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.

Phlebovirus-associated diseases transmitted by phlebotominae in Spain: Are we at risk?

The genera Phlebovirus transmitted by Diptera belonging to the Psychodidae family are a cause of self-limited febrile syndrome in the Mediterranean basin in summer and autumn. Toscana virus can also cause meningitis and meningoencephalitis. In Spain, Toscana, Granada, Naples, Sicily, Arbia and Arrabida-like viruses have been detected. The almost widespread distribution of Phlebotomus genus vectors, and especially Phlebotomus perniciosus, in which several of these viruses have been detected, makes it very likely that there will be regular human infections in our country, with this risk considered moderate for Toscana virus and low for the other ones, in areas with the highest vector activity. Most of the infections would be undiagnosed, while only Toscana virus would have a greater impact due to the potential severity of the illness.

Hantavirus Pulmonary Syndrome in Traveler Returning from Nepal to Spain.

Most human hantavirus infections occur in Asia, but some cases have been described in Europe in travelers returning from Asia. We describe a case of hantavirus pulmonary syndrome in a previously healthy traveler occurring shortly after he returned to Spain from Nepal. Serologic tests suggested a Puumala virus-like infection.

Rapid detection of important human pathogenic Phleboviruses.

BACKGROUND: Rapid diagnostics are not available for several human pathogens in the genus Phlebovirus of the Bunyaviridae. OBJECTIVES: To develop RT-PCR assays for Sandfly Fever Sicilian virus (SFSV), Sandfly Fever Naples virus (SFNV), Toscana virus (TOSV) and Rift Valley Fever virus (RVFV). STUDY DESIGN: RNA standards were generated and used to test the performance of the assays. RESULTS: A detection limit of 10-100 RNA molecules was determined for the SFSV, TOSV and RVFV assays. The sensitivity of the SFNV assay was not determined. The TOSV and the RVFV assays detected recent isolates from Spain and Africa, respectively. CONCLUSION: The assays should help to improve surveillance of pathogenic Phleboviruses.

Virus West Nile Antonio Tenorio / No disponible

Tras casi dos décadas de aparente silencio en Europa, el virus West Nile (WNV), un virus de aves transmitido por mosquitos, reapareció en 1996 en Bucarest, asociado por primera vez a un brote epidémico de encefalitis. Desde entonces, se ha ido describiendo en la mayor parte de los países del sur de Europa, del próximo Oriente y del norte de África. En 1999, el virus apareció por primera vez en América, en los alrededores de la ciudad de Nueva York, desde donde se expandió rápida y progresivamente por América del Norte y Central, hasta llegar a detectarse, siete años más tarde, en Buenos Aires y provincias limítrofes en la Argentina. Sorprendentemente, mientras el virus está aún causando en los EE.UU. la peor epidemia conocida de enfermedad por WNV, produce sólo brotes autolimitados en los países de la cuenca del Mediterráneo. El control de las futuras epidemias por WNV y por otros virus relacionados dependerá, en gran medida, del conocimiento que pueda ahora extraerse sobre los factores ecológicos, ambientales y sociales que influyen en el diferente comportamiento epidémico de la infección a uno y otro lado del Atlántico (AU)

After a twenty years period without described activity, the virus West Nile (WNV), an arthropod borne virus, re-emerged in Bucharest in 1996, associated to an outbreak of encephalitis. Since then, the virus has been described in most of the southern countries in Europe, the middle Orient and northern Africa. In 1999 the virus was described by the first time in America, around the New York City. Since then, the WNV spread through North, Central and South America, being described in Argentina in2006. Surprisingly, whereas the virus is causing its worst known epidemics in America, it is associated to small outbreaks in the Mediterranean basin. The control of future epidemics due to WNV and other related viruses depends on the study of the ecological, ambient and social factors influencing the distinct epidemic behaviour of the virus in the Old World and in the New World (AU)

Fiebre por el Virus Chikungunya / No disponible

El virus de Chikungunya (CHIKV) - género Alphavirus, familia Togaviridae -endémico en África y Asia, es transmitido al hombre por la picadura de mosquitos infectados, habitualmente del género Aedes. Las manifestaciones clínicas de la fiebre de Chikungunya (CHIKF), son, habitualmente, fiebre, mialgias, artralgias/artritis y exantema maculopapular generalizado. La enfermedad se autolimita en pocos días, pero las artralgias/artritis pueden seguir un curso crónico, de meses a años de duración. No existe tratamiento específico alguno, sólo sintomático (AU)

Chikungunya (CHIKV) virus -genus Alphavirus and family Togaviridaeendemicin Africa and Asia, is transmitted to humans by the bite of infected mosquitoes, usually of the genus Aedes. Clinical manifestations, Chikungunya fever (CHIKF), are, usually, fever,muscle pain, arthralgias/arthritis, and maculopapular rash. Disease isself limited in few days, but arthralgias - arthritis may last several months/years. Management is supportive with respect to the arthralgias (AU)

[Meningitis by Toscana virus in Spain: description of 17 cases]. / Meningitis por el virus Toscana en España: descripción de 17 casos.

BACKGROUND AND OBJECTIVE: We aimed to analyze the clinical and epidemiological data from the first series of patients with meningitis by Toscana virus in Spain. PATIENTS AND METHOD: We analyzed a total of 724 cerebrospinal fluid (CSF) samples from patients with suspicion of aseptic meningitis for virus isolation in cell culture. The clinical records of patients in whom Toscana virus was isolated were analyzed. RESULTS: Toscana virus was isolated in CSF in 17 patients (7% of all viral isolates). The first case was diagnosed in June 1988 and the last one in August 2002. The mean age was 27 years (range: 10-64 years). Most patients were based in rural area (n = 11, 64.7%). Most common symptoms were headache (holocranial or focal) present in all patients and moderate fever observed in 76.5% of them with a mean duration of 48 h (range: 18 h-5 days). Nuchal rigidity was present in 9 patients (53%). All cases were seen between June and October, and predominantly in August (53%). The outcome was favorable in all cases, and the mean time of duration of the disease was 7 days (range: 3-10 days). CONCLUSIONS: Toscana virus must be taken into account among those agents responsible of lymphocytic meningitis in Spain.

Meningitis por el virus Toscana en España: descripción de 17 casos / Meningitis by Toscana virus in Spain: description of 17 cases

FUNDAMENTO Y OBJETIVO: Hemos analizado los datos clínicos y epidemiológicos de los primeros 17 casos de meningitis por el virus Toscana en España. PACIENTES Y MÉTODO: Se procesaron 724 muestras de líquido cefalorraquídeo de pacientes con sospecha de meningitis aséptica para aislamiento de virus en cultivo celular, y se analizaron las historias clínicas de los pacientes con aislamiento del virus Toscana. RESULTADOS: Se aisló el virus Toscana en el líquido cefalorraquídeo de 17 pacientes (7 por ciento de los aislamientos virales). El primer caso se diagnosticó en junio de 1988 y el último en agosto de 2002. La edad media fue de 27 años (intervalo, 10-64 años). La mayoría de los pacientes procedían del medio rural (n = 11; 64,7 por ciento). Los síntomas predominantes fueron la cefalea (holocraneal o focalizada), que se presentó en todos los pacientes, y fiebre moderada, que apareció en el 76,5 por ciento, con una duración media de 48 h (intervalo, 18 h-5 días). La rigidez de nuca se presentó en 9 enfermos (53 por ciento). Todos los casos se presentaron en los meses comprendidos entre junio y octubre, con predominio en el mes de agosto (53 por ciento). La evolución fue buena en todos los casos, con un tiempo medio de duración de la enfermedad de 7 días (intervalo, 3-10 días). CONCLUSIONES: El virus Toscana debe considerarse entre los agentes causantes de meningitis linfocitaria en España (AU)