Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa

West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded. Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a two-year-old boy in December 2013 (ref. 2). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak.status: publishe

Exonuclease domain of the Lassa virus nucleoprotein is critical to avoid RIG-I signaling and to inhibit the innate immune response

International audienceLassa virus (LASV), which causes a viral hemorrhagic fever, inhibits the innate immune response. The exonuclease (ExoN) domain of its nucleoprotein (NP) is implicated in the suppression of retinoic acid-inducible gene I (RIG-I) signaling. We show here that a LASV in which ExoN function has been abolished strongly activates innate immunity and that this effect is dependent on RIG-I signaling. These results highlight the key role of NP ExoN function in the immune evasion that occurs during LASV infection

Ebola viral dynamics in nonhuman primates provides insights into virus immuno-pathogenesis and antiviral strategies

Optimization of antiviral therapy can be crucial in the management of Ebola virus outbreaks. Here, Madelain et al. use an integrative mathematical model to correlate the dose and the time of treatment initiation with survival rate, enhanced immune response and viral clearance

SURVEILLANCE DES INFECTIONS HUMAINES PAR HANTAVIRUS EN FRANCE MÉTROPOLITAINE, 2012-2016

International audienceSurveillance of human hantavirus infection has been carried out for about 30 years in mainland France. From 2012-2016, a network of 15 clinical laboratories, the National Reference Center (NRC) for Hantavirus and the French Public Health Agency (Santé publique France) were involved in the surveillance. Data were obtainedfrom the analysis of the information sheet records of the hantavirus cases diagnosed by the laboratory network and confirmed by the NRC.The global situation was similar as the ones observed in the previous periods: an average of about one hundred cases, mostly hospitalized, was reported annually (incidence of 0.15 case per 100,000 inhabitants) with high annual variations. Active people were more concerned (median age 40 years), and were mostly males (75% of the cases). Cases were detected all year round with peaks of detection at the end of spring and at fall. Most of the cases were due to Puumala virus, but interestingly Seoul and Tula viruses were also detected, underlying other high-risk behavior. The geographic distribution of the cases in the North-Eastern quarter of France had a limited peripheral extension. However, this incidence and this geographic distribution are probably under-estimated because of the use of too specific serological diagnostic tests, and the low request of laboratory tests outside the hantavirus endemic area or for outpatients.Les infections par les hantavirus chez l'homme font l'objet d'une surveillance en France, en particulier en métropole, depuis une trentaine d'années. Cette surveillance associait sur la période 2012-2016 un réseau d'une quinzaine de laboratoires de biologie médicale, le Centre national de référence (CNR) des Hantavirus et Santé publique France. Les données de surveillance ont été obtenues par l'analyse des fiches de renseignements accompagnant les échantillons des cas diagnostiqués par les laboratoires du réseau et confirmés par le CNR. La situation observée était proche de celles rapportées pour les périodes précédentes : une centaine de cas, la plupart hospitalisés, était dénombrée en moyenne annuellement (incidence de 0,15 cas pour 100 000 habitants) avec de fortes variations annuelles. La population active était toujours la plus touchée (médiane d'âge de 40 ans) et les hommes étaient les plus concernés (75% des cas). Les cas étaient détectés toute l'année, avec des pics de détection à la fin du printemps ou à l'automne. La majorité des cas étaient dus au virus Puumala, mais le fait marquant sur la période était la détection de cas d'infection par les virus Seoul et Tula et la nature des expositions à ces virus. La distribution géographique des cas, concentrée sur le quart nord-est de la France, a connu une extension très limitée dans sa périphérie. Cependant, cette incidence et cette distribution géographique pourraient être sous-estimées du fait de l'utilisation de tests de diagnostic sérologique trop spécifiques et de la faible demande de diagnostic pour des patients non hospitalisés ou en dehors de la zone d'endémie connue

Clinical, virological, and biological parameters associated with outcomes of Ebola virus infection in Macenta, Guinea

International audienceBACKGROUND. The pathogenesis of Ebola virus (EBOV) disease (EVD) is poorly characterized. The establishment of well-equipped diagnostic laboratories close to Ebola treatment centers (ETCs) has made it possible to obtain relevant virological and biological data during the course of EVD and to assess their association with the clinical course and different outcomes of the disease. METHODS. We were responsible for diagnosing EBOV infection in patients admitted to two ETCs in forested areas of Guinea. The pattern of clinical signs was recorded, and an etiological diagnosis was established by RT-PCR for EBOV infection or a rapid test for malaria and typhoid fever. Biochemical analyses were also performed. RESULTS. We handled samples from 168 patients between November 29, 2014, and January 31, 2015; 97 patients were found to be infected with EBOV, with Plasmodium falciparum coinfection in 18%. Overall mortality for EVD cases was 58%, rising to 86% if P. falciparum was also present. Viral load was higher in fatal cases of EVD than in survivors, and fatal cases were associated with higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT), C-reactive protein (CRP), and IL-6 levels. Furthermore, regardless of outcome, EVD was characterized by higher creatine kinase (CPK), amylase, and creatinine levels than in febrile patients without EVD, with higher blood urea nitrogen (BUN) levels in fatal cases of EVD only. CONCLUSION. These findings suggest that a high viral load at admission is a marker of poor EVD prognosis. In addition, high AST, ALT, CRP, and IL-6 levels are associated with a fatal outcome of EVD. Damage to the liver and other tissues, with massive rhabdomyolysis and, probably, acute pancreatitis, is associated with EVD and correlated with disease severity. Finally, biochemical analyses provide substantial added value at ETCs, making it possible to improve supportive rehydration and symptomatic care for patients. FUNDING. The French Ministry of Foreign Affairs, the Agence Française de Développement, and Institut Pasteur

Analysis of diagnostic findings from the european mobile laboratory in Gueckedou, Guinea, march 2014 through march 2015

A unit of the European Mobile Laboratory (EMLab) consortium was deployed to the Ebola virus disease (EVD) treatment unit in Guéckédou, Guinea, from March 2014 through March 2015.; The unit diagnosed EVD and malaria, using the RealStar Filovirus Screen reverse transcription-polymerase chain reaction (RT-PCR) kit and a malaria rapid diagnostic test, respectively.; The cleaned EMLab database comprised 4719 samples from 2741 cases of suspected EVD from Guinea. EVD was diagnosed in 1231 of 2178 hospitalized patients (57%) and in 281 of 563 who died in the community (50%). Children aged <15 years had the highest proportion of Ebola virus-malaria parasite coinfections. The case-fatality ratio was high in patients aged <5 years (80%) and those aged >74 years (90%) and low in patients aged 10-19 years (40%). On admission, RT-PCR analysis of blood specimens from patients who died in the hospital yielded a lower median cycle threshold (Ct) than analysis of blood specimens from survivors (18.1 vs 23.2). Individuals who died in the community had a median Ct of 21.5 for throat swabs. Multivariate logistic regression on 1047 data sets revealed that low Ct values, ages of <5 and ≥45 years, and, among children aged 5-14 years, malaria parasite coinfection were independent determinants of a poor EVD outcome.; Virus load, age, and malaria parasite coinfection play a role in the outcome of EVD

Analysis of diagnostic findings From the European mobile laboratory in Guéckédou, Guinea, March 2014 through March 2015

 A unit of the European Mobile Laboratory (EMLab) consortium was deployed to the Ebola virus disease (EVD) treatment unit in Guéckédou, Guinea, from March 2014 through March 2015.status: publishe

Unique human immune signature of Ebola virus disease in Guinea.

Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology

Correction: Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea.

[This corrects the article DOI: 10.1371/journal.pmed.1001967.]