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 Zambia HIV National Guidelines
 


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 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. and Khalil G. Ghanem, M.D.
04-29-2009

  • 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.

REFERENCES

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)

Maintenance (Suppressive) Phase

Prophylaxis

  • 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.
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

DrugRecommendations/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   trophozoites, 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.

Basis for Recommendations

  • Dedicoat M, Livesley N; Management of toxoplasmic encephalitis in HIV-infected adults (with an emphasis on resource-poor settings).; Cochrane Database Syst Rev; 2006; Vol. 3; pp. CD005420;
    ISSN: 1469-493X;
    PUBMED: 16856096
    Rating: 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; 2002; Vol. 51; pp. 1-52;
    ISSN: 1057-5987;
    PUBMED: 12081007
    Rating: 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; 1996; Vol. 22; pp. 268-75;
    ISSN: 1058-4838;
    PUBMED: 8838183
    Rating: Basis for recommendation
    Comments:Comparative trial demonstrates equivalence of pyrimethamine-sulfadiazine and pyrimethamine-clindamycin acutely, but better efficacy of pyrimethamine-sulfadiazine in preventing relapse.

REFERENCES

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