Pyrimethamine and the Market

The latest controversy in the world of infectious disease is the price increase of the drug pyrimethamine, the primary component of the treatment of the parasitic disease Toxoplasmosis. Toxoplasmosis is a ubiquitous infection which, for most people, causes mild to no symptoms. It is acquired by eating undercooked meat or ingesting the cysts shed by cats. It is really a fascinating disease that is responsible for changing the behavior of infected rats, making them less afraid of cats--the ultimate destination of the parasite. It is estimated that 11% of the US population is infected.

The parasite causes problems, like many microbes, in those that are immunosuppressed. Those with AIDS and a CD4 count less than 100 are particularly prone to developing a brain infection with the parasites as are newborns borne to infected mothers, transplant patients, and others with immuno-suppressing conditions. 

Pyrimethamine is a drug that was initially FDA approved in 1953 and is no longer under patent, meaning any company is free to manufacture it. The fact is, however, that there is currently one US approved manufacturer who recently increased prices substantially. This has provoked a heated societal debate regarding drug prices. 

I have a few thoughts about this event (similar to those I have regarding hepatitis C medications) which many in my field no doubt disagree with but I think they are worth contemplating even if it changes no one's mind. As an infectious disease physician, who has taken care of several patients with toxoplasmosis, I don't want to see toxoplasmosis morbidity and mortality rise but pyrimethamine, in its current formulation, is the property of Turing Pharmaceuticals which has the right to set the price wherever they choose. I do not believe that anyone has a right to this product and strongly oppose any effort to expropriate or set price controls on this, or any other medication. While I have no understanding of how the new price was determined, it will eventually have to withstand the scrutiny of the market. If the price is set higher than the market will bear, because it is no longer under patent, other manufacturers will enter the market lowering prices. Ideally this would happen near instantaneously but, because of legislative barriers to entry, which include a multi-step approval process, it will take some time. Better alternatives to the current regimen may also appear in time as well.

Overall, however, infectious disease products have become less attractive to pharmaceutical companies and this, at root, is why we are left with just one manufacturer for many important non-patented products. The disincentives to enter this market are myriad and the ultimate answer to this scenario is not more intervention but to remove artificial barriers to entry, inviting the appearance of competitors in the market. The anger directed at Turing would be better employed if used to facilitate dynamism in the infectious disease market--it's the only long term solution.

Could Infectious Disease Physicians Replace Psychiatrists?

Infectious disease physicians always like to imagine that every type of pathology is due to an infection. Cancer-causing viruses and ulcer-inducing bacteria are cases that illustrate the ubiquity of microbes as etiologic agents for conditions long thought to be non-infectious. Psychiatric illnesses have, thus far, not demonstrated a definitive link to infection. A growing body of fascinating new research, however, is beginning to change that.

Many science and evolutionary biology enthusiasts are familiar with the parasitic infection toxoplasmosis, an organism that often has pregnant woman avoiding kitty litter boxes. It is well established that toxoplasmosis infections in the brain of rodents change their behavior by attracting them to a substance they naturally avoid, cat urine. Such a behavior change renders them much more likely to be devoured by a feline allowing the Toxoplasma parasite to reach its beloved primary host.

Could this infection also influence human behaviors?

Perhaps it is behind the plague of humans who display a zombie-like obsession with endlessly watching cat videos on the internet? 

About a quarter of humans are infected with toxoplasmosis and it is generally considered to not be a major problem except for in certain circumstances such as pregnancy, HIV, or transplantation. What really is striking is the fact that those with certain mental conditions are harbor the organism at a higher rate than the general public. For example, schizophrenics are 2.7 times more likely to be antibody positive than members of the general public. Associations have also been noted for generalized anxiety disorder and bipolar disorders.

Correlation is not causation and an infection cannot override the volitional nature of human consciousness. However many questions remain to be answered such as: is toxoplasmosis a surrogate marker for something else that lies behind these conditions, if the organism plays a causative role is it the infection or the post-infection immune response that is operative, would treatment change the course of illness? 

It is also important to remember that not every case shows this association and multifactorial explanations for psychiatric illnesses are the norm. 

Nevertheless that an infectious disease may play a partial role in some of these illnesses would represent an important breakthrough that could lead to new means of both prevention and treatment.

HIV & The Will (or its absence) to Live

Although I primarily practice infectious diseases and critical care medicine, I am also trained and board-certified in emergency medicine. To keep somewhat active in the field, I work about one shift per month in an emergency department (ED). I don't often have my infectious disease world intrude into the ED, but yesterday it did. 

I was involved in the care of a AIDS patient with toxoplasmosis who came to the ED for an unrelated reason. However, the infectious disease issue soon supplanted the original reason for the visit. 

Toxoplasmosis occurs in AIDS patients who are severely immunosuppressed. This opportunistic infection, which is treatable, was much more common in earlier eras in which individuals with HIV had no effective treatments. In the modern era, in those who have access to medications, it is quite rare. In my ID fellowship, I think I only saw one case in an individual newly diagnosed with HIV. 

Yesterday's case wasn't like that--this person had willfully stopped taking anti-retrovirals and anti-toxoplasmosis medications. 

I found the entire experience frustrating as I, like many other physicians before me, was futile in  persuading the patient that without treatment death would soon occur. 

As I've learned by myriad interactions with individuals recalcitrant to complying with treatment recommendations, a fundamental choice to live has to be the precondition for anything anyone says to matter.