Monday, September 26, 2016

Cytauxzoonosis in Cats

Cytauxzoonosis in Cats

Also known as “bobcat fever”, this hard to diagnose, hard to treat (and hard to pronounce) blood parasite spells bad news for cats.

            In 1987, during my senior year at the University of Florida College of Veterinary Medicine, the teaching hospital began seeing a few puzzling cases of acutely ill cats.  All of these cats had fevers, were lethargic, and refused all food.  All of the cats were anemic, and most were jaundiced.  Sadly, despite aggressive treatment, all of the cats died within a week of hospitalization.  After much investigative work, a diagnosis was finally elucidated. These cats had succumbed to cytauxzoonosis, a parasitic blood disorder.

             Cytauxzoonosis is a life-threatening blood disorder caused by the parasite Cytauxzoon (“site-awk-zo-an”) felis.  It used to be considered a rare disease, confined to a small geographic area.  The first reported case was in Missouri in 1976.  Since then, the geographic range has progressively expanded, and has now been confirmed in domestic cats in 17 states. (See Sidebar 1) The organism has been documented in bobcats from Pennsylvania and North Dakota, although no domestic cats have been reported with the disease there.  For many years, cytaxzoonosis was reported in North America and South America, but in recent years the infection has also been documented in Europe (in the south of Spain, in France, and in Italy.)

            Cats acquire the illness through the bite of a tick, specifically the lone star tick.  The tick picks up the parasite from bobcats, which are the reservoir host.  Bobcats, when infected with Cytauxzoon felis, develop only mild clinical signs of illness.  The bobcats recover, and then become persistent carriers.  When a tick feeds on an infected bobcat, the tick acquires the pathogen. These ticks can bite and infect other bobcats, or they can bite a domestic cat instead, which leads to severe illness and often death.  All felids are susceptible to infection; cytauxzoonosis has never been described in a non-felid. 

            Because ticks transmit the disease, it should be no surprise that infection is far more likely in cats that go outdoors, especially in rural areas where tick contact is more common.  Cats of any age and either sex may be infected, although young adults are more commonly affected.  Most infections occur between April and September. 

            The most common presenting signs are poor appetite and lethargy.  High fever and jaundice are consistently seen.  Dehydration, rapid and/or labored breathing, rapid heart rate, pale gums, abdominal or generalized pain, increased vocalization, enlarged lymph nodes, and enlarged spleen and/or liver have all been reported. 

            In order to diagnose it, you have to first have it on your list of possibilities.  In endemic areas, veterinarians must suspect cytauxzoonosis for any acutely ill cat with a high fever and outdoor exposure during the spring, summer, or early fall.   Of the routine tests we perform on sick cats – a complete blood count, serum chemistry panel, urinalysis, x-rays – the complete blood count is the most useful diagnostic test.  Microscopic identification of the parasites inside the red blood cell confirms the infection.  The parasite has been described as “signet ring” shaped.  Unfortunately, a major limitation of this test is that the parasite may not be visible inside the red blood cells early in the disease.  Evaluating a blood smear every day increases the chances of finding the parasite, but it may be several days before the parasite is identified.  Initially, only a few red blood cells may be parasitized.  As the disease progresses, however, up to 50% of the red cells may become infected.

            There is a molecular test for that is very sensitive and specific for identifying infected cats, however, this test must be mailed out to diagnostic laboratory, and given the rapid progression of the disease, treatment should not be delayed while waiting for test results.

            Because 90% of cats infected with Cytauxzoon felis die from the disease (most within a week of onset of clinical signs), it is imperative to begin treatment in any cat suspected of having the disease, even if a definite diagnosis hasn’t been made.  Many antiprotozoal drugs have been tried.  Recently, the administration of the antimalarial drug atovaquone, in combination with the antibiotic azithromycin, has shown the best results, with 60% of naturally infected cats surviving.  Treatment is administered for ten days.  Supportive care is essential during the treatment period, because these cats are critically ill.  Intravenous fluids, pain medication, anti-nausea drugs, and aggressive nutritional support are important aspects of treatment, as these supportive measures keep the cat alive while the antiprotozoal drugs and the cat’s own immune system do their work.  Severely anemic cats may require a blood transfusion.  Cats fortunate enough to recover from the illness are apparently immune from ever getting the disease again, however, they may continue to harbor the parasite in their red blood cells for months or years.

            There is no vaccine for cytauxzoonosis, so prevention is based on tick control.  A recent study showed that a collar containing 10% imidacloprid/4.5% flumethrin (Seresto, Bayer) was effective for prevention of Cytauxzoon felis transmission.  In that study, two groups of cats (with and without a collar) were exposed to ticks that were infected with the organism.  None of the cats wearing the collar contracted the disease, while 90% of cats without the collar got infected. Although infected cats cannot transmit the disorder to other cats through physical contact, cats that have recovered from the disease may become carriers, able to transmit the organism to ticks, and therefore indirectly to other cats. It goes without saying that the most sensible way to prevent infection is to keep cats completely indoors, thereby eliminating tick exposure.

            An alternative to the atovaquone-azithromycin combination would be highly welcome, because atovaquone is expensive, tough to obtain, and difficult to administer. (Atovaquone is a thick, viscous, citrus-flavored liquid that must be given every 8 hours, and cats greatly resent being medicated with it.) Until a better treatment is discovered, however, the combination of these two drugs offers the best chance for survival and remains the treatment of choice for infected cats. 

Sidebar 1: States where cytauxzoonosis has been reported in domestic cats

West Virginia
North Carolina
South Carolina

Sidebar 2:  Clinical signs of cytauxzoonosis in domestic cats

Jaundice (yellow coloration to the skin and whites of the eyes)
Rapid breathing
Fast heart rate
Labored breathing
Pale gums
Abdominal pain
Lymph node enlargement
Enlarged spleen

Monday, September 12, 2016

Body Parts – The Intestines

We use the term intestinal fortitude to describe someone with “the courage to endure and go on.”  Well, I have a “gut” feeling that my readers will have the intestinal fortitude to read this blog post despite these bad puns, and that you’ll have no trouble “digesting” the information within. 

At mealtime, after your cat swallows, the food goes to the back of the throat (the pharynx), and then into the esophagus - the muscular tube connecting the pharynx to the stomach. It then enters the stomach where some digestion occurs, before making its way to the organ that is the focus of our column today: the intestines.

The intestinal tract is divided into two major portions: the small intestine and the large intestine. 

When food leaves the stomach, it enters the small intestine.  The small intestine is the longest portion of the gastrointestinal tract.  Expanded end-to-end, it is approximately 3 to 4 times the length of the cat’s body!  The small intestine is divided into three regions: the duodenum, the jejunum, and the ileum. 

The duodenum is the very first part of the intestine, and sits relatively stationary in the abdomen. The jejunum is the longest part of the small intestine and is free to move around, often occupying whatever unoccupied space available within the abdomen.  The ileum is the short, terminal portion of the small intestine. 

Digested food leaves the small intestine and enters the next portion, the large intestine.  We tend to use the term “colon” interchangeably with “large intestine”, but this isn’t entirely correct.  The large intestine actually includes the cecum, colon, rectum, and anal canal.  The cecum is a small pouch at the junction of the ileum and the colon.  It is analogous to our appendix.  The colon has thinner walls and is baggier than the small intestine. The last few inches of the colon is the rectum, followed by the anal canal – the short, terminal part of the gastrointestinal tract that is found just inside the anus.  For consistency, I’ll mostly use the term “large intestine”, but I’m mainly referring to the colon.
The small intestine is where most of the action occurs, digestion-wise.  After a little initial digestion and processing in the stomach, food arrives in the intestine where digestive juices from the pancreas, and bile from the gall bladder both empty into the duodenum through small openings in the duodenum wall. These enzymes and bile digest the food even further, breaking it down into smaller molecules which are absorbed from the small intestine into the bloodstream. Food then passes from the ileum to the large intestine. 

The large intestine is involved in the final phase of digestion.  The bulk of the water and electrolytes gets absorbed from the food, resulting in the formation of feces.  The feces then move into the rectum and anal canal where it is stored until defecation occurs.

As you might imagine, there are many disorders of the feline intestinal tract, and a discussing all of them would certainly be beyond the scope of this column.  Two common ailments, however, warrant a mention:  inflammatory bowel disease and colitis.

Inflammatory bowel disease (IBD) is a condition in which the immune system mounts an excessive inflammatory response, sending inflammatory cells inappropriately into the gastrointestinal tract.  Any part of the GI tract  - stomach, small intestine, large intestine – may be affected, although the small intestine is most commonly affected.  People mistakenly use the term “irritable bowel syndrome” interchangeably with IBD.  When inflammatory cells infiltrate the small intestine, a number of clinical signs may be seen.  The most common are poor appetite, weight loss, vomiting, and diarrhea.  These signs can occur singly, or in any combination.  Making the diagnosis of IBD requires ruling out other common causes of gastrointestinal inflammation, for example: parasites, food allergy, and metabolic disorders such as hyperthyroidism.  Routine lab tests tend to be normal in cats with IBD.  Ultimately, a definitive diagnosis requires obtaining biopsy specimens from the intestinal tract.  Corticosteroids are usually effective in controlling IBD in cats.  In fact, my own cat, Mittens, was diagnosed with IBD three years ago, and she has been symptom-free on medication.

Colitis is inflammation of the large intestine.  Cats with colitis often have diarrhea, occasionally with blood and/or mucus.  They show increased frequency of defecation, and may show straining to defecate.  Vomiting is a common sign.  A common cause of colitis is a sudden change of diet.  Stress is another trigger for colitis.  Cats are creatures of habit and like to have a consistent environment.  A new cat in the house, relatives visiting over the holidays, or a change in the owner’s work schedule can stress out a cat and induce colitis.  Most cases of colitis resolve spontaneously after a few days.  A prescription diet that is high in fiber is helpful in speeding the recovery. Stubborn cases may require medication in addition to a therapeutic diet.

Tuesday, August 30, 2016

SDMA: A New Test Designed to Detect Chronic Kidney Disease Earlier than Before

Chronic kidney disease (CKD) is a common cause of illness in cats, especially older cats.  Previous studies estimated that 1 in 3 cats were likely to develop kidney disease in their lifetime.  A recent study in cats, however, has shown the prevalence of CKD is even higher than formerly believed, with 50% of cats of all ages, and up to 81% of cats aged 15 years and older, having CKD.  The reason for the revision in these numbers is the development of a new test that can detect kidney impairment much earlier than ever before. 

Diagnosing CKD in cats has been relatively straightforward once the disease is in its later stages.  Typically, cats begin showing clinical signs of CKD, for example, increased thirst, increased urination, decreased appetite, weight loss,  and increased nausea or vomiting, as they become elderly.  Upon examination, your veterinarian will likely perform a few standard blood and urine tests, the most informative being a serum biochemistry profile and a urinalysis.  The biochemistry profile may show “azotemia”, an increased level of waste products (primarily creatinine, a breakdown product of muscle) in the bloodstream.  The urinalysis usually reveals a loss of urine concentrating ability.  In other words, the urine is more watery than normal.  This combination of azotemia and poorly concentrated urine confirms that the cat has CKD.

Cats are very good at producing concentrated urine.  As they lose the ability to manufacture concentrated urine, cats will begin to drink more and urinate more.  However, cats, being the unique creatures that they are, seem to maintain their urine concentrating ability pretty far into the disease process, so by the time cats start showing signs of weakening kidneys (excessive thirst and urination, and subsequent watery urine), about 66% of kidney function is compromised.  In many cases, this occurs gradually, and cat owners often fail to notice these initial signs.  If the serum biochemistry panel reveals azotemia, this means that not only does that cat have CKD, but now at least 75% of the kidney’s filtering ability is compromised.  This bears repeating:  by the time we can detect an impairment of the kidney’s filtering ability on our blood tests, there is already a 75% reduction in kidney function.

Unless the underlying cause of the initial kidney injury can be discovered and treated, CKD invariably progresses. In most cases, an underlying cause for the initial renal insult cannot be found.

Sadly, CKD is incurable.  Once the diagnosis is made, the focus is to delay the progression of renal failure, improve the cat’s quality of life, and extend a cat’s survival time through a variety of diet and drug interventions.  If would be ideal if we could recognize cats with early kidney disease before they developed azotemia.  Well, now we can.

The gold standard for measuring kidney function has always been to measure the “glomerular filtration rate” (GFR).  This is an indicator of how effectively the kidneys are filtering the toxins from the blood.  It is cumbersome and impractical to measure GFR routinely in a veterinary practice.  Instead, veterinarians have always used the level of creatinine in the bloodstream to approximate the GFR. However, as mentioned above, creatinine does not increase until 75% of the filtration ability is lost.

Symmetric dimethylarginine (SDMA) is a methylated form of the amino acid arginine. It is a breakdown product of protein that is excreted by the kidneys.  The SDMA levels in the bloodstream correlate closely with GFR.  Therefore, as the kidneys start to lose the ability to filter, the SDMA level will rise.  However, the key advantage of the test is that the SDMA levels rise earlier than creatinine.  In fact, a study of 21 cats revealed that SDMA increases, on average, when there is a 40% reduction in filtration ability.  In some cases, SDMA rose with as little as a 25% reduction in filtration.  This translates to being able to detect a decline in kidney function approximately 17 months earlier than a rise in creatinine, allowing for a significantly earlier diagnosis of CKD.   The test is included as part of every chemistry panel run by the Idexx company.  Veterinarians who do not use Idexx as their primary diagnostic laboratory can run the test “a la carte” from Idexx for a small fee. 

What are the implications of being able to diagnose CKD so much earlier than before?   As with all medical conditions, early detection is key to increasing the chances of successful treatment.  As noted above, if an underlying cause for the kidney disease can be discovered, it may be possible to slow or halt the progression of the disorder.  Cats with an elevated SDMA should have a urine culture promptly performed if there is any suspicion at all that a urinary tract infection may be present.  Bacteria in the bladder may ascend up the ureters, resulting in pyelonephritis, an infection of the kidneys.  Discovering this early and addressing the infection may reverse some of the damage to the kidneys and help prevent progression of the CKD. Ultrasound and/or x-rays should be considered, as these tests might reveal the presence of stones in the ureters or the kidneys.  Again, early detection may allow for surgical or medical intervention, improving the prognosis.  Cats with elevated CKD levels should have their blood pressure evaluated, because up to 20% of cats with CKD have high blood pressure. If untreated, high blood pressure can lead to accelerated progression of CKD.  Urine protein levels should also be monitored in cats with elevated SDMA levels.  Cats with significant proteinuria (protein in the urine) tend to fare worse than cats with low or undetectable levels of protein in the urine.  Early recognition and treatment can improve the prognosis for cats with CKD. 

In addition to identifying and treating any underlying causes of CKD, there are other management strategies for cats with CKD that have proven beneficial in slowing the progression of the disorder and improving quality of life.  Dietary therapy is the cornerstone of long-term management of feline CKD.  The benefits of feeding a prescription diet  - one that is restricted in protein, phosphorus, and sodium – have been well documented.  There is still debate on exactly when to start feeding these diets, but most researchers believe that earlier may be better because transitioning to a new food will likely be more successful when the cat’s appetite is still good.  Because the SDMA test allows for an earlier diagnosis of CKD, dietary alterations can be made promptly.  A low potassium level (hypokalemia) is a common finding in cats with CKD.   Hypokalemia contributes to the progression of CKD.  Kidney function improves when low potassium levels are restored using oral supplementation.  Potassium levels should be regularly monitored in cats with CKD, and adjustments made when appropriate.

CKD is an extremely common condition in cats, and the prevalence increases with age.  Incorporating the SDMA test along with a standard serum biochemistry panel may facilitate the early diagnosis of CKD in cats.  Once identified, the swift investigation for an underlying cause may lead to more effective treatment options, slowing the progression of CKD and extending the life of affected cats.

Thursday, August 18, 2016

Disorders of the Feline Spleen

We’ve all heard of the spleen, but do you really know what it does?  And what does a big spleen mean?

Most people can give you a reasonably accurate description if asked to describe the function of the heart, the kidneys, or the lungs. But ask about the spleen and you’re met with blank stares, despite the fact that everyone’s heard of it.  Let’s end the mystery and delve into the world of the feline spleen.

The spleen is a dark red organ located near the stomach.  It is longer than it is wide, and has the appearance of a giant tongue.  It is covered by a capsule made of sturdy fibrous tissue.   Blood vessels enter and exit the spleen on the same side, in an area called the “pedicle”.  The spleen is usually found in the cranial part of the abdomen on the left side, although the exact location isn’t fixed.  Depending on its size and shape, and the size of the surrounding organs (for example, if the stomach is full), the spleen can shift position to the right side of the body, or to the caudal part of the abdomen.

The spleen isn’t essential for life. It can be surgically removed if necessary, and most animals will be fine.  However, the spleen performs important functions and it’s certainly much better to have one than to not have one.

The spleen has several important functions.  It plays a role in “hematopoiesis”, the production of red blood cells.  The bone marrow is the major site of red blood cell production. The spleen is the next major site.  The spleen is also a storage site for red blood cells and platelets.  If the body was suddenly in need of additional red blood cells in the circulation, the spleen has the ability to contract, flooding the bloodstream with additional blood.  Another function of the spleen is filtration.  The spleen acts as a giant filter that traps and removes old or abnormal blood cells from the circulation.  A fourth function of the spleen is the trapping and removal of bacteria, foreign proteins, and old cells through a process called phagocytosis, in which cells of the immune system within the spleen engulf the offending particles.  A final important function of the spleen is the participation in the immune response. 

Anatomically, the internal structure of the spleen consists of areas of “red pulp” and areas of “white pulp”, as well as a “marginal zone” which separates the white and red pulp.  The red pulp contains many sinuses that are engorged with blood, giving the spleen its characteristic red color.  It is in the red pulp that the filtration of foreign proteins, microorganisms, and defective or old red blood cells occurs.  The white pulp is where the red blood cells are produced and where the cells of the immune system reside.  The marginal zone is the area that separates the red pulp from the white pulp.  Its primary role is that of blood filtration.

Disorders of the spleen can be generally categorized as either primary or secondary.   In primary spleen disorders, the spleen itself is the site of the illness.   The spleen can also be secondarily affected by a systemic disease occurring elsewhere in the body.   The most common abnormal finding indicating a problem with the spleen is splenomegaly – enlargement of the spleen.  This can usually be detected on physical examination, by carefully feeling the contents of the abdominal cavity during the physical exam. 

Enlargement of the spleen occurs in two forms: localized and generalized.  Localized splenomegaly is a focal enlargement of the spleen, i.e. a splenic mass.  Generalized splenomegaly is a diffuse enlargement of the entire spleen.  Localized splenomegaly is more common in dogs.  Generalized splenomegaly is more common in cats.

Once splenomegaly is detected on physical examination, there are several diagnostic tests that are helpful in evaluating the cause for the enlargement.  A complete blood count, serum chemistry panel, urinalysis and abdominal radiographs may provide useful information.   Abdominal ultrasound is an excellent, non-invasive tool to distinguish whether the enlargement is localized vs. generalized, and to help further define the underlying disease process. 

In many cases, a definitive diagnosis can only be achieved by obtaining a sample of the cells from the spleen.  This can be accomplished either by aspiration or by biopsy.  Fine-needle aspiration is a procedure in which a needle, attached to a syringe, is inserted into the spleen.  A sample from the spleen is then aspirated into the hub of the needle and the contents sprayed onto a microscope slide.  The slides are then sent to a laboratory to be evaluated by a clinical pathologist.  Aspiration can be performed under ultrasound guidance, usually with only mild sedation. This is a safe, reliable method of evaluating patients with splenomegaly. 

If a diagnosis cannot be obtained by the diagnostic tests described above, exploratory surgery of the abdomen may be required to identify the underlying disease process.  Because the entire spleen is likely to be affected in cats, rather than obtain a small piece of the spleen as a biopsy specimen, the entire spleen is removed. The spleen is then submitted to the laboratory for review by a pathologist.  As stated previously, the spleen is an important organ but it is not necessary for survival, and most animals live healthy lives following splenectomy.

In cats, unfortunately, infiltration of the spleen with cancer cells is the most common cause of splenomegaly.  The most common cancer is mast cell tumor or mastocytosis.  Lymphoma and hemangiosarcoma are two other common splenic cancers.  In a study published several years ago evaluating 19 cats who had undergone surgical removal of their enlarged spleen, 10 of the 19 (53%) had mast cell tumor, 4 had hemangiosarcoma (21%) and 2 had lymphoma (11%).   These were the three most common diseases resulting in splenectomy. 

Feline splenic disease is a much rarer entity than its canine counterpart, but it is still an important condition in veterinary medicine.  The prognosis for cats with splenomegaly varies depending on the cause. 
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