TOXOPLASMOSIS

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TOXOPLASMOSIS

• Dr. S.GOPALAKRISHNAN. M.D
• Asst. Prof.
• Govt. Hospital for Thoracic Medicine
• Tambaram.

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INTRODUCTION

• Toxoplasma Gondii is worldwide in distribution.
• Most common Chronic infection with Obligate
  intracellular Protozoan in Humans.
• 3-4 of all Patients with AIDS may develop CNS
  Toxoplasmosis at some stage.
• Greatest incidence when CD4 lt 100 cells/mm3
• Decrease in CMI in chronically infected at risk
  of reactivation of infection.

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EPIDEMIOLOGY

• Definite Host CAT
• Sexual Cycle----Oocyst
• Intermediate Host Human,Mouse,Pig,Sheep.
• 
  Asexual Cycle----Tissue cyst

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EPIDEMIOLOGY

• Transmission to humans
• Oral
• Ingestion of under cooked Pork or Lamb
• meat tissue cyst.
• Exposure to oocysts
• Ingestion of contaminated vegetables
• direct Contact with cat feces.
• Others
• Transplacental.
• Blood Product Transfusion.
• Organ Transplantation.

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PATHOGENESIS

• ORAL INGESTION
• TACHYZOITE (INVASIVE FORM)
• DISSEMINATES THROUGH OUT THE BODY
• INFECTION -gtANY NUCLEATED CELL-gtMULTIPLICATION -gt
  
• CELL DESTRUCTION -gt NECROTIC FOCI -gt
• SURROUNDING INFLAMMATION
• TISSUE CYST
• LIFE LONG CHRONIC INFECTION
• ONSET OF CMI

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SUSCEPTIBILITY MECHANISM IN HIV

• Depletion of CD4 T cells
• Decreased production of IL-2 ,IL-12,IFN-g
• Decreased cytotoxic T-lymphocyte activity.

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CLINICAL PRESENTATION

• Immuno compromised
• Cerebral
• Manifests primarily as toxoplasmic encephalitis
• Altered mental status 75
• Focal Neurological deficit 70
• Motor weakness
• Speech Disturbances
• Cranial Nerve Palsy
• Movement Disorders
• Visual Field Defects
• Sensory ,Cerebellar Dysfunction

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Cont

• Head ache 56
• Fever 45
• Seizures 30
• Extra Cereberal
• Ocular
• Choreoretinitis Less common than CMV
• Lesions adjacent to disc, old scar
• Multi focal, bilateral lesions typically more
  confluent, thick, opaque.
• Anterior Uveitis

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Cont

• Pulmonary
• Highly Lethal sepsis like syndrome
• Difficult to distinguish from Pneumocystis
  cari. pneumonia
• Cardiac
• Asymptomatic
• Cardiac tamponade
• Biventricular Failure

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IMMUNOCOMPETENT

• LYMPHADENOPATHY
• Common CERVICAL (Single or Multiple
  non tender,Discrete)
• Generalized 20-30
• Fever,Myalgia,Rash , Meningo-Encephalitis.
• Rare Pneumonia,Myocarditis,Polymyositis.

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DIAGNOSIS

• Serology
• Anti-IgG Antibodies
• Peaks within 1-2 months after infection.
• Remain elevated for life.
• False negative 10-15
• Sabin-feldman dye test-gold standard
• IFA-indirect
• Elisa

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Cont

• IgM Anti-body tests
• Double sandwich Elisa
• IFA
• Immunosorbent agglutination assay
• (IgM-ISAGA)

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SEROLOGY

• To diagnose recent infection
• Serial specimens at 3 weeks apart-4 fold increase
  in IgG titre.
• OR
• Elevated IgM, IgA or IgE titres with differential
  agglutination test.
• Useful to Identify - HIV at risk of developing
  toxoplasmosis. 97-100 HIV with toxo
  encephalitis have anti IgG anti bodies.

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CSF

• Non specific
• Mild cell count mononuclear, protein
• Intrathecal Anti IgG antibodies production
• Ratio gt 1 supports the diagnosis of toxoplsmic
  encephalitis
• Wright Giemsa stain of CSF

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DNA

• POLYMERASE CHAIN REACTION (PCR)
• CSF Sensitivity 50 60
• - Specificity 100
• Bronchoalveolar lavage fluid
• Vitreous and aqueous humor
• Blood samples low sensitivity toxo.encpha.
• Amniotic fluid
• Culture Time consuming

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NEURORADIOLOGIC STUDIES

• C T
• Multiple, bilateral, hypodense,
  contrast-enhancing focal brain lesions 70 to
  80
• Lesions basal ganglia, hemispheric
  corticomedullary junction.
• Contrast enhancement often with ringlike pattern

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MRI

• More sensitive than CT
• Identify more lesions than seen on CT, new
  lesions not seen on CT

NEWER IMAGING TECHNIQUES 201T1 SPECT Thallium
201 single- photon emission computed
tomography 18F FDG PET Fluoride 18 - Flouro
2 deoxyglucose positron emission tomography.
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Toxoplasmosis
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Toxoplasmosis- Response to therapy
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Toxoplasmosis
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DEFINITE DIAGNOSIS

• Excisional Brain Biopsy
• Usually not performed
• Reserved for patients who fail to respond to
  therapy

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DIFFERENTIAL DIAGNOSIS

• Primary CNS Lymphoma
• Mycobacterial infections
• Cryptococcal meningitis
• Herpes simplex encephalitis
• PML
• CMV infection
• Infectious mononucleosis

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MANAGEMENT IN HIV

• Therapy empiric in most cases
• Neurologic response
• 51 by day 3
• 91 by day 14
• Neuroradiologic study repeated 2-4 weeks after
  initiation of therapy

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Cont

• Acute Therapy
• Maintenance Therapy
• (Secondary Prophylaxis)
• Prevention (Primary Prophylaxis)
• Discontinuation of Prophylaxis

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ACUTE THERAPY

• Preferred
• Pyrimethamine 200mg po loading dose followed by
  75-100 mg po qd plus folinic acid 15-20 mg po qd
  plus sulfadiazine 1-1.5g po q6h - 6 weeks.
• Alternatives
• Pyrimethamine with folinic acid (as standard)
  with one of the following
• Clindamycin 600 mg po q6h
• Clarithromycin 1g po bid
• Azithromycin 1.2-1.5g po qd
• Dapsone 100mg po qd - 6 weeks

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MAINTENANCE THERAPY

• Preferred
• Pyrimethamine 25 mg po qd folinic acid 10 mg po
  qd and Sulfadiazine 500-1000 mg po
• q 6h
• Alternative
• Pyrimethamine 25 mg po qd folinic acid 5-10 mg
  qd po Clindamycin 300-450 mg po q6-8h.
• Atovaquone 750 mg po bid

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PREVENTION

• To eat well cooked meat - internal temperature of
  1160C, or no longer pink inside.
• Proper hand washing.
• Fruits and vegetables should be washed prior to
  consumption.
• To avoid contact with materials contaminated with
  cat feces, handling cat litter boxes.
• To wear gloves during gardening.

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Cont

• Recommended
• T gondii - Seropositive patients with CD4 T cell
  counts lt100 regardless of clinical status.
• Patients with CD4 T cell counts lt200 if an
  opportunistic infection or malignancy develops.
• Trimethorprim / sulfamethazole 1 ds tab po qd
• Dapsone 50 m po qd pyrimethamine 50 mg po q
  week plus folinic acid 25 mg po q week

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DISCONTINUATION OF PROPHYLAXIS

• CD4 T cell counts increase to more than 200 over
  a period of 3- 6 months in response to HAART
• Restarting prophylaxis in patients CD4 T cell
  counts decrease to lt 200

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Thank you