A 38-year old male with recently diagnosed HIV (CD4 count 95, not currently on any medications) presents to the hospital with subacute onset of fever and headache. His partner reports that the patient has had worsening confusion over the last few days. Vital signs are stable and exam notable for ataxia.
T2 MRI imaging of the brain shows the following:
Serum Toxoplasma IgG: Positive Serum CMV IgG: Positive
Serum Cryptococcal Ag: Negative
- Lumbar Puncture CSF studies:
- mild mononuclear pleocytosis elevated protein
- Gram stain and culture negative at 24 hours
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Correct Answer: Initiate sulfadiazine and pyrimethamine therapy
This case emphasizes the criteria from which a presumptive diagnosis of toxoplasma gondii encephalitis (TE) in an immunocompromised host can be made and describes the first-line recommended treatment of sulfadiazine and pyrimethamine.
A presumptive diagnosis of TE can be made in the following setting:
- Compatible clinical syndrome
- Positive T. gondii IgG antibody
- Brain imaging with typical radiographic appearance (eg, multiple ring-enhancing lesions)
- CD4 count <100 cells/microL in a patient not receiving effective prophylaxis to prevent toxoplasmosis
When these criteria are met (as in our patient), there is a 90% probability that the diagnosis is TE. If toxoplasmosis is identified on CSF PCR, the diagnosis of TE is even more likely (although absence of positive PCR testing does not exclude the possibility of TE given limitations of PCR sensitivity for toxoplasma).
First-line treatment for toxoplasma gondii encephalitis is sulfadiazine and pyrimethamine, with clinical improvement anticipated within the first two weeks of therapy.
Distractor answer choices
- Corticosteroids would be indicated for mass effect related to focal brain lesions or edema. Their use may confound clinical/radiographic assessments of response to therapy and impair future histologic testing if brain biopsy is required to rule out CNS lymphoma
- Ganciclovir: Ganciclovir would treat CMV encephalitis, however the CD4 cell count >50, and MRI findings are inconsistent with this diagnosis. CMV typically causes periventricular lesions. PCR should be ordered but wouldn’t direct therapy towards this
- Brain biopsy: Is not required for diagnosis of TE and our patient has sufficient clinical findings to support empiric trial of therapy to avoid this invasive procedure
- Cryptococcal antigen from CSF should be checked but in patient with AIDs and neurologic symptoms the sensitivity of serum crypto antigen is > 90%.
For more information on the diagnosis and management of toxoplasmosis and other OI’s in patients with HIV:
DHHS Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV section on toxoplasma gondii Encephalitis
- https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic- infection/toxoplasma-gondii-encephalitis?view=full
- https://www.hiv.uw.edu/go/co-occurring-conditions/opportunistic-infections-treatment/core- concept/all#em toxoplasma-gondii em-encephalitis
Question written by S. Evan Cooper from Cornell, mentor Kruti Yagnik