Update on Felid Diseases (submitted by Linda Munson)
(taken from reports presented at the Felid TAG Meeting 1998)

Two important diseases have emerged in the captive cheetah population during the last year, necrotizing
leukoencephalomalacia and oxalate nephrosis, which has resulted in the death of at least 16 cheetahs. The cause
of both diseases has yet to be identified.

Leukoencephalomalacia, a disease in which there is extensive damage to the white matter of the brain, has
caused the death of at least 10 cheetahs, and three additional cheetahs are affected. Because of the vague
clinical signs and the fact that brains were not available from all cheetahs that have recently died, we suspect that
an even greater number of cheetahs are affected. The most notable clinical signs have been slowly progressing
blindness and change of behavior. Some cheetahs were noted to "star gaze," and a few have experienced lack of
coordination or convulsions. Near death, all affected cheetahs have been weak and unresponsive. All cheetahs
affected to date have been 10 or more years old, and both sexes have been afflicted. The disease was first
recognized in the Spring of 1997 and has been confirmed at four different sites. At only two of those sites were the
cheetahs related, suggesting that this is unlikely to be a genetic disease. Only the source of diet is common
among the affected animals.

The severity and distribution of the changes in the brain are unlike any disease affecting other species, but is most
similar to diseases caused by fungal and other toxins or severe deficiencies of micronutrients, such as B-vitamins.
It is likely that something the cheetahs have ingested over a period of time has interfered with normal metabolism
in the brain leading to necrosis. An unusual reaction to a virus has been considered, but is less likely. This
disease is not the same at the one causing lack of coordination in young cheetahs from European zoos (under
investigation by Dr. Chris Walzer), nor is this disease spongiform encephalitis observed in cheetahs that ate beef
in England. Investigations are in progress to identify the cause of this emerging problem.

Oxalate nephrosis was the cause of death of five cheetahs, a snow leopard, a serval and several canids during the
past year. Because ingestion of ethylene glycol is the most common cause of oxalate nephrosis in carnivores, we
suspect that a food source was contaminated, although this has yet to be confirmed. Other causes, such as
vitamin B6 deficiency, are also being investigated.

Helicobacter gastritis continues to be a major problem in captive cheetahs (moderate to severe
gastritis occurs in >70% of cheetahs that have died since 1995), and most cheetahs with
gastritis develop amyloidosis in the kidneys. Amyloid is a major cause of death in the
population because amyloid deposits in the kidney cut off the blood supply and lead to acute
kidney failure. We have determined that the amyloid in the kidneys is not unique to cheetahs,
but is secondary to chronic inflammation (Papendick RE, Munson L, O'Brien TD, Johnson
KH, Systemic AA, Amyloidosis in captive cheetahs, Acinonyx jubatus; Veterinary Pathology
34:549-556, 1997; Johnson KH, Sletten K, Munson L, O'Brien TD, Papendick R, Westermark
P, Amino acid sequence analysis of amyloid protein A from cheetahs, Acinonyx jubatus, with
a high prevalence of AA amyloidosis, International Journal of Experimental Clinical
Investigations 4:171-177, 1997). Therefore, the primary problem in the captive cheetah
population is gastritis and not a genetic predisposition to develop amyloidosis.

Because gastritis occurs in captive, but not wild cheetahs, several questions need to be addressed:

Why has this disease emerged in the last 6-7 years?

Why is it only seen in captive cheetahs?

Why is gastritis so severe in cheetahs compared to other species?

We are focusing research on two issues: 1) identifying the exact type of spiral bacteria associated with gastritis in
cheetahs; and 2) determining if the severity of gastritis is associated with stress. Our bacterial identification
studies are focusing on several unanswered questions:

Are the spiral bacteria that are associated with gastritis in captive cheetahs different from the spiral
bacteria seen in the stomachs of wild cheetahs that do not have gastritis?

Are there specific types of bacteria that cause gastritis?

Do these types differ among zoo locations?

Where do cheetahs acquire these bacteria (mother to cub or food/water source)?

To pursue these questions, Dr. Karen Terio from my laboratory has been working with Dr. Jay Solnick to develop a
method of deriving DNA from fixed cheetah stomachs and then determining the exact genetic composition of those
bacteria. This procedure can now be used to identify bacteria that we were unable to culture. Through these
studies, we will determine the exact identification of the spiral bacteria in wild Namibian and captive cheetahs and
determine if the type of bacteria differ among zoos and among cheetahs with severe or mild gastritis. These
methods will also assist in tracking the source of infection and determine which bacteria is resistant to antibiotic
treatments. To date, she has successfully identified spiral bacteria from cheetahs at two zoos and in two wild
Namibian cheetahs as Helicobacter sp. She now is in the process of determining whether these are a new type of
Helicobacter.

The role of stress in the development of gastritis and other diseases will be determined by fecal corticoid hormone
assays. Fecal corticoids reflect the amount of adrenal cortisol in the blood, which, in turn, is a measure of chronic
stress. Levels of fecal corticoids will be measured in cheetahs moved between zoos and the results correlated
with the degree of gastritis. Also, fecal corticoids will be compared among cheetahs with severe gastritis and mild
or no gastritis to determine if stress impairs the normal immune response to these bacteria.

During the past year, more evidence has been accrued implicating stress in two other unusual and fatal diseases
of captive cheetahs, veno-occlusive disease and glomerulosclerosis. We have recently completed investigations
on the epidemiology and detailed pathology of glomerulosclerosis in cheetahs and determined that it most closely
resembles the kidney diseases of diabetic humans caused by leakage of sugar in the kidney (Bolton L, Munson L,
Glomerulosclerosis in captive cheetahs, Veterinary Pathology, in press, 1998). Because these lesions occur under
conditions of hyperglycemia and yet no cheetahs had lesions of diabetes, other causes of hyperglycemia (such as
hyperadrenocorticism from chronic stress) are considered likely. We now plan to measuring fecal corticoids and
compare levels in cheetahs with and without glomerulosclerosis. Veno-occlusive disease also may be caused by
stress in cheetahs. Analysis of blood from recently captured wild Namibian cheetahs has provided convincing
evidence that the stress results in liver damage. Liver damage leading to fatal veno-occlusive disease also has
occurred in cheetahs recently moved between zoos. Therefore, we also plan to monitor the impact of moving
cheetahs, through fecal corticoids and blood tests of liver function. Dr. Terio has worked with Dr. Janine Brown
(Conservation & Research Center) to validate fecal corticoid assays for cheetahs. She also has some interesting
preliminary data demonstrating that fecal corticoids in captive cheetahs are up to five times higher than levels in
wild cheetahs. More samples are needed from captive cheetahs before we can determine if these preliminary
results reflect the population as a whole. The results of these studies will have wide applicability in determining the
optimal management conditions needed to prevent diseases in captive cheetahs. The studies also will aim to
identify a safe, nutritious diet for captive cheetahs.

Diseases have not been a major problem in other felid species, except those affected by oxalate nephrosis. The
black-footed cat population has problems with amyloidosis in the kidneys similar to cheetahs, and studies are in
process to determine if this amyloid is unique to this species or secondary to chronic infections. Comprehensive
pathology surveillance of lions was initiated this year under the AZA Lion SSP to monitor diseases in the
population and acquire sufficient information on lion diseases to determine if FIV is a medical problem.



Recommendations:

Remain alert for behavioral changes or blindness in cheetahs. Freeze food samples and record
types of food and lot numbers.

Remain alert for signs of kidney failure in cheetahs or other felids. Check urine for unusual amounts
of oxalate crystals. Treat aggressively (dialysis if available) if crystals are noted.

Continue participating in the Cheetah SSP Pathology Survey if a cheetah dies from any cause.
Submit complete sets of fixed tissues (as per the protocol) including entire brain (after a small
section of the frontal cortex is removed for freezing) to the Cheetah SSP Pathologist (Dr. Linda
Munson).

Participate in projects monitoring stress during inter-zoo movement and its effects on gastritis and
veno-occlusive disease in cheetahs.

Continue monitoring the lion population for diseases that might be associated with FIV infection.