EBOLA OVERVIEW

My First Taste of EbolaAs an Infectious Diseases specialist practicing clinical medicine these near 40 years, I have had to not only focus on each new patient as I enter their room, but also to keep abreast of biological phenomena emerging and evolving in my community as well as across the globe. Because we have cultivated expertise in dealing with medical problems arising during or after foreign travel, a new onset fever in Exam Room 2 could be a urinary tract infection, infected gallbladder, prostatitis, typhoid fever, malaria, dengue fever, Ebola virus (EV),… It is an ID doc’s business to have an expansive view on all the possibilities for the interests of our patients who are acutely ill, wherein timely, accurate actions are often outcome-critical. But we must also be aware for ourselves, as well. I and my staff have yet to acquire an infection from a patient.Realizing that in this world of high-mortality infections from developing countries that are human-human transmissible (multi-drug resistant TB, avian-asian flu, MERS, SARS, Ebola virus, etc), exposure is a real possibility and only a plane flight away.So, I have been watching closely the EVD story unfolding in West Africa since early 2014. I first became aware of EVD during my Infectious Diseases fellowship training in 1980, just a few years after Ebola emerged in a lethal, local outbreak in Zaire (Congo), killing the majority of those infected quickly. Many of those were first case-contact healthcare workers, unaware of their jeopardy. EVD had started in rural communities with no medical sophistication, no really legitimate medical supportive diagnostic testing or treatment. So, the outbreak was self-limited – a biological flare-out. EVD killed most everyone before they knew what hit them. It was an amazingly efficient killing machine, with no implications for the rest of us – killed them before it could be spread. This very much suggested that EV was a virus naturally residing in the animal kingdom, with humans only accidental hosts (with no immunity). I was fascinated by the Darwinian modeling of this and so decided to do my annual research fellow’s talk to my Infectious Diseases department on viral hemorrhagic fevers – dengue, yellow fever, Marburg virus, Lassa virus, Junin virus, Crimean vole fever, and on and on. Since then, there had been periodical, similarly confined EVD outbreaks. The New Ebola EmergesThen there was 2014, a very different picture than anything before. What to make of it? I have listened to public health officials from the U.S. CDC and World Health Organization tabulate the cases and deaths (around 1450 to this point) and the geographic extent – 4 countries, so far. And, in the past week, EVD has broken out in the Congo, but it is unclear whether this is the same or a different EV strain. WHO officials estimate current overall figures are at least 20% on the low side. And this has gone on since December, 2013, with the official position that the epidemic has not peaked. I am not clear why this is not being called “a pandemic” – multi-site epidemics. But, I will comment on that later.Public officials imply that modernity in afflicted African nations accounts for the EVD dissemination – that radical changes in mobility and transportation in Liberia, Sierra Leone, Guinea, and Nigeria are the explanation for the expansive and sustained nature of this epidemic. It does not seem plausible to me that those countries have changed so radically in how human beings move about in these past 35 years to account for this devastation. And, surely the handling of bodies for burial rituals would seem a culturally embedded behavior highly unlikely to have changed from immemorial custom. In fact, since there have been several outbreaks since the 70’s and EVD is well-known biologically and medically, especially for a 50-90% mortality (60% with the current outbreak), one would think focused attention on containment would be working by now. Unless this Ebola virus has or is changing from its original, native (wild) form that resided in the animal kingdom (fruit bats and possibly non-human primates) prior to the 1970’s. Lessons From the 1918 Spanish Flu Pandemic HolocaustWhen the novel H1N1 influenza pandemic arose in 2009, I was challenged to dig deeply into that as a risk since it would surely be coming to my doorstep. Researching flu pandemics and then giving a talk to my medical community to bring them up to speed on how pandemic flu might play-out gave me unexpected insights into the nature of viral biological behavior across human populations. Since influenza is a respiratory transmissible agent and, as far as we know or are told, Ebola agent is not, the analogy I will make is not perfect. However, reviewing what happened in the 1918 Spanish Flu Pandemic still provides potentially valuable perspectives. After all, taking into account the differences between flu and EVD, biological principles still are at work – and are similar, even if not identical. A couple principles about pandemics first,

1. Pandemic*: multicentric, concurrent, community-based epidemics (increased disease activity in a population over the usual baseline). This term does not imply anything about individual case severity or mortality, just rate of occurrence of cases.*There has been a human-to-human transmission virus mutation, causing a novel (to humans) virus to emerge against which little or no human immunity exists.
2. Where? Everywhere, virtually, infecting between 15-40% of the entire population in waves of increased case numbers every 8-12 weeks over a year, on average.
3. Viral mutations occur randomly affecting mainly 2 clinically relevant inherent properties that are independent of each other (many combinations are possible),
   1. Virulence – the ability of a virus to cause tissue/cell damage (= disease pathogenesis)
   2. Transmissibility (human-to-human)
      • Airborne
      • Body fluids(/li>

As time goes on in a pandemic, and there is sustained passage of the virus through the human herd, the virus can mutate to a more synergistic form – such that it is more easily transmissible (good for it, since it gets to infect more hosts) and less virulent (kills less of its hosts – good for it, since it gets to live to infect another day). So, the Darwinian process of selection evolves the virus into a symbiosis: mutually beneficial (neither dies) biological relationship of tolerance with its hosts. It may be less of a killer, but still kills, especially the weaker hosts in the herd – very young, very old, very infirm; rather than those in the prime of their biological lives (the age of optimal reproductive capability – early teens to late 30’s). Those in their prime die fastest and the most in pandemics with a “novel” virus. Their immune systems are a nuclear weapon unleashed against an invader (pathogen) entirely foreign to them; so they ravage their own bodies in all-out war. An irrational (evolution-wise) biological meltdown.To provide a thumbnail view of the evolving horror of a virus novel to humans that mutates in virulence and transmissibility there is no better example than a brief recounting of the 1918 Spanish Flu Pandemic. Let me first shock you with facts that will make you wonder how you never heard of this, or that you don’t recall it,1918 H1N1 Spanish FluDeath Rate = 2.5% (20x normal flu)20-100 Million Worldwide Deaths (1.8 Billion World Population)550,000 - 675,000 U.S. Deaths (105 Million U.S. Population)1/3 World Population Infected>5% Total World Population Died5-10% World’s Young Adults DiedMore deaths than WWI & IIMore deaths than 100-yr. Black Death (Bubonic Plague) in EuropeWhy? Only one gene (Texas/39/91) mutated, such that there was a change in a hemagglutinin protein that was the cell binding receptor of the H1N1 flu virus for the cells of its human hosts. This single change made human-to-human transmission extremely easy (by airborne droplets, such as with sneezing); the virus could readily hook-up with host cells.  And, this was a “novel” virus – a new variant of flu unknown to the immune systems of humans (crossed over from the usual animal kingdom reservoir species). These two facts killed about 5% of all humans in existence – 1 in every 20 people, everywhere.Now, a synopsis of the story. 1918 Spanish Flu Horror StoryThe First WaveToward the end of February, 1918, 1,100 troops stationed in Haskell County, Kansas were suddenly hospitalized over a 3 week period.By March 18^th, 10% of troops were sick with influenza at a fort in Georgia.In April, 24 of 36 of the largest army camps had illness, and then 30 of 50 U.S. cities saw a spike in flu epidemic mortality. At the same time, troop movements associated with WWI brought illness to a port in France, Brest. Straightway illness arose in the French (and Paris), British, and German armies.By May, there were 36,500 cases in the British Army and outbreaks appeared in India and China. Interestingly, the movement of this pandemic was first reported to the worldwide public by a Spanish newspaper, a war-neutral country. Wartime censorship (remember this) was in effect in the WWI engaged countries to maintain national calm and order, especially among troops.In June, disease was rampant in England, and then throughout Europe and Scandinavia. By this time, transmission was explosive, but most cases were mild. However, as the virus spread across Europe, some unusually violent cases of hemorrhagic pneumonia (fatal within 24-48hrs of illness onset) surfaced, suggesting another mutation in flu virus virulence. This, coupled with extreme transmissibility, was a deadly development that threatened the entire human race.However, by late July, British High Command declared the epidemic over. That was wishful thinking, and probably wartime propaganda (again, remember this). The disease was smoldering after its first wave had killed off those most susceptible to its first version of the novel flu virus, and now was persisting and passaging through remaining human hosts. Each day of this stage, as innumerable viral particles replicated, was an opportunity for the genetic slot machine in the virion to re-align and mutate genes for another run at the host. The Second WaveThe incidence of new flu cases progressively increased again throughout the summer, until late August/early Sept. when there was a soaring death rate in Boston at U.S. Army Camp Devens, where 1,543 soldiers fell ill in one day, and 100/day were dying. Remember, these were young men in their biological and fitness prime, co-habiting in tight barracks. This was the turning point to something unprecedented and unthinkable. Why? Many of these cases were fulminant, hemorrhagic pneumonia. Within 2 hours of admission to the hospital, patients were in respiratory failure with their lungs dissolving into necrotic blood. A few hours later they were cyanotic (blue) from inability to oxygenate tissues. A few hours more, dead. There were deaths 16H after symptom onset.In major U.S. cities, corpses were stacked in morgues, on front porches, and on sidewalks. There were no more caskets and morgues were overflowing with corpses. Every home had someone ill. There was legitimate fear that this pandemic could wipe out civilization. The virus did not need human hosts. Birds and swine were its natural hosts, so it could run through the human species lethally with no threat to its ultimate existence.Fortuitously, as it had done in its earlier sustained human tissue passage, the virus mutated back toward a less virulent form. The Third Wave and BeyondThe flu persisted in smaller waves all the way to 1922. And through this last protracted wave it still was the 2^nd or 3^rd highest flu mortality phenomenon of the 20^th century. DISCUSSIONThe Current EVTo be very clear, Ebola virus is not influenza virus. Influenza viruses are very prone to mutation. It is not clear how mutable is Ebola. Ebola is an RNA virus and they are known for rapid genetic changes. At this time we are told it is not easily transmissible. That has always been the book on EV. However, it has also always occurred in explosive, but short-lived, geographically circumscribed outbreaks. But, it is a virus and, with sustained passage through human tissues, could mutate with respect to virulence and/or transmissibility. Even officials at the WHO have expressed concern for such a happenstance – EV with airborne capability is a doomsday scenario. Has that happened? We have not been told. But, take a look at the austere measures being imposed in Liberia and Sierra Leone regarding community-wide quarantine and travel restrictions, as well as the ensuing social chaos. When Dr. Thomas Frieden, CDC’s Director, was recently asked if the current EV is airborne, he responded that it has not been “proven” to be airborne. He did not say he knew it was not. It is very calculated language. This in the mantra of the newly embraced “evidence-based medicine”: if it is not proven, you state it is not so (though it may be). But, on July 29, the CDC acknowledged EVD human-to-human airborne risk by instructing US commercial flight crews to place a respiratory mask on sick passengers to decrease risk of virus spreading by airborne droplets from sneezing and coughing.  A 2012 study using 4 macaque monkeys with no physical contact showed spread of EV among them, validating its airborne spread between animals, if not humans… yet.During the 1918 Flu Pandemic, government officials in San Francisco censored (here it is again) information to minimize social disorder and economic disruption. Officials did not want panic and fear stoked by citizens walking about with respiratory mask on causing others to stay home from work and school, as well as diminished commerce from travel to their city. It is felt that thousands died because of withholding information real-time. The military adversaries in WWI did the same. I am not saying that government-employed officials at CDC are doing that. But, I am saying maybe. There is precedent for this. And we now have a series of epidemics in the African subcontinent that, if it goes beyond to another continent, will be properly a pandemic. There has been no convincing fact-basis regarding African culture or societal changes over the past 40 years since the first of the periodical, self-limited Ebola outbreaks to explain what is happening.So, we are left to speculate on whether there has been a fundamental change in the nature of the Ebola virus. Until we are provided such information by scientists and public officials, we must keep attentive to the EV story for features suggestive of a developing pandemic, which would imply a change in the virus itself,

1. Shift of highest death rates to younger populations
2. Increased overall death rate (at this time about 60%) – figures as high as 90% have been quoted, but remember that that high mortality figure may be when the ill are undernourished, rural Africans with no access to the most fundamental medical interventions, like IV fluids; and many of those probably have system – weakening chronic infections with parasites, HIV, etc. Furthermore, they are also more prone to Ebola high-risk cultural and religious rituals such as hands-on body preparation for burial (and unlikely to heed prohibitions by public health officials)
3. Exponential increase in case numbers suggesting higher than traditional transmissibility
4. Waves of disease occurrence with ongoing viral passage through human tissues bringing the risk of mutation to increased virulence (though it can go the other way, too)
5. The nature of NOVEL viruses (those that jump across the animal kingdom from one species [birds] to another [humans]) is a sudden evolutionary jump resulting in biological chaos where an immune system never having seen such an invader “goes nuclear” instead of mounting a moderate response – a response that kills the host; using a shotgun to remove a fly from a wall because you have never seen a fly before.

An Unsettling PresentThink briefly of my abridged 1918 Pandemic story. Take the time to read more in depth about it from other sources. That will be a story of the future (if not present). In honesty, virological and epidemiological science did not exist then. They did not know with what they were dealing. We now have the benefit of scientific surveillance and diagnostic tools and globally interconnected communications, as well as integrated public health organizations, such as the U.S. Centers for Disease Control and the World Health Organization (WHO). And, at least in urban centers of fully developed societies, we have medical interventions that can be life-saving. But, not nearly enough to meet the need in a major pandemic. And don’t count on the expertise of the U.S. medical system which has no broad experience with such matters. Our system will make errors if EV comes to the U.S. that show shocking ineptitude and incapability. The battle will be won or at least losses mitigated by real-time, accurate information provided transparently to the general public along with public health measures to effect containment through quarantine and contact/exposure avoidance.If you take all of this in, you must agree that it is highly irresponsible or medically insane to deliberately bring anyone harboring this virus to countries free of the disease. It risks further viral propagation and mutation. Yet, our CDC officials saw fit to do this. And, I have heard no one question the wisdom of that move as the media and officials show-cased the U.S. Ebola survivors as a public relations showcase for U.S. – based care, attempting to allay the fears of a public disconnected from ominous reality. Foolishness. Indefensible, medically. With highest level containment procedures, the risk of spread to the U.S. public at large was probably very small – but you cannot know this unless you are sure the current EV is the original EV. And no one knows that. The features of the current epidemics speak strongly against that. Walking A Fine Line: Official StatementsThe reflexive response to this type of piece is to say it is alarmist, especially by those who are charged with maintaining order. However, note that, on 8/26/14, Dr. Frieden (CDC) stated the outbreak “is even worse than we feared” and that “the world is losing the fight against Ebola.” His statements just weeks before were reassuring to cautious. Recall the official censorship and propaganda that was evident after-the-fact regarding the 1918 Flu. He apparently even approved bringing the two EV cases to the U.S. for hospitalization at Emory U. He also said, “There are more Ebola cases (in Liberia) than have been reported. There are more cases than have been diagnosed and there are patients that are just far, far, far too many for the treatment services. And what that means is that Ebola is spreading widely in communities. This is absolutely unprecedented.”In another interview, Frieden, who is currently traveling through the epidemic areas, said, “unfortunately, we are definitely not at the peak. It’s going to get worse before it gets better. The real question is how much worse will it get?” These are chilling words from a high-public official, suggesting that the extremity of this situation cannot be exaggerated. They are worried about a multi-national pandemic if the virus has mutated from its wild-type (natural form).To be clear, other factors can be at play in the severity and extent of this epidemic – improper handling and disposal of corpses and inability to completely trace and contain contacts of infected cases. Part of the problem also is an up to 21-day incubation period (during which an infected individual is supposedly not contagious) from acquiring EV until the first onset of clinical illness… which can mean lack of recognition of the problem, and so exposure of others. So, part of the problem is a killer virus working through a dysfunctional, backward social and medical system – a lethal combination. And, the longer this goes on, the more the chance of a novel, pandemic virus mutation, which will then become the world-at-large’s problem. The language of officials is finally catching up to this reality.I place disproportionate value on hindsight. History teaches, but you must know history. Review the 1918 Flu Pandemic narrative and then stay close to unfolding EV events.Is this a doomsday scenario? Again, look at the 1918 Flu Pandemic for the reassuring answer. It is a Darwinian model where adaptation is the operative word. Life sustains by finding a niché that allows it to continue to… live. That being so, we can expect that mutant, killer variants of a virus will… kill, up to a point. Kill their hosts; hosts which the viruses need to survive. Then they have no home – it is incidental suicide. So, biologically, it should be a self-limiting process… good for us. Of course, biology is so complex that one could almost always draw an exception to a statement. The exception here? The mutant, novel virus that is highly or completely lethal for humans resides intact in other parts of the animal kingdom where it smoulders until, at some random moment, when conditions create a favorable pathway, it crosses over to a human – the course and outcome (whether a single person dies or there is a devastating epidemic or pandemic) depends on what you already learned – transmissibility, virulence, and novelty. However, if such a virus has other hosts, it does not “need” the human race to survive as a reservoir/home. That is the doomsday model. We are not there yet. Remember, the 1918 Pandemic burned itself out in diminishing successive waves of less virulent, less deadly infection up to 1922.Until this epidemic is over (not just on the wane – remember 1918-22), the world must be on lockdown. Most certainly the medical profession – all physicians, all facilities – must be thoroughly informed on EVD and follow strict, proactive public health procedures of EV containment and handling (see other Ebola content on this website) with regard to the living and the dead.We do not need to be fearful or to panic. We need to be intelligent, develop information, and then form a rational response to protect ourselves while this biological event runs its course. Life is not risk-free, never was. This problem will play itself out as we work our way through it and then have a more well-formed, learned approach the next time it or something similar surfaces. Edward R. Rensimer, MDDirector, International Medicine Center