Gaps in the clinical management of influenza a century since the 1918 pandemic

This year marks the centennial of the devastating 1918 influenza A(H1N1) pandemic, which killed an estimated 50 million people worldwide. Prevention and control activities were limited in 1918 because global surveillance did not exist, influenza viruses were not yet discovered, and no influenza vaccines had been developed. Diagnostic tests for influenza were unavailable prior to isolation of influenza viruses in the 1930s, so spread of the pandemic virus was tracked by news reports of increased respiratory disease and related deaths. Establishment of the World Health Organization’s Global Influenza Surveillance Network in 1952 has contributed substantially to coordinated surveillance, vaccine development, and influenza vaccine strain selection

To the editor

To the Editor: In their study, van Griensven et al. (Jan. 7 issue)1 found no significant survival benefit of using convalescent plasma with unknown levels of neutralizing antibodies in patients with Ebola virus disease (EVD)

Doing today's work superbly well - Treating ebola with current tools

The Ebola outbreak that is ravaging West Africa is a daily staple of the lay press and of scholarly medical publications. Ebola evokes fear among both the public and clinicians. It also evokes a sort of therapeutic nihilism — after all, if there is no treatment, what can be done? And without an Ebola-specific antiviral medication, of what use are infectious-disease clinicians? Without oxygen, let alone mechanical ventilators, how can acute and critical care clinicians possibly contribute

Reproductive health sequelae among women who survived Ebola virus disease in Liberia

Objective: To estimate the incidence of failed pregnancy and menstrual irregularities among Liberian women who had survived Ebola virus disease (EVD) and to identify host-specific and disease-specific factors associated with these outcomes. Methods: A cross-sectional questionnaire-based study was conducted between August 10, 2016, and February 7, 2017. The study population comprised 111 women aged 18–45 years who had survived EVD and were enrolled in the Longitudinal Liberian Ebola Survivor study based at the Eternal Love Winning Africa Hospital, Monrovia, Liberia. Self-reported data on outcomes related to pregnancy and menstrual changes since recovery from EVD were collected. Results: In all, 29 (26.1%) of the participants had become pregnant since surviving EVD. Of the 23 women whose pregnancies continued to term, 10 (43.4%) reported live birth, 11 (47.8%) reported spontaneous abortion, and two (8.7%) reported stillbirth. Of the 105 women who reported having regular menstruation before EVD, 27 (29.0%) reported experiencing irregular menstruation for unknown reasons after EVD. In bivariate logistic models, no associations were found between failed pregnancy or irregular menstruation and any of the factors of interest. Conclusions: Adverse pregnancy outcomes and irregular menstruation were frequently reported among EVD survivors in Liberia

Shifting the paradigm - Applying universal standards of care to Ebola virus disease

As the Democratic Republic of Congo’s (DRC’s) 10th outbreak of Ebola virus disease (EVD) rages in this resource-limited, wartorn region, advances in the delivery of supportive care and the introduction of investigational therapies provide a glimmer of hope amid the mounting infections. In the absence of effective therapies or vaccines, EVD outbreak response has centered around the most basic of public health principles — identification and isolation of patients with suspected and confirmed EVD and tracking of all the contacts of the confirmed patients, who are then rapidly isolated if they show signs of disease. This strategy of “identify, isolate, and track” allows public health responders to curtail and eventually eliminate virus transmission in the community and has been the foundation of EVD outbreakcontrol efforts since the disease was first described in 1976

Apheresis for collection of Ebola convalescent plasma in Liberia

Purpose: This report describes initiation of apheresis capability in Liberia, Africa to support a clinical trial of convalescent plasma therapy for Ebola Virus Disease. Methods: A bloodmobile was outfitted in the United States as a four-bed apheresis unit with capabilities including pathogen reduction, electronic blood establishment computer system, designated areas for donor counseling and laboratory testing, and onboard electrical power generation. After air transport to Liberia, the bloodmobile was positioned at ELWA Hospital, Monrovia, and connected to the hospital's power grid. Liberian staff were trained to conduct donor screening, which included questionnaire and onsite blood typing and transfusion transmitted infection (TTI) testing, and plasma collection and processing. Results: The bloodmobile was operational within 3 weeks after arrival of the advance team. Of 101 donors who passed the pre-screening questionnaire, 32 were deferred. Twenty-eight of ninty-nine tested survivors were deferred for positive transfusion transmitted infection (TTI) tests; twenty-one were positive for hepatitis B, hepatitis C, or human immunodeficiency virus. The majority of donors had type O blood; all but one were Rh positive. Forty-three survivors donated at least once; eighty-nine apheresis attempts resulted in eighty-one successful collections. Conclusions: Apheresis capability was emergently established in Liberia to support an efficacy trial of Ebola Convalescent Plasma. Extensive cooperation among multinational team members, engineers, logisticians, and blood safety technical personnel at the operational site was required to surmount challenges to execution posed by logistical factors. The high proportion of positive TTI tests supported the use of a pathogen reduction system to enhance product safety

Ebola virus disease

Ebola virus disease (EVD) is a severe and frequently lethal disease caused by Ebola virus (EBOV). EVD outbreaks typically start from a single case of probable zoonotic transmission, followed by human-to-human transmission via direct contact or contact with infected bodily fluids or contaminated fomites. EVD has a high case–fatality rate; it is characterized by fever, gastrointestinal signs and multiple organ dysfunction syndrome. Diagnosis requires a combination of case definition and laboratory tests, typically real-time reverse transcription PCR to detect viral RNA or rapid diagnostic tests based on immunoassays to detect EBOV antigens. Recent advances in medical countermeasure research resulted in the recent approval of an EBOV-targeted vaccine by European and US regulatory agencies. The results of a randomized clinical trial of investigational therapeutics for EVD demonstrated survival benefits from two monoclonal antibody products targeting the EBOV membrane glycoprotein. New observations emerging from the unprecedented 2013–2016 Western African EVD outbreak (the largest in history) and the ongoing EVD outbreak in the Democratic Republic of the Congo have substantially improved the understanding of EVD and viral persistence in survivors of EVD, resulting in new strategies toward prevention of infection and optimization of clinical management, acute illness outcomes and attendance to the clinical care needs of patients

Ebola virus disease: an update on post-exposure prophylaxis

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

Stigma and Ebola survivorship in liberia: Results from a longitudinal cohort study

Background Survivors of the 2014–2016 West Africa Ebola epidemic have been reported to suffer high levels of stigmatization after return to their communities. We sought to characterize the stigma encountered by a cohort of Ebola survivors in Liberia over time. Methods Ebola-related stigma was assessed from June 2015 to August 2017 in 299 adolescent and adult Liberian Ebola Survivor Cohort participants at three month intervals using adapted HIV stigma scales scored from 0 to 10 according to the proportion of answers indicating stigmatization. Findings The median time from Ebola Virus Disease (EVD) to study entry was 393 days (IQR 336–492). Participants (43% female) had a median age of 31 (IQR 25–40) years. Mean self-reported stigma levels were greater at baseline (6.28 ± 0.15 [IQR: 4.38–8.75]) compared to the first post-baseline visit (0.60 ± 0.10 [IQR: 0–0]; p<0.0001). During follow-up, stigma levels were stable. Baseline stigma significantly increased during enrollment and following clusters of Ebola re-emergence in Liberia. Survivors encountered primarily enacted and perceived external stigma rather than internalized stigma. Conclusions Ebola-related stigma was prevalent among Liberian survivors more than a year after EVD recovery. Self-reported stigma was greater in the period before cohort enrollment; however, some degree of stigmatization persisted years after EVD. Transient rises in stigma were observed following episodic Ebola re-emergence of EVD in Liberia. During future EVD outbreaks, enhanced public health interventions designed to prevent and mitigate Ebola-related stigma that is enacted and external should be implemented to support survivor recovery and community re-integration

Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) are among the treatments recommended for high-risk ambulatory persons with coronavirus 2019 (COVID-19). Here, we study viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial (ClinicalTrials.gov: NCT04518410). Viral load by qPCR and viral culture are performed from anterior nasal swabs collected on study days 0 (day of treatment), 1, 2, 3, and 7. Treatment with mAbs results in rapid clearance of culturable virus. One day after treatment, 0 of 28 (0%) participants receiving mAbs and 16 of 39 (41%) receiving placebo still have culturable virus (p < 0.0001). Recrudescence of culturable virus is detected in three participants with emerging mAb resistance and viral RNA rebound. While further studies are necessary to fully define the relationship between shed culturable virus and transmission, these results raise the possibility that mAbs may offer immediate (household) and public-health benefits by reducing onward transmission., Using longitudinal samples from the ACTIV-2 clinical trial of the monoclonal antibody bamlinivimab, Boucau et al. investigate the duration of shedding culturable virus. Treatment with monoclonal antibody results in rapid clearance of culturable virus. The emergence of mutations in a subset of participants coincides with viral rebound and resurgent culturable virus