Gibbons & Great Apes

Question 1

What are the six species of great apes?

What are their scientific names?

Answer 1

Question 2

What are the unique features of apes?

What is their dental formula?

What is unique anatomy to orangutans?

Answer 2

• No tails
• Dental formula: I 2/2 C 1/1 PM 2/2 M 3/3 = 32
• Laryngeal sacs - expand with age into pectoral, clavicular, and axillary regions
• Mature male orangutans: extend around mandible towards ears and cheeks and along thoracic wall
• Cheek pads (flanges): only male orangutans, fat and fibrous tissue

Question 3

Describe teh general diet for great apes?

What vitamin supplementation do they reuquire?

Describe routine preventative examinations for great apes?

What testing would you recommend be done? How frequently should that be accomplished?

Answer 3

Diet (Fowler 8)

• Primarily herbivorous: high-fiber, low-sugar (wild-type diet)
• Require exogenous vitamin C
• ME (kcal) = 100 x BW ^0.75

Preventive Medicine (Fowler 8)

• WEAR PPE
• Viruses easily transmitted between humans and apes (colds and influenza)
• Zoonotic GI concerns: Salmonella, Campylobacter, Yersinia, Shigella
  
  • Ebola virus: large mortality in wild African great ape populations
• Preship: CBC, Chem, fecal parasite exam and bacterial cultures, Tb testing
• +/- total cholesterol, thyroid hormone, screening for viral/bacterial agents, CV eval, orangutans resp eval
• Quarantine: 30-90d with 1-2 PE: CBC, chem, Tb testing, infectious disease screening, minimum 3 fecal exams, bacterial fecal cultures

Question 4

What vaccinations should be considered for great apes?

What is the dosing schedule like?

Answer 4

Question 5

Describe the anatomy of apes that can make anesthesia difficult?

Why is intubation challenging?

What vascular access is available?

How long should apes be fasted?

Answer 5

Anatomy

• Laryngeal air sacs (most extensive gorillas and orangutans)
• Short tracheas
• Excessive caudal pharyngeal tissue, thick tongues, long flaccid soft palates
• Avoid darting in genital tumescence - very vascular and friable
• Venous access: femoral, saphenous (posterior lower leg), cephalic

Fast and water withheld 12-24 hours prior to anesthesia

Question 6

What preanesthetic medications should be considered prior to induction of anesthesia in a great ape?

What oral sedatives have been used?

What are some tricks for increasing absorption of these oral medications?

Answer 6

Preanesthetics

• Metoclopramide (0.4 mg/kg) PO to prevent emesis prior to oral anesthetics
• Atropine anecdotally to control hypersalivation and/or bradycardia
• Diazepam PO 2 hr prior to induction or midazolam 0.7-1.2 mg/kg PO in orange juice (chimps and orangutans - effects ranged from slight to marked)
• Fentanyl lollipop 10-15 ug/kg *requires training 4-6 wk prior
  
  • orangutans and gorillas accepted lollipop and had adequate sedation
  • Plasma concentrations supported transmucosal absorption
  • chimps had suboptimal compliance and no visible sedation - might need higher dose
• Zuclopenthixol (neuroleptic) PO BID for prolonged travel - gorillas calm and maintained appetite
• Oral transmucosal carfentanil premed: profound sedation in chimps in 25 min
  
  • Then induction with Telazol and naltrexone (100 x carfentanil dose)
  • Primary side effect: respiratory depression managed by naltrexone
  • Side effect of facial pruritis in some
  • Oral carfentanil in fruit: lighter sedation likely due to poor gastric absorption compared to transmucosal
• Medetomidine transmucosal in marshmallow creme and induction with ketamine - variable effects

Question 7

Describe the process for intubating great apes.

What are the pros and cons of using a laryngeal mask airway?

Answer 7

Intubation

• Best in dorsal recumbency, head extended off the table
• Prone to hypersalivation and laryngospasm, especially high dose ketamine
• Lidocaine on glottis recommended
• Cuffed tube, auscult both sides for bronchial intubation
• Laryngeal mask airway (LMA): effective in western lowland gorilla
  
  • Arterial oxygen significantly greater in LMAs than endotracheal - authors suspect bronchial intubation in that study
  • LMA does not protect against aspiration

Question 8

Describe monitoring of anesthesia in a great ape.

What parameters should you be concerned about? Where can you aquire blood for arterial blood gases?

What is the recovery of agreat ape like? What housing reocmmendations should be made?

Answer 8

Monitoring

• BP reported to increase with age in chimps
• Chimps given telazol: VPCs most common arrhythmias, also APCs, 2nd degree AV block, RBBB, trigeminy, and accelerated idioventricular rhythm
• Higher incidence of arrhythmias in males with structural heart disease
• Frequent arterial blood gases
  
  • Dorsal pedal A, tibial or femoral aa.

Recovery

• Can be sudden once reversed
• Recover in isolation to avoid conspecific trauma
• If separated for more than a few hours, may see behavioral problems with reintroduction

Question 9

What are some of the most common complications of anesthesia in great apes?

What age group has more complications?

Why is it dificult to maintain an airway?

What other respiratory concerns are common?

Answer 9

Complications

• 30-fold increase in risk of peri-anesthetic mortality in animals >30 yr compared to 10-3 yrs, increased risk with pre-anesthetic illness
• Overall peri-anesthetic mortality 1.35%
• 80% of deaths in postanesthetic period
• Difficulty maintaining airway - primary problem reported in San Diego zoo retrospective
  
  • Excessive salivation and upper airway obstruction from pharyngeal tissue
• Risk of fatal pneumonia from aspiration of laryngeal air sac infection (bact or yeast)
• Fatal acute respiratory distress syndrome: negative pressure pulmonary edema in orangutans under Telazol
  
  • Speculated from acute upper respiratory obstruction due to head flexion

Question 10

Discuss some of the most common nutritional issues of great apes.

Why is regurgitation and reingestion an issue? How can it be mitigated?

How does protein defieciency in orphaned gorillas typically present?

What are the four parameters that compose metabolic syndrome?

Obesity in great apes is linked to what other disorders?

Answer 10

1. Nutritional
   
   1. Regurgitation and reingestion in zoo-housed great apes
      
      1. Mitigate by increasing dietary fiber, browse, and opportunities to feed
      2. Can produce damage to dental enamel
   2. Protein deficiency in orphaned gorillas:
      
      1. Alopecia on back and legs
      2. Hair color change to gray/brown
      3. Poor growth, weight loss
      4. Normocytic, normochromic anemia
      5. Hypoalbuminemia
   3. Metabolic syndrome = increased abdominal fat, fasting BG, triglycerides, and blood pressure
      
      1. Described in female chimpanzee but presumed to exist in other apes
   4. Obesity is linked to hypothyroidism, hypertensive heart disease, and stroke in adult orangutans
   5. Iron overload in zoo-housed gorillas, orangutans, and gibbons
      
      1. My have orange/brown duodenal mucosa
      2. Diets low in iron and high in vitamin C are risk factors for iron overload

Question 11

What are the two most common congenital defects of great apes?

Answer 11

1. Congenital/Genetic
   
   1. Syndactyly (interdigital webbing) is the most common congenital defect in eastern gorillas
      
      1. Webbing between digit 2 and 3 is normal in siamang
   2. Linear Enamel Hypoplasia (LEH) is the most common dental anomaly in captive apes
      
      1. Enamelogenesis is disrupted by stressors (e.g. climactic events that disrupt food availability)
      2. Susceptibility: Orangutan >> gorillas > chimpanzees

Question 12

Cardiovascular pathology is common in great apes.

What is the most common lesion? Which demographic groups is it most common in?

What species is most predisposed to aortic dissection? How do these lesion appear? How do those animals typiclaly appear clinically?

Atherosclerosis occurs most commonly in what locations?

What species often has valvular disease?

Answer 12

1. Age-Related/Degenerative
   
   1. Cardiovascular disease most common lesions across great apes:
      
      1. Dissecting myocardial fibrosis
         
         1. Common in adult, male gorillas and chimpanzees
         2. Pale streaks/patches = fibrosis / steatosis
         3. Often seen with left ventricular hypertrophy (LVH)
      2. Female gorillas, orangutans, and some chimps have fibrosis without LVH
      3. Evidence of myocardial infarction (large blocks of fibrosis) is rare
      4. Cause is heterogeneous but may be related to hypertension
      5. Inflammation is rare is seen associated with ECMV, Coxsackie virus, and trypanosomes
   2. Thoracic aortic dissection
      
      1. Gorillas >> bonobos >>>>>>> chimpanzees, orangutans
      2. Typically, starts at ascending aorta (Debakey type II, Stanford type A)
      3. May have a double-barreled aorta with blood in lumen and mural defect
      4. Sudden death from hemopericardium with tamponade, adventitial hemorrhage that disrupts conduction pathways, or hemothorax
   3. Atherosclerosis
      
      1. Most common locations: abdominal aorta, iliac arteries, and aortic arch
      2. Coronary atherosclerosis only in older apes who had bad husbandry
      3. Fatty streaks to raised, ulcerated plaques
   4. Valvular disease
      
      1. Gorillas often have mild mitral regurgitation
      2. Mitral valve endocardiosis is seen geriatric great apes
      3. Vegetative endocarditis most commonly affects aortic and mitral valves in gorillas

Question 13

What is the most common renal disease of great apes?

What is cardiorenal syndrome? What species does it occur with? What are the typical lesions?

Answer 13

1. Renal disease
   
   1. Common in older apes
   2. Interstitial nephritis is most common but glomerular disease is also reported
   3. _Cardiorenal syndrome in chimpanzee_s = glomerulosclerosis and tubulointerstitial fibrosis associated with myocardial fibrosis
      
      1. Chronic renal disease increases resistance
      2. Heart disease can cause poor renal perfusion or primary hypertension

Question 14

Describe some of the more common reproductive pathologies of great apes.

What are two common conditions in males?

What are teh four most common lesions in females?

Reproductive malignancies are common in females of which species?

What are some complications from pregnancy in this group?

Answer 14

• Reproductive
  
  • Testicular hypoplasia is common in gorillas
  • Benign prostatic hyperplasia has been reported in older chimpanzees
  • Most common female reproductive lesions:
    
    • Ovarian atrophy
    • Uterine leiomyoma - Common in chimpanzees
    • Adenomyosis - True endometriosis is rare
    • Endometrial atrophy
  • Female repro malignancies are common in gorillas (cervical/uterine/ovarian adenocarcinoma, uterine leiomyosarcoma)
  • Pregnancy
    
    • Placental abruption and previa → vaginal bleeding, dystocia, death
    • Ascending infection in gorillas because they allow copulation throughout gestation
    • Twinning is common in chimpanzees
    • Infants die from trauma (e.g. infanticide in gorillas) and prematurity

Question 15

What type of virus in monkey pox?

How is it transmitted? What is the natural reservoir?

What are the three clinical syndromes of Monkey pox?

How serious of a disease is this to great apes?

Answer 15

• Poxviruses
  
  • Monkeypox virus infection (genus Orthopoxvirus)
    
    • Reservoir = African rope squirrels and other rodents
    • Transmitted by direct contact, ingestion, inhalation, +/- arthropod vectors
    • Papules → vesicles all over face, mucous membranes, body, and soles of the feet
    • Three clinical syndromes:
      
      • Benign upper respiratory signs followed by cutaneous lesions
      • Mucous membrane lesions, facial/pharyngeal edema → death from asphyxia
      • Bronchopneumonia
    • Fatal in chimpanzees, orangutans, and gibbons
  • Molluscum contagiosum (MC) = human molluscipoxvirus seen in lab chimpanzees

Question 16

What are the most common alphaherpesviruses affecting great apes?

How do HHV-1 lesions differ in gorillas, infant apes, or gibbons?

What lesions does HHV-2 produce in bonobos and chimpanzees?

What lesions occur with chimpanzee alphaherpesvirus?

What is disease like with HHV-3?

Answer 16

• Alphaherpesviruses
  
  • Human herpesvirus-1
    
    • Young gorillas: nonfatal disease with malaise, anorexia, and gingival/labial vesicles
      
      • Lesions identical to B-virus infection in macaques
    • Infant ape: fatal disease with dyspnea/vomiting/diarrhea
    • Gibbons: acute death in gibbons from encephalitis
    • Cowdry type A intranuclear inclusion bodies
    • Human herpesvirus-2 → genital ulcers in bonobos and chimpanzees
    • Chimpanzee alphaherpesvirus → self-resolving oroesophageal ulceration
  • Varicellovirus (HHV-3, chicken pox) = similar to human disease
    
    • Serological evidence of exposure in zoo-housed great apes

Question 17

Cytalomegalovirus is what type of herpesvirus? What lesions does it cause in apes?

Epstein-Barr like viruses are what type of herpesvirus? What lesions does it cause in apes?

Answer 17

• Betaherpesviruses
  
  • Cytomegalovirus (CMV)
    
    • Only cause serious disease in infants, fetuses and immunocompromised hosts
    • Clinical signs = anorexia, abdominal pain, respiratory signs
• Gammaherpesviruses
  
  • Gamma-1 lymphocryptoviruses (Epstein-Barr-like viruses, EBV)
    
    • All apes have antibodies that cross react with EBV
    • Unknown pathogenicity
    • Gorillas: oroesophageal leukoplakia in adults and lymphoid hyperplasia in infants?

Question 18

What is the tropism for papillomaviruses in great apes?

What lesions do they cause?

What are the classic lesions and inclusion bodies?

Answer 18

• Papillomaviruses
  
  • Tropic for epithelial surfaces → epithelial hyperplasia with amphophilic intranuclear inclusion bodies
  • Oral papillomatosis in chimpanzees and bonobos

Question 19

Describe the common respiratory viruses of great apes.

How common is human metapneumovirus? How serious is infection? What bacteria is a common co-infection? What are the clinical signs?

What respiratory virus has teh highest prevalence of any human respiratory viruse in zoo-housed apes? What are the clincial signs associated with infection?

What type of virus is the measles virus? How does it cause disease? What are the clinical signs?

What parainfluenza viruses affect apes? What lesions do they cause? When do mortalities occur?

How does the mumps virus affect great apes?

Answer 19

• Respiratory Disease Viruses
  
  • Human metapneumovirus (HuMPV)
    
    • Widespread exposure in apes
    • Can be fatal alone +/- Staphylococcus pneumoniae infection
    • Clinical signs: cough, nasal discharge
  • Respiratory syncytial virus (RSV)
    
    • Humans are natural host
    • Highest prevalence of any human respiratory virus in zoo-housed apes
    • Clinical signs: sneezing, rhinorrhea, catarrh, cough → bronchitis and pneumonia
      
      • Variable severity
  • Measles (rubeola) virus
    
    • Morbillivirus with high morbidity and mortality in apes
    • Replicates in T and B lymphocytes → immunosuppression → secondary infection
    • Death from pneumonia, diarrhea, +/- CNS
  • Parainfluenza viruses types 1, 2, and 2 (HPIV-1, HPIV-2, HPIV-3)
    
    • HPIV-1 and -2 → laryngotracheitis
    • HPIV-3 → bronchitis
    • Only reported fatalities are infants
  • Mumps virus (Paramyxoviridae)
    
    • Chimpanzees: sialadenitis and pharyngeal/palatine erosions
    • Humans are the natural host
  • Influenza A & B
    
    • Seroprevalence is common in apes
    • Susceptibility depends on sialic acid cell surface receptors

Question 20

What is the natural reservoir of encephalomyocarditis virus?

What type of virus is this?

What are the susceptible hosts?

How is it transmitted?

What are teh clinical signs that occur in primates?

Answer 20

• Picornaviruses
  
  • Encephalomyocarditis virus (EMCVV)
    
    • Reservoir = rodents
    • Hosts = primates, swine, carnivores, elephants, exotic hoofstock
    • Transmitted orally from contaminated food/water
    • Placental infection and fetal death may occur in primates
    • Clinical signs: sudden death or congestive heart failure with pulmonary edema
    • Necropsy: pericardial effusion and severe pulmonary edema
    • Diagnosis via PCR or culture

Question 21

What are the four enteroviruses that affect great apes?

What family do these viruses belong to?

What is the virus responsible for the common cold?

What are the clinical signs and lesions that occur with cocksacieviruses? What is an important differential to consider?

What are the clinical signs of poliomyelitis virus?

What are the clinical signs associated with enterovirus C99? What species is affected?

Answer 21

• Enteroviruses (Picornaviridae)
  
  • Rhinoviruses = common cold
  • Cocksacieviruses (A and B)
    
    • Fecal-oral transmission
    • Clinical signs: diarrhea, respiratory signs, +/- death
    • Necropsy: pneumonia, visceral congestion, cardiac enlargement
    • Myocarditis needs to be differentiated from EMCV
  • Poliomyelitis virus
    
    • Primary host = humans
    • Clinical signs: enteritis +/- CNS or motor neuron signs
    • Polio transmission = fecal-oral
  • Enterovirus C99 → acute flaccid paralysis in a chimpanzee

Question 22

What are the viruses that produce hepatitis in great apes?

What types of viruses are these?

What are the lesions that occur as a result?

Answer 22

• Hepatitis viruses
  
  • Hepatitis A (HAV)
    
    • Picornavirus transmitted by fecal-oral
    • Zoonosis and reverse zoonosis possible
    • Acute, severe increase in ALT when active
  • Hepatitis B (HBV) - Hepadnaviridae
    
    • Chronic active infection → cirrhosis and hepatocellular carcinoma in humans but not chimps
    • 2% prevalence in zoo-housed chimpanzees (affects management decisions)

Question 23

What are the etiologic agents that cause ebola hemorrhagic disease?

Where do these viruses originate from?

What family do they belong to?

What species are the natural reservoirs?

Answer 23

Ebola Virus Disease

• Major cause of population declines of western lowland gorillas
• Ebolavirus, family Filoviridae
• Zaire Ebolavirus (ZEBOV) – most associated with EVD in apes
  
  • 8 human outbreaks of this linked to contact w/ gorilla or chimp meat/carcasses
• Four additional spp identified:
  
  • Africa
    
    • Sudan (SUDV)
    • Tai forest (TAFV)
    • Bundibugyo (BDBV)
  • Asia
    
    • Reston (RESTV)
• Impact on great apes
  
  • Only ZEBOV and TAFV identified in great apes
  • African apes
    
    • West and Central only; many outbreaks
    • 1990s-2000s  98% decline in gorilla and chimp populations (>5000 individuals) before and after outbreaks (along w/ human outbreaks)
    • Duikers also affected
    • Ape mortality (95%)> human
  • Asian apes
    
    • RESTV is the only spp known to occur in Asia. Found in lab non-ape primates imported to US from Phillipines
    • Not believed to be pathogenic to humans or Asian monkeys and no cases reported in Asian apes
    • One questionable study found antibodies to ZEBOV in human care bornean orangs (??)
• Reservoir
  • Great apes and humans considered dead end hosts
  • African fruit bats – experimentally found to amplify virus, seroconvert and shed it w/o developing c/s
    
    • Antibodies and RNA found in several species
  • African insectivorous bats also possible
  • Never isolated from wild-caught animal
  • Live marburgvirus (Filoviridae) isolated from Egyptian fruit bats

Epizootiology

• Filovirus family = Ebolavirus (EBOV) and Margburgvirus; enveloped, non-segmented, negative strand RNA viruses
• 5 Ebolavirus spp:
  
  • Zaire ebolavirus (ZEBOV)
  • Sudan ebolavirus (SEBOV)
  • Cote d’Ivoire ebolavirus (CIEBOV)
  • Reston ebolavirus (REBOV)
  • Bundibugyo ebolavirus
• Viral Distribution
  
  • Geographic Range: humid tropical forests sub-saharan Africa and Phillipines
  • Confirmed human and animal outbreaks- Côte d’Ivoire (CIEBOV), Democratic Republic of Congo, Republic of Congo, Gabon (ZEBOV), Sudan (SEBOV), and Uganda (SEBOV and Bundibugyo ebolavirus).
  • REBOV – Outbreaks in U.S. and European facilities traced back to facility in Phillipines
  • Endemic in Cameroon, Madagascar, Mozambique, Tanzania
• Reservoirs
  
  • Very low titers in naturally infected reservoir species
  • Bats suspected as primary reservoir
    
    • Viral amplification has only occurred in bats
    • EBOV gene sequences detected in 13 bats of 3 species- hammer-headed fruit bat, Franquet’s epauletted bat, little collared fruit bat
    • Recent detection of ZEBOV specific IgG in 95 bats of 6 spp
    • Confirmation as reservoir will take isolation of live virus from bats, establishing persistence of infection, and confirming transmission to target species

Question 24

Describe the outbreaks and epizootics of Ebola that have affected managed and free-ranging primates.

Where have outbreaks occurred in the wild?

What are some other potential taxa that may be dead end hosts of Ebola?

Answer 24

Epizootics

• Captive Primates
  
  • REBOV isolated in cynomolgus macaques showing signs of hemorrhagic fever
  • Outbreak in US/Europe from Philippines- 82% animals died; many co-infected w/ simian hemorrhagic fever virus (significance unknown)
  • Almost all cases from single breeding facility in Laguna Province
    
    • 14% mortality rate at facility with viral antigen detected in 32% of symptomatic and 4% of asymptomatic monkeys
• Free-Ranging Primates:
  
  • ZEBOV- Chimps and Western lowland gorillas = dead end hosts
    
    • ZEBOV Ag detected in 16 chimps and gorillas found during epizootics associated with large declines in great apes in central Africa
    • Case fatality in great apes estimated at 90%
      
      • Western lowland gorilla reclassified as critically endangered due in large part to EHF
    • Ebolavirus specific Ab detected in 31 western lowland gorillas and chimps
      
      • Survivors vs. asymptomatic infections vs. cross-reaction with unidentified less virulent strain
  • CIEBOV- associated with death of 12 chimps in Cote d’Ivoire in 1994
    
    • 6d prior to outbreak, chimps ate red colobus that was Ab + for CIEBOV
  • SEBOV and Bundibugyo ebolavirus- no morbidity and mortality reported yet
• Other Potential Hosts
  
  • African domestic hunting dogs- positive serology suggests canines may be naturally and asymptomatically infected
  • Elephant, rodents, pythons, pangolin, raptor, mongoose, small wild cats, pigs, med/small antelope found dead in proximity to ZEBOV outbreaks
  • 50% reduction in duiker population concurrent w/ ZEBOV outbreak
    
    • Republic of Congo
    • Duikers thought to be dead end hosts
  • REBOV – isolated from domestic swine

Question 25

How is ebolavirus transmitted?

When is the risk of transmission highest?

Where does the virus persist longest in survivors?

How does transmission occur in great ape populations?

Answer 25

Transmission

• Direct contact with body fluids
  
  • Evidence of ZEBOV transmission b/w monkeys separated by 3 meters
    
    • Suspected conjunctival exposure via aerosolization from urination or cage cleaning
• Highest risk transmission in acute phase (viremia)
  
  • Exception: semen and breast milk- ZEBOV detected in patients at 15 & 91d post-infection
• Handling of great ape carcasses and consumption of bats also implicated (ZEBOV)
• No evidence aerosol transmission in humans
  
  • Once in human communities- spreads rapidly via person to person contact and in health care settings (limited resources, barrier nursing protocols not implemented)
• Route of initial infection in great apes presumed to be direct or indirect contact w/bats at feeding sites (ex/ fruit in same tree)
  
  • Once in great ape pop- transmission may be propagated by contact with infected animal carcass and direct contact with other infected apes

Transmission

• Humans
  
  • Highly infectious
  • Direct contact of bodily fluids with mucus membranes or broken skin
  • Higher risk in acute phase when viremic
    
    • Little risk before clinical signs and once virus is cleared
  • ZEBOV may persist in urine and placenta, amniotic fluid, and fetus in women who were infected when pregnant, or in breast milk if infected when breastfeeding
  • Viral persistence in ‘privileged’ sites (eyes, brain, testes)
  • Isolated from human semen up to 7-9 months postonset
• Apes – not definitively established
  
  • May consume food contaminated w/ bodily fluids from reservoirs (i.e. fruit bats); viral shedding of ZEBOV in bat urine/feces not reported
  • Likely direct contact
  • Occurs over large geographic ranges
    
    • Group to group transmission
    • Multiple spillover events (more likely)

Question 26

Describe the clinical signs of ebola virus in humans and in great apes.

What is the incubation period of this virus?

When is it infectious?

What are teh signs of initial infection?

What is post-ebola syndrome?

How do signs differ in apes?

Answer 26

Clinical signs

• Humans: incubation period of 2-21 days; infectious once symptoms start
  
  • Sudden onset
  • Fever, fatigue, muscle pain, headache, sore throat, vomiting, diarrhea, rash, internal/external bleeding
  • Post ebola syndrome: Sequelae in survivors: msk pain, headache, ocular signs, abdominal pain, sexual dysfunction
    
    • Months to years
• Apes
  
  • Somewhat unknown
  • Severe diarrhea, emaciation
  • Other NHP: vomiting, diarrhea, hair loss, emaciation, epistaxis
  • Experimentally infected non-apes: variety of c/s; death in 8 days withZEBOV and 12-14 days w/ TAFV
  • Some may survive

Question 27

How is ebola diagnosed?

What is the ideal sample?

What are some important differentials to consider in people and in apes?

Answer 27

Diagnostics

• Viral RNA, antigen, or antibodies
• ELISAs, antigen capture detection tests, serum neutralization, RT PCR, EM, virus isolation via culture
• Sample: whole blood or oral fluid sample
• Challenging in ape carcasses in tropical locations (degradation – false negatives)
• DDX
  
  • Humans: malaria, typhoid, shigellosis, cholera, lepto, plague, rickettsiosis, relapsing fever, meningitis, hepatitis, yellow fever, other viral hemorrhagic fevers
  • Apes: above + anthrax

Question 28

Describe the control measures to contain ebola outbreaks.

What vaccines are available?

How should carcasses be handled? How long do they remain infective?

How is ebola treated?

Answer 28

Control Measures

• Vaccination
  
  • Under development
  • Recombinant
    
    • ChAd3-EBO-Z (chimp adenovirus vectored)
    • rVSV-EBOV (Replication-competent vesicular stomatitis viruses based )
    • both have gone through human clinical trials and provide immunity after single dose
  • Self-replicating vaccine based on cytomegalovirus designed to spread from ape to ape (only have to give to a few individuals!)
    
    • Concerns about safety in target and nontarget spp
• Carcass disposal
  
  • Debated, practical issue
  • Degradation varies by environment
  • One study – remain infective for 3-4 days; another up to 7 days
  • Risk of exposure to personnel – bury or incinerate at the cite
  • Not good to transport carcass for disposal
• Outreach

Treatment: supportive care, no vaccines for humans, but vaccine reported to be effective in post-ZEBOV exposure treatment of rodents and non-human primates

Question 29

Describe the pathologic findings associated with ebola infection.

What are the gross lesions?

What are the histologic lesions?

Answer 29

Pathology and Postmortem Findings

• Info on postmortem lesions primarily from experimentally ZEBOV-infected primates, but supplemented with observations associated with REBOV-infected macaques, CIEBOV-infected chimpanzee, and few human autopsies
• Gross- petechiae, ecchymoses, frank hemorrhages in many organs (kidneys, liver, spleen, lung, testes), also may see maculopapular rash, SQ hemorrhages at venipuncture sites, hepatomegaly, splenomegaly, DIC
• Histo- necrosis of liver, lymphoid tissue, adrenal cortex, pulmonary epithelium

Question 30

Describe the retroviruses that affect great apes.

What are the lesions associated with Gibbon ape leukemia virus (GALV)?

What are the pathogenesis of Simian immunodeficiency virus?

What are the clinical signs of foamy viruses?

Answer 30

• Retroviruses
  
  • Gibbon ape leukemia virus (GALV) → hemolymphatic malignancies
    
    • Malignant lymphoma, lymphoblastic leukemia, myelogenous leukemia
    • Myelogenous leukemia → greenish hue (chlorosis) in bone marrow, liver, LN, spleen
  • Primate T lymphotropic viruses (PTLVs)
  • Simian immunodeficiency virus (SIVcpz, SIVgor)
    
    • SIVcpzPtt affects central chimpanzees; SIVcpzPts affects eastern chimpanzees
    • SIVcpzPtt is likely source of HIV-1 group M and N
    • SIVgor is likely source of HIV-1 group O and P
    • Both horizontal and vertical transmission
    • Depletion of CD4+ lymphocytes
  • Foamy viruses = nonpathogenic

Question 31

What are the clincial signs with Streptococcus penumoniae infection in great apes?

What viral infections predispose apes to infection?

How is this transmitted?

What clinicopathologic changes may be appreciated with infection?

Answer 31

• Streptococcus pneumoniae = Gram +, diplococcus
  
  • Pneumonia, meningitis, and pericarditis in apes
  • Air sacculitis and sinusitis in gibbons, bonobos, gorillas, and orangutans
  • Viral infections (HPIV-3, HuMPV, RSC) predispose to infection
  • Transmitted by aerosols
  • Marked leukocytosis, neutrophilia with left shift; CSF tap with increase WBC & Protein

Question 32

Which apes have the largest airsacs? Which have hyoid air sacs?

What are the clincial signs associated with airsacculitis?

What are the risk factors for airsacculitis?

What is the most common pathogen? Which is the primary pathogen?

Answer 32

• Air sacculitis
  
  • Air sac volume: orangutan and gorillas (well-developed under clavicles and axilla) >> chimpanzee, bonobo >> siamang (gular sac) >>> gibbons
    
    • Hyoid air sac gibbons, chimpanzees, and gorillas but NOT orangutans
  • = air sacculitis pathogens
  • Clinical signs: cough, halitosis, purulent nasal discharge
  • Risk factors: male, hand-reared, Bornean (vs. Sumatran) orangutans
  • Pathogens
    
    • Pseudomonas aeruginosa = most common
    • Klebsiella pneumoniae = primary pathogen
    • Pasteurella multocida
    • Streptococcus pneumoniae

Question 33

Describe the normal anatomy and physiology of the ape upper respiratory system.

Which species has the most elaborate sinus and air sac system?

What are the two paranasal sinuses of orangutans?

How does laryngeal anatomy compare to humans?

Where do the air sacs come off the larynx? How is this expanded in orangutans?

Describe the epithelium of the air sac.

What are the proposed functions of the air sac?

Answer 33

• Normal Anatomy and Physiology
  
  • Varies considerably between humans and apes
  • Distinct to orangutans- extent of sinuses and laryngeal air sacs
  • Anatomy simpler than carnivores – not olfactory dependent
  • Orangutans – paranasal sinuses include
    
    • Maxillary sinus
      
      • Occupies entire maxilla and extends into lacrimal, frontal, ethmois, zygomatic, palatine, and sphenoid bones
      • Sphenoidal extension is dorsal to true sphenoidal sinus and invades the pterygoid and zygomatic processes of the temportla bone
      • Nasolacrimal duct, infraorbital, and ethmoidal neurovascular structures pass the maxillary sinus, and optic nerve and internal carotid artery encroach on its sphenoidal extension
    • Sphenoidal sinus
      
      • Significantly reduced in orangutans
      • Divided into right and left sinuses by the septum
  • No frontal sinus, but in adult orangutans a frontal recess of the maxillary sinus may extend superiorly to border much of the inferomedial corner of the orbit posterior to the lacrimal duct
    
    • May sometimes pneumatize the inter-orbital region of the frontal bone
  • Before age of 8 to 12 years, frontal recess is less developed and nasal cavity is in direct contact with medial orbital wall
  • Maxillary sinuses drain through ostia into the middle meatus
  • Sinus sphenoidalis opens into the upper meatus
• Cilia transport mucous toward the external nasal cavity
  
  • Maxillary sinus- flow directed toward the ostium, middle meatus, and nasopharynx
  • Sphenoidal sinus- flow enters the superior meatus, then the nasopharynx
• Larynx
  
  • Connects pharynx with the trachea- anatomy similar to humans
  • Made up of 9 cartilages –
    
    • 3 single (thyroid, cricoid, and epiglottic)
    • 3 paired (arytenoid, corniculate, and cuneiform)
  • Hyoid connected to larynx
  • Slight differences in larynx anatomy key factor in evolution of human speech
• NHPs-have laryngeal air sac
  
  • Accessory mucosal membrane pouch extending from secondary valve formed by inferior thyroarytenoid folds
  • All great apes have expansion of the unilateral sac from the ventricles, which fuse with another sac inferiorly in the late juvenile period
  • Orangutans- extends inferiorly from the ventricles to the neck and axillary region, meet in the midline beneath the pectoral muscles, and are connected to the upper respiratory tract via two opening in the lateral larynx wall.
  • Air sac lined with ciliated epithelium with a lamina propria consisting of a layer of loose elastic and collagenous fibers and variable numbers of seromucinous glands
  • Suggested functions-
    
    • Storage of expired air to increase O2 intake
    • Reduction of hyperventilation during repetitive loud calls
    • Generating sound in laryngeal ventricles
    • Resonating the laryngeal voice source for loud and long calls
    • Buffer against pressure from expiratory air flow following air trapping during arboreal locomotion

Question 34

What are the indications to CT the URT of affected orangutans?

Why is this a high-risk procedure?

How can the risks be mitigated?

How is airsacculitis scored?

When is treatment indicated?

What medications are recommended?

What surgical procedures can be performed? When are they indicated?

Answer 34

• Indications for CT of URT in orangutans = high-risk immobilization
  
  • Chronic nasal discharge, facial swellings, suspected air sacculitis
  • Expect pulmonary aspiration of exudates from sinuses or air sac
  • Intubate immediately
  • Position in ventral recumbency for best display of possible fluid levels
• Treatment:
  
  • Based on CT scoring system (Table 55-3) pp. 428
  • Healthy- no treatment, anatomical variations may require CT rechecks
• Medical Management-
  
  • Goal – reduce mucosal swelling and clear sinuses and air sacs from infection and fluid
  • Broad-spectrum antibiotics based on C&S for 4-6 weeks, then reassess
  • Steroids and mucolytics recommended
  • Antimycotic tx if warranted
• Surgical Management-
  
  • Indicated for any animal classified as having severe disease
  • Recommend medical treatment for 3 weeks prior to reduce infection and swelling
  • Air sacculitis-
    
    • Marsupialization of air sac or complete resection
  • Sinusitis-
    
    • Functional endoscopic sinus surgery (FESS) – future treatment of choice
      
      • Opens natural ostium and preserves the mucosa

Question 35

What is the typical signalment for a gorilla with an intraabdominal abscess?

What are teh typical clinical signs?

What are common sequelae to these abscesses?

Answer 35

• Intrabdominal and retroperitoneal abscesses
  
  • Common in gorillas, especially overweight, reproductively inactive females
  • Clinical signs: lethargy, recto-genital discharge, constipation, +/- abdominal distension
  • Caudal abdomen/intrapelvic region with excessive fibrous adhesions
  • +/- Perirectal/lumbar/pervaginal fistulas
  • Intraabdominal adhesions are common in all apes even without peritonitis

Question 36

What are the most common bacterial pathogens that cause enterocolitis in great apes?

What are the clinical signs associated with campylobacter?

What are the clinical signs with E coli?

What are the signs with salmonella? What clinicaopathologic changes may occur?

What are the signs with Shigella? What clinicaopathologic changes may occur?

What about Yersiniosis? How do those signs differ?

Answer 36

• Bacterial enterocolitis
  
  • Common bacterial agents: Campylobacter, Yersinia, Campylobacter, Shigella
  • Campylobacter, Salmonella, Shigella have been found in health apes
  • Shigella flexneri can be diagnosed with culture or PCR

Question 37

What are the species of Mycobacteria that affect great apes?

How are these transmitted?

What are teh clinical signs?

Answer 37

• Mycobacterium tuberculosis complex (including M. bovis, M. africanum)
  
  • Humans are the main host of Mtb
  • Transmitted via aerosols, fomites, or oral ingestion (in cow/goat milk)
  • Clinical signs = anorexia, weight loss, dyspnea, cough
  • Granulomas in lungs/air sacs or GI tract
  • No antemortem diagnostic is perfect, so may need multiple tests

Question 38

What is the etiologic agent of Yaws in apes? What are the two variations of clinical signs? How is it transmitted?

What is the etiologic agent of tularemia? How is it transmitted? What are the lesions?

What are the effects of infection with Chromobacterium violaceum?

Answer 38

• Yaws (Treponema pallidum pertenue)
  
  • Two types of clinical signs:
    
    • Gangosa: severe destruction of palate and nasopharynx
    • Gondou: bony proliferation of maxilla
  • Seen in one population of wild gorillas (alpha males > other males > females)
  • Transmitted by direct contact (biting) or flies
• Franciscella tularensis = Gram - coccobacilli
  
  • Both type A (lagomorph-associated) and type B (rodent-associated)
  • Prevent with good pest control
  • Pyogranulomatous inflammation of oral cavity, skin, LN, lungs
• Chromobacterium violaceum = motile, Gram - bacillus in water and soil
  
  • Transmission: oral ingestion or would
  • Abscesses in liver and lungs → death

Question 39

Describe the common fungal infections of great apes.

What are the typical dermatophytes?

How does candidiasis typically appear? What animals are particularly susceptible?

What fungal infection is common in the southwestern US? How unique presentation occurs with chimpanzees with this infection?

Answer 39

• Fungi
  
  • Dermatophytosis = ringworm
    
    • Microsporum caninum, Microsporum gypsum, Trichopyton rubrum
    • Similar to domestic animals
  • Candidiasis → oroesophageal and tracheal plaques
  • Geotrichosis (Geotrichum candidum) → watery diarrhea
  • Coccidiomycosis (Coccidioides immitis or posadasii)
    
    • Cause of disease in southwestern US and Mexico
    • Conidia in soil → spores in lungs → endosporulation → systemic dissemination via macrophages
    • Associated with hypertrophic osteoarthropathy in chimpanzees
  • Cryptococcosis (Cryptococcus neoformans, gattii)
    
    • C. neoformans = opportunistic and worldwide
    • C. gattii = in tropical areas and pacific NW US and can affect immunocompetent hosts

Question 40

What is the etiologic agent of the human pinworm? What clinical signs does it cause in apes?

What strongyloides species affect great apes? What species is particularly susceptible? What is the life cycle like?

What are the clinical signs associated with Oesophagustomum infestation?

What about Capillariasis?

Larval migrans can occur with what species?

Answer 40

• Metazoa
  
  • Pinworms
    
    • Colon of chimpanzees, gorillas, and orangutans are natural hosts
    • Can see colonic mucosal roughening
    • Fatal case in chimpanzees associated with human pinworms (Enterobias vermicularis)
  • Strongyloidiasis
    
    • Can cause fatal disease in young apes in captivity, especially organgutans
    • OW monkeys and apes are natural hosts of Strongyloides fuelleborni
    • Humans are natural hosts of Strongyloides stercoralis
    • Infection at mucous membrane → migrate to lungs → coughed up and swallows → parthenogenetic females in colon → shed eggs
  • Esophagostomiasis (Oesophagustomum stephanostomum [chimp, gorilla], O. birfucum [zoonotic])
    
    • Direct life cycle with no migration
    • Subclinical infection to severe diarrhea, weight loss, and death
  • Capillariasis
    
    • Host = rodents
    • Calodium hepatic → typically asymptomatic in mountain gorillas
    • Capillaria brochieri → fatal diarrhea in bonobos
  • Larval Migrans
    
    • Baylisascaris sp. → neural larval migrans in gibbons and orangutans
      
      • Definitive host = raccoons (B. procyonis) and skunks (B. columnaris)
    • Parastrongylus sp. Larval migrans in gibbons, orangutans, OW monkeys, callitrichids
      
      • P. canontensis → pulmonary larval migrans or meningoencephalitis
      • P. costaricensis → abdominal larval migrans
      • Definitive host = rat
      • Intermediate host = snail
      • Native to SE US
  • Hydatid disease (Echinococcus spp.) → multiloculated cysts with larvae → peritonitis in gorillas
    
    • Definitive host = fox (E. multilocularis), dog (E. granulosa)

Question 41

What are the clinical signs associated with balantidiasis in apes?

What is the etiologic agent of aemobic encephalitis in apes?

What is enteric amoeba that causes ulcerative colitis?

What protozoa can lead to heart failure in apes in the southeastern US?

What are teh most common mites to affect great apes?

Answer 41

• Protozoa
  
  • Balantidiasis (Balantidium coli) = commensal cilia protozoa
    
    • Can cause ulcerative thyphocolitis +/- death in immunocompromised apes
  • Balmuthia mandrillaris = soil-dwelling ameoba primarily affecting gorillas
    
    • Transmission via aerosol or wound contamination from soil
    • Lethal lesions in brain
  • Entameoba histolytica → pathogenic enteric amoeba → ulcerative colitis
  • Trypanosomiasis (Trypanosoma cruzi) → heart failure in apes in SE US
    
    • Transmission = Triatomid (“kissing bug”) feces on skin, in wounds, or ingestion of triatomids
    • Megaesophagus is common in humans but not found in apes
    • Blood smears are not sensitive to detect trypanosomes
• Ectoparasites
  
  • Mange
    
    • Sarcoptes scabiei can cause pruritic alopecia in wild gorillas and chimpanzees
    • Pangorillalges gorilla = gorilla-specific mite
  • Demodex-like mites live in large sebaceous glands on brow, cheeks, lips, and genital
    
    • Eccrine and apocrine sweat glands found all over the body are not affected

Question 42

Describe the natural diet of gorillas and orangutans.

How does this differ from chimpanzees and bonobos?

How does the GI anaomty and physiology differ between these two groups of apes?

Answer 42

Wild Diets and Digestive Physiology

• Free-ranging apes: largely plant-based diets
  
  • GI tract anatomy determines spp’s relative ability to digest fiber
• Gorillas and orangutans (similar GI anatomy and diet)
  
  • Lengthier small intestine; more voluminous large intestine – fermentative capabilities (like horses)
  • Very herbivorous; naturally eat plant leaves/stems/pith/bark/roots/flowers/fruit (and clay-rich soil)
    
    • Gorillas – most herbivorous of all great apes
    • Orangutans – prefer fruit; also eat insects
• Chimpanzees and bonobos (similar GI anatomy and diet)
  
  • Relatively short small intestine; longer large intestine (lower fiber fermentative capacity but still can)
  • Omnivorous frugivores (mostly eat fruit); also leaves/shoots/stems/flowers/pith/seeds/insects/meat
    
    • Protein contribution from insects/meat is insignificant; may be more of a social behavior

Question 43

What are the benefits of offering a pelleted diet to great apes?

What are the benefits of adding browse?

What about vegetables? What vegetables should be offered? How should they be prepared?

What about fruit, seeds, or nuts?

What about vitamin or mineral supplementation?

What about animal products? When are they appropriate?

Answer 43

Recommended Diet Plan

• Water – unlimited access; clean water containers daily
• Kibble/pellets – primate biscuits contain appropriate amounts of vitamins/minerals/fats/proteins
  
  • Supplement micronutrients that would otherwise be deficient (basis for healthy/balanced diet)
  • Higher concentration of fiber than produce items
  • Can also use horse pellets (more economical)
• Browse – important source of fiber; may offer as much as possible
  
  • Leafy tree branches (nontoxic; no pesticides/herbicides), dried alfalfa (leafy material and stems)
  • Increases feeding time; decreases regurgitation and reingestion
• Vegetables – leafy greens; low-starch
  
  • Increases foraging time without adding a lot of calories
  • May offer with peels/cores intact – fiber; enrichment
  • Offer raw (cooked items contain more easily digested sugars – good for geriatric/dental animals)
  • Avoid toxins (avocado) and choking hazards for younger animals (fibrous skins or seeds)
• Fruit – wild fruits are higher in fiber and lower in sugars than fruits cultivated for humans
  
  • High sugar intake à GI dz (disrupted microflora), obesity, regurgitation/reingestion, addiction
• Seeds/nuts/grains/legumes/lentils – protein, fat, fiber, vitamins, minerals
  
  • Seeds/nuts/some legumes (peanuts) – high in fat; use in moderation
• Vitamin/mineral supplementation – may use a complete multivitamin formulated for humans
  
  • Not necessary if receiving pellets; providing a variety of food sources will reduce the risk of deficiencies
  • Unfiltered sunlight for 30+ mins/day (or give vitamin D) – especially young animals (growing bones)
• Animal products – not normally recommended
  
  • Hard to digest, promote obesity, increase incidence of regurgitation/reingestion
  • Hand-raising infants: dairy-based human formulas supplemented w/ omega fatty acids
  • Hardboiled eggs: for animals having difficulty maintaining weight (high-quality protein source)

Question 44

Describe how diets should be presented to apes in managed settings?

What food items should be broadcast fed? What should be target or hand fed?

How should diversity be incorporated into the diet?

How can food be incorporated into enrichment?

Answer 44

Feed Presentation

• Group feeding
  
  • Prevent faster/dominant animals from consuming the most desired items
  • Target feed desirable items to individual animals; group feed less calorically dense foods
  • Variety: offer large amounts of 4-5 items daily and rotating selection throughout the week
    
    • As opposed to small amounts of 20+ items daily
• Enrichment
  
  • Provide food that is part of the diet in stimulating manner that encourages natural behaviors
  • Hide it, cut into small pieces and spread it, mix it with hay, keep it whole and hang it, puzzle feeders
  • Several smaller meals per day is better than one large meal
  • Must keep track of calories being offered in enrichment items (often high-fat/sugar content)

Question 45

What dietary considerations should be given to orangutans with air sacculitis?

Obesity in great apes predisposes them to what diseases?

Describe an ideal weight loss plan for a great ape?

What dietary considerations should be made for an ape with heart disease?

Answer 45

Health

• Leading causes of great ape morbidity/mortality: infectious, cardiovascular, respiratory, GI diseases
• Wash hands and wear PPE during diet prep – decrease risk of anthropozoonotic disease
• Orangutan air sacculitis - most common respiratory dz of orangutans
  
  • Diet considerations – prevent aspiration of food into air sacs by discouraging foods that stimulate regurgitation/reingestion (sugary foods, dairy, tofu); obesity à physical constriction of air sacs
  • Antibiotic treatment can cause dysbiosis; may perform fecal transplant
• Obesity - predisposes to hypertension, cardiac dz, neoplasia, arthritis, respiratory dz, diabetes, hepatic lipidosis, decreased fertility
  
  • Weight loss diets – should not lose more than 2% body weight weekly (slow)
    
    • Get animal accustomed to weekly weigh-ins
    • Transition to more ideal diet if necessary (5-10% at a time to avoid GI upset)
    • Reduce all diet categories by 10% to keep adequate proportions
    • Decrease high-sugar items (may cause temporary withdrawal: headaches/irritability/nausea)
    • Has been shown to reduce negative stereotypic behaviors (begging, self-mutilation)
  • Expending energy
    
    • Encourage activity (climbing, swinging, hanging, foraging for food)
• Cardiovascular disease
  
  • Most common: fibrosing cardiomyopathy (do not get atherosclerosis like humans)
  • Monitor sodium intake to prevent potential hypertension à cardiovascular disease

Question 46

Cardiovascular disease as a major cause of mortality occurs how frequenly in each of the four great ape taxa?

Answer 46

Cardiovascular disease is a major cause of mortality in all four great ape taxa managed in captivity:

1. Gorillas (Gorilla gorilla gorilla)- 41% incidence
2. Orangutans (Pongo pygmaeus)- 20% incidence
3. Chimpanzees (Pan troglodytes)- 38% incidence
4. Bonobos (Pan paniscus)- 45% incidence
5. Cadiovascular disease has also been noted in wild mountain gorillas, but this is usually a contributory, not primary cause of death and occurs at much lower incidence than captive apes.

Question 47

What is the most common cardiac disease in great apes?

What are some potential causes?

How does this affect the heart or lead to sudden death?

Answer 47

Fibrosing Cardiomyopathy (Gorilla, orang, bonobo) or Idiopathic Myocardial Fibrosis (Chimps)

• myocardial replacement fibrosis with atrophy and hypertrophy of cardiac myocytes, absent or minimal inflammation and no apparent etiology or associated disease
• good histo pictures pg 409 (Fig 53-2)
  
  • patches of fibrosis arise near intrinsic coronary arterioles, which are often thick-walled and hyalinized (arteriosclerosis)
• heart may be enlarged with left ventricular hypertrophy or dilated and flabby
• myocardial fibrosis is a end-stage lesion
• fibrosis can be caused by different types of injury to the myocardium
  
  • hypoxia, ischemia, necrosis, inflammation
  • etiology is likely multi-factorial
• hypertension may be present (transient [catecholamine-induced vasospasm] or systemic) based on changes seen in intrinsic arteries of myocardium
• death – may be sudden with no premonitory signs, though others may develop CHF

Most common finding at necropsy = interstitial myocardial fibrosis

• Can be due to inflammation, ischemia, vasospasm, hypertension
• Results in myocardial stiffness, loss of contractility, increase in arrhythmogenic potential, cardiac dysfunction, death

Question 48

Aortic dissection is common in which species? How does this occur? What other changes in the heart are common in these animals? What causes sudden death?

Are apes clinical for their myxomatous valvular degeneration?

Atherosclerosis in apes is most common in which vessels?

What are four causes of infectious myocarditis in apes?

Answer 48

Great Ape CVD

• Types: myocardial fibrosis in absence of coronary infarction, aortic dissections, atherosclerosis, arteriosclerosis, valvular degeneration, infectious myocarditis, congestive heart failure
• Predominantly males
• Adults and older adults mostly

Other types of ape cardiac/vascular disease

• aortic dissection
  
  • gorillas, 3 bonobos
  • A tear in the ascending aorta near valve; not associated w/ atherosclerosis
  • hypertension may be factor (similar in humans)
  • LV hypertrophy present – may indicate hypertension or increased workload due to the dissection, which is often chronic and forms a double-barreled aorta
  • Death due to vessel wall failure ->cardiac tamponade or hemorrhage
• myxomatous valvular degeneration (endocardiosis or nodular mucinosis)
  
  • Degenerative valvular disease: nodular thickening and mucinosis of valve margins.
  • low frequency in captive population
  • has been seen in wild mountain gorillas
  • may be incidental finding vs. more severe disease in humans and dogs
• atherosclerosis
  
  • may cause coronary arterial disease
  • most often atherosclerosis is an incidental finding
  • often confined to descending abdominal aorta and internal iliac vessels
  • reports more common in older literature when ape diets were based on human diets (ie, more appropriate diets now have decreased incidence?)
• congenital heart defects
  
  • intra-atrial/ intraventricular septal defects – seen in all ape taxa
  • usually diagnosed in young animals
• infectious myocarditis
  
  • Encephalomyocarditis Virus EMCV (orangs, bonobos)
  • Coxsackie B4 viral infection in orangs
  • Chagas dis (Trypanosoma cruzi) in chimps
  • Vegetative endocarditis associated w/ alpha Strep and Gemella sp (gorillas)
• valvular endocarditis
• hypertensive CHF

Question 49

List proposed etiologies for the development of cardiovascular disease in great apes.

What role does diet play?

What metabolic conditions contribute to cardiovascular disease? How prevalent are these conditions?

Answer 49

• Diet
  
  • Predominantly vegetarian, low fat, high fiber, low cholesterol diet in wild
  • HDL, LDL, total cholesterol do change w/ age but do not appear to correlate to increased risk of ape CDV
  • Addition of salt into chimp diets leads to increased body weight, and BP
• Metabolic syndrome
  
  • Presence of at least 3 of the following: obesity, increased serum triglycerides, reduced HDL, hypertension, increased fasting glucose, increased serum insulin levels
  • Risk factor w/ caridomyoathy
  • One geriatric chimp study: 43.8% met criteria. 81% of them had CVD

Possible etiologies and pathogenesis

• obesity/inactivity
• dietary factors and chemical imbalances:
• hi lipids
• iron overload
• hypovitaminosis D and E
• high salt content
• absence of plants eaten in wild that might be cardioprotective
• personality type/behavioral issues associated w/ psychosocial stress and catecholamine release
• endocrinopathies (diabetes, hypothyroidism)
• Type 1 or 2 hypertension
• other disease – renal, dental, osteoarthritis
  
  • statistically significant association b/w renal disease and fibrosing cardiomyopathy
  • chronic renal dz can cause secondary hypertension or primary hypertension can damage renal vasculature and lead to renal failure.

Question 50

What are the clinical signs in an ape with cardiovascular disease?

What cardiovascular changes occur?

What are the three clinical assessment categories in apes with cardiovascular disease?

Answer 50

• Clinical signs
  
  • Lethargy, anorexia, weight changes, avoidance of antagonistic or aggressive interactions w/ conspecifics, loss of social ranking
  • Sudden death, esp if they have resp illness, stress
  • Progression signs: weight gain, peripheral edema, respiratory signs
• Cardiovascular Changes
  
  • LV wall thickening, increased myocyte size and decreased numbers, increased interstitial connective tissue, loss of elasticity
  • Fibrosis around small intrinsic coronary arterioles, often w/ hyalinization (arteriosclerosis) and larger areas of fibrosis through the chamber walls.
  • Clinical assessment categories:
    
    • Apes w/ LVH and intact systolic function
    • Apes w/ LVH and systolic dysfunction
    • Apes w/ dilated cardiomyopathy phenotype
  • Aortic dissection is 2^nd leading cause of CV related deaths in gorillas and bonobos
  • Other findings: aortic root dilation, left atrial enlargement, thromboembolism, right sided enlargement, arrhythmogenic right ventricular dysplasia/ cardiomyopathy, pulmonary hypertension, inflammatory disease, pericardial effusion
  • Valvular regurgitation usually not clinically significant

Question 51

How do gorilla hearts differ from human hearts?

What should be part of the standard cardiac workup in a great ape?

What views of the heart should be taken? What is the best positioning for echocardiography?

What effects to alpha 2 agonists have on the echocardiogram?

How frequently should these cardiac workups occur?

Answer 51

Antemortem considerations:

• Antemortem detection is challenging due to limited access to species specific norms
  
  • Become familiar w/ diff b/w human and ape CVD patterns
• Gorilla cardiac database (when compared to humans)
  
  • Model for standardization of ape cardiac evaluation (created in 2000 by Dr. H Murphy)
  • Normal gorilla heart rates are faster
  • BP higher
  • LV muscle is thicker and hyperdynamic
  • LV ejection fraction is higher (~60%)
  • Preliminary gorilla specific ranges have been published
• Gorilla health project
  
  • Standardization of cardiac exams, medical history reporting, sample collection, etc
  • Recommendations
    
    • Standardized cardiac exam
      
      • Parasternal transthoracic (or transesophageal) US
      • Measure certain parameters: aortic root diamater, LA, RA, and ventricular chamber sizes
      • Measurements of the LV (by mitral leaflets), short and long axis, internal diameter in systole (LVIDs) & diastole (LVIDd), diastolic interventricular septal thickness (IVS), posterior wall thickness (LVPW)
      • Fractional shortening (calculate)
      • Ejection fraction (calculate)
      • 6 or 12 (ideal) lead ECG
      • chest radiographs
      • HR
      • BP
      • Anesthetic regimen
      • PE results
      • Collect blood: CBC, chem, brain natriuretic peptide (BNP), insulin:glucose ratio, insulin, LDL, leptin, cholesterol
      • Metabolic syndrome in humans = grouping of obesity, hyperglycemia, hyperinsulinemia, dyslipidemia, hypertension
• Cardiac health monitoring
  
  • Echocardiography
  • Every anesthetized exam once an adult; q2-3y w/ normal cardiac health. Risk analysis to determine anesthesia and exam frequency once animal has CVD
• Echocardiograms
  
  • Left lateral recumbency w/ left arm extended cranially
  • If doing it awake, may need to be done in multiple sessions (within 30 days = 1 exam)
• Electrocardiogram
  
  • Male chimps – 75% of geriatrics have some kind of ectopy, most commonly ventricular premature complexes
• Anesthesia considerations
  
  • Alpha 2’s – CV effects
    
    • LV enlargement
    • Alpha2 induced mitral valve regurge, LA enlargement
    • Can make normal heart look abnormal
    • *Nondiagnostic per GAHP

Question 52

Discuss the use of cardiac biomarkers in diagnosing heart disease in great apes.

What is BNP? How useful is it?

What about c-reactive protein?

What about cardiac troponin T & I? Are they useful?

Answer 52

• Biomarkers
  
  • B-type natriuretic peptide (BNP)
    
    • Cardiac neurohormone secreted from cardiac ventricles (mainly from the left) in response to ventricular volume expansion and increased pressures
    • Elevated in chimps w/ cardiomyopathy
    • High specificity for CVD
  • C-Reactive protein
    
    • No useful in chimps
    • Nonspecific indicator of inflammation
  • Troponins
    
    • Cardiac troponin T and troponin I are cardiac regulatory proteins that control the calcium mediated interaction between actin and myosin
    • Detects myocardial infarction in humans
    • Can be increased in nonischemic disease, LV dysfunction, HCM
    • Study of chimps showed that it was predictive of only severe and not mild-moderate disease

Question 53

Discuss the treatment of cardiovascular disease in great apes.

What drugs classes would you use? Specifically for left ventricular hypertrophy or depressed ejection fraction?

What drugs are not recommended for gorillas?

Answer 53

Treating CVD in Great Apes

• Beta-blockers
• ACE inhibitors
• No studies have been performed (PK or PD)
• Experience, off label
• Aspirin in cases of thromboembolism, cerebral infarcts

Treatment and monitoring:

1. Some risk is involved treatment with cardiac drugs, especially when underlying cause is unclear and monitoring isn’t possible
2. Great apes are harder to monitor to allow fine-tuning of drugs
3. In humans you would closely monitor: body wt, fluid/salt intake, awake bp measurements, ECG, echo

Management Options:

1. ACE-inhibitor – for left ventricular hypertrophy
2. Beta-blocker – if cardiomyopathy present (ie, depressed ejection fraction)
3. Diuretic as needed
4. Digitalis-based cardioglycosides have been used but not recommended for gorillas
5. Monitor diet, exercise tolerance, fluid retention, body weight

Question 54

When do apes generally become sexually mature?

How long are typical cycles?

How long is pregnancy typically?

What contraception methods are recommended for male great apes?

What about for female great apes?

What are some common reproductive issues?

What systemic diseases may contribute to gestational issues?

Answer 54

Reproduction (Fowler 8)

• Male contraception: vasectomy, vas ligation or open-ended vasectomy (potentially reversible), GnRH agonists
• Female contraception: IUDs, GnRH agonists, progestin +/- estrogen contraceptives
  
  • MGA implants: melengestrol acetate
  • Depo-Provera injections: medroxyprogesterone acetate
  • Oral: megestrol acetate
  • Progestins in humans: weight gain, may exacerbate subclinical diabetes
• Disorders: extensive abdominal adhesions, endometriosis, uterine neoplasia
• Concurrent diabetes, obesity, and hypothyroidism may contribute to gestational issues
• Gestation is 7.3 months (230 ish in bonobos & chimps) and about 8.3 months (255, 245) in gorillas and orangutans.

Question 55

What are some of the common neuroleptics used in great apes?

What are some important side effects to be aware of?

When should these drugs be avoided?

Answer 55

Categories:

• Butyrophenones (haloperidol, azaperone,)
• Phenothiazines (perphenazine, fluphenazine)
• Thioxanthenes (flupenthixol, zuclopenthixol)
• Substituted benzamides (sulpiride)
• Atypical (risperidone)

Neuroleptics = antipsychotics for humans

General effects – extra pyramidal symptoms, sedation, alpha-adrenoceptor blocking activity, antimuscarinic effects.

Side effects, contraindications:

• Avoid with renal or hepatic impairment or CV disease
• Avoid during pregnancy
• Most significant sides = extrapyramidal signs
• Occur with piperazine phenothiazines and the butyrophenones
• Extrapyramidal signs : parkinsonian-like symptoms (incl tremor), dystonia (abn face and body movements), akathisia (restlessness), and tardive dyskinesia ( involuntary rhythmic movement of tongue, face, jaw)
• Neuroleptic malignant syndrome: hyperthermia, fluctuating level consciousness, muscular rigidity, autonomic dysfunction with pallor, tachycardia, labile blood pressure, sweating, urinary incontinence.

Other sides

• Drowsiness, insomnia, convulsions, dissiness, gi disturbances, cv disturbances incl sudden death, photosensitization and corneal and lens opacities.

Question 56

A recent study evaluated the heart rate and blood pressure of chimpanzees to four different field protocols.

What were the four different protocols?

How did the addition of isoflurane to MK affect heart rate?

Answer 56

Atencia, R., Stöhr, E. J., Drane, A. L., Stembridge, M., Howatson, G., Del Rio, P. R. L., … & Shave, R. E. (2017). Heart rate and indirect blood pressure responses to four different field anesthetic protocols in wild-born captive chimpanzees (Pan troglodytes). Journal of Zoo and Wildlife Medicine, 48(3), 636-644.

Question 57

A recent study evaluated teh vitamin D status of gorillas in zoos with different husbandry and management practices.

What are some of the important functions of vitamin D?

Which metabolite is the most reliable indicator of vitamin D status?

How was the vitamin D concentrations of indoor-housed, but supplemented gorillas?

Is supplementation alone sufficient?

What husbandry changes could be made?

Answer 57

Bartlett, S. L., Chen, T. C., Murphy, H., Holick, M. F., Tlusty, M., & Baitchman, E. (2017). Assessment of serum 25-hydroxyvitamin d concentrations in two collections of captive gorillas (gorilla gorilla gorilla). Journal of Zoo and Wildlife Medicine, 48(1), 144-151.

Abstract: Serum 25-hydroxyvitamin D concentrations were assessed in subadult to adult captive lowland gorillas (Gorilla gorilla gorilla) br(n = 26) at two institutions with different husbandry and management practices. Serum 25-hydroxyvitamin D (25[OH]D) concentrations for gorillas managed predominantly indoors was low (14.2 ± 5.9 ng/ml), despite consuming commercial biscuits fortified with vitamin D₃. Concentrations of 25(OH)D in gorillas with near daily outdoor access were significantly higher than gorillas managed indoors, although many individuals still had serum values below concentrations recommended for adult humans. Consideration should be given to assessing 25(OH)D concentrations in all captive gorillas and providing specific supplementation, particularly to juveniles without access to direct sunlight.

• Humans – Vit D important for skeletal development, Ca homeostasis, immune function, modulation of cell proliferation (certain cancers).
• Serum 25-hydroxyvirD (25OHD) best indicator of vit D status, reflects vit D cutaneously synthesized (D3) and orally absorbed (D2).
• MBD seen in an infant gorilla at Zoo New England.
• This study: Assessment of baseline serum 25OHD and comparison to another group with exposure to sunlight for at least 4 hours per day.
• Sources of Vit D for gorillas – dietary or sunlight.
• Human infants rely on direct supplementation and endogenous production.
• Mean 25OHD concentrations at ZNA significantly lower than ZA (sunlight exposed).
  
  • Animals at ZA fed diet with higher D3 conc had lower serum concentrations.
    
    • Possibly due to inaccurate fortification of biscuits, variation in palatability and consumption.
• Serum concentrations should be at least 30 ng/ml.
  
  • None of the ZNE animals had sufficient concentrations.
  • 6 considered deficient, 4 considered severe.
• Humans – increased skin pigment is assoc with reduced synthesis of D3, possible this occurs in gorillas. Should not influence maintenance of adequate serum concentrations.
• Low vit D concentrations assoc with dc GI Ca absorption and increased PTH and BP => hypertrophy and fibrosis of the left ventricle.
  
  • Vit D should be considered in development of fibrosing cardiomyopathy in gorillas.
• Oral supplementation appears to be an efficient method for supplementation in gorillas.
• Providing UVB lighting in large exhibits not really practical, but gorillas may seek exposure if offered. May increase endorphin levels.

Takeaway: Advisable to monitor 25OHD conc in captive gorillas, consider supplementation if less than 30 ng/ml.

Question 58

A recent study described diffuse idiopathic skeletal hyperostosis in managed gorillas.

What is DSIH?

How does it differ form spondylarthritis and spondylosis?

What anatomic sites in gorillas are predisposed to DSIH?

Answer 58

Journal of Zoo and Wildlife Medicine 51(3): 578–590, 2020

DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS IN CAPTIVE GORILLAS (GORILLA SPP.): APPEARANCES AND DIAGNOSIS

Brian Livingstone, FRCS, FLS, Andrew C. Kitchener, BSc, PhD, Gordon Hull, Tobias Schwarz, Dr med vet, FRCVS, Sanjay Vijayanathan, MRCP, FRCR, Matthew J. Allen, Vet MB, PhD, MRCVS, Matyas Liptovszky, DVM, Dipl ECZM, and Roberto Portela Miguez, BA

Abstract: Diffuse idiopathic skeletal hyperostosis (DISH) is a disorder of unknown cause, in which new bone forms in soft tissues attached to the skeleton. Originally described in humans, in whom it is quite common, it is usually asymptomatic. New bone may completely bridge across joints, especially in the spine. However, it can be difficult to distinguish from diseases such as spondyloarthritis and spondylosis. With safer and increased use of radiography in diagnosis, the unfamiliar skeletal changes of asymptomatic DISH may now be coincidentally revealed during investigation of other disorders and result in misdiagnosis and unnecessary treatment. There have been case reports of its occurrence in great apes, but this is the first study to illustrate its appearances in a series of 11 skeletons of western and eastern lowland gorillas (Gorilla gorilla gorilla and Gorilla beringei graueri) from zoos in Europe and the United States. The study combines a review of available clinical and postmortem records with examination of the skeletons and radiologic investigation, such as computed tomography (CT). The results indicate that the disorder is probably common in older (>30 yr) captive gorillas, but that it is asymptomatic. It was not symptomatic during life in any of these animals. Several cases had unexpected features, such as extensive involvement of the thorax and extra-articular sacroiliac and tibiofibular joint fusions that are not typical in humans. By illustrating these skeletons, the study should aid differentiation of DISH from spondylosis (syn spondylosis deformans) and spondyloarhritis. It illustrates those features that are atypical of human DISH. CT scanning is valuable in such cases for examining diagnostically important areas such as sacroiliac joints. Increased awareness of DISH should help with understanding its cause, both in gorillas and humans.

Key Points

• Diffuse idiopathic skeletal hyperostosis (DSIH)
  
  • New bone forms within ligaments and at attachment of tendons or ligaments to bone – cause is unknown and in humans it is usually asymptomatic
  • Can be confused with spondylarthritis & spondylosis
  • Spondylarthritis would result in prominent pain & deformity
  • Spondylosis results from degenerative changes in intervertebral discs including some arthritis in the zygapophyseal joints (facet joints between spinous processes)
• Common in older gorillas and should be differentiated between the other two processes
• Gorillas have extensive DSIH of the thorax, extra-articular sacroiliac, and tibiofibular joints – different than humans

Take Home: DSIH is a differential for bridging hyperostosis of the spine, sacroiliac joint, and tibiofibular joint

Question 59

A recent study evaluated the cardiac structure and function of wild-born chimpanzees in santuaries in Africa.

How does heart function differ in adult chipanzees compared to younger animals?

How do male hearts compare to female hearts?

What is the typical pattern of cardiac remodeling in managed chimpanzees? What is the suspected cause of that? Was that observed in this study?

Answer 59

Drane, A. L., Atencia, R., Cooper, S. M., Rodriguez, P., Sanchez, C., Simcox, S., … & Unwin, S. (2019). Cardiac structure and function characterized across age groups and between sexes in healthy wild-born captive chimpanzees (Pan troglodytes) living in sanctuaries. American journal of veterinary research, 80(6), 547-557.

OBJECTIVE - To comprehensively characterize cardiac structure and function, from infancy to adulthood, in male and female wild-born captive chimpanzees (Pan troglodytes) living in sanctuaries.

ANIMALS - 290 wild-born captive chimpanzees.

PROCEDURES - Physical and echocardiographic examinations were performed on anesthetized chimpanzees in 3 sanctuaries in Africa between October 2013 and May 2017. Results were evaluated across age groups and between sexes, and potential differences were assessed with multiple 1-way independent Kruskal-Wallis tests.

RESULTS - Results indicated that left ventricular diastolic and systolic function declined at a younger age in males than in females. Although differences in right ventricular diastolic function were not identified among age groups, right ventricular systolic function was lower in adult chimpanzees (> 12 years old), compared with subadult (8 to 12 years old) and juvenile (5 to 7 years old) chimpanzees. In addition, male subadult and adult chimpanzees had larger cardiac wall dimensions and chamber volumes than did their female counterparts.

CONCLUSIONS AND CLINICAL RELEVANCE - Results of the present study provided useful reference intervals for cardiac structure and function in captive chimpanzees categorized on the basis of age and sex; however, further research is warranted to examine isolated and combined impacts of blood pressure, age, body weight, and anesthetic agents on cardiac structure and function in chimpanzees.

Background: Cardiac morbidity/mortality high in captive chimps. Myocardial fibrosis suggested as primary COD in heart related fatalities in chimps, but limited studies/data to actually draw from.

Discussion:

• Findings: male chimpanzees had larger hearts than females and that between age groups and sexes there were differences in cardiac function, specifically related to earlier decline in diastolic and systolic function in males, compared with females
• Typical pattern of concentric cardiac remodeling (increasing LV wall thickness + decreased LV chamber dimensions, often the result of hypertension) did not occur in chimpanzees in this study but cardiac volumes and wall thicknesses increased proportionally
• In previous study captive chimps almost all showed evidence of concentric remodeling - but BP’s weren’t obtained at time of study. Later reports of BP in this population showed higher BP’s than obtained in this study → higher BP could lead to higher rates of concentric remodeling

Take Home Points: Concentric cardiac remodeling not observed in this study. Males had larger hearts than females and showed earlier decline in diastolic and systolic function compared to females.

Question 60

A recent paper described colonic diverticulosis in a geriatric female oragutan.

HOw did this animal present?

What was found on colonoscopy?

What is the anatomy of the orangutan colon like?

How does colonic diverticulosis develop? How does it lead to bleeding?

What are risk factors for diverticular bleeding?

Answer 60

Vitali, S., Eden, P., Payne, K., & Forbes, G. (2017). Colonic diverticulosis and diverticular hemorrhage in a geriatric female orangutan (pongo abelii). Journal of Zoo and Wildlife Medicine, 48(4), 1264-1266.

Abstract: A 57-yr-old female Sumatran orangutan (Pongo abelii) presented with signs of intermittent lethargy and inappetence, then subsequently developed profuse hemorrhagic diarrhea. Colonoscopy under anesthesia revealed diverticulosis of the descending colon, with multiple large diverticula containing fecoliths. There was no evidence of diverticulitis, but a regenerative anemia had developed following an acute diverticular bleed. The orangutan recovered with conservative therapy. Colonic diverticulosis has been reported in nonhuman primates and appears to have a similar clinical presentation to the condition as it occurs in humans. This is the first published report of colonic diverticulosis in a great ape.

• Same patient had a similar episode of hematochezia 2 yr prior, responded to oral ibuprofen.
• CS – abdominal discomfort, diarrhea, hematochezia.
  
  • Rx ibuprogen, amoxicillin, bismuth subsalicylate, electrolyte replacement solution.
  • Following morning passed several stools (formed), bloody mucous.
  • Intermittent lethargy -> colonoscopy.
    
    • Multiple diverticula in colonic wall, many containing fecoliths, fresh and coagulated blood present, no active hemorrhage.
    • Tx ampicillin, clavamox, PPG, benzathine penicillin, iron, meloxicam, medroxyprogesterone acetate.
• Orangutan colon – haustrated, primary site of bacterial fermentation of nonstarch polysaccharides.
  
  • Diverticulosis common in geriatric humans.
  • Segmental increases in colon pressure lead to mucosal bulging and subsequent development of diverticula.
  • Fecoliths can complicate.
  • Characterized by rectal bleeding, inflammation (mucosal erosion into a local blood vessel within a diverticulum). Painless, self-limiting.
  • Affected animals may be clinically normal.
  • Unlike colonic diverticulum, small intestinal diverticular bleeding has high likelihood of recurrence and mortality when managed by conservative tx alone.
  • Humans – due to increased intraluminal pressure, impairment of colonic mucosal barrier, abnormal colonic motility, low-grade bowel inflammation, alterations in gut microbiota.
    
    • Risk of symptomatic diverticular disease may be diminished by use of high-fiber diet and vigorous physical activity.
    • Obesity, NSAIDs associated with increased risk of bleeding.

Question 61

A recent study evaluated the effects of snare-related injuries in endangered mountain gorillas.

What is the most common cause of morbidity and mortality in wild mountain gorillas?

What age group is most likely to be snared?

How many gorillas recovered after snare removal?

What factors were associated with a poor outcome?

Answer 61

Haggblade, M. K., Smith, W. A., Noheri, J. B., Usanase, C., Mudakikwa, A., Cranfield, M. R., & Gilardi, K. V. (2019). Outcomes of snare-related injuries to endangered mountain gorillas (gorilla beringei beringei) in rwanda. Journal of wildlife diseases, 55(2), 298-303.

ABSTRACT: Mountain gorillas (Gorilla beringei beringei) are one of the most critically endangered great apes in the world. The most common cause of mountain gorilla morbidity and mortality is trauma (e.g., injury from conspecifics or snare entrapment). We conducted a retrospective case-control study of freeranging, human-habituated mountain gorillas to evaluate factors associated with snare entrapment and the results of clinical intervention. Data were collected from clinical records on all clinical intervention cases (n¼132) in Volcanoes National Park, Rwanda, conducted between 1995–2015. Wildlife veterinarians treated 37 gorillas entrapped in snares and 95 gorillas for other clinical conditions (including trauma and respiratory illness). Multivariate statistical analyses revealed that young gorillas (<8 yr old) were more likely than older gorillas to become snared; that comorbidities delayed times to intervention (3 d); and that severity of wounds at the time of intervention were associated with increased risk of lasting impairment (including loss of limb or limb function, or death) within 1 mo after intervention. Our results may influence decisions for gorilla health monitoring and treatment to most effectively conserve this critically endangered species.

• Population declined to 250 in the 80s, now 1004 (as of 2018)
• Most common causes of mortality are traumatic injury and respiratory disease
• 86% of gorillas recovered within 1 month after snare removal
• Factors associated with death/impairment of gorillas included comorbidity, delayed interventions and severe wounds
  
  • Comorbidity were 21x more likely to show poor survival
  • Interventions over 3 days of observation were more likely to have poor outcome

Takeaways:

• Prompt veterinary intervention improved likelihood of recovery for injured gorillas
• Included only 1 population of gorillas

Question 62

A recent study reviewed the causes of western lowland gorilla mortality in European zoos.

What was the most common cause of mortality?

How did causes of mortality differ between males and females?

How much more likely was death from cardiac disease in males?

How much more likely was death from external causes in females?

Answer 62

Strong, V., Baiker, K., Brennan, M. L., Redrobe, S., Rietkerk, F., Cobb, M., & White, K. (2017). A retrospective review of western lowland gorilla (Gorilla gorilla gorilla) mortality in European zoologic collections between 2004 and 2014. Journal of Zoo and Wildlife Medicine, 48(2), 277-286.

Abstract: An understanding of the main causes of mortality among captive gorillas is imperative to promoting their optimal care, health, and welfare. A retrospective observational review of mortality among the European zoo–housed western lowland gorilla (Gorilla gorilla gorilla) population from 2004 to 2014 was carried out. This is the first published study of mortality in this population. Relevant postmortem data were requested from each collection reporting a death during the study period. Age at death enabled grouping into discrete age categories. Deaths were classified according to cause. The main causes of death overall and for each age category and sex were identified. In total, 151 gorillas from 50 European collections died during the study period. Postmortem data were available for 119 (79%) of the deaths, of which 102 (86%) were classified by cause. Diseases of the digestive system were responsible for most (23%) deaths overall. Also of significance (each accounting for 15% overall mortality) were deaths due to external causes (especially trauma) among young gorillas and cardiovascular disease among adult and aged animals. Being a male gorilla was associated with an 8.77- and 5.40-fold increase in risk of death due to cardiovascular and respiratory disease, respectively. Death due to external causes was 4.45 times more likely among females than males. There was no statistically significant difference in life expectancy between male and female gorillas. The authors conclude that further work is needed to understand risk factors involved in the main causes of death and suggest a need for standardization with regard the approach to postmortem examination and data collection, sample collection, and storage across European zoos.

• Digestive system disease responsible for largest number of deaths, followed by diseases of cardiovascular system and death due to external causes
  
  • Peritonitis common
  • Intra-abdominal abscesses have also previously been identified as a significant problem among female gorillas in North American zoos
• Deaths occurring due to external causes (especially trauma) were identified as being a particular problem before sexual maturity
• cardiovascular disease only identified as a cause of death among adult and aged gorillas
• majority of animals dying due to disease of digestive system were also classified as adult or aged, although deaths within this category were reported across the ages
• females three main causes of death - disorders of digestive system (28%), external causes (21%), and neoplastic disorders (12%)
• males three main causes of death - diseases of circulatory (30%), respiratory (19%), and digestive (16%) systems

Question 63

A recent study described congenital hypothyroidism in orangutans.

How did these cases present?

What were the results of thyroid testing?

How did they respond to levothyroxine supplementation?

Answer 63

Fayette, M. A., Tocidlowski, M. E., Brown, B. P., Trautman, M. S., & Bowman, M. R. (2019). Congenital hypothyroidism in a bornean orangutan (pongo pygmaeus) and a sumatran orangutan (pongo abelii). Journal of Zoo and Wildlife Medicine, 50(2), 461-465.

Abstract: Congenital hypothyroidism (CH) in humans is most commonly caused by disruption of thyroid gland development (dysgenesis) or an inherited defect in thyroid hormone biosynthesis (dyshormonogenesis). CH has not been previously documented in great apes. This report describes the clinical presentation, diagnosis, and treatment of CH in a 9-mo-old male Bornean orangutan (Pongo pygmaeus) and a 6-wk-old female Sumatran orangutan (Pongo abelii). Primary CH due to thyroid dysgenesis was confirmed in the Bornean orangutan using sonography and radioisotope scintigraphy. Although commercial thyroid immunoassays are not validated for use in orangutans, in comparison to age-matched controls, thyroid-stimulating hormone level was markedly elevated, and serum thyroxine (T4) and free T4 levels were markedly decreased in both cases. Oral supplementation with levothyroxine sodium resulted in noticeable clinical improvement in both orangutans within 30 days of initiating treatment.

• Congenital hypothyroidism (CH) in humans is uncommon. First congenital CH in a great ape
• Case 1: 9-mo-old, parent-reared, male Bornean orangutan evaluated for delayed growth and development
• Case 2: 6-wk-old, hand-reared, female Sumatran orangutan (Pongo abelii)
  
  • Lethargy, poor growth and feeding response, and impaired thermoregulation.
• Case 1:
  
  • Exam : hypotonia, myxedematous facies, macroglossia, lack of tooth eruption, abdominal distension, and poor hair growth
  • Diminished motor skills and impaired cognition compared to clinically normal infant orangutans. Serum biochemical abnormal: mild hyperbilirubinemia
  • Thyroid sonography revealed no discernible glandular tissue present in the expected region of the thyroid. Thyroid scintigraphy negative
  • Serum TSH level markedly elevated, and T4 and free T4 levels were decreased
  • Oral supplementation w/ levothyroxine sodium was initiated daily
  • At 3 wk of treatment–>orangutan showed marked improvement
• Case 2:
  
  • Exam: jaundice, abdominal distension, and a grade IV/VI continuous murmur at the left heart base. CBC and biochem abnormals: mild anemia, moderate hyperbilirubinemia. Rads showed subjective enlargement of the cardiac silhouette.
  • Echocardiogram performed by a human cardiologist detected a small patent ductus arteriosus (later spontaneously closed). All four cardiac chambers were of normal size and cardiac function was deemed adequate
  • Serum TSH level markedly elevated, and T4 and free T4 levels were decreased
  • Oral supplementation w/ levothyroxine sodium was initiated daily
• Pathogenesis of CH is still largely unknown. Early detection of CH through routine newborn screening w/ rapid initiation of treatment carries an excellent prognosis

Takeaway: Thyroid dysfunction in these 2 orangutan cases was suspected based on a combination of clinical signs, laboratory values, and a positive response to treatment. Imaging may confirm diagnosis of CH due to thyroid dysgenesis.

Question 64

A recent study reviewed veterinarary intervention in gorilla reproduction.

What are some reproductive concerns in female gorillas?

When is the highest gorilla mortality rate? What is this usually due to?

How well do gorilla neonates successfully reintroduce to their dams? Does this differ with introduction to a surrogate?

How has the live birth rate changed over time?

How was the rate of assist-reared gorillas changed?

How has neonatal mortality changed?

What are the most common reasons to remove an infant?

Answer 64

Berlin, E., Thurber, M. I., & Lamberski, N. (2019). Review of veterinary intervention in reproduction of captive western lowland gorillas (gorilla gorilla gorilla) from 1996 to 2016. Journal of Zoo and Wildlife Medicine, 50(3), 539-546.

Abstract: In order to gain an understanding of the frequency of veterinary intervention during the periparturient period of western lowland gorillas (Gorilla gorilla gorilla) in captivity between 1996 and 2016, a survey was sent to institutions associated with the Association of Zoos and Aquariums’ Gorilla Species Survival Plant. A total of 193 births were reported during the survey period, from 51/53 institutions. There were six incidences of prolonged labor (longer than 6 hr; 3%), six cases of cesarean section (3%), and three incidences of veterinary intervention that did not involve a cesarean section (2%). Fifty-one gorilla neonates (26%) were assistreared (required intervention lasting longer than 24 hr). Out of 51 attempts to reintroduce neonates to dams or surrogates, 42 were accepted (82%), while nine attempts (18%) were deemed failures. The age group with the highest rate of maternal or surrogate acceptance after reintroduction was between 6 and 12 mo of age. Compared to data from a 1981 survey, the percentage of assist-reared gorillas decreased from 64% to 26%. Results show that veterinary intervention in the periparturient period is low, and there is a high rate of acceptance of neonates by either the dam or a surrogate after intervention. Advances in captive husbandry and veterinary knowledge have led to a reduced risk of veterinary intervention during gorilla parturition; however, the long-term effects on behavioral development of the neonate should be considered before removal of the infant from the dam for any period of time.

• Western lowland gorillas: IUCN critically endangered
  
  • Past literature: medical concerns in great apes in captivity include abortion, eclampsia, dystocia, metritis.
  • Several case reports of C-sections for various reasons including previous infanticide, pelvic fracture, prolonged labor. One case of assisted parturition not requiring C-section.
  • Recent retrospective showed highest gorilla mortality in first 5 yrs of life with 81% within first 12 mo. Wild lowland gorillas infant mortality rates 22-65% most commonly from trauma, followed by respiratory infection. Captive survey in 1981 showed 28% infants died in first 3 yr of life from illness, trauma, or unknown cause. Individual case reports of infant/juvenile gorilla mortality from neoplasia, hypocalcemia, congenital defects, and gastric dilatation.
  • No previous reviews of acceptance of neonate reintroductions to dam or surrogate in captive western lowland gorillas.
    
    • Pros: lower mortality rate in first 6 mo of life (suspect decreased risk of conspecific trauma, easier medical care/intervention)
    • Cons: negative impacts on behavior development and reproductive success, may affect whole troop dynamic if others learn these behaviors
    • Lit in monkeys showed surrogate-reared do not have sig developmental delays
• 1996-2016: births, veterinary intervention, reintroduction to dam/troop/surrogate.
• 193 births at 51 institutions
  
  • 97% live birth rate (3% stillborn or death during labor) - increased from 83% in 1981
  • 3% (6/193) prolonged labor (> 6hr based on wild parturition time <1 hr)
  • 3.6% (7/193) instances of veterinary intervention
    
    • 6 C-sections (3 for prolonged delivery, 2 for vaginal hemorrhage, 1 due to placenta abnormality seen on U/S), 1 assisted vaginal delivery
    • 1 born without intervention, 1 died without intervention, 1 dystocia <6hr long resulting in infant death
• 27% (51/187 live births) assist-reared or intervention > 24hr - decreased from 64% in 1981
  
  • Reasons for removal from dam: maternal neglect (33%), difficult parturition or neonatal illness (14%), unspecified reason (37%)
• 82% (42/51) successful reintroduce - no sig diff btw success of dam vs surrogate
  
  • 82% successful reintroduction to dam, 88% successful introduction to surrogate
  • 83% C-sections successfully reintroduced to dam or surrogate
  • 18% reintroduction failures, 1 resulting in infant death (suffocation)
  • 5% reintroduction not attempted/reported
  • Timing varied (several days to 3 yr), highest success (100%) in 6-12mo old, sig higher than > 1yr old
  • 91% (10/11) male gorilla acceptance of unrelated neonates into troop
• Increased live birth rate (97%) compared to 1981 (83%)
• Decreased veterinary intervention (4%) - all 6 C-sections successful (live birth), 6/7 safely reintroduced to dam or surrogate
  
  • Most common reason for removal from dam: lack of maternal care, then infant injury/illness
• Decrease in assist-reared gorillas (27%) compared to 1981 (64%)
  
  • 14% infants in 1980s removed from dam as ‘precaution’ vs 0% in this study
  • SSP recommends maximizing maternal-rearing potential of troops to avoid long term negative impacts on reproduction of infant and behavior of troop as a whole
  • Suggests 72 hr postpartum observation protocol to ensure successful dam rearing
• Successful acceptance of neonates by dam or surrogate after intervention
  
  • 2 days to 3 yr of age - highest success rate in 6-12 mo old, sig decline in >12 mo old.
• Neonatal gorilla mortality prior to or during parturition has declined since 1981 (now 98% live birth rate)
• Most common reason for removal of an infant is lack of maternal care, then infant injury/illness

Take home points: Intervention in periparturient period low with high rate of acceptance of neonates by dam/surrogate if intervention necessary

Question 65

A recent study described an outbreak of parainfluenza 2 in a group of managed western lowland gorillas.

What are some other respiratory viruses that wild populations have contracted from human visitors? How relevant is this to conservation tourism?

How did these gorillas acquire the infection?

What was the result?

Answer 65

Couture, É. L., Ferrell, S. T., Desmarchelier, M., Hamelin, M. È., Mendoza, L. J. S., Carbonneau, J., … & Lair, S. (2019). Human parainfluenza 2 related illness and a death in a group of captive western lowland gorillas (gorilla gorilla gorilla). Journal of Zoo and Wildlife Medicine, 50(3), 713-717.

Abstract: An onset of respiratory disease in a captive bachelor group (n = 3) of western lowland gorillas (Gorilla gorilla gorilla) was concomitant with peak attendance of visitors at the institution and with unwanted occurrences of food items being thrown in the gorillas’ enclosure. While the condition of two individuals improved with supportive therapy and antibiotics, the third gorilla died three days following initiation of treatment. A fatal bacterial pneumonia, secondary to an infection by a human parainfluenza virus 2 (HIPV-2), was considered to be the cause of death based on histopathology, lung cultures, and reverse transcription PCR. HPIV- 2 activity in the human population of the province was detected for that period, including the same viral strain. This report confirms a HPIV-2 respiratory illness and associated death in a gorilla. Clinical presentation and context suggest conspecifics were also affected and that contaminated food thrown by visitors may have been the source of infection.

• Gorillas shown to be seropositive to many human resp viruses
  
  • Parainfluenza virus 2 included
• Susceptibility to disease documented in wild populations infected with Pneumoviridae viruses
  
  • Human resp syncytial virus (HRSV), human metapneumovirus (HMPV)
• Resp disease second most common cause of M&M in human habituated mountain gorillas and second most common cause of death in captive male gorillas
• Attempts to confirm presence of viral antigen in lesions by IHB inconclusive (no positive control)
• NHP used in research → African green monkeys and chimps = permissive hosts for HPIV-1,-2,-3 replication
• Secondary bacterial infections with S. pneumoniae and K. pneumoniae frequent

Take home points: human visitors are a source of possible respiratory viral infection to NHP’s, secondary bacterial pneumonia can increase M&M

Question 66

A recent paper described the surgical management of uterine lesions in orangutans.

What are fibroids?

What is adenomyosis?

What is endometriosis?

What is the most common proliferative uterine disease in nonhuman primates?

What is the mainstay of treatment for these disorders?

What is dysmenorrhea? What is menorrhagia?

Answer 66

Kruse, T. N., Bowman, M. R., Ramer, J. C., Fayette, M. A., Greer, L. L., Stadler, C. K., … & Proudfoot, J. S. (2018). Surgical management of uterine lesions in two captive orangutans (pongo spp.). Journal of Zoo and Wildlife Medicine, 49(1), 210-213.

Abstract: Uterine lesions in two orangutans were effectively managed with surgical intervention. A 26-year-old hybrid orangutan (Pongo spp.) was diagnosed with uterine adenomyosis based on advanced imaging. Histologic evaluation identified multifocal myometrial endometriosis, a variant of adenomyosis. A 27-year-old Bornean orangutan (Pongo pygmaeus) was diagnosed with a focal uterine fibroid based on histologic examination. The animals were housed at separate institutions and initially presented with dysmenorrhea and menorrhagia. Both animals were treated intermittently for episodes of dysmenorrhea, with recurrence of clinical signs after each treatment. Due to the lack of consistent response to medical management, an ovariohysterectomy in the hybrid orangutan and a myomectomy in the Bornean orangutan were performed and resulted in complete resolution of clinical signs. Surgical management of adenomyosis and neoplasia has previously been reported in nonhuman primates. These cases are the first known documentation of surgical management of multifocal myometrial endometriosis and a fibroid in orangutans.

• Neoplastic and proliferative uterine dz in NHP – leiomyomas or fibroids most common.
  
  • Fibroids – benign, from smooth muscle of uterine wall.
  • Adenomyosis – non-neoplastic, benign invasion of ectopic endometrium into the myometrium with hyperplasia of adjacent smooth muscle.
    
    • May be misidentified on US as fibroid and vice versa.
    • Fibroids have been successfully tx in a gorilla with OHE, oral megestrol acetate, medroxyprogesterone acetate.
    • Orangutan was successfully tx with OHE for clinical signs of dysmenorrhea and menorrhagia.
  • Endometriosis - invasion of ectopic endometrium outside of the uterus (fallopian tube or abdominal organs)
  • This report – surgical management of multifocal myometrial endometriosis and a uterine fibroid in two orangutans.
    
    • 26yo nulliparous female – sporadic, irregular dysmenorrhea (painful menstrual cramps), menorrhagia (excesses menstrual bleeding), characterized by lethargy, decreased appetite, hunched position.
      
      • US – 4 cm uterine mass, OHE performed due to persistent CS.
        
        • Numerous adhesions seen during surgery, repro tract submitted for histo.
        • Histo – hypertrophied muscular tunics, glandular implantation, chronic hemorrhage with scarring in muscular tunics of uterus.
        • Robust endometrial stromal tissue, streaming spindle cells. No evidence of malignancy.
    • 27yo nulliparous female, similar CS.
    • Transvaginal US showed a 6.3 cm mass in myometrium of posterior uterine wall, consistent with fibroid.
    • Lupron was used but mass doubled in size. CS persisted.
    • MRI, planned for hysterectomy. Multiple adhesions. Myomectomy was performed due to inability to clamp parauterine and paracervical tissues for a complete hysterectomy.
    • Histo – uterine fibroid. CS resolved.
  • CS – dysmenorrhea and menorrhagia are common in menstruating women with adenomyosis, also seen with other urogenital disorders i.e. endometriosis.
    
    • Mainstay of tx for adenomyosis in humans is hysterectomy.
    • MRI useful to differentiate between adenomyosis, uterine fibroid, and MME in humans.
  • Pathogenesis unknown – genetics, growth factors, steroid hormone stimulation have been considered as contributing factors.

Takeaway: Uterine adenomyosis, fibroids, and endometriosis should be considered possible in any aged, intact female great ape with menorrhagia and dysmenorrhea. Surgical intervention should be considered for adenomyosis and uterine fibroids in orangutans in lieu of long term medical management.

Question 67

A recent study used electroencephalograms to monitor the anesthetic depth of chimpanzees.

What is the patient state index? What would a value of 0, 25-50, or 100 indicate?

How did the PSi during the phases of anesthesia correlate with human values?

Answer 67

POTENTIAL FOR ELECTROENCEPHALOGRAPHIC MONITORING OF ANESTHETIC DEPTH IN CAPTIVE CHIMPANZEES (PAN TROGLODYTES) USING A NOVEL BRAIN FUNCTION MONITOR.

Mulreany, L.M., Cushing, A.C., Ashley, A.L. and Smith, C.K.

Journal of Zoo and Wildlife Medicine, 2020;51(3):729-732.

The electroencephalogram (EEG) waveform can predictably change with depth of anesthesia, and algorithms such as the Patient State index (PSi) have been developed to convert the waveform into a user-friendly objective reading of anesthetic depth. In this study, PSi values were measured in 10 captive chimpanzees (Pan troglodytes) during three phases of an anesthetic event. Phase 1 included sedation with dexmedetomidine, midazolam, and ketamine. Phase 2 started with administration of an α-2 antagonist and isoflurane. Phase 3 started with discontinuing isoflurane and ended with spontaneous movement and extubation. Initial PSi readings for phase 1 were high at 74.5 ± 12.2 (mean ± SD), before declining to 24.1 ± 5.3 for the remainder of the phase. Phase 2 PSi values were recorded as 21.4 ± 5.4 and then climbed during phase 3. Spontaneous movement was recorded at PSi values of 72 to 79. Electroencephalographic monitoring via PSi was successfully performed during three phases of anesthesia in the chimpanzees and was consistent with human values reported during general anesthesia. This paper serves as a preliminary investigation into EEG monitoring of chimpanzees, and further work is needed for its validation.

Background

• Electroencephalogram (EEG) waveform in humans correlates with depth of anesthesia
  
  • Real-time unitless PSi, 0 - cortical silence, 100 - awake, 25-50 surgical plane
  • EEG waveform, density spectral array (DSA), suppression ratio, artifact, and electrode status
• Center of the forehead (shaved and cleaned): primary left and right active channels, separated by ground channel, with reference channel directly above. Other two active channels over temporal skull laterally.

Key Points

• Phase 1 (sedation): initially mean 75 then declined and stayed at 24
• Phase 2 (anesthesia induction, maint): mean 21.4
• Phase 3 (recovery): spontaneous movement recorded at 72-79
• Average PSi during GA and recovery for chimpanzees was similar to human reported values
• 2 large males unable to get readings due to excess impedance at contact points - possible interference from frontalis muscle

Conclusions

• EEG-guided anesthetic protocols in chimpanzees may allow reduced overall drug use and reduced awareness/spontaneous arousal events
• Chimpanzee PSi was reduced compared to humans under GA

Question 68

A recent study by the Great Ape Heart Project outlined the echocardiographic guidelines for the cardiac assessment of great apes.

What anesthetic protocol has the least effect on the anesthetized echo?

HOw should patients be positioned?

What species is most challenging to image?

Describe the landmarks, probe placement, and what structures can be assessed with the following views:

Parasternal long axis

Parasternal short axis

Apical 4/5/2 chamber views

Subcostal view

Suprasternal notch view

Answer 68

Boyd, R., Danforth, M. D., Rapoport, G., Sleeper, M. M., Devlin, W. H., Kutinsky, I., … & Murphy, H. W. (2020). Great Ape Heart Project guidelines for the echocardiographic assessment of great apes. Journal of Zoo and Wildlife Medicine, 50(4), 822-836.

Abstract: Cardiovascular disease (CVD) has been identified as a major cause of mortality in all four great ape taxa in zoologic institutions. In an effort to better understand and treat CVD in captive great apes, a program called the Great Ape Heart Project (GAHP), based at Zoo Atlanta, collects and maintains a database of echocardiograms and other relevant medical information relating to the cardiac health status of great apes. Cardiac health assessments have become standard practice among North American zoos that house great apes and are recommended by all four great ape Species Survival Plans (SSP) for the assessment of CVD in captive great apes. As of December 31, 2017, more than 70 ape-holding institutions have submitted approximately 1,100 cardiac examinations of great apes to the GAHP, information from which is stored in the GAHP database. Transthoracic echocardiography is one of the most practical and cost-effective diagnostic imaging techniques for the evaluation of cardiac function in great apes. Standardization of echocardiographic measurements is critical for maximizing the diagnostic value of an echocardiographic exam and for utilization of stored information in comparative studies within and between the great ape taxa. The following manuscript offers suggestions for standardization of nomenclature, imaging technique, echocardiographic measurements, data storage, and reporting of cardiac exams for submission into the GAHP database with the goal of promoting consistency and quality in data collection.

• Great Ape Heart Project est. 2010, out of Zoo Atlanta
• Online submission form www.greatapeheartproject.org/forms with measurements page
• Cardiovascular disease major cause of mortality in great apes
• Dissociative agent alone has least effect on anesthetized echo, inhalents have minimal effect alone on systolic function despite systemic vasodilation
• Echo: concurrent ECG, 2 sec loops, still images, DICOM image exporting, ideally ‘cardiac software package’
• Positioning: left lateral, left arm extended cranially.
• Male adult orangs most challenging to image due to heart on midline (often image better from right side) and chronic air sac/respiratory issues
• Multiple awake ‘sessions’ to obtain all views should occur within a 4 week period to be considered one ‘study’
• Majority left-sided disease so prioritize left measurements, partial submissions accepted
• Acoustic windows:
  
  • Parasternal long axis (PLAX) (A)
    
    • Landmarks - between sternum & left nipple, between 3-4 ICS
    • Probe angled to 10:00-11:00 (towards ape’s right shoulder)
    • View - LA, MV, LV, LV outflow, AV, IVS, RV, cardiac function
    • If angle is changed towards RH will allow for better view of TV
    • If angle is changed towards LS will allow for pulmonary valve & RV outflow tract
  • Parasternal short axis (PSAX)(A)
    
    • Landmarks - between sternum & left nipple, between 3-4 ICS
    • Probe angled to 2:00-3:00 (towards apes R hip - 90 degree turn from PLAX)
    • View - TV, AV, PV, MV, Papillary Muscles, IVS - center on base of the aorta - see LA, IAS, RA, RV, PA - best view for MV
  • Apical view: 4/5/2 chamber views (B)
    
    • Four Chamber
      
      • Landmarks - left lateral chest - 5th ICS, below L nipple
      • Proble angled at 2:00-3:00 with beam towards head
      • VIew IVD - inflow of gradients of MV & TV can be measured
    • Five Chamber
      
      • Move beam cranially to get LV outflow tract and aortic valve
    • Two Chamber
      
      • Rotate probe 45 degree (12:00) angled toward R shoulder - fo rbiplanar measurements
  • Subcostal (C)
    
    • Landmarks - level of the liver
    • Probe - marker to 3:00, angled cranially towards L shoulder
    • View - atrial septal defects or for confirming excessive pericardial fluid
  • Suprasternal notch (D)
    
    • Landmarks - at thoracic inlet with transducer at 1:00 angled towards abdomen
    • Views - ascending, transverse, adn descending aorta with head and neck vessels
• 2D, M-mode, color doppler (regurg), spectral doppler (velocities)

Takeaways:

• Great Ape Heart Project echo guidelines to promote consistency and diagnostic value
• Consider having a human sonographer or veterinary cardiologist with experience performing the echo

Question 69

A recent study descrbied teh use of human transfusion products in great apes.

What were some of the conditions these animals were being treated for?

Which survived?

Were there any suspected transfusion reactions? Were they to a specific product?

What anticoagulant was used?

Answer 69

Hahn, A., Sturgeon, G., & Rossi, J. (2017). Blood product transfusions in great apes: a retrospective review of 12 cases. Journal of Zoo and Wildlife Medicine, 48(2), 461-465.

Abstract: Although the administration of blood and blood products can be lifesaving, transfusions in exotic species are less common because of the lack of knowledge of a species’ blood groups, the availability of species-specific donors, and possible adverse effects. Recently, blood groups were elucidated in great apes; however, few reports have been published regarding actual transfusion situations in these species. This information is critical because poorly executed transfusions can compromise already weakened patients or result in the death of the recipient. In 2014, a retrospective survey of U.S. zoos housing great apes received 45 of 67 responses; from which, 12 transfusion cases in great apes were identified, including Sumatran orangutans (Pongo pygmaeus sumatraensis, n = 4), chimpanzee (Pan troglodytes, n = 1), and western lowland gorillas (Gorilla gorilla gorilla, n = 7). These animals, ranging from birth to 31 yr, received intravenous transfusions of whole blood, packed red blood cells, or human albumin. Overall, animals that received transfusions for anemia because of chronic illness or blood loss survived, but those individuals with concurrent life-threatening issues did not survive. No adverse reactions related to the transfusion occurred, except in two orangutans given human albumin.

• CS assoc with anemia – Weakness, depression, tachycardia, tachypnea, pale MM, weak pulses.
• Cases:
  
  • 10 of the animals received transfusions secondary to variety of conditions – fetal erythroblastosis, renal inflammation or failure, GI hemorrhage, parasitic intestinal perforation, septicemia, DIC, acute lymphocytic B cell leukemia, chronic infection.
  • One received human albumin after dx with hypoalbuminemia and ascites secondary to C section.
  • One animal transfusion before and after sx for ASD repair.
  • Some animals pretreated before transfusion.
  • Most animals with anemia from chronic dz survived (6), others with life-threatening preexisting dz (4) died.
  • Two suspected transfusion reactions – Orangutans, human albumin.
  • Most cases used citrate-based anticoagulants (human blood transfusion bags).
• Takeaways:
  
  • Animals generally recovered from anemia following transfusion, some required multiple.
  • Reactions uncommon, except with transfusions involving human albumin.

Question 70

A recent report described the use of citalopram hydrobromide to manage aggression in a male chimpanzee.

What is the mechanism of citalopram?

What effect did this have on this aggressive animal?

Are there any potential paradoxical effects?

Answer 70

Richard, R., Boren, B., & Becker, J. (2020). The use of citalopram hydrobromide to manage aggression in a male chimpanzee (pan troglodytes). Journal of Zoo and Wildlife Medicine, 50(4), 1005-1007.

Abstract: At times severe, and occasionally fatal, aggression plays an intrinsic role in chimpanzee behavior and social dynamics, particularly among male chimpanzees in both managed and free-ranging troops. At the Los Angeles Zoo, one adult male’s natural aggressive behavior developed into unmanageable violence during a period of social and emotional instability consequent to the lack of an established alpha male in the colony. The severity and duration of resulting attacks on a subdominant member of the community, despite environmental and behavioral modification, indicated the need for psychopharmaceutical intervention. Prior treatment of this animal with haloperidol and gabapentin had produced undesirable side effects. Administration of citalopram hydrobromide, a selective serotonin reuptake inhibitor, successfully reduced both the intensity and duration of this male chimpanzee’s attacks upon a conspecific animal with minimal observable side effects or adverse behavioral changes.

• 25 yo M chimpanzee at the LA zoo presented for ongoing conspecific aggression
• Removal of the primary alpha male from this group 3 years prior resulted in social instability
• Aggression could not be managed with environmental and behavioral modifications alone
• Prior treatment with haloperidol and gabapentin had produced undesirable side effects
• Administration of citalopram hydrobromide, a selective serotonin reuptake inhibitor significantly reduced aggression
• This drug can have initial paradoxical effects in humans, with increased anxiety and antisocial behavior for the first few weeks—this was not noted
• Still, it is recommended to start with a low dose and build up over time

Question 71

A recent paper described echinococcosis in a western lowland gorilla.

What is the etiologic agent and what is its definitive host?

How do metacestodes behave pathologically?

What organ is primarily affected? What other organs can be affected?

What is teh current recommended protocol?

How can this disease be prevented?

Answer 71

Wenker, C., Hoby, S., Wyss, F., Mengiardi, B., Vögtli, R., Posthaus, H., … & Gottstein, B. (2019). Alveolar echinococcosis in western lowland gorillas (gorilla gorilla gorilla): albendazole was not able to stop progression of the disease. Journal of Zoo and Wildlife Medicine, 50(1), 243-253.

Abstract: Echinococcus multilocularis is the etiologic agent of alveolar echinococcosis (AE), a severe and potentially fatal larval cestode infection primarily affecting the liver. AE is known to occur in dead-end intermediate hosts, including humans and nonhuman primates. Between 1999 and 2016, AE was diagnosed in seven western lowland gorillas (Gorilla gorilla gorilla), all from a Swiss zoo. Six gorillas died of the disease. One individual is still alive, receives continuous albendazole medication, and shows no clinical signs. Most infected animals remained asymptomatic for years. Only one young gorilla showed early signs of acute discomfort and abdominal pain. In the final stage of the disease, affected animals died suddenly, or showed a short course of nonspecific but severe clinical signs, including lethargy, recumbency, abdominal enlargement, and anorexia. Postmortem examination confirmed hepatic AE complicated by peritonitis in most cases. Echinococcus multilocularis infection may remain undetected because of a very long incubation period. Hematological and biochemical parameters rarely showed abnormalities in this phase. Thus, inclusion of abdominal hepatic ultrasound examination and serology is recommended for early AE detection in routine examinations of gorillas in endemic areas or where food is potentially contaminated with E. multilocularis eggs. Ultrasound or computed tomography was useful to monitor progression and to estimate the volumetric extension of the hepatic lesions. Current medication with albendazole, which proved to be effective for human patients, was not able to stop progression of hepatic lesions in gorillas. Therefore, its therapeutic value remains questionable in gorillas. However, long-term oral albendazole treatment proved to be safe, and therapeutic plasma levels published for humans were achieved. Preventive measures such as thermo-treatment of food or vaccination of gorillas and other nonhuman primates should be considered in areas where E. multilocularis is present.

• Echinococcus multilocularis
  
  • Life cycle comprises a definitive carnivore host and an intermediate rodent host
  • Carnivores = definitive hosts, once ingested, protoscoleces develop into gravid adult tapeworms in small intestine of animal
  • Primates are dead end hosts when infected
  • Metacesodes behave like a malignant liver tumor, characterized by infiltrative proliferation of parasite tissue & potential to induce serious disease with high mortality rates if untreated
  • The infection potentially metastasizes to other organs, including lungs and brain
• AE - emerging disease of nonhuman primates in zoos, diagnosed since 1980s in Central Europe
  
  • Western lowland gorillas - high morbidity and mortality
  • Incubation of disease takes years; early diagnosis is rare
  • Rapid progression of the disease in the affected gorillas occurred despite oral treatment with albendazole
  • AST, ALT, and GGT are not reliable parameters to detect hepatic AE
  • Specific serologic tests for AE and abdominal ultrasound is recommended
  • Recent protocols recommend continuous life-long treatment with albendazole
  • In contrast to most human cases, chemical treatment was not able to stop progression of AE in two out of three gorillas using albendazole
  • Environmental control has been initiated at this facility to decrease risk
    
    • Steaming of food items
    • Harvesting leafy greens from regions free of AE
• TAKE HOME:
  
  • AE - serious concern for captive gorillas in endemic areas for E. multiocularis. Dx with serology, US. Oral albendazole recommended in humans did not work in gorillas.

Question 72

A recent report described the management of cecal perforation and focal peritonitis in a gorilla.

How did this animal present?

What is the cecal blind sac?

What surgical procedure was perofmed?

What antibiotic was used?

Answer 72

Therio, S. R., Dadone, L. I., Garner, M. M., Arble, J., Lalonde, C. J., Baesl, T. J., … & Johnston, M. S. (2017). Successful management of cecal perforation and focal peritonitis in a gorilla (gorilla gorilla gorilla). Journal of Zoo and Wildlife Medicine, 48(2), 540-543.

Abstract: An 18-yr-old female Western lowland gorilla (Gorilla gorilla gorilla) presented with acute-onset severe lethargy, bloody vaginal discharge, decreased appetite, and an abnormal posture. The gorilla was diagnosed with a ruptured cecal blind sac with severe adhesions to the right ovary. A typhlectomy and unilateral ovariectomy were performed. Histologic examination identified a severe transmural circumferential typhlitis with rupture and adhesions to the infundibulum and chronic typhlitis. Postoperative management included antibiotics, analgesics, short-term dietary modifications, and probiotics for suspect oral candidiasis. The gorilla made a full clinical recovery and was pregnant within 1 yr of surgery. To the authors’ knowledge, this is the first case of successful management of typhlitis in a gorilla. Typhlitis and intestinal rupture should be considered as a differential diagnosis for acute onset severe abdominal pain in gorillas.

• Typhlectomy and unilateral ovariectomy performed, ruptured cecal blind sac with extensive adhesions and assoc with R ovary identified; pockets of purulent material.
• Opioids discontinued after 3 days – gorilla developed moderate pruritis (side effect in humans).
• Cecal blind sac = appendix in humans.
  
  • 50% human patients with appendicitis present with acute severe pain in region of right iliac fossa.
  • Cefovecin – recent research shows active renal reabsorption of cefovecin does not occur in nonhuman primates.

Takeaway: Typhlitis and intestinal rupture should be considered as a differential diagnosis for acute onset severe abdominal pain in gorillas.

Question 73

A recent report describe invasive mammary gland adenocarcinoma in a male orangutan.

What was this treated with?

How long was survival?

Answer 73

Carpenter, N. A., & Crook, E. K. (2017). Mammary gland adenocarcinoma in a male bornean orangutan (pongo pygmaeus). Journal of Zoo and Wildlife Medicine, 48(1), 224-227.

Abstract: An adult male Bornean orangutan (Pongo pygmaeus) was diagnosed with invasive, poorly differentiated grade 9/9 mammary gland adenocarcinoma from a subcutaneous mass that was surgically removed during a routine preventative health examination. The tumor was tested for estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and HER2 fluorescence in situ hybridization (HER2 FISH). Whole blood was tested for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. The orangutan was treated orally with two common human breast cancer drugs; tamoxifen and anastrozole. The orangutan lived for 4.5 yr post detection, dying from an unrelated cause. This is the first reported case of mammary gland adenocarcinoma in a male great ape.

• First report of mammary adenocarcinoma in a male great ape
  
  • Rare in apes, unreported in male great apes
• Mammary mass first noted 2 years prior and removed once started growing (remained static prior)
• Mammary adenocarcionoma with high-grade malignancy extending into surrounding tissue
  
  • Poorly differentiated ductal carcinoma grade 9/9
  • After second surgery achieved clean margins
  • No metastases on CT scan 6 weeks post
• TNM system for grading mammary gland tumors on scale of 1-9 (T: tumor presence, N: LN invasion, M: metastasis)
  
  • T2/N0/M0 despite high grade of tumor
• Tested for hormone receptors, HER2, HER2 FISH, BRAC1 gene, BRCA2 gene
  
  • Positive for estrogen and progesterone receptors
  • Human epidermal growth factor 2 (HER2) equivocal
  • Unable to interpret HER2 FISH (confirmatory test for HER2)
  • BRAC1 and 2 negative – showed not prerequisite for great apes
• TX with Tamoxifen, an estrogen blocker (20mg PO SID), first line anti-breast cancer therapy
  
  • Discontinued at 7mo due to enlargement R axillary LN and switched to anastrozole
• Anastrozole, antiestrogen aromatase inhibitor (1mg PO SID), prevents estradiol conversion in breast tissue and initially slowed LN enlargement
  
  • Seemed to have the most success of the two treatments
  • Continued until orangutan’s death >1 yr later on anesthetic induction for anorexia/laryngeal mass (bacterial)
• NO neoplastic cells on necropsy except for R axillary LNs
• Lived 55 mo from original mass detection (compared to >60mo in human males)

Take home: First report mammary adenocarcinoma in male great ape

Question 74

A recent study evaluated the effects of alpha-2 protocols on echocardiographic varialbes and blood pressure in chimpanzees.

What parameters were lower in chimpanzees anesthetized with TZM as opposed to TZ only?

When do the alpha-two agonists cause an increase in blood pressure?

Answer 74

THE INFLUENCE OF ANESTHESIA WITH AND WITHOUT MEDETOMIDINE ON CARDIAC STRUCTURE AND FUNCTION IN SANCTUARY CAPTIVE CHIMPANZEES (PAN TROGLODYTES)

Journal of Zoo and Wildlife Medicine 52(3): 986–996, 2021

Abstract: Dependent on timing of assessment, anesthetic agents and specifically medetomidine negatively affect cardiac function in great apes. The aim of this study was to determine the influence of tiletamine–zolazepam (TZ) with and without medetomidine on cardiac structure and function in healthy chimpanzees (Pan troglodytes) during a period of relative blood pressure stability. Twenty-four chimpanzees living in an African wildlife sanctuary undergoing routine health assessments were stratified by age, sex, and body mass and randomized to be anesthetized using either TZ (6 mg/kg; n = 13; seven males and six females) or a combination of TZ (2 mg/kg) and medetomidine (TZM; 0.02 mg/kg; n =11; five males and six females). During health checks, regular heart rate and blood pressure readings were taken and a standardized echocardiogram was performed 20–30 min after induction. Data were compared between the two anesthetic groups using independent-samples t or Mann–Whitney U tests. Although heart rate (mean 6 SD; TZ: 76 6 10 bpm; TZM: 65 6 14 bpm, P = 0.027), cardiac output (TZ: 3.0 6 0.7 L/min; TZM: 2.4 6 0.7 L/min, P = 0.032), and mitral A-wave velocities (TZ: 0.51 6 0.16 cm/s; TZM: 0.36 6 0.10 cm/s, P = 0.013) were lower in the TZM group, there were no statistically significant differences in cardiac structure or the remaining functional variables between groups. Furthermore, there were no statistical differences in systolic (TZ 114.6 6 14.9 mmHg; TZM: 123.0 6 28.1 mmHg; P = 0.289) or diastolic blood pressure (TZ: 81.8 6 22.3 mmHg, TZM: 83.8 6 20.1 mmHg; P = 0.827) between the groups during the echocardiogram. This study has shown that during a period of relative blood pressure stability, during the first 20–30 min after induction there are few differences in measures of cardiac structure and function between protocols using TZ with or without medetomidine in healthy chimpanzees

Intro

• Heart disease is increasingly reported in captive chimpanzees
• Medetomidine is a commonly used anesthetic drug, but may have negative cardiac effects
• The aim of this study was to determine the influence of tiletamine–zolazepam (TZ) with and without medetomidine on cardiac structure and function in healthy chimpanzees (Pan troglodytes) during a period of relative blood pressure stability.

Discussion

• The main finding from this study was that heart rate, cardiac output, and mitral A-wave velocities were lower in chimpanzees anesthetized with TZM when compared with TZ only. Cardiac structural measures and all other functional variables were not different between the two anesthetic protocols
• Moreover, despite an initial elevation in blood pressure with medetomidine as has been noted previously, there were no significant differences in blood pressure between anesthetic protocols during the echocardiogram. These findings suggest that if cardiac assessments are completed during the period of relative blood pressure stability there are few differences in cardiac structure and function between these two protocols in healthy chimpanzee
• Studies involving animals with known cardiac disease are warranted
• There were limitations to the current study: 1) the use of ketamine top-ups with chimpanzees anesthetized with TZ; 2) the between-subject design; 3) the echocardiographer was not blinded to anesthetic protocol; 4) the relatively small sample size; 5) blood pressures were assessed noninvasively; and 6) we only completed a single echocardiogram

Question 75

A recent report described management of tetanus infection in a Bornean orangutan.

What is the etiologic agent of tetanus?

What are the typical clinical signs?

How was this case managed?

Were there any complications?

What was the outcome?

What are the recommended vaccination protocols for tetanus?

Answer 75

MANAGEMENT OF MEDICAL COMPLICATIONS ASSOCIATED WITH A PRESUMED TETANUS INFECTION IN A NORTHWEST BORNEAN ORANGUTAN (PONGO PYGMAEUS PYGMAEUS)

Mary Irene Thurber, DVM, DACZM, Grayson Doss, DVM, DACZM, Pierre Kory, MD, MPA, Erick Tarula, MD, and Kurt Sladky, MS, DVM, DACZM, DECZM (ZHM), DECZM (Herpetology)

Abstract: An 18-yr-old female orangutan (Pongo pygmaeus pygmaeus) developed opisthotonus after sustaining conspecific bite wounds 3 wk earlier. The orangutan developed progressive tetraparesis and dysphagia, despite normal mentation, suggestive of tetanus. A tetanus vaccine had been administered at 2 yr of age, but none since. Brain magnetic resonance imaging, computed tomography, cerebral spinal fluid tap, and bloodwork were unremarkable. Viral, Baylisascaris, and tetanus toxin testing were negative. A femoral central venous catheter (CVC) was placed to provide medications, fluids, and parenteral nutrition. The orangutan received human tetanus immunoglobulin, tetanus toxoid, penicillin, methocarbamol, and analgesia. After 1 wk, the catheterized limb became edematous; a deep vein thrombosis (DVT) was diagnosed ultrasonographically. A cephalic CVC was placed, the limb casted, intravenous therapy reinitiated, and enoxaparin started. The orangutan became mobile days later, and progressively improved. Despite no compliance with enoxaparin, the DVT resolved without residual signs. This is the first reported case of presumptive tetanus and DVT in a great ape.

CLINICAL BRIEF:

• Tetanus- disease secondary to neurotoxin produced by Clostridium tetani
• Initial presentation = opisthotonus, back stiffness, hyporexia (3 week after bite wounds)
  
  • Vaccinated at 2 years old, now 18 years old, no tetanus vx since then
  • On exam, found healing bite wounds, no other explanation for clinical signs, negative for C. tetani toxin gene
    
    • Given human tetanus immune globulin, tetanus toxoid vx, abx, pain meds, supportive care
  • Progressive tetraparesis + dysphagia over the next few days
  • Placed a right femoral central venous catheter due to inability to eat/drink
  • Started regaining distal limb function within 9 days- started on midazolam CRI for safety of staff, ketamine added a few days later due to increased mobility
  • Limb edematous and painful when CVC removed, patient regressed- found a deep vein thrombosis (diagnosed via ultrasound- see below); put catheter in cephalic vein and continued supportive care, started on enoxaparin
  • Complete resolution of tetraparesis 5.5 weeks after presentation; continues to be normal 5 mo post presentation
• Tetanus presumed based on clinical signs- in humans, is a diagnosis of exclusion, incomplete vaccination and response to therapy
• Tetanus has been previously reported in primates but not great apes- usually present acutely with slow, stiff gait, progressing to lateral recumbency
• Humans get human tetanus immune globulin (TIG) to remove circulating toxin, but this does not remove toxin bound to nerve endings- should be given with 24 hr of onset of clinical signs for max effect
• Current tetanus vaccine recommendations- 3 vaccines before 1 year old, boosters at 15-18 months and 11-12 years, then every 10 years
• Femoral vein CVCs have higher complication rates in humans vs. subclavian and jugular catheters, but in orangs, difficult to access with air sacs and hard to bandage

Question 76

A recent study described the use of human indreict immunofluorescence antibody assays for Balamuthia mandrillaris in Bornean orangutans.

What is malamuthia mandrillaris? What are the typical clincial signs associated with infection?

How is it transmitted?

How useful was this diagnostic?

Answer 76

• Balamuthia mandrillaris - free-living amoeba, in soil and water, hot and dry climates
  
  • Granulomatous amoebic encephalitis, highly fatal, rare
  • CS – progressive CNS signs or chronic nonspecific signs
  • Old world primates and humans
• Inhalation or broken skin – suspect if skin lesion and neuro signs
• Human B. mandrillaris IFA positive only in affected orangutan
  
  • Suggests novel diagnostic option for antemortem diagnosis
  • Demonstrated chronic >2 yr infection (unexpected finding)

Question 77

A recent study evaluated computed tomography as a tool for respiratory disease in orangutans.

What is orangutan respiratory disease syndrome?

How common is it?

What are the typical clinical signs in acute and chronic cases?

Why is CT the gold standard diagnostic?

Answer 77

USE OF COMPUTED TOMOGRAPHY (CT) TO DETERMINE THE SENSITIVITY OF CLINICAL SIGNS AS A DIAGNOSTIC TOOL FOR RESPIRATORY DISEASE IN BORNEAN ORANGUTANS (PONGO PYGMAEUS).

Aronson RK, Sriningsih AP, Sulistyo F, Taylor-Cousar JL, Aronson SA, South A, Nutter F, Lung NP.

Journal of Zoo and Wildlife Medicine. 2021;52(2):470-478.

Orangutans are noteworthy among great apes in their predilection for chronic, insidious, and ultimately fatal respiratory disease. Termed Orangutan Respiratory Disease Syndrome (ORDS), this cystic fibrosis–like disease is characterized by comorbid conditions of sinusitis, mastoiditis, airsacculitis, bronchiectasis, and recurrent pneumonia. The aim of this retrospective study was to determine the sensitivity of clinical signs in the diagnosis of ORDS in Bornean orangutans (Pongo pygmaeus) compared with the gold standard for diagnosis via computed tomography (CT). We retrospectively compared observed clinical signs with CT imaging in a population of clinically affected animals at an orangutan rescue center in southeastern Borneo. From August 2017 to 2019, this center housed 21 ORDS-affected animals (6-29 yo), all of which underwent CT imaging to delineate which areas of the respiratory tract were affected. We reviewed clinical signs recorded in medical records and keeper observation notes for each individual for the period of 2 years prior to the date of the CT scan. A chi-square test of association was used to assess whether the observed clinical signs could predict the results of CT imaging. Results show that clinical signs may not be sensitive indicators in predicting respiratory disease identified by CT imaging. Based on the results of this study, clinical signs appear to be very poor predictors of underlying respiratory pathology in orangutans, based on high P-values, low sensitivity, and low specificity. This result is observed even with clinical signs data gathered over a full 24-mo period prior to CT scan performance. The findings of this study suggest the need for advanced imaging to properly diagnose and manage the most common health issue of captive orangutans.

Background

• Orangutan - IUCN critically endangered; widespread deforestation in Borneo and Sumatra
• Orangutan Respiratory Disease Syndrome (ORDS) - cystic-fibrosis like disease: sinusitis, mastoiditis, airsacculitis, bronchiectasis, recurrent pneumonia
  
  • 20% of all orangutans under managed care, mortality as young as 2 yo
  • Often become unreleasable in rescue centers
  • CS: nasal discharge, cough, tachypnea, increased resp effort, fever, malaise, anorexia, pendulous air sac
  • Chronic: cyclic progressive inflammation, airway destruction, bronchiectasis, body destruction of mastoids leading to meningitis, chronic sinus structural changes
  • CT - gold standard diagnostic tool
    
    • WBC count - not a reliable measure of resp disease, culture likely grows many opportunistic pathogens, survey rads are sensitive for parenchymal disease (pneumonia) but not bronchiectasis

Key Points

• No statistically significant correlations between clinical signs and disease - likely n too low for statistical evaluation (not enough true positives and negatives)
  
  • Highest sensitivity was clinical signs of upper respiratory tract disease (nasal discharge)

Conclusions

• Clinical signs appear to be poor predictors of underlying respiratory pathology in orangutans: high P-values, low Sn, low Sp
• CT is gold standard for imaging all areas of the respiratory tract except laryngeal air sacs

Question 78

A recent study compared hand injection versus darting to induce anesthesia in chimpanzees.

What is the risk of anesthetic mortality in great apes?

What were the findings in a similar study in gorillas?

How do catecholamines change with darting? How does this affect alpha-two efficacy?

What was significantly different in the chimps that were hand injected as opposed to darted in this study?

Answer 78

J Zoo Wildl Med. 2021;52(2):445-452

PHYSIOLOGICAL AND ANESTHETIC EFFECTS OF HAND INJECTION VERSUS DARTING TO INDUCE ANESTHESIA IN CHIMPANZEES (PAN TROGLODYTES)

Burrows A, Liptovszky M, Self I

ABSTRACT: Great ape anesthesia is reported to carry a significant risk. Therefore, techniques aiming to reduce stress and increase welfare, such as hand injection of anesthesia induction agents, have received considerable attention in zoo, laboratory, and captive wildlife environments. However, there is little evidence to support the superiority of such techniques. To investigate this issue, anesthesia records of healthy zoo-housed chimpanzees (Pan troglodytes) between 2012 and 2017 in which the animal was either darted or hand injected were analyzed (n = 50). Sex, age, induction, muscle relaxation, and overall anesthesia quality as well as recovery ratings, heart rate, systolic, mean and diastolic blood pressure, respiratory rate, end-tidal CO__₂__, oxygen saturation (SpO__₂__), and body temperature were analyzed. Chimpanzees that were darted showed statistically significantly higher heart rate, SpO__₂__, and body temperature than those that were hand injected. It was found that darted chimpanzees were also significantly more likely to have poorer perianesthetic muscle relaxation and overall anesthesia rating scores. This study provides further evidence that the use of hand injection can reduce factors associated with stress and improve the quality of chimpanzee anesthesia

Study Design: Retrospective epidemiological study

Goal: Assess the effects that hand injection vs. darting for anesthesia induction have upon physiological parameters and anesthesia-related ratings in healthy managed chimpanzees

Key Points:

· Rapid, low-stress induction and smooth recovery are critical in great ape anesthesia

· In managed chimpanzees heart disease has been cited as a leading cause of death

· Risk of mortality in the perianesthetic period in great apes was found to be 1.35%

o Main risk factors are age and health status

· Gorillas that were darted, compared with a group immobilized via hand injection had increased RR, MAP, and diastolic pressure

· In chimpanzees, an increase in sympathetic drive associated with darting was likely responsible for some degree of hemodynamic variability

· In gorillas and chimpanzees darting was associated with increased circulating concentration of catecholamines, which in turn reduced the potency of medetomidine

· Anesthesia protocol (darted or hand injection):

o +/- 0.6-1 mg/kg midazolam PO (premedication)

o 0.2 mg/kg medetomidine IM + 2 mg/kg Telazol IM (induction)

o mg/kg atipamezole (reversal)

TLDR:

· HR and temp were significantly higher when darted across the duration of anesthesia

· Hand injection was more likely to result in good muscle relaxation and better overall anesthesia scorings

Question 79

A recent report described necrotizing eosinophilic myocarditis in a chimpanzee.

What is the most common form of cardiovascular disease in chimpanzees?

What clinicopathologic findings are associated with this disease?

Can other organs potentially be affected?

Answer 79

J Zoo Wildl Med 2021;52(2):853-857

ACUTE NECROTIZING AND EOSINOPHILIC MYOCARDITIS IN A CHIMPANZEE (PAN TROGLODYTES)

de Oliveira AR, Oliveira Santos D, de Paula NF, et al.

ABSTRACT: Cardiac disease is of importance in captive chimpanzee (Pan troglodytes) health. Here we report an eosinophilic and necrotizing myocarditis in a 17-y-old chimpanzee with no previous history of cardiac disease that progressed to death within 48 h. Toxic and infectious causes were ruled out. The chimpanzee had eosinophilia at different occasions in previous years. The animal had a severe, diffuse, and acute monophasic necrotizing myocarditis, with a moderate lymphoplasmacytic infiltrate that was rich in eosinophils. Ante- and postmortem investigations are compatible with an unusual eosinophilic myocarditis with clinical evolution and morphology comparable with human eosinophilic myocarditis secondary to hypereosinophilic syndrome.

Study Design: Case report

Key Points:

• Cardiovascular disease is a leading cause of death in captive chimpanzees
• Most common = diffuse interstitial/idiopathic fibrosing cardiomyopathy
• Myocarditis and acute myocardial necrosis are less common
• Eosinophilic myocarditis (EM) is a rare disease in humans
• EM is often characterized by peripheral eosinophilia and may mimic an acute coronary syndrome
• EM commonly develops during hypereosinophilic episodes, but can occur with normal or mildly elevated peripheral eosinophil counts
• Diagnosis is based on endomyocardial biopsy with focal to diffuse myocardial eosinophilic inflammation and necrosis
• A 17-y-old male chimpanzee presented with mild lethargy and hyporexia for 48 h
• No treatment or diagnostics were attempted and he died acutely at 48 h
• The affected chimpanzee had eosinophilia in 2002 (as an infant) and at his last two exams performed in 2009 and 2017
• In NHPs, there is a report of a presumptive hypereosinophilic syndrome causing multisystemic eosinophilia in a juvenile owl monkey that developed respiratory distress
• An eosinophilic gastritis and colitis were also described with EM in this case

TLDR: Describes a rare condition of eosinophilic necrotizing myocarditis in a chimpanzee

Question 80

A recent study evaluated the effects of reversing alpha-two agonists during anesthesia for echocardiographic evaluation of chimpanzees.

What are the most common cardiac disease in chimpanzees?

What were the anesthetic and reversal protocols used in this study?

What changes do alpha-two agonists produce?

What effect did reversal of alpha-two agonists have?

How does this corroborate a previous chimpanzee study?

Answer 80

J Zoo Wildl Med. 2021;52(2):479-489

ECHOCARDIOGRAPHY AND DIRECT ARTERIAL BLOOD PRESSURE MEASUREMENT IN CAPTIVE CHIMPANZEES (PAN TROGLODYTES) DURING TWO PHASES OF AN ANESTHETIC PROTOCOL

Ashley AL, Smith CK, Köster LS, Mulreany L, Cushing AC

ABSTRACT: The effects of α-2 agonists on echocardiographic findings in great apes are not well documented, and knowledge of these effects would expand the understanding of cardiac examinations of chimpanzees under anesthesia with protocols using these drugs. Ten adult chimpanzees (Pan troglodytes), four males and six females, underwent echocardiographic examinations after anesthesia with dexmedetomidine, midazolam, and ketamine (phase 1). Four animals required isoflurane to achieve an adequate plane of anesthesia. Atipamezole was used to antagonize dexmedetomidine, and all remaining animals were placed on isoflurane (phase 2), and then a second echocardiogram was performed. Direct arterial blood pressure was monitored during the anesthetic event. Measurements and recordings were assessed for statistically significant differences between the two phases and sex. There were no significant differences between phases or sex for any two-dimensional echocardiographic measurement of systolic function, although interventricular septum thickness at end systole approached a significant decrease from phase 1 to phase 2 (P = 0.058) when sex was considered a between-subject factor. Left ventricular outflow tract (*P* = 0.017) and pulmonary artery (*P* = 0.028) velocities increased after reversal of the dexmedetomidine. Diastolic transmitral flow was consistent with grade 3 diastolic dysfunction (median early to late ventricular filling velocities (E/A) of 2.02, interquartile range [IQR], 1.53-2.13) with a nonsignificant decrease of E velocity and increase in A velocity and decreased E/A after reversal. Trace mitral and tricuspid regurgitation were common findings in the sample population. Arterial blood pressure significantly decreased between phase 1 and phase 2 (*P* < 0.01). All chimpanzees entered a hypotensive state (mean arterial pressure < 60 mm Hg) during phase 2. Although limited by the small number of chimpanzees, this study showed an increase in afterload, potential diastolic dysfunction, and a decrease in blood pressure after the antagonism of dexmedetomidine. Additional studies to further assess the effects of α-2 agonists in chimpanzees are warranted

Goal:

1. Present echo findings in clinically healthy adult chimps
2. Determine the difference between echo and BP in chimps before and after antagonism of dexmedetomidine with atipamezole

Key Points:

• Cardiac disease is common in managed chimps and is often the primary cause of death
  
  • Geriatric and male animals are most commonly affected
  • Idiopathic myocardial fibrosis, recently characterized by interstitial and replacement fibrosis, is the most frequent cardiomyopathy
  • Changes postmortem and/or on echo also include LV hypertrophy and dilatation
  • Valvular regurgitation was seen in ~80% of chimps in one study (Drane AL et al AJVR 2019)
• Dosages: 0.02 mg/kg dexmedetomidine + 0.06 mg/kg midazolam + 5 mg/kg ketamine IM
  
  • +/- 1-2% isoflurane (phase 1)
  • 0.2 mg/kg atipamezole IM + 1-2% isoflurane (phase 2)
• The use of α-2 agonists is controversial, and the GAHP discourages their use, because drug-induced cardiac changes may mimic cardiac disease in healthy animals
  
  • Generally, this is manifested as an initial hypertensive state caused by vasoconstriction and a compensatory bradycardia, followed by a persistent bradycardia and typically either normo- or hypotension
  • α-2 agonists produce marked reductions in systolic function in dogs and gorillas
  • In this study, antagonism of dexmedetomidine had no significant effect, although some changes in diastolic function and LVOT velocities were found
    
    • This corroborates a previous study, where no differences were found on echo in chimps anesthetized with Telazol vs. Telazol + medetomidine
• Isoflurane’s effect on echo measurements is considered negligible and was not different in this study. However, the effects may be time and dose dependent
• Systolic, diastolic, and mean arterial BP were monitored via an arterial catheter in the medial tibial artery
  
  • All decreased in phase 2, likely because of the antagonism of dexmedetomidine and the use of inhalant anesthesia
  • Every chimp entered a hypotensive state (< 60 mmHg) during phase 2
    
    • Four chimpanzees entered a profound hypotensive state (< 40 mmHg)

TLDR:

• Antagonism of dexmedetomidine had a minor effect on echocardiographic measurements
• This study showed an increase in afterload due to dexmedetomidine, potential diastolic dysfunction that could be exacerbated by dexmedetomidine, and a decrease in blood pressure after the antagonism of dexmedetomidine

Question 81

A recent study evaluated the use of ECG as a way to predict cardiac changes seen on echocardiogram in chimpanzees.

What are the most common cardiac abnormalities in chimpanzees? How common is cardiac remodeling?

What ECG parameters were associated with cardiac disease?

Can ECG be used to accurately predict cardiac chamber size?

Answer 81

Evaluation of relationships between results of electrocardiography and echocardiography in 341 chimpanzees (Pan troglodytes)

Drane AL, Atencia R, Cooper SM, Feltrer Y, Calvi T, Strike T, Palmer C, Simcox S, Rodriguez P, Sanchez C, van Bolhuis H.

American Journal of Veterinary Research. 2020 Jun;81(6):488-98.

Taxa: Mammalia → Hominidae → Homininae

Abstract: Objective: To examine potential relationships between ECG characteristics and echocardiographic measures of cardiac structure in chimpanzees (Pan troglodytes).

Animals: 341 chimpanzees (175 males and 166 females) from 5 sanctuaries and 2 zoological collections.

Procedures: Chimpanzees were anesthetized for routine health examinations between May 2011 and July 2017 as part of the International Primate Heart Project and, during the same anesthetic events, underwent 12-lead ECG and transthoracic echocardiographic assessments. Relationships between results for ECG and those for echocardiographic measures of atrial areas, left ventricular internal diameter in diastole (LVIDd), and mean left ventricular wall thicknesses (MLVWT) were assessed with correlational analysis, then multiple linear regression analyses were used to create hierarchical models to predict cardiac structure from ECG findings.

Results: Findings indicated correlations (r = -0.231 to 0.310) between results for ECG variables and echocardiographic measures. The duration and amplitude of P waves in lead II had the strongest correlations with atrial areas. The Sokolow-Lyon criteria, QRS-complex duration, and R-wave amplitude in leads V6 and II had the strongest correlations with MLVWT, whereas the Sokolow-Lyon criteria, QRS-complex duration, and S-wave amplitude in leads V2 and V1 had the strongest correlations with LVIDd. However, the ECG predictive models that were generated only accounted for 17%, 7%, 11%, and 8% of the variance in the right atrial end-systolic area, left atrial end-systolic area, MLVWT, and LVIDd, respectively.

Conclusions and clinical relevance: Results indicated that relationships existed between ECG findings and cardiac morphology in the chimpanzees of the present study; however, further research is required to examine whether the predictive models generated can be modified to improve their clinical utility.

Background:

• Common cardiac diseases in chimpanzees: arterial hypertension, congestive heart failure, idiopathic myocardial fibrosis
• ECG can detect cardiovascular remodelling in humans

Key Points:

• Common cardiac abnormalities: left ventricular hypertrophy, left ventricular dilation, atrial dilation
• Cardiac remodeling was relatively rare (~8%)
• Body mass was not related to cardiac measurements
• Correlations were found between some ECG and cardiac measurements:
• P-wave amplitude in lead II and duration with left and right atrial end systolic area
• SLV15, SLV25, QRS duration, R-wave amplitude in lead II with left ventricular wall thickness
• SLV15, SLV25, QRS duration, S-wave amplitude with left ventricular diameter in diastole
• ECG cannot accurately predict cardiac chamber sizes and wall thickness

Conclusions: Some ECG parameters are associated with cardiac dimensions but not strongly predictive

Question 82

A recent study evaluated the use of medetomidine-ketamine and dexmedetomidine-ketamine anesthetic protocls in moutain gorillas.

What protocols were used in the field previously? What were some issues with those?

How quickly were animals induced and recovered with this protocol?

Answer 82

ANESTHESIA WITH MEDETOMIDINE–KETAMINE AND DEXMEDETOMIDINE–KETAMINE IN MOUNTAIN GORILLAS (GORILLA BERINGEI BERINGEI)

Jenny E. Jaffe, Balbine Jourdan, Michael R. Cranfield, Kirsten Gilardi, Dawn Zimmerman

J. of Zoo and Wildlife Medicine, 51(3):507-513 (2020)

Between December 2002 and September 2017, 125 anesthetic procedures involving free-living and orphaned captive mountain gorillas(Gorilla beringei beringei) were performed in the Virunga Massif and Bwindi Impenetrable Forest in East-Central Africa. Of these 125 immobilizations, 114 records were complete enough for inclusion into this study. Anesthetic and physiologic data from these 114 cases were analyzed, of which 57 used medetomidine–ketamine and 57 used dexmedetomidine–ketamine administered intramuscularly. With the use of estimated weights, the mean induction dosage (mg/kg ± SD) for medetomidine was 0.033 ± 0.003 (n = 42), for dexmedetomidine 0.018 ± 0.005 (n = 53), and for ketamine 3.66 ± 0.95 (n = 95). Mean time from injection of induction dose to recumbency was 6.8 ± 3.1 min (n = 74). Atipamezole was administered intramuscularly to reverse anesthesia. First signs of recovery occurred at 5.0 ± 4.0 min, and full recovery was 19.0 ± 17.0 min after administration of the reversal agent. No significant differences in physiologic parameters or anesthetic time variables were noted between healthy and unhealthy individuals. Mean heart rate was 72.0 ± 17.6 beats/min (n = 83) and mean oxygen saturation was 96.5% ± 4.2 (n = 62). Mean respiratory rate was 27 ± 9 breaths/min (n = 84) and mean body temperature 36.6°C ± 1.2 (n = 61). The current protocol has several advantages for field use in this species given its quick induction, few observed side effects, and ability to reverse so that the animal can return more quickly to its social group.

· No differences in physiologic parameters nor recovery between healthy and unhealthy gorillas

· Primarily darted unless extremely ill (then hand-injected) or infant

· Previous protocols

o Ketamine: repeated doses may cause prolonged recoveries

o Tiletamine-zolazepamL: prolonged recovery compared to ketamine

· Some animals did start to recover prior to administration of atipamezole

Take Home: Medetomidine-ketamine or dexmed-ketamine appear safe and effective for immobilization of mountain gorillas; maintain w/ isoflurane via ETT.

Question 83

A recent study evaluated the factors affecting tear production and IOP in anesthetized chimpanzees.

How was tear production affected by administration of medetomidine?

How did positioning change IOP?

Answer 83

FACTORS AFFECTING TEAR PRODUCTION AND INTRAOCULAR PRESSURE IN ANESTHETIZED CHIMPANZEES (PAN TROGLODYTES)

Milnes EL, Calvi T, Feltrer Y, Drane AL, Howatson G, Shave RE, Curry BA, Tremblay JC, Williams DL

Journal of Zoo and Wildlife Medicine. 2020 Nov;51(3):687-90.

Measurements of intraocular pressure (IOP) and tear production are key components of ophthalmic examination. Chimpanzees (Pan troglodytes) were anesthetized using either tiletamine-zolazepam (TZ; 2 mg/kg) combined with medetomidine (TZM; 0.02 mg/kg), or TZ alone (6mg/kg). Tear production was lower (P = 0.03) with TZM (5.63 ± 6.22 mm/min; n=16) than with TZ (11.13 ± 4.63 mm/min; n=8). Mean IOP, measured using rebound tonometry in an upright body position (n=8) was 18.74 ± 3.01 mm Hg, with no differences between right and left eyes. However, positioning chimpanzees in left lateral recumbency (n = 27) resulted in higher IOP in the dependent (left) eye (24.77 ± 4.49 mm Hg) compared to the nondependent (right) eye (22.27 ± 4.65 mm Hg) of the same animal (P < 0.0001). These data indicate medetomidine anesthesia markedly lowers tear production in chimpanzees, and that body position should be taken into consideration when performing rebound tonometry.

• Tear production lower in Telazol-medetomidine than Telazol alone
• IOP higher in dependent eye when placed in lateral recumbency

Conclusions: Medetomidine decreases tear production in chimps. Body position affect IOP measurement.

Question 84

A recent study evaluated the use of oscillometric blood presure measurement methods against direct BP measurements in anesthetized chimpanzees.

What oscillometric measurement and method were most reliable when compared against the direct methods?

How does peripheral SAP change with distance from the aorta?

Answer 84

Agreement between oscillometric and direct blood pressure measurements in anesthetized captive chimpanzees (Pan troglodytes)

Christopher K. Smith dvm Anthony L. Ashley dvm Xiaojuan Zhu phd Andrew C. Cushing bvsc

AJVR Vol 82 No 12 Dec 2021I (Rev by AJC)

Abstract:

OBJECTIVE: To evaluate the level of agreement (LOA) between direct and oscillometric blood pressure (BP) measurements and the ability of oscillometric measurements to accurately detect hypotension in anesthetized chimpanzees (Pan troglodytes).

ANIMALS: 8 captive, adult chimpanzees.

PROCEDURES: During prescheduled annual examinations, each chimpanzee underwent general anesthesia and patient monitoring for their examination, echocardiography for a concurrent study, and measurement of direct BP with the use of tibial artery catheterization and oscillometry with the use of a cuff placed around a brachium and a cuff placed around the second digit of the contralateral forelimb for the present study. Bland-Altman plots were generated to compare results for direct and oscillometric BP measurements. Mean bias and 95% LOAs were calculated for oscillometric measurements of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) for each cuff site. Sensitivity and specificity in detecting hypotension were also determined for each cuff site.

RESULTS: There were 74 paired direct and brachial oscillometric measurements of each, SAP, MAP, and DAP and 66 paired direct and digit oscillometric measurements of each, SAP, MAP, and DAP. Only brachial oscillometricmeasurements of MAP had adequate sensitivity (78%) and specificity (95%) to accurately detect hypotension, and this technique also had the least mean bias (0.8 mm Hg; 95% LOA, –29 to 31 mm Hg).

CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that brachial oscillometric measurement of MAP provided reasonable agreement with tibial arterial direct MAP measurement and performed well in diagnosing hypotension in anesthetized chimpanzees.

Key Points:

• Cardiomyopathies predominant pathology in chimpanzeees - arteriosclerosis/atherosclerosis seem to be coexisting factor (particularly in females)
• Recent paper published on reference ranges for chimp BP oscillometry (J Med Primatol., 2011)
• Anesthesia: dexmed/ketamine/midazolam + isoflurane maintenance
• Findings indicated BP measurements in chimps w/brachial oscillometry agreed reasonably with direct BP measurement and could be used to detect hypotension
• ACVIM guidelines- mean difference (bias) < or= 10mmHg and SD < or = 15 mmHg for SAP and DAP to be considered accurate
• Present study- mean bias when measuring SAP/MAP/DAP was < 5mmHg for oscillometricmeasurements of with a brachial cuff and < 10mm Hg for digit cuff
• Peripheral SAP often increases as distance from the aorta increases- they found brachial oscillometryperformed well when measuring MAP and DAP but not SAP (similar to other canine studies)
• ACVIM criteria for accurate BP measurement were only met by brachial oscillomery of MAP, whereas the ACVIM criteria were not met with digit oscillometry for SAP/MAP/DAP- brachial cuff performs better
• Oscillometry overestimated BP when it was low (positive bias) and underestimated BP when it was high (negative bias). - this complicates diagnosis of hypo- and hyper- tension
• As direct BP measurements deviate from reference limits, oscillometry accuracy declines

Take Home Message/Conclusions: Only brachial oscillometric measurements of MAP had adequate sensitivity and specificity to detect hypotension. The sensitivities of brachial and digit cuffs in measuring SAP and of digit cut in measuring MAP were too low to accurately detect hypotension

Question 85

A recent paper evaluated the use of an interferon gamma release assay for the detection of mycobacteriosis in apes.

What diagnostics are typically performed for tuberculosis in apes? What are some limits with this?

What other diagnostic methods are available for tuberculosis?

How early in the disease process can GIFT (gamma interferon tuberculosis) assay detect disease?

How did it compare against traditional skin testing?

Answer 85

Am J Vet Res. 2021 Nov 10;83(1):15-22.

Yee JL, Prongay K, Van Rompay KKA, Meesawat S, Kemthong T, Halley B, Carpenter A, Nham P, Rogers K, Hasselschwert D, Villinger F, Jay AN, Warit S, Malivijitnond S, Roberts JA. TUBERCULOSIS DETECTION IN NONHUMAN PRIMATES IS ENHANCED BY USE OF TESTING ALGORITHMS THAT INCLUDE AN INTERFERON-Γ RELEASE ASSAY.– reviewed by ZCR

Abstract

Objective: To develop a testing algorithm that incorporates multiple assays to evaluate host cellular and humoral immunity and antigen detection concerning Mycobacterium tuberculosis complex (MTBC) infection in captive nonhuman primates.

Animals: Cohorts of captive-bred and wild-caught macaques from 5 different geographic regions.

Procedures: Macaques were tested for MTBC infection by use of a γ interferon tuberculosis (GIFT) assay, an interferon-γ release assay, and other assays. In the first 2 cohorts (n = 15 and 181), initial validation of the GIFT assay was performed by use of experimentally infected and unexposed control macaques. In the next 3 cohorts (n = 59, 42, and 11), results were obtained for opportunistically collected samples from macaques exposed during spontaneous outbreaks.

Results: Sensitivity and specificity of the GIFT assay in the control cohorts were 100% and 97%, respectively, and were variable but enhanced by incorporating results from multiple assays in spontaneous outbreaks.

Clinical relevance: The detection and management of MTBC infection in captive nonhuman primate populations is an ongoing challenge, especially with animal imports and transfers. Despite standardized practices of initial quarantine with regular intradermal tuberculin skin testing, spontaneous outbreaks continue to be reported. Since infection encompasses a range of disease manifestations over time, a testing algorithm that incorporates multiple assays, such as the GIFT assay, to evaluate host cellular and humoral immunity in addition to agent detection is needed. Testing a combination of samples from controlled studies and spontaneous outbreaks of MTBC infection in nonhuman primates would advance the development and validation of a functional algorithm that incorporates promising tools such as the GIFT assay.

Key points:

• Mycobacterium tuberculosis complex (MTBC) detection and identification is an ongoing concern in management of NHP colonies
  
  • Tuberulin skin test (TST) remains the primary screening tool, despite lack of sensitivity for latent infections and issues historically with quality control
  • Series of neg TST required to exit Q, but still cases of TB documented despite this
  • Need for for multi-assay algorithm to improve MTBC detection in NHPs
• Case study 1- controls – macaques with TB infection confirmed
  
  • GIFT assay -reactivity beginning day 14
  • PPD reactivity bay day 14
  • TB-Plex assay detected antibodies by day 28
• Case study 2 – macaques – negative controls
  
  • No skin reactors
• Case study 3 – wild caught macaques
• Case study 4 – captive macaques
  
  • 1 animal with reaction to TST, all animals neg on TB Plex assay
• Case study 5 – captive macaques
• TB Methods
  
  • GIFT assay – similar to the IGRAs widely used in cattle and humans
  • TB-plex assay – Tb antibody detection using antigen coupled microbeads
  • T spot TB assay – ELISPOT (enzyme linked immunosorbent assay) that quantifies IFN-y releasing cells
  • TST only evaluated cell mediated immunity. IGRAs represent an alternative
• GIFT assay performed well in NHPs, detection as early as 14d post inoculation, beyond day 48 the amt of IFN-y appeared to decrease
• ELISPOT measured IFN-y response detected by 14d postinfection, increased to ,multiple antigens by 5-6 weeks postinfection
• As infection progresses, increase in magnitude and range of antigens
• Infected animals had high baseline IFNy values compared to non infected animals
• Higher response to avian PDD in infected animals vs non infected; response to avian PDD is stronger than bovine PDD at early time pts (day 14), response converts to bovine PDD > avian PDD by 28d
• GIFT assay detected positives in colonies 3-5 even when those animals were negative on the TST series mandated by the CDC
• TST and IGRA in colonies 3-5 corresponded sometimes but not always, so combining them could increase sensitivity for detecting infection
• Antibodies were not detected in any cases (Tb plex assay, T spot TB assay) not surprising given this takes months
• Testing algorithm developed by authors for MTBC detection.

Take home message

• TST by itself does not appear to be sensitive enough for MTBC detection, and other methods such as IGRAs like the GIFT assay, which performed with high sensitivity and specificity, should be used in combination for screening.

Question 86

A recent study evaluated antibiotic therapy for orangutan respiratory disease syndrome (ORDS).

What is ORDS? What human disease is it similar to?

What two antibiotics were used?

What bacteria is associated with worse disease in ORDS?

How effective was this antibiotic combination?

Answer 86

EVALUATING THE EFFICACY OF HUMAN BRONCHIECTASIS BASED ANTIBIOTIC THERAPY IN THE TREATMENT OF ORANGUTAN RESPIRATORY DISEASE SYNDROME

Agnes P. Sriningsih,* DVM, Nancy P. Lung,* VMD, MS, Fransiska Sulistyo, DVM, MVS, Stuart A. Aronson, MD, Riley K. Aronson, DVM, and Jennifer L. Taylor-Cousar, MD, MSCS

JZWM 52(4), 2021

Abstract: Unique among apes, orangutans (Pongo spp.) develop a chronic respiratory disease called orangutan respiratory disease syndrome (ORDS). The authors define ORDS as intermittent bacterial infection and chronic inflammation of any region or combination of regions of the respiratory tract, including the sinuses, air sacs, cranial bones, airways, and lung parenchyma. Infection in any of these areas can present acutely but then becomes recurrent, chronic, progressive, and ultimately fatal. The closest model to this disease is cystic fibrosis (CF) in people. We hypothesized that use of a 4–8-wk course of combined oral antibiotics used in the treatment of bronchiectasis in CF patients would lead to prolonged symptomatic and computed tomography (CT) scan improvement in orangutans experiencing early signs of ORDS. Nine adult Bornean orangutans (Pongo pygmaeus, eight males, one female, 18–29 yr of age) diagnosed with early ORDS-like respiratory disease underwent CT scan before initiation of treatment. Each animal received a combined course of azithromycin (400 mg 3/wk, mean 7 mg/kg) and levofloxacin (500 mg PO q24h, mean 8.75 mg/kg) for a period of 4–8 wk. CT scan was repeated 6–14 mon after completion of antibiotic treatment. Pretreatment CT showed that six of nine animals had lower respiratory pathology (airway disease, pneumonia, or both). All six orangutans had concurrent sinusitis, mastoiditis, airsacculitis, or a combination of these conditions. Upper respiratory disease alone was observed in three animals. CT showed improvement or resolution in four of five sinusitis cases, improvement in one of two instances of mastoiditis, resolution in five of six instances of airsacculitis, improvement or resolution in six of six instance of lower airway disease (P = 0.03, 95% CI 0.54–1.0], and resolution in five of five cases of pneumonia. Resolution of pretreatment clinical signs was observed in all nine animals. Two developed signs not present at pretreatment. These results show that combination antibiotic therapy with azithromycin and levofloxacin provides improvement in clinical signs and CT evidence of ORDS-related pathology, resulting in symptom-free status in some animals for up to 33 mon.

Key Points:

• Respiratory illness is the leading cause of death in juvenile and adolescent orangutans in NA zoos and claims as many lives as cardiac disease in adults
• Unique among apes, orangutans develops a species-specific chronic respiratory disease ORDS- consists of bacterial infection and chronic inflammation of any region or combination of regions of the respiratory tract, including sinuses, air sacs, cranial bones, and airways
• Can present acutely, but then become recurrent, chronic, and progressive
• Resulting pathologies= chronic sinusitis, mastoiditis, airsacculitis, pneumonia, and bronchiectasis
• Ultimately fatal disease reduces QOL, disrupts social groups, removes animals from breeding pop, and drain on institution resources
• Closest disease model= cystic fibrosis (CF) - caused by mutations in the CFTR gene, patients have thick respiratory mucus that is difficult to clear from the airways, reduced clearance provides ideal environment for bacteria to grow resulting in structural changes
• Similarities are strong- hypothesize CF-based therapies could be useful in ORDS management
• Genetic basis is currently being investigated

Discussion

• results showed marked improvement in both clinical signs and CT appearance in 9/9 orangutans at time of 6-14 month post treatment CT scan
• Shift standard of care to early detection and aggressive management, potentially preventing conversion of early cases to chronic, fatal form.
• Diagnosis typically based on presentation of clinical signs- nasal drainage, cough, fever, pendulous air sac.
• Treatment typically includes surgical drainage of the air sac and antibiotics , histamines for nasal discharge, and longer term antibiotics with adjunctive therapies for pneumonia
• Bronichiectasis is the hallmark of chronicity
• Suggest that if intervention occurs early, mild cylindrical bronchiectasis may be reversible
• Azithromycin= macrolide antibiotic reduce exacerbations and improve sputum consistency. Anti-inflammatory properties that reduce chronic inflammation in the airways
• Levofloxacin= broad-spectrum FQ that has good efficacy against Pseudomonas aeruginosa and other gram-neg bacteria commonly isolated from people with bronchiectasis and orangutans with ORDS
• P. aeruginosa- associated with decreased QOL, more severe disease, and higher rates morbidity/mortality
• Cultures of respiratory secretions should be periodically performed to ID different bacterial species present and to ID P. aeruginosa
• In present study, treatment initiation was not based on culture and sensitive, but on CT findings of respiratory infection/disease
• The A-L combo led to marked reduction in clinical signs and resolution/improvement in CT findings- all animals had resolution of the pretreatment clinical signs
• Improvement lasts at least 14 month, potentially longer
• Upper respiratory clinical signs were generally more common than lower respiratory clinical signs
• Pendulous air sac was most common presenting sign
• Mastoiditis is underappreciated cause of reduced animal welfare and as cause of death when infection ultimately erodes through the bone and into the brain
• Oral antibiotics directed at respiratory pathogens commonly seen in human bronchiectasis significantly improved clinical signs and CT findings in adult orangutans affected by ORDS with recurrence-free period lasting up to 33 mo in some patients.

Question 87

A recent study described the management of a complete molar pregnancy in a bonobo.

What is a molar pregnancy?

How did this bonobo present?

How was this case managed?

Answer 87

Meredith E. Persky, Yousuf S. Jafarey, Tracy A. Moegenburg, Annette Laubscher, Michael J. Lasser, Victoria L. Clyde, and Michael M. Garner. ANTEMORTEM DIAGNOSIS AND SUCCESSFUL TREATMENT OF A COMPLETE MOLAR PREGNANCY IN A GERIATRIC BONOBO (PAN PANISCUS). JZWM 2018 49(3) 828–832

Abstract: A 47-yr-old multiparous female bonobo (Pan paniscus) tested positive for pregnancy on a routine urine test. Because this geriatric animal was considered postreproductive, oral contraception had been discontinued. Sequential transabdominal ultrasound evaluations were performed under voluntary behavior and revealed that the uterus contained a mass of heterogenous tissue which was rapidly increasing in size. Due to a lack of normal fetal development and the ultrasonographic appearance of the uterine tissue, a molar pregnancy was suspected. Ovariohysterectomy was performed, and a complete hydatidiform mole was confirmed through human chorionic gonadotropin levels as well as gross and histological examination of the uterus. To the authors’ knowledge, this is the first time a complete molar pregnancy has been reported antemortem in a nonhuman great ape, although a single case of partial hydatidiform mole was previously documented in a chimpanzee on postmortem examination. This case describes the successful medical and surgical management of complete molar pregnancy in a bonobo and provides support for extending the age range of birth control recommendations in geriatric captive great apes that exhibit active breeding behavior.

Key points:

• Gestational trophoblastic disease refers to rare group of placental derived tumors that occur following aberrant fertilization
  
  • Hydatidiform mole or molar pregnancy is a common form of GTD
    
    • Complete mole occurs when an ovum devoid of maternal chromosomes is fertilized by one or two spermatozoa
    • Uterus becomes enlarged and beta human chorionic gonadotropin (hCG) are slightly elevated secondary to trophoblastic proliferation
  • Standard treatment for women includes dilating cervix to curettage uterine contents or OHE

47 yo bonobo was positive for pregnancy on urine test

• Ultrasound revealed irregular anechoic structure
• Two weeks later, free fluid within uterus but previous gestational sac no longer present
  
  • Initially thought spontaneous abortion and treated with Misoprostol to expel placental/fetal tissues
  • A uterine mass was detected 2 days later which increased in size, was consistent with molar pregnancy
  • OHE was elected and performed successfully by OB/GYN
    
    • Right ovary was cystic and adhered to the uterus
• Serum hCG measured 121,542 consistent with human women having hCG >100,000 with complete HM
• T4 was mildly elevated
  
  • Historically accompanied with advanced human molar pregnancies but has become less common due to earlier diagnosis in human medicine
• Chronic villi were swollen with edema and cytotrophoblasts surrounding the entire villous – no evidence of fetal tissue or choriocarcinoma = confirmed molar pregnancy
• Recovered from surgery and hCG and T4 decreased post operatively
• Urine pregnancy test 6.5wk later was positive suggesting hCG was at least 20mIU/ml, sequential tests at 10, 15, and 57 wk were negative

Take home: First report of complete molar pregnancy in a nonhuman great ape

References: None

Question 88

A recent study investigated the prevalence of drug-resistant bacteria from Chimpanzees in a wildlife sanctuary.

What is the scientific name of the Chimpanzee?

What bacteria were they specifically studying?
- What group do they belong to?
- What drugs do ESBLs confer resistance to?

Was there a difference in drug resistance with increased proximity to humans?

Answer 88

GENOMIC CHARACTERIZATION OF MULTIDRUG-RESISTANT EXTENDED-SPECTRUM b-LACTAMASE–PRODUCING ESCHERICHIA COLI AND KLEBSIELLA PNEUMONIAE FROM CHIMPANZEES (PAN TROGLODYTES) FROM WILD AND SANCTUARY LOCATIONS IN UGANDA
Sandra L. Bager,1,2 Isaac Kakaala,2 Egle Kudirkiene,1 Denis K. Byarugaba,2,3 and John Elmerdahl Olsen1
Journal of Wildlife Diseases, 58(2), 2022, pp. 269–278

Abstract
Farm and wild animals may serve as reservoirs of antimicrobial-resistant bacteria of human health relevance. We investigated the occurrence and genomic characteristics of extended spectrum blactamase (ESBL)–producing bacteria in Ugandan chimpanzees (Pan troglodytes) residing in two environments with or without close contact to humans. The ESBL-producing Escherichia coli and Klebsiella pneumoniae were isolated from fecal material of chimpanzees from Budongo Forest and Ngamba Island Chimpanzee Sanctuary in Uganda and were more commonly isolated from chimpanzees in Ngamba Island Chimpanzee Sanctuary, where animals have close contact with humans. Selected ESBL isolates (E. coli n=9, K. pneumoniae n=7) were analyzed by whole-genome sequencing to determine the presence of resistance genes, as well as sequence type and virulence potential; the blaCTX-M-15 gene was present in all strains. Additionally, the ESBL genes blaSHV-11 and blaSHV-12 were found in strains in the study. All strains were found to be multidrug resistant. The E. coli strains belonged to four sequence types (ST2852, ST215, ST405, and ST315) and the K. pneumoniae strains to two sequence types (ST1540 and ST597). Virulence genes did not indicate that strains were of common E. coli pathotype, but strains with the same sequence types as isolated in the current study have previously been reported from clinical cases in Africa. The findings indicate that chimpanzees in close contact with humans may carry ESBL bacteria at higher frequency than those in the wild, indicating a potential anthropogenic transmission.

Key Points
- Extended spectrum beta lacatamases (ESBLs) confer resistance to cephalosporins and monobactams but not carbapenems or cephamycins
– Many found within Enterobacteriaceae family, with E coli most common
- Increasingly finding ESBLs in healthy wildlife, including migratory birds and rodents that may act as carriers and contribute to dissemination of ESBL genes
- Aim: determine occurrence of Enterobacteriaceae with ESBL resistance in chimpanzees in sanctuaries and forest reserves in Uganda.
- E. coli and K. pneumoniae harboring ESBL genes were present in chimpanzees in both Budongo National Park and Ngamba Island Chimpanzee Sanctuary in Uganda
– All classified as multidrug resistant
– E coli was the most commonly isolated ESBL producer
– Higher number of ESBL producing strains in chimps living in close contact with humans
– Higher risk of transmission associated with close contact of humans with livestock, mountain gorillas and chimps
– Carbapenemase-producing Klebsiella was not detected. Did not detect the globally disseminated E coli clone ST131.
- Most commonly identified ESBL gene was blaCTX-M-15, detected in all strains
– Most widely distributed gene in the world – most display coresistance to aminoglycosides, tetracycline, sulfonamides, and fluoroquinolones
– Followed by blaSHV-11 in K. pneumoniae and blaSHV-12 in E. coli.
- Both E. coli and K. pneumoniae can be transmitted from humans to animals through the fecal-oral route, probably through indirect contact with contaminated environmental sources
- Harboring of unrelated sequence type resistant bacteria was seen - concern for transmission of resistance

Take home
- ESBL-producing K. pneumoniae and E. coli were isolated more frequently from chimpanzees in close contact with humans; however, they could also be obtained from free-living chimpanzees without known human contact.
- All ESBL strains were multidrug resistant.
- Establishment of strict hygiene guidelines while working with chimpanzee in sanctuaries should be instituted to limit the spread of antimicrobial-resistant bacteria

Question 89

A recent paper described compartment syndrome in a western lowland gorilla.

What is the scientific name of this species?

What procedure was performed in this gorilla that led to the suspected abdominal compartment syndrome?
- How was it managed?

Answer 89

ACUTE ABDOMINAL COMPARTMENT SYNDROME DURING COLONOSCOPY IN A WESTERN LOWLAND GORILLA (GORILLA GORILLA GORILLA)
Abstract
A novel case report of acute abdominal compartment syndrome (ACS) with respiratory and hemodynamic collapse during colonoscopy in a western lowland gorilla (Gorilla gorilla gorilla), notably, without colonic perforation is presented here. ACS is a rapidly progressive and sustained increase in intra-abdominal pressure leading to shock with multisystem organ failure. Surgical intervention was mandatory, and abdominal decompression was immediately life-saving, although the patient died 1 wk later of surgical complications. Colonoscopy is a widely performed procedure that is generally considered safe, and serious complications during colonoscopy are rare. ACS has been previously reported during colonoscopy with perforation in four cases (human)1,4,6,8. In this instance there was no evidence of perforation, representing not only a rare complication of the procedure, but also a novel cause of ACS. This is the first report of ACS in a nonhuman primate and of nonperforation-associated ACS in human or nonhuman primates.

Key points
- Insufflation of the colon with air or CO2 is necessary for visualization during colonoscopy. Transient hypotension and hypoxia are side effects of the procedure, related to sedation.
- ACS is a rare complication where the bowel perforates and the gas used gets trapped in the abdomen, leading to multiple organ dysfunction → intestinal ischemia, renal failure
- This case required emergent surgical decompression, but NO tear was found.
- Western lowland gorilla presented d/t chronic constipation from extensive intestinal adhesions
– Mass with structure identified in sigmoid colon during a previous colonoscopy 1 mo before
- 30 min into procedure, “rock hard” abdomen identified, RR and ETCO2 increased
– Rads identified gas, unclear location
– Severe respiratory acidosis
– Needle decompression attempted but unsuccessful
– Vitals improved after laparotomy, although no “rush of air” was seen
- Surgical team resected a colonic mass; dehisced 1 week later leading to euthanasia

Take home message: Abdominal compartment syndrome without bowel perforation is a potential risk of colonoscopy in gorillas

Question 90

A recent study evaluated the use of finger cuffs for oscillometric blood pressure measurement in Chimpanzees.

What is the scientific name of this species?

What are teh most common cardiac disorders in this species?

How did finger cuff placements agree with invasive blood pressure measurements?

Answer 90

JZWM 2023 54(1) 16-22
EVALUATION OF OSCILLOMETRIC BLOOD PRESSURE MEASUREMENT USING A FINGER CUFF IN ANESTHETIZED CHIMPANZEES (PAN TROGLODYTES)

Abstract: Cardiovascular disease is common among chimpanzees (Pan troglodytes), and serial blood pressure monitoring in conscious animals may improve disease surveillance and guide hypertension treatment strategies. The objective of this study was to compare the accuracy of a noninvasive, oscillometric blood pressure monitor using a finger blood pressure cuff with invasively measured blood pressure in anesthetized chimpanzees. Twelve chimpanzees were anesthetized with tiletamine–zolazepam intramuscularly, intubated, and maintained on inhaled isoflurane to effect. Blood pressure measurements, which included systolic arterial pressure (SAP), mean arterial pressure (MAP), and diastolic arterial pressure (DAP), were collected simultaneously from an oscillometric blood pressure cuff placed on a forelimb digit (FBP) and a direct arterial catheter (IBP) every 5–10 min while anesthetized. One hundred paired samples were collected, and results were compared using Bland–Altman plots and analysis. FBP showed good agreement with IBP for SAP, MAP, and DAP but consistently overestimated values compared with IBP. FBP may be useful for serial blood pressure monitoring in conscious chimpanzees.

Intro
- Cardiovascular disease is a prevalent cause of morbidity and mortality in great ape populations
- Most common: systolic dysfunction, arrhythmias, and myocardial fibrosis.
- The development of left ventricular hypertrophy lends credence to the likelihood that hypertension may be contributing to myocardial fibrosis with subsequent left heart enlargement
- Hard to obtain BP awake–no blood pressure RR for conscious apes have been established
- The objectives of this study were to evaluate the use of a finger blood pressure (FBP) cuff in anesthetized chimpanzees and compare the obtained blood pressure measurements to invasive blood pressure (IBP) measurements.

M&M
- 12 chimps anesthetized with telazol, compared IBP to FBP
- 100 paired samples were collected

Results and discussion
- 5 chimps became hypotensive during anesthesia
- Overall, FBP measurements were significantly higher than IBP measurements
- However, good agreement with SAP, MAP, and DAP
- FBP measurements approached or met nearly all validation criteria outlined by the ACVIM except SAP
- Based on human criteria (AAMI), only fulfilled for MAP.
- Left lateral positioning had a significant effect on SAP (but not MAP or DAP), with values an average of 6.2 mmHg higher for FBP compared with IBP.
- It is possible that the device accuracy may be higher in awake (non-hypotensive) animals

Takeaway: blood pressure measurements obtained using a finger cuff in anesthetized chimpanzees showed good agreement to invasive blood pressure measurements; however, overestimation occurred for all readings.

Question 91

A recent study described efforts for weight management of Chimpanzees in managed care.

What is the scientific name of this species?

What are the recommended components of a chimpanzee diet?

What changes were made to the diet and feeding strategy in this study?
- How did the two approaches differ and what was their success rate?

How did the behaviors of the chimpanzees change with appropriate body condition scores?

Answer 91

Weight management towards physiological and behavioral wellbeing for chimpanzees living under human care.
Clay AW, Crane MM, Bloomsmith MA.
Zoo Biology. 2022;41(3):200-217.

Across a period of 54 months, several changes were made to the feeding protocols of 32 adult chimpanzees living at the Yerkes National Primate Research Center Field Station. Before implementing any changes in diet, baseline data were collected for 6 months. During Baseline (BS), the chimpanzees received unlimited amounts of primate biscuits twice a day and a limited amount of produce as enrichment. Treatment One (T1) dietary modifications included an increased amount of vegetables, primarily leafy greens, and biscuit feedings scheduled to occur an hour after vegetables were provided to the chimpanzees. T1 lasted for 1 year. At the end of T1, most of the chimpanzees had gained weight. Treatment Two (T2) occurred over the span of 3 years, during which all the chimpanzees were switched from unlimited, group-distributed primate biscuits to individually prescribed amounts of biscuits, fed in\dividually, and increased daily feedings of leafy greens. By the end of T2, 10 of 15 chimpanzees who were overweight or obese at the start of the project were within range of ideal body condition, and 4 of the remaining 5 were improved. All the chimpanzees who started the project within ideal range were still within ideal range. **Significantly more time was invested in eating, foraging, and processing food during T2 (p < .05), more appropriately replicating the natural time budget for a chimpanzee. **There were not any increases in abnormal, stress-related, or agonistic behaviors as a function of dietary modifications. Inactivity, however, was significantly higher (p < .05) during the later protocol, and locomotion was concurrently lower (p < .05).

Background
- Obesity in chimps predisposes to inflammatory conditions, cardiac disease (females), diabetes
- Chimpanzee Care Handbook recommends increased fiber and decreased fat in primate biscuits; 50% of diet should be dark, leafy greens
- Ethogram
– Self-directed: idiosyncratic manipulation, eye-directed behaviors, self-oral behaviors
– Appetitive: aberrant fecal behavior, urophagy, regurgitation/reingestion
– Stress-related: yawning, rough scratching

Key Points
- Increased overall daily amount and number of dark leafy greens, restricted primate biscuits, fed individually based on MER - 32 chimps monitored over 5 yrs
– Body condition score correlated well with weight and was considered representative
- Obesity worsened with first diet change to larger amounts of high-fiber produce fed before biscuits (still ad lib) in enrichment devices designed to slow consumption
- Improved BCS with individual feeding of biscuits based on MER and increased leafy produce
– Healthy rate of weight loss without increases in agonism, stress, or abnormal behavior
– Increased time foraging, obtaining, and processing foods
– No change in stationary activity, increased activity, or locomotion
– No effect of age and sex
*-10/15 chimps with abnormal BCS were within ideal range, none starting in ideal range changed
- Developing a feeding protocol with more time for feeding and foraging behavior did not increase agonistic, stress-related, or abnormal behaviors and improved BCS over time
– Chimps in ideal BCS had more play, locomotion, contact and noncontact agonism
– Inactivity was higher in chimps with poor BCS
- Ideal BCS - lower triglycerides but triglycerides increased with individual biscuit feeding (not sure why)

Conclusions
- Improving the body condition of chimps through increased leafy produce and individual feeding of primate biscuits based on MER improved behavior wellbeing but did not increase overall activity level of chimps
- Personnel time required to individually feed was worthwhile.

Question 92

A recent study evaluated the activity of wild mountain gorillas compared to managed western lowland gorillas.

What are the scientific names of these two species?

What is a gorilla’s daily activity budget like?

How did the wild gorilla behaviors compare to the managed ones?

Answer 92

Zoo Biology. 2022;41:503–511
Distinguishing mobility and immobility when establishing species‐specific activity budgets: A case study with gorillas (Gorilla berengei berengei and Gorilla gorilla gorilla)
Jean D. Nsekanabo1,2 | Austin Leeds3,4 | Winnie Eckardt1 |Deogratias Tuyisingize1 | Aisha Nyiramana2 | Kristen E. Lukas3,4– Rev by AJC

Abstract: Activity budgets characterize the distribution of behavior over a specified time period. In some cases, having comparable data from free‐ranging populations can help inform the management of wildlife in zoos and sanctuaries. For example, although variations exist across subspecies, seasons, and study sites, diurnal activity budgets for free‐ranging gorillas largely consist of feeding and resting. Unfortunately, most studies do not consistently differentiate between the type of activities gorillas exhibit while locomoting versus stationary. Therefore, it can be difficult to characterize optimal levels of aerobic activity that might enhance body condition or promote gorilla health in zoos and sanctuaries. In this study, we concurrently measured the mobility state and activity of mountain gorillas (Gorilla beringei beringei) in Volcanoes National Park, Rwanda. From June to August 2015, behavioral data were collected using group scan sampling with 15‐min intervals in two groups (N = 29 gorillas) monitored by the Dian Fossey Gorilla Fund International. Overall, gorillas spent significantly more time immobile (85.2% of observations) than mobile (14.8%), revealing energy expenditure levels comparable to western lowland gorillas living in zoos. There was no difference in behavioral diversity when gorillas were mobile versus immobile but adult females exhibited substantially less behavioral diversity while immobile than other age‐sex classes. There was more diversity in behaviors following the transition from immobile to mobile than vice versa, particularly for adult females. Future studies should concurrently measure mobility state and behavior to improve the precision of activity budget data and serve as a more useful tool for evaluating optimal activity levels for wildlife in human care.

Key Points:
- Studying mobility states can provide insight on environmental stressors and thermoregulation
- Impnt to distinguish time spent idle (immobile and resting) from immobile but still feeding/grooming
- These activity budget studies can serve as a baseline for comparison to primates in managed care
- Overall gorillas spent more time immobile than mobile and no difference in behavioral diversity by mobility state
– Great diversity of behaviors following the transition from immobile to mobile
– Adult female had lower behavioral diversity while immobile
– Efforts to increase activity levels in zoo gorillas may emphasize diversity of behaviors while immobile (puzzle devices, cognitive tasks, sensory enrichment)
*-Time spent immobile was similar to that of gorillas in managed care (~80% of the time)
– Potential for activity level as a risk factor for cardiovascular disease in gorillas?
– Gorillas in managed care spend limited time in locomotion and most of their time resting
– Based on natural history, resting to digest high fiber, low starch diets is normal

Take Home:
- Concurrent measurement of mobility state and activity increases the accuracy of activity budget assessments, particularly when estimating energy expenditure of behaviors.
- In this study, mountain gorillas spent 85.2% of their time immobile, which is comparable to the 87.2% time spent immobile reported in zoo-housed western lowland gorillas.

Question 93

A recent study validated measurement of fecal dehydroepiandrosterone in gibbons and siamangs.

What is dehydroepiandrosterone (DHEAS)?
- What incites its production?
- What hormone has some cross reactivity?
- What physiologic event lead to high DHEAS levels in siamangs?

Answer 93

Zoo Biology 41(6): 588-594
Validation of an enzyme immunoassay for measurement of fecal dehydroepiandrosterone sulfate in gibbons and siamangs
Rafaela Takeshita – rev AJC

Abstract: Monitoring wildlife stress levels is essential to ensure their quality of life in captivity or in the wild. One promising method to assess the stress response is the comeasurement of glucocorticoids (GC) and dehydroepiandrosterone sulfate (DHEAS), adrenal hormones involved in the modulation of the stress response. Although noninvasive methods to measure GCs have been validated in several species, only a few studies have validated DHEAS assays. The aims of this study were (1) to describe an enzyme immunoassay (EIA) to measure DHEAS levels, (2) to validate this assay for fecal samples in gibbons and siamangs, and (3) to test hormonal stability after one freeze‐thaw cycle and over time at two freezer temperatures (−20°C and −80°C). Subjects included 32 gibbons and siamangs from U.S. zoological parks. The EIA was validated analytically by parallelism and accuracy tests, and biologically by confirming a DHEAS response 1–2 days after a stressful event (accident, vaccination, or transportation) in three individuals. In addition, fecal DHEAS levels in a pregnant female were above nonpregnant/nonlactating levels and declined progressively the following parturition. The hormonal stability experiments revealed no significant changes in fecal DHEAS levels after one freeze‐thaw cycle. Hormonal levels in fecal extracts were stable for 2 months, regardless of the storage temperature, with no significant differences between −20°C and −80°C conditions. The EIA described has high sensitivity and it is suitable for fecal DHEAS measurement in gibbons and siamangs, with a potential to be applied to other species.

Key points:
- GC levels can be measured from feces, urine, hair and saliva
- Intrinsic factors can influence GC levels – body mass, sex and time of day that may limit interpretation
- Dehydroepiandrosterone (DHEAS) is an adrenal hormone involved in modulation of stress response 🡪 during acute stress, DHEAS increase and antagonize GC receptors – a high GC/DHEAS ratio associated with inability to cope with stress and assoc with inflammation, disease or poor envir conditions
- Objectives of this study were to validate the EIA for measuring DHEAS in siamang and gibbon feces and test hormonal stability after freeze thaw cycle and diff temps
- There was mild cross-reactivity with testosterone when measuring DHEAS but the EIA protocol was successful using feces from gibbon and siamang
– Levels peaked within 1-2 days after a stressful event – response varies according to event and can be reduced with previous training or exposure to these procedures
– High DHEAS in siamang during pregnancy
– Neither fecal freeze-thaw cycle nor storage temp affected DHEAS concentrations

Take-Home Message:
- Validated a noninvasive method to measure DHEAS levels in gibbons and siamang feces.
- Samples are unchanged after a free-thaw cycle and there is no difference between ultracold and normal freezer if assayed within 2 months.

Question 94

A recent paper described vaginal foreign bodies in nonhuman primates.

What species were observed with the foreign bodies in this study?

What conditions did these FB cause?

What underlying conditions were found in these cases on necropsy or biopsy?

Answer 94

ZB 2022 41(6) 595-600
Vaginal foreign bodies in six nonhuman primates with underlying pathological conditions

Abstract: Four female Japanese macaques (Macaca fuscata) from the same group as well as Wolf’s guenon (Cercopithecus wolfi) and a Western lowland gorilla (Gorilla gorilla gorilla) from a second institution presented with vaginal foreign bodies in parallel with diseases of the urogenital tract or with endocrine disorders. These foreign bodies were associated with a mild to marked, diffuse vaginitis in all cases. Underlying pathological conditions consisted of a cavernous uterine hemangioma in a 20‐ year‐old macaque, diffuse endometritis in a 21‐year‐old macaque, an in situ endometrial carcinoma in a 24‐year‐old macaque, endometritis and an ovarian cyst‐like structure in the 27‐year‐old Western lowland gorilla, chronic cystitis and chronic renal disease in a 24‐year‐old macaque, and a history of hypothyroidism with irregular reproductive cycles in the 12‐year‐old Wolf’s guenon. Vaginal foreign bodies have been reported in nonhuman primates used in biomedical research, but their concurrence with underlying conditions has not been explored. In women, vaginal foreign bodies have been linked to serious underlying medical conditions. This case series emphasizes the recommendation to investigate this abnormal behavior for underlying medical or adverse psychosocial conditions in primates under human care.

Case series
- This case series describes six cases of VFBs in nonhuman primates under human care with concurrent health impairment
- Four geriatric (older than 20 years old) female Japanese macaques (Macaca fuscata) from the same captive group presented with VFBs associated with diseases of the reproductive (n = 3) or the urinary (n = 2) tracts over a 2‐year period
- Three of the four affected females were multiparous, and all had received contraceptive depot medroxyprogesterone acetate injections
- VFBs were identified by vaginal examination with a speculum and/or endoscopic vaginoscopy under general anesthesia and consisted of decomposed wood shavings and plant material which were acquired from their indoor or outdoor enclosures.
- Histopathology performed on collected biopsies or necropsies revealed the presence of inflammatory, degenerative, and neoplastic processes in the urogenital tracts.
- An adult nulliparous Wolf’s guenon (Cercopithecus wolfi) from another institution was also diagnosed with VFBs while being assessed for infertility–rocks in the vagina–vaginitis
- The final case is an adult, nulliparous Western lowland gorilla–hx of failure to reproduce, irregular menses, and intermittent vaginal bleeding.
– not on contraception at the time of diagnosis of VFBs but had received oral contraception previously
– Decomposing wood found in the vagina, histo revealed endometritis
- The cause of VFBs in nonhuman primates remains unclear but based on the literature in women, sexual gratification (masturbation), psychosocial factors, and underlying health issues are potential explanations for this behavior
- In this case series, the co‐occurrences of health issues in all cases suggest that the self‐insertion of VFBs could be a response to pathological conditions of the urogenital tract, possibly associated with discomfort or pain
- some lesions may be secondary to the presence of VFBs themselves, such as the vaginitis detected histologically in Cases #1 and #5.

Takeaway:
- VFBs in primates may be underdiagnosed and may be causing or caused by repro disease.
- Routine examination of the vagina is recommended