ST398 carriage and infections in farmers, United States

I’ve been working on livestock-associated Staphylococcus aureus and farming now for almost a decade. In that time, work from my lab has shown that, first, the “livestock-associated” strain of methicillin-resistant S. aureus (MRSA) that was found originally in Europe and then in Canada, ST398, is in the United States in pigs and farmers; that it’s present here in raw meat products; that “LA” S. aureus can be found not only in the agriculture-intensive Midwest, but also in tiny pig states like Connecticut. With collaborators, we’ve also shown that ST398 can be found in unexpected places, like Manhattan, and that the ST398 strain appears to have originated as a “human” type of S. aureus which subsequently was transmitted to and evolved in pigs, obtaining additional antibiotic-resistance genes while losing some genes that help the bacterium adapt to its human host. We also found a “human” type of S. aureus, ST5, way more commonly than expected in pigs originating in central Iowa, suggesting that the evolution of S. aureus in livestock is ongoing, and is more complicated than just ST398 = “livestock” Staph.

However, with all of this research, there’s been a big missing link that I repeatedly get asked about: what about actual, symptomatic infections in people? How often do S. aureus that farmers might encounter on the farm make them ill? We tried to address this in a retrospective survey we published previously, but that research suffered from all the problems that retrospective surveys do–recall bias, low response rate, and the possibility that those who responded did so *because* they had more experience with S. aureus infections, thus making the question more important to them. Plus, because it was asking about the past, we had no way to know that, even if they did report a prior infection, if it was due to ST398 or another type of S. aureus.

So, in 2011, we started a prospective study that was just published in Clinical Infectious Diseases, enrolling over 1,300 rural Iowans (mostly farmers of some type, though we did include individuals with no farming exposures as well, and spouses and children of farmers) and testing them at enrollment for S. aureus colonization in the nose or throat. Like previous studies done by our group and others in the US, we found that pig farmers were more likely to be carrying S. aureus that were resistant to multiple antibiotics, and especially to tetracycline–a common antibiotic used while raising pigs. Surprisingly, we didn’t find any difference in MRSA colonization among groups, but that’s likely because we enrolled relatively small-scale farmers, rather than workers in concentrated animal feeding operations (CAFOs) like we had examined in prior research, who are exposed to many more animals living in more crowded conditions (and possibly receiving more antibiotics).

What was unique about this study, besides its large size, was that we then followed participants for 18 months to examine development of S. aureus infections. Participants sent us a monthly questionnaire telling us that they had a possible Staph infection or not; describing the infection if there was one, including physician diagnosis and treatment; and when possible, sending us a sample of the infected area for bacterial isolation and typing. Over the course of the study, which followed people for over 15,ooo “person-months” in epi-speak, 67 of our participants reported developing over 100 skin and soft tissue infections. Some of them were “possibly” S. aureus–sometimes they didn’t go to the doctor, but they had a skin infection that matched the handout we had given them that gave pictures of what Staph infections commonly look like. Other times they were cellulitis, which often can’t be definitively confirmed as caused by S. aureus without more invasive tests. Forty-two of the infections were confirmed by a physician, or at the lab as S. aureus due to a swab sent by the patient.

Of the swabs we received that were positive, 3/10 were found to be ST398 strains–and all of those were in individuals who had contact with livestock. A fourth individual who also had contact with pigs and cows had an ST15 infection. Individuals lacking livestock contact had infections with more typical “human” strains, such as ST8 and ST5 (usually described as “community-associated” and “hospital-associated” types of Staph). So yes, ST398 is causing infections in farmers in the US–and very likely, these are flying under the radar, because 1) farmers really, really don’t like to go to the doctor unless they’re practically on their deathbed, and 2) even if they do, and even if the physician diagnoses and cultures S. aureus (which is not incredibly common–many diagnoses are made on appearance alone), there are very limited programs in rural areas to routinely type S. aureus. Even in Iowa, where invasive S. aureus infections were previously state-reportable, we know that fewer than half of the samples even from these infections ever made it to the State lab for testing–and for skin infections? Not even evaluated.

As warnings are sounded all over the world about the looming problem of antibiotic resistance, we need to rein in the denial of antibiotic resistance in the food/meat industry. Some positive steps are being made–just the other day, Tyson foods announced they plan to eliminate human-use antibiotics in their chicken, and places like McDonald’s and Chipotle are using antibiotic-free chicken and/or other meat products in response to consumer demand. However, pork and beef still remain more stubborn when it comes to antibiotic use on farms, despite a recent study showing that resistant bacteria generated on cattle feed yards can transmit via the air, and studies by my group and others demonstrating that people who live in proximity to CAFOs or areas where swine waste is deposited are more likely to have MRSA colonization and/or infections–even if it’s with the “human” types of S. aureus. The cat is already out of the bag, the genie is out of the bottle, whatever image or metaphor you prefer–we need to increase surveillance to detect and mitigate these issues, better integrate rural hospitals and clinics into our surveillance nets, and work on mitigation of resistance development and on new solutions for treatment cohesively and with all stakeholders at the table. I don’t think that’s too much to ask, given the stakes.

Reference: Wardyn SE, Forshey BM, Farina S, Kates AE, Nair R, Quick M, Wu J, Hanson BM, O’Malley S, Shows H, Heywood E, Beane-Freeman LE, Lynch CF, Carrel M, Smith TC. Swine farming is a risk factor for infection with and high prevalence of multi-drug resistant Staphylococcus aureus. Clinical Infectious Diseases, in press, 2015. Link to press release.