RESUMO
BACKGROUND: Measles can lead to serious complications and remains an important cause of morbidity and mortality worldwide. In this study we aimed to assess the etiological diagnosis of discarded measles cases in the context of an outbreak among a highly immunized population. METHODS: We conducted a retrospective observational study of discarded measles cases from an outbreak that occurred from October 2006 to July 2007 in Catalonia. A confirmed case was defined as having a positive measles serum IgM result and/or a positive result by RT-PCR in urine and/or nasopharyngeal swab; or an epidemiological link to a confirmed case. Serum specimens were tested by a commercially available indirect-format and by an in-house capture-format measles IgM enzyme immunoassays. RESULTS: Testing of 89 samples discarded for measles determined the etiologies for 10 (11.2%), including one rubella, three human herpes virus 6, and six measles infections. Of 381 confirmed cases in the outbreak, 10% had received at least one dose of the measles-mumps-rubella vaccine versus 54% of the discarded for measles (OR: 0.09; 95% CI: 0.06, 0.14; p < 0.001). CONCLUSIONS: Highly sensitive surveillance systems are critical to identifying cases, responding to outbreaks and verifying progress towards measles elimination. Molecular tools for measles detection and differential diagnosis, and collection of appropriate specimens for molecular and serological testing are essential to correctly diagnose suspected measles infection.
Assuntos
Sarampo , Rubéola (Sarampo Alemão) , Humanos , Sarampo/diagnóstico , Sarampo/epidemiologia , Sarampo/prevenção & controle , Rubéola (Sarampo Alemão)/epidemiologia , Vírus do Sarampo/genética , Surtos de Doenças , Imunoglobulina M , Anticorpos AntiviraisRESUMO
In the past decade, multiple mumps outbreaks have occurred in the United States, primarily in close-contact, high-density settings such as colleges, with a high attack rate among young adults, many of whom had the recommended 2 doses of mumps-measles-rubella (MMR) vaccine. Waning humoral immunity and the circulation of divergent wild-type mumps strains have been proposed as contributing factors to mumps resurgence. Blood samples from 71 healthy 18- to 23-year-old college students living in a non-outbreak area were assayed for antibodies and memory B cells (MBCs) to mumps, measles, and rubella. Seroprevalence rates of mumps, measles, and rubella determined by IgG enzyme-linked immunosorbent assay (ELISA) were 93, 93, and 100%, respectively. The index standard ratio indicated that the concentration of IgG was significantly lower for mumps than rubella. High IgG avidity to mumps Enders strain was detected in sera of 59/71 participants who had sufficient IgG levels. The frequency of circulating mumps-specific MBCs was 5 to 10 times lower than measles and rubella, and 10% of the participants had no detectable MBCs to mumps. Geometric mean neutralizing antibody titers (GMTs) by plaque reduction neutralization to the predominant circulating wild-type mumps strain (genotype G) were 6-fold lower than the GMTs against the Jeryl Lynn vaccine strain (genotype A). The majority of the participants (80%) received their second MMR vaccine ≥10 years prior to study participation. Additional efforts are needed to fully characterize B and T cell immune responses to mumps vaccine and to develop strategies to improve the quality and durability of vaccine-induced immunity.
Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Imunidade Humoral/imunologia , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Vírus da Caxumba/imunologia , Caxumba/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Feminino , Humanos , Imunidade Humoral/efeitos dos fármacos , Imunização , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Masculino , Vacina contra Sarampo-Caxumba-Rubéola/farmacologia , Caxumba/prevenção & controle , Caxumba/virologia , Adulto JovemRESUMO
BACKGROUND: The burden of rotavirus morbidity and mortality is high in children aged <5 years in developing countries, and evaluations indicate waning protection from rotavirus immunization in the second year. An additional dose of rotavirus vaccine may enhance the immune response and lengthen the period of protection against disease, but coadministration of this dose should not interfere with immune responses to concurrently given vaccines. METHODS: A total of 480 9-month-old participants from Matlab, Bangladesh, were enrolled in a study with a primary objective to establish noninferiority of concomitant administration of measles-rubella vaccine (MR) and a third dose of human rotavirus vaccine (HRV; MR + HRV), compared with MR given alone. Secondary objectives included noninferiority of rubella antibody seroconversion and evaluating rotavirus IgA/IgG seroresponses in MR + HRV recipients. RESULTS: Two months after vaccination, 75.3% and 74.3% of MR + HRV and MR recipients, respectively, had seroprotective levels of measles virus antibodies; 100.0% and 99.6%, respectively, showed anti-rubella virus immunoglobulin G (IgG) seroprotection. In the MR + HRV group, antirotavirus immunoglobulin A and IgG seropositivity frequencies before vaccination (52.7% and 66.3%, respectively) increased to 69.6% and 88.3% after vaccination. CONCLUSIONS: Vaccine-induced measles and rubella antibody responses are not negatively affected by concomitant administration of HRV. The HRV dose increases antirotavirus serum antibody titers and the proportion of infants with detectable antirotavirus antibody. CLINICAL TRIALS REGISTRATION: NCT01700621.
Assuntos
Vacina contra Sarampo/imunologia , Vacinas contra Rotavirus/imunologia , Rotavirus/imunologia , Vacina contra Rubéola/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Relação Dose-Resposta Imunológica , Humanos , Imunidade , Imunogenicidade da Vacina , Lactente , Vacinas Combinadas/imunologiaRESUMO
BACKGROUND: Two doses of measles, mumps, and rubella (MMR) vaccine are 97% effective against measles, but waning antibody immunity to measles and failure of the 2-dose vaccine occur. We administered a third MMR dose (MMR3) to young adults and assessed immunogenicity over 1 year. METHODS: Measles virus (MeV) neutralizing antibody concentrations, cell-mediated immunity (CMI), and immunoglobulin G (IgG) antibody avidity were assessed at baseline and 1 month and 1 year after MMR3 receipt. RESULTS: Of 662 subjects at baseline, 1 (0.2%) was seronegative for MeV-neutralizing antibodies (level, <8 mIU/mL), and 23 (3.5%) had low antibody levels (8-120 mIU/mL). One month after MMR3 receipt, 1 subject (0.2%) was seronegative, and 6 (0.9%) had low neutralizing antibodies, with only 21 of 662 (3.2%) showing a ≥ 4-fold rise in neutralizing antibodies. One year after MMR3 receipt, no subject was seronegative, and 10 of 617 (1.6%) had low neutralizing antibody levels. CMI analyses showed low levels of spot-forming cells after stimulation, suggesting the presence of T-cell memory, but the response was minimal after MMR3 receipt. MeV IgG avidity did not correlate with findings of neutralization analyses. CONCLUSIONS: Most subjects were seropositive before MMR3 receipt, and very few had a secondary immune response after MMR3 receipt. Similarly, CMI and avidity analyses showed minimal qualitative improvements in immune response after MMR3 receipt. We did not find compelling data to support a routine third dose of MMR vaccine.
Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Imunidade Celular/fisiologia , Imunoglobulina G/sangue , Vírus do Sarampo/imunologia , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Adolescente , Adulto , Afinidade de Anticorpos , Estudos de Coortes , Feminino , Humanos , Esquemas de Imunização , Estudos Longitudinais , Masculino , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Testes de Neutralização , Razão de Chances , Adulto JovemRESUMO
BACKGROUND: Children with perinatal human immunodeficiency virus (HIV) infection (PHIV) may not be protected against measles, mumps, and rubella (MMR) because of impaired initial vaccine response or waning immunity. Our objectives were to estimate seroimmunity in PHIV-infected and perinatally HIV-exposed but uninfected (HEU) children and identify predictors of immunity in the PHIV cohort. METHODS: PHIV and HEU children were enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) at ages 7-15 years from 2007 to 2009. At annual visits, demographic, laboratory, immunization, and clinical data were abstracted and serologic specimens collected. Most recent serologic specimen was used to determine measles seroprotection by plaque reduction neutralization assay and rubella seroprotection and mumps seropositivity by enzyme immunoassay. Sustained combination antiretroviral therapy (cART) was defined as taking cART for at least 3 months. RESULTS: Among 428 PHIV and 221 HEU PHACS participants, the prevalence was significantly lower in PHIV children for measles seroprotection (57% [95% confidence interval {CI}, 52%-62%] vs 99% [95% CI, 96%-100%]), rubella seroprotection (65% [95% CI, 60%-70%] vs 98% [95% CI, 95%-100%]), and mumps seropositivity (59% [95% CI, 55%-64%] vs 97% [95% CI, 94%-99%]). On multivariable analysis, greater number of vaccine doses while receiving sustained cART and higher nadir CD4 percentage between last vaccine dose and serologic testing independently improved the cumulative prediction of measles seroprotection in PHIV. Predictors of rubella seroprotection and mumps seropositivity were similar. CONCLUSIONS: High proportions of PHIV-infected children, but not HEU children, lack serologic evidence of immunity to MMR, despite documented immunization and current cART. Effective cART before immunization is a strong predictor of current seroimmunity.
Assuntos
Anticorpos Antivirais/sangue , Infecções por HIV/imunologia , Sarampo/imunologia , Caxumba/imunologia , Rubéola (Sarampo Alemão)/imunologia , Adolescente , Anticorpos Neutralizantes/sangue , Criança , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Testes de Neutralização , Estados Unidos , Ensaio de Placa ViralRESUMO
PURPOSE: Hypomorphic mutations in RAG1 and RAG2 are associated with significant clinical heterogeneity and symptoms of immunodeficiency or autoimmunity may be late in appearance. As a result, immunosuppressive medications may be introduced that can have life-threatening consequences. We describe a previously healthy 13-month-old girl presenting with rash and autoimmune hemolytic anemia, while highlighting the importance of vigilance and consideration of an underlying severe immunodeficiency disease prior to instituting immunosuppressive therapy. METHODS: Given clinical deterioration of the patient and a temporal association with recently administered vaccinations, virus genotyping was carried out via 4 real-time Forster Resonance Energy Transfer PCR protocols targeting vaccine-associated single nucleotide polymorphisms. Genomic DNA was extracted from whole blood and analyzed via the next-generation sequencing method of sequencing-by-synthesis. Immune function studies included immunophenotyping of peripheral blood lymphocytes, mitogen-induced proliferation and TLR ligand-induced production of TNFα. Analysis of recombination activity of wild-type and mutant RAG2 constructs was performed. RESULTS: Virus genotyping revealed vaccine-strain VZV, mumps, and rubella. Next-generation sequencing identified heterozygosity for RAG2 R73H and P180H mutations. Profound lymphopenia was associated with intense corticosteroid therapy, with some recovery after steroid reduction. Residual, albeit low, RAG2 protein activity was demonstrated. CONCLUSIONS: Because of the association of RAG deficiency with late-onset presentation and autoimmunity, live virus vaccination and immunosuppressive therapies are often initiated and can result in negative consequences. Here, hypomorphic RAG2 mutations were linked to disseminated vaccine-strain virus infections following institution of corticosteroid therapy for autoimmune hemolytic anemia.
Assuntos
Anemia Hemolítica Autoimune/diagnóstico , Herpes Zoster/diagnóstico , Herpesvirus Humano 3/fisiologia , Síndromes de Imunodeficiência/diagnóstico , Vacinas Virais/imunologia , Adolescente , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/tratamento farmacológico , Células Cultivadas , Proteínas de Ligação a DNA/genética , Feminino , Herpes Zoster/complicações , Herpes Zoster/tratamento farmacológico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/tratamento farmacológico , Terapia de Imunossupressão , Ativação Linfocitária/efeitos dos fármacos , Proteínas Nucleares/genética , LinhagemRESUMO
BACKGROUND: By 2005, vaccination had reduced the annual incidence of mumps in the United States by more than 99%, with few outbreaks reported. However, in 2006, a large outbreak occurred among highly vaccinated populations in the United States, and similar outbreaks have been reported worldwide. The outbreak described in this report occurred among U.S. Orthodox Jewish communities during 2009 and 2010. METHODS: Cases of salivary-gland swelling and other symptoms clinically compatible with mumps were investigated, and demographic, clinical, laboratory, and vaccination data were evaluated. RESULTS: From June 28, 2009, through June 27, 2010, a total of 3502 outbreak-related cases of mumps were reported in New York City, two upstate New York counties, and one New Jersey county. Of the 1648 cases for which clinical specimens were available, 50% were laboratory-confirmed. Orthodox Jewish persons accounted for 97% of case patients. Adolescents 13 to 17 years of age (27% of all patients) and males (78% of patients in that age group) were disproportionately affected. Among case patients 13 to 17 years of age with documented vaccination status, 89% had previously received two doses of a mumps-containing vaccine, and 8% had received one dose. Transmission was focused within Jewish schools for boys, where students spend many hours daily in intense, face-to-face interaction. Orchitis was the most common complication (120 cases, 7% of male patients ≥12 years of age), with rates significantly higher among unvaccinated persons than among persons who had received two doses of vaccine. CONCLUSIONS: The epidemiologic features of this outbreak suggest that intense exposures, particularly among boys in schools, facilitated transmission and overcame vaccine-induced protection in these patients. High rates of two-dose coverage reduced the severity of the disease and the transmission to persons in settings of less intense exposure.
Assuntos
Surtos de Doenças , Judeus , Vacina contra Caxumba , Caxumba/etnologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Criança , Pré-Escolar , Transmissão de Doença Infecciosa , Exposição Ambiental , Feminino , Humanos , Imunização Secundária , Lactente , Masculino , Pessoa de Meia-Idade , Caxumba/complicações , Caxumba/transmissão , Vacina contra Caxumba/administração & dosagem , Vacina contra Caxumba/imunologia , New Jersey/epidemiologia , New York/epidemiologia , Orquite/etiologia , Instituições Acadêmicas , Distribuição por Sexo , Adulto JovemRESUMO
A 29-year-old pregnant woman developed progressively worsening encephalopathy, left hemiparesis, and hemodynamic instability over a 6-week period. Initial brain MRI and work-up for infectious and autoimmune causes were normal, although elevated IgG and oligoclonal bands were seen on analysis of the cerebrospinal fluid (CSF). After uncomplicated spontaneous delivery of a preterm healthy infant, her condition worsened. Repeat brain MRI demonstrated generalized volume loss and evidence of corticospinal tract degeneration. She underwent a brain biopsy, which showed characteristic viral inclusions of the type seen in subacute sclerosing panencephalitis (SSPE). The diagnosis was confirmed by immunohistochemistry and electron microscopy, and additional CSF analysis also showed markedly elevated IgG titer for measles. Sequence analysis of the nucleoprotein gene N-450 demonstrated a close relationship to the sequences of viruses in genotype D7. This case documents an ~ 6-month progression to death of SSPE in a pregnant woman.
Assuntos
Encéfalo/patologia , Complicações na Gravidez/patologia , Panencefalite Esclerosante Subaguda/patologia , Adulto , Encéfalo/fisiopatologia , Evolução Fatal , Feminino , Hemodinâmica/fisiologia , Humanos , Imageamento por Ressonância Magnética , Gravidez , Complicações na Gravidez/fisiopatologia , Panencefalite Esclerosante Subaguda/fisiopatologiaRESUMO
BACKGROUND: Measles was eliminated in the United States through high vaccination coverage and a public health system able to rapidly respond to measles. Measles may occur among vaccinated individuals, but secondary transmission from such individuals has not been documented. METHODS: Suspected patients and contacts exposed during a measles outbreak in New York City in 2011 were investigated. Medical histories and immunization records were obtained. Cases were confirmed by detection of measles-specific immunoglobulin M and/or RNA. Tests for measles immunoglobulin G (IgG), IgG avidity, measurement of measles neutralizing antibody titers, and genotyping were performed to characterize the cases. RESULTS: The index patient had 2 doses of measles-containing vaccine; of 88 contacts, 4 secondary patients were confirmed who had either 2 doses of measles-containing vaccine or a past positive measles IgG antibody. All patients had laboratory confirmation of measles infection, clinical symptoms consistent with measles, and high-avidity IgG antibody characteristic of a secondary immune response. Neutralizing antibody titers of secondary patients reached >80 000 mIU/mL 3-4 days after rash onset and that of the index was <500 mIU/mL 9 days after rash onset. No additional cases of measles occurred among 231 contacts of secondary patients. CONCLUSIONS: This is the first report of measles transmission from a twice-vaccinated individual with documented secondary vaccine failure. The clinical presentation and laboratory data of the index patient were typical of measles in a naive individual. Secondary patients had robust anamnestic antibody responses. No tertiary cases occurred despite numerous contacts. This outbreak underscores the need for thorough epidemiologic and laboratory investigation of suspected cases of measles regardless of vaccination status.
Assuntos
Sarampo/transmissão , Vacinação , Adulto , Idoso , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Afinidade de Anticorpos , Surtos de Doenças , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Sarampo/epidemiologia , Sarampo/imunologia , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/uso terapêutico , Pessoa de Meia-Idade , Cidade de Nova IorqueRESUMO
Virologic surveillance is a critical component of measles management. One of the criteria for verification of elimination of endemic measles is genetic analysis of wild-type viruses to demonstrate lack of an indigenous genotype. Measles is yet to be eliminated in China, and genotype H1 has been detected continuously since virologic surveillance was initiated in 1993. Virologic surveillance has been very active in China, providing a unique opportunity to conduct a detailed study of the evolution of a single, endemic genotype over a timespan of nearly two decades. Phylogenetic analysis performed on the 450 nt coding sequence for the C-terminal 150 amino acids of the nucleoprotein (N-450), fusion (F) gene and haemagglutinin (H) gene confirmed the continued circulation of genotype H1 viruses for 19 years. No evidence of selective pressure for the H protein was found. The substitution rates ranged from 0.75×10(-3) substitutions site(-1) year(-1) for H to 1.65×10(-3) substitutions site(-1) year(-1) for N-450. The time of most recent common ancestor (TMRCA) for genotype H1 was estimated as approximately 1985 (95â% highest probability density, 1979-1989). Finally, the overall diversity of measles sequences from China decreased from 2005 to 2012, coincident with a substantial decrease in measles cases. The results suggest that detailed evolutionary analyses should facilitate the documentation of eventual measles elimination in China. Moreover, the molecular approaches used in this study can be applied in other countries approaching measles elimination.
Assuntos
Hemaglutininas Virais/genética , Vírus do Sarampo/genética , Sarampo/epidemiologia , Proteínas Virais de Fusão/genética , Proteínas Virais/genética , Animais , Sequência de Bases , Evolução Biológica , Callithrix , Linhagem Celular , China/epidemiologia , Chlorocebus aethiops , Variação Genética , Genótipo , Sarampo/virologia , Vírus do Sarampo/classificação , Filogenia , Alinhamento de Sequência , Análise de Sequência de RNA , Células VeroRESUMO
Measles is a highly contagious, acute viral illness that can lead to serious complications and death. Although measles elimination (i.e., interruption of year-round endemic transmission) was declared in the United States in 2000, importations of measles cases from endemic areas of the world continue to occur, leading to secondary measles cases and outbreaks in the United States, primarily among unvaccinated persons. To update national measles data in the United States, CDC evaluated cases reported by states from January 1 through May 23, 2014. A total of 288 confirmed measles cases have been reported to CDC, surpassing the highest reported yearly total of measles cases since elimination (220 cases reported in 2011). Fifteen outbreaks accounted for 79% of cases reported, including the largest outbreak reported in the United States since elimination (138 cases and ongoing). The large number of cases this year emphasizes the need for health-care providers to have a heightened awareness of the potential for measles in their communities and the importance of vaccination to prevent measles.
Assuntos
Surtos de Doenças , Sarampo/epidemiologia , Adolescente , Adulto , Idoso , Centers for Disease Control and Prevention, U.S. , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Sarampo/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Pessoa de Meia-Idade , Risco , Viagem , Estados Unidos/epidemiologia , Vacinação/estatística & dados numéricos , Adulto JovemRESUMO
Measles virus (MV) remains an important pathogen in children worldwide. The morbidity and mortality of MV is associated with severe immune suppression. Dendritic cells (DCs) were identified as initial target cells in vivo, and DCs were efficiently infected by MV in vitro. MV infection of DCs likely contributes to functional deficiency in these cells; therefore playing a role in MV-induced immunosuppression. DCs appeared to mature phenotypically; however, the ability of infected cells to stimulate T cells was compromised. Phenotypic maturation of infected immature DCs was partially controlled by IFN production; however, infected DCs also maintained markers of an immature phenotype such as the continued uptake of antigen and lack of expression of chemokine receptor CCR7. Furthermore, mature DCs did not appear to maintain phenotypic maturation following infection demonstrated by decreased MHC and co-stimulatory molecule expression. Several mechanisms of MV-induced DC dysfunction have been suggested, each likely contributing to the immunosuppressive effect of MV-infected DCs. Infected DCs responded aberrantly to secondary maturation stimuli such as CD40L or TLR4 stimulation. MV infection resulted in apoptosis in DC/T-cell cocultures, which may contribute to a reduced T-cell response. Additionally, the immunological synapse between infected DCs and T cells was compromised resulting in reduced T-cell interaction times and activation signaling. The mechanisms of MV contribution to DC dysfunction appear multifaceted and central to MV-induced immunosuppression.
Assuntos
Células Dendríticas/imunologia , Evasão da Resposta Imune , Vírus do Sarampo/imunologia , Apoptose , Humanos , Tolerância Imunológica , Vírus do Sarampo/patogenicidade , Linfócitos T/imunologiaRESUMO
BACKGROUND: Sporadic cases of parotitis are generally assumed to be mumps, which often requires a resource-intensive public health response. This project surveyed the frequency of viruses detected among such cases. METHODS: During 2009-2011, 8 jurisdictions throughout the United States investigated sporadic cases of parotitis. Epidemiologic information, serum, and buccal and oropharyngeal swabs were collected. Polymerase chain reaction methods were used to detect a panel of viruses. Anti-mumps virus immunoglobulin M (IgM) antibodies were detected using a variety of methods. RESULTS: Of 101 specimens, 38 were positive for a single virus: Epstein-Barr virus (23), human herpesvirus (HHV)-6B (10), human parainfluenza virus (HPIV)-2 (3), HPIV-3 (1), and human bocavirus (1). Mumps virus, enteroviruses (including human parechovirus), HHV-6A, HPIV-1, and adenoviruses were not detected. Early specimen collection did not improve viral detection rate. Mumps IgM was detected in 17% of available specimens. Patients in whom a virus was detected were younger, but no difference was seen by sex or vaccination profile. No seasonal patterns were identified. CONCLUSIONS: Considering the timing of specimen collection, serology results, patient vaccination status, and time of year may be helpful in assessing the likelihood that a sporadic case of parotitis without laboratory confirmation is mumps.
Assuntos
Parotidite/virologia , Vírus , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , DNA Viral/análise , DNA Viral/genética , Feminino , Herpesvirus Humano 4 , Herpesvirus Humano 6 , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Vírus da Caxumba , Parotidite/diagnóstico , Parotidite/epidemiologia , RNA Viral/análise , RNA Viral/genética , Estações do Ano , Estados Unidos/epidemiologia , Vírus/genética , Vírus/isolamento & purificaçãoRESUMO
During outbreaks of infectious diseases or in cases of severely ill patients, it is imperative to identify the causative agent. This report describes several events in which virus isolation and identification by electron microscopy were critical to initial recognition of the etiologic agent, which was further analyzed by additional laboratory diagnostic assays. Examples include severe acute respiratory syndrome coronavirus, and Nipah, lymphocytic choriomeningitis, West Nile, Cache Valley, and Heartland viruses. These cases illustrate the importance of the techniques of cell culture and electron microscopy in pathogen identification and recognition of emerging diseases.
Assuntos
Viroses/diagnóstico , Vírus/isolamento & purificação , Vírus/ultraestrutura , Arenaviridae/isolamento & purificação , Arenaviridae/ultraestrutura , Bunyaviridae/isolamento & purificação , Bunyaviridae/ultraestrutura , Técnicas de Cultura de Células , Coronaviridae/isolamento & purificação , Coronaviridae/ultraestrutura , Flaviviridae/isolamento & purificação , Flaviviridae/ultraestrutura , Humanos , Microscopia Eletrônica , Paramyxoviridae/isolamento & purificação , Paramyxoviridae/ultraestrutura , Estados Unidos/epidemiologia , Viroses/epidemiologia , Viroses/virologiaRESUMO
BACKGROUND: Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)-infected children in the absence of highly active antiretroviral therapy (HAART). METHODS: HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30,000 copies/mL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4-5 years later, and PRN antibody was measured before and 7 and 28 days later. RESULTS: At entry, 52% of 193 subjects were seroprotected (PRN ≥120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4-5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load ≤400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects. CONCLUSIONS: Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression. CLINICAL TRIALS REGISTRATION: NCT00013871 (www.clinicaltrials.gov).
Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Imunização Secundária/métodos , Memória Imunológica , Vacina contra Sarampo/efeitos adversos , Vacina contra Sarampo/imunologia , Adolescente , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Feminino , HIV-1/isolamento & purificação , Humanos , Lactente , Masculino , Vacina contra Sarampo/administração & dosagem , Testes de Neutralização , Carga Viral , Ensaio de Placa ViralRESUMO
Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes fatal encephalitis in humans. The initial outbreak of NiV infection occurred in Malaysia and Singapore in 1998-1999; relatively small, sporadic outbreaks among humans have occurred in Bangladesh since 2001. We characterized the complete genomic sequences of identical NiV isolates from 2 patients in 2008 and partial genomic sequences of throat swab samples from 3 patients in 2010, all from Bangladesh. All sequences from patients in Bangladesh comprised a distinct genetic group. However, the detection of 3 genetically distinct sequences from patients in the districts of Faridpur and Gopalganj indicated multiple co-circulating lineages in a localized region over a short time (January-March 2010). Sequence comparisons between the open reading frames of all available NiV genes led us to propose a standardized protocol for genotyping NiV; this protcol provides a simple and accurate way to classify current and future NiV sequences.
Assuntos
Surtos de Doenças , Infecções por Henipavirus/epidemiologia , Vírus Nipah/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Bangladesh/epidemiologia , Criança , Sequência Conservada , Feminino , Variação Genética , Genoma Viral , Infecções por Henipavirus/virologia , Humanos , Dados de Sequência Molecular , Tipagem Molecular , Vírus Nipah/isolamento & purificação , Filogenia , Análise de Sequência de DNA , Estudos Soroepidemiológicos , Proteínas Virais/química , Proteínas Virais/genéticaRESUMO
In 2009, measles outbreaks in Pennsylvania and Virginia resulted in the exposure and apparent infection of 2 physicians, both of whom had a documented history of vaccination with >2 doses of measles-mumps-rubella vaccine. These physicians were suspected of having been infected with measles after treating patients who subsequently received a diagnosis of measles. The clinical presentation was nonclassical in regard to progression, duration, and severity. It is hypothesized that the 2 physicians mounted vigorous secondary immune responses typified by high avidity measles immunoglobulin G antibody and remarkably high neutralizing titers in response to intense and prolonged exposure to a primary measles case patient. Both of the physicians continued to see patients, because neither considered that they could have measles. Despite surveillance for cases among contacts, including unvaccinated persons, no additional cases were identified.
Assuntos
Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Sarampo/prevenção & controle , Sarampo/transmissão , Adulto , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Afinidade de Anticorpos , Criança , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Sarampo/diagnóstico , Sarampo/epidemiologia , Pennsylvania/epidemiologia , Fatores de Risco , Virginia/epidemiologiaRESUMO
BACKGROUND: Previously, we demonstrated that measles antibody prevalence was lower at age 12 months among children infected with human immunodeficiency virus (HIV) than uninfected children following measles vaccination (MV) at ages 6 and 9 months. Among HIV-uninfected children, measles antibody prevalence was lower among 1- than 2-dose MV recipients. Here, we report results through age 24 months. METHODS: Children born to HIV-infected mothers received MV at 6 and 9 months, and children of HIV-uninfected mothers were randomized to MV at 6 and 9 months or MV at 9 months. We followed children through age 24 months. The child's HIV status was determined and measles immunoglobulin G (IgG) level was measured by enzyme immunoassay (EIA) and by plaque reduction neutralization (PRN) on a subset. RESULTS: Among HIV-uninfected children, the difference in measles antibody prevalence at age 12 months between one- and two-dose recipients reported previously by EIA was shown to be smaller by PRN. By age 24 months, 84% and 87% of HIV-uninfected children receiving 1 or 2 doses, respectively, were seroprotected. Only 41% of 22 HIV-infected children were measles seroprotected at age 20 months. DISCUSSION: Measles seroprotection persisted through age 24 months among HIV-uninfected children who received 1 or 2 doses of MV. HIV-infected children demonstrated seroprotection through age 12 months, but this was not sustained.
Assuntos
Anticorpos Antivirais/sangue , Infecções por HIV/imunologia , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Sarampo/prevenção & controle , Relação Dose-Resposta Imunológica , Esquema de Medicação , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Técnicas Imunoenzimáticas , Lactente , Malaui/epidemiologia , Masculino , Vírus do Sarampo/imunologia , Testes de NeutralizaçãoRESUMO
An important aspect of laboratory surveillance for measles and rubella is the genetic characterization of circulating wild-type viruses to support molecular epidemiologic studies and to track transmission pathways. Virologic surveillance that is sufficient to document the interruption of transmission of measles and rubella viruses will be an essential criterion for verification of elimination. Laboratories in the World Health Organization (WHO) Measles and Rubella Laboratory Network have worked to improve and expand virologic surveillance as many regions move toward elimination of measles and rubella/congenital rubella syndrome. As countries approach elimination, it will be necessary to obtain genetic information from as many chains of transmission as possible. In addition, baseline virologic surveillance, especially for rubella, needs to be improved in many countries. This report contains a summary of recent improvements to the methods used for virologic surveillance.
Assuntos
Saúde Global , Laboratórios/normas , Sarampo/epidemiologia , Rubéola (Sarampo Alemão)/epidemiologia , Animais , Chlorocebus aethiops , Técnicas de Laboratório Clínico/normas , Humanos , Vírus do Sarampo/isolamento & purificação , Vigilância da População , Controle de Qualidade , Vírus da Rubéola/isolamento & purificação , Manejo de Espécimes , Fatores de Tempo , Células VeroRESUMO
Waning immunity or secondary vaccine failure (SVF) has been anticipated by some as a challenge to global measles elimination efforts. Although such cases are infrequent, measles virus (MeV) infection can occur in vaccinated individuals following intense and/or prolonged exposure to an infected individual and may present as a modified illness that is unrecognizable as measles outside of the context of a measles outbreak. The immunoglobulin M response in previously vaccinated individuals may be nominal or fleeting, and viral replication may be limited. As global elimination proceeds, additional methods for confirming modified measles cases may be needed to understand whether SVF cases contribute to continued measles virus (MeV) transmission. In this report, we describe clinical symptoms and laboratory results for unvaccinated individuals with acute measles and individuals with SVF identified during MeV outbreaks. SVF cases were characterized by the serological parameters of high-avidity antibodies and distinctively high levels of neutralizing antibody. These parameters may represent useful biomarkers for classification of SVF cases that previously could not be confirmed as such using routine laboratory diagnostic techniques.