Guidelines for Prevention and Treatment of
Opportunistic Infections in HIV-Infected
Adults and Adolescents
Toxoplasma gondii Slide Set
Prepared by the AETC National Resource Center
based on recommendations from the CDC,
National Institutes of Health, and HIV Medicine
Association/Infectious Diseases Society of America
About This Presentation
These slides were developed using recommendations
published in May 2013. The intended audience is
clinicians involved in the care of patients with HIV.
Users are cautioned that, because of the rapidly
changing field of HIV care, this information could
become out of date quickly. Finally, it is intended that
these slides be used as prepared, without changes in
either content or attribution. Users are asked to honor
this intent.
-AETC National Resource Center
http://www.aidsetc.org
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Toxoplasma gondii Encephalitis:
Epidemiology
 Caused by the T gondii protozoan
 Disease almost always caused by reactivation of
latent tissue cysts
 Primary infection may be associated with acute
cerebral or disseminated disease
 Seroprevalence varies widely: 11% in the United
States, 50-80% in some European, Latin
American, and African countries
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Toxoplasma gondii Encephalitis:
Epidemiology (2)
 In advanced AIDS, 12-month incidence of TE
was 33% among Toxoplasma-seropositive
patients who were not on prophylaxis or ART
 Among seronegative persons, toxoplasmosis is
rare
 Occurs primarily in patients with CD4 counts of
<200 cells/µL, especially <50 cells/µL
 Incidence and mortality lower in United States
and Europe owing to widespread use of
prophylaxis and potent ART
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Toxoplasma gondii Encephalitis:
Epidemiology (3)
 Primary infection acquired from tissue cysts
in undercooked meat or raw shellfish, or
ingestion of sporulated oocysts (from cat
feces) in soil, water, or food
 No transmission by person-to-person
contact
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Toxoplasma gondii Encephalitis:
Clinical Manifestations
 Focal encephalitis with headache,
confusion, or motor weakness and fever
 May have nonfocal symptoms, including
nonspecific headache and psychiatric
symptoms
 May have focal neurological abnormalities;
may progress to seizures, altered mental
status, coma
 Retinochoroiditis, pneumonia, other organ
involvement are rare
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Toxoplasma gondii Encephalitis:
Clinical Manifestations
 CT or MRI:
 Typical findings are multiple contrast-enhancing
lesions in gray matter of cortex or basal ganglia,
often associated edema
 May show single brain lesion, or diffuse
encephalitis without focal lesions
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Toxoplasma gondii Encephalitis:
Diagnosis
 Serum anti-Toxoplasma IgG
 Positive in almost all patients with TE; negative
IgG makes diagnosis unlikely but not impossible
 IgM usually negative
 Definitive diagnosis: compatible clinical
syndrome + mass lesion(s) on imaging +
detection of organism in a clinical sample
(brain biopsy)
 CT, MRI of brain: typically multiple contrast-enhancing
lesions, often with edema
 MRI better than CT for radiological diagnosis
 PET or SPECT may help distinguish TE from
lymphoma
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Toxoplasma gondii Encephalitis:
Diagnosis (2)
 Check CSF (if safe and feasible) for T gondii
PCR, cytology, culture, cryptococcal antigen, PCR
for M tuberculosis, EBV, JC virus
 CSF PCR specificity for T gondii is 96-100%,
sensitivity 50%
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Toxoplasma gondii Encephalitis:
Diagnosis (3)
 Differential diagnosis of focal neurological
disease
 CNS lymphoma, PML, mycobacterial infection
(TB), fungal infection, Chagas disease,
abscess
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Toxoplasma gondii Encephalitis:
Diagnosis (4)
CT scan of the brain
showing contrastenhancing lesion of
toxoplasmosis
Credit: P. Volberding, MD; UCSF Center for HIV Information
Image Library
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Toxoplasma gondii Encephalitis:
Diagnosis (5)
 May initially make empiric diagnosis,
established on basis of clinical and
radiographic improvement to TE therapy,
in absence of a likely alternative diagnosis
 Brain biopsy if failure to respond to
therapy, or if initial studies suggest
etiology other than TE
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Toxoplasma gondii Encephalitis:
Preventing Exposure
 All HIV+ should be tested for IgG to
Toxoplasma at baseline, to detect latent
infection
 Toxoplasma seronegative: counsel about
sources of infection
 Patients: avoid eating raw or undercooked
meat or shellfish; wash hands after handling
raw meat and after contact with soil; wash
fruits/vegetables; clean cat-litter boxes daily
and wash hands afterward; cats should not
be fed raw/undercooked meats
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Toxoplasma gondii Encephalitis:
Primary Prophylaxis
For all Toxoplasma IgG positive with CD4 count <100
cells/µL
 Recommended:
 TMP-SMX 1 DS QD
 Alternative:
 TMP-SMX 1 DS PO TIW
 TMP-SMX 1 SS QD
 Dapsone* 50 mg PO QD + pyrimethamine 50 mg PO Q week +
leucovorin 25 mg PO Q week
 Dapsone* 200 mg PO Q week + pyrimethamine 75 mg PO Q
week + leucovorin 25 mg PO Q week
 Atovaquone 1,500 mg PO QD +/- pyrimethamine 25 mg PO QD
+ leucovorin 10 mg PO QD
* Avoid dapsone if patient has G6PD deficiency; screen before treatment
with dapsone, if possible.
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Toxoplasma gondii Encephalitis:
Primary Prophylaxis (2)
 Toxoplasma seronegative patients: retest
for Toxoplasma IgG if CD4 count declines
to <100 cells/µL, unless taking PCP
prophylaxis that also is active against TE
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Toxoplasma gondii Encephalitis:
Discontinuing Primary Prophylaxis
 Discontinue if on effective ART with CD4
count of >200 cells/µL for >3 months
 Restart prophylaxis if CD4 count decreases
to <100-200 cells/µL
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Toxoplasma gondii Encephalitis:
Treatment
 Preferred:
 Pyrimethamine 200 mg PO 1 dose, then:
 For weight ≤60 kg: pyrimethamine 50 mg PO QD
+ sulfadiazine 1,000 mg PO Q6H + leucovorin 1025 mg PO QD
 For weight >60 kg: pyrimethamine 75 mg PO QD
+ sulfadiazine 1,500 mg PO Q6H + leucovorin 1025 mg PO QD
 Duration: ≥6 weeks, longer if extensive disease
or incomplete response at 6 weeks
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Toxoplasma gondii Encephalitis:
Treatment (2)
 Alternative:
 Pyrimethamine as above + clindamycin 600 mg IV or
PO Q6H + leucovorin as above
 TMP-SMX (5 mg/kg TMP and 25 mg/kg SMX) IV or
PO BID
 Atovaquone 1,500 mg PO BID + pyrimethamine, as
above + leucovorin as above
 Atovaquone 1,500 mg PO BID + sulfadiazine (weightbased as above)
 Atovaquone 1,500 mg PO BID (variable absorption)
 Pyrimethamine as above + azithromycin 900-1,200
mg PO QD + leucovorin as above
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Toxoplasma gondii Encephalitis:
Treatment (3)
 Adjunctive corticosteroids only if
indicated for treatment of mass effect;
monitor closely and discontinue as soon
as possible
 Anticonvulsants if history of seizures;
continue at least through period of acute
therapy
 Should not be given prophylactically to all
patients
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Toxoplasma gondii Encephalitis:
ART Initiation
 No data to guide recommendation on
when to start ART
 Many recommend starting ART within 2-3
weeks after diagnosis of TE
 In one study, lower rate of AIDS progression
or death with early ART
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Toxoplasma gondii Encephalitis:
Monitoring and Adverse Events
 Follow clinical and radiologic improvement
 Ab titers not useful
 Monitor for adverse events
 Pyrimethamine: rash, nausea, bone marrow
suppression
 May be reversed with increase in leucovorin dosage
 Sulfadiazine: rash, fever, leukopenia, hepatitis, nausea,
vomiting, diarrhea, renal insufficiency, crystalluria
 Clindamycin: rash, fever, nausea, diarrhea (including
Clostridium difficile colitis), hepatotoxicity
 TMP-SMX: rash, fever, leukopenia, thrombocytopenia,
hepatotoxicity
 Atovaquone: nausea, vomiting, diarrhea, rash,
headache, hyperglycemia, fever
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Toxoplasma gondii Encephalitis:
Monitoring and Adverse Events (2)
 IRIS appears to occur rarely
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Toxoplasma gondii Encephalitis:
Treatment Failure
 Clinical or radiologic deterioration during
first week of therapy, or lack of clinical
improvement within 10-14 days
 Brain biopsy, if not done previously
 If confirmed TE, consider switch to
alternative treatment regimen
 In patients who adhere to treatment,
recurrence is unusual during maintenance
therapy following initial clinical and
radiographic response
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Toxoplasma gondii Encephalitis:
Preventing Recurrence
 Secondary prophylaxis:
 Preferred:
 Pyrimethamine 25-50 mg PO QD + sulfadiazine 2,000-4,000
mg PO daily in 2-4 divided doses + leucovorin 10-25 mg PO
QD
 Alternative:
 Clindamycin 600 mg PO Q8H + pyrimethamine 25-50 mg PO
QD + leucovorin 10-25 mg PO QD (not effective as PCP
prophylaxis)
 TMP-SMX DS 1 tablet BID
 Atovaquone 750-1,500 mg PO BID + pyrimethamine 25 mg
PO QD (+ leucovorin 10 mg PO QD)
 Atovaquone 750-1,500 mg PO BID + sulfadiazine 2,000-4,000
mg PO daily in 2-4 divided doses
 Atovaquone 750-1,500 mg PO BID
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Toxoplasma gondii Encephalitis:
Preventing Recurrence (2)
 Discontinuing maintenance therapy: consider in
asymptomatic patients after successful initial
therapy for TE, resolution of signs and symptoms
of TE, and sustained increase in CD4 count to
>200 cells/µL for >6 months, on ART
 Consider brain MRI before treatment discontinuation;
continue therapy if mass lesions present or
enhancement persists
 Restart secondary prophylaxis if CD4 count
decreases to <200 cells/µL
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Toxoplasma gondii Encephalitis:
Considerations in Pregnancy
 Check T gondii IgG during pregnancy
 If suspected or confirmed T gondii
infection, evaluate and manage with a
maternal-fetal specialist
 Diagnostic considerations same as for
nonpregnant women
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Toxoplasma gondii Encephalitis:
Considerations in Pregnancy (2)
 Perinatal transmission usually occurs only with
acute maternal infection; case reports of
transmission with reactivation of chronic infection
in women with severe immunosuppression
 If toxoplasmosis during pregnancy (primary
infection or reactivation of chronic
toxoplasmosis):
 Detailed ultrasound of fetus
 Consider PCR of amniotic fluid in select circumstances
 Neonate should be evaluated for evidence of
congenital infection
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Toxoplasma gondii Encephalitis:
Considerations in Pregnancy (3)
 Primary prophylaxis: recommended
 TMP-SMX preferred
 Balance possible risks with expected benefits
 Treatment: as in nonpregnant adults
 Secondary prophylaxis: as in nonpregnant
women
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Toxoplasma gondii Encephalitis:
Considerations in Pregnancy (4)
 Pyrimethamine appears safe in human
pregnancy
 Sulfadiazine appears safe though, if given
around time of delivery, may increase risk of
neonatal kernicterus
 Clindamycin considered same in pregnancy
 Dapsone: risk of mild maternal hemolysis with
long-term therapy; low risk of hemolytic anemia
in exposed fetuses with G6PD deficiency
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Toxoplasma gondii Encephalitis:
Considerations in Pregnancy (5)
 Consider immediate initiation of ART, to
decrease risk of perinatal HIV transmission,
especially for women diagnosed with TE in 3rd
trimester
 Preconception care for women receiving TE
prophylaxis: discuss option of deferring
pregnancy until TE prophylaxis can be
discontinued safely
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Websites to Access the Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov
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About This Slide Set
 This presentation was prepared by
Susa Coffey, MD, and Oliver Bacon,
MD, for the AETC National Resource
Center in May 2013
 See the AETC NRC website for the
most current version of this
presentation:
http://www.aidsetc.org
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