Just in case know the rules of Zombieland…

In the past several weeks the world has seen the horrible images of what the Ebolavirus can do to a human thrust into the public eye. Understandably there has been a lot of discussion, fear and misunderstanding in regards to Ebola. I’m hoping to lay out some information about the disease, assuage some fears, correct some of the misunderstanding and give the non-scientific public (or at least people I know) a glimpse into what is known about the disease.

First off, I have a Masters in Cell Biology/Immunology with a special emphasis in Infectious Disease Research. I currently do mucosal HIV research, looking at the dynamics of how HIV and the gut microbiome interact and how these interactions affect disease progression and pathogenesis. My Masters Thesis focused on the recognition of Mycobacterium tuberculosis by Dendritic Cells (a key piece of our immune system) and how the bacteria are able to corrupt our own host responses in order to avoid recognition and survive. So, in short, I have a fairly strong background in working with various infectious diseases, including Level 3 pathogens, though I am by no means an expert on Ebolavirus specifically. The thoughts below are merely my interpretations of the literature which I have read, the discussions I’ve had with others in the field, and observations on how our hospital (University of Colorado Anschutz) is preparing for this threat.

Images of Ebolavirus (top) with a schematic of its structure below.

What is Ebola?

The Ebolavirus is part of the Filoviridae family, a group of single-stranded negative sense RNA viruses. What the hell does that mean, basically it’s a virus. They are tiny structures of RNA with an envelope wrapped around the outside, they have a very basic genome, are able to form multi-virion strands (up to 6), but require the full intact structure to replicate (the RNA itself is non-infectious). There are 5 different subtypes of Ebola, each one slightly different in how virulent (infectious and deadly) it is, the current outbreak in Guinea, Sierra Leone and Liberia is caused by a variant of Zaire Ebolavirus. In most people the virus causes what’s know as hemorrhagic fever, a not so fun complex process by which the immune system is hyperactivated to such an extent that the virus literally destroys you from the inside, causing massive blood vessel leakage and organ damage. This is not a new disease, first officially discovered in 1976 in the Democratic Republic of the Congo (Zaire strain), and it has flared up numerous times in the past 40years, though the previous flare ups have all burned themselves out in more rural areas. The current outbreak has spread to the urban areas in West Africa and continues to spread uncontrolled as of this moment (10/21/14). Below I will discuss the general pathology (what happens with disease), the current state of Ebolavirus research, and what all of this means for both the US and the World (in my opinion). (Ansari AA et al 2014, Feldman H et al 2011)

A map showing the location of the 2014 Ebolavirus outbreak. As of Oct 21st there have been over 9000 cases and 4500 confirmed deaths. Making this the largest Ebola outbreak in history.

Infection and Symptoms

The Ebolavirus, like other filoviruses, survives in and is transmitted through contact with bodily fluids such as; blood, vomit, stool, saliva, semen, urine, puss, etc. The current research and epidemiology show no evidence for generalized aersole transmission (unlike flu or cold viruses), though Ebolavirus has been shown to survive in body fluids outside of the host for several hours on surfaces, making it much easier to contract than a virus like HIV. Infection occurs when infectious materials/fluids come into contact with the mucus membranes or open wounds of a new individual (eyes, mouth, throat, nose, cuts/scrapes, etc). After infection there is what is known as an incubation period (average 4-10days), in which the virus is replicating in the individual but they don’t show any obvious signs of being sick, during this stage the new individual is not known to be infectious. During this latter part of this incubation period the initial symptoms are very general and include; fever, chills, malaise and myalgia. During the later stages of disease (typically 6-16 days) the disease takes on its more severe form in which excessive immune activation leads to coagulation disorders, blood vessel leakage, multiorgan failure and shock, often leading to death. The current Ebolavirus strain (Zaire) has a 60-90% fatality rate, though some do recover from the disease back to (apparently) full health. We still do not know exactly what leads to Ebolavirus immunity, but high levels of specific neutralizing antibodies seem to be one of the leading candidates. (Ansari AA et al 2014, Feldman H et al 2011, Hoenen T et al 2012)

Treatment Options

There are not currently any officially FDA approved vaccines or treatment options available to the general public, though there are many strong candidates in the works. Several different vaccine candidates are in development, but none have gone beyond animal trials as of this writing (Oct 2014). Several have shown very strong abilities to protect Non-Human Primates (monkeys) from infection and thus may also work in humans, TBD. Post exposure treatments are in a similar state, with several treatments having shown to be effective in animal models, but none have been extensively tested in humans. The two most common experimental treatments are the use of serum from previously immune (recovered patients) and a synthetic antibody cocktail known as ZMAPP. Both are based on the premise that specific antibodies against Ebolavirus can help the patient neutralize the infection and thus recover. All of these treatments are experimental and have NOT been extensively tested for safety and efficacy in humans, but due to the high mortality rate of Ebolavirus infection they are being used in a life saving experimental fashion. NOTE: The makers of ZMAPP are now working with Amgen to see if it would be possible to scale up its production in order to have larger quantities of this therapeutic on hand in case its needed. (Ansari AA et al 2014, Feldman H et al 2011, Hoenen T et al 2012)

Why All the Confusion?

Ebolavirus research lags behind many other disease for several reasons. One, there is not as much funding for Ebolavirus as there is for HIV, TB, and many other more prominent diseases. Two, since Ebolavirus is a Biosafety Level 4 pathogen there are only a dozen or so research laboratories that have the facilities to properly and safely study this virus. Even though the Ebolavirus research is in its infancy, it is much further along than HIV research was when the initial HIV outbreak happened in the 80s and 90s, thus there is much more promise for containing its spread.

A lot of the current fear instilled in populations of the developed world revolves around several health care workers becoming infected, and thus the concern that the virus may easily spread throughout the world. Note that just as in Africa, those becoming infected are people who have direct contact with highly infectious patients, and not simple casual bystanders. What these secondary infections in health care workers do highlight is the need for a more coordinated plan on how to deal with isolated patients in order to properly protect the care givers from the infectious virus. Many hospitals (Emory and Nebraska are two exceptions) don’t have the proper containment wards setup and Personal Protective Equipment (PPE) protocols in place to deal with an Ebolavirus infected patient if they were to walk into their facilities today. This is very disconcerting for healthcare workers who would be at high risk for transmission as they treat the patient. After the transmissions in Dallas many hospitals have implemented procedures and specific protocols on how to identify and deal with a potentially infected patient (UC Denver Anschtuz is working on this now). This is where I feel the CDC has dropped the ball the most, in not implementing an extremely detailed Nation wide protocol for hospitals on how to identify and deal with a potential Ebola case, their hospital guidelines were initially very general and in my opinion not adequate for something that is so deadly.

Evolution of the CDC recommended Personal Protective Equipment (PPE) for those treating Ebola patients. http://www.nytimes.com/interactive/2014/10/15/us/changes-to-ebola-protection-worn-by-us-hospital-workers.html

What Does This Mean For Me?

For most of us (me included) this outbreak in West Africa, while tragic, does not pose a direct threat to us individually. It is definitely something worth watching to see how well the CDC and WHO are able to help control the spread of the disease in the impoverished countries, but spread in the developed world has been halted by simple containment protocols and proper handling. I wouldn’t go traveling to West Africa any time soon though. If you are a healthcare worker, specifically one who works in a hospital, ER or ICU I would be more concerned until I knew my facility had the proper protocols, PPE and containment facilities in place to handle a patient potentially infected with Ebolavirus. These are the people who are at high risk because they are asked to care for the highly infectious and to put themselves directly in harms way. For now, unless you are a healthcare worker there are many more things to worry about, Ebola being quite a ways down the list. Information on the current status of the West African Outbreak, where the disease has been treated outside West Africa, and the state of the current coordinated effort on the CDCs website.

If all else fails, just remember the rules of Zombieland…

References

CDC website, http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/index.html

Ansari AA, Clinical features and pathobiology of Ebolavirus infection, Journal of Autoimmunity (2014), http://dx.doi.org/10.1016/j.jaut.2014.09.001

Feldman H et al, Ebola haemorrhagic fever, Lancet. 2011 March 5; 377(9768): 849–862.

Hoenen T, Current Ebola vaccines, Expert Opin Biol Ther. 2012 July; 12(7): 859–872.

Gatherer D, The 2014 Ebola virus disease outbreak in West Africa, Journal of General Virology (2014), 95, 1619–1624.

It seems the NY Times has been on a microbiome binge the last several weeks. Two articles on the topic is more than I’ve seen in the public forum in several years, but it’s a good thing. This past weekend I wrote about the human microbiome and commented on the role our internal biodiversity  plays in a host of things; from digestion, to overall immune health, to how we tolerate different foods. See “Guts and Bugs” for more on that. On May 27th the NY Times post an article about the house hold microbiome. Not just the bacteria that colonize your internal personal compartments, but those that colonize all the surfaces and every little nook and cranny around your house, “Getting to Know Our Microbial Roommates”.

Another interesting topic for those germaphobes out there, and the sciencey folk. I found this article to be a much simpler and less comprehensive discussion than the previous article I mentioned, but none the less a good topic for discussion. It’s fairly common knowledge that within our homes reside hundreds of different microscopic species (bacteria, fungi, virus, phages…) that we interact with on a day to day basis. A common misconception is that all of these are evil and need to be bleached to high heaven. I think what the article relays and what the early results coming out show (data from another CU Boulder lab!) is that most of these household microbes are what is commonly found on our skin, in our noses, in the soil and within the inhabitants of the household. Basically, most of them are nothing to be scared of and a little bacteria never hurt anyone (well most of us).

Of course there are the exceptions, don’t eat that raw chicken (and clean up after) or lick that mold growing on the old cantaloupe in your fridge, but for the most part we can relax a little bit. The one thing that scares me a lot more than the home is the hospital. The author briefly touches on this, a topic that is becoming increasing problematic in the healthcare industry and is most prominently seen in the rise of MRSA infections (Methicillin-resistant Staphylococcus aureus). These places are breeding grounds for microorganisms, and with the constant flow of sick patients in and out, combined with the use of anti-microbial agents and antibiotics, we’re selecting for only the strongest of all these bugs. I’m not saying don’t go to a hospital if you’re injured or sick, but I am saying that its a real rising danger that everyone should be aware of. The health care industry is doing its best to understand the issue and how to deal with it long term, but its still a work in progress. Fresh air, sunshine and a strong immune system are always the best ways to circumvent this possible danger.

A topic I’ve often brushed aside or been very curt on to date is what my lab research deals with, there is more to me than just running 🙂  The overall focus of my group is mucosal and intestinal HIV infection, but one of the largest areas of focus is the relationship between bacteria and HIV infection, specifically one’s commensal bacteria. Within each and every one of us lives a diverse microbiome, consisting of hundreds of different bacterial species. Each one colonizing a specific niche within us, many having beneficial and symbiotic roles, and yes some pathogenic species we’d be better off without. In the past several years technological advancements have allowed for rapid and very thorough analysis of these bacterial species that reside within the various compartments of the human body; leading to a better understanding of the complexity of the human microbiome and many more questions yet to be answered. In the past several months I’ve received a flurry of questions from friends about the human microbiome, personal microbiome sequencing and fecal transplants. I’ll avoid the latter for now, but know that I am familiar with them and I do know Dr’s that I can recommend if people want a recommendation.

In the past year I’ve read dozens of articles about the human microbiome and probiotics and attended several talks on the subjects as well, but most of these have been in science papers relegated to the small community of scientist who study the topic. This past week I was sent a link to an article published in the New York Times on May 15th by Michael Pollan entitled “Some of My Best Friends are Germs” (click link for the article). It was one of the first articles on the Human Microbiome I’ve read that was not only written for the general audience, but where the author not only did his homework, but did a very comprehensive job discussing many of the reasons why we should ALL care about our microbiome just as much as we do our diet. In fact you’ll see that in many instances these two items (diet and the microbiome) are very intimately related.

In the article Pollan participates in a microbiome sequencing project based at CU Boulder and interviews some of the biggest players in the microbiome world, people at CU Boulder and CU Denver with whom I’ve worked, collaborated and interacted with. I won’t summarize the article, as I strongly encourage all readers to take 15-20min to read it on their own, but I will respond to and comment about a few of the points made in the article. If you want to discuss the specifics or have science questions feel free to ask me and I’ll do my best to answer.

Humane Microbiome sequencing data generated by Eric Lee.

I think one of the most critical discussions the article brings up is the ongoing ‘cleansing’ of the Western microbiome. Through our diet and daily practice we’re slowly killing off much of the diversity within our microbiome, something that may be associated with a lot of our immune disorders, obesity issues and digestive troubles that ail an increasing number of people in the ‘developed’ world. The shift in our diets away from a more plant based diet toward large amounts of meat consumption and our overuse of antibiotics and antimicrobial agents may be slowly depleting our guts of the diversity that is hypothesized to be necessary for optimal gut health.

In addition to the affects one’s microbiome has on digestive health is the lesser known idea that all the bacteria that make up our gut microbiome also play a key role in creating and modulating our immune system. Bacteria from the gut are constantly translocating across the gut wall and into our circulatory system, I can corroborate this from my personal studies looking at human gut tissue. As these bacteria move from your intestine into your body, the body is forced to respond and either identify the microbe as ‘friend’ or ‘foe’. One might think, ‘well if I have bacteria inside me, isn’t that a bad thing?’, not necessarily. Many of the commensal bacteria that live in our gut want nothing to do with colonizing the rest of us, thus simply die off and do no harm to the rest of the body, it’s our immune system’s job to recognize these and to realize that they pose no threat. Then there are the pathogenic bacteria that once they are released into our tissue want to colonize, reproduce and spread, here it’s the immune system’s job to recognize these and kill them off before one get’s a full blown infection (ie salmonella and pathogenic E.coli).

If the body isn’t trained properly and simply tries to attack EVERY BACTERIA that enters the tissue we’d be in a constant state of inflammation, ie many of the autoimmune and inflammatory bowel disorders seen in the Western world today. Alternatively if our gut isn’t properly colonized by the good comensals this creates a niche for all those bad bacteria and pathogenic bacteria (the weeds) to grow up and do damage to our body, without the benefits of good bacteria. Just like the “Hygeine Hypothesis” that was made popular in the 90s and early 2000s, we’re starting to realize that bacteria might not be so bad, in fact it appears they are necessary for us to live a healthy life.

As Pollan says in the article we are no where near having a complete understanding of all the nuances of the Human Microbiome, and what a healthy microbiome might be. Every bacterial species plays a unique role, but what these roles are is not fully understood. Probiotics and Prebiotics may be beneficial, but we don’t yet know enough to say there is a ‘best’ formula for people to take for optimum gut health. What we as scientist do know is that the health and diversity of our microbiomes is critical for many aspects of our lives, not just digestion and these are affected by many factors starting as early as birth. The goal of my ramblings isn’t to tell you to eat less meat, to go guzzle gallons and gallons of probiotic yougart or to stop sanitizing your house. All I want is for you to think about the consequences that many of your actions have on the health of those little microscopic organisisms that colonize the various niches of our body, you know, the one’s that outnumber your human cells 10 to 1. Next time you are thinking about taking antibiotics because you just don’t feel well, rub that hand sanitizer all over your child because she/he was crawling on the floor or the you pick up that big steak for dinner; remember the bacteria.