LHS Infectious disease 2: FIP and FIA Flashcards
Outline FIP
- fatal dz
- domestic and non-domestics
- feline coronavirus (infection common, clinical dz uncommon)
What was feline coronavirus previously classified as?
- feline enteric coronavirus (FECV)
- feline infectious peritonitis virus (FIPV)
- now thought to be biotypes of same virus
What type of virus is FIP?
- enveloped, ssRNA
- large, pleiomorphic
- mutates
- 2 types: 1 wholly feline, 2 - arises by recombination with canine coronavirus
- 70-90% field isolates type 1, 10-30% type 2
Where does FIP (coronavirus) live/replicate/ etc?
- replicates: cytoplasm, newly synthesised virions acquire membranes from ER and golgi, released by cell lysis or vesicle fusion with plasma membrane
- relatively unstable outside host: inactivated at room temp in 24 h at 56 degrees for 1h, may live up to 7 wks in environment if protected (heat, light, chemicals)
Describe FECV
- present in large % helahty cats
- oronasal transmission
- virus replicates in enterocytes
- CS mild/inapparent: V, D, URT signs
Describe FIPV
- FCoV mutation (‘internal mutation theory’ questioned by recent work showing identical nucleotide sequences of enteric and non-enteric FCoV in cat that died of FIP)
- infects macrophages –> systemc infection
- FIP = clinical dz syndrome from ineffective I.R.
Outcomes of FCoV infection
- transient infection: 60-70%
- PI: 10-15%
- FIP 5-10%
- resistance to FCoV infection 2-5%
What type of dz is FIP?
immune complex dz
What is FIP characterised by?
- vasculitis
- complement activation
- excessive cytokine production
Pathophysiology - FIP
Viral Ag + anti-viral Ab + coplement –> complement fixation –> release of vasoactive amines –> endothelial cell retraction –> increased vascular permeability (protein rich exudate, neutrophils produce lysosomal enzymes and vessel wall necrosis)
How does the strength of the FIP cell-mediated I.R. affect outcome?
- strong response –> protection
- partial response –> non-effusive dz
- poor response –> effusive dz
What are the CS of FIP the consequence of?
vasculitis and secondary organ damage
Incubation period - FIP
weeks to months (onset of CS sudden or insidious)
CS - early signs
- generally non-specific
- pyrexia
- inappetance/ anorexia, wt loss
- diarrhoea
- listless, dehydration
- icterus
T/F: in FIP, some cats may show a mixed form
True (mixed of effusive and non-effusive)
Describe the effusive form of FIP
- 60-75% caes
- abdominal effusion –> ascites
- pleural effusion –> dyspnoea
- pericardial effusion (less common)
Describe the dry form of FIP
- dry or granulomatous form
- predisposition for: eye, brain, CNS, kidney, liver, localised regions of intestine
Dx - FIP
- often difficult ante-mortem (especially dry gorm)
- hx and CS
- PE (always include ocular + fundic exam, look for uveitis and chorioretinitis)
- lab / imaging findings
- alorithms may help
Describe CBC for FIP
- lymphopaenia
- neutrophilia with mild left shift
- mild non-rgenerative anaemia
- may also be normal
Describe biochem for FIP
- hyperglobulinaemia (by serum electrophoresis, polyclonal increse in gamma globulins, increased APPs)
- hyperbilirubinaemia
- usually NOT azotaemic
- may also be normal
Describe fluid analysis in FIP
- clear, straw-yellow
- high protein count (may clot in tube)
- viscous, may become frothy whne shaken
- variable cellularity (
How is FIP coronavirus titre determined?
- IFA most commonly: for anti-FCoV Ab, use FIP virus-infected feline cell lines as substrate, ELISA available
- IFA and ELISA tests don’t distinguish cats infected with FCoV or FIPV: positive titre indicates prior exposure to FCoV, not necessarily the presence of FIP, rare negative titres in FIP, predictive significance of high titres
What other diagnostic tests can you use for FIP?
- CSF: dry tap or increased protein and cells
- OTHER TESTS TO DEMONSTRATE FCoV: direct FA adn IHC (tissue sections), RT-PCR detects viral genomic RNA (positive in healthy cat), new RT-PCR detects sub-genomic mRNA therefore replicating virus in circulating
What is alpha1-acid glycoprotein?
- an APP produced by liver in response to inflammatory stimuli
- increased serum not specific for FIP but can be useful in combination with other clinical findings
- if 1500 increased index of suspicion
Histopathology of FIP
- light plaques on serosal surfaces, adhesions of omentum and mesentery
- liver, spleen, kidney, omentum, mesenteric LN, most commonly affected
Tx / prognosis - FIP
- grave prognosis: no cure for dz in large majority of cases, tx palliative
- remission/ cure reported - questionable
- options:
- supportive/ palliative care: ABs, SQ fluids, nutrition, rest, thoracocentesis
- immune-modulators
- GCs +/- chlorambucil
- aspirin? (care - cats)
- oral polyprenyl immunostimulant
Outline vaccination against FIP
- strong cell-mediated immune response without strong Ab response
- Primucell: T-sensitive mutant of serotype 1 FCoV, IN administration, local I.R., induced low IgG titres, efficacy controversial, but safe, no ADR
Key points with FIP
- difficult to diagnose
- only way to confirm is histopath
- non-effusive dz hardest to dx
- cannot predict which cats will develop dz
What is the reclassification of feline infectious anaemia (FIA)?
Haemotropic mycoplasma (haemoplasmas) - small epicellular parasites, no cell wall, TC-sensitive
What can cause FIA?
- Mycoplasma haemofelis: most pathogenic form (–> anaemia)
- Candidatus Mycoplasma haemominutum: less pathogenic
- Canididatus Mycoplasma turicensis: documented in swiss cat with haemolytic anaemia, SPF cats mild to severe anaemia
Outline pathogenesis of FIA
- Mycoplasma attach to RBCs –> I-M destruction
- concurrent dz, immunosuppression –> enhanced dz
- if recover from infection –> chronic infection for variable time (reactivation and recurrence possible)
Describe Mycoplasma haemofelis
- associated with anaemia
- pleiomorphic: rods, rings or spherical
- gram negative
Possible routes of transmission of haemotropic mycoplasmas
- fleas
- blood transfusion
- female cats to neonates (in utero, nursing)
- fighting
- oral
- experimenting (IP, IV and PO infected blood, urine and saliva not thought to be infective)
Describe infection with Mycoplasma haemofelis
- dz more common in young, entire males
- often infection ‘latent’
- stress/ concurrent illness –> acute disease
- recovered cat may have relapse with stress
Outline PCV changes with FIP
- may cases: rapid decrease in PCV, organisms in blood (go to spleen)
- PCV rises as organisms disappear
- some cats (PCV continues to decrease after parasitaemic episode, result of RBC destruction)
Outline anemia in FIA cats
- direct damage to RBC
- I-M injury: Coombs’ test may be positive, extravascular haemolysis by macrophages in liver, spleen, lungs and BM
CS - M.haemofelis
acute and chronic signs
ACUTE INFECTION: - lethargy - inappetance/ anorexia - fever - anaemia (39-41 degrees) - splenomegaly - icterus CHRONIC INFECTION: - normal to subnormal temperature - weakness - depression - wt loss/ emaciation - icterus and splenomegaly less likely
Outline CBC for FIA
- REGENERATIVE ANAEMIA: varies in severity (PCV 15-18%), reticulocytosis, regenerative morphology
- If acute onset anaemia, may be pre-regenerative
- Eryhthrophagocytosis and autoagglutination may be present
- leukocyte count variable: leucocytosis with monocytosis in acute forms, normal counts in chronic forms, leucopaenia in moribund
How can M.haemofelis be detected?
- fresh blood smear: EDTA may displace organism
- organisms only noted in about 50% acute dz cases (fluctuating numbers): repeat daily for 5-10d
- diferentiate from Howell-Jolly bodies, basophilic stippling, stain precipittes
- apparent absence doesn’t r/o dx
- acridine orange stain, IFA
- PCR: sensitive, amplification of DNA from organism in vitro, can distinguish b/w M. haemofelis and Candidatus M haemomintum
- evaluate for other dz
Tx - FIA
- DOXYCYCLINE: 5-10mg/kg, orally BID for 14-21d
- potential AEs: GIT, abdominal discomfort, vomiting, inappetence/ anorexia, oesophagitis, oesophgeal stricture formation
- POSS ALTERNATIVE = enrofloxacin 5-10mg/kd orally SID for 2wks but acute irreversible retinal degeneration, blindness. Marbofloxacin
- FLEA CONTROL: especially FeLV or FIV positive cats, likely to relapse
- SUPPORTIVE CARE: blood transfusion if necessary (compatible blood type essential), immunosuppressive therapy (prednisolone) to inhibit erythrophagocytosis, gradually reduce dose
Px - FIA
- no tx: approxiamtely 1/3 with uncomplicated acute dz die
- regeneration –> destruction + immune response to organism –> recovery
- recovery phase: last parasitaemia to PCV stabilisation > 1 month
- carrier state
Distinguish enzootic and epizootic - FIP
- ENZOOTIC (commonest): sporadic, infrequent, unpredictable losses
- EPIZOOTIC: high losses (50%, esp juveniles), may last 6-12 mo then reverts to enzootic, may be d/t intro of new sttrain
Control - FIP
- ↓ stress
- ↓ faecal contam.
- small groups by age and Ab status
- FeCoV seronegative household
- test incoming cats
- prepare kitten room
- barrier nurse
- wean/isolate kittens early (5-6wks) if seropositive queen
- test for anti-FCoV Ab after 10 wks
Actions - cat with FIP
- don’t introduce new kitten
- coronavirus can persist up to 7 wks in environement (wait 2 mo after removal)
Effect of Candidatus mycoplasma haemominutum
- common isolate of healthy cats
- experimental infection (minimal CS of acute dz and minimal haematological changes)
- experimental co-infection with FeLV causes more severe anaemia
- chronic infxn (may promote neoplastic transformation of haemopoietic cells in cats with FeLV)
Effect of splenectomy in FIA
fewer parasites (Candidatus Mycoplasma haemomintum) removed but splenectomy nt as significant in cats as other spp
Ddx - FIA
- FelV-induce HA
- IMHA of other causes
- tx prior to results is for FIA and IMHA
Serum biochemistry - FIA
- increased ALT and AST
- hyperbilirubinaemia
- increased [TP]
- hypoglycaemia (moribund cats)
Describe FIA carrier state
- clinically normal
- recovered from acute dz (chronically infected, possibly for life)
- normal PCV/ mild regen. anaemia
- organisms: low #s or absent
- opportunistic? may observe acute dz with stress