Thursday, October 23, 2014

Ebolavirus 2014 Outbreak - #3

Ebolavirus 2014 Outbreak
October 16, 2014 Update #3
Paul Herscu, ND, DHANP, MPH
Herscu Laboratory

When you turn on the news just now, there is a great deal of media attention on the Ebolavirus outbreak. And as importantly, there is a sort of hysteria in the general public, as well as in the healthcare community, including those in CAM. In this recent Kaiser poll about half of all Americans believe their family is at risk of contracting Ebola. (
Let me say here clearly, that unless something unusual occurs such as 1) a change in the transmission mode, as in it becoming airborne (which is a difficult thing to happen and despite what some at CDC and in the government have said, has absolutely NOT happened. Ebolavirus has not become airborne. They are wrong here, but will explain their mistake in the next post), 2) a change in vectors, as in animals that have yet to transmit to humans, and/or 3) a change in incubation time, as in a lengthening of incubation time while still being contagious (which both may be difficult to occur at the same time), there will NOT be an epidemic in the USA, in North America, or in Europe. Nor will there be a greatly widening epidemic within Africa itself. And as shocking as it seems to you just now, the average person will hardly, sadly, think about it by the end of the year. I have tried to say this in a variety of ways, but I thought I would say it again here. In essence people are worrying about the wrong thing, the wrong epidemic, the wrong focus. I hope that by reading these communiqués, you will be better prepared to handle the media, assess the information you hear, and not become overly anxious because of hyped up media offerings. As promised, I wanted to discuss treatments that occur at this time. 

As mentioned in the first post, aside from treatment aimed at supportive care, we have at least two major pathways for treatmentantivirals and plasma products. While no drug is yet approved, there are a host of medications being tested. 

Emerging treatments
As predicted, a great deal of media has shifted to reporting on any number of antiviral drugs tested for the treatment of Ebolavirus Disease. It is not going to be just the antiviral medication that make sense but, ‘as long as we have drugs, let’s try any of them, and see what success might be had.’ There has been a plethora of articles on this topic already, using a variety of existing drugs. Here are some highlights:

Interferon is currently thought to help slow down but not change mortality rate, but new research may show that earlier use might help there. It is just in the last month that a mechanism of action helps us understand why Interferon may be helpful as part of a regimen for Ebolavirus Disease.

Lamivudine, by GlaxoSmithKline, is an antiretroviral used for HIV and Hepatitis B patients. Specifically, it is a reverse-transcriptase inhibitor, which is the enzyme that helps make the cDNA complementary DNA, off of a RNA template. Retroviruses need to do this reverse transcription to replicate and therefore if you inhibit this process, you slow down replication.

Brincidofovir, made by Chimerix, originally designed for other viruses such as cytomegalovirus is in the experimental stage for Ebolavirus Disease treatment as well. As you may have heard the patient Thomas Eric Duncan, in Dallas, was treated with this medication died, but that does not necessarily mean that the drug is a failure as that particular patient may have been too far progressed in the disease. In short, it is too early to tell, but I suspect this drug is going to be used to treat some virus in the future.

TKM-Ebola, by Tekmira Pharmaceuticals, is a combination of Small or Short, or Silencing interfering RNA (siRNA), aiming at 3 of the 7 proteins in Ebolavirus. siRNA are double stranded RNA molecules with a length of 20-25 base pairs. Primarily interesting in that they cause RNA interference by stopping expression of specific genes with complementary nucleotide sequences, making mRNA break after transcription, so no translation. So in a way, we are giving the virus a virus. Oddly interesting.

BCX4430 made by BioCryst Pharmaceuticals was tried originally for Hepatitis C, but more recently has been used for Ebolavirus. BCX4430 is a viral Nucleoside RNA-dependent RNA polymerase (RdRp) inhibitor, which gets metabolized to a nucleotide form, binding to viral enzyme active sites, becoming part of the viral RNA which prematurely shortens the RNA, stopping efficient replication.

ZMapp, by Mapp Biopharmaceutical, is a combination of 3 monoclonal antibodies, essentially created by exposing mice to a part of the Ebola virus and then waiting for a reaction to occur, harvesting the antibodies, and injecting into patient, with hopes that the antibodies attach to the Ebolavirus.  This drug works on passive immunity by attaching to the virus, so the virus cannot attach to the human cell receptor, so it does not enter the cell, and secondly it is easier to recognize the bound virus antibody and the body is able to get rid of it.

Budding drugs. Oddly, any drug that may impact budding off of the new virion may stop the spread of the virus within the individual. Here there are numerous potential drugs, many will likely be tried. And here the main target is VP40. Below are 3 articles on this target and the potential of using chemotherapeutic agents, like leukemia drugs.  

The most interesting and common treatment though, is the one that is most intuitive, and perhaps I should have mentioned first. Only a minority of people exposed to Ebolavirus contract Ebolavirus Disease, and of those that contract the disease, around half survive. That half that survived fought the disease, and when looking at their blood we can see the effects of that fight. To a certain extent you can think of that blood as rich in the ability to recognize/alert the immune system to fight Ebolavirus successfully. As a result, using other people’s blood makes sense. In fact that is the concept behind using Fresh Frozen Plasma (FFP) as a therapeutic intervention, technically called Human Convalescent Plasma (HCP), which is what you hear when it is reported that a patient has received a survivor’s blood. In fact, using FFP is a common enough treatment for a variety of diseases that are immune mediated but do not have a specific treatment. So with that in mind, it makes sense why some of the treatments above are considered. They are in one way or another trying to mimic our own immune system, to trick the system to act as if it was previously exposed and can easily recognize Ebolavirus. Also, with that in mind, it should be easy to predict how other treatments will develop.

For example, beside human-derived plasma, hyperimmune equine immunoglobulin G (IgG) has been used as another example of passive immunity. And in one episode, in Russia, goat-derived anti-Ebola immunoglobulin plus interferon was given to individuals exposed to Ebolavirus and all survived.

In one way or another the best forms of treatment are going to be ones than mimic nature, which is the main point I will come to in another letter. Here I think giving the virus a virus is how to deal with the Ebolavirus itself, and for us to also think of the terrain, the human host, and mimic what it is supposed to do already, give it passive immunity, as in the above examples, help the virus be recognized by the immune system.

Prevention, and good prevention, is the main focus, and should stay the main focus for everyone. If it is, then no one reading this post, except the folks at CDC and the facilities treating the ill will be exposed to someone who has EVD. And if it goes badly, really badly and out of control, then in the developed world, we are still talking about a nominal few becoming ill and dying, as in less than a 1,000. The reason I am giving a number is that really, in the best case there will be much less than 50 in our whole continent. However this year, even in the best case, in the next few months, 30,000 people are going to die of influenza, and that is not even mentioning other epidemics that are currently in play. I am just trying to keep everyone’s focus where it should be. For those in the CAM world, it is still the wrong question to be asking about the treatment. Absolutely the wrong focus. Prevention needs to be the main focus. Prevention makes this episode become a non-event in the developed world. Prevention helps limit the spread, contain the outbreak, and end this disaster in Western Africa.

Turn off your TV
As an aside, when I was younger, during the times of the black power movement in the USA, there was a song written by Gil Scott-Heron named, “The Revolution Will Not Be Televised”. It was about the times when social order changes and how during those times the biggest changes will shift what is ‘commercially acceptable’, what sells newspapers and what glues eyes to the TV screen, and therefore those things will not be televised. Well, I think he might have gotten it partially right and partially wrong. I think closer was Elvis Costello writing the song Invasion Hit Parade: “Incidentally the revolution will be televised, with one head for business and another for good looks, until they started arriving with their rubber aprons.”

The good things about the media coverage, in no particular order:

More people around the world have heard of a disease that is somewhat endemic to a region and kills people and other species.

That media coverage allows for more money to be spent on research and treatment and hopefully on the prevention of spreading of the disease.

As they say, a disaster is a great opportunity to fix chronic problems. As a result, it is conceivable that the extra funds moving into Western Africa may help develop a much improved infrastructure and health care system, long overdue.

All the money being spent on viral pathways, antiviral prevention and treatment will definitely migrate to other viral infections, both acute and chronic. Just as the space program gave us technology that we all use every day, so will our understanding of viruses improve with the media coverage shifting funds towards research.

And the panic caused by the media coverage should translate to more funds in medical research in general.

Because of all of these things, then well, yes, we are seeing that the revolution is being televised is a good thing.

The bad things about the media coverage, in no particular order:

Ultimately, most people are not aware of what the real issues are. No matter how many times it is said, most do not understand that in fact, the virus is not like the flu, does not pass easily that way, and that ultimately you have to have actual contact with an ill person’s bodily fluids to become ill.

What is not being explained clearly enough is that the health care structure is such, in the developed world, that when someone falls ill, there are processes in place that will absolutely limit the spread. Can those processes be improved upon? Yes, but will we see in the UK, or the US or France the sort of spread that we see in Liberia? Absolutely not. It is not a medical issue, again. It is an economic one. If we include sunk costs, we spend many millions of dollars into every American who develops Ebolavirus disease. And we continue doing that. That is why unless the virus changes in a drastic fashion, the epidemic that people fear will not arrive here.

It appears as though the media can only focus on one sensational virus at a time. Even though, as we speak, there are several virus outbreaks that gather no attention, there is HIV that kills so many. There is influenza that kills tens of thousand of people every year, and other viral infections that are present as I write this. My worry, and the worry of many in public health is as follows. When the Ebolavirus epidemic does not develop in developed countries, and as we run into November and December and the epidemic is contained in Western Africa, people will forget about viruses. Governments will stop funding prevention and surveillance, and treatment programs. And then we will have to wait for the next sensational news to continue the innovative and essential work necessary to prevent these events.

In short, DON’T PANIC. This news will pass you in the next months. Your anxiety will pass. The media will move on to the next sensation. However, to help this along and to help the common good, donate to health agencies, stay informed, donate your time, communities in the developed world can partner with developing world communities to help them encourage health care infrastructure that is needed for this and many other reasons.

Here is one site that seems interesting

In the next update, I want to highlight the threats and nightmares that I described before, and see how those have developed in the news, and I think that by describing those specifically, you will see why you should balance appropriate worry with appropriate action.

In health,
Paul Herscu, ND, DHANP, MPH