Zambian HIV Guidelines:: Toxoplasmosis

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	Zambia HIV National Guidelines
	Introduction HIV Counseling and Testing Sexually Transmitted Infections (STIs) General Principles of Antiretroviral Therapy for Chronic HIV Infection in Adults and Adolescents When to Start ARV Therapy for Chronic HIV Infection in Adults and Adolescents Initial Regimen for ARV Therapy Adherence Baseline evaluation and Monitoring Calculations: Ideal Body Weight, Body Mass Index and Creatinine Clearance ARV Therapy for Individuals with Tuberculosis Co-Infection Adverse Effects and Toxicity Immune Reconstitution Inflammatory Syndrome (IRIS) Changing or Stopping ART Treatment Failure Stopping ARV Therapy Post Exposure Prophylaxis Cotrimoxazole Prophylaxis WHO Staging in Adults and Adolescents Nutrition Care and Support Palliative Care in HIV and AIDS
	Guide Editors
	Editor In Chief Joel E. Gallant, MD, MPH Pharmacology Editor Paul Pham, PharmD, BCPS Zambia Guideline Team Peter Mwaba MMed PhD FRCP Alywn Mwinga MMed Isaac Zulu MMed MPH Velepie Mtonga MMed Albert Mwango MBChB Jabbin Mulwanda MMed FCS

Diagnosis>Opportunistic Infections>

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Toxoplasmosis

Emily J. Erbelding, M.D., M.P.H.
05-01-2008

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.

PATHOGENS

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.

CLINICAL

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).

DIAGNOSIS

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.

TREATMENT

General Principles

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.

Induction Phase (6 wks)

Pyrimethamine 100-200 mg loading dose, then 50-100 mg qd for 6 wks PLUS sulfadiazine 4-8 g/day PLUS leucovorin 10-20 mg/d.
Alternative: pyrimethamine 100-200 mg loading dose, then 50-100 mg qd for 6 wks PLUS clindamycin 600 mg IV or PO q6h for 6 wks PLUS leucovorin 10-20 mg/day.
Alternative: pyrimethamine + leucovorin (above doses) PLUS azithromycin 1200 mg qd.
Alternative: pyrimethamine + leucovorin (above doses) PLUS atovaquone 1500 mg bid with food.

Maintenance (Suppressive) Phase

Pyrimethamine 25-50 mg qd +sulfadiazine 2-4 g/d + leucovorin 10-20 mg/d.
Alternative: Pyrimethamine 25-50 mg qd +clindamycin 300 mg PO q6-8h +leucovorin 10-20 mg/d.
Alternative: Pyrimethamine + leucovorin (above doses) PLUS azithromycin 600-900 mg qd (limited data to support best maintenance dose).
Alternative: Pyrimethamine + leucovorin (above doses) PLUS atovaquone 1500 mg bid with food.
Maintenance therapy can be discontinued with CD4 >200 x 6 mos when pt on HAART with effective virologic control.

Prophylaxis

Indicated if anti-Toxoplasma IgG + and CD4 <100.
TMP-SMX 1 DS qd (preferred).
Alternative: dapsone 50 mg qd +pyrimethamine 50 mg qwk +leucovorin 25 mg qwk.
Alternative: atovoquone 1500 mg qd +/- pyrimethamine 25 mg qd +leucovorin 10 mg qd.
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.

Non-CNS toxoplasmosis

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.

Drug Comments

Drug	Recommendations/Comments
Atovaquone	Limited data for clinical efficacy as salvage agent; should not be used unless risk of more proven therapies outweighs likely benefit.
Azithromycin	More limited data for clinical efficacy;should not be used unless risk of more proven therapies outweighs likely benefit.
Clindamycin	Preferred alternative agent with pyrimethamine; less effective but better tolerated than pyrimethamine + sulfadiazine combination.
leucovorin	Folinic acid (calcium leucovorin) lessens bone marrow toxicity and does not antagonize pyrimethamine action on trophyzoites, thus is standard component of therapy with pyrimethamine.
Pyrimethamine	Common component of treatment regimens with the most proven effectiveness.
Sulfadiazine	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.

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