Human pegivirus identified in severe myelitis and optic neuritis in immunocompromised patients: A pathogenic role for a forgotten virus?

The role of Human pegivirus (HPgV) in patients with encephalitis has been recently questioned. We present cases of 4 patients with similar clinical, biological, and radiological characteristics, including a past history of transplantation with long-term immunosuppression and a progressive course of severe and predominantly myelitis, associated in 3 cases with optic neuropathy causing blindness. Extensive workup was negative but analysis of the CSF by use of pan-microorganism DNA- and RNA-based shotgun metagenomics was positive for HPgV. This case series further supports the hypothesis of HPgV CNS infection and highlights the utility of metagenomic next-generation sequencing of CSF in immunocompromised patients.

Cutaneous granulomas with primary immunodeficiency in children: a report of 17 new patients and a review of the literature.

BACKGROUND: Paediatric cutaneous granuloma with primary immunodeficiency (PID) is a rare condition. The physiopathology is unclear, and treatment is challenging. We report on 17 paediatric cases and review the literature. OBJECTIVES: To make dermatologists and dermatopathologists aware of the diagnostic value of skin granulomas in paediatric PID. METHODS: We collected data on 17 patients with cutaneous granulomas and PID registered with us and also reviewed 33 cases from the literature. RESULTS: Cutaneous granuloma was the presenting feature of the PID in 15 of the 50 collated cases. The lesions presented as red-brownish nodules and infiltrated ulcerative plaques, predominantly on the face and limbs. Scleroderma-like infiltration on a single limb was observed in 10% of the cases. The associated PID was ataxia-telangiectasia (52%), combined immunodeficiency (24%), cartilage-hair hypoplasia (6%) and other subtypes (18%). The granulomas were mostly sarcoidal, tuberculoid, palisaded or undefined subtypes. In some patients, several different histopathologic granulomatous patterns were found in the same biopsy. Some granulomas were associated with the presence of a vaccine strain of rubella virus. CONCLUSION: Cutaneous granulomas associated with a PID have a variable clinical presentation. A PID can be suspected when crusty, brownish lesions are found on the face or limbs. The concomitant presence of several histological subtypes in a single patient is suggestive of a PID.

Untargeted next-generation sequencing-based first-line diagnosis of infection in immunocompromised adults: a multicentre, blinded, prospective study.

OBJECTIVE: Infections are the major cause of morbidity and mortality in immunocompromised patients. Improving microbiological diagnosis in these patients is of paramount clinical importance. METHODS: We performed this multicentre, blinded, prospective, proof-of-concept study, to compare untargeted next-generation sequencing with conventional microbiological methods for first-line diagnosis of infection in 101 immunocompromised adults. Patients were followed for 30 days and their blood samples, and in some cases nasopharyngeal swabs and/or biological fluids, were analysed. At the end of the study, expert clinicians evaluated the results of both methods. The primary outcome measure was the detection rate of clinically relevant viruses and bacteria at inclusion. RESULTS: Clinically relevant viruses and bacteria identified by untargeted next-generation sequencing and conventional methods were concordant for 72 of 101 patients in samples taken at inclusion (κ test=0.2, 95% CI 0.03-0.48). However, clinically relevant viruses and bacteria were detected in a significantly higher proportion of patients with untargeted next-generation sequencing than conventional methods at inclusion (36/101 (36%) vs. 11/101 (11%), respectively, p <0.001), and even when the latter were continued over 30 days (19/101 (19%), p 0.003). Untargeted next-generation sequencing had a high negative predictive value compared with conventional methods (64/65, 95% CI 0.95-1). CONCLUSIONS: Untargeted next-generation sequencing has a high negative predictive value and detects more clinically relevant viruses and bacteria than conventional microbiological methods. Untargeted next-generation sequencing is therefore a promising method for microbiological diagnosis in immunocompromised adults.

Preface - Biological threat reduction.

It has been 11 years since the World Organisation for Animal Health (OIE) published a Scientific and Technical Review on bioterrorism, which was entitled 'Biological disasters of animal origin: The role and preparedness of veterinary and public health services'. Highlights of this issue included an overview and history of biological agent use, details of the threats that were prevalent at the time, a description of the available capabilities/tools to respond to such a threat, and a summary of the requirements/recommendations for ensuring preparedness to address the changing landscape over the next 20 years. Since the 2006 review, much in our world has changed. Although many of the same challenges related to biological agents remain, others have emerged. The world has experienced an increase in social unrest and war, and this has led to increased food insecurity and the displacement of entire populations of people from their homelands. We have witnessed an increase in the occurrence and severity of emerging pathogens (the Ebola virus outbreak in West Africa, 2014; the Zika virus outbreak in the Americas and Caribbean, 2015), an increase in antimicrobial resistance, and technological advances that have resulted in the ability to more easily produce a genetically engineered biological agent/weapon.

Onze années se sont écoulées depuis la publication par l'Organisation mondiale de la santé animale (OIE) du numéro spécial de la Revue scientifique et technique intitulé « Catastrophes biologiques d'origine animale : le rôle et la préparation des Services vétérinaires et de santé publique ¼. Ce numéro retraçait l'utilisation des agents biologiques dans l'histoire, définissait les menaces du monde contemporain, décrivait les capacités et les outils mobilisés pour répondre à cette menace et faisait le point sur les principaux critères et préconisations permettant de se préparer aux évolutions attendues des vingt années à venir. Notre monde a beaucoup changé depuis la publication en 2006 de cette première vue d'ensemble. Nombre des problèmes mis en lumière à l'époque en lien avec les agents biologiques restent toujours posés aujourd'hui ; s'y ajoutent de nouvelles problématiques d'apparition récente. Le monde est secoué de troubles sociaux et de conflits armés de plus en plus intenses qui accentuent l'insécurité alimentaire et l'exode de populations entières fuyant leur terre natale. Nous voyons émerger de nouveaux agents pathogènes dont la gravité et l'incidence ne cessent de croître (foyer dû au virus Ebola en Afrique occidentale en 2014 ; foyer dû au virus Zika dans les Amériques et dans les Caraïbes en 2015) tandis que le phénomène de la résistance aux agents antimicrobiens prend une ampleur de plus en plus inquiétante ; à cela s'ajoute le fait que la fabrication d'agents ou d'armes biologiques par manipulation génétique est désormais une procédure bien plus facile et accessible que par le passé, en raison des avancées technologiques.

Han pasado 11 años desde que la Organización Mundial de Sanidad Animal (OIE) publicó un número de su Revista científica y técnica dedicado al terrorismo biológico, que llevaba por título «Desastres biológicos de origen animal: papel y preparación de los servicios de sanidad animal y salud pública¼. Entre otros aspectos destacados, en aquel número se hacía un repaso histórico del uso de agentes biológicos generales, se definían las amenazas existentes a la sazón, se caracterizaban las capacidades y herramientas disponibles para conjurarlas y se formulaban una serie de requisitos o recomendaciones de preparación para afrontar el mudable panorama que parecía anunciarse para los veinte años subsiguientes. Desde aquel número de 2006, muchas cosas han cambiado en nuestro mundo. Aunque aún subsisten muchos de los problemas de entonces vinculados al uso de agentes biológicos, otros nuevos han surgido. El mundo ha conocido un incremento de los disturbios sociales y las guerras, lo que ha provocado una mayor inseguridad alimentaria y el desplazamiento de poblaciones enteras lejos de su tierra natal. Hemos asistido a una «explosión¼ de patógenos emergentes que causan afecciones de creciente gravedad (brote de enfermedad por el virus del Ebola en África Occidental en 2014; brote de enfermedad por el virus Zika en las Américas y el Caribe en 2015), a un incremento de las resistencias a los antimicrobianos y a progresos tecnológicos que nos capacitan para producir más fácilmente, por ingeniería genética, agentes (armas) biológicos.

Diversity of viruses in Ixodes ricinus, and characterization of a neurotropic strain of Eyach virus.

Ticks transmit more pathogens-including bacteria, parasites and viruses-than any other arthropod vector. Although the epidemiological status of many tick-borne bacteria is very well characterized, tick-borne viruses are still relatively under-studied. Recently, several novel tick-borne viruses have been isolated from human febrile illnesses following tick bites, indicating the existence of other potential new and unknown tick-borne viruses. We used high-throughput sequencing to analyse the virome of Ixodes ricinus, the main vector of tick-borne pathogens in Europe. The majority of collected viral sequences were assigned to two potentially novel Nairovirus and Phlebovirus viruses, with prevalence rates ranging from 3.95% to 23.88% in adults and estimated to be between 0.14% and 72.16% in nymphs. These viruses could not be isolated from the brains of inoculated immunocompromised mice, perhaps indicating that they are unable to infect vertebrates. Within the I. ricinus virome, we also identified contigs with >90% identity to the known Eyach virus. Initially isolated in the 1980s, this virus was indirectly associated with human disease, but had never been extensively studied. Eyach virus prevalence varied between 0.07% and 5.26% in ticks from the French Ardennes and Alsace regions. Eyach virus was successfully isolated following intracerebral inoculation of immunocompromised mice with Eyach virus-positive tick extracts. This virus was also able to multiply and persist in the blood of immunocompetent mice inoculated by intraperitoneal injection, and caused brain infections in three of nine juveniles, without any obvious deleterious effects.