No, Kelly Brogan, germs are not “trying to kill us.” And yes, they are real.

I’m honestly not even sure where to start with this. 








This claim comes from Kelly Brogan, “holistic psychiatrist” and noted HIV denier. She claims, “Goodbye to germ theory! Can we really maintain the childish illusion that there are a handful of identified ‘bad germs’ out there trying to kill us?”

She bases this on the fact that there are a lot of different microbial species in sand.  I wish I was kidding. Why this undermines the germ theory, I’m not quite sure.

But beyond the whole bizarre claim, it’s not the germ theory that is childish–it’s her (mis)understanding of it. There aren’t a bunch of “bad germs” out there “trying to kill us.” There are just bacteria, and viruses, and parasites, and fungi who, if you can say they “want” anything at all, only want to reproduce. Period.

Sometimes that survival means harming humans who come into contact with these pathogens. Take cholera, for example. Cholera isn’t “normally” a human pathogen. It’s an environmental bacterium, that prefers to live in brackish waters in association with marine copepods and other animals. On occasion, the cholera bacteria are removed from this environment and swallowed by humans. The bacteria, trying to survive, release toxins that evolved in their “regular” environment–but just happen to devastate humans, causing us to lose liters of water and even our intestinal epithelial cells in response to the bacterial toxin.


We know this through an enormous combination of studies. Epidemiological studies, dating back to John Snow before we even understood the bacterial cause (Snow just figured out that the disease was transmitted by water, and other contemporaries had seen “comma-like” organisms in the water, but no one put two and two together until years later). Animal models, experimentally infecting them with cholera. In vitro studies using cell culture. Ecological and genomic studies, tracing the cholera bacterium through the environment and people’s guts to examine how it’s spread all around the world.

And this is just a singular example; many more are explained in this story by Ed Yong, and many more could be listed than are described there. Lucky for us, the vast, vast majority of microbes out there don’t do us harm.

Maybe Brogan thinks the germ theory is wrong because all of those bacteria don’t kill us (but we wouldn’t expect them to!). Or maybe because not everyone who is exposed to a pathogen becomes sick (but that’s not news–even Pasteur and Koch knew that, and it has nothing to do with the article Brogan linked).

Or maybe she just has no understanding of science or medicine, and wants to shamelessly mislead her followers so they buy what she’s selling.

I bet it’s that one.

Is there such a thing as an “evolution-proof” drug? (part the third)

A claim that scientists need to quit making:

I’ve written about these types of claims before. The first one–a claim that antimicrobial peptides were essentially “resistance proof,” was proven to be embarrassingly wrong in a laboratory test. Resistance not only evolved, but it evolved independently in almost every instance they tested (using E. coli and Pseudomonas species), taking only 600-700 generations–a relative blip in microbial time. Oops.

A very similar claim made the rounds in 2014, and the newest one is out today–a report of a “super vancomycin” that, as noted above, could be used “without fear of resistance emerging.” (The title of the article literally claims “‘Magical’ antibiotic brings fresh hope to battle against drug resistance”, another claim made in addition to the “no resistance” one in the Scripps press release by senior author Dale Boger). This one claims that, because the modified vancomycin uses 3 different ways to kill the bacteria, “Organisms just can’t simultaneously work to find a way around three independent mechanisms of action. Even if they found a solution to one of those, the organisms would still be killed by the other two.”

A grand claim, but history suggests otherwise. It was argued that bacteria could not evolve resistance to bacteriophage, as the ancient interaction between viruses and their bacterial hosts certainly must have already exploited and overcome any available defense. Now a plethora of resistance mechanisms are known.

Within the paper itself, the limitations are much more clearly laid out. Discussing usage of the antibiotic, the authors note of these conventional semisynthetic vancomycin analogs:

“However, their use against vancomycin-resistant bacteria (e.g., VRE and VRSA), where they are less potent and where only a single and less durable mechanism of action remains operative, likely would more rapidly raise resistance, not only compromising its future use but also, potentially transferring that resistance to other organisms (e.g., MRSA).”

So as they acknowledge, not really so resistance-proof at all–only if they’re used under perfect conditions and without any vancomycin resistance genes already present. What are the odds of that once this drug is released? (Spoiler alert: very low).

Alexander Fleming, who won the 1945 Nobel Prize in Physiology or Medicine, tried to sound the warning that the usefulness of antibiotics would be short-lived as bacteria adapted, but his warnings were (and still are?) largely ignored. There is no “magic bullet;” there are only temporary solutions, and we should have learned by now not to underestimate our bacterial companions.

Part of this post previously published here and here.

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

Is there such a thing as an “evolution-proof” drug?

Eleven years ago, two scientists made a bet. One scientist wagered that a new type of antimicrobial agent, called antimicrobial peptides, would not elicit resistance from bacterial populations which were treated with the drugs. Antimicrobial peptides are short proteins (typically 15-50 amino acids in length) that are often positively charged. They are also a part of our body’s own innate immune system, and present in other species from bacteria to plants. It is thought that these peptides work primarily by disrupting the integrity of the bacterial cell, often by poking holes in them. Sometimes they work with the host to ramp up the immune response and overwhelm the invading microbe. Because the peptides are frequently targeted at the bacterial cell wall structure, it was thought that resistance to these drugs would require a fundamental change in membrane structure, making it an exceedingly rare event. Therefore, these antimicrobial peptides might make an excellent weapon in the fight against multiply drug-resistant bacteria.

Additionally, the remarkable diversity of these peptides, combined with the presence of multiple types of peptides with different mechanisms of action present at the infection site, rendered unlikely the evolution of resistance to these molecules (or so some reasoning went). However, evolutionary biologists have pointed out that therapeutic use of these peptides would differ from natural exposure: concentration would be significantly higher, and a larger number of microbes would be exposed. Additionally, resistance to these peptides has been detailed in a few instances. For example, resistance to antimicrobial peptides has been shown to be essential for virulence in Staphylococcus aureus and Salmonella species, but we didn’t *witness* that resistance develop–therefore, it might simply be that those species have physiological properties that render them naturally resistant to many of these peptides, and were never susceptible in the first place.

The doubter of resistance, and the bet instigator, was Michael Zasloff of Georgetown University, who wrote in a 2002 review of antimicrobial peptides:

Studies both in the laboratory and in the clinic confirm that emergence of resistance against antimicrobial peptides is less probable than observed for conventional antibiotics, and provides the impetus to develop antimicrobial peptides, both natural and laboratory conceived, into therapeutically useful agents.

Certainly in the short term, resistance may be unlikely to evolve for reasons described above. However, if these peptides are used over an extended period of time, could the mutations necessary to confer resistance accumulate? This was the question asked in a new study by Dr. Zasloff along with colleagues Gabriel Perron and Graham Bell. Following publication of his 2002 paper where he called evolution of resistance to these peptides “improbable,” Bell challenged Zasloff to test this theory. Zasloff took him up on the offer, and they published their results in Proceedings of the Royal Society

The result?

Zasloff had egg on his face. Resistance not only evolved, but it evolved independently in almost every instance they tested (using E. coli and Pseudomonas species), taking only 600-700 generations–a relative blip in microbial time. Oops.

Well, everything old is new again. A very similar claim has been making the rounds recently, originating from the press release for a new paper claiming to have found bacteria’s “Achilles’ heel,” advancing the claim that “Because new drugs will not need to enter the bacteria itself, we hope that the bacteria will not be able to develop drug resistance in future.”  A grand claim, but history suggests otherwise. It was argued that bacteria could not evolve resistance to bacteriophage, as the ancient interaction between viruses and their bacterial hosts certainly must have already exploited and overcome any available defense. Now a plethora of resistance mechanisms are known.

Alexander Fleming, who won the 1945 Nobel Prize in Physiology or Medicine, tried to sound the warning that the usefulness of antibiotics would be short-lived as bacteria adapted, but his warnings were (and still are?) largely ignored. There is no “magic bullet;” there are only temporary solutions, and we should have learned by now not to underestimate our bacterial companions.

Part of this post previously published here.

Guest post: Will new FDA guidelines reduce threat from superbugs?

Guest post by Tim Fothergill, Ph.D.

In January of this year the British Chief Medical Officer urged her government to add  threat posed by superbugs to the official list of “Apocalypses to Worry About” along with catastrophic terrorist attacks and massive flooding. With typical British understatement, its actual name is the National Risk Register of Civil Emergencies but a very stark picture was painted of a post-antibiotic world in which routine operations, such as hip replacements, could prove fatal. In September, The Centers for Disease Control in the US issued a similar statement which estimated that 23,000 people die every year in the US from antibiotic resistant infections. So what is it that has Dame Sally Davies and so many others so worried?

“Superbug” is a term used to describe bacteria which are resistant to many common antibiotics which are used to treat infection. Resistance to these drugs makes treatment more difficult and has increased mortality rates. As resistance to individual antibiotics becomes more prevalent the number of deaths is only set to increase, especially because there is a dearth of research into new antibiotics. Antibiotics are used medically in the short term, so don’t offer the same kind of return on investment for the pharmaceutical companies as drugs for chronic diseases or long-term treatments, such as anti-depressants or hypertension medications. Even more worryingly of all is that strains of potentially deadly infectious bacteria, such tuberculosis have already been identified that are resistant to every potential drug.

Against this background the FDA’s announcement of a plan to phase out the agricultural use of antibiotics is very welcome. Many animals raised for human production are fed antibiotics as a matter of course to boost growth rates. The animals are not suffering from infection, but the drugs can help them grow faster, resulting in a more efficient production of meat for the market. For most drugs, there is a mandatory withdrawal period during which the animals are fed no antibiotics so that they will clear out of the meat prior to slaughter. However, the antibiotics can impact the food supply and human health in other ways. Not only is there concern about meat contaminated with resistant bacteria but the standard agricultural practice of using animal waste as fertilizer only increases the risk of releasing resistant bacteria into the environment contributes to the spread of resistance. This is of particular concern if the land fertilized in this manner is subsequently used to grow food crops that are typically consumed raw. Previous recalls due to bacterial contamination have included spinach and cantaloupe melons. The potential for harm would only have been greater if these cases had involved superbugs, but this possibility is becoming more and more likely. Resistant bacteria that are spread onto crops via animal manure fertilizer have been demonstrated to not only persist in the soil but to also pass the genes for antibiotic resistance onto other species. As we have no control over this genetic transfer it is quite possible that they spread to even more pathogenic species.

The FDA’s proposal to limit antibiotics in cattle feed would seem like good news then. However, the most significant caveat with this plan is that it is voluntary and as such is dependent on the cooperation of the drug producers and farmers. Two of the largest antibiotic producers, Zoetis and Elanco, have indicated that they will no longer labelling their products as suitable for growth promotion. Any subsequent use of these antibiotics for growth promotion would be “off-label” and something that the FDA can and does regulate. However, as with all regulation the devil will be in the details. We do not know yet what the change in labelling will actually say. If their new label can be interpreted in such a way that cattle are still regularly fed antibiotics then nothing will have been achieved.

For example, in Denmark they found that after introducing a ban on antibiotic use for growth promotion in cattle that the quantities of antibiotics actually increased. Animals no longer fed a sub-therapeutic level of antibiotic became more susceptible to infection and thus need therapeutic treatment more often. At first glance this might seem as if little has changed but antibiotics taken at therapeutic levels for the prescribed duration will result in fewer occurrences of resistance to the antibiotic in question. Anybody who has been told by their doctor to ensure that they take the full course for an infection will know this. By reserving antibiotic use for therapeutic use only, where it is needed in greater quantities to fight infections, not only will there be fewer superbugs released into the environment, but the drug companies will stand to increase their sales. This might explain their willingness to cooperate with these proposals. Their other option would be to switch production to antibiotics which are not regarded as being important for human health (such as the ionophores) as these are not covered by these new proposals. However, this is something that would presumably involve some cost to them.

It is also worth comparing the timescale for voluntary phase-out (three years) with the length of time it would take the FDA (presumably in collaboration with the USDA) to implement a strategy for an obligatory regulatory framework, which might have more teeth in terms of enforcement, but which is not yet on the table. The FDA has many admirable qualities but turning on a dime is not one of them. This process would take at least that long if not longer. What we do not know at this point is whether there are plans for the FDA to pursue such mandatory regulation if this voluntary arrangement is found not to be working. Such efforts would presumably require specific budgeting and it seems unlikely that this will happen any time soon given the current state of Congressional deliberations on budget matters. Another possible mandatory option would be Louise Slaughter’s PAMTA bill which is currently with the Health Subcommittee.

If our goal is to reduce the spread of antibiotic resistant bacteria from agriculture then the FDA plan may in fact be the best option, and it is certainly better than doing nothing. Mandatory regulation seems unlikely at this point. However, accountability is still vital to the success of this voluntary agreement. What form could this accountability take? The FDA must be prepared to state publicly if insufficient progress is being made. Also, it is to be hoped that increased demand from major chains like Chipotle, McDonalds and KFC will help. If they were to make this demand then cattle production would change at a much faster pace than that proposed currently. This means that consumers are in a position to contribute by choosing to support suppliers of meat produced in a way consistent with these new guidelines.


Tim Fothergill, Ph.D. is a microbiologist with over a decade of experience in researching the mechanisms for the spread of antibiotic resistance. This interest has led him to the intersection of antibiotic resistance in bacteria and policy, where his is now looking at the implications and consequences of legislation and regulation around antibiotic use. As a result, he has become concerned that the threat posed by overuse of antibiotics needs to be taken more seriously. But it’s not all doom and gloom: his interest in instrumentation and general microbiology extends to brewing his own beer.


Student guest post: New Study Finds that the Flu has Multiple Ways of Spreading

Student guest post by Sean McCaul

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The next time somebody in your office or household has the flu, you might want to consider keeping your distance.  A new study published this month in Nature Communications suggests that about half of the transmission of influenza A results from inhalation of microscopic infectious droplets created by the coughing and sneezing of people infected with the flu.  The flu virus hitches a ride in these droplets, and may infect nearby susceptible people who breathe them in.1

The influenza A virus generally causes fever, coughing, body aches, runny nose, sore throat, headache, and fatigue.  Vomiting and diarrhea may occur, but are more common in children.3 Fever and most other clinical signs usually resolve within 5 to 7 days, but coughing may last two weeks or more.2 Children under 2 years old and the elderly are at greatest risk for complications such as pneumonia, and over 90% of influenza deaths are in people over age 65.2

Seasonal outbreaks of influenza are common in the United States, and typically occur during winter months.  During and average outbreak, 5% to 20% of the people in a community may become ill with the flu, and up to half of the people in environments like schools and nursing homes may get sick.2

In adults with healthy immune systems, the flu virus is shed in highest numbers during the first 3 to 5 days of illness, making spread of the flu most likely during this time.  Children may shed the virus for up to 10 days, and people with weakened immune systems may shed the virus even longer.2 In a typical outbreak, a person sick with the flu passes the illness on to an average of 1 to 2 other people.1,2

Previously, influenza A viruses were thought to be transmitted primarily by direct contact and by larger (but still very tiny) droplets generated by coughing, sneezing, and talking.1,2,3  These droplets are capable of travelling 1 to 2 meters, where they may come to rest in the eyes, nose, or mouth of a susceptible person and cause them to become sick with the flu.  These droplets may also fall upon nearby surfaces and objects, where the flu virus can survive for hours.  A person touching these surfaces or objects may get the flu virus on their hands, and then transfer the virus to their eyes, nose or mouth and become ill.1,2

The recent study, published on June 4, 2013, used a mathematical model of influenza virus transmission to evaluate the data from two previously published studies of the effectiveness of hand hygiene and facemasks for the reduction of transmission of influenza A viruses.   It suggests that the flu virus may survive in very tiny droplets created by coughing and sneezing that can remain suspended in the air as an aerosol long enough to be inhaled by nearby susceptible people.   The study shows that aerosols are an important route of transmission of the virus, and may account for as much as 50% of the spread of the flu.1

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How you get the flu may determine, in part, how ill you get.  Influenza researchers have long suspected that inhalation of aerosols containing the flu virus can lead to more severe illness than exposure to the flu virus by direct contact or by the settling of larger droplets in the eyes, mouth or nose of susceptible people.  This is thought to be because larger droplets are trapped by the defense mechanisms of the upper respiratory tract, such as the large surface area of the nasal turbinates and the mucus lining the nose, pharynx, and trachea.  Smaller droplets, meanwhile, are capable of being inhaled deep into the lungs, resulting in infection in the lower respiratory tract which can cause more severe disease.  The current study found that there was an increased risk for fever plus cough in people suspected to have contracted the flu by inhalation of infective aerosols, which is consistent with current ideas regarding the importance of the route of infection.1

Understanding the routes of transmission of influenza is also important for designing control measures to reduce the spread of this disease.    Interventions such as increased hand hygiene and facemasks help to limit transmission of influenza by larger droplets produced by coughing and sneezing, but may offer little protection from inhaled aerosols.1 Additional methods for controlling the spread of influenza through aerosols, such as improved ventilation of enclosed spaces, ultraviolet lights (which are capable of killing the flu virus), and minimizing exposure to those infected with the flu could reduce the risk of becoming sick.1

So, what can you do avoid getting the flu?  The most effective way is to get vaccinated before flu season.  In the United States, flu season can start as early as October, though the peak months for flu are January and February, and sometimes even later.3 Because the flu strains circulating through the population change from year to year, you should be vaccinated each year.  The vaccine is developed to prevent illness caused by the flu strains likely to cause outbreaks during the flu season, but may not prevent illness from novel or unanticipated strains causing outbreaks.  Some people, such as babies less than 6 months old and those with allergies to eggs should not receive the flu vaccine.3  So the CDC recommends that you take additional preventive measures, such as good hand hygiene, avoid close contact with people who are sick with the flu, avoid touching your eyes, nose, and mouth, and practice good health habits such as remaining well hydrated, eating a healthy diet, exercising, and getting plenty of rest.5

If you do get the flu, what can you do to avoid infecting your family, friends, and colleagues?  First, avoid close contact with others.  Stay home from school or work if at all possible, and don’t run errands while you are sick.  In this way, you can avoid exposing others to your illness.  Second, cover your nose and mouth when you cough or sneeze.  Experts recommend that you cough and sneeze into a cloth or into your elbow, so that you don’t contaminate your hands, which are commonly implicated in the spread of the flu.  This simple practice can reduce the amount of infectious material you spread into your environment.  Practice good hand hygiene, particularly before touching doorknobs and other items that may leave the virus where others are likely to become exposed.5


  1. Cowling, B.J., Dennis, K.M., Fang, V.J., Suntarattiwong, P., Olsen, S.J., Levy, J., Uyeki, T.M., Leung, G.M., Malik Peiris, J.S., Chotpitayasunondh, T., Nishiura, H., & Simmerman, J.M. (2013).  Aerosol Transmission is an Important Mode of Influenza A Virus Spread.  Nature Communications, DOI: 10.1038/ncomms2922  LINK
  2. Bridges, C.B., Fry, A., Fukuda, Shindo, N., & Stohr, K. (2010).  Influenza (Seasonal).  In Heymann, D.L. (Ed.).  Control of Communicable Diseases Manual.  American Public Health Association, Unbound™ Mobile Platform
  3. Centers for Disease Control (February 13, 2013), Key Facts About Influenza (Flu) and Flu Vaccine, accessed at , June 8, 2013
  4. Centers for Disease Control (May 6, 2013), What You Should Know for the 2013-2014 Flu Season, accessed at, June 8, 2013
  5. Centers for Disease Control (January 11, 2013) Preventing the Flu: Good Health Habits Can Help Stop Germs, accessed at, June 8, 2013
  6. Flu Virus Image:  Tom Yulsman (May 26, 2009), U.S. and Other Countries Fail to Adequately Monitor Pigs for Flu, accessed at, June 8, 2013
  7. Sneeze Image:  Ben Mauk, photo credit Andrew Davidhazy/RIT (November 28, 2012), Why Do Bright Lights Make Me Sneeze?, accessed at, June 8, 2013

Eastern Equine Encephalitis: The Mosquito that bit the Snake

Guest post by Hillary Craddock

Last week a new study regarding Eastern Equine Encephalitis (EEE) was published online (Bingham EEE is a mosquito-borne virus that can cause serious, and sometimes deadly, disease in humans and equines. In warmer parts of North America, the virus is spread year-round, but in areas where mosquitoes get killed off in the winter it has been something of a mystery as to how the virus makes it from year to year. Humans and equines are both dead-end hosts, which means that a mosquito can not be infected from biting an infected person or horse. Researchers in Alabama found that wild snakes in the Tuskegee National Forest were positive for  Eastern Equine Encephalitis virus (EEEV), which could explain how EEE was maintained after the first frosts killed off infected mosquitoes. Essentially, what would happen is that an infected mosquito bites a snake, probably during the summer or early fall, and the snake harbors the virus in its blood during the winter. Then, in the spring, an uninfected mosquito (which overwinters as a larva) bites the snake and acquires the virus. This now-infected mosquito can bite a horse or a human, who can then get sick. (I’m sensing a Chad Gadya theme here. Just me? Ok…)

Amphibians and/or reptiles as the winter reservoir of EEE is not a recent research question. A book, Reptiles as possible reservoir hosts for eastern encephalitis virus, (which I was unfortunately unable to get my hands on, since apparently only the University of Alberta has an available copy) was published in 1961, and another  study in 1980 by Smith and Anderson stated that two New England species of turtles could be infected by the virus. Interestingly enough, a 2012 study by Graham et. al. (same research group as Bingham found that, out of 27 species surveyed, only snakes showed high seropositivity (positive for virus antibodies in the blood), while amphibians, turtles, and lizards had low to no seropositivity. A 2004 study by Cupp, also in Alabama, found that mosquitoes carrying EEEV had fed on amphibians and reptiles in addition to birds and mammals. Now, it’s all well and good to show that a reptile can act as a host, but just because something can be the host doesn’t mean that it is the host in the actual system. The crucial step was testing their hypothesis in a wild population.

And test they did. The researchers were careful to state that the question of snakes acting as reservoir hosts is “unresolved,” but there is “mounting evidence” that snakes are the winter hosts of the virus. Cottonmouths (Agkistrodon piscivorus) were the most common snake sampled, making up 41% of sampled reptiles. They were also frequently seropositive, with 35.4% testing positive for EEEV. Of the five species sampled, one other, the copperhead (Agkistrodon contortrix) was found to be positive. The researchers tested for active infection in addition to antibodies, and found that some snakes were actively infected. This means that, if a mosquito bit the snake, the mosquito could possibly acquire the virus and pass it on to other creatures.

So why am I so excited? When I took my first Emerging Infectious Diseases class in college, the professor explained to us that zoonotic infectious diseases were most likely to jump between closely related species. Granted, I’m using the word “close” loosely here. She meant that diseases were far more likely to jump mammal to mammal or bird to mammal than, say, fish to mammal or reptile to mammal. I was also taught that if you can understand how a disease is transmitted, you’re one step closer to controlling it.

Which answers the ultimate question – so what does this all mean? When we better understand how a disease is transmitted, it’s easier to control it. Further research in other parts of the country is needed to see if snakes are harboring the virus in the North East and Midwest regions, but the implications for disease control are there. If we understand where or when snakes congregate, we might be able to better predict disease dynamics, specifically outbreaks. If the first outbreaks in the summer originate from mosquitoes biting snakes, then it’s possible that scientists could conduct heavier surveillance in areas where snakes are known to congregate. In this case, we have two entire categories of experts – herpetologists (reptile specialists) and wildlife scientists – that public health practitioners can work with to try to control the disease. This paper is amazing because it unlocks a whole new cavalcade of questions and potential solutions.


This post was republished with permission by the author, and was originally published at Mind the Science Gap.

Hillary is a second year master’s student in Epidemiology at the University of Michigan, and she is currently working in influenza research. Her primary interests include zoonotic, emerging, and vector-borne infectious diseases, disaster preparedness and response, and public health practice.

Scarlet fever–past and present

While “flesh-eating infections” caused by the group A streptococcus (Streptococcus pyogenes) may grab more headlines today, one hundred and fifty years ago, the best known and most dreaded form of streptococcal infection was scarlet fever. Simply hearing the name of this disease, and knowing that it was present in the community, was enough to strike fear into the hearts of those living in Victorian-era United States and Europe. This disease, even when not deadly, caused large amounts of suffering to those infected. In the worst cases, all of a family’s children were killed in a matter of a week or two. Indeed, up until early in the 20th century, scarlet fever was a common condition among children. The disease was so common that it was a central part of the popular children’s tale, The Velveteen Rabbit, written by Margery Williams in 1922.

Luckily, scarlet fever is much more uncommon today in developed countries than it was when Williams’ story was written, despite the fact that we still lack a vaccine for S. pyogenes. Is it gone for good, or is the current outbreak in Hong Kong and mainland China a harbinger of things to come? More below…
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Hemolytic uremic syndrome (HUS) in history–part 4: the bigger picture

As I’ve laid out this week (part 1, part 2, part 3), the realization that a fairly simple, toxin-carrying bacterium could cause a “complex” and mysterious disease like hemolytic uremic syndrome came only with 30 years’ of scientific investigation and many false starts and misleading results. Like many of these investigations, the true cause was found due to a combination of hard work, novel ways of thinking, and simple serendipity–being able to connect the dots in a framework where the dots didn’t necessarily line up as expected, and removing extraneous dots as necessary. It’s not an easy task, particularly when we’ve had mostly culture-based methods to rely on since the dawn of microbiology.

If you read start digging around in the evolutionary medicine literature, you’ll see that one oft-repeated tenet is that many more “chronic” and “lifestyle” diseases are actually caused by microbes than we currently realize. (I’ll note that there is active disagreement here in the field–one reason noted is that many of these diseases would decrease one’s fitness and thus they are unlikely to be genetic, but many of them also have onset later in life than the prime reproductive years, so–still controversial). But whether you agree on the evolutionary reasoning or not, I think it’s safe to say that those who make this claim (like the Neese & Williams book I linked) are probably right on the overall assertion that more and more of these “lifestyle/genetics” diseases are going to be actually microbial in cause than we currently realize.

Why do I agree with this claim? History is a great indicator. Many infectious diseases were thought to be due to complex interactions of genetics (or “breeding,” “lineage,” etc.) with “lifestyle.” Think of syphilis and tuberculosis in the Victorian era. Syphilis (and many other diseases which we know now to be sexually-transmitted infections) was considered a disease which affected mainly the lower social classes (“bad breeding”), and was thought to be rooted in both family history as well as an over-indulgence in sex or masturbation. Tuberculosis, because it affected those throughout the income spectrum, was still blamed on “poor constitution” in the lower classes, but was a disease of the “sensitive” and “artistic” in the upper classes. It was also thought to be due to influences of climate in combination with genetics. Or, look to more recent examples of Helicobacter pylori and gastric ulcers, which were also ascribed to dietary habits and stress for a good 30 years before their infectious nature was eventually proven. And from that same era, HIV/AIDS–which even today, some are still all too ready to write off as merely a behavioral disease, rather than an infectious one.

So, we still view many of these diseases of unknown etiology as multi-factorial, “complex” diseases. And undoubtedly, genetic predisposition does play a role in almost every infectious disease, so I’m not writing off any kind of host/pathogen interplay in the development of some of these more rare sequelae, such as HUS as a consequence of a STEC infection. But looking back over history, it’s amazing how many diseases which we view now as having a documented infectious cause were studied for years by researchers thinking that the disease was the result of exposure to a toxin, or diet, or behavior, or a combination of all three.

I’ve mentioned the example of multiple sclerosis in previous posts. Multiple sclerosis is an autoimmune disease; the body produces antibodies that attack and eventually destroy parts of the myelin sheath covering our nerves. The cause of MS, like HUS 40 years ago, is unknown, though it’s thought to be a combination of genetics and environmental influences. Going through the literature, it seems like almost everything has been implicated as playing a causal role at one point or another: pesticides, environmental mercury, hormones, various other “toxins,” and a whole host of microbes, including Chlamydia pneumoniae, measles, mumps, Epstein-Barr virus, varicella zoster (chickenpox), herpes simplex viruses, other herpes families viruses (HHV-6 and HHV-8), even canine distemper virus. They’ve done this looking at both microbe culture (from blood, brain tissue, CNS, etc.) as well as using serology and DNA/RNA amplification in various body sites. None have shown any strong, repeatable links to the development of MS–much like the spurious associations that were seen with adenovirus and HUS.

Although no microbial agent has been convincingly implicated to date, there are tantalizing hints that MS is caused by an infectious agent. There have been “outbreaks” of MS; the most famous occurred in the Faroe Islands in the 1940s. Studies of migrants show that the risks of developing MS seem to be tied to exposures in childhood, suggesting a possible exposure to an infectious agent as a kid. And one of the most common mouse models used to study MS has the disease induced by infection with a virus called Theiler’s murine encephalitis virus (TMEV). If it can happen in mice, why not humans?

It might seem implausible that infection with some microbe could lead to the eventual neurological outcomes of MS, but again, examples abound of weird connections between microbes and health outcomes. For STEC, it might not be intuitively obvious at first glance how a fecal organism could be a cause of kidney failure. The respiratory bacterium Streptococcus pyogenes usually causes throat infections (“strep throat”), but if left untreated, it can also cause kidney damage (glomerulonephritis) or even heart failure due to rheumatic heart disease. A microbial cause of MS could lie in a virus, bacterium, parasite, or fungus–maybe one that we haven’t even discovered yet, but that perhaps will pop up as we learn more and more about our metagenome. Perhaps 30 years down the road, the way we view many of these “complex” diseases will look as short-sighted as it does looking back at old HUS papers from today’s vantage point.

When is MRSA not MRSA?

…when it contains a weird gene conferring methicillin resistance that many tests miss.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a big issue in the past 15 years or so, as it turned up outside of its old haunts (typically hospitals and other medical facilities) and started causing infections–sometimes very serious–in people who haven’t been in a hospital before. Typically MRSA is diagnosed using basic old-school microbiology techniques: growing the bacteria on an agar plate, and then testing to see what antibiotics it’s resistant to. This can be done in a number of ways–sometimes you can put a little paper disc containing antibiotics right onto a plate where you’ve already spread out a bacterial solution and see which discs inhibit growth, or sometimes you can grow the bacteria in a plate with increasing concentrations of antibiotics, to see when the drugs are high enough to stop growth. Both look at the phenotype of these bacteria–the proteins they’re expressing which lead to the bacteria’s drug resistance.

However, these culture-based methods are slow–they can take days between when the patient first is seen by a doctor and the time the results come back from the clinical lab. For this reason, increasingly labs are moving to molecular methods, which are much quicker than the culture-based methods. Indeed, detection of the gene responsible for methicillin resistance, mecA, has been the gold standard for *really* identifying MRSA, even beyond phenotypic methods.

A new pair of papers demonstrate the limitations of this reliance. Like many science discoveries, this one started with a “huh, weird” moment. Investigators noticed that a number of their S. aureus samples were categorized as MRSA using the traditional phenotypic methods, but were negative when it came to the mecA DNA test. Genetic analysis showed that these isolates carried a different mecA gene, dubbed mecALGA251. The investigators searched their isolate collection in England, and also worked with collaborators in Scotland and Denmark to search through their banks for additional mecA-negative MRSA, and found almost 70 isolates, including one dating back to 1975. (A second paper by a different group examined two isolates in Ireland).

Now is when it starts to get really interesting. (Continued below)
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