Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents Toxoplasma gondii Slide Set Prepared by the.

Guidelines for Prevention and Treatment of Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Opportunistic Infections in HIV-Infected Adults and AdolescentsAdults and Adolescents

Toxoplasma gondiiToxoplasma gondii Slide Set 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

May 2013 www.aidsetc.org2

About This PresentationAbout 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Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis:EpidemiologyEpidemiology

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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Epidemiology Epidemiology (2)(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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Epidemiology Epidemiology (3)(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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Clinical ManifestationsClinical 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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Clinical ManifestationsClinical 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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: DiagnosisDiagnosis

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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Diagnosis Diagnosis (2)(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%



Differential diagnosis of focal neurological disease CNS lymphoma, PML, mycobacterial infection

(TB), fungal infection, Chagas disease, abscess



Credit: P. Volberding, MD; UCSF Center for HIV Information Image Library

CT scan of the brain showing contrast-enhancing lesion of toxoplasmosis



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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Preventing ExposurePreventing 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 notbe fed raw/undercooked meats


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Primary ProphylaxisPrimary 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 treatmentwith dapsone, if possible.


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Primary Prophylaxis Primary Prophylaxis (2)(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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Discontinuing Primary ProphylaxisDiscontinuing 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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: TreatmentTreatment

Preferred: Pyrimethamine 200 mg PO 1 dose, then:

For weight ≤60 kg: pyrimethamine 50 mg PO QD + sulfadiazine 1,000 mg PO Q6H + leucovorin 10-25 mg PO QD

For weight >60 kg: pyrimethamine 75 mg PO QD + sulfadiazine 1,500 mg PO Q6H + leucovorin 10-25 mg PO QD

Duration: ≥6 weeks, longer if extensive disease or incomplete response at 6 weeks


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Treatment Treatment (2)(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 (weight-

based as above) Atovaquone 1,500 mg PO BID (variable absorption) Pyrimethamine as above + azithromycin 900-1,200

mg PO QD + leucovorin as above


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Treatment Treatment (3)(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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: ART Initiation 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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Monitoring and Adverse EventsMonitoring 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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Monitoring and Adverse Events Monitoring and Adverse Events (2)(2)

IRIS appears to occur rarely


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Treatment FailureTreatment 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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Preventing RecurrencePreventing 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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Preventing Recurrence Preventing Recurrence (2)(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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Considerations in PregnancyConsiderations 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


Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Considerations in Pregnancy Considerations in Pregnancy (2)(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



Primary prophylaxis: recommended TMP-SMX preferred

Balance possible risks with expected benefits

Treatment: as in nonpregnant adults Secondary prophylaxis: as in nonpregnant

women



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



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


Websites to Access the GuidelinesWebsites to Access the Guidelines

http://www.aidsetc.org http://aidsinfo.nih.gov


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

About This Slide SetAbout This Slide Set

Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents Toxoplasma gondii Slide Set Prepared by the.

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