RESUMO
BACKGROUND: Kawasaki disease (KD) is a febrile illness of young childhood that can result in coronary artery aneurysms and death. Coronavirus disease 2019 (COVID-19) mitigation strategies resulted in a marked decrease in KD cases worldwide, supporting a transmissible respiratory agent as the cause. We previously reported a peptide epitope recognized by monoclonal antibodies (MAbs) derived from clonally expanded peripheral blood plasmablasts from 3 of 11 KD children, suggesting a common disease trigger in a subset of patients with KD. METHODS: We performed amino acid substitution scans to develop modified peptides with improved recognition by KD MAbs. We prepared additional MAbs from KD peripheral blood plasmablasts and assessed MAb characteristics that were associated with binding to the modified peptides. RESULTS: We report a modified peptide epitope that is recognized by 20 MAbs from 11 of 12 KD patients. These MAbs predominantly use heavy chain VH3-74; two-thirds of VH3-74 plasmablasts from these patients recognize the epitope. The MAbs were nonidentical between patients but share a common complementarity-determining region 3 (CDR3) motif. CONCLUSIONS: These results demonstrate a convergent VH3-74 plasmablast response to a specific protein antigen in children with KD, supporting one predominant causative agent in the etiopathogenesis of the illness.
Assuntos
COVID-19 , Síndrome de Linfonodos Mucocutâneos , Humanos , Criança , Epitopos , Formação de Anticorpos , Anticorpos Monoclonais , PeptídeosRESUMO
BACKGROUND: Cardiac evaluations, including cardiovascular magnetic resonance (CMR) imaging and biomarker results, are needed in children during mid-term recovery after infection with SARS-CoV-2. The incidence of CMR abnormalities 1-3 months after recovery is over 50% in older adults and has ranged between 1 and 15% in college athletes. Abnormal cardiac biomarkers are common in adults, even during recovery. METHODS: We performed CMR imaging in a prospectively-recruited pediatric cohort recovered from COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We obtained CMR data and serum biomarkers. We compared these results to age-matched control patients, imaged prior to the SARS-CoV-2 pandemic. RESULTS: CMR was performed in 17 children (13.9 years, all ≤ 18 years) and 29 age-matched control patients without SARS-CoV-2 infection. Cases were recruited with symptomatic COVID-19 (11/17, 65%) or MIS-C (6/17, 35%) and studied an average of 2 months after diagnosis. All COVID-19 patients had been symptomatic with fever (73%), vomiting/diarrhea (64%), or breathing difficulty (55%) during infection. Left ventricular and right ventricular ejection fractions were indistinguishable between cases and controls (p = 0.66 and 0.70, respectively). Mean native global T1, global T2 values and segmental T2 maximum values were also not statistically different from control patients (p ≥ 0.06 for each). NT-proBNP and troponin levels were normal in all children. CONCLUSIONS: Children prospectively recruited following SARS-CoV-2 infection had normal CMR and cardiac biomarker evaluations during mid-term recovery. Trial Registration Not applicable.
Assuntos
COVID-19/complicações , Coração/diagnóstico por imagem , Coração/fisiologia , Imageamento por Ressonância Magnética/métodos , Síndrome de Resposta Inflamatória Sistêmica/complicações , Adolescente , Biomarcadores/sangue , COVID-19/sangue , Criança , Feminino , Humanos , Masculino , Estudos Prospectivos , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica/sangueRESUMO
BACKGROUND: Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause but specific antigenic targets of the disease are unknown. Peripheral blood plasmablasts are normally highly clonally diverse but the antibodies they encode are approximately 70% antigen-specific 1-2 weeks after infection. METHODS: We isolated single peripheral blood plasmablasts from children with KD 1-3 weeks after onset and prepared 60 monoclonal antibodies (mAbs). We used the mAbs to identify their target antigens and assessed serologic response among KD patients and controls to specific antigen. RESULTS: Thirty-two mAbs from 9 of 11 patients recognize antigen within intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells of fatal cases. Five of these mAbs, from 3 patients with coronary aneurysms, recognize a specific peptide, which blocks binding to inclusion bodies. Sera from 5/8 KD patients dayâ ≥â 8 after illness onset, compared with 0/17 infant controls (Pâ <â .01), recognized the KD peptide antigen. CONCLUSIONS: These results identify a protein epitope targeted by the antibody response to KD and provide a means to elucidate the pathogenesis of this important worldwide pediatric problem.
Assuntos
Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Formação de Anticorpos/genética , Células Sanguíneas/imunologia , Epitopos/imunologia , Síndrome de Linfonodos Mucocutâneos/genética , Síndrome de Linfonodos Mucocutâneos/imunologia , Feminino , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart disease in children in developed countries. METHODS AND RESULTS: To revise the previous American Heart Association guidelines, a multidisciplinary writing group of experts was convened to review and appraise available evidence and practice-based opinion, as well as to provide updated recommendations for diagnosis, treatment of the acute illness, and long-term management. Although the cause remains unknown, discussion sections highlight new insights into the epidemiology, genetics, pathogenesis, pathology, natural history, and long-term outcomes. Prompt diagnosis is essential, and an updated algorithm defines supplemental information to be used to assist the diagnosis when classic clinical criteria are incomplete. Although intravenous immune globulin is the mainstay of initial treatment, the role for additional primary therapy in selected patients is discussed. Approximately 10% to 20% of patients do not respond to initial intravenous immune globulin, and recommendations for additional therapies are provided. Careful initial management of evolving coronary artery abnormalities is essential, necessitating an increased frequency of assessments and escalation of thromboprophylaxis. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as Z scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up. CONCLUSIONS: These recommendations provide updated and best evidence-based guidance to healthcare providers who diagnose and manage Kawasaki disease, but clinical decision making should be individualized to specific patient circumstances.
Assuntos
American Heart Association , Síndrome de Linfonodos Mucocutâneos/diagnóstico por imagem , Síndrome de Linfonodos Mucocutâneos/terapia , Algoritmos , Tomada de Decisão Clínica , Consenso , Procedimentos Clínicos/normas , Técnicas de Apoio para a Decisão , Humanos , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados UnidosAssuntos
Brucella , Brucelose , COVID-19 , Anfíbios , Animais , Criança , Trato Gastrointestinal , Humanos , Miocárdio , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
BACKGROUND: Kawasaki Disease (KD) can cause potentially life-threatening coronary arteritis in young children, and has a likely infectious etiology. Transcriptome profiling is a powerful approach to investigate gene expression in diseased tissues. RNA sequencing of KD coronary arteries could elucidate the etiology and the host response, with the potential to improve KD diagnosis and/or treatment. METHODS: Deep RNA sequencing was performed on KD (n = 8) and childhood control (n = 7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Non-human RNA sequences were subjected to a microbial discovery bioinformatics platform, and microbial sequences were analyzed by Metastats for association with KD. RESULTS: T lymphocyte activation, antigen presentation, immunoglobulin production, and type I interferon response were significantly upregulated in KD arteritis, while the tumor necrosis factor α pathway was not differentially expressed. Transcripts from known infectious agents were not specifically associated with KD coronary arteritis. CONCLUSIONS: The immune transcriptional profile in KD coronary artery tissues has features of an antiviral immune response such as activated cytotoxic T lymphocyte and type I interferon-induced gene upregulation. These results provide new insights into the pathogenesis of KD arteritis that can guide selection of new immunomodulatory therapies for high-risk KD patients, and provide direction for future etiologic studies.
Assuntos
Arterite/etiologia , Doença da Artéria Coronariana/etiologia , Síndrome de Linfonodos Mucocutâneos/complicações , Transcriptoma , Apresentação de Antígeno/imunologia , Arterite/diagnóstico , Biomarcadores , Estudos de Casos e Controles , Análise por Conglomerados , Biologia Computacional/métodos , Doença da Artéria Coronariana/diagnóstico , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fatores Reguladores de Interferon/genética , Interferon Tipo I/metabolismo , Metabolismo dos Lipídeos/genética , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/terapia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Receptores de Reconhecimento de Padrão/genética , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoAssuntos
COVID-19/fisiopatologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , COVID-19/diagnóstico , Criança , Pré-Escolar , Diagnóstico Diferencial , Humanos , Lactente , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Pandemias , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica/diagnósticoRESUMO
Background: Kawasaki disease (KD) is an acute febrile illness of childhood that can lead to coronary artery aneurysms (CAAs) and myocardial infarction. Intravenous immunoglobulin reduces the prevalence of CAA when given to patients with KD within 10 days of fever onset. Children with KD may undergo evaluation for other diagnoses before treatment, particularly those with incomplete KD criteria. If KD outcomes are improved with early treatment, a delay in treatment while evaluating for other causes might place these patients at risk. Methods: We performed a retrospective cohort study of children treated for KD within the first 10 days of illness at our KD center from 2014 to 2021 to determine the prevalence of CAA by day of treatment. Results: A total of 290 patients met the study criteria. No statistically significant difference was found in the odds of developing a maximum z score ≥2.5 for each day of delayed treatment within 10 days of fever onset (adjusted odds ratio, 0.87; 95% CI, .72-1.05; P = .13). Subgroup analyses by age, sex, and year of treatment did not reveal a significant association between treatment day and maximum z score ≥2.5, although the number of patients <6 months of age was small. Conclusions: Our study supports current recommendations. We found similar odds of developing adverse coronary outcomes regardless of treatment day within 10 days from fever onset.
RESUMO
Kawasaki disease (KD) is a vasculitis of young childhood that particularly affects the coronary arteries. Molecular analysis of the oligoclonal IgA response in acute KD led to production of synthetic KD antibodies. These antibodies identify intracytoplasmic inclusion bodies in acute KD tissues. Light and electron microscopic studies indicate that the inclusion bodies are consistent with aggregates of viral proteins and RNA. Advances in molecular genetic analysis and completion of the Human Genome Project have sparked a worldwide effort to identify genes associated with KD. A polymorphism of one such gene, ITPKC, a negative regulator of T cell activation, confers susceptibility to KD in Japanese populations and increases the risk of developing coronary artery abnormalities in both Japanese and U.S. children. Identification of the etiologic agent and of genes conferring KD susceptibility are the best means of improving diagnosis and therapy and enabling prevention of this important disorder of childhood.
Assuntos
Predisposição Genética para Doença/genética , Síndrome de Linfonodos Mucocutâneos/genética , Anticorpos/imunologia , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/genética , Doenças Transmissíveis/imunologia , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/imunologia , Estudo de Associação Genômica Ampla , Substâncias Perigosas/efeitos adversos , Humanos , Imunoglobulina A/imunologia , Corpos de Inclusão/genética , Corpos de Inclusão/imunologia , Corpos de Inclusão/patologia , Japão/epidemiologia , Masculino , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/imunologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/imunologia , Polimorfismo Genético , Prevalência , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Kawasaki disease (KD) can result in fatal coronary artery (CA) aneurysms, especially if left untreated. Our recent studies of its vascular pathology revealed subacute/chronic vasculitis that begins early in the illness with the proliferation of smooth muscle cell-derived myofibroblasts in a complex extracellular matrix (ECM). We hypothesized that a dysregulation of specific ECM and adhesion molecules occurs in KD CAs. METHODS: Gene expression profiling for ECM and adhesion molecules was performed on six acute KD and eight control CAs using a targeted real-time PCR array approach. RESULTS: Integrins α4 and αM (ITGA4, ITGAM), collagen type I, α1 (COL1A1), and matrix metalloproteinase 7 (MMP7) were significantly upregulated in KD CAs as compared with controls. Immunohistochemistry with anti-ITGAM antibodies revealed expression on inflammatory cells within the CA wall in patients with KD but not in controls. CONCLUSION: Integrins ITGA4 and ITGAM are upregulated in KD vasculopathy, probably promoting inflammatory recruitment that stimulates smooth muscle cell transition to myofibroblasts and their proliferation. MMP7 probably enhances myofibroblast proliferation and luminal lesion expansion, and overexpression of COL1A1 may lead to CA stenosis. Identification of the molecular pathogenesis of KD vasculopathy may lead to the development of circulating biomarkers and to directed therapeutic interventions.
Assuntos
Antígeno CD11b/metabolismo , Colágeno Tipo I/metabolismo , Vasos Coronários/patologia , Regulação da Expressão Gênica/fisiologia , Integrina alfa4/metabolismo , Metaloproteinase 7 da Matriz/metabolismo , Síndrome de Linfonodos Mucocutâneos/metabolismo , Moléculas de Adesão Celular/metabolismo , Matriz Extracelular/metabolismo , Perfilação da Expressão Gênica , Imuno-Histoquímica , Síndrome de Linfonodos Mucocutâneos/patologia , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Kawasaki disease (KD; OMIM 611775) is an acute vasculitis syndrome which predominantly affects small- and medium-sized arteries of infants and children. Epidemiological data suggest that host genetics underlie the disease pathogenesis. Here we report that multiple variants in the caspase-3 gene (CASP3) that are in linkage disequilibrium confer susceptibility to KD in both Japanese and US subjects of European ancestry. We found that a G to A substitution of one commonly associated SNP located in the 5' untranslated region of CASP3 (rs72689236; P = 4.2 x 10(-8) in the Japanese and P = 3.7 x 10(-3) in the European Americans) abolished binding of nuclear factor of activated T cells to the DNA sequence surrounding the SNP. Our findings suggest that altered CASP3 expression in immune effecter cells influences susceptibility to KD.
Assuntos
Caspase 3/genética , Predisposição Genética para Doença , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático/genética , Sítios de Ligação/genética , Estudos de Casos e Controles , Caspase 3/metabolismo , Caspase 3/fisiologia , Criança , Pré-Escolar , Feminino , Frequência do Gene , Testes Genéticos , Humanos , Lactente , Desequilíbrio de Ligação , Masculino , Fatores de Transcrição NFATC/metabolismo , Polimorfismo de Nucleotídeo Único/fisiologia , Ligação Proteica , População Branca/genéticaRESUMO
BACKGROUND: Intracytoplasmic inclusion bodies (ICI) have been identified in ciliated bronchial epithelium of Kawasaki disease (KD) patients using a synthetic antibody derived from acute KD arterial IgA plasma cells; ICI may derive from the KD etiologic agent. METHODS: Acute KD bronchial epithelium was subjected to immunofluorescence for ICI and cytokeratin, high-throughput sequencing, and transmission electron microscopy (TEM). Interferon pathway gene expression profiling was performed on KD lung. RESULTS: An intermediate filament cytokeratin "cage" was not observed around KD ICI, making it unlikely that ICI are overproduced or misfolded human protein aggregates. Many interferon-stimulated genes were detected in the bronchial epithelium, and significant modulation of the interferon response pathway was observed in the lung tissue of KD patients. No known virus was identified by sequencing. Aggregates of virus-like particles (VLP) were detected by TEM in all 3 acute KD patients from whom nonembedded formalin-fixed lung tissue was available. CONCLUSIONS: KD ICI are most likely virus induced; bronchial cells with ICI contain VLP that share morphologic features among several different RNA viral families. Expedited autopsies and tissue fixation from acute KD fatalities are urgently needed to more clearly ascertain the VLP. These findings are compatible with the hypothesis that the infectious etiologic agent of KD may be a "new" RNA virus.
Assuntos
Corpos de Inclusão Viral/patologia , Síndrome de Linfonodos Mucocutâneos/virologia , Vírus/isolamento & purificação , Vírus/patogenicidade , Pré-Escolar , Células Epiteliais/virologia , Feminino , Imunofluorescência , Humanos , Lactente , Recém-Nascido , Masculino , Microscopia Eletrônica de Transmissão , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/patologia , RNA Viral/genética , RNA Viral/isolamento & purificação , Mucosa Respiratória/virologia , Virossomos/imunologia , Virossomos/ultraestrutura , Vírus/imunologia , Vírus/ultraestruturaRESUMO
Importance: Public health measures implemented during the COVID-19 pandemic had widespread effects on population behaviors, transmission of infectious diseases, and exposures to environmental pollutants. This provided an opportunity to study how these factors potentially influenced the incidence of Kawasaki disease (KD), a self-limited pediatric vasculitis of unknown etiology. Objectives: To examine the change in KD incidence across the United States and evaluate whether public health measures affected the prevalence of KD. Design, Setting, and Participants: This multicenter cohort study included consecutive, unselected patients with KD who were diagnosed between January 1, 2018, and December 31, 2020 (multicenter cohort with 28 pediatric centers), and a detailed analysis of patients with KD who were diagnosed between January 1, 2002, and November 15, 2021 (Rady Children's Hospital San Diego [RCHSD]). Main Outcomes and Measures: For the multicenter cohort, the date of fever onset for each patient with KD was collected. For RCHSD, detailed demographic and clinical data as well as publicly available, anonymized mobile phone data and median household income by census block group were collected. The study hypothesis was that public health measures undertaken during the pandemic would reduce exposure to the airborne trigger(s) of KD and that communities with high shelter-in-place compliance would experience the greatest decrease in KD incidence. Results: A total of 2461 KD cases were included in the multicenter study (2018: 894; 2019: 905; 2020: 646), and 1461 cases (median [IQR] age, 2.8 years [1.4-4.9 years]; 900 [61.6%] males; 220 [15.1%] Asian, 512 [35.0%] Hispanic, and 338 [23.1%] White children) from RCHSD between 2002 and 2021 were also included. The 28.2% decline in KD cases nationally during 2020 (646 cases) compared with 2018 (894 cases) and 2019 (905 cases) was uneven across the United States. For RCHSD, there was a disproportionate decline in KD cases in 2020 to 2021 compared with the mean (SD) number of cases in earlier years for children aged 1 to 5 years (22 vs 44.9 [9.9]; P = .02), male children (21 vs 47.6 [10.0]; P = .01), and Asian children (4 vs 11.8 [4.4]; P = .046). Mobility data did not suggest that shelter-in-place measures were associated with the number of KD cases. Clinical features including strawberry tongue, enlarged cervical lymph node, and subacute periungual desquamation were decreased during 2020 compared with the baseline period (strawberry tongue: 39% vs 63%; P = .04; enlarged lymph node: 21% vs 32%; P = .09; periungual desquamation: 47% vs 58%; P = .16). School closures, masking mandates, decreased ambient pollution, and decreased circulation of respiratory viruses all overlapped to different extents with the period of decreased KD cases. KD in San Diego rebounded in the spring of 2021, coincident with lifting of mask mandates. Conclusions and Relevance: In this study of epidemiological and clinical features of KD during the COVID-19 pandemic in the United States, KD cases fell and remained low during the period of masking and school closure. Mobility data indicated that differential intensity of sheltering in place was not associated with KD incidence. These findings suggest that social behavior is associated with exposure to the agent(s) that trigger KD and are consistent with a respiratory portal of entry for the agent(s).
Assuntos
COVID-19 , Síndrome de Linfonodos Mucocutâneos , COVID-19/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Febre/epidemiologia , Humanos , Masculino , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Pandemias , Estados Unidos/epidemiologiaRESUMO
Purpose of Review: We highlight the new clinical entity multisystem inflammatory syndrome in children (MIS-C), the progress in understanding its immunopathogenesis, and compare and contrast the clinical and immunologic features of MIS-C with Kawasaki disease (KD). Recent Findings: Studies show immune dysregulation in MIS-C including T lymphocyte depletion and activation, T cell receptor Vbeta skewing, elevated plasmablast frequencies, increased markers of vascular pathology, and decreased numbers and functional profiles of antigen-presenting cells. Summary: MIS-C is a late manifestation of infection with SARS-CoV-2 associated with marked immune activation and many potential mechanisms of immunopathogenesis. MIS-C and KD have clinical similarities but are distinct. Myocardial dysfunction with or without mild coronary artery dilation can occur in MIS-C but generally corrects within weeks. In contrast, the coronary arteries are the primary target in KD, and coronary artery sequelae can be lifelong. Supportive care and anti-inflammatory therapy appear to hasten improvement in children with MIS-C, and there is hope that vaccines will prevent its development.
RESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mitigation policies have been associated with profound decreases in diagnoses of common childhood respiratory infections. A leading theory of etiology of Kawasaki disease (KD) is that it is triggered by presently unidentified ubiquitous respiratory agent. We document that mitigation policies instituted in mid-March 2020 were associated with strikingly fewer diagnoses of KD in April-December 2020 compared with the same period in the previous 8 years (P = .01), a >67% decline. This finding supports the hypothesis that KD is caused by a respiratory-transmitted agent.
Assuntos
COVID-19 , Síndrome de Linfonodos Mucocutâneos , Infecções Respiratórias , Criança , Humanos , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Distanciamento Físico , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/etiologia , SARS-CoV-2RESUMO
Primary prevention of acute rheumatic fever is accomplished by proper identification and adequate antibiotic treatment of group A beta-hemolytic streptococcal (GAS) tonsillopharyngitis. Diagnosis of GAS pharyngitis is best accomplished by combining clinical judgment with diagnostic test results, the criterion standard of which is the throat culture. Penicillin (either oral penicillin V or injectable benzathine penicillin) is the treatment of choice, because it is cost-effective, has a narrow spectrum of activity, and has long-standing proven efficacy, and GAS resistant to penicillin have not been documented. For penicillin-allergic individuals, acceptable alternatives include a narrow-spectrum oral cephalosporin, oral clindamycin, or various oral macrolides or azalides. The individual who has had an attack of rheumatic fever is at very high risk of developing recurrences after subsequent GAS pharyngitis and needs continuous antimicrobial prophylaxis to prevent such recurrences (secondary prevention). The recommended duration of prophylaxis depends on the number of previous attacks, the time elapsed since the last attack, the risk of exposure to GAS infections, the age of the patient, and the presence or absence of cardiac involvement. Penicillin is again the agent of choice for secondary prophylaxis, but sulfadiazine or a macrolide or azalide are acceptable alternatives in penicillin-allergic individuals. This report updates the 1995 statement by the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee. It includes new recommendations for the diagnosis and treatment of GAS pharyngitis, as well as for the secondary prevention of rheumatic fever, and classifies the strength of the recommendations and level of evidence supporting them.
Assuntos
Antibacterianos/uso terapêutico , Faringite/tratamento farmacológico , Cardiopatia Reumática , Doença Aguda , American Heart Association , Humanos , Faringite/microbiologia , Cardiopatia Reumática/diagnóstico , Cardiopatia Reumática/tratamento farmacológico , Cardiopatia Reumática/prevenção & controle , Prevenção Secundária , Estados UnidosRESUMO
Kawasaki disease (KD) is an acute systemic inflammatory illness of childhood that can result in coronary artery aneurysms, myocardial infarction, and sudden death. Clinical and epidemiologic data point to an unknown infectious agent as the cause. We discovered that an oligoclonal IgA immune response is present in arterial tissue in acute KD. Synthetic versions of prevalent IgA antibodies in the KD arterial wall identify cytoplasmic inclusion bodies in acute KD ciliated bronchial epithelium and other inflamed KD tissues. Light and electron microscopic studies show that the inclusion bodies are consistent with aggregates of viral protein and RNA, and are likely formed by the KD etiologic agent. KD susceptibility is likely to be polygenic. Treatment of gammaglobulin nonresponders usually consists of additional intravenous immunoglobulin, methylprednisolone, and/or infliximab. Additional data regarding KD pathogenesis are urgently needed to provide other targets for therapy for those patients at highest risk of developing coronary artery abnormalities.
RESUMO
Propagation of new human respiratory virus pathogens in established cell lines is hampered by a lack of predictability regarding cell line permissivity and by availability of suitable antibody reagents to detect infection in cell lines that do not exhibit significant cytopathic effect. Recently, molecular methods have been used to amplify and identify novel nucleic acid sequences directly from clinical samples, but these methods may be hampered by the quantity of virus present in respiratory secretions at different time points following the onset of infection. Human airway epithelial (HAE) cultures, which effectively mimic the human bronchial environment, allow for cultivation of a wide variety of human respiratory viral pathogens. The goal of the experiments described here was to determine if propagation and identification of a human respiratory virus may be achieved through inoculation of HAE cultures followed by whole transcriptome amplification (WTA) and sequence analysis. To establish proof-of-principle human coronavirus NL63 (HCoV-NL63) was evaluated, and the first visualization of HCoV-NL63 virus by transmission electron microscopy (TEM) is reported. Initial propagation of human respiratory secretions onto HAE cultures followed by TEM and WTA of culture supernatant may be a useful approach for visualization and detection of new human respiratory pathogens that have eluded identification by traditional approaches.