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CHAPTER 1 - COMPANION ANIMAL HEALTH PROBLEM
This chapter provides a brief overview of some major health problems affecting dogs, cats and horses, and outlines current methods of prevention, treatment or control. It is not intended to be comprehensive - rather, it addresses conditions that either generate substantial demand for animal health products or are driving the development of new or growing market niches.
Products indicated for the management of individual conditions are discussed in detail in chapter 2 of the study.
1.1 Infectious diseases
Companion animals face challenges from a broad range of infectious pathogens, with causative agents including viruses, bacteria, mycoplasmas and protozoa. Prophylaxis against many viral infections and some parasite species (mainly protozoa) is available in the form of vaccines or toxoids. Prevention has traditionally been achieved through the regular administration of multivalent products offering protection against a range of pathogens. The current trend - especially in the US - is towards more tailored vaccination protocols, however, while periods between the administration of booster vaccine doses are also being increased.
Bacterial infections are common in all three major companion animal species. They often occur as secondary or opportunistic infections following challenge with a viral disease. They are also a threat at open wound sites caused by environmental or surgical trauma, or by dermatological problems.
Common sites of bacterial infection include the respiratory, urogenital and gastrointestinal tracts, the oral cavity, skin and soft tissues. Anti-infective drugs are administered to combat existing bacterial infections and, during surgery or following trauma, to prevent infection at wound sites.
Skin infections are a common problem in both dogs and cats, with pyoderma - which often involves infection with more than one organism - among the most widely diagnosed skin diseases. Allergic conditions may also expose animals to skin infections, with flea allergy dermatitis (FAD) representing one of the most widely-recognized causes.
1.1.1 Canine infectious diseases
Routine vaccination of dogs against a range of common (mainly viral) pathogens has traditionally been advised, usually through the administration of multi-valent products, while vaccination of companion animals against rabies is compulsory in some parts of the world. Protection is conferred initially through the vaccination of puppies before they are exposed to environmental infection, with regular booster shots administered to adult dogs. Products offering protection against other 'non-core' infections may also be administered according to prevailing patterns of disease incidence and the lifestyle of individual animals.
In recent years, concerns have been raised that 'over-vaccination' of pets may be contributing to subsequent health problems, and might also be generating unnecessary expense for owners. As a result, the veterinary profession has also begun to take a more discerning approach to vaccination protocols for individual animals and, pressured by owners, has also begun to extend periods between the administration of booster vaccines. The net result is that many animals are being vaccinated against a slightly narrower range of pathogens, and that protection is being conferred increasingly via mono- or divalent products rather than the multivalent vaccines that previously dominated the market.
1.1.1.1 Bordetella bronchiseptica
Bordetella bronchiseptica is the most common bacteria isolated in dogs suffering from infectious tracheobronchitis, or kennel cough. B. bronchiseptica can act as a primary pathogen, especially in puppies, but is more often a secondary cause of infection in what often develops into a multi-factorial disease condition.
B. bronchiseptica bacterins containing live avirulent bacteria are administered to at-risk animals (usually those housed in kennels or other crowded environments). These are often part of divalent products that also contain a canine parainfluenza vaccine fragment. Intranasal vaccination is the preferred method of administration for such products.
1.1.1.2 Coronavirus
The canine coronavirus is an RNA virus related to the feline coronaviruses, feline infectious peritonitis (FIP) virus and feline enteric coronavirus. Coronaviral gastroenteritis, which is highly infectious, is characterized by vomiting and diarrhea. Asymptomatic coronaviral infection may cause damage to the intestinal epithelium of affected animals, and can also increase the severity of opportunistic enteric infections.
Vaccines against canine coronavirus (usually inactivated) have been available for some time, but the prevalence of clinical disease associated with CCV infection is generally considered to be extremely low - even in animals boarded in crowded kennel environments. As a result, this is among the targets that is increasingly being dropped from vaccination regimes recommended by the veterinary profession to animal owners in some countries.
1.1.1.3 Distemper
Canine distemper is caused by a paramyxovirus related closely to the measles and rinderpest viruses. Only one antigenic type is known to exist, but differential syndromes may be associated with particular strains. Some suppress or impair the immune system, leading to complicating secondary infections.
Distemper is highly contagious, since the virus is spread via aerosol droplets exhaled by infected animals. Viral replication occurs initially in the lymphatic tissue of the respiratory tract. Infection is characterized by a diphasic fever, inflammation of the gastrointestinal and respiratory tracts, and leukopenia.
Vaccination (usually with modified live virus products) is recommended in puppies. The trend is away from annual booster doses to less frequent vaccination in adult animals, however, and products with proven three-year duration of immunity are now available commercially.
1.1.1.4 Hepatitis
Canine viral hepatitis, which is associated with liver, kidney, eye and respiratory disease, is caused by canine adenovirus type 1 (CAV-1), a non-enveloped DNA virus. Most adult dogs recover from infection, but viral hepatitis is often fatal in young animals. As a result, routine vaccination is recommended in puppies, beginning at six to eight weeks through to around three months of age. Protection is usually provided via combination vaccines that also include distemper virus fractions.
1.1.1.5 Influenza
A new strain of the influenza virus (H3N8) related closely to the equine influenza virus was identified in US racing greyhounds during 2004, and spread to the general canine population in parts of the country during 2005. Mortality in some populations was reported at rates in excess of 5%, but was generally much lower.
Symptoms in clinically affected animals resemble closely those associated with kennel cough, and veterinary surgeons were urged by the US Centers for Disease Control to consider differential diagnosis where dogs presented with cough and nasal discharge. Work on the development of a vaccine against the new viral strain is being undertaken, but no product is available commercially to date.
1.1.1.6 Kennel cough
Canine infectious tracheobronchitis, or kennel cough, is an acute respiratory disease usually resulting in laryngitis, tracheitis and bronchitis. Any one or a combination of viral pathogens, bacteria and mycoplasmas can cause the condition, though canine parainfluenza virus, adenovirus (usually CAV-2), herpesvirus and the Bordetella bronchiseptica bacterium are isolated most commonly in affected animals. B. bronchiseptica may act as a primary pathogen, but is more often a trigger for secondary infections where other pathogens are involved (see above).
Kennel cough usually takes the form of a relatively mild but often persistent respiratory infection. It affects animals of all ages, causing loss of appetite, lethargy and loss of condition. Secondary infection can lead to fatal bronchopneumonia in puppies, or to chronic bronchitis in older dogs. The infection spreads rapidly among susceptible animals housed in close confinement, while stress and climatic extremes can increase the severity of clinical disease. Vaccination of at-risk animals is recommended.
1.1.1.7 Leptospirosis
Leptospirosis is an acute bacterial disease that can cause haemorrhagic enteritis, kidney failure and stomatitis. Leptospira canicola, L. icterohaemorrhagiae and L. interrogans are among the most common causative organisms in dogs. Clinical signs of infection include weakness, vomiting, fever, jaundice, loss of appetite, depression and pinpoint haemorrhages around the lips and mucous membranes.
Rodents, which are common carriers of the disease, excrete leptospira organisms in their urine. Warm, damp conditions encourage their survival in the environment. Once circulating in a canine population, they are usually spread via the urine of affected animals, which remain contagious for some time after they have recovered from the disease.
Inactivated vaccines against some of the most common serovars are available for use in dogs, but the inclusion of leptospirosis cover in routine vaccine protocols has been a matter of some discussion in recent years. Increases in the incidence of the disease in the US canine population towards the end of the 1990s were attributed in some quarters to a reduction in the number of dogs being vaccinated against leptospirosis, however, and many veterinary surgeons still recommend its inclusion in protocols. Vaccines may not prevent infection, but they do reduce the severity of clinical disease significantly.
1.1.1.8 Lyme disease
Lyme disease is a tick-borne, immune-mediated inflammatory condition caused by the spirochete, Borrelia burgdorferi. Major vectors include Ixodes dammini, I. pacificus, I. ricinus and I. scapularis.
Lyme disease can affect dogs, cats, horses and a range of other domesticated and wild mammals. It is also zoonotic in nature, which has raised the profile of the infection, contributing to relatively widespread vaccination of dogs in countries such as the US.
Clinical signs of infection include arthritis and fever, but anorexia and fatigue are also common. Arthritis is usually episodic, but may become chronic in some animals. Neurological, cardiac, renal and reproductive signs have also been observed. Removal of ticks can prevent infection, since they do not transmit B. burgdorferi immediately.
Vaccines against Lyme disease in dogs have been available for over a decade now, and have been administered widely to dogs in parts of the US where animals are deemed to be at particular risk of exposure. A recombinant vaccine allows administration of an initial dose to puppies at nine weeks of age, with a second dose recommended 2-3 weeks later. Annual booster doses are recommended for dogs in at-risk areas.
1.1.1.9 Parvovirus
Canine parvovirus is a single-stranded DNA virus related closely to feline panleukopenia virus. Infection is often asymptomatic, and clinical disease may be triggered by stress factors. Puppies aged between six and 20 weeks are most at risk of infection, since this is the period during which levels of maternal antibody decline and vaccination has not yet conferred protection.
Vomiting is often the first clinical sign of infection, with diarrhea usually occurring within 24-48 hours. Anorexia, lethargy and rapid dehydration are also common, though clinical signs vary and may be exacerbated by the presence of opportunistic enteric infections. Extreme cases can result in death within hours of clinical infection, but most dogs recover within a few days.
Canine parvovirus can remain viable in the environment for long periods, and vaccination is recommended almost universally as part of canine protocols. The duration of immunity provided by modified live virus vaccines has been the subject of some debate, however, and an increasing number of veterinary surgeons are switching away from annual booster regimes. The duration of immunity provided by inactivated products is briefer, and annual boosters are still recommended where these vaccines are used.
1.1.1.10 Rabies
Rabies is caused by a lyssavirus of the rhabdovirus group. It affects all warm-blooded animals and is present in all continents with the exception of Australasia. Viral transmission usually occurs through the bite of infected animals. The disease is one of the most serious zoonotic infections monitored by international health agencies, and vaccination programs involving both domesticated and wild animals are undertaken regularly in many countries.
Dogs are an important vector of the rabies virus in Asia and South America, where vaccination is compulsory in a number of countries. Wild animals are the most common causes of viral spread in Europe and North America, where baits containing rabies vaccine have been used widely as part of eradication programs.
1.1.1.11 Feline infectious diseases
Like dogs, cats are exposed to a number of infectious disease challenges against which they are vaccinated on a routine basis. Calicivirus, Chlamydophila, panleukopenia and rhinotracheitis are among the most common, though feline leukaemia, feline immunodeficiency virus and infectious peritonitis present serious, if less widespread challenges.
1.1.1.12 Feline influenza
Feline viral rhinotracheitis (caused by feline herpesvirus-1) and calicivirus are common causes of highly contagious, often multi-factorial respiratory infections referred to generally as feline influenza. Both are host-specific, and account together for more than three-quarters of all feline upper respiratory tract infections. Viral transmission occurs via aerosol droplets.
Clinical signs of FHV-1 infection include fever, frequent sneezing, conjunctivitis and rhinitis. Death is relatively uncommon, but infection is often more severe in kittens and older cats. It can also be complicated by secondary bacterial infections.
There are many related strains of feline calicivirus, ranging from some that are non-pathogenic to others that cause severe respiratory problems. The epithelium of the oral cavity and deep lung tissues are the main sites of infection, and ulceration of the oral mucosa is common in affected animals. More virulent strains can destroy bronchial epithelial cells and cause pulmonary oedema.
Vaccines against both major calicivirus strains and FHV-1 are administered widely, and are part of most feline vaccination protocols.
1.1.1.13 Chlamydophila
Chlamydophila psittaci is a bacterium responsible for a range of health problems in a number of species. In cats, infection usually affects the eye and the upper respiratory tract, causing conjunctivitis, rhinitis, sinusitis or pharyngitis. Fever may occur as the disease progresses, and some animals may experience relapses after apparent recovery.
Vaccines are available for use in cats, and are prescribed widely as part of feline vaccination protocols. They do not protect treated animals completely, but do reduce the severity of the disease and can also significantly reduce infection rates in at-risk populations.
1.1.1.14 Feline infectious peritonitis
Feline infectious peritonitis (FIP) is a progressive, contagious viral disease that is usually fatal in clinically infected animals. Infection is characterized by fibrinous polyseositis, accumulation of fluid in body cavities, disseminated pyogranuloma formation, hypergammaglobulinaemia and immune-mediated phenomena.
The feline infectious peritonitis virus is a mutant of the more common form of feline coronavirus, and is often generated during primary or secondary coronavirus infection. Virus is shed in the faeces, saliva and urine of affected animals, through direct contact, and possibly by maternal transmission. The vast majority of cats exposed to coronavirus become infected with FIP, but only about 10% develop the clinical form of the disease. A vaccine against the FIP virus has been available commercially since the early 1990s.
1.1.1.15 Feline leukaemia
Feline leukaemia virus (FeLV) is a major cause of morbidity and mortality in cats, despite the widespread use of vaccines against the disease. Three subgroups of the virus are recognized. Type A viruses, which are found in all naturally infected cats, are generally less pathogenic than other subgroups. Type B viruses are isolated in around half of infected animals, while type C viruses are uncommon, being isolated in only 1% of cases.
FeLV causes several different disease syndromes, including leukaemia, anaemia, tumors, reproductive failure and neurological problems. The simultaneous presence of viral subtypes A and B is often associated with tumor development, while subtype C is associated with erythroid hypoplasia, leading to severe anaemia.
Infected animals either develop a persistent infection or recover and acquire immunity. Persistently infected animals are the main reservoir of the virus, the incidence of which is related directly to feline population densities. Virus is excreted in saliva, tears, urine and faeces.
Persistently infected cats frequently become emaciated, suffering from anaemia, lethargy and anorexia. Most eventually die as a consequence of the acquired immunodeficiency syndrome, feline immunodeficiency virus (FIV).
Diagnostic tests for FeLV are available, but are not capable of differentiating between viral subtypes. Vaccines against the disease have been available since the 1980s. The second-generation products available today offer significantly improved levels of protection against the development of persistent viraemia.
1.1.1.16 Panleukopenia
Feline panleukopenia (also known as infectious enteritis or feline distemper) is caused by a highly infectious parvovirus similar to the mink enteritis virus. It is a highly contagious, sometimes fatal condition. Mortality rates are especially high in kittens. Clinical signs of infection include fever, depression and anorexia, followed by the development of vomiting and diarrhea. Virus is shed in the urine and faeces of affected animals for several weeks after apparent recovery, and is present in all secretions.
Antibodies to feline panleukopenia virus (FPV) are found in a high proportion of unvaccinated cats, and most infections are subclinical. It is often more serious in young animals, however, with mortality rates among young, unvaccinated kittens sometimes reaching 90%. Widespread vaccination means that the disease is now observed relatively infrequently in most developed markets.
1.1.1.17 Feline immunodeficiency virus
Feline immunodeficiency virus (FIV) is a lentivirus that was first isolated in 1986. It is endemic in free-roaming cats, with rates of infection exceeding 10% in some areas. FIV often develops in cats with persistent feline leukaemia infection, but the virus can also be transmitted independently of FeLV. Virus is shed mainly in the saliva of affected animals, and bites are the principal mode of transmission. As a result, the lifestyle of individual animals has a major bearing on their degree of risk to exposure, with free-roaming male and elderly animals most widely affected.
Most cats recover from an initial syndrome that includes fever, lymphadenopathy and neutropenia, and may show no clinical signs of disease for months or even years. Infection is permanent, however, and an unknown proportion of affected animals eventually succumb to an immunodeficiency syndrome that results in chronic secondary or opportunistic infections of the respiratory, gastrointestinal and urinary tracts as well as the skin.
Diagnostic tests for FIV are available commercially, and a vaccine against the disease was brought to market by Fort Dodge at the beginning of this decade. The similarity between FIV and the human immunodeficiency virus (HIV) has elicited much interest in the human medical research community, and recent studies in the US appear to show that vaccines against the respective viruses may offer a certain level of protection in both species. Scientists at the University of Florida college of veterinary medicine, where FIV was discovered, and where the feline vaccine was developed, vaccinated cats with an experimental strain of HIV vaccine. Results showed that they were at least as well protected against FIV as animals immunized with the commercially available veterinary vaccine.
1.1.2 Equine infectious diseases
Horses are particularly prone to respiratory syndromes caused by equine influenza virus and the equine herpesviruses 1 and 4 (EHV-1 and EHV-4), and these pathogens are among the most common causes of equine infectious disease. Vaccination against these and a number of other common infectious diseases is practised widely, while immunological products offering protection against some other infections have also reached the market recently.
1.1.2.1 African horse sickness
African horse sickness (AHS) is an acute or sub-acute viral disease characterized by signs of respiratory and circulatory impairment. Transmission of the orbivirus responsible for the condition is via arthropods, with Culicoides spp representing the principal vectors. Nine immunologically distinct viral types have been identified.
AHS is endemic to the African continent, and has been recorded in the Middle East and parts of southern Europe. Outbreaks usually follow periods of heavy rain that alternate with hot and dry conditions. Mortality can reach up to 90%, depending on the virulence of the viral strain involved in an outbreak and the susceptibility of affected animals. Rates of mortality are highest where the acute respiratory form of the virus is involved. Clinical signs of infection include high fever followed by dyspnea and spasmodic coughing. Death usually occurs within a week of the first clinical signs.
Vaccines are available for the protection of horses against all nine serotypes of the virus, while insecticides are used to control arthropod vector populations in susceptible areas. Affected animals are slaughtered immediately following the confirmation of an outbreak, while unaffected animals are vaccinated. Most countries in which the disease is regarded as an exotic infection impose strict quarantine requirements on horses imported from affected areas.
1.1.2.2 Equine encephalomyelitis
Arboviruses are the most common cause of equine encephalomyelitis, but Sarcocystis neurona and Neospora spp may also cause encephalitis. Virus is carried by mosquitoes and other insect vectors, and can affect a range of vertebrate hosts, including humans. In horses, infection is characterized by signs of CNS dysfunction, and results in moderate-to-high rates of mortality.
The most pathogenic viruses affecting horses are alphaviruses of the family Togaviridae, including Eastern, Western, Highlands J and Venezuelan viruses. The North American variant is the most pathogenic and antigenically homogenous of two distinct antigenic variants of Eastern equine encephalomyelitis (EEE). It is found in eastern areas of Canada and the US, and in the Caribbean islands. The South American variant is less pathogenic. Mortality resulting from infection with the North American strain can reach 90%. Clinical signs of infection include lymphopenia, leukopenia and fever. Neurological signs usually become evident at a later stage.
Insecticides and other insect control strategies are used to reduce the risk of infection in areas where the virus circulates. Vaccines are also available in both mono- and multivalent form. Vaccination protocols usually consist of an initial two-shot regime followed by annual or biannual boosters, depending on geographical risk factors.
1.1.2.3 Equine infectious anaemia
Equine infectious anaemia (EIA) is an acute or chronic viral disease that affects horses worldwide. The virus responsible for the disease is related to the human immunodeficiency virus (HIV), but is not known to be zoonotic. Transmission occurs via the transfer of blood cells from infected animals. EIA is usually detected sporadically, but epidemics may occasionally be witnessed when blood-sucking fly populations are particularly abundant.
Clinical signs of infection with EIA include intermittent fever, depression, weakness, weight loss, oedema and progressive or transitory anaemia. Mortality is relatively infrequent, and many affected animals may not exhibit clinical signs of infection. Nevertheless, testing and control programs are operated in many countries, with animals testing positive for the disease being quarantined or slaughtered.
Experimental vaccines against EIA have been developed and trialled, but providing complete protective immunity against infection remains a challenge, and no vaccine has yet been made available commercially.
1.1.2.4 Equine influenza
Equine influenza is an acute, highly contagious respiratory disease caused by Orthomyxoviridae type A influenza viruses. Two distinct viruses (Orthomyxovirus A/Equi-1 and Orthomyxovirus A/Equi-2) have been found in equine populations across much of the world. They are endemic in many countries, causing sporadic clinical cases and mild infection in susceptible horses. Viral transmission occurs through contact with infective respiratory secretions.
Onset of the disease is abrupt, with a fever that usually lasts less than three days in uncomplicated infections. Coughing is a common clinical sign, and may last for several weeks, especially where secondary bacterial infections are involved. Mildly affected animals usually recover in 2-3 weeks, but severely affected horses may take several months to recover fully. Mortality is rare, and is usually the result of complications caused by secondary infections.
Vaccines against both viruses are available, and are used widely, especially in areas where large equine populations are kept in close proximity (usually Thoroughbred training centres). Levels of efficacy and duration of immunity provided by some vaccines are relatively limited, however, due to antigenic drift, which has resulted in the emergence of new viral strains. Several leading vaccine manufacturers have updated their equine influenza products in recent years in a bid to provide improved levels of protection against major strains encountered in Europe and North America.
1.1.2.5 Equine protozoal myeloencephalitis
Equine protozoal myeloencephalitis (EPM) is a neurological disease caused by the protozoan parasite, Sarcocystis neurona. The disease is prevalent in North America and parts of South America, but has not been recorded elsewhere except in horses exported from affected countries.
Infection is via the ingestion of sporocysts contained in contaminated feed or water. S. neurona can infect all parts of the central nervous system, and neurological signs of infection vary. Treatment with antifolate drugs such as sulfadiazine or sulfamethoxazole, in combination with pyrimethamine, is indicated in affected animals. Bayer introduced a new EPM treatment containing ponazuril at the beginning of this decade.
1.1.2.6 Equine viral arteritis
Equine viral arteritis (EVA) is an acute, contagious disease caused by an RNA virus of the Arterivirus family. Only one serotype has been identified, but antigenic variation has been observed in isolates from different countries.
Viral transmission is largely via respiratory or venereal routes, with aerosol transmission from infected animals implicated in most cases. Outbreaks are relatively uncommon, but are often associated with the movement of horses.
Most cases of acute infection are sub-clinical, and clinical signs of infection vary widely in both nature and severity. Leukopenia, depression, anorexia and limb oedema may all be associated with infection. Clinical signs are usually more severe in young, old or weak animals. Abortion may occur in the acute phase of the disease, and can also affect sub-clinically infected mares. Abortion rates are usually less than 10% in affected populations, but have been known to reach 50%.
Modified live virus vaccines are available for the protection of horses against EVA, but are not recommended for use in pregnant mares. Symptomatic treatment in severe cases usually includes the administration of antipyretic, anti-inflammatory and diuretic drugs.
1.1.2.7 Equine viral rhinopneumonitis
Infection with equine herpesviruses 1 and 4 (EHV-1 and EHV-4) can cause respiratory disease, abortion, neonatal death and paresis. The respiratory form of the infection, known as equine viral rhinopneumonitis (EVR), is characterized by fever, coughing and nasal and ocular discharge. The severity of the disease is dependent on the viral strain involved, the immune status of affected animals, pregnancy status and, in some cases, age.
Transmission occurs most frequently via direct or indirect contact with infective nasal discharges, but infection can also be contracted following contact with aborted foetuses, placentas or placental fluids. Some infected animals appear to be latent carriers of both virus types.
Vaccines are available against both EHV-1 and EHV-4. Reliable humoral immunity is not long lasting, however, and not all strains to which horses may be exposed are covered by available vaccines.
1.1.2.8 Strangles
Strangles, or equine distemper, is a bacterial infection caused by Streptococcus equi equi. Infection, which is characterized by inflammation of the upper respiratory tract and the development of abscesses on adjacent lymph nodes, is via inhalation or ingestion of S. equi equi. Toxins released by the organism cause inflammation of the respiratory tract, followed by lymphadenitis. Mortality is rare, but morbidity can reach 100% in equine populations not previously exposed to infection.
Vaccines against strangles are available, but do not always prevent infection. The disease takes a milder form in vaccinated animals, however. Intervet has introduced a new live bacterial vaccine developed using recombinant DNA technology in Europe recently.
1.1.2.9 Tetanus
Horses are particularly susceptible to the neurotoxin of Clostridium tetani, which can cause tetanus in a broad range of species. Infection of wounds with clostridial spores is the most usual cause of the disease, with clinical signs of infection including hyperaesthesia, tetany and tonic convulsions.
Vaccination with the toxoid confers immunity against infection, and is practised widely. Tetanus toxoids are often administered as part of combination products that also contain equine influenza vaccine components.
1.1.2.10 West Nile virus
West Nile fever is a zoonotic disease caused by infection with the flavivirus, West Nile virus. Wild birds and horses are among the most commonly affected species, with viral transmission occurring via insect vectors (often mosquitoes). WNV is common in parts of Africa and Asia, and has been present in North America since the late 1990s, with several human deaths reported as a result of infection there.
In horses, clinical symptoms of infection usually include weakness, ataxia, depression, fever, tremors and reduced appetite, though some affected animals show few or no signs of infection. Paralysis, recumbency and eventual death may occur in severe cases. Approximately 30% of US horses in which the disease has been confirmed have either died or been euthanized.
The number of equine cases reported in the US and Canada rose rapidly in the early years of this decade, but vaccines against the disease in horses are now available, and have contributed to a reduction in the incidence of WNV more recently.
1.2 Parasitic infections
Dogs, cats and horses face challenges from a range of both internal and external parasites. Even modest parasite populations can affect the condition and wellbeing of host animals while, left unchecked, some parasites can eventually cause severe health problems and even death. Effective parasite control is essential to the health and welfare of companion animals, and regular administration of antiparasitic products is recommended, though the type of medication and frequency of dosing may be dependent on geographic and climatic factors, as well as the lifestyle of individual hosts.
1.2.1 Endoparasites
Gastrointestinal nematodes, tapeworms, lungworms, heartworm, protozoa and larval stages of arthropods are among the internal parasite challenges faced by companion animal species. Endoparasites may inflict damage on the host animal directly, forming cysts, feeding on tissue or blood, or by larval migration. Damage to tissues and internal organs causes loss of condition and increases host animal susceptibility to secondary infections. Young animals are most susceptible to infection, but regular treatment of both young and adult animals with worming products is recommended.
Broad-spectrum anthelmintics from a range of chemical classes are used to treat and control infections. Many broad-spectrum products are not effective against tapeworms or heartworm, however. Active ingredients with specific activity against cestodes are available, and are included increasingly in combination products, while the use of drugs from the macrocyclic lactone class (avermectins and milbemycins) at low doses is effective in the prevention of adult heartworm infestation.
Table 1.1: Common endoparasites by host species
| Parasite | Dogs | Cats | Horses |
| GI nematodes | Toxocara canis Toxascaris leonine Ancylostoma caninum Uncinaria stenocephala | Toxocara cati Toxascaris leonine Ancylostoma tubaeforme Uncinaria stenocephala Trichuris spp | Paracaris spp Strongylus spp Trichostrongylus axei Oxyuris spp Habronema spp |
| Tapeworms | Dipylidium caninum Echinococcus granulosus Taenia hydatigena | Dipylidium caninum taenia taeniaeformis | Anoplocephala perfoliata Anoplocephala magna Anoplocephaloides mammillana |
| Lungworms | Oslerus osleri Angiostrongylus vasorum | Aelurostrongylus abstrusus | Dictyocaulus arnfeldi |
| Heartworms | Dirofilaria immitis | Dirofilaria immitis | |
| Protozoa | Leishmania spp Giardia spp | Toxoplasma gondii Giardia cati | Sarcocystis neurona |
| Bots | | | Gasterophilus spp |
The large roundworms, Toxocara canis (dogs) and T. cati (cats) are common in small animals, especially puppies and kittens. T. canis is most significant, causing occasionally fatal infections in untreated puppies. It can also be passed on to humans if infected eggs are ingested. In puppies, transplacental transfer is the most usual method of infection.
Hookworm infestation (Ancylostoma spp and Uncinaria spp) may result from the ingestion of infective larvae from the environment, but A. caninum, which is the most significant parasite of this type in most tropical and subtropical regions, is also passed to offspring through the colostrum and milk of infected bitches. U. stenocephala is the most common canine hookworm in cooler, more temperate regions. Hookworms feed on host blood, and congenital infection can cause anaemia and general debility in young animals.
The whipworm, Trichuris vulpis, usually inhabits the caecum of host animals. Eggs are passed in faeces and can remain viable for long periods in suitable conditions. Heavy worm burdens cause inflammatory reactions in the caecum, with weight loss and diarrhea often observed in affected animals.
Horses are susceptible to infection by a broad range of gastrointestinal parasites, including large and small strongyles, stomach worms and tapeworms. The three major species of large strongyle are Strongylus vulgaris, S. edentatus and S. equinus. Infection is through the ingestion of infective larvae, which migrate extensively before developing to maturity in the large intestine of host animals. S. vulgaris larvae migrate extensively in the cranial mesenteric artery, where they can cause parasitic thrombosis and arteritis. More than 40 species of small strongyles have been identified in horses. Most are significantly smaller than Strongylus spp, but some may be almost as large, and one of these - Triodontophorus tenuicollis - can cause severe ulceration of the colon wall.
Other common gastrointestinal parasites affecting horses include Strongyloides westeri, which can be a problem in young foals; the small stomach worm, Trichostrongylus axei, which can cause chronic catarrhal gastritis (a condition also associated with stomach worm infections); and the pinworm, Oxyuris equi.
1.2.1.2 Heartworms
Heartworm disease, or dirofilariasis, is caused by a filarial nematode, Dirofilaria immitis, whose immature stages are transmitted via insect hosts (usually mosquitoes). The parasite can affect a number of species, but its impact is most significant in dogs. Cats are also affected, however, and heartworm preventatives are administered to both species in areas where the risk of infection is significant. This includes parts of the US, Australia, Japan and southern Europe. The geographical extent of infection in Europe has spread gradually northwards in recent years.
Adult female parasites inhabit the right ventricle of the heart and adjacent large blood vessels, causing cardiovascular and pulmonary damage. Adult worms shed microfilariae, which are ingested by mosquitoes feeding on infected hosts. Clinical signs of infection include respiratory disease, exercise intolerance, weight loss and fever. Heavy worm burdens can cause heart failure in affected animals.
Adulticides may be administered to eliminate adult worms in infected animals, but this can cause serious complications in hosts with heavy parasite burdens. Regular treatment with avermectin or milbemycin compounds, which prevent the development of adult worms, is preferable, and is advised routinely in at-risk areas.
1.2.1.3 Horse bots
Horse bots are the larvae of botflies (Gasterophilus spp). Several minor species are recognized, but the common bot (G. intestinalis), lip bot (G. haemorrhoidalis) and nose bot (G. nasalis) are most important. The larvae of all three species remain embedded in the tongue or oral mucosa before migrating to the stomach, where ulceration may be caused at attachment sites. They eventually pass out in the faeces of host animals and pupate in the soil for a period of several weeks before emerging as adult botflies. Products from the avermectin and milbemycin chemical classes are effective bot controls.
1.2.1.4 Lungworms
Lungworms affect the lower respiratory tract of host animals, causing bronchitis or pneumonia where parasite loads reach significant levels. Dictyocaulus arnfeldi is the parasitic nematode responsible for lungworm infection in horses. It can cause severe coughing and lung lesions. Differential diagnosis with problems caused by other respiratory conditions can be difficult.
In dogs, the tracheal worm, Filaroides (Oslerus) osleri is the most commonly observed lungworm parasite. Infected bitches often pass on infection to their offspring through saliva. Larvae pass into the bloodstream of host animals and are carried to the lungs and bronchi. A dry cough is the most common symptom of infection.
Aelurostrongylus abstrusus is the most common lungworm parasite found in cats. Worms become deeply embedded in the lungs of affected animals, and eggs are forced into alveolar ducts, where they form small nodules. Once hatched, they are coughed up, swallowed or passed out in the faeces.
1.2.1.5 Protozoa
Of the protozoan parasites that affect companion animals, Leishmania spp, which are responsible for the zoonotic disease, leishmaniasis, are among the most significant. Cats and a number of other domestic species are rarely affected, but dogs are a common host. Leishmania donovania and L. infantumi are implicated in the Mediterranean region, while L. chagasi, L. brazilensisi and L. mexicana are most important in central and south America.
Infection in dogs is prevalent in both regions, while several areas of the US are also affected. Leishmaniasis is a visceral, often fatal disease characterized by cutaneous or mucocutaneous lesions, intermittent fever, anaemia, enlarged lymph nodes, weight loss, lameness and renal failure.
A vaccine against leishmaniasis in dogs has been developed by scientists in Brazil, and was approved for commercial use there in 2003. It is marketed by Fort Dodge Animal Health. Work on human vaccines is also under way in several countries. An estimated 200,000 people a year are killed by visceral leishmaniasis.
Toxoplasmosis caused by the zoonotic protozoa, Toxoplasma gondii, is often spread from cats to sheep, and is a common cause of abortion in the latter species. In cats, infection can be fatal, though subclinical infection is more common. Infected pregnant women can pass the parasite on to their children, where it can cause blindness and mental retardation. Researchers at the University of Illinois (US) are among those working on the development of toxoplasmosis vaccines for use in cats.
Giardiasis is a chronic intestinal infection caused by Giardia spp. Infection is common in dogs and cats, but is also seen in other species, including horses. Giardia infections in dogs and cats can result in weight loss and chronic diarrhea, especially in young animals. A vaccine against Giardia lamblia infection in dogs was launched by Fort Dodge in the US during 1999.
1.2.1.6 Tapeworms
Dipylidium caninum (dogs) and Taenia taeniaeformis (cats) are the most common tapeworms affecting domestic pets, but hunting dogs and both dogs and cats allowed to roam freely in rural areas may be exposed to a range of other tapeworm species. Adult cestodes rarely cause serious health problems in dogs and cats, though clinical signs of infection may present in cases of heavy infestation. These include loss of condition, irritability, poor appetite, colic and mild diarrhea.
Fleas and lice act as intermediate hosts for D. caninum. Eggs are ingested and passed on to end hosts by the adult parasite during the larval stage. Taenia spp have more than one larval stage, and require two or three hosts, including humans and livestock as well as dogs and cats.
Treatment and control of tapeworm infestation in small animals and horses is achieved through the administration of drugs such as praziquantel, which features in a growing number of combination wormers for all three species. Work on the development of tapeworm vaccines has been in progress for many years, and immunological approaches to control in companion animal species may eventually be offered commercially.
1.2.2 Ectoparasites
Fleas, flies ticks, lice and mites can all cause intense irritation in host animals, leading to dermal infections where skin is damaged as a result of constant scratching or chewing. Ticks can also spread infectious agents such as the spirochete, Borrelia burgdorferi, which causes Lyme disease, while allergic reactions to the bite of ectoparasites such as fleas can cause serious problems, especially in dogs.
Table 1.2: Common ectoparasites by host species
Source: Adapted from the Merck Veterinary Manual and other sources.
1.2.2.1 Fleas
Ctenocephalides felis and C. canis are the most common fleas affecting small animal species. C. felis is the most significant, feeding and breeding on both cats and dogs. The flea life-cycle averages 18-21 days, including egg laying, three larval stages and the emergence of adult fleas, when conditions are favorable.
Fleas are blood sucking parasites that cause severe irritation to host animals. Scratching and biting by animals attempting to relieve itching can result in skin damage and subsequent infection. A significant proportion of host animals also experience an allergic reaction to flea bites, and flea allergy dermatitis (FAD) is among the most commonly diagnosed skin diseases in companion animals. Allergic reactions to flea saliva cause inflammation and itching. In hypersensitive animals, protracted clinical signs have been observed following a single exposure to fleas.
Ectoparasite controls are available in many forms for administration both directly to host animals and for use on bedding or other materials in the home, which may harbour flea eggs. Many are insecticidal in nature, but some act as insect growth regulators, preventing completion of the flea life cycle.
1.2.2.2 Ticks
Ticks are responsible for the transmission of a wide variety of infectious disease agents. In dogs, these include Lyme disease, babesiosis and erlichiosis. In horses, piroplasmosis is caused by Babesia spp spread by ticks.
Simultaneous infection with multiple tick-borne pathogens is common in dogs exposed to high tick populations. Ticks may also harm host animals directly, causing skin wounds that are susceptible to secondary infections, and in some cases inducing toxicosis or even paralysis.
Of the three tick families, Ixodidae and Argasidae are most significant as companion animal ectoparasites. Common vectors of Borrelia burgdorferi, the spirochete responsible for Lyme disease, include Ixodes dammini, I. pacificus, I. ricinus and I. scapularis. The tropical horse tick, Dermacentor nitens, is another species that has emerged as an important parasite in the US following its spread from more southerly regions. D. nitens is responsible for the transmission of Babesia caballi in horses - an infection that is of growing importance in the US horseracing industry.
Ticks are difficult to control effectively because they exist on a variety of hosts. They also possess natural resistance to some chemical classes. High concentrations of acaricidal chemicals and rapid action are required to eliminate infestations successfully. Control is achieved using long-acting acaricides in spot-on, spray and collar formulations. Fipronil possesses activity against some tick species as well as fleas, while selamectin also possesses claims against both parasite types as well as a range of other targets.
1.2.2.3 Mites
Mites cause irritation, rubbing, scratching, restlessness and hair loss on host animals. They are responsible for mange in a broad range of species, including dogs, cats and horses.
Demodectic mange is caused by Demodex canis in dogs. Mites infest the hair follicles and sometimes the sweat glands of host animals, transmitting mange when they move from an infested to a susceptible host. Puppies can be exposed at an early age if they are nursed by an infected bitch. Symptoms of demodectic mange range from small patches of hairlessness around the eyes or over the body, to extensive bloody lesions covering the entire body. The condition is often associated with immunosuppression in dogs.
Sarcoptic mange, caused by the Sarcoptes scabiei mite, is more severe than demodectic mange. Individual subspecies affect dogs, cats and horses, respectively. Sarcoptes mites gather initially on the head, throat and shoulders of host animals, and are readily transmitted by contact to other animals. Eggs are laid in tunnels formed by females burrowing into the skin. Infestation causes intense itching, prompting affected animals to scratch, chew or rub affected areas. This causes inflammation, and can result in secondary infections. Affected skin becomes dry, thickened and wrinkled. In untreated animals, emaciation, debilitation and even death can eventually result.
Otodectic mange is caused by the burrowing mites, Otodectes cynotis and Psoroptes cuniculi. Otodectes affects aural and facial areas of both cats and dogs. In horses, Psoroptes is found on either the body or the ears. Chorioptes spp are found on the lower legs and hocks of horses.
A range of established insecticides are indicated for the treatment of mite infestations in companion animals. Selamectin (Pfizer's Revolution/ Stronghold) is approved for the treatment of sarcoptic mange in dogs, and of ear mites (Otodectes cynotis) in cats. Other avermectin compounds have been used on an extra-label treatment for mange, but are contra-indicated at effective dosages in Collie dogs, while serious side-effects have also been reported in kittens treated with ivermectin.
1.2.2.4 Lice
Lice are wingless, flattened insects with legs adapted for clinging to hairs and feathers on host species. The biting louse, Trichodectes canis, and the sucking louse, Linognathus setosus, are among the most prevalent species affecting dogs. Felicola subrostrata is a biting louse found on cats, while the biting louse Bovicola and the sucking louse Haematopinus affect horses.
Lice infestation causes irritation, and affected animals often have an unthrifty appearance and rough coats. In horses, early sites of infestation include the main and tail. Bovicola spp cause hair loss and irritation, with consequent rubbing, while infection with Haematopinus spp causes loss of condition and, in some cases, anaemia.
1.2.2.5 Flies
Flies are a common nuisance parasite of horses. Most species cause intense irritation when present in large numbers, but some biting flies can inflict direct damage and are also vectors for other parasitic diseases. The stable fly, Stomoxys, is a blood sucking species, which acts as an intermediate host of the nematode parasite, Habronema. Non-biting flies such as Hydrotaea and Musca are often the source of intense irritation in horses.
Horses are also prone to dermatitis caused by hypersensitivity to the saliva of biting midges (Culicoides spp). Exposure to this parasite and some fly species can be reduced in the summer months by the application of fly repellents, spraying with insecticides or stabling in the afternoon hours, when parasites are at their most active.
1.3 Musculoskeletal problems
Bone and joint disorders are the most common musculoskeletal problems diagnosed in companion animals. In treatment terms, lameness is the most frequent condition observed in horses, with problems especially common in racing and other competition animals. In the small animal sector, arthritic conditions are being diagnosed more frequently as the longevity of pets increases, with osteoarthritis particularly prevalent in the canine population.
1.3.1 Canine osteoarthritis
Osteoarthritis can affect animals of all ages, but is more common in older dogs. Primary osteoarthritis is caused by wear and tear associated with age, while secondary osteoarthritis is often diagnosed following infectious disease episodes, maligned fractures or hip dysplasia.
Surveys indicate that around one-fifth of all adult dogs are affected by osteoarthritis, with that figure rising to 40% in animals aged seven years and older. The condition is the most common cause of chronic pain in dogs, and is being recognized increasingly as a problem in cats. It is still under-reported, however, with many owners attributing mild or even moderate symptoms to general ageing without seeking veterinary attention for their pets.
The condition initially affects the articular cartilage in joints, which begins to crack and fibrillate. Cartilage softens and connective tissue within the cartilage matrix degrades, destroying the matrix. Inflammation of the synovial membrane contributes to cartilage degradation, while surrounding muscles atrophy and joints begin to thicken. Affected animals experience constant dull pain, are less mobile, and can bear less weight on affected limbs. Pain is exacerbated by low temperatures, sudden changes of climate and heavy exercise.
Walking and swimming can help to keep affected muscles and joint capsules mobile, while rest and weight loss can also be beneficial. Anti-inflammatory drugs are prescribed widely in animals with osteoarthritis. While these do not halt the progression of the underlying disease, they do relieve pain associated with the condition, helping to keep affected animals mobile. A number of non-steroidal anti-inflammatory drugs were brought to market for use in small animals and/or horses during the 1990s, with carprofen (Pfizer's Rimadyl) emerging as the most widely prescribed product in dogs. Active ingredients from the coxib NSAID subclass have been commercialized for use in dogs more recently, with Novartis marketing deracoxib (Deramaxx) and Merial handling firocoxib (Previcox).
1.3.2 Equine lameness
Horses are prone to a broad range of musculoskeletal problems that often result in lameness. Competition animals are at particularly high risk, with exercise-related injuries such as fractures or tendon damage diagnosed much more frequently in performance horses than in the equine population as a whole. Degenerative joint diseases such as osteoarthritis, and conditions such as laminitis and navicular disease are among other causes of equine lameness.
Surgical intervention is required for serious fractures or tendon injuries, but anti-inflammatory drugs are used widely in the treatment of acute or chronic inflammatory conditions. Phenylbutazone and flunixin meglumine are among the most established equine anti-inflammatory drugs, but several NSAIDs have been commercialized for equine use since the beginning of the 1990s. Merial's coxib NSAID, firocoxib, was approved for use in horses by regulators in the US during the first half of 2006. In Europe, Ceva has commercialized a veterinary-approved version of the bisphosphate drug, tiludronate, as a treatment for equine lameness.
1.4 Cardiovascular disease
Like other mainly age-related conditions, cardiovascular problems are being diagnosed with increasing frequency in small animals as the longevity of pet populations continues to rise. Treatment has traditionally involved the use of long-established drug classes or off-label prescribing of human drugs, but a number of veterinary-approved cardiovascular products have been commercialized recently.
1.4.1 Congestive heart failure
Heart failure is caused most often by reductions in the volume of blood pumped to the heart, or by abnormal heart rates. Three stages (asymptomatic, mild-to-moderate and advanced) and three types (left-sided, right-sided and generalized) are recognized. All follow a similar path, with reduced cardiac output triggering increased heart rate and cardiac contractility, and the constriction of arteries and veins.
Declining blood pressure prompts the release of rennin by the kidneys, which converts angiotensin to angiotensin I. This in turn is transformed to angiotensin II by angiotensin-converting enzyme (ACE), a potent vasoconstrictor that also promotes sodium retention by the kidneys and stimulates the secretion of aldosterone by the adrenal cortex, resulting in further sodium and water retention. This compensatory chain of events is beneficial in the short term, but causes problems in chronically affected animals. It is responsible for a number of conditions associated with further reductions in cardiac output and the eventual progression to terminal heart failure.
Dietary management of animals with congestive heart failure (CHF) is usually recommended, but drug therapy is also indicated in many cases. Advanced cases may entail the use of several drug types to treat or control the various conditions associated with the syndrome, which can include pulmonary congestion and oedema, cardiac arrhythmias, reduced cardiac output and vasoconstriction.
Diuretics are widely prescribed in the treatment of pulmonary oedema, while vasodilating drugs such as ACE inhibitors are used to block the vasoconstriction that occurs as a result of chronic reductions in cardiac output. Veterinary-approved versions of several ACE inhibitors have been brought to market since the early 1990s.
1.4.2 Degenerative valve disease
Degenerative valve disease, or endocarditis, is the most common form of heart disease encountered in older dogs, with studies indicating that it affects more than half of all animals aged eight years and over. It is particularly common in some small breeds.
The condition is a degenerative disorder of the heart valves, which become thickened and distorted, leaking blood into other chambers when the heart contracts. The mitral valve is most commonly affected, but both the mitral and tricuspid valves are affected in a significant proportion of cases. Pulmonary oedema is a common result of increases in pressure within the left atrium where the mitral valve is affected, while atrial arrhythmias are also likely, resulting in further reductions in cardiac output. Excessive vasoconstriction and sodium and water retention are characteristic in chronic cases.
Symptoms of endocardiosis develop gradually, and affected animals can live with the condition for years if treatment is administered to slow the progression of early clinical signs. Four stages are recognized, with vasodilator therapy recommended at stage two, diuretic treatment at stage three and inotropic agents at stage four, when vasodilators and diuretics become less effective.
1.4.3 Cardiomyopathy
Primary muscle disorders such as dilated hypertrophic cardiomyopathy (HCM) are among the most common diseases of the myocardium in dogs, while HCM is also recognized as the most common acquired cardiac condition in cats. HCM is most common in middle aged male dogs, and is also more prevalent in large breeds. Incidence of the disease in cats has been reduced significantly since the discovery that taurine deficiency was responsible for a large proportion of cases. Prescription diets containing appropriate concentrations of taurine are now widely available.
HCM is characterized by loss of cardiac contractility, resulting in reduced cardiac output. Like many other degenerative cardiac conditions, this triggers compensatory mechanisms that include excessive vasoconstriction and retention of sodium and water, precipitating congestive heart failure. Diuretics are often prescribed to control congestion, with positive inotropes indicated for improved contractility and vasodilators for the reduction of cardiac stress. Beta-blockers may also be used to control tachydysrhythmias such as atrial fibrillation.
1.5 Cancer
Surveys indicate that cancer is now the leading disease-related cause of mortality in the US canine population. Advances in the diagnosis and treatment of cancer in companion animals, increases in the incidence of tumor-related problems in ageing pets and requests from a growing number of owners that their animals be treated for cancer rather than euthanized have all combined to raise the profile of neoplastic disorders in dogs and cats.
To date, chemotherapeutic treatment of companion animal cancers is undertaken entirely through the off-label use of human medicines. Many human treatments are suitable for use in pets because of the similarities that exist between cancers in humans and those observed in dogs and cats. As a result, companion animal studies are performed widely on development-stage oncology drugs. This should benefit the veterinary profession in future, with veterinary-specific versions of some human drugs expected to be commercialized. Research into new approaches such as gene therapy and the development of cancer vaccines may also result eventually in the launch of veterinary-specific products.
1.5.1 Mast cell tumors
Skin cancers are among the most common tumor types observed in dogs, while mast cell tumors are the most widely-recognized form of skin cancer, accounting for around 20% of all canine cases. Incidence is particularly high in certain breeds, including Boxers and Labrador Retrievers. Cutaneous mast cell tumors are common in cats, but are usually benign, with less than one in five recurring after initial surgical removal of the tumor mass. Mast cell tumors are diagnosed most often in middle-aged or elderly animals. They can occur at any point on the body surface as well as in internal organs, though the limbs, thorax and abdomen are most commonly affected.
Preferred treatment options depend on the clinical stage at which disease is diagnosed, but surgical removal of the tumor mass is usually indicated in early-stage cases. Surrounding tissue and regional lymph nodes may also be removed. Radiotherapy is administered where tumors are believed to have spread beyond surgical margins, and to prevent recurrence of the tumor at the surgical site.
Late-stage or inoperable tumors are usually treated with a combination of radio- and chemotherapy, though partial removal of inoperable tumors may also be indicated in some cases. Treatment with prednisone followed by injections of triamcinolone at the lesion site is one recommended regime. Chemotherapy with vinca alkaloids (vincristine or vinblastine), L-asparaginase and cyclophosphamide has also been practised with a degree of success.
1.5.2 Lymphosarcoma
Lymphosarcomas or lymphomas are solid tumors that form in the organs of the lymphatic system. They are caused by the invasion of these organs by cancerous lymphocytes. Malignant canine lymphosarcoma is among the most commonly diagnosed cancers in dogs.
In cats, a substantial proportion of lymphosarcoma cases are believed to be caused by infection with the feline leukaemia virus (FeLV). It is possible that viral infections may also trigger the development of tumors in some canine cases, though genetic factors and other immune system abnormalities are also thought to be involved. Lymphosarcoma can affect animals of all ages, but is more common in middle-aged and older dogs.
Standard protocols for the treatment of canine lymphosarcoma include combination chemotherapy, which is used to affect remission. This can last for a year or more, depending on the characteristics of individual tumors and the stage at which the condition is diagnosed. Lymphomas formed by T-lymphocytes are believed to be more aggressive than those developed from B-lymphocytes, and the prognosis for affected animals is less positive as a result.
A five-drug chemotherapy regime, including the administration of vincristine, L-asparaginase, prednisone, cyclophosphomide and doxorubicin has been practised widely in dogs, eliciting tumor regression in the majority of patients for at least six months. Maintenance therapy is administered thereafter, with asparaginase and prednisone usually withdrawn at this stage. Single drug therapy with doxorubicin or prednisone can elicit briefer remissions.
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