Mutations in Coding and Non-Coding Regions in Varicella-Zoster Virus Causing Fatal Hemorrhagic Fever Without Rash in an Immunocompetent Patient: Case Report.

INTRODUCTION: We report the case of a fatal hemorrhagic varicella primary infection in an immunocompetent man and whole-genome characterization of the virus for the investigation of biomarkers of virulence. CASE: A 38-year-old patient born in Nigeria presented to the emergency department with abdominal pain and subsequently developed fatal hemorrhagic disease without skin rash. Extensive laboratory tests including serology and PCR for arenaviruses, bunyaviruses and ebolaviruses were negative. Varicella-zoster virus (VZV) PCR of sera, liver and spleen tissue samples from autopsy revealed the presence of VZV DNA. Primary infection by varicella-zoster virus with hemorrhagic manifestations was diagnosed after virological testing. The VZV genome was sequenced using a mWGS approach. Bioinformatic analysis showed 53 mutations across the genome, 33 of them producing non-synonymous variants affecting up to 14 genes. Some of them, such as ORF11 and ORF 62, encoded for essential functions related to skin or neurotropism. To our knowledge, the mutations reported here have never been described in a VZV causing such a devastating outcome. DISCUSSION: In immunocompetent patients, viral factors should be considered in patients with uncommon symptoms or severe diseases. Some relevant mutations revealed by using whole genome sequencing (WGS) directly from clinical samples may be involved in this case and deserves further investigation. CONCLUSION: Differential diagnosis of varicella-zoster virus in immunocompetent adults should be considered among patients with suspected VHF, even if the expected vesicular rash is not present at admission and does not arise thereafter. Whole genome sequencing of strains causing uncommon symptoms and/or mortality is needed for epidemiological surveillance and further characterization of putative markers of virulence. Additionally, this report highlights the recommendation for a VZV vaccination policy in non-immunized migrants from developing countries.

Guía clínica para la resección mucosa endoscópica de lesiones colorrectales no pediculadas / Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions

Este documento resume el contenido de la Guía de resección mucosa endoscópica elaborada por el grupo de trabajo de la Sociedad Española de Endoscopia Digestiva (GSEED de Resección Endoscópica) y expone las recomendaciones sobre el manejo endoscópico de las lesiones neoplásicas colorrectales superficiales (AU)

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions (AU)

Guía clínica para la resección mucosa endoscópica de lesiones colorrectales no pediculadas / Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions

Este documento resume el contenido de la Guía de resección mucosa endoscópica elaborada por el grupo de trabajo de la Sociedad Española de Endoscopia Digestiva (GSEED de Resección Endoscópica) y expone las recomendaciones sobre el manejo endoscópico de las lesiones neoplásicas colorrectales superficiales (AU)

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions (AU)

Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions.

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.

Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions. / Guía clínica para la resección mucosa endoscópica de lesiones colorrectales no pediculadas.

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.

Comparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection.

Hepatitis E virus (HEV) acute infection is often diagnosed only by anti-HEV IgM ELISA methods, whose sensitivity varies, according to different reports. Reports assessing the specificity of commercial assays for anti-HEV IgG testing are scarce, and estimates of sensitivity and specificity are both controversial. The aim of this work is to assess the sensitivity of different commercial techniques for HEV genotype 3 antibody (anti-HEV) IgM and IgG detection in entirely specific sample panels including both high and low antibody concentrations. The anti-HEV IgM and IgG ELISA methods compared were: DSI, Mikrogen, Wantai, Euroimmun, MP, and Dia.pro. The rapid test All Diag was also included in the anti-HEV IgM comparison. Our results show that low anti-HEV IgM concentrations were better detected by DSI, Mikrogen, and All Diag, these tests being the most sensitive in our study. Euroimmun, MP and Dia.pro gave concordant results, showing lower sensitivity than the others. Regarding anti-HEV IgG our results revealed similar anti-HEV IgG sensitivity. Furthermore, there was a striking overall lack of concordance among the results. We present a thorough review of previous comparative reports, with particular reference to the anti-HEV IgG comparison, since published results differ from ours. This discrepancy may be related to the improved versions of the tests for MP and Dia.pro that we employed.

Epidemiología de la infección por el virus de la hepatitis E en España / Epidemiology of hepatitis E virus infection in Spain

La información generada durante los últimos 20 años permite ya describir los rasgos generales de la epidemiología y la ecología del virus de la hepatitis E en España. Las cepas del genotipo 3, y en especial las del subgenotipo 3f, circulan entre el ganado porcino y entre algunos mamíferos salvajes, y se transmitirían esporádicamente a las personas por contacto directo con los reservorios o por el consumo de alimentos procedentes de ellos. Asimismo, los mariscos bivalvos contaminados por el virus a través de las aguas residuales podrían desempeñar algún papel en dicha transmisión. Con las dificultades que aún plantea la interpretación de los datos, puede estimarse que la prevalencia de anticuerpos frente al virus de la hepatitis E en la población española sería inferior al 10%, aumentando significativamente con la edad. Entre los, aproximadamente, 150 casos de hepatitis E aguda comunicados ya en la literatura internacional, predominan los casos autóctonos observados en varones mayores de 40 años. Por otra parte, la enfermedad podría ser más frecuente en las regiones del norte de España que en otras. Aunque las hepatitis E agudas que suceden en nuestro medio no suelen presentar gran trascendencia clínica, los hallazgos puntuales de casos de hepatitis fulminante y de infecciones crónicas en pacientes inmunodeprimidos que no responden bien a la terapia con ribavirina aconsejan vigilar esta infección e incorporar su diagnóstico etiológico a la rutina de los laboratorios clínicos en mayor medida que la actual

The general features of the epidemiology and ecology of hepatitis E virus in Spain are already known after 20 years of investigations. Genotype 3 strains, mainly from sub-genotype 3f, circulated among swine livestock and certain wild mammals, and would be sporadically transmitted to humans through direct contact with the reservoirs or by consumption of foods derived from them. Bivalve shellfish contaminated by hepatitis E virus from sewage could also play a role in transmission. Although the interpretation of results from seroprevalence studies in low endemic settings is still controversial, antibody to hepatitis E virus displays an overall prevalence less than 10% among the population of Spain, increasing significantly with age. From the, approximately, 150 cases of acute hepatitis E recorded in the international literature, males older than 40 years, suffering a mild, locally acquired disease predominate. In addition, hepatitis E might be more frequent in the North of the country than in other regions. Although the disease does not usually have a great clinical relevance, the occasional finding of cases of fulminant hepatitis, and of ribavirin-resistant, chronic hepatitis E virus infections among the immunocompromised would recommend the surveillance of the infection by the public health authority and a better implementation of specific diagnostic procedures in clinical laboratorie

[Epidemiology of hepatitis E virus infection in Spain]. / Epidemiología de la infección por el virus de la hepatitis E en España.

The general features of the epidemiology and ecology of hepatitis E virus in Spain are already known after 20 years of investigations. Genotype 3 strains, mainly from sub-genotype 3f, circulated among swine livestock and certain wild mammals, and would be sporadically transmitted to humans through direct contact with the reservoirs or by consumption of foods derived from them. Bivalve shellfish contaminated by hepatitis E virus from sewage could also play a role in transmission. Although the interpretation of results from seroprevalence studies in low endemic settings is still controversial, antibody to hepatitis E virus displays an overall prevalence less than 10% among the population of Spain, increasing significantly with age. From the, approximately, 150 cases of acute hepatitis E recorded in the international literature, males older than 40 years, suffering a mild, locally acquired disease predominate. In addition, hepatitis E might be more frequent in the North of the country than in other regions. Although the disease does not usually have a great clinical relevance, the occasional finding of cases of fulminant hepatitis, and of ribavirin-resistant, chronic hepatitis E virus infections among the immunocompromised would recommend the surveillance of the infection by the public health authority and a better implementation of specific diagnostic procedures in clinical laboratories.

Light and Darkness: Prevalence of Hepatitis E Virus Infection among the General Population.

Human hepatitis E virus (HHEV) spreads early in life among the population in areas endemic for genotype 1 and infects mainly adults in areas endemic for genotype 3, where it would be responsible for about 10% of cases of suspected acute viral hepatitis of unknown etiology and for a number of subclinical, unrecognized infections. The overall prevalence of antibody to HHEV is high in most of the former areas and low in most of the later ones, but wide regional differences have been recorded in both cases. "Hot spots" of HHEV infection would exist for both types of strains in particular regions or among particular populations of the world. Studies on pork derivatives, shellfish bivalves, and vegetables for HHEV contamination at the sale point need to be extended for evaluating the impact of the agent on food safety, and the meaning of the finding of HHEV genotype 1 genomes in urban sewage from developed countries should be established through active surveillance. Consensus about technical issues in regard to anti-HEV testing would improve the knowledge of the HHEV epidemiology. Studies in particular regions and populations, and introduction of molecular diagnosis in the clinical setting as a routine tool, would also be required.

Percepciones de los médicos alicantinos sobre la pandemia de gripe de 2009 / Perceptions of Alicante (Spain) doctors on the 2009 influenza pandemic

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Autochthonous Hepatitis E Virus Infection in Europe: A Matter of Concern for Public Health?

Human hepatitis E virus (HHEV) is the proposed name for a diverse group of RNA viruses from the family Hepeviridae that cause acute hepatitis among humans. Waterborne strains are regularly imported into Europe by international travelers, and virus transmission of zoonotic strains via contaminated aliments is involved in autochthonous cases. Therefore, in Europe, hepatitis E displays a unique dual character, having features of both imported and autochthonous infections. Environmental involvement of waterborne and zoonotic diseases puts alimentary safety at risk. In addition, it may lead to serious health problems derived from persistent infection among patients with immune impairment due to organ transplant, cancer, or human immunodeficiency virus infection. Although the European health authorities know at present that HHEV represents a problem worthy of consideration, the actual incidence of the disease in Europe is unknown, and attempts to ascertain the prevalence of the infection is hampered by unresolved technical issues. In order to determine the burden of hepatitis E in Europe, the World Health Organization Regional Office and the European Centre for Disease Prevention and Control should pay specific attention to hepatitis E, and research efforts in the continent should be transnational and collaborative. Development of a specific European network for hepatitis E would help to achieve these goals.

[The Alliance for the Prevention of Colorectal Cancer in Spain. A civil commitment to society]. / Alianza para la Prevención del Cáncer de Colon en España: un compromiso cívico con la sociedad.

Colorectal cancer (CRC) is the most common malignant tumor in Spain, when men and women are considered together, and the second leading cause of cancer death. Every week in Spain over 500 cases of CRC are diagnosed, and nearly 260 people die from the disease. Epidemiologic estimations for the coming years show a significant increase in the number of annual cases. CRC is a perfectly preventable tumor and can be cured in 90% of cases if detected in the early stages. Population-based screening programs have been shown to reduce the incidence of CRC and mortality from the disease. Unless early detection programs are established in Spain, it is estimated that in the coming years, 1 out of 20 men and 1 out of 30 women will develop CRC before the age of 75. The Alliance for the Prevention of Colorectal Cancer in Spain is an independent and non-profit organization created in 2008 that integrates patients' associations, altruistic non-governmental organizations and scientific societies. Its main objective is to raise awareness and disseminate information on the social and healthcare importance of CRC in Spain and to promote screening measures, early detection and prevention programs. Health professionals, scientific societies, healthcare institutions and civil society should be sensitized to this highly important health problem that requires the participation of all sectors of society. The early detection of CRC is an issue that affects the whole of society and therefore it is imperative for all sectors to work together.

Efficacy of hepatitis B virus (HBV) DNA screening and characterization of acute and occult HBV infections among blood donors from Madrid, Spain.

BACKGROUND: Screening of blood units for hepatitis B virus (HBV) DNA identifies donations collected during the window period (WP) of the acute infection and may improve viral safety of the blood supply. It also leads to the detection of occult hepatitis B infection (OBI). STUDY DESIGN AND METHODS: From January 2005 to December 2006, a total of 383,267 blood units were screened for hepatitis B surface antigen (HBsAg) and HBV DNA in two transfusion centers in Madrid, using either individual-donation nucleic acid testing (ID-NAT) or minipool (MP-NAT) of eight donations (MP8). Samples positive for HBV DNA and negative for HBsAg were confirmed by a second molecular test, the viral DNA was quantified, and a genome fragment including the region encoding the major hydrophilic region (MHR) of HBsAg was sequenced. RESULTS: The overall yield of HBV DNA-positive, HBsAg-negative units was 1 in 21,282 (18 cases), higher when using ID-NAT than MP8-NAT (1:9862 vs. 1:51,011; p < 0.01). Four donations (1/95,817) were collected during the infectious pre-HBsAg WP, one during an early recovery stage, and the remaining 13 (1/29,482) were OBIs, six of whom had no detectable antibody to HBsAg. Low-level Genotype D HBV DNA was detected in all OBI cases; the frequencies of this genotype and MHR amino acid substitutions were significantly higher than reported from unselected Spanish HBsAg carriers. Donors with OBI had normal aminotransferase levels and were significantly older than donors carrying HBsAg. CONCLUSIONS: Blood donors in the WP and with OBI are not uncommon in Madrid and are detected at a higher frequency with ID-NAT than MP-NAT.

Estudio de seroprevalencia de hepatitis B en deportistas de orientación / Seroprevalence study of hepatitis B among orienteers

Fundamento y objetivo: Detectar casos asintomáticos relacionados con un brote, valorar la seroprevalencia de hepatitis B (HB) en deportistas de orientación y establecer recomendaciones. Pacientes y método: Se realizó un estudio transversal de seroprevalencia entre 116 deportistas de orientación que habían competido en las categorías implicadas en un brote previo y una muestra estratificada de 166 corredores del resto de otras categorías de competición. Se analizaron marcadores de HB: antígeno de superficie del virus de la HB (VHB) (HBsAg), anticuerpo contra el antígeno core del VHB (anti-HBc), anticuerpos contra el HBsAg, anti-HBc tipo inmunoglobina M y antecedentes de vacunación. Los resultados se expresan utilizando pesos ponderados. Resultados: La seroprevalencia de HB (anti-HBc positivos) fue del 6,7% (n=12; intervalo de confianza [IC] del 95%: 0,6 a 12,9). No se observó ningún caso de HB aguda o crónica. Todos los marcadores fueron negativos para el 61,1% (n=64; IC del 95%: 46,3 a 75,6), y el 32,3% (n=29; IC del 95%: 18,2 a 46,4) tenía marcadores de inmunidad por vacunación. Entre los sujetos menores de 25 años, el 28,4% estaba sin vacunar a pesar de que entraban en el calendario vacunal. Conclusiones: Los resultados muestran que la seroprevalencia de HB entre deportistas de orientación no difiere de la población general. Sin embargo, es necesario reforzar la vacunación entre adolescentes y adultos jóvenes. Se dan recomendaciones generales para la prevención de HB a las federaciones de orientación (AU)

Background and objective: Our objectives were to detect asymptomatic cases involved in an outbreak of hepatitis B, to assess the seroprevalence of hepatitis B (HB) in orienteers and to establish recommendations. Patients and method: One hundred sixteen orienteers who had competed in the categories involved in the previous outbreak as well as a stratified random sample of 166 of the remaining orienteers in other competition categories were included in a cross-sectional serological prevalence study. HB surface antigen (anti-HBs); total antibody to HB core antigen (total anti-HBc); HB surface antigen (Ag HBs); and antibody IgM to HB core antigen (anti-HBcIgM) along with the history of vaccination for hepatitis B were analyzed. The results were weighted. Results: The seroprevalence of HB (total anti-HBc positive) was 6.7% (n=12, 95%CI 0.6-12.9). No case of acute HB or chronic infection was observed. All the serological markers were negative for 61.1% (n=64, 95%CI 46.3-75.6), and 31.5% (n=29, 95%CI 18.2-46.4) had markers of immunity due to vaccination. Among individuals under 25 years of age, 28.4% were unvaccinated, although they were covered by vaccination programs. Conclusion: Our results suggest that the seroprevalence of HB among orienteers is not different from the general population in Spain. However, it is necessary to reinforce the vaccination among adolescents and young adults. General recommendations for the prevention of HB were made to orienteering federations (AU)