Clinical Examination of Goats

A complete clinical examination consists of three major ele­ments: history taking, physical examination, and inspection of the environment. Many diseases seen in individual goats are likely to represent potential herd problems; therefore, prompt diagnosis of clinical cases is essential so that, in addition to therapy, appropriate preventive measures can be introduced into the overall management program.

History Taking

Very few diseases or health-related problems are randomly distributed in a flock or herd of goats; rather, they are

Table 1.1 Goat diseases characterized by chronic infection or a carrier state.

concentrated in specific groups, usually by sex, function, production status, or age. Always establish early on what age, sex, breed, or group of goats is dying, showing signs of illness, aborting, or showing decreased productivity. If it is a mixed farm operation, the number of other types of live­stock and their degree of contact with goats should be ascertained.

Detailed history should include a determination of the total flock or herd population and estimation of its break­down by sex, age, breed, and pregnancy status. Having determined the total animal population, the population at risk, and the number of animals affected and dying, it is possible to determine rates of disease occurrence and case fatality rates. By counting cases, the investigator is also in a better position to determine the actual significance of a problem as compared to the farmer's perception of it. In some cases, the loss of a few animals may be insignificant compared to a more serious unrecognized problem such as endoparasitism or ectoparasitism.

Such an epidemiologically based history should aim to identify not only specific problems, but also specific risk factors that appear to be associated with mortality, morbid­ity, or suboptimal performance. For example, when a pri­mary complaint of kids developing diarrhea after weaning suggests coccidiosis, additional questions concerning the segregation of kids from adults, the manner in which kids are fed, the design of feeders, the frequency and manner of barn cleaning, and details on the use of coccidiostats are necessary. In such cases, modification of management practices may halt the spread of disease.

Temporal relationships are important to note. Some dis­eases may occur seasonally, in association with abrupt weather changes, or in relation to specific events such as breeding, pregnancy, shearing, parturition, and lactation. For example, an unexpected cold snap or heavy rain right after shearing of Angora goats can increase pneumonia, abortion, and death rates, particularly if adequate shelter and supplemental feed have not been provided.

Localization of death or disease to specific areas on the premises is helpful. For example, if losses are seen only in certain areas of the farm, specific pastures, or particular barns, then suspicion of poisoning is increased.

Other important aspects of the history include ques­tions pertaining to the actual ration being fed and its consumption, methods of feeding, changes in feeding, access to grazing, and water supply type and water availability.

If management interventions or preventive health proce­dures have been undertaken recently, they should be iden­tified. Handling of animals for shearing, drenching, dehorning, spraying or dipping, castration, or vaccination may be associated with increases in morbidity and mortal­ity. When range animals are mobbed for such procedures, sudden close confinement, temporary feed deprivation, and abrupt weather changes can predispose to outbreaks of conditions such as abortion, coccidiosis, salmonellosis, hypocalcemia, or starvation as a result of mismothering. When drugs or vaccines are used, the products and dos­ages, number of treatments, and method of administration should be determined, particularly because many goat farmers traditionally obtain their drugs and biologicals from non-veterinary sources.

If animals have been transported recently, dates, origins, means of transportation, and quarantine times should be determined. Information should also be collected on visits to shows or fairs and on the origin of purchased animals, be it other farms, stockyards, or specialized goat sales. If animals have come from out of state, the relevant health certificates should be examined and the disease situation in the state of origin reviewed.

Finally, the reliability of information obtained should be checked with the actual goat keepers if the owner is not involved with day-to-day management decisions. If the vet­erinarian has prior knowledge of the local disease patterns in goats, such knowledge should not be used to make hasty and possibly incorrect judgments.

Special Considerations for Range and Pastured Goats

Extensively managed animals may not be closely observed, and histories can be sketchy. With large flocks, it should be determined if the animals are managed as a single flock or in smaller, self-contained units. The seasonal pattern of grazing and the length of grazing periods should be noted. Pasture composition, seasonal stocking rates per acre, the degree of pasture subdivision, and length of resting periods between grazing should be established.

The type of grazing, whether set stocked or rotational, may be relevant to some disease outbreaks, particularly to gastrointestinal helminthiasis. The presence of other live­stock species and feral, predatory, or scavenging animals or birds should be established if relevant to the problem under investigation.

Special Considerations for Intensively Managed Goats

A complete history can usually be obtained from the owner or person responsible for the intensively managed goats. The patterns of disease are also likely to be different, with pneumonia and enteric diseases of young goats assuming much greater significance than the foot rot, helminthiasis, predation, or toxic plant problems more often seen under grazing systems. Feed composition and intake are more regulated, but the veterinarian must inquire about episodes of sudden changes, excesses, or deprivations in feed and water supplies.

Under close quarters, the movement, mixing, or intro­duction of new animals is more likely to cause an outbreak of disease. Kidding is often assisted in intensively managed operations, and artificial kid-rearing methods are com­monly used. These procedures should be carefully reviewed when morbidity and mortality are concentrated in young kids. Weather, per se, should not adversely affect inten­sively managed animals. However, extremes in tempera­ture may tax the ventilatory capacity of confinement buildings and extremely cold weather may freeze water supplies or incapacitate mechanized feeding equipment.

Special Considerations for Hobby Farms

Because hobbyists often have little previous agricultural or livestock experience, it might be helpful to practitioners to gauge the owners' knowledge and attitudes regarding basic animal husbandry before history taking. Some fundamen­tal misunderstandings about the care and management of goats may be revealed, such as non-recognition of basic ruminant physiology and the need for roughage in the diet. In other situations, owners may know about basic hus­bandry and disease problems, but may have seemingly unorthodox ideas about management and treatment. A good deal of tact may be required to obtain a useful history and prescribe appropriate therapy while not offending the hobbyist's sensibilities.

In addition, hobby farmers often perceive goats more as companion animals than as livestock production units. While they may seek the expertise of a livestock clinician, they often expect the “bedside manner” of the companion animal practitioner. Therefore, the veterinarian who appears insensitive to the client's emotions or indifferent to pain of the goat, or who emphasizes only the economic value of the animal, may not be called to the farm again.

Special Considerations for Organic

Goat Production

Consumer interest in organically produced food has grown considerably over the past 20 years or so and producers have responded by producing and marketing an expanding variety of foodstuffs certified as organic. Increasingly, this includes foods of animal origin. Goat owners may choose to raise their goats under organic conditions. Veterinary practitioners with such clients need to be aware of and familiar with the constraints on conventional therapy that are associated with organic livestock production, which is now strictly regulated by law (Karreman 2006).

In the United States, the Organic Food Production Act (OFPA) was signed into law in 1990, creating the frame­work for regulation and certification of organically pro­duced foods of plant and animal origin.

Vaccination is promoted as an organic livestock health­care practice under 7 CFR 205, but the use of antibiotics and most anthelmintics is prohibited. Veterinarians must approach therapeutic interventions in organically raised animals differently than in conventionally raised animals, relying heavily on so-called natural treatments, including botanicals, acupuncture, etc. The standards of livestock healthcare practice that must be observed under the OFPA are given in 7 CFR 205.238. Veterinarians should be aware, however, that 7 CFR 205.238 considers the welfare of organ­ically raised livestock by stipulating that an organic live­stock producer may “not withhold medical treatment from a sick animal in an effort to preserve its organic status. All appropriate medications must be used to restore an animal to health when methods acceptable to organic production fail. Livestock treated with a prohibited substance must be clearly identified and shall not be sold, labeled, or repre­sented as organically produced.” The synthetic substances allowed for use in organic livestock production are found in 7 CFR 205.603. The full text of the regulations can be found at https://www.govinfo.gov/content/pkg/CFR-2011-title7- vol3/pdf/CFR-2011-title7-vol3-part205.pdf.

In Europe, organic production is regulated throughout the European Union (EU). EU regulation number 1804/99, which became effective in 2000, sets forth the rules for organic livestock production, including animal health and veterinary interventions. All EU member states at a mini­mum comply with these rules, but some individual coun­tries have included additional rules of their own. EU rules prohibit the use of antibiotics and synthetic anthelmintics in organically raised livestock for prevention of disease and growth promotion, but do allow the use of these drugs for treatment of disease on humane grounds under the super­vision of a veterinarian when other treatments are ineffec­tive, with the caveat that meat and milk withdrawal times be suitably extended (Alliance to Save our Antibiotics 2021). Specifications of the European and US regulations have been compared (Nardone et al. 2004). The International Federation of Organic Agriculture Movements (IFOAM) is a source of information on standards for organic agricul­ture in other regions and countries (https://www.ifoam.bio). The global situation regarding organic goat production has been reviewed (Lu et al. 2010).

Special Considerations for Genetically Modified (Transgenic) and Cloned Goats

Production of transgenic or genetically modified animals using microinjection (MI) or somatic cell nuclear transfer (SCNT; or “cloning”), and also the propagation of desira­ble animals using cloning, are no longer just scientific research endeavors. They have become established pro­duction systems for the propagation and management of transgenic goats for a number of scientific and commer­cial applications. It behooves veterinarians with an active goat practice, or in a laboratory animal setting, to be famil­iar with the basic techniques and potential health issues associated with transgenic or cloned goat generation and management.

The first foray into animal gene transfer was reported (Jaenisch and Mintz 1974) by injecting virus directly into blastocyst-stage mouse embryos and demonstrating viral genome in numerous tissues in the adult animals. The field of transgenic technology was further codified when the first transgenic mouse was developed (Gordon et al. 1980) by the use of MI into the pronucleus at the one-cell embryo stage. Thereafter, the first transgenic goat was developed to produce rhtPA (recombinant human tissue plasminogen activator) in the milk (Ebert et al. 1991) as a potential human therapeutic agent. Since then, the field has mark­edly expanded, with transgenic animals in multiple species becoming commonplace within many programs and facili­ties around the world.

The applications for transgenic animals are considerable and include not only the investigation of gene function, but also the development of animal models, increased disease resistance through either transgene insertion or knock-out techniques, and production of recombinant, biopharma­ceutical proteins in a number of biological fluids such as milk, blood, urine, and semen (Nieman and Kues 2003). In fact, the first transgenically derived human therapeutic recombinant protein from goat milk (ATryn*, rEVO Biologics, Framingham, MA, USA) was approved by the European Agency for the Evaluation of Medicinal Products (EMA) in 2006 and by the Food and Drug Administration (FDA) in the United States in 2009.

In the United States, most genetically modified or trans­genic goats are maintained in USDA-APHIS-AC-licensed research facilities. Under the terms of the Animal Welfare Act (AWA), these licensed facilities must maintain strict adherence to rules and regulations specifically governing animal care, health, and welfare (housing, lighting, feed­ing, veterinary care, and environmental enrichment at a minimum). Depending upon the type of research and the funding source, the National Institutes of Health (NIH) may also be involved through their Office of Laboratory Animal Welfare (OLAW), as government funding brings along its own slightly different set of rules and regulations for animals used in a research setting. A growing number of institutions are also striving for accreditation by the Association for the Assessment and Accreditation of Laboratory Animal Care, International (AAALAC-Int), considered by many to set the gold standard for animal care in licensed research programs and facilities. Most recently, depending upon the intended use of any tissues/ fluids from the transgenic animal, the FDA's Center for Veterinary Medicine (FDA-CVM) may also have regulatory oversight and impose its own set of guidance and regula­tions (FDA-CVM 2017).

The two primary and long-standing techniques employed for making transgenic animals are MI and SCNT, also known as cloning. While MI was the first technology to be used in making large transgenic animals (Hammer et al. 1985), and specifically the goat (Gavin 1996), the pro­cess is inefficient, with only a small percentage of the resulting animals being transgenic. Large animal SCNT was developed many years later by the cloning of sheep (Campbell et al. 1996; Wilmut et al. 1997) and provides for a near 100% transgenic rate when compared to MI. The cloning of the first transgenic goat soon followed (Baguisi et al. 1999; Keefer et al. 2001). There are now other tech­niques (as reviewed in Kalds et al. 2019) that have also been developed subsequently over the years for producing transgenic animals, such as retroviral gene transfer, artifi­cial chromosome insertion, and the use of advanced gene­editing tools such as recombinases, transposons, and endonucleases, for example meganucleases such as zinc finger nucleases (ZFNs), transcription activator-like effec­tor nucleases (TALENs), and clustered, regularly inter­spaced short palindromic repeats (CRISPRs).

The use of MI to produce a transgenic animal involves actually microinjecting the transgene into the pronucleus of a fertilized, one-cell embryo and then the transfer of sur­viving embryos to a surrogate mother. One of the first areas for possible concern, and for which observation and moni­toring are appropriate, is the physical/mechanical effects on the nucleus/gene due to the actual MI process at the one-cell stage. If any negative impacts occur or gene func­tions are altered or impaired, one may see outcomes rang­ing from decreased pregnancy rates from transferred embryos to increased pregnancy loss, late-term abortions, or possible physiologic abnormalities at birth with clinical sequelae. However, years of experience in transgenic goat generation (Gavin et al. 2018) have shown that these phe­nomena, while possible, occur at a very low incidence, as evidenced by the lower metrics/efficiencies in key repro­ductive parameters monitored.

Regardless of the technology or technique used to pro­duce a transgenic goat, another possible concern involves endogenous gene function and potential transgene inser- tional site effects. The gene of interest either inserts ran­domly or at a specified location into the genome following transgene introduction. Hence, there is a chance that an endogenous gene could be negatively impacted, leading to potential adverse physiologic effects and a transgenic goat presenting with clinical signs of abnormal physiology or health. Therefore, appropriate postparturitional monitor­ing of animal health is warranted for any transgenic founder animal and subsequent generational offspring.

Introduction of a transgene primarily is aimed at gener­ating a transgenic goat that is hemizygous for a given transgene. However, the newer gene-editing technologies may be utilized to produce a homozygous animal from the start. Alternatively, subsequent breeding within a lineage (between hemizygous animals) may be aimed at achieving this homozygous state for the transgene. With a homozy­gous state for a given transgene or genetic modification, possible additional concerns may arise through this genetic aim as well. First, inbreeding of related goats is the primary route to achieving a homozygous animal. Therefore, inbreeding coefficients need to be considered and animals need to be monitored for ill effects from this relatedness and for possible impacts on overall health and ability to thrive. Second, achieving a homozygous state may bring to light an insertional gene effect, since both copies of an endogenous gene may now be affected, thereby causing physiologic or clinical issues that were not seen in the hemizygous state. Again, appropriate monitoring of ani­mal health is warranted for the first homozygous animals produced for any line carrying a specific transgene or genetic modification. Lastly, the potential exists that breed­ing for the production of a transgenic homozygous animal will reveal a lethal outcome. A lethality issue may be sus­pected when breeding of two hemizygous animals pro­duces no detectable pregnancies; pregnancies do not hold to term with either resorptions or abortions; or offspring succumb during the perinatal or postnatal periods. Thus, production of a homozygous transgenic animal may not always be possible, and close animal health monitoring is warranted when homozygosity is pursued.

One additional set of concerns related to transgene effects (for example when the aim is to produce a recombi­nant protein in any tissue or fluid type) is the possibility of systemic circulation of the recombinant protein being expressed and the potential health impacts arising from expression of pharmacologically active molecules. Depending on the tissue or fluid where the recombinant protein may be directed for expression (e.g., milk, blood, urine, semen, etc.), one must be vigilant for systemic effects, as the protein usually will be found systemically due to leaky vasculature and normal lymphatic drainage. Therefore, the biological nature and function of the recom­binant protein being introduced must be known, so that any effects that may be exerted can be anticipated and rec­ognized. Consideration must also be given to potential adverse health impacts if this is a new gene and novel pro­tein not normally physiologically found in the genome or animal. Lastly, the quantity of the recombinant protein that is expressed and then found systemically in the trans­genic animal must be considered. Even if the target protein is endogenous to the animal, it may be found at signifi­cantly higher levels than normal now in the transgenic ani­mal with this transgene inserted, and this may cause physiologic effects that alter normal homeostasis.

With the development of the SCNT or cloning technol­ogy, nuclear transfer has become one of the preferred methods for producing transgenic goats and has improved the overall efficiency of the process compared to standard MI. However, the use of nuclear transfer has added some additional health concerns in a small percentage of ani­mals. Nuclear transfer starts by removing the maternal DNA from an unfertilized oocyte through enucleation. A full complement of genetic material is subsequently replaced by addition of a somatic cell (e.g., fetal or adult skin fibroblast cell) through a process termed “reconstruc­tion.” Thereafter, in vitro techniques are used to fuse the oocyte and somatic cell and activate the couplet to begin dividing normally. Following a brief in vitro culture period, these newly developed cloned embryos are then trans­ferred to recipient goats using traditional embryo-transfer techniques.

With nuclear transfer, a decreased in utero fetal survival rate can be seen very early in pregnancy and has been well documented in many species (Campbell et al. 1996; Wilmut et al. 1997; Baguisi et al. 1999). This inability to thrive may be associated with inappropriate or inadequate reprogram­ming (Dean et al. 2001) of the nuclear/genetic material of the donor cell line or karyoplast, and has been postulated to be at the level of the DNA (e.g., methylation patterns). An altered inheritance of cellular mitochondria (Wells 2005) has also been shown to occur in cloned embryos, adding to the possible causes for some of the abnormalities in homeo­stasis. These phenomena (inadequate reprogramming and mitochondrial inheritance patterns) may be directly linked to the small percentage of physiologic problems seen in utero for some cloned animals, such as abnormal placenta­tion and/or organogenesis (Farin et al. 2006; Loi et al. 2006; Fletcher et al. 2007). Abnormal placentation can also lead to abnormal uterine fluid homeostasis and fluid retention in does carrying cloned embryos, which may warrant close clinical monitoring or intervention where appropriate. Other possible outcomes of abnormal placentation include a tendency toward decreased pregnancy rates for animals receiving cloned embryos, an increased in utero loss rate through resorption, or an increased level of abortions if there is late-term fetal loss.

The potential abnormal physiology with or without clinical presentations may continue after birth and into the neonatal and early prepuberal stages (Hill et al. 1999). Documented abnormalities in a few large animal species have been shown at the level of the renal, cardiac, res - piratory, hepatic, hematopoietic, and immune systems. However, if the small percentage of animals, includ­ing goats, that present with these abnormal physiologic entities can be clinically supported over time, as the animals grow, many of these abnormalities resolve and they can lead normal and healthy lives (Chavatte-Palmer et al. 2002).

With regard to the newer approaches for transgenic animal generation available with gene-editing technolo­gies (e.g., the meganucleases), the potential for addi­tional or new concerns at the level of the genome and the actual transgenic animal produced needs to be monitored closely as this field matures. Specifically, “off-target” hits in the genome from a given gene-editing technology have been documented and raised as a con­cern. This phenomenon should be investigated fully to ensure that no other potential unexpected physiologic sequelae arise or are overlooked in a transgenic or geneti­cally modified animal.

Lastly, as with any traditional goat agricultural produc­tion operation for meat, milk, or fiber, optimizing health and product output starts with a sound nutritional pro­gram. Relative to transgenic production, nutritional pro­grams should consider the nature of the recombinant protein to be produced or the genetic modification cre­ated. Specifically, if the recombinant protein is novel to the physiologic output of the goat's normal cellular machinery, or if quantities are above what is normally pro­duced in vivo, then one may need to augment the diet. This modified or fortified diet may need to contain increased levels of vitamins, minerals, or specific amino acids. One should understand the normal cellular machinery and biochemical pathways involved in protein production to know if supplementation may be appropriate or necessary and what kind.

In summary, the vast majority of transgenic and cloned animals are normal and healthy (Walsh et al. 2003; Enright et al. 2002; Tayfur Tecirlioglu et al. 2006) and subsequent generations of animals produced from first-generation clones have not to date shown any of the health-related issues seen in a small percentage of original founder clones (Wells 2005). Additionally, passage through the germ line has been reported to reverse any abnormal patterns detected at the DNA level in first-generation clones (Wells 2005), thereby further reducing the concern for ani­mals generated via these technologies.