Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and...
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Transcript of Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and...
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Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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
May 2013 www.aidsetc.org3
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
May 2013 www.aidsetc.org4
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
May 2013 www.aidsetc.org5
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
May 2013 www.aidsetc.org6
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
May 2013 www.aidsetc.org7
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
May 2013 www.aidsetc.org8
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
May 2013 www.aidsetc.org9
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%
May 2013 www.aidsetc.org10
Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Diagnosis Diagnosis (3)(3)
Differential diagnosis of focal neurological disease CNS lymphoma, PML, mycobacterial infection
(TB), fungal infection, Chagas disease, abscess
May 2013 www.aidsetc.org11
Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Diagnosis Diagnosis (4)(4)
Credit: P. Volberding, MD; UCSF Center for HIV Information Image Library
CT scan of the brain showing contrast-enhancing lesion of toxoplasmosis
May 2013 www.aidsetc.org12
Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Diagnosis Diagnosis (5)(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
May 2013 www.aidsetc.org13
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
May 2013 www.aidsetc.org14
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.
May 2013 www.aidsetc.org15
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
May 2013 www.aidsetc.org16
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
May 2013 www.aidsetc.org17
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
May 2013 www.aidsetc.org18
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
May 2013 www.aidsetc.org19
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
May 2013 www.aidsetc.org20
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
May 2013 www.aidsetc.org21
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
May 2013 www.aidsetc.org22
Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Monitoring and Adverse Events Monitoring and Adverse Events (2)(2)
IRIS appears to occur rarely
May 2013 www.aidsetc.org23
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
May 2013 www.aidsetc.org24
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
May 2013 www.aidsetc.org25
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
May 2013 www.aidsetc.org26
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
May 2013 www.aidsetc.org27
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
May 2013 www.aidsetc.org28
Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Considerations in Pregnancy Considerations in Pregnancy (3)(3)
Primary prophylaxis: recommended TMP-SMX preferred
Balance possible risks with expected benefits
Treatment: as in nonpregnant adults Secondary prophylaxis: as in nonpregnant
women
May 2013 www.aidsetc.org29
Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Considerations in Pregnancy Considerations in Pregnancy (4)(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
May 2013 www.aidsetc.org30
Toxoplasma gondiiToxoplasma gondii Encephalitis: Encephalitis: Considerations in Pregnancy Considerations in Pregnancy (5)(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
May 2013 www.aidsetc.org31
Websites to Access the GuidelinesWebsites to Access the Guidelines
http://www.aidsetc.org http://aidsinfo.nih.gov
May 2013 www.aidsetc.org32
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