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Toxoplasmosis
A diagnosis of exclusion
‘Kenzie’ McLaren
• One-year-old castrated male British Shorthair
• One-day history of hindlimb ataxia and paresis
• 20% weightloss in 11 weeks
• Initial PE: unremarkable
• PCV low: 22% [29-45%]
• Pelvic radiography unremarkable
• Referred to neurology service
Initial Presentation
Summary of Findings
• Pyrexia (39.3 to 40.3°C)
• Initial stiff hindlimb gait
• Reduced exercise tolerance: forelimbs became
stiff to the point of collapse
• Normal spinal reflexes, but some myoclonus
• No proprioceptive deficits
• Suggestive of a neuromuscular disorder
DDx: neuropathy, myopathy or junctionopathy
Summary of Findings
• Pyrexia (39.3 to 40.3°C)
• Initial stiff hindlimb gait
• Reduced exercise tolerance: forelimbs became
stiff to the point of collapse
• Normal spinal reflexes, but some myoclonus
• No proprioceptive deficits
DDx: neuropathy, myopathy or junctionopathy
Summary of Findings
• Pyrexia (39.3 to 40.3°C)
• Initial stiff hindlimb gait
• Reduced exercise tolerance: forelimbs became
stiff to the point of collapse
• Normal spinal reflexes, but some myoclonus
• No proprioceptive deficits
• Initial CK and ACh-R antibody (pending) tests
DDx: neuropathy, myopathy or junctionopathy
Electromyography (EMG)
• Abnormal spontaneous muscle activity
• Normal nerve conduction velocities
• Normal repetitive nerve stimulation
DDx: myopathy or junctionopathy
Problem List
Neurological
Ataxia
Stiff gate
Reduced exercise tolerance
Myoclonus (EMG confirmed)
Dx: Myopathy (idiopathic or secondary)
DDx: Infectious, Autoimmune, Neoplastic
Other
Weightloss (too acute)
Pyrexia
Anaemia (rarely)
CK elevated (84X upper ref.)
Haematology
Erythrocytes
• Low haematocritt
• Polycythaemia
• Haemaglobinaemia
Leukocytes
• Leukopaenia
• Neutropaenia
• Lymphopaenia
Blood Smear
• Anaemia poorly regenerative
• Howell-Jolly bodies in RBCs
• Occasional poikilocytes
• Mild toxic left shift
• Pro-eosinophils containing basophilic granules
• Occasional hyperchromatic lymphoid cells
• Direct Coombs Test Negative
DDx: chronic infectious, autoimmune, neoplastic
Biochemistry
• Hypoproteinaemia
• Low globulin levels
• High AST (2X upper ref.)
• High ALT (3X upper ref.)
• High CK (now 180X upper ref.)
• High fasting bile acids (2X upper ref.)
– Need bile acid stimulation test
DDx: myopathy, mild cholangiohepatitis
Biochemistry
• Hypoproteinaemia
• Low globulin levels
• High AST (2X upper ref.)
• High ALT (3X upper ref.)
• High CK (now 180X upper ref.)
• High fasting bile acids (2X upper ref.)
– Need bile acid stimulation test
DDx: myopathy, mild cholangiohepatitis
Thoracic Radiography
Excessive mild bronchial pattern
and cardiomegaly
L
R
DDx: chronic bronchitis, early onset asthma
DDx: myocarditis, HCM
Microbiology Report
• Mucal swab taken from endotracheal tube
due to respiratory noise during anaesthesia
• Culture: Gram negative cocci & large rods
• Sensitive to
– Clavunated amoxicillins
– Azithromycin
– Doxycycline
– Marbofloxacin
Problem List
Neurological
Ataxia
Stiff gate
Reduced exercise tolerance
Myoclonus (EMG confirmed)
Dx: Myopathy (idiopathic or secondary)
Dx: Mild cholangiohepatitis (potentially)
Dx: Chronic bacterial bronchitis
DDx: Infectious, Autoimmune, Neoplastic
Other
Weightloss
Pyrexia
Poorly regenerative anaemia
CK elevated (180X upper ref.)
Elevated liver enzymes
Cardiomegaly (DDx: myocarditis)
Feline Infectious Disease Panel
• NEGATIVE: Feline Leukaemia Virus (FeLV)
Antigen
• NEGATIVE: Feline Immunodeficiency Virus
(FIV) Immunofluorescent Assay
• NEGATIVE: Feline Corona Virus (FCoV)
Antibody Titre
• POSITIVE: Toxoplasma Antibody Titre
– IgG Seropositive (4X upper ref.)
Problem List
Neurological
Ataxia
Stiff gate
Reduced exercise tolerance
Myoclonus (EMG confirmed)
Dx: Myopathy
Dx: Mild cholangiohepatitis (potentially)
Dx: Chronic bacterial bronchitis
Dx: Myocarditis (potentially)
Dx: Chronic Toxoplasmosis (Infectious)
Other
Weightloss
Pyrexia
Poorly regenerative anaemia
CK elevated (180X upper ref.)
Elevated liver enzymes
Cardiomegaly
Explains secondary
symptoms and disease
Initial Treatment
• Pyrexia & Liver: IV fluids (0.9% saline)
• Neutropaenia and Bronchitis: Augmentin 40
mg slow IV TID, then oral Synulox 50 mg BID
• Toxoplasmosis: Clindamycin 25 mg BID
5-days Post-Treatment
Continued Treatment & Monitoring
• Clindamycin 25 mg BID for 4 weeks
• Retest Toxoplasma antibody levels in 4 weeks
• Recheck biochemistry and haematology
• Ensure pulmonary infection has resolved and
hepatic markers are within normal limits
• Consider further cardiac evaluation
Toxoplasma gondii
• Worldwide zoonosis
• Obligate, intracellular
parasitic protozoan
• Only sexually reproduce in
cats – the definitive host
• Chronic infection can occur
for the lifetime of the host,
periodically rupturing cysts
and re-encysting to increase
numbers
Clinical Signs
General Signs
Anorexia
Lethargy
Pyrexia
Weightloss
Ataxia
Specific Disease
Bronchopneumonia
Hepatitis
Myocarditis
Encephalitis
Uveitis
• Acute or chronic progression
• Transplacental infection most severe
• Poorer prognosis with hepatic or pulmonary signs
Life Cycle
Questions?
Special thanks
Kate Stalin
Rodrigo Gutierrez Quintana
Emma Roberts
Katie Grove

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Grand Rounds: Toxoplasmosis

  • 2. ‘Kenzie’ McLaren • One-year-old castrated male British Shorthair • One-day history of hindlimb ataxia and paresis • 20% weightloss in 11 weeks • Initial PE: unremarkable • PCV low: 22% [29-45%] • Pelvic radiography unremarkable • Referred to neurology service
  • 4. Summary of Findings • Pyrexia (39.3 to 40.3°C) • Initial stiff hindlimb gait • Reduced exercise tolerance: forelimbs became stiff to the point of collapse • Normal spinal reflexes, but some myoclonus • No proprioceptive deficits • Suggestive of a neuromuscular disorder DDx: neuropathy, myopathy or junctionopathy
  • 5. Summary of Findings • Pyrexia (39.3 to 40.3°C) • Initial stiff hindlimb gait • Reduced exercise tolerance: forelimbs became stiff to the point of collapse • Normal spinal reflexes, but some myoclonus • No proprioceptive deficits DDx: neuropathy, myopathy or junctionopathy
  • 6. Summary of Findings • Pyrexia (39.3 to 40.3°C) • Initial stiff hindlimb gait • Reduced exercise tolerance: forelimbs became stiff to the point of collapse • Normal spinal reflexes, but some myoclonus • No proprioceptive deficits • Initial CK and ACh-R antibody (pending) tests DDx: neuropathy, myopathy or junctionopathy
  • 7. Electromyography (EMG) • Abnormal spontaneous muscle activity • Normal nerve conduction velocities • Normal repetitive nerve stimulation DDx: myopathy or junctionopathy
  • 8. Problem List Neurological Ataxia Stiff gate Reduced exercise tolerance Myoclonus (EMG confirmed) Dx: Myopathy (idiopathic or secondary) DDx: Infectious, Autoimmune, Neoplastic Other Weightloss (too acute) Pyrexia Anaemia (rarely) CK elevated (84X upper ref.)
  • 9. Haematology Erythrocytes • Low haematocritt • Polycythaemia • Haemaglobinaemia Leukocytes • Leukopaenia • Neutropaenia • Lymphopaenia
  • 10. Blood Smear • Anaemia poorly regenerative • Howell-Jolly bodies in RBCs • Occasional poikilocytes • Mild toxic left shift • Pro-eosinophils containing basophilic granules • Occasional hyperchromatic lymphoid cells • Direct Coombs Test Negative DDx: chronic infectious, autoimmune, neoplastic
  • 11. Biochemistry • Hypoproteinaemia • Low globulin levels • High AST (2X upper ref.) • High ALT (3X upper ref.) • High CK (now 180X upper ref.) • High fasting bile acids (2X upper ref.) – Need bile acid stimulation test DDx: myopathy, mild cholangiohepatitis
  • 12. Biochemistry • Hypoproteinaemia • Low globulin levels • High AST (2X upper ref.) • High ALT (3X upper ref.) • High CK (now 180X upper ref.) • High fasting bile acids (2X upper ref.) – Need bile acid stimulation test DDx: myopathy, mild cholangiohepatitis
  • 13. Thoracic Radiography Excessive mild bronchial pattern and cardiomegaly L R DDx: chronic bronchitis, early onset asthma DDx: myocarditis, HCM
  • 14. Microbiology Report • Mucal swab taken from endotracheal tube due to respiratory noise during anaesthesia • Culture: Gram negative cocci & large rods • Sensitive to – Clavunated amoxicillins – Azithromycin – Doxycycline – Marbofloxacin
  • 15. Problem List Neurological Ataxia Stiff gate Reduced exercise tolerance Myoclonus (EMG confirmed) Dx: Myopathy (idiopathic or secondary) Dx: Mild cholangiohepatitis (potentially) Dx: Chronic bacterial bronchitis DDx: Infectious, Autoimmune, Neoplastic Other Weightloss Pyrexia Poorly regenerative anaemia CK elevated (180X upper ref.) Elevated liver enzymes Cardiomegaly (DDx: myocarditis)
  • 16. Feline Infectious Disease Panel • NEGATIVE: Feline Leukaemia Virus (FeLV) Antigen • NEGATIVE: Feline Immunodeficiency Virus (FIV) Immunofluorescent Assay • NEGATIVE: Feline Corona Virus (FCoV) Antibody Titre • POSITIVE: Toxoplasma Antibody Titre – IgG Seropositive (4X upper ref.)
  • 17. Problem List Neurological Ataxia Stiff gate Reduced exercise tolerance Myoclonus (EMG confirmed) Dx: Myopathy Dx: Mild cholangiohepatitis (potentially) Dx: Chronic bacterial bronchitis Dx: Myocarditis (potentially) Dx: Chronic Toxoplasmosis (Infectious) Other Weightloss Pyrexia Poorly regenerative anaemia CK elevated (180X upper ref.) Elevated liver enzymes Cardiomegaly Explains secondary symptoms and disease
  • 18. Initial Treatment • Pyrexia & Liver: IV fluids (0.9% saline) • Neutropaenia and Bronchitis: Augmentin 40 mg slow IV TID, then oral Synulox 50 mg BID • Toxoplasmosis: Clindamycin 25 mg BID
  • 20. Continued Treatment & Monitoring • Clindamycin 25 mg BID for 4 weeks • Retest Toxoplasma antibody levels in 4 weeks • Recheck biochemistry and haematology • Ensure pulmonary infection has resolved and hepatic markers are within normal limits • Consider further cardiac evaluation
  • 21. Toxoplasma gondii • Worldwide zoonosis • Obligate, intracellular parasitic protozoan • Only sexually reproduce in cats – the definitive host • Chronic infection can occur for the lifetime of the host, periodically rupturing cysts and re-encysting to increase numbers
  • 22. Clinical Signs General Signs Anorexia Lethargy Pyrexia Weightloss Ataxia Specific Disease Bronchopneumonia Hepatitis Myocarditis Encephalitis Uveitis • Acute or chronic progression • Transplacental infection most severe • Poorer prognosis with hepatic or pulmonary signs
  • 24. Questions? Special thanks Kate Stalin Rodrigo Gutierrez Quintana Emma Roberts Katie Grove

Notas del editor

  1. Hypotonia = poor muscle tone OOH = out-of-hours Any way to find out the temperature, etc. that was monitored in the kennel?
  2. Myoclonus = involuntary muscle twitching Myasthenia gravis = type of junctionopathy (disease of the muscle or neuromuscular junction); autoimmune complexes block Ach-R function Only a small blood sample was attainable ACh-R Ab titre (80-96% sensitive) results take a few weeks to come back Neuropathy = clinical signs rule out due reduced exercise tolerance and lack of proprioceptive and reflex deficits
  3. Myoclonus = involuntary muscle twitching Myasthenia gravis = type of junctionopathy (disease of the muscle or neuromuscular junction); autoimmune complexes block Ach-R function Only a small blood sample was attainable ACh-R Ab titre (80-96% sensitive) results take a few weeks to come back Neuropathy = clinical signs rule out due reduced exercise tolerance and lack of proprioceptive and reflex deficits
  4. Myoclonus = involuntary muscle twitching Myasthenia gravis = type of junctionopathy (disease of the muscle or neuromuscular junction); autoimmune complexes block Ach-R function Only a small blood sample was attainable ACh-R Ab titre (80-96% sensitive) results take a few weeks to come back Neuropathy = clinical signs rule out due reduced exercise tolerance and lack of proprioceptive and reflex deficits
  5. Evaluates and records the electrical potential of skeletal muscle cells (depolarisation) Identifies neuromuscular diseases, assesses pain, kinesiology, and motor control disorders Myopathy more likely than a junctionopathy (myasthenia gravis) because of normal nerve conduction velocities and repetitive nerve stimulation THEN, they ran a gambit of bloodwork
  6. Howell-Jolly bodies = remnant DNA (suggests splenic damage) Poikilocytes = abnormal-shaped RBCs Toxic left shift = immature features still present in mature neutrophils with band neutrophils also present Pro-eosinophils containing basophilic granules = often seen in chronic granulocytic leukaemia CRONIC REGENERATIVE ANAEMIA (bone marrow exhausting)
  7. Cholangiohepatitis? Shunts? Need a bile acid stimulation test.
  8. Cholangiohepatitis? Shunts? Need a bile acid stimulation test.
  9. Is the first radiograph a VD or DV, is it marked incorrectly or does it need to be flipped? Congenital HCM based on age Chronic bronchitis or early onset asthma Vestigial 14th rib
  10. Resp. noise during anaesthetic; the 5 days of antibiotics should have cleared up the infection
  11. Titres can remain high years after exposure
  12. All of these diagnoses are possible secondary to chronic Toxoplasmosis in transplacentally-acquired infection.
  13. Do we need to retest of Abs can stay in the system years after infection?
  14. Image 1: http://www.businessinsider.com/how-insects-and-animals-are-turned-into-zombies-by-parasites-2012-12?op=1 Image 2: http://www.ufrgs.br/para-site/siteantigo/Imagensatlas/Protozoa/Toxoplasma.htm
  15. Change rat behaviour in the brain and make them attracted to cat urine. Image: http://cmr.asm.org/content/25/2/264.full.pdf
  16. Image: http://www.catchannel.com/images/articles/2-2008/catmouse-200px.jpg