Emily J. Erbelding, M.D., M.P.H. and Khalil G. Ghanem, M.D.
- Only one older study (1991) looked at serologic prevalence of Toxoplasma in Zambia found only 4% seropositivity in HIV + pts; seropositivity rates vary widely in recent studies from sub-Saharan Africa (~10% in S. Africa to ~50% in Uganda; Hari KR, Modi MR, Mochan AH, et al. and Lindström I, Kaddu-Mulindwa DH, Kironde F, et al. references).
- As HAART becomes more widespread in Zambia, incidence of CNS toxoplasmosis should decline (as in developed countries in HAART era).
- Differential Dx for CNS mass lesions in Zambia is same as elsewhere (noted below).
- Definitive Dx of CNS toxoplasmosis in Zambia difficult without serology or brain imaging, but presumptive clinical Dx usually made based on presenting Sx.
- In Zambia an HIV+ pt with CD4 <100 and focal neurologic Sx is usually treated first for CNS toxoplasmosis with monitoring of response before treatment of other possible conditions.
- Treatment options in Zambia include: pyrimethamine (200 mg PO x 1, then > 50-75 mg/d) + folinic acid 10-20 mg/d + sulfadiazine 1.5 g q6h) or TMP-SMX (2 DS tabs PO bid). Alternative: pyrimethamine-sulfadoxine.
Zambia Information Author: David Riedel, M.D.
Toxoplasma gondii, an obligate intracellular protozoan
- Environmental exposure to oocysts (cat feces) or food exposure (undercooked meat) leads to human infection.
- Infection lifelong; disease manifestations occur with severe immunocompromise.
- Most frequent CNS OI in many HIV settings, occurring with CD4 <100.
- Focal neurologic signs, +/- seizures, cranial nerve deficits, rapid mental status decline if lesions hemorrhagic; presence of fever inconsistent.
- PE: Focal motor deficits, ataxia, tremor, altered mental status.
- Infection outside CNS rare; pneumonia/pneumonitis, retinitis are reported.
- DDx (CNS lesions): primary CNS lymphoma (PCNSL), PML, other malignancy, nocardiosis, tuberculoma, cryptococcoma, syphilitic gumma, Trypanosoma cruzi if pt from endemic area (i.e. rural Brazil, Argentina, Chile).
- Mass lesion(s) on MRI or CT of brain with ring enhancement; CSF examination rarely helpful in confirming diagnosis, but may be very useful in ruling out other CNS processes.
- Positive anti-Toxoplasma IgG defines those at risk, though may be negative in 10-15% of those with AIDS and proven toxoplasmosis.
- Therapy usually presumptive based upon clinical and radiographic findings; response to therapy (clinical and radiographic) establishes presumptive diagnosis.
- Brain Bx indicated if unchanged or worse at 10-14 days of presumptive therapy.
- If etiology of CNS lesions remains unclear based upon lab/imaging findings, Thallium-201 brain imaging (SPECT) showing intense focal uptake with +CSF EBV PCR makes PCNSL most likely diagnosis.
- HAART with effective immune reconstitution is most effective primary and secondary prevention strategy.
- Relapse or side effects may limit success of induction or maintenance therapy; relapse occurs in up to 20-30% of pts on long-term therapy; interventions to support adherence may be beneficial.
- Corticosteroids (dexamethasone 4 mg PO/IV q6hr) often used if mass effect or significant edema evident on neuroimaging; may confound assessment of response to therapy if lesions due to PCNSL.
- Indicated if anti-Toxoplasma IgG + and CD4 <100.
TMP-SMX 1 DS once-daily (preferred).
- Alternative: dapsone 50 mg once-daily + pyrimethamine 50 mg qwk + leucovorin 25 mg qwk.
- Alternative: atovoquone 1500 mg once-daily +/- pyrimethamine 25 mg once-daily + leucovorin 10 mg once-daily.
- Discontinue primary prophylaxis when CD4 >200 x >3 mos on HAART.
Toxoplasma seronegative pts should be counseled to avoid environmental exposure: No raw/undercooked meat, strict handwashing with meat preparation or gardening, avoid changing cat litter.
- Limited treatment data on non-CNS disease in HIV; therefore, pulmonary, ocular, or proven disease in other organ system should be treated with regimens proven to be effective in CNS.
||Limited data for clinical efficacy as salvage agent; should not be used unless risk of more proven therapies outweighs likely benefit.
||More limited data for clinical efficacy;should not be used unless risk of more proven therapies outweighs likely benefit.
||Preferred alternative agent with pyrimethamine; less effective but better tolerated than pyrimethamine + sulfadiazine combination.
||Folinic acid (calcium leucovorin) lessens bone marrow toxicity and does not antagonize pyrimethamine action on trophozoites, thus is standard component of therapy with pyrimethamine.
||Common component of treatment regimens with the most proven effectiveness.
||Drug of choice (in combination with pyrimethamine and leucovorin) Crystal-induced nephrotoxicity minimized with hydration and alkalinization of urine; hypersensitivity reaction (fever + progressive rash) may be severe and require discontinuation of therapy.
- Dedicoat M, Livesley N;
Management of toxoplasmic encephalitis in HIV-infected adults (with an emphasis on resource-poor settings).;
Cochrane Database Syst Rev;
Basis for recommendation
Comments:In this systematic review, TMP-SMX was found to be effective alternative therapy for toxoplasmosis in resource-poor settings where preferred regimens not available.
- Kaplan JE, Masur H, Holmes KK, et al.;
Guidelines for preventing opportunistic infections among HIV-infected persons--2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America.;
MMWR Recomm Rep;
Basis for recommendation
Comments:Overview on OI prevention strategies in HIV management, including toxoplasmosis.
- Katlama C, De Wit S, O'Doherty E, et al.;
Pyrimethamine-clindamycin vs. pyrimethamine-sulfadiazine as acute and long-term therapy for toxoplasmic encephalitis in patients with AIDS.;
Clin Infect Dis;
Basis for recommendation
Comments:Comparative trial demonstrates equivalence of pyrimethamine-sulfadiazine and pyrimethamine-clindamycin acutely, but better efficacy of pyrimethamine-sulfadiazine in preventing relapse.