Toxoplasmosis Flashcards
What is Toxoplasma gondii?
A protozoan that can cause asymptomatic infection, mononucleosis-like syndrome, retinochoroiditis, or congenital infection in immunocompetent individuals
What is the most common manifestation of toxoplasmosis in people with HIV?
Toxoplasma encephalitis (TE)
How does primary infection of Toxoplasma gondii commonly occur?
Through consumption of undercooked meat, unwashed fruits or vegetables, contaminated water, unpasteurized milk, or ingestion of oocysts from cat feces
What is the seroprevalence of anti-Toxoplasma antibody in the United States?
Approximately 11%
What is the incidence of toxoplasmosis in people with HIV who are seronegative for T. gondii?
Very low incidence, representing primary infection or reactivation of latent disease
What CD4 T lymphocyte count indicates the greatest risk for clinical disease in people with HIV?
CD4 counts <50 cells/mm3
What are common symptoms of focal encephalitis due to Toxoplasma gondii in people with HIV?
Headache, focal neurologic deficits (e.g., hemiparesis), and sometimes fever
True or False: The absence of anti-toxoplasma immunoglobulin G (IgG) antibodies makes a diagnosis of toxoplasmosis unlikely.
True
What imaging findings are typical for toxoplasmosis?
Contrast-enhancing lesions, typically ring-enhancing, with a predilection for the basal ganglia
What is required for a definitive diagnosis of Toxoplasma encephalitis?
Compatible clinical syndrome, identification of mass lesions by CT or MRI, and detection of the organism in a clinical sample
What should be performed if safe and feasible for diagnosing Toxoplasma gondii?
Lumbar puncture for T. gondii PCR, cytology, culture, and other relevant tests
What is the preferred regimen for primary prophylaxis against Toxoplasma gondii encephalitis?
TMP-SMX one double-strength tablet daily
When should primary prophylaxis against toxoplasmosis be discontinued?
When CD4 count >200 cells/mm3 for >3 months and sustained HIV RNA below limits of detection
What is the indication for restarting primary prophylaxis against Toxoplasma gondii?
CD4 count <100 cells/mm3 or CD4 count 100–200 cells/mm3 with HIV RNA above detection limits
What is the preferred treatment regimen for acute Toxoplasma gondii encephalitis?
Pyrimethamine 200 mg PO once, followed by weight-based dosing with sulfadiazine and leucovorin
What alternative regimen can be used for treating acute Toxoplasma gondii encephalitis?
TMP-SMX (TMP 5 mg/kg and SMX 25 mg/kg) twice daily
Fill in the blank: The most common clinical presentation of T. gondii infection among people with HIV is _______.
focal encephalitis
What does a positive cerebrospinal fluid (CSF) toxoplasma polymerase chain reaction (PCR) indicate?
Detection of the organism in cases of Toxoplasma encephalitis
What should be advised to people with HIV regarding cat litter?
A nonpregnant person without HIV should change the litter box daily, or gloves should be worn if done by a person with HIV
What is a common complication in patients with AIDS presenting with CNS lesions?
Differential diagnosis includes primary CNS lymphoma, tuberculosis, and endemic fungal infections
What does the presence of EBV in CSF by PCR suggest?
Concern for CNS lymphoma
What is the significance of JCV by PCR in CSF in patients with HIV receiving ART?
Highly suggestive of progressive multifocal leukoencephalopathy (PML)
True or False: All people with HIV need to part with their cats to prevent toxoplasmosis.
False
What is the initial therapy of choice for Toxoplasma Encephalitis (TE)?
The combination of pyrimethamine plus sulfadiazine plus leucovorin (AI)
Pyrimethamine penetrates the brain parenchyma efficiently even in the absence of inflammation. Leucovorin reduces the likelihood of hematologic toxicities associated with pyrimethamine therapy.
What is the recommended dosage of pyrimethamine for body weight >60 kg?
75 mg PO daily
Along with sulfadiazine 1,500 mg PO every 6 hours + leucovorin 10–25 mg PO daily.
What should be used if pyrimethamine is unavailable?
TMP-SMX (TMP 5 mg/kg and SMX 25 mg/kg) twice daily (AII)
TMP-SMX should be utilized if pyrimethamine-sulfadiazine cannot be obtained without delay.
What is the total duration for treating acute Toxoplasma infection?
At least 6 weeks (BII)
Longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks.
What are the preferred regimens for chronic maintenance therapy for TE?
Pyrimethamine 25–50 mg PO daily + sulfadiazine 2,000–4,000 mg PO daily + leucovorin 10–25 mg PO daily (AI)
Alternatively, TMP-SMX DS one tablet twice daily (AII).
What are the criteria for discontinuing chronic maintenance therapy for TE?
- Successfully completed initial therapy
- Asymptomatic of signs and symptoms of TE
- CD4 count >200 cells/mm3 for >6 months in response to ARVs
These criteria ensure that the patient is stable before discontinuation.
What initiates treatment for fetal infection during pregnancy?
Positive amniotic fluid PCR, and/or fetal ultrasonographic findings suggestive of congenital toxoplasmosis
Treatment for fetal infection includes pyrimethamine + sulfadiazine + leucovorin until delivery.
Fill in the blank: For patients with a history of sulfa allergy, rapid sulfa _______ may be attempted.
desensitization
This involves using one of several published strategies.
True or False: Antiseizure medications should be used prophylactically in patients without seizures.
False
Antiseizure medications should only be administered to patients with TE associated with seizures (AII).
What is the recommended dosage of spiramycin for suspected or confirmed acute toxoplasmosis during pregnancy before 14 weeks?
1.0 g (or 3 million U) every 8 hours (total dosage of 3 g or 9 million U per day) (AII)
This is the initial therapy for primary infection during pregnancy.
What must be added to the regimen when using pyrimethamine plus leucovorin plus clindamycin?
Additional agent for PCP prophylaxis (AII)
This is necessary as this combination does not prevent PCP.
What are common toxicities of pyrimethamine?
- Rash
- Nausea
- Bone marrow suppression (neutropenia, anemia, thrombocytopenia)
These toxicities can often be reversed by increasing leucovorin dose.
What is the common treatment response rate for acute therapy in TE patients within 14 days?
Approximately 90%
If no improvement is seen by that time, other diagnoses should be considered.
What should be monitored in patients receiving corticosteroids for TE?
Development of other opportunistic infections (OIs)
Patients should be monitored closely for infections like cytomegalovirus retinitis and tuberculosis.
What is the preferred alternative regimen for patients intolerant of sulfadiazine?
(Pyrimethamine + leucovorin) plus clindamycin 600 mg IV or PO every 6 hours (AI)
This regimen is preferred for patients who do not respond to first-line therapy.
What is the recommended dosage of atovaquone for treating TE?
1,500 mg PO twice daily (BII)
Atovaquone should be taken with meals or nutritional supplements to ensure adequate absorption.
What is the recommended follow-up for fetal assessment during pregnancy?
- Amniocentesis for toxoplasmosis PCR at 18 weeks gestation or later (BIII)
- Fetal ultrasonography every 4 weeks until delivery (AIII)
This is to monitor for evidence of fetal infection.
What is the significance of achieving plasma levels >18.5 µg/mL of atovaquone?
Associated with an improved response rate
However, therapeutic drug monitoring for atovaquone is not routinely available.
What are common toxicities associated with clindamycin?
Fever, rash, nausea, diarrhea (including pseudomembranous colitis), hepatotoxicity
Pseudomembranous colitis is diarrhea related to Clostridium difficile toxin.
What are common toxicities associated with TMP-SMX?
Rash, fever, leukopenia, thrombocytopenia, hepatotoxicity
What are common toxicities associated with atovaquone?
Nausea, vomiting, diarrhea, rash, headache, hepatotoxicity, fever
What should be evaluated carefully when considering drug interactions?
Anticonvulsants (e.g., phenytoin, phenobarbital, carbamazepine), dexamethasone, and antiretroviral agents
When should a brain biopsy be considered in patients with TE?
In patients who did not have an initial biopsy prior to therapy and who fail to respond to initial therapy for TE
What is the recommended chronic maintenance therapy for patients who have completed initial therapy for TE?
Pyrimethamine plus sulfadiazine plus leucovorin
What is the dosing recommendation for sulfadiazine in chronic maintenance therapy?
Four-times-a-day regimen, although twice-daily dosing is also effective
What should be done if a patient’s CD4 count is >200 cells/mm3 for >6 months?
Chronic maintenance therapy for TE can be discontinued
When should primary prophylaxis be reintroduced?
If the CD4 count decreases to <100 cells/mm3
What is the risk of congenital toxoplasmosis highest?
In the setting of a primary infection during pregnancy
What should be evaluated for pregnant people with HIV who have evidence of primary toxoplasmic infection?
Consultation with appropriate specialists
What is the recommended initial therapy for patients presumed to have acquired/reactivated infection at less than 14 weeks gestation?
Spiramycin
What should be done for patients with suspected primary or symptomatic reactivation of T. gondii during pregnancy?
Detailed ultrasound examination of the fetus and amniocentesis with PCR testing for T. gondii DNA
What is the preferred alternative regimen for pregnant patients with TE who cannot tolerate first-line therapy?
Pyrimethamine plus clindamycin plus leucovorin
What should be done if a patient started on spiramycin is found to have a positive PCR in the amniotic fluid?
Escalate therapy to pyrimethamine/sulfadiazine/leucovorin
What is the recommendation for pyrimethamine use in the first trimester of pregnancy?
Avoid due to teratogenicity concerns
What is the safety profile of sulfadiazine in pregnancy?
Appears safe without clear evidence of adverse fetal or neonatal outcomes
What is the recommendation regarding clindamycin during pregnancy?
Considered safe throughout pregnancy
What should be discussed with patients of pregnancy potential receiving TE prophylaxis?
Deferring pregnancy until TE prophylaxis can be safely discontinued
What is the risk associated with dapsone during pregnancy?
Mild hemolysis and a potential risk of hemolytic anemia in fetuses with G6PD deficiency
