|Important key words or phrases.|
|Important concepts or main ideas.|
OCW Zoological Medicine2008
Diagnostic and Therapeutic Challenges (2009)
G. Kaufman, DVM
Cummings School of Veterinary Medicine at Tufts University
Fundamental statement: differences between wild and domestic animals
Almost all of our therapeutic choices in treating various disease states in non-domestic species are based on our experience in similar domestic animals. From these well known models we have learned what antibiotics are effective against which bacteria, how to revive animals in cardiovascular collapse or shock, what techniques result in the best repair of complicated long-bone fractures, how to sustain a cachectic anorexic animal, to name just a few examples. This is the well of knowledge that forms the basis of wildlife or zoological medicine.
Beyond this well of knowledge we need to be able to be creative, because there are many differences between our domestic patients and our wild ones that prevent us from simply applying our basic knowledge to such unusual circumstances. Some of these challenges will be discussed below.
1. Captive Animals
Three main issues often impede the administration of medication to wildlife. One is danger, another is fear, and the other is stress. Wildlife are not comfortable being in the presence of humans, are often not comfortable being in a captive setting, with or without the presence of humans, and most will try to escape and or avoid contact with humans. This clearly makes giving medication a challenge and requires creativity and patience on the part of the attending veterinarian. Compromises often have to be made, so monitoring must be vigilant, or a failure in therapy will go undetected.
1.2. Difficulty in assessing progress (SOAP)
An initial hurdle in monitoring treatments is assessing the problem and the progress of chosen therapy. In many cases the initial workup is accomplished under anesthesia with full access to the animal. This initial opportunity must be maximized to accomplish as much as possible before returning to a remote access situation.
This may mean:
Radical surgical debridement with primary closure
Placement of semi-permanent access ports or PEG tubes, etc.
Casting or developing harnesses
Placing stay sutures for easy bandage changes
Remote assessment often involves interpreting tertiary indicators of progress such as evaluation of appetite, water intake, attitude, postural cues, eliminations, etc. Remote observation with video equipment may be utilized. Traditional assessment parameters such as body temperature, heart rate, and hands on examination are usually not available.
Some problems may require frequent close examination (infections/wounds, ophthalmologic injuries, some fractures). In these situations a choice for repeated (perhaps daily) sedation must be weighed against the stress and/or harm that might result.
1.3. Attitude towards foreign objects - castes, bandages, fluid lines
Many animals will not cooperate with external devices of any sort. In some instances they will be tolerated while the patient is depressed, but once feeling better, the animal will attempt to remove the device. This includes IV lines and catheters, sutures, castes, bandages, external fixators, PEG tubes, etc. Choices for initial repair and/or therapy must take this into account, or else the original problem may be made worse instead of better. Wild animals are even capable of extreme self-mutilation under certain circumstances.
Some choices that might be considered include:
Fracture: internal fixation rather than external
Wound closure: Absorbable subcuticular closure rather than external skin closure
Fluid therapy: BID subcutaneous fluids in a squeeze rather than IV fluid drip
1.4. Creative delivery systems
Delivery of medications can be extremely challenging due to accessibility problems and the stress factor. Options for oral or injectable delivery may be considered, each with their own set of compromises.
Considerations for oral delivery might include:
Availability of formulation? - reasonable concentration, compounding options
Palatability/acceptability of formulation - need to combine with food or water?
Medicated feed option (BioServe)
Bioavailability for patient's species
Dosing interval required
Considerations for injectable delivery might include:
Concentration available - reasonable volume, compounding options
Dosing interval required for effective treatment
Darting options vs. hand-syringe - acceptability for patient
Use of Wydase (hyaluronidase) to promote absorption
1.5. Problems in determining drug dosing
Determining drug-dosing options for our domestic animals is usually fairly straightforward. Most of us turn to established formularies such as Plumb's formulary and readily find what we are looking for. Finding appropriate drug dosages for non-domestic species can be quite challenging and often requires a 'leap of faith' to try something new or unproven for the first time. Fortunately there are an increasing number of sources of information on non-domestic animal drug recommendations to be found. Suggested references are cited at the end of this chapter.
Many of the drug dosages cited in these sources are based on quality experience; some are merely extrapolated from the well established dog dose without adjustment; and a few are actually determined through pharmacokinetic research. Often enough, one is unable to find a dosage at all for the particular drug one wants to use. What are the options?
Developing a rational therapeutic plan requires several basic things:
Understanding the drug in question - researching available pharmacological information
Understanding the use of the drug in known species
Understanding the patients physiology, etc. - researching species information
Once these facts are known one can:
Determine the closest related species for which drug experience is well established
Extrapolate an 'optimal' therapeutic plan based on the available information
Carefully adjust the 'optimal' plan to a safe and effective 'practical' plan considering the limitations of the case at hand (remote delivery?, frequency of administration options, formulation options, etc.)
1.5.1. Extra-label use of drugs
Very few drugs are approved for use in non-domestic species. Extra label use is practiced every day, but still must be justified by the case and records should be carefully kept. Best judgment should be used regarding the use of drugs in animals that might end up in the food chain. The full text of the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA) may be found at http://www.fda.gov/cvm/amducatoc.htm
1.6. Use of Metabolic Scaling for rational drug dosing
Please review the theory of allometrics in the Supplementary Material folder. Metabolic or allometric scaling can be used to help determine a drug plan for an animal for which information is not available. It should never be used in place of available pharmacokinetic information.
Limitations of this method:
It produces only an approximation based on comparison between two species
There may be variation depending on choice of model species
One cannot take into account variables in drug metabolism including
bile acid composition
The key is to choose the appropriate model species as close to the patient species as possible.
Use the pharmacokinetic information for ceftazadime available on a small snake to extrapolate dose for a large python
Use the pharmacokinetic information for albendazole available for a cow to determine the dose for a wild ruminant
An appropriate related model may not be available. The most often encountered species for which information is available are humans, dogs, rats and mice. Hence, the margin of error grows. However, using this technique is most often a better alternative than merely choosing to use the human or dog dose (based on body weight) for your elephant, alligator or tree shrew....
Essential Formulae for Metabolic Scaling
MEC = K x BWkg0.75 = kcal/day
Frequency ( SMEC ) = MEC/BW = K x BWkg-0.25
K = 10 Reptiles
K = 49 Marsupial mammals
K = 70 Placental mammals
K = 78 Non-passerine birds
K = 129 Passerine birds
1.6.1. ALLOMETRIC SCALING WORKSHEET
Download printable worksheet for calculating the Universal MEC dose from published dosages in the literature (found in Supplementary Material folder).
Amoxicillin for a 500 kg polar bear with an infection
MEC = 70 x 500kg 0.75 = 7401.6
SMEC = MEC/500kg = 7401.6/500 = 14.8
UNIVERSAL MEC DOSE x Patient's MEC = 0.665 x 7401.6 = 5 g therapeutic dose
FREQUENCY COEFFICIENT x Patient's SMEC =0.06 x 14.8 = 0.89 times per day
Adjusted dose for Amoxicillin in the polar bear = 4.5 g once daily
Cisapride in an 8 kg tortoise with GI stasis
MEC = 10 x 8 kg 0.75 = 47.6
SMEC = MEC/8kg = 47.6/8 = 6
UNIVERSAL MEC DOSE x Patient's MEC = 0.006 x 47.6 = 0.29 mg therapeutic dose
FREQUENCY COEFFICIENT x Patient's SMEC = 0.1 x 6 = 0.6 times per day
Adjusted dose for Cisapride in the tortoise = 0.35 mg every other day
2. Free-ranging Wildlife
2.1. Assessing health of wild populations
Assessing health and disease in free-ranging populations is a major challenge. Active surveillance is expensive and requires significant support from all groups involved (government, NGO's, scientists, etc.) Often, investigations into wildlife disease are prompted by a major die-off or identification of a particular species as a disease reservoir important to human or livestock health. Some techniques for monitoring or assessing health in free-ranging animals include:
Demographic studies (indicating population health, reproductive status, etc.)
Routine necropsy of found dead animals or hunted specimens
Capture (mass or individual) and sampling
Telemetry, remote sampling
Countries that actively monitor wildlife diseases are better prepared for and can more readily anticipate disease outbreaks. Such information is also very useful in designing animal management strategies (domestic and wild).
Free-ranging wildlife are increasingly gaining attention as important players in diseases of concern for domestic animals and humans. Wildlife can act as disease reservoirs, populations for emergence of new diseases, and vectors of disease through wildlife translocation. Diseases in and of themselves are also creating real threats to certain critically endangered species, in some cases, bringing animals very close to extinction.
Should we try to control disease in wild populations? Historically, disease has been a normal part of a species natural life. However, increasingly, human activities have stressed or upset the ecology of wild populations so much that the natural balance controlling the impact of disease on a given population is disrupted. Diseases are therefore having a greater impact.
Medicating populations of wild animals is usually too difficult to employ as a technique for disease control. However, some small critical populations, already intensively managed, might be handled in this way (e.g. treating sarcoptic mange with ivermectin in Arctic Fox). Massive use of antibiotics or anthelmintics also carries the risk of developing drug resistance. This technique is generally very expensive and not sustainable. It should be considered only as a short term solution to a critical threat, with longer term strategies for overall health simultaneously employed (habitat management). Direct treatment is indicated in cases of translocation to prevent translocation of disease along with the host species (see above discussion in Conservation Medicine section).
Preventing disease spread may take several different forms. One simple and fairly inexpensive strategy is removal of dead animal carcasses to prevent spread to other animals (e.g. anthrax, botulism).
Another strategy might include habitat modification to decrease disease transmission. Care must be taken not to cause more environmental harm. Examples include burning, cutting trees, altering habitat to decrease vector species (draining wet areas for mosquitoes, removing woodpiles for rodents, clearing vegetation, etc.). Initially discouraging human development practices that alter the environment in a way that promotes disease transmission is very important.
Treating the environment to reduce vectors, such as mosquitoes, potentially carries a great price with the use of insecticides. These chemicals are generally indiscriminant and will also kill other invertebrates important to the ecology of the area. In addition, chemical resistance often develops and renders this method ineffective and possibly harmful. Careful risk analysis of the impact of chemicals should be made prior to their use.
Biological control has been tried in several instances utilizing sterile insects to displace disease organisms or vector species (screwworm, tse-tse fly). This is a high-tech very specialized effort. Other instances have used parasitic or infective agents for population control of the vector species ( Bacillus thuringeinsis ) as a substitute for chemical treatments. Use of bio-control agents is not without potential harmful consequences for non-target species and their use should be assessed carefully in any given situation. Biocontrol should be considered a form of introduced species and can disrupt the ecological balance.
Vaccination as a means of prevention or even eradication has been successful in many instances. This technique is generally very expensive and requires a strong commitment. Some examples include: mass vaccination of foxes in Europe for rabies using oral bait (others) anthrax vaccination of bison in contaminated areas.
Population management techniques have also been employed to reduce the number of host species capable of harboring a particular disease. Reducing the number of animals or the distribution of animals will decrease the opportunity for transmission. Methods of reducing or redistributing a particular population may be controversial and may be politically difficult to employ. Passive techniques such as physically separating infected from non-infected populations with fencing, etc. are generally more acceptable. Culling is a form of population management used to directly reduce the number of diseased hosts. Selective culling requires identifying infected individuals (test and slaughter) and is rarely practical with wildlife. Indiscriminant population reduction has been tried many times to gain control of a disease problem, but will not be effective if the disease dynamics are complicated. This method is often not socially or environmentally acceptable and depending on the techniques used may be harmful to non-target species, or considered inhumane (poisoning). Eradication of a species altogether is generally not acceptable or achievable.
2.4. Disease Monitoring
Disease monitoring is vital to an accurate understanding of the state and dynamic behavior of a particular disease and its impact on species of concern. Diseases often move through an ecosystem in a very complicated fashion and the more we understand their behavior, the better equipped we are to interrupt disease spread through the least harmful, least costly and most effect means.
3. Case Study – Diagnosing and Treating elephants for Tuberculosis
In the past 10-20 years, captive elephants have been diagnosed with tuberculosis in many American and European zoos and circuses. In North America, the incidence is about 12%. Recently, investigations in Southeast Asia are finding similar or higher rates of infection in their captive populations, which are estimated to be about 15,000 animals. The rates of infection in wild populations in these range countries has not been studied and therefor is unknown. Most cases of tuberculosis in North America involve Mycobacterium tuberculosis , the human pathogen. Since M. bovis is prevalent in livestock in Southeast Asia, it is suspected that elephants in that region may be infected with either or both M. tb and M. bovis .
How and why are elephants getting TB?
TB is spread through direct contact. Humans are the natural reservoir for M. tb . Thus the infections seen in captive animals points to direct contact with infected people. In North America, there is a tradition of training and managing elephants with intensive human contact (zoos and circuses). In Asia, there is an older and broader based tradition of using trained elephants for work in logging, for ceremonial use, forestry management, and for tourism. The rate of human tuberculosis is much higher than in the US, approaching 50% in some countries, providing iIncreased opportunity for transmission in Asia. If these animals are also mingling with livestock infected with M. bovis , their risks are even greater.
Culture has inherent limitations as a primary diagnostic technique. 1) Failure to isolate the organism does not rule out infection. The characteristic intermittent shedding of mycobacterial organisms provides a potential for false-negative results, allowing the disease to progress undetected. 2) The method of sample collection results in variable sample quality. Overgrowth due to contamination from trunk wash samples is common and may compromise the reliability of culture results, especially if overgrowth is not reported. 3) Reporting time is slow. Mycobacteria are fastidious, typically requiring 8 weeks for isolation. Infected elephants that are shedding while culture results are pending pose a risk to other elephants and humans. 4) Culture (requiring 3 samples from each elephant) is neither practical nor affordable to screen large numbers of elephants in Asia where surveillance is urgently needed.
3.1. Diagnostic challenges
Diagnosis of tuberculosis is extremely challenging in elephants. The intradermal test has been shown to be so inaccurate that it is no longer used. Culture is the “gold standard” for diagnosis, however the isolation and identification rate, even with repeated sampling is as low as 40% and is likely missing many positive infections. Successful culture requires
active shedding of the organism at the time of culture - intermittent shedding is characteristic of TB infection, so shedding may be missed
good sample quality – difficult to obtain from an elephant without contamination
precise and controlled laboratory conditions to support the fastidious and slow growing nature of the TB organism – these conditions are subject to failure and may not be available in some countries
The USDA approved culture method for elephants requires 3 trunk wash samples following a very prescribed protocol detailed in the GUIDELINES FOR THE CONTROL OF TUBERCULOSIS IN ELEPHANTS 2008 . All elephants in the US are tested on an annual basis, or more frequently with this method.
Serology can also be used in diagnosis of TB in elephants but measures a different parameter than culture and doesn’t necessarily reflect active disease or active shedding of the organism.
Definitive diagnosis is often not possible until necropsy
4. References and Resources
4.1. Compounding Pharmacies
BioServ, One 8th St. Suite 1, Frenchtown, NJ 08825 908-996-2155 http://www.bio-serv.com
Hopkinton Drug, 52 Main Street Hopkinton, MA 01748 (508) 435-4441
Island Pharmacy Service, Inc., PO Box 1412 Woodruff, WI 54568 (715) 358-7712
Mortar & Pestle Pharmacy, PO Box 12124 Des Moines, Iowa 50312 (800)-279-7054
4.2. Texts and Articles
The domestic animal/wildlife interface: issues for disease control, conservation, sustainable food production, and emerging diseases. Annals of the New York Academy of Sciences . 2002. Volume 969.
Exotic animal formulary / James W. Carpenter, Ted Y. Mashima, David J. Rupiper. 2nd edition, W B Saunders Co ., 2001.
Getting Cynomologus (and others) to take their medicine. Laboratory Primate Newsletter vol. 36 (3), 1997.
Guidelines for Zoo and Aquarium Veterinary Programs and Veterinary Hospitals, AAZV.
Infectious diseases of wildlife: detection, diagnosis and management. Scientific and Technical Review of OIE , vol. 21 (1,2), 2002
Johnson-Delaney, Cathy A. Exotic Companion Medicine Handbook for Veterinarians . Wingers Pub. Inc., 1996
Marx, Keath L., and ML Roston. The Exotic Animal Drug Compendium : An International Formulary . VLS, 1997
Plumb, DC. Veterinary Drug Handbook 4th ed., Iowa State University Press, 2002.
Drug information from Food Animal Residue Avoidance Databank - A National Food Safety Project of U.S. Department of Agriculture, Cooperative State Research, Education, and Extension http://www.farad.org/
International Species Information System https://www.isis.org/
National Biological Information Infrastructure http://www.nbii.gov/index.html
Wildlife Rehabilitation Database - the site contains baseline hematology data and basic biological information for some avian and mammalian species http://www.wpi.edu/Projects/Tufts/
Wildlife Conservation Society Technical pages for wildlife disease surveillance http://wcs.org/sw-high_tech_tools/wildlifehealthscience/fvp/168570