1.1. Accessibility

Three main issues often impede the administration of medication to wildlife. One is danger another is fear, and the other is stress. Wildlife is not comfortable being in the presence of humans, 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 are often discussed, each with their own set of compromises.

Oral delivery

• 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
• Cost

Injectable delivery

• 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
• Cost

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

1. Understanding the drug in question - researching available pharmacological information
2. Understanding the use of the drug in known species
3. 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.)

1.6. Use of Metabolic Scaling for rational drug dosing

Please review the theory of allometrics. 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:

• Only an approximation based on comparison between two species
• Great variation depending on choice of model species
• Cannot take into account variables in drug metabolism including
  • liver metabolism
  • renal metabolism/excretion
  • protein binding
  • bile acid composition
  • bioavailability

The key is to choose the appropriate model species as close to the patient species as possible.

• PK data available on a small snake - use to extrapolate ceftazadime to a large python
• PK data available on a cow - use to extrapolate albendazole to 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....

Some examples:

• Ampicillin for a 500 kg polar bear with an infection
  • Worksheet (see Allometric Scaling of Ampicillin in a Polar Bear document)
  • 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 =0.09 x 14.8 = 1.3 times per day
  • Adjusted dose for Ampicillin in the polar bear = 6.6 g once daily
• Cisapride in an 8 kg tortoise with GI stasis
  • Worksheet (see Allometric Scaling of Cisapride in a Tortoise document)
  • 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

2.1. Assessing health of wold 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
• GIS

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.

2.2. Treatment

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 discussion in Conservation Medicine section).

2.3. Prevention

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 importan

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.

3.1. Readings

3.2. Websites

• 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 Service http://www.farad.org/
• International Species Information System ISIS 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

3.3. 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