Toxoplasma gondii

1. Epidemiology
   1. Immunocompetent patients (asymptomatic) Prevalence
      1. Adolescents: 23% have Toxoplasmosis antibodies
      2. Young women: 15%
   2. Congenital Toxoplasmosis (Intrapartum exposure)
      1. Cases in U.S. per year: 400 to 4000
   3. HIV Patients
      1. Most common cause of cerebral mass lesions in HIV
2. Pathophysiology
   1. Intracellular coccidian protozoan
   2. Main host: Feidae family including domestic cats
      1. Cats pass oocysts in feces during acute infection
      2. Oocysts sporulate (infectious) in environment
      3. Oocysts infectious for >1 year in warm, moist soil
      4. Indoor cats not fed raw meat unlikely to be infected
      5. Serologic testing of cats is not useful
   3. Stages of life cycle
      1. Tachyzoite (invade cells and replicate)
      2. Bradyzoite (dormant as tissue cysts)
      3. Sporozoite (oocysts in environment)
   4. Sites of infection (most common)
      1. Muscle
      2. Liver
      3. Spleen
      4. Lymph nodes
      5. Central nervous system
   5. Trasmission
      1. Raw or under-cooked meat (pork, mutton, wild game)
         1. Responsible for 50% of cases in U.S.
      2. Vertical Transmission across placenta (intrapartum)
         1. Toxoplasmosis infection before conception
            1. Rare transmission unless immunocompromised
         2. First trimester infection: 10-25% transmission
         3. Third trimester infection: 60-90% transmission
      3. Ingesting items contaminated with infected cat feces
         1. Incubation to infectious state requires >1 day
         2. Litter box exposure
         3. Gardening soil
         4. Unfiltered water
         5. Unwashed vegetables or fruits
   6. Incubation
      1. Under-cooked meat ingestion: 10-23 days
      2. Infected cat feces ingestion: 5-20 days
   7. Reactivation
      1. Occurs only in immunosuppressed groups (e.g. HIV)
      2. CNS Infection is the most common site of reactivation
   8. HIV patients
      1. Reactivation of latent infection is common
      2. Cerebral infection occurs in 30-50% of patients with:
         1. Preexisting Antibody to Toxoplasmosis
         2. CD4 Counts <100 cells
3. Presentation
   1. Immunocompetent patients
      1. Usually asymptomatic
      2. Generalized symptoms may be briefly present
         1. Fever
         2. Malaise
         3. Lymphadenopathy
   2. Congenital Toxoplasmosis
      1. Classic triad
         1. Chorioretinitis
         2. Hydrocephalus
         3. Intracranial calcifications
      2. General signs
         1. Hepatosplenomegaly
         2. Lymphadenopathy
         3. Fever
         4. Anemia and Thrombocytopenia
   3. HIV patients
      1. Common
         1. Encephalitis (most common)
         2. Pneumonia
         3. Chorioretinitis
         4. Disseminated disease
      2. General Signs
         1. Fever
         2. Headache
         3. Cognitive Impairment is frequent presenting symptom
            1. Altered Mental status
            2. Altered behavior
         4. Focal neurologic deficit (60%)
            1. Hemiparesis
            2. Aphasia
            3. Ataxia
            4. Visual field defects
            5. Cranial Nerve palsies
            6. Tremor
4. Labs: Screening
   1. Indications
      1. HIV patients or other immunosuppression
      2. Pregnant women with suspected exposure
         1. Routine screening in pregnancy not recommended
   2. Diagnostic Tests (protocol for age over 1 year)
      1. Step 1: Serum IgG Toxoplasmosis antibodies (97%)
         1. If positive, go to Step 2
         2. Stop if IgG negative
         3. Positive within 1-2 weeks of infection
         4. Consider retest in 3 weeks if negative, equivocal
      2. Step 2: Serum IgM Toxoplasmosis antibodies
         1. If positive, go to Step 3
            1. May be positive up to 18 months after infection
            2. Confirm positive test with a reference lab
               1. Checks for false positives
         2. If negative, infection occurred >6 months ago
      3. Step 3: Serum IgG Toxoplasmosis avidity status
         1. If low, go to Step 4
         2. If high, infected 12 weeks or longer ago
      4. Step 4: Resend IgG, IgM and avidity after 3 weeks
         1. Go back to Step 1 to interpret findings
         2. If still not diagnostic, go to Step 5
      5. Step 5: Advanced testing
         1. Toxoplasmosis differential agglutination
         2. Serum Toxoplasmosis IgA
         3. Serum Toxoplasmosis IgE
5. Labs: Fetal testing (Congenital Toxoplasmosis)
   1. Amniocentesis for Toxoplasmosis PCR
      1. Risk of false positive and false negative tests
6. Labs: HIV patients with mass lesion
   1. Brain biopsy (confirms the diagnosis)
   2. False negatives may occur
7. Radiology in HIV patients: Head CT scan or Head MRI
   1. MRI is more sensitive
   2. Ring enhancing lesions on CT with contrast
   3. Multiple bilateral lesions
      1. Basal ganglia
      2. Corticomedullary junction
8. Management: Pregnancy
   1. Active Toxoplasmosis infection in pregnancy
      1. Spiramycin (Rovamycine)
   2. Fetal Toxoplasmosis confirmed by Amniocentesis
      1. General
         1. Use not recommended before 13-18 weeks
      2. Protocol
         1. Pyrimethamine (Daraprim) and
         2. Sulfadiazine and
         3. Folinic acid (leucovorin)
            1. Prevents marrow suppression of Pyrimethamine
9. Management: Congenital Toxoplasmosis
   1. Treatment administered for 1 year
   2. Additional management needed for ocular infection
   3. Protocol
      1. Pyrimethamine (Daraprim) and
      2. Sulfadiazine and
      3. Folinic acid (leucovorin)
10. Management: HIV
    1. Most treatment started empirically
    2. Regimen (90% response rate in 1-2 weeks)
       1. Pyrimethamine and
       2. Sulfadiazine (or Clindamycin or Dapsone)
       3. Folinic acid (Leucovorin)
    3. Drugs
       1. Pyrimethamine
          1. Initial: 100 mg/day
          2. Later: 25 mg/day
       2. Sulfadiazine
          1. Initial: 4 gram
          2. Later: 1 gram qid
       3. Clindamycin
          1. Indication: allergy to sulfadiazine
          2. Initial: 200 mg q6 hours
          3. Later: 300-450 mg q6-8 hours
       4. Leucovorin
          1. Indication: less pyrimethamine marrow suppression
          2. Dose: 10-20 mg/day
       5. Dapsone
          1. Indication: alternative to sulfadiazine
          2. Dose: 100 mg qd
    4. Other medications: Corticosteroids
       1. Indication: severe cerebral edema
    5. Adverse Reactions (common) to treatment
       1. Neutropenia
       2. Rash
       3. Fever
       4. Renal Impairment
    6. Course
       1. Continue treatment until symptoms and imaging normal
       2. Continue low dose maintenance for patients life
          1. Pyrimethamine and sulfadiazine low dose daily
11. Complications
    1. Congenital Toxoplasmosis (up to 80% of cases)
       1. Mental Retardation (may not be evident until school)
       2. Blindness
       3. Seizure Disorder
    2. HIV patients
       1. Seizures in a third of patients
       2. Coma is rare
12. Prevention
    1. General Measures
       1. Peel or carefully wash all fruits and vegetables
       2. Fully cook all meats (especially beef, lamb, game)
       3. Carefully wash all items for preparing food
       4. Wear gloves when handling soil (i.e. gardening)
       5. Pet cat care
          1. Patients at risk should not change cat litter
             1. Immunosuppressed patients (e.g. HIV)
             2. Pregnant patients
          2. Wear gloves when changing cat litter
          3. Wash hands carefully after changing litter box
          4. Change litter daily (before infectious)
          5. Keep cat inside and avoid strays
          6. Use only commercial or cooked cat food
    2. HIV Patients: Toxoplasmosis Prophylaxis
       1. See Prevention of Secondary Infection in HIV
       2. Baseline toxoplasma serology in all HIV patients
       3. Prophylaxis is indicated if CD4 Count <100 cells/mm3 or if seropositive
          1. Trimethoprim-Sulfamethoxazole, Bactrim, or Septra DS daily (same as for Pneumocystis prophylaxis) or
          2. Dapsone and Pyrimethamine has also been used
13. References
    1. (2000) MMWR Morb Mortal Wkly Rep 49:57-75
    2. Jones (2003) Am Fam Physician 67(10):2131-46
    3. Weller (2001) BMJ 322:1350-4