Toxoplasmosis & HIV

Is a parasite helping HIV thwart the immune system?

by Jeannie Wraight

A new study published in the Journal of Immunology suggests that co-infection with toxoplasmosis (toxo), a parasitic infection common in people with AIDS, may play an important role in strengthening HIV’s ability to overcome the immune system.

Until the introduction of ARVs, toxo encephalitis (TE) was a leading cause of death in people with AIDS. While instances of TE have diminished, toxo infection still has consequences that may have significant immunological consequences.

Toxoplasmosis made headlines in 2015 when Martin Shkreli, former CEO of Turing Pharmaceuticals, raised the price of its toxo drug Daraprim (pyrimethamine), by 5,456 percent (from $13.50 to $750), making it the second most expensive drug in the U.S. Not long after, Shkreli, dubbed “the most hated man in America,” received what some saw as his karmic fate in the form of a seven-year prison sentence for securities fraud. Public outrage highlighted the importance of Daraprim and toxo, a disease contracted by over 60 million Americans. Research suggests toxo may be connected to neurocognitive disorders, diabetes, and a myriad of other disease manifestations. Despite this and the CDC’s designation of toxo as a neglected parasitic infection targeted as a priority for public health action, toxo receives little attention or research funding.

In a recent study, researchers looked at the effect of toxoplasmosis on plasmacytoid dendritic cells (pDCs), which secrete interferon alpha (IFN-α), a substance involved in HIV suppression and immune modulation. During HIV infection, pDCs decrease in number and those that remain produce less IFN-α, which reduces the immune system’s ability to suppress HIV. Researchers found toxo inhibited IFN-α produced in response to HIV, preventing pDCs from functioning. pDC cells are a critical mediator of interleukin-10 (IL-10), which has been associated with more rapid disease progression in late stages of HIV infection. However, the role of IL-10 in HIV is controversial, possibly maintaining both protective and detrimental effects. Researchers also found that toxo decreased tumor necrosis factor-alpha (TNF-α) produced in response to HIV.

Decreasing TNF-α could be detrimental as an important function of TNF-α is to activate neutrophil cells, stimulating the response by neutrophils and macrophages that inhibit HIV infection.

According to researchers, “[o]ur findings [further] imply a convergent mechanism of inhibition of TLR [toll-like receptor] signaling by T. gondii (toxo) and IL-10 and suggest potential negative consequences of HIV/T. gondii coinfection.” TLR is involved in permitting HIV infection in latent mass cells, part of the HIV reservoir. The results of this NIH-supported research suggest that toxoplasmosis/HIV co-infection may have important implications for HIV cure research and further investigations to uncover the role of toxoplasmosis in HIV’s evasion of the immune system are needed.

Approximately 1.1 million people acquire toxo each year in the U.S. Although acute infection is treatable, there is no cure for toxoplasmosis. Under constant pressure from a competent immune system, the parasites persist within cysts where they slowly replicate in the body for the duration of their host’s life. This latent stage may be reactivated if the immune system becomes suppressed, causing potentially devastating effects to the brain, lungs, eyes, and other organs. People living with HIV or cancer, the elderly, transplant patients, and pregnant women are at high risk of reactivation. Mothers with active toxo can pass the infection to their unborn children, potentially causing birth defects and miscarriage.

Toxo can infect all mammals and birds, but it can only complete its life cycle in cats. Upon a cat’s primary infection, hundreds of millions of infectious spores, called oocysts, are distributed into the environment through the cat’s feces for a short time until the cat develops an immune response or receives appropriate treatment. Humans can develop toxo by inhaling or ingesting the microscopic oocysts or by consuming the undercooked meat of an infected animal. The CDC recommends the best approach to minimizing the risk of contracting toxo for people who are immune comprised is to avoid exposure to anything that may be contaminated by cat feces.

It can’t be stressed enough that this does not mean you need to or should get rid of your cat. Studies have shown that the bond between people and their pets can improve their quality of life by increasing fitness, lowering stress, and evoking a sense of happiness; however, improved methods for handling and disposing of cat feces are needed. The best approach to minimizing the risk of contracting toxoplasmosis, particularly for those who are immune-compromised, is by avoiding exposure to cat feces when possible and cooking meats to a minimum internal temperature of 165° F. A new self-contained, yet-unnamed litter box system, created by an inventor in Middlebury, Connecticut, Christopher Romano, will be available soon to protect against possible exposure to toxo through cat feces.

Prevention of toxo through stronger designation and promotion of federal guidelines, as well as studies to ascertain the consequences of toxo co-infection with HIV and other diseases, should be made a priority by the NIH and the CDC in order to prevent continued public health burden by this neglected parasitic infection.
