Small Animal Infectious Diseases PDF

DR C. Hankanga Malombola 1 2  Damage done to intestine by The Virus virus  Puppies infected in utero die suddenly or develop cardiomyopathy if maternal antibodies are absent  Over-crowding, GIT parasites, concurrent infections with giardia, salmonell...

DR C. Hankanga Malombola 1 2  Damage done to intestine by The Virus virus  Puppies infected in utero die suddenly or develop cardiomyopathy if maternal antibodies are absent  Over-crowding, GIT parasites, concurrent infections with giardia, salmonella, or campylobacter spp can increase severity of disease  Susceptible breeds: Rottweilers, dobermans, english springer spaniels, bull terriers  Death attributed to dehydration, hypercoagulability, endotoxic shock/sepsis due to mucosal barrier disruption and leucopaenia  Infected animals are immunosupressed and susceptible to catheter infections  Endotoxemia, TNF activity, coliform septicaemia, and proliferation of enteric C. Perfringens determine morbidity and mortality 4  Diagnosis ◦ Clinical features, hematology, faecal ELISA, serology, virus isolation. ◦ Hematology – severe leucopenia and neutropenia leading to secondary bacterial infection. ◦ In absence of leukopenia difficult to differentiate from intussception , other bacterial and viral diarrhoeas, FB obstruction etc ◦ Histology on small intestines – villous atrophy 6 Villi are collapsed, and crypt lumina are dilated and filled with necrotic debris (H&E stain, ×100  Treatment- supportive ◦ Fluid therapy – lactated ringers solution until the dog can retain oral fluids. ◦ NPO for 24 hrs but small amounts of glutamine-rich solutions have been shown to reduce bacterial translocation, bland diet once vomiting has stopped. ◦ Antiemetics e.g. Prochlorperazine, Metoclopromide or Ondansetron for intractable vomiting ◦ To prevent fatal sepsis- Broad spectrum antibiotics e.g. ampicillin, Cefazolin. ◦ Antiendotoxin serum therapy has been useful in some patients but timing with antibiotic therapy vital.  Antibiotics may increase endotoxin release therefore preferable to administer serum before antibiotics  One study showed the use of antiendotoxin rBPI21 had no beneficial effects on survival and another showed a correlation between use of the serum with decreased survival time. 8 ◦ Study showed that use of recombinant human granulocyte colony- stimulating factor (G-CSF) in neutropaenic patients may raise neutrophil counts but is of no clinical benefit ◦ Study showed use of feline interferon-omega was found to improve clinical signs and reduce mortality. ◦ Flunixin Meglumine may be used but care! As has adverse effects on GIT and kidneys! ◦ Plasma/blood transfusion in cases with severe hypoproteinaemia and anaemia ◦ Oral fluids and kaolin (aluminium silicate) based preparations once vomiting has stopped 9  Prognosis ◦ Severe infection with leucopaenia associated with high mortality ◦ Most dogs recover if dehydration and sepsis are treated appropriately ◦ Complications include: hypoglycaemia, hypoproteinaemia, anaemia, intussusception and secondary bacterial and viral infections  Prevention-Vaccination and disinfection ◦ Modified-live CPV2 vaccine (common)  Maternal derived antibodies may persist for up to 18 weeks, but most vaccines overcome MDAs by 10-12 weeks  Note: Feline parvoviral enteritis also exists and presents similar to that in canines. 10  CORONAVIRAL ENTERITIS  Behaves similar to parvovirus and it may be difficult to differentiate.  Transmission faecal-oral  Destroys the mature cells of villi  But typically less severe and does not usually cause hemorrhagic diarrhea or death.  May occur simultaneously with parvoviral enteritis.  Ocular and nasal discharge may also be present  Treatment  Similar to that for parvoviral enteritis  Signs may last 3-20 days  Does not affect bone marrow like parvovirus. 11  large RNA virus of the Morbillivirus genus. It is closely related to the viruses which cause measles, Rinderpest and distemper  The CDV single-stranded RNA is surrounded by a lipoprotein envelope composed of viral glycoproteins incorporated into the host cell membrane.  Different strains of virus exist and account for variation in pathogenicity: these may have tropisms for ◦ pulmonary (pneumotropic), ◦ neural (neurotropic) or ◦ epidermal tissues. Virulence is likely to be determined by variations in viral glycoproteins. 12  CDV is most commonly spread by aerosol or droplet exposure reflecting its high concentration in respiratory secretions.  It is also spread in urine and faeces.  It is an extremely labile virus and is susceptible to heat and drying, and UV light.  As an envelope virus it is susceptible to most modern disinfectants e.g. benzalkylonium and glutaraldehyde or tertiary amines 13  Following exposure CDV multiplies in tissue macrophages and spreads via the local lymphatics to tonsils and bronchial lymph nodes.  Subsequent widespread virus replication within lymphoid tissues results in pyrexia and leukopenia approximately 4-6 days post-infection.  Within 8-10 days of infection, CDV spreads haematogenously to epithelial cells and the CNS tissues.  Colonisation of the epithelium results in shedding of virus even in subclinical cases. 14  The clinical outcome depends on the level of CDV antibody titres and adequacy of cell-mediated immune response; ◦ Individuals with adequate CDV antibody titres and cell- mediated cytotoxicity clear virus from most tissues and show no clinical signs, although they can still shed virus. ◦ Intermediate levels of cell-mediated immuno-responsiveness with delayed antibody production results in infection of the epithelial tissues and development of clinical signs. ◦ Exposure to a highly virulent strain or high-dose exposure may result in significant morbidity. ◦ Poor immune status results in severe disease and virus usually persists until death ◦ Recovery is associated with long-term immunity and cessation of viral shedding 17  Respiratory Tract ◦ infection of respiratory epithelium gives rise to bilateral serous to mucopurulent oculonasal discharge, with concurrent coughing and dyspnoea due to bronchopneumonia with secondary bacterial infection. Mildly affected cases need to be differentiated from “kennel cough”.  Ocular Disease ◦ serous to mucopurulent bilateral conjunctivitis ◦ keratoconjunctivitis sicca (“dry eye”) may occur following systemic or subclinical infection ◦ mild anterior uveitis (asymptomatic) and degeneration/necrosis of the retina ◦ optic neuritis may be seen with neurological involvement 18  Gastrointestinal Tract  damage to the intestinal epithelium results in vomiting and diarrhoea with associated anorexia, dehydration and weight loss.  Dermatological Effects  pustular dermatitis may be observed  nasal and digital hyperkeratosis (“hard-pad”) 19  Neurologic Signs  may include seizures, vestibular disease, ataxia or myoclonus (“chorea”)  acute meningio-encephalitis may occur in conjunction with other systemic signs due to direct viral injury to the CNS  chronic relapsing neurological signs often in the absence of other systemic signs. May be seen many years after infection when the dog develops “Old Dog Encephalitis 21  Dental disease  neonatal infection prior to eruption of permanent dentition results in damage to enamel and dentine, resulting in “distemper rings”.  Transplacental Infection  abortion and stillbirth or persistent excretors of virus depending of the stage of gestation 22  A presumptive diagnosis can be made on the basis of characteristic clinical signs in an unvaccinated dog, especially 3-6 month old puppies once Maternal derived antibodies (MDA) levels have fallen.  It should be remembered that subclinical infection occurs in 50-70% of cases, and that transient upper respiratory tract infections in older dogs may in fact be due to CDV, not infectious tracheobronchitis. 23  Laboratory findings ◦ Absolute lymphopenia (virus strain dependent) ◦ Distemper inclusions on peripheral blood smears (clustering of nucleocapsid) – false negative results common ◦ Non-specific biochemical changes relating to dehydration, polyclonal gammopathy.  Immunocytology ◦ Immunofluorescent antibody (IFA) on conjunctival smears, or on tonsilar tissue, leukocytes or respiratory epithelium – helpful in the acute phase of disease 24  Serology ◦ ELISA to detect anti-CDV IgG and IgM. Demonstration of a rising antibody titre may be useful for confirmation of infection. Interpretation may be difficult in vaccinated individuals.  Virus Isolation (rarely carried out) ◦ Culture of lymphocytes from the buffy coat, or from target tissues at post-mortem  CSF analysis in dogs with neurological signs ◦ Increased CSF protein content, & cell count (predominantly mononuclear) ◦ Increased anti-CDV antibody within the CSF 27  Kennel cough  Enteric signs (differentiate from Parvovirus and corona infection, parasitism (giardiasis), bacterial infections,IBD  CNS Form; Differentiate from other other CNS diseases 28  Supportive therapy including good nursing care ◦ Intravenous fluid therapy ◦ Anti-emetics ◦ Antibiotics for secondary infections ◦ Coupage & nebulisation if bronchopneumonia present. ◦ Anticonvulsants for seizures ◦ Development of neurological signs carries a guarded prognosis.  In addition even if neurological signs are absent initially warn the owners that they may develop subsequently (weeks to months to years later). 29  Vaccination ◦ Live attenuated vaccines in dogs ◦ Maternal derived antibodies (MDA) obtained primarily from colostrum & confer protection for the initial 6-12 weeks. MDA are usually absent by 12-14 weeks. ◦ Puppies should be vaccinated from 6-8 weeks with at least 2 doses of CDV vaccine at 2-4 weeks intervals; the last vaccine being administered at over 12 weeks of age.  Currently booster vaccination is recommended every year. Immunity is both humoral (antibodies) and cell- mediated immunity (CMI) and therefore antibody titres do not necessarily reflect immune status. 30   Environmental control ◦ High level of hygiene ◦ Isolate any infected individuals since virus shedding in aerosols is the main source of infection ◦ Vaccination prior to admission to boarding kennels is essential ◦ In breeding units, isolate incoming animals for a minimum of 7-10 days (virus incubation period) 31  ICH is caused by Canine Adenovirus-1 (CAV-1), a double- stranded DNA virus with haemagglutinating surface antigens. CAV-1 is closely related to, although antigenically and genetically distinct from, CAV-2, which causes respiratory tract disease.  CAV-1 is transmitted via the oronasal route from infected urine, faeces and fomites (including feeding utensils and hands).  Urinary excretion of virus may persist for 6-9 months following active infection.  CAV-1 is resistant to environmental inactivation, surviving for days on soiled fomites at room temperature.  Inactivation occurs at 50-60oC (steam cleaning) or using phenol, sodium hydroxide or iodine based disinfectants. 32 o After oronasal infection CAV-1 initially localises in the tonsils, before progressing along the lymphatics to regional lymph nodes and via the thoracic duct to the blood. o Viraemia results in dissemination to various tissues, with hepatic parenchyma and vascular endothelium being primarily targets. o Viraemia persists for 4-8 days and is associated with pyrexia. o CAV-1 is cytotoxic and results in cellular injury of affected tissues, particularly the liver and vascular endothelium. 33 Target Organs ◦ Liver; widespread centrilobular to panlobular necrosis may occur. ◦ Clinical outcome depends on various factors including level of pre-existing immunity and viral load/dose;  Dogs with high antibody titres on the day of infection are usually asymptomatic. A sufficient antibody response by day 7 PI clears virus and restricts hepatic damage.  A partial neutralising antibody response within 4-5 days PI may develop chronic active hepatitis and subsequent hepatic fibrosis. Chronic latent hepatic infection may be present.  Persistently low antibody titres are associated with widespread hepatic necrosis which may be fatal. Unvaccinated, immunosuppressed or immature dogs are at greatest risk of severe/fatal consequences. 34  Vascular endothelium; damage results in bleeding diatheses, including vasculitis and DIC.  Kidney; localisation in the glomerular endothelium results in glomerular injury. ◦ In addition glomerular deposition of circulating-immune- complexes results in transient proteinuria. Persistence of virus in renal tubular epithelium results in prolonged viral excretion. 35  Eye; direct cytotoxic damage and deposition of immune-complexes within the cornea and uveal tract result in corneal oedema and uveitis  Peracute ◦ rapid death several hours after the onset of clinical signs.  Acute ◦ pyrexia, anorexia, vomiting, abdominal pain, and diarrhoea, with or without evidence of a bleeding disorder. 38  Lymphandenopathy  Pharygitis/tonsilar enlargement  Epistaxis  Harsh lung sounds (pneumonia)  Bleeding at venipuncture  Abdominal pain sites  Hepatomegaly  CNS signs (depression,  Abdominal distention disorientation, seizures)  Jaundice  Petechiation  Ecchymotic hemorrhages Clinical signs last for 5-7 days prior to improvement Corneal oedema and anterior uveitis develop during the recovery phase in 20% of cases (“blue eye”) 39  Laboratory findings  Leukopenia, lymphopenia, neutropenia initially followed by leukocytosis and neutrophilia on recovery  Raised ALT, AST and SAP, with reduced hepatic function (elevated bile acids +/- ammonia) +/- hyperbilirubinaemia. Hypoglycaemia may occur with acute hepatic necrosis.  Proteinuria  Coagulation abnormalities; thrombocytopenia, prolonged APTT, PT, increased FDPs 41   SEROLOGY  CAV-1 antibody levels typically increase after infection to higher levels than post-vaccination  Demonstration of a rising antibody titre may be useful for confirmation of infection  Histopathology  Typical findings of centrilobular necrosis on liver biopsy  Nuclear inclusion bodies from impression smears of liver  Virus Isolation  From body tissues or secretions including urine (not liver)  Immunocytology  IFA on infected tissue 42 Swollen rounded lobes of liver, oedematous gall bladder Centrilobular necrosis  Intranuclear inclusion bodies  As with CDV infection treatment is symptomatic and supportive:  Intravenous Fluid Therapy +/- IV glucose administration  Blood/Plasma Transfusion +/- anticoagulant therapy for DIC (heparin)  Therapy for hepatic encephalopathy; lactulose and antibiotics (ampicillin, neomycin)  Anti-emetic therapy  S-adenosyl methionine as a glutathione precursor/replacement  The prognosis is guarded. Partial immunity may result in progressive hepatic disease with eventual hepatic insufficiency. 45 Vaccination  Live attenuated vaccination with CAV-2 confers good neutralising antibody titre without the clinical signs associated with administration of a modified live CAV-1.  Vaccination recommendations vary between manufacturers but the primary course should consist of 2 vaccinations given 3-4 weeks apart at 8-10 and 12-14 weeks of age.  Booster vaccination is recommended every year. 46  Leptospirosis is an important zoonotic disease with world-wide distribution caused by infection with Leptospira interrogans.  Subclinically infected wild and domestic animals act as reservoir hosts and have the potential to infect humans and other incidental animal hosts.  Clinical signs in incidental hosts tend to be more severe. 47  Leptospira interrogans is a thin, filamentous, spiral bacteria. ◦ It can be divided into distinct serovars based on antigenic differences in its outer envelope mucopeptides. The most commonly incriminated serovars in canine leptospirosis are:  Leptospira icterohaemorrhagica (primary reservoir host; Rat)  Leptospira canicola ( primary reservoir host; Dog)  Leptospira grippotyphosa  Leptospira pomona (reservoir pig)  Leptospira bratislava (reservoir pig, horse, dog?) 48  Leptospires can be transmitted by either direct or indirect contact:  Direct via contact with urine, venereal and placental transfer, bite wounds or ingestion of infected tissue. Recovered dogs may excrete organisms in urine intermittently for months.  Indirect via exposure to contaminated water sources (especially slow flowing, stagnant water), soil, food and bedding. NB leptospires do not replicate once outside the host. 49  Leptospires penetrate mucous membranes and abraded skin and rapidly divide in the blood before spreading to other tissues including the liver and kidneys, spleen, CNS, eyes and genital tract.  The extent of target organ damage depends on  dose of infection,  host susceptibility  and the virulence of the organism;  Serovars canicola and grippotyphosa are primarily associated with RENAL dysfunction  Serovars icterohaemorrhagica and pomona tend to cause severe HEPATIC dysfunction. 51  Peracute disease may result in sudden death due to massive leptospiraemia. ◦ Pyrexia, anorexia and shivering with muscle tremors may be noted. ◦ In addition vomiting, rapid dehydration and rapid cardiovascular collapse ensue. 52  Pyrexia  Congested m.  Anorexia membranes  Depression  Icterus  Vomiting  Petechiae and  Dehydration ecchymoses  Polydipsia  Reluctance to move  oliguria  Abdominal pain  Para-spinal pain 53  Chronic or subclinical: Make up the majority of leptospiral infections  Leptospirosis should be considered in dogs with pyrexia of unknown origin, unexplained renal or hepatic disease or anterior uveitis.  In chronic cases organ dysfunction is often progressive leading to end-stage organ failure. 54  Laboratory findings  Routine haematology may reveal leukocytosis with left-shift, +/- thrombocytopenia  Indicators of renal dysfunction; urea, creatinine, electrolyte abnormalities  Indicators of hepatic damage and dysfunction; ALT, SAP, bilirubin and bile acid elevations. NB bilirubinuria usually precedes hyperbilirubinaemia.  Urinalysis may reflect renal tubular damage; glucosuria, tubular proteinuria, granular casts, active sediment.  Laboratory evidence of DIC; thrombocytopenia, increased FDPs, low serum fibrinogen 55  Organism Identification  Dark field microscopy for detection of organism in urine  Culture; from urine (multiple samples due to intermittent shedding), blood (early in acute disease), or tissue.  Light microscopy using Giemsa or silver-staining techniques  IFA on liver and kidney (or on urine)  Serology  Demonstrate a rising antibody titre; may be negative in first 7-10 days, rising after 2-4 weeks. 56  Specific therapy – Antibiotics:  Penicillins are the antibiotics of choice for terminating leptospiraemia. They immediately terminate replication of the organism and reduce fatal complications – give ampicillin of penicillin-G IV during the acute phase, followed by oral amoxycillin.  Elimination of the carrier state is achieved by administering tetracyclines, erythromycin or fluoroquinolones after an appropriate course of penicillins (penicillins, cephalosporins, chloramphenicol and sulphonamides are ineffective at eliminating organisms). 59  Supportive therapy:  Aggressive intravenous fluid therapy to correct dehydration and maintain urine output.  Antiemetics.  Blood/plasma transfusions +/- anticoagulants  Therapy for anuric/oliguric renal failure should include IV fluid therapy, diuresis with frusemide +/- mannitol (only once dehydration has been corrected), dopamine infusions +/- peritoneal dialysis (ARF due to leptospirosis infection is potentially reversible) 60  Elimination of the carrier state in affected dogs (see above).  Vaccination ◦ Combined killed vaccine containing the 2 main serovars; L. canicola and L. icterohaemorrhagica. ◦ Initial primary vaccination at 9 and 12 weeks of age. ◦ Immunity to challenge lasts 6-8 months, therefore a minimum of annual vaccination is recommended. Consider giving biannual (twice yearly) vaccinations in endemic areas.  Vaccination reduces the prevalence and severity of clinical disease but does not prevent infection and the carrier state. Clinically healthy dogs may be carriers. 61  Primary Pathogens ◦ Canine Parainfluenza Virus (CPiV or PI3) ◦ CAV-2 ◦ Bordetella bronchiseptica  Secondary pathogens ◦ CDV (may result in respiratory disease independent of other systemic signs) ◦ Pasteurella sp, Streptococcus sp, Pseudomonas sp ◦ Mycoplasma sp 62  Environmental conditions play an important role in the epidemiology of KC, with high-density population environments such as boarding kennels, pet-shops and breeding kennels providing ideal conditions for transmission of these viral and bacterial pathogens, resulting in high levels of morbidity.  Mortality is however uncommon in adult dogs unless concurrent immunosuppression exists.  Most outbreaks are associated with direct dog-to-dog contact or airborne dissemination of infectious respiratory secretions. ◦ CAV-2 and PI3 are transmitted for up to 2 weeks post- infection ◦ B bronchiseptica & Mycoplasma are shed for up to 3 months post-infection 63  CPiV ◦ Infection is restricted to the respiratory epithelium (CPiV does not replicate in macrophages). ◦ Damage to the respiratory epithelium allows secondary infection with other pathogens. Incubation period of 3-10 days.  CAV-2 ◦ Following oronasal exposure CAV-2 replicates in local epithelia of the nasopharynx, tonsilar crypts, trachea and bronchi. ◦ Infection of type 2 alveolar cells may be associated with interstitial pneumonia. Viral replication and shedding peaks at 3-6 days PI. 64  B.bronchiseptica ◦ Following exposure (either direct contact or aerosolised droplets) B bronchiseptica attaches to and replicates on the cilia of the respiratory epithelium.  Production of various toxins which impair phagocytosis and induce stasis of the cilia facilitates colonisation of the respiratory tract by opportunistic pathogens.  Although a primary pathogen in its own right, B bronchiseptica is most commonly associated with mixed respiratory tract infections. 65  Mycoplasma ◦ Mycoplasma sp are endogenous to the nasopharynx of dogs and cats, but not typically found in the lower respiratory tract. ◦ Colonisation of both ciliated and non-ciliated epithelia results in purulent bronchitis, bronchiolitis and interstitial pneumonia. Chronic shedding occurs following infection. 66  Dogs with KC present classically with sudden onset paroxysmal episodes of coughing and often associated retching, 3-10 days following exposure to KC agents.  Typically there will be a history of a visit to boarding kennels.  Coughing is often brought on by excitement, and tends to be characterised by a dry or “hacking” cough. Expectoration of mucus may occur and should be differentiated from vomiting. Usually the dog is otherwise healthy and active.  Without treatment the clinical course is 2-3 weeks. 67  Occasionally secondary opportunistic bacterial infection will result in the development of bronchopneumonia +/- mucopurulent rhinitis and conjunctivitis. In this instance the affected dog will be systemically unwell, with pyrexia, lethargy, anorexia and/or dyspnoea. 68  Typical clinical presentation with history of exposure should prompt a diagnosis of KC. ◦ Laboratory findings  Stress leucogram may be present in uncomplicated cases.  Inflammatory leucogram +/- left shift may be present with bronchopneumonia ◦ Thoracic radiographs  Evidence of bronchopneumonia in systemically unwell dogs.  Lobar consolidation may develop 69 ◦ Isolation of Pathogen  CAV-2 or CPiV isolation from nasal, pharyngeal or tracheal swabs.  Culture does not necessarily reflect primary pathogens but may help with antibiotic selection for bronchopneumonia ◦ Serology  Rising antibody titres may demonstrate exposure but are of little clinical value 70 Uncomplicated cases  Antibiotic therapy may reduce the duration of coughing & may reduce the risk of developing bronchopneumonia. ◦ Consider tetracyclines, amoxycillin-clavulanate, Trimethoprim Suphonamides.  Antitussives to interrupt the cough cycle, but not if concurrent bronchopneumonia is suspected. ◦ Consider codeine or butorphanol. 71  KC plus bronchopneumonia  Appropriate antibiotic therapy ideally based on culture and sensitivity results  Supportive care; nebulisation & coupage to encourage expectoration of bronchial secretions. Oxygen therapy may be required in severe cases (see Respiratory System notes). IV fluids and nutritional support may also be required.  Remember that these dogs are likely to be INFECTIOUS and isolate during hospitalisation. 72 Vaccination  CDV, CAV-2 and CPiV are available as parenteral vaccines and should be integrated into routine vaccination programmes. ◦ CPiV vaccine should be administered annually following initial primary course.  Intranasal vaccines are available for B.bronchiseptica and CPiV, conferring protection for approximately 6 months. Annual vaccination is advised or alternatively vaccination may be administered prior to (at least 5 days) anticipated exposure. 73 Environmental Considerations  Minimise the number of dogs in a single airspace – ensure adequate ventilation.  Isolate affected dogs immediately – remember that B.bronchiseptica and Mycoplasma sp may be shed for up to 3 months. Viruses may be excreted for 10-14 days. Consider closing the kennels for 2 weeks in conjunction with extensive disinfection/cleaning  Hygiene – sodium hypochlorite, chlorhexidine, benzalkylonium solutions for cleaning. 74  Rabies is a highly fatal viral disease of the nervous system of all warm-blooded animals.  It is a Rhabdovirus (genus lyssavirus) a single stranded RNA virus, truly neurotropic (damages only nerve tissue) and easily killed by sunlight, heat and most disinfectants.  Present throughout the world with the exceptions of Australia, Antarctica and certain island groups such as Japan, British Isles and Northern Scandinavia, Uruguay/Chile.  World Health Organisation survey in 1997: 85 out of 103 mainland countries had epizootic rabies 35,000- 50,000 people killed  India reported 500 cases in dogs and estimates human deaths at 35,000  Unofficial reports from China estimated 500 human deaths.  Source is always a rabid animal.  Disease is maintained in two inter-related cycles:  Urban - Stray & feral dogs/cats (responsible for 99% human rabies deaths).  Sylvatic - Wild carnivores  Biting is almost always the cause so the domestic carnivores are the greatest threat to man i.e. dogs & cats. However only 15% of bites from rabid dogs result in infection  Virus can enter through skin wounds but not unbroken skin.  Inhalation or contact with mucous membranes may be possible routes.  PATHOGENESIS  Bite injects virus into wound and? replicates in local muscle fibres.  4 to 5 hours - virus enters local nerve cells.  Virus invades brain and destroys cells  Virus invades brain and destroys cells ◦ Spreads stepwise to adjacent areas - Hypothalamus, hippocampus, cerebellum, medulla oblongata. ◦ Location of damage may determine "furious" (higher brain and cerebellum) or "dumb" form (spinal cord and brainstem). ◦ Lesions of non-suppurative encephalomyelitis. Pathognomonic "Negri bodies" (basophilic intracytoplasmic inclusion bodies). ◦ Virus enters salivary glands, replicates (infectious rabid animal). ◦ Anterograde axoplasmic flow to all nerves of the body. ◦ Incubation period : 10 days to 2 years (exceptionally) in man. ◦ 12 days to 25 days usually in dogs.  Severity of Disease Depends On:  Amount of virus in bite (wolf more saliva than a squirrel)  Size of victim. Child more vulnerable than adult (distance to brain).  Site of bite. Cats worse than dogs (have claws and attack face).  Change of behavior- hides, seeks seclusion.  Friendly dogs become aggressive, unprovoked attacks, self mutilation.  High pitched howling  Staring eyes  Paralysis of lower jaw and unable to eat  NO HYDROPHOBIA - unlike man.  Attacks wooden/metal objects and damages teeth and claws.  Runs long distances in straight lines, biting on the way (NOT foxes).  Exhaustion, muscle tremors and paralysis. Convulsions and collapse.  Coma and death from respiratory paralysis.  Cats- furious form more common ◦ deeper wounds ◦ attack face with teeth and claws.  Insidious onset, pain and tingling in affected limb.  Excitement, fever and convulsions interspersed with full lucidity.  Localised paralysis - often of throat.  Hydrophobia - violent spasms.  Copious dribbling of saliva and tears - death in 2 to 6 days.  Differential diagnoses include hysteria, tetanus, alternative encephalitis, and epilepsy.  Soap and water or disinfect locally.  Pre or post exposure vaccine.  Antiserum?  Excellent chance of survival if given before clinical signs appear. Otherwise invariably fatal.  Clinical signs/history: Vaccinated?  Fluorescent Antibody Test (FAT) 99% accurate. Result in 2 to 4 hours.  Histopathology - Negri bodies in hippocampus and cerebellum. Result 3 to 4 days.  Mouse test - Cultivation and isolation of virus by intracerebral inoculation of young mice. Standard confirmatory test (3 weeks).  More recently cell culture techniques using mouse neuroblastoma cells have been shown to be capable of replacing mice and giving quicker results. Negri body in body of neuron and positive IF test for rabies antigen (Source: CDC)  Vaccination  Elimination of stray dogs  Quarantine  ETIOLOGY AND PATHOGENESIS ◦ Erhlichia spp are tick-borne rickettsia that form intracellular clusters called morulae ◦ Spp that infect dogs include  E. canis  E. platys  E. ewingii  E. Chaffeensis ◦ Vectors include Rhipicephalous sanguinous and ixodes spp 91  Infected mononuclear cells marginate in small vessels or migrate into endothelial tissues inducing vasculitis during the acute phase (Begins 1-3 weeks PI and lasts 2-4 weeks), most immunocompetent animals survive.  Subclinical phase lasts months to years (some dogs may clear infection during this phase)  The organism may persist intracellularly leading to the chronic phase of infection (most clinicopathological changes in chronic phase due to immune reaction against the organism) 92  Severity depends on ◦ Organism ◦ Host factors (dogs with depressed cell mediated immunity develop severe disease) ◦ Presence of co-infections  Clinical findings in dogs with e. canis infections vary with the timing of infection ◦ Acute ◦ Subclinical ◦ chronic 93  ACUTE ◦ Fever ◦ Serous or purulent oculonasal discharge ◦ Anorexia ◦ Weight loss ◦ Dyspnoea ◦ Lymphadenopathy ◦ Tick infestation often obvious  SUBCLINICAL ◦ No clinical abnormalities ◦ Ticks often not present 94   Dyspnea, increased lung  Tick often not present sounds, interstitual or  Weightloss alveolar lung infiltrates  Depression  Ocular; perivascular retinitis, hyphema, retinal  Pale m. membranes detachments, anterior  Abdominal pain uveitis, corneal oedema  Evidence of  CNS; paresis, cranial n. deficits, seizures hemmorrhage; epistaxis,  Hepatomegaly retinal hemmorrhage etc  PU/PD  Lymphadenopathy  Stiffness and swollen,  Splenomegaly painful joints 95 Epistaxis, Hyphema Scleral haemorrhage  Retinal detachment and haemorrhage  ACUTE ◦ Thrombocytopenia ◦ Leukopenia followed by neutrophillic leukocytosis and monocytosis ◦ Morulae ◦ Low grade nonregenerative anemia ◦ Variable Ehrlichia titer ◦ PCR positive 99  Hyperglobulinemia  Thrombocytopenia  Neutropenia  Lymphocytosis  Monocytosis  Positive Ehrlichia titer  PCR positive 10 0  Monocytosis  Proteinuria  Lyphocytosis  Polyclonal gammopathy  Thrombocytopenia  Nonseptic polyarthritis  Nonregen. Anemia  Increased ALT, ALP  Hyperglobulinemia  Positive Ehrlichia titer  Hypocellular bone  PCR positive marrow  hypoalbuminemia 10 1  Polyclonal gammopathy Normal Monoclonal gammopathy  IFA tests  Buffy coat from ear vein blood increase chances of finding morulae  Culture; some ehrlichia can be cultured but this procedure is low yield and expensive  PCR; used commercially to detect organism specific DNA in peripheral blood 10 3  IFA for e. chaafensis  Supportive care including: ◦ Doxycycline (10 mg/kg PO q24 h for 28 days) reccomended drug. (clinical signs should resolve within 7 days) ◦ Others; Tetracycline, chloramphenicol and imidocarb dipropionate ◦ Immune mediated events in this disease leads to use of Prednisolone (2.2 mg/kg PO divided q12 during first 3-4 days) 10 5  Prognosis: good in acute cases, guarded in chronic cases  Zoonotic/controls aspects: ◦ E. canis, chaffeensis are zoonotic ◦ Rigorous Tick control ◦ Screen potential blood donors 10 6  The organisms ◦ A. Platys and A. phagocytophilum are small obligate intracellular bacteria that replicate within canine thrombocytes. ◦ A. phagocytophilum also resides in granulocytic white blood cells (neutrophils)  May cause infection in dogs, cats, horses, small ruminants and humans 10 7  Ticks believed to be primary vector ◦ A. phagocytophilum by ixodid ticks ◦ A. platys transmitted by R. sanguineous 10 8  Signs seen 1-2 weeks post experimental innoculation  Thrombocytopenia and recovery seen cyclically at 1-2 week intervals (thrombocytopenia lessens with cycle)  Signs related to thrombocytopenia have been reported occasionally 10 9  Identification of morulae ◦ A. Platys- seen in platelets ◦ A. phagocytophilum seen also in granulocytes (seen 4-18 days post infection)  Thrombocytopenia  Serology- IFA available and no cross reactivity seen with E. canis  PCR has also been used 11 0  Tetracyclines mainstay of therapy ◦ 5- 10 mg/kg orally, q12- 24hr (optimum duration of therapy 10-28 days)  No vaccine,  Recovered animals susceptible to reinfection with A. phagocytophilum  Tick control 11 1  Etiology and epidemiology ◦ Piroplasma are intraerythrocytic protozoan parasites of the phylum Apicomplexa  Include babesiidae and Theileridae.  Babesia have no pre-erythrocytic stage wheres as Theileria first infect leukocytes then RBCs ◦ Most commonly associated with B. canis and B. Gibsoni, protozoan parasites that parasitise RBCs leading to progressive anemia ◦ Has worldwide distribution 11 2 Genotype/sp Distribution vector Risk factors virulence p B. Canis worldwide R. sanguinous Greyhounds, + vogeli dog bites, transfusion B. Canis rossi South africa Haemaphysalis ticks +++ leachi B. Canis Europe Dermacenter Ticks ++ canis reticulates B. gibsoni Worldwide Haemaphysalis American ++ spp, Pitbull terriers, dog bites, ticks, blood transfusion B. microti-like Spain Ixodes Ticks +++ (theileria hexagonus annae) B. conradae US ? ? +++ 11 3  Following infection, incubation period varies from 10-21 days  Parasitemia seen days 1, 14 and 20  Organism replicates intracellularly in the RBCs resulting in intravascular hemolytic anemia  Immune mediated reactions to the parasite or altered self antigens worsen hemolysis resulting in a positive coombs test  Stimulation of macrophages leads to fever and hepatosplenomegaly 11 4  Severe hypoxia occurs due to breakdown of RBCs  DIC occurs in some infected dogs during acute infection  Severity of disease depends on the species and strain of babesia and the host immune status; subclinical, chronic infection can occur  Administration of glucocorticoids or splenectomy may activate chronic disease 11 5 ◦ Peracute or acute babesiosis  Anemia and fever, leading to pale m.m., tachycardia, tachypnea, depression anorexia and weakness  Icterus, petechiae and hepatosplenomegaly are present in some dogs depending on the stage of infection and presence of DIC  Severe anemia, DIC, metabolic acidosis and renal disease are common in during acute infection (main DDX is IMHA) 11 6  B. canis rossi- highly virulent, associated with DIC, CNS signs and hypoglycemia and sometimes death  A babesia microti-like parasite has been associated with classic signs of prioplasmosis associated with renal failure and proteinuria possibly due to glomerular disease 11 7 ◦ Chronic  Weight loss and anorexia ◦ Atypical infection  causes ascites, GIT signs, CNS disease, edema, cardiopulmonary disease or  Thrombocytopenia and hyperglobulinemia without anaemia ◦ Subclinical infection occurs as well 11 8  Regenerative anemia, hyperbilirubinemia, hemoglobulinemia, thrombocytopenia, metabolic acidosis, azotemia, polyclonal gammopathy, and renal casts are common in dogs with babesia  Definitive diagnosis: demonstration of organism in RBCs using wright`s or Giemsa {B. canis(paired piriform bodies) and gibsoni (single annular bodies)} ◦ Specific but method has low limit of detection, sensitivity is poor, thus now not recommended as sole screenin test 11 9  Indirect immunofluorescent antibody ◦ Sensitive as screening test, may give false positive in clinical case ◦ test available several genotypes ( B. canis and gibsoni)  PCR – ◦ Overall sensitivity in one assay for diagnosis of chronic B. gibsoni infection was 90% ◦ Concern- lack of standardisation between labs, marked variability in sensitivity/specificity 12 0  Supportive therapy including blood transfusion, sodium bicarbonate for acidosis, and fluid therapy  Imidocarb dipropionate (5 - 6.6 mg/kg SC or IM and repeated after 14 days) or 7.5 mg/kg SC or IM once) ◦ Adverse effects:transient salivation, diarrhoea, dyspnea, depression and lacrimation  Penamidine isethionate (15 mg/kg of 5% solution SC once daily for two days 12 1  Other drugs which may be used if nothing else is available ◦ Metronidazole (25 mg/kg PO q8-12 h, for 2-3 weeks ◦ Clindamycin HCl (12.5 mg/kg PO q12h, for 2-3 weeks  Other drugs that have been used: ◦ Diminazene aceturate, pentamidine isethionate, parvaquone, niridazone 12 2  Atovaquone (13.3 mg/kg PO, TID) and azithromycin (10 mg/kg PO q24hr) are effective for clearing B. canis vogeli infection but are very expensive 12 3  No evidence to suggest zoonosis  Tick control important for prevention  Avoid splenectomy of previously infected dogs  Dogs to be used as blood donors must be assessed  In france a vaccine composed of an aduvant and soluble antigens collected from supernatants of B. canis cultures is available ◦ Produces partial protection (less severe clinical signs) but does not prevent infection 12 4  Babesia spp. detected in naturally infected domestic cats include B. felis and B. leo from Africa, B. cati , B. canis canis , B. microti-like and B. canis presentii.  The most common Babesia species to affect domestic cats, B. felis, is a highly pathogenic, small piroplasm southern Africa.  B. felis usually occurs in cats less than three years of age and does not appear to have a predilection related to sex or breed.  Babesia herpailuri and B. pantherae are large intraerythrocytic piroplasms of wild felids in Africa that have been transmitted experimentally to the domestic cat. 12 5  Feline babesiosis often presents as a chronic, low-grade disease.  The most common clinical signs of symptomatic feline babesiosis are anorexia, lethargy, weakness, and a rough haircoat.  Unlike dogs with babesiosis, fever and icterus are uncommon in cats.  In most instances when fever is present, concurrent illness is diagnosed. 12 6  Complications of babesiosis include renal failure, pulmonary edema, hepatopathy, and central nervous system signs.  Many clinical signs are secondary to hemolytic anemia that results from intraerythrocytic infection by the piroplasms.  Cats, however, usually adapt to the anemia and may have only mild clinical signs until they are stressed.  Concurrent infection with Mycoplasma hemofelis , feline leukemia virus (FeLV), or feline immunodeficiency virus (FIV) may contribute to the clinical presentation and severity of disease 12 7  In cats, the most consistent hematologic finding is a macrocytic, hypochromic, regenerative anemia with inconsistent presence of intraerythrocytic piroplasms.  The anemia is hemolytic, presumably from both intravascular and intravascular erythrolysis.  In experimental infection, anemia was most profound approximately 3 weeks after infection.  Blood smears reveal increased polychromatophils, Howell- Jolly bodies, nucleated erythrocytes, and anisocytosis indicative of regenerative anemia 12 8  Erythrophagocytosis by monocytes may also be observed.  Secondary IMHA is seen occasionally with a positive agglutination test.  Cats lack characteristic changes in the leukogram.  Thrombocytopenia is common in other species with babesiosis but is an inconsistent finding in cats. 12 9  Serum ALT activity is significantly elevated in the majority of cases whereas ALP and GGT activities generally are within reference intervals.  Increased total bilirubin concentration is commonly detected and is most likely a result of hemolysis, but secondary hepatocellular injury may be a contributing factor.  Polyclonal gammopathy has been observed in cats with hypergammaglobulinemia. 13 0  A tentative diagnosis - identifying intracellular piroplasms within erythrocytes on a Romanowsky or Giemsa- stained peripheral blood smear.  However, piroplasms of B. felis and other small piroplasms, including B. leo and Cytauxzoon felis, may be morphologically indistinguishable 13 1  Observing the organisms on a blood smear may also be difficult since the level of parasitemia may be low.  definitive diagnosis of intraerythrocytic piroplasms is by molecular methods. 13 2  Polymerase chain reaction (PCR) detection of Babesia spp. DNA is a useful technique  Once the presence of piroplasms is ascertained, the individual species of organisms may be identified by comparing genetic sequences of the 18S ribosomal subunit of the parasite’s RNA. 13 3  Serologic testing has mainly been used to diagnose canine babesiosis.  This technique cannot be used reliably in domestic cats because reference intervals for babesiosis- related serologic titers have not been established. 13 4  Primaquine phosphate, 0.5mg/kg, PO or IM has been effective but frequently caused vomiting when administered orally and was lethal at dosages exceeding 1mg/kg. ◦ Primaquine is capable of clearing the parasitemia but does not eliminate B. felis infections.  Buparavaquone, enrofloxacine, and danofloxacin have no significant anti- babesial effect.  Rifampicin and a sulfadiazine-trimethoprim combination appear to have an anti-parasitic effect but are inferior to primaquine administration.  Finally, repeated or chronic antiprotozoal therapy may be necessary to effectively treat feline babesiosis. 13 5  In a published review of 20 cats with experimental babesiosis and 70 cats with naturally acquired babesiosis, all untreated animals eventually died.  Response to appropriate treatment is generally good, but recurrence of clinical disease and chronic infection are possible.  Concurrent infection with Mycoplasma hemofelis, FeLV, and FIV has been identified in a number of cats with feline babesiosis and may have profound effects on response to treatment and outcome of disease. 13 7 Life cycle  This infection has been known as Haemobartonellosis as the organism that causes it used to be called Haemobartonella ◦ Hemobartonella felis is now Mycoplasma haemofelis ◦ Hemobartonella canis is now Mycoplasma haemocanis  Collectively known as haemoplasmas  Different species found that differ in pathogenicity 14 0  Feline ◦ M. haemofelis-  acute haemolytic anaemia in splenectomised and immunocompromised cats ◦ Candidatus M. Haemominutum (less pathogenic than M. haemofelis) and Candidatus M. turicensis (mild to severe anemia  Splenectomy not required for disease induction but immunocompromise may play a role 14 1  Canine ◦ M. haemocanis infection results in haemolytic anaemia only in splenectomised or immunocompromised dogs  A new canine haemoplasma, Candidatus M. haematoparvum recently been decribed in association with anaemia in a dog that had been splenectomised and immunosupressed 14 2  Candidatus M. haemominutum most common and identifed in 10-32% of cats sampled in different studies  M. haemofelis and candidatus M. turicensis less common, 1.4 - 6.4% and 1.3 - 26%, respectively  In one study kenneled dogs were found to have higher prevalence of infection with M. haemocanis than pet dogs 14 3  parasites adhere to red blood cells changing their cell surface and making them antigenic or ‘foreign’ Cells removed by the RE system of the spleen and liver The replication cycle of this parasite takes 2 to 8 weeks so clinical disease tends to be cyclic. Infection may be subclinical, but is most likely to resulting disease when the cat is co-infected with FeLV. 14 4  Candidatus M. Haemominutum (does not usually lead to significant clinical signs or anaemia) ◦ Significant anemia was seen Candidatus M. Haemominutum infection in retrovirus-infected cats ◦ Most studies of naturally infected cats have failed to find an association between Candidatus M. Haemominutum infection and anaemia ◦ Candidatus M. Haemominutum infection has been reported in a cat undergoing chemotherapy for lymphoma 14 5  M. haemofelis ◦ Experimental infection results in severe anaemia ◦ Some studies on naturally infected cats have found an association between anaemia and M. haemofelis infection, but others have not. ◦ Hypothesised that acute infections lead to severe anaemi where as chronically infected cats are not anaemic 14 6  Candidatus M. turicensis ◦ Naturally infected cats often have concurrent diseases ◦ Moderate – severe anemia seen two cats, being more sever in the cat receiving methyprednisolone to induce immunosuppression 14 7  The route of transmission is believed to be via fleas.  Transmission from queen to kittens either in utero or via milk may also occur.  Persistent infections, clinically normal carriers, and recurrent infections can all occur. 14 8  Cats may be asymptomatic.  Other cats develop acute disease with signs of ◦ lethargy, pale mucus membranes, tachypnoea, tachycardia and occasionally dyspnoea. ◦ Splenomegaly is common and pyrexia is variable. ◦ Where the anaemia is severe a haemic murmur may be detected and jaundice may develop. ◦ Autoimmune haemolytic anaemia (IMHA) usually develops concurrently. 14 9  Parasitaemia waxes and wanes, but Giemsa or acridine orange stained blood smears can be used for detection of the organism attached to red cells.  The organism may appear as rods, cocci or chains.  Detection of the organism is variable and repeat smears may be required.  Artefacts due to poor staining are common. Fresh blood smears are essential, preferable made from blood collected from a small peripheral vein.  Method shows poor sensitivity and variable specificity 15 0  PCR-based tests are now available and are very reliable– they are the most sensitive and accurate way of making a diagnosis.  A regenerative anaemia should be present, with polychromasia and normoblasts  IMHA is often present, resulting in autoagglutination and/or a positive Coomb’s test 15 2  Doxycycline 5 - 10mg/kg/day PO (which to reduce the risk of oesophageal inflammation and secondary stricture formation should always be given with a syringe of water PO or before food) or Oxytetracycline at 10 to 20mg/kg q8h po, or fluroquinolones.  Where IMHA is present, give prednisolone at 2 - 4 mg/kg/day tapering over 8 weeks. However, use of steroids may lead to an increased risk of generating a chronic carrier.  Blood transfusion in severe cases of anaemia. 15 3  AETIOLOGY/ EPIDEMIOLOGY ◦ FIV exogenous single strand virus in the family retroviridae, subfamily lentivirinae ◦ Morphologically similar to HIV ◦ Produces reverse transcriptase to catalyse the insertion of viral RNA into the host genome 15 4  Route of infection: aggressive biting behavior 1o route ◦ Older, male, outdoor cats commonly affected ◦ Transplacental and perinatal transmission from infected queens to kittens ◦ Experimental vaginal route also shown 15 5  FIV replicates in T-lymphocytes (CD4+ and CD8+), B-lymphocytes, macrophages,  Virus then disseminated throughout body leading to initially low grade fever, neutropenia, and generalised lymphadenopathy (primary phase)  Subclinical latent period of variable length then develops  The cat will then remain clinically normal for an indefinite period until immunosuppression develops (when the virus affects both T and B lymphocyte function). 15 7  The clinical progression of FIV infection can be divided into five stages, using the system described for HIV infection in humans: ◦ Acute infection (the first four to sixteen weeks of infection); ◦ Asymptomatic carrier (this stage may last months to years); ◦ Persistent generalized lymphadenopathy (PGL-this stage is usually very short and difficult to observe in FIV-infected cats); ◦ AIDS-related complex (ARC-signs of gastrointestinal and respiratory disease are usually apparent); and ◦ Acquired immunodeficiency syndrome (AIDS cats develop opportunistic infections accompanied by fever and wasting). Cats in the ARC or AIDS stage of infection generally live for less than one year. 15 8  The signs seen in the immunosuppressive stage of the disease are related to secondary infections and are therefore extremely variable.  Common signs include gingivitis/stomatitis, weight loss, rhinitis, diarrhoea, skin disease and ocular signs (most commonly a uveitis which can result in glaucoma).  Neurological signs may be seen due to meningoencephalitis.  FIV immunosuppressed cats are predisposed to infection with other organisms against which healthy cats usually show resistance, e.g. toxoplasmosis, salmonellosis and demodecosis.  There is also increasing evidence that the incidence of neoplasia is increased in FIV cats 16 0  Non-specific hematological, bichemical, urinalysis and radiographic findings  Cats with Lymphosarcoma (LSA) have mass lesions radiographically  LSA diagnosed by cytology and histopathology  IFA, ELISA, PCR, virus isolation confirm infection 16 2  Many of the antiviral agents used to treat HIV in humans are costly and/or toxic to cats, and are not routinely used in cats.  However success has been seen using 3`-azido-2` 3`- dideoxythymidine (AZT: 5-10 mg/kg, PO, SC, or IV q12h, stop if PCV