Toxoplasma - AIDS Education and Training Centers National
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Transcript Toxoplasma - AIDS Education and Training Centers National
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become out of date quickly.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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