Publications by authors named "Pauline Vetter"

23 Publications

  • Page 1 of 1

Feasibility and safety of rVSV-ZEBOV vaccination of humanitarian health workers against Ebola virus disease: an observational study.

J Travel Med 2021 Jun 15. Epub 2021 Jun 15.

Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 6, Geneva 1205, Switzerland.

Background And Rationale: Geneva University Hospitals were granted a temporary authorization to administer the recombinant live vesicular stomatitis virus rVSV-ZEBOV (Ervebo®) vaccine to expatriate humanitarian frontline workers (FLWs) prior to mission deployment.

Objectives: Our aims were to assess the feasibility of FLW vaccination before deployment and to report adverse events (AEs).

Methods: FLWs received a single injection of rVSV-ZEBOV (>7.2E7 plaque forming unit) during their pre-deployment medical check-up at the Travel Medicine Clinic of the Geneva University Hospitals (Day 0). A safety questionnaire regarding potential AEs was emailed to FLWs on Days 3 and 21. Early and delayed AEs were those starting within 3 or 21 days of vaccination, respectively.

Results: Between 1 August 2019 and 30 June 2020, 124 FLWs received the rVSV-ZEBOV vaccine. Eighty-six volunteers (86/124; 69%) received a concomitant vaccine. The response rate to the follow-up questionnaire was 88 and 55% at Days 3 and 21, respectively. Most respondents (105/109; 96.3%), experienced at least one AE, with a mean of three (±SD 1.75) AEs per person. The most common AE was injection site pain, followed by fever (53/109; 48.6%), fatigue (51/109; 46.7%) and myalgia (49/109; 44.9%). Most early AEs (360/377; 95.4%) resolved within 3 days, reflecting vaccine reactogenicity. Delayed AEs were reported by 6/69 (7.2%) subjects, the median time to symptom onset was 11 days (range: 5-14); half of them were joint-related AEs (3/6). Four serious adverse events (SAE) were observed: two cases of high grade fever, one rash and one case of arthritis. Two suspected unexpected serious adverse reactions were observed: one case of continuing recurrent transient dizziness and fatigue considered related to the vaccine; and one case of presbyopia that was deemed unrelated.

Conclusion: AEs to rVSV-ZEBOV were common but in general transient and were well tolerated, pre-deployment rVSV-ZEBOV vaccination in FLW is feasible and can be included with pre-mission check-up.
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http://dx.doi.org/10.1093/jtm/taab086DOI Listing
June 2021

Risk of reinfection after seroconversion to SARS-CoV-2: A population-based propensity-score matched cohort study.

Clin Infect Dis 2021 May 27. Epub 2021 May 27.

Division of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland.

Background: Serological assays detecting anti-SARS-CoV-2 antibodies are being widely deployed in studies and clinical practice. However, the duration and effectiveness of the protection conferred by the immune response remains to be assessed in population-based samples. To estimate the incidence of newly acquired SARS-CoV-2 infections in seropositive individuals as compared to seronegative controls we conducted a retrospective longitudinal matched study.

Methods: A seroprevalence survey including a representative sample of the population was conducted in Geneva, Switzerland between April and June 2020, immediately after the first pandemic wave. Seropositive participants were matched one-to-two to seronegative controls, using a propensity-score including age, gender, immunodeficiency, BMI, smoking status and education level. Each individual was linked to a state-registry of SARS-CoV-2 infections. Our primary outcome was confirmed infections occurring from serological status assessment to the end of the second pandemic wave (January 2021).

Results: Among 8344 serosurvey participants, 498 seropositive individuals were selected and matched with 996 seronegative controls. After a mean follow-up of 35.6 (SD 3.2) weeks, 7 out of 498 (1.4%) seropositive subjects had a positive SARS-CoV-2 test, of whom 5 (1.0%) were classified as reinfections. In contrast, the infection rate was higher in seronegative individuals (15.5%, 154/996) during a similar follow-up period (mean 34.7 [SD 3.2] weeks), corresponding to a 94% (95%CI 86% to 98%, P<0.001) reduction in the hazard of having a positive SARS-CoV-2 test for seropositives.

Conclusions: Seroconversion after SARS-CoV-2 infection confers protection against reinfection lasting at least 8 months. These findings could help global health authorities establishing priority for vaccine allocation.
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http://dx.doi.org/10.1093/cid/ciab495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241483PMC
May 2021

Novel SARS-CoV-2 variants: the pandemics within the pandemic.

Clin Microbiol Infect 2021 Aug 17;27(8):1109-1117. Epub 2021 May 17.

Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, 1205 Geneva, Switzerland; Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals & Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland.

Background: Many new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been termed variants of concern/interest (VOC/I) because of the greater risk they pose due to possible enhanced transmissibility and/or severity, immune escape, diagnostic and/or treatment failure, and reduced vaccine efficacy.

Aims: We sought to review the current knowledge of emerging SARS-CoV-2 variants, particularly those deemed VOC/Is: B.1.351, B.1.1.7, and P.1.

Sources: MEDLINE and BioRxiv databases, as well as the grey literature, were searched for reports of SARS-CoV-2 variants since November 2020. Relevant articles and their references were screened.

Content: Mutations on the spike protein in particular may affect both affinity for the SARS-CoV-2 cell receptor ACEII and antibody binding. These VOC/Is often share similar mutation sets. The N501Y mutation is shared by the three main VOCs: B.1.1.7, first identified in the United Kingdom, P.1, originating from Brazil, and B.1.351, first described in South Africa. This mutation likely increases transmissibility by increasing affinity for ACEII. The B.1.351 and P.1 variants also display the E484K mutation which decreases binding of neutralizing antibodies, leading to partial immune escape; this favours reinfections, and decreases the in vitro efficacy of some antibody therapies or vaccines. Those mutations may also have phenotypical repercussions of greater severity. Furthermore, the accumulation of mutations poses a diagnostic risk (lowered when using multiplex assays), as seen for some assays targeting the S gene. With ongoing surveillance, many new VOC/Is have been identified. The emergence of the E484K mutation independently in different parts of the globe may reflect the adaptation of SARS-CoV-2 to humans against a background of increasing immunity.

Implications: These VOC/Is are increasing in frequency globally and pose challenges to any herd immunity approach to managing the pandemic. While vaccination is ongoing, vaccine updates may be prudent. The virus continues to adapt to transmission in humans, and further divergence from the initial Wuhan sequences is expected.
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http://dx.doi.org/10.1016/j.cmi.2021.05.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127517PMC
August 2021

Clinical, virologic and immunologic features of a mild case of SARS-CoV-2 reinfection.

Clin Microbiol Infect 2021 Feb 20. Epub 2021 Feb 20.

Geneva Centre for Emerging Viral Diseases, Geneva, Switzerland; Laboratory of Virology, Division of Laboratory Medicine, Geneva, Switzerland.

Objectives: To report a case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection 6 months after the first infection in a young healthy female physician. Both episodes led to mild coronavirus disease 2019 (COVID-19).

Methods: SARS-CoV-2 infections were detected by real-time reverse transcriptase PCR (RT-PCR) on nasopharyngeal specimens. Reinfection was confirmed by whole-genome sequencing. Kinetics of total anti-S receptor binding domain immunoglobulins (Ig anti-S RBD), anti-nucleoprotein (anti-N) and neutralizing antibodies were determined in serial serum samples retrieved during both infection episodes. Memory B-cell responses were assessed at day 12 after reinfection.

Results: Whole-genome sequencing identified two different SARS-CoV-2 genomes both belonging to clade 20A, with only one nonsynonymous mutation in the spike protein and clustered with viruses circulating in Geneva (Switzerland) at the time of each of the corresponding episodes. Seroconversion was documented with low levels of total Ig anti-S RBD and anti-N antibodies at 1 month after the first infection, whereas neutralizing antibodies quickly declined after the first episode and then were boosted by the reinfection, with high titres detectable 4 days after symptom onset. A strong memory B-cell response was detected at day 12 after onset of symptoms during reinfection, indicating that the first episode elicited cellular memory responses.

Conclusions: Rapid decline of neutralizing antibodies may put medical personnel at risk of reinfection, as shown in this case. However, reinfection leads to a significant boosting of previous immune responses. Larger cohorts of reinfected subjects with detailed descriptions of their immune responses are needed to define correlates of protection and their duration after infection.
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http://dx.doi.org/10.1016/j.cmi.2021.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896115PMC
February 2021

[Treatment of SARS-CoV-2 in paediatrics : what is the evidence to date?]

Rev Med Suisse 2021 Feb;17(726):344-348

Service de pédiatrie générale, Département de la femme, de l'enfant et de l'adolescent, HUG, 1211 Genève 14.

Although SARS-CoV-2 infects individuals of all ages, children show less severe symptoms. Nevertheless, the very rare COVID-19 severe cases in paediatrics require our full attention. Much research has been conducted and is still ongoing on effective treatments. On the antiviral front, no molecule has been proven effective yet and the results of several studies on the benefit of monoclonal antibodies and convalescent plasma are pending. On the side of immunomodulators, the benefit of steroids has been demonstrated for patients severely ill. Other molecules are being investigated. However, all these studies focused on adults and paediatric data are warranted.
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February 2021

Puumala Virus Infection in Family, Switzerland.

Emerg Infect Dis 2021 02;27(2):658-660

We report 3 cases of Puumala virus infection in a family in Switzerland in January 2019. Clinical manifestations of the infection ranged from mild influenza-like illness to fatal disease. This cluster illustrates the wide range of clinical manifestations of Old World hantavirus infections and the challenge of diagnosing travel-related hemorrhagic fevers.
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http://dx.doi.org/10.3201/eid2702.203770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853570PMC
February 2021

Maladies infectieuses.

Rev Med Suisse 2021 Jan;17(720-1):42-49

Service des maladies infectieuses, Département de médecine, HUG, 1211 Genève 14.

What's new in infectious diseases in 2020 ? This year has been marked by the COVID-19 pandemic, prompting a review of the current knowledge on SARS-CoV-2 and its management in this article. The results of the Swiss project « PIRATE » indicate non-inferiority between CRP-guided antibiotic durations or fixed 7-day durations and 14-day durations for Gram-negative bacteremia. A Mongolian study did not show any benefit of vitamin D substitution in protecting children from tuberculosis. Baloxavir, a new antiviral against the flu, has been approved by Swissmedic. Finally, new American recommendations for therapeutic monitoring of vancomycin and universal screening for hepatitis C virus have been published.
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January 2021

Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs.

Swiss Med Wkly 2020 12 31;150:w20446. Epub 2020 Dec 31.

Division of Prison Health, University of Geneva and University Hospitals of Geneva, Thônex, Switzerland / Office of Corrections, Department of Justice and Home Affairs of the Canton of Zurich, Zurich, Switzerland.

Aims Of The Study: Hydroxychloroquine and lopinavir/ritonavir have been used as experimental therapies to treat COVID-19 during the first wave of the pandemic. Randomised controlled trials have recently shown that there are no meaningful benefits of these two therapies in hospitalised patients. Uncertainty remains regarding the potential harmful impact of these therapies as very early treatments and their burden to the health care system. The present study investigated the length of hospital stay (LOS), mortality, and costs of hydroxychloroquine, lopinavir/ritonavir or their combination in comparison with standard of care among patients hospitalised for coronavirus disease 2019 (COVID-19).

Methods: This retrospective observational cohort study took place in the Geneva University Hospitals, Geneva, Switzerland (n = 840) between 26 February and 31 May 2020. Demographics, treatment regimens, comorbidities, the modified National Early Warning Score (mNEWS) on admission, and contraindications to COVID-19 treatment options were assessed. Outcomes included LOS, in-hospital mortality, and drug and LOS costs.

Results: After successful propensity score matching, patients treated with (1) hydroxychloroquine, (2) lopinavir/ritonavir or (3) their combination had on average 3.75 additional hospitalisation days (95% confidence interval [CI] 1.37–6.12, p = 0.002), 1.23 additional hospitalisation days (95% CI −1.24 – 3.51, p = 0.319), and 4.19 additional hospitalisation days (95% CI 1.52–5.31, p <0.001), respectively, compared with patients treated with the standard of care. Neither experimental therapy was significantly associated with mortality. These additional hospital days amounted to 1010.77 additional days for hydroxychloroquine and hydroxychloroquine combined with lopinavir/ritonavir, resulting in an additional cost of US$ 2,492,214 (95%CI US$ 916,839–3,450,619).

Conclusions: Prescribing experimental therapies for COVID-19 was not associated with a reduced LOS and might have increased the pressure put on healthcare systems.
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http://dx.doi.org/10.4414/smw.2020.20446DOI Listing
December 2020

Diagnosis of latent tuberculosis infection is associated with reduced HIV viral load and lower risk for opportunistic infections in people living with HIV.

PLoS Biol 2020 12 7;18(12):e3000963. Epub 2020 Dec 7.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.

Approximately 28% of the human population have been exposed to Mycobacterium tuberculosis (MTB), with the overwhelming majority of infected individuals not developing disease (latent TB infection (LTBI)). While it is known that uncontrolled HIV infection is a major risk factor for the development of TB, the effect of underlying LTBI on HIV disease progression is less well characterized, in part because longitudinal data are lacking. We sorted all participants of the Swiss HIV Cohort Study (SHCS) with at least 1 documented MTB test into one of the 3 groups: MTB uninfected, LTBI, or active TB. To detect differences in the HIV set point viral load (SPVL), linear regression was used; the frequency of the most common opportunistic infections (OIs) in the SHCS between MTB uninfected patients, patients with LTBI, and patients with active TB were compared using logistic regression and time-to-event analyses. In adjusted models, we corrected for baseline demographic characteristics, i.e., HIV transmission risk group and gender, geographic region, year of HIV diagnosis, and CD4 nadir. A total of 13,943 SHCS patients had at least 1 MTB test documented, of whom 840 (6.0%) had LTBI and 770 (5.5%) developed active TB. Compared to MTB uninfected patients, LTBI was associated with a 0.24 decreased log HIV SPVL in the adjusted model (p < 0.0001). Patients with LTBI had lower odds of having candida stomatitis (adjusted odds ratio (OR) = 0.68, p = 0.0035) and oral hairy leukoplakia (adjusted OR = 0.67, p = 0.033) when compared to MTB uninfected patients. The association of LTBI with a reduced HIV set point virus load and fewer unrelated infections in HIV/TB coinfected patients suggests a more complex interaction between LTBI and HIV than previously assumed.
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http://dx.doi.org/10.1371/journal.pbio.3000963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721132PMC
December 2020

Daily Viral Kinetics and Innate and Adaptive Immune Response Assessment in COVID-19: a Case Series.

mSphere 2020 11 11;5(6). Epub 2020 Nov 11.

Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland.

Viral shedding patterns and their correlations with immune responses are still poorly characterized in mild coronavirus (CoV) disease 2019 (COVID-19). We monitored shedding of viral RNA and infectious virus and characterized the immune response kinetics of the first five patients quarantined in Geneva, Switzerland. High viral loads and infectious virus shedding were observed from the respiratory tract despite mild symptoms, with isolation of infectious virus and prolonged positivity by reverse transcriptase PCR (RT-PCR) until days 7 and 19 after symptom onset, respectively. Robust innate responses characterized by increases in activated CD14 CD16 monocytes and cytokine responses were observed as early as 2 days after symptom onset. Cellular and humoral severe acute respiratory syndrome (SARS)-CoV-2-specific adaptive responses were detectable in all patients. Infectious virus shedding was limited to the first week after symptom onset. A strong innate response, characterized by mobilization of activated monocytes during the first days of infection and SARS-CoV-2-specific antibodies, was detectable even in patients with mild disease. This work is particularly important because it simultaneously assessed the virology, immunology, and clinical presentation of the same subjects, whereas other studies assess these separately. We describe the detailed viral and immune profiles of the first five patients infected by SARS-CoV-2 and quarantined in Geneva, Switzerland. Viral loads peaked at the very beginning of the disease, and infectious virus was shed only during the early acute phase of disease. No infectious virus could be isolated by culture 7 days after onset of symptoms, while viral RNA was still detectable for a prolonged period. Importantly, we saw that all patients, even those with mild symptoms, mount an innate response sufficient for viral control (characterized by early activated cytokines and monocyte responses) and develop specific immunity as well as cellular and humoral SARS-CoV-2-specific adaptive responses, which already begin to decline a few months after the resolution of symptoms.
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http://dx.doi.org/10.1128/mSphere.00827-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657589PMC
November 2020

Long-term consequences of COVID-19: research needs.

Lancet Infect Dis 2020 10 1;20(10):1115-1117. Epub 2020 Sep 1.

Research Authority, Beilinson Hospital, Rabin Medical Center, Petah-Tiqva 49100, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(20)30701-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462626PMC
October 2020

Clinical features of covid-19.

BMJ 2020 Apr 17;369:m1470. Epub 2020 Apr 17.

Laboratory of Virology, Geneva University Hospitals, 1211 Geneva 14, Geneva, Switzerland.

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http://dx.doi.org/10.1136/bmj.m1470DOI Listing
April 2020

[Ebola : an uncontrolled outbreak despite vaccines and new treatments].

Rev Med Suisse 2020 Apr;16(690):739-743

Centre des maladies virales émergentes et laboratoire de virologie, HUG, 2015 Genève.

The Ebola virus disease outbreak raging in the North-Kivu and Ituri provinces of Democratic Republic of the Congo already accounts for more than 3400 cases, from which 2200 died. Major progress have been achieved since the 2014-2016 West Africa outbreak. A vaccine is now approved by the European Medicine Agency and has been administered to more than 250 000 volunteers in the field. New specific antiviral treatments are now available. Ebola virus disease shifted from a deadly disease to a preventable, curable one. However, the long-lasting conflict and repeated attacks of civilians and health workers hampers the control of the outbreak.
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April 2020

Covid-19: a puzzle with many missing pieces.

BMJ 2020 02 19;368:m627. Epub 2020 Feb 19.

Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, 1211 Geneva 14, Switzerland.

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http://dx.doi.org/10.1136/bmj.m627DOI Listing
February 2020

Ebola virus disease: an update on post-exposure prophylaxis.

Lancet Infect Dis 2018 06 15;18(6):e183-e192. Epub 2017 Nov 15.

Department of Infection, Royal Free London NHS Foundation Trust, London, UK. Electronic address:

The massive outbreak of Ebola virus disease in west Africa between 2013 and 2016 resulted in intense efforts to evaluate the efficacy of several specific countermeasures developed through years of preclinical work, including the first clinical trials for therapeutics and vaccines. In this Review, we discuss how the experience and data generated from that outbreak have helped to advance the understanding of the use of these countermeasures for post-exposure prophylaxis against Ebola virus infection. In future outbreaks, post-exposure prophylaxis could play an important part in reducing community transmission of Ebola virus by providing more immediate protection than does immunisation as well as providing additional protection for health-care workers who are inadvertently exposed over the course of their work. We propose provisional guidance for use of post-exposure prophylaxis in Ebola virus disease and identify the priorities for future preparedness and further research.
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http://dx.doi.org/10.1016/S1473-3099(17)30677-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636351PMC
June 2018

Ebola Virus Shedding and Transmission: Review of Current Evidence.

J Infect Dis 2016 10 20;214(suppl 3):S177-S184. Epub 2016 Jul 20.

Division of Infectious Diseases, Geneva University Hospitals Laboratory of Virology and Swiss Reference Center for Emerging Viral Diseases University of Geneva Medical School, Switzerland.

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.
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http://dx.doi.org/10.1093/infdis/jiw254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283352PMC
October 2016

Sequelae of Ebola virus disease: the emergency within the emergency.

Lancet Infect Dis 2016 06 22;16(6):e82-e91. Epub 2016 Mar 22.

Pandemic and Epidemic Diseases, World Health Organization, Geneva, Switzerland. Electronic address:

As the massive outbreak of Ebola virus disease (EVD) in west Africa wanes, it has become increasingly clear that thousands of survivors have many sequelae, some of which might be very severe, such as arthritis and vision-threatening uveitis. The mental health effects of EVD on survivors and other family and community members is similarly profound. Furthermore, it is increasingly being recognised that Ebola virus might persist for weeks or months in selected body compartments of survivors, most notably in the semen of men, bringing risk of renewed transmission where it has previously been eliminated. These challenges to EVD survivors constitute a new emergency in terms of addressing individual patient need and to control the disease spread. In this Review, we assess what is known regarding the sequelae of EVD, including possible delayed virus clearance. We discuss some of the key challenges regarding the provision of care to survivors and implementation of necessary future research.
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http://dx.doi.org/10.1016/S1473-3099(16)00077-3DOI Listing
June 2016

Ebola Virus Disease Complications as Experienced by Survivors in Sierra Leone.

Clin Infect Dis 2016 06 21;62(11):1360-1366. Epub 2016 Mar 21.

Médecins Sans Frontières.

Background: Thousands of people have survived Ebola virus disease (EVD) during the ongoing outbreak. However, data about the frequency and risk factors of long-term post-EVD complications remain scarce. We describe the clinical characteristics of EVD survivors followed in a survivor clinic in Freetown, Sierra Leone.

Methods: A survivor clinic opened within an Ebola treatment center compound in Freetown, Sierra Leone. At each visit, clinical and psychological assessments were conducted and free treatment was offered. Survivors were referred to a partner's hospitals if their condition could not be managed in the clinic. We used routinely collected data from the clinic to describe long-term complications of EVD and their risk factors.

Results: A total of 1001 medical consultations for 166 patients were performed between 3 February and 21 June 2015. The most frequent complaints and diagnoses were arthralgia (n = 129 [77.7%]), fatigue (n = 116 [69.8%]), abdominal pain (n = 90 [54.2%]), headache (n = 87 [52.4%]), anemia (n = 83 [50%]), skin disorders (n = 81 [48.8%]), back pain (n = 54 [32.5%]), and alopecia (n = 53 [31.9%]). Ocular complications were diagnosed in 94 survivors (56.7%); uveitis was the most common (n = 57 [34%]). Survivors were 10 times more likely to develop uveitis post-EVD if they presented with red/injected eyes during the acute phase of their illness.

Conclusions: Post-EVD complications among our patients were similar to those described previously and were detected early following the acute phase of disease. Follow-up of survivors should begin immediately after discharge to address sequelae as they arise and reduce the potential for development of long-term disabilities such as blindness.
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http://dx.doi.org/10.1093/cid/ciw158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872294PMC
June 2016

Clinical Management of Ebola Virus Disease in the United States and Europe.

N Engl J Med 2016 Feb;374(7):636-46

From the Centers for Disease Control and Prevention (T.M.U., J.G.) and the Division of Infectious Diseases, Emory University School of Medicine (A.K.M.) - both in Atlanta; the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (R.T.D.); Texas Health Presbyterian Hospital Dallas, Dallas (A.M.L.); the Department of Infectious Diseases, University Hospital Frankfurt, Frankfurt am Main (T.W.), the First Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg (S.S.), and Leipzig Treatment Center for Highly Contagious Diseases, Klinikum St. Georg, Leipzig (T.G.) - all in Germany; the Division of Infectious Diseases and Laboratory of Virology, Geneva University Hospitals, Geneva (P.V.); the Department of Infection, Royal Free London NHS Foundation Trust, London (M.J.); the Internal Medicine Department, Infectious Diseases Unit Madrid, Hospital La Paz-Carlos III IdiPAZ, Madrid (J.R.A.); New York University School of Medicine-Bellevue Hospital Center, New York (L.E.); University of Nebraska Medical Center, Omaha (A.L.H.); the Departments of Infectious Diseases and Acute Medicine, Oslo University Hospital, Oslo (A.B.B.); Lazzaro Spallanzani National Institute for Infectious Diseases, Rome (G.I.); the Infectious and Tropical Diseases Department, Bégin Military Hospital, Saint-Mandé, France (C.R.); and the Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands (A.I.M.H.).

Background: Available data on the characteristics of patients with Ebola virus disease (EVD) and clinical management of EVD in settings outside West Africa, as well as the complications observed in those patients, are limited.

Methods: We reviewed available clinical, laboratory, and virologic data from all patients with laboratory-confirmed Ebola virus infection who received care in U.S. and European hospitals from August 2014 through December 2015.

Results: A total of 27 patients (median age, 36 years [range, 25 to 75]) with EVD received care; 19 patients (70%) were male, 9 of 26 patients (35%) had coexisting conditions, and 22 (81%) were health care personnel. Of the 27 patients, 24 (89%) were medically evacuated from West Africa or were exposed to and infected with Ebola virus in West Africa and had onset of illness and laboratory confirmation of Ebola virus infection in Europe or the United States, and 3 (11%) acquired EVD in the United States or Europe. At the onset of illness, the most common signs and symptoms were fatigue (20 patients [80%]) and fever or feverishness (17 patients [68%]). During the clinical course, the predominant findings included diarrhea, hypoalbuminemia, hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia; 14 patients (52%) had hypoxemia, and 9 (33%) had oliguria, of whom 5 had anuria. Aminotransferase levels peaked at a median of 9 days after the onset of illness. Nearly all the patients received intravenous fluids and electrolyte supplementation; 9 (33%) received noninvasive or invasive mechanical ventilation; 5 (19%) received continuous renal-replacement therapy; 22 (81%) received empirical antibiotics; and 23 (85%) received investigational therapies (19 [70%] received at least two experimental interventions). Ebola viral RNA levels in blood peaked at a median of 7 days after the onset of illness, and the median time from the onset of symptoms to clearance of viremia was 17.5 days. A total of 5 patients died, including 3 who had respiratory and renal failure, for a mortality of 18.5%.

Conclusions: Among the patients with EVD who were cared for in the United States or Europe, close monitoring and aggressive supportive care that included intravenous fluid hydration, correction of electrolyte abnormalities, nutritional support, and critical care management for respiratory and renal failure were needed; 81.5% of these patients who received this care survived.
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http://dx.doi.org/10.1056/NEJMoa1504874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972324PMC
February 2016

Ebola virus disease diagnosis by real-time RT-PCR: A comparative study of 11 different procedures.

J Clin Virol 2016 Apr 2;77:9-14. Epub 2016 Feb 2.

Swiss National Reference Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland; Laboratory of Virology, Geneva University Hospitals, Geneva, Switzerland; University of Geneva Medical School, Geneva, Switzerland.

Background: The diagnosis of Ebola virus disease relies on the detection of viral RNA in blood by real-time reverse-transcription PCR. While several of these assays were developed during the unprecedented 2013-2015 Ebola virus disease outbreak in West Africa, few were applied in the field.

Objectives: To compare technical performances and practical aspects of 11 Ebola virus real-time reverse-transcription PCR procedures.

Study Design: We selected the most promising assays using serial dilutions of culture-derived Ebola virus RNA and determined their analytical sensitivity and potential range of quantification using quantified in vitro transcribed RNA; viral load values in the serum of an Ebola virus disease patient obtained with these assays were reported. Finally, ease of use and turnaround times of these kits were evaluated.

Results: Commercial assays were at least as sensitive as in-house tests. Five of the former (Altona, Roche, Fast-track Diagnostics, and Life Technologies) were selected for further evaluation. Despite differences in analytical sensitivity and limits of quantification, all of them were suitable for Ebola virus diagnosis and viral load estimation. The Lifetech Lyophilized Ebola Virus (Zaire 2014) assay (Life Technologies) appeared particularly promising, displaying the highest analytical sensitivity and shortest turnaround time, in addition to requiring no reagent freezing.

Conclusions: Commercial kits were at least as sensitive as in-house tests and potentially easier to use in the field than the latter. This qualitative comparison of real-time reverse transcription PCR assays may serve as a basis for the design of future Ebola virus disease diagnostics.
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http://dx.doi.org/10.1016/j.jcv.2016.01.017DOI Listing
April 2016

Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report.

Lancet Infect Dis 2015 Sep 19;15(9):1034-1040. Epub 2015 Jul 19.

Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland; Laboratory of Virology and Swiss Reference Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland; University of Geneva Medical School, Geneva, Switzerland.

Background: A detailed description of viral kinetics, duration of virus shedding, and intraviral evolution in different body sites is warranted to understand Ebola virus pathogenesis. Patients with Ebola virus infections admitted to university hospitals provide a unique opportunity to do such in-depth virological investigations. We describe the clinical, biological, and virological follow-up of a case of Ebola virus disease.

Methods: A 43-year-old medical doctor who contracted an Ebola virus infection in Sierra Leone on Nov 16, 2014 (day 1), was airlifted to Geneva University Hospitals, Geneva, Switzerland, on day 5 after disease onset. The patient received an experimental antiviral treatment of monoclonal antibodies (ZMAb) and favipiravir. We monitored daily viral load kinetics, estimated viral clearance, calculated the half-life of the virus in plasma, and analysed the viral genome via high-throughput sequencing, in addition to clinical and biological signs.

Findings: The patient recovered rapidly, despite an initial high viral load (about 1 × 10(7) RNA copies per mL 24 h after onset of fever). We noted a two-phase viral decay. The virus half-life decreased from about 26 h to 9·5 h after the experimental antiviral treatment. Compared with a consensus sequence of June 18, 2014, the isolate that infected this patient displayed only five synonymous nucleotide substitutions on the full genome (4901A→C, 7837C→T, 8712A→G, 9947T→C, 16201T→C) despite 5 months of human-to-human transmission.

Interpretation: This study emphasises the importance of virological investigations to fully understand the course of Ebola virus disease and adaptation of the virus. Whether the viral decay was caused by the effects of the immune response alone, an additional benefit from the antiviral treatment, or a combination of both is unclear. In-depth virological analysis and randomised controlled trials are needed before any conclusion on the potential effect of antiviral treatment can be drawn.

Funding: Geneva University Hospitals, Swiss Office of Public Health, Swiss Agency for Development and Cooperation, and Swiss National Science Foundation.
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http://dx.doi.org/10.1016/S1473-3099(15)00229-7DOI Listing
September 2015

[Infections disease update: 2014 is viral].

Rev Med Suisse 2015 Jan;11(456-457):72-7

Chikungunya's phenomenal dissemination imposes now infection suspicion when returning from endemic areas. Colorectal cancer screening may be dependent of the microbiome. Even a small amount of E. coli in catheter sampled urine is predictive for a urinary infection. Prevention of pharyngitis suppurated late complications doesn't justify systematic antimicrobial therapy. A bitherapy is probably better for severe community acquired pneumonias. Due to epidemiology and resistances, management of gonorrhoea has changed. Enterovirus 68 is particular because of its almost exclusive lung tropism in children. The question is no longer how to treat hepatitis C but which patients to treat and when. Pritelivir clearly improves herpes genitalis symptoms. The first confirmed case of Ebola has reach our contry.
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January 2015
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