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CRYPTOSPORIDIOSIS APPEARING MORE IN BEEF HERDS

by: Heather Smith Thomas

Cryptosporidiosis is a disease caused by a protozoan, creating diarrhea in young calves. Originally a problem in dairy cattle, this problem is now appearing with increasing frequency in beef herds. Anthony Blikslager, DVM, PhD, diplomate ACVS, Associate Professor of Surgery at North Carolina State University, has worked on cryptosporidiosis research for many years.

Some of the research was aimed at ways to treat the diarrhea more effectively. "In many instances these calves have mixed infections. They have Cryptosporidium and other organisms, too, like rotavirus. This becomes much more serious. Cryptosporidiosis is usually endemic on a certain farm, and the parasite is difficult to get rid of. You keep seeing it again and again in the calves," says Blikslager.

"The organism attaches to the intestinal lining, but does not actually penetrate it. It sits on the lining itself. But the calf reacts to the organism and mounts a strong inflammatory response. Diarrhea results from the calf trying to mount an immune response to the organism," he says. A lot of white blood cells migrate to the site, and there is intense inflammation--which causes the lining to shed. The compromised gut is not due to the organism damaging the lining, but due to the calf trying to shed the organism -- and the only way he can get rid of it is to get rid of the cell it's attached to, so the lining is shed, he explains.

"The organism prefers to bind to the lining of the ileum, the very last portion of the small intestine. Because the cell lining in that location is either sloughing off to try to get rid of the organism or has inflammation associated with it, it loses the ability to absorb fluid, electrolytes and nutrients," he says. Everything is shooting on through, creating a watery diarrhea.

"The entire lining seems to be directed at trying to get rid of this organism, without any concern for how it's supposed to function. So our studies looked at specific oral rehydration solutions that might be more effectively absorbed than what is regularly used. The latter are essentially salt solutions that have glucose included in them. The reason the sugar is in there is because the transporter that takes up glucose also transports salt at the same time." The whole basis behind oral rehydration solutions is to enhance the absorption of the salts.

"A long time ago people discovered this in human patients with cholera in developing nations. They found that if you give a salt solution it has some benefit, but if you put sugar in it, this makes a huge difference -- because a lot of the transporters for sodium are waiting for a sugar molecule before they do anything. What happens with the cryptosporidium is that the transporters that have the glucose/sodium transport ability are some of the cells that are damaged a lot. So we looked at another nutrient that could potentially stimulate transport, and that was glutamine -- an amino acid. It's a protein nutrient," he says.

"The glutamine is transported in exactly the same way that glucose is, except that in a cryposporidium infection there are more cells left that are able to transport it. It looks like the glutamine transporter is trying to compensate for the loss of cells. The body increases the amount of the glutamine transporter," explains Blikslager.

"The small intestine has adapted to use glutamine -- rather than glucose -- as a nutrient for itself, and prefers to go after that. So in the studies, we compared using glutamine-containing salt solutions instead of glucose-containing salt solutions. We showed in our clinical trials that glutamine solutions were more effective and the calves had more absorption. We put the calves in a cage and were able to measure the total amount of fluid we put into them and the total amount they lost, either throuugh urine or diarrhea; they lost less and were better hydrated than the calves getting the original glucose/salt solution," he says.

"There is a new product, a glutamine-containing salt solution, that is now on the market in Britain. We are hoping it comes to the U.S. very soon. Practitioners should be looking for it -- a new oral rehydration powder mix that contains glutamine rather than glucose. You can probably get better rehydration on these calves if you use this," says Blikslager.

If you don't have access to this, you should still keep using the electrolyte mixes that contain dextrose. "Dextrose is the powder that has glucose in it. You can also buy glutamine, and make your own solution. It comes hooked to another amino acid called alanine. You can buy this as a powder and mix it yourself. "The alanyl-glutamine can be safely combined with milk replacer or rehydration solution (8 grams per liter of fluid for a daily dose, divided into several feedings). It can be purchased from Sigma Chemical Company in St. Louis, Mo. There are also other sources you can find on the internet. You have to be careful about feeding too much, however; it can be toxic in high doses because the liver converts the amino acid to ammonia," says Blikslager.

The trouble with glutamine by itself is that it's a little unstable in solution. If you use it right away, it's fine, but if you mix up a batch (such as enough for a whole day's dosings), it won't keep. Mix it before each use," he says. "You can get around that by buying it in the form that's hooked to the alanine. That combination makes it more stable and you can mix it up and save it," he says. A discussion about the glutamine transporter was published in an article by Blikslager in the American Journal of Physiology. A lot of this research is on a very basic level and doesn't make it into the veterinary literature, so veterinarians often miss out on this, he says.

"The other thing that really helps a calf with crypto diarrhea is giving Banamine. One thing that happens during the inflammation associated with cryptosporidium, there are a lot of prostaglandins released. They have an inhibitory effect on salt and fluid uptake. You can block this by putting the calf on Banamine (which reduces the inflammation and action of the prostaglandins). Banamine also tends to make animals more comfortable and look better (reducing pain and fever), but some people worry about what it does to the gut (it can lead to ulcers). But we showed that if you use Banamine, particularly in conjunction with one of these oral rehydration solutions, it makes a big difference," says Blikslager.

"Use the regular dose -- a miligram per kilo, twice a day. For calves that are not too weak and down, the Banamine can also make them feel better enough to keep nursing. This makes a big difference, too. A lot of what the calves need is actually in the milk or milk replacer," he says.

The best way to treat this disease is to give the calf good supportive care to keep him hydrated and strong. "He will get rid of the organism by himself. The peak diarrhea is usually between three to five days after calves ingest the organism. The following three to five days they actually get rid of it themselves. But part of the reason some of them struggle to survive is that they not only have crypto; they might also have rotavirus. It acts the same way in the intestine, with inflammation of the lining. The lining is lost, and the calf has reduced absorption ability," he says.

"Once a calf has lost the lining, it takes about three to five days to get that back to functioning normally. The gut heals pretty fast, but that's still a three to five day period in which the calf is very compromised. Once you hit the peak diarrhea (say at five days after ingesting the organism), it's going to take another three to five days to get things back to normal," says Blikslager. Very young calves may take longer to regenerate the gut lining than a calf three weeks old or older, just because they are not absorbing nutrients normally and ability to heal is reduced. They are not healthy enough to heal as fast as they should.

"One thing the group did here to try to make the gut heal faster was give oral bovine serum. You can buy this in powder form. The Bovine Serum concentrate can be purchased from Proliant, Inc. at Ames, Iowa. We mixed 57 grams with an oral rehydration solution for one day's dosings. This can speed up a calf's recovery from crypto scours. An article published in Pediatric Research (a human pediatric journal) discusses the use of this oral bovine serum concentrate.

The key to successfully dealing with cryptosporidiosis in calves is to spot the problem early and get the fluid and Banamine treatment started quickly. "Even just a sugar/salt rehydration solution can help, even though the glutamine works better. It is very important to get the fluid into them. They are losing fluid from the diarrhea and are not able to absorb more, so they get into trouble very fast. A lot of these calves cannot be saved with injections alone; they need good nursing care and fluids to get them hydrated. Past a certain point they will need IV fluids."

The life cycle of cryptosporidium is a little different than coccidiosis (another protozoan parasite). In the latter disease, calves don't show signs of diarrhea until they are at least three weeks of age because it takes longer for the organism to get to the point of multiplying in the gut and damaging the lining. By contrast, a calf can break with crypto scours as young as four days of age (if born face down in contaminated manure, for instance, picking up the organism immediately after birth). Most commonly they develop the diarrhea by about seven to ten days of age. If calves get diarrhea very early (within the first few days of life) it is generally something like E. coli, instead.

Young calves one to three weeks of age are also likely to have picked up rotavirus or salmonella. "Sometimes a calf will have one or more of these infections going on at the same time and this is hard to treat. In calves this age, a lot of them can be mixed infections. You are purely down to nursing care and trying to keep the calf alive long enough that it can start to heal. There is a rotavirus vaccine (given to the cow ahead of calving to create antibodies in colostrum) but there is no vaccine for salmonella -- and the crypto vaccine is still in the research phase," he says.

Calves with cryptosporidiosis generally have a watery diarrhea that might be greenish--or sometimes yellow, cream colored or gray -- but it does not have blood in it like coccidiosis (which is red or brownish). The gut is not damaged that badly.

Successful treatment hinges a lot on how early you start. "If a calf comes here to the clinic and we're catching them on the way down, we can save them. If you measure their blood pH (which is indirectly a measure of how well hydrated they are) and catch them before the pH gets down to about 7, you can save them. If it gets down to 7 or below, then you are usually out of luck, no matter what you do. Sometimes it's worth calling out a veterinarian to run a blood test on sick calves. Some of them you will pour a lot of fluid, time and effort into and they still won't make it. This would be one way you could tell."

If you had a number of sick calves, this could help you focus on the ones that had the most chance. The veterinarian could also check their systemic condition to see if they were worth trying to save. Antibody levels in the blood can be checked, to see how much colostrum they've absorbed. "If they have not absorbed enough, their immunity will be too low to get rid of the organism fast enough. For treatment, they just need packets of solution to mix up for oral rehydration, and Banamine injections. The vet may call back and say the calf is pretty hopeless, looking at his bloodwork -- let's just try to catch the next one earlier." The tests will also tell if there's a problem with colostrum absorption and the rancher can work on that, for the next calves.

Colostrum is a very important factor, giving the calves some antibody protection. "In all the studies we did with crypto, taking calves and trying to get them all on the same playing field for the tests--before we infected them to study them--the ones without adequate colostrum were very vulnerable. From the dairies, the colostrum absorption on these calves was very poor. It made a huge difference in how they did. If there is any problem with colostrum uptake, this must be tackled from a herd standpoint. If calves have good colostrum absorption, this will protect most of them from infection, and the ones that do get infections are able to reject it much faster than a calf with no protection." This is one more reason to make sure calves nurse quickly enough and adequately, immediately after birth.

RESEARCHING A VACCINE

Some of the research at NCSU was aimed toward creating a vaccine that could be given to cows before calving, to protect their calves from cryptosporidiosis with antibodies in the cows' colostrum.

"I don't know if this vaccine will ever make it to the market. They've had some problems producing it; it's been difficult to know what part of the crypto organism to target, to get rid of it. So until we get that, we have to rely on some of the traditional therapies, such as the rehydration solutions you mix up to give the calf orally, and Banamine.



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