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Authors: DVM Lucy H. Spelman

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Death of a Lemur:
An Unsolved Mystery

by Amy Rae Gandolf, DVM

I
stiffened with anxious tension as I opened my e-mail to read the final pathology report on Brass, the red-ruffed lemur. I hoped for confirmation of the immune disease I'd suspected, or at least some sort of clue to the cause of the lemur's fatal illness. But as I scanned the report, anticipation gave way to disappointment and my questions remained unanswered. I sighed and slumped in my chair, studying the screen to review the details I'd hurried through on the first read. No, I hadn't missed anything. I sat back, replaying the case in my mind in a last-ditch search for answers to the bizarre illness.

I couldn't help feeling as if I'd failed Brass. Part of my reaction was personal. This case hit a little too close to home. I'd wanted to find an answer in the report not only to satisfy myself but also to share it with my mom. Coincidentally, she too had been suffering from strange chronic ailments. The past few months, we'd talked over the phone every week or two about both her case and the lemur's. Where they overlapped, we'd compared clues as we tried to solve the mysteries.

Lemurs are primitive tree-dwelling primates with long, furry tails. They are distinct from monkeys and found only in Madagascar. Most photographs show the ring-tailed species; they tend to gather in photogenic groups that display their brilliant raccoonlike faces, white bellies, and striking black-and-white striped tails.

Brass was a red-ruffed lemur, equally attractive and curious. The red-ruffs are orange-red with black hands and faces. Their bodies are more compact and their coats fluffier than those of the ring-tails. With their unhurried gait, boundless curiosity, fuzzy bodies, and little hands, they sometimes look like creatures straight out of Dr. Seuss.

Early in my position as associate veterinarian at the Pittsburgh Zoo, the red-ruffs in the collection became favorites. Two of them had minor medical issues, and they all required routine health checks, so I got to know the group fairly quickly. I developed a great fondness for them and always enjoyed an excuse to visit. For a closer look at Brass or one of the others, I'd walk into their enclosure with their keeper and some food treats. I'd hold out a grape and await the inevitable eager response—inquisitive big brown eyes and open hands. While my attention was fixed on one lemur, I often felt another sneaking up behind me to toy curiously with my keys or radio. The more time I spent with the lemurs, the more endearing they became.

Brass's medical problems surfaced in July 2005, with his regularly scheduled health exam. As with most zoo animals, the exam required anesthesia. On that particular day, we examined him and Copper, the other male in the group. The morning went smoothly and according to plan, a team effort among myself; the zoo's head veterinarian, Dr. Cindy Stadler; our technician, Libby; and Karen, the lead primate keeper. A writer and photographer from a local newspaper viewed Brass's exam as part of an ongoing zoo storyline they'd been developing.

Each exam took about an hour, including a full physical, radiographs, teeth cleaning, blood and stool collection for testing, and a tuberculosis (TB) skin test, a routine screening test in primates. To check for TB, we inject a tenth of a milliliter of a special reagent, tuberculin, in the upper eyelid and watch for swelling over the next few days. This test is used in people too, but the injection is given in the forearm. A human will readily extend an arm so the nurse can read the test, but primates aren't usually that cooperative. Instead, we use the eyelid so that any resultant swelling can be easily seen from a short distance.

Brass was in great condition and received a clean bill of health. His laboratory results would return the following week and show no cause for concern, although his red blood cells were at the low end of the normal range. When Brass was checked the day after his exam, however, his eyelid TB test site was swollen. Over the next two days, the swelling increased to include both eyes and his muzzle. We interpreted this response as a nonspecific TB test reaction rather than a true positive, since positive tests have distinct features that we didn't see in Brass, including a very red and inflamed eyelid.

We regarded Brass's strange facial swelling as a nonspecific reaction to something in the tuberculin. Or he could have been exposed to any number of TB-like organisms found naturally in the environment that can cause a false positive test. We made plans to reanesthetize Brass in a few weeks for follow-up testing to prove he didn't have TB.

Meanwhile, a nice article about Brass's checkup came out in the paper, with a picture of Karen holding him as he recovered from anesthesia. I clipped it and sent it to my mom, who didn't remember what a lemur was until she saw the picture. An avid amateur photographer, she'd planned to come down from Connecticut to visit me at the zoo for a behind-the-scenes tour—a chance to photograph the animals up close. Unfortunately, she had been experiencing some sort of progressive illness for the past several months, and wouldn't be able to make the trip until things turned around.

Most TB test reactions subside within a week. Brass's swelling lasted longer, though he seemed fine otherwise and had only minimal swelling after two weeks and several doses of ibuprofen and Benadryl. A few days before the follow-up exam was due, I was surprised and perplexed when Karen reported that the dramatic swelling had returned. That's when the case became unusual. We began to wonder if, among other possibilities, the condition could somehow be related to a particular problem known to affect red-ruffed lemurs, called proliferative bone disease.

We put Brass on prednisone (a stronger anti-inflammatory medicine than ibuprofen) and switched him to a different antihistamine. I sought advice from the official veterinary Species Survival Plan advisor for lemurs, Dr. Randy Junge. During our phone conversation, Dr. Junge said the only similar case in a lemur that he was aware of involved a less severe TB reaction that lasted a week before resolving on its own.

Since the strange swelling persisted, we decided it was time to reevaluate Brass under anesthesia in order to recheck his blood and obtain a tissue biopsy from his face. We also collected tracheal and stomach wash samples, a much more involved method of testing for TB. Those results came back negative several weeks later. Able to examine Brass closely with the anesthesia, we saw that he had some mild bleeding around his gums. We took radiographs of his skull; they were normal, as was the rest of his exam. We didn't find any sign of the bone disease that we'd wondered about. We collected blood in a special tube to check for bleeding disorders, but found no problems there, either.

Then, as Brass was waking up from the procedure, our technician, Libby, called from the microscope with alarming news: Brass had a dangerously low number of both red and white blood cells. Given that the lemur's behavior had been normal, this finding stunned everyone. It did explain, though, why Brass subsequently took an unusually long time to wake up from anesthesia.

I left a message that afternoon for Dr. Guillermo Couto, a renowned veterinary hematologist and oncologist, and coincidentally one of my professors in veterinary school. He was someone whose opinion I valued greatly. I went through the case with him the next morning, and faxed him the lemur's laboratory results. After reviewing the information, he said Brass was not making new blood cells to nearly the degree he should be. We narrowed the likely causes to cancer, various possible infections, or an immune-mediated disease. The prognosis, he concluded, could be anywhere from treatable to catastrophic.

We started Brass on a strong antibiotic, continued his prednisone, and planned a bone marrow biopsy to narrow the list of possible diagnoses, or differentials, further. Because immature white and red blood cells are found in the bone marrow, the biopsy would show Dr. Couto which cells were involved in the lemur's disease. Blood cell abnormalities fall into only so many categories, regardless of the species, so the biopsy would help categorize Brass's illness. If Dr. Couto couldn't make a definitive diagnosis from the biopsy, he could at least suggest the two or three most likely possibilities.

Though the lemur now showed some signs of fatigue, he appeared normal otherwise. The bone marrow procedure went well, but we found a new swelling between Brass's rear legs during the exam. We sent one biopsy each to the local pediatric hospital, to Dr. Couto, and to a pathologist specializing in zoo animals. Two days later, the results brought good news, and all three labs concurred. We were able to rule out cancer. Even though Brass's blood cell counts were still well below normal, the sample showed that his bone marrow was functioning normally, trying to replace the cells at a rapid rate.

With these results, we'd narrowed our differentials to two broad disease categories: chronic infection and immune-mediated disease. Like humans, animals can develop autoimmune disease that causes their immune systems to recognize their own blood cells as foreign, destroying them as they are produced from the bone marrow. Often it's not known what triggers this abnormal immune response.

That's when I started to think almost daily about my mom and her own puzzling illness. Wishing I could help her more, I'd tried to offer encouragement and suggestions over the phone as her undiagnosed symptoms became more dramatic. Until a few weeks ago, there'd been no explanation for why she'd been able to kayak and take photographs two years ago but now could hardly hold up a camera, never mind paddle across a lake. After a year of increasing frustration and despair, the problem had recently become severe enough to cause abnormalities in her blood tests. She was finally diagnosed with polymyositis, an immune disease in which the muscle cells, including the diaphragm, are damaged by the body—as if they are foreign.

As I researched articles and talked to my mom, I began to see similarities between her condition and the lemur's. For instance, they were both on prednisone to keep an undesirable immune system response at bay. As Brass had ups and downs, I asked a lot about her medication doses and how they affected her, as well as about her other treatments and symptoms. In the past, we'd never talked much about the details of my job, but now we often spoke about the lemur.

I was so used to comparing and contrasting conditions in all sorts of species, including humans, it didn't occur to me that my mom might be offended by my “comparing her to a monkey” until she commented on it. (I tried to explain that lemurs aren't actually monkeys, but I guess that wasn't the point.) She quickly got over that and became interested in the case. As she searched the Web about her own condition, she relayed tidbits and articles that she thought might apply to Brass. As I researched the lemur's condition, I did the same for her.

The week after his bone marrow biopsy, Brass looked brighter and less swollen than he had in two months. I was encouraged, thinking that whether the problem was a subsiding infection or an abnormal immune response, he was finally headed in the right direction. But the respite was short-lived. A week later, he was badly swollen once again. The pathologist felt that results of his initial facial biopsy in conjunction with those of his bone marrow supported the diagnosis of immune-mediated blood cell disease—with a poor prognosis. Dr. Couto agreed but thought that remission might still be a possibility.

Soon the struggle to control Brass's immune system became more difficult. We tried to strike a balance: dial down the response attacking his own cells, but not so far that he could no longer fight off ordinary bacteria and other infections. Karen sadly reported that Brass was finally beginning to look the way his lab results said he should. He began to suffer from various new problems related to his abnormal immune system. We tried to tackle new infections with strong antibiotics and antifungal medicines.

Brass submitted to being captured in a towel once a week so we could monitor his condition and blood work. Over the next two months, his blood counts and swellings fluctuated. We suspected his immune disease had become refractory—that is, it would no longer respond to our treatments. The lemur felt better on some days than others, putting his caregivers on an emotional roller coaster.

I tried to keep my own emotions suppressed. I think every veterinarian struggles with this at times. We get attached to our patients, but if we start worrying too much about the outcome, it's hard to stay focused on the diagnosis and treatment. So I try to strike a balance in my own mind, and create some degree of emotional distance. In some cases it's easier said than done, especially with chronically ill animals whom we inevitably get to know well. But I couldn't deny my bond with this charming and forgiving little lemur. I wanted so much to find the answer, and I held on to hope for his recovery.

Meanwhile my mom began to sound more hopeful over the phone. She wasn't feeling any better, but she had seen a new specialist and was going to start an intravenous immunoglobulin treatment regimen we'd considered for the lemur. As with Brass, the other drugs she was taking weren't helping nearly enough and were causing her many new problems. When I'd called Dr. Couto to ask his opinion about the possibility of immunoglobulin treatment, he wasn't very encouraging. I later discovered that at ten thousand dollars per treatment for a human, this very slim possibility for a cure could not have been an option for the lemur. I was thankful for my mom's health insurance, and hoped this treatment would give her the help she needed.

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