Zika: what we’re still missing

As you’ve probably seen, unless you’ve been living in a cave, Zika virus is the infectious disease topic du jour. From an obscure virus to the newest scare, interest in the virus has skyrocketed just in the past few weeks:

 
I have a few pieces already on Zika, so I won’t repeat myself here. The first is an introductory primer to the virus, answering the basic questions–what is it, where did it come from, what are its symptoms, why is it concerning? The second focuses on Zika’s potential risk to pregnant women, and what is currently being advised for them.

I want to be clear, though–currently, we aren’t 100% sure that Zika virus is causing microcephaly, the condition that is most concerning with this recent outbreak. The circumstantial evidence appears to be pretty strong, but we don’t have good data on 1) how common microcephaly really was in Brazil (or other affected countries) prior to the outbreak. Microcephaly seems to have increased dramatically, but some of those cases are not confirmed, and others don’t seem to be related to Zika; and if Zika really is causing microcephaly, 2) how Zika could be causing this, whether timing of the infection makes a difference, and whether women who are infected asymptomatically are at risk of medical problems in their developing fetuses.

The first question needs good epidemiological data for answers. This can be procured in a few ways. First, babies born with microcephaly, and their mothers, can be tested for Zika virus infection. This can be looked at a few ways: finding traces of the virus itself; finding antibodies to the virus (suggesting a past infection–but one can’t know the exact timing of this); and asking about known infections during pregnancy. Each approach has advantages and limitations. Tracking the virus or its genetic material is a gold standard, but the virus may only be present in body fluids for a short time. So if you miss that window, a false negative could result. This could be coupled with serology, to look at past infection–but you can’t be 100% certain in that case that the infection occurred during pregnancy–though with the apparently recent introduction of Zika into the Americas, it’s likely that infection would be fairly recent.

Serology coupled with an infection in pregnancy that has symptoms consistent with Zika (headache, muscle/joint pain, rash, fever) would be a step up from this, but has some additional problems. Other viral infections can be similar in symptoms to Zika (dengue, chikungunya, even influenza if the patient is lacking a rash), so tests to rule those out should also be done. On the flip side, about 80% of Zika infections show no symptoms at all–so a woman could still have come into contact with the virus and have positive serology, but she wouldn’t have any recollection of infection.

None of this is easy to carry out, but needs to be done in order to really establish with some level of certainty that Zika is the cause of microcephaly in this area. In the meantime, there are a few other possibilities to consider: that another virus (such as rubella) is circulating there. This is a known cause of multiple congenital issues, including microcephaly. This could explain why they’re seeing cases of microcephaly in Brazil, but none have been reported thus far in Colombia. Another is that there is no real increase in microcephaly at all–that, for some reason, people have just recently started paying more attention to it, and associated it with the Zika outbreak in the area–what we call a surveillance bias.

This is a fast-moving story, and we probably won’t have any solid answers to these questions for some time. In the interim, I think it’s prudent to take this as a possibility, and raise awareness of the potential this virus *may* have on the developing fetus, so that women can take precautions as they’re able. Public health is about prevention, and there have certainly been cases in the past of links between A and B that fell apart under further scrutiny. Zika/microcephaly may be one, but for now, it’s an unfortunate case where “more research is needed” is about the best answer one can currently give.

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

Ebola is already in the United States

It’s odd to see otherwise pretty rational folks getting nervous about the news that the American Ebola patients are being flown back to the United States for treatment. “What if Ebola gets out?” “What if it infects the doctors/pilots/nurses taking care of them?” “I don’t want Ebola in the US!”

Friends, I have news for you: Ebola is *already* in the US.

Ebola is a virus with no vaccine or cure. As such, any scientist who wants to work with the live virus needs to have biosafety level 4 facilities (the highest, most secure labs in existence–abbreviated BSL4) available to them. We have a number of those here in the United States, and people are working with many of the Ebola types here. Have you heard of any Ebola outbreaks occurring here in the US? Nope. These scientists are highly trained and very careful, just like people treating these Ebola patients and working out all the logistics of their arrival and transport will be.

Second, you might not know that we’ve already experienced patients coming into the US with deadly hemorrhagic fever infections. We’ve had more than one case of imported Lassa fever, another African hemorrhagic fever virus with a fairly high fatality rate in humans (though not rising to the level of Ebola outbreaks). One occurred in Pennsylvania; another in New York just this past April; a previous one in New Jersey a decade ago. All told, there have been at least 7  cases of Lassa fever imported into the United States–and those are just the ones we know about, who were sick enough to be hospitalized, and whose symptoms and travel history alerted doctors to take samples and contact the CDC. It’s not surprising this would show up occasionally in the US, as Lassa causes up to 300,000 infections per year in Africa.

How many secondary cases occurred from those importations? None. Like Ebola, Lassa is spread human to human via contact with blood and other body fluids. It’s not readily transmissible or easily airborne, so the risk to others in US hospitals (or on public transportation or other similar places) is quite low.

OK, you may say, but Lassa is an arenavirus, and Ebola is a filovirus–so am I comparing apples to oranges? How about, then, an imported case of Ebola’s cousin virus, Marburg? One of those was diagnosed in Colorado in 2008, in a woman who had traveled to Uganda and apparently was sickened by the virus there. Even though she wasn’t diagnosed until a full year after the infection (and then only because *she* requested that she be tested for Marburg antibodies after seeing a report of another Marburg death in a tourist who’d visited the same places she had in Uganda), no secondary cases were seen in that importation either.

And of course, who could forget the identification of a new strain of Ebola virus *within* the United States. Though the Reston virus is not harmful to humans, it certainly was concerning when it was discovered in a group of imported monkeys. So this will be far from our first tango with Ebola in this country.

Ebola is a terrible disease. It kills many that it infects. It *can* spread fairly rapidly when precautions are not carefully adhered to: when cultural practices such as ritual washing of bodies are continued despite warnings, or when needles are reused because of a lack of medical supplies, or when gloves and other protective gear are not available, or when patients are sharing beds because they are brought to hospitals lacking even such basics as enough beds or clean bedding for patients. But if all you know of Ebola is from The Hot Zone or Outbreak, well, that’s not really what Ebola looks like. I interviewed colleagues from Doctors without Borders a few years back on their experiences with an Ebola outbreak, and they noted:

“As for the disease, it is not as bloody and dramatic as in the movies or books. 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 transmission is rather ordinary, just contact with infected body fluids. It does not occur because of mere proximity or via an airborne route (as in Outbreak if I recall correctly). The outbreak control organizations in the movies have no problem implementing their solutions once these have been found. In reality, we know what needs to be done, the problem is getting it to happen. This is why community relations are such an issue, where they are not such a problem in the movies.”

So, sure, be concerned. But be rational as well. Yes, we know all too well that our public health agencies can fuck up. I’m not saying there is zero chance of something going wrong. But it is low. As an infectious disease specialist (and one with an extreme interest in Ebola), I’m way more concerned about influenza or measles many other “ordinary” viruses than I am about Ebola. Ebola is exotic and its symptoms can be terrifying, but also much easier to contain by people who know their stuff.

 

Find more of my writing on Twitter or Facebook

 

Repost: What’s it like to work an Ebola outbreak?

In the light of the current Ebola outbreak, I thought this post from 2007 was once again highly relevant. 

As another Ebola outbreak simmers in Uganda (and appears to be increasing), I recently was in touch with Zoe Young, a water and sanitation expert with Médecins Sans Frontières (MSF*, known in the US as Doctors without Borders), who was working in the Democratic Republic of Congo during the DRC Ebola outbreak earlier this fall (and blogging it!)

Regular readers know of my interest in this virus, but I’m obviously geographically removed from any of the outbreaks. As such, Zoe and her colleague, physician Armand Sprecher, were generous enough to answer my questions about their work with MSF and the Ebola outbreak in particular.

First, just a bit of background on Zoe and Armand. Armand is a native of Philadelphia, and received his Bachelor’s degree in cognitive science from Brown University. He followed that with his MD from Jefferson Medical College, then headed west for a residence in emergency medicine at the University of Missouri Kansas City, then back to the east coast for a degree in public health from Johns Hopkins. He’s worked in the field with the International Medical Corps (IMC) in Bosnia, and with MSF in Sri Lanka, East Timor, Uganda, and Burindi. He’s been working in the headquarters of MSF’s Operational Center of Brussels (OCB) as the medical department’s public health support person since 2004.

From 1997 to 2001, while not in the field, he worked in emergency rooms in Wisconsin, Nebraska, New Jersey, and Wyoming.

Zoe is London born and bred. She graduated from the University of Manchester with a BSc in Biology and Geology and received an MSc from Edinburgh in Environmental Protection and Management. She has extensive field experience, having worked for Action Against Hunger (ACF) in Sierra Leone in 1996-7 and in Burma from 1997-98. She worked with Oxfam in Sierra Leone 1999 and in Eritrea 2000; with International Federation of Red Cross and Red Crescent Societies (IFRC) in El Salvador in 2001, and with International Rescue Committee in East Timor in 2002. She started work with MSF headquarters in the medical department as part of the water, hygiene and sanitation unit in 2004.

Zoe also worked elsewhere when she wasn’t in the field, including stints with Interact Worldwide, a sexual and reproductive health organization in London. She also helps to run a web-based fair trade business importing recycled items and silver.

I asked them first how they both ended up working with MSF, and in the DRC on Ebola:

Armand: During my emergency medicine residency, I spent my elective time in Bosnia with IMC. The medical coordinator there was a former MSF expat and his recommendation led me to volunteer when I finished my residency. As for the DRC, it was both a matter of assignment and choice (as are most MSF postings). I had experience and interest in filovirus outbreaks, and MSF needed me there.

Zoe: A friend of mine sent me the link to the job when it was advertised and I applied – never really thinking that I would get it and move to Brussels! A few months after I started I took over as the focal point for haemorrhagic fever from one of my watsan (water and sanitation) unit colleagues when he left – he had made it all sound very interesting and challenging.

Can you describe your previous experience with outbreaks of this type?

Armand: I worked with MSF in the Ebola-Sudan outbreak in Gulu in 2000 as their isolation ward physician. This is where I met my wife, who was the field coordinator at the time. She went to the Gabon outbreak in 2002 while I was at Hopkins, and the problems with that outbreak led me to do my masters thesis on health communication in Ebola outbreaks. Once in headquarters, I went to the Marburg outbreak in Angola in 2005 as medical coordinator. Since then, I have been working on, among other things, revision of MSF’s filovirus outbreak management manual.

Zoe: I went to join the team in Angola for the Marburg outbreak. I was lucky as there were several watsans there including my former colleague, so I got a very good job briefing. Then in July this year I went to Uganda to help do some training for a very small Marburg outbreak, which was a good refresher for the DRC Ebola outbreak in September.

What was the situation like when you arrived in the DRC?

Armand: I arrived in the first week of October, so things were almost over by then. The last patient was hospitalized shortly before my arrival (though of course we did not know that then). Many of the people who had been there from the beginning were ready to leave. The project coordinator was tired, so I replaced her in addition to being the medical coordinator for the ensuing two and a half weeks. The community was happy with our presence and the general feeling was that things had improved. Though there was still fear of the disease, this was not interfering with outbreak control.

Zoe: I arrived about a week after the first teams had got there. Basic isolation was in place with disinfection procedures, but it was a bit chaotic. As more medical staff were arriving, it needed to be improved because otherwise with all these new people moving about, it would have been difficult to ensure correct procedures. It was good that there was something in place to build on because it made it much easier to make big improvements very quickly. Also, we were lucky in that there was plenty of space and the local administrator was happy for us to extend the perimeter of the isolation to make a better flow.

What was a “typical” day like (if there was one?) How long were each of you there?

Armand: I was there for two and a half weeks. These interventions are many-headed hydras, and coordinating means spending the day touching base with everyone to make sure that they know what needs to be done and provide any necessary support. It also means keeping in touch with the other organizations (MoH, WHO, CDC, Public Health Agency of Canada, Médecins du Monde, etc.). In practice, this means sitting down with team members or people from other agencies individually, or collectively in MSF team meetings or WHO coordination meetings (quite the change from Gulu, where I spent all day in personal protective gear with patients in the isolation ward). It is fascinating though. It requires that one have a good understanding of epidemiology, clinical medicine, infection control, health promotion, medical anthropology, etc.

Zoe: I think that the typical day changes during the outbreak. To begin with, it was much more about trying to get everything correct and safe in the isolation. Training of staff for burials, collecting patients, disinfection, etc. Sometimes training is a bit by osmosis because there just isn’t time to talk to everyone about every aspect, or it is ad hoc, talking in the car to the drivers about procedure, etc. Then of course activities depend on the number of patients and whether they have died or not. Some days were a bit more fraught than others. There was one day with three burials that I mentioned in my blog (which was edited because it was so awful) where we were literally trying to match the body with coffin – get the body into the small coffin, then to the grave – perhaps not yet dug, back to pick up the next body, etc. Some days, there were reasonably healthy patients in the ward, so perhaps improvements in flow planned and then everything in the air because new patients coming in or people dying outside the isolation. I found the whole experience really tiring but very enjoyable and it certainly kept everyone on their toes.

During an outbreak like this, I know there are many responsibilities: patient care, education of both local people and your co-workers, contact tracing, diagnostics, scientific research, and I’m sure many others. I also know you wear many hats while you’re there as well, doing everything from setting up isolation wards to burying the dead. I’m wondering about the logistics of all this–do you all work together, or is it more that everyone does their own thing?

Armand: So now you get to why coordination is important. Everyone has their principle domain of responsibility, but there needs to be communication within the group. If the epidemiologist doing case investigation finds a novel transmission method of importance (such as a local traditional medical practice), then this would need to be passed to the people doing health promotion. If the team in the isolation ward notes that the patients have been receiving little in the way of visits or inquiries from the patients’ families, this bodes ill for the welcome that survivors may receive when discharged, and how they are treated may have an impact on the willingness of those who become ill to be detected and isolated themselves. This would be something to discuss with the mobile teams working in the community, that they may investigate further. Even PCR has false negatives, and interpretation of a negative result that should result in a patient’s discharge from isolation needs to be interpreted in light of their clinical appearance and epidemiologic risk. These are just a few examples of how people need to work together. I have not been involved in another sort of intervention that had people so interested in each other’s work. It is also the reason why poor coordination can be so detrimental to outbreak control (as, alas, it has been too frequently the case).

Zoe: Also every evening we had a kind of round up of the days’ events, like hearing about the road making [a road between villages was built while they were there–TS] or meetings or what the CDC was planning to get a general overview, not just the specifics. It was a great team as well and as Armand says, everyone is very interested in the whole process, not just their speciality.

Ebola is a pathogen that’s been so mythologized in the media and popular press. How does working during an actual epidemic like this contrast with what’s been shown in movies such as “Outbreak?”

Armand: As for the disease, it is not as bloody and dramatic as in the movies or books. 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 transmission is rather ordinary, just contact with infected body fluids. It does not occur because of mere proximity or via an airborne route (as in Outbreak if I recall correctly). The outbreak control organizations in the movies have no problem implementing their solutions once these have been found. In reality, we know what needs to be done, the problem is getting it to happen. This is why community relations are such an issue, where they are not such a problem in the movies.

Zoe: As Armand says, there is not as much blood as you think there will be, although I also think that I have been lucky when I hear about some patients that colleagues have dealt with where there was more blood and horror. I haven’t seen Outbreak; perhaps I will save that for viewing during the next outbreak as those sorts of films are great tension reliever and also useful educational tools (how not to……….).

I’d like to ask about a few quotes from your posts, Zoe. The first, from here, regarding workers’ appearances in their protective gear:

“What really struck me was how un-human she looked, completely dressed up, making strange jerky movements and impossible to see her face. I saw, really for the first time, how we might be perceived by the patients.”

How *do* you feel you were perceived by the people there, both patients and not? You mention in another post about a driver (I think it was a policeman) who no longer wanted to help once he saw you had a body under a sheet. Was that a common reaction?

Armand: I cannot say much about Zoe’s experiences, but I will add what I can from my own. When I was in Gulu, the outfits were a bit different, but not too much so. It was important that people have their names written on their aprons, or we would have had a hard time recognizing each other. I can imagine what this meant for the patients. This is one of the reasons that maybe face shields would be better than goggles and masks, if the protection were similar.

In the community, we have made an effort to keep people from overusing protective gear so that we do not give the impression of mysterious invaders from another planet coming to take people away as we spray chlorine solution everywhere.

Zoe: In fact it was a soldier who wanted a lift. There were quite often policemen and soldiers by the sides of the road who wanted to be dropped at the next guard post or town. The rule is that we don’t pick up people that we don’t know to take in the cars and certainly not someone from the army. So, we passed this guy without slowing down (we were going pretty slowly because of the road and because of the body in the back) so the driver spoke to him as we passed. A hundred yards or so further on there was a big pothole and one of the spray machines in the back tipped over so we stopped to get out and right it. The soldier thought we had stopped for him and came running up to jump in. More difficult now, since we had stopped, not to take him but luckily at the mention of the body under the plastic sheeting he backed right off.

I think that most people were happy that we were there. Quite often there were comments about that and of course for the staff it was the opportunity for work as well. But, of course the people didn’t want to touch anything contaminated and even the drivers to begin with would be very careful about washing the whole surface of their cars, not just the back that had had the patient in it.

Because of the set up it was possible to see the patients and talk to them without all the protective gear on which was nice – of course they didn’t necessarily realize that you had been the one in the space suit standing next to them 10 minutes before. But it did mean that they could see that they were being taken care of by (friendly) human beings.

Zoe, you wrote, regarding contact follow-up:

“When I went out this morning with the team one of the first houses we visited belonged to one of the patients that we buried last week. His wife was sitting there, looking extremely desolate. I asked how she was and she said, ‘not sick’. Of course, I hadn’t meant that. What was very difficult was that it wasn’t really possible to touch her arm or take her hand to show a bit of empathy. She is a contact and has to be monitored.”

Many of the stories you shared on your blog ended badly, with the death of the patient. But as you note, you stayed removed, even though it was difficult for you. These outbreaks must be hugely emotional–how do you cope?

Armand: When I was doing clinical care, I focused on treating what I could (i.e. other infections that resembled Ebola enough to get the patient isolated – dysentery, malaria, etc.), keeping the patients comfortable, keeping the staff safe, and making sure the survivors recovered well. That worked well enough, but that was Ebola-Sudan, so we had a few more survivors. Coordination removes one from the patients, so it is easier in that regard.

Zoe: In a way the openness of the structure made it all more difficult because all the time, even when inside, it was possible to look out and see the family members and see their sadness. Also, because we were at the end of the epidemic there were not that many patients there at any one time so you build up a bit of a relationship with them–especially the ones that come in earlier on in the disease, and who are talking and walking about. But there are plenty of things to think about and ways to improve what we are doing, so it is not possible to spend too long dwelling on things – and of course there were lots of fun and funny people working in the team so there was lots of laughter and joking as well.

Regarding local conditions and infrastructure, you wrote:

“The man in the isolation unit at the moment comes from Kalombayi. This is a village which has had no road access, just a track for bicycles and motorbikes. Martin has had hundreds of people clearing a path so that cars can pass and so that patients can be collected if necessary. He has also had to make three bridges.”

You make it sound like building roads and bridges is old hat. How much of this has to be done in outbreaks such as these? How widely scattered were the cases you were dealing with?

Armand: I think Martin’s road work impressed even the experienced MSF folks. That being said, we do what needs doing. Zoë didn’t mention the airstrip that he did? The cases and their villages where we traced contacts were within a 1-1½ hour drive by Landcruiser (under 30 kilometers, I think).

Zoe: Yes, as Armand says Martins’s road work was amazingly impressive and now that I read the paragraph I wrote again, I certainly didn’t do him justice. I think that the total length of that particular road was 20km. He also improved the road to Luebo, which was a relief as there was a lot of to-ing and fro-ing for meetings and trainings. Although it was fun to be on such an excitingly precarious road on the first day, it is exhausting to travel like that every day. And of course Martin found a forgotten airstrip and remade it with waiting area and latrine, Kampungu International. All this work involved hundreds of labourers scraping and shoveling the road surface and cutting back trees and bushes, and Martin and his assistants would supervise all of it every day.

Finally, can you give the readers some information about where things stand now? You mention an overlapping outbreak of typhoid, which I also read about in the news; was that confirmed? Do they know anything about the subtype of virus (I assume Zaire strain…?)

Armand: It was Zaire. The typhoid was confirmed, as were some cases of Shigella. However, it is not clear that these were above their normal incidence, so I would hesitate to say there were parallel epidemics (as has been said). The outbreak was declared over on the 19th of November.

Zoe: Yes, that’s over and the next one has begun!

The epidemic was confirmed rather late and was winding down when we arrived, so our impact may not have been great. However, it was a useful experience for us, as is each outbreak, in preparation for the next.

We had good relations with the community, which has not always been the case. It would be nice to know if it was something that we did, which could be repeated, or a result of contextual factors.

Many thanks to Zoe and Armand for taking the time to respond to my questions–and best of luck to them as risk life and limb taking on new epidemics.

*MSF has built considerable experience in previous outbreaks of hemorrhagic fever, especially caused by Ebola or Marburg: in Angola (2005), Gabon (1997 and 2002), Uganda (2001), Congo-Brazzaville (2003/2004), southern Sudan (2004). In DRC, MSF responded to a big Ebola outbreak in Kikwit, capital of the neighbouring province of Bandundu, in 1995. This epidemic killed 244 people between May and August 1995.

 

Find more of my writing on Twitter or Facebook

Ebola reemerges from the forest

Ebola has surfaced again. After a hiatus of over a year without any new identified outbreaks, the virus has reemerged in western Africa, in the first-ever multi-country outbreak of the Zaire strain of Ebola. As of this writing, there have been 122 suspected cases of the disease in Guinea (24 laboratory-confirmed per the WHO) and 80 deaths (66% mortality rate). Most of these cases have been in Guekedou and Macenta in rural Guinea, about 35 miles apart, but what’s really concerning is that at least 11 cases have also been identified in Guinea’s capital of 2 million people, Conakry. Conakry is over 400 miles away by the main road and contains the only major hospital in the country (and even that hospital is certainly less than ideal). A direct route from Guekedou to Conakry as the crow flies takes one right through Sierra Leone. It’s probably not too surprising then that this country has also reported 8 possible cases of Ebola, and another neighbor, Liberia, suspects 6 cases of the disease. Guinea’s northeast neighbor, Mali, has also just reported 3 potential cases, but these have not yet been confirmed. Senegal has closed its border to prevent importation of the virus.

Nurses tend to a patient during the 1976 Ebola outbreak in Zaire (now DRC). From Wikipedia.

All evidence points to Ebola having a reservoir in fruit bats. The virus can spread to other species when they come into contact with bats, and has caused massive great ape die-offs in addition to human outbreaks. Humans can become infected in a few suspected ways: direct contact with bats (such as visiting bat-infested caves or working in factories where large numbers of bats roost); butchering or consuming animals (particularly non-human primates, who can also acquire the infection via bats); consuming the bats themselves, as has been suggested may play a role in the current outbreak. Finally, once humans have been infected, human-to-human transmission can also spread the infection via contact with viral-laden body fluids (blood, saliva, feces). 

Though Ebola has a very high mortality rate, the one good thing is that it’s really not easily transmitted between people. Though there have been some experimental evidence that it could be airborne, in epidemiologic studies during outbreaks, no airborne transmission has been confirmed. Instead, most people who contract it from another person have very close contact with that patient: they’re hospital workers, or caretakers of infected family members, or are preparing a body for burial and are exposed to fluids during cleansing rituals. It may also be transmitted via semen and has been found in breast milk.  Casual contact doesn’t seem to readily spread the virus. That fact also makes the ongoing outbreak that much more tragic: new infections and deaths can be minimized if money, supplies, and education are provided.

Many of the more recent outbreaks in the Democratic Republic of Congo and Uganda have had much smaller numbers of cases than earlier outbreaks in these countries (Wikipedia has a nice summary here). Early detection and the use of basic personal protective equipment (gloves, etc.) and environmental disinfection stem transmission of the virus fairly effectively. Outbreaks in the 1970s and 1990s were amplified in hospital settings due to close contact between patients, shared/reused needles, and spread to healthcare workers who were inadequately trained and protected. Unfortunately, this is happening now as well, with 14 healthcare workers infected and 8 killed to date.

Though this is the first significant outbreak in West Africa, it’s not the first time Ebola has been found. One of the types of Ebola, Tai Forest ebola virus, originated in Ivory Coast after a primate researcher became infected while carrying out a necropsy on a chimpanzee. However, this is the only known case of that type of Ebola, and the current outbreak is caused not by the Tai Forest strain, but by the Zaire strain–which is the most virulent of the bunch. This strain has been most commonly found in Central Africa (Democratic Republic of Congo, Republic of Congo, Gabon), and based on analyses of these outbreaks, it was suggested that the Zaire strain had originated near Yambuku, DRC in the early 1970s, and had spread/diverged since then. However, it looks like this outbreak would be too distal for that model. Sequence data could clear that up but is not yet available.

 While every outbreak of Ebola represents a golden opportunity to study this rare virus in nature, it’s an opportunity that no one wants or relishes. This one went almost 6 weeks before a definitive diagnosis was made, and now has the distinction of becoming the largest Ebola outbreak in at least 7 years–possibly more, depending on how quickly they can but the brakes on new cases. Unfortunately because these outbreaks start in rural, resource-poor areas, one thing we can be confident about is that we’ve not seen the last of this virus.

The microbiology of zombies, part III: “We’re all infected”

Warning: here be spoilers

In many latter-day zombie movies, books, and TV shows, zombie-ism has a biological cause. In 28 Days Later, the infection is caused by the “Rage” virus, which escaped from a lab when animal rights activists break in and release a group of infected chimpanzees. Of course, one of the animals promptly bites one of its “liberators,” and the infection spreads rapidly throughout Great Britain. In Zombieland, it’s a mutated form of “mad cow” disease. The Crazies, it’s the Trixie virus; World War Z, the Solanum virus; Resident Evil, the T virus. I could go on and on. Zombie causation has clearly evolved from the early days of radiation or curses, and has become a biological phenomenon in most modern zombie tales.

The Walking Dead is no exception. Though the claim is made in season 1, episode 6 (“TS-19”) that the outbreak could be caused by just about anything–bacteria, virus, parasite, act of God–I call shenanigans. In the previous episode (“Wildfire”), Jenner, the CDC scientist, is processing tissue taken from Test Subject 19, and the visualization under his microscope looks very viral. Of course, take this with a few pounds of salt, since he’s using a light microscope and can also see the nice alpha-helical DNA strains within the pathogen (in real life, things just don’t look like this) and unless you’re one of the giant viruses, you can’t see viruses, much less DNA, under the microscope Jenner uses anyway. But still, it looks pretty viral-y to me, which is why I typically refer to it that way:

screenshot wildfire virus

Microbial zombification makes sense in today’s culture. My colleague Brooks Landon notes: “…zombies represent a better monster for the modern, post-9/11 world. They provide a release for feelings of being overwhelmed by abstract and intractable events like global economic crises, terrorism, and pandemics.” In the past decade or so, we’ve seen the emergence of SARS, multiple outbreaks of influenza including a new pandemic strain, the continuing HIV crisis, Nipah, Hendra, more Ebola, just to name a handful. Infectious diseases are commonly in the news, and many times are unfortunately over-hyped, leading to a collective nervousness of all things microbial.

The infected zombie is further boosted by a number of recent studies, largely in insects, that demonstrate a type of pathogen-directed “mind control:” zombie ants, zombie grasshoppers, and zombie cockroaches, just to name a few. A recent video game has exploited the ant fungus idea, mutating it into a form that infects humans. Even rodents (and possibly humans) can have their behavior apparently influenced by a parasite called Toxoplasma gondii, which makes rodents lose their fear of cat scents and may influence the development of schizophrenia in humans, or more controversially, even affect sexual inhibitions. If germs are already controlling our minds–why couldn’t they turn us into zombies?

And certainly, there are some candidate microbes which could, in theory, cause at least the “living” form of zombie-ism, even if they couldn’t necessarily raise you from the dead. The Trixie virus, for example, is supposed to be a weaponized rhabdovirus–the family of viruses that includes rabies. Rabies virus infection certainly causes aggression and biting. The virus is spread via saliva, so biting is the main way it is transmitted between animals. In a recent book, Rabid, the authors trace rabies through history, and note that it may be at the root of many zombie (and vampire) tales. Rabies can also hide out in the body for awhile before showing symptoms, as the virus travels up the nerves toward the brain. This is why a bite near the head progresses to symptoms much faster than, say, one to the foot. Typical time from bite to symptoms is in the neighborhood of 6 weeks, depending on the location of the bite and dose of virus one receives, but extreme cases have been documented, with symptoms not showing up for as long as 8 years. And, like has been done on The Walking Dead, one of the ways that bitten victims would try to avoid symptoms would be to cut off the affected limb before the infection spread. (Ouch).

Could something like the “we’re all infected” scenario used in the Walking Dead occur in real life? Maybe. With rabies, victims could appear physically fine for months to years. Even more extreme, there are a number of germs which can remain with people throughout their entire life. The virus that causes chicken pox, for example, doesn’t ever really go away. Your body fights it off enough to keep it in check after the initial rash, but it hides out  in your nerves and can come back in later years as shingles. Other herpes family viruses have a similar lifestyle: symptoms can come and go, but the virus never really leaves. The human papilloma virus (HPV) can also persist for years in some people (most infected people appear to clear this one, though). A bacterium called Helicobacter pylori can live very happily in a person’s stomach–sometimes causing ulcers, but going completely undetected and causing no symptoms in most people. And of course, HIV, which does not go away except in a few notable and high-profile cases. So the concept is, as they say, biologically plausible.

The problem isn’t necessarily with the microbiology, then, but with the epidemiology. How did everyone get infected so quickly? We know that the plague took an incredibly short time to spread (Jenner says less than 200 days in the first season, and “less than 63 days” since it went pandemic)–but how? That’s a missing link in this scenario. We know the pathogen can certainly be spread by bites and then cause zombification that way, but other forms of inoculation (such as getting sprayed in the eyes or nose with zombie blood) don’t seem to have that effect. Is it in the water? If so, that would be some damn rapid spread, since early on Jenner noted that this appeared to be a true pandemic–present around the world. How would that happen?

In the air? Possibly, but even most airborne microbes don’t hang out indefinitely; they’re dispersed by wind to levels below those able to cause infection, or killed by sunlight or other environmental conditions. So even if you had a herpes- or HIV-like virus that could hide out in the body for an extended period of time without causing symptoms, how did *everyone* get it in such a short timeframe? Some scenarios in other books and movies put the blame on bioterrorism. The above-mentioned Trixie virus, for example, was a bioweapon which was only accidentally released when the plane carrying it crashed. Spread of Trixie in the movie ended up being only local, but transmission beyond that is hinted at the end. A true bioterrorist attack could, theoretically, account for simultaneous outbreaks all over the world.

Finally, though the “infected zombie” is now the most common type, it should be noted that this isn’t really new. George Romero, widely recognized as the grandfather of the modern zombie, acknowledges that he “ripped off” his idea for Night of the Living Dead from Richard Matheson’s I am Legend–a vampire story from 1954. The cause of that vampirism?

Bacillus vampiris–a bacterium.

 

See also:

Part I: the microbiology of zombies

Part II: ineffective treatments and how not to survive the apocalypse

Part IV: hidden infections

Student guest post: Mission Impossible: Fighting Zoonotic Infections in Nicaragua

Student guest post by Brandon Woods

A Dangerous Paradise

From jungles with jaguars to crystal blue lakes with freshwater sharks, Nicaragua is one of the most beautiful and dangerous countries in Central America. The brilliant biodiversity attracts millions of tourists each year and the looming volcanoes that pepper the landscape can be an exciting yet unsettling sight. However, in reality much of the danger in Nicaragua comes from the risk of infectious diseases. For example, if you’re planning to travel to this tropical paradise anytime soon, the Center for Disease Control (CDC) states that international travelers are at risk of contracting Typhoid fever, hepatitis A, hepatitis B, Leishmaniasis, malaria, dengue, rabies, and more! As a dual degree veterinary medical and public health student, I am fascinated by these infectious diseases and want to learn how they interact with the environment, people and animals. Many of the diseases that the CDC listed are called zoonotic diseases, or diseases that are transmissible between animals and humans. Other zoonotic diseases you may know include ringworm, Lyme disease, and Cat scratch disease. Whether you own a pet, like to travel, or simply enjoy spending time outdoors, you are at risk of infection because these zoonotic diseases are increasingly emerging worldwide and are becoming a serious public health threat. During the spring break of my first year of veterinary school, I traveled to Nicaragua on a mission trip and got first-hand experiences of these frightening infectious diseases.

 Brandon picture 1

Bed Nets and Bug Spray

Planning for this trip was time-intensive and reminded me of planning for my semester study abroad adventure to Tasmania, Australia. However, unlike my semester Down Under, this trip was coordinated through the national non-profit Christian Veterinary Mission (CVM) whose goal has been to help veterinarians serve others and live out their Christian faith for more than 30 years. Out of all the fundraising and logistics meetings we had, the meeting that stands out the most was when the Iowa State University travel nurse described the laundry list of potential pathogens we could encounter. Our team of 8 veterinary students, 3 veterinarians, and 1 pharmacist would be treating animals in a remote village called Espavel in the jungles of eastern Nicaragua. When I saw that my destination was in the middle of the red zone for malaria on the CDC map, my eyebrows escalated and my stomach dropped.

I was going to fly to an unstable, earthquake-prone country of approximately 5.7 million Spanish-speaking people where malaria was endemic. My Spanish was scarce, but my drive to serve was strong. After I heard that malaria was essentially eliminated from Nicaragua, my blood pressure dropped a few millimeters of mercury. Approximately 84% of the Nicaraguan population is at risk of contracting malaria, according to a UCLA study. However, Nicaragua has experienced a 97% decrease in reported malaria cases between 2000 and 2010. This significant decrease in prevalence was a result of Nicaragua partnering with the Pan American Health Organization (PAHO) in 2006 which heavily implemented stronger surveillance, prevention, vector control, and treatment. Despite this progress, I learned from my undergraduate Lyme disease Honors project that there are always numerous challenges to completely eliminate vector-borne diseases like malaria. For instance, controlling mosquito breeding populations is particularly vexing due to the complex ecology of the parasite life-cycle. In addition, you may have heard about the controversy surrounding toxic pesticides like DDT. My colleagues and I were fortunate for our DEET bug spray and Permethrin treated clothes and bed nets that we brought after skyping our host-country missionaries. I was also relieved that our trip in March 2013 was during the dry season and not during the September-to-January rainy season, when disease transmission is highest.

Rambunctious Rabies

Escaping the endless hours in the frigid, formaldehyde laden anatomy lab and flying to a third-world tropical country to practice preventative medicine was slightly shocking, but totally worth it. On our first day, we drove through the littered streets of Catarina to an outdoor shelter where we set up a temporary clinic. The local children brought their pet dogs and we treated them with Ivermectin and other anti-parasitic medication. Many animals were very thin and infested with fleas and ticks. However, it was rewarding to interact with the children and walk them through a brochure that described both healthy animal care and the Gospel of Jesus Christ. Then suddenly one of my colleagues was bitten by a dog! He was trying to give a rambunctious mixed-breed a pill to protect against heartworm disease and the next thing he knew, the dog bit him in the hand. He quickly washed the wound with soap and water and bandaged it. Fortunately, everyone on our veterinary team was already vaccinated for rabies prior to the trip because it’s a requirement to enter veterinary school. He also followed up with post-exposure rabies prophylaxis when he returned home.Brandon picture 2

Rabies is one of the deadliest and most notorious zoonotic diseases in the world. Rabies is endemic to Nicaragua, often occurs in poor rural communities, and the most common source of transmission is when a dog bites a human and delivers the fatal RNA virus. According to the World Health Organization, potentially any mammal can contract rabies, and common reservoirs in the USA include skunks, foxes, raccoons, and bats. Although rabies cases can be successfully treated, it still persists worldwide killing more than 55, 000 people each year. The Center for Food Security and Public Health (CFSPH) at Iowa State University is an excellent resource that provides more information on rabies and preventing zoonotic diseases. Reducing the prevalence of rabies globally requires a multinational effort and the World Rabies Day Initiative was founded solely for this mission and has already collaborated with 150 countries and vaccinated over 7.7 million dogs.

Tasting Iguana and Tackling Typhoid

It’s a good thing I like rice and beans, because that was the bread and butter of most of my meals every day. Hiking to farms builds an appetite and one day we had to traverse across a narrow blank that stretched precariously over a ravine. After we arrived, we vaccinated over 100 head of cattle for clostridium, anthrax, and Dectomax. Dectomax is an injectable drug used to control parasites like hookworms, round worms, grubs and mites. When we returned to the main village and got out of the blazing 90+ degree sun, the crispy, plantain chips with a glass of freshly squeezed tamarind juice was an irresistible snack. However, the most memorable meal of all was the morning the villagers surprised us with two 5 foot long iguanas! A few hours later, I was savoring some delicious iguana meat seasoned with local spices and vegetables. Cooking wild reptiles is foreign to us in the developed world; likewise, the way many Nicaraguans prepare their food is also different.

Brandon picture 3

Sayings like, “Don’t drink the water,” or ‘Boil it, cook it, peel it or forget it,” come to mind when traveling abroad, and they couldn’t ring more true for my experience. Food-borne illnesses are another great example of how veterinary medicine and public health overlap. I’m enrolled in the dual DVM-MPH degree program at the University of Iowa’s College of Public Health and learned that food-borne epidemics are a major focus of research in epidemiology. From mild cases of spoiled potato salad on romantic picnics to church dinner outbreaks from contaminated home-made ice cream, food-borne illnesses can range in their severity depending on your pre-existing health and the dose and type of microorganism ingested. One of the Nicaraguan diseases that I was vaccinated for before my trip was a food-borne illness known as Typhoid fever. Thankfully I avoided this illness; however, I couldn’t escape the wrath of Montezuma’s revenge, or traveler’s diarrhea, most commonly caused by enterotoxigenic Escherichia coli.

Typhoid fever is transmitted through contaminated food or water and is unique among food-borne pathogens because it only affects humans. In fact, some individuals can unwittingly become carriers of the bacterium and transmit the disease to others through improperly prepared food, like the infamous Typhoid Mary. This disease is caused by the bacterium Salmonella typhi, which is one of over 2,300 species of Salmonella and can be treated with antibiotics, according to the USDA. Other Salmonella species are also common among household, cold-blooded critters like turtles, frogs, iguanas, and snakes, so it’s important to always wash your hands after handling these pets.  Like malaria and rabies, Typhoid fever presents challenges for eradication in developing countries where poverty limits accessibility to clean water, pasteurization, and proper sanitation and hygiene. For example, I had never taken a well-water bucket shower before, and although the murky water felt refreshing after a long days’ work, I came to more deeply appreciate the luxuries of everyday plumbing and electricity.

Collaboration is Key

An empowering lesson that continues to inspire me was when I participated in a humanitarian collaboration. Before our departure, we communicated with another mission team from an Arkansas Baptist church that would work at the same time as our Iowa State Christian veterinary mission team would work over spring break. The goal of the Arkansas team was to provide humanitarian care while the goal of the Iowa State team was to provide veterinary care. For instance, the Arkansas team brought donated shoes and eyeglasses, provided nutrition education and had a dentist and nurse that pulled teeth. On the other hand, the Iowa State team vaccinated dogs, cats, horses, cattle, and pigs, performed surgeries and provided agricultural advice to farmers. Even though the two teams set up separate clinics to work on different species, we still felt united as one team because we traveled together, ate meals together, and worshiped together.

Brandon picture 4

One sunny afternoon, we asked the human dentist to come over to our animal clinic to pull a rotten tooth out of a horses’ mouth. The dentist had hardly been around horses in his life, let alone stuck his hand in one’s mouth before, but after the novelty wore off, he quickly agreed to help our team. The sedated horse was lying on its side surrounded by curious villagers and veterinary students. The dentist was nervous and the 3 inch long decayed molar kept wiggling out of his grip. Finally, he extracted the tooth and everyone was amazed and overjoyed. It’s a simple story like this that showcases the successful collaboration between veterinarians and other medical professionals that is the goal of the One Health Initiative or the new concept of interdisciplinary healthcare collaboration. In order for us to eradicate these infectious diseases and save lives, it is vital that veterinarians, physicians, dentists, and epidemiologists collaborate and communicate to find solutions.

A Future Fighting Infections

Going on this short-term veterinary mission trip put me in harm’s way, but it gave me real-life experience with infectious diseases, deepened my faith, and strengthened my clinical skills. It was bittersweet to say adios to my amigos, but I know I’ll return to that perilous paradise.  I enjoyed the international fieldwork and cross-cultural partnership because it embodies the One Health Initiative that I highly esteem. From hiking in the jungle on my 23rd birthday to taste-testing iguana to teaching children about pet care and the Word of God, this trip was a remarkable adventure that has forged a new trail for me. I don’t believe it’s an impossible mission, and I am committed to pursue veterinary public health as a career and control zoonotic diseases in developing countries.

All photos courtesy and copyright Brandon Woods. 

Resources:

http://www.who.int/en/

http://new.paho.org/hq/

http://www.merckmanuals.com/vet/index.html

http://www.cfsph.iastate.edu/Zoonoses/

https://www.cia.gov/library/publications/the-world-factbook/geos/nu.html

http://www.fsis.usda.gov/factsheets/foodborne_illness_&_disease_fact_sheets/index.asp

http://amestrib.com/sections/news/ames-and-story-county/student-traces-lyme-disease-ames.html

http://wwwnc.cdc.gov/travel/destinations/traveler/none/nicaragua

http://www.fda.gov/forconsumers/consumerupdates/ucm048151.htm

http://www.cvmusa.org/Page.aspx?&pid=183

http://en.wikipedia.org/wiki/Zoonosis

http://www.worldrabiesday.org/

http://www.onehealthinitiative.com/

http://www.public-health.uiowa.edu/epi/

Can we “catch” breast cancer?

Third of five student guest posts by Dana Lowry

In 1911, Peyton Rous first discovered viruses can cause cancer.  A chicken with a lump in her breast had been brought to Rous by a farmer.  Rous prepared an extract that eliminated bacteria and tumor cells and injected this extract into other chickens—tumors grew.  Rous suggested “a minute parasitic organism” was causing the tumor growth, which is now known to be a virus.  However, Rous’ discovery remained very controversial, and it wasn’t until 1966 that he was awarded a Nobel Prize for his discovery.  Since Rous’s discovery, researchers have found an estimated 15 percent of all cancers worldwide are associated with viruses.  Some common virus and cancer associations are: human papilloma virus (HPV) and cervical cancer, hepatitis B and liver cancer and human T lymphotropic virus type 1 (HTLV-1) and T-cell leukemia.

Epstein-Barr virus (EBV), a member of the herpesvirus family, is one of the most common viruses worldwide.  Among 35 to 40 year olds in the U.S., up to 95% have been infected with EBV.  Oftentimes, children infected with EBV have no clinical signs or symptoms; however, 30% to 50% of adolescents and young adults exposed to EBV for the first time will develop infectious mononucleosis, commonly known as mono.  In the U.S., individuals are usually exposed to EBV in adolescence or young adulthood compared to developing countries, where oftentimes individuals are exposed as infants or young children.  EBV usually remains dormant in the body throughout an individual’s lifetime, similar to the varicella-zoster virus, the virus responsible for the chicken pox.  EBV is known to play a role in Burkitt ’s lymphoma (cancer of the immune cells), nasopharyngeal cancer (cancer of the upper throat) and Hodgkin’s lymphoma (cancer of the lymphatic system), but can EBV also play a role in breast cancer?

In 2010, James Lawson and Benjamin Heng reviewed 27 papers concerning EBV and breast cancer associations. EBV infections are universal in high and low risk breast cancer groups, making it unlikely that EBV is the sole contributor to forms of breast cancer [1].  However, the age at which EBV is contracted seems to play a role in the risk of developing breast cancer. Women in Western countries are at higher risk of developing breast cancer and tend to be infected with EBV during adolescence or young adulthood, whereas women from non-Western countries have a lower risk for developing breast cancer and tend be infected during infancy or early childhood.  Hodgkin’s lymphoma shares a similar correlation with higher rates in Western countries [2].  Although there seems to be a relationship between age of EBV infections and risk of breast cancer, potential confounders need to be considered.  Women in developing countries tend to have more children, have children at a younger age and breastfeed their children for longer periods of time.  Breastfeeding, having more children and having children earlier in life all seem to be protective factors against breast cancer.

Beyond epidemiological evidence, lies biological evidence.  Twenty two of the studies Lawson and Heng reviewed were based on polymerase chain reaction (PCR) techniques. Issues have been found with standard PCR procedures, but it is becoming widely accepted that EBV can be identified in breast cancer tissue through specific PCR techniques [1].  EBV genes have been found in breast cancers through polymerase chain reaction (PCR) analyses.  EBV has not only been shown to shed in human breast milk [3], but it has also been shown to stimulate growth of human breast-milk cells [4]. The mechanism by which EBV actually causes cell alterations is not known, but it is thought to be different from the mechanisms used in lymphomas and nasopharyngeal cancer [1].

It is unlikely that we can actually “catch” breast cancer, as EBV doesn’t seem to be the sole cause of breast cancer.  EBV may contribute to breast cancer by altering genes in the breast cells which eventually leads the uncontrolled cell division, known as cancer.  More importantly, it seems the age an individual is infected with EBV may play an even bigger role in the outcome of disease.  An EBV vaccination is in the works that will hopefully prevent infectious mononucleosis and EBV-associated cancers.  However, the vaccination may not prevent the EBV infection itself; it is targeted towards the most abundant protein on the virus and on virus-infected cells.  If the vaccination proves to be successful, it will be interesting to see if a reduction in breast cancer rates will follow, along with the known cancers associated with EBV. Only time will tell.

 

References:

  1. Lawson, J. and Heng, B. (2010). Viruses and Breast Cancer. Cancers 2010, 2(2), 752-772; doi: 10.3390/cancers2020752.

 

  1. Yasui et al. (2001). Breast cancer risk and “delayed” primary Epstein-Barr virus infection. Cancer Epidemiology, Biomarkers & Prevention, 10:9-16. http://cebp.aacrjournals.org/content/ 10/1/9.long.

 

  1. Junker et al. Epstein-Barr virus shedding in breast milk. (1991). The American Journal of the Medical Sciences, 302: 220–223. http://www.ncbi.nlm.nih.gov/pubmed/1656752.

 

  1. Xue et al. (2003). Epstein-Barr virus gene expression in human breast cancer: protagonist or passenger?. British Journal of Cancer, 89:113–119. http://www.nature.com/bjc/journal/ v89/n1/full/6601027a.html

 

 

Pig-to-monkey Ebola: is there something in the air?

Ebola has long been known to be a zoonotic virus–one which jumps between species. Though it took several decades to find evidence of Ebola virus in bats, these animals had previously been associated with human index cases of Ebola disease have worked in bat-infested warehouses or traveled to caves where bats roost. Non-human primates have also become infected with the virus, sometimes transmitting the virus to humans when killed primates are butchered for food. Ebola has also been suggested to infect dogs and other wild animals. However, livestock are a newer angle to Ebola virus ecology.

Ebola was first found in pigs in 2008 in the Philippines. This was the Reston virus, named after its discovery in imported Filipino monkeys in a facility in Reston, Virginia, in 1989. Though this virus spread among the captive monkeys, no humans came down with symptoms. However, follow-up studies showed that some humans did develop an immune response to the Reston virus–suggesting they had been infected, even if they didn’t realize it. At the time, there was suggestion that perhaps Reston might be spread via aerosol, as the virus appeared to spread amongst monkeys in two different rooms who did not come into physical contact with one another. However, this was not proven at the time and alternative explanations were possible.

When Reston resurfaced in swine and swine farmers in 2008, a similar phenomenon was observed. Though it was not known how the pigs initially became infected with the virus, they did appear to be able to spread it to humans working amongst them, even if those farmers didn’t have contact with blood or other secretions (the most efficient way to transmit Ebola viruses). Suggestive of possible transmission from pigs to people via air, but far from conclusive. Since then, two experimental studies have examined airborne transmission of Ebola via pigs.

The first study examined transmission of the Zaire strain of Ebola–the nastiest one, which can kill up to 90% of those infected–within laboratory pigs. Pigs were inoculated with the Zaire virus and housed with uninfected pigs, who were later tested and found to have acquired the virus. Interestingly, when the pigs got sick with Ebola Zaire, the symptoms were mainly respiratory and the virus replicated in the lungs. This was quite unlike what Zaire does in humans and our other primate cousins, where it’s a systemic disease and we can find virus in the blood. This suggests that pigs could be infected with even nasty types of Ebola, and we wouldn’t realize it.

Last week, Ed Yong reported on a new paper examining transmission of Zaire virus from experimentally-infected pigs to co-housed macaques. Like the previous paper, they observed that Ebola in pigs was a respiratory disease, and that it could spread to other animals (in this case, non-human primates). The macaques they tested developed the symptoms of Ebola that were expected–a systemic disease, with virus isolated from the blood. In this study, they also added in an air sampling component, and were able to detect evidence of virus (via PCR) in the air. However, the authors do note that this could have been aerosolized in other manners than directly from the exhaling pigs (such as during the floor-cleaning process). Finally, even if it does become aerosolized and spread in this manner, as noted in Ed’s article, Ebola is not “suddenly an airborne virus, like influenza.” Certainly more efficient transmission takes place via close contact with infected secretions during hospital procedures and funeral rites.

Interestingly, the authors note that other experimental studies that have looked specifically at airborne, primate-to-primate transmission of Ebola have come up negative, and that swine are known to generate “infectious short range large aerosol droplets more efficiently then other species.” Is there something specific about pig physiology that may make them better respiratory virus shedders? We know that pigs can be intermediate hosts for other viral pathogens as well, such as Nipah virus and of course influenza.  Are pigs playing any role in Ebola ecology, either in Asia or Africa? Might Ebola have more airborne potential than we previously thought? According to Ed, the authors of the second study are currently working on field studies in Africa to examine the pig question outside of the laboratory. The timing may be good for them, as Uganda is currently experiencing another Ebola outbreak;–the country’s third Filovirus outbreak in five months.

Reference

Weingartl, H., Embury-Hyatt, C., Nfon, C., Leung, A., Smith, G., & Kobinger, G. (2012). Transmission of Ebola virus from pigs to non-human primates Scientific Reports, 2 DOI: 10.1038/srep00811