Toxoplasmosis

See Also

Epidemiology

Immunocompetent patients (asymptomatic) Prevalence
1. United States: 60 Million (11% of U.S. population over age 6 years old)
2. Adolescents: 23% have Toxoplasmosis antibodies
3. Young women: 15%
Congenital Toxoplasmosis (Intrapartum exposure)
1. Cases in U.S. per year: 400 to 4000
HIV Patients
1. Most common cause of cerebral mass lesions in HIV

Pathophysiology

Intracellular coccidian Protozoan
Main host: Feidae family including domestic cats
1. Small rodents become infected by ingesting oocysts
2. Outdoor cats become infected by eating small rodents
3. Cats pass oocysts in feces during acute infection
4. Oocysts sporulate (infectious) in environment
5. Oocysts infectious for >1 year in warm, moist soil
6. Indoor cats not fed raw meat unlikely to be infected
7. Serologic Testing of cats is not useful
Stages of life cycle
1. Tachyzoite (invade cells and replicate)
2. Bradyzoite (dormant as tissue cysts)
3. Sporozoite (oocysts in environment)
Sites of infection (most common)
Trasmission
1. Raw or under-cooked meat (pork, lamb, deer, cattle, sheep, goats)
  1. May also me transmitted by contaminated utensils and cutting boards
  2. Responsible for 50% of cases in U.S.
2. Vertical Transmission across placenta (intrapartum, congenital infection)
  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
    1. Cats shed for weeks when newly infected
  2. Litter box exposure
  3. Gardening soil
  4. Unfiltered water
  5. Unwashed vegetables or fruits
4. Blood-borne pathogen
  1. Blood Transfusion
  2. Organ Transplantation
Incubation
1. Under-cooked meat ingestion: 10-23 days
2. Infected cat feces ingestion: 5-20 days
Reactivation
1. Organism stays remains inactive after infection until immunosupression
2. Occurs only in immunosuppressed groups (e.g. HIV)
3. CNS Infection is the most common site of reactivation
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

Presentation

Immunocompetent patients
1. Usually asymptomatic
2. Generalized symptoms may be briefly present for 1-2 weeks (mild flu-like symptoms)
  1. Fever
  2. Malaise
  3. Myalgias
  4. Lymphadenopathy (cervical or occipital)
Congenital Toxoplasmosis
1. Often asymptomatic at birth
2. Classic triad
  1. Chorioretinitis
  2. Hydrocephalus
  3. Intracranial calcifications
3. General signs
  1. Jaundice
  2. Hepatosplenomegaly
  3. Lymphadenopathy
  4. Fever
  5. Anemia and Thrombocytopenia
  6. Ocular changes occur in 20-80% of cases (but may not minifest until adulthood)
    1. Chorioretinitis presents with Blurred Vision, Eye Pain, photophobia
HIV patients (or otherwise immunosuppressed)
1. Common
  1. Encephalitis (most common)
  2. Pneumonia
  3. Chorioretinitis
  4. Disseminated disease
2. General Signs
  1. Fever
  2. Headache
  3. Seizure
  4. Cognitive Impairment is frequent presenting symptom
    1. Altered Mental Status (confusion)
    2. Altered behavior
  5. Focal neurologic deficit (60%)
    1. Hemiparesis
    2. Aphasia
    3. Ataxia or other altered coordination
    4. Visual Field Defects
    5. Cranial Nerve palsies
    6. Tremor

Labs
Screening

Indications
1. HIV Infection or other Immunosuppression
2. Pregnant women with suspected exposure
  1. Routine screening in pregnancy not recommended
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 PCR
  2. Toxoplasmosis differential Agglutination
  3. Serum Toxoplasmosis IgA
  4. Serum Toxoplasmosis IgE

Labs
Other Testing

Fetal testing (Congenital Toxoplasmosis)
1. Amniocentesis for Toxoplasmosis PCR
2. Risk of False Positive and False Negative tests
3. May be performed as early as 18 weeks gestation
Immunosuppressed Patients in whom Immunoglobulin testing may be unreliable
1. Toxoplasmosis PCR
2. Microscopy of blood, tissue biopsy or cerebrospinal fluid
HIV patients with mass lesion
1. Brain biopsy (confirms the diagnosis)
2. False Negatives may occur

Imaging
HIV patients (Head CT scan or Head MRI)

Brain MRI is more sensitive
Ring enhancing lesions on CT with contrast
Multiple bilateral lesions
1. Basal Ganglia
2. Corticomedullary junction

Management
Pregnancy

Active Toxoplasmosis infection in pregnancy
1. Infection in first or second trimester
  1. Spiramycin (Rovamycine)
    1. Most effective if started within 8 weeks of seroconversion
    2. Continue through remainder of pregnancy if no fetal infection
2. Infection in Third Trimester (or late second trimester)
  1. See triple protocol for fetal Toxoplasmosis as below
Fetal Toxoplasmosis confirmed by Amniocentesis (or third trimester infection)
1. General
  1. Use not recommended before 13-18 weeks
  2. Also indicated in third trimester maternal infection (without known fetal infection)
2. Protocol
  1. Pyrimethamine (Daraprim) and
  2. Sulfadiazine and
  3. Folinic acid (leucovorin)
    1. Prevents marrow suppression of Pyrimethamine

Management
Congenital Toxoplasmosis

Treatment administered for 1 year
Additional management needed for ocular infection
Protocol
1. Pyrimethamine (Daraprim) and
2. Sulfadiazine and
3. Folinic acid (leucovorin)

Management
HIV

Most treatment started empirically
Regimen (90% response rate in 1-2 weeks)
1. Pyrimethamine and
2. Sulfadiazine (or Clindamycin or Atovaquone)
3. Folinic acid (Leucovorin)
Drugs
1. Pyrimethamine
  1. Initial Treatment: 200 mg orally for first dose
  2. Next
    1. Weight >60 kg: 75 mg orally daily
    2. Weight <60 kg: 50 mg orally daily
2. Sulfadiazine
  1. Treatment Dose: 1.5 g (1.0 g if wt <60 kg) orally every 6 hours
3. Clindamycin
  1. Indication: allergy to Sulfadiazine
  2. Initial: 600 mg every 6 hours
4. Folinic Acid (Leucovorin)
  1. Indication: Less Pyrimethamine marrow suppression
  2. Dose: 10-25 mg orally daily
5. Atovaquone
  1. Dose: 1500 mg orally twice daily
Other medications: Corticosteroids
1. Indication: severe cerebral edema
Adverse Reactions (common) to treatment
1. Neutropenia
2. Rash
3. Fever
4. Renal Impairment
Course
1. Continue treatment until symptoms and imaging normal
2. Continue low dose maintenance for patients life
  1. Pyrimethamine and Sulfadiazine low dose daily

Complications

Congenital Toxoplasmosis (up to 80% of cases)
1. Mental Retardation (may not be evident until school)
2. Blindness
3. Seizure Disorder
HIV patients
1. Seizures in a third of patients
2. Coma is rare

Prevention

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
HIV Patients: Toxoplasmosis Prophylaxis
1. See Prevention of Secondary Infection in HIV
2. Baseline toxoplasma Serology in all HIV patients
3. Primary 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
4. Chronic Suppression (Secondary Prophylaxis, until CD4 Count >200 for 6 months)
  1. Sulfadiazine 2-4 g/day orally divided bid to qid (or Clindamycin 600 mg every 8 hours) AND
  2. Pyrethamine 25-50 mg orally every 24 hours AND
  3. Folinic Acid 10-25 mg orally every 24 hours

References

(2016) Sanford Guide, accessed 4/9/2016
(2000) MMWR Morb Mortal Wkly Rep 49:57-75 [PubMed]
Cantey (2021) Am Fam Physician 104(3): 277-87 [PubMed]
Jones (2003) Am Fam Physician 67(10):2131-46 [PubMed]
Weller (2001) BMJ 322:1350-4 [PubMed]
Woodhall (2014) Am Fam Physician 89(10): 803-11 [PubMed]