The Disease

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. Roughly one-third of the global population carries it, usually without symptoms. In people with weakened immune systems, it can cause brain abscesses, seizures, blindness, and death.

Daraprim (pyrimethamine) has been the standard treatment since its FDA approval in 1953. No replacement drug has emerged in the past 50 years.

How It Spreads

Toxoplasma gondii completes its reproductive cycle in cats. The parasite is shed in cat faeces and can survive in soil for months. Humans usually become infected in three ways:

  • Contact with contaminated cat litter or soil
  • Eating undercooked or raw meat, particularly pork, lamb, and venison, that contains tissue cysts
  • Congenital transmission from mother to foetus during a first infection in pregnancy

The parasite then forms dormant cysts, mainly in the brain and muscle tissue. A functioning immune system keeps these cysts contained but cannot eliminate them.

Who Is at Risk

For most people, toxoplasmosis causes little harm. The greatest danger is to patients whose immune systems cannot keep the dormant cysts suppressed.

HIV/AIDS patients are the most affected group. When CD4+ T-cell counts fall below 100 to 200 cells per microlitre, dormant cysts in the brain can reactivate. The active parasites multiply rapidly and cause toxoplasmic encephalitis, which inflames and destroys brain tissue. Before antiretroviral therapy became widely available, toxoplasmic encephalitis was the most common cause of focal brain lesions in AIDS patients. Approximately 30% of seropositive AIDS patients develop reactivation disease without prophylaxis.

Organ transplant recipients take immunosuppressive drugs to prevent organ rejection. Those drugs also weaken the immune response that keeps cysts contained.

Cancer patients on chemotherapy face similar immunosuppression, which can allow cysts to reactivate.

Newborns infected during pregnancy are at highest risk. Congenital toxoplasmosis can cause hydrocephalus (fluid buildup in the brain), intracranial calcifications, retinochoroiditis (inflammation of the retina and choroid), and permanent neurological damage. Infected infants may need up to one year of continuous treatment.

Pregnant women who acquire a new infection during pregnancy can transmit the parasite to the foetus. Without treatment, the transmission rate is approximately 45%. With treatment, it falls to approximately 9%.

Why Pyrimethamine Is the Standard Treatment

Treatment combines three drugs: pyrimethamine, sulfadiazine, and leucovorin.

Pyrimethamine blocks dihydrofolate reductase, an enzyme the parasite needs to replicate its DNA. Sulfadiazine blocks an earlier step in the same biochemical pathway. Hitting two sequential steps kills far more parasites than either drug alone. Leucovorin (folinic acid) protects the patient's bone marrow from pyrimethamine's side effects without weakening the drug's action against the parasite.

The CDC, NIH, HIV Medicine Association, and Infectious Diseases Society of America designate this combination as the preferred initial therapy. It has remained the standard of care for more than 60 years.

Pyrimethamine penetrates the central nervous system effectively, which is essential for brain infections. Its long half-life, approximately 96 hours, allows once-daily dosing. The drug kills only active parasites (tachyzoites) and cannot eradicate dormant cysts.

Why the Price Mattered

When Turing Pharmaceuticals raised the price of Daraprim from $13.50 to $750 per tablet in September 2015, patients who needed it had no therapeutic alternative with comparable clinical evidence. That included HIV/AIDS patients, transplant recipients, and families of infected newborns.

Hospitals reported switching patients to less effective regimens. One large public hospital documented a 20-fold increase in toxoplasmosis drug costs. Infectious disease specialists reduced their prescribing frequency from roughly five times per month to once per month or less. These changes in clinical practice followed directly from the price increase.

Generic pyrimethamine became available in February 2020, five years after the price increase and after the FTC documented the anticompetitive practices that delayed its arrival.