Ebola Virus Shedding and Transmission: Review of Current Evidence

BACKGROUND: The magnitude of the 2013-2016 Ebola virus disease outbreak in West Africa was unprecedented, with >28 500 reported cases and >11 000 deaths. Understanding the key elements of Ebola virus transmission is necessary to implement adequate infection prevention and control measures to protect healthcare workers and halt transmission in the community. METHODS: We performed an extensive PubMed literature review encompassing the period from discovery of Ebola virus, in 1976, until 1 June 2016 to evaluate the evidence on modes of Ebola virus shedding and transmission. FINDINGS: Ebola virus has been isolated by cell culture from blood, saliva, urine, aqueous humor, semen, and breast milk from infected or convalescent patients. Ebola virus RNA has been noted in the following body fluids days or months after onset of illness: saliva (22 days), conjunctiva/tears (28 days), stool (29 days), vaginal fluid (33 days), sweat (44 days), urine (64 days), amniotic fluid (38 days), aqueous humor (101 days), cerebrospinal fluid (9 months), breast milk (16 months [preliminary data]), and semen (18 months). Nevertheless, the only documented cases of secondary transmission from recovered patients have been through sexual transmission. We did not find strong evidence supporting respiratory or fomite-associated transmission

Treatment challenges associated with bone echinococcosis

Objectives In this literature review, we concentrate on epidemiology and therapy of osseous echinococcosis, with an emphasis on the recurrence risk. Methods Literature review 1930-2012. Results We retrieved 200 publications based upon single case reports or case series, mostly from resource-poor settings. Among the 721 rural patients (22% females; median age 37 years), 60% of all reported cases were from the Mediterranean region and almost all patients were immune competent. Echinococcus granulosus was identified as the most frequent species. Most infections involved a single bone (602/721; 83%) and often the spine (321 cases; 45%). In eight cases (8/702; 1%), a secondary bacterial surgical site infection was reported. Surgical intervention was performed in 702 cases (97%), with single intervention in 687 episodes (95%). Complete excision of the lesion was possible in only 117 episodes (16%). Albendazole was by far the most frequently used agent in monotherapy with various dosages, while mebendazole in monotherapy was less frequent (32 cases). The median duration of antihelminthic therapy was 6 months (range 0.7-144 months). There were 124 recurrences (17%) after a median delay of 2 years (range 0.4-17 years). In multivariate analysis, the presence of visceral organ involvement increased the odds of recurrence by 5.4 (95% CI 3.1-9.4), whereas the number of surgical interventions, the duration of antihelminthic therapy or the use of hypertonic saline did not influence recurrence. Conclusions Bone echinococcosis is a rare parasitic disease. While treatment modalities vary considerably, combined surgical and medical approaches are the standard of care with a 17% risk of recurrenc

E119D Neuraminidase Mutation Conferring Pan-Resistance to Neuraminidase Inhibitors in an A(H1N1)pdm09 Isolate From a Stem-Cell Transplant Recipient

Background. An influenza A(H1N1)pdm09 infection was diagnosed in a hematopoietic stem cell transplant recipient during conditioning regimen. He was treated with oral oseltamivir, later combined with intravenous zanamivir. The H275Y neuraminidase (NA) mutation was first detected, and an E119D NA mutation was identified during zanamivir therapy. Methods. Recombinant wild-type (WT) E119D and E119D/H275Y A(H1N1)pdm09 NA variants were generated by reverse genetics. Susceptibility to NA inhibitors (NAIs) was evaluated with a fluorometric assay using the 2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid (MUNANA) substrate. Susceptibility to favipiravir (T-705) was assessed using plaque reduction assays. The NA affinity and velocity values were determined with NA enzymatic studies. Results. We identified an influenza A(H1N1)pdm09 E119D mutant that exhibited a marked increase in the 50% inhibitory concentrations against all tested NAIs (827-, 25-, 286-, and 702-fold for zanamivir, oseltamivir, peramivir, and laninamivir, respectively). The double E119D/H275Y mutation further increased oseltamivir and peramivir 50% inhibitory concentrations by 790- and >5000-fold, respectively, compared with the WT. The mutant viruses remained susceptible to favipiravir. The NA affinity and velocity values of the E119D variant decreased by 8.1-fold and 4.5-fold, respectively, compared with the WT. Conclusions. The actual emergence of a single NA mutation conferring pan-NAI resistance in the clinical setting reinforces the pressing need to develop new anti-influenza strategie

Diagnostic Challenges in Acute Central Nervous System Infections in the 2020s

Acute central nervous system (CNS) infection can manifest as various distinct entities, according to the affected anatomic structures, hence the terms encephalitis, meningitis, meningoencephalitis, myelitis, encephalomyelitis, amongst others. Most of these syndromes are caused by viruses and bacteria, and less frequently by fungi and parasites. Some CNS diseases are caused by an aberrant immune response to microorganisms. Noninfectious CNS inflammation causes mimicking CNS infection include autoimmunity, as well as drug- related reactions. Given the numerous etiologies, which most often cannot be identified based on clinical manifestations, diagnosing CNS infections is challenging and requires broad knowledge in the field and sharp clinical sense, in order to appropriately tailor diagnostic and therapeutic strategies. This thesis comprises four original publications illustrating two aspects regarding the implication of routine and emerging diagnostic tools that can be used for viral CNS infection diagnosis. The first two deal with the use of high throughput sequencing (HTS) in cases of CNS inflammation of undetermined cause, and the last two exemplify how the judicious application of routine microbiological diagnostic means can help to decipher a complex CMV encephalitis case, as well as to extend the understanding of CNS disease caused by an emerging viral disease, such as COVID-19. This selected work is put into perspective with a more global approach aimed at improving and optimizing CNS infection diagnosis

Recombinaison expérimentale intra-et interespèce chez les Rhinovirus et Quantification d'ARN de Rhinovirus par RT-PCR en temps réel

Les rhinovirus sont des petits virus à ARN positif appartenant au genre Enterovirus de la famille des Picornaviridae, caractérisée par une importante variabilité génétique acquise par mutation et recombinaison. La première partie de cette thèse est consacrée à l'étude de la recombinaison des rhinovirus en utilisant des génomes chimériques synthétisés in vitro ainsi que la recombinaison non réplicative, résultant de la co-transfection de génomes défectifs complémentaires. Nous avons ainsi observé que la région 5'non codante est interchangeable entre membres d'espèces differentes, alors que seule la recombinaison intraespèce semble viable dans la région codante. Les sites de recombinaison obtenus sont décrits. La seconde partie de ce travail consiste en une analyse critique des erreurs possibles liées à la quantification d'ARN de rhinovirus dans des échantillons cliniques par RT-PCR en temps réel. Différentes expériences de validation montrent qu'une quantification relative est possible avec une marge d'erreur de plus ou moins 10%

Nécrose rétinienne aiguë due au virus de la varicelle et du zona et vaccin recombinant contre le zona

Varicella zoster virus (VZV) is responsible for chickenpox. Like all herpes viruses, after primary infection it enters into latency and can be reactivated afterwards. Many forms of symptomatic reactivation of VZV exist including acute retinal necrosis (ARN), an ophthalmic emergency which can lead to blindness. ARN is treated starting with high-dose intravenous acyclovir then with oral valaciclovir for a total duration of up to 3 months. Symptomatic reactivations of VZV are public health issues. The new Swiss 2022 vaccination plan includes the recombinant vaccine Shingrix. It effectively prevents VZV symptomatic reactivations even in elderly and immuno suppressed patients.Le virus de la varicelle et du zona (VZV) est responsable de la varicelle. Comme tous les virus herpétiques, après la primo-infection, il entre en latence et peut se réactiver plus tard. Il existe de nombreuses formes de réactivations symptomatiques du VZV, dont la nécrose rétinienne aiguë (NRA), qui est une urgence ophtalmique pouvant aboutir à la cécité. La NRA est traitée par aciclovir intraveineux à haute dose dans sa prise en charge initiale puis par valaciclovir per os pour une durée totale pouvant aller jusqu’à 3 mois. Les réactivations symptomatiques de VZV sont un enjeu de santé publique. Le nouveau plan de vaccination suisse 2022 intègre le vaccin recombinant Shingrix, qui permet de prévenir efficacement les réactivations symptomatiques de VZV chez les patients même âgés et immunosupprimés

Chimeric rhinoviruses obtained via genetic engineering or artificially induced recombination are viable only if the polyprotein coding sequence derives from the same species

Recombination is a widespread phenomenon that ensures both the stability and variation of RNA viruses. This phenomenon occurs with different frequencies within species of the Enterovirus genus. Intraspecies recombination is described frequently among non-rhinovirus enteroviruses but appears to be sporadic in rhinoviruses. Interspecies recombination is even rarer for rhinoviruses and mostly is related to ancient events which contributed to the speciation of these viruses. We reported that artificially engineered 5' untranslated region (UTR) interspecies rhinovirus/rhinovirus or rhinovirus/non-rhinovirus enterovirus recombinants are fully viable. Using a similar approach, we demonstrated in this study that exchanges of the P1-2A polyprotein region between members of the same rhinovirus species, but not between members of different species, give rise to competent chimeras. To further assess the rhinovirus intra- and interspecies recombination potential, we used artificially induced recombination by cotransfection of 5'-end-deleted and 3'-end-deleted and replication-deficient genomes. In this system, intraspecies recombination also resulted in viable viruses with high frequency, whereas no interspecies rhinovirus recombinants could be recovered. Mapping intraspecies recombination sites within the polyprotein highlighted recombinant hotspots in nonstructural genes and at gene boundaries. Notably, all recombinants occurring at gene junctions presented in-frame sequence duplications, whereas most intragenic recombinants were homologous. Taken together, our results suggest that only intraspecies recombination gives rise to viable rhinovirus chimeras in the polyprotein coding region and that recombination hotspots map to nonstructural genes with in-frame duplications at gene boundaries. These data provide new insights regarding the mechanism and limitations of rhinovirus recombination

Quelle place pour les stéroïdes dans le traitement des maladies infectieuses ?

The addition of a corticosteroid has become a common practice for the treatment of some infectious diseases, such as meningitis, septic shock, moderate to severe Pneumocystis jirovecii pneumonia. The belief that steroids may have a beneficial effect in the early stage of pro-inflammatory infections explains the renewed interest for these treatments. This review of recent literature helps determine the use of steroids in the treatment of infectious diseases as formal guidance, questionable or rather contraindicated. When there is a clear scientific indication for the use of corticosteroids regardless of the current infection, the latter is never a formal contraindication

Ebola: le point au crépuscule d'une épidémie inattendue

In one year, Ebola virus disease has already been responsible of around 10000 deaths. 24 patients have been medically evacuated in different University Hospitals in Europe or in the United States. One medical doctor, infected during a humanitarian mission in the field has been treated in Geneva at the end of 2014. This review aims to summarize the epidemiology of the current outbreak, to describe the main virological and clinical characteristics of Ebola virus disease, and to address the most important experimental treatments available. Although the number of cases has fallen the last two months, the outbreak is not over. A safe and proctective vaccine is still needed in the race to fight this emerging viral disease.La maladie à virus Ebola sévissant actuellement en Afrique de l’Ouest a fait près de 10 000 morts en une année. 24 patients ont été rapatriés en Europe ou aux Etats-Unis. Un médecin infecté sur le terrain au cours d’une mission humanitaire a été pris en charge aux Hôpitaux universitaires de Genève à la fin de l’année 2014. Cette revue a pour but de faire le point sur l’épidémiologie actuelle, d’exposer les principales caractéristiques virologiques, physiopathologiques, cliniques et diagnostiques de la maladie, et d’aborder les possibilités thérapeutiques. Bien que les derniers rapports épidémiologiques soient rassurants, l’épidémie n’est pas encore sous contrôle. Le développement d’un vaccin efficace et sûr reste nécessaire pour éviter une nouvelle crise humanitaire d’une telle ampleur