Clinical Notes - Individual Specimen Report

OREGON ZOO
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ELEPHAS MAXIMUS INDICUS
Sex: Male
Acc. #: 0801
Indian elephant
Age: 52Y 11M 26D Birth: 14.Apr.1962
Name: PACKY Tattoo: OY 0801
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21.Nov.2013
Problem: BIOLOGICAL SAMPLE REQUEST ; fracture - left front digit 4 (Confirmed); fracture - right front digit 4 (Confirmed);
nuclear sclerosis - OU (Confirmed); scoliosis - tail (Confirmed) fracture - right front digit 5 (Confirmed); fracture – left front digit 5
(Suspected); ulcer - right front digit 4 (Confirmed)
S: Keepers report more "musty" behavior from Packy. This is probably not real musth but some behaviors that are similar to those
seen in musth. These include lack of cooperation with the keepers and decreased appetite. No urinary incontinence or temporal
drainage is present. The Sr. keeper also reported that they discovered several fist-sized balls of partially masticated hay in the
exhibit after he was brought in today.
A: Unusual musth-like behaviors. Possibly related to rectal antibiotic treatment. Dropping food is a new issue and may be a sign of
tooth issues.
P: Will weigh tomorrow and try to get a look in his mouth. (MVF)
22.Nov.2013

Weight: 5228 Kg (11526 Lb)

S: Packy only ate hay sporadically throughout the day and ate very little overnight. He was not treated with enrofloxacin or
isoniazid today and blood was collected for CBC and chemistry profile. His weight is down again. Keepers were able to get a good
oral exam on him and did not see anything unusual.
Again, keepers are reporting signs similar to musth – uncooperative for shifting, some urine dribbling although recent hormone
analysis not compatible with musth.
A: Unknown cause partial anorexia. Probably not musth. Possibly related to antibiotic administration.
P: Recheck tomorrow. CBC/chem panel are pending. (MVF)
23.Nov.2013
S: Packy is BAR and eating hay well this AM. Partial results from bloodwork turned in yesterday show elevated hepatic enzymes.
Will discontinue oral antibiotics for now and monitor. Recheck CBC and chem panel on Monday (11/25)
P: Will discontinue rectal medications for now.
ADDN - CBC results show slightly higher than typical WBC and anemia. (MVF)
26.Nov.2013
S: Recheck CBC and chem panel were submitted yesterday and the results came back today. The CBC shows no signs of anemia and
all values are similar to other recent CBCs. It looks as though the previous CBC's anomalous findings may have been due to
hemodilution (not enough blood in the EDTA tube).
The chem panel shows normalization of many values although the GGT and AST remain very high and both are approx. 10x normal
means.
A: Probable hepatopathy in response to anti-tuberculosis drugs.

 P: Will continue off drugs until his values come back down and will restart at an every other day dosing plan with isoniazid if this
occurs. (MVF)
29.Nov.2013

Weight: 5504 Kg (12134 Lb)

S: Packy continues to do well and is eating normally. Weight was taken today and is up from last week.
P: Will leave off treatment for now and will recheck CBC/chem panel next week to monitor for hepatosis. (MVF)
7.Dec.2013
S: Packy is clinically WNL but his chemistry panel from earlier this week shows continued elevation of some hepatic enzymes –
particularly the GGT.
P: Will keep off of treatment and recheck in one week. (MVF)
14.Dec.2013
Problem: mycobacteriosis (Confirmed)
O: Verbal communication from NVSL that they were isolating an M tb from one of Packy's recent TB cultures.
P: Will notify local health authorities and state veterinarian. (MVF)
17.Dec.2013
O: NVSL reports that the lab isolated Mycobacteria tuberculosis from the mucus sample that was collected on 10/25/13. Trunk
washes collected on 10/24, 10/25 and 10/26/13 were all negative for Mycobacteria.
A: Positive TB status
P: Will begin researching TB protocol in light of the difficulties we have had medicating him (both rectally and orally). (MVF)
18.Dec.2013
S: Packy eating well and last chem panel shows further decrease of hepatic enzymes closer to normal range.
P: Looking into starting on EOD isoniazid at 10 mg/kg, pyrazinamide at 30 mg/kg. Am pursuing alternative isoniazid dosing
regimens (waiting to hear back from others) and also looking into compounding rifampin into capsules or tablets. (MVF)
20.Dec.2013
S: Latest chemistry shows return to normal of all chem values except for the GGT. The GGT is near Packy's normal historical range
and is approx. 1/4 of what it was at its most recent greatest elevation.
P: Will start back on TB medications. Will put on SID pyrazinamide at 30 mg/kg and isoniazid. The isoniazid will start at 5 mg/kg q
48 hours for 7 doses and then increase to 10 mg/kg if he tolerates it at 5 mg/kg. Will check CBC and chemistry profile once a week
as standard monitoring while he is on treatment. (MVF)
21.Dec.2013

Weight: 5511 Kg (12150 Lb)

S: Restarted administration of antimicrobials for tuberculosis as per Rxs below. Administered both drugs today so he will only need
pyrazinamide tomorrow.

 P: Monitor appetite and attitude. Keepers will draw additional blood for CBC and chem. profile once a week UFN to monitor CBC
and hepatic enzymes. If he does well with isoniazid at 5 mg/kg (28 g) we will increase dose to 55 g in approx. 2 weeks.
Rx: ISONIAZID 28 gm rectally q48h for 7 doses.
Rx: PYRAZINAMIDE 165 gm rectally SID for 564 days. (MVF)
22.Dec.2013
S: Packy inadvertently received a rectal dose of isoniazid in error today. He was scheduled to receive only pyrazinamide. (TS)
24.Dec.2013
S: Administered pyrazinamide rectally as per Rx. Keepers report Packy doing well although he was slow to shift to the restraint
device for this afternoon's treatment. Appetite still good. Fecal boluses on the dry side.
P: Continue with Rxs as per plan. Monitor. (MVF)

28.Dec.2013

Weight: 5638 Kg (12430 Lb)

S: Packy is showing signs of possible musth. He is not training well today and not taking treats from keepers although he is still
eating normally otherwise. His weight is up from last week. CBC and chem panel from 12/26 do not show definitive signs of
isoniazid toxicity.
His GGT is still higher than the ref. range but is continuing to decrease and is within his historical range. The AST is up slightly
since his last blood work and is slightly higher than the ref. range high end.
A: Possible musth behavior or reaction to isoniazid.
P: Will monitor appetite and attitude closely. If he continues to act strangely we may need to discontinue the INH again. (MVF)
31.Dec.2013
S: Packy is still doing well. He is eating his full diet but is refusing food while he is in the ERD during treatments. Otherwise he
is essentially behaviorally normal.
Administered PZA and INH rectally today.
A: Apparently doing well still on low-dose INH therapy
P: Will give two more 28g INH doses EOD and then switch to 55g EOD if he continues to do well. (MVF)
1.Jan.2014
Problem: BIOLOGICAL SAMPLE REQUEST; CULTURE (MYCOBACTERIAL) - trunk
P: Trunk wash specimen 1 of 3 collected for mycobacterial culture using standard technique (60 ml saline installation into trunk).
Specimen frozen at -80C and will be shipped to the NVSL when the remainder of the specimens are collected. (TS)
2.Jan.2014
P: Trunk wash specimen 2 of 3 collected for mycobacterial culture using standard technique (60 ml saline installation into trunk).
Specimen frozen at -80C and will be shipped to the NVSL when the remainder of the specimens are collected. (TS)
3.Jan.2014

 P: Trunk wash specimen 3 of 3 collected for mycobacterial culture using standard technique (60 ml saline installation into trunk).
Specimen frozen at -80C and will be shipped to the NVSL (TS)
4.Jan.2014
Rx: ISONIAZID 55 gm rectally q48h for 550 days. (MVF)
6.Jan.2014
S: Packy was inappetant last night per night keeper notes, and this has continued this morning, consuming little hay. He is behaving
otherwise normally. He received the increased isoniazid dose two days ago and is due for it again today.
A: inappetance--rule out musth, drug intolerance, open.
P: continue as planned, and keepers to report appetite (TS)
7.Jan.2014
S: Still inappetant. He is eating small training food items (cheerios, etc.) but not eating appreciable amounts of hay or produce. He
is otherwise acting normally. There was a small amount of blood coating one fecal bolus in the yard, from him. It was fresh in
appearance, and there was no discoloration of the interior of the bolus. No blood seen on subsequent fecal boluses when removed
manually before treatment.
A: inappetance continuing, rectal irritation (likely from rectal treatments)
P: blood was collected yesterday--sending out for CBC/chemistry panel. Will continue to monitor. He received only pyrazinamide
today. (TS)
8.Jan.2014
S: Improved appetite today, eating 5 flakes of hay overnight (but normal is 24 flakes), and eating hay this morning. He continues to
act normally, and no further blood was found on stools.
O: CBC/chemistries WNL from 6 Jan
A: Improved appetite, but still reduced
P: Continue medications as planned. Today is an isoniazid + pyrazinamide day. (TS)
9.Jan.2014
S: Packy worsened again overnight, eating nothing and not drinking much either. He refused all food offered. On visual exam, he
looks okay, no sign of GI or respiratory problems, but resistant to shifting into the ERD. Blood collected from the medial saphenous
vein (left). While holding his LR leg up for phlebotomy, he began trembling in that leg, and when release, showed muscle trembling
of all four limbs. It was difficult to assess whether it was marked shivering, tremors, or weakness, but no other neuro signs were
noted and no other evidence of weakness. Due to return of anorexia and these clinical signs, opted to forego rectal MB treatment
today (received no isoniazid or pyrazidamine). Advised them to administer a warm water enema--10 min of flow, wait 20 min, then
repeat 10 min. Immediately after the first portion of the enema, the muscle trembling ceased, and did not recur.
Submitted CBC/chemistry panel, and performed an in-house PCV/TS.
O: PCV = 34%, TS = 10.0--this is relatively unchanged from two days prior, and does not indicate dehydration.
A: Anorexia--appears to be drug intolerant (most likely Isoniazid at higher dose)
P: Keep indoors tonight and offer an array of browse and hay to encourage consumption, along with plenty of water. Will reassess

 tomorrow to make decision about TB medications. (TS)
10.Jan.2014
Keepers reported this morning that Packy is looking much better and is eating bamboo and orchard hay at a normal rate. His
attitude appears normal as well. There is no sign of shaking. It was decided by the veterinarians to hold off today's TB treatment
and re-evaluate tomorrow. (MIM)
15.Jan.2014
S: Packy remains BAR and eating well. Blood work form 1/10 shows spike in AST, CPK, bilirubin, ALP and GGT compared to blood
work from 1/7.
A: Probable drug reaction - possibly isoniazid (most likely).
P: Will continue to not treat until enzymes come back down. (MVF)
17.Jan.2014
S: Continues to do well. Keepers report normal behavior and appetite
P: Will wait for enzymes to come down before trying antibiotics again. (MVF)

18.Jan.2014

Weight: 5627 Kg (12405 Lb)

S: Packy still clinically normal. Huge weight gain seen this week compared to last (up >450 kg).
P: Recheck CBC/chem next week. (MVF)
24.Jan.2014
S: Packy doing well. Latest blood work shows hepatic enzymes are back down. Will start on gradual intro of INH and PZA starting
on 28 Jan. (MVF)
28.Jan.2014
S: Started back on isoniazid and pyrazinamide. Will administer INH in ascending doses going from 28gm q 48 hr x 7 doses to 42 gm
q 48 hr x7, to 55 gm q 48 hr UFN if he will tolerate it. Pyrazinamide will be given at 165 grams SID. Once he is on the final dosing
schedule and if he seems to be doing well, we will perform pharmacokinetics to be sure the doses are dialed in correctly. Will also
continue to monitor CBC and chemistry panels weekly. Monitor closely for attitude and appetite. Discontinue medications if he
becomes anorexic.
Rx: PYRAZINAMIDE 165 gm rectally SID until further notice.
Rx: ISONIAZID 28 gm rectally q48h for 7 doses. (MVF)
30.Jan.2014
S: Packy did not eat hay well overnight but ate almost continuously throughout the day. He reacted similarly the last time we
started the per-rectum medications and then eventually settled down to eat normally when until the dose was increased. Keepers
pulled blood for CBC and chemistry panel.
P: Will continue on with medications. CBC and chemistry panel are pending. (MVF)
11.Feb.2014

 Rx: ISONIAZID 42 gm rectally q48h for 7 doses. (MVF)
15.Feb.2014
S: Packy continues to do well at intermediate isoniazid dose. Eating normally and behaving normally as well.
P: Cont. with INH/PZA Rxs as per plan. (MVF)
25.Feb.2014
Problem: TWO DRUG TB TREATMENT STARTED
S: Administered first full-strength dose of isoniazid. Packy has tolerated the treatment very well thus far and is eating and behaving
normally.
P: Cont. to monitor closely.
Rx: ISONIAZID 55 gm rectally q48h until further notice. (MVF)
26.Feb.2014
S: Packy was uncooperative for shifting and the keepers could not get him into the restraint device today. Is still BAR and eating
but was simply uncooperative for shifting.
P: We decided to give him the day off of treatments and try again tomorrow. (MVF)
1.Mar.2014
S: Packy loaded without any trouble every day since 2/26 when he refused. Administered treatment without a problem today. HE
is eating well and looks good otherwise.
P: Continue with treatment as per Rxs. (MVF)
2.Mar.2014
S: Appetite is reduced, but not complete. He is otherwise acting normally and cooperative.
P: Medications as directed. (TS)
3.Mar.2014
S: Appetite continues to be reduced, refusing food overnight and eating 1/2 bale of hay this morning. No other adverse signs
noted. Today was the fourth dose of 55 g Isoniazid.
P: Administered medications as directed. Will likely stop isoniazid if inappetance continues tomorrow. (TS)
4.Mar.2014
Serum amyloid A levels for all elephants were tested at the University of Miami via IDEXX. The comment that came back with the
results stated: "SAA levels have been examined in elephants and it appears that this is a major APP in this species. Clinically
abnormal elephants have been described with levels from 30-300mg/l. As a major APP, this test may provide the best prognostic
value in animals under treatment to monitor the progression of a disease process.
The SAA level for the sample from this animal was 28.67, which is clinically normal. (MIM)

 S: Continued depressed appetite. Packy is taking small amounts of hay and eating fresh bamboo fairly well. Passing small amounts
of normally sized hydrated boluses. Water intake is reduced (when hand watered by hose).
Blood work from yesterday shows slight increase in GGT compared to ISIS normals but it is similar to what it typically is for Packy.
Other values are WNL.
A: Possible reaction to INH therapy. It is possible for the decreased appetite to manifest without enzyme elevation or before
enzyme elevation.
P: Discontinued TB chemotherapeutics. (MVF)
5.Mar.2014
S: Continued partial anorexia. Packy is not taking hay very well although he is eating bamboo very well. He is eating all bamboo
offered. He started taking water when offered by hand (via hose) this morning for the first time since this started. Passing slightly
reduced amount of otherwise normal manure. Packy otherwise is BAR and moving normally.
A: Appears mildly improved. Possible INH reaction.
P: Will continue to offer bamboo as he will take it. Recheck lab work tomorrow. (MVF)
6.Mar.2014
S: Packy is BAR and doing well. He ate hay in intervals throughout the day at normal amounts. Normal manure passed. Collected
blood for recheck CBC and chemistry profile.
P: Still formulating new chemotherapeutic plan. (MVF)
7.Mar.2014
S: Continues doing well. Eating normally still. Activity and attitude are WNL. (MVF)
12.Mar.2014
O: NVSL reports that trunk wash samples taken on 1/1, 1/2 and 1/3/2014 were negative for Mycobacteria spp. on culture. (MVF)
18.Mar.2014
Problem: CULTURE (MYCOBACTERIAL) – trunk
S: Trunk wash sample collected using standard method for Mycobacteria spp. culture. 30 ml saline were instilled into each nostril,
the trunk was held elevated for 30 seconds and then the animal was asked to forcibly exhale into a 1 gallon zip loc bag. The
contents were transferred to a sterile specimen cup and frozen at -80C pending shipment to NVSL for culture.
P: Perform two more trunk washes within the next 7 days. (MVF)
19.Mar.2014
Problem: BIOLOGICAL SAMPLE REQUEST ; CULTURE (MYCOBACTERIAL) - trunk
S: Collected second of three scheduled trunk washes for mycobacterial culture.
P: One more sample to collect in this series. (MVF)
20.Mar.2014
Problem: BIOLOGICAL SAMPLE REQUEST ; CULTURE (MYCOBACTERIAL) - trunk

 S: Collected final (3rd) trunk wash for mycobacterial culture.
P: Submit to NVSL for culture. (MVF)
31.Mar.2014
S: Delivered "Paramount Crystals" for keepers to use as a potential vehicle for oral medication. The Crystals are composed of
partially hydrogenated vegetable oil and lecithin. They are intended to be used to smooth/thin chocolate recipes and melt at
approx. body temperature. Our intention with them is to use them as a vehicle for oral rifampin.
The crystals were melted and mixed with sugar (250 grams of crystals mixed with 1/4 cup fine sugar). The liquid was poured into
candy molds and the result were small rectangles approx 15 mm by 25 mm by 4 mm. The idea is that the waxy material will keep
most of the rifampin locked into its waxy matrix and will not be released until it is melted/digested in the stomach. The intention is
to keep the material refrigerated or frozen until immediately prior to feeding to increase the chances that it will be swallowed
prior to melting. Human taste tests showed that the material appears to make the rifampin essentially flavorless.
P: Keepers are to work on getting Packy to take oral medications. We will start by using unflavored (sweetened with sugar)
Paramount rectangles and if these are successful we will move to Paramount rectangles with rifampin. (MVF)
9.Apr.2014
S: Wrote Rxs to re-start isoniazid (INH) and pyrazinamide (PZA) at doses below. We will start treating today, but will instill only
water via enema tube for the first 7 days (14 treatments) to see how well Packy does with twice daily dosing and to work the bugs
out of the logistics of moving him through the barn and into the ERD twice a day before we start with the drugs. He is in musth
now so understanding how the drugs vs. manipulation to administer the drugs affects his appetite is important.
Today the treatments went well and Packy was cooperative.
P: 6 more days of sham treatments before starting the medications. May need to modify the procedure as we go.
Rx: ISONIAZID 13.5 gm rectally BID until further notice.
Rx: PYRAZINAMIDE 163.0 gm rectally SID until further notice. (MVF)

10.Apr.2014
S: Packy is doing well and is remaining cooperative with shifting for treatments.
P: Will continue with a full week of placebo treatments before starting on the PZA and INH via enema. (MVF)
11.Apr.2014
S: Packy is BAR and still behaving normally and loading into the ERD for BID treatments without any problems.
Currently the treatments consist of manual evacuation of the rectum and installation of 3 syringes (1200 ml) in the morning and 2
syringes (800 ml) in the PM. Treatment target times are 08:00 and 15:00.
Examined right front #3 nail which had a solar abscess that delaminated the face of the nail along the laminae and exited at the
cuticles. Keepers have been keeping the lesion beveled and exteriorized and it appears to be slowly improving.
P: Keepers will continue to debride the edges of the solar aspect of the Rt front #3 nail lesion to keep it from closing prematurely.
The face of the lesion seems to be filling in and should be allowed to harden and grow down from the cuticle if possible (dry
weather permitting).
Continue with BID sham (placebo) treatments to make sure that Packy's behavior is solid enough to start using drugs next week.
(MVF)

 14.Apr.2014
S: Per curator, Packy appears to be not laying down to sleep—unsure of for how long this has been the case. He showed some brief
trembling of his legs this morning during the bath routine, as in possible weakness. He is not showing weakness while walking or
other activities (normal behavior and gait), no signs of musculoskeletal pain or lameness, no abdominal distention or evidence of
discomfort, and his appetite and fecal output is normal. In fact, he has gained some weight recently (300#). We discussed adapting
his environment to make it easier to lay down (sand piles, etc), and considering a plan to help him rise if he were to have trouble
rising. (TS)
16.Apr.2014
Problem: BIOLOGICAL SAMPLE REQUEST ; BLOOD COLLECTION ; TWO DRUG TB TREATMENT STARTED
S: Curator still concerned about apparent lack of laying down and appearing slightly unsteady while stretching out (but only then).
Still no evidence of any discomfort, lameness, colic signs, stool abnormalities, or lethargy. Some inappetance noted today, with
reduction in hay consumption. Collected blood sample for CBC/chemstries. Started this morning on rectal medications (BID
isoniazid and SID pyrazidamide) as prescribed. No problems with administration. (TS)
17.Apr.2014
Problem: abnormal stool (Suspected); INAPPETANCE (Suspected)
S: Consumed some hay overnight but only about 10%; he did eat grain fairly well. Not taking produce items from keepers as
normal but eagerly eating bamboo. Stools are somewhat soft and odorous, with increased liquid surrounding them. He is behaving
musthy, somewhat uncooperative during training session, but no other abnormalities noted. Still no evidence of lameness or other
discomfort noted.
O: CBC/chemistries results WNL
A: Reduced appetite and soft stools, possibly but unlikely due to treatments, since they just started yesterday. May be due to
musth or a primary GI issue, and may be connected to his reluctance to lay down.
P: Continue treatments, and KUO. Collect feces for analysis tomorrow if still abnormal, and recheck bloodwork if indicated. (TS)
18.Apr.2014
S: Continued refusal of hay but is eating pelleted feed and bamboo well. Temporal drainage, behavior (aggression and wariness,
ear flapping, head held high, rumbling), and failure to drop penis when urinating are all compatible with musth as is the timing
(historically he tends to enter musth this time of year). Blood work from yesterday and today do not show significant hepatic
enzyme elevations.
He loaded without problems and received two doses of isoniazid and one of pyrazinamide.
A/P: This appears to be a musth and not a reaction to isoniazid, but the timing is suspicious and of concern. Will monitor closely
and discontinue meds if hepatic enzymes spike, feeding drops off even more, or other signs occur to make us believe that this is
not musth and is a reaction to the drugs instead. (MVF)

19.Apr.2014
S: Administered rectal meds as per Rxs for INH and PZA. Packy's attitude remains BAR and he is still showing signs of mild musth.
He ate hay much better overnight and left consumed approx. 210 lbs of hay overnight. He did not eat much hay during the day but
continued feeding on bamboo well.

 P: Continue with meds as per Rxs. If he continues to tolerate the meds we will need to schedule a pharmacokinetic trial for next
week to be sure we are achieving expected plasma values. (MVF)
25.Apr.2014
Problem: PHARMACOKINETIC TRIAL
S: Performed pharmacokinetic trial for PZA and INH to see if current doses are appropriate.
Packy is BAR and appears to be in musth still. Appetite is variable. He eats bamboo and pelleted feed consistently, but his appetite
for hay is variable. In most regards this appears to be a typical musth. It differs in that his appetite for hay shows some more
variation than usual and he is behaving slightly more aggressively than typical for him (normal for other bulls though).
P: Will continue with current medications and await PK results.
(MVF)
26.Apr.2014
S: Continued doing relatively well. Variable appetite continues (ate little hay overnight) but consistently eating bamboo and
pelleted feed. Went after a keeper today so aggression is high. Temporal drainage and urine dribbling positive. Cooperative for
treatments.
P: Frozen plasma will be sent in next week for PK evaluation of INH and PZA. (MVF)
1.May.2014
S: Reduced fecal output seen today. Packy retained the morning's dose until it was manually removed with feces in the afternoon.
Little spontaneous fecal production since yesterday although normal boluses were stacked up in the rectum for both treatments.
Otherwise Packy is BAR, reacting like a normal musth bull. He is eating bamboo well and hay intermittently.
Bled for CBC and chemistry profile.
A: Lack of fecal production is a possible side effect of antibiotics for TB.
P: Will assess via blood work, attitude/appetite and fecal production tomorrow. If this continues will discontinue TB antibiotics.
(MVF)
2.May.2014
Problem: INAPPETANCE (Confirmed)
S/A: CBC/chem from yesterday shows mild anemia and moderate spherocytes noted on CBC. Chemistry shows mild incr. in GGT
and Creatinine.
Packy is BAR and behaviorally normal to work with - musth-like but otherwise normal. Temporal drainage is decreasing but he still
does not drop his penis to urinate. He ate no hay and little bamboo overnight and had only one small pile of manure from the
night.
Discontinued INH and PZA today. Instead of treatment he received two enemas which were given using warm water at a slow rate
to maximize retention. The enemas were used to help maintain hydration rather than as a means of treating constipation.
A: Long discussion with curator and Sr keeper about what these behaviors mean. Were it not for Packy's diagnosis the curator
would ascribe the behaviors to musth. Given the degree of anorexia and lack of feces it is concerning however. There is a slight
increase in GGT but not a severe one.
P: Recheck tomorrow. (MVF)

 3.May.2014
Weight: 5171 Kg (11400 Lb)
Problem: INAPPETANCE (Confirmed)
S: Continued inappetance with normal attitude. Packy is BAR and mildly aggressive. Refusing nearly all food. Weight is down over
500 lb in past 1 month. Scant fecal production. Administered two enemas today - one at 8AM and one at 2PM to help maintain
hydration. Enemas were given using warm water given slowly over 10 minutes.
CBC submitted yesterday to recheck on spherocytes seen on previous CBC showed none and the CBC was nearly completely
normal although the momocytes were elevated. Collected more blood today to recheck CBC, chem panel, uric acid and serum
amylase A. Free catch urine submitted for UA and culture. Review of in-house sediment showed moderate granular casts.
A: Possible isoniazid intolerance although he is definitely showing musth signs as well.
P: CBC, chem panel and UA pending. Will recheck in the morning and consider continuing BID enemas if he is not eating. (MVF)
4.May.2014
Problem: INAPPETANCE (Confirmed); BLOOD COLLECTION; ENEMA; URINALYSIS
S: Packy is still refusing all food--not eating anything, including bamboo or browse. There is also little fecal production. He appears
to not be drinking much water, but is urinating well and it does not appear concentrated. His attitude remains surly and otherwise
the same. He has not laid down to sleep in some time.
O: Bloodwork from yesterday shows further slight increase in GGT (25) and Creatinine (2.3), and his PCV is 33.7 (but no
spherocytes).
A: Concerned about elevated creatinine, and the upward trend as such. Will consider renal insufficiency as well as pyelonephritis.
There is no evidence of an inflammatory leukogram at this point. He is urinating well in response to enemas, and it appears we are
diuresing him.
P: Continued warm water enemas today as previous, at 8:00 am and 1:30 pm. Administered for 10 minutes at low flow rate, with a
5 minute rest mid-way. He cooperated well and retained much of the enema, save for several gallons early on that were mixed
with loose feces. Will continue focusing on fluid diuresis via rectal fluids. (TS)

5.May.2014
Problem: INAPPETANCE (Confirmed); ENEMA
S: Still not eating or drinking anything--senior keeper continuing to offer creative options but he has not shown interest yet. This
morning he was acting more recalcitrant than normal, but then cooperated and entered ERD. Urinated well today during
afternoon session--it appeared and smelled a bit stronger today. Appears well-hydrated.
A: Unchanged, but remaining well-hydrated and urinating well.
P: Continued warm water enemas, 10 min in each of two sessions. Retained most, although tube became kinked in afternoon
session and lost several gallons of water mixed with fecal material. Tomorrow will reassess the plan. (TS)

6.May.2014
Problem: INAPPETANCE (Confirmed); ENEMA; musth.
O: UF Pharmacokinetics lab reported values from isoniazid (INH) and pyrazinamided (PZA) pharmacokinetic testing that was
collected on 25 April.
INH: Dosed at 8:16am. Dose the day before was at 3:00PM. This is a twice daily dosage.

 Pre-dose (8:10AM): Trace
15 min (8:31aM): 3.01 mcg/mL
30 min (8:46AM): 2.94 mcg/mL
45 min (9:01AM): 2.97 mcg/mL
60 min (9:16AM): 2.53 mcg/mL
Second Dose administered at 3:22pm
Pre-dose (3:12PM): 0.56 mcg/dl
15 min (3:37PM): 2.76 mcg/dl
30 min (3:52PM): 3.06 mcg/dl
45 min (4:09PM): 3.47 mcg/dl
60 min (4:23PM): 2.77 mcg/dl
PZA: Dosed at 8:16AM. Dose the day before was at 8:00AM
Pre-dose (8:10AM): Trace
45 min (9:01 AM): 27.43
60 min (9:16AM): 26.67 mcg/mL
A: Target range for INH is 3-5 mcg/mL which was achieved (barely). Target range for PZA is 20-60 mcg/ml which was also barely
achieved.
Still not eating anything but good production of urine in the morning which would indicate that Packy is drinking and continuing to
stay hydrated. Some fecal material was passed during the morning enema. (MIM)
S: Packy continues to be anorexic and not drinking water, although has played with and scattered hay a bit, and there may have
been very brief drinking or investigation of water with his trunk overnight. He is urinating well, but still not dropping his penis
when he urinates. There are other continuing behavioral signs that support the presence of musth. His behavior is essentially
unchanged, with no decrease in activity and remaining somewhat uncooperative as we would expect for musth.
A: Continued anorexia concerns--still unknown if musth is playing a role here vs. urinary disease (bladder or renal), lingering side
effects of TB drugs (unlikely at this point), or other background problem. Still no sign of neuropathy or GI symptoms, colic or
otherwise.
P: Continue as planned--still awaiting urine culture results. Today we are backing off of enema frequency, to see if that makes a
difference in his cooperativity and hunger. One session only, in morning, but for 20 min (in 5 minute increments with breaks in
between). (TS)
7.May.2014
Problem: INAPPETANCE (Confirmed); ENEMA;
S: No alteration in his attitude, cooperativity, hunger, thirst, or condition. Continued querying staff on his gait, foot condition,
strength, any presence of colic or other GI signs, discomfort, depression--no abnormalities related to these that can explain his
anorexia besides the elevated renal values. He is still urinating well. The elimination of the afternoon enema yesterday did not
seem to cause a change, so tried the opposite today--no morning enema, but did the afternoon enema as previous.
Conference call with USDA veterinarians to update on Packy's health and M. tb treatment status, with myself and curator. Notified
them that he is currently not receiving treatments, and discussed retesting with MAPIA and DPP. (TS)
8.May.2014
Problem: INAPPETANCE (Confirmed); BLOOD COLLECTION; ENEMA;
S: This elephant showing some mild interest in water--was seen drinking briefly by night keeper. Showed some interest in grape
mash and alfalfa but did not consume much to speak of. We are now at day 6 of anorexia, and are getting increasingly concerned
about this trend. Today he started acting more amenable to training, and more cooperative in the ERD, not as antsy, etc. Keepers

 feel this may be the onset of alleviation of musth behaviors. We are also considering that this could be a negative sign, if he is
feeling more ill.
O: Urinalysis (5/4/14): SG 1.014, negative for protein, pH 6.0, 0-2 WBC, 0-2 RBC, rare epi cell, no bacteria seen
Culture results from urine collected on 5/4/14--grew > 3 colony types, indicative of contamination (this was a free-catch sample).
The dominant two organisms were 1) Staph. sciuri (1,000-10,000 orgs/ml) which is methicillin-resistant (sensitive to gentamicin,
enrofloxacin, erythromycin, and rifampin) and 2) Enterococcus sp. (1,000-10,000 orgs/ml) (sensitive to amoxicillin, imipenem,
erythromycin, tetracycline; intermediate sensitivity to enrofloxacin)
A: Unsure of relevance of urine culture results vs. UA, though presence of RBC and WBCs supports a real finding of urinary tract
inflammation and likely infection. Will repeat urinalysis asap—asked for sample.
Discussed case with external consulting veterinarian with extensive elephant experience--she concurs that the creatinine elevation
is concerning and that the UA findings of WBCs and RBCs support actual disease, but reminded that as elephants do not
concentrate their urine we cannot use SG as a good measure of renal function. Discussed starting antibacterials--prefers a
fluoroquinolone such as enrofloxacin (which works for the sensitivities). Discussed whether we should consider IV fluid therapy,
but consultant feels that IV electrolyte therapy has the effect of creating hyperosmolarity, and that rectal fluids are equally
effective for diuresis. We also discussed using gastroprotectants (omeprazole is preferred) and considering analgesics if his
behavior does not improve. Also discussed sending blood and urine samples on Monday to a separate lab with greater elephant
expertise, to look for band heterophils (good gauge of left shift which would illuminate the severity of disease) and look more
closely at the urine, including fractional excretion of protein.
P: Will continue with diuresis by rectal enemas, and begin antibacterial and gastroprotectant medications tomorrow. Using
enrofloxacin at 5 mg/kg BID rectally, which equals 22.5 g each dose. We will submit blood and urine to second lab on Monday, and
try to ultrasound his kidneys to get more information. (TS)
9.May.2014
Problem: ENEMA;
S/O: Keepers reported this morning that Packy dropped his penis to urinate, which is a sign he may be emerging from musth. He
also ate a small trunkful of mashed grapes, the most he has eaten in several days. Between the bloodwork which indicates a high
creatinine level and red/white blood cells in the last urine sample evaluated, TS would like to rule out renal disease. Per TS' plan as
discussed last evening, Packy will be receiving BID enemas to maintain hydration followed by a rectal dose of enrofloxacin. Keepers
will collect a urine sample to run a repeat urinalysis. Oral omeprazole paste to be started to combat any potential gastric problems
and, depending on how Packy responds the next few days, analgesia may be added as well.
ADDENDUM: Keepers report that throughout the day today, Packy has eaten a box' worth of sweet potatoes as well as several
alfalfa cubes.
Both enema/enrofloxacin treatments went well. (MIM)
Rx: ENROFLOXACIN 22.5 gm rectally BID for 14 days.
Rx: OMEPRAZOLE 2.28 gm PO SID for 14 days. (TS)
10.May.2014
Problem: ENEMA; URINALYSIS
S: Packy eating sweet potatoes and alfalfa cubes today. Drinking water from pool only.
O: Keepers able to catch urine midstream in the afternoon.
A: Inappetance, r/o kidney disease/failure
P: Rectal enro treatments going well post-warm water enema. Asked the keepers to perform enemas for 15-20 minutes in order
to help water absorption via rectum to keep Packy hydrated and support his kidneys. Urinalysis shows trace protein and low
specific gravity at 1.011. Urine sent to lab for complete urinalysis, and may consider adding on a urine protein to creatine ratio if
the test comes up positive for proteinuria. (KF)

 11.May.2014
Problem: ENEMA; URINALYSIS
S: This morning, Packy is continuing to eat sweet potatoes and alfalfa cubes very well, and drinking water from hose and pool.
After morning enema and antibacterial treatment, he drank water and then proceeded to start eating hay with gusto. By 1:00 pm
he had consumed about 6-7 flakes of hay and lots of bamboo in addition to the other items. Continuing to urinate a lot, and
dropping the penis when he does. He continues to exhibit calmer and more cooperative behaviors, although still interacting with
Rama through doors as if musth could still be happening. Consulted with another elephant veterinarian about enrofloxacin dose,
and they recommended a dose of 2.5 mg/kg BID due to concerns about possible side effects at 5 mg/kg over a long period--this
equals 11.25 g dose BID.
O: UA results from yesterday--SG 1.015, pH 8.0, negative protein, 0-2 WBC, 2-5 RBC, no bacteria seen, rare epi cell, occasional
ammonium Mg phosphate crystals, 1+ calcium carbonate crystals, amorphous debris
Received Testosterone results from SG: Packy was 22.78 on 4/25, 10.39 on 5/9, and 2.16 on 5/9.
A: Much improved appetite and thirst, good frequent urinations, and normalizing behaviors correlate with the return of his
testosterone level toward baseline, reinforcing the possibility that his anorexia was due to musth at least in part. Will continue to
consider and treat renal or other urinary issue, but he has had historical fluctuations of creatinine in this range before.
P: Continue BID enemas and enrofloxacin (but reduce dose to 11.25 g BID), and once daily gastrogard. Will collect daily blood and
urine. Tomorrow this will be send out to University of Florida for review. Will hold off on instituting analgesic medications, since he
has perked up considerably.
Emailed Chembio to pursue rechecking MAPIA and DPP testing--the last samples were evaluated from 10/6/13. Will likely retest
the entire herd. (TS)
12.May.2014
Problem: BLOOD COLLECTION; ENEMA
S: Packy is eating sweet potatoes, carrots, alfalfa cubes, timothy hay, and bamboo--not in "normal" quantities, but he is definitely
continuing to show good interest. He is also drinking water pretty well. His behaviors are now typical for his non-musth periods. He
is continuing to receive twice daily enemas for 20 min each, as well as rectal enrofloxacin BID and gastrogard q 24 hr. We collected
blood for a CBC/chemistries and blood smear through University of Florida, as well as urine for UA and fractional excretion.
O: Attempted rectal ultrasonography of kidneys using metallic extender, but was not able to visualize them. Did obtain images of
what I presume are testes. The right testis appears to have a 3 cm ovoid cystic area within it.
P: Continuing enemas and medications as prescribed. Contacted external elephant veterinarian about visiting the zoo for a consult
on Packy's condition and getting a good ultrasound of his kidneys. A second veterinarian with extensive elephant ultrasound
experience was recommended, and we will pursue bringing them in very soon. Will ask them to evaluate other elephants as well
while they are here. (TS)
13.May.2014
S: Packy continues to eat and drink well, and behave more normally. His activity level is good. He continues to receive twice daily
enemas and enrofloxacin, and once daily gastrogard.
O: UF blood chemistry results show a normalization of creatinine (1.6) and a slightly low albumin (2.9). His AST = 106 and GGT = 60.
A: Continued resolution of recent anorexic period and creatinine elevation.
P: Continue as planned. Will reduce enema frequency soon if continues improving. (TS)

 14.May.2014
S: Eating and drinking well, improving daily. Also behaving more normally and is active. Starting to appear a bit impatient with
enema treatments but is cooperating well.
O:
CBC (UF):
WBC 7.78 K/uL
WBC(CORR) K/ul
RBC 2.38 M/uL
HGB 13.5 g/dL
HCT (CALC) 30.1 %
PCV (SPUN) 27 %
MCV 126.4 fL
MCH 56.6 pg
MCHC 44.8 g/dL
CHCM 33.2 g/dL
CH 41.5 pg
RDW 18.7 %
HDW 4.16 g/dL
PLT K/uL
MPV 9.9 fL
ICTERUS IN mkd heme Units
PL PROTEIN NA g/dL
FIBRINOGEN NA mg/dL
%PROGRAN %
%MYELO %
%METAMYELO %
%BANDS %
%NEUT 23.6 %
%LYMPH 14.3 %
%MONO 56.9 %
%EOS 2.2 %
%BASO 9.6 %
%OTHER %
#PROGRAN K/ul
#MYELO K/ul
#METAMYELO K/ul
#BANDS K/ul
#NEUT 1.84 K/uL
#LYMPH 1.11 K/uL
#MONO 4.42 K/uL
#EOS 0.17 K/uL
#BASO 0.74 K/uL
#OTHER K/ul
NRBC/100 W
#NRBC K/ul
TOXICITY
RBC MORPH normal
Blood smear review (UF):
WBC count/æl [Adviar 120] 7,780
Band heterophils/æl 0 0%
Heterophils/æl 1,400 18%
Lymphocytes/æl 1,400 18%
Monocytes/æl 4,900 63%
Eosinophils/æl 80 1%

 Basophils/æl 0 0%
Leukocyte morphology NSCF
Erythrocyte morphology NSCF
Thrombocytes Adequate in number and morphology
A: Continuing to do well.
P: Resubmitted whole blood and serum, along with urine to both UF and IDEXX for CBC/chemistries, SDH, urinalysis, serum and
urine osmolarity, and fractional excretion and P:C ratio. Based on these results, will make a decision about treatments, including
weaning off of enemas. For now, will continue. (TS)
17.May.2014
CBC/CHEM from Idexx received. Creatinine continues to drop down into normal levels (1.4 mg/dl). All other findings are similar to
those from the chemistry panel from UF. (KF)
18.May.2014
S: Packy continues to do well per keepers, and has gain over 600 lbs from last week. Eating and drinking well.
A: Resolving azotemia/inappetance.
P: Instructed keepers to start to decrease enemas from 20 minutes SID to 10 minutes SID starting tomorrow assuming his behavior
continues to trend upward. (KF)

19.May.2014
S: Continuing to exhibit normal behaviors and eat/drink well.
O: Lab results from UF from 5/15:
Blood film path review:
WBC count [Adviar]/æl N/A
WBC estimate//æl 7,200
Band heterophils/æl 0 0
Heterophils/æl 1,500 20%
Lymphocytes/æl 940 13%
Monocytes/æl 4,800 67%
Eosinophils/æl 0 0
Basophils/æl 0 0
Leukocyte morphology NSCF
Erythrocyte morphology NSCF
Platelets Adequate in number and morphology
Chemistries:
ALK PHOS 93 U/L
AST P-5-P 120 U/L
T BILIRUBI 0.3 mg/dL
T PROTEIN 8.2 g/dL
ALBUMIN 2.8 g/dL
GLOBULIN 5.4 g/dL
A/G RATIO 0.5
CALCIUM 11.0 mg/dL
PHOSPHORUS 4.0 mg/dL
CREATININE 1.3 mg/dL

 BUN 14 mg/dL
GLUCOSE 85 mg/dL
TRIGLYCERI
MAGNESIUM 2.6 mg/dL
GGT 62 U/L
CPK 205 U/L
SODIUM 130 mEq/L
POTASSIUM 4.1 mEq/L
CHLORIDE 90 mEq/L
TCO2 26 mEq/L
ANION GAP 18.1 mEq/L
Urinalysis:
COLLECTION = unk
COLOR = yellow
CLARITY = hazy
SP GRAVITY = 1.008
GLUCOSE = negative
KETONE = negative
BLOOD = negative
PH = 8.5
DS PROTEIN = negative
BILIRUBIN = negative
VOL. SPUN = 5
CONC. VOL. = 1
CASTS/LPF = negative
EPITH/LPF = 0-1 sq
WBC/HPF = negative
RBC/HPF = negative
BACTERIA = negative
URINE PROT = 12 mg/dL
URINE CREA = 7.8 mg/dL
PROT/CREAT = 1.5
URINE NA+ =
URINE K+ = 65.3 mEq/L
Fractional Excretion of Sodium:
Potassium: 2.6
A: Good resolution of azotemia and apparent cystitis, but elevated urinary Protein:creatinine along with some proteinuria,
suggesting possible glomerular disease.
Interpretation comments from consultant:
“Looking at the Blood film review, his white count is a bit low, but he has no band heterophils, which are indicative of systemic
inflammation/infection.
His alk phos continues to be on the high side, as is his GGT (don't think I commented on that with his last sample) and his albumin
is low. I don't like seeing albumin below 3 g/dL in elephants. Creatinine and BUN are good as are his electrolytes.
This urine has no blood cells in it, which is great. I don't know what to think of the hippuric acid crystals. They've never been
reported in elephants. Eles do produce some very weird looking struvites and calcium carbonate crystals that can be confused
with other types of crystals, so it would probably be worthwhile rechecking it, and not getting too worried it now. This
protein/creatinine ratio is high to me, and the urine protein is elevated as it was in the last sample.
When the rest of the results come in I will comment on those, but my feeling is that Packy's glomerular function is not ideal, but
you're making good headway on whatever caused the elevated creatinine and the blood cells in the urine. Assuming he had a
cystitis, your antibiotics were on target, and your rectal fluids were exactly right too. There's something going on with the liver,

 but because elephant livers are so different from other species, it's hard to be more specific. It will be interesting to see the SDH.
There is, unfortunately, no way to assess bile alcohols.
Although most of the TB drugs are metabolized in the liver, they're all excreted to some degree in the urine. I wonder if the
glomerular issues account for some of his problems he has with these drugs. Pyrazinamide, I know undergoes glomerular filtration;
I would have to check on the others.”
P: Continue weaning off of rectal fluids--is now receiving once daily for 10 minutes. Will decrease blood sampling to twice weekly,
and then return to normal weekly sampling. (TS)
20.May.2014
S: Packy continuing to act normally and eat/drink well. No problems with treatments. Still receiving once daily enema, for 10 min.,
as well as enrofloxacin twice daily. (TS)
21.May.2014
S: Packy continuing to act normally and eat/drink well. No problems with treatments. Still receiving once daily enema, for 10 min.,
as well as enrofloxacin twice daily. (TS)
22.May.2014
S: Packy still doing well, urinating copious amounts and eating and drinking well. Tomorrow will be the last day of receiving a single
10 min enema and enrofloxacin BID. Will discontinue both of these treatments starting 24 May. (TS)
23.May.2014
S: No change in Packy's condition--still doing well. He received a 5 min enema this morning (his last) and his last enrofloxacin dose.
P: Arranged for serum collection on Tuesday for MAPIA testing. Reviewing TB treatment to date and will formulate a plan for this
moving forward. (TS)
26.May.2014
S: Packy still doing very well. We are proceeding with blood collection tomorrow for MAPIA testing. (TS)
27.May.2014
S: Received preliminary report from NVSL that they are growing a small amount of material on one of three culture plates from
Tusko from trunk wash samples collected 3/27/14 and submitted with samples from the rest of the herd at the same time. This
growth was a single colony on one plate, and was replated to accelerate the growth after testing it with a gene probe, which
identified it as being in the M. tuberculosis complex (but it is not yet speciated). They will notify us when speciation is possible, and
I also requested genotyping and sensitivity testing of this organism.
Packy and Rama both had no growth on all three of their trunk wash samples from 3/27/14.
P: Pursuing additional testing. Will collect five trunk wash samples this next week (Tusko, Rama and Packy), and divide each into
three portions: 1/3 frozen and banked, 1/3 submitted to NVSL for culture, and 1/3 submitted to National Jewish lab for culture. At
NVSL, will also run a PCR on the trunk wash samples that is not validated for elephants but that they have been using for cattle. It
has high sensitivity and specificity, but will pick up any DNA fragment, not just living organisms. This test will be performed
alongside the cultures on all trunk wash samples for all three bulls.
O: CBC/chemistries (IDEXX): ALP 68, AST 31, GGT 34, BUN 18, Creat 1.0 (TS)

 1.Jun.2014
S: Given the improvement in Packy's condition and the lessening of overall concern, elected to put on hold arranging for an
external consultant visit. Will revisit this at a later date if deemed necessary. (TS)
2.Jun.2014
Problem: BIOLOGICAL SAMPLE REQUEST ; CULTURE (MYCOBACTERIAL) - trunk
S: Trunk wash collected for Mycobacterial culture. (EWL)
3.Jun.2014
Problem: BIOLOGICAL SAMPLE REQUEST ; CULTURE (MYCOBACTERIAL) - trunk
Performed 2/5 trunk washes on Packy this morning. (KF)
S: Results received from Chembio MAPIA/DPP for Packy. There is now an increase in apparent circulating antibodies to M.
tuberculosis antigens compared with the sample from October 2013. This is a poor prognostic indicator and correlates with his less
than successful treatment course.
Comments from Chembio: "Attached please find MAPIA results obtained with sera form your elephants. For Rama, Packy and
Tusko, we have included their earlier samples for comparison. As you can see, the antibody levels in Rama continue declining good news - reflecting successful treatment so far. This does not seem to be the case for Packy though, as the last serum shows
further increase of the antibody response, particularly to CFP10/ESAT-6 antigen, which is not a good sign. Tusko did not show any
reactivity in MAPIA, in contrast to DPP VetTB. As I recall, MAPIA was not clearly positive (borderline/suspect) last year. To confirm
this result, we will try to re-run Tusko's samples when we do MAPIA next time." (TS)
4.Jun.2014
Problem: BIOLOGICAL SAMPLE REQUEST; CULTURE (MYCOBACTERIAL) - trunk
Performed 3/5 trunk washes today on Packy. (KF)
5.Jun.2014
Problem: BIOLOGICAL SAMPLE REQUEST; CULTURE (MYCOBACTERIAL) – trunk
Performed 4/5 trunk washes today. Samples will be split to be submitted to several labs for testing. (KF)
6.Jun.2014
Problem: BIOLOGICAL SAMPLE REQUEST; CULTURE (MYCOBACTERIAL) - trunk
O: Received speciation of the mycobacterial organism recovered from 1 out of 3 trunk wash samples from Tusko on 3/27/14, by
DNA probe = M. tuberculosis. Due to the very small amount of material recovered from Tusko (they commented that this was on
the very edge of detection by culture, in contrast to our previous positives), this requires further growth before being able to
speciate by normal methodology--this will be finished in 10-14 days from now. We will formulate a plan for treatment of Tusko to
begin ASAP, and will re-initiate treatments for Packy as well.
P: Performed 5 of 5 trunk wash collections today. As mentioned previously, all 5 samples collected this week will be split into three
portions--1/3 submitted to NVSL for MB culture and PCR, 1/3 submitted to National Jewish Health for AFS and MB culture, and 1/3
saved frozen. (TS)
11.Jun.2014

 O: AFS results from National Jewish Health: All five trunk wash samples (6/2-6/6) were negative for acid-fast bacilli. Will report
further AFS results at 1, 3, 6, and 8 weeks (the latter only reported if positive). (TS)

13.Jun.2014
S/P: Decided on treatment plan for Packy to start ASAP. Will start him on rectal PZA at 30 mg/kg (163 g) SID, and after 1-2 weeks of
successful treatment introduce INH rectally at 2.5 mg/kg (13.5 g) EOD for 2 weeks, then 5.0 mg/kg (27 g) EOD for 2 weeks, then 10
mg/kg (54 mg) EOD thereafter. Will pursue training for capsule administration and revisit Rifampin orally, at 10 mg/kg (54 g) SID.
O: CBC/chemistries (IDEXX): ALP 65, AST 16, GGT 21, BUN 16, Creat 1.2 (TS)
16.Jun.2014
S: Packy is eating but a reduced amount. His weight is 12,110 lbs as of 6/13/14. He has entered musth again, supported by his
recent testosterone level. Will need to watch appetite and behavior closely, and monitor blood chemistries as previous.
O: Testosterone from 6/12/14 = 12.67 (elevated).
NVSL Mycobacterium tuberculosis PCR was negative on five of five trunk wash samples obtained 6/2-6/6. These five samples were
also set up for MB culture.
P: Restarted Packy on pyrazinamide this morning as described below. Will monitor weight and appetite, and proceed with
treatment plan described on 6/13/14.
Rx: PYRAZINAMIDE 163 gm rectally SID for 90 days. (TS)
17.Jun.2014
Problem: BIOLOGICAL SAMPLE REQUEST; BLOOD COLLECTION
O: CBC/chemistry results from blood collected today:
ALP 65
AST 15
CK 111
GGT 20
BUN 14
Creat 1.1
A: No creatinine or hepatic enzyme elevations.
P: Continue with treatment and monitor lab work to assess response to treatment and/or musth. (TS)
20.Jun.2014
S: Packy is continuing to eat a reduced amount of hay, but consuming all produce items offered. There has been no change in his
demeanor or cooperativity. Continuing once daily PZA treatments as were begun on
6/16. (TS)
24.Jun.2014
O: CBC/chemistries (IDEXX): ALP 58, AST 18, GGT 17, BUN 15, Creat 1.2
A: No chemistry alterations due to medications thus far. (TS)
27.Jun.2014

 S/P: Packy's appetite increased some compared with the last entry, but still eating a reduced amount of hay. He continues eating
produce items very well. His stools are soft and moist, but still formed. He is otherwise acting normally, but is still not laying down
and is reluctant to do a full stretch when requested to. He is still receiving daily PZA and we are planning to start INH as described
(13.5 g q 48 hr) on 6/28/14. (TS)
28.Jun.2014
Problem: TWO DRUG TB TREATMENT STARTED
Rx: ISONIAZID 13.5 gm rectally q48h for 14 days. (TS)
30.Jun.2014
S: this elephant was started back on isoniozide and pyrazinamide together yesterday. He was administered medications rectally by
elephant keepers and vet staff. (KA)
3.Jul.2014
S: Packy is continuing to receive PZA and INH, the latter at the initial dose. His appetite has improved, with increased hay
consumption reported by keepers. His stools have been somewhat soft.
A: Tolerating INH thus far, at 13.5 g q 48 hr.
P: Continue as planned. Will plan to assess drug levels of PZA and INH prior to the next INH dose increase. (TS)
11.Jul.2014
S: Created plan for the near future for Packy's treatment course:
1. We will collect blood for INH and PZA drug levels on Saturday 7/12/14, at 1.0, 1.5, and 2.0 hr post-administration.
2. Will start RIF at 2.5 mg/kg PO SID on Sunday, 7/13/14, for 3 days.
3. Will increase INH dose to 27.0 g per rectum EOD for 2 weeks, starting Monday, 7/14/14.
4. Will increase RIF to 5.0 mg/kg PO SID on Wednesday, 7/16/14, for 4 days.
5. We will collect blood for INH and PZA drug levels on Saturday 7/19/14, at 1.0, 1.5, and 2.0 hr post-administration, and for RIF
drug levels at 2.0, 3.0, and 4.0 hr post-administration.
6. Will increase the RIF dose to 10 mg/kg PO SID on Sunday, 7/20/14.
7. We will collect blood for INH and PZA drug levels on Saturday 7/26/14, at 1.0, 1.5, and 2.0 hr post-administration, and for RIF
drug levels at 2.0, 3.0, and 4.0 hr post-administration.
8. Will increase the INH dose to 55 g per rectum EOD, on Monday, 7/28/14. (TS)

12.Jul.2014
P: Drug blood levels for INH and PZA drawn today at 60min, 90min, and 120min post rectal administration of medication. (KF)
12.Jul.2014
Rx: ISONIAZID 27 gm rectally q48h for 14 days.

 Note: this dose increase will take effect on 7/14/14, not 7/12. (TS)
13.Jul.2014
Rx: RIFAMPIN 14 gm PO SID for 3 days. (TS)
16.Jul.2014
Rx: RIFAMPIN 28 gm PO SID for 4 days. (TS)

17.Jul.2014
O: UF Infectious Disease PKA Laboratory:
ISONIAZID plasma concentrations (mcg/ml) from 7/12/14:
Drug administered - 11:01
Sample 1 - 12:00 pm = 1.51
Sample 2 - 12:30 pm = 1.15
Sample 3 - 1:00 pm = 0.97
Recommended concentration is 3-5 mcg/ml 2 hr after oral dose
PYRAZINAMIDE plasma concentrations (mcg/ml) from 7/12/14:
Drug administered - 11:01 am
Sample 1 - 12:00 pm = 19.32
Sample 2 - 12:30 pm = 17.29
Sample 3 - 1:00 pm = 16.59
Recommended concentration is 20-60 mcg/ml 2 hr after oral dose
A: Continuing to increase isoniazid dosing--will continue increasing as planned. Will consider slight increase in PZA dose. (TS)
19.Jul.2014
O: Blood collected 2hr, 4hr, and 6hr post rifampin for pharmacokentics. (KF)
20.Jul.2014
Rx: RIFAMPIN 56 gm PO SID for 60 days. (TS)

26.Jul.2014
Rx: ISONIAZID 56 gm rectally q48h until further notice.
Note: this dose increase will take place on 7/28/14. (TS)
28.Jul.2014
O: MB culture results from National Jewish Health: All five trunk wash samples (6/2-6/6) are negative for Mycobacteria culture at 6
weeks. This is a final report, with additional reporting only if positive growth in the next two weeks. (TS)

 30.Jul.2014
P: Drug blood levels for INH and PZA drawn today at 60 min, 90 min, and 120 min post-rectal administration of medications. Also,
blood levels for RIF were drawn at 120 min, 180 min, and 240 min post-oral administration. (TS)

3.Aug.2014
O: NVSL reports that the trunk wash cultures collected on 3/18, 3/19 and 3/20/2014 were negative for mycobacterial growth on
culture.
Genetic analysis of the original isolate from Packy showed it to be very closely related to the isolate from Tusko (A50080) - close
enough to be considered the same organism. The isolate from Rama (83009) has not been sequenced yet. (MVF)
5.Aug.2014
S: Packy did not eat any hay overnight and was difficult to load this morning. Would not take rifampin (took 10%) but was BAR
otherwise.
Blood drawn for CBC/chem.
A: Anorexia - possible drug reaction (INH most likely), musth, other illness or problem.
P: Packy was due for an INH dose today but it was skipped due to anorexia. Will reevaluate tomorrow and dose then if he is back
on food. (MVF)
6.Aug.2014
S: Packy began eating hay last night but did not eat as much as normal (about 50% normal). He is shifting better today although he
is still not food motivated nor taking his oral rifampin.
Today was scheduled to be a pyrazinamide-only day so it was kept the same and he was not given INH. If he continues to improve
as he has we will re-start the INH tomorrow as per schedule (so he will have missed only one dose).
P: Recheck tomorrow. (MVF)
7.Aug.2014
S: Packy is BAR and ate very well last night. Normal manure. Medicated with PZA today and did not give INH. RIF dosing is still
inconsistent and difficult.
P: Will review PK data and see if a change in INH dosing is warranted. Will discontinue RIF dosing due to laborious and inconsistent
dosing. (MVF)

8.Aug.2014
S: Packy is BAR and eating well today. Dosed with rectal PZA in morning.
Reviewed pharmacology data and discussed chemotherapy plan with experienced pharmacologist with elephant experience.
P: The current Rx plan is:
1. Continue with INH but reduce dose to 13.5g and increase frequency to SID. We have PK data to show that this was a successful
(successful = blood levels >3 mcg/ml) dose previously.
2. Develop plan to start on rectal or oral levofloxacin.

 3. Plan to discontinue pyrazinamide after levofloxacin is successfully initiated (and confirmed by PK data).
4. Discontinue rifampin as of today due to poor acceptance.
Will also look into creating an INH suppository to simplify treatment. (MVF)
9.Aug.2014
Problem: PHARMACOKINETIC TRIAL
S: Packy remains BAR and eating well. Dosed with rectal PZA and new lower INH dose (see below) and took serial blood samples to
determine serum levels of the medications.
Blood samples for INH determination were taken at 15, 30, 45 and 60 minutes after rectal administration. Sample for PZA
determination were taken at 60, 90 and 120 minutes. Plasma was separated and frozen at -80C until they are shipped out for
analysis.
P: For now we are planning to Rx with SID dosing of PZA and INH.
Rx: ISONIAZID 13.5 gm rectally SID until further notice (MVF)
26.Aug.2014
O: PK data from trial run for PZA and INH on 8/9/14 showed inadequate levels of both PZA and INH (PZA max 11.41mcg/ml @ 60
min; INH max 1.21mcg/ml @ 30 and 45 min).
P: Will discuss with vet crew and consider changing method of administration and/or dosage. Plan anon. (MVF)
29.Aug.2014
Problem: BIOLOGICAL SAMPLE REQUEST; CULTURE (MYCOBACTERIAL) - trunk
S: Performed first of a scheduled three daily trunk washes for culture for Mycobacterium spp. Standard technique using 60 ml
sterile saline (30 ml per nostril); trunk up for thirty seconds; forcible exhalation into a gallon plastic bag. Samples transferred to
plastic sample bottles and then frozen at -80C pending shipment to NVSL for culture.
P: Will alter sampling frequency for mycobacterial culture: positive animals on treatment will be cultured once a month and
negative animals will be cultured q 3 months. (MVF)
30.Aug.2014
Problem: CULTURE (MYCOBACTERIAL) - trunk
S: Performed second of a schedule three daily trunk washes for mycobacterial culture. Samples frozen at -80C pending shipment to
NVSL for culture.
P: Collect one more trunk wash tomorrow to complete the series. (MVF)
31.Aug.2014
Problem: CULTURE (MYCOBACTERIAL) - trunk
S: Performed third of a schedule three daily trunk washes for mycobacterial culture. Samples frozen at -80C pending shipment to
NVSL for culture.
P: Trunk wash complete. Cultures pending. (KF)
3.Sep.2014
Problem: PHARMACOKINETIC TRIAL

 S: Performed recheck PK trial for isoniazid and pyrazinamide using current doses. For this trial all drugs were suspended in approx.
400 ml and given via one syringe.
P: Awaiting results. If the values are low again we will try diluting in to 800 ml and giving via two syringes prior to increasing dose.
(MVF)
13.Sep.2014
S: Results of most recent PK studies show that both PZA and INH are below optimal levels. Increased doses incrementally to try to
hit minimum desired levels.
P: New doses to start tomorrow. Will need to run new PK studies to evaluate to confirm minimum levels have been met. (MVF)
14.Sep.2014
Rx: ISONIAZID 19 gm rectally SID until further notice.
Rx: PYRAZINAMIDE 217 gm rectally SID until further notice. (MVF)
16.Sep.2014
O: Lab work from last week (9/12) shows slightly increased GGT and monocytosis. Serum amyloid A was well within the normal
range.
A: The GGT on this animal has fluctuated and it typically over the ISIS normal range. It is toward the lower end of his typical value.
Monoctosis is probably an indicator of chronic infection (Mtb).
P: Will monitor regularly. (MVF)
20.Sep.2014
Problem: ulcerative dermatitis - GLUTEAL REGION (RIGHT) (Confirmed)
S: Examined skin following keeper report of abnormal skin on the right rump area near his hip. Exam showed erosive dermatitis
with macerated tissues and multiple coalescing ulcers and erosions. The affected area is oval and roughly 36cm by 30 cm and is
located over his Rt gluteal area. The erosions leave islands of skin which are rimmed with white epithelium (macerated). The
eroded areas are covered with white material that looks to be macerated epithelium. A scraping was done and examined
microscopically. The slide consisted of keratinaceous debris, some pyknotic nuclei and a nearly monomorphic bacterial
population of cocci in pairs. There were fewer large cocci in sets of 4. No yeast or hyphae seen. No signs of bacterial ghosts. No
inflammatory cells observed.
Discussion with keepers revealed that Packy is spending a lot of time in the pool overnight and is often seen sleeping in the pool
when they arrive in the AM. His Rt gluteal area is often pressed up against the rock work in the pool.
A: Ulcerative dermatitis, Rt gluteal region. Possible pool use related.
P: Will Rx conservatively at first. Will start on oral phenylbutazone in case his pool use is related to joint pain. Will also have
keepers scrub the affected area in the AM with Nolvasan Scrub and then coat it with Silvadene cream. If the lesion fails to respond
or gets worse will pursue Bx and culture and work with curator and keepers to come up with a way to limit his access to the pool
but still allow him outside and give him a comfortable place to rest.
Rx: PHENYLBUTAZONE 18.0 gm PO q48h for 10 doses.
Rx: SILVER SULFADIAZINE CREAM 5.0 ml topically SID for 21 days. (MVF)
21.Sep.2014

 Problem: ulcerative dermatitis - GLUTEAL REGION (RIGHT) (Confirmed)
S/O: Recheck of Packy's wound today. Ulcers appear stable, however the area of skin affected by the ulcers feels generally more
firm to the touch. This could be potentially from inflammation in the epidermis/dermal layer, or skin that is about to ulcerate.
Wound was cleaned with chlorohexadine, rinsed with the hose and then SSD was applied, per Rx. Packy was very tolerant of the
procedure.
A: Skin ulceration
P: Continue conservative treatment. If no resolution, consider skin biopsies. (KF)
25.Sep.2014
Problem: ulcerative dermatitis - GLUTEAL REGION (RIGHT) (Confirmed) CULTURE (MYCOBACTERIAL) -trunk
S: Performed first of three scheduled routine trunk washes for mycobacterial culture. 60 ml of saline was instilled into the trunk
(30 ml per nostril); the trunk was held up for 30 seconds; saline was collected into a zip-loc bag after forcable exhalation. The
sample was frozen at -80C pending shipment to lab for culture.
P: Perform two more cultures for this series. (MVF)
26.Sep.2014
Problem: ulcerative dermatitis - GLUTEAL REGION (RIGHT) (Confirmed); CULTURE (MYCOBACTERIAL) -trunk
S: Performed second of three scheduled routine trunk washes for mycobacterial culture.
Rechecked Rt gluteal wounds/skin lesion. The lesions have not progressed since first noticed. They are now dry and the small
islands of intact epidermis appear stable. Scrubbed with nolvasan scrub and applied silvadene cream.
Keepers noted that there are no obvious changes in his behavior (resting or otherwise) since starting on phenylbutazone.
A: Skin lesions may be due to a one time event rather than an on-going behavioral issue as originally thought.
P: Perform one more culture for this series. Advised keepers to complete Rx for phenylbutazone and be especially watchful when it
is stopped as changes may be more apparent when it is discontinued compared to when it is started. (MVF)
27.Sep.2014
Problem: ulcerative dermatitis - GLUTEAL REGION (RIGHT) (Confirmed); CULTURE (MYCOBACTERIAL) -trunk
S: Collected final trunk wash for culture for this monthly series. Rechecked Rt gluteal skin lesion and the lesion is clean and dry and
appears little changed compared to yesterday.
P: Recheck skin lesion in several days. Re-culture for Mycobacteria in approx. 1 month. (MVF)
2.Oct.2014
Problem: ulcerative dermatitis - GLUTEAL REGION (RIGHT) (Confirmed) PHARMACOKINETIC TRIAL
S: Skin lesions on Rt gluteal area appear essentially unchanged. Will continue to observe. Drew serial blood samples for
pharmacokinetics to check serum levels of isoniazid and pyrazinamide. (MVF)
10.Oct.2014
Problem: ulcerative dermatitis - GLUTEAL REGION (RIGHT) (Confirmed)
S: Packy has a new abrasion cranial-lateral to the heal abrasions on the right thigh.

 P: Asked keepers to scrub this area, as previously described for these abrasions. (KF)
14.Oct.2014
S/A: Review of Packy's latest blood work from yesterday shows hemoconcentration and markedly increased AST, bilirubin and
GGT. Additionally the creatinine is up as well. Keepers have not noticed signs of illness although he is showing typical signs of
musth including temporal drainage, urinary incontinence, aggression and partial anorexia. Because of these typical musth signs
they may have missed signs of illness.
P: The elevations are high enough to cause concern about hepatotixicity secondary to anti-TB antibiotics. Therefore will
discontinue antibiotics. Keepers to give three 15 minute enemas today with warm water to superhydrate him. Recheck tomorrow.
(MVF)
15.Oct.2014
S/O: Univ of Florida lab reports the following PK data from samples drawn on 2 October showed the following:
Isoniazid:
5 min: 0.78 mcg/mL
10 min: 1.04 mcg/mL
15 min: 1.56 mcg/mL
20 min: 2.16 mcg/mL

Pyrazinamide:
32 min: 11.45 mcg/mL
47 min: 17.94 mcg/mL
60 min: 17.35 mcg/mL
32 min: 2.46 mcg/mL

Today Packy remains BAR. He has been seen urinating large volumes (normal) and was given two 15 min enemas for suppl.
hydration today.
A: Biochemically this looks like a combination of musth and intolerance of oral anti-TB meds. We did not achieve target ranges for
either TB drug during the sampling periods.
P: Continue to hold off TB meds and recheck CBC/chem tomorrow. (MVF)
16.Oct.2014
S: Packy is BAR. performed two enemas today. He is still not eating but is drinking water. Showing overt signs of musth aggressive, not dropping penis when he urinates and has copious temporal drainage. Submitted blood for recheck CBC and chem
panel.
P: Continue with BID warm water enemas. (MVF)

17.Oct.2014
S/A: Lab work from yesterday shows improvement of some parameters compared to his last lab work (10/14) and no values have
worsened. Notably the signs of hemoconcentration have improved and HCT, BUN, TP, and PO4 have all decreased significantly.
Creatinine is down slightly but not by as much as other parameters. Liver related values show some improvement. AST has
decreased by half from 442 to 211 (usually in the mid to high 20s). ALP is down slightly (119 to 107). GGT remains elevated (46,
was 45 on last check and usually runs in the mid-teens). Bilirubin is increased at 2.0 (was 1.2 on 10/14 and usually runs 0.1 -0.2).
Urine submitted for UA shows bilirubinuria.
Packy is otherwise BAR but musthy - not eating, has temporal drainage and is aggressive. He is eating very little but drinking and
urinating.
A: Hepatosis probably secondary to antituberculin medications. Probable musth

 P: Continue with BID warm water enemas. Recheck blood work in a couple of days. (MVF)
18.Oct.2014
S: Packy is BAR. Eating browse in small amounts now. Bled for CBC and chem panel recheck. Continuing with BID 15 min long
enemas. Still showing musth signs although keepers noted that his penis dropped partially while he urinated last night which is a
sign that he may be coming out of musth.
Skin lesion on the Rt gluteal area has healed.
A: Possible combination of musth and hepatotoxicity secondary to tuberculosis chemotherapeutics.
P: Continue with BID enemas until creatinine comes down or he starts eating on his own. (MVF)

19.Oct.2014
S: Packy remains about the same - eating a little browse but not much else. He remains BAR and aggressive. Did not see him
urinate today. Blood work from yesterday is essentially static compared to most recent samples. Hepatic enzyme and bilirubin
elevations are about the same and creatinine is similar. MCV declined to a fairly low level that has not been seen since earlier this
year. Electrolytes are declining a bit.
A: Still presume that he has a combination of hepatotoxicity from his medications and musth or pre-musth.
P: Continue to withhold TB medications and monitor blood work every other day. Asked keepers to give him 2 cups of trace
mineral salt SID. He seemed interested in the salt today and ate some of it immediately after it was offered this AM.
Rx: TRACE MINERAL SALT 2 cups PO SID until further notice. (MVF)

21.Oct.2014
Problem: BIOLOGICAL SAMPLE REQUEST; CULTURE (MYCOBACTERIAL) -trunk
S: Packy is BAR today and eating some bamboo. Keepers are continuing to perform BID enemas. First of three trunk washes
performed today.
O: Packy's blood work from yesterday is slightly improved. Kidney and liver values remain elevated, but are decreasing when
compared to the levels from blood collected last week.
A: TB medication reaction
P: Continue enemas as planned. Send trunk wash samples out for routine cultures. (KF)
22.Oct.2014
Problem: CULTURE (MYCOBACTERIAL) -trunk
S: Packy is BAR and ate much better last night. Estimates are that he ate 7-8 flakes of hay. Blood work from Monday (10/20)
showed continuing decrease in most enzymes and creatinine but GGT and bilirubins are still high.
Performed second of three scheduled trunk washes for Mycobacteria spp. culture. Used standard technique of instilling 30 ml
sterile saline into each nostril, having animal hold trunk elevated for 30 seconds and then expelling the solution into a gallon ziploc bag. All samples transferred to sterile vials and frozen at -80C pending shipment to lab.
A: Chem panel shows signs of continued cholestasis.

 P: One more culture tomorrow. Will discontinue the BID enemas as of today now that he is eating and recheck chem panel in a
couple of days to see what the creatinine is doing without the enemas. (MVF)
23.Oct.2014
Problem: CULTURE (MYCOBACTERIAL) - trunk
S: Packy is BAR and continuing to eat overnight. Today he passed the first significant quantity of manure since this began. The
manure was normal in appearance. Blood work from yesterday shows all values of concern (AST, alk phos, bilirubin, creatinine)
decreasing except fot GGT which remains stable and elevated.
Performed third of three scheduled routine trunk washes for M tb culture. Used standard technique of instilling 30 ml saline per
nostril, elevating trunk for 30 seconds then expelling into a gallon zip-loc. All samples frozen at -80C pending shipment to lab for
culture.
A: Overall improving condition though still probably has cholestasis.
P: Continue to monitor CBC/chem every other day. Discontinued enemas (yesterday). Females will be cultured again in approx. 3
months. Males will be cultured again at the beginning of next month to get them back on their monthly schedule. (MVF)
24.Oct.2014
S: Continued improvement. Passed two small piles of normal manure and ate overnight.
P: Will recheck blood work (CBC/chemistry) tomorrow. (MVF)
25.Oct.2014
S: Packy remains BAR. He is showing signs of musth with heavy temporal drainage. Ate a small amount of hay overnight and
bamboo that was offered during the day. Did not eat produce or pelleted feed offered today. Blood drawn to recheck CBC and
chemistry panel to monitor hepatic enzymes (GGT esp) and bilirubin.
25.Oct.2014
Recalculated drug doses for when Packy is restarted on anti-TB chemotherapy. Will discontinue use of INH and go with a
combination of rectal levofloxacin and pyrazinamide. Pyrazinamide dose will be increased to 300 grams per dose (58 mg/kg - based
on last PK study) and the levofloxacin will be dosed at 83 grams per dose (16mg/kg).
Deactivated dermatitis of Rt gluteal region as a problem because it has resolved completely.
A: Hepatopathy presumed due to anti-TB antibiotics (INH esp).
P: Continue to monitor closely. Resume rectal fluids if creatinine starts going up again. (MVF)
30.Oct.2014
Problem: BIOLOGICAL SAMPLE REQUEST ; CULTURE (MYCOBACTERIAL) - trunk
S: Performed routine trunk wash for TB monitoring using standard technique (30 ml sterile saline per nostril). This set of cultures is
coming close on the heels of the last set of cultures in order to get the animals caught up and back on schedule with monthly trunk
washes that will occur near the beginning of each month.
Most recent blood work shows continuing resolution of abnormal values. The GGT is still staying high although it has come down
slightly. The Bilirubin is nearly normal now. Packy is eatng normally now.

 P: Sample frozen at -80C pending shipment. Collect two more samples to complete this series. (MVF)
31.Oct.2014
Problem: CULTURE (MYCOBACTERIAL) - trunk
S: Performed second of three scheduled monthly trunk washes for TB surveillance.
Packy is doing well overall and is eating normally and producing normal amounts of normal appearing manure.
P: Reduced blood monitoring to once a week again since the GGT is changing so slowly and the other values are near normal
ranges. Collect one more TB trunk wash sample tomorrow. (MVF)
1.Nov.2014
Problem: CULTURE (MYCOBACTERIAL) - trunk
S: Collected final trunk wash of the series of three for TB monitoring.
P: Cultures pending. Culture again in approx. 30 days. (MVF)
15.Nov.2014
O: GGT is continuing to decrease.
P: Continue to monitor. Will resume TB chemotherapy if the trend continues into next week. (MVF)