Thursday, August 28, 2014

Ebola PPE: How the 1995 Kikwit Outbreak Taught Us to Dress for Ebola


Hi Friends,

Well, we've beaten the airborne Ebola angle into the ground but there is still a lot of confusion about what PPE (personal protective equipment) is actually necessary to protect oneself in an Ebola epidemic. It's a fair concern and I think it really depends on where you are. Risk in a Liberian clinic that's overrun with patients and only a few HCW (health care workers) is much higher than in a fully staffed modern western hospital with caregivers who are well rested and highly trained. In that case, it's not the virus that dictates precautions, so much as the environment. But what do you really need, in a real world epidemic situation, to be protected from Ebola? Well, this question has already been answered.

In 1995, the town of Kikwit, Democratic Republic of the Congo and surrounding villages were the epicenter of a serious Ebola outbreak between January and June. During this outbreak 317 people were infected and 245 people lost their lives. In May of that year an international team was called in to help. This team did everything they could to effectively intervene: they went house-to house searching for patients, reviewed hospital and dispensary logs, performed retrospective contact tracing and interviewed everyone involved. One of the most interesting things to note about this outbreak is that a close look at the case definition showed that merely dying during the outbreak was as good a definition as any, with a 95% predictor of Ebola.

In Kikwit, there were two powerful ways by which aerosol transmission of Ebola was ruled out and the necessary PPE was defined.

The first of these was through transmission data collected from patients and family members. Once all the information was in, it was clear that only the person who took care of an Ebola patient got infected. There were zero cases of people becoming infected without direct contact with an Ebola patient. Zero. This is taken from the paper published on it by Dowell et al 1999:

"All secondary cases had direct physical contact with the ill person (rate ratio [RR], undefined; P,.001), and among those with direct contact, exposure to body fluids conferred additional risk (RR, 3.6; 95% confidence interval[CI], 1.9-6.8). None of the 78 household members who had no physical contact with the case during the clinical illness were infected (upper 95% CI, 4%)"

Did you catch that? Every secondary case was due to direct contact with a symptomatic Ebola patient. This is why it's so frustrating to see people in W. Africa without gloves, wearing respirators or covering their mouths and noses with their t-shirt, like this man in a WHO photo. They clearly don't know where the real danger is and we're not effectively helping them understand it.

The second way in which aerosol transmission was ruled out in Kikwit was by the way they contained it. When Pierre Rollin got to the Kikwit General Hospital it was a mess. There were contaminated needles scattered around the floors, blood and other bodily fluids smeared everywhere. It was filthy and patients weren't being treated. No one was providing supportive care because they were afraid to start an IV or give an injection. Pierre initiated and supervised clean-up efforts, starting with PPE, and it got the outbreak under control. He gave the health care workers and family members the basics, including gowns, surgical masks and gloves and once that was implemented the transmission stopped. It. Stopped. The only case that occurred in that outbreak after that, occurred in a small nun-run hospital outside of Kikwit.

They didn't have tyvek suits and PAPRs. All they had was protection from liquids, not aerosols, and they didn't get any more infections. This was striking evidence that Ebola is not airborne. It also argues that when the basics are used early and used correctly, Ebola can be contained. This was also the case for the Marburg outbreak in the DRC that occurred from 1998-2000. For me, this just illustrates how seriously under supplied W. Africa is. Had basic PPE been available at the beginning of this epidemic, things would have been different. But now we're behind it, unable to catch up and terrified people are lying about exposure and fleeing the area. Because of this, Ebola is going to keep killing a lot of people in Africa.

There have also been three other Ebola cases treated in modern western hospitals that support this basic PPE requirement. Before Kikwit, in 1994, a 34 year old female veterinarian working with a group studying chimpanzees in Tai Forest, Côte d'Ivoire, performed a necropsy on a dead wild chimp. Eight days later she got sick and was flown back to Switzerland and treated for what they suspected was Yellow Fever. She was cared for with no special precautions and she recovered. A sample from her was sent to the Pasteur Institute where it tested positive for Yellow Fever. So the sample was given to Bernard Le Guenno, a noted hemorrhagic fever virologist, so that he could isolate Yellow Fever for confirmation. Bernard did virus isolation but he didn't get Yellow Fever, he got Ebola. The Tai Forest species. Oops. By then, the patient had recovered and there were no secondary cases. 

The other two cases were in Johannesburg, S. Africa. A physician treating Ebola patients in an outbreak in Gabon in October of 1996 got infected and flew to Johannesburg without telling anyone. He was cared for at the Morningside Medi Clinic and in November recovered and returned home. No special precautions were taken for his care. During the placement of a central line in the Gabonese doctor, a nurse was exposed to a lot of blood and she became ill soon after, on November 2nd. By November 9th she'd not responded to any treatments and her symptoms were consistent with VHF. They suspected Crimean Congo. ***They sent samples to Bob Swanepoel, at what is now called NCID, to test for CCHF and his technician ran it against all VHFs. It turned out to be Ebola. Public Health then stepped in and transferred the patient to Johannesburg Hospital where she was cared for by Guy Richards and his team who used Ebola appropriate PPE. The nurse didn't make it. However, once again, with the initial absence of special precautions, there were no other secondary cases.

So as you can see, there's powerful evidence that basic PPE to protect against fluids is actually enough to protect against Ebola. Unfortunately, in the current outbreak, there are very few HCWs, with very few resources, to care for an exploding numbers of patients. This leads to, and combines with, exhaustion to create an epidemic that's out of control. In addition, the inability to communicate that Ebola is in fluids, but not airborne is seemingly impossible. Many educated Americans I try to explain it to don't get it, so how can we expect a terrified population in the middle of the horror to understand?

The Kikwit Ebola outbreak provided an unprecedented opportunity for us to learn about Ebola in all regards and those involved took advantage of it. They studied and they learned. Experts who worked extremely hard under deplorable conditions published papers, and the real tragedy here is this:
In all of the papers published regarding the Kikwit outbreak, there are recommendations for handling future outbreaks including containment, health care worker safety, patient physical and psychological care, and information campaigns to both educate people and prevent discrimination against survivors. It's all there.



Apparently no one bothered to look for it.


Cheers,

Heather

***this was updated on Sept 7 2014 to include additional specifics that should clear up any confusion about how the nurse was treated or her samples tested. Thanks to Ian Mackay and Raina McIntyre for providing the missing pieces.

References

Scott F. Dowell, RoseMukunu, Thomas G. Ksiazek, Ali S. Khan, Pierre E. Rollin and C. J. Peters forthe Commission de Lutte contre les Epidémies à Kikwit. Transmission of EbolaHemorrhagic Fever: A Study of Risk Factors in Family Members, Kikwit, DemocraticRepublic of the Congo, 1995. J Infect Dis. (1999)179 (Supplement 1): S87-S91.







Wednesday, August 27, 2014

Fireside Chat with Dr. C.J. Peters: How will the 2014 W. Africa Ebola epidemic play out?

Greetings Friends,

While scientific advancement greatly depends on controlled experimentation, and knowledge and comprehension of the literature, hanging out with an expert and engaging in relaxed but highly stimulating intellectual discourse can be just as valuable. It's often during these informal chats that you become privy to important anecdotal information that can only be gotten through personal experience. While this information might not make it into an article, it is still very valuable and revealing about the subject at hand. Pioneers in the field of emerging infectious disease are often on the front lines during epidemics and have great stories. Just listening is not only educational, it's a whole lot of fun.

This Fireside Chat is my way of sharing one of these conversations with you, of providing what I believe is valuable and relevant information straight from someone who knows because his career is built upon pioneering Ebola research and outbreak response efforts. And as luck would have it, I recently got to sit down with Dr. C.J. Peters and discuss the current Ebola epidemic.


If you don't know C.J. by name, I'm sure you'll recognize his career. He is the original virus hunter and the real man behind Dustin Hoffman's character in "Outbreak". His career is filled with honors and distinction, not the least of which is that the Army created "The C.J. Peters Award" in his honor. The award states: "In the inception and granting of this award, we honor Colonel C.J. Peters, Medical Corps, a brilliant and innovative scientist, scholar and physician...whose work is a lesson not only in science, but in humanity." If you want to read about his amazing career, read his autobiography Virus Hunter. His is truly a remarkable journey. Although to make it even more riveting he should consider updating it with a chapter on being my PhD mentor. That was probably more exciting than he expected. Anyway, I had the pleasure of sitting down with C.J. and discussing this outbreak. This man is brilliant and agreed with everything I said, but he also brought up some things that I hadn't thought of. I am very pretty smart too, so I agreed with everything he said. As you can imagine, it was a lot of fun.


As we discussed the current epidemic, many of the factors contributing to the rampant spread of Ebola in West Africa became a little clearer. I have not been to Africa, so C.J.'s experience here was invaluable. He explained to me how very different hospitals over there are. No surprise there, right? Well, the differences are even greater than you might imagine. Yes, as we've already discussed at length, they lack many basic resources, but they also do things very differently. For example, hospitals don't provide food and laundry services for patients, family members are responsible for those. And they don't have reclining chairs or other places for family members to sleep, so they often sleep in bed with the patient. Since direct contact is the single most important risk factor for Ebola transmission, those things combine into a very effective transmission pipeline.

C.J. also stressed the problem of disposable needles and syringes. It turns out that infected needles/syringes play an even bigger role than you might think in Ebola transmission, both between patients and between patients and HCW. In the U.S. we use disposable syringes one time and toss 'em. You'd think that the switch from stainless steel needles and glass syringes that had to be sterilized, to disposables would help. But the problem is that they don't have enough. They hardly have any. Disposable syringes can't be sterilized by the customary heat methods and disposable needles might survive one or two rounds of sterilization, after which they're unusable. So they do what they have to: use the same needle/syringe in different vials or multi-use vials, and between patients. This is a very effective way to spread a virus.

In addition, glove shortages aren't the only problem with gloves. Here in the U.S., whenever doctors or nurses see a patient in the E.R. they wear gloves. It became standard with the advent of HIV. C.J. explained that that's not the case in these hospitals treating Ebola patients. Gloves are hard to come by, and if they are there, they are saved for only the most overt needs. Ebola patients don't have signs on their foreheads, so they may be cared for without gloves before Ebola is suspected. C.J. made the point that using gloves correctly for every single patient contact would go far in slowing the transmission of this virus, if they were available. You see, Ebola doesn't actually spread that easily.

To illustrate this, let's consider a concept that epidemiologists useR0 (R naught). This is the basic reproduction number of an infection: the average number of cases that a single infectious case will cause in an uninfected population. Basically, it's how many people one person can infect. While this number is based on a mathematical model, with assumptions etc., it's been shown to be very relevant to what we see in epidemics. The higher the R0 the more the virus spreads. For Ebola, even with environmental factors that increase its transmission (lack of sanitation and resources), the R0 is relatively low: 2.7 for both the 1995 Kikwit, and 2000 Uganda outbreaks.

So it's clearly not magically infectious. They just need PPE and the training to use it. C.J. was clear that they need trained people with the basics, including gloves, gowns, masks and goggles, to go from town to town and hand them to the nurses, doctors and family members caring for Ebola patients, and explain to them when and how to use them. These people must be able to not only train locals in proper use of PPE, but also communicate effectively while respecting cultural differences. Even if you have such people, and we don't have enough of them, this isn't always easy in communities rife with fear and mistrust.

And there are other factors making the logistics of supplying hospitals even more difficult. Turns out, supplies don't always make it to their intended destinations. Delivery trucks can be raided or willingly detoured for the sake of profit for a small few. C.J. described this as a very real problem during the Kikwit Ebola outbreak in 1995, and in 2014 we've seen the armed invasion of medical facilities to steal supplies and "liberate" patients. These additional challenges are incredibly complex, and packed on top of minimal health care infrastructures that are already overtaxed. It's a heartbreaking and nearly foolproof formula for tragedy.

So what does it all mean? Well, C.J. made it clear that it means that Africa is in real trouble. This virus is likely to keep spreading within Africa before this is over and those countries already affected are in it for the long haul. They face the very real possibility of rapid depletion of resources and the death toll will keep rising. But it also means that, as I said in my first post, this virus won't cause real problems outside of Africa, and it certainly won't cause a pandemic. Those suffering with Ebola infection generally don't have the resources for international travel. Those that do are unlikely to get on a plane while symptomatic; the symptoms of Ebola are debilitating. Even if a few people travel internationally and then come down with symptoms, most other countries will be able to contain it. Especially since it's now on our radar.


Of everything we discussed, the one thing that C.J. said that stuck with me the most, was how the Rof Ebola compares to that for measles. Measles has an Rof 12-18. That means that someone infected with measles could infect, on average, up to six times more people than someone with Ebola. Six times. And the incidence of measles, a serious and potentially life-threatening illness, is rising in the U.S. because people are choosing to not vaccinate their children. Did you know that between Jan 1st and August 15th of this year (2014) there have been 593 diagnosed cases of measles in the U.S. and 18 outbreaks? It hasn't been that high since...I don't know when and most of those cases were in the unvaccinated. This boggles my mind. The measles vaccine became available in 1963 and before that, when it wasn't an option, each year ~500,000 people were infected in the US with 48,000 hospitalizations and 500 deaths. Now adjust that for the current population density and it becomes even more frightening. That is the power of a vaccine. And yet today, we face people choosing to not vaccinate, usually with only enough information to be dangerous. Clearly.


So guess what happens if an unvaccinated person gets measles? They go to the doctor. Guess who they transmit it to while in the waiting room? Almost everyone (90%). Guess who will get really sick? Those in that waiting room who aren't vaccinated will be in trouble and sometimes that means an infant who has not yet been vaccinated, only because he/she is too young. Read about just such an infant here.

My point is this: We live in a country with resources and access to things like vaccines against life-threatening illnesses, and yet we have people who are making the uneducated, arrogant and selfish choice to not vaccinate, and in so doing put their entire family and community at risk. Looking at images from this epidemic, I imagine these same people would be first in line for an Ebola vaccine, and yet they risk their children's lives every day by leaving them susceptible to diseases that are a far bigger problem. But until it hits home they won't realize the flaws in their logic.

Unfortunately, when it does hit home, it will hit hard.

C.J. agrees.


Cheers,

Heather



Thank you for the chat C.J.! 


References

Legrand,J., Grais,R. F.,  Boelle, P. Y., Valleron, A. J. and Flahault,A. Understanding the dynamics of Ebola epidemics. Epidemiol Infect. May 2007;135(4): 610–621

http://www.cdc.gov/measles/

Monday, August 25, 2014

Ebola Unburied: Does Improper Burial of Ebola Victims Leave Communities at Risk of Exposure Through Dogs?

The Ebola epidemic in West Africa has taken a gruesome turn as we learn of dogs digging into fresh, shallow graves to partake in an Ebola feast. But what does this mean for those in the community and what does it mean for the dogs? This story actually didn't surprise me. In the 2001-2002 Gabon Ebola outbreaks, when dogs were tested, a whopping 30% were seropositive for Ebola. Let me take a minute to explain exactly what that means.

"Seropositive" means the dogs had antibodies against Ebola in their blood. Antibodies are proteins made by effector B cells, (plasma cells). B cells are white blood cells that develop into effector B cells/plasma cells when needed to make antibodies. Antibodies recognize a part of a foreign body like a virus, and target it for destruction.  This part they recognize is the "antigen" or "antibody generator" and it provokes an adaptive immune response, AKA the antibody response. Antibodies can be made to order, in response to specific antigens, therefore their role in immunity is considered "adaptive".

OK, so when there is Ebola in your blood it is recognized as foreign and antibodies are generated to get rid of it. Blood tests can be done to detect either the Ebola antigen, or antibodies against Ebola. When antigen is detected, it means there are virus particles in the blood. When antibodies are detected it means the virus had been there and an immune response was mounted. When an antibody encounters it's antigen, it will bind to it, making both undetectable to the blood tests. Early in an infection the number of antigen molecules will be greater than the number of antibody molecules, so all the antibodies will be bound to antigen and there will be excess unbound antigen.  This excess unbound antigen will be detectable by blood tests and it will indicate that there is virus in the blood. As the fight rages on, there will come a point, hopefully, where there are more antibodies in the blood than antigen, and the reverse will happen: all the antigen will be bound to antibodies and there will be excess antibodies in the blood. At this point the antibodies will be detectable. This point is called "seroconversion" and the blood test will indicate that there are antibodies and therefore be "seropositive". At the early stage of seroconversion, when the amount of antibody and antigen are nearly the same, it's possible that there won't be enough of either unbound, for detection. This can lead to false negative blood tests. This period is called the "window period".

OK. So now we know that there were dogs that were seropositive during the Gabon outbreak, so they had Ebola antibodies in their blood and thus had had Ebola virus in their blood. In other words, the dogs had been infected and lived. In fact there was no evidence that the dogs showed any symptoms. Considering that the likelihood of a dog feasting on a non-human primate that had died of Ebola in the forest is pretty good, it's not surprising that they would have antibodies in their blood. It's important to note that in this study, they were not able to detect viral antigen in the blood and they were not able to isolate virus from the blood. This suggests that the dogs were infected and fought the infection without symptoms and without acting as an amplifying host. An amplifying host is an animal in which an infectious agent can reproduce to high numbers. Without a lot of virus in its system, a dog wouldn't be able to transmit Ebola.

So what does it mean for the people and dogs in this community in which the dogs are digging up shallow corpses? Well, first and foremost it means the people in the community have to live through a horrific nightmare as their loved ones are unburied and the fear of exposure increases as someone has to handle the bodies and properly rebury them. But does it mean the dogs can infect people? Well, based on the information we have, I don't think it's likely that dogs are reservoir hosts. However, It would depend on many factors like how much virus is in the blood and bodily fluids of the dog before it seroconverts. And certainly, if there is fresh bodily fluid or tissue on a dogs muzzle or paw  it could infect someone it touches. Now how long that would remain a genuine threat, I don't know. Again it would depend on factors such as whether or not the dogs muzzle/paw was washed off in puddles or streams etc. Because it's a relatively unknown factor in transmission, and because it's not worth the risk in an epidemic already out of control, while sad, I think putting down the dogs is a wise move.

[Edit 10/7/14: The topic of a pet dog has come up in a recent Ebola case in Spain and I don't think this pet should be put down. I think it should be tested for virus and since we have data on a relatively narrow time frame of infection, if the dog is infected, we should monitor infection and find out whether it sheds virus during an asymptomatic infection. This is a very different scenario than the dogs I discussed in this post who were likely repeatedly exposed in this out of control epidemic situation.]

Here's hoping they will have the wisdom and the manpower to bury the deceased properly from now on.

Cheers,

Heather



References

Allela L. Ebola virus antibody prevalence in dogs and human risk. Emerg Infect Dis. 2005 Mar;11 (3):385-90

Weingartl HM, Review of Ebola virus infections in domestic animals. Dev Biol (Basel). 2013;135:211-8. doi: 10.1159/000178495. Epub 2013 May 14

Wednesday, August 20, 2014

Ebola, Karma And The Cell Membrane: Vulnerabilities of an enveloped virus

[Edit 8/21/14 - I realized that I should have begun this post with the following disclaimer: Warning! Gratuitous anthropomorphizing for the sake of communicating science fun of it follows. Just remember that viruses are passive and we'll be good. Thanks. end edit]

There's been a lot of discussion lately about what methods of disinfection will actually kill the Ebola virus. I can imagine that in the middle of this epidemic, in a place with very few options, the idea of not having, or not choosing, the right method is a terrifying prospect. Soap? Hand sanitizer? Bleach? What to do?

Well, actually they all work well against Ebola. You see, Ebola is what is called an "enveloped" virus. This means that the virus particle is encased in a lipid membrane; a lipid membrane that it steals from those it infects. A membrane it steals from us. Let me explain.



Viruses are non-cellular infectious agents composed of a genome (genetic material, either RNA or DNA) and proteins. Ebola's genome is made of single stranded negative-sense RNA. This means that Ebola has one relatively small strand of RNA that contains all the information it needs to make more Ebola virus particles. And it's backwards. That's amazing, by the way. The "negative sense" description means that the RNA can't serve as messenger RNA. Messenger RNA (mRNA) if you remember, is the message from which proteins are made: the coding sequence of the mRNA dictates the amino acid sequence in the resulting protein. So for negative sense RNA, mRNA is made by using the backwards copy as a template (this link provides details of this). Then the mRNA can be used as a template to make the proteins. To make more virus particles Ebola also must make copies of its genome. This, of course, must all be  done using our cellular machinery.

Stay with me.

Once the necessary proteins are made, the Ebola proteins and copies of the genome get together to form new virus particles. This all happens within the cells that the virus has infected. Oh, and while the virus is keeping your cellular machines busy, they aren't available to do what they need to do to keep your cells happy. This can play a role in making you sick.

The last thing that needs to happen before the newly made virus particle can go on to infect other cells or other organisms, is that it must leave your cell. And instead of politely declining that last round of synthesis and using the door, it busts through your cell membrane, taking part of it in the process. Yes, it  inserts some of its own proteins into the membrane, sidles right up and gets cozy (doesn't even buy it a drink) and BAM wraps it around itself and rips it off. Now it is a complete virus particle safely surrounded by what had been your cell's lipid membrane, with viral proteins embedded. This is what we refer to as the viral envelope and the completed viral particle is called a virion. Ebola virions are shed through bodily fluids which can transmit the virus. I'm sure you can tell by the shape that the budding virus in this graphic representation(wikimedia commons) is not Ebola. Ebola is long and filamentous, but this one is better for illustrating the concept. Here's a really nice paper on the Ebola life cycle if you want to read more about this amazing process.



Still with me?

Well, it turns out this new shiny viral envelope is actually Ebola's Achilles' heel. Not all viruses have envelopes, and those that don't are actually much more stable in the environment. Those viruses are encapsulated in what is known as the viral capsid, which is made of proteins, not lipids, so it's very sturdy. All the viral proteins are tucked safely into the capsid so it's much more difficult to inactivate those viruses. Unfortunately for an enveloped virus like Ebola, that lipid membrane it stole is pretty susceptible to many environmental factors like sunlight (UV radiation), heat and drying, but also to all sorts of disinfectants and detergents, even alcohol. So even hand sanitizers work on Ebola, as long as the concentration of alcohol is over 60%.

So washing with soap and water is good, disinfecting with a 10% solution of bleach in water works well and hand sanitizer is effective, as are all medical grade disinfectants. When washing or sanitizing hands, sing Row Your Boat three times and you've done it long enough. ;)

So, because Ebola steals our cell membranes it is more susceptible to disinfectants and environmental factors, and given enough resources and training, the people fighting it will prevail.

And I like to think of that as a bit of microbial Karma.

Cheers,


Heather


PS. Check out these links if you want to make a difference in this outbreak!
Africare
Global Giving
Direct Relief
Action Aid
Caitlin Rivers blog has a ton of links to help! Thanks Caitlin!!




References



McDonnell, G. and Russel, A.D. Antiseptics and Disinfectants: Activity, Action, and Resistance. Clin. Microbiol. Rev. January 1999 vol. 12 no. 1 147-179


Friday, August 15, 2014

A Prescription for Pestilence

We are all engrossed in the current Ebola epidemic, and rightly so. However, as tragic as this epidemic is, Ebola is not the only or deadliest, Global public health concern. In fact there's some microbial trouble brewing, it's been brewing for some time and it scares me. So, without discounting Ebola, I'd like to start a new discussion. A very important discussion




For those of us lucky enough to live in parts of the world where clinics and antibiotics are easily accessible, diseases that could decimate families 100 years ago are mere inconveniences. My son had scarlet fever last year and instead of watching him suffer horribly with no assurance of his survival, I missed a couple of days of work while he recovered in relative comfort with the help of antibiotics and another modern miracle, acetaminophen.Yet I wonder for how long we will have the luxury of these medicines? We are slowly paving the way for antibiotic-resistant bacteria to rule the planet.

Seem melodramatic? I wish.

"A post-antibiotic era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century."

That is a quote from the 2014 World Health Organization report on antimicrobial resistance, and as a mother and scientist it is terrifying.

Now, before I get into antibiotic resistance, I just want to clarify: this is not meant to be a treatise on "Global microbial evolution with or without human advances in infection prevention or treatment". I know that viruses also evolve mechanisms to overcome our interference, and that introduction of resistance genes into bacteria not subject to antibiotic pressure can occur. They are independent pieces of a very large puzzle and are for another day. This post is limited to the generalized basics of our role in bacterial resistance to antibiotics. I just want you to understand why it's important and how we can begin to address it. OK.

The problem is two-fold. We are constantly warned by scientists and physicians to 1) use antibiotics with discernment and 2) take the entire course of antibiotics as prescribed. And we all know why: antibiotic resistance and other health problems could result if we don't. And yet many physicians prescribe antibiotics without actually having a definitive diagnosis, and when they are prescribed, most of us still do not take them as directed. It's a real and dangerous phenomenon and we are beginning to reap the tragic harvest that will eventually lead to that post-antibiotic era.

Let's take a minute to really appreciate what "post-antibiotic era" means. It means that the antibiotics we are using now will no longer work. It means bacterial infections will once again be able to kill and maim. It means drastic surgical intervention, such as amputation, will be used to save lives. Can you imagine the toll it would take on a preschool, elementary school, or daycare? How about a college campus fighting gonorrhea? The reality of life without effective antibiotics is frightening. Does every bacterial infection require antibiotics? No. Does every bacterial infection lead to a global pandemic if not treated with antibiotics? No. Am I fear mongering? Absolutely! I really hope you are paying close attention because this needs our attention now.

This isn't the first time you've heard this, I'm sure.So why are we still so cavalier about prescribing and taking antibiotics? Why aren't we taking this seriously?

When it comes to prescribing antibiotics, I've spoken with physicians who admit to feeling pressured to provide medicine and to do so quickly without the time and money required to run tests. For example, a sore throat could be viral or bacterial, and antibiotics won't do anything for a viral infection, they only work against bacteria, some fungi and parasites. But the parent of the sick child may want action, right? They need to get back to work, the child needs to get back to school. Life must go on!! Besides, who wants to take a suffering child to the doctor's office, urgent care or ER, wait for who knows how long, only to be told that there's nothing the doctor can do to help the child recover? No one, that's who. So either physicians feel it's the right call because, in the absence of a definitive test all signs point to the bacterial culprit, or they feel pressured to prescribe antibiotics because a parent insists on getting them, and the parent then feels like they're getting their money's worth.



When it comes to taking antibiotics, my best guess is that for the general non-scientist public, this idea of antibiotic resistance is too abstract. People don't really understand how misusing antibiotics can, and will, actually render them useless. If people really understood that concept, then I have to believe that we would not be so dismissive about requesting and using antibiotics. We are also a bit spoiled. We've either not seen first-hand how bacteria can kill (thank you antibiotics), or we're just convinced that scientists will come up with new antibiotics as "easily" as they came up with the first ones. So why worry? Unfortunately both outlooks are dangerously ignorant.

I've spoken to 5 people within my circle of friends and family in the last week who admitted to never following the instructions for taking antibiotics. The most common logic for their decisions was that the person taking them had "recovered", so why use them all? The leftovers were saved for the next time someone got sick. Seems reasonable until you learn a little more about how this all works.

So how does it work? Well. Let's consider an infection with the bacteria that causes scarlet fever: Streptococcus pyogenes. This bacteria is fascinating. It not only causes strep throat and scarlet fever, it also causes impetigo, acute glomerulonephritis (inflammation of the tiny filters in your kidneys), and most notably, necrotizing fasciitis - a pretty nasty flesh-eating infection. It's also on the rise, especially in the UK. The current standard treatment of care for this infection is penicillin, or for those allergic, erythromycin.

OK, so now you're infected with  S. pyogenes. Generally speaking, and with the right conditions, a population of bacteria can double in 20 minutes. Scarlet fever has an incubation period of about 2-3 days, which means you will feel symptoms between 2-3 days after you're infected. During that incubation time, the bacteria is reproducing in, and spreading throughout, your tissues. By the time you start feeling sick, you've got quite a load of bacteria in you and a rash that makes the people in the clinic congregate on the other side of the waiting room. The doctor examines you and scarlet fever is  clearly the diagnosis and he sends you off with explicit instructions to take penicillin for 10 days. The penicillin prescription bottle reiterates his instructions: "take all medicine as directed". In case you were wondering, this translates to "Take every single pill in this bottle, at the time you are supposed to take it, you buffoon!" And yet...

You start taking the medicine and 24 hours later the rash is gone and you feel so much better already! You continue taking the antibiotics for four more days, but by then the fever's been long gone and you feel fine. So you quit taking them and save the rest of the bottle in case it turns out that you had infected someone in your family.

But what's really going on inside of your body during those five days you're taking the antibiotics, and what happens when you stop? As I mentioned, by the time you start taking those antibiotics, you have a substantial population of bacteria festering in you. This population of bacteria is not homogeneous. By that I mean that the individuals making up the population are not all the same; there are differences among them, genetic differences as are seen in any large population of an organism. Not all differences are relevant to antibiotic tolerance but those are the ones we care about today. So within this population of S. pyogenes that's making you sick, there is an entire spectrum of antibiotic susceptibility, including some that are really susceptible to penicillin and some that are more tolerant. Take note here, I said "more tolerant", not "resistant".  So you begin the course of antibiotics and it takes time for them to get into your system at the concentration needed to fight the infection. When it does, the first bacteria affected are those that are the most susceptible. As the antibiotics continue to remain in your system at the needed dose, i.e., you are taking them every 6 hours as prescribed, more bacteria are killed. These would not have been as susceptible as the first ones, but they are more susceptible than others among them. As the bacteria population dwindles you feel better! Of course you do! There are fewer bugs! Yay antibiotics!

This goes on day after day as the antibiotics and your immune system continually attack the bacteria, slowly chipping away at those that are less susceptible until the remaining bacteria are those that are hardly susceptible at all. Those remaining are the really nasty ones and we do not want them to get away. If they do, they will continue replicating and more mutations will occur and it is only a matter of time before they get that mutation that will shift their "strong tolerance" of antibiotics, to total resistance. However, if you continue the antibiotics for as long as prescribed, at the intervals indicated in the directions, you will kill even those most tolerant bacteria. If you stop after only several days, then you have not only allowed those most nasty ones to survive, you've provided an environment for them in which to grow without competition. You've killed all the other bacteria, so now the nasty ones have all the nutrients and space they need to really explode, which means even more replication and opportunities for mutation. Basically you've set them up to become completely antibiotic resistant and you've also set yourself up to spread them to other people, because even if you don't get sick again, you will be transmitting them. 

Way to go.

In addition to cleaning up an S. pyogenes infection quickly and preventing its spread, antibiotic treatment of scarlet fever prevents complications like rheumatic fever which can develop when S. Pyogenes is left untreated or is insufficiently treated. Rheumatic fever is an inflammatory disease; excess inflammation in the wrong places can cause severe tissue injury. Rheumatic fever can permanently damage the heart.

One of the most amazing things about modern antibiotics is their specificity: they specifically target bacterial cells. And while yes, this means they affect the populations of beneficial bacteria that we all have and need, they do not kill our own cells. This is one of the most critical traits for a good antibiotic. Bleach is a great antibiotic right? It really kills those little buggers. Well, sure, but you can't drink it or wash with it without serious injury to your own tissues or death. Generating new, safe and effective antibiotics is not going to be easy and research to that end is limited. Tim Sandle gives a nice rundown of this research in a recent blog post. [Edit: 8/18/14: Tim just published a review of two new antibiotics. This is great, but still not enough.] While there may be some hope with these, our best chance is to make sure that the effective antibiotics we already have, stay effective for as long as possible. The only way to do that is to be responsible about prescribing and taking them. If you are concerned about losing your own beneficial bacteria, replenish them! There are bacteria supplements you can take and yogurt works too. Talk to your pharmacist about it!

So please. Make sure your physician is positive that what you have is treatable with antibiotics, before you ask for them and before he prescribes them.  If your physician suspects a virus, ask him or her why that is. Ask them to explain it to you until you understand. Also ask if there are any tests to help differentiate between a bacterial or viral infection. There are quick tests that can verify if you have the flu or strep. Ask for them if they are suspected. If the doctor finds a lot of evidence to support the idea of a viral infection then ask what you can do to alleviate symptoms and help your immune system fight it. Resting, staying hydrated and controlling pain are important and will help your body heal itself. There are also successful anti-flu medications, and many over the counter drugs that can help. Communicate with your doctor, he does actually know a thing or two. Also ask what to expect during recovery so you will know if you are getting better or if something else is going on. Viral infections can often weaken us and make us more susceptible to bacteria so if you are feeling worse when you should be feeling better, get back to the doctor ASAP. Once you've been told that antibiotics are indeed necessary, then take them responsibly. Take them all, on the specified schedule. Protect your family and generations to come by following the instructions carefully. It's up to each of us to make the changes that will help prevent or at least delay the onset of a post-antibiotic era.

Finally, don't forget that an ounce of prevention really is worth a pound of cure. Hand washing and covering our mouths when we cough are still the best ways to prevent infection of transmissible illnesses. For your children, remember to find the balance between preventing disease and encouraging the development of their immune system. Vaccination prevents a wide range of diseases, some of which really are life-threatening. If you or your family members don't get vaccinated, and the antibiotics aren't effective, then you've set yourself (& others in your community) up for tragedy. So please don't let celebrity propaganda influence important decisions about your health or the health of your family. Get vaccinated. OK. Enough of that. That topic deserves a post all its own.


Cheers,

Heather

[edit 8/19/14: P.S. just came across a great blog post by Sarah Hird that explains this with really cool graphics. Check it out.]

References

WHO 2014 Antimicrobial Resistance Global Report on Surveillance

Understanding the basis of antibiotic resistance: A platform for drug discovery. Piddock LJ. Microbiology. Aug 13, 2014 

Origins and Evolution of Antibiotic Resistance. Julian Davies and Dorothy Davies. Microbiol. Mol. Biol. Rev. September 2010 74:417-433

Antimicrobial resistance: A Primer. Laura A. Stokowski, RN, MS 2010 http://www.medscape.com/viewarticle/729196

Evolutionary consequences of antibiotic use for the resistome, mobilome, and microbial pangenome. Michael R. Gillings. Front. Microbiol., 22 January, 2013

Natural antibiotic resistance and contamination by antibiotic resistance determinants: the two ages in the evolution of resistance to antimicrobials. José L. Martínez* Front. Microbiol., 13 January 2012

2011 Feb 3 Eurosurveillance report on increased S pyogenes and S pneumoniae infections





Tuesday, August 12, 2014

Debunking Airborne Ebola: What You Need To Know About Aerosols, Droplets and Fomites


I briefly discussed aerosols and droplets in my first Ebola post, but because there is still so much online discussion about Ebola transmission and because it's relevant to all infectious diseases, I decided to move that section of the post here and expand upon it so that those interested specifically in this topic wouldn't have to wade through the rest of that riveting post  to find it (although I highly recommend it). There is still some minor redundancy between the posts, but redundancy when dealing with BSL4 pathogens is a very good thing. References are listed at the end of the post.


First, What Does "Airborne" Mean?
Let me clarify. Bodily secretions that make it into the air from various orifices (e.g., nose, mouth) are called droplets and are classified based on size and distance traveled. The smaller the droplet, the longer it stays suspended in the air, the farther it travels and the deeper into the respiratory tract it can go upon inhalation by the person sitting down the aisle from you on the airplane. Teeny-tiny droplets (less than 5 microns) are generally referred to as "aerosols" and can be generated by a cough, a sneeze, exhaling, talking, vomiting, diarrhea, passing gas etc. Aerosols can also be generated mechanically by things like flushing a toilet, mopping, or rinsing out a bloody wash cloth. When aerosols are infectious, they transmit disease when they are inhaled by an organism and its called "aerosol transmission". When droplets are larger than 10 microns they are called "large-droplets" and if infectious, they transmit disease by inhalation if the organism being infected is close enough to inhale the particles before they settle out of the air. They can also transmit virus if someone gets showered with droplets from, for example, a sneeze, or touching a droplet that is on the surface of an object(fomite) or someone's skin and it's called "large-droplet transmission".

When we say that a virus is airborne, we specifically mean it is capable of aerosol transmission via inhalation, even when not in close proximity to the source of the aerosol. For example, someone two aisles over at the market has the measles and coughs up a lung. When you get into that aisle you inhale the teeny aerosol droplets that are still hanging out in the air and they begin depositing virus particles in your respiratory tract. These particles then enter your cells and begin to replicate. You are infected. I hope you were vaccinated!

Large-droplet transmission is not considered airborne. An ebola patient sneezing directly on you will get virus particles on you, but those large droplets that landed on your lip weren't technically airborne, they settled out of the air and onto your lip fairly quickly and they weren't inhaled. If you're close enough for this, then I'm sure you are inhaling some aerosol sized droplets as well, and at this close range they are likely infectious. However, to be considered "airborne", those aerosol particles would have to remain infectious while they hang out or move through the air. Evidence indicates that while Ebola is found in the respiratory tract and theoretically could produce infectious aerosols and be airborne, for unknown reasons we don't see this happen between primates/humans in studies or in outbreaks (for detailed discussion of these studies read this post).

Not all viruses can form infectious aerosols. It depends on where the virus goes in your body and what happens when it gets there. Aerosol infectivity of a virus is determined by how long the virus remains infectious in the air, how deep into the lungs it can travel, and how many virus particles are actually in each droplet compared to how many are required to actually establish an infection. If a viral infection generates aerosols containing 10 virus particles per droplet, but it takes 1000 virus particles per human cell to establish an infection, then those aerosols are not infectious, even though they contain virus. In addition, while airborne, aerosols begin to lose water content by evaporation and virus particles, especially enveloped particles like Ebola, can be affected by other environmental conditions such as humidity, air currents, and sunlight. These particles are also subject to the laws of physics and mechanical forces. A good example of a virus for which these characteristics have been better defined is influenza and this is an excellent article that really explains the different kinds of aerosols and how they are transmitted.

One question we got repeatedly during the Twitter #Ebolachat session was, "If it's not airborne, then why are health care workers not only wearing head-to-toe protective gear, but dying in spite of it?"

Fair question and one I discuss in another post but I will reiterate here. Ebola patients exude many types of droplets, of all sizes from all orifices, and sometimes large volumes are lost violently through vomiting or diarrhea. These events generate a lot of droplets/aerosols/fomites with high viral loads, often in close proximity to HCW. Once deceased, victims continue to lose fluids for some time. It's a real problem. Protection is critical. Mucus membranes and broken/abraded skin are susceptible and the infectious dose of Ebola is low: 1-10 individual virus particles. Protecting every potentially susceptible inch is the goal. But protective gear, if available, is only as good as technique. Those suits are extraordinarily hot and exhaustion sets in quickly. Wipe sweat from your eye with a contaminated glove? You're infected. Accidents and mistakes happen easily in these conditions. Cleaning up messes also generates more droplets unless you're specifically trained to minimize that risk. And remember, many HCW are caring for people even without gear. They are not abandoning the sick. They are reaching out with ungloved hands to offer comfort and ease suffering. For these heroes, the only thing worse than reaching out without gloves...is not reaching out. For a truly remarkable account of what this is like in a field clinic, read emails from Dr. William Fischer II, a physician from UNC who has been on the front lines in Gueckedou, Guinea since May. [EDIT 8/15/14 A new story in the Wall Street Journal illustrates this point all too poignantly]

So, although Ebola laden fluids are infectious and can transmit virus, they are not considered airborne. Larger droplets splatter and splash, even in tiny amounts and contaminate surfaces creating fomites. Puddles, droplets and fomites, in a situation with limited personnel, training and resources, are the concern. Ebola is not airborne. If it were, the casualties in this epidemic would be far higher.


Please feel free to ask questions or make comments. Discussions are always welcome.

Cheers,

Heather


Update 8/20/14: Check out these links if you want to make a difference:
Africare
Global Giving
Direct Relief
Action Aid
Caitlin Rivers blog has a ton of links to help! Thanks Caitlin!!


References
Tellier R. Review of aerosol transmission of influenza A virus. Emerg Infect Dis. 2006 Nov [accessed 8/12/14]. 

Nicas M, Nazaroff WW, Hubbard A. Toward understanding the risk of secondary airborne infection: emission of respirable pathogens. J Occup Environ Hyg. 2005;2:143–54. 


Knight, V. Viruses as agents of airborne contagion. Annals of the New York Academy of Sciences. 1980; 353: 147–156.

Judie Alimonti, Anders Leung, Shane Jones, Jason Gren, Xiangguo Qiu, Lisa Fernando, Brittany Balcewich, Gary Wong, Ute Ströher, Allen Grolla, James Strong & Gary Kobinger. Evaluation of transmission risks associated with in vivo replication of several high containment pathogens in a biosafety level 4 laboratory. Sci Rep. 2014; Jul 25; 4:5824.










Sunday, August 10, 2014

Ebola-Infected Healthcare Workers: What Does It Mean?

As I read comments on Ebola articles, it's apparent that many are still terrified that the virus responsible for this Ebola epidemic is worse somehow, more virulent or more easily transmitted because physicians and health care workers who are wearing protective gear are dying for God's sake! These people are highly trained and covered head to toe and they are getting infected!!! PANIC!

Actually, there's no need to panic.

For those who are genuinely worried about this I'd like to offer some information that will ease your mind.


Generally speaking, the health care workers treating Ebola patients in these countries have little resources or training to deal with Ebola, especially on this scale. Hospitals and clinics, like the one in Nigeria pictured above, don't have Swiffer wet jets, Clorox wipes or hand sanitizer dispensers mounted on every wall. If they do have full protective gear, it's extremely hot, adding to the exhaustion. These facilities have a lot of really sick people who are too weak to get up when they need to vomit or have a bout of severe diarrhea. It's a constant battle to treat patients and stay clean and it's hard to know where every infected droplet landed. Doctors and nurses are overworked, underpaid, exhausted and either still doing their best, or not showing up for work. I can't blame them but it adds that much more work to those who remain.

In addition to supplies and gear, training is critical. There are specific techniques you can use when cleaning spills, or handling infectious material that will significantly reduce the risk of infection if you know how to do it. Most of these health care workers weren't there specifically to fight Ebola, but they were there when the patients started coming in. Efforts at training are limited and when you are exhausted and overrun with patients, its easy to make a mistake or have an accident, and here, even those that seem minor can be deadly.

For comparison, here is what a facility designed to treat an Ebola patient looks like in a developed city (London)...


There really is no comparison.

Still, the health care workers in West Africa do what they can with the little they have. This Ebola is not some super Ebola that is airborne or can magically penetrate protective gear. There simply aren't enough trained people with the right resources to fight it. 

The nitty gritty details important for at-risk healthcare workers are in CDC Director Tom Frieden's recent blog post and for a truly remarkable account of what this is like in a field clinic, read emails from Dr. William Fischer II, a physician from UNC who has been on the front lines in Gueckedou, Guinea since May. It's a must-read for anyone who wants to understand why this virus is out of control over there.

The bottom line, and the reason this epidemic is out of control, is that these countries need help, a lot of help. Liberia's President, Ellen Johnson Sirleaf, even apologized for the lack it: "If we haven't done enough so far, I have come to apologize to you."

IF? Well, certainly they haven't done enough and the international community has taken far too long to rally. No one has done enough...except for the heroic doctors and nurses who have been, and are still, reaching out to help and comfort the sick, whether or not they have what they need. [EDIT 8/15/14 A new story in the Wall Street Journal illustrates this point all too poignantly]

Heroes indeed.

Heather

Saturday, August 9, 2014

NIH Did Not Renew Funding for Critical Sierra Leone Project


We've heard some devastating news for those battling Ebola in Sierra Leone. The Thomas Reuters Foundation published an article indicating that the NIH has not renewed funding for a project run by Tulane University whose original funding contract expires in November. NIH funded projects are renewed through a process of proposal submission, review and scoring. Reviewers reading the proposal may not have been aware of the importance of the project to the current Ebola outbreak.

The Tulane run facility in Kenema was originally set up to help study Lassa Fever, an acute viral illness that can progress to hemorrhagic disease, caused by an arenavirus. According to "crude" estimates by the CDC, "The number of Lassa infections  per year in West Africa is between 100,000 to 300,000, with ~5000 deaths." Kenema, in the Eastern Province of Sierra Leone has the highest incidence of Lassa Fever in the world. Now the facility is being used to treat Ebola patients and they have lost more than 20 health care workers to Ebola including the Chief Physician and facility Director - Dr. Sheik Umar Khan, the Chief Nurse - Mbalu Sankoh and Senior Nurse - Alex Moigboi.

NIH proposals that are not funded can be resubmitted with changes made to address reviewer concerns. Hopefully they will be able to resubmit and get that funding.

Cheers,

Heather

Thursday, August 7, 2014

Ebola: Stop The Madness!

Recently, 2 American citizens stricken with hemorrhagic fever caused by infection with the virus, Ebola, have been returned to the U.S. for treatment...

And...cue the uninformed, ignorant  masses to protest, criticize and incite fear. People with platforms to express themselves are even irresponsibly leveraging this fear to further provoke criticism of the handling of immigration. Here's but one example, courtesy of Laura Ingraham, from The Laura Ingraham Show, 8/4/2014 (horrific grammar is hers):
"All the people who are upset about the Ebola-infected patients being treated in the United States. I will say this, at least we know who they are and where they're being treated. We currently have a border that is much like Swiss cheese that anyone could be coming across the border right now, with any type of illness. And we have a very limited ability to stop them, track them, prevent the disease from spreading. So before you get all upset about Ebola, we could have Ebola people coming across the border right now."

"Ebola people". Seriously?

What terrifies me is the blatant disregard for the truth and the perpetuation of ignorance, by people who should know better.

Actual experts in the pertinent fields: epidemiology, virology and emerging infectious diseases, are trying to get the truth out, but the voice of reason is hard to hear over the din of doomsday propaganda extremists. Clearly, we need to learn a little more about Ebola and the real, or imagined, threat to those of us here in the U.S.

My friends, I'm here to help. But before I get into the nitty gritty, let me first say this:

The current Ebola epidemic in West Africa will not lead to an Ebola epidemic in the U.S..

And how can I be so sure?

I have a PhD!

Just kidding. Well, I do, but that's not why I can say that. In order to understand why we are not currently at risk for an Ebola epidemic here in the States, we need to understand a little bit about the virus. Virus life cycles and the processes of transmission and infection are very complex and one blog post cannot address every aspect. Therefore, what follows is a brief description specifically designed to help us understand what's relevant for this discussion.

What is a virus?
A virus is a microscopic infectious agent that can only make copies of itself (replicate) inside of a living cell. Who cares? Well, the only thing a virus has on its agenda is to replicate. That's it. Once it replicates it can get out and see the world! To do this, a virus hijacks cellular machinery for its own dastardly purposes, makes millions of copies of itself and enters a new organism through transmission and infection. Every type of organism on earth can be infected by a virus, including bacteria. Cool, right? Because a virus cannot replicate on its own, most experts do not consider it to be "alive" although I'm sure the debate still rages somewhere. Oh, and by the way....ascribing human characteristics to a virus (e.g, its agenda and dastardly purposes), while fun, is a no-no. Viruses are passive. Their genetic code dictates what the virus particle does in response to environment stimuli, but they don't make plans or actively do things, although some of them make us very sick or kill us. Kinda like Congress.

Many viruses that infect mammals, (e.g, humans, gorillas), survive in nature by residing within a "reservoir" organism: an animal that is not sickened by the virus, but can carry and transmit it. The virus replicates in this reservoir and when there are enough virus particles in the right places, they are "shed", or released via saliva, urine, feces, sweat, tears, semen, mucus etc.  The specific route of shedding depends on the virus and its tropism (where it goes in the body). So even though the animal harbors the virus, it doesn't get sick (also called "asymptomatic") and it can infect other organisms.

Back to Ebola. Ebola is a fascinating virus that is classified within the virus family Filoviridae. It is microscopic and an Ebola virus particle is comprised of only some RNA and several proteins. That's it. Scientists have found evidence of asymptomatic Ebola infection in some fruit bat species. So some fruit bat species are likely Ebola reservoirs. The bats can then transmit viruses to humans or other primates through contact with infectious excrement, saliva on partially eaten fruit, or blood while butchering. The good news is these Ebola reservoir species do not naturally live in the U.S., so Ebola does not naturally occur in the U.S.  Nifty. The bad news? Once inside a human, Ebola replicates quickly and spreads throughout the body, especially the liver. It is shed through blood and other bodily fluids. However, the virulent (makes you really sick) strains of Ebola are not airborne.



[EDIT 8/12/14- I moved the detailed info about aerosol, droplets and fomites to a dedicated post and expanded upon it both to make this post easier to read, and make that information easier to find. End Edit]



What Does "Airborne" Mean?
Let me clarify. Bodily secretions that make it into the air from various orifices (e.g., nose, mouth, John Boehner) are called droplets and are classified based on size and distance traveled. The smaller the droplet, the longer it stays suspended in the air, the farther it travels and the deeper into the respiratory tract it can go upon inhalation by the person sitting down the aisle from you on the airplane.

When we say that a virus is airborne, we specifically mean it is capable of aerosol transmission via inhalation, even when not in close proximity to the source of the aerosol.

Large-droplet transmission happens when heavier droplets are splattered or splashed onto people or surfaces and is not considered airborne.

So, is Ebola Zaire airborne? No. While it is possible that the non-virulent (doesn't make you sick) Ebola Reston strain was transmitted between primates that were not in close contact in a small monkey outbreak in 1989, other modes of transmission couldn't be ruled out. In addition, it did not cause clinical symptoms in humans that were exposed. If you want to read more about that, check out Richard Preston's The Hot Zone. I agree that Richard has a flair for the dramatic, but he gets much of the detail right. In 1996 one of the world's pioneers in the field (and my PhD Advisor), CJ Peters and his group, published a paper characterizing Ebola infection in cynomolgus macaques (a type of monkey). They had this to say, "...abundant virus was visualized in alveolar interstitial cells [cells found in the lungs] and free in the alveoli suggesting the potential for generating infectious aerosols. Thus, taking precautions against aerosol exposures to filovirus infected primates, including humans, seems prudent." There have been other studies, and anecdotal evidence during epidemics, also showing evidence that aerosol transmission of Ebola might be possible.

So then it IS airborne, right?

Nope. We've yet to see aerosol transmission actually happen during an outbreak. Experience shows us that it doesn't happen. [edit 9/18/14: For more clarification on this my post on the 1995 Kikwit outbreak]. So while the wise thing to do is caution people to take precautions against infectious aerosols, direct contact, large-droplets and poor sanitation are the culprits here.

But what about the 2012 pig study You ask? Everyone's talking about it! Well, I've read the study and while interesting, there are key findings that seem to get left out of the media hype. This study was done to determine if pigs could transmit Ebola to cynomolgus macaques;  the study's primate surrogate for humans. The authors found that if pigs infected with Ebola Zaire were kept in a room with monkeys in cages, the monkeys got infected. While fascinating, as a scientist, I'm not convinced this actually provides any information regarding primate-to-primate, and therefore human-to-human, transmission. My doubts stem from two things:

1.) There are significant differences between the diseases caused by Ebola Zaire in pigs compared to that in monkeys and humans. In primates, Ebola Zaire causes widespread severe immune dysregulation that leads to hemorrhagic fever and in 90% of cases, death. In pigs, however, the disease is very different: infection is limited to mostly the respiratory tract and illness lasts for about 9 days and then the animals recover. This clearly indicates that there are significant differences in the way the virus spreads through the body and causes disease in the pig compared to the primate. Unfortunately one serious design flaw in this study, that was pointed out by the authors, was that "The design and size of the animal cubicle did not allow to distinguish whether the transmission was by aerosol, small or large droplets in the air, or droplets created during floor cleaning which landed inside NHP cages (fomites)." In addition, the principal investigator (head scientist on the study),  Dr. Gary Kobinger, indicated in an interview in 2012 that, based on the kinds of respiratory secretions that pigs produce, he believes the transmission they observed between pigs and monkeys was via larger droplets.

and 2.) The observation also made by the study authors that, "Interestingly, transmission between macaques in similar housing conditions was never observed." Yeah, that IS interesting!

And it was CONFIRMED in a recently published study!!!! Primates do not transmit Ebola to other Primates via aerosol transmission. The End. [EDIT 8/8/14: I realized after posting this that I was missing a golden opportunity to communicate a very important scientific concept regarding these studies. It's easy for non-scientists to look at this example and think that the 2012 pig-monkey study was either wrong or useless, but the truth is, it was a great study. The problem was that people with no scientific background, heard about it and assumed it gave us information about human-to-human transmission. Therein lies the problem. The study gave us very important information about their model under their conditions, and the authors were clear about its limitations, as good scientists are. The takeaway is this: be careful about extrapolating data from model systems to humans, and be more careful about spewing those extrapolations out into the world. End Edit]

So these are the protective measures you need to take....if you are in West Africa:


So what does this mean for a potential U.S. epidemic? It comes back to this: Close contact with someone during the infectious stage of disease is necessary for human-to-human transmission of Ebola. This is one of the key reasons why the Ebola epidemic in West Africa is out of control and why this won't happen in the U.S.

Unfortunately, in West Africa, one major problem with this epidemic was the lack of effective diagnostics and isolation at the beginning of the outbreak. These countries simply do not have the resources. Many infected people moved around before anyone knew the disease was present and more people got infected. By the time clinics and treatment centers were set up, the numbers of patients shedding virus into the environment were too high, and sanitation too inadequate, for the limited precautionary measures being taken. Not all health care workers have access to protective gear at all times and the gear they get is often meager. Disinfecting protective gear by hand is the only option, but it just isn't effective on that scale. There are also enduring cultural practices that contribute to disease spread, and when combined with inadequate infectious disease containment infrastructure the results are tragic. Richard Preston's recent New Yorker article does a great job of helping us understand this reality. If that weren't enough, all of the everyday struggles these people face compound the problem: weather, restricted access to clean water, sanitation, ongoing civil/political unrest and the list goes on. For a nice in-depth explanation read Laurie Garrett's article from last week. You probably remember Laurie from The Coming Plague, also an excellent a pretty good read. [edit 8/30/14: after speaking with someone directly involved in some of the incidents described in The Coming Plague, I learned that some such incidents were described inaccurately . Because of this, while I recommend it as a great read, I can no longer suggest that it's wholly accurate.]

Can you begin to see how this won't happen here in the U.S.? We screen people at our borders and ports of transit. Suspected cases are immediately isolated in facilities that actually have the resources necessary to do so effectively. People have the luxury of information here and are quick to get themselves or their family members to the hospital because they understand what's at stake. Physicians are well trained and even more well equipped. Protective gear is either disposable and disposed of correctly, or used once then sterilized, not merely disinfected and certainly not by hand. Patients are isolated under stringent conditions and are provided superb supportive care that includes sanitation and cleaning measures. Simply put, the U.S. has the resources needed to handle Ebola patients in a way that will prevent an epidemic. The worst that could happen is a small outbreak in which a few people are infected before they are correctly diagnosed and treated. But once discovered, we would be able to effectively stop Ebola from spreading. So relax people. Seriously.

One last thing I'd like to address is the fear of a naturally occurring worldwide epidemic (pandemic) of Ebola. Also, not going to happen, and the physicians out there claiming it is coming should be ashamed. An important factor that reduces the potential for an Ebola pandemic is that Ebola isn't actually very good at being a virus. When it infects and sickens an organism, it kills it quickly. It renders the patient sick enough, fast enough, that transmission is actually limited. Sure it will spread through heavily populated areas quickly under the right conditions (lack of resources, sanitation, leadership, medical care and effective preventive measures), but it will burn itself out eventually and it certainly won't spread that easily in developed countries. If you are interested in this concept I highly recommend checking out the game Plague Inc in which you can design an infectious agent and give it different properties that will affect severity of disease, transmission route and rate and ultimately demonstrate why the agent either does or does not cause epidemics. It is a bit morbid, and I'm not sure how I feel about my husband and son shouting for joy when they "win" because their infectious agent decimated the world. Nonetheless, it's based on real world epidemiology models and is a very practical way to learn about the fundamentals of infectious disease epidemiology. If you plugged Ebola's characteristics into the system, it would demonstrate that Ebola is self-limiting.

So, instead of fear mongering and hate-filled political rhetoric, let's focus on being compassionate to those who are suffering. Just because we aren't expecting an epidemic on our soil doesn't mean we shouldn't be working hard on behalf of those facing the disease right now. Let's celebrate the heroes who are already there, working tirelessly under horrific conditions with severely limited resources and focus our energy on helping. They can't do it alone. Let's quiet the divisive ignorance, and act. Each of us can make a difference in the lives of those in need. The question is, will we?

Go to these websites to learn how you can help:
Africare
Global Giving
Direct Relief
Action Aid

Update 8/20/14: Here's where to go for great specific info about how you can make a difference:
Caitlin Rivers  Thanks Caitlin!!

And for more great updates on this and other infectious disease topics I highly recommend Tara Smiths' Aetiology Blog. It's well written and insightful!

Cheers,

Heather