RESUMEN
Traditional epidemiological investigation of nosocomial transmission of influenza involves the identification of patients who have the same influenza virus type and who have overlapped in time and place. This method may misidentify transmission where it has not occurred or miss transmission when it has. We used influenza virus whole-genome sequencing (WGS) to investigate an outbreak of influenza A virus infection in a hematology/oncology ward and identified 2 separate introductions, one of which resulted in 5 additional infections and 79 bed-days lost. Results from WGS are becoming rapidly available and may supplement traditional infection control procedures in the investigation and management of nosocomial outbreaks.
Asunto(s)
Infección Hospitalaria/virología , Virus de la Influenza A/genética , Gripe Humana/virología , Infección Hospitalaria/epidemiología , Brotes de Enfermedades , Humanos , Control de Infecciones/métodos , Gripe Humana/epidemiología , Epidemiología Molecular/métodos , Secuenciación Completa del Genoma/métodosRESUMEN
Metagenomic next-generation sequencing (NGS) was used to diagnose an unusual and fatal case of progressive encephalitis in an immunocompromised adult presenting at disease onset as bilateral hearing loss. The sequencing and confirmatory studies revealed neuroinvasive infection of the brain by an astrovirus belonging to a recently discovered VA/HMO clade.
Asunto(s)
Infecciones por Astroviridae/diagnóstico , Encefalitis Viral/diagnóstico , Mamastrovirus/genética , Mamastrovirus/aislamiento & purificación , Adulto , Encéfalo/patología , Proteínas de la Cápside/genética , Encefalitis Viral/complicaciones , Resultado Fatal , Pérdida Auditiva Bilateral/etiología , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Leucemia Linfoide/complicaciones , FilogeniaRESUMEN
Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel, potentially zoonotic human coronavirus (HCoV). We investigated MERS-CoV antibodies using a staged approach involving an immunofluorescence assay (IFA), a differential recombinant IFA, and a plaque-reduction serum neutralization assay. In 130 blood donors sampled during 2012 in Jeddah and 226 slaughterhouse workers sampled in October 2012 in Jeddah and Makkah, Saudi Arabia, 8 reactive sera were seen in IFA but were resolved to be specific for established HCoVs by discriminative testing. There is no evidence that MERS-CoV circulated widely in the study region in fall 2012, matching an apparent absence of exported disease during the 2012 Hajj.
Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Coronavirus/epidemiología , Coronavirus/inmunología , Adolescente , Adulto , Anticuerpos Neutralizantes/sangre , Donantes de Sangre , Infecciones por Coronavirus/inmunología , Técnica del Anticuerpo Fluorescente , Humanos , Persona de Mediana Edad , Pruebas de Neutralización , Arabia Saudita/epidemiología , Estudios Seroepidemiológicos , Adulto JovenAsunto(s)
Neoplasias Hematológicas/virología , Hepatitis E/etiología , Adulto , Anciano , Femenino , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/epidemiología , Hepatitis E/epidemiología , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Medición de Riesgo , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Detection of a retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), has recently been reported in 67% of patients with chronic fatigue syndrome. We have studied a total of 170 samples from chronic fatigue syndrome patients from two UK cohorts and 395 controls for evidence of XMRV infection by looking either for the presence of viral nucleic acids using quantitative PCR (limit of detection <16 viral copies) or for the presence of serological responses using a virus neutralisation assay. RESULTS: We have not identified XMRV DNA in any samples by PCR (0/299). Some serum samples showed XMRV neutralising activity (26/565) but only one of these positive sera came from a CFS patient. Most of the positive sera were also able to neutralise MLV particles pseudotyped with envelope proteins from other viruses, including vesicular stomatitis virus, indicating significant cross-reactivity in serological responses. Four positive samples were specific for XMRV. CONCLUSIONS: No association between XMRV infection and CFS was observed in the samples tested, either by PCR or serological methodologies. The non-specific neutralisation observed in multiple serum samples suggests that it is unlikely that these responses were elicited by XMRV and highlights the danger of over-estimating XMRV frequency based on serological assays. In spite of this, we believe that the detection of neutralising activity that did not inhibit VSV-G pseudotyped MLV in at least four human serum samples indicates that XMRV infection may occur in the general population, although with currently uncertain outcomes.
Asunto(s)
Síndrome de Fatiga Crónica/virología , Infecciones por Retroviridae/diagnóstico , Retroviridae/aislamiento & purificación , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/sangre , Estudios de Cohortes , ADN Viral/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Neutralización/métodos , Reacción en Cadena de la Polimerasa/métodos , Reino Unido/epidemiología , Adulto JovenRESUMEN
BACKGROUND: We sought to investigate the impact of different immunosuppressive regimens on human cytomegalovirus (HCMV) incidence and replication dynamics in a cohort of 256 patients after liver transplantation. METHODS: A time-updated approach was used to determine the risk of developing HCMV replication (>200 genomes/mL blood) within the first 100 days after liver transplantation according to the immunosuppressive regimen being received at specific time points. RESULTS: In patients receiving tacrolimus, the addition of prednisolone was associated with a significant increased risk of HCMV replication both at baseline (relative rate of infection [RRI]=4.34; P=0.0001) and in a time-updated analysis (RRI=4.68; P=0.0001). However, the addition of azathioprine substantially reduced the risk of HCMV replication to that observed with tacrolimus alone. As expected donor/recipient HCMV serostatus was also a risk factor for viraemia. Multivariable models showed that the tacrolimus plus prednisolone regimen and donor/recipient serostatus were independent risk factors for HCMV replication. Viral replication dynamics showed that the duration of HCMV viraemia, the peak viral load, and the growth rate of HCMV were greatest in patients receiving tacrolimus plus prednisolone although these differences did not reach statistical significance. CONCLUSIONS: The combination of prednisolone plus tacrolimus as baseline immunosuppression after liver transplantation is associated with a high risk of HCMV replication. This effect can be negated by the addition of azathioprine.
Asunto(s)
Azatioprina/farmacología , Infecciones por Citomegalovirus/virología , Citomegalovirus/efectos de los fármacos , Citomegalovirus/fisiología , Trasplante de Hígado , Prednisolona/farmacología , Replicación Viral/efectos de los fármacos , Adolescente , Adulto , Anciano , Femenino , Humanos , Inmunosupresores/farmacología , Masculino , Persona de Mediana EdadRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0163722.].
RESUMEN
Mass gatherings at major international sporting events put millions of international travelers and local host-country residents at risk of acquiring infectious diseases, including locally endemic infectious diseases. The mosquito-borne Zika virus (ZIKV) has recently aroused global attention due to its rapid spread since its first detection in May 2015 in Brazil to 22 other countries and other territories in the Americas. The ZIKV outbreak in Brazil, has also been associated with a significant rise in the number of babies born with microcephaly and neurological disorders, and has been declared a 'Global Emergency by the World Health Organization. This explosive spread of ZIKV in Brazil poses challenges for public health preparedness and surveillance for the Olympics and Paralympics which are due to be held in Rio De Janeiro in August, 2016. We review the epidemiology and clinical features of the current ZIKV outbreak in Brazil, highlight knowledge gaps, and review the public health implications of the current ZIKV outbreak in the Americas. We highlight the urgent need for a coordinated collaborative response for prevention and spread of infectious diseases with epidemic potential at mass gatherings events.
Asunto(s)
Salud Pública , Infección por el Virus Zika/epidemiología , Virus Zika , Brasil/epidemiología , Brotes de Enfermedades/prevención & control , Humanos , Lactante , Microcefalia/epidemiología , Microcefalia/virología , Deportes , Organización Mundial de la Salud , Infección por el Virus Zika/complicacionesRESUMEN
BACKGROUND: To help decide when to start and when to stop pre-emptive therapy for cytomegalovirus infection, we conducted two open-label randomized controlled trials in renal, liver and bone marrow transplant recipients in a single centre where pre-emptive therapy is indicated if viraemia exceeds 3000 genomes/ml (2520 IU/ml) of whole blood. METHODS: Patients with two consecutive viraemia episodes each below 3000 genomes/ml were randomized to continue monitoring or to immediate treatment (Part A). A separate group of patients with viral load greater than 3000 genomes/ml was randomized to stop pre-emptive therapy when two consecutive levels less than 200 genomes/ml (168 IU/ml) or less than 3000 genomes/ml were obtained (Part B). For both parts, the primary endpoint was the occurrence of a separate episode of viraemia requiring treatment because it was greater than 3000 genomes/ml. RESULTS: In Part A, the primary endpoint was not significantly different between the two arms; 18/32 (56%) in the monitor arm had viraemia greater than 3000 genomes/ml compared to 10/27 (37%) in the immediate treatment arm (p = 0.193). However, the time to developing an episode of viraemia greater than 3000 genomes/ml was significantly delayed among those randomized to immediate treatment (p = 0.022). In Part B, the primary endpoint was not significantly different between the two arms; 19/55 (35%) in the less than 200 genomes/ml arm subsequently had viraemia greater than 3000 genomes/ml compared to 23/51 (45%) among those randomized to stop treatment in the less than 3000 genomes/ml arm (p = 0.322). However, the duration of antiviral treatment was significantly shorter (p = 0.0012) in those randomized to stop treatment when viraemia was less than 3000 genomes/ml. DISCUSSION: The results illustrate that patients have continuing risks for CMV infection with limited time available for intervention. We see no need to alter current rules for stopping or starting pre-emptive therapy.
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Anticuerpos Monoclonales/uso terapéutico , Antivirales/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Huésped Inmunocomprometido , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Ribavirina/uso terapéutico , Adulto , Anticuerpos Monoclonales Humanizados , Esquema de Medicación , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad , PalivizumabAsunto(s)
Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Infecciones por Enterovirus/inducido químicamente , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Meningoencefalitis/inducido químicamente , Neuronas/virología , Anticuerpos Monoclonales de Origen Murino , Ataxia Cerebelosa/inducido químicamente , Ataxia Cerebelosa/virología , Resultado Fatal , Humanos , Masculino , Meningoencefalitis/virología , Persona de Mediana Edad , RituximabRESUMEN
Recurrence of Hepatitis C (HCV) post-liver transplantation (LT) is universal and its course is more aggressive than in immunocompetent individuals. Human cytomegalovirus (CMV) infection is a common post-LT infection and has immunomodulatory effects that could adversely affect the outcome of HCV. To date, the effect of HCV replication on the dynamics of CMV have not been investigated. From 2000 to 2004, a cohort of 69 HCV-infected liver transplant recipients and 188 HCV-negative liver transplant recipients (NON-HCV cohort) were monitored for CMV infection twice weekly by CMV polymerase chain reaction (PCR) with preemptive therapy initiated after 2 consecutive positive results. None of the patients received CMV prophylaxis. A subset of 18 HCV-infected patients had their HCV viral load monitored regularly post-LT by quantitative PCR. CMV DNAemia (>200 genomes/mL blood) did not influence the level of HCV replication within 150 days posttransplantation or the stage of liver fibrosis in liver biopsies at 1 yr post-LT. There were no differences in the incidence of CMV DNAemia or replication dynamics in the HCV cohort compared to the NON-HCV cohort. In conclusion, short term CMV viremia does not enhance the replication of HCV after LT, while HCV replication does not alter the replication dynamics of CMV.
Asunto(s)
Citomegalovirus/metabolismo , Hepacivirus/metabolismo , Hepatitis C/cirugía , Trasplante de Hígado/métodos , Replicación Viral , Adulto , Estudios de Cohortes , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/etiología , Femenino , Genotipo , Hepatitis C/terapia , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del TratamientoRESUMEN
We aimed to assess the temperature distribution in the cryolesion during hepatic cryotherapy and the association with postoperative histological changes to optimise the technique and allow better preoperative planning. Hepatic cryolesions were produced in 22 pigs following laparotomy using a CMS-cryosystem and 8mm-AccuProbe-Cryoprobes. The temperature was measured in 1 min intervals at different distances from the probe during freezing. The animals were treated in 5 groups: (i) single freezing of 20 min; (ii) double freezing of 20 min each; (iii) single freezing of 40 min; (iv) single freezing of 20 min (n=4), histology at 1 week p.o., and (v) single freezing of 20 min and Pringle manoeuvre; [(i)-(iii) and (v): histology at 24 h p.o.]. The mean diameter of the -38 degrees C isotherm, i.e., the zone of effective treatment for colorectal metastases was 37 mm for group (i) with a mean iceball diameter of 59 mm and about 46 mm for groups (ii, iii, and v) with mean iceball diameters of 78, 75, and 75 mm, respectively. At 7 days postoperatively secondary necrosis was seen in the largest central part of the lesion, wherever temperatures of -15 degrees C or lower were achieved during cryosurgery. Under the hypothesis that -38 degrees C is the effective temperature for the destruction of colorectal liver metastases, a lesion of 37-mm diameter may be effectively treated with a single 8mm-AccuProbe-Cryoprobe and a 20 min single freeze cycle and a lesion of 46 mm may be effectively treated when a double freeze-thaw cycle of 20 min each, a single freeze cycle of 40 min, or a 20 min single freeze cycle with additional Pringle manoeuvre is used, when it is perfectly placed in the lesion.
Asunto(s)
Criocirugía/métodos , Hipotermia Inducida , Hígado/patología , Hígado/cirugía , Animales , Frío , Criocirugía/instrumentación , Femenino , Congelación , Modelos Animales , Tasa de Supervivencia , PorcinosRESUMEN
Forty-eight patients who provided 2 consecutive blood samples that tested positive for cytomegalovirus DNA by polymerase chain reaction (PCR) were randomized to receive either full-dose ganciclovir (5 mg/kg intravenously [iv] twice daily) or half-dose ganciclovir (5 mg/kg iv once daily) plus half-dose foscarnet (90 mg/kg iv once daily) for 14 days. In the ganciclovir arm, 17 (71%) of 24 patients reached the primary end point of being CMV negative by PCR within 14 days of initiation of therapy, compared with 12 (50%) of 24 patients in the ganciclovir-plus-foscarnet arm (P = .12). Toxicity was greater in the combination-therapy arm. In patients who failed to reach the primary end point, baseline virus load was 0.77 log10 higher, the replication rate before therapy was faster (1.5 vs. 2.7 days), and the viral decay rate was slower (2.9 vs. 1.1 days) after therapy. Bivariable logistic regression models identified baseline virus load, bone-marrow transplantation, and doubling time and half-life of decay as the major factors affecting response to therapy within 14 days. This study did not support a synergistic effect of ganciclovir plus foscarnet in vivo.