidence to support measles elimination in the future, not only in China but also in other countries worldwide. In addition, the information will be very useful to other countries for tracing their sources of measles cases and for identifying transmission links, which can help prevent potential measles outbreaks.


Assuntos
Vírus do Sarampo/genética , Sarampo/epidemiologia , Sarampo/virologia , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Surtos de Doenças , Doenças Endêmicas , Feminino , Genótipo , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Sarampo/prevenção & controle , Vírus do Sarampo/classificação , Vírus do Sarampo/imunologia , Tipagem Molecular , Filogenia , Análise de Sequência de DNA , Vacinação , Adulto Jovem
5.
Mayo Clin Proc ; 94(9): 1834-1839, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31235278

RESUMO

Recent measles epidemics in US and European cities where vaccination coverage has declined are providing a harsh reminder for the need to maintain protective levels of immunity across the entire population. Vaccine uptake rates have been declining in large part because of public misinformation regarding a possible association between measles vaccination and autism for which there is no scientific basis. The purpose of this article is to address a new misinformed antivaccination argument-that measles immunity is undesirable because measles virus is protective against cancer. Having worked for many years to develop engineered measles viruses as anticancer therapies, we have concluded (1) that measles is not protective against cancer and (2) that its potential utility as a cancer therapy will be enhanced, not diminished, by prior vaccination.


Assuntos
Comunicação , Vírus do Sarampo/imunologia , Sarampo/epidemiologia , Sarampo/prevenção & controle , Terapia Viral Oncolítica/métodos , Vacinação/efeitos adversos , Criança , Pré-Escolar , Controle de Doenças Transmissíveis/organização & administração , Europa (Continente) , Feminino , Humanos , Masculino , Prevalência , Medição de Risco , Estados Unidos , Vacinação/métodos
6.
Am J Trop Med Hyg ; 101(1): 260-262, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31134883

RESUMO

Subacute sclerosing panencephalitis (SSPE) is still a common disease in India which is characterized by a progressive mental decline, myoclonus, periodic encephalographic abnormalities, and raised anti-measles antibody titter in the cerebrospinal fluid. Acute fulminant SSPE is characterized by a rapid course of disease culminating in death, within 6 months. We report of a 10-year-old boy, who came with a 14-day history of continuous involuntary jerky movements of the left half of the body, including the head. There was a highly increased anti-measles IgG antibody titer, both in the cerebrospinal fluid and serum. We conclude that acute rapidly progressive SSPE can present as acute encephalitis syndrome.


Assuntos
Sarampo/complicações , Panencefalite Esclerosante Subaguda/diagnóstico , Anticorpos Antivirais/sangue , Anticorpos Antivirais/líquido cefalorraquidiano , Criança , Diagnóstico Diferencial , Evolução Fatal , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Masculino , Sarampo/imunologia , Vírus do Sarampo/imunologia
7.
Biologicals ; 59: 20-28, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30992162

RESUMO

Patients with primary immunodeficiency disorders are vulnerable to infectious diseases. Intravenous immunoglobulin (IVIG) therapeutic products manufactured from human plasma are employed widely to protect patients from pathogens such as measles virus, which causes a potentially fatal and contagious disease. Therefore, health authorities stipulate a minimum titer of measles neutralizing antibodies (mnAbs) in IVIG products to ensure efficient protection. In general, mnAb titers are measured in a cell-based neutralization assay; however, this assay is labor intensive and time consuming, and the results are variable. Here, we compared a cell-based neutralizing assay with several ELISA tests to evaluate whether ELISAs can overcome the limitations of cell-based assays. The mnAb concentrations measured by the ELISAs showed a strong and significant positive correlation with those measured in a cell-based assay. Also, strong positive correlations were identified for measurement of individual source plasmas, which are used as raw materials for manufacturing IVIG products. Measurement by ELISA revealed that about 80% of 198 source plasmas had mnAb concentrations of <500 mIU/mL. These results suggest that quantitative ELISAs based on relevant antigens allow reliable and comprehensive measurement of mnAb concentrations in source plasmas and drug product; these ELISAs are also faster and more accurate than cell-based assay.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Imunoglobulinas Intravenosas/imunologia , Síndromes de Imunodeficiência/imunologia , Vírus do Sarampo/imunologia , Testes de Neutralização/métodos , Contaminação de Medicamentos/prevenção & controle , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Reprodutibilidade dos Testes
9.
Jpn J Infect Dis ; 72(3): 185-192, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-30700655

RESUMO

In Turkey, the Measles Elimination Program has been implemented since 2002. The aim of this study was to evaluate the measles-specific antibody levels of mothers admitted to a hospital for birth and their infants, to determine the factors influencing the antibody levels of both, and to evaluate the transplacental transport ratio. We selected healthy women who came to the hospital for birth and their healthy newborns. We collected blood samples from 1,547 mothers and 1,529 infants. The protective prevalence of measles antibody levels of mothers was 80% (95% confidence interval [CI]: 78-82%) and that of newborns was 85% (95% CI: 83-86%). The antibody levels of mothers and newborns were positively linearly correlated (R: 0.922, p < 0.001) and were associated with parity (p < 0.001). The ratio of neonatal to maternal antibody levels increased with gestational age. The protective levels were 1.6 times higher (95% CI: 1.1-2.4) in mothers ≥ 32 years of age and 2.1 times higher (95% CI: 1.4-3.3) in naturally immune mothers. Two factors affecting the antibody levels of newborns were the mothers' antibody levels and their immunization status. The antibody level of mother was the most significant factor that influenced the infant's antibody level. Vaccination of women before pregnancy could enhance passive antibody protection by increasing the level of transplacental transmission.


Assuntos
Imunidade Materno-Adquirida/imunologia , Vacina contra Sarampo/imunologia , Vírus do Sarampo/imunologia , Sarampo/imunologia , Adulto , Anticorpos Antivirais/sangue , Feminino , Sangue Fetal , Hospitais , Humanos , Imunoglobulina G/sangue , Recém-Nascido/imunologia , Troca Materno-Fetal , Sarampo/prevenção & controle , Mães , Gravidez , Prevalência , Análise de Regressão , Inquéritos e Questionários , Turquia , Adulto Jovem
10.
Med Sci Monit ; 25: 903-912, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30705250

RESUMO

BACKGROUND The purpose of this study was to explore the immune mechanism of dendritic cells (DCs) against measles virus (MV), and to identify potential biomarkers to improve measles prevention and treatment. MATERIAL AND METHODS The gene expression profile of GSE980, which comprised 10 DC samples from human blood infected with MV (RNA was isolated at 3, 6, 12, and 24 h post-infection) and 4 normal DC control samples, was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between the MV-infected DC samples and the control samples were screened using Genevestigator software. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed using GenCLip 2.0 and STRING 10.5 software. The protein-protein interaction (PPI) network was established using Cytoscape 3.4.0. RESULTS The gene expression profiles of MV-infected DCs were obviously changed. Twenty-six common DEGs (0.9%, MV-infected DCs vs. normal DCs) were identified at 4 different time points, including 14 down-regulated and 12 up-regulated genes (P=0.001). GO analysis showed that DEGs were significantly enriched in defense response to virus, type I interferon signaling pathway, et al. ISG15 and CXCL10 were the key genes in the PPI network of the DEGs, and may interact directly with the type I interferon signaling and defense response to virus signaling. CONCLUSIONS The DEGs increased gradually with the duration of MV infection. The type I interferon signaling pathway and the defense response to viral processes can be activated against MV by ISG15 and CXCL10 in DCs. These may provide novel targets for the treatment of MV.


Assuntos
Biologia Computacional/métodos , Células Dendríticas/imunologia , Vírus do Sarampo/imunologia , Biomarcadores , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Vírus do Sarampo/patogenicidade , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Software , Transcriptoma/genética
11.
Virus Res ; 263: 145-150, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30684519

RESUMO

Measles virus (MV), a paramyxovirus, is one of the most contagious human pathogens and is responsible for thousands of deaths annually. Wild-type MV evolved to counter the innate immune system by avoiding both type I interferon (IFN) induction and inhibiting IFN signaling through the JAK/STAT pathway. However, virus replication is significantly inhibited in IFN-pretreated cells. Similarly, MV vaccine derived strains are inhibited by IFN pretreatment, but vaccine strains also induce IFN. Despite the significant progress in understanding the interactions between MV and the IFN pathway, the IFN stimulated genes (ISGs) that inhibit MV replication remain largely unknown. The aim of this study is to identify specific ISGs that mediate restriction of MV. In this study, we report that Radical S-adenosyl methionine domain containing 2 (RSAD2) restricts MV infection at the stage of virus release in infected 293T cells. Furthermore, attenuated MV strains are currently being developed as a novel treatment for solid and hematological malignancies. Therefore, we tested the impact of RSAD2 expression in an oncolytic virotherapy context using a MV permissive ovarian cancer line (SR-B2). As measured in 293T cells, MV release was also impaired in SR-B2 cells transduced to express RSAD2 in vitro. Additionally, oncolytic MV therapeutic efficacy was impaired in SR-B2 cells transduced to express RSAD2 in vivo. Overall, we identify RSAD2 as a novel restriction factor for MV by inhibiting the release of virus. These results provide important information regarding the interaction between MV and the innate immune system, as well as implications for the design of oncolytic MV platforms.


Assuntos
Interações Hospedeiro-Patógeno , Imunidade Inata , Vírus do Sarampo/imunologia , Vírus do Sarampo/fisiologia , Proteínas/metabolismo , Liberação de Vírus , Linhagem Celular , Células Epiteliais/imunologia , Células Epiteliais/virologia , Humanos
12.
BMC Infect Dis ; 19(1): 90, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30683064

RESUMO

BACKGROUND: Measles is one of the most infectious diseases with a high mortality rate worldwide. It is caused by the measles virus (MeV) which is a single stranded RNA virus with genetic diversity based on the nucleoprotein gene, including 24 genotypes. In Gabon, several outbreaks occurred in the past few years, especially in 2016 in Libreville and Oyem. A surveillance network of infectious diseases highlighted a measles outbreak which occurred in the south of Gabon from April to June 2017. METHODS: Clinical specimens of urine, blood, throat and nasal swabs were collected in the two main cities of the Haut-Ogooue province, Franceville and Moanda. Virological investigations based on real-time polymerase chain reaction for molecular diagnosis and conventional PCR for genotype identification were done. RESULTS: Specimens were collected from 139 suspected measles patients. A total of 46 (33.1%) children and adults were laboratory-confirmed cases among which 16 (34.8%) were unvaccinated, 16 (34.8%) had received one dose, and 11 (23.9%) had received two doses of the measles vaccine. Phylogenetic analysis revealed that all the sequences of the nucleoprotein gene belonged to genotype B3. CONCLUSIONS: Measles infection was more commonly confirmed among those with one recorded dose compared to suspect cases with none, unknown or two recorded doses. The molecular characterization of the strains showed the circulation of the B3 genotype which is endemic on the African continent, thirty years after the B2 genotype was described in an outbreak in Libreville, the capital of Gabon. These findings highlight that surveillance and molecular investigation of measles should be continued in Gabon.


Assuntos
Surtos de Doenças , Vírus do Sarampo/isolamento & purificação , Sarampo/virologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Gabão/epidemiologia , Variação Genética , Genótipo , Humanos , Lactente , Masculino , Sarampo/epidemiologia , Vacina contra Sarampo/administração & dosagem , Vírus do Sarampo/genética , Vírus do Sarampo/imunologia , Pessoa de Meia-Idade , Nucleoproteínas/genética , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Virais/genética , Adulto Jovem
13.
Biol Chem ; 400(5): 629-638, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-30504522

RESUMO

Analyses of the peptide sharing between five common human viruses (Borna disease virus, influenza A virus, measles virus, mumps virus and rubella virus) and the human proteome highlight a massive viral vs. human peptide overlap that is mathematically unexpected. Evolutionarily, the data underscore a strict relationship between viruses and the origin of eukaryotic cells. Indeed, according to the viral eukaryogenesis hypothesis and in light of the endosymbiotic theory, the first eukaryotic cell (our lineage) originated as a consortium consisting of an archaeal ancestor of the eukaryotic cytoplasm, a bacterial ancestor of the mitochondria and a viral ancestor of the nucleus. From a pathologic point of view, the peptide sequence similarity between viruses and humans may provide a molecular platform for autoimmune crossreactions during immune responses following viral infections/immunizations.


Assuntos
Autoimunidade , Vírus da Doença de Borna/imunologia , Vírus da Influenza A/imunologia , Vírus do Sarampo/imunologia , Vírus da Caxumba/imunologia , Peptídeos/imunologia , Vírus da Rubéola/imunologia , Sequência de Aminoácidos , Humanos
14.
Lancet ; 392(10165): 2718-2727, 2019 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-30409443

RESUMO

BACKGROUND: Chikungunya fever is an emerging viral disease and substantial threat to public health. We aimed to assess the safety, tolerability, and immunogenicity of a live-attenuated, measles-vectored chikungunya vaccine (MV-CHIK). METHODS: In this double-blind, randomised, placebo-controlled and active-controlled phase 2 trial, we enrolled healthy volunteers aged 18-55 years at four study sites in Austria and Germany. Participants were randomly assigned to receive intramuscular injections with MV-CHIK (5 × 104 or 5 × 105 50% tissue culture infectious dose), control vaccine, or measles prime and MV-CHIK, in two different administration regimens. Randomisation was done by use of three-digit randomisation codes in envelopes provided by a data management service. The participants and investigators were masked to treatment assignment, which was maintained by use of sterile saline as a placebo injection. The primary endpoint was immunogenicity, defined as the presence of neutralising antibodies against chikungunya virus, at day 56, which is 28 days after one or two immunisations. The primary endpoint was assessed in all participants who completed the study without major protocol deviations (per-protocol population) and in all randomised participants who received at least one study treatment (modified intention-to-treat population). The safety analysis included all participants who received at least one study treatment. This trial is registered with ClinicalTrials.gov (NCT02861586) and EudraCT (2015-004037-26) and is completed. FINDINGS: Between Aug 17, 2016, and May 31, 2017, we randomly assigned 263 participants to receive control vaccine (n=34), MV-CHIK (n=195), or measles prime and MV-CHIK (n=34). 247 participants were included in the per-protocol population. Neutralising antibodies against chikungunya virus were detected in all MV-CHIK treatment groups after one or two immunisations, with geometric mean titres ranging from 12·87 (95% CI 8·75-18·93) to 174·80 (119·10-256·50) and seroconversion rates ranging from 50·0% to 95·9% depending on the dose and administration schedule. Adverse events were similar between groups, with solicited adverse events reported in 168 (73%) of 229 participants assigned to MV-CHIK and 24 (71%) of 34 assigned to control vaccine (p=0·84) and unsolicited adverse events in 116 (51%) participants assigned to MV-CHIK and 17 (50%) assigned to control vaccine (p=1·00). No serious adverse events related to the vaccine were reported. INTERPRETATION: MV-CHIK showed excellent safety and tolerability and good immunogenicity, independent of pre-existing immunity against the vector. MV-CHIK is a promising candidate vaccine for the prevention of chikungunya fever, an emerging disease of global concern. FUNDING: Themis.


Assuntos
Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/imunologia , Vacinas Virais/imunologia , Adolescente , Adulto , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/sangue , Relação Dose-Resposta Imunológica , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/efeitos adversos , Vacina contra Sarampo/imunologia , Vírus do Sarampo/imunologia , Pessoa de Meia-Idade , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Adulto Jovem
16.
J Immunol Methods ; 464: 1-8, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30056035

RESUMO

Because of measles outbreaks there is a need for continuous monitoring of immunological protection against infection at population level. For such monitoring to be feasible, a cost-effective, reliable and high-throughput assay is necessary. Herein we describe an ELISA protocol for assessment of anti-measles antibody levels in human serum samples that fulfills the above criteria and is easily adaptable by various laboratories. A serum bank of anonymous patient sera was established (N > 3000 samples). Sera were grouped based on measles immunization schedules and/or changes in vaccine components since the introduction of the first measles vaccine in Hungary in 1969. Newly designed ELISA was performed by using Siemens BEP 2000 Advance System and data were confirmed using commercially available kits. Our indirect ELISA was compared to indirect immunfluoresence and to anti-measles nucleocapsid (N) monoclonal antibody-based sandwich ELISA. The results obtained are in high agreement with the confirmatory methods, and reflect measles vaccination history in Hungary ranging from pre-vaccination era, through the initial period of measles vaccination, to present. Based on measurement of 1985 sera, the highest ratio of low/questionable antibody level samples was detected in cluster '1978-1987' (~25.4%), followed by cluster '1969-1977' (~15.4%).Our assay is suitable for assessment of anti-measles immunity in a large cohort of subjects. The assay is cost-effective, allows high-throughput screening and has superior signal-to-noise ratio. This assay can serve as a first step in assessment of the effectiveness of all three components of the MMR vaccine.


Assuntos
Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Imunogenicidade da Vacina , Imunoglobulina G/sangue , Vírus do Sarampo/imunologia , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Sarampo/prevenção & controle , Biomarcadores/sangue , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Hungria , Imunidade Coletiva , Limite de Detecção , Sarampo/sangue , Sarampo/imunologia , Sarampo/virologia , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Valor Preditivo dos Testes , Vacinação
17.
J Virol ; 93(3)2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30429338

RESUMO

The impact of the Zika virus (ZIKV) epidemic highlights the need for vaccines that reduce or prevent infection and reliably prevent teratogenic complications. The live-attenuated measles virus (MV) vaccine strains are a promising vaccine platform, since they induce robust humoral and cellular immune responses against additional antigens and have an excellent safety record. To explore its potential to protect against ZIKV, we compared a recombinant Schwarz strain MV that encodes ZIKV prM and soluble E proteins (MV-Zika-sE) with a prototypic alum-adjuvanted whole inactivated ZIKV particle vaccine. Analysis of MV-Zika-sE-infected cells confirmed antigen expression, and the virus replicated with vaccine strain characteristics. Immunized IFNAR-/--CD46Ge mice developed E protein-specific and neutralizing antibodies, and ZIKV E-specific cellular immune responses were observed by gamma interferon (IFN-γ) enzyme-linked immunospot (ELISpot) and in vitro T cell proliferation assays. To analyze protective efficacy, vaccinated female mice were challenged with ZIKV after allogeneic mating. In MV-Zika-sE-vaccinated mice, weight gain was similar to that in uninfected mice, while no plasma viremia was detectable in the majority of the animals. In contrast, infected control animals gained less weight and experienced about 100-fold higher viremia over at least 3 days. Moreover, vaccination with MV-Zika-sE reduced the ZIKV load in different organs and the placentas and prevented infection of the fetus. Consequently, no fetal growth retardation, anemia, or death due to ZIKV infection was seen in MV-Zika-sE-vaccinated dams. In contrast, the inactivated ZIKV vaccine had little to no effect in our studies. Therefore, the MV-derived ZIKV vaccine is a promising candidate for further preclinical and clinical development.IMPORTANCE Zika virus (ZIKV) is a mosquito-borne flavivirus that causes a variety of neurological complications, including congenital birth defects. Despite the urgent need, no ZIKV vaccine has yet been licensed. Recombinant vaccine strain-derived measles viruses (MV) constitute a promising vector platform to induce immunity against foreign pathogens by expressing antigens from additional transcription units while at the same time possessing a remarkable safety profile. This concept has already been validated against different pathogens, including at least 3 other flaviviruses, and our data show that vaccination with MV expressing soluble ZIKV E protein significantly diminishes infection and prevents fetal loss or damage in an allogeneic mouse pregnancy model. It can thus be regarded as a promising emergency vaccine candidate with the potential for inclusion in routine vaccination settings in areas of endemicity to prevent teratogenic effects of circulating ZIKV during pregnancy, comparable to standard rubella virus vaccination.


Assuntos
Modelos Animais de Doenças , Vacina contra Sarampo/administração & dosagem , Vírus do Sarampo/imunologia , Proteínas do Envelope Viral/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Animais , Anticorpos Antivirais/sangue , Feminino , Genoma Viral , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Vacina contra Sarampo/imunologia , Proteína Cofatora de Membrana/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Gravidez , Receptor de Interferon alfa e beta/fisiologia , Vacinação , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Zika virus/genética , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologia
18.
Biomed Environ Sci ; 32(11): 804-811, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31910938

RESUMO

OBJECTIVE: To identify measles vaccine failures in Tianjin, China using a measles virus IgG avidity assay. METHODS: The China Information System for Disease Control and Prevention (CISDCP) was used to collect information about measles cases and blood specimens in Tianjin from 2013 to 2015. Measlesspecific IgM and IgG antibodies were detected using Enzyme-Linked Immunosorbent Assay (ELISA). Avidity testing for measles IgG was performed using a commercial enzyme immunoassay (EIA). RESULTS: A total of 284 confirmed measles cases were identified. Of this total, 262 (92.25%) were in patients aged ⪖ 20 years. High avidity was exhibited in 172 (60.56%) cases, while 80 (28.17%) cases demonstrated low avidity. High avidity was detected in only 21.43% of cases in patients aged < 1 year. The proportion of high avidity increased with age, and was significantly higher in patients aged 30-39 years at 70.07% (χ2 = 17.27, P = 0.002). Of the 52 measles cases in patients with a history of vaccinations, 41 (78.85%) cases showed high avidity, indicating secondary vaccine failures (SVF). In these vaccinations, there was no significant difference (P > 0.05) in clinical severity between high avidity and low avidity cases. However, regardless of vaccination status, clinical severity was significantly lower in high avidity cases (P < 0.001) than in low avidity cases. The percentages of positive measles IgM results in high avidity and low avidity cases were 66.28% and 91.25%, respectively. Geometric Mean Concentration (GMC) was significantly lower in high avidity cases at 33.73 U/mL, compared to 166.07 U/mL in low avidity cases. CONCLUSION: Low clinical severity and inconclusive IgM antibody results are more likely in high avidity measles cases. Measles cases were more common in adults. Therefore, a further dose of vaccines should be recommended for 30-39 years in Tianjin..


Assuntos
Anticorpos Antivirais/imunologia , Imunoglobulina G/imunologia , Vírus do Sarampo/imunologia , Sarampo/imunologia , Sarampo/virologia , Adolescente , Adulto , Afinidade de Anticorpos , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Sarampo/epidemiologia , Sarampo/prevenção & controle , Vírus do Sarampo/genética , Pessoa de Meia-Idade , Vacinação , Adulto Jovem
19.
PLoS Pathog ; 14(12): e1007493, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30592772

RESUMO

Measles virus (MV) is a highly contagious member of the Morbillivirus genus that remains a major cause of childhood mortality worldwide. Although infection induces a strong MV-specific immune response that clears viral load and confers lifelong immunity, transient immunosuppression can also occur, leaving the host vulnerable to colonization from secondary pathogens. This apparent contradiction of viral clearance in the face of immunosuppression underlies what is often referred to as the 'measles paradox', and remains poorly understood. To explore the mechanistic basis underlying the measles paradox, and identify key factors driving viral clearance, we return to a previously published dataset of MV infection in rhesus macaques. These data include virological and immunological information that enable us to fit a mathematical model describing how the virus interacts with the host immune system. In particular, our model incorporates target cell depletion through infection of host immune cells-a hallmark of MV pathology that has been neglected from previous models. We find the model captures the data well, and that both target cell depletion and immune activation are required to explain the overall dynamics. Furthermore, by simulating conditions of increased target cell availability and suppressed cellular immunity, we show that the latter causes greater increases in viral load and delays to MV clearance. Overall, this signals a more dominant role for cellular immunity in resolving acute MV infection. Interestingly, we find contrasting dynamics dominated by target cell depletion when viral fitness is increased. This may have wider implications for animal morbilliviruses, such as canine distemper virus (CDV), that cause fatal target cell depletion in their natural hosts. To our knowledge this work represents the first fully calibrated within-host model of MV dynamics and, more broadly, provides a new platform from which to explore the complex mechanisms underlying Morbillivirus infection.


Assuntos
Imunidade Celular/imunologia , Vírus do Sarampo/imunologia , Sarampo/imunologia , Modelos Teóricos , Animais , Tolerância Imunológica/imunologia , Macaca mulatta , Camundongos
20.
BMC Infect Dis ; 18(1): 680, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30567502

RESUMO

BACKGROUND: The widespread use of an effective and safe vaccine to measles has substantially decreased morbidity and mortality from this epidemic. Nevertheless, HIV-infected children vaccinated against measles may develop an impaired vaccine response and remain susceptible to this disease. In Morocco, infants are routinely vaccinated against measles, regardless of their HIV serostatus. An evaluation of the immunization of these children may be of paramount importance to implement timely measures aimed at preventing measles transmission. METHODS: In this study, we have enrolled 114 children vaccinated against measles, 50 children prenatally infected with HIV and 64 HIV-uninfected children. For all children, blood samples were taken to measure anti-measles IgG by EIA and CD4 count by flow cytometry. Additionally, HIV viral load was determined by automated real time PCR, for HIV-infected children. RESULTS: The seroprotective rate of IgG anti-measles antibodies was significantly lower among HIV-infected children (26%) compared with HIV-uninfected children (73%) (p < 0.001). Within HIV-infected children group, the comparison of variables between children without seroprotective seroconversion to measles and those with seroprotective immunity, displayed that sex and age were not statistically different, p > 0.999 and p = 0.730, respectively. However, CD4 count was lower among children with negative serostatus to measles (23% versus 32%, p < 0.001). Furthermore, viral load was higher, with 2.91 log10 ± 2.24 versus 1.7 log10 ± 1.5 (p = 0.042). Finally, 62% of children with a negative vaccine response to measles were under HAART therapy, versus 92% (p = 0.008). CONCLUSION: The majority of HIV-infected children vaccinated against measles develop a suboptimal seroprotective titer, and therefore remain at risk for this highly infectious disease. These data in combination with international recommendations, including recent WHO guidance on vaccination of HIV-infected children, suggest there is a need for national measures to prevent these children from measles.


Assuntos
Anticorpos Antivirais/sangue , Formação de Anticorpos , Infecções por HIV/epidemiologia , Transmissão Vertical de Doença Infecciosa , Vacina contra Sarampo/uso terapêutico , Sarampo/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , HIV , Infecções por HIV/sangue , Infecções por HIV/complicações , Infecções por HIV/imunologia , Humanos , Lactente , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Masculino , Sarampo/sangue , Sarampo/complicações , Vacina contra Sarampo/imunologia , Vírus do Sarampo/imunologia , Marrocos/epidemiologia , Estudos Soroepidemiológicos , Vacinação
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