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U.S. Department of Health and Human Services

Animal & Veterinary

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Methicillin-Resistant Staphylococcus aureus in the United States - Is There a Connection Between Retail Foods and Human Infection? by Brandi Limbago, Ph.D.

DR. LIMBAGO: Thank you all for the opportunity to speak here. I am trying to get my timer -- okay, good.

So my talk today is MRSA in the United States. Is There a Connection Between Retail Foods and Human Infection? I do not intend to answer this question, just in case you have any expectations. This is just to present some data and raise some questions.

(Slide)

Since you all had to meet here and did not get to come to CDC I would just like to show you where all the magic happens. It is hard to get into these days, but it looks better. It is prettier.

(Slide)

Okay. So I am going to talk about first of all the MRSA collection at CDC and what we know about MRSA circulating in this country. Then a little bit about the isolates and what kind of infections they are associated with. Then I will get on to ST398 livestock-associated MRSA and MRSA from food.

(Slide)

So this is -- and I apologize for the horrible colors. They have changed templates on us at CDC and this is what happens.

So this is our collection of MRSA at CDC.  We have more than 12,000 isolates. These represent colonization isolates, infecting isolates, and isolates from animals and from food. They are mostly from the U.S. We have isolates from other countries as well.

The vast majority of them have been collected through surveillance system, including the ABCs, Active Bacterial Core Surveillance System, but we also get a lot of isolates for reference susceptibility testing as well.

The vast majority of these isolates though do represent our ABCs collection. It is actually about half of our isolates that have PFGE patterns that have been assigned to them. What you can see here is that the two main strains that we encounter are USA100, a traditional health care-associated MRSA strain, it has an SCCmec type II. 

Also USA300 which is the community-type MRSA  strain. This is the PVL-positive SCCmec type IV strain that we hear a lot about.

These guys each are more than 30 percent of all of our isolates. The next most common group is the USA500/Iberian. It is hard to distinguish those from each other. That is also a traditionally health care-associated group. It is also characteristically trimethoprim/sulfamethoxazole resistant, so that makes it a little bit easier to identify. 

There is a smattering of other MRSA types and I wanted to just point out here that we have never detected any ST398 through our routine surveillance activities at CDC. We do have a couple of those isolates in our collection because we have requested them so we would know how to handle them and what to expect if we did see one, but we have not gotten them either through reference routes or through our surveillance systems.

We have seen a single isolate that was nontypeable, Sma1 by PFGE, but it turned out to be not an ST398 and is a novel type strain.

(Slide)

So as I said, a lot of our isolates come from the ABCs surveillance system. This is a -- oh sorry, I am getting ahead of myself -- I am not talking about that yet.

MRSA causes a lot of skin and soft tissue infections. We do not actually have surveillance mechanisms for skin and soft tissue infections at CDC or any nationally representative way of tracking those. But there have been a number of studies looking at skin and soft tissue infections or SSTIs and the strains associated with them.

The two most common studies were the EIDNet study. The one from 2004 has been published, the one from 2008 is currently in progress, but I am giving you a preview of the data. Basically, these are people presenting to emergency rooms with skin and soft tissue infections and, you know, MRSA or staph infections are usually treated empirically. There is not usually culture for SSTIs but for the purposes of these studies, these isolates were cultured.

What we see is that in 2004, 97 percent of the isolates causing severe skin and soft tissue infections were USA300, the community-type strain. Again, the preview from the paper that is still in the works is that the data is basically identical for 2008. So it is not really changing.

I just have a couple of recent studies here as well, just to give you a slightly different perspective. We know that there are a lot of skin and soft tissue infections associated with correctional institutions. There was a recent study from a Midwestern jail. They had an outbreak and basically all of the isolates that they recovered looked to be community associated. They did type only a subset of them and they were all USA300.

I also wanted to point out the effective intervention here was access to soap and laundry for these prisoners.

Also, there was a big study published describing isolates collected as part of the Linezolid trial. These were collected from the U.S. and Europe but just describing the U.S. MRSA isolates, again the breakdown of them is just about 80 percent USA300 and about 14 percent USA100.

So again, just to reiterate, what do we see at CDC? Pretty much USA300 and 100 and those are associated with human infections in various places.

(Slide)

So the invasive infections are the ones that we are tracking through the ABCs surveillance system. They are mostly bloodstream infections. That is just because that is what we have. This encompasses data from eight sites. It is population-based surveillance for case finding and incidence, but it is only a convenience sample of isolates. 

So far we have tested more than 5,000 isolates. They fall into three categories: healthcare onset, healthcare-associated community onset, or community-associated infection types. They all come from sterile sites; that is why it is called invasive isolates. 

This is just a breakdown of the isolates we have seen through this surveillance mechanism from 2005 through 2008. Again, you know, just to -- I am sorry. I feel like I am repeating myself, but it kind of mirrors what we are seeing for the other mechanisms that it is primarily USA100 and then USA300, followed by USA500.

USA100 in the ABC system again is mostly associated with healthcare facility exposure, either for hospital onset or for people who have exposure or risk factors for healthcare. USA300 is more associated with community disease.

(Slide)

So what do we know about MRSA colonization? So I have been talking about true clinical infections. The first study was have is the NHANES Survey. This is a National Health and Nutrition something survey where they go around the country and take a representative sampling of the US population. It is a giant study. You have to plan years in advance. It is expensive to get in, so we only have data for 2001 to 2004. We do not have anything more recent than that. 

But what we can say is overall MRSA carriage in NHANES was about one to three percent. Actually the average was a little bit closer to one percent. It changed over that time and it was closer to three percent in 2004. Just contrast that with Staph aureus carriage which runs at around 30 percent.

When we look at the type of MRSA that were found in these studies, you can again see that USA100 was very common. Again, these are people in the community. These are not people in healthcare facilities. But what is interesting is the second most common was USA500, although they did see some USA300s as well.

Some other data we have for colonization status in the US was data from a veterinary conference in 2008. This was people specifically attending this veterinary conference. They are people who have exposure to animals. In that setting, 17 percent of the people they surveyed looking at nasal swabs were positive for MRSA.

We also know some data from a recent study that we are performing at our Atlanta VA facility in the HIV clinic that colonization rates are much higher among the HIV-positive population. They are about 14 percent, again compared to one to three percent in the general population. But what we are seeing there for the strain types is again primarily community-type USA300.

Then finally for colonization, we have some data by Tara Smith’s group looking at people who worked with swine. This is two large operations in the Midwest. They only found MRSA in one of these operations. They were looking at nasal swabs for both the pigs and the people who worked with the pigs.

So one farm was completely negative and one had MRSA. In that population, where the animals were positive, they found 45 percent nasal colonization in the people who worked with the pigs. They were able to find the livestock -associated strain ST398.

So I am going to tell you a little bit about ST398. Again, this is called livestock-associated MRSA now. It emerged in Europe in the mid 2000s. Originally it was from pig and cattle farmers in France and the Netherlands. Now we have seen it pretty much widespread throughout Europe. 

Originally it started out as a colonizing strain that eventually started causing skin and soft tissue infections, eventually causing more severe infections including pneumonias. It was eventually transmitted from people who had contact with live animals to people who didn’t, including in healthcare facilities.

In early 2000s, they did not detect any of this particular strain, but now it looks like about 20 percent of the MRSA that they do isolate is ST398. I just wanted to mention that they do have an active search and destroy policy in the Netherlands so their baseline MRSA should be pretty low.

When they looked at where they would find these ST398 strains, they compared it to the population base and then to the centers where pig farming was common. You can see on panel A, these are the non-typeable MRSA or ST398 and those are in blue. I think you can kind of see them here.

This is overlaid over a red map of the country. The darker the red, the more pigs there are. So the Netherlands is a big pig-producing country. You can see the correlation between the nontypeable strains of the ST398 type strains and the pig population.

On panel B, we are looking at typeable MRSA strains. These are again the ones usually associated with human infection. You see those are clustered on the other side of the country, although they are sporadic across the entire country and it is overlaid with a wrap of the human population.

So human strains tend to cluster with humans and the livestock-associated MRSA from humans tends to cluster with pigs. Is that clear, I hope?

(Slide)

So it is called nontypeable because it is resistant to digestion with Sma1 which is the enzyme we use for most of our standard PFGE of MRSA. It can be digested with other enzymes.

ST398 corresponds to several spa types including t011, t108, and t567. There is actually quite a bit of diversity in the SCCmec elements associated with this strain. Originally it was described as having a mec element IV or V and now it is kind of running the gamut. It could have any kind of mec. 

It does appear to be of animal origin and animal adaptive.  I mentioned before, it has been associated with skin and soft tissue infections and also with sporadic outbreaks in the Netherlands. It is primarily associated with exposure to live animals, so people who work with live pigs have high colonization rates. People who work in slaughterhouses tend to have lower rates on the side of the house where the animal is dead versus the side where they are actually working with the live animals.

I mentioned before that colonization with ST398 has been documented in the US and it is only among people who have exposure to pigs. 

I should also mention that there is also a report of the MSSA, the susceptible version of ST398 documented in New York of all places among populations with frequent travel to the Dominican Republic. So for what that is worth, I don’t know.

(Slide)

So let’s move on to foods. Before I mentioned that Staph aureus is a frequent contaminant of food and probably everyone knows about staphylococcal intoxication. This is what you can get if you leave your food sitting out in the sun at the picnic. It is caused primarily by Staph multiplying in the food and then ingestion of the toxin. That is what causes the disease. So that is just the intro.

MRSA has been detected in retail meats. Again, first in the Netherlands because they were finding this link earliest. In a couple of different studies there, the numbers of MRSA on the retail meats has been low, so they had to do broth enrichment to detect it. You can see that Staph aureus contamination is high, ranging from 33 to 42 percent, but MRSA contamination of meats is much lower. It is running about 2.5 percent in one study. In the other study which is actually quite a bit larger, it was up to about 12 percent.

I also want to mention that in the first study they did find this livestock-associated strain, again ST398, but they also found USA300 which is a human-associated strain. It kind of, you know, leads one to think about which direction this is going. Whether it is coming from the animals to the meats or from the humans to the meats.

In the second study, like I said, where the incidence was much higher, the majority of those were ST398. What is interesting here again is that they looked in that study in a number of different meat types, not just in the ones that are raised in high intensity situations, but they also looked at wild game and fowl and found MRSA and found ST398 as well. 

So there is one study published in the U.S. looking at retail foods. This was in Louisiana. Again, a lot of contamination with Staph aureus, but MRSA only about five percent of the meats. In this particular case, no ST398, only USA100 and 300, again in my mind suggesting that maybe the MRSA was introduced by the humans.

I want to mention finally that there are no documented cases of MRSA infection via food.

(Slide)

So in conclusion, ST398 is common in Europe and it may be emerging in the United States. It is primarily associated with live animals, mostly pigs and cattle. The at-risk populations tend to be those people who work with live pigs and cattle.

There is no evidence that ST398 has caused infection in the United States, but again we do not have great data for that. We know that MRSA skin and soft tissue infections are pretty much treated empirically and no one is culturing for those, so we don’t have surveillance for those particular kinds of infections, especially among farmers. I am guessing these are the people who are probably least likely to go to the emergency room because they have a pimple on their hand.

We also don’t have any evidence of MRSA transmission via the food supply, that is infection. Of course you can get intoxication by MRSA, just as you can from MSSA, but there is the possibility that people who are working in slaughterhouses may have a risk of acquiring MRSA.

Finally, I just want to emphasize that we do know that the majority of MRSA is transmitted human-to-human and the most effective interventions that we know of are still good hygiene and hand hygiene.

(Slide)

If you have questions, here is my contact information.

(Applause)

DR. LIMBAGO: Our next speaker will be Shaouha Zhao. She will be speaking on Resistance in Pathogenic E. coli From Retain Meat.