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Médecine et Santé Tropicales

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La fièvre Ébola revisitée : une rivière tranquille au cœur de l’Afrique Volume 28, numéro 1, Janvier-Février-Mars 2018

Introduction

In 1995, Jean-Paul Gonzalez wrote an article about Ebola Virus Disease [1], capturing the panic at the time of the Ebola outbreak in Kikwit, Zaire, and discussing the future of viruses in our world. Now, 20 years later, in the wake of the West African Ebola pandemic, we revisit the editorial, asking the question: what have we learned (or forgotten) since 1995?

Methods

Dr. Gonzalez's article, included below, was translated from the original publication,1 and reviewed as a comparative reference for a scientific and cultural perspective of the emergence and rise of an Ebola fever outbreak in 1995. A subsequent review of Ebola outbreaks since this publication, as well as the authors’ knowledge and experiences, was used to comprehend any changes in the knowledge, attitudes, and practices associated with Ebola; this review is in our Results section.

“At the origin, in the heart of Africa, between the Congo and Ubangi Rivers, between savannah and forest, flowed the Ebola River. Humanity has lived on its banks since its birth. Centuries later, when the world was thought to hold no more secrets, humans trained as scientists watched in amazement as an epidemic of sudden and violent illness unfolded in this peaceful valley. The culprit, a deadly virus, was named after the small eponymous Ebola River. A new species of germs was thereby described. Together with the already known and feared Marburg virus, the Ebola virus formed the Filovirus family of viruses, taking its place in the Linnaean kingdom of known animal species.

This Ebola virus, discovered once again in Ivory Coast just a few months ago,2 has alerted the rare scientists who are constantly seeking to understand its strange and elusive nature. Today once again, for the third time in 20 years, Ebola has appeared as an epidemic in Kikwit,3 Zaire, located on the other side of the equator from the Ebola River. This time, the epidemic has assumed an unexpected geographical dimension, due to the increased density and mobility of the indigenous population.

Media alarmists, informed of the previous Ivorian outbreak and armed with the latest news of literary and film trends, were quick to show that reality exceeded fiction. Should we be expecting to see Ebola fever spread across Hollywood Boulevard in Los Angeles? Ignorance is the source of fear, and some abuse it successfully. The Ebola virus is not the influenza virus; its maintenance in nature is different in essence, and it will not cause the pandemic of the century. From the bushfire in Kikwit, only a few embers still burn. As always, at the conclusion of a new episode of a virus or a viral disease, the scientific work continues, bolstered at times with new funding delivered by “responsible” leaders. The watch and the research will continue, with the aim of understanding, treating, and preventing it.

Don’t forget that besides these epidemic outbursts of highly pathogenic viruses, there are other viruses, much more devastating, such as dengue and yellow fever. Despite the effectiveness of the yellow fever vaccine, the yellow fever virus4 causes more deaths each year than the Ebola virus has ever caused since its discovery. We also observe that overall in the wake of these threatening epidemics, dengue viruses advance, with clinical presentations ranging from influenza-like illness to hemorrhagic fever, and the viruses responsible for human acquired immunodeficiency spread and diversify, invariably. Other infectious diseases, such as malaria, tuberculosis, influenza, and Hantavirus diseases, are also of an entirely different magnitude than hemorrhagic fever viruses such as Ebola.

The history of epidemics shows us that diseases follow human channels of communication and migration. Of course, the risk of seeing Ebola virus emerge on the banks of the Seine or the Californian coast exists. Air travel is rapid and any infected person can reach any destination of their choosing anywhere on the planet before the virus has reached the end of its silent incubation period. Nonetheless, the barriers are many and varied and the virus will find a difficult and often hopeless path on these journeys.

Silence, you peddlers of fear; knowledge remains our best weapon. As proof of the utility of knowledge, note well the examples of rabies and smallpox, viral diseases known for 2000 years: one must agree that these are scourges that are fading away or have disappeared. Despite the extreme pathogenicity of the rabies virus that killed mercilessly before Pasteur, despite the extreme infectivity of the smallpox virus that spread like wildfire before Jenner invented vaccination, our societies have prevailed in its confrontation with these viruses.

Science “discovered” the Ebola virus in 1976. The disease it caused fit within the framework of the viral hemorrhagic fevers such as Lassa fever, already known to Africa. In the late 1980s, other viral diseases, including acute lung injury syndrome, caused by a new Hantavirus found in the heart of North America, as well as Venezuelan and Brazilian hemorrhagic fevers and others known to reside in humans, animals, and even plants, were added to the list of previously known but newly described diseases such as the Argentinian, Bolivian, and Crimean-Congo hemorrhagic fevers.

Fed by the anxiety of the scientists facing these new pathologies, the concepts of new viral diseases, and new, emerging, or reemerging viruses, were born. The number of known viruses has grown considerably, and each viral epidemic event has provided an opportunity to isolate the germ, which was sometimes found to be new, sometimes different, sometimes forgotten and rediscovered. From concept to application, we have identified many risk factors associated with these emerging diseases, often factors recognized as anthropic (such as environmental alterations, increased trade, or social and cultural variations within human societies). This revisited role of viruses has proved to be essential yet complex in defining the concept,5 for the host is infected by a highly heterogeneous population of virus particles of the same species. The clinical picture is defined by the phenotype of the dominant genome of this virus population that, from host to host, through selection and mutations, maintains equilibrium. A risk factor foreign to this natural cycle can promote the dominance of another viral genome and result in changing the course of infection, thus promoting the emergence of these new viral diseases. Most viruses evolve slowly when the balance remains undisturbed. However, there are exceptions to this rule, such as the influenza virus, which in one revolution around the planet, changes its appearance, forcing us to reinvent the vaccine each time.

The Ebola virus is not expected to disturb the kingdom of Patagonia [3]. A vaccine against dengue hemorrhagic fever might well be discovered before the mechanisms of its pathogenicity are fully elucidated. For 20 years, Ebola remained unchanged, in a stable natural yet undiscovered refuge, with imbalance introduced but rare. The stage is only half set when the curtain goes up: has HIV, which shares the same African territories, participated in this imbalance? Other viruses of the Ebola type circulate in Africa and Asia, and some are not pathogenic in humans? Why? Could they point us to the path of the vaccine?

It is commonly agreed that viruses populated our planet and perhaps other planets, long before the appearance of the first vertebrates. The RNA that makes up the genome of the Ebola virus would be one of these prebiotic elements that promoted the evolution of life on Earth. Despite this ancient companionship between viruses and humans, the former have successfully colonized all ecosystems. Viruses, however, remain contained in their niches, which are by definition those of their reservoirs, and their wandering is restricted to their mode of transmission in a limited environment.

In this late 20th century, we are all concerned, separately and together, for the health of others, as for human massacres and attempts at genocide. Certainly, the tools for containing successive epidemics have multiplied, but the inequalities that allow them remain an open door to new pests or old suffering, have reawakened. The biodiversity of viruses is tremendous, but the discipline that studies them is less than a century old. We must learn and understand much more about viruses and the epidemics they cause to be able to determine their origins, how and why they evolve, and their mechanisms of pathogenicity. The answers are to be found by decoding their genome and by tracking them in nature. These highly pathogenic viruses attract our attention because they represent a major inherent risk. Understanding them may allow us to describe a model capable of warding off the worst. Some of us have chosen to study these rare but fortunately contained diseases. This knowledge, which is not without risk, is the price that must be paid so that health, in turn, may become epidemic.

Results

It has been 23 years since this essay was published, and 41 years since the “discovery” of Ebola, and we are still emerging from the worst Ebola outbreak in history. Gonzalez's prediction was arguably correct: Ebola was not the pandemic of the 20th century, but rather just one of the pandemics of the 21st century, together with SARS and avian influenza. Although it did not reach California or the Seine, this virus has extended its reach, thanks to air travel and the previously overestimated barriers mentioned in 1995 [1]. By June 2016, 11,325 people had died [4], as the once hidden, local virus, carried by an elusive wild reservoir, suddenly wandered across borders into major metropolitan areas. The virus, as we suspected it would, boarded passenger planes and travelled across continents and oceans.

For the past 40+ years, despite the instability of research funding and the overwhelming technical difficulties of studying such an infectious and deadly pathogen, the scientific community has been engaged in a tremendous effort to understand the arcane nature of the disease and evasive virus. Although a 15-year silent inter-epidemic period pushed available sources of financial support out of the forefront, the next series of Ebola epidemics prompted funding to resume Filovirus research. In total, 22 outbreaks have been documented from Yambuku in Mongala province in 1976 to Likati in the province of Bas Uélé in 2017. Five species of Ebolavirus have been identified so far, including four from Africa (Zaire, Sudan, Bundibugyo from Uganda, and Taï Forest from Cote d’Ivoire) and one from the Philippines (Reston). Other Filoviruses have also been discovered [5], both in the Marburgvirus genera and in the newly created Cuevavirus genus in the Filoviridae family. Nevertheless, it took more than 20 years (2005) to unveil just a fraction of the natural history of the Ebolavirus, to identify chiropterans (i.e., bats) as a potential Ebolavirus reservoir, and to link other mammalian species (non-human primates) to Ebola emergence events. The Ebola endemic zone has spread widely throughout Africa, but is entrenched within specific ecosystems of the tropical rainforest. Although it has become clear that the initial spark of a human epidemic often comes from bloody contact between a hunter and his infected prey, be it the carcass of a chimpanzee or a speared bat, the factors explaining the emergence of the virus in the wild at a given time and place remain mysterious to the scientific community. Does the reservoir shed the virus continuously throughout its life, or only at specific moments during gestation or infancy? Does it need help from an additional intermediary and unidentified host? Do other factors need to be taken into consideration, that is, do climate (e.g., humidity, temperature), season (e.g., abundance of wild virus reservoir), and/or increased human contact (e.g., hunting) influence occurrence? In other words, where does the virus hide during interepidemic interludes and how does its emergence occur as a zoonotic phenomenon? Answers to these questions comprise the fundamental knowledge necessary for understanding virus emergence and, ultimately, for being able to prevent and control future emerging events [6].

In March 2014, when the first case of Ebola fever surfaced in what would become an enormous, unprecedented epidemic of Ebola Virus Disease6 in West Africa, 22 emerging events had already taken place in sub-Saharan Africa. All were recorded, described, and well-documented, including epidemic patterns, point of emergence, spread, and disappearance. The most important characteristics of the disease were well understood before the 2014 West African outbreak, including, most importantly, the high risk that increased human-to-human transmission would scale up a limited outbreak into an epidemic. Another lesson clearly learned over the preceding events was that disease spread is linked to the population mobility and that multiple epidemic chains can start from one infected symptomatic individual introduced to a naive or distant population. Ultimately, finding and isolating all potential contacts is one of the most important tasks in interrupting any epidemic extension. Ebolavirus is highly virulent but has limited infectivity, therefore close contact with an infected, symptomatic person is necessary for transmission.

Discussion

So, with 40+ years of knowledge and fruitful experience, how did we fail to prevent the emergence of Ebola Virus Disease in West Africa that led to such a horrific and widespread outbreak? Initially, the limited national and regional surveillance systems for highly dangerous pathogens did not foresee the rapid and widespread dissemination of this disease in West Africa. The collective memory of each previous outbreak in Central Africa faded within a few months, so that experts and local health authorities thought that the response could be handled and supported by their historical partners alone. Moreover, as before, the international first response was limited, late, and began timidly, while response strategies involving multiple actors were discouraged. Ultimately, international responders had to circumvent heavy administrative workloads before engaging.

The West Africa Ebola outbreak also points to the systemic failure to produce financial mechanisms and deliver expeditious resource allocation. Targeted funding was only mobilized nine months after the first cases were reported. Ultimately, the financial impact of the outbreak left nations broken and their people vulnerable, while the epidemic continued to spread.

This outbreak was marginally, yet importantly, different from previous outbreaks in several ways. First, even though the index case occurred, as before, in a remote, rural area, people were now accustomed to moving nationwide. Transportation was much more available and accessible than ever. Next, although the primarily-affected population, the Kissi people, had customarily and for centuries inhabited, interacted, and communicated within their ancestral territories, spanning the borders of Guinea, Sierra Leone, and Liberia, now more than 386 millions cell phones in sub-Saharan Africa were available to contact the nearby traditional healer, thus overcoming any difficulties associated with accessing distant health facilities and delaying early warnings to the public health system. Finally, large metropolitan areas were affected for the first time in the history of ebolavirus, forcing responders to invent new strategies, and thus diverting resources from the ongoing outbreak.

As West African cases travelled to Nigeria and the US, carrying the virus with them, how were responders able to stop them from igniting other epidemic chains? It is important to understand that the level of awareness was already at its highest, particularly in these airports welcoming planes and travellers from West Africa. Moreover, like all African countries exposed regularly to viral hemorrhagic fevers, the Nigerian public health system was and still is accustomed to dealing with the endemic Lassa virus hemorrhagic fever; health authorities deal with this threat on a yearly basis, and health workers work together with communities to manage highly infectious patients. This national-level experience led to the rapid containment of imported cases. All strategies worked efficiently, including a massive public health response, proper expenditure of resources, and a “full court press” of contact tracing [7].

In past Ebola outbreaks in Africa, national health authorities have always identified EVD emergence two to three months after the presumed index case, and international responses have been mounted within two months of the confirmation of the first case. In comparison, another independent EVD outbreak, concurrent with that in West Africa, began in August 2014 in the remote Boende village of the Democratic Republic of Congo, just 500 km south of Yambuku. This outbreak was ultimately controlled by experienced Congolese health workers in 10 weeks, in what was certainly the most rapid response against an Ebola outbreak, one initiated less than two weeks after identification of the index case by the local health authorities.

We have learned much throughout the years, but we remember little when it counts, perhaps because the risk appears to be distant or exotic. Nevertheless, from the West African Ebola outbreak, we have learned again the same lessons that vaccine and therapies need–obviously–to be ready for use before an outbreak occurs. Several attempts at developing vaccines and therapies took place years ago. Nonetheless, it was only six months after the West African epidemic evolution began that the first “Phase I” assays of Ebola vaccine were authorized under the WHO International Health Regulation “compassionate use” provision for unregistered products. While the hope for a vaccine is rising fast, effective treatment has yet to be discovered. Therapies against other more common pathogens such as malaria or HIV must also be readily available. With a higher overall numbers of cases, the likelihood that patients will have several concomitant diseases increases, particularly in geographic regions where numerous pathogens are known to circulate. What are the effects of co-infections on mortality, duration, and severity of the post-Ebola syndrome? Many other pathogens of concern are indigenous to Sierra Leone, Guinea, and Liberia, such as the Lassa fever virus, a unique viral hemorrhagic fever that mimics the hemorrhagic symptoms of EVD [8]. If clinicians had in their arsenal of treatments effective weapons against these other diseases and were adequately armed to provide early and adequate supportive therapy [9], might EVD mortality rates drop significantly? Vaccines against Ebola will certainly make a difference in future outbreaks [10, 11]. Reviewing post-outbreak mathematical models that show the “salience of immunization” could perhaps enhance outbreak predictability. Finally, beyond the realm of drugs and therapies, the psychological trauma is extremely difficult to manage in this epidemic context. Primary health care systems in remote areas of Africa are ill-equipped to provide adequate mental health care, but this is much needed, not only for patients but also for survivors and affected families, long after the end of an epidemic.

We have certainly learned that early alerts are essential, that special funding for health emergencies is rapidly exhausted, and that an extremely high social factor (fear, ignorance, and denial) hinder response. Here it promoted expansion of the outbreak into a pandemic, from traditional Kissi territory to Madrid, Dallas, and New York City. Now, we must be prepared. Community counselling, education, and social mobilization, all social tasks that require an in-depth knowledge of the affected population's history and culture, are needed to promote early warnings and patient isolation, which must occur simultaneously to stop the chain of transmission. Capacity-building in endemic areas needs to be prioritized for an efficient early response and patient management. International response must be coordinated in total synergy and transparence with local health authorities. These requirements are known to responders today, just as they were known to the responders to the first Ebola outbreak [12].

Finally, any preparedness and response requires emergency funding. It has been estimated by the African Risk Capacity Agency of the African Union that the Ebola response, had it been initiated only two months earlier, might have reduced the total number of deaths by 80 % in Liberia and Sierra Leone [13]. Therefore, in March 2015, the African Union's Minister of Finance requested this agency to help Member States to improve planning, preparation, and response to devastating outbreaks, and to develop new applications from existing financial tools, such as insurance databases, that can significantly improve the speed of transfer of funds to affected countries and shorten the time between event and response. The agency is now developing an outbreak and epidemic insurance product primarily based on responsible and timely budget reallocation. Moreover, the World Bank's Pandemic Emergency Facility has been designed to finance surge capacity and support international government partners to actively participate in the response [14]. Ultimately, epidemics are not one-off events, but rather demonstrate financial patterns similar to other natural catastrophes. Classified as natural catastrophes, large epidemics can eventually be insured by creating financial mechanisms to facilitate the movement of critical resources within affected countries and ultimately manage the spread of disease and minimize its macroeconomic impact [13, 14].

We can hope that, perhaps, in a shrinking global community, with all the lessons learned cumulatively up to the 22nd Ebola outbreak in Likati, we will be more prepared for future epidemic challenges.

Conflicts of interest

The authors declare no conflict of interest. This article was prepared by the authors in their personal capacity. The opinions expressed in this article are the authors’ own and do not reflect the views of their affiliations.


1 With permission from the publisher.

2 Ebola Ivory Coast was first identified in a human host in November 1994, three months before the original editorial was published.

3 The Ebola virus re-emerged in Kikwit, Zaire (former Democratic Republic of the Congo) in April 1995 and caused 315 cases (250 deaths).

4 A 2014 study determined that African deaths in 2013 (a year before the Ebola fever outbreaks in West Africa) due to yellow fever numbered 78,000 [2].

5 Indeed, according to the quasispecies theory, which has become dogma, hosts are infected by heterogeneous populations of mutated strain of the same virus species, while a dominant mutated population drives the phenotypic expression (or not) of the pathogenesis in the host. Ultimately the dominant mutant will generate another heterogeneous population of mutant of the same species when transmitted from host to host, while such population maintains the species equilibrium and survival.

6 Renamed during the West African outbreak.