This handout is for cerebral toxoplasmosis (hiv-associated and immunocompromised) — dhhs 2024 oi + dannemann actg (ann intern med 1992 pmid 1727093) + katlama european rct (cid 1996 pmid 8838183). Your care team identified this based on: focal neurologic deficit (hemiparesis, aphasia, cranial nerve palsy) + headache ± fever in hiv cd4 < 100 or other immunocompromised host — subacute over 2-3 wk (luft/remington cid 1992 pmid 1520757).
Other reasons your team may use this plan: ams / encephalopathic features + immunocompromise → cerebral toxoplasmosis high on differential when toxo igg+ and cd4 < 100 (dhhs 2024 oi; dannemann ann intern med 1992 pmid 1727093); new-onset seizure in immunocompromised adult — toxoplasmosis is a leading cause of focal seizure in advanced hiv (dhhs 2024 oi); ring-enhancing brain lesion(s), often multifocal, basal ganglia / corticomedullary junction on mri brain with contrast in immunocompromised host — > 90% probability of cerebral toxoplasmosis when toxo igg+ and hiv cd4 < 100 (luft/remington pmid 1520757; dhhs 2024 oi).
Take these medications exactly as prescribed. Do not stop or change a dose without talking to your provider.
| Medication | Starting dose | How | When | What it does |
|---|---|---|---|---|
| pyrimethamine | 200 mg PO × 1 load → 75 mg PO daily (50 kg-60 kg) OR 100 mg PO daily (> 60 kg) | PO | daily after load | DHFR inhibitor (active against tachyzoite); load improves time to therapeutic level; co-administration with leucovorin mitigates myelosuppression (DHHS 2024 OI; Dannemann PMID 1727093) |
| sulfadiazine | 1500 mg PO q6h (> 60 kg) OR 1000 mg PO q6h (< 60 kg) | PO | q6h | Synergistic DHPS inhibition with pyrimethamine; sulfadiazine specifically (NOT sulfamethoxazole) is the partner of choice in classic Pyr-Sdz regimen; hydrate + alkalinize urine to mitigate crystalluria + AKI; SJS/TEN risk per Caumes CID 1995 PMID 8527561 |
| leucovorin | 10-25 mg PO daily; titrate to 50 mg if cytopenias develop | PO | daily (continue 1 wk after pyrimethamine cessation) | Mandatory co-therapy with pyrimethamine; rescues host DHFR pathway without rescuing parasite (parasite lacks folinic-acid uptake); reduces megaloblastic anemia / neutropenia / thrombocytopenia (DHHS 2024 OI) |
Plan: Cerebral toxoplasmosis induction (≥6 wk; longer if not improving) — Pyr-Sdz-leucovorin first-line; Pyr-Cm-leucovorin sulfa-allergy alternative; TMP-SMX resource-limited / pyrimethamine-unavailable; atovaquone-based salvage (DHHS 2024 OI; Dannemann Ann Intern Med 1992 PMID 1727093; Katlama CID 1996 PMID 8838183)
Contact your care team if any of the following happen:
Call 911 or go to the nearest emergency room right away if you have:
Maintenance / secondary prophylaxis after ≥6 wk induction: pyrimethamine 25-50 mg PO daily + sulfadiazine 2-4 g/day (in divided doses) + leucovorin 10-25 mg daily (OR pyrimethamine + clindamycin + leucovorin for sulfa-allergic) OR atovaquone 750-1500 mg PO BID; Discontinue secondary prophylaxis when CD4 > 200 × 6 mo on suppressive ART + clinically asymptomatic (DHHS 2024 OI); Primary prophylaxis re-initiate / continue when HIV CD4 < 100 + Toxo IgG+ — TMP-SMX 1 SS PO daily (same as PJP prophylaxis); Transplant recipients: prophylaxis per protocol (TMP-SMX is standard PJP + toxo + Nocardia prophylaxis post-SOT/HSCT). Lifelong ophtho + neurology surveillance for sequelae (DHHS 2024 OI; Luft/Remington PMID 1520757)
Guideline: DHHS/NIH/CDC/IDSA Adult/Adolescent Opportunistic Infection Guidelines 2024 (Toxoplasmosis section; clinicalinfo.hiv.gov web-anchored) + Dannemann ACTG (Ann Intern Med 1992) + Katlama European RCT (CID 1996) + Luft/Remington foundational review (CID 1992) + Robert-Gangneux/Dardé epidemiology (Clin Microbiol Rev 2012) + AST IDCOP transplant ID guidance