Chapter 1 Vaccinations and Minimum Disease Prevention

 

  1.1 Immunoprophylaxis or minimum disease prevention 

• 1. Enhancement of a specific immune response in an attempt to protect it against an infectious disease. 
• 2. Active induction of an immune response requires exposure to the antigens of the infectious agent
• 3. Passive disease prevention involves the use of humoral or cellular factors obtained from a previous sensitized donor.
• 4. Vaccination is more commonly used in the prevention of viral and bacterial diseases. 

1.2 Passive Immunizations

1.2.1 Indications

• a. Protection of colostrum deprived neonates (< 2 days old). 
• b. Protection of dogs and cats receiving cancer chemotherapy and exposed to infectious agents during hospitalization. 
• c. Prophylactic or therapeutic use in treating litters of puppies clinically affected with neonatal herpesvirus infections.
• d. Used in the initial treatment of dogs and cats with tetanus.
• e. May be used in other emergency situations in which the rapid onset of protection is necessary.

1.2.2 Efficacy

• a. Antibody titer to the specific agent involved
• b. Importance of serum antibody in controlling the particular infection involved
• c. The time of administration of antibody compared with exposure 

1.2.3 Complications

• a. Protection is low and of shorter duration than that generated from vaccination.
• b. Allergic reactions are more likely with passive immunization.
• c. Transfer of infectious agents is more likely with administration of serum when noncommercially prepared products are used.
• d. The administration of immunoglobulins also delays the ability to stimulate active immunity in the host by vaccination.

1.2.4 Source

• a. Commercial preparations are available. (From Laboratories, 703 Lake Shore Road, Grafton, WI 53024)
• b. Immune serum derived from healthy individuals or from groups of animals that have recovered from the disease in question.
• c. Hyperimmune serum is obtained from animals that have been hyperimmunized by repeated vaccination against specified infectious agents. 

1.2.5 Administration

• a. Oral administration with serum alone or in milk substitute most effective in neonates.
• b. Parenteral administration routes that are accepted are intramuscular (IM), subcutaneous (SQ) and intraperitoneal (IP).
• c. Dose is 2-4 ml/kg depending on the titer of the preparation.

1.2.6 Maternal immunity and immunoprophylaxis

• a. Amount of immunoglobulin absorbed give the neonate a titer almost equal to that of the dam.
• b. Decline of serum antibody in the neonate is similar to that for passively administered imunoglobulins.
• c. Quantity of immunoglobulin in the serum of the dam depends on the disease considered.
• d. The titer of maternal antibody in the serum of the neonate determines the susceptibility to both virulent and vaccine virus.
• e. This titer depends upon the quantity of immunoglobulin received during nursing and the absolute titer of the dam.
• f. Due to the variability of individual animals direct measurements of antibody titer of the puppy or dam is required but not practical. 
• g. Veterinarians use multiple vaccination schedules in young puppies or kittens over a certain range of ages.
• h. Vaccines are given at 2-4 week intervals in an attempt to break through maternal immunity prior to exposure with virulent virus. 

1.3 Active Immunization

1.3.1 General principles

• a. The vaccine must induce the right type of immune response.
• b. The vaccine should induce an immune response in the right place.
• c. The vaccine should induce an immune response to the right antigens.
• d. The disease should be serious enough to justify vaccination. 

1.3.2 Types of vaccines

1.3.2.1 Live vaccines

• i. must be modified (attenuated) adaptation to unusual hosts prolonged storage serial passage
• ii. retain antigenicity
• iii. able to replicate in the intended host
• iv. heterotypic vaccines developed (cross-protection)
• v. quality control essential
• vi. lyophilization increases stability and storage lifespan
• vii. usually contain excess antigen

1.3.2.2 Inactivated vaccines

• i. subjected to various forms of denaturation without destroying antigenicity formalin
  • ethyleneimine
  • betapropriolactone
• ii. adjuvants are added increase vaccine duration and level of immunityemulsified water in oil preparations mineral gels containing alum, aluminum phosphate or aluminum hydroxide
•  iii. do not replicate in the host
•  iv. antigenic mass determines the efficacy of a particular product
•  v. must be given twice to get the anamestic response equal to 1 modified live vaccine

1.3.2.3 Subunit vaccine

• i. purified products containing bacterial antigenic determinants or viral structural components important for the immune response
• ii. efficacious for diseases in which key structural proteins have been identified from the infectious agent that enable the host to recognize the organism and eliminate it
• iii. used if sufficient attenuation cannot be achieved or the agent has the potential for producing disease 

1.4 Vaccination failures

1. Host factors

• a. Hereditary or acquired immunodeficiencies
• b. Maternal immunity
• c. Age
• d. Pregnancy
• e. Concurrent immunosuppressive therapy
• f. Body temperature
• g. Anesthesia or surgery 

2. Vaccine factors

• a. manufacture
• b. storage and handling
• c. strain differences

3. Human factors

• a. veterinary hospital procedures
• b. concurrent administration of antimicrobials
• c. improper use of disinfectants
• d. vaccine interference
• e. mixing of products
• f. route of administration 

1.5 Postvaccinal complications

1.5.1 Immunological complications

1.5.1.1 Type I hypersensitivity

• i. associated with inactivated products containing large amounts of foreign proteins
• ii. local or systemic reactions
• iii. occur within an hour after administration
• iv. should not repeat vaccination with the same antigen in single or combined vaccines
• v. revaccination may be attempted after puppy reaches maturity
• vi. IgE response may be generated in atopic dogs 

1.5.1.2 Type II hypersensitivity

• i. reported following the use of MLV
• ii. autoimmune hemolytic anemia
• iii. autoimmune nonregenerative anemia
• iv. occur within 1-2 weeks following parvoviral vaccinations
• v. transient thrombocytopenia or autoimmune thrombocytopenia may require glucocorticoid therapy for several weeks subsequent boosters must be avoided or minimized to prevent a recurrence of the problem 

1.5.1.3 Type III hypersensitivity

i. immune complex formation involved with anterior uveitis (CAV-1 vaccine) local Arthus reaction results from antibody antigen complex in eye secondary glaucoma may occur

ii. generalized serum sickness widespread immune complex deposition microvasculature of certain structures such as renal glomeruli, joints and uveal tract are affected usually seen with large amounts of passively given immunoglobulin 

1.5.1.4 Type IV hypersensitivity

• i. seen in two incidences 
• ii. BCG as an immunostimulator (granuloma formation) 
• iii. use of suckling mouse brain inactivated rabies vaccine (postvaccinal encephalomyelitis)

1.5.2 Nonimmunologic complications

1.5.2.1 local reactions

• i. local irritation
• ii. swelling
• iii. abscess formation
• iv. noticed with inactivated products containing adjuvants
• v. seen with bacterial vaccines containing large amounts of tissue culture proteins

1.5.2.2 Systemic illness

• i. characterized by fever, malaise and inappetence
• ii. result of self-limiting infection of MLV
• iii. usually does not last longer than 1-2 days following vaccination 

1.5.2.3 Prenatal and neonatal infections

• i. if given during pregnancy can cause fetal death and abortion particularly MLV vaccines
• ii. neonatal infection can occur following the use of MLV canine and feline paroviral vaccines in puppies and kittens less than 4-5 weeks of age

1.5.2.4 Respiratory disease

• i. can occur as an expected postvaccinal complication
• ii. usually occurs with intranasal vaccines
• iii. mild clinical symptoms are usually self-limiting
• iv. immunity superior to parenteral counterpart
• v. can get the same reaction from parenteral products inadvertently or accidentally released into the environment 

1.5.2.5 Shedding of vaccine agent

• i. occurs with MLV intranasal products
• ii. occurs with administration of parenteral vaccines
  • canine parvoviral vaccine (feces)
  • CAV-1 vaccine (urine)
  • CAV-2 vaccine (respiratory secretions)
• iii. shedding may serve to vaccine other susceptible animals
• iv. reversion to virulence a potential

1.5.2.6 Postvaccinal encephalomyelitis

• i. low passage MLV Rabies vaccine in dogs
• ii. high passage MLV Rabies vaccine have produced clinical disease in cats
• iii. disease begins with paralysis in vaccinated limb 7 to 21 days after vaccination
• iv. progresses bilaterally and in an ascending fashion
• v. cats - progressive lower motor neuron paralysis with an unusual extensor rigidity of the limbs
• vi. pain and reflex function decrease in an ascending fashion
• vii. recovery after 1-2 months in dogs have been reported
• viii. do not present health hazard because vaccine is attenuated and is not shed in the saliva
• ix. Public health and expert virologists should be consulted
• x. Other causes of postvaccinal encephalomyelitis

combined distemper virus and CAV-1 vaccine MLV measles vaccine feline or canine parvoviral vaccines used in animals less than 4-5 weeks of age 

1.6 IMMUNIZATION SCHEDULE FOR PUPPIES

Any immunization schedule must be tailored to the specific needs of the individual. If a healthy puppy is presented with no history of disease exposure, and the puppy is not from a high risk area (i.e. pet shop, animal shelter, etc.) the following schedule may be used for the convenience of the owner in rescheduling visits.

Age of Puppy When First Presented	A Vaccination
Less than 6 weeks	Vaccination not usually recommended. Bordetella products may be used.***
6-7 Weeks	1st Distemper-Measles (D-M) intramuscular (IM).If D-M is used, a Distemper-CAV-2-parainfluenza-leptospirosis vaccine is administered when pup is14 weeks old. Parvovirus vaccine may also be given at that time; see below.*lst Parvovirus vaccination.
7-8 Weeks	1st D-M, (IM), D-CAV2-P-L at 14-16 weeks. *lst Parvovirus vaccination.
8-9 Weeks	1st D-M, (IM) D-CAV2-P-L at 14-16 weeks or:1st D-CAV2-P-L 2nd D-CAV2-P-L at 10-11 weeks 3rd D-CAV2-P-L at 12-13 weeks *lst Parvovirus vaccination
9-10 Weeks	1st D-CAV2-P-L 2nd D-CAV2-P-L at 11-12 weeks 3rd D-CAV2-P-L at 12-13 weeks *lst Parvovirus vaccine 2nd at 12-13 weeks 3rd at 16 weeks
10-11 Weeks	1st D-CAV2-P-L 2nd D-CAV2-P-L at 12-13 weeks *lst Parvovirus vaccine 2nd at 13-14 weeks 3rd at 16 weeks
11-12 Weeks	1st D-CAV2-P-L 2nd D-CAV2-P-L at 13-14 weeks *lst Parvovirus vaccine 2nd at 14-15 weeks 3rd at 17-18 weeks
Over 12 Weeks	1st D-CAV2-P-L (no booster needed) **lst Rabies vaccination (intramuscular) *lst Parvovirus vaccination

2nd at 3-4 weeks after these 2 doses of parvovirus vaccine should be given (at 3-4 week intervals) after the puppy is 14 weeks of age. Yearly revaccination (single dose) with parvovirus vaccine is recommended. If a dog is entering a high risk area (i.e. boarding kennel, dog shows,

• ii. swelling
• iii. abscess formation
• iv. noticed with inactivated products containing adjuvants
• v. seen with bacterial vaccines containing large amounts of tissue culture proteins

b. Systemic illness

i. characterized by fevfield trial, etc.) for exposure to parvovirus that dog should be re vaccinated if his last parvovirus vaccination was more that 6 months earlier.

D-CAV2-P-L (or D-H-P-L) is repeated yearly.

**Rabies vaccine given at 3-4 months of age (or up to 1 year of age) is repeated one year later. After the first yearly booster, vaccination may be good for 3 years (see Compendium of Rabies Vaccines and Local Ordinances).

***Under certain circumstances in high risk area, Bordetella bacterins by either the systemic or intranasal route may be indicated. In infected kennels puppies may be vaccinated as early as 3 weeks of age with parenteral Bordetella bacterin which should be repeated 3-4 weeks later (2 doses are needed). The intranasal Bordetella product (a live avirulent product) may be given to pups as young as 2 weeks of age. Only one dose is given and protection lasts for 6 months. 

1.7 MINIMUM DISEASE PREVENTION RECOMMENDATIONS FOR CATS

Age	Recommendations

---

Weaning to Physical examination

6_7 weeks Feeding instructions - grooming and care instructions Fecal examination for internal parasites; worming if needed. Panleucopeneia passive immunization with hyperimmune or normal serum (1&endash;2ml/lb) in high risk area. Repeat in 10-14 days, Intranasal feline herpes&endash;calici virus vaccination in high risk areas.

9&endash;10 weeks Panleucopenia vaccination with either (l) TCO inactivated vaccine repeat in 2-4 weeks and for maximum protection a third dose is given at 16 weeks of age. or (2) TCO modified live (MLV) virus with a second vaccination in 2&endash;4 weeks. Herpes Calici virus vaccine with either: (l) Parenteral (SQ or IM) inactivated or attenuated (MLV) virus vaccine. Repeat in 2&endash;3weeks and again 2-3 weeks later (May be combined with MLV or inactivated panleucopenia virus vaccine). or (2) Intranasal (MLV) herpes&endash;calici virus vaccine. The intranasal vaccine may be repeated in 2&endash;3weeks. Pneumonitis vaccination (SQ or IM) in high risk areas. May be repeated in 2&endash;3weeks.

Feline Leukemia (sub&endash;unit) vaccine IM. This vaccination is repeated in 2-3 weeks and again 2 months after the first vaccination.

3&endash;4 months Rabies vaccination with a vaccine (inactivated) which will provide three years protection. The rabies vaccine should be repeated in one year and again every three years.

MLV, intranasal, herpes&endash;calici virus given at this time requires only a single dose, it is repeated yearly thereafter.

MLV TCO panleucopenia vaccine if given at this time requires only a single dose and should then be repeated yearly.

If parenteral herpes calici virus vaccine (attenuated or inactivated) is used, it should be repeated in 2&endash;3weeks and yearly thereafter.

• Annually Panleucopenia vaccination
• Rabiea vaccination (if necessary)
• Feline Herpes&endash;calici virus vaccination
• Feline Pneumonitis vaccine (in high risk areas)
• Feline leukemia vaccination
• Physical examination with particular attention to teeth, ears,and urinary system.
• In cats over 8 years of age an annual physical examination is
• recommended with urinalysis, CBC, SGP&endash;T, creatinine, and 3UN evaluation. 

1.8 IMMUNIZATION SCHEDULE FOR KITTENS

Any immunization schedule must be tailored to the needs of the individual. If a healthy kitten is presented, with no history of disease exposure, and the kitten is not from a high risk area (i.e. animal shelter, pet shop, etc.), the following schedule may be used for the convenience of the owner in rescheduling visits.

Less than 6 weeks Vaccination not usually recommended. (May need panleucopenia antiserum if entering a high risk area.)

All vaccines (Panleucopenia, Herpes-calici, Pneumonitis and Rabies are repeated (one dose)yearly.

*Intramuscular herpes-calici virus vaccine is available as an MLV or inactivated vaccine.

Intramuscular herpes-calici virus vaccine may be administered as a combined vaccine with either MLV or inactivated panleucopenia vaccine. Intranasal herpes-calici virus vaccine may be administered as a combined vaccine with MLV panleucopenia vaccine. 

1.9 RABIES 

1.9.1 Synonyms

Lyssa, hydrophobia, sylvatic plague, campestoral plague 

1.9.2 Etiology

The virus that causes rabies is in the family rhabdovirus. Rhabdoviruses are enveloped ssRNA virus with a characteristic bulletshape. Virus replication results in the formation of intracytoplasmic inclusions. Free virus infects new or adjacent cells by fusing their envelopes with the host cell membrane allowing direct entry into the host cell. Easily destroyed by most disinfectants. 

1.9.3 Transmission

The primary mode of infection is deep exposure to virus infected saliva (bite of a rabies infected animal). Aerosol exposure (transmission by droplets in caves heavily populated by bats) and and ingestion of infected material have also been documented as a mode of transmission. 

1.9.4 Susceptibility

All mammals - highest incidence for dogs and cats is in areas where wildlife rabies is epizootic. 

1.9.5 Pathogenesis

Variation in incubation period is based on:

• a. the site of bite
• b. the amount of virus introduced
• c. the species that is bitten 

Average incubation periods are:

• Dogs 3 to 8 weeks
• Cats 2 to 6 weeks
• Humans 3 to 8 weeks

Experimental variation in pathogenesis is based on the mode on inoculation.

After intramuscular inoculation the virus replicates in myocytes of infected muscle. Viral spread occurs centripetally via neuromuscular junctions to the peripheral nerves and then to brain. The greater the innervation at the site of the bite the shorter the incubation time.

After intranasal inoculation, the virus enters trigeminal nerves or cribiform plate and olfactory bulbs and travels to the brain.

In oral inoculation the virus infects cells of the oral mucosa, taste buds, pulmonary and intestinal mucosa. It travels via the cranial nerves to the brainstem. 

Once in the brain or spinal cord, virus replicates in neuronal perikaryon. Interneuronal spread corresponds with the progression of clinical signs. Following replication within the CNS the virus moves to other body tissues via peripheral, sensory and motor nerves and to the nerves to the salivary glands. The spread of the virus to the saliva indicates that the brain has already been infected. 

1.9.6 Clinical signs

Clinical signs are divided into 3 phases.

Prodromal phase (2 to 3 day duration) is associated with changes in behavior such as apprehension, anxiety, and solitude. Other signs infrequently seen are; fever, pupillary dilation, sluggish palpebral reflex, and pruritis at site of the bite causing self mutilation. In cats the prodromal stage is shorter (1 day) and signs are more eratic.

Furious phase (duration 1 to 7 days) is characterized by restlessness and irritability. The infected animal becomes hyperexcitable, photophobic, and hyperesthetic. Disorientation and a loss of muscle coordination may lead to ataxia. Generalized grand mal seizures may develop and usually lead to the death of the dog. Cats more consistently develop the furious form of rabies.

Paralytic phase develops within 10 days after the first clinical signs are noted. The paralytic phase is associated with lower motor neuron dysfunction that leads to paralysis of certain muscle groups. Change in the bark, dropped jaw and excessive salivation are all clinical signs of the paralytic phase in dogs. In cats the paralytic phase begins at about the 5th day of clinical illness. There is generalized paralysis and coma resulting in death. 

1.9.7 Diagnosis

History and Physical exam - Rabies should be considered in any case where there are characteristic signs of behavior change and/or lower motor neuron paralysis.

• Hematology and biochemistry - no abnormal findings
• Cerebrospinal fluid - increase protein content
• Virus isolation and identification - Tests used for the detection of viral antigen
• Direct immunofluorescence
• Intracellular inclusions
• Mouse inoculation
• Monoclonal antibody
• Serology - Tests used for the detection of antibody to virus
• Neutralization tests
• Indirect immunofluorescence
• Rapid Fluorescent-Focus inhibition test
• Pathologic findings

No gross lesions detectable in CNS. Histologic lesions are acute polioencephalitis, neuronophagia, neuronal degeneration and nonsuppurative inflammation seen early.

Necrotizing encephalitis seen later as titer to rabies rise in CSF. The longer the course of illness, the more pronounced is the nonsuppurative inflammatory response in the brain and spinal cord. 

1.9.8 Therapy

Supportive care and symptomatic treatment of seizures. 

1.9.9 Prevention

• Zoonotic potential
• Human vaccines
• Canine and Feline vaccines
• Vaccine recommendations
• Postvaccinal Reactions
• Control of Epizootic Rabies in Dogs and Cats
• Postexposure management of dogs and cats 

1.10 PSEUDORABIES 

1.10.1 Synonyms

mad-itch, Aujeszky's disease, infectious bulbar paralysis 

1.10.2 Etiology

An enveloped ds DNA virus of the herpesvirus family. The virus is antigenically related to the infectious bovine rhinotracheitis virus. Many strains have been found. Strains differ in ability to cause cytopathic effect. Since viral DNA is incorporated into host cell genome there is a potential for latent infection. The virus is resistant to environmental factors and can survive outside the host for several months. 

1.10.3 Epizootiology

Many mammalian species are susceptible. The virus is predominantly a problem in pigs. It does not appear to affect humans. The main reservoir is the pig where the infection is often subclinical. Dogs have developed pseudorabies after biting infected pigs. Direct spread from dog to dog has not been shown to occur. 

1.10.4 Pathogenesis

Incubation period in dogs and cats irrespective of inoculation site is 3 to 6 days. Pseudorabies virus enters the nerve endings at the inoculation site and travels in a retrograde fashion via the axoplasm of the nerve fibers to the brain. This mode of viral spread has been demonstrated in the cow. The virus replicates in the tonsils and travels from the oral mucosa via the sensory branches of the ninth and tenth cranial nerves to the nucleus. 

1.10.5 Clinical findings

The onset of clinical illness is very acute and progress rapidly until death occurs. Total course of disease rarely lasts longer than 48 hours. Pseudorabies is always fatal in dogs. Cats are more resistant. The initial sign is a change in behavior (inactivity, lethargy, indifference). Eating of inanimate objects may be observed (pica). Dyspnea, diarrhea and vomiting are sometimes seen. Hypersalivation is a common finding. The most characteristic sign is intense pruritus which usually occurs in the head region. Excoriations of the face and neck may be seen due to self-mutilation. 

1.10.6 Diagnosis

• Laboratory findings
• Hematology and Biochemistry - no abnormal findings
• Viral isolation and identification
  • a. Animal Inoculation
  • b. Fluorescent antibody testing
  • c. Virus Isolation
• Serology
• Pathologic Findings

No gross necropsy findings are pathognomonic for pseudorabies. Skin lesions are present from intense pruritis and abnormalstomach contents due to pica. Pulmonary edema and congestion and focal myocarditis are

reported findings. Histological lesions in the CNS are exclusively located in the brainstem and involvecranial nerve nuclei. These lesions consist of perivascular cuffing with mononuclear cells and proliferation of astrocytes and microglia cells. Microabcesses and severe necrolysis and degenerative changes in neurons. Inflammatory changes may also be seen in ganglia at site of entry of virus (alimentary myenteric plexus). 

1.10.7 Therapy

Heavy sedation and anesthesia to lessen the itching and convulsions. 

Prevention1.10.8

Contact with pigs and eating raw pork avoided in endemic areas. Vaccination of dogs and cats in endemic areas. Vaccination efficacy questionable and postvaccinal reactions occur. 

1.11 CANINE DISTEMPER 

1.11.1 Synonyms

Carre's disease 

1.11.2 Etiology

An enveloped ss RNA virus of the family paramyxovirdae and the genus moribillivirus. The virus is antigenically related to measles and rinderpest viruses. There are numerous isolates that vary in virulence and ability to cause neurological disease. The virus is rapidly inactivated by heat and light. Many chemical are lethal to the canine distemper virus but the virus is more protected in body secretions. The virus survives in the environment longer at lower temperatures. 

1.11.3 Transmission

Direct and indirect transmission is possible. Portal of entry is respiratory tract. Virus is shed in all secretions and excretions. Recovering dogs may shed the virus for several weeks. 

1.11.4 Susceptibility

Young dogs become susceptible when they lose maternal antibody, usually between 6-12 weeks of age. Young dogs between 3 to 6 months of age are thus more prone to infection. Most infections are subclinical. Subclinically or clinically diseased dogs are responsible for maintenance of virus in environment.

Other susceptible species are:

• family felidae: cat, lion, tiger*
• family viverridae: bintotong, civit
• family hyaenidae: hyenas
• family canidae: dog, fox, dingo, coyote, wolf
• family procyanidae: kinkajou, raccoon, coati mundi, badger, lesser and greater panda
• family mustelidae: mink, ferret, skunk, weasel
• family ursidae: bears *

*canine distemper vaccination not recommended 

1.11.5 Pathogenesis

Incubation period is variable (3 to 8 days with an average of 5 days). Following natural exposure the virus in droplets contacts the epithelium of the upper respiratory tract. Within 24 hours it multiplies in the tissue macrophages and spreads in these cells, via local lymphatics to tonsils and bronchial lymph nodes. Two to 4 days postinoculation virus numbers increase in tonsils and retropharyngeal and bronchial lymph nodes. By days 4 to 6 the virus multiplication occurs within lymphoid follicles in the spleen, lamina propria of the stomach, small intestine, mesenteric lymph nodes, and Kuppfer`s cells in the liver. This widespread proliferation corresponds with a rise in temperature and leukopenia mainly affecting lymphocytes (B and T lymphocytes affected equally). Hematogenous spread of canine distemper occurs 9 days postinoculation. Virus is spread to central nervous system and epithelial surfaces. Severe clinical signs are associated with viremic spread of virus and lack of protective antibodies provided by vaccination program. There is an inverse relationship between the development of antibodies and the severity of infection.

Central nervous system infection differ according to whether signs develop before or after development of an immune response. Acute encephalitis develops due to entry of virus into CNS and direct damage to neuronal cells with secondary demyelination. Chronic encephalitis develops due to the local immune response with anti-myelin antibodies and primary demyelination. 

1.11.6 Clinical signs

Clinical signs are related to involvement of some or all of the major epithelial sites with eventual progression to the central nervous system. Common early signs are fever which persists for 1-2 days then subsides for 1-2 days and then recurs. Later there is the development of serous ocular and nasal discharges. These discharges may become mucopurulent with secondary bacterial infection. Progression to interstitial and bronchopneumonia occurs and coughing develops. Other related clinical signs are mild dyspnea and crackling lung sounds on thoracic ausculation. Diarrhea and vomiting unassociated with feeding reflect gastrointestinal involvement. The diarrhea is watery and may contain blood. Tenesmus and subsequent intussusception may occur with severe gastrointestinal disease. Diarrhea leads to dehydration, depression and weight loss. Sudden death may occur if animal does not receive treatment.

Dermal lesions occur and consist of a skin rash (impetigo, or pustular dermatitis) occurring on thinly haired areas of the body. The pustular dermatitis is found with early clinical disease. A thickening of the dermis of the footpads (hardpads disease or hyperkeratosis of the foot pads) and nose may occur after systemic illness. Hard pads disease is found with chronic disease.

Neurological signs usually occur late in the course of the disease. Neurological signs seen are paresis or paralysis, myoclonus (clonic-tonic convulsions, chewing gum fits), or convulsions may occur and the disease course is weeks to months. The neurological signs are more associated with chronic encephalitis and the development of immune-mediated demyelination of large axons.

1.11.7 Diagnosis

• History
• Clicinal signs
• Hematology - related to secondary infection elevated WBC
• Biochemistry - elevated BUN, slightly elevated liver enzymes
• Inclusion bodies
• Virus isolation and identification
• Serology
• Pathology

Gross pathology consists of thymic atrophy, interstitial pneumonia, bronchopneumonia, catarrhal enteritis, hyperkeratinizedfootpads, pustular dermatitis, conjunctivitis, rhinitis, meningealcongestion, and dilation of ventricles of the brain.

Histological lesions are lymphoid depletion, thickened alveolar septa, proliferation of respiratory epithelium, swelling of transitional cell epithelium of the bladder, degenerative changes in the adrenal gland, necrosis and cystic degeneration of ameloblasticepithelium, perivascular lymphoplasmacytic infiltration of CNS. Characteristic eosinophilic inclusions may be present in cells of the bladder, conjunctiva, brain, respiratory tract, renalpelvis, and lymphoid tissue. Inclusions typical for canine distemper virus have been identified in the bladder of normaldogs.

1.11.8 Treatment and prophylaxis

Treatment is supportive and non-specific. The treatment is aimed at making the dog comfortable, correcting fluid imbalances and aiding the immunosuppressed dog in combating secondary bacterial infections. Canine distemper causes a secondary immunodeficiency state.

1.12 CANINE INFECTIOUS TRACHEOBRONCHITIS

1.12.1 Synonyms

CIT, CITB, Kennel cough 

1.12.2 Etiology

CIT is caused by multiple etiological agents. These agents may act singly or in groups to cause disease. Some are considered to be contributing causes of disease. The etiological agents associated with CIT are: 

• a. Canine parainfluenza virus - A paramyxovirus (enveloped ss RNA virus) in which strains 2,4, and 5 are found in respiratory infections in dogs. Local replication has been demonstrated experimentally. The virus has the ability to spreadrapidly from direct exposure.
•  b. Canine adenovirus 1 and 2 - Adenoviruses are naked ds DNA viruses. CAV-2 (Toronto, A26/61) is also called infectious laryngotracheitis virus. CAV-2 is more significant than CAV-1 in causing respiratory disease. Rapid spread by direct exposure occurs.
•  c. Canine reovirus (respiratory-enteric-orphan) - Reoviruses are naked ds RNA viruses. Three serotypically different species have been found. Types I and II are found in the U.S. This virus has potential for zoonoses. Commercial vaccines are not available in the U.S.
•  d.Canine herpesvirus - enveloped ds DNA virus, has been isolated from dogs with respiratory disease.
•  e. Mycoplasma cynos - Ten different other species of mycoplasma have been isolated from clinically normal and affected dogs. The organism is more of a contributing than a causal agent.
•  f. Bordetella bronchiseptica - most common bacterial agent isolated from dogs with upper respiratory tract disease. In certain instances can cause primary respiratory infection.

 1.12.3 Transmission

Portal of entry is the respiratory tract. The primary mode of transmission is direct (aerosol or airborne). Indirect transmission via fomites possible. 

1.12.4 Susceptibility

Canidae, type and severity of disease varies with:

• a. age and resistance of the host
• b. type and severity of infection
• c. vaccination 

1.12.5 Incubation period

Incubation period varies with etiological agent (usually 8-10 days). Canine parainfluenza has an incubation period of 4 days, canine adenovirus-2 2-4 days, and bordetella bronchiseptica 4-5 days. Clincal course of disease is usually 2-3 weeks. 

1.12.6 Clinical signs

Paroxysms of coughing is the primary sign. The cough is a dry non-productive cough followed by retching of phlegm. It may be elicited on tracheal palpation. A serous nasal and ocular discharge may also be present. With multiple infectious agents the disease may be more severe with fever, anorexia, depression, and lung sounds on thoracic auscultation.  

1.12.7 Differential diagnosis

• Canine distemper Systemic fungal disease
• Allergic bronchitis Trauma
• Bronchiectasis Lungworms
• Bronchialforeign bodies Congestive heart failure
• Neoplasia of bronchialtree
• Clinical Diagnosis
• History
• Clinical signs
• Physicalexamination
• Symptomatic therapy
• Hematology*
• Radiograph*
• Transtracheal wash* Serology - paired serum from acute and convalescent phases *may be necessary only with severe disease

 1.12.8 Therapy

Therapy is symptomatic. Mild coughs may be treated by keeping animal in a warm, well-ventilated area. Feeding the dog a palatable diet is advocated. Avoiding situations that may cause the onset of the paroxsyms of coughing is also advised. In more severe cases antibiotics are used. 

1.13 FELINE UPPER RESPIRATORY VIRAL DISEASES  

1.13.1 Synonyms

URI (upper respiratory infection), FURD (feline upper respiratory disease), Coryza, Feline influenza, Feline distemper, Pneumonitis 

1.13.2 Etiology

There are many etiological agents that may cause upper respiratory disease of the cat. Of these respiratory pathogens viruses comprise the majority of clinical cases of upper respiratory infections. Diagnosis of a particular pathogen may be difficult due infection with multiple pathogens or subclinical infection. The following are the most common etiological agents of upper respiratory infections in cats: 

1.13.2.1 Feline rhinotracheitis virus 

etiology - enveloped ds DNA virus, found mainly in the respiratory and urogenital tract, rapidly inactivated out side of host, easily destroyed by most disinfectants, antigenically similar serotypes. 

epizootiology - felidae only, multiplies mainly in upper respiratory tract, transmission may be direct or indirect, chronic carrier cats responsible for maintenance of virus in environment, rapid spread under conditions where cats are confined, virus present in saliva and nasal secretions. 

clinical course - incubation period 2-10 days, course and severity variable, virus shed 1-3 weeks, virus has an affinity for sites of osteogenesis (sequellae - persistent frontal sinusitis).

 symptoms - fever, depression, paroxysmal sneezing, serous nasal and/or ocular discharge that may become mucopurulent with secondary bacterial infection, conjunctivitis, corneal lesions, ulcerative keratitis, ulcerative glossitis, coughing, bronchopneumonia, abortions in infected queens, keratoconjunctivitis neonatorum in kittens born to infected queens.

1.13.2.2 Feline calicivirus 

etiology - naked ss RNA virus, more stable than FVR, remains infective for 10 days at room temperature, resistant to ether and chloroform, inactivated by hypochloric acid (Clorox), numerous serological strains exist 

epizootiology - all Felidae (not as common in exotic cats as FVR), shed continuously in oropharynx, pathogenecity limited to oral mucosa and respiratory tract, carrier cats (shed virus continuously up to one year), transmission occurs direct or indirect.

 clinical course - incubation period 1-2 days, clinical signs persist 3-5 days, severity of disease varies due to presence of many strains, shed from oropharynx, urine and feces, clinical signs vary according to virus strain. 

symptoms - fever, depression, ulcers, dyspnea, pneumonia (more of a potential than FVR for development of lower respiratory and lung lesions, oculonasal discharge (infrequent), transient fever and lameness associated with FCV, urologic syndrome (manx calicivirus).

 1.13.2.3 Chlamydia Psittaci

Etiology - classification bacteria, rickettsiae, and viruses, propagated in yolk sac suspension, remains infective for 1 week at low temperatures. 

epizootiology - mice, hamsters, guinea pigs, rabbits, man (Public health consideration), transmission direct contact with secretions or contaminating organism, shed in ocular and nasal discharges, present in lungs also, chronic carrier state shed organism 1-2 months.

 clinical course and symptoms - incubation period 3-10 days, variable clinical signs, generally mild, rapid recovery, recurrences common, conjunctivitis and rhinitis, discharge serous or mucopurulent, fever uncommon. 

1.13.2.4 Reoviruses

Naked ds DNA viruses cause mild conjunctivitis in affected cats.

1.13.2.5 Mycoplasma

Secondary invader causes conjunctivitis 

1.13.3 Diagnosis

• History
• Clinical signs - difficult to diagnose causative agent
• based on clinical signs
• Hematology
• Conjunctival smears - cytology
• Viral isolation
• Serology - paired serum samples from acute and convalescent
• phases

 1.13.4 Treatment 

Treatment varies according to clinical symptoms and causative agent. Antibiotics used are tetracycline, chloramphenicol for mycoplasma. The common ophthalmic preparations used are those containing tetracycline for mycoplasma, and idoxuridine for FVR corneal ulcers. Decongestants (Phenylephrine HCl) have also been used to dry nasal discharges. Supportive care with fluid therapy is necessary with severe disease. Other supportive care consists of keeping the cat in a warm and well ventilated area, keeping nose and eyes free of discharge, force feeding or placement of a nasal gastric tube may be necessary. 

1.13.5 Prevention and control

• Good husbandry for breeding kennels
• isolation of new cats
• separation of young and older cats
• separation of pregnant queens
• adequate space between cages
• culling of affected cats
• vaccination of young and new cats 

1.14 FELINE INFECTIOUS PERITONITIS AND ENTERIC CORONAVIRUS 

1.14.1 Synonyms

FIP, FEC, FECV 

1.14.2 Etiology

An enveloped ssRNA virus of the coronaviridae family antigenically related to coronaviruses of other species (transmissible gastroenteritis, canine coronavirus, and human coronavirus 229E). There are 5 antigenically similar strains that vary both in pathogenicity and rate of replication in tissue culture. The virus is inactivated by most disinfectants. The virus of FIP is antigenically indistinct from the virus of FEC. 

1.14.3 Epizootiology

Exotic and domestic cats are affected. The incidence of disease shows age variation. High incidence is seen in cats less than 2 years of age and those 13 years and older. Young cats are extremely susceptible to disease with whole litters often affected from infected queens. Mortality rate is 100% in clinically diseased animals. Natural incubation period and route of infection is unknown. Virus is shed in urine, saliva, and feces. Viral infection has been associated with immunosuppression caused by feline leukemia virus. 

1.14.4 Pathogenesis

Two routes of infection are considered important (in utero and ingestion). After ingestion the virus replicates in the mature apical epithelium of the intestine. For feline enteric coronavirus this replication is associated with gastroenteritis. For FIP there is no associated gastroenteritis the virus is phagocytized by macrophages. The macrophages are responsible for a cell-associated viremia. Viremia leads to the dissemination of virus to target organs (liver, peritoneum, pleura, uveal tract, meninges and ependyma of brain and spinal cord).

The immunity that develops after dissemination determines the course of disease. A good humoral and cell-mediated immune response leads to complete recovery or development of a latent infection. There are no clinical signs associated. A good humoral immune response with a partial cell-mediated immune response leads to the development of the dry (non-effusive) form of FIP. A good humoral immune response without any cell-mediated immune response leads to the development of the wet (effusive) form of FIP. The wet form of FIP is an immune vasculitis (pyogranulomatous reaction) around small venules in target organs. This vasculitis is responsible for the outpouring of protein and fibrin rich fluid into body cavities. In the dry form of FIP,the cell mediated immune response is sufficient to contain virus infection in target organ but cannot abort viral infection therefore there is pyogranuloma formation in the organ. The presence of high antibody titer does not protect the cat from development of disease. Often the signs of disease are more severe and occur more rapidly in cats with high antibody titer (experimental evidence with vaccine to FIP). 

1.14.5 Clinical signs 

General signs - fever, gradual weight loss, partial anorexia

Signs of effusive FIP - abdominal distention, ascites, dyspnea, muffled heart sounds, decreased exercise tolerance, and fluctuating bouts of diarrhea and constipation 

Signs of noneffusive FIP - organ specific and varies in manifestation according to the organ affected. CNS involvement seen more commonly with this form of the disease. signs - paralysis, paresis, incoordination, hyperesthesia, nerve palsies, dementia, personality changes, tremors, nystagmus, headtilt, circling. Liver involvement - icterus, enlarged liver, bilirubinuria. Ocular involvement - hyphema, keratitic plaques. Kidney involvement - proteinuria, small kidneys with an irregular shape. 

Kitten mortality Syndrome - FIP and other infectious diseases have been associated with a clinical entity involving

reproductive problems in cats and less vigorous kittens. The syndrome is associated with reproductive failures, endometritis, pyometritis, repeat breeders, fetal resorptions, abortions, stillbirths, congenital malformations, neonatal deaths and weak small kittens that fade away due to congestive cardiomyopathy.

1.14.6  Diagnosis 

Differential for wet form - cardiomyopathy, chylothorax, pyothorax, trauma with hemothorax or diaphragmatic hernia. Dry form may mimic primary liver or kidney disease. CNS lesions may mimic rabies, toxoplasmosis or other infectious diseases that may affect the brain.

• Clinical diagnosis 
• Clinical signs and history often not helpful
• Pleural or Abdominal centesis and cytology of fluid - fluid high in proteins and cells
•  Hematology - elevated white blood cell count with a neutrophilia and lymphopenia

 Biochemistry - elevated plasma proteins, elevated plasma fibrinogen levels, elevated bilirubin, slight elevation of liver enzymes, slight elevation of BUN. disseminated intravascular coagulation in some cats may lead to prolonged prothrombin and partial thromboplastin times.

• Urinalysis - proteinuria 
• CSF - elevated protein concentration and elevated amount of cells
• FeLV test 

FIP titer - please know that a positive titer means that the cat has been exposed to FIP and that it is only important if the titer is negative. If the titer is negative then the disease process is not FIP. If the titer is positive then FIP must be kept on the rule out list. Many cats without clinical disease will have high titers to FIP. Since there is crossreactivity with FECV it is not known whether the titer is to FIP or FECV. 

1.14.7 Treatment and Prevention

Therapy for FIP patients rely on the use of immunosuppressive agents. Due to the infectious nature of this disease longterm remissions have not been achieved. Successful therapy using prednisolone or prednisone 5 mg/kg divided twice a day combined with melphalan (Alkeran) tablets 0.2mg/kg every 3rd day has been reported. 

Due to the nature of FIPV to cause more rapid disease in some antibody positive cats vaccines to date have been unsuccessful. Since the test used to detect FIPV also detects FECV the use of programs to detect antibody positive animals and cull is not advisable.

 1.15 FELINE PANLEUKOPENIA

 1.15.1 Synonyms

Feline infectious enteritis, infectious agranulocytosis, cat plague, cat fever, and feline distemper 

1.15.2 Etiology

A naked ss DNA virus of the Parvoviridae family demonstrating an affinity for rapidly dividing cells. The virus is very stable but may be inactivated by chlorox, formaldehyde and paraformaldehyde. The virus is antigenically related to parvovirus of mink and dog but not parvoviruses of other species. 

1.15.3 Epizootiology

All felidae are affected. Other species affected are coati mundi, kinkajou, racoon, ferret, mink, skunk, otter, sable, badger, etc. (all procyonidae and mustelidae). The virus is constantly encountered and maintained in the environment due to its stability. Transmission occurs by direct contact and may be transmitted by contaminated fomites. Virus is present in all body secretions during active infection. The virus may be shed for up to 6 weeks postinfection. The virus can cross the placenta barrier in pregnant queens. It causes lesions in tissues with the greatest mitotic activity due to its affinity for rapidly dividing cells. 

1.15.4 Pathogenesis

Direct or indirect contact in the cat leads to replication of the virus in the lymphoid tissue of the oropharynx (18-24 hours). Afterwards the cat becomes viremic (2-7 days). If the cat is not vaccinated the antibodies do not prevent the spread of the virus to tissues with the greatest mitotic activity. Therefore the virus is spread to the intestinal crypt cells, bone marrow, and lymph nodes. Spread to intestinal tract leads to signs of gastroenteritis exhibited in clinically affected cats. Spread to lymph nodes leads to lymphoid depletion or thymic atrophy in very young cats making the cat more susceptible to other infection. Spread to bone marrow leads to myeloid depletion leading to susceptibility to infection. This is why panleukopenia is considered to be a causative agent of secondary immunodeficiency in the cat.

Infections that occur in utero may lead to infertility, fetal death, and resorption if the queen is infected early in gestation. Infections that occur mid to late gestation lead to abortion or mummified fetuses. Infections that occur in late gestations have effects on either the fetus or the early neonate and may lead to optic nerve atrophy, retinopathy, hydranencephaly, cerebellar hypoplasia, bone marrow depression and lymphoid depletion. Direct or indirect contact with the virus in the early neonate (2-3 weeks of age) may also lead to cerebellar hypoplasia, lymphoid depletion, and bone marrow depression. 

1.15.5 Clinical findings

The clinical findings were related to the age of the animal, vaccination status and pregnancy status of queens. Clinical signs range from subclinical to mild and consist of elevated temperatures, dehydration, depression, anorexia, and diarrhea (less common). 

In kittens less than 3 months of age the symptoms are more severe. These symptoms consist of fever, anorexia, depression, dehydration, vomitting, and diarrhea. Kittens with peracute infections may develop fever, depression, become prostrate and dies within 8-12 hours of clinical onset of disease. 

Pregnant queens suffer abortions, still births and resorption infertility. Prenatal or neonatal infections lead to cerebellar hypoplasia. Clinical signs shown are a wide base stance, ataxia, incoordination, and intention tremors. These signs may not be seen until the kittens began to try to walk.

 The febrile response in panleukopenia is biphasic. The first febrile response lasts about 24 hours. Two days later the animal may become febrile again. The first febrile response may be related to the viremia and the second due to secondary infection as the virus causes immunosuppression.

 The diarrhea that develops is fluid feces dark brown in color. It may become blood-tinged later with shreds of intestinal mucosa. Loops of gas and fluid filled intestines may be palpated on physical examination. Elevation of the third eyelids may be seen along with tenting of the skin. 

1.15.6 Diagnoses 

Differential diagnosis - Feline leukemia, enteritis caused by other enteric viruses (rotavirus, reovirus, feline enteric coronavirus), intestinal parasitism (ascarids, giardia, coccidia), acute toxoplasmosis

Diagnosis is made on  

• History
• Physical examination
• Hematology - low WBC count
• Biochemistry - elevated BUN, elevated total proteins, and slight elevation of liver enzymes
• FeLV test
• Toxoplasmosis titer
• FIP titer
• Serology
• Complement fixation
• Hemagglutination inhibition
• Viral isolation and identification 

Pathology - gross lesions of dilated loops of bowel particularly the jejeunum and ilium are seen. There are enlarged mesenteric lymph nodes. Fetid fluid feces is found in the intestinal tract. Prenatal or early neonatal infection a small cerebellum may be seen. Prenatally hydrocephalus and hydrancephaly may be observed. Neonatal infection thymic atrophy may occur.

 Histological lesions consist of shortening of the villi in the intestines. The intestinal crypts are dilated and there is sloughing of cells into the lumen. Lymphocyte depletion is observed in the lymphoid follicles of the Peyer's patches. In the cerebrum there may be dilation of the ventricles and necrosis of ependymal cells. Cerebellar degeneration is noted by reduced population of the granular and Purkenje cell layers. Eosinophilic intranuclear inclusions maybe seen in panleukopenia infections but are usually transient.

 1.15.7 Therapy

Supportive therapy consist of replacement of fluid loss to counteract dehydration. Withholding oral intake of food and water acts to decrease vomiting and slows bowel mitotic activity. Plasma or blood transfusion therapy may be needed with severe anemia, panleukopenia, hypotension and hypoproteinemia. Broad spectrum antibiotics may be used for secondary bacterial infections. Combination B vitamin therapy may be used for decreased food intake. Gastric protectorants may be used to decrease toxins absorbed by the intestinal tract and to coat the mucosal lining. 

1.15.8 Prevention and Prophylaxis

Colostral antibodies last for about 3 weeks or longer depending on the antibody titer in the queen. Passive immunization may be used in which homologous antisera from cats with a high titer to infection may be locally or commercially produced. Commercial preparations vary in titer and therefore vary in amount that should be given. The administered immunoglobulin persists for up to 4 weeks. If passive immunization is given subsequent vaccinations must be delayed due to interference from passive immunoglobulins. Passive immunization should only be administered to unvaccinated kittens or cats that have had prior contact with known infected animals or fomites. 

1.15.9 Active immunization

• inactivated vaccines - given to febrile kittens less than 4 weeks of age
• Modified live vaccines - best to use vaccines of feline origin. Mink enteritis vaccines have been used in the past with success.

1.16 CANINE VIRAL ENTERITIS 

1.16.1 Etiology

Minute virus of canine (MVC, Parvovirus-1), canine adeno-associated virus (CAAV, incomplete parvovirus), Parovovirus-2 (variation of feline parvovirus responsible for outbreak of hemorrhagic diarrhea in 1978).

Other viral causes of diarrhea - adenovirus, picornaviruses, paramyxovirus, coronavirus, rotavirus, canine herpesvirus, reoviruses

Parvoviruses are naked ssDNA viruses. The virus is very stable and may be inactivated by chlorox and formaldehyde. It has an affinity for rapidly dividing cells. Believed to be a strain variant of FPV or MEV. Canine parvovirus is antigenically related to both. 

1.16.2 Epizootiology

Dogs are the primary reservoir for infection. Other canidae that may be infected are coyotes, bush dogs, crab-eating foxes, maned wolves. In cats this is a self-limiting infection in which disease is not produced. Maintenance in the environment is due to the stability of the virus. The most common route of transmission is fecal contaminated fomites. Feces is the primary mode of spread. Predisposing factors are increased crowding, stress and concurrent disease. 

1.16.3 Pathogenesis

After oral inoculation the virus replicates in local lymphoid tissue and then is spread throughout the body in a non-cell associated viremia (2-5 days PI). The viremia may be terminated at this time by serum neutralizing antibodies or may be spread to other sites of rapidly dividing cells. Clinical signs occur 5-10 days PI. 

The course of disease depends on the age and the immune status of the dog affected. In puppies less than 8 weeks of age the virus may infect intestinal crypt cells, bone marrow, lymphoid tissue, and myocardium. In dogs and puppies 3 months or older, the virus may infect the intestinal crypt cells, lymphoid tissue, and bone marrow. Acute death is common in generalized disease in neonates. 

1.16.4 Clinical signs

Mild disease is characterized by depression, anorexia, fever, diarrhea (mucoid), and enlargement of superficial lymphoid tissue. Severe disease is characterized by bloody diarrhea, vomiting, endotoxemia, dehydration, and weight loss. There may be neurological signs such as seizures that are associated with a septicemia/endotoxemia due to secondary bacterial infection (lymphoid and myeloid depletion makes dog very susceptible to infections). A reflux of gastric material vomited may lead to a nasal discharge. 

Myocardial disease is distinct from gastrointestinal disease and occurs in two clinical forms. Acute sudden death may occur in the neonate due to acute myocarditis. Clinical signs noted are continuous crying, dyspnea, seizures, and non-productive vomiting. Death may occur after excitement, stress, or eating. Subacute form of myocardial disease may lead to subclinical arrhythmias, decompensated heart failure, stunted growth, and poor body condition. Clinically the myocardial disease may be indistinct from other causes of decompensated heart disease. Clinical signs seen are increase pulse rate, enlarged liver, jugular pulse, and increased respiratory sounds. 

1.16.5 Diagnosis

• History
• Clinical signs
• Hematology - leukopenia which is primarily a lymphopenia
• Biochemistry - hypoproteinemia, increase in LDH, SGOT, and CPK
• Electrocardiography - premature ventricular contractions, ventricular tachycardia, decreased R wave amplitude
• Radiography - left sided heart enlargement
• Serology - IgM, or specific for parvovirus
• Hemagglutination-Inhibition
• Virus neutralization
• Indirect immunofluorescence
• Virus Detection
• Electron microscopy
• Hemagglutination
• Direct Fluorescence
• Enzyme linked immunosorbent assay
• Tissue culture 

Pathology - Gross pathology of dogs with gastrointestinal signs only show a dog that is thin, pale, and dehydrated. The intestinal lumen may be filled with a hemorrhagic watery exudate. The intestinal lumen is red and may be covered with a pseudomembrane. In puppies with acute myocarditis, the lungs may be heavy and wet with frothy fluid in the trachea. The enlarged heart is characterized by pale streaks and dilated ventricles. In older dogs gross pathology is indistinguishable from decompensated heart failure. 

Microscopic lesions - blunting of the villi and denuding of the intestinal epithelium. Necrosis and depletion of lymphoid tissue may also be seen. Degeneration and necrosis of myocardial cells may also be seen. 

1.16.6 Therapy

Fluid therapy should be vigorous and potassium supplementation may be needed. Glucose supplementation is also advised. Whole blood or plasma may be used to combat hypoproteinemia. Antibiotics commonly used are kanamycin, gentamycin, and penicillin. Gastric protectorants are also suggested.

• Prophylaxis
• Maternal immunity
• Vaccines
• Inactivated feline and canine origin vaccines
• Mink enteritis vaccines
• Modified live vaccines of canine and feline origin  

1.17 FELINE LEUKEMIA VIRUS AND OTHER RETROVIRUSES OF THE CAT 

1.17.1 Viral Properties 

• Double-stranded rna virus, of the retrovirus family and oncovirinae subfamily.
• Order of genes left to right
• LTR-gag-pol-env-LTR

proteins encoded by genes; group specific antigen (gag), reverse transcriptase (pol), envelope proteins (env). The LTR serve as promoters for the transcription of the genes into mrnas. 

Group specific antigen p 27 accumulates in the cytoplasm of viremic cats. This antigen is the primary antigen used in detection of the virus.

 The major envelope protein gp 70 is the subgroup or type specific antigen. There are three subgroups of Felv that differ due to the gp 70 protein. This causes a difference in infectivity, host range, and pathogenecity. This protein is also responsible for the attachment of virus to cells therefore virus neutralizing antibodies are directed against gp 70.

The minor envelope protein is p 15E. This protein causes intense immunosuppression by direct action on T cells and by complement activation.

 Viral replication involves the attachment of virus to the cell. After penetration the virus sheds its envelope and using its reverse transcriptase produces a complementary strand of dna. This dna integrates into cellular dna. This integration event can only occur following dna synthesis therefore cycling cells are highly susceptible to Felv.

 After integration disease can occur due to

•  productive infection
• latent infection
• insertional mutagenesis 

Even if the virus fails to integrate disease may occur because failure of integration causes an accumulation of unintegrated viral dna in the cytoplasm of the infected cell which is toxic. This the mechanism of disease in immunodeficiency caused by Felv or the FAIDS syndrome seen in cats. 

1.17.2 Felv Subgroups 

Felv A - most common, responsible for latent infection, causes disease slowly by itself, mutation leads to other subgroups. 

Felv variant A - directly lyses bone marrow and lymphoid cells, leads to lymphopenia, nodal depletion, immunosuppression, causes Felv-FAIDS, variant virus is defective, finding of this viral form in cats indicates a grave prognosis and short life span for the infected cat.

 Felv B - recombinant virus, created each time Felv A recombines with endogenous Felv, replicates well in fibroblasts but poorly in cat leukocytes, incorporates into Felv A envelope to infect cat leukocytes, associated with fatal hemolymphatic disease, thymic lymphomas, myeloproliferative disease, myelopdysplastic disease.

 Felv C - derived from Felv A by recombination or mutation, associated with fata erythroid aplasia, close antigenically to feline oncornavirus associated cell membrane antigen (FOCMA)

 FOCMA - present on Felv and Fesv induced neoplastic lymphoid cells, rarely found in non-neoplastic cells, get regression of lymphoid tumors containing FOCMA when antibodies are mounted to these antigens, antigenically crossreactive with Felv C subgroup gp 70.

 Felv is not very stable in the environment due to its envelope. It is easily destroyed by most detergents. Therefore it is safe to place an uninfected cat in the cage of an infected cat immediately after adequately cleaning that cage. Also transmission is difficulty indirectly.

 Saliva is the major source of infection. Susceptible cats may be infected during grooming, fighting or eating from the same bowl with an infected cat. Prolonged exposure leads to disease.

 The incidence of Felv infection is higher than the incidence of Felv disease. The highest incidence of Felv related disease is due to immunosuppression and subsequent infections. Tumors that are Felv related have the lowest incidence of occurrence.

1.17.3  Pathogenesis

 Six stages of Felv infection:

• 1. Replication in lymphoid tissue around exposure site
• 2. Infection of small numbers of circulating lymphocytes and monocytes.
• 3. Felv replication amplified in spleen, lymphnodes and gut- associated lymphoid tissue.
• 4. Replication progresses to involve bone marrow neutrophis and platelets, and intestinal crypt epithelial cells.
• 5. Peripheral viremia occurs via bone marrow-derived neutrophils and platelets.
• 6. Widespread epithelial infection causes excretion of virus in saliva and urine. 

Cats undergoing transient infections usually develop a virus neutralizing antibody response by stages 3 or 4. Cats undergoing persistent viremia are unable to develop neutralizing antibody by stage 4. Therefore stage 4 is considered the pivotal stage.

 1.17.4 Consequences of persistent viremia

•  1. Recognizable signs of disease attributable to Felv infection that occur only after a long induction period. 
• 2. After a long induction period there is tumor development.
•  3. About 50% of persistently viremic cats will die within 6 months of detection of infection, and about 80% will succumb within 3 years. 

1.17.5 Latent infections 

In 30-80% of cats undergoing transient Felv infections, virus is not immediately eliminated from cat. The latent infection may be abnormal stage of the recovery process. These latent infection are probably maintained by virus-neutralizing antibody. There is no difference in antibody titer between cats with latent infection and those which recover completely. The duration of latency is short in most cats and elimination of virus occurs within 30 months of exposure. Cats with true latent infections test negative on the ELISA and IFA tests. Latent infection may be responsible for persistently high anti-gp70 and anti-FOCMA antibody titers seen in some cats. Latent infections may be reactivated by: stress, immunosuppressive therapy, complement depletion, and serious concurrent disease. Reactivated latent infections may result in relapsing or persistent viremia with shedding of virus in the saliva. If virus neutralizing antibody levels are high at the item of reactivation, immune complexes may be formed. If these are phagocytized and removed form the circulation the ELISA test may be negative while the cats tests positive on the IFA test. Although cats with true latent infections are not considered infectious to other cats, the latent state is a fragile phase of infection. 

A subgroup of cats has been identified which are nonviremic, yet remain persistently ELISA (+) for p27 antigen. These patients are defined as "persistently discordant". They are thought to be immune carriers of Felv. Transmammary transmission may occur in these cats. It is inadvisable to allow persistently discordant cats to breed or live communally with other cats. 

1.17.6 Felv-associated diseases 

Diseases caused by Felv is related to the cell type infected. These diseases are in the text and are not very different than those that are now published. There are at least three clinical syndromes that occur alone or in combination in persistently infected cats.

• 1. Uncontrolled proliferation of virus-transformed cell (tumor).
• 2. Degeneration of progenitor (blast) cell (atrophy, aplasia).
• 3. Generalized immunosuppression. 

1.17.7 Diagnostic Tests for Felv 

Presently 3 tests are available for detection of p27 antigen 

1.17.8 Indirect immunofluorescence test 

This test detects p27 in infected leukocytes and platelets. There is a strong correlation between positive IFA results and ability to isolate infectious virus from blood and saliva. About 97% of IFA (+) cats remain viremic for life. False (-) IFA results may occur if smears are prepared poorly or low numbers of infected cells are present. False (+) results may arise from nonspecific immunofluorescence in eosinophils or in platelet clumps. There has bee a subgroup of cats identified that are IFA and ELISA (-) on blood samples, yet is strongly IFA (+) on bone marrow smears. 

1.17.9 ELISA test 

This test uses antibody-linked enzymatic color change to detect p27 antigen. Most of antigen detected is a soluble form. This test is more likely to detect weak, early or transient infections. False (+) ELISA reactions are usually due to inadequate washing of the test wells at each stage of the test. False (+) ELISA reactions may result from the presence of anti-mouse antibodies in the cat being tested. Healthy ELISA (+) cats should be evaluated with an IFA test before a long term prognosis is given. 

Healthy cats which ELISA (+) and IFA (-) on a single examination may be:

• 1. Undergoing a transient regressive infection.
• 2. Undergoing the early stages of a progressive infection.
• 3. Immune carriers of a localized infection.
• 4. May have a false (+) ELISA test.
• 5. May have a false (-) IFA test.

Differentiation of the first 3 groups is accomplished by repeating both tests 12 weeks after the initial detection of the discordant state. 

1.17.10 Noninvasive ELISA tests 

• 1. ClinEase-VIRASTAT from Norden Laboratories detects p27 in saliva.
• 2. Tear strip ELISA for home sampling 

1.17.11 FelV Antibody Assays 

• 1. Anti-gp70 antibodies - ELISA test, maintenance ofprotective levels requires periodic exposure to Felv. Single titer is of little prognostic value, but may be useful to detect recent infection. 
• 2. Anti-FOCMA antibodies - Indirect immunofluorescence test, cats with titers >1:32 may be protected against the neoplastic effects of Felv, high levels of anti-FOCMA antibody do not protect against viremia or the development of the more common nonneoplastic diseases caused by the virus.
•  3. Virus neutralization - ability of cat serum to prevent replication of a standardized quantity of Felv in an indicator cell line, available through specific laboratories. Subgroup neutralization can be detected with this test. This test is not cost effective for the practicing veterinarian. 

1.17.12 Treatment of Felv infections 

Palliative and symptomatic at the present time. No readily available methods to reverse persistent viremia. Experimental protocols have involved the use of extracorporeal removal of immune complexes, passive immunotherapy, biological response modifiers (fibronectin, blood constituent therapy), bone marrow transplantation, macrophage activation and macrophage transfer, reverse transcriptase inhibitor therapy (suramin, 3'azido-3' deoxy thymidine [AZT], dideoxycytidine]. In addition to specific therapy for any neoplastic or degerative disorders that may be present, the persistently viremic cat should receive aggressive therapy for opportunistic microbial infections which may be present. Bactericidal antimicrobials are preferred due to underlying immunosuppression. Corticosteroids should be used with great caution in viremic cats. 

1.17.13 Felv vaccination 

Two vaccines are presently available for the prevention of Felv infection (leukocell [Norden laboratories], covenant [Diamond Scientific]). The efficacy of both of these vaccines remains to be determined. A screening ELISA test should be taken before or at the time of first vaccine. Peripheral blood or buffy coat smears are reserved for an IFA test, should the ELISA test be positive. The vaccination of persistently viremic cats offers no benefits.  

1.18 EHRLICHIA PLATYS INFECTION 

1.18.1 Synonym:

Infectious Cyclic Thrombocytopenia 

1.18.2 Etiology

Ehrlichia platys, ricketsial organism that specifically infects platelets. It does not cross react with E. canis serologically although it is similar to E canis in ultrastructural appearance. Megakaryocytes donto seem to be parasitized therefore organism enters platelets after adhering. Thus far attempts to culture organism have been unsuccessful. Experimental transmission experiments have been successful. 

1.18.3 Epizootiology

Natural mode of transmission unknown. It is thought to be transmitted by the tick. There has been one reported case of a dog that was infected, therefore the host range is unknown. 

1.18.4 Pathogenesis

The incubation period is 8-15 days. Afterwards parasitized platelets are seen followed by a drop in platelet number to 20,000 cells/microliter. When the platelet count drops the parasite disappears from peripheral blood smears this is followed by an increase in platelets numbers. The parasite again becomes evident in platelets and the whole cycle of platelet decrease, parasite absence and platelet increase begins again. The parasitemia and thrombocytopenia continue to recur at 1-2 week intervals. The percentage of platelets infected decreases with each cycle but the thrombocytopenia remains as severe due to immune mechanisms. After a time the cyclic nature disappears and the animal become mildly thrombocytopenic, sporadic episodes of severe thrombocytopenia occurs occasionally. 

1.18.5 Clinical findings

The disease is believed to exist as a co-infection with E. canis or Babesia. If this occurs more severe clinical signs occur than those listed below. As a single infection there is an increase in rectal temperature, blood in the feces, bleeding tendencies (extra bleeding on venipuncture or after surgical procedures). While the clinical signs may not be lifethreatening it should always be considered in a differential list for thrombocytopenia.

 1.18.6 Diagnosis

This is based on finding the organism in platelets of infected animals on stained blood films. An IFA serological assay has been explored

 Therapy - Possibly tetracyclines are effective but experimental therapy has not been evaluated.

 1.19 RICKETTSIA RICKETTSI INFECTION

 1.19.1 Synonyms

Rocky Mountain Spotted Fever, RMSF

1.19.2  Etiology

Rickettsia Rickettsi - There are two other antigenically related rickettsia that must be tested for serologically when rickettsia rickettsi is suspected. 

1.19.3 Epizootiology

This organism is transmitted by three ticks Dermacentor andersoni, D. variablis, Rhipicephalus sanguineous. The susceptible tick becomes infected while feeding side by side with an infected. There is not usually enough organisms in the blood to infect an adult tick unless the dog is infested with ticks carrying the organism. However since the organism is transovarially transmitted the offspring of the tick may have enough organisms in it to transmit infection. The sylvan cycle between immature ticks and small rodents is important in outbreaks and maintenance of organism in the environment. Dogs are important carriers of infected ticks for other dogs and humans. Outbreaks are sporadic. The tick requires high humidity, warm temperatures, and increased vegetation. Disease when seen is seen in April-September. During the periods of cold the rickettsial organism becomes inactive. Therefore after a cold winter an infected tick cannot immediately infect a new host unless attached for a minimum reactivation period of 5-20 hours. Dogs may be affected subclinically. These dogs are probably present in households in which there is a clinical human infection. 

1.19.4 Pathogenesis

Infected tick transmits the organism while feeding on a susceptible host. There is replication of the rickettsia in the endothelial cells of small blood vessels. This leads to a vasculitis and subsequent vasoconstriction. Endothelial damage leading to increased vascular permeability and increased plasma loss. The damaged endothelium leads to microvascular hemorrhage thrombocytopenia, and disseminated intravascular coagulation. This process is enhanced by immune complex formation. The end result is hypotension leading to shock, petechial hemorrhage, decreased renal perfusion, azotemia, and organ damage.

1.19.5 Clinical findings

The disease is usually subclinical. Severe clinical signs are associated with a high innoculum of rickettsiae. Clinical signs occur more rapidly than E. canis. Signs of severe disease include fever, vomiting, diarrhea, and depression occurring 2-3 days following tick inoculation, later during the course of illness then scleral injection, conjunctivitis, mucopurulent oculonasal discharges, non-productive coughing, weight loss dehydration, lymphadenopathy, depression and muscle or joint tenderness. Signs related to the thrombocytopenia are petechia and ecchymotic hemorrhages of the mucous membranes and depigmented areas of the body, epistaxis, melena, and hematuria. Ocular lesions consist of retinal hemorrhages and anterior uveitis. Early cutaneous lesions consist of edema, hyperemia of lips, sheath of penis, scrotum and dependent portions of the body. Neurologic signs consist of lethargy, confusion stupor, convulsions, coma, paraparesis, ataxia, and hyperesthesia. Shock, cardiovascular collapse, oliguria are apparent during terminal stages of the disease. 

Hematology and Biochemistry - Mild leukopenia that progresses to severe leukocytosis as the disease progresses. Thrombocytopenia is the most consistent finding. There is a normocytic normochromic anemia and an elevated erythrocyte sedimentation rate. Hyperfibrogenemia occurs in dogs with DIC. There is an increase in SAP, SGPT, SGOT, cholesterol and a decrease in albumin, Na, and Cl. There is an associated metabolic acidosis. Clotting abnormalities occur in the face of DIC. In terminal stages there is an increase in the BUN with proteinuria and oliguria. In the CSF there is an increase in protein and PMN's. In dogs where there the muscle is affected there may be an increase in the CPK. 

1.19.7 Electrocardiographic changes

ST segment and T wave depression 

1.19.8 Thoracic radiographic changes

diffuse interstitial infiltration pattern 

1.19.9 Differential diagnoses

Same as E. canis 

1.19.10 Serology

Weil Felix test is not specific but may be used as screening test. For this test the antibodies increase the second week of infection and remain high.

Complement fixation is the primary test in human. This requires paired serum samples titers with a four fold rise over 2-3 week postinfection sample.

1.19.11 Microimmunofluorescence test

MIF test is a IFA test that can distinguish R. rickettsi from the other two antigenically similar rickettsiae. It also has the advantage that it classifies the antibody on the basis of IgM or IgG. Paired serum samples must be run at the same time. Unaffected dogs have titers of <1:64. Infected dogs have titers > 1:128. Active infection is indicated by an increase in titer from > 1:128 to >1:32,768. High titers decrease after 3-5 months but may remain above exposed levels for at least 10 months. 

1.19.12 Rickettsial isolation

Monocyte cultures on clotted blood, liver, spleen, and brain can be performed. These tissues may also be used to infect chick embryo culture to detect rickettsial organism. Organisms in culture can be detected by direct immunofluorescence. This detection is usually accompanied by paired serum samples for MIF.

1.19.13  Therapy

Tetracyclines 22mg/kg tid. Chloramphenicol 15-20 mg/kg tid. Clinical improvement occurs within 12-48 hours, organ failure, lymphadenopathy, and spleenomegaly takes longer to resolve. Therapy is aimed at decreasing the amount of organism until the immune response is able to clear the organism. Supportive care - Intravenous fluid therapy must be used with caution due to increase vascular permeability. Expanded fluid volume may lead to pulmonary and cerebral edema.

 1.19.14 Prevention

Avoidance of tick infested areas, rapid removal of ticks from animal, repeated dips during April to September, and application of insecticides or dust to surrounding vegetation to decrease tick population. A new experimental tissue culture origin vaccine shows some promise in laboratory animals. Dogs recovering are immune to infection for 6-12 months later.

1.19.15  Public Health Considerations

Increase possibility of infection due to increase contact with infected ticks on dogs. Infection is known to also occur through intact of abraded skin and conjunctiva. Effluents from ticks are highly infectious so handling of ticks should be avoided as removed from pets. 

1.20 LEPTOSPIROSIS 

1.20.1 Synonyms:

Canicola fever, Weils Disease, Stuttgarts disease, Canine typhus 

1.20.2 Etiology:

A gram negative spirochete is the causative agent of leptospirosis. All pathogenic letospires are classified as Leptospria interogans. This species includes 16 serogroups and 150 serovars. The serovars of importance in the dog are Leptospira canicola, and L. icterohemorrhagiae within U.S. Outside U.S. L. ballum, L. gryptyphosa, L. autumnalis, L. bataviae, L. janvanica and others. L. pomona rarely ever involved in the canine disease. 

1.20.3 Transmission:

Both direct and indirect transmission can occur. Routes of direct transmission are venereal, bite wounds and ingestion of infected meats. The most common portals of entry are the nasal mucosa and conjunctival sac. Oral ingestion of Leptospira is a less common route of entry. Infected dogs can shed Leptospira in their urine for up to 3 years (more commonly 6-18 months). The rat is an asymptomatic carriere of L. icterohemorrhagiae but not L. canicola. Indirect transmission can occur from contaminated vegetation, oil, food , water, and bedding. The organism can survive for several weeks under optimal conditions. Optimal conditions are a warm wet environment with neutral or alkaline water. Incidence is higher in summer and early fall. The organism is susceptible to iodine based disinfectants. 

1.20.4 Susceptibility:

The dog is obviously susceptible as are many specieis of animals (including cattle, sheep, pigs and wild animals, etc) The cat very rarely suffers from clinical Leptospirosis and some feel the cat possesses a species immunity. The dog can serve as a reservoir host for Leptospirosis of man. The disease is most common in young adult (18 mo.-3 years) male dogs. 

Incubation Period: Experimental and probably natural infections have an incubation period of 7-19 days; however, Leptospira may be cultured from the blood prior to the appearance of clinical signs. 

1.20.5 Signs:

The majority of dogs infected with Leptospira species show no clinical signs (inapparent infection). The early signs of Leptospirosis - fever, depression, anorexia - cannot be differentiated from those of CD, ICH, and many other canine diseases. Leptospirosis may be acute, subacute, or chronic and a wide variety of clinical signs may be seen. In addition to fever, depression and anorexia an infected and ill dog may show any one or several of the following signs: vomiting, diarrhea, dehydration, petechial to ecchymotic hemorrhages on visible mucous membranes, iritis, conjunctivitis, coughing, hematuria (not hemoglobinuria), jaundice, death.

1.20.6 Course of disease:

In fatal cases, death may issue in 4 days or the patient may linger for 7-10 days. Recovery is never rapid and although the patient may show signs of improvement in 7-10 days, it will take 4 months for kidney function to return to normal.

 1.20.7 Lesions:

A wasted carcass with signs of dehydration. Hemorrhagic lesions on all serous and mucous surfaces plus a hemorrhagic enteritis from cardia to anus. Fatty degeneration of the liver and acute or chronic nephritis.

1.20.8  Differential diagnosis:

Kidney function tests and urinalysis are important guides to diagnosis and prognosis. Liver function tests are less reliable for this purpose. Early leucopenia followed by leucocytosis on 4th to 5th day of illness. Rapid sedimentation rate. Thrombocytopenia, specific tests include darkfield examination of the urine, animal inoculation, blood and urine culture, agglutination, agglutination-lysis, and fluorescent antibody tests. 

1.20.9 Treatment:

Supportive fluids and perhaps blood transfusions. Specific treatment includes penicillin (50,000 IU/lb body weight/day). Tetracyclines are perhaps better for some species of Leptospira as L. sejoe, gryptyphosa, and mitis. Streptomycin (7-10 mg/lb/bid) is used to eliminate the carrier state and should be given for at least 7-10 days.

1.20.10  Prophylaxis:

Commercial bacterins. One, two or three doses at two week intervals followed by annual revaccination.

1.20.11  Public Health Considerations

• 1. Leptospirosis is thought to be the most widespread zoonosis.
• 2. Contaminated urine is highly infectious to humans and animals.
• 3. Contaminated areas should be washed with detergent and treated with iodine-based disinfectants.
• 4. Animals that are shedding organisms should be treated wit dihydrostreptomycin of streptomycin. 

1.21 CANINE BRUCELLOSIS 

1.21.1 Synonyms:

Canine abortion, Epizootic Canine abortion, Contagious Abortion of dogs, Beagle fever

 1.21.2 Etiology:

Brucella canis a small, gram negative coccobacillus. The organism is relatively short-lived outside the dog and is readily inactivated by common germicidal disinfectants.

 1.21.3 Transmission:

Both direct and indirect. Venereal transmission occurs. The seminal fluid of the male dogs has been incriminated as a vehicle of venereal transmission. Oral infection as a result of ingestion of aborted feti, mammary secretions, placental tissues of vaginal discharges of infected female is most frequent a mode of transmission.

1.21.4 Susceptibility:

Dogs of all breeds and mixed breeds (infection is significantly higher in stray dogs than in single dog households). Man is mildly susceptible. Foxes are susceptible to experimental infection.

1.21.5  Incubation period:

Difficult to evaluate. Dog or bitch may demonstrate a bacteremia 1-3 weeks after oral infection yet bitch may not show signs (abortion) until bred 6 months to a year post infection. 

1.21.6 Clinical Signs:

Abortion, without precursing signs, at 30th to 57th day of pregnancy (85% of abortions fall with the 44th-55th day of pregnancy) in the bitch. Persistent vaginal discharge for 1-6 weeks after abortion. Males may show scrotal swelling, epididymitis and painful, swollen testicles plus a scrotal dermatitis. Testicular atrophy may occur. Abnormal sperm (80-90%) appear in ejaculate of males 2-20 weeks post infection. 

1.21.7 Course of disease:

Infection is prolonged, likely for 1-2 years, Recovered animal are immune to reinfection.

1.21.8 Lesions:

Lymphadenitis, testicular atrophy in males.  

1.21.9 Diagnosis:

Plate (slide) and tube agglutination test and blood culture. Plate test is set to record only as positive those animals with a tube agglutination of 1:200 or more. A negative slide agglutination test is 99.7% specific; however, a positive slide agglutination test is only 62.5% accurate and a diagnosis therefore should not be based on a positive slide agglutination test. 

1.21.10 Treatment:

Treatment is of questionable value and may produce a false sense of security insofar as potential transmission to dogs or man is concerned. The following regimen has been reported as successful in some instances.

Tetracyclines 60mg/kg/day divided tid for 3 weeks rest 3-4 weeks and then repeat Tetracycline dosage and include Streptomycin at 40mg/k