Monday, September 29, 2014

Ebolavirus 2014 Outbreak - #1

Ebolavirus 2014 Outbreak
September 2014 Update #1
Paul Herscu, ND, MPH
Herscu Laboratory
In the context of teaching about epidemics I began writing about the topic in the 1990s. Much of that work can be found on our website I have spoken about Ebolavirus since the late 1990s, in comparison to influenza in its various forms as well as laying out strategies to implement during epidemics. What follows are my general thoughts and understanding of Ebolavirus, and how they relate to practitioners of naturopathic medicine, complementary and alternative medicine (CAM), homeopathy and other integrative medicine approaches, as of September, 2014. Practitioners have remained mostly silent, yet many search for a framework to assist in humanitarian aid at this time. I would like to elucidate information about the Ebolavirus in general, and then move to specific thoughts about the Ebola 2014 Outbreak. The first section might be read by anyone interested on the topic. The second part is aimed at practitioners.

Filoviridae Family
The Ebolavirus is one of a couple of genera that are taxonomically organized within the Filoviridae Family. Aside from Ebolavirus, the other famous genus is Marburgvirus, along with the lesser Cuevavirus. The highlight of this Family is that it causes hemorrhagic fever and death in humans at a high rate.
Since 1997, but especially after 9/11, the US government with CDC and other international agencies, decided to catalogue more carefully and track biological agents that might be employed in bioterrorism or had a high level of potential harm if epidemic infection rates were reached. These were ‘Select Agents’, and on that list, Ebolavirus was a Tier 1 agent, meaning it was classified as an emerging potential threat for a widespread epidemic, with easy communicability, low infectious dose (even a few virions are enough to cause illness), and potential weaponization of the infectious agent.
The CDC had it right. If you would like to see the list and further information, here are the links:
In the Filoviridae family, viruses are single stranded and small, negative sense RNA. RNA viruses have RNA as their genetic material and can be single or double stranded; Ebolavirus is single stranded. The family name ‘Filoviridae‘ refers to the ‘filament’ appearance of the virus. Single stranded RNA viruses are further separated into possessing positive, negative and ambisense polarity. Positive sense viruses, known as Group IV on the Baltimore Method are very similar to the host’s mRNA, and therefore the human ribosome directly translates the genetic material as if it were part of a human cell, making protein. Examples of positive sense RNA viruses include SARS, West Nile Virus, Dengue virus, and Poliovirus, an auspicious and challenging group of viruses by any estimation. The negative sense viruses, such as Ebolavirus (Group V), are complementary to the host cell’s mRNA. This viral genetic material must go through a change, it must be transcribed into several positive sense RNA using a RNA-dependent RNA polymerase in order to turn into a positive sense RNA. Then they act similar enough to the above positive sense RNA virus. Examples of Negative sense RNA viruses aside from Ebolavirus, are Marburgvirus, Rabies virus, and Crimean-Congo hemorrhagic fever virus, also a very difficult group of viruses for humans to interface with. Just to round out the dangerous viruses, there are some single stranded RNA positive sense viruses that eventually need a DNA phase to complete their cycle, called Retroviruses, that are also threatening. HIV-1 and HIV-2, the viruses causing AIDS fit here. A list of viruses separated by Baltimore’s virus classification method that groups viruses into families based on their genome and replication method, can be found by clicking below:
As is common in viruses, the virion attaches to the cell surface of the host cell, fuses with it, releasing the viral nucleocapsid into the host cell cytosol. At this point the RNA-dependent RNA polymerase transcribes the genetic code into positive stranded mRNA, which eventually translates into proteins, eventually creating more virus, which bud off the host cell only to start the process once more.
The virus is small with a genome of around 19 kb in length, with each virion looking like a long strand of hair, straight or curved like a number 9 or a ‘u’ shape, which is around 80 nm wide and hundreds nm-14 μm long.
Aside from the description above, I should add that by use of genetic mutational clocks, we can tell that the family has been around for tens of millions of years, meaning that it has a long line of success to continue to build upon. RNA viruses have a very high rate of mutation or change when compared to DNA viruses. On the one hand this makes it hard to target the virus with vaccine, but on the other hand, not all genetic material is equal. There are some portions that are highly important for the virus to replicate; scientists are targeting those areas when looking to control the disease.
Actually, the first virus found in the family was Marburgvirus, described in 1967, named after the great city of Marburg, Germany. Researchers were handling tissue from Ugandan grivets (a monkey used to develop vaccines) and became sick, though the natural vector is more commonly known to be bats. All told, in the original outbreak in Marburg, 31 people were exposed and fell ill; seven died from hemorrhagic fever. In the wild, Angola and Uganda have taken the brunt of recurring outbreaks.
The high level of lethality made it a natural pathogen to weaponize. And this happened in the former Soviet Union, in today’s Sergiev Posad and at the State Research Center of Virology and Biotechnology in Koltsovo. When people raise concerns about bioterrorism, it is real and potentially exceedingly dangerous. All epidemics have been small, either in nature or in the lab, as has been the case with Ebola Virus Disease to date.
Which brings up the last point, but the most important one, as of September, 2014. The virus passes by direct contact with blood, bodily fluids, organs from a contaminated host or from the corpses of those who have died from this virus. While this shows a certain level of communicability, in that an individual need only come in contact with a few virions before falling ill, we are incredibly fortunate in that the virus is not passed by air as in aerosolized molecules, such as occurs with influenza. This is why, in general, the Filoviridae outbreaks have been short lived and except for those working with the tissues or viruses directly in research labs, have occurred mostly in developing countries in Africa. Historically, surrounded by poverty and in small villages, people got sick, they died, and the outbreak was soon contained.
Ebola Virus Disease (EVD)
The Genus Ebolavirus, identified in 1976, 9 years after Marburgvirus, follows all the biological tendencies described above. At the moment there are only a handful of species of Ebolavirus but this number is likely to grow as more research uncovers them. There is an unusually fast mutation rate in Ebolavirus, as one person passes to the next person being infected. Once someone has been exposed and becomes sick from the Ebolavirus, we say they have ‘Ebola Virus Disease’, but some call it simply ‘Ebola’, and others add ‘hemorrhagic fever’ to the name, though to be technically accurate, ‘Ebola Virus Disease’, is the correct name. This current epidemic is called ‘Ebola 2014 Outbreak’, though this name is likely to change to ‘Ebola 2014 Epidemic,’ as we are past the outbreak phase. We also shorten the name to EVD. However, please be aware that currently, in North America there is a separate viral epidemic called either EVD68 or EV-D68, which is an enterovirus Species D, serotype 68, causing the respiratory infections we hear much about.
Someone becomes infected with Ebolavirus by having the virion enter through the mouth, broken skin or mucous membrane. The virus then advances to a variety of cells, eventually spreading through the lymph channels, liver and spleen. The virus takes over protein production, releases pro-inflammatory cytokines, leading to vascular leakage, and clotting problems. The virus also makes a protein that helps attach the virus to the endothelial cells inside blood vessel walls, which eventually weakens the blood vessels. Liver cells die off, breaking down clotting processes, the adrenals and kidneys cell die and blood pressure control is compromised. Organs begin to shut down.
The specifics around EVD are as follows.
Incubation period is anywhere from as short as 2 days, to a more typical 8-10 day period. However, infections have been known to arise 3 weeks after exposure; if someone is not symptomatic in 21 days, it is not likely that they will become symptomatic.
The symptoms that arise with early EVD are typical to viral infections such as influenza. Here we find complaints of chills, fever higher than 101.5F or 38.6C and significant fatigue and tiredness, which commonly takes the patient to bed. There are skin complaints such as flat or slightly raised rash on the face, trunk and arms.
After this initial influenza like illness, on day 5-7, more GI and musculoskeletal symptoms develop. Here we find muscle aches, joint pain and severe headache.
GI complaints, such as loss of appetite, abdominal pains, nausea, vomiting, severe watery diarrhea ensue.
Respiratory complaints, such as sore throat, difficulty swallowing, shortness of breath and chest pain are often present.
Up to this point, someone may think they have a common, albeit severe, viral infection. It is after this that the patient can either improve and have a long recovery period, or may take a turn for the worse, usually after around a week or two of being ill. This worsening is characterized by hematological complaints. In about half the people infected, bleeding begins from an injury or spontaneously, subcutaneously (purpura, ecchymoses, or bleeds from punctures), or from any mucus membrane, such as GI tract, mouth, nose, vagina, eyes, but also internally, with organ damage, especially in the liver and/or kidney.
Death may ensue around the 2-week mark.
Treatment is aimed at supportive care to contain the symptoms and this by itself saves lives. Aside from that, we have at least two major pathways that may offer solutions:
1. Antivirals. It is likely that drugs used to treat other viruses will be tried to see if there is any success, even drugs used for non RNA viruses. This makes sense in that the virus may be stopped at various targets, such as at attachment or even at the budding off stage or during any phases of replication. This means that over the next few weeks and months you are likely to hear that this or that antiviral has a certain amount of benefit for patients with EVD.
2. Plasma products. Plasma products that mimic those of survivors of EVD will be tried and will have different levels of success. This means everything from plasma transfusions from survivors to fresh frozen plasma, to antibodies manufactured in the lab. Plasma products may control both the inflammatory response as well as vascular breakdown.
As mentioned above, one positive attribute about the virus, up to now, is that it can only be passed by direct contact with body fluids. No contact equals no transmission. Also in our favor, as I had previously mentioned, is that the ill are so weak they tend to isolate, not move around a lot. In fact, the vast majority of people who become infected come to the ill person, either to provide care or to perform funeral rites/burial practices with the patient’s remains. But in this case unfortunately, the patient’s remains may still infect those who come in contact with the body.
This particular outbreak may have begun with a human being coming in contact with an infected host, such as a primate or a bat, or in some other way in contact with fluids from those species, along a short or longer chain of the ecology or predator/prey relationship. Many primates, such as gorillas die of Ebolavirus. Humans may have eaten bushmeat where that animal had eaten something that had the virus in it. Recently it has been found that both pigs and dogs may be able to carry the virus, a point I will return to in a moment. In general though, the disease is so severe that, by nature, it should be self-limiting in humans. We are too weak to move about, too secluded, and therefore die and the outbreak dies with us. Before. Up to now.
I hope with the above, we can come to the following conclusions, as to why this epidemic is spreading.
First, Africa is changing. More people are leaving villages and congregating in more densely populated areas, making likelihood of transmission greater. To date, no very large city has gotten the epidemic yet, though if it does, the number of dead will climb at an alarming rate.
Second, the countries where the epidemic flourishes are poor. The poverty can be seen reflected in the health care system where there is both a severe lack of infrastructure to oversee an epidemic halting effort and where there are few to no physicians or other health care workers to care for the sick properly or to disseminate helpful information effectively.
Third, lack of education in general, related to poverty and lack of education as to what EVD is and more specifically how it is transmitted are all factors making the epidemic worse. Traditional burial rites unchanged, perpetuate the transmission of the disease. Most people suffering from EVD during this 2014 epidemic lack the knowledge of how the virus is transmitted and therefore become infected from taking care of the ill or from preparing a body for burial.
Adequate and ongoing funding is needed for proper education and healthcare infrastructure.
My worries & concerns
In no specific order, I would like to tell you what I worry about most when thinking about this moment in history.
At the moment, Ebolavirus 2014 has not infiltrated any large city, but if and when it does, the number of people who will be impacted will skyrocket.
At the moment, leaving out other vectors and reservoirs, Ebolavirus is transmitted human to human, only by touching human tissue and fluid. However, if it mutates in such a way as to allow aerosolizing methods of transmission, then this story will take a tragic turn. We might see a potential 50% lethality but with very high levels of transmission. For this to happen, a number of things need to take place. First the virus must mutate and at the same time, not mutate in its lethality, and simultaneously remain stable during transmission. It is unlikely that these three things would occur at once, but it is potentially possible.
Related, I worry about someone weaponizing the virus. I believe government should play a bigger role limiting exposure of anyone to the virus not just for their own health but potentially for future devious purposes. It is akin to having loose radioactive material lying around. I believe governments of the world need to be proactive and forward thinking on this note.
The longer the epidemic goes, the more mutations there are. Sooner or later it may become easier to pass it to pigs and dogs, though it already does this to a small extent. There are wild dogs all over Africa and if there becomes a version of the virus that is passed easily between dogs and/or pigs, their proximity to humans could be a source of infection. Again, this becomes more of a possibility the longer the epidemic ensues.
Any discussion here must address deep-seated poverty. In almost all respects, this epidemic is caused by lack of political will to bear enough and rapid economic relief. Yes, the Ebolavirus causes the disease, but that is only the start. For it to become an epidemic you need a poor and uneducated population, which has neither the education or resources to stop an epidemic.
There will either be 10,000-30,000 people killed from this epidemic or the number will be in the millions. The difference is not the virus, but the delays our and other governments have had in addressing needs of the public good. If you were to go to the CDC website, you can find all the specifics of how the USA can deal with Ebolavirus, how to make the diagnosis, how to transport the ill, how to take care of the ill, how to handle samples, how to handle the dead, etc. In all instances, if the virus does not change, we should be in good enough shape. However, when you look at the list of tasks, what is striking is how impossible it is to implement those tasks because of where the epidemic is taking place at the moment. If we want to stop millions from dying, we have to act now, with the appropriate, relevant level of funding and medical care. This epidemic could kill only 10,000 people, but that number can pass within a month if we do not bring the full plan to where it is needed now. See below for the CDC references on Ebolavirus treatment recommendations if it were to reach the shores of the USA:
The point I am making and what is frustrating is that we know we know how to clean a hospital or a home to get rid of the Ebolavirus, we know that after proper cleaning and disinfecting, Ebolavirus will not be found in an area after a short time (one day with proper cleaning). We know how to take care of human remains. We know how to handle tissue, waste, fluids, and blood samples properly. We know how to manage ill patients and those suspected of being ill with Ebolavirus, in terms of keeping them from infecting others.
We know how to wash hands and we know how to rehydrate the ill. While many people will die due to the severity of this disease, many die needlessly from the effects that we may be able to control, oral rehydration and IV hydration being on that short list. Half of those infected do not die as of now. In short, we can detect those that are ill, and keep them from infecting other people. In other words, 10,000 dead. A sad disheartening number, but a very different story than millions dead. It is not science missing here, but the political will to spend enough money and resources quickly to do what needs to be done.
Most embarrassingly, and to make my point here, when it is all said and done, and proper statistics are applied what will be found is that the poor and uneducated were disproportionately effected by death in this epidemic. In other words, it is less about the virus and more about how as a society, we chose to address the infrastructure issues, the allocation of resources in a timely fashion and the dispatching of medical care where needed.
The role of those practicing in naturopathic, homeopathic, CAM, and integrative medicine settings in general and during  the time of Ebola 2014 Outbreak, September, 2014
The highest level of any physician should be to function at the primary prevention level. In this instance, primary prevention means limiting the number of people who are exposed to the virus so that the epidemic may end. The majority of energy should be spent not on treatment, but in the prevention of exposure to the virus. Prevention is the essential way we can see ourselves out of this potential disaster, prevention as soon as possible. The natural medicine community has a role to play.
The natural medicine community, like any organization of individuals can and should bring its political voice to bear urging politicians in charge of the purse strings to adequately fund prevention protocols.
Like every other medical and nonmedical organization, civic group or religious community, at the very least, we can assist in the collection and distribution of products needed to decrease exposure. Here I mean everything from surgical gloves and masks to gowns. I also mean cleaning agents such as soap and pH changing products such as bleach. Assisting with the removal of potentially exposed substances and surfaces will also be needed. Please remember that these ‘simple’ acts will save millions of lives.
Those trained in public health measures can assist within the current public health command. This means everything from assisting in surveillance, finding both exposed and sick individuals, transporting exposed and ill patients while limiting travel of those individuals and providing quarantine assistance, helping with communication of status in a defined area, and assisting in the safe removal and processing of the remains of the deceased. Simply put, as is true in every large-scale emergency, either be part of the larger command and control or try to stay out of the way. There is always a great deal of confusion on the ground; we do not want to add to it. This is also true for all other needed physicians and medical staff who are best employed within the extant structure.
CAM practitioners can help provide lower level medical support such as rehydration and palliative care. And if during this time, one finds themselves in the situation that they are either presented with an ill patient and/or presented with a person who was exposed to the virus, then I believe that a CAM approach, such as a homeopathic remedy, matching the symptoms of the individual can be given. I base this on both basic humanitarian principles, as well as a form of precautionary principle. You are not preventing any other treatment that may be tried, you are protecting the society at large, the family of the ill person by quarantine, and there, in that instance, there is nothing to lose. The medicine and care is free to the patients. In all countries around the world, there are compassionate and early use clauses for application of early investigational therapies, for unapproved medicines under compassionate rules, even when the therapy has a potential of harm, but this is especially so if the medicine is safe, but not yet proven effective. For example in the USA, we have the following from the FDA, though there are more:
Availability of Investigational Drugs for Compassionate Use,” and
“IDE Early/Expanded Access”
Indeed this is why so many antiviral drugs are currently being tested.
Under these circumstances, to prevent, ridicule, deride, or in other way diminish the likelihood of potential care to be given is in fact limiting access to healthcarerecognized by most civil society as a basic human right —and limiting access is contrary to the public good as well as decency. Put simply, there is no proof that homeopathy or other CAM approaches may help in this circumstance, but likewise there is no proof that they will not help, and with homeopathy, we have 200 years of proof that it does not hurt. In any other situation, any reasonable, nonbiased scientist would try this. Indeed this is the premise of the current treatments that have been tried recently during this epidemic. So many antivirals are being tested as I write, on this basic premise. For example, Zmapp, the experimental biopharmaceutical agent was used on people before proper preclinical trials were concluded to show safety and efficacy, and there we had real potential for harm. See below:
Anything short of allowing access is an example of the ‘tomato effect’ seen in people acting unscientifically, and not in keeping step with the rest of science at the moment as it relates to Ebola Virus Epidemic 2014. In fact, I would say that in the circumstance I described above, where the patient is receiving the best care possible, given the resources available, it would be interesting for everyone to test out whether a safe CAM approach like homeopathic medicine actually provides benefit. This would be interesting for all; likewise, if the substance is completely useless, this would be valuable information, too. Join me in this call for a rational approach, unfettered by bias. Rational prudent thought should prevail.
The response of all CAM to the Ebola 2014 Epidemic should be to help highlight and advocate for prevention, assist in identification, stabilization and quarantining of exposed and ill individuals, and support cleaning and disinfection processes, and provide CAM aid where and when appropriate. There should be the push from every medical community to their government to support relief efforts. If you are still asking what is the best drug or herb or homeopathic remedy here, then your focus needs to change. It is time to act. Individuals and groups should donate resources and material as well as professional expertise.
If you would like to write to your US Senator and Representative, to encourage support of immediate increase in funding to contain Ebolavirus epidemic, you can find their contact information here by entering your zip code:
When you write to your national lawmaker, be sure to include your name and address.
To donate funds, here is a list of top rated charities, graded for how much of funds donated are used for the intended cause (to fight Ebolavirus, for example) and what percent of their funding is spent on raising more money:
If you are so moved to do more and want to donate your time on the ground, training is available through the CDC. For further information see:
Doctors without Borders needs help in many areas, a listing is found here:
We encourage you to work within your state and national associations to create policy and framework for your members to understand Ebolavirus and make policy and contributions as relevant.

In health,
Paul Herscu, ND, DHANP, MPH