RESUMO
Background: Healthcare-associated infections represent a major threat to patient, staff and visitor safety. Identification of episodes that are likely to have resulted from nosocomial transmission has important implications for infection control. Routinely collected data on ward admissions and sample dates, combined with pathogen genomic information could provide useful insights. We describe a novel, open-source, application for visualising these data, and demonstrate its utility for investigating nosocomial transmission using a case study of a large outbreak of norovirus infection. Methods: We developed the application using Shiny, a web application framework for R. For the norovirus case study, cases were defined as patients who had a faecal sample collected at the hospital in a winter season that tested positive for norovirus. Patient demographics and ward admission dates were extracted from hospital systems. Detected norovirus strains were genotyped and further characterised through sequencing of the hypervariable P2 domain. The most commonly detected sub-strain was visualised using the interactive application. Results: There were 156 norovirus-positive specimens collected from 107 patients. The most commonly detected sub-strain affected 30 patients in five wards. We used the interactive application to produce three visualisations: a bar chart, a timeline, and a schematic ward plan highlighting plausible transmission links. Visualisations showed credible links between cases on the elderly care ward. Conclusions: Use of the interactive application provided insights into transmission in this large nosocomial outbreak of norovirus, highlighting where infection control practices worked well or could be improved. This is a flexible tool that could be used for investigation of any infection in any hospital by interactively changing parameters. Challenges include integration with hospital systems for extracting data. Prospective use of this application could inform better infection control in real time.
RESUMO
Of the two human herpesvirus 6 (HHV-6) species, human herpesvirus 6B (HHV-6B) encephalitis is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplant. Guidelines for the management of HHV-6 infections in patients with hematologic malignancies or post-transplant were prepared a decade ago but there have been no other guidelines since then despite significant advances in the understanding of HHV-6 encephalitis, its therapy, and other aspects of HHV-6 disease in this patient population. Revised guidelines prepared at the 2017 European Conference on Infections in Leukaemia covering diagnosis, preventative strategies and management of HHV-6 disease are now presented.
Assuntos
Neoplasias Hematológicas/complicações , Herpesvirus Humano 6 , Guias de Prática Clínica como Assunto , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/etiologia , Infecções por Roseolovirus/terapia , Antivirais/farmacologia , Antivirais/uso terapêutico , Transformação Celular Viral , Terapia Combinada , Europa (Continente) , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Hospedeiro Imunocomprometido , Resultado do TratamentoRESUMO
The influence of the donor (D) and recipient (R) pre-transplant Epstein-Barr Virus (EBV) serostatus on transplant outcomes (overall survival, relapse-free survival, relapse incidence, non-relapse mortality, acute and chronic GVHD) in 12,931 patients with lymphomas or chronic malignancies undergoing allogeneic hematopoietic cell transplant (allo-HCT) between 1997-2016 was analyzed. In multivariate analysis, the risk of development of chronic GVHD was increased for EBV R+/D+ (HR = 1.26; p = 0.003), R+/D- (HR = 1.21; p = 0.044), and R-/D + (HR = 1.21; p = 0.048) in comparison to R-/D- transplants. No significance was shown for other transplant outcomes; however, in univariate analysis, EBV-seropositive patients receiving grafts from EBV-seropositive donors (EBV R+/D+transplants) had inferior transplant outcomes in comparison to EBV-seronegative recipients of grafts from EBV-seronegative donors (EBV R-/D-): inferior overall survival (59.6% vs 65.9%), inferior relapse-free survival (51.1% vs 57.5%), increased incidence of chronic GVHD (49.5% vs 41.8%), and increased incidence of de novo chronic GVHD (30.5% vs 24.0%). In conclusion, an EBV-negative recipient with lymphoma or chronic malignancy can benefit from selection of an EBV-negative donor in context of chronic GVHD, while there are no preferences in donor EBV serostatus for EBV-seropositive recipient.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4/patogenicidade , Linfoma/complicações , Neoplasias/complicações , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Doença Crônica , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Prognóstico , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adulto JovemRESUMO
Cytomegalovirus is one of the most important infections to occur after allogeneic haematopoietic stem cell transplantation (HSCT), and an increasing number of reports indicate that cytomegalovirus is also a potentially important pathogen in patients treated with recently introduced drugs for hematological malignancies. Expert recommendations have been produced by the 2017 European Conference on Infections in Leukaemia (ECIL 7) after a review of the literature on the diagnosis and management of cytomegalovirus in patients after HSCT and in patients receiving other types of therapy for haematological malignancies. These recommendations cover diagnosis, preventive strategies such as prophylaxis and pre-emptive therapy, and management of cytomegalovirus disease. Antiviral drugs including maribavir and letermovir are in development and prospective clinical trials have recently been completed. However, management of patients with resistant or refractory cytomegalovirus infection or cytomegalovirus disease is a challenge. In this Review we summarise the reviewed literature and the recommendations of the ECIL 7 for management of cytomegalovirus in patients with haematological malignancies.
Assuntos
Infecções por Citomegalovirus/diagnóstico , Neoplasias Hematológicas/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/complicações , Guias de Prática Clínica como Assunto , Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Citomegalovirus/imunologia , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/uso terapêutico , Humanos , Leucemia/tratamento farmacológico , Ribonucleosídeos/uso terapêuticoRESUMO
PURPOSE: We investigated the effect of Epstein-Barr virus (EBV) serostatus on the overall outcome of allogeneic hematopoietic stem-cell transplantation (allo-HSCT). PATIENTS AND METHODS: The study included 11,364 patients who underwent allogeneic peripheral-blood or bone marrow transplantation for acute leukemia between 1997 and 2012. We analyzed the impact of donor and recipient EBV serologic status on overall survival, relapse-free survival, relapse incidence, nonrelapse mortality, and incidence of graft-versus-host disease (GVHD) after allo-HSCT. RESULTS: Patients receiving grafts from EBV-seropositive donors had the same overall survival as patients who received grafts from EBV-seronegative donors (hazard ratio [HR], 1.05; 95% CI, 0.97 to 1.12; P = .23). Seropositive donors also had no influence on relapse-free survival (HR, 1.04; 95% CI, 0.97 to 1.11; P = 0.31), relapse incidence (HR, 1.03; 95% CI, 0.94 to 1.12; P = .58), and nonrelapse mortality (HR, 1.05; 95% CI, 0.94 to 1.17; P = .37). However, in univariate analysis, recipients receiving grafts from seropositive donors had a higher risk of chronic GVHD than those with seronegative donors (40.8% v 31.0%, respectively; P < .001; HR, 1.42; 95% CI, 1.30 to 1.56). When adjusting for confounders, higher risk was identified for both acute and chronic GVHD. In seronegative patients with seropositive donors, the HR for chronic GVHD was 1.30 (95% CI, 1.06 to 1.59; P = .039). In seropositive patients with seropositive donors, the HR was 1.24 (95% CI, 1.07 to 1.45; P = .016) for acute GVHD and 1.43 (95% CI, 1.23 to 1.67; P < .001) for chronic GVHD. Seropositive patients with seronegative donors did not have an increased risk of GVHD. CONCLUSION: Our data suggest that donor EBV status significantly influences development of acute and chronic GVHD after allo-HSCT.
Assuntos
Anticorpos Antivirais/sangue , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4/isolamento & purificação , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Doadores de Tecidos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Leucemia Mieloide Aguda/virologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologiaRESUMO
BACKGROUND: The use of a cytomegalovirus (CMV)-seronegative donor for a CMV-seronegative allogeneic hematopoietic stem cell transplant (HSCT) recipient is generally accepted. However, the importance of donor serostatus in CMV-seropositive patients is controversial. METHODS: A total of 49 542 HSCT patients, 29 349 seropositive and 20 193 seronegative, were identified from the European Group for Blood and Marrow Transplantation database. Cox multivariate models were fitted to estimate the effect of donor CMV serological status on outcome. RESULTS: Seronegative patients receiving seropositive unrelated-donor grafts had decreased overall survival (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.06-1.21; P < .0001) compared with seronegative donors, whereas no difference was seen in patients receiving HLA-matched sibling grafts. Seropositive patients receiving grafts from seropositive unrelated donors had improved overall survival (HR, 0.92; 95% CI, .86-.98; P < .01) compared with seronegative donors, if they had received myeloablative conditioning. This effect was absent when they received reduced-intensity conditioning. No effect was seen in patients grafted from HLA-identical sibling donors. The same association was found if the study was limited to patients receiving transplants from the year 2000 onward. CONCLUSIONS: We confirm the negative impact on overall survival if a CMV-seropositive unrelated donor is selected for a CMV-seronegative patient. For a CMV-seropositive patient, our data support selecting a CMV-seropositive donor if the patient receives a myeloablative conditioning regimen.
Assuntos
Infecções por Citomegalovirus/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doadores de Tecidos , Transplante Homólogo/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Condicionamento Pré-Transplante , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE OF REVIEW: This review evaluates publications on human herpesvirus 6 (HHV-6) encephalitis recognizing firstly that HHV-6A and HHV-6B are separate species with differing properties, and secondly the phenomenon of chromosomal integration; this occurs in a minority of persons and the complete viral genome of either HHV-6A or HHV-6B is present in every nucleated cell in the body. Although chromosomal integration has not been associated with disease, the resulting very high level of viral DNA in human tissues and blood has sometimes been wrongly misinterpreted as active infection. RECENT FINDINGS: No disease has been linked to HHV-6A, whereas HHV-6B may cause encephalitis. Encephalitis due to primary HHV-6B infection in young children is commonly reported from Japan, but very rarely elsewhere in the world, suggesting a genetic predisposition. Reports of HHV-6A or HHV-6B encephalitis in immunocompetent older children/adults are most likely due to chromosomal integration and not active infection. HHV-6B reactivation is well established as causing limbic encephalitis after haematopoietic stem cell transplantation, particularly after receipt of cord blood; the outcome is poor and preventive strategies are ineffective. SUMMARY: Understanding the pathophysiology of HHV-6B encephalitis remains incomplete, especially regarding young children. Clinical trials of antiviral therapy are warranted for treatment and prevention of HHV-6B encephalitis after transplantation.
Assuntos
DNA Viral , Encefalite Viral/imunologia , Herpesvirus Humano 6/genética , Hospedeiro Imunocomprometido/imunologia , Infecções por Roseolovirus/imunologia , Adulto , Povo Asiático/genética , Criança , Encefalite Viral/epidemiologia , Encefalite Viral/genética , Predisposição Genética para Doença , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/uso terapêutico , Infecções por Roseolovirus/epidemiologia , Infecções por Roseolovirus/genéticaRESUMO
BACKGROUND: Primary human herpesvirus 7 (HHV-7) infection occurs almost universally during the first 5 years of life and is rarely accompanied by central nervous system (CNS) symptoms such as febrile seizures. The present retrospective study investigated the role of primary HHV-7 infection in CNS disease in children, including adolescents. METHODS: The study included all children who had neurologic disease aged younger than 18 years seen at the Hospital for Sick Children, Toronto, Canada, between April 1, 1998 and December 31, 2011, whose cerebrospinal fluid (CSF) was found by polymerase chain reaction to contain HHV-7 DNA. Where sera were available, HHV-7 IgG antibody titers and avidity were measured to differentiate primary from past infection. RESULTS: HHV-7 DNA was detected in the CSF of 57 (1.9%) of the 2972 children tested. In 3 adolescents primary HHV-7 infection (low avidity IgG) was confirmed as the cause of neurologic disease, 2 who had encephalitis and 1 who had Guillain-Barré syndrome. Eighteen children had possible HHV-7 disease (no alternative cause identified and indeterminate antibody result or serum not available), 7 encephalitis, 8 meningitis, and 3 demyelinating disorders. HHV-7 disease was excluded in 36 children on the basis of past infection (high IgG avidity) and/or an alternative cause. CONCLUSIONS: Primary HHV-7 infection delayed into adolescence can cause serious neurologic disease. HHV-7 DNA in CSF alone is insufficient to prove an etiologic association. Combining CSF polymerase chain reaction with serology is essential to prove primary infection when investigating HHV-7 CNS disease.
Assuntos
Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/epidemiologia , Herpesvirus Humano 7/patogenicidade , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/epidemiologia , Fatores Etários , Estudos Transversais , DNA Viral/líquido cefalorraquidiano , Encefalite Viral/diagnóstico , Encefalite Viral/epidemiologia , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/epidemiologia , Herpesvirus Humano 7/genética , Humanos , Meningite Viral/diagnóstico , Meningite Viral/epidemiologia , Ontário , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
Community-acquired respiratory virus (CARV) infections have been recognized as a significant cause of morbidity and mortality in patients with leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). Progression to lower respiratory tract infection with clinical and radiological signs of pneumonia and respiratory failure appears to depend on the intrinsic virulence of the specific CARV as well as factors specific to the patient, the underlying disease, and its treatment. To better define the current state of knowledge of CARVs in leukemia and HSCT patients, and to improve CARV diagnosis and management, a working group of the Fourth European Conference on Infections in Leukaemia (ECIL-4) 2011 reviewed the literature on CARVs, graded the available quality of evidence, and made recommendations according to the Infectious Diseases Society of America grading system. Owing to differences in screening, clinical presentation, and therapy for influenza and adenovirus, ECIL-4 recommendations are summarized for CARVs other than influenza and adenovirus.
Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/terapia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/terapia , Viroses/diagnóstico , Viroses/terapia , Infecções Comunitárias Adquiridas/etiologia , Infecções Comunitárias Adquiridas/prevenção & controle , Coronavirus , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia/complicações , Leucemia/terapia , Metapneumovirus , Paramyxovirinae , Guias de Prática Clínica como Assunto , Vírus Sinciciais Respiratórios , Infecções Respiratórias/etiologia , Infecções Respiratórias/prevenção & controle , Rhinovirus , Viroses/etiologia , Viroses/prevenção & controleRESUMO
BACKGROUND: Adenovirus infection is a potentially serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) and has been reported to occur more frequently following T-cell-depleted reduced-intensity HSCT. However, the true incidence and clinical significance as well as the relationship of disease to viremic titer remain unclear due to wide variation in study populations and methodology. METHODS: We performed weekly surveillance blood testing by quantitative polymerase chain reaction on all adult recipients of alemtuzumab-based reduced-intensity HSCT at our institution between January 2008 and January 2011. We collated this with clinical data on treatment and outcomes of adenovirus infection. RESULTS: Of 116 HSCT patients analyzed, 14 (12.1%) had adenoviremia with a titer >200 copies/mL. Median time to first detectable titer was 28 days post-HSCT (range, 10-347), and median time to maximum titer was 49 days (range, 16-368). Underlying disease diagnosis (lymphoid > myeloid) and recipient cytomegalovirus (CMV) serostatus (positive > negative) were significantly correlated with adenoviremia. Only 5 patients (with high peak titers of 99 000-2 500 000 copies/mL) received cidofovir; 1 died from complications relating to adenovirus and concurrent CMV infection. CONCLUSIONS: We detected adenoviremia at quantifiable levels in only 12.1% of HSCT patients. Attributable mortality was low (0.9% of the entire cohort, 7% of those with adenoviremia) because even infections associated with high viral titers responded to reduction in immunosuppression and treatment with cidofovir in the majority. The clinical significance of adenoviral infection in patients receiving alemtuzumab-based HSCT appears to be less than that previously reported, and only rarely does infection lead to significant morbidity and mortality.
Assuntos
Infecções por Adenoviridae/etiologia , Adenoviridae/isolamento & purificação , Anticorpos Monoclonais Humanizados/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Viremia/etiologia , Infecções por Adenoviridae/virologia , Adolescente , Adulto , Alemtuzumab , Análise de Variância , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Transplante Homólogo , Resultado do Tratamento , Carga Viral , Viremia/virologiaRESUMO
OBJECTIVE: To determine the contribution of herpes simplex virus (HSV) to serious neurological disease. SETTING AND PATIENTS: A 3-year prospective survey of children aged 2-23 months in Britain and Ireland. RESULTS: 19 children had HSV central nervous system (CNS) infection; 13 aged 2-11 months had focal neuroimaging abnormalities and 11 long-term neurological sequelae. Of six aged 12-35 months, one had abnormal neuroimaging and three long-term neurological sequelae. 17 of the 19 had serious neurological disease. HSV CNS infection accounted for 23% of serious neurological disease in children aged 2-11 months and 4.5% in older children. CONCLUSIONS: The incidence of HSV-induced serious neurological disease in the UK was estimated at 1 in 64 000/year in younger children and 1 in 230 000 in older children. HSV CNS infection has clinical effects ranging from frank encephalitis to severe illness with fever and convulsions to milder disease lacking encephalopathy.
Assuntos
Encefalite por Herpes Simples/epidemiologia , Fatores Etários , Encefalite por Herpes Simples/complicações , Encefalite por Herpes Simples/diagnóstico , Feminino , Febre/epidemiologia , Febre/virologia , Humanos , Incidência , Lactente , Irlanda/epidemiologia , Masculino , Prognóstico , Estudos Prospectivos , Convulsões/epidemiologia , Convulsões/virologia , Reino Unido/epidemiologiaRESUMO
Chromosomally integrated human herpesvirus 6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV-6 levels in whole blood that exceed 5.5 log10 copies/ml are strongly suggestive of ciHHV-6. Monitoring DNA load in plasma and serum is unreliable, both for identifying and for monitoring subjects with ciHHV-6 due to cell lysis and release of cellular DNA. High HHV-6 DNA loads associated with ciHHV-6 can lead to erroneous diagnosis of active infection. Transplant recipients with ciHHV-6 may be at increased risk for bacterial infection and graft rejection. ciHHV-6 can be induced to a state of active viral replication in vitro. It is not known whether ciHHV-6 individuals are put at clinical risk by the use of drugs that have been associated with HHV-6 reactivation in vivo or in vitro. Nonetheless, we urge careful observation when use of such drugs is indicated in individuals known to have ciHHV-6. Little is known about whether individuals with ciHHV-6 develop immune tolerance for viral proteins. Further research is needed to determine the role of ciHHV-6 in disease.
Assuntos
Cromossomos Humanos/virologia , Herpesvirus Humano 6/fisiologia , Infecções por Roseolovirus/virologia , Integração Viral , Herpesvirus Humano 6/genética , Humanos , Infecções por Roseolovirus/genéticaRESUMO
During 2009, a new strain of A/H1N1 influenza appeared and became pandemic. A prospective study was performed to collect data regarding risk factors and outcome of A/H1N1 in hematopoietic stem cell transplant recipients. Only verified pandemic A/H1N1 influenza strains were included: 286 patients were reported, 222 allogeneic and 64 autologous recipients. The median age was 38.3 years and the median time from transplant was 19.4 months. Oseltamivir was administered to 267 patients and 15 patients received zanamivir. One hundred and twenty-five patients (43.7%) were hospitalized. Ninety-three patients (32.5%) developed lower respiratory tract disease. In multivariate analysis, risk factors were age (OR 1.025; 1.01-1.04; P=0.002) and lymphopenia (OR 2.49; 1.33-4.67; P<0.001). Thirty-three patients (11.5%) required mechanical ventilation. Eighteen patients (6.3%) died from A/H1N1 infection or its complications. Neutropenia (P=0.03) and patient age (P=0.04) were significant risk factors for death. The 2009 A/H1N1 influenza pandemic caused severe complications in stem cell transplant recipients.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Pandemias , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Criança , Pré-Escolar , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Influenza Humana/complicações , Influenza Humana/mortalidade , Linfopenia/complicações , Pessoa de Meia-Idade , Oseltamivir/uso terapêutico , Pneumonia/complicações , Fatores de Risco , Resultado do Tratamento , Vacinação , Adulto JovemRESUMO
BACKGROUND: Encephalitis has many causes, but for most patients the cause is unknown. We aimed to establish the cause and identify the clinical differences between causes in patients with encephalitis in England. METHODS: Patients of all ages and with symptoms suggestive of encephalitis were actively recruited for 2 years (staged start between October, 2005, and November, 2006) from 24 hospitals by clinical staff. Systematic laboratory testing included PCR and antibody assays for all commonly recognised causes of infectious encephalitis, investigation for less commonly recognised causes in immunocompromised patients, and testing for travel-related causes if indicated. We also tested for non-infectious causes for acute encephalitis including autoimmunity. A multidisciplinary expert team reviewed clinical presentation and hospital tests and directed further investigations. Patients were followed up for 6 months after discharge from hospital. FINDINGS: We identified 203 patients with encephalitis. Median age was 30 years (range 0-87). 86 patients (42%, 95% CI 35-49) had infectious causes, including 38 (19%, 14-25) herpes simplex virus, ten (5%, 2-9) varicella zoster virus, and ten (5%, 2-9) Mycobacterium tuberculosis; 75 (37%, 30-44) had unknown causes. 42 patients (21%, 15-27) had acute immune-mediated encephalitis. 24 patients (12%, 8-17) died, with higher case fatality for infections from M tuberculosis (three patients; 30%, 7-65) and varicella zoster virus (two patients; 20%, 2-56). The 16 patients with antibody-associated encephalitis had the worst outcome of all groups-nine (56%, 30-80) either died or had severe disabilities. Patients who died were more likely to be immunocompromised than were those who survived (OR = 3·44). INTERPRETATION: Early diagnosis of encephalitis is crucial to ensure that the right treatment is given on time. Extensive testing substantially reduced the proportion with unknown cause, but the proportion of cases with unknown cause was higher than that for any specific identified cause. FUNDING: The Policy Research Programme, Department of Health, UK.
Assuntos
Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/etiologia , Encefalite/epidemiologia , Encefalite/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/microbiologia , Encefalite/imunologia , Encefalite/microbiologia , Inglaterra/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Análise de Regressão , Adulto JovemRESUMO
Two patients with the characteristic high human herpesvirus 6 (HHV-6) DNA loads in peripheral blood caused by chromosomally integrated (CI) virus received a haematopoietic stem cell transplant (HSCT) from a donor without CI HHV-6. Both patients died in consequence of cytomegalovirus (CMV) pneumonitis. At autopsy, high amounts of CMV DNA were detected in lungs but at much lower levels in other organs. In contrast HHV-6 DNA was detected at high levels throughout the organs with the exception of donor-derived haematopoietic tissue. In individuals with chromosomal integration, HHV-6 DNA is found in every tissue of recipient origin indicating inheritance through the germ line.
Assuntos
Cromossomos Humanos/virologia , DNA Viral/análise , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 6/genética , Infecções por Roseolovirus/virologia , Integração Viral/genética , Adulto , Criança , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/mortalidade , Evolução Fatal , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/virologia , Pulmão/virologia , Masculino , Pneumonia/mortalidade , Pneumonia/virologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Infecções por Roseolovirus/genéticaRESUMO
Fluorescent in situ hybridization (FISH) was used to investigate the chromosomal integration sites of human herpesvirus 6 (HHV-6) in phytohemagglutinin-stimulated leukocytes and B lymphocytes from Epstein-Barr virus transformed lymphoblastoid cell lines (LCLs). Five different chromosomal integration sites were found in nine individuals. Only one site was identified in each individual, each site was in the vicinity of the telomeric region and was on either the p or q arm of only one of the two chromosome homologues. The sites were 9q34.3, 10q26.3, 11p15.5, 17p13.3, and 19q 13.4, of which three have not been previously identified. For 9q34.3 the site of integration was further mapped using a locus-specific probe for 9q34.3 together with a pan-telomeric probe and both co-localized with the HHV-6 signal. Similarly an arm-specific telomeric probe for 19q co-localized with the HHV-6 signal. It was therefore concluded that the site of integration is actually within the telomere. The number of viral DNA copies/cell was calculated in blood, LCL cells and hair follicles and was one or more in every case for each of the nine individuals. This result was confirmed by FISH where 100% of cells gave an HHV-6 signal. These findings add to previous reports suggesting that integrated HHV-6 DNA is found in every cell in the body and transmitted vertically. Finally, including our data, worldwide seven different chromosomal sites of HHV-6 integration have now been identified. Large epidemiological studies of chromosomal integration are required to identify further telomeric sites, geographical or racial variation and possible clinical consequences.
Assuntos
Herpesvirus Humano 6/fisiologia , Telômero/virologia , Integração Viral , Adolescente , Adulto , Cromossomos Humanos/virologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Leucócitos/virologia , Masculino , Pessoa de Meia-IdadeRESUMO
Human herpesvirus-6 (HHV-6) exists as two closely related variants: A and B. Whereas no disease has been firmly associated with HHV-6A, variant B causes febrile illness in young children and is pathogenic in immunosuppressed transplant recipients. Chromosomally integrated HHV-6 (with either variant A or B) occurs in a minority of people. This phenomenon has the potential to confound the diagnosis of active HHV-6 infection, since chromosomally integrated HHV-6 DNA sequences are inherited through the germline. Therefore, viral DNA is in every nucleated cell in the body and can be found in a range of body fluids including whole blood, serum, plasma and cerebrospinal fluid. There are characteristically very high viral loads in whole blood (> 6 log10 HHV-6 genomes/ml) and serum (5 log10 HHV-6 genomes/ml); these can be used to differentiate individuals with viral chromosomal integration from those with active HHV-6 infection, where viral loads are significantly lower. Increasingly, the polymerase chain reaction (to detect viral nucleic acid) is used for diagnosis; therefore, it is important to exclude HHV-6 chromosomal integration before concluding that there is evidence of active HHV-6 infection.
Assuntos
Herpesvirus Humano 6/genética , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/virologia , Carga Viral , Integração Viral/genética , Diagnóstico Diferencial , Humanos , Hibridização in Situ Fluorescente , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: We sought to investigate the risk of serious neurologic disease after immunization in early childhood. METHODS: The results of a 3-year prospective study of children (2-35 months old) in Britain and Ireland with encephalitis and/or severe illness with convulsions and fever were linked to each child's vaccine history. Cases were reported via the British Paediatric Surveillance Unit's network. The self-controlled case-series method was used to investigate associations between immunization and acute potential adverse events. The risk periods investigated were 0 to 3 and 0 to 7 days post-diphtheria, tetanus, whole cell pertussis, Haemophilus influenzae type b or meningococcal C conjugate vaccine and 6 to 11 and 15 to 35 days post-measles, mumps, rubella vaccine. RESULTS: A total of 157 disease episodes from 155 children met the analytical case definition. There were 11 cases of herpes simplex encephalitis and 23 cases of primary human herpesvirus 6 and/or 7 infection. There was no evidence of a raised relative incidence of serious neurologic disease in any of the specified risk periods with the exception of a raised relative incidence of 5.68 in the 6-11 days after measles, mumps, rubella vaccine. Based on this relative incidence, between 3 and 6 of the 6 cases in this period were estimated to be attributable to the vaccine with a best estimate of 5. The 6 cases all had fever with convulsions lasting >30 minutes; in all but 1, there was complete recovery by discharge from hospital. Of the 5 patients who recovered, 1 had a concurrent primary human herpesvirus 6 infection and one a primary human herpesvirus 7. CONCLUSIONS: Six to 11 days after measles, mumps, rubella vaccine there is an increased risk of fever and convulsions lasting >30 minutes. All 6 of the episodes temporally related to immunization met the criteria for complex febrile convulsions. The estimated attributable risk of serious neurological disease was similar to that previously found for measles vaccine.
Assuntos
Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/virologia , Vacinação/efeitos adversos , Pré-Escolar , Inglaterra/epidemiologia , Humanos , Lactente , Irlanda/epidemiologia , Vacina contra Sarampo/efeitos adversos , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/efeitos adversos , Vacinas Meningocócicas/imunologia , Vacina contra Caxumba/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Vacina contra Rubéola/efeitos adversosRESUMO
A large simultaneous outbreak of respiratory syncytial virus (RSV) and parainfluenza type 3 (PIV-3) infections occurred on an adult hematology unit. Implementation of enhanced infection control was complicated by cocirculation of the two different viruses, with prolonged viral shedding from infected patients, and placed great pressure on health care staff; of 27 infected hematopoietic stem cell transplant patients, 9 died, and the unit was closed for 2 months. Retrospective molecular investigation of the virus strains involved in the outbreak was performed by analyzing part of the fusion gene of PIV-3 and part of the glycoprotein gene of RSV. Reverse transcription-PCR on nasopharyngeal aspirates from patients infected before and during the simultaneous outbreak generated amplicons for sequence analysis. A single strain of RSV and a single strain of PIV-3 had spread from person to person within the unit; 7 patients were infected with RSV, 22 were infected with PIV-3, and 4 were infected with both viruses. The PIV-3 outbreak had started at the beginning of August 3 months before the RSV outbreak; it had arisen when PIV-3 was introduced from the community by a patient and passed to another patient, who became chronically infected with the identical strain and, in spite of being nursed in isolation, was most likely the source from which widespread infection occurred in November. Had these early cases been linked to a common PIV-3 strain at the time of diagnosis, enhanced infection control precautions might have prevented the eventual extensive spread of PIV-3, making it much easier to deal with the later RSV outbreak.
Assuntos
Surtos de Doenças , Hematologia , Unidades Hospitalares , Vírus da Parainfluenza 3 Humana/genética , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sincicial Respiratório Humano/genética , Infecções por Respirovirus/epidemiologia , Adolescente , Adulto , Sequência de Bases , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/mortalidade , Infecção Hospitalar/virologia , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Vírus da Parainfluenza 3 Humana/classificação , Vírus da Parainfluenza 3 Humana/isolamento & purificação , Filogenia , Reação em Cadeia da Polimerase/métodos , RNA Viral/isolamento & purificação , Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/classificação , Vírus Sincicial Respiratório Humano/isolamento & purificação , Infecções por Respirovirus/mortalidade , Infecções por Respirovirus/virologia , Análise de Sequência de DNARESUMO
The prevalence and concentration of human herpesvirus 6 (HHV-6) DNA in the cerebrospinal fluid (CSF) of the immunocompetent in primary infection was compared with that in viral chromosomal integration. Samples from 510 individuals with suspected encephalitis, 200 young children and 310 older children and/or adults, and 12 other patients were tested. HHV-6 DNA concentration (log(10) copies/ml) was measured in CSF, serum, and whole blood using PCR. Serum HHV-6 immunoglobulin G antibody was measured by indirect immunofluorescence. Primary infection was defined by antibody seroconversion and/or a low concentration of HHV-6 DNA (<3.0 log(10) copies/ml) in a seronegative serum. Chromosomal integration was defined by a high concentration of viral DNA in serum (>/=3.5 log(10) copies/ml) or whole blood (>/=6.0 log(10) copies/ml). The prevalences of CSF HHV-6 DNA in primary infection and chromosomal integration were 2.5% and 2.0%, respectively, in the young children (<2 years) and 0% and 1.3%, respectively, in the older children and/or adults. The mean concentration of CSF HHV-6 DNA in 9 children with primary infection (2.4 log(10) copies/ml) was significantly lower than that of 21 patients with viral chromosomal integration (4.0 log(10) copies/ml). Only HHV-6B DNA was found in primary infection, whereas in viral integration, 4 patients had HHV-6A and 17 patients HHV-6B. Apart from primary infection, chromosomal integration is the most likely cause of HHV-6 DNA in the CSF of the immunocompetent. Our results show that any diagnosis of HHV-6 encephalitis or other type of active central nervous system infection should not be made without first excluding chromosomal HHV-6 integration by measuring DNA load in CSF, serum, and/or whole blood.