“The Hot Zone” and the mythos of Ebola

The Hot Zone was first released in 1994, the year I graduated high school. Like many readers, that book and Laurie Garrett’s The Coming Plague* really sparked my interest in infectious diseases. In some sense, I have those books to thank (or blame?) for my career.

But I’m still going to criticize The Hot Zone, because as a mature infectious disease epidemiologist and a science communicator in the midst of the biggest Ebola outbreak in history, The Hot Zone is now one of the banes of my existence. A recent article noted that the book is back on the bestseller list, going as high as #7 on the New York Times list recently, and #23 on Amazon. It’s sold over 3.5 million copies, and it’s reported as “a terrifying true story.” Many people have gotten almost all of their Ebola education from just The Hot Zone (as they’ve told me over, and over, and over in the comments to this blog and other sites).

Here’s why The Hot Zone is infuriating to so many of us in epidemiology and  infectious diseases.

First–the description of symptoms.Preston himself admits that these were exaggerated. Over and over, he uses words like “dissolving,” “liquefy,” “bleeding out” to describe patient pathology. (If I had been playing a drinking game while reading and did a shot every time Preston uses “liquefy” in the book, I’d be dead right now).

Of a Marburg patient, pseudonymously named Charles Monet, he describes him as

“…holding an airsickness bag over his mouth. He coughs a deep cough and regurgitates something into the bag. The bag swells up….you see that his lips are smeared with something slippery and red, mixed with black specks, as if he has been chewing coffee grounds. His eyes are the color of rubies, and his face is an expressionless mask of bruises. The red spots…have expanded and merged into huge, spontaneous purple shadows; his whole head is turning black-and-blue…The connective tissue of his face is dissolving, and his face appears to hang from the underlying bone, as if the face is detaching itself from the skull…The airsickness bag fills up to the brim with a substance known as the vomito negro, or black vomit. The black vomit is not really black; it is a speckled liquid of two colors, black and red, a stew of tarry granules mixed with fresh red arterial blood. It is hemorrhage, and smells like a slaughterhouse….It is highly infective, lethally hot, a liquid that would scare the daylights out of a military biohazard specialist…The airsickness bag is brimming with black vomit, so Monet closes the bag and rolls up the top. The bag is bulging and softening, threatening to leak, and he hands it to a flight attendant.

“…the body is partly transformed into virus particles…The transformation is not entirely successful, however, and the end result is a great deal of liquefying flesh mixed with virus…The intestinal muscles are beginning to die, and the intestines are starting to go slack…His personality is being wiped away by brain damage…He is becoming an automaton. Tiny spots in his brain are liquefying…Monet has been transformed into a human virus bomb.

“…The human virus bomb explodes…The victim has “crashed and bled out.”…He becomes dizzy and utterly weak, and his spine goes limp and nerveless and he loses all sense of balance….He leans over, head on his knees, and brings up an incredible quantity of blood from his stomach and spills it onto the floor with a gasping groan. He loses consciousness and pitches forward onto the floor. The only sound is a choking in his throat as he continues to vomit while unconscious. Then comes a sound like a bedsheet being torn in half, which is the sound of his bowels opening and venting blood from the anus. The blood is mixed with intestinal lining. He has sloughed his gut. The linings of his intestines have come off and are being expelled along with huge amounts of blood. Monet has crashed and is bleeding out.”

And later, at autopsy:

“His liver…was yellow, and parts of it had liquefied–it looked like the liver of a three-day-old cadaver. It was as if Monet had become a corpse before his death…Everything had gone wrong inside this man, absolutely everything, any one of which could have been fatal: the clotting, the massive hemorrhages, the liver turned into pudding, the intestines full of blood.”

And I didn’t even get to what Preston says about Ebola and testicles. Or pregnant women. Seriously, there’s pages upon pages upon pages of this stuff.

Throughout the book, Preston presents these types of symptoms as typical of Ebola. Not “in worst case, this is what Ebola could do,” but simply, “here’s what happens to you when you get Ebola.” It’s even beyond a worst case scenario, as he notes in part: “In the original ‘Hot Zone,’ I have a description of a nurse weeping tears of blood. That almost certainly didn’t happen.”

Compare that to just about any blog post by actual workers with Médecins Sans Frontières, healthcare workers on the front lines of this and many previous Ebola outbreaks. Stories are scary enough when the reality of the virus is exposed, and with it the dual affliction of poverty and the terrible health system conditions of affected countries. I interviewed MSF’s Armand Sprecher a few years back during a different Ebola outbreak, and he noted this about symptoms–quite different from the picture Preston paints:

The patients mostly look sick and weak. If there is blood, it is not a lot, usually in the vomit or diarrhea, occasionally from the gums or nose.

The clinical picture of Ebola that people take away from The Hot Zone just isn’t accurate, and with 3.5 million copies sold, is certainly driving some (much? most?) of the fear about this virus.

Second, airborne Ebola. Though this trope is often traced back to “Outbreak,” Preston clearly suggests that both Zaire Ebolavirus and Reston Ebolavirus can be airborne. What he never discusses nor clarifies is that the “evidence” for this potential airborne spread is really thin, and not even indicative of animal-to-animal or animal-to-person transmission.

Rather, it’s much more likely that if airborne spread was involved, it was aerosols generated by husbandry (such as spraying while cleaning cages), rather than ones which would have been generated by infected primate lungs (a necessary step for primate-to-primate transmission via a respiratory route). Indeed, this is the paper that Nancy Jaax et al. published on the findings Preston talks to Jaax about, 13 years after the fact (the experiment is marked as 1986 in The Hot Zone), and noting that transmission due to husbandry practices could not be completely ruled out. It’s unclear also that the Reston strain moved through the primate facility via air, rather than via spread due to caretakers, equipment, or husbandry. Nevertheless,  it’s frequently cited as fact and without any qualification that Reston is an airborne type of Ebola.

Instead, here is what Preston says about it:

“If a healthy person were placed on the other side of a room from a person who was sick with AIDS, the AIDS virus would not be able to drift across the room through the air and infect the healthy person. But Ebola had drifted across a room. It had moved quickly, decisively, and by an unknown route. Most likely the control monkeys inhaled it into their lungs. ‘It got there somehow,’ Nancy Jaax would say to me as she told me the story some years later. ‘Monkeys spit and throw stuff. An when the caretakers wash the cages down with water hoses, that can create an aerosol of droplets. It probably traveled through the air in aerosolized secretions. That was when I knew that Ebola can travel through the air.'”

He then comes back to “airborne Ebola” several times, based in part on this idea.

But here’s the thing. Just about any virus or bacterium could be aerosolized this way–via high pressure washing of cages, for example. If it can bind to lung cells and replicate there, as we already know Ebola can, it can cause an active infection.

But that’s not the same as saying “Ebola can drift across the room” from one sick person to a healthy person and cause an active infection, as Preston tries to parallel with HIV in the above paragraph. Even in Jaax’s experiment and others like it, there’s zero evidence that primates are expelling Ebola from their lungs in a high enough concentration to actively infect someone else. And that is the key to effective airborne transmission. Think of anthrax–if it’s released into the air, we can inhale it into our lungs. It can replicate and cause a deadly pneumonia. But anthrax isn’t spread person-to-person because we don’t exhale the bacteria–we’re dead ends when we breathe it in. This is what happens with primates as well who are experimentally infected with Ebola in a respiratory route, but Preston implies the opposite.

Third, if it wasn’t for points one and two, The Hot Zone really could be read as a “damn, Ebola really isn’t that dangerous or contagious so I have little to worry about” narrative. Preston describes many “near misses”–people who were exposed to huge amounts of “lethally hot” Ebola-laden body fluids, but never get sick–but doesn’t really bother to expose them as such. All 35 or so people on the little commuter plane Monet flies on between his plantation in western Kenya and Nairobi, deathly ill, vomiting his coffee grounds and dripping nasal blood into the airsickness bag he handed to a flight attendant–none of them come down with the disease.

The single secondary infection Monet causes is in a physician at the hospital where he’s treated, after his bowels “ripped open” like a bedsheet. That physician, Shem Musoke, not only swept out Monet’s mouth until “his hands became greasy with black curd” but also was “showered” with black vomit, striking him in the eyes and mouth. Monet’s blood covered Musoke’s “hands, wrists, and forearms,” because “he was not wearing rubber gloves.” Musoke developed Marburg virus disease, but survived–one of the few secondary cases of infection described in the book.

Another “close call” was that of Nurse Mayinga N. She had been caring for one of the Ebola-infected nuns at Ngaliema Hospital in Kinshasa during the 1976 outbreak in Zaire, the first detected entry of Zaire Ebolavirus into the human population. Beginning to feel ill herself, she ditched her job and disappeared into the city for two days. She took a taxi to a different, larger, hospital in the city, but was sent away with a malaria shot. She’s examined at a third hospital and sent away. Finally she returns to Ngaliema hospital and is admitted, but by that time, had caused a panic. Preston says:

“When the story reached the offices of the World Health Organization in Geneva, the place went into full-scale alert…Nurse Mayinga seemed to be a vector for an explosive chain of lethal transmission in a crowded third-world city with a population of two million people. Officials at WHO began to fear that Nurse Mayinga would become the vector for a world-wide plague. European governments contemplated blocking flights from Kinshasa. The fact that one infected person had wandered around the city for two days when she should have been isolated in a hospital room began to look like a species-threatening event.”

How many secondary cases were the result of Mayinga N’s wanderings? That possibly “species-threatening” event? Preston again devotes several paragraphs to Mayinga’s gruesome illness and death, and notes that 37 people were identified as contacts of hers during her time wandering Kinshasa. He tells us they were quarantined “for a couple of weeks.”

The fact that exactly zero people were infected because of Mayinga’s time in Kinshasa merits half a paragraph, and not dramatic or memorable. “She had shared a bottle of soda pop with someone, and not even that person became ill. The crisis passed.” <–Yes, that is a direct quote and the end of the chapter on Mayinga. Contrast that to Preston’s language above.

Finally, beyond the science and the fear-mongering about Ebola, beyond everything and everyone in the story “liquefying” and “dissolving” and “bleeding out,” reading this book again as an adult, as a woman in a science career with a partner and kids, I was also left annoyed at the portrayal of the scientists. All of the major characters except one, Nancy Jaax, are men of course, ranging in age from late 20s to 50s-60sish. Understandable since this is in a mostly-male military institution and in a BLS4 setting to boot, but the one Preston focuses on for much of the narrative is Jaax.

While Preston may have been trying to portray Jaax as the having-it-all, tough-as-nails woman scientist, the fact that she’s the only one with any kind of home life is telling–mostly because he devotes more paragraphs to how she neglects both her children and her dying father than any success she has in her life outside of work. She is told early on by one of her colonels that “This work is not for a married female. You are either going to neglect your work or neglect your family.” This thought comes up repeatedly for Jaax, and in the end, while she was accepted and even honored by her colleagues and bosses, we hear over and over again how her children are left on their own to microwave meals and tend to their homework. How they desperately wait up for her to get home after work, often eventually falling asleep in her bed before she arrives. How she tells her father, dying of cancer back in Kansas and both knowing he only has a few hours to days to live, good-bye and “I’ll see you at Christmas” over the phone. How she barely arrives on time for his funeral after he passes.

We hear one paragraph about how another colleague, Thomas Geisbert, had a crumbling marriage with two small children, and how he left the children at his parents’ house for a weekend. Other than that, the personal lives of any other characters are practically absent, save for Jerry Jaax, Nancy’s husband. Even with him, much of the character development revolves around his fears of his wife working in a BSL4 lab.

The Hot Zone, for me, is unfortunately one of those books that you read as a young person and think is amazing, only to revisit years later and see it as much more shallow and contrived, the characters one-dimensional and the plot predictable. The problem is that The Hot Zone is not just a young adult novel–it’s still presented and defended as an absolutely true story, especially by huge Preston fans who seem to populate comment threads everywhere. And now it looks like there will be a sequel. At least it should be good for a drinking game.

 

*I’ll note that The Coming Plague is much more measured when it comes to Ebola–the two were grouped together because temporally, they were released close together, not because they display the same type of hype regarding the virus.

Ebola fears at Kent State

Though I haven’t had a chance to write about this here, I have an article at Mic.com on Kent’s experience with Ebola exposure in our area. Amber Vinson, the second Ebola-infected nurse in Texas, is a Kent State alumna and has relatives that work here. Our experience on campus so far is described here in this article.

HIV denial: alive and well in 2014 [UPDATED]

Everything old is new again. For years on this blog, I wrote about HIV denial and the few fringe scientists and journalists who espoused it. I attracted a host of trolls, some of whom repeatedly attacked my credibility, my appearance, even showed up at my academic office. One of the most prolific of these was Henry Bauer, who posts long-debunked ideas on HIV/AIDS (and the Loch Ness Monster to boot).

That was, oh, 2007-ish and prior. In that same year Steven Novella and I co-authored an article on HIV denial for PLoS Medicine. In 2008, a leader of the denial movement, Christine Maggiore of “Alive and Well AIDS alternatives,” died of AIDS. In 2009, books were released from Seth Kalichman  (Denying AIDS)  and Michael Specter (Denialism), both further outlining the reasons why HIV denial is so, so, so incredibly flawed and dangerous. Seth still runs his blog, and HIV denial hasn’t gone away, but it’s lost some prominence in recent years–at least in the US.

For whatever reason, this week has been a hotbed of it.

First, MD/blogger Kelly Brogan had a post in support of HIV denial , specifically addressing pregnant women (currently taken down but the internet never forgets).

Now even worse, Frontiers in Public Health, an actual, peer-reviewed journal, has published a paper that is straight-out, unvarnished, HIV denial. Full stop. This journal is part of the “Frontiers in” series, that many readers will probably be familiar with. FPH claims that

Each Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world’s best academicians. Frontiers is well aware of the potential impact of published research both on future research and on society and, hence, does not support superficial review, light review or no-review publishing models. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public – and shape society. Therefore, Frontiers only applies the most rigorous and unbiased reviews, established in the high standards of the Frontiers Review System. Furthermore, only the top certified research, evaluated through the democratic Frontiers Evaluation System, is disseminated to increasingly wider communities as it gradually climbs the tiers of the Frontiers Tiering System from specialized expert readership towards public understanding.

Except, no way in hell is that accurate after the publication of this manuscript: “Questioning the HIV-AIDS hypothesis: 30 years of dissent,” by a professor at Texas A&M University named Patricia Goodson. Goodson’s qualifications appear to be in health education, including sexual health (and many publications related to abstinence-only education and to abortion), but nowhere do I see any publications or training relevant to epidemiology or virology.

The paper itself consists entirely of the old claims that have been debunked time and time and time and time again, using tactics we defined in our paper: quote-mining, cherry-picking evidence, moving goalposts, citing prominent deniers and denial groups, and more. There is nothing of value here, and the only real nod she gives to orthodox opinions on HIV are to cite Kalichman’s book ever-so-briefly and dismissively (characterizing it as “a harsh critique of unorthodox views and of Duesberg in particular”). 

And who is behind the curtain? Well, for one, Henry Bauer, who appears immediately in the comments of the paper, pimping his list of HIV denial resources. Goodson comments (click to embiggen):

Goodman and Bauer

So how in the world did this paper make it into a peer-reviewed journal with the stamp of approval of the Frontiers line and backing of Nature Publishing Group?  (EDITED via comments: Grace Baynes of NPG notes that Frontiers journals are editorially independent from NPG; see my response below). The two reviewers, Preeti Negandhi and Lalit Raghunath Sankhe are also apparently both members of the FPH editorial board, despite almost no academic record. Neither has experience in HIV/AIDS , but the latter appears to be the editor,  Sanjay P Zodpey‘s go-to reviewer, while the former only has one publication listed on the FPH page, co-authored with Zodpey on public health capacity development in India. No publications are listed on Sankhe’s page, but there was one I could find which may possibly be associated with this name. Other than that, zero record in PubMed.

Why were these people, who clearly have as little background in this area as Goodson does, chosen as reviewers? This is, at the best, a pathetic excuse for peer review and editing, and completely unprofessional and unacceptable. Did Zodpey, who does appear to have some background in HIV, even read the article before passing it along to two unqualified reviewers? This type of review makes a mockery of the entire system and makes us all look bad.

Even worse, papers like this are clearly dangerous. I wrote not even a week ago about the deadly distrust so many have in our medical system, and cited HIV denial as an example. South African policies regarding HIV (and the denial that the virus was behind AIDS) led to an estimated 330,000 premature deaths from AIDS, and 35,000 infants born with HIV infections that could have been prevented in that country alone.  This is what Goodson and Bauer (among others) are supporting. Frontiers and Nature, do you really want to be a part of this as well?

(Tip o’ the hat to Kenneth Witwer and Brian Foley for bringing this to my attention.)

UPDATED 9/26 The Frontiers Editorial Office has posted a Statement of Concern on their site regarding the paper:

Statement of Concern: The article “Questioning the HIV-AIDS hypothesis: 30 years of dissent” (Goodson 2014), was accepted for publication on the 7th September 2014. In its duty to publish responsibly, and in light of numerous complaints received about the paper, Frontiers has launched an investigation, the outcome of which will be made public once all adequate procedures have been completed. September 26, 2016. Frontiers Editorial Office, Lausanne, Switzerland.

 

Deadly distrust

Gregg Mitman’s article in the September 17th New England Journal of Medicine, “Ebola in a Stew of Fear,” is unfortunately all too prescient. Dr. Mitman highlighted “the ecology of fear” in Western Africa. Fear is present on both the part of Westerners (scared of Africa’s yellow fever, malaria, Ebola, its mere “different-ness”), and by native Africans (of whites’ history of colonization and slavery, of medical exploitation dating back well over a century). Fear of each other.

This history of fear, the cultural legacy of decades of mistrust of both Western people and their medical science, played a role in the murders of 8 people working on the Ebola outbreak in Guinea–journalists, medical officers, local administrators, and a preacher who were just trying to educate locals about the virus. The hostile crowd first threw stones at the team, and ended in their brutal deaths. The steps in-between have not been reported.

This is the extreme end of the science and medical denial continuum. We can scoff in America and attribute such horrors to the “brutal, savage Africans,” who cut their daughters and rape virgins to cure AIDS, as I’ve unfortunately already seen in some Twitter comments–some of our notions of “them” not so dissimilar from American colonists of centuries past regarding the slaves they once owned.

We can accept this scape-goating and ignore the West’s own modern-day culpability, with our fake vaccination campaigns that have left others dead in the aftermath; with our movies and popular culture depicting Africans as the West’s guinea pigs, and our shady pharmaceutical dealings that make that characterization all too believable.

No, it isn’t always a battle of Africans against Westerners. In South Africa, former President Thabo Mbeki was deceived by false claims about the relationship between HIV and AIDS that he had read on the internet, suggesting that HIV was not the cause of AIDS, and that  Western science should be distrusted in favor of traditional herbal remedies recommended by his health minister, such as garlic and beetroot. Because of his suspension of Western medical treatments, an estimated 330,000 South Africans died prematurely from HIV/AIDS between 2000 and 2005 , and at least 35,000 babies were born with HIV infections that could have been prevented.

Denialism kills. Distrust kills. Fear kills.

Here in the U.S., Natural News, a site run by the self-dubbed “Health Ranger,” Mike Adams, ran a piece this past summer suggesting that journalists and scientists who defended genetically-modified organisms (GMOs) were similar to Nazis, accelerating “heinous crimes being committed against humanity” and collaborating with an “with an anti-human regime,” and that such individuals should be named as such for future crimes:

“Just as history needed to record the names and deeds of Nazi war criminals, so too must all those collaborators who are promoting the death and destruction caused by GMOs be named for the historical record. The true extent of their collaboration with an anti-human regime will all become readily apparent once the GMO delusion collapses and mass global starvation becomes an inescapable reality.

I’m hoping someone will create a website listing all the publishers, scientists and journalists who are now Monsanto propaganda collaborators. I have no doubt such a website would be wildly popular and receive a huge influx of visitors, and it would help preserve the historical record of exactly which people contributed to the mass starvation and death which will inevitably be unleashed by GMO agriculture (which is already causing mass suicides in India and crop failures worldwide).”

Adams is similarly anti-vaccine, and currently is featuring on his website “11 horrible truths about Ebola the government doesn’t want you to know.” These “truths” include suggesting that infected individuals should avoid hospitals, and that citizens everywhere should prepare for the inevitable quarantine at gunpoint.

The worst part of Adams’ misinformation of this type is that it doesn’t stay within the borders of the U.S.–misinformation on Ebola epidemiology and quack cures like those Adams promotes are also being spread in African nations via Facebook pages and other types of social media

Denialism kills. Distrust kills. Fear kills.

Because of distrust of Western medicine, a recent article noted that parts of Africa have better vaccination rates than many wealthy neighborhoods in Los Angeles–and as a result, 10 babies died in a 2010 outbreak of whooping cough in California.

The deaths of the workers in Guinea show this fear and denial writ large; the purposeful killing of those only wanting to help their local and global neighbors in the face of a terrible epidemic. Those murdered are the latest victims of the most malignant form of distrust. They will not be the last.

Baby on board–in a BSL4 lab

I’m happy to welcome Dr. Heather Lander to the blogosphere and Twitterverse. She’s a virologist who has done work with some of the world’s deadliest pathogens in a high-security biosafety level 4 laboratory. This is the type of lab where one must wear “space suits” to work with organisms. You’ve probably seen in dramatized in various movies and TV shows (such as The Walking Dead). Heather describes what it’s really like to work in one–even while pregnant.

Heather 9 months pregnant in BSL4
Dr. Lander, 9 months pregnant in a BSL4 lab

 

TS: Can you tell readers a bit about your background and research? How did you get interested in studying viruses, especially some of the deadliest on earth that require BSL4 containment?

HL: I began my college career as a music major but I also loved science so I enrolled in many science classes, weighing my options. When I took a molecular cell bio class I was hooked. I changed majors and didn’t look any farther ahead than my Bachelor’s degree. But then the news exploded with tale of deadly virus outbreaks, and books and movies started coming out. I was fascinated, as are most people, so with permission from the professor I enrolled in a graduate level molecular virology course. Turns out viruses are beyond interesting. They blew my mind: microscopic, consist of hardly anything and can take us down in a matter of days. I wanted to know what was going on. At this point I thought all viruses were insanely interesting, but I found myself drawn to those that cause hemorrhagic fevers (HFV), and not only because of the media attention. I started reading the literature and these viruses were pretty different than the more familiar ones. They were confounding and I wanted to help figure them out.

Because I hadn’t planned ahead, I wasn’t ready to apply to grad school. So to improve my chances of working with these viruses, I got a job as a technician in a very highly regarded lab that worked on angiogenesis; basically the biology of blood vessels. Because HFVs either damage blood vessels or make them leaky, I thought it would be a good knowledge base. From there I got into the University of Texas Medical Branch as a PhD student and ended up working with CJ Peters, one of the premier experts in HFVs. Our interests aligned and he was great at listening to and encouraging the ideas of a neophyte.

We wanted to investigate viral infection of the cells that line the blood vessels, endothelial cells, and UTMB was getting ready to open their new BSL4 facility – The Robert E. Shope, MD Laboratory – the first of its kind at a U.S. university. In deciding which virus to work with, we took Ebola off the table because it was pretty clear that Ebola caused blood vessel leakiness through overt damage. Other HFVs did not, so the mechanisms of vessel leakiness were still unknown. Of these viruses, the arenaviruses were good options for me. One in particular, Junín virus, which causes Argentine hemorrhagic fever,  was a nice model because we had access to virulent and attenuated strains. I could work with the attenuated BSL2 virus, to get my model and systems up and working, and then repeat the experiments with the virulent BSL4 virus. So I researched the effects of  Junín virus infection on human endothelial cells.

TS: For readers who aren’t familiar with what working in a BSL4 entails, can you describe what it’s like to work in such a laboratory? 

HL: Working in a BSL4 lab adds a lot of steps to any lab work so everything takes longer. Before you can even go inside you are required to have extensive training, health and psychological assessments and be granted Department of Justice security clearance – many BSL4 organisms are Select Agents. After training at all other levels: BSL2 and 3, you are required to complete 100 hours of mentored, supervised BSL4 training, and assessment by the mentor, before being granted independent access. So, BSL4 research is only done if you can’t answer the scientific questions another way. Now, UTMB has the Galveston National Lab, a second BSL4 lab that is much larger, but the Shope lab is relatively small, only a few people can be in there at the same time. This means you have to plan ahead and schedule. Do you have all the supplies you need? You can only carry so much in at one time and you can’t go in and out, it’s too time consuming. So you have to make sure you know what you’ll need and I would often go in a day ahead of time, just to take supplies and make sure I would be ready to go.

During training you do a lot of practice. One of the most important things to practice initially is how to safely hold and open cryovials while wearing bulky rubber gloves. You also learn all safety and decontamination protocols as well as some practical things like moving around the lab safely. Seems silly, but in the lab, you are connected to an air supply through a hose that is attached to the air supply system on the ceiling. Those hoses don’t move with you. They stretch only so far and then you have to disconnect, move to where you need to be and connect a hose at that location. The suits are positive pressure with a constant inflow of air, with ports for air exhaust, otherwise they’d pop like a balloon. The air-flow is wonderful. The suits are cool and relatively comfortable, much more so than the stuff you wear for BSL3. Another important thing to learn and practice is how to enter and exit the lab. Seems simple but there are many steps involved. Here’s a description of what is is like to enter and exit the UTMB Shope Lab. Other labs are different, so this description isn’t meant to apply to all BSL4 labs in general, although the principles would be the same.

One of the best things about working in BSL4 is that, once you’re inside no one bothers you, no one interrupts you. There is a phone, but you don’t use it unless you have to.  So there are no annoying deliveries, phone calls or bored people stopping by to chat. It’s great. Though there was one very important thing I learned early: if you’re disconnect from the air hose, don’t bend over! When you do, you force the air that’s in the suit, out through the exhaust valves, so when you stand back up, the suit is sucked to you like a vacuum sealed bag with no air. Yeah, I did it. They laughed. It only happened once.

TS: Did you or your husband have any reservations about you continuing to work while pregnant? What convinced you that it was safe?

HL: We never had any reservations, and I’ll explain why. When I started working in the BSL4, I made sure I explained the work and the risks, to my family and my husband. So when I got pregnant, I had been working in the lab for a couple of years and he was very familiar with what I did. We had many long conversations about it and, as a couple, sat down with CJ and also our environmental health safety officer, the go-to person at UTMB for Select Agent biosafety, and member of the ASBA council. CJ had been head of USAMRIID’s containment lab and then he was Chief of Special Pathogens at the CDC. CJ and out EHS officer both know their stuff and were very helpful. I never felt pressured to continue working in the BSL4. It was my decision, with input from my husband of course, but he let me make the call. He trusted me and knew I wouldn’t be foolish. Aside from the obvious, the concern with Junín virus is that the case fatality rate is much higher than normal for pregnant women and fetuses, so it was not a cavalier decision by any means.

The bottom line, was that the entire time I worked in the BSL4, I valued my life and I was exacting and followed protocols to the letter. BSL4 protocols are designed to prevent any chance of contamination or infection and if they are followed, then the lab is clean. It’s the cleanest lab I’ve ever been in. I think a big misconception is that there are viruses floating around everywhere in the BSL4 and that’s why you wear the suit, but that’s just not true. The BSL4 protocols prevent contamination and infection. The suits are back-up – meant more to prevent exposure in the event of an accident than as a first line of defense. If someone in the BSL4 goes into cardiac arrest, we would remove the suit and administer first aid. This of course depends completely on each scientist adhering to protocols, and they do. And they are watched to make sure they do. The director’s office has cameras so he can see who is working and what they are doing. Every action is documented. And the people working in there are highly trained. I trusted those people and I trusted myself. I never deviated from the protocols, and I knew that. I was already being as careful and exacting as I could be, so there was no way for me to be more careful because I was pregnant. In addition, I wasn’t working with animals at that point, so the risks were lower. I was never worried and neither was my husband.

TS: How did your superiors take it when you first met with them to discuss continuing to do such work while pregnant? Was there anything you had to sell them on to allow you to work in there during your pregnancy?

HL: This was hard. I was terrified that they would make me stop working. No pregnant woman had ever been knowingly allowed to work in a BSL4 lab in the U.S. prior to this. I say “knowingly” because CJ pointed out that it’s possible that there were women at the CDC or USAMRIID who went into the BSL4 while pregnant and either didn’t know it yet, or they knew but waited as long as they thought they could before telling their supervisor, because they knew they would be told to stop. And here I was, a student at a university.

I broke the news in a committee meeting, my last powerpoint slide was an ultrasound photo. The reactions were mixed, to say the least, but CJ was my advisor so they deferred to him. I didn’t have to sell it to CJ, or to our EHS officer. They were very supportive and seemed to welcome the opportunity to advance the rights of pregnant women in biosafety, in a safe way. We discussed the risks and my work and when my husband and I decided to go ahead and push for me to be allowed to keep working, consulting with the Director of the Shope Lab, and the safety experts at USAMRIID and the CDC.

We also involved my physician, who really advocates to prevent unneeded limitations of pregnant women. It took about 3 months for these negotiations, during which time, I did not go into the BSL4. With the help of my doctor we came up with a plan that would allow me to work in the BSL4, with limitations designed specifically to mitigate any difficulties that the pregnancy itself might cause. We drafted a contract and everyone signed it and it went into my UTMB file along with my OBGYN medical records.

Because sometimes unexpected things can happen during pregnancy, some limitations imposed included that I would not be allowed to go into the BSL4 alone. We also decided I would not stay in the lab for more than 3 hours at a time. This was to prevent me from getting both too tired, or dehydrated.  Turns out this one really didn’t need to be written down, my bladder was always screaming at me before the three hours were up and that meant exiting the lab. I also couldn’t work with animals, which wasn’t something I was doing anyway. When all was said and done, USAMRIID, the CDC, my Physician and UTMB were all on board and I went back in. After I paved the way, others have done it. You’re welcome. 😉

Heather in BSL4 with first successful Junin Romero plaque assay!
Dr. Lander displays her Junin Romero plaque assay.

 

TS: How was it, logistically, working in there while pregnant? I know I always felt huge and clumsy while pregnant and I wasn’t working with anything above BSL2 level and wearing a normal lab coat.

HL: Because the suits are cool, it was still pretty comfortable. It slowed me down for sure, especially the last couple of months. Moving with deliberation was already ingrained in me so that didn’t change, but I definitely moved more slowly. And I was huge, and the suit was definitely cumbersome. My belly pushed against the suit near the end but it wasn’t painful or even uncomfortable, I just had to give myself enough clearance when moving around tables and things. I also had to ask for help when doing normal everyday housekeeping kinds of things in the lab like emptying a trash bin or lifting autoclave pans. Everyone I worked with was very helpful and kind, so it was not a problem. I had the normal aches and tiredness, but if I ever felt too tired to go in, and there were a few times I did, I would cancel my time for that day and reschedule. I knew my limits and respected them.

TS: Any good stories?

Oh boy do I. Unfortunately I can’t share the best ones. When I was still in the 100-hours-of-mentored-training segment of my BSL4 experience, I was in the lab with a professor and we were working with Rift Valley Fever inmice. We had finished the work and had already put the animals away and cleaned up. We were just getting ready to exit the animal room, to go into the main section of the lab, and the air hose connection valve on my suit broke. Without the air hose, there’s no air, not to mention the suit had a hole in it. The professor realized what happened before I did and grabbed the air hose and shoved it against the broken valve, allowing air to get inside the suit. He and I took turns holding air hoses in place while we showered and exited. Because of the incident we had to fill out paperwork and I had to go to the university hospital’s BSL4 exposure unit for a potential exposure. Because we hadn’t been working with anything when the valve broke, I wasn’t actually exposed to anything, but it was standard protocol. I was released fairly quickly and have a story to tell. The experience taught me a lot about how to handle those situations and even though those kinds of things are REALLY rare, the BSL4 director made changes to specifically prevent anything like that from ever happening again, and it hasn’t happened since.

TS:  What are you working on now and what are your longer-term career goals?

HL: I want to put my expertise to good use and I’ve come to realize that I love writing so I’m hoping to find something that can incorporate that. In the meantime, I have a really interesting job doing grant development for faculty at UTMB. This involves high-level assessment of the science, grantsmanship and presentation/writing of proposals, in an effort to help make faculty more competitive. To get my pathogen fix and dispel some emerging disease misconceptions, I recently started the blog and I’m really enjoying it. I also have ideas for a novel (don’t we all?), so…who knows?

Many thanks to Heather for participating! Be sure to check her out at Pathogen Perspectives or Twitter

New paper on Ebola–no primate-to-primate transmission seen

By the same lead author that published the pig Ebola transmission paper comes a new publication examining airborne transmission among primates. In these, Ebola did *not* spread between non-human primates (NHPs) via air. I sent an email to the PI to comment; will update the post if he responds, but in the meantime, some money quotes directly from the publication:

“One experiment reported contact free transmission between infected NHPs to one uninfected NHP although cross-contamination due to husbandry practices could not be ruled out with certainty26. Interestingly, EBOV infected swine transmitted the virus to naïve NHPs over a 0.3 meter buffer zone that prevented direct contact between the 2 species27. …However, airborne transmission in natural outbreaks cannot be a common occurrence and is possibly insignificant by the account of several reports49282930.”

and

“The presence of transmission in the pig-NHP experiment and not the NHP-NHP experiment, both performed under similar conditions and environments, could be explained by the fact that EBOV disease in pigs is respiratory in nature with high amounts of infectious particles present in the oro-nasal cavities in the symptomatic phase of the disease which provided an opportunity for release into the environment35. On the receiving end, NHPs are known to be susceptible to lethal EBOV infection through the respiratory tract242731 putting the onus of the transmission on the ability of the source to shed infectious particles.”

Translation: even though previous reports in primates had suggested the potential for airborne transmission, other factors couldn’t be ruled out, and epidemiologically, it’s insignificant. In the experiments they did, pigs just handle Ebola differently than primates (as I mentioned here), and so make them more likely to spread the virus via a respiratory route.

Significance: No airborne transmission between primates in this controlled experiment, strengthening the evidence that Zaire ebolavirus isn’t a risk in this manner. So Donald Trump, you can stop freaking out now.

A historical perspective on Ebola response and prevention

Yambuku, Zaire, 1976. A new disease was spreading through the population. Patients were overcome by headaches and bloody diarrhea. The disease was spreading through entire families and wiping them out.

Eight hundred and twenty-five kilometers to the northeast, a similar epidemic was reportedly raging across the border in Maridi, Sudan. Were these outbreaks connected? Despite enormous challenges trying to navigate both the logistics of crossing a landscape of unpaved and unmarked roads, as well as the political difficulties of an attempt to enter and collect samples in an area marked by recent civil strife, samples were finally collected and shipped to the World Health Organization for testing.

All told, these outbreaks caused 602 cases and 431 deaths. The Zaire outbreak wasn’t stopped until the hospital was closed, because 11 of its 17 workers (65%) had died of the disease. Investigators went door-to-door in 550 villages in the Yambuku area  to find and isolate new cases. Roadblocks were set up to restrict access to the area.

In Sudan, a number of cases were traced to workers in a cotton factory (probably due to bat exposure) and their families. The epidemic increased when one case went to the Maridi hospital, and the virus then was transmitted within that hospital. Note what the write-up describes:

“The hospital served as an efficient amplifier from which the virus was disseminated throughout the town. The number of cases gradually increased until mid-September and at the end of the month there was a large number of cases, particularly in hospital staff. The number of cases declined in early October, possibly as a result of the use of protective clothing. A considerable increase in the number of cases was observed in late October and early November, which may have been partly due to a lack of protective clothing when supplies ran out in mid-October.”

In Maridi, the doctor-in-charge, along with 61 members of the nursing staff came down with Ebola. Thirty-three of them died. Eight additional deaths occurred among the ancillary and cleaning staff. This outbreak was only contained because, again, the hospital was made safer via extensive training and the use of good personal protective equipment, and cases were identified in the town by going door-to-door. Buy-in from local officials was obtained, which is critical–while families may not trust outsiders, they more often will listen to local leaders. Cases were isolated in their homes or taken to the hospital. Eventually every village in a 30-mile radius from Maridi was screened, and the outbreak burned out.

Now imagine you’re looking at this in real time, via 24-hour news networks, from halfway across the world. You’re hearing news reports of cases spiking. Healthcare workers are contracting the disease. You don’t have all the information but you’re coming to your own conclusion that the virus must be mutating in Sudan.

You would, however, be wrong. These outbreaks were actually separate epidemics (and led to the identification of Zaire ebolavirus and Sudan ebolavirus, respectively), but collectively, that was a lot of Ebolavirus disease in 1976–the most deadly single year for Ebola until 2014, in fact. It took an enormous effort on the ground in these two areas to stop the outbreak.

Though not wholly analogous to today’s West African epidemic, there are lessons here to take away. There is a steep learning curve for dealing with Ebola. Besides the single case from the Ivory Coast, Ebola has not historically been a West African disease. Liberia, and Guinea and Sierra Leone in particular, do not have a great history of governmental stability, and are still recovering from civil wars, government coups, and a general lack of stable national leadership. Infrastructure is also substandard, as early reports on the main hospital in Conakry, Guinea noted. Each country seems to be dealing with this largely on their own without solid cross-border cooperation, and since the borders tend to be flexible in any case, patients and those incubating Ebola have been able to travel and move the virus into new areas. The public in general does not understand the disease, and in some cases keeping doctors out with knives and machetes, accusing physicians of murdering their loved ones and bringing Ebola to their villages.

It’s reasons like this–structural and sociological issues, by and large–that have led the WHO to declare the outbreak to be “out of control.” As far as has been reported, there is nothing particularly notable about the virus itself, which is very closely related to previous Zaire ebolavirus isolates. The infection rate in healthcare workers–about 60 out of 1300 total cases reported at the time–is actually quite low, given the conditions they’re working in and the lack of experience most of them would have had with Ebola. (Again, in Sudan, it was 61 out of 284 cases–so 21% of the total cases were doctors and nurses–versus about 5% in this outbreak).

The outbreaks in these countries are bad currently, but for the future, we can look at Uganda as a model. The first outbreak in that country, beginning in 2000, resulted in 425 cases and 224 deaths. The second outbreak in 2008 resulted in 149 cases and 37 deaths. In 2011, they had a single case with no secondary spread. In 2012, 11 cases and 4 deaths. 2012, 6 cases and 3 deaths. It’s probably impossible to stop Ebola from spilling over into the human population, but Uganda has done a great job responding. They are able to do early detection of suspected cases in their biosafety level 4 lab in Gulu. They alert local authorities if something is suspected, then send a task force to assist with containment. They communicate effectively with the public about what they can do, and how effective treatment in hospitals can lower the mortality rate. They work with community leaders when a quarantine needs to be put in place. These things can all be employed in West Africa as well, but it takes time and a lot of commitment to get such networks up and running. We need this cooperation as much as we need PPE and even more than we need “secret serums,” because it is only with prevention of new cases that this epidemic will finally die out.

 

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