scholarly journals Maternal and Infant Death and the rVSV-ZEBOV Vaccine Through Three Recent Ebola Virus Epidemics-West Africa, DRC Équateur and DRC Kivu: 4 Years of Excluding Pregnant and Lactating Women and Their Infants from Immunization

2019 ◽  
Vol 6 (4) ◽  
pp. 213-222 ◽  
Author(s):  
David A. Schwartz

Abstract Purpose of Review Ebola virus infection has one of the highest overall case fatality rates of any viral disease. It has historically had an especially high case mortality rate among pregnant women and infants—greater than 90% for pregnant women in some outbreaks and close to 100 % in fetuses and newborns. The Merck recombinant vaccine against Ebola virus, termed rVSV-ZEBOV, underwent clinical trials during the 2013–2015 West Africa Ebola epidemic where it was found to be 100% efficacious. It was subsequently used during the 2018 DRC Équateur outbreak and in the 2018 DRC Kivu Ebola which is still ongoing, where its efficacy is 97.5 %. Pregnant and lactating women and their infants have previously been excluded from the design, clinical trials, and administration of many vaccines and drugs. This article critically examines the development of the rVSV-ZEBOV vaccine and its accessibility to pregnant and lactating women and infants as a life-saving form of prevention through three recent African Ebola epidemics—West Africa, DRC Équateur, and DRC Kivu. Recent Findings Pregnant and lactating women and their infants were excluded from participation in the clinical trials of rVSV-ZEBOV conducted during the West Africa epidemic. This policy of exclusion was continued with the occurrence of the DRC Équateur outbreak in 2018, in spite of calls from the public health and global maternal health communities to vaccinate this population. Following the onset of the DRC Kivu epidemic, the exclusion persisted. Eventually, the policy was reversed to include vaccination of pregnant and lactating women. However, it was not implemented until June 2019, 10 months after the start of the epidemic, placing hundreds of women and infants at risk for this highly fatal infection. Summary The historical policy of excluding pregnant and lactating women and infants from vaccine design, clinical trials, and implementation places them at risk, especially in situations of infectious disease outbreaks. In the future, all pregnant women, regardless of trimester, breastfeeding mothers, and infants, should have access to the Ebola vaccine.

2020 ◽  
Vol 35 (3) ◽  
pp. 247-253
Author(s):  
Pedro Arcos González ◽  
Ángel Fernández Camporro ◽  
Anneli Eriksson ◽  
Carmen Alonso Llada

AbstractIntroduction:Ebola Virus Disease (EVD) is the international health emergency paradigm due to its epidemiological presentation pattern, impact on public health, resources necessary for its control, and need for a national and international response.Study Objective:The objective of this work is to study the evolution and progression of the epidemiological presentation profile of Ebola disease outbreaks since its discovery in 1976 to the present, and to explore the possible reasons for this evolution from different perspectives.Methods:Retrospective observational study of 38 outbreaks of Ebola disease occurred from 1976 through 2019, excluding laboratory accidents. United Nations agencies and programs; Ministries of Health; the US Centers for Disease Control and Prevention (CDC); ReliefWeb; emergency nongovernmental organizations; and publications indexed in PubMed, EmBase, and Clinical Key have been used as sources of data. Information on the year of the outbreak, date of beginning and end, duration of the outbreak in days, number of cases, number of deaths, population at risk, geographic extension affected in Km2, and time of notification of the first cases to the World Health Organization (WHO) have been searched and analyzed.Results:Populations at risk have increased (P = .024) and the geographical extent of Ebola outbreaks has grown (P = .004). Reporting time of the first cases of Ebola to WHO has been reduced (P = .017) and case fatality (P = .028) has gone from 88% to 62% in the period studied. There have been differences (P = .04) between the outbreaks produced by the Sudan and Zaire strains of the virus, both in terms of duration and case fatality ratio (Sudan strain 74.5 days on average and 62.7% of case fatality ratio versus Zaire strain with 150 days on average and 55.4% case fatality ratio).Conclusion:There has been a change in the epidemiological profile of the Ebola outbreaks from 1976 through 2019 with an increase in the geographical extent of the outbreaks and the population at risk, as well as a significant decrease in the outbreaks case fatality rate. There have been advances in the detection and management capacity of outbreaks, and the notification time to the WHO has been reduced. However, there are social, economic, cultural, and political obstacles that continue to greatly hinder a more efficient epidemiological approach to Ebola disease, mainly in Central Africa.


2017 ◽  
Vol 372 (1721) ◽  
pp. 20160297 ◽  
Author(s):  
Cordelia E. M. Coltart ◽  
Benjamin Lindsey ◽  
Isaac Ghinai ◽  
Anne M. Johnson ◽  
David L. Heymann

Ebola virus causes a severe haemorrhagic fever in humans with high case fatality and significant epidemic potential. The 2013–2016 outbreak in West Africa was unprecedented in scale, being larger than all previous outbreaks combined, with 28 646 reported cases and 11 323 reported deaths. It was also unique in its geographical distribution and multicountry spread. It is vital that the lessons learned from the world's largest Ebola outbreak are not lost. This article aims to provide a detailed description of the evolution of the outbreak. We contextualize this outbreak in relation to previous Ebola outbreaks and outline the theories regarding its origins and emergence. The outbreak is described by country, in chronological order, including epidemiological parameters and implementation of outbreak containment strategies. We then summarize the factors that led to rapid and extensive propagation, as well as highlight the key successes, failures and lessons learned from this outbreak and the response. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Wayne M. Getz ◽  
Jean-Paul Gonzalez ◽  
Richard Salter ◽  
James Bangura ◽  
Colin Carlson ◽  
...  

We present a stochastic transmission chain simulation model for Ebola viral disease (EVD) in West Africa, with the salutary result that the virus may be more controllable than previously suspected. The ongoing tactics to detect cases as rapidly as possible and isolate individuals as safely as practicable is essential to saving lives in the current outbreaks in Guinea, Liberia, and Sierra Leone. Equally important are educational campaigns that reduce contact rates between susceptible and infectious individuals in the community once an outbreak occurs. However, due to the relatively low R0 of Ebola (around 1.5 to 2.5 next generation cases are produced per current generation case in naïve populations), rapid isolation of infectious individuals proves to be highly efficacious in containing outbreaks in new areas, while vaccination programs, even with low efficacy vaccines, can be decisive in curbing future outbreaks in areas where the Ebola virus is maintained in reservoir populations.


2017 ◽  
Vol 372 (1721) ◽  
pp. 20160294 ◽  
Author(s):  
Amanda M. Rojek ◽  
Peter W. Horby

Although, after an epidemic of over 28 000 cases, there are still no licensed treatments for Ebola virus disease (EVD), significant progress was made during the West Africa outbreak. The pace of pre-clinical development was exceptional and a number of therapeutic clinical trials were conducted in the face of considerable challenges. Given the on-going risk of emerging infectious disease outbreaks in an era of unprecedented population density, international travel and human impact on the environment it is pertinent to focus on improving the research and development landscape for treatments of emerging and epidemic-prone infections. This is especially the case since there are no licensed therapeutics for some of the diseases considered by the World Health Organization as most likely to cause severe outbreaks—including Middle East respiratory syndrome coronavirus, Marburg virus, Crimean Congo haemorrhagic fever and Nipah virus. EVD, therefore, provides a timely exemplar to discuss the barriers, enablers and incentives needed to find effective treatments in advance of health emergencies caused by emerging infectious diseases. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.


2020 ◽  
Author(s):  
Angela R. Harrison ◽  
Megan Dearnley ◽  
Shawn Todd ◽  
Diane Green ◽  
Glenn A. Marsh ◽  
...  

AbstractMany viruses target signal transducers and activators of transcription (STAT) 1 and 2 to antagonise antiviral interferon (IFN) signalling, but targeting of signalling by other STATs/cytokines, including STAT3/interleukin (IL-) 6 that regulate processes important to Ebola virus (EBOV) haemorrhagic fever, is poorly defined. We report that EBOV potently inhibits STAT3 responses to IL-6 family cytokines, and that this is mediated by the IFN-antagonist VP24. Mechanistic analysis indicates that VP24 effects a unique strategy combining distinct karyopherin-dependent and karyopherin-independent mechanisms to antagonise STAT3-STAT1 heterodimers and STAT3 homodimers, respectively. This appears to reflect distinct mechanisms of nuclear trafficking of the STAT3 complexes, revealed for the first time by our analysis of VP24 function. These findings are consistent with major roles for global inhibition of STAT3 signalling in EBOV infection, and provide new insights into the molecular mechanisms of STAT3 nuclear trafficking, significant to pathogen-host interactions, cell physiology and pathologies such as cancer.Author summaryEbola virus (EBOV) continues to pose a significant risk to human health globally, causing ongoing disease outbreaks with case-fatality rates between 40 and 60%. Suppression of immune responses is a critical component of EBOV haemorrhagic fever, but understanding of EBOV impact on signalling by cytokines other than interferon is limited. We find that infectious EBOV inhibits interleukin-6 cytokine signalling via antagonism of STAT3. The antagonistic strategy uniquely combines two distinct mechanisms, which appear to reflect differing nuclear trafficking mechanisms of critical STAT3 complexes. This provides fundamental insights into the mechanisms of pathogenesis of a lethal virus, and biology of STAT3, a critical player in immunity, development, growth and cancer.


2015 ◽  
Vol 14 (2) ◽  
pp. 47-52
Author(s):  
Clifford Lisk ◽  
◽  
Luke Snell ◽  
Michael Haji-Coll ◽  
Jayne Ellis ◽  
...  

Viral Haemorrhagic Fevers (VHF) such as Ebola Virus Disease (EVD) are of increasing concern of increasing concern to clinicians and public heath bodies across Europe and America due to the on-going epidemic in West Africa. We conducted an online study to assess clinicians’ knowledge of VHF across six hospital sites in London. This showed suboptimal knowledge of Public Health England guidance, EVD epidemiology and the risk factors for acquiring VHF. Knowledge about VHF was dependent on seniority of grade with the most junior grade of doctors performing worse in several areas of the survey. Poor knowledge raises concerns that those at risk of VHF will be inappropriately risk stratified and managed. Education of doctors and other healthcare professionals about VHF is necessary to address these knowledge gaps.


2019 ◽  
Vol 11 (520) ◽  
pp. eaaw1049 ◽  
Author(s):  
Lori E. Dodd ◽  
Dean Follmann ◽  
Michael Proschan ◽  
Jing Wang ◽  
Denis Malvy ◽  
...  

Recent Ebola virus disease outbreaks affirm the dire need for treatments with proven efficacy. Randomized controlled clinical trials remain the gold standard but, during disease outbreaks, may be difficult to conduct due to ethical concerns and challenging field conditions. In the absence of a randomized control group, statistical modeling to create a control group could be a possibility. Such a model-based reference control would only be credible if it had the same mortality risk as that of the experimental group in the absence of treatment. One way to test this counterfactual assumption is to evaluate whether reasonable similarity exists across nonrandomized control groups from different clinical studies, which might suggest that a future control group would be similarly homogeneous. We evaluated similarity across six clinical studies conducted during the 2013–2016 West Africa outbreak of Ebola virus disease. These studies evaluated favipiravir, the biologic ZMapp, the antimalarial drug amodiaquine, or administration of convalescent plasma or convalescent whole blood. We compared the nonrandomized control groups of these six studies comprising 1147 individuals infected with Ebola virus. We found considerable heterogeneity, which did not disappear after statistical modeling to adjust for prognostic variables. Mortality risk varied widely (31 to 66%) across the nonrandomized control arms of these six studies. Models adjusting for baseline covariates (age, sex, and cycle threshold, a proxy for viral load) failed to sufficiently recalibrate these studies and showed that heterogeneity remained. Our findings highlight concerns about making invalid conclusions when comparing nonrandomized control groups to cohorts receiving experimental treatments.


2015 ◽  
Vol 20 (1) ◽  
pp. 32-39
Author(s):  
O. I Kiselev ◽  
L. M Tsybalova ◽  
E. G Deeva ◽  
V. V Tsvetkov ◽  
G. S Golobokov ◽  
...  

Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever is severe acute infectious diseases accompanied by the development of severe systemic inflammatory response followed by the addition of disseminated intravascular coagulation and multiple organ failure. Since 1976 in Africa regularly observed disease outbreaks among humans caused by different types of Ebola virus. Modern epidemic in West Africa began in Guinea in February 2014 and is still going on, coming out of the country and distributed in Liberia, Sierra Leone and Nigeria. According to the World Health Organization (WHO) on December 14, 2014 recorded 18,603 cases of them confirmed EVD 11807, fatal 6915. From July 2014 to currently registered sporadic cases EVD among health care workers caring for patients, as well as among tourists returning from countries affected by the epidemic is already outside of West Africa. Due to the limited use of specific antiviral therapy with special attention to the management ofpatients with EVD should be paid to the intensive and timely pathogenetic therapy. Today, the only way to reduce morbidity and mortality among people from EVD is awareness on the risk factors of infection and the use ofpersonal protective measures.


2014 ◽  
Vol 6 (2) ◽  
pp. 0-0
Author(s):  
Ayush Agarwal ◽  
Omkar Singh ◽  
VK Rastogi

ABSTRACT • Ebola virus disease (EVD), also known as Ebola hemorrhagic fever, is a severe, often fatal illness of human beings having a case fatality rate of up to 90%. • Ebola virus disease outbreaks occur primarily in remote Central and West Africa, near the tropical rainforests. • The virus is transmitted to humans from wild animals and spreads in the human beings through physical contact. • It does not transmit through vectors or air-borne droplets. • Severely ill patients require intensive supportive care. No specific treatment or vaccine is available for use.


Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 81 ◽  
Author(s):  
David Schwartz

As evidenced from recent epidemics, both Ebola and Zika virus infection are potentially catastrophic when occurring in pregnant women. Ebola virus causes extremely high rates of mortality in both mothers and infants; Zika virus is a TORCH infection that produces a congenital malformation syndrome and pediatric neurodevelopmental abnormalities. Production of efficacious vaccines has been a public health priority for both infections. Unfortunately, during the clinical trials and subsequent deployment of a vaccine for the Ebola virus, pregnant and lactating women were, and continue to be, excluded from receiving the life-saving vaccine. The most serious consequence of Zika virus infection, congenital Zika syndrome, results from fetal infection during pregnancy. Thus, pregnant women have a major stake in the ongoing development of a vaccine for Zika virus. The exclusion of pregnant women from the development, clinical trials and administration of a potential Zika vaccine unfairly deprives them and their infants of the protection they need against this potentially catastrophic intrauterine infection. When creating policy about these issues, it is important to critically evaluate vaccine safety in pregnancy in the context of the substantial risk of infection for the pregnant woman and her fetus in the absence of immunization.


Sign in / Sign up

Export Citation Format

Share Document