So God created advertising

I didn’t grow up on a farm, but my dad did. He was the youngest of 13 kids, several of them who grew up to own farms of their own. As a kid, my family had almost an acre in the country, but the only animals we kept on it were stray cats and the occasional opossum (the latter, not on purpose). Still, the school I attended was definitely in a rural, farming community, and I frequently spent time at my Grandma’s farm. She’d downsized since her kids were young and working the farm, but even when I was a kid and she was in her early 80s, she still kept chickens for eggs, cows for milk and meat, and sheep for wool. Some of my favorite childhood memories are of being at her house, gathering eggs, helping my uncle shear sheep, or just playing in the hay loft.

Her farm was small, with a big white barn and a little white house. This is what most people picture when they think of “family farm,” and what the recent “So God Made a Farmer” ad exploits. This makes us feel cozy. We admire the work ethic and values of farmers, as my friend and high school classmate Matt Reese notes, and the ad painted farmers in a very positive light–a stark contrast to the other Superbowl commercials selling their products on sex appeal with half-naked models. I grew up listening to Paul Harvey and “the rest of the story,” and honestly love this speech. It reminds me of home. However, Harvey passed away almost 3 years ago, and his speech was from 1978–I was 2 years old, and farming was much different then than it is now.

Today, while small, family farms of the type romanticized in the Dodge commercial certainly still exist, more and more are becoming industrialized–more land, more animals, and all of the issues that come with those. Contrary to the white men portrayed in the commercial, approximately half of the hired workers on farms today are Hispanic, and are paid roughly $10 per hour for their work. Many of these are undocumented, making it difficult for them to raise their voices when safety or health violations have occurred, or even to receive treatment should they be injured on the farm. Farms employing less than 10 people (the majority of all farms today) are exempt from OSHA inspections, so corners may be cut regarding safety. I won’t go into all the details; others have covered modern-day farming and even made a revised video featuring Latinos. “Funny or Die” also got in on the act, swinging the pendulum about as far from the original Dodge commercial as one could go.

No matter large or small, farming is an important and incredibly difficult job. For many, it is a calling rather than just a job, and some incredible people are out there working to feed all of us. However, changes in farming over the past several decades are killing off the family farms that we (and Dodge) still idealize. As David Hinckley noted, “As it ran, it felt a little like erecting a beautiful statue to a species we are hunting into extinction.” Indeed.

Waste not, want not? Poultry “feather meal” as another source of antibiotics in feed

The ecology of antibiotic resistance on farms is complicated. Animals receive antibiotic doses in their food and water, for reasons of growth promotion, disease prophylaxis, and treatment. Other chemicals in the environment, such as cleaning products or antimicrobial metals in the feed, may also act as drivers of antibiotic resistance. Antibiotic-resistant organisms may also be present in the environment already, from the air, soil, or manure pits within or near the barns. Ecologically, it’s a mess and makes it more difficult to attribute the evolution and spread of resistance to one particular variable.

A new paper emphasizes just what a mess it really is, and what animals are exposed to in addition to “just” antibiotics. Led by Keeve Nachman at the Johns Hopkins University Center for a Livable Future, his team took a different approach to examining farm exposures, by looking at “feather meal.” What is feather meal, you may ask? I did when I met with Keeve last month at Hopkins as we discussed his research. Well, feathers are one obvious byproduct of chicken slaughtering, and waste not, want not, right? So feathers are processed into meal, which can then be used in a number of ways–among them fertilizer, and as an additive to feed for chickens, pigs, fish, and cattle.

We already knew that chickens receive antibiotics in their food and water supplies, just as other farm animals do. It was also known that some antibiotic residues persisted on chicken feathers–another potential driver of resistance in farm animals. However, Nachman and colleagues wanted to assess what other chemicals may be present in this feed meal besides antibiotics, and also whether those antibiotic residues persisted in the feather meal after processing/treatment of the feathers. As lead author David Love notes:

Why study feather meal? We know that antibiotics are fed to poultry to stimulate growth and to make up for crowded living conditions in poultry houses, but the public does not know what types of drugs are used and in what amounts. It turns out that many of these drugs accumulate in poultry feathers, so by testing feathers we have a non-invasive way of learning about what drugs are actually fed to poultry.

To do this, they examined 12 feather meal samples from the U.S. (n=10) and China (n=2). All 12 samples contained at least one antibiotic residue, and some contained residues of 10 different drugs (both of those were from China). While many of the antibiotics were ones used in poultry farming (or their metabolites), they also found drugs they did not expect. Most significantly, this included residues of fluoroquinolones, which they found in 6 of 10 U.S. feather meal samples. Why is this important? Fluoroquinolone use was banned in U.S. poultry production as of 2005 because of the risk to human health–so where are these residues coming from? The authors make a few suggestions for this:

These findings may suggest that the ban is not being adequately enforced or that other pathways, for example, through use of commodity feed products from livestock industries not covered by the ban, may inadvertently contaminate poultry feed with fluoroquinolones. Furthermore, if feather meal with fluoroquinolone residues is fed back to poultry, this practice could create a cycle of re-exposure to the banned drugs. Unintended antimicrobial contamination of poultry feed may help explain why rates of fluoroquinolone-resistant Campylobacter isolates continue to persist in poultry and commercial poultry meat products half a decade after the ban.

Interestingly, the authors tested whether antibiotic residues at the level they found could influence bacterial growth, and found that they did inhibit growth of wild-type E. coli, but allowed a resistant strain to flourish.

Besides antibiotic residues, a number of other chemicals were also detected, including many I’d never thought to associate with farming. In the U.S. samples, they found caffeine–apparently chickens may be fed coffee pulp and green tea powder, which may account for this finding; acetaminophen (Tylenol), which can be used to treat fevers in poultry just as it can for humans; diphenhydramine (the active ingredient in Benadryl), which apparently is used for anxiety issues in poultry; and norgestimate, a sex hormone. Any kind of health significance to these (either to people or to the animals who are ingesting these via feather meal) is uncertain. In an interview with Nick Kristof in the New York Times, Nachman noted:

“We haven’t found anything that is an immediate health concern,” Nachman added. “But it makes me question how comfortable we are feeding a number of these things to animals that we’re eating. It bewilders me.”

So what we’re seeing here are the presence of antibiotics and other drugs in feather meal, which is spread around as a fertilizer or fed to many species of domestic animals as an additive. It’s difficult to keep up with these additional feed additives–in addition to feather meal, many animals could also receive distiller’s grains in their diet, ethanol by-products which are another potential source of antibiotic residues.

This, my friends, is a clusterfuck.

Though I’ve focused on the U.S. data here, the paper notes that the Chinese samples are relevant as well–while most feather meal used here is domestically produced, we do import some, and about a quarter of what we import is from China, where antibiotics that are restricted or banned in the U.S. may still be in use. Furthermore, farmers may not even know this is in the feed they’re using, as many mixes are proprietary. (And if farmers don’t know, you can imagine how difficult it is for a researcher to determine if this is playing a role in antibiotic resistance or other public health issues on these farms).

Works cited

Love, D., Halden, R., Davis, M., & Nachman, K. (2012). Feather Meal: A Previously Unrecognized Route for Reentry into the Food Supply of Multiple Pharmaceuticals and Personal Care Products (PPCPs) Environmental Science & Technology, 46 (7), 3795-3802 DOI: 10.1021/es203970e

The human origins of “pig” Staph ST398

I recently gave a talk to a group here in Iowa City, emphasizing just how frequently we share microbes. It was a noontime talk over a nice lunch, and of course I discussed how basically we humans are hosts to all kinds of organisms, and analysis of our “extended microbiome” shows that we share not only with each other, but also with a large number of other species. We certainly do this with my particular organism of interest, Staphylococcus aureus. There are many reports in the literature showing where humans have apparently spread their strains of S. aureus to their pets (dogs, cats, hamsters)–and sometimes the pets have been nice enough to share it right back. My own research looks at S. aureus in pigs and the humans who care for them, and many studies have shown that a “pig” type of MRSA, dubbed sequence type 398 (ST398), can be transmitted from pig carriers to their human caretakers. The assumption has been that this is truly a “pig” strain, originating in swine, and has spread to humans (and other animals, including cattle, poultry, dogs and horses) from pig hosts, either directly or indirectly via contaminated meat products.

According to a new study (open access in mBio), it seems that there has been more sharing of ST398 than we’d realized. Led by Lance Price at TGEN (full disclosure–I’m a coauthor on the paper), his group analyzed 89 ST398 isolates from China, Europe, and North America, including isolates from humans and animals as well as both methicillin-susceptible and -resistant strains. Using whole genomic sequence typing, the evolutionary history of these isolates was reconstructed.

The findings throw the ST398 story a bit on its head. Instead of being a true pig strain, ST398 appears to have originated as a methicillin-susceptible human strain which was transferred into the pig population, picked up antibiotic resistance genes (including resistance to methicillin and tetracyclines), and then has been passed back to farmers as more resistant organisms. Some prophages were also gained or lost along the way, probably due to selection by host factors.

This also suggests that there is still likely a low level of “native human” ST398 circulating in people. There have been a few case reports of ST398 colonization and/or infection in people without any known livestock contact. Some of these have been resistant to methicillin and/or tetracycline, which are more frequently associated with livestock-adapted strains. Are these truly “human” strains which aren’t involved in livestock at all, or are these ST398 findings in people lacking livestock contact still due to some livestock exposure along the chain of transmission (farmer neighbors? Transmission via food?) We still don’t know, but carrying out more of this WGST will give us better targets in order to be able to differentiate true “human” ST398 strains from those that have been hanging out in animals, and then transmitted back to people.

Now, for long-time science blog readers, this story may sound a bit familiar. Indeed, it looks like ST398 has taken a very similar path to that of another animal-associated S. aureus strain, ST5. As Ed Yong described back in 2009, humans are also the ultimate origin of a “chicken” type of S. aureus ST5, which spread around the world in broiler chicken flocks. In Ed’s article, the first author of the chicken ST5 paper, Bethan Lowder, notes that the change in chicken farming from small farms to multinational corporations likely aided the spread of this organism–and the exact same thing has happened with pig farming.

One difference between the two is that ST5 causes disease in chickens, whereas ST398 seems to be a very rare cause of illness in pigs. This is likely one reason that ST398 in pigs went undetected until relatively recently–it’s simply not much of an economic issue for pig producers, whereas in chickens, S. aureus can cause several nasty diseases (such as bumblefoot and BCO) leading to animal loss (and thus, less money for the farmer).

So, where do we go from here? Clearly studies like this show the utility of using WGST to examine the evolution and spread of these strains. If you look at how spa types are distributed throughout the tree, you can see that those alone don’t tell you much about where the strain came from, or if it’s fully “human” or a pig-adapted lineage. Ideally, a set of simple markers could be found to distinguish ancestral human strains from livestock strains (as methicillin-sensitive ST398 can also be found in pigs, so methicillin resistance alone isn’t enough of an indicator that it’s a “pig” strain). We’ll be working on this in ST398 and other strains we see being shared between animals and humans, in order to better understand this generous sharing we’re doing amongst species.

Reference:

Lance B. Price, Marc Stegger, Henrik Hasman, Maliha Aziz, Jesper Larsen, Paal Skytt Andersen, Talima Pearson, Andrew E. Waters, Jeffrey T. Foster, James Schupp, John Gillece, Elizabeth Driebe, Cindy M. Liua, Burkhard Springer, Irena Zdovc, Antonio Battisti, Alessia Franco, Jacek Żmudzki, Stefan Schwarz, Patrick Butayej, Eric Jouy, Constanca Pomba, M. Concepción Porrero, Raymond Ruimy, Tara C. Smith, D. Ashley Robinson, J. Scott Weese, Carmen Sofia Arriola, Fangyou Yu, Frederic Laurent, Paul Keima,, Robert Skov, & Frank M. Aarestrup (2012). Staphylococcus aureus CC398: Host Adaptation and Emergence of Methicillin Resistance in Livestock mBio, 3 (1), 305-311 : 10.1128/mBio.00305-11

New paper: Staphylococcus aureus ST398 in a childcare worker

One of the reasons I’ve not been blogging as much over the past 2 years or so is that it’s been just insane in the lab. As I was still living off start-up funds and pilot grants, I didn’t have anyone full-time to take care of everything, so all the work has been done by myself and a handful of excellent graduate & undergrad students. Happily, some of the initial projects are wrapping up, and publications are starting to come out (I’ll be blogging about others in the coming days/weeks). One of them was published yesterday in Emerging Infectious Diseases: Livestock-associated Staphylococcus aureus in Childcare Worker. More after the jump.
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