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The Immune Inflammatory Reconstitution Syndrome and Central Nervous System Toxoplasmosis

Ivo W. Tremont-Lukats, MD; Pedro Garciarena, MD; Rubén Juarbe, MD; and Rima N. El-Abassi, MD
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From University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, and Louisiana State University, New Orleans, LA 70119.

Acknowledgment: The authors thank Marc K. Rosenblum, MD, who provided panel D of the Figure.

Potential Financial Conflicts of Interest: None disclosed.

Ann Intern Med. 2009;150(9):656-657. doi:10.7326/0003-4819-150-9-200905050-00025
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The immune inflammatory reconstitution syndrome in a patient infected with HIV-1 who had central nervous system toxoplasmosis.

A. Pretreatment brain magnetic resonance imaging. B. Improvement 15 days after highly active antiretroviral therapy and antimicrobial therapy. C. On readmission 40 days after start of treatment. D.Toxoplasma gondii tachyzoites stained with immunolabeled antitoxoplasma IgG (magnification, ×400).

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IRIS or not IRIS?
Posted on June 10, 2009
Guillaume Martin-Blondel
Infectious disease department, CHU Toulouse, France
Conflict of Interest: None Declared

Tremont-Lukats et al (1) have published in the last issue of Annals of Internal Medicine a very interesting and well documented case report about a paradoxical worsening of a central nervous system (CNS) toxoplasmosis in a patient with HIV-1 infection occurring precociously after HAART initiation. Authors have concluded that this exacerbation was linked to an immune inflammatory reconstitution syndrome (IRIS). Indeed, this worsening has occurred after an initial improvement under trimethoprim-sulfamethoxazole therapy and contemporary to a significant CD4 cell count increase. Moreover, a clinical improvement was observed with the same therapy (uninterrupted HAART and trimethoprim-sulfamethoxazole therapy) and a higher steroid dose. This outcome might suggest hypothesis of a paradoxical IRIS.

However this case report leads to questions about the diagnosis of a paradoxical IRIS. IRIS is the consequence of the restoration of an immune response against pathogen-specific antigens that results in immunopathology. In the paradoxical form of IRIS, immune response appears to be directed against antigens of nonviable pathogens, while the infection is eradicated (2). In this case report immunohistochemical analysis of the mass biopsy saw abundant tachyzoites in cerebral parenchyma, which is a replicative viable form of Toxoplasma gondii (3). Examination of affected tissue did not reveal evidence of an immune response (such as infiltrating lymphocytes or granulomatous inflammation). In our opinion, this is conflicting with the diagnosis of IRIS and suggests more an unfavourable course of a previously diagnosed toxoplasmosis than a real IRIS. Moreover, decrease in the plasma HIV RNA level, which is a major criteria for the diagnosis of IRIS was not documented.

Few cases of suspected IRIS linked with CNS toxoplasmosis have been published, often with insufficient clinical details to be able to verify diagnoses. While toxoplasmosis is a common end-stage opportunistic infection in industrialized countries and the fact that only few cases have been reported raises questions over the association of this infection with IRIS (4). In this case report, even if outcome was favourable with steroid therapy, presence of tachyzoite on cerebral biopsy challenging the diagnosis of IRIS.


1. Tremont-Lukats IW, Garciarena P, Juarbe R, El-Abassi RN. The immune inflammatory reconstitution syndrome and central nervous system toxoplasmosis. Ann Intern Med. 2009;150(9):656-7.

2. French MA. HIV/AIDS: immune reconstitution inflammatory syndrome: a reappraisal. Clin Infect Dis. 2009;48(1):101-7.

3. Dubey JP, Lindsay DS, Speer CA. Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts. Clin Microbiol Rev. 1998;11(2):267-99.

4. Lawn SD. Immune reconstitution disease associated with parasitic infections following initiation of antiretroviral therapy. Curr Opin Infect Dis. 2007;20(5):482-8.

Conflict of Interest:

None declared

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