¿Es el filovirus Lloviu una amenaza para la salud mundial?

Artículo de divulgación publicado en The Conversation España el día 18/05/2022.Muchos medios aseguran que el virus Lloviu, hallado en Asturias y estudiado ahora por investigadores húngaros, es una amenaza para la salud humana, y hasta el potencial causante de una pandemia. ¿Hay razones objetivas para semejantes temores?N

Long-term survival in a patient with progressive multifocal leukoencephalopathy after therapy with rituximab, fludarabine and cyclophosphamide for chronic lymphocytic leukemia

A 50-year-old male with chronic lymphocytic leukemia (CLL) was treated with fludarabine, cyclophosphamide and rituximab, which produced a complete remission. Eight months after the last dose of rituximab he had visual disturbance, diminished muscular strength in the right arm and vesicular-papular lesions in the left ophthalmic branch region of the V cranial nerve. These were initially interpreted as herpes virus encephalopathy (HVE), but brain magnetic resonance imaging (MRI) showed evidence of demyelination consistent with progressive multifocal leukoencephalopathy (PML). Cerebrospinal fluid (CSF) analysis was negative for varicella zoster virus (VZV) and John Cunningham virus (JCV) DNA. The clinical suggestion of PML prompted us to perform a brain biopsy and to start treatment with mefloquine. In the brain biopsy, histopathological features of demyelination were described and the polymerase chain reaction (PCR) identified JCV, confirming the diagnosis of PML. Treatment with mefloquine (250 mg/week) and dexamethasone (4 mg/day) was started and maintained for 6 months. A year later there was an almost complete resolution of the MRI lesions and the patient achieved a stable clinical state with persisting motor impairment and severe epilepsy. The patient is alive 38 months after diagnosis of PML, which is the longest known survival to date.Supported by grants from the Fondo de Investigaciones Sanitarias - Ministerio de Ciencia e Innovación (PI12/1832), Plan Nacional of I + D + I co-financed by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER). HG has a grant from Fundación BBVA - Fundación Carolina.S

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.This work was supported by a grant from Instituto de Salud Carlos III. Project code MPY1372/12. The journal’s Rapid Service fee was paid by Consorcio Centro de Investigación en Red (CIBER). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Programas de Vigilancia Microbiológica. Centro Nacional de Microbiología

Este libro recoge en pequeñas “cápsulas” de unas pocas páginas la información condensada de los Programas de Vigilancia Microbiológica del CNM en los últimos años. Una de las principales actividades del Centro Nacional de Microbiología (CNM) se fundamenta en dar soporte al Sistema Nacional de Salud en el control y prevención de las enfermedades infecciosas, incluyendo la detección precoz de infecciones emergentes o infrecuentes, de nuevas variantes problemáticas de agentes infecciosos más comunes, y la caracterización de brotes. Todo ello forma parte de la vigilancia microbiológica, que en el CNM se estructura en torno a los Programas de Vigilancia que abordan la mayoría de los principales microorganismos patógenos para el ser humano.Programa de Enfermedad Meningocócica Invasiva. Programa de Listeriosis. Programa de Infección Gonocócica. Sensibilidad Antimicrobiana, 1991-2020. Programa de Streptococcus pneumoniae. Programa de enfermedad invasiva por Streptococcus pyogenes. Programa de Haemophilus influenzae. Programa de Resistencia a Antibióticos. Programa de infecciones producidas por los estafilococos. Programa de infecciones entéricas bacterianas transmitidas por agua y alimentos. Programa de Legionelosis. Programa de infecciones causadas por especies toxigénicas del género Corynebacterium. Programa de resistencias en el complejo tuberculoso. Programa de micobacterias no tuberculosas. Programa de GRIPE. Programa de SARS-CoV-2. Programa de Enterovirus y Parálisis Flácida en menores de 15 años. Programa de Parotiditis. Programa de Sarampión y Rubeola. Enfermedades víricas transmitidas por vectores. Programa de Rabia. Programa de Variantes del Virus de la Hepatitis B de Impacto en Salud Pública y Estudio de Brotes de Hepatitis. Programa de Leishmaniasis Humana en el Area-9 de la Comunidad Autónoma de Madrid. Programa de la Enfermedad de Chagas. Programa de la Resistencia a los antifúngicos en España.N

Varicella-zoster virus clades circulating in Spain over two decades

BACKGROUND: Despite childhood universal VZV immunization was introduced in 2015, there are no data on VZV clade distribution in Spain. OBJECTIVES: To characterize the varicella-zoster virus strains circulating in Spain between 1997 and 2016. STUDY DESIGN: In this retrospective study, we determined the VZV clades in 294 patients with different pathologies (mainly encephalitis, zoster and varicella) by sequencing three fragments within ORF 22, ORF 21 and ORF 50 and, subsequently analyzing 7 relevant SNPs. RESULTS: Among these 294 patients, 132(44.9%) patients were infected by clade 1, 42(14.3%) patients by clade 3, 19(6.5%) by clade 5, 29(9.9%) by clade VI and 3(1%) by clade 4. Four patients (1.4%) were infected by clade 2 vOKA strains, who received one dose of live-attenuated varicella vaccine. Putative recombinant clade 1/3 was identified in 6 cases (2.0%). Results obtained from partial sequences were assigned to clade 1 or 3 in 56(19%) patients and clade 5 or VI in 3(1.0%) patients. In the multivariate analysis, encephalitis was independently associated with clades 1 and 3 and age >14y.o. (P = 0.035 and P = 0.021, respectively). Additionally, Madrid had significant fewer cases of encephalitis compared with the rest of regions analyzed (P = 0.001). CONCLUSIONS: Higher prevalence of clades 1 and 3 and their relation with encephalitis and age >14y.o. suggest earlier introduction of this clades in Spain. Putative interclade 1 and 3 recombinants are circulating in patients with encephalitis, herpes zoster and varicella. Several cases were related to vOKA vaccination but vaccine strains do not seem to circulate in the general population.This work was supported by a grant from Instituto de Salud Carlos III. Project code MPY1372/12. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Enteroviruses in Spain: virological and epidemiological studies over 10 years (1988-97)

A total of 15,662 clinical samples were analysed for enterovirus (EV) isolation in cell cultures during a 10-year period (1988-97). Furthermore, 210 isolates of EV obtained in primary laboratories within Spain from patients with meningitis were characterized. The total number of EV typed was 758, including 727 non-polio EV and 31 Sabin-like (SL) polioviruses. Twenty-eight EV serotypes were represented. Echoviruses comprised 90% (653/727) of fully typed non-polio EV. The four most prevalent serotypes were echovirus 30, echovirus 9, echovirus 6 and echovirus 4. Echovirus 30 was the main serotype associated with meningitis. Echovirus 9 was the aetiological agent in 20 outbreaks of meningitis while the occurrence of echovirus 6 was localized in 1 year (1997). Coxsackieviruses A and B occurred in 3 and 7% of the non-polio EV respectively. Coxsackievirus B5 presented the relative greater abundance. This paper examines the epidemiology of EV in Spain to serotype level over a 10-year period with special attention to non-polio EV associated with meningitis.Dr I. Casas is a postdoctoral fellow supported by the Institute de Salud Carlos III, Becas de Perfeccionamiento (97/4165). We acknowledge the assistance provided by clinical colleagues in other virology laboratories: Gurutze Rubio (Cruces, Bilbao, Hospital), Nuria Rabella (Santa Cruz y San Pablo, Barcelona Hospital), Joaquin Otero (Doce de Octubre, Madrid Hospital). We also thank Raquel Noguerol, Hortensia del Pozo and Isidoro Bustillo for their technical assistance and an anonymous referee for many useful suggestions. This work was partially supported by Fondo de Investigación Sanitaria grant FIS 96/0304.S

Measles in Vaccinated People: Epidemiology and Challenges in Surveillance and Diagnosis in the Post-Elimination Phase. Spain, 2014-2020

The MMR vaccination program was introduced in Spain in 1981. Consistently high vaccination coverage has led to Spain being declared free of endemic measles transmission since 2014. A few imported and import-related cases were reported during the post-elimination phase (2014 to 2020), with very low incidence: three cases per million of inhabitants a year, 70% in adults. In the post-elimination phase an increasing proportion of measles appeared in two-dose vaccinated individuals (up to 14%), posing a challenge to surveillance and laboratory investigations. Severity and clinical presentation were milder among the vaccinated. The IgM response varied and the viral load decreased, making the virus more difficult to detect. A valid set of samples (serum, urine and throat swab) is strongly recommended for accurate case classification. One third of measles in fully vaccinated people was contracted in healthcare settings, mainly in doctors and nurses, consistent with the important role of high intensity exposure in measles breakthrough cases. Surveillance protocols and laboratory algorithms should be adapted in advanced elimination settings. Reinforcing the immunity of people working in high exposure environments, such as healthcare settings, and implementing additional infection control measures, such as masking and social distancing, are becoming crucial for the global aim of measles eradication.This research was funded by the “Instituto de Salud Carlos III” and is one of the objectives of Research Project number PI19ICIII/0041.S

Anodic oxidation of titanium for implants and prothesis: processing characterization and potential improvement of osteointegration

Among all biomaterials used for bone replacement, it is recognized that both commercially pure titanium (Ti c.p.) and Ti6Al4V alloy are the materials that show the best in vivo performance due to their excellent balance between mechanical, physical-chemical and biofunctional properties. However, one of its main drawbacks, which compromise the service reliability of the implants and its osteointegration capacity, is the thin film of fibrous tissue around the implant due to the bioinert behaviour of titanium. One of the alternatives more studied to improve the titanium osteointegration is the surface modification through the control of the roughness parameters within a specific range which is recognized that improve the osteoblasts adhesion. In this work is investigated the influence of different electrochemical processing conditions for surface modification of c.p. Ti, in their microstructural, morphological, topographical and mechanical properties, as well as in their biological behaviour. The electrochemical anodizing treatment was performed by using different electrolytes based on phosphoric acid (H3PO4), sulphuric acid (H2SO4) with a fluoride salt; and the Focused Ion Beam (FIB) technique, normally named as Nanolab, was used for the microstructural, chemical and morphological characterization, as well as the confocal laser microscopy technique which also served for roughness measurements. The mechanical response of the anodic layers was evaluated through the using of a scratch tester which showed the critical loads for the coating damages. The characterization results showed that both, concentrations and electrolyte species, clearly influenced the morphological and topographical features, as well as the chemical composition of the anodic layer. By using the FIB was possible to detect nanopores within both the surface and the bulk of the coating. Some of the conditions generated a very special coating morphology which promoted a better osteoblasts adhesion. Contrary to what it was a priory expected, all anodic coatings showed high critical loads for damages during scratch test, despite their high porosity, which could be related with some defects coalescence mechanism that allows dissipating the high stress concentration applied during the test.Postprint (published version

Utility of MF-non coding region for measles molecular surveillance during post-elimination phase, Spain, 2017-2020

Background: In countries entering the post-elimination phase for measles, the study of variants by sequencing of 450 nucleotides of the N gene (N450) does not always allow the tracing of chains of transmission. Indeed, between 2017 and 2020, most measles virus sequences belonged to either the MVs/Dublin.IRL/8.16 (B3-Dublin) or the MVs/Gir Somnath.IND/42.16 (D8-Gir Somnath) variants. We evaluated the additional use of a non-coding region (MF-NCR) as a tool to enhance resolution and infer case origin, chains of transmission and characterize outbreaks. Methods: We obtained 115 high-quality MF-NCR sequences from strains collected from Spanish patients infected with either B3-Dublin or D8-Gir Somnath variants between 2017 and 2020, performed epidemiological, phylogenetic and phylodynamic analyses and applied a mathematical model to determine relatedness among identified clades. Results: Applying this model allowed us to identify phylogenetic clades potentially derived from concomitant importations of the virus rather than single chain of transmission, inferred based on only N450 and epidemiology data. In a third outbreak, we found two related clades that corresponded to two chains of transmission. Discussion: Our results show the ability of the proposed method to improve identification of simultaneous importations in the same region which could trigger enhanced contact tracing. Moreover, the identification of further transmission chains indicates that the size of import-related outbreaks was smaller than previously found, supporting the interpretation that endemic measles transmission was absent in Spain between 2017 and 2020. We suggest considering the use of the MF-NCR region in conjunction with the study of N450 variants in future WHO recommendations for measles surveillance.This work was supported by the “Instituto de Salud Carlos III” (PI15CIII/00023, PI19ICIII/0041). AG was funded by CIBER de Epidemiología y Salud Pública (CIBERESP), ISCIII. CJ was funded by the ECDC/EUPHEM fellowship.S

Rare Recombinant GI.5[P4] Norovirus That Caused a Large Foodborne Outbreak of Gastroenteritis in a Hotel in Spain in 2021

Noroviruses are among the most important causes of acute gastroenteritis (AGE). In summer 2021, a large outbreak of norovirus infections affecting 163 patients, including 15 norovirus-confirmed food handlers, occurred in a hotel in Murcia in southeast Spain. A rare GI.5[P4] norovirus strain was identified as the cause of the outbreak. The epidemiological investigation determined that norovirus transmission might have been initiated through an infected food handler. The food safety inspection found that some symptomatic food handlers continued working during illness. Molecular investigation with whole-genome and ORF1 sequencing provided enhanced genetic discrimination over ORF2 sequencing alone and enabled differentiation of the GI.5[P4] strains into separate subclusters, suggesting different chains of transmission. These recombinant viruses have been identified circulating globally over the last 5 years, warranting further global surveillance. IMPORTANCE Due to the large genetic diversity of noroviruses, it is important to enhance the discriminatory power of typing techniques to differentiate strains when investigating outbreaks and elucidating transmission chains. This study highlights the importance of (i) using whole-genome sequencing to ensure genetic differentiation of GI noroviruses to track chains of transmission during outbreak investigations and (ii) the adherence of symptomatic food handlers to work exclusion rules and strict hand hygiene practices. To our knowledge, this study provides the first full-length genome sequences of GI.5[P4] strains apart from the prototype strain.We thank the Genomics and Bioinformatic Departments at the ISCIII for technical assistance. This study was partially funded through project PI20CIII/00005.S