Toxoplasmosis with a weakened immune system

Why a weakened immune system changes everything

In a healthy person, the first encounter with Toxoplasma ends with the immune system driving the parasite into dormant cysts, mostly in brain and muscle, where it sits quietly for life. It never leaves, and it never stops being watched. Interferon-gamma and the T cells that produce it are what hold the line¹. Understanding how that control works, and how the parasite resists it, is what this laboratory studies.

Take the immune control away and the dormant cysts can reactivate. The parasite starts multiplying again, and the disease that follows is not the mild illness of a first infection in a healthy adult. In the great majority of cases the problem is not a new infection at all, but an old one coming back¹.

Who is at risk

• Advanced HIV infection. The classic setting, historically at CD4 counts below about 100 cells per microlitre. Effective antiretroviral therapy has made this much less common where that treatment is available.
• Transplant recipients. Both from reactivation in the recipient and, in heart transplantation in particular, from a seropositive donor organ given to a seronegative recipient.
• Cancer treatment and haematological malignancy, where chemotherapy suppresses cell-mediated immunity.
• Prolonged high-dose corticosteroids and some biologic immunosuppressants, especially agents that interfere with T-cell function or with tumour necrosis factor.

Toxoplasmic encephalitis: the main danger

The brain is where reactivation usually shows itself, because that is where the cysts preferentially sit. Toxoplasmic encephalitis presents with headache, confusion, fever, focal neurological deficits such as weakness on one side, and seizures, usually developing over days to weeks rather than hours¹. On a CT or MRI scan it typically produces multiple ring-enhancing lesions, often in the basal ganglia, which is a picture that overlaps with primary central nervous system lymphoma and is the reason the two are considered together.

Diagnosis in this setting is often made presumptively: in a patient with advanced HIV, positive Toxoplasma IgG and the characteristic scan appearance, treatment is started and the response over the following two weeks is itself used as the diagnostic test². A negative IgG makes toxoplasmosis much less likely but does not entirely exclude it. Note the contrast with testing in pregnancy, where IgM and avidity carry the weight; in the immunocompromised patient IgM is usually absent, because this is reactivation of an old infection rather than a new one. Antibody testing generally is covered on the blood tests page.

Beyond the brain

Reactivation is not confined to the brain. The eye is the next most common site, and ocular disease in an immunocompromised patient tends to be more extensive and more aggressive than the self-limiting episodes seen in otherwise healthy people; that is discussed on the ocular toxoplasmosis page. The lungs can be involved, producing a pneumonitis that resembles other opportunistic pneumonias, and disseminated disease affecting multiple organs occurs in the most profoundly immunosuppressed¹.

Treatment and prevention

The standard regimen is pyrimethamine and sulfadiazine with folinic acid, the same combination used elsewhere in toxoplasmosis, given at higher doses and for longer. Trimethoprim-sulfamethoxazole is an alternative where that combination cannot be used². Because the drugs act on the multiplying parasite and not on the dormant cysts, treatment does not eradicate the infection: after the acute episode is controlled, maintenance therapy continues until immune function recovers, for example until antiretroviral therapy has restored the CD4 count. The same logic explains why there is no cure for latent infection, discussed on the treatment page.

Prevention has two halves. In people who are already seropositive and becoming immunosuppressed, prophylaxis, typically trimethoprim-sulfamethoxazole prescribed for Pneumocystis and which covers Toxoplasma as well, prevents reactivation². In people who are seronegative, the goal is to avoid a first infection altogether, and the ordinary food and soil precautions apply with more force than usual³. Knowing which group a patient is in is the reason IgG testing is done before immunosuppressive treatment begins.

Sources

1. Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet 2004;363:1965-76. PubMed · DOI
2. Dunay IR, Gajurel K, Dhakal R, Liesenfeld O, Montoya JG. Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice. Clin Microbiol Rev 2018;31:e00057-17. PubMed · DOI
3. Centers for Disease Control and Prevention. Toxoplasmosis. Accessed 15 October 2026.