Diagnosis is based on "post mortem" examination (necropsy) and testing; examination of the dead body is not definitive as many animals die early in the course of the disease and conditions found are non-specific; general signs of poor health and Aspiration pneumonia, which may be the actual cause of death, are common. On microscopic examination, lesions of CWD in the central nervous system resemble those of other TSEs. In addition, scientists use immunohistochemistry to test brain, lymph, and neuroendocrine tissues for the presence of the abnormal prion protein to diagnose CWD; positive IHC findings in the obex is considered the gold standard.

As of 2015 there were no commercially feasible diagnostic tests that could be used on live animals. It is possible to run a bioassay, taking fluids from cervids suspected of infection and incubating them in transgenic mice that express the cervid prion protein, to determine if the cervid is infected, but there are ethical issues with this and it is not scalable.

Definite diagnosis of brucellosis requires the isolation of the organism from the blood, body fluids, or tissues, but serological methods may be the only tests available in many settings. Positive blood culture yield ranges between 40% and 70% and is less commonly positive for "B. abortus" than "B. melitensis" or "B. suis". Identification of specific antibodies against bacterial lipopolysaccharide and other antigens can be detected by the standard agglutination test (SAT), rose Bengal, 2-mercaptoethanol (2-ME), antihuman globulin (Coombs’) and indirect enzymelinked immunosorbent assay (ELISA). SAT is the most commonly used serology in endemic areas. An agglutination titre greater than 1:160 is considered significant in nonendemic areas and greater than 1:320 in endemic areas. Due to the similarity of the O polysaccharide of "Brucella" to that of various other Gram-negative bacteria (e.g. "Francisella tularensis", "Escherichia coli", "Salmonella urbana", "Yersinia enterocolitica", "Vibrio cholerae", and "Stenotrophomonas maltophilia") the appearance of cross-reactions of class M immunoglobulins may occur. The inability to diagnose "B. canis" by SAT due to lack of cross-reaction is another drawback. False-negative SAT may be caused by the presence of blocking antibodies (the prozone phenomenon) in the α2-globulin (IgA) and in the α-globulin (IgG) fractions. Dipstick assays are new and promising, based on the binding of "Brucella" IgM antibodies, and found to be simple, accurate, and rapid. ELISA typically uses cytoplasmic proteins as antigens. It measures IgM, IgG, and IgA with better sensitivity and specificity than the SAT in most recent comparative studies. The commercial Brucellacapt test, a single-step immunocapture assay for the detection of total anti-"Brucella" antibodies, is an increasingly used adjunctive test when resources permit. PCR is fast and should be specific. Many varieties of PCR have been developed (e.g. nested PCR, realtime PCR and PCR-ELISA) and found to have superior specificity and sensitivity in detecting both primary infection and relapse after treatment. Unfortunately, these have yet to be standardized for routine use, and some centres have reported persistent PCR positivity after clinically successful treatment, fuelling the controversy about the existence of prolonged chronic brucellosis. Other laboratory findings include normal peripheral white cell count, and occasional leucopenia with relative lymphocytosis. The serum biochemical profiles are commonly normal.

According to a study published in 2002, an estimated 10–13% of farm animals are infected with "Brucella" species. Annual losses from the disease were calculated to be around 60 million dollars. Since 1932, government agencies have undertaken efforts to contain the disease. Currently, all cattle of ages 3–8 months is required to be given the "Brucella abortus" strain 19 vaccine.

In laboratory animals, prevention includes a low-stress environment, an adequate amount of nutritional feed, and appropriate sanitation measurements. Because animals likely ingest bacterial spores from contaminated bedding and feed, regular cleaning is a helpful method of prevention. No prevention methods are currently available for wild animal populations.

In pet rabbits, myxomatosis can be misdiagnosed as pasteurellosis, a bacterial infection which can be treated with antibiotics. By contrast, there is no treatment for rabbits suffering from myxomatosis, other than palliative care to ease the suffering of individual animals, and the treatment of secondary and opportunistic infections, in the hopes the treated animal will survive. In practice, the owner is often urged to euthanize the animal to end its suffering.

The differential diagnosis in a case of suspected human rabies may initially include any cause of encephalitis, in particular infection with viruses such as herpesviruses, enteroviruses, and arboviruses such as West Nile virus. The most important viruses to rule out are herpes simplex virus type one, varicella zoster virus, and (less commonly) enteroviruses, including coxsackieviruses, echoviruses, polioviruses, and human enteroviruses 68 to 71.

New causes of viral encephalitis are also possible, as was evidenced by the 1999 outbreak in Malaysia of 300 cases of encephalitis with a mortality rate of 40% caused by Nipah virus, a newly recognized paramyxovirus. Likewise, well-known viruses may be introduced into new locales, as is illustrated by the outbreak of encephalitis due to West Nile virus in the eastern United States. Epidemiologic factors, such as season, geographic location, and the patient's age, travel history, and possible exposure to bites, rodents, and ticks, may help direct the diagnosis.

The origin and mode of transmission of the prions causing CWD is unknown, but recent research indicates that prions can be excreted by deer and elk, and are transmitted by eating grass growing in contaminated soil. Animals born in captivity and those born in the wild have been affected with the disease. Based on epidemiology, transmission of CWD is thought to be lateral (from animal to animal). Maternal transmission may occur, although it appears to be relatively unimportant in maintaining epidemics. An infected deer's saliva is able to spread the CWD prions. Exposure between animals is associated with sharing food and water sources contaminated with CWD prions shed by diseased deer.

The disease was first identified in 1967 in a closed herd of captive mule deer in contiguous portions of northeastern Colorado. In 1980, the disease was determined to be a TSE. It was first identified in wild elk and mules in 1981 in Colorado and Wyoming, and in farmed elk in 1997.

In May 2001, CWD was also found in free-ranging deer in the southwestern corner of Nebraska (adjacent to Colorado and Wyoming) and later in additional areas in western Nebraska. The limited area of northern Colorado, southern Wyoming, and western Nebraska in which free-ranging deer, moose, and/or elk positive for CWD have been found is referred to as the endemic area. The area in 2006 has expanded to six states, including parts of eastern Utah, southwestern South Dakota, and northwestern Kansas. Also, areas not contiguous (to the endemic area) areas in central Utah and central Nebraska have been found. The limits of the affected areas are not well defined, since the disease is at a low incidence and the amount of sampling may not be adequate to detect it. In 2002, CWD was detected in wild deer in south-central Wisconsin and northern Illinois and in an isolated area of southern New Mexico. In 2005, it was found in wild white-tailed deer in New York and in Hampshire County, West Virginia. In 2008, the first confirmed case of CWD in Michigan was discovered in an infected deer on an enclosed deer-breeding facility. It is also found in the Canadian provinces of Alberta and Saskatchewan. In February 2011, the Maryland Department of Natural Resources reported the first confirmed case of the disease in that state. The affected animal was a white-tailed deer killed by a hunter.

CWD has also been diagnosed in farmed elk and deer herds in a number of states and in two Canadian provinces. The first positive farmed elk herd in the United States was detected in 1997 in South Dakota.

Since then, additional positive elk herds and farmed white-tailed deer herds have been found in South Dakota (7), Nebraska (4), Colorado (10), Oklahoma (1), Kansas (1), Minnesota (3), Montana (1), Wisconsin (6) and New York (2). As of fall of 2006, four positive elk herds in Colorado and a positive white-tailed deer herd in Wisconsin remain under state quarantine. All of the other herds have been depopulated or have been slaughtered and tested, and the quarantine has been lifted from one herd that underwent rigorous surveillance with no further evidence of disease. CWD also has been found in farmed elk in the Canadian provinces of Saskatchewan and Alberta. A retrospective study also showed mule deer exported from Denver to the Toronto Zoo in the 1980s were affected. In June 2015, the disease was detected in a male white-tailed deer on a breeding ranch in Medina County, Texas. State officials euthanized 34 deer in an effort to contain a possible outbreak.

Species that have been affected with CWD include elk, mule deer, white-tailed deer, black-tailed deer, and moose. Other ruminant species, including wild ruminants and domestic cattle, sheep, and goats, have been housed in wildlife facilities in direct or indirect contact with CWD-affected deer and elk, with no evidence of disease transmission. However, experimental transmission of CWD into other ruminants by intracranial inoculation does result in disease, suggesting only a weak molecular species barrier exists. Research is ongoing to further explore the possibility of transmission of CWD to other species.

By April 2016 CWD had been found in captive animals in South Korea; the disease arrived there with live elk that were imported for farming in the late 1990s.

Outbreaks of zoonoses have been traced to human interaction with and exposure to animals at fairs, petting zoos, and other settings. In 2005, the Centers for Disease Control and Prevention (CDC) issued an updated list of recommendations for preventing zoonosis transmission in public settings. The recommendations, developed in conjunction with the National Association of State Public Health Veterinarians, include educational responsibilities of venue operators, limiting public and animal contact, and animal care and management.

Currently, antibiotic drugs such as penicillin or tetracycline are the only effective methods for disease treatment. Within wild populations, disease control consists of reducing the amount of bacterial spores present in the environment. This can be done by removing contaminated carcasses and scat.

A notifiable disease is any disease that is required by law to be reported to government authorities. The collation of information allows the authorities to monitor the disease, and provides early warning of possible outbreaks. In the case of livestock diseases, there may also be the legal requirement to destroy the infected livestock upon notification. Many governments have enacted regulations for reporting of both human and animal (generally livestock) diseases.

The OIE (World Organisation for Animal Health) monitors specific animal diseases on a global scale.

- Diseases Notifiable to the OIE

Contact with farm animals can lead to disease in farmers or others that come into contact with infected animals. Glanders primarily affects those who work closely with horses and donkeys. Close contact with cattle can lead to cutaneous anthrax infection, whereas inhalation anthrax infection is more common for workers in slaughterhouses, tanneries and wool mills. Close contact with sheep who have recently given birth can lead to clamydiosis, or enzootic abortion, in pregnant women, as well as an increased risk of Q fever, toxoplasmosis, and listeriosis in pregnant or the otherwise immunocompromised. Echinococcosis is caused by a tapeworm which can be spread from infected sheep by food or water contaminated with feces or wool. Bird flu is common in chickens. While rare in humans, the main public health worry is that a strain of bird flu will recombine with a human flu virus and cause a pandemic like the 1918 Spanish flu. In 2017, free range chickens in the UK were temporarily ordered to remain inside due to the threat of bird flu. Cattle are an important reservoir of cryptosporidiosis and mainly affects the immunocompromised.

An anthroponotic disease, or anthroponosis, is an infectious disease in which a disease causing agent carried by humans is transferred to other animals. It may cause the same disease or a different disease in other animals. Since humans do not generally inflict bite wounds on other animals, the method of transmissions is always a "soft" contact such as skin to skin transmission. An example is chytridiomycosis which can be spread by humans with the fungus on their skin handling frogs with bare hands.

The reverse situation, a disease transmitted from animals to humans, is known as zoonotic.

It can also be defined as a human-to-human infection with no animal vector.

Rabies can be difficult to diagnose, because, in the early stages, it is easily confused with other diseases or with aggressiveness. The reference method for diagnosing rabies is the fluorescent antibody test (FAT), an immunohistochemistry procedure, which is recommended by the World Health Organization (WHO). The FAT relies on the ability of a detector molecule (usually fluorescein isothiocyanate) coupled with a rabies-specific antibody, forming a conjugate, to bind to and allow the visualisation of rabies antigen using fluorescent microscopy techniques. Microscopic analysis of samples is the only direct method that allows for the identification of rabies virus-specific antigen in a short time and at a reduced cost, irrespective of geographical origin and status of the host. It has to be regarded as the first step in diagnostic procedures for all laboratories. Autolysed samples can, however, reduce the sensitivity and specificity of the FAT. The RT PCR assays proved to be a sensitive and specific tool for routine diagnostic purposes, particularly in decomposed samples or archival specimens. The diagnosis can be reliably made from brain samples taken after death. The diagnosis can also be made from saliva, urine, and cerebrospinal fluid samples, but this is not as sensitive and reliable as brain samples. Cerebral inclusion bodies called Negri bodies are 100% diagnostic for rabies infection but are found in only about 80% of cases. If possible, the animal from which the bite was received should also be examined for rabies.

Some light microscopy techniques may also be used to diagnose rabies at a tenth of the cost of traditional fluorescence microscopy techniques, allowing identification of the disease in less-developed countries.

Foot-and-mouth disease or hoof-and-mouth disease (Aphthae epizooticae) is an infectious and sometimes fatal viral disease that affects cloven-hoofed animals, including domestic and wild bovids. The virus causes a high fever for approximately two to six days, followed by blisters inside the mouth and on the feet that may rupture and cause lameness.

Foot-and-mouth disease (FMD) has very severe implications for animal farming, since it is highly infectious and can be spread by infected animals comparatively easily through contact with contaminated farming equipment, vehicles, clothing, feed and by domestic and wild predators. Its containment demands considerable efforts in vaccination, strict monitoring, trade restrictions, quarantines and occasionally the culling of animals.

Susceptible animals include cattle, water buffalo, sheep, goats, pigs, antelope, deer, and bison. It has also been known to infect hedgehogs and elephants; llamas and alpacas may develop mild symptoms, but are resistant to the disease and do not pass it on to others of the same species. In laboratory experiments, mice, rats, and chickens have been successfully infected by artificial means, but they are not believed to contract the disease under natural conditions. Humans are very rarely infected.

The virus responsible for the disease is a picornavirus, the prototypic member of the genus "Aphthovirus". Infection occurs when the virus particle is taken into a cell of the host. The cell is then forced to manufacture thousands of copies of the virus, and eventually bursts, releasing the new particles in the blood. The virus is genetically highly variable, which limits the effectiveness of vaccination.

MAP is capable of causing Johne's-like symptoms in humans, though difficulty in testing for MAP infection presents a diagnostic hurdle.

Clinical similarities are seen between Johne's disease in ruminants and inflammatory bowel disease in humans, and because of this, some researchers contend the organism is a cause of Crohn's disease. However, epidemiologic studies have provided variable results; in certain studies, the organism (or an immune response directed against it) has been much more frequently found in patients with Crohn's disease than asymptomatic people.

Diagnosis is based on symptoms and upon finding an embedded tick, usually on the scalp.

In the absence of a tick, the differential diagnosis includes Guillain–Barré syndrome. Early signs of tick poisoning could be a change of an animals' ‘voice’, weakness in the back legs or vomiting.

After its discovery in 1896 in imported rabbits in Uruguay, a relatively harmless strain of the disease spread quickly throughout the wild rabbit populations in South America.

In an endemic herd, only a minority of the animals develops clinical signs; most animals either eliminate the infection or become asymptomatic carriers. The mortality rate is about 1%, but up to 50% of the animals in the herd can be asymptomatically infected, resulting in losses in production. Once the symptoms appear, paratuberculosis is progressive and affected animals eventually die. The percentage of asymptomatic carriers that develop overt disease is unknown.

Antibody (Ig) ELISAs are used to detect historical BVDV infection; these tests have been validated in serum, milk and bulk milk samples. Ig ELISAs do not diagnose active infection but detect the presence of antibodies produced by the animal in response to viral infection. Vaccination also induces an antibody response, which can result in false positive results, therefore it is important to know the vaccination status of the herd or individual when interpreting results. A standard test to assess whether virus has been circulating recently is to perform an Ig ELISA on blood from 5–10 young stock that have not been vaccinated, aged between 9 and 18 months. A positive result indicates exposure to BVDV, but also that any positive animals are very unlikely to be PI animals themselves. A positive result in a pregnant female indicates that she has previously been either vaccinated or infected with BVDV and could possibly be carrying a PI fetus, so antigen testing of the newborn is vital to rule this out. A negative antibody result, at the discretion of the responsible veterinarian, may require further confirmation that the animal is not in fact a PI.

At a herd level, a positive Ig result suggests that BVD virus has been circulating or the herd is vaccinated. Negative results suggest that a PI is unlikely however this naïve herd is in danger of severe consequences should an infected animal be introduced. Antibodies from wild infection or vaccination persist for several years therefore Ig ELISA testing is more valuable when used as a surveillance tool in seronegative herds.

Removal of the embedded tick usually results in resolution of symptoms within several hours to days. If the tick is not removed, the toxin can be fatal, with reported mortality rates of 10–12 percent, usually due to respiratory paralysis. The tick is best removed by grasping the tick as close to the skin as possible and pulling in a firm steady manner.

Unlike the other species of ticks, the toxin of Ixodes holocyclus (Australian Paralysis Tick) will not resolve itself and will be fatal if medical assistance is not immediately sought after pulling the tick off of the animal. Contrary to popular belief, if the head detaches from the body while being pulled off, leaving the head will not inject more venom. The head may cause a skin irritation but it will not inject any more venom. Once the tick is removed, place it in a clear bag [preferably ziplock] so the vet can identify it.

Water and food can worsen the results of the animal as the venom can prevent the animal from swallowing properly. If you find an Australian Paralysis Tick on your animal, immediately remove the tick and seek veterinary assistance even if you do not think the tick has been on the animal long enough to inject venom.

The incubation period for foot-and-mouth disease virus has a range between one and 12 days. The disease is characterized by high fever that declines rapidly after two or three days, blisters inside the mouth that lead to excessive secretion of stringy or foamy saliva and to drooling, and blisters on the feet that may rupture and cause lameness. Adult animals may suffer weight loss from which they do not recover for several months, as well as swelling in the testicles of mature males, and in cows, milk production can decline significantly. Though most animals eventually recover from FMD, the disease can lead to myocarditis (inflammation of the heart muscle) and death, especially in newborn animals. Some infected ruminants remain asymptomatic carriers, but they nonetheless carry FMDV and may be able to transmit it to others. Pigs cannot serve as asymptomatic carriers.

Many human diseases can be transmitted to other primates, due to their extensive biological similarities. As a result, centers that hold, treat, or involve close proximity to primates and some other kinds of animals (for example zoos, researchers, and animal hospitals), often take steps to ensure animals are not exposed to human diseases they can catch. In some cases animals are routinely immunized with the same vaccines given to humans.

- Leishmaniasis - Both zoonotic and anthroponotic.

- Influenza, Measles, pneumonia and various other pathogens - Many primates.

- Tuberculosis - Both zoonotic and anthroponotic, with birds, cows, elephants, meerkats, mongooses, monkeys, and pigs known to have been affected.

Antigen ELISA and rtPCR are currently the most frequently performed tests to detect virus or viral antigen. Individual testing of ear tissue tag samples or serum samples is performed. It is vital that repeat testing is performed on positive samples to distinguish between acute, transiently infected cattle and PIs. A second positive result, acquired at least three weeks after the primary result, indicates a PI animal. rtPCR can also be used on bulk tank milk (BTM) samples to detect any PI cows contributing to the tank. It is reported that the maximum number of contributing cows from which a PI can be detected is 300.

On infection the microorganism can be found in blood and cerebrospinal fluid (CSF) for the first 7 to 10 days (invoking serologically identifiable reactions) and then moving to the kidneys. After 7 to 10 days the microorganism can be found in fresh urine. Hence, early diagnostic efforts include testing a serum or blood sample serologically with a panel of different strains.

Kidney function tests (blood urea nitrogen and creatinine) as well as blood tests for liver functions are performed. The latter reveal a moderate elevation of transaminases. Brief elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) levels are relatively mild. These levels may be normal, even in children with jaundice.

Diagnosis of leptospirosis is confirmed with tests such as enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). The MAT (microscopic agglutination test), a serological test, is considered the gold standard in diagnosing leptospirosis. As a large panel of different leptospira must be subcultured frequently, which is both laborious and expensive, it is underused, especially in developing countries.

Differential diagnosis list for leptospirosis is very large due to diverse symptoms. For forms with middle to high severity, the list includes dengue fever and other hemorrhagic fevers, hepatitis of various causes, viral meningitis, malaria, and typhoid fever. Light forms should be distinguished from influenza and other related viral diseases. Specific tests are a must for proper diagnosis of leptospirosis.

Under circumstances of limited access (e.g., developing countries) to specific diagnostic means, close attention must be paid to the medical history of the patient. Factors such as certain dwelling areas, seasonality, contact with stagnant contaminated water (bathing, swimming, working on flooded meadows, etc.) or rodents in the medical history support the leptospirosis hypothesis and serve as indications for specific tests (if available).

"Leptospira" can be cultured in Ellinghausen-McCullough-Johnson-Harris medium (EMJH), which is incubated at 28 to 30 °C. The median time to positivity is three weeks with a maximum of three months. This makes culture techniques useless for diagnostic purposes but is commonly used in research.