Wednesday, October 29, 2014

Ebola Patient Zero: What we do, and do not, need to know about an epidemic index case

Whenever there is an infectious disease epidemic there will also be an index case, or patient zero: the first recognized case of the disease in a population; the case that alerts you to the presence of the disease. From an epidemiologic perspective, identifying this case is critical because it can provide really important information. How the index case got infected can offer insight into the pathogen's natural reservoirs or modes of transmission, and can also help clarify at what point in disease progression the patient was infectious and how the disease initially moved through the population. All are critical in helping define strategies for future epidemic prevention, control and health care approaches. For these reasons there are things we need to know about an index case. We need to know where they lived, where they went and what they did on the days they might have become infected. Who did they have contact with? When did symptoms start? What did they eat? Did anything unusual happen? Did they go hunting? Was there an insect or animal bite? An injury? A fall? A swim? Who helped them? Are they sick now? These are all important and can help pinpoint the original source of infection.

But do we actually need a name?

Epidemics aren't only about hard science. And while learning all we can about the virus and its transmission will allow us to better fight future epidemics, we shouldn't neglect the human element in the pursuit of knowledge. We have numbers on graphs and charts: cases, deaths, beds. But these statistics are about people and it's often the human stories that drive us. Maybe that's why we look for the names. But should we look for that name?

Many index cases are known, some even famous. You've heard of Typhoid Mary no doubt? Her real name was Mary Mallon and she was forced into isolation after it was discovered she was the (unintentional) cause of dozens of typhus infections. We also know the names of the index cases for the 2003 SARS, the 1854 cholera, and the 2009 swine flu outbreaks. We even know the name of the very first Ebola index case ever recorded, from the 1976 outbreak.

And now we know the name of the index case in this Ebola epidemic. We have had the information regarding the index case for a while now. We've known it was a child in Guinea and we've known that, as the first family afflicted by this epidemic, their losses were great. But now we've also been given the name of the two-year old child who was Ebola's first victim last year.

Did we need that? Did we need to see the family photos? Did it teach us anything about the epidemic? Did this information give us anything useful or just headlines? Did it serve only to exploit the tragedy of a family that lost everything? Did it do anything useful other than put a name to the epidemic? Did it give us someone to blame?

I believe there are many (maybe most) who will not blame this child or his family, but there are those who will. This tragedy will be replayed again and again and the stigma that's already been borne by the family and community will also be replayed. How can it not? This is the largest, most horrific Ebola epidemic in history. Thousands are dead, more dying and it's not over. Who knows what the final toll will be when all is said and done? We can't know that now, but when we do we will be able to trace it all back to one chance encounter with something infectious; one innocent child, one loving family, one community that had no idea what they were up against. A horrific tragedy in every sense of the word.

And by publishing this precious child's name and family photos for our consumption, have we added to our understanding of the epidemic, or is this a new tragedy - one that we must own?


Pathogen Scribe

Wednesday, October 15, 2014

Ebola in Texas: Take a Deep Breath Y'all

Alright folks. Here in Texas two nurses have turned up positive for Ebola and it's possible other healthcare professionals who worked with Mr. Duncan, or who will work with the nurses, will turn up infected.

So now what? What does this mean?

Well, We know how Ebola is transmitted and we know how to prevent that transmission. But knowing how, watching a youtube video about it, and putting that knowledge into practice in a frightening real life situation, are very different things.

The reason that personal protective equipment (PPE) works, is because people use it and use it correctly. I really don't think anyone would intentionally treat an Ebola patient in what they knew was an unsafe manner, but there are nuances and subtleties involved with PPE that, if not well understood, can mean the difference between safe and unsafe, and with Ebola the room for error is incredibly small. And while you wouldn't leave the gloves on the shelf when examining an Ebola patient, and you might know that removing contaminated gloves incorrectly is just as dangerous as not wearing them, it's easier to misjudge what it really means to remove those gloves safely than one might think. Without practical experience, it's very easy to think you are doing it correctly.

And Texas Health Presbyterian nurses and doctors got thrown into a very tough situation with a very sick patient and we are hearing that they had no protocols in place. Which also means they hadn't done any real prep in case an Ebola patient showed up. But I doubt that situation is any different than most other US hospitals, so instead of castigating them, we should focus on finding ways to better prepare every US hospital. And I think one of the most important things for hospital supervisors to realize is that thinking that you or your staff are doing it correctly isn't enough. You need to make sure that everyone knows what to do and can do it without fail.

So how do you do this?

Training, drills and testing.

From the beginning of this epidemic, we've been horrified about the number of HCW being infected, and untrained and unsupervised HCWs anywhere are susceptible to infection from an Ebola patient. On October 3rd, Dr. Tom Ksiazek, the most eminent Ebola epidemiologist working today in my opinion, gave a talk about his 6 weeks as the CDC team leader in Sierra Leone and said the biggest problem with PPE (when they had it) where he'd been, was training, especially removal of contaminated PPE and supervision.

And it's clear that, while most US hospitals have the capability of containing Ebola to a handful of cases should it appear, whether they will or won't depends on training and the practical application of what is known to effectively protect against Ebola transmission.

Do HCWs in the US have more training in general than W. Africa? Probably. Are they specifically trained in the dangers unique to the very high profile task of caring for Ebola patients who are exhibiting frightening symptoms and exuding copious amounts of infectious bodily fluids, all while performing medical procedures? Not most of them.

In fact Anthony Fauci, Director of the NIAID, said HCW need more training and that you "gotta have drills". You can't just send an email containing a link to nurses and tell them to learn how to use extensive PPE in their spare time.

So how can you find out if you or your staff are disinfecting correctly, or removing PPE without contaminating yourselves? Someone needs to show you how to do it correctly, let you practice under supervision, then test you. A really effective way to do this is to use a fluorescent powder or liquid that is only visible under UV light. Something like Glo Germ. Toss it around a HCW in full PPE, get it on their gloves and shoe covers and mask - all over the place. Then have them disinfect and remove the PPE as they would in a real life situation. Then illuminate them with the UV light to see what lights up. With Ebola you only need a tiny bit of residual contamination transferred from a finger to an eye to cause an infection.

And then understand that this doesn't necessarily mean that the person was careless or cavalier, but more likely that it's really really really hard to decontaminate and remove contaminated PPE safely. This is why there is a buddy system. This is why training and supervision are paramount.

And if you're a nurse or a doctor and you have any hesitation about whether you're prepared to safely enter an Ebola patient's room, you need to be able to feel like you can bow out without the risk of losing your job. Your supervisor should not only respect your professional assessment, but should applaud you for it.

Can this be contained? Absolutely. But unless someone takes charge and shows people how to do this job safely, there will likely be other HCW infections in the process.

Who should be in charge? Well, hopefully State Public Health Departments will play a role in guidance and training, and hopefully the CDC will also provide some oversight. But if I were a hospital, I would assign a small team of HCW (w/enough for redundancy) specifically to handle potential Ebola patients. This team would be the only staff to have any interaction with any possible Ebola patient, from initial evaluation, to diagnosis and testing and through treatment. This team should be on call and given both on call and hazard pay. And this team should be identified now and trained extensively, before another  Ebola patient arrives at an unprepared hospital door.

But in the meantime I think moving the newest Ebola patient, nurse #2, to Emory is a really great idea. Let THP take a deep breath and regroup, and maybe all of our hospitals can start implementing some protocols that will help us move forward and prevent more infections.


Cheers,

Pathogen Scribe

Sunday, October 5, 2014

Why Ebola Airborne Mutation(s) are "Highly Unlikely": Let's Talk Mutation and Natural Selection

Note: This post is not an exhaustive treatise on the evolution or adaptation of filoviruses, but an applicable discussion on certain principles.

When Ebola experts say that mutation to become airborne is “highly unlikely”, they are basing this on what they know, as experts, about Ebola molecular virology, cumulative transmission data and natural selection. While they’ve all said it, I think Heinz Feldmann, one of the foremost experts in Ebola molecular virology, said it best in his interview with Kai Kupferschmidt (17 September 2014):

Q: "There has been speculation that the virus could mutate or has already mutated to spread more easily. How likely is that?"

A: "I don’t think there is any data right now to support that. If you look at the virus sequence, it falls within the normal range of Zaire Ebola strains. Of course any of these mutations could have a dramatic effect, which we don't know right now. But there is nothing obvious that would point to a more transmissible, more virulent virus, or a change of transmission route.

You can speculate in every direction, of course, but I think it should be fact-based, it should be data-based, and I think it makes absolutely no sense to bring in aerosol transmissibility as a potential. I think this is really not helpful, unless you have data to support that."

What he is saying there is that he knows Ebola genetics and he doesn't see anything in the new genetic data that indicate the virus is mutating in that direction. Being an excellent scientist, he also acknowledges that we don’t know what all changes mean yet, but based on the data he sees, there’s no evidence to speculate that this Ebola variant is becoming airborne.

Aside from the genetic data they have, Ebola scientists consider the way in which Ebola is already successfully transmitted, as well as Natural Selection.

So let’s talk about Natural Selection for a little bit. In his 1930 book, “The Genetical Theory of Natural Selection”, Ronald A. Fisher made this important distinction, “Natural Selection is not evolution.” It’s “…a convenient abbreviation for the Theory of Evolution by means of Natural Selection…” We will be coming back to Fisher soon, but I wanted to make sure we were all on the same page. So as far as Natural Selection goes, I think Dr. Laurence Loewe described it really well in his educational piece for Nature (1) when he said, “…selection constantly sorts through the variation that is produced by mutations to select the fit and remove the unfit, while ignoring neutral changes.”

Fitness refers to an organism’s ability to compete in its environment in so far as survival or reproductive ability. Can it eat? Protect itself? Have fit offspring? During replication of any organism’s genetic material mutations are possible. For viruses, the speed of replication makes the rate of mutations higher than for a human.(2)  And mutations can be classified with regard to how they affect the organism’s fitness. When a mutation provides a selective advantage in this regard, it will be selected for; the frequency of the genotype (genetic profile) containing that mutation will increase. If a mutation is deleterious, it will be selected against and the frequency of that genotype will decrease.

So what drives mutation? Well, Natural Selection moves an organism toward an adaptive optimum; the point at which the organism would be most fit in its environment. This doesn't mean that Natural Selection causes mutations, but that it determines whether or not a mutation would be kept or discarded. And Fisher thought this occurred in small steps rather than in large leaps. He thought that small advantageous mutations would happen more often than large ones, because large mutations would be more likely to have negative side effects. Well, a group studying RNA viruses actually found evidence to support this theory: they showed “…that adaptation proceeds by multiple mutations, but that among the set of all possible mutations, adaptation proceeds by the subset of mutations with small effects.”(2)

This supports what Ebola experts have said, that it’s not likely that a single mutation would cause this virus to go airborne, and the likelihood of the virus acquiring all the needed mutations at the same time is extremely low.

In addition, there’s no selective advantage to becoming airborne for Ebola. It is clear that Ebola’s current mode of transmission is working well. The virus is spreading and reproducing successfully. This means there is no selective pressure on the virus to keep any mutations that might confer airborne transmission, especially when this kind of significant change would most likely bring with it some serious deleterious side effects. And while some argue that this is the first time Ebola has been replicating to this extent in humans, we need to keep in mind that it’s been doing this for far longer in the wild in the primate species it infects and in its bat reservoir host. And yet, this mutation hasn't happened.

[edit 10/6/14]: WHO agrees with me and has also pointed out today, that viruses entirely changing their transmission mode is not something we've seen before. They must have read my blog. ;-)]  

So, can we say it's impossible? No. But I'm not losing any sleep over it.

Cheers,

Pathogen Scribe


References