SSP/TAG:



SSP/TAG: Bonobo DATE: 6 February 2019

VETERINARY ADVISOR CONTACT INFORMATION:

Victoria L. Clyde, DVM

Milwaukee County Zoo, 10001 W. Blue Mound Rd, Milwaukee, WI 53226

414-256-5471 ofc; 414-256-5441 main AHC; fax 414-256-2522

victoria.clyde@

Priya Bapodra-Villaverde, BVetMed (Hons), MSc, DACZM MRCVS

Columbus Zoo, 9990 Riverside Drive, Powell, OH 43065-0400

614-724-3643 ofc; 740-255-4504 cell; 614-645-3465 fax

Priya.bapodra@

PATHOLOGY ADVISOR CONTACT INFORMATION:

Karen Terio DVM, PhD, DACVP Zoological Pathology Program

c/o Chicago Zoological Society, 3300 Golf Road,Brookfield, IL 60513

312-585-9094; kterio@illinois.edu

RECENT MORTALITY:

Bonobo Mortalities from January 1, 2016 to present (North America)

SB# Sex/Age Cause of Death

0094 M / 36 yr Severe chronic myocardial fibrosis, concentric LVH,

arteriosclerosis, aortic jet lesion; eosinophilic colitis

0142 F / 31 yr Aortic dissection with aneurysmal rupture;

retinal hemorrhage and detachment

0268 F / 16 yr Bronchopneumonia

0534 F / 3 yr Baylisacaris neural larval migrans

Pattern of mortality remains consistent with previous reviews. Cardiovascular disease remains the most common cause of mortality with adult onset (males 20 yr+, females 30 yr+). Respiratory disease is second-most common cause of mortality in bonobos, with mortality usually highest in juvenile/early adult years.

Aortic aneurysms continue to be reported. Bonobos in NA known to have aortic aneurysm at death include:

0111 M / 30 yr Yenge

0127 M / 25 yr Lomako

0137 M / 14 yr Congo I

0142 F / 31 yr Marilyn-Lori

Three bonobos in NA appear to have aortic dilation on ultrasound:

0108 F / 36 y Ascending aorta appears slightly prominent; incomplete study

0116 F / 37 y Probable dissecting aneurysm of ascending thoracic aorta

0202 M / 23 y LVH with reduced diastolic function; mildly dilated

ascending aorta; hypertension

MORBIDITY (Significant illnesses/issues facing this species this period):

1. CARDIOVASCULAR DISEASE:

(ACEI = angiotensin converting enzyme inhibitor; LV = left ventricular)

SB# Sex/Age Clinical Synopsis

0040 F/ 51 y LVH with hyperdynamic left ventricular wall motion. On high

dose ACEI enalapril and beta-blocker carvedilol.

Epistaxis stopped and some improvement in LV size after

dosage increases but finger BP remains high. Trained for awake

BP and echocardiogram.

0051 F / 46 y 2014 echo showed LV hypertrophy with hyperdynamic contraction, but 2016 echo shows normal LV size and function.

No cardiac medications. Not trained for awake echo or finger

BP.

0058 M / 48 y LVH, reduced LV function. Global hypokinesis with reduced EF

of 30%. On ACEI enalapril and high dose beta-blocker

carvedilol. Trained for awake echos. One finger BP submitted.

0083 F / 39 y Improvement in LV size but has hyperdynamic LV contraction

and tachycardia – risk for hypertension. No cardiac meds.

Trained for awake echo. High priority to train for finger BP?

0104 M / 39 y Concentric LV hypertrophy with hyperdynamic wall function. On ACE inhibitor lisinopril. Some improvement in wall

size on 2018 echo. Trained for awake echo and finger BP.

0105 M / 39 y LVH (2018 similar to previous exams) with reduced diastolic

function. On ACEI lisinopril and baby aspirin.

Trained for awake echo and finger BP.

0108 F / 36 y *2018 incomplete study - ascending aorta appears slightly

Prominent. High priority to train for awake finger BP.

0116 F / 37 y *2017 – probable dissecting aneurysm of ascending thoracic

aorta. On low dose beta-blocker carvedilol. Might benefit from

additional anti-hypertensive medications, but awake finger BP

appears non-elevated.

0128 M / 31 y Mild LVH. On ACEI lisinopril. Trained for awake echo and finger

BP.

0146 M / 29 y Mild LVH. On ACEI enalapril.

0157 M / 28 y Mild LVH with mildly reduced ejection fraction. Irregular heart

rhythm. Training for awake ECG. On ACEI enalapril.

0173 F / 26 y Concentric LVH with hyperdynamic wall motion. LV walls thicker

in 2018 vs 2017. BP is high with systolic reported as 173 – 230

during recent examination. On low dose beta-blocker carvedilol.

Might benefit from additional antihypertensive medication such

as ACEI, calcium channel blocker or diuretic.

0180 F / 25 y Moderate LV hypertrophy with hyperdynamic wall motion and suspected previous stroke and hyperthyroidism. On ACEI

lisinopril, beta-blocker carvedilol, diuretic hydrochlorothiazide

and aspirin, as well as allergy medications, Miralax for bloating

and fecal retention; progesterone only contraceptive pills.

0184 M / 24 y Mild LV hypertrophy, 2018 echo improved vs. 2016.

On ACEI lisinopril. Trained for awake finger BP.

0199 M / 23 y Severe concentric LV hypertrophy with hyperdynamic systolic

wall motion. On beta-blocker carvedilol, ACEI lisinopril, diuretic

hydrochlorothiazide. Trained for awake finger BP but not echo.

0202 M / 23 y *LVH with reduced diastolic function and mildly dilated

ascending aorta. Very high systolic finger BP. Recently switched

from ACEI enalapril to lisinopril, added beta-blocker carvedilol,

and added calcium channel blocker amlopidine. Some reduction

in systolic BP with new medications. Trained for awake echo

and finger BP.

0247 M / 20 y LVH. On ACEI lisinopril and beta-blocker carvedilol. Trained for

awake finger BP and awake echocardiogram. Systolic finger BP

high, but improved slightly with recent switch from enalapril to

lisinopril. Trained for awake echo and finger BP.

0396 F / 8 y Suspect for LVH. MRI showed bilateral thalamic infarcts, most

likely result of single infarct to a branch of the posterior

cerebral artery. Probable hypertension. On low dose ACEI

enalapril. Not trained for awake echo or finger BP.

Some bonobos with LVH have shown improvement in LV wall size with anti-hypertensive medication or increases in doses: 0040; 0104; 0184

However, a few animals show possible improvements in heart size or BP after move to a different troop while not receiving medical treatment:

0051 F / 46 y Improvement in echo with no cardiac medication

0198 M / 23 y Marked improvement in finger BP after move from MCZ to Jax

Recommendation: Investigate effect of group size, group dynamics, and holding space on blood pressure and development of cardiac disease.

Several bonobos have marked hypertension despite treatment with one class of anti-hypertensive medications. Human patients frequently require more than one class of anti-hypertensive medications to control their blood pressure. Recently, a few bonobos have been treated with higher doses and additional classes of drugs. 

The most common classes of anti-hypertensive medications include:

1. angiotensin-converting enzyme inhibitors (ACEIs) and the angiotensin II receptor antagonists (ARBs, or angiotensin receptor blockers)

2. diuretics (thiazides, potassium-sparing, and loop)

3. calcium channel blockers

4. beta-blockers

 

A recent review of anti-hypertensive medication and their use in human patients is available from Emedicine online at: Hypertension Medication (updated July 17, 2018) Alexander MR chief editor.

 

ACEIs are the treatment of choice in human patients with hypertension. They suppress the renin-angiotensin-aldosterone system. Side effects can include cough and angioedema. ACEIs can cause injury or even death to a developing fetus. ACEIs used in bonobos include enalapril, lisinopril and ramipril. No adverse effects have been reported.

In humans, ARBs are typically used in patients unable to tolerate ACE inhibitors due to cough or angioedema. ARBs competitively block angiotensin-II to angiotensin type I receptors, thereby reducing vasoconstriction, sodium retention, and aldosterone release; the breakdown of bradykinin should not be inhibited. ARBs can cause injury or even death to a developing fetus. ARBs have not been used in bonobos to date.

Calcium channel blockers (CCBs) bind to L-type calcium channels resulting in vasodilatation and a decrease in blood pressure. In human patients, they are considered effective as monotherapy in black patients and elderly patients. Two bonobos have been treated with amlopidine. No adverse effects have been reported.

Thiazide diuretics inhibit reabsorption of sodium and chloride and long-term use of these drugs may result in hyponatremia. Hydrochlorothiazide has been used in 3 bonobos. No adverse effects have been reported. Bonobo Cardiac Advisor Dr. Sam Wann recommends considering using chlorthalidone in bonobos, based on improved outcomes in human patients compared to hydrochlorothiazide.

Potassium-sparing diuretics interfere with sodium reabsorption at the distal tubules decreasing potassium secretion. Potassium-sparing diuretics have a weak diuretic and antihypertensive effect when used alone. None have been used in bonobos to date, but this class of drugs could be very beneficial and has been used successfully in gorillas.

 

Loop diuretics act on the ascending limb of the loop of Henle, inhibiting the reabsorption of sodium and chloride. They are commonly used to control volume retention and used in patients with decreased glomerular filtration rate or heart failure. Loop diuretics do not reduce blood pressure as effectively as thiazide diuretics when they are used as monotherapy. Three bonobos with congestive heart failure have been treated with furosemide.

Beta-blockers are not recommended as first-line agents for hypertension; however, they are suitable alternatives when a compelling cardiac indication (eg, heart failure, myocardial infarction, diabetes) is present. Caution should be used in administering these agents in the setting of asthma or severe chronic obstructive pulmonary disease (COPD). Doses should be gradually reduced over a few weeks, as angina and myocardial infarction have been reported following abrupt discontinuance. Seven bonobos have been treated with carvedilol. No adverse effects have been reported.

Bonobo Cardiovascular Database/Great Ape Heart Project Update:

Recent publications:

Clyde, V. 2018. Management of Cardiac and Respiratory Diseases in Bonobos. VMX 2018, Orlando, FL. February 2018. See Appendix I of this report for abstract.

Murphy, H.W., Danforth, M.D. and Clyde, V.L. (2018), The Great Ape Heart Project. International Zoo Yearbook 52: 103-112 (includes information on clinical signs and treatment of cardiac disease in apes including bonobos).

Murphy, H.W., & Danforth, M.D. (2018). Update on the Great Ape Heart Project. Fowler's Zoo and Wild Animal Medicine Current Therapy (Vol. 9, pp. 581- 587

Great Ape Heart Project 2015 IMLS Research Grant

In the fall of 2015, the Great Ape Heart Project (GAHP) was awarded its third IMLS Grant. This research grant focused on cardiovascular issues facing bonobos:

• Bonobo Finger Blood Pressure Research Project

In Year 1 (2016), blood pressure devices were shipped out to eight participating institutions. In Years 1 and 2, feedback and blood pressure data were received monthly from all institutions. The goal was not only to obtain finger blood pressure measurements from bonobos, but also to better understand the efficacy of the equipment as a tool for use in apes. Useful feedback was received from institutions about body positioning, cuff sizes and placement on fingers, as well as social responses from the apes that affect the readings. Over 2,700 blood pressure readings of 50 bonobos from eight participating bonobo institutions have been submitted. The data are being analyzed for each bonobo to determine blood pressure trends over time including when changes are made blood pressure medications.

|  |INSTITUTIONS |Inst. Total # |# Bonobos |Number of readings |Start of Submissions |Months of |

| | |Bonobos |participating |submitted to GAHP | |participation |

|1 |ACCI |5 |5 |235 |28-Jun-18 |6 |

|2 |Cincinnati |13 |3 |14 |25-Sep-16 |7 |

|3 |Columbus |22 |9 |381 |8-Jun-16 |23 |

|4 |Fort Worth |12 |3 |187 |6-Jun-17 |14 |

|5 |Jacksonville |10 |8 |228 |4-Sep-16 |23 |

|6 |Memphis |7 |3 |47 |14-Jan-18 |6 |

|7 |MCZ since 2016 |19 |13 |790 |2-Jan-16 |17 |

|8 |San Diego Zoo |9 |6 |827 |1-Jul-16 |29 |

|  |  |Total AZA |Total bonobos |Total Number of |  |Avg. months |

| | |population |participating |Readings | |participation |

|  |  |97 |50 |2,709 |  |15.63 |

TABLE 1. List of AZA accredited institutions participating in the GAHP’s Bonobo Blood Pressure Project. NB: Milwaukee County Zoo (MCZ) piloted the program beginning in 2011. Table reflects data collected during IMLS funding.

FIGURE 1. Examples of individual blood pressure trend evaluations performed for bonobos participating in the finger blood pressure project.

• Postmortem cardiac evaluations: Some funding remains available from the GAHP Bonobo Grant to support post-mortem cardiac evaluations. Contact Bonobo SSP Veterinary Advisor Dr. Vickie Clyde for more information.

Great Ape Heart Project 2019 IMLS Pathology Grant has been submitted.

The goal of this next project is to investigate the pathology underlying CVD development. A key activity of this grant will be to mine the pathology data in the GAHP database to look for post-mortem patterns that correlate with clinical data from the live ape, in order to more fully determine the prevalence of hypertension and any association between lesions typical of hypertension at necropsy and clinical cardiac disease in apes.

This grant has four major goals: 1) Correlate clinical diagnostic test results and pathologic lesions of heart disease; 2) Assess tissues for evidence of hypertension; 3) Assess the evidence for atherosclerosis; and 4) Understand causes of fatal aortic aneurysms and dissections.

Projects included in this grant include digitization of pathology slides, use advanced pathology techniques to archived tissues, and apply of advanced pathology protocols to new post-mortem cases.

2. Respiratory Disease Updates:

Jax: Two outbreaks respiratory disease Dec 2016 & 2018. Respiratory disease was more severe in 2018, and a 4 yr old male required anesthesia for suctioning, fluids, IV and IM antibiotics (non-compliant with oral medication), and anti-inflammatory dose of short-acting steroid. Recovered in Shoreline cage for nebulizations and treatment, and made full recovery.

MCZ: Major respiratory disease outbreak Nov 2016 involved entire troop.

• 16.5 yr old female found dead after showing only minimal signs of respiratory disease yet severe bronchopneumonia was noted on post-mortem. Clinical signs do not always correlate to actual pulmonary pathology!

• 3 yr old female weak and collapsed at morning check required continuous anesthesia with ketamine and midazolam for 2 days of mechanical ventilation with pediatric ventilator and warmed moistened airway. Ventilator initially set up with PEEP at 6-8 mmHg and maximum inspiratory pressure of 30 mmHg until improved enough to switch to CPAP mode on respirator. Required IO catheter due to dehydration. Severe hypoventilation with respiratory acidosis. Treated with repeated suctioning, IV antibiotics and short-acting steroids, nebulization with albuterol, IV fluids with dextrose and KCl. Made full recovery.

• 21 yr old male developed bronchitis after initial respiratory infection which only resolved after oral treatment with prednisolone for 1 week

Publications of interest to respiratory disease in apes:

Clyde, V. 2018. Management of Cardiac and Respiratory Diseases in Bonobos. VMX 2018, Orlando, FL. February 2018. See Appendix I of this report for abstract.

University of Wisconsin-Madison & Goldberg T. "Human respiratory viruses continue to spread in wild chimpanzees." ScienceDaily. ScienceDaily, 22 January 2019. .

Maiback V and Vigilant L. 2019. Reduced bonobo MHC class I diversity predicts a reduced viral peptide binding ability compared to chimpanzees. BMC Evolutionary Biology 19:14;

Trevelline BK, Fontaine SS, Hartup BK, Kohl KD. 2019. Conservation biology needs a microbial renaissance: a call for the consideration of host-associated microbiota in

wildlife management practices. Proc. R. Soc. B 286: 20182448.



3. Endocrinology Update - TSH:

Bonobo serum run at the Milwaukee County Zoo’s consulting medical lab had non-detectable levels of TSH in apparently euthyroid bonobos. That lab uses the Siemens Immulite system which uses a Siemens-propriety monoclonal antibody for its TSH chemiluminescence assay. TSH levels from MCZ gorilla serum remain detectable with this system.

The Columbus Zoo reports normal TSH values from bonobo serum run at their human medical lab on the Roche Diagnostics Electrochemiluminescence Immunoassay.

Interestingly, a 2014 publication (Drees JC et. al. Falsely Undetectable TSH in a Cohort of South Asian Euthyroid Patients. Journal of Clinical Endocrinology & Metabolism 99(4): 1171–1179,  ) found all 4 types of Siemens machines failed to detect TSH in 20 patients with a South Asian heritage, speculating that the monoclonal antibody used in the Siemens products is so selective that it misses functional mutations of TSH. Those 20 patients had normal levels of TSH measured assays from 4 other manufacturers.

Current recommendation: Do not use Siemens technology to measure bonobo TSH levels.

4. Reproductive updates

Recent Publication:

Persky ME, Jafarey YS, Moegenburg TA, Laubscher A, Lasser MJ, Clyde VL, Garner MM. 2018. Antemortem diagnosis and successful treatment of a complete molar pregnancy in a geriatric bonobo (Pan paniscus). Journal of Zoo and Wildlife Medicine: 49 (3):828-832.

Abstract: A 47-yr-old multiparous female bonobo tested positive for pregnancy on a routine urine test. Because this geriatric animal was considered post-reproductive, 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.

BONOBO PROTOCOLS:

1. Bonobo specific veterinary information can be found in the Guidelines for Ape Preventive Health Program and Guidelines for Preshipment Testing, Transport and Quarantine of Apes on the AAZV website under “Resources”. Click on “SSP/TAG/VAG and Related Information”, then click on the red link entitled “Reports, Protocols, Guidelines and Information” and select Bonobo, then click on the two Ape Guidelines at the top of this list. Information on bonobos, as well as information for gorilla, orangutan and chimpanzee, is included in these documents, which are due for updates. Please email SSP Veterinary Advisor Dr. Vickie Clyde at Victoria.clyde@ with any comments or suggested changes. Previous SSP Veterinary Advisor reports are also available on that webpage.

2. Great Ape Heart Project Echocardiogram Submission Forms and instructions for submitting exams can be found at:

3. The Standardised Necropsy Report for Great Apes and Other Primates - fillable form can be found on the AAZV website under “Resources”. Click on “Pathology and Necropsy Protocols” at the bottom of the page, then select “Great Ape”.

4. You can also find the Great Ape Heart Project Recommended Cardiac Necropsy Guide and the Great Ape Heart Project Recommended Cardiac Sectioning Protocol for Pathologists on the same page of the AAZV website or on the GAHP website at:

5. The Bonobo Semen Analysis and Cryopreservation Manual (version March 2013) was previously sent on DVD to all bonobo-holding institutions. It is too large to email, but you can get a copy via Dropbox by contacting Auriana Gilliland-Lloyd at aurianag@. Facilities for storing cryopreserved bonobo semen can be found at the Cincinnati Zoo CREW, the Milwaukee County Zoo or the San Diego Zoo Institute for Conservation Research.

6. Cardiovascular Recommendations: The Great Ape Heart Project is working on standardized recommendations for ape cardiac evaluations, research and therapeutic management, but until those recommendations are released, please continue to follow the recommendations of the Bonobo Cardiovascular Database and Bonobo SSP:

• Collect baseline echocardiograms in all bonobos by 15 yr and repeat every 3-5 years if asymptomatic; every 0.5 – 1.5 yrs if symptomatic. Forward copies of echocardiograms and cardiac measurements to the SSP Veterinary Advisor Dr. Vickie Clyde through the Great Ape Heart Project as outlined above:

• Train adult bonobos for voluntary participation in awake echocardiograms and awake finger blood pressure measurements

• React promptly to signs of social withdrawal. Behavior changes noted by keepers a few weeks to months before sudden deaths in bonobos due to cardiovascular disease have included social withdrawal and avoidance of altercations/aggression. Immobilization for complete physical examination, bloodwork, blood pressure measurement, ECG, echocardiogram and radiographs should be scheduled quickly and cardiac medications initiated if signs of cardiac disease are found. Cardiovascular function can be improved if appropriate medications are started early.

• Do not use alpha-2 adrenergic receptor agonists such as dexmedetomidine, medetomidine or xylazine in any bonobo being immobilized for an echocardiogram or in any animal suspected of having cardiovascular disease. These drugs can worsen cardiac function even in apes with normal cardiac function.

• Evaluate dietary sodium and potassium levels. The exact amount of dietary salt intake appropriate for apes is unknown, but high dietary salt intake may lead to hypertension in genetically prone individuals and can exacerbate existing disease. Current recommendation is to feed less than 1200 mg of sodium per bonobo each day. This amount is based on the American Heart Association recommendation for a human to consume less than 2300 mg/day. Sodium levels in any pelleted diet product should be less than 0.25%. Many institutions are currently feeding much lower levels of sodium and restricting the amount of pelleted feed offered. Sufficient potassium intake may be helpful.

Restrict caloric intake to prevent obesity in bonobos.

• Increase exercise by increasing useable space and appropriate enrichment.

• Evaluate stress levels of individual bonobos. Animals with higher stress levels, including those at the top and bottom of the social hierarchy, seem more prone to hypertension and the development of cardiovascular disease, thus warranting more frequent cardiac assessments.

• Start anti-hypertensive medications earlier rather than later. Hypertension appears to be a significant factor in the development of cardiovascular disease in bonobos. Ideally, medication decisions are based on blood pressure measurement in awake animals. If that is not possible, a blood pressure reading taken early (at first hands on) during immobilizations using ketamine with or without a benzodiazepine sedative and before inhalant gases are used, seem to accurately reflect a bonobo’s overall blood pressure status. If elevated pressures are seen or suspected, or if left ventricular hypertrophy is found on echocardiogram, start anti-hypertensive medications.

7. Respiratory Disease Recommendations:

• Restrict access to bonobo troops over the fall/winter when respiratory infection rates are highest in surrounding human community. Bonobos remain highly susceptible to most respiratory viruses and bacteria carried by humans.

• Monitor severe respiratory disease closely. Mortality due to bronchopneumonia or Acute Respiratory Distress Syndrome (ARDS) is occasionally reported in bonobos and has also been reported in a common chimpanzee.

• Antibiotics: choose a drug with efficacy against both Streptococci and Staphylococci, such as cephalexin, cefpodoxime or azithromycin. Ceftriaxone can be given by injection or via dart if necessary.

• Bronchodilators: give albuterol via nebulization if possible to relax airways and improve ventilation. If animal will not allow nebulization, albuterol can be given orally but avoid overdose which can induce lactic acidosis leading to rapid shallow breathing. Use only one route of administration for albuterol at a time; do not give oral medication and nebulize concurrently.

• Anti-inflammatory medication: reduce fever and alleviate pain and discomfort through use of nonsteroidal anti-inflammatory medication. Short-acting steroids may be helpful with bronchitis or pneumonia with inflammation.

• If respiratory disease worsens, persists, or respiratory distress or dyspnea develop, intervene with an anesthetic event to allow radiographic evaluation, diagnostic testing and therapeutic treatment with intravenous antibiotics and nebulized bronchodilators. Do not continue to “wait and see” once severe respiratory disease or dyspnea with increased respiratory effort is observed.

• If ventilation-perfusion mismatch results in decreased oxygen saturation, or if animal becomes too exhausted to continue the work of breathing, anesthetize animal for ventilatory support using low tidal volume with rapid shallow breaths. Limit fluid therapy to just enough to maintain blood pressure and urine output to avoid pulmonary edema. Monitor blood gases if possible, and attempt to keep PaCO2 in 30’s to low 40’s, although levels of us to 50 mmHg can be tolerated as long as pH stays above 7.3. Avoid barotrauma to lung. Ideally, use a ventilator with positive end-expiratory pressure (PEEP), setting pressure no higher than 5-10 cm H20 to avoid barotrauma to the lung. The ability to mix room air with O2 and the use of a warmed, humidified air circuit will benefit the bonobo. If a humidified circuit is not available, nebulizing with a small amount of hypertonic saline will pull fluids into the trachea to loosen mucous.

• Record symptomology and clinical course of all respiratory infections in bonobos, and report outcome to SSP Veterinary Advisor Dr. Vickie Clyde.

8. Contraceptive Options for Bonobos:

Ideally, all breeding age female bonobos should be in a breeding situation and breeding should be allowed. However, contraception is being used in bonobos due to medical issues, space issues, prior to shipment, when optimal mate choice is not available, to increase age prior to first pregnancy and for females that lack maternal skills.

There are several methods of non-permanent birth control that have been used in bonobos:

a. Separation from fertile males when in estrus. Be aware that bonobo males as young as 6 years of age have successfully impregnated females.

b. Allow females to breed with vasectomized males during peak fertility (available at Columbus, Milwaukee, San Diego, Kumamoto and ACCI).

c. Combination oral contraceptive (COC) pills contain synthetic forms of both progesterone and estrogen hormones. The estrogen component is typically dosed at 20, 35 or 50 micrograms per pill. The AZA Reproductive Management Center (RMC) recommends using the lowest estrogen dose that effectively suppresses bleeding, usually a 1/20 or 1/35 formulation, in bonobos. Higher levels of estrogens (1/50) may put females at greater risk for Deep Vein Thromboses (DVT). COCs are the most frequent form of contraception currently reported in bonobos. They are easy to administer and clear from the system quickly once discontinued. Females starting on combination pills for the first time should receive a monophasic pill with either norethindrone (or possibly levonorgestrol) as the progestin component in a dose of 20-35 mg. Pills containing drosprienone are not recommended.

A placebo week is not needed and can be eliminated to help control estrus behavior. It is considered safe to use continuous pills, which has been reported in 3 bonobos. Institutions report crushing the pills and hiding in food or placing in juice with no negative effect on contraceptive efficacy. No unintended pregnancies have been reported for COCs in bonobos. At least nine pregnancies have been reported in bonobos after cessation of COC use.

COCs are not recommended during the first year of lactation, but most bonobos appear amenorrheic during their first year of lactation.

A chart listing human medical conditions and associated contraceptive recommendations can be found at:



d. Progesterone-only oral contraceptive birth control pills (POP) are considered less effective than COC in humans but can be used by lactating females 2-6 weeks after parturition. POPs use have been reported in 2 bonobos as well as in other ape and primate species. POPs must be taken continuously with no pill free days and taken every day around the same time of day to be effective. POPs do not contain estrogen so may be used when bonobo is at risk for stroke or blood clots.

e. Depo-Provera (depot progesterone) contraceptive injections every 2-3 months. Can be used for temporary contraception especially in bonobos who are not consistent or compliant in taking oral medication. Five bonobos are reported to have received a total of 15 injections in the RMC database. Subsequent pregnancies have occurred after Depo-Provera injections. Since this is a longer acting hormone which binds to androgen receptors, it can have more side effects which can include weight gain.  Duration of efficacy is unpredictable and it may not reverse as quickly as other methods. Does not contain estrogen so may be used when bonobo is at risk for stroke or blood clots.

f. Melengestrol Acetate (MGA) implants have been used in other ape and primate species but have not been reported in bonobos. Must be surgically inserted and removed/replaced every 2 years. May be lost or picked out by primates. Does not contain estrogen so may be used when bonobo is at risk for stroke or blood clots. Dose is 0.06 g/kg

g. Implanon or Nexplanon progestin implants last 3 years in women, but RMC recommends replacing every 2-2.5 yr since they have less data in apes. No use reported in bonobos. Implant is smaller (matchstick-sized) but would still require immobilization for insertion. Humans report a large percentage of breakthrough bleeding. Does not contain estrogen so may be used when bonobo is at risk for stroke or blood clots.

Recommendations: Document all contraceptive events in bonobos to the AZA Reproductive Management Center (RMC) as contraception is administered. And annual reminder will go out in the spring as well. To register for access to the online survey, please go to  or contact the RMC at contraception@.

 

For additional contraceptive information, please check the RMC website at animals/scienceresearch/reproductivemanagementcenter

 

Acknowledgements: Information on contraception for this report was provided in part by the AZA Reproductive Management Center and consulting medical OB/Gyn Dr. Mike Lasser.

Appendix I

CHALLENGES TO BONOBO HEALTH: Cardiac and Respiratory disease in the Pygmy Chimpanzee

Presented at VMX 2018 by Victoria L. Clyde, DVM, Milwaukee County Zoo, Milwaukee, WI, USA

BONOBO OVERVIEW

Bonobos (Pan paniscus) are perhaps the least known of the great apes. In the wild, their native habitat is limited to the rain forests south of the Congo River in the center of the Democratic Republic of Congo. While this area remains undeveloped, populations of wild bonobos are declining due to illegal harvesting for bush meat, habitat degradation for slash and burn agriculture, and the influx of locals and soldiers into the forest as a result of the recent Congolese wars. Bonobos are classified as endangered by the International Union for Conservation of Nature (IUCN).1 The number of bonobos in captivity is very small, with approximately 200 bonobos living in accredited zoos in the USA and European Union. The Bonobo Species Survival Plan® (SSP) of the Association of Zoos and Aquariums (AZA) collaboratively manages the North American population of bonobos through the development of plans that identify population management goals and recommendations to ensure the sustainability of a healthy, genetically diverse, and demographically varied population. The Bonobo SSP works with their European counterpart, the Bonobo Endangered Species Programme (EEP), to maintain genetic diversity and captive bonobo health on a global basis.

One of the roles of an SSP Veterinary Advisor is to evaluate health challenges for the species of interest. An initial review of bonobo mortality, performed by the author and based on information reported to the SSP and EEP between 1990-2000, showed that respiratory disease (27%) and cardiovascular disease (46%) were the two most common causes of death in bonobos greater than 1 year of age living in zoos.2 A second review of mortality, based on necropsy results of bonobo deaths between 2004 – 2014, shows very similar percentages, with respiratory disease causing 25% of deaths of bonobos greater than 1 year of age, and cardiovascular disease causing 46%.3

RESPIRATORY DISEASE

Bonobos are very susceptible to anthropozoonotic respiratory disease, transferred to the bonobos from humans. This transfer can occur either through direct contact with human caretakers, or more passively when air from visitor spaces is allowed to enter bonobo exhibits. Respiratory disease has been observed in both wild and captive troops of bonobos at the same time that similar disease is present in the surrounding human population.4, 5 A review of respiratory outbreaks in the Bonobo SSP between 2000 – 2005 found that factors associated with infection may include larger group size, higher stocking density, presence of infants/young animals in group, movement of animals between different troops, exposure to humans and other primates, and ambient temperature and humidity.5

In most cases of respiratory disease in bonobos, the underlying etiologic agent is not identified. Suspected bacterial causes of respiratory disease in bonobos include Streptococcal bacteria, including Streptococcus pneumoniae, Staphylococcus sp. and Haemophilus sp.. Many common human respiratory viruses are thought to cause disease in bonobos, including respiratory synctial virus, human metapneumovirus, parainfluenza viruses, influenza viruses, and adenoviruses.

Respiratory infection in bonobos can cause mild, moderate, severe or fatal disease. Most disturbingly, the disease can progress rapidly and at times bonobos have died after showing only mild signs of an upper respiratory infection. Infected animals may present with an asymptomatic swelling of the largyngeal air sac, a mild upper respiratory infection with nasal discharge, occasional cough and mild lethargy, or can progress to open-mouth breathing and hyperpnea which can lead to respiratory exhaustion and fatal Acute Respiratory Distress Syndrome (ARDS). Pneumonia is often suspected when animals become lethargic, hyperneic, have a significant cough or marked anorexia but has been documented by radiography in animals displaying only minimal signs.

Whenever possible, exposure of bonobos to respiratory infections should be prevented by restricting access of humans to bonobo areas during the fall and winter when respiratory infection rates are highest in the surrounding community. Care staff should change clothes and footwear, wash hands and don a face mask and gloves before entering bonobo areas. Caretakers who are ill should not work with bonobos. Of special concern are caretakers with school-age children or with ill family members. Bonobo enclosures should be kept at optimal temperatures and humidity for this tropical species, with good air flow that does not include inflow of air from visitor spaces. Pneumococcal vaccinations of juveniles followed by a geriatric booster is recommended, as bonobos vaccinated against multiple strains of Pneumococcus have shown lessened intensity of infection during a troop outbreak (R. Wallace and V. Clyde, pers. comm).

Once respiratory disease is present, affected bonobos should be separated from unaffected animals if possible. If pharyngeal swabs can be collected, they should be submitted to a human laboratory for respiratory pathogen PCR panels and bacterial culture with susceptibility testing. Symptomatic therapy may include increased intake of oral fluids and anti-inflammatory medication. If antibiotics are needed, select a drug with efficacy against both Streptococci and Staphylococci, such as cephalexin, cefpodoxime or azithromycin. Ceftriaxone can be given by injection or via dart for animals refusing to take oral medication. Bronchodilators such as albuterol can relax airways and improve ventilation. Albuterol can be given orally or by nebulization, but avoid overdosing this medication as it can induce tachycardia and lactic acidosis leading to rapid shallow breathing. Only one route of administration should be utilized at a time; do not give oral albuterol and nebulize it concurrently.

If respiratory disease worsens, persists, or respiratory distress or dyspnea develop, intervene with an anesthetic event for radiographs, diagnostic testing and therapeutic treatment with intravenous antibiotics and nebulized bronchodilators. Do not continue to “wait and see” once severe respiratory disease or dyspnea with increased respiratory effort is observed. If ventilation-perfusion mismatch results in decreased oxygen saturation, or if the bonobo becomes too exhausted to continue the work of breathing, maintain anesthesia in order to provide ventilatory support with assisted or mechanical ventilation, using a low tidal volume with rapid shallow breaths. Consultation with a medical respiratory therapist or pulmonologist is strongly advised. Limit fluid therapy to just enough to maintain blood pressure and urine output in order to avoid pulmonary edema. Monitor blood gases if possible, and attempt to keep PaCO2 in the 30’s to low 40’s mm Hg, although levels of up to 50 mm Hg can be tolerated as long as pH stays above 7.3. Ideally, use a ventilator with positive end-expiratory pressure (PEEP), setting pressure no higher than 5-10 cm H20 to avoid barotrauma to the lung. The ability to mix room air with oxygen and the use of a warmed, humidified air circuit will also benefit the bonobo.

CARDIOVASCULAR DISEASE

Cardiovascular disease is the most frequent cause of death in adult bonobos.6, 7 It is more common in males, and occurs at an earlier age in males compared to females.3 Puberty in bonobos occurs around 8-10 years of age and deaths from cardiovascular disease have occurred in animals as young as 15 years of age. Males are most often affected in their 20’s and 30’s, while females are more likely to be affected in their 40’s and 50’s. Clinical signs are infrequent and difficult to recognize. As recently as 10 years ago, prior to routine echocardiography, the most common “sign” of cardiovascular disease in a bonobo was sudden death. In hindsight, care staff often recognized that the bonobo had been subtly withdrawing from troop activities, and voluntarily refraining from antagonistic or aggressive interactions over the previous months. Intermittent epistaxis in bonobos may be a sign of underlying hypertension and unilateral weakness may indicate stroke. Only when CVD progresses to congestive heart failure (CHF), will more obvious signs such as weight gain, peripheral edema, marked anorexia, and progressive respiratory compromise be observed. At any stage of cardiovascular disease, sudden death can occur, possibly due to arrhythmias secondary to extensive myocardial fibrosis, aortic dissections, or strokes. Routine bloodwork is not particularly helpful in the diagnosis of cardiovascular disease in bonobos. Brain natriuretic peptide (BNP) is a hormone secreted by cardiomyocytes in the ventricles in response to stretching caused by increased ventricular blood volume. Bonobos with BNP levels above 150 pg/ml should be evaluated for possible LVH or congestive heart failure. BNP levels will also be elevated with renal insufficiency or pulmonary disease.

Common postmortem findings in bonobos with cardiovascular disease are characterized by pale streaks in the heart which correspond to dissecting fibrosis in the muscles of the ventricles. Most commonly, the left ventricle is hypertrophied, although dilation of ventricles is seen in a few cases. Aortic dissections and strokes can also be present. Typical histologic lesions include myocardial fibrosis (also termed interstitial myocardial fibrosis or fibrosing cardiomyopathy in earlier publications) in which the normal contractile myocytes are replaced by fibrous “scar” tissue, thought to be the result of injury to the myocardial cells. Fibrosis extends from around the small intra-myocardial arteries, separating and entrapping myocytes. Inflammation is minimal and often not present.6, 7 Significant atherosclerosis, a common finding in human cardiovascular disease, is not typically present in apes.8 Arteriolosclerosis or hardening of the small arteries with onion skin fibrosis has been observed in the tissues including the brain and kidneys. Taken altogether, these postmortem findings are suggestive of occult hypertension as a possible underlying cause of myocardial fibrosis in bonobos. Other hypotheses include previous viral infection, captive diet, salt intake, obesity, decreased exercise or genetics.

After the initial mortality review in 2000, the Bonobo SSP initiated the Bonobo Cardiovascular Database (BCD) with the assistance of ultrasonographer Leann Beehler, RDCS and medical cardiologist Samuel Wann, MD, MACC, FAHA, FESC. Echocardiograms performed on bonobos were collected and evaluated with the aim of helping zoos understand the cardiac health of their bonobos and to advise on possible therapeutic interventions. In 2009, the Milwaukee County Zoo and the Zoological Society of Milwaukee hosted a meeting of all four great ape SSP Veterinary and Pathology Advisors (gorilla, orangutan, bonobo and chimpanzee) along with medical cardiologists and researchers. The goal of the meeting was to bring together species experts to collaborate at the taxon level in order to better understand and reduce the frequency of cardiovascular disease of apes. The following year, funded by a grant of the Institute of Museum and Library Services (IMLS), the Great Ape Heart Project based at Zoo Atlanta® (GAHP) was formed. The Bonobo SSP, the Bonobo Cardiovascular Database, the Milwaukee County Zoo and other AZA institutions caring for bonobos have been active collaborators with the GAHP since its formation.

Echocardiograms are now routinely performed when bonobos are anesthetized for examination and many bonobos have been trained to voluntarily cooperate for awake echocardiograms. The most common finding on echocardiograms of bonobos with cardiovascular disease is left ventricular hypertrophy (LVH), which is often concentric and may progress over time. Hypermotility of ventricular muscles has been noted in 2 older female bonobos. High quality echo studies in DICOM format with multiple views are needed to fully assess cardiac function in bonobos and other apes. Apes, especially bonobos, have a craniocaudally compressed thorax like humans, unlike the laterally compressed thorax of more typical veterinary patients. Echo “windows” and probe angles in apes are more similar to humans but differ slightly between all species. Veterinary ultrasonographers are often initially challenged in obtaining an acceptable echocardiograms in apes, as the required views are different that those standardly obtained in veterinary medicine. Likewise, medical ultrasonographers have to adjust probe angles and pressures due to the deep thoracic cavity and different musculature of apes, as well as learn to adapt to the time pressure imposed by the zoo veterinarian during an anesthetic event. More information on required views for a complete ape echocardiographic study can be found at:

Effective treatment of cardiovascular disease is still being developed in bonobos. Currently, treatment in most bonobos is modeled after treatment of human patients with LVH and is aimed at reducing systemic blood pressure through the use of antihypertensive medication, including ACE inhibitors, beta-blockers and diuretics. At this point, there have been no studies on the efficacy, safety or pharmacokinetics of these drugs in bonobos or other apes. Experience to date in a limited number of bonobos indicates that initial cautiously chosen lower drug dosages may be too low to be effective, that clinical and echocardiographic improvement has been seen at higher doses in some bonobos. To date, very few adverse effects have been observed in bonobos under treatment.

The ability to measure indirect blood pressure in awake bonobos is a critical need, as it would allow for the diagnosis of hypertension, allow for timely anti-hypertensive treatment and would allow clinicians to modulate medication dosages based on a measureable therapeutic endpoint. Many of the AZA-accredited zoos that care for bonobos are working to train the bonobos for voluntary finger blood pressure measurement. The GAHP is collating this data to evaluate whether this methodology can reliably assess blood pressure in non-anesthetized bonobos.

CURRENT RECOMMENDATIONS OF THE BONOBO SSP VETERINARY ADVISOR

1. Collect baseline echocardiograms in all bonobos by 15 years of age and repeat every 3-5 years if asymptomatic.

2. Train adult bonobos for voluntary participation in awake echocardiograms and awake finger blood pressure measurements.

3. React promptly to signs of social withdrawal. Immobilization for complete physical examination, bloodwork, blood pressure measurement, ECG, echocardiogram and radiographs should be scheduled quickly and cardiac medications initiated if signs of cardiac disease are found. Cardiovascular function can be improved if appropriate medications are started early.

4. Do not use alpha-2 adrenergic receptor agonists such as dexmedetomidine, medetomidine or xylazine in any bonobo being immobilized for an echocardiogram or in any animal suspected of having cardiovascular disease. These drugs can be unsafe for bonobos with cardiovascular disease and can worsen function in apes with normal hearts, thus preventing accurate evaluation of cardiac status.

5. Evaluate dietary sodium and potassium levels. The exact amount of dietary salt intake appropriate for apes is unknown, but high dietary salt intake may lead to hypertension in genetically prone individuals and can exacerbate existing disease. Sodium levels in pelleted diet products should be less than 0.25%. Many institutions are currently feeding lower levels of sodium and restricting the amount of commercially prepared pelleted feed being offered.

Restrict caloric intake to prevent obesity in bonobos.

Increase exercise by increasing useable space and appropriate enrichment.

6. Evaluate stress levels of individual bonobos. Animals with higher stress levels (often those at the top and bottom of the social hierarchy) seem more prone to the development of cardiovascular disease and warrant more frequent cardiac assessments.

7. Start anti-hypertensive medications earlier rather than later. Hypertension may be a significant factor in the development of cardiovascular disease in bonobos. Ideally, medication decisions are based on blood pressure measurement in awake animals. If that is not possible, a blood pressure reading taken early (at first hands on) during immobilizations using ketamine with or without a benzodiazepine sedative and before inhalant gases are used, seem to accurately reflect a bonobo’s overall blood pressure status. If elevated pressures are seen or suspected, or if left ventricular hypertrophy is found on echocardiogram, start anti-hypertensive medications.

SELECTED REFERENCES

1. Fruth, B., Hickey, J.R., André, C., Furuichi, T., Hart, J., Hart, T., Kuehl, H., Maisels, F., Nackoney, J., Reinartz, G., Sop, T., Thompson, J. & Williamson, E.A. 2016. Pan paniscus. (errata version published in 2016) The IUCN Red List of Threatened Species 2016: e.T15932A102331567. . Downloaded on 03 September 2017.

2. Clyde, VL. 2000 Bonobo SSP Veterinary Advisor Report. (members only section)

3. Stong, V., VL Clyde, JMG Stevens, K Baiker, S Redrobe, J Pereboom, M Cobb and K. White. A restrospective review of Bonobo (Pan paniscus) mortality in European and North American Zoological Collections between 2004 and 2014. Zoo Biology: in revision.

4. Sakamaki, T., M. Mulavwa, and T. Furuichi. 2009. Flu-like epidemics in wild bonobos (Pan paniscus) at Wamba, the Luo Scientific Reserve, Democratic Republic of Congo. Pan Africa News 16(1).

5. Janssen DL, Clyde V, Lowenstine L, Killmar K, Morris P, Rideout B, Oosterhuis JE, Sutherland-Smith M, Lamberski N. 2006. Medical management of respiratory diseases in bonobos (Pan paniscus): workshop report. In: Proceedings of the American Association of Zoo Veterinarians; 2006. p. 148-150.

6. Lowenstine, LJ, R McManamon, KA Tersio. 2015. Comparative Pathology of Aging Great Apes. Veterinary Pathology 53(2): 250-276. 10.1177/0300985815612154

7. McManamon, R. and Lowenstine, L.J., 2011. Cardiovascular disease in great apes. Zoo and wild animal medicine, 7, pp.408-415.

8. Varki, N., Anderson, D., Herndon, J.G., Pham, T., Gregg, C.J., Cheriyan, M., Murphy, J., Strobert, E., Fritz, J., Else, J.G. and Varki, A., 2009. Heart disease is common in humans and chimpanzees, but is caused by different pathological processes. Evolutionary Applications, 2(1), pp.101-112.

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download