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1.
An Bras Dermatol ; 95(2): 238-240, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32146012

RESUMO

Some epidermal alterations in measles has been described, such as keratinocytes apoptotic, parakeratosis, giant-cell formation, intranuclear and cytoplasmic inclusions, dyskeratosis, spongiosis, and intracellular edema. The authors report for the first time in human a case of measles with the presence of multinucleated giant cells in the hair follicle and dyskeratosis in acrosyringium.


Assuntos
Epiderme/patologia , Folículo Piloso/patologia , Sarampo/patologia , Biópsia , Criança , Células Gigantes/patologia , Humanos , Queratinócitos/patologia , Masculino , Paraceratose/patologia
2.
PLoS One ; 15(1): e0218239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31951608

RESUMO

BACKGROUND: We explored the contributions of the Family Health Days (FHDs) concept, which was developed by the Uganda Ministry of Health (MOH) and UNICEF as a supplementary quarterly outreach program in addition to strengthening the routine expanded program for immunization (EPI), with the aim to increase coverage, through improved access to the unimmunized or unreached and under-immunized children under 5 years. METHOD: A cross-sectional descriptive study of the Uganda MOH, Health Management Information Systems (HMIS) and UNICEF in house FHDs data was conducted covering six quarterly implementations of the program between April 2012 and December 2013. The FHDs program was implemented in 31 priority districts with low routine vaccination coverage from seven sub-regions in Uganda in a phased manner using places of worship for service delivery. RESULTS: During the six rounds of FHDs in the 31 districts, a total of 178,709 and 191,223 children received measles and Diphtheria-Pertussis-Tetanus (DPT3) vaccinations, respectively. The FHDs' contributions were 126% and 144% for measles and 103% and 122% for DPT3 in 2012 and 2013, respectively of the estimated unreached annual target populations. All implementing sub-regions after two rounds in 2012 attained over and above the desired target for DPT3 (85%) and measles (90%). The same was true in 2013 after four rounds, except for Karamoja and West Nile sub-regions, where in some districts a substantial proportion of children remained unimmunized. The administrative data for both DPT3 and measles immunization showed prominent and noticeable increase in coverage trend in FHDS regions for the months when the program was implemented. CONCLUSION: The FHDs program improved vaccination equity by reaching the unreached and hard-to-reach children and bridging the gap in immunization coverage, and fast tracking the achievement of targets recommended by the Global Vaccine Action Plan (GVAP) for measles and DPT3 (85% and 90% respectively) in implementing sub-regions and districts. The FHDs is an innovative program to supplement routine immunizations designed to reach the unreached and under immunized children.


Assuntos
Vacina contra Difteria, Tétano e Coqueluche/uso terapêutico , Sarampo/prevenção & controle , Vacinação , Criança , Pré-Escolar , Estudos Transversais , Saúde da Família , Feminino , Humanos , Programas de Imunização , Lactente , Masculino , Sarampo/epidemiologia , Sarampo/patologia , Uganda/epidemiologia , Cobertura Vacinal
4.
Am J Dermatopathol ; 41(12): 914-923, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31021834

RESUMO

Despite available vaccination, measles is one of the leading causes of death among young children in developing countries. In clinical practice, the spectrum of differential diagnoses of morbilliform exanthemas associated with fever is wide, and it can be hard to differentiate from other infectious eruptions, especially in adults or in atypical courses in immunocompromised patients. The goal of our study was to identify characteristic histomorphological and immunohistochemical patterns of measles exanthema through the study of 13 skin biopsy specimens obtained from 13 patients with this disease and a review of cases in the literature. Histopathological features of measles exanthema are quite distinctive and characterized by a combination of multinucleated keratinocytes, and individual and clustered necrotic keratinocytes in the epidermis with pronounced folliculosebaceous as well as acrosyringeal involvement. Immunohistochemical staining of skin biopsies with anti-measles virus (MeV) nucleoprotein and anti-MeV phosphoprotein can be of great value in confirming the diagnosis of measles. Both methods can serve as quick additional diagnostic tools for prompt implementation of quarantine measures and for providing medical assistance, even in patients in whom the clinician did not consider measles as a differential diagnosis of the rash due to the rarity of the disease in a putatively vaccinated community.


Assuntos
Exantema/diagnóstico , Imuno-Histoquímica , Vírus do Sarampo/patogenicidade , Sarampo/diagnóstico , Sarampo/patologia , Nucleoproteínas/análise , Fosfoproteínas/análise , Dermatopatias Virais/diagnóstico , Pele , Proteínas Virais/análise , Adolescente , Adulto , Biópsia , Diagnóstico Diferencial , Exantema/metabolismo , Exantema/patologia , Exantema/virologia , Feminino , Humanos , Masculino , Sarampo/metabolismo , Sarampo/virologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Pele/química , Pele/patologia , Pele/virologia , Dermatopatias Virais/metabolismo , Dermatopatias Virais/patologia , Dermatopatias Virais/virologia , Adulto Jovem
6.
Am J Dermatopathol ; 41(4): 289-292, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30252698

RESUMO

We report the case of a 32-year-old man with measles in which skin biopsy helped to establish a definitive diagnosis. Follicular involvement is a common histopathologic feature of measles. Multinucleated epidermal and follicular cells are distinctive findings.


Assuntos
Células Gigantes/patologia , Folículo Piloso/patologia , Queratinócitos/patologia , Sarampo/patologia , Glândulas Sebáceas/patologia , Adulto , Biópsia , Humanos , Masculino , Sarampo/diagnóstico
7.
BMC Med ; 16(1): 177, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30333039

RESUMO

BACKGROUND: A sequence of annual measles epidemics has been observed from January 2013 to April 2017 in the South West Shoa Zone of the Oromia Region, Ethiopia. We aimed at estimating the burden of disease in the affected area, taking into account inequalities in access to health care due to travel distances from the nearest hospital. METHODS: We developed a dynamic transmission model calibrated on the time series of hospitalized measles cases. The model provided estimates of disease transmissibility and incidence at a population level. Model estimates were combined with a spatial analysis to quantify the hidden burden of disease and to identify spatial heterogeneities characterizing the effectiveness of the public health system in detecting severe measles infections and preventing deaths. RESULTS: A total of 1819 case patients and 36 deaths were recorded at the hospital. The mean age was 6.0 years (range, 0-65). The estimated reproduction number was 16.5 (95% credible interval (CI) 14.5-18.3) with a cumulative disease incidence of 2.34% (95% CI 2.06-2.66). Three thousand eight hundred twenty-one (95% CI 1969-5671) severe cases, including 2337 (95% CI 716-4009) measles-related deaths, were estimated in the Woliso hospital's catchment area (521,771 inhabitants). The case fatality rate was found to remarkably increase with travel distance from the nearest hospital: ranging from 0.6% to more than 19% at 20 km. Accordingly, hospital treatment prevented 1049 (95% CI 757-1342) deaths in the area. CONCLUSIONS: Spatial heterogeneity in the access to health care can dramatically affect the burden of measles disease in low-income settings. In sub-Saharan Africa, passive surveillance based on hospital admitted cases might miss up to 60% of severe cases and 98% of related deaths.


Assuntos
Acesso aos Serviços de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Sarampo/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Epidemias , Etiópia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Sarampo/mortalidade , Sarampo/patologia , Pessoa de Meia-Idade , Mortalidade , Taxa de Sobrevida , Adulto Jovem
8.
BMC Med ; 16(1): 102, 2018 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-29970074

RESUMO

BACKGROUND: Equitable access to vaccines has been suggested as a priority for low- and middle-income countries (LMICs). However, it is unclear whether providing equitable access is enough to ensure health equity. Furthermore, disaggregated data on health outcomes and benefits gained across population subgroups are often unavailable. This paper develops a model to estimate the distribution of childhood disease cases and deaths across socioeconomic groups, and the potential benefits of three vaccine programs in LMICs. METHODS: For each country and for three diseases (diarrhea, measles, pneumonia), we estimated the distributions of cases and deaths that would occur across wealth quintiles in the absence of any immunization or treatment programs, using both the prevalence and relative risk of a set of risk and prognostic factors. Building on these baseline estimates, we examined what might be the impact of three vaccines (first dose of measles, pneumococcal conjugate, and rotavirus vaccines), under five scenarios based on different sets of quintile-specific immunization coverage and disease treatment utilization rates. RESULTS: Due to higher prevalence of risk factors among the poor, disproportionately more disease cases and deaths would occur among the two lowest wealth quintiles for all three diseases when vaccines or treatment are unavailable. Country-specific context, including how the baseline risks, immunization coverage, and treatment utilization are currently distributed across quintiles, affects how different policies translate into changes in cases and deaths distribution. CONCLUSIONS: Our study highlights several factors that would substantially contribute to the unequal distribution of childhood diseases, and finds that merely ensuring equal access to vaccines will not reduce the health outcomes gap across wealth quintiles. Such information can inform policies and planning of programs that aim to improve equitable delivery of healthcare services.


Assuntos
Diarreia/mortalidade , Sarampo/mortalidade , Pneumonia/mortalidade , Fatores Socioeconômicos , Diarreia/patologia , Feminino , Humanos , Masculino , Sarampo/patologia , Pneumonia/patologia
9.
J Med Internet Res ; 20(7): e236, 2018 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-29986843

RESUMO

BACKGROUND: Timely understanding of public perceptions allows public health agencies to provide up-to-date responses to health crises such as infectious diseases outbreaks. Social media such as Twitter provide an unprecedented way for the prompt assessment of the large-scale public response. OBJECTIVE: The aims of this study were to develop a scheme for a comprehensive public perception analysis of a measles outbreak based on Twitter data and demonstrate the superiority of the convolutional neural network (CNN) models (compared with conventional machine learning methods) on measles outbreak-related tweets classification tasks with a relatively small and highly unbalanced gold standard training set. METHODS: We first designed a comprehensive scheme for the analysis of public perception of measles based on tweets, including 3 dimensions: discussion themes, emotions expressed, and attitude toward vaccination. All 1,154,156 tweets containing the word "measles" posted between December 1, 2014, and April 30, 2015, were purchased and downloaded from DiscoverText.com. Two expert annotators curated a gold standard of 1151 tweets (approximately 0.1% of all tweets) based on the 3-dimensional scheme. Next, a tweet classification system based on the CNN framework was developed. We compared the performance of the CNN models to those of 4 conventional machine learning models and another neural network model. We also compared the impact of different word embeddings configurations for the CNN models: (1) Stanford GloVe embedding trained on billions of tweets in the general domain, (2) measles-specific embedding trained on our 1 million measles related tweets, and (3) a combination of the 2 embeddings. RESULTS: Cohen kappa intercoder reliability values for the annotation were: 0.78, 0.72, and 0.80 on the 3 dimensions, respectively. Class distributions within the gold standard were highly unbalanced for all dimensions. The CNN models performed better on all classification tasks than k-nearest neighbors, naïve Bayes, support vector machines, or random forest. Detailed comparison between support vector machines and the CNN models showed that the major contributor to the overall superiority of the CNN models is the improvement on recall, especially for classes with low occurrence. The CNN model with the 2 embedding combination led to better performance on discussion themes and emotions expressed (microaveraging F1 scores of 0.7811 and 0.8592, respectively), while the CNN model with Stanford embedding achieved best performance on attitude toward vaccination (microaveraging F1 score of 0.8642). CONCLUSIONS: The proposed scheme can successfully classify the public's opinions and emotions in multiple dimensions, which would facilitate the timely understanding of public perceptions during the outbreak of an infectious disease. Compared with conventional machine learning methods, our CNN models showed superiority on measles-related tweet classification tasks with a relatively small and highly unbalanced gold standard. With the success of these tasks, our proposed scheme and CNN-based tweets classification system is expected to be useful for the analysis of tweets about other infectious diseases such as influenza and Ebola.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Sarampo/epidemiologia , Redes Neurais de Computação , Mídias Sociais/tendências , História do Século XXI , Humanos , Sarampo/patologia , Percepção , Opinião Pública , Reprodutibilidade dos Testes
10.
Jpn J Infect Dis ; 71(6): 413-418, 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29962488

RESUMO

The incidence of modified measles (M-Me), characterized by milder symptoms than those of typical measles (T-Me), has been increasing in Japan. However, the outbreak dominated by M-Me cases has not been thoroughly investigated worldwide. The largest importation-related outbreak of measles with genotype D8 occurred in Yamagata Prefecture, Japan, from March to April 2017. This phenomenon was observed after Japan had achieved measles elimination in 2015. We confirmed 60 cases by detecting the genome of the measles virus (MeV). Among the cases, 38 were M-Me and 22 were T-Me. Thirty-nine (65.0%) patients were 20-39 years of age. Three out of 7 primary cases produced 50 transmissions, of which each patient caused 9-25 transmissions. These patients were 22-31 years old and were not vaccinated. Moreover, they developed T-Me and kept contact with the public during their symptomatic periods. Considering that M-Me is generally caused by vaccine failure, some individuals in Japan may have insufficient immunity for MeV. Accordingly, additional doses of measles vaccine may be necessary in preventing measles importation and endemicity among individuals aged 20-39 years. Furthermore, to accurately and promptly diagnose individuals with measles, particularly those who can be considered as primary cases, efforts must be exerted to detect all measles cases using epidemiological and genetic approaches in countries where measles elimination had been achieved.


Assuntos
Surtos de Doenças , Sarampo/epidemiologia , Sarampo/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Controle de Doenças Transmissíveis/métodos , Doenças Transmissíveis Importadas/epidemiologia , Doenças Transmissíveis Importadas/patologia , Doenças Transmissíveis Importadas/prevenção & controle , Doenças Transmissíveis Importadas/transmissão , Transmissão de Doença Infecciosa , Feminino , Genótipo , Humanos , Incidência , Lactente , Japão/epidemiologia , Masculino , Sarampo/prevenção & controle , Sarampo/transmissão , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Vírus do Sarampo/classificação , Vírus do Sarampo/genética , Vírus do Sarampo/isolamento & purificação , Pessoa de Meia-Idade , Adulto Jovem
11.
mSphere ; 3(3)2018.
Artigo em Inglês | MEDLINE | ID: mdl-29743202

RESUMO

Characterization of human measles cases is essential in order to better assess the data generated in model systems of morbillivirus infection. To this end, we collected formalin-fixed tissue samples from 23 natural measles cases from different areas in the world and different phases of disease ranging from prodromal and acute measles to a persistent infection in an immunocompromised subject. We show that the vast majority of measles virus (MV)-infected cells in epithelia were intraepithelial immune cells that were, in most cases, positive for the CD11c myeloid cell marker. Small numbers of measles virus-infected cytokeratin-positive epithelial cells were also detected in bronchial and appendix epithelia. Dissolution and disruption of uninfected and MV-infected alveolar and bronchial epithelia were prominent features of the measles cases, especially in the established and late phases of the disease. In some instances, this was associated with the formation of MV-infected multinucleated giant cells which expressed CD11c and/or macrophage cell marker 68, a pathological feature also prominently observed in closely associated mucosa-associated lymphoid tissue. Collectively, these data show that resident and inflammatory infiltrating immune cells alter the architecture of respiratory tract epithelia and highlight the necessity for additional research into the function(s) and expression of nectin-4 in human tissues.IMPORTANCE We have brought together a unique collection of 23 human cases of measles infection and studied the types of cells that are infected. This work has not been done with modern technologies such as double labeling with antibodies and confocal microscopy in human cases primarily due to the fact that it is difficult to obtain the material because, fortunately, measles is fatal in only a very small fraction of infected patients. During the past decades, the receptors for measles virus have been elucidated and monkey models have been developed. We found that, in most cases, independently of whether the tissues were obtained early or later in the infection, the primary cell types that were infected were those of the immune system such as lymphocytes, macrophages, and dendritic cells. A very small number of epithelial cells were also found to be infected.


Assuntos
Células Dendríticas/virologia , Células Gigantes/virologia , Macrófagos/virologia , Sarampo/virologia , Morbillivirus/crescimento & desenvolvimento , Mucosa Respiratória/virologia , Adolescente , Idoso , Antígeno CD11c/análise , Criança , Pré-Escolar , Células Dendríticas/química , Feminino , Células Gigantes/química , Humanos , Lactente , Macrófagos/química , Masculino , Sarampo/patologia , Mucosa Respiratória/patologia
12.
J Virol ; 92(8)2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29437964

RESUMO

Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils to in vitro MV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (TH) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that TH1TH17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression.IMPORTANCE Measles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing the importance of MV infection of B cells in vivo However, information on the relative susceptibility of B-cell subsets is scarce. Here, we compared the susceptibility and permissiveness to in vitro MV infection of human naive and memory T- and B-cell subsets isolated from peripheral blood or tonsils. Our results demonstrate that both naive and memory B cells are more permissive to MV infection than T cells. The highest infection levels were detected in plasma cells and germinal center B cells, suggesting that infection and depletion of these populations contribute to reduced host resistance.


Assuntos
Linfócitos B/imunologia , Memória Imunológica , Vírus do Sarampo/imunologia , Sarampo/imunologia , Células Th1/imunologia , Células Th17/imunologia , Adulto , Linfócitos B/patologia , Linfócitos B/virologia , Criança , Feminino , Humanos , Masculino , Sarampo/patologia , Células Th1/patologia , Células Th1/virologia , Células Th17/patologia , Células Th17/virologia
13.
Am J Med ; 131(6): e249-e250, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29476743
14.
Med Hypotheses ; 111: 70-72, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29407001

RESUMO

Subacute sclerosing panencephalitis (SSPE) is a progressive disease caused by persistent measles virus (MV). It has an incidence of 0.4-2.0/million in Turkey. Immune thrombocytopenia (ITP) is a bleeding disorder whose estimated incidence is 4.2/100.000 person/years in the pediatric age group. We observed three cases with ITP in our cohort of 315 pediatric SSPE cases, an incidence higher than coincidentally expected in the general population. We hypothesize an association between SSPE and ITP. Our three cases had measles 1-2 years before the onset of ITP and 8-10 years before first symptoms of SSPE. A common immunogenetic background creating susceptibility to infection and autoimmunity might play a role. Alternatively, chronic antigenic stimulation by the MV leading to synthesis of cross-reacting antibodies against platelets, or treatment of ITP with immunoglobulins or steroids might affect or alter the development and manifestation of SSPE. The co-occurrence of these two disorders of viral and immune pathogenesis may draw attention to similar observations and provide clues for their mechanisms.


Assuntos
Púrpura Trombocitopênica Idiopática/complicações , Panencefalite Esclerosante Subaguda/complicações , Adolescente , Criança , Comorbidade , Feminino , Humanos , Sistema Imunitário , Masculino , Sarampo/complicações , Sarampo/patologia , Vírus do Sarampo , Modelos Teóricos , Púrpura Trombocitopênica Idiopática/diagnóstico , Risco , Panencefalite Esclerosante Subaguda/diagnóstico , Trombocitopenia
15.
J Virol ; 92(6)2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29298883

RESUMO

Measles virus (MV) usually causes acute infection but in rare cases persists in the brain, resulting in subacute sclerosing panencephalitis (SSPE). Since human neurons, an important target affected in the disease, do not express the known MV receptors (signaling lymphocyte activation molecule [SLAM] and nectin 4), how MV infects neurons and spreads between them is unknown. Recent studies have shown that many virus strains isolated from SSPE patients possess substitutions in the extracellular domain of the fusion (F) protein which confer enhanced fusion activity. Hyperfusogenic viruses with such mutations, unlike the wild-type MV, can induce cell-cell fusion even in SLAM- and nectin 4-negative cells and spread efficiently in human primary neurons and the brains of animal models. We show here that a hyperfusogenic mutant MV, IC323-F(T461I)-EGFP (IC323 with a fusion-enhancing T461I substitution in the F protein and expressing enhanced green fluorescent protein), but not the wild-type MV, spreads in differentiated NT2 cells, a widely used human neuron model. Confocal time-lapse imaging revealed the cell-to-cell spread of IC323-F(T461I)-EGFP between NT2 neurons without syncytium formation. The production of virus particles was strongly suppressed in NT2 neurons, also supporting cell-to-cell viral transmission. The spread of IC323-F(T461I)-EGFP was inhibited by a fusion inhibitor peptide as well as by some but not all of the anti-hemagglutinin antibodies which neutralize SLAM- or nectin-4-dependent MV infection, suggesting the presence of a distinct neuronal receptor. Our results indicate that MV spreads in a cell-to-cell manner between human neurons without causing syncytium formation and that the spread is dependent on the hyperfusogenic F protein, the hemagglutinin, and the putative neuronal receptor for MV.IMPORTANCE Measles virus (MV), in rare cases, persists in the human central nervous system (CNS) and causes subacute sclerosing panencephalitis (SSPE) several years after acute infection. This neurological complication is almost always fatal, and there is currently no effective treatment for it. Mechanisms by which MV invades the CNS and causes the disease remain to be elucidated. We have previously shown that fusion-enhancing substitutions in the fusion protein of MVs isolated from SSPE patients contribute to MV spread in neurons. In this study, we demonstrate that MV bearing the hyperfusogenic mutant fusion protein spreads between human neurons in a cell-to-cell manner. Spread of the virus was inhibited by a fusion inhibitor peptide and antibodies against the MV hemagglutinin, indicating that both the hemagglutinin and hyperfusogenic fusion protein play important roles in MV spread between human neurons. The findings help us better understand the disease process of SSPE.


Assuntos
Hemaglutininas Virais/metabolismo , Vírus do Sarampo/metabolismo , Sarampo/transmissão , Neurônios/metabolismo , Panencefalite Esclerosante Subaguda/transmissão , Proteínas Virais de Fusão/metabolismo , Animais , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Chlorocebus aethiops , Hemaglutininas Virais/genética , Humanos , Sarampo/genética , Sarampo/metabolismo , Sarampo/patologia , Vírus do Sarampo/genética , Vírus do Sarampo/patogenicidade , Neurônios/patologia , Neurônios/virologia , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária/genética , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Panencefalite Esclerosante Subaguda/genética , Panencefalite Esclerosante Subaguda/metabolismo , Panencefalite Esclerosante Subaguda/patologia , Células Vero , Proteínas Virais de Fusão/genética
17.
Pediatr Dev Pathol ; 21(5): 497-501, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28882091

RESUMO

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is a common cause of periodic fever in children. The pathogenesis of PFAPA is unknown but likely involves immune system dysregulation and may be initiated by an environmental trigger. Tonsillectomy resolves or improves symptoms in some patients, but the reason for this is unknown; moreover, specific abnormalities in tonsillectomy specimens from PFAPA patients have not been described. Here, we report measles virus in tonsil from a child with PFAPA. Measles-type viral cytopathic effect was discovered on histological examination of tonsillar tissue after therapeutic tonsillectomy for PFAPA. Molecular testing showed the left tonsil was positive for measles RNA by reverse transcription polymerase chain reaction (RT-PCR) while the right tonsil was inconclusive (weakly positive). Real-time RT-PCR specific for measles vaccine strain RNA (genotype A) was weakly reactive in the left tonsil tissue when tested in 3 independent replicates, but this result could not be confirmed with conventional genotyping by sequencing. The relationship and clinical significance between measles virus and PFAPA in this case is unclear but may be related to PFAPA-associated immune dysregulation. Additional investigation of measles virus in PFAPA patients would be helpful in further exploring this potential association.


Assuntos
Febre/complicações , Linfadenite/complicações , Sarampo/complicações , Tonsila Palatina/patologia , Faringite/complicações , Estomatite Aftosa/complicações , Pré-Escolar , Febre/patologia , Humanos , Linfadenite/patologia , Masculino , Sarampo/patologia , Morbillivirus/isolamento & purificação , Faringite/patologia , Estomatite Aftosa/patologia , Síndrome
18.
PLoS One ; 12(10): e0187077, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29073265

RESUMO

Measles virus (MV) infects a variety of lymphoid and non-lymphoid peripheral organs. However, in rare cases, the virus can persistently infect cells within the central nervous system. Although some of the factors that allow MV to persist are known, the contribution of host cell-encoded microRNAs (miRNA) have not been described. MiRNAs are a class of noncoding RNAs transcribed from genomes of all multicellular organisms and some viruses, which regulate gene expression in a sequence-specific manner. We have studied the contribution of host cell-encoded miRNAs to the establishment of MV persistent infection in human neuroblastoma cells. Persistent MV infection was accompanied by differences in the expression profile and levels of several host cell-encoded microRNAs as compared to uninfected cells. MV persistence infection of a human neuroblastoma cell line (UKF-NB-MV), exhibit high miRNA-124 expression, and reduced expression of cyclin dependent kinase 6 (CDK6), a known target of miRNA-124, resulting in slower cell division but not cell death. By contrast, acute MV infection of UKF-NB cells did not result in increased miRNA-124 levels or CDK6 reduction. Ectopic overexpression of miRNA-124 affected cell viability only in UKF-NB-MV cells, causing cell death; implying that miRNA-124 over expression can sensitize cells to death only in the presence of MV persistent infection. To determine if miRNA-124 directly contributes to the establishment of MV persistence, UKF-NB cells overexpressing miRNA-124 were acutely infected, resulting in establishment of persistently infected colonies. We propose that miRNA-124 triggers a CDK6-dependent decrease in cell proliferation, which facilitates the establishment of MV persistence in neuroblastoma cells. To our knowledge, this is the first report to describe the role of a specific miRNA in MV persistence.


Assuntos
Divisão Celular/genética , Sarampo/genética , MicroRNAs/genética , Neuroblastoma/patologia , Apoptose/genética , Linhagem Celular Tumoral , Quinase 6 Dependente de Ciclina/metabolismo , Regulação para Baixo , Humanos , Sarampo/patologia
19.
J Korean Med Sci ; 32(11): 1876-1878, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28960044

RESUMO

Measles has been declared eliminated from the Korea since 2006. In April 2014, a measles outbreak occurred at a University in Seoul. A total of 85 measles cases were identified. In order to estimate vaccine effectiveness of measles vaccine, we reviewed the vaccination records of the university students. The vaccine effectiveness of two doses of measles containing vaccine was 60.0% (95% CI, 38.2-74.1; P < 0.05). Transmission was interrupted after the introduction of outbreak-response immunization. The outbreak shows that pockets of under-immunity among college students may have facilitated the disease transmission despite the high 2-dose vaccination coverage in the community.


Assuntos
Surtos de Doenças , Sarampo/epidemiologia , Adulto , Grupo com Ancestrais do Continente Asiático , Emigrantes e Imigrantes , Feminino , Humanos , Masculino , Sarampo/patologia , Sarampo/transmissão , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Universidades , Adulto Jovem
20.
BMC Med ; 15(1): 151, 2017 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-28793891

RESUMO

BACKGROUND: Decreasing trends in measles mortality have been reported in recent years. However, such estimates of measles mortality have depended heavily on assumed regional measles case fatality risks (CFRs) and made little use of mortality data from low- and middle-income countries in general and India, the country with the highest measles burden globally, in particular. METHODS: We constructed a dynamic model of measles transmission in India with parameters that were empirically inferred using spectral analysis from a time series of measles mortality extracted from the Million Death Study, an ongoing longitudinal study recording deaths across 2.4 million Indian households and attributing causes of death using verbal autopsy. The model was then used to estimate the measles CFR, the number of measles deaths, and the impact of vaccination in 2000-2015 among under-five children in India and in the states of Bihar and Uttar Pradesh (UP), two states with large populations and the highest numbers of measles deaths in India. RESULTS: We obtained the following estimated CFRs among under-five children for the year 2005: 0.63% (95% confidence interval (CI): 0.40-1.00%) for India as a whole, 0.62% (0.38-1.00%) for Bihar, and 1.19% (0.80-1.75%) for UP. During 2000-2015, we estimated that 607,000 (95% CI: 383,000-958,000) under-five deaths attributed to measles occurred in India as a whole. If no routine vaccination or supplemental immunization activities had occurred from 2000 to 2015, an additional 1.6 (1.0-2.6) million deaths for under-five children would have occurred across India. CONCLUSIONS: We developed a data- and model-driven estimation of the historical measles dynamics, CFR, and vaccination impact in India, extracting the periodicity of epidemics using spectral and coherence analysis, which allowed us to infer key parameters driving measles transmission dynamics and mortality.


Assuntos
Sarampo/patologia , Sarampo/transmissão , Modelos Estatísticos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia/métodos , Causas de Morte , Criança , Pré-Escolar , Feminino , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Sarampo/mortalidade , Sarampo/prevenção & controle , Pessoa de Meia-Idade , Vacinação , Adulto Jovem
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