Life Changing Medicine: More Than a Slogan & Tougher than Mold

As I write this, the institution I work for is in the midst of a comprehensive investigation into a small outbreak of mucormycosis in transplant patients. The discovery of these often deadly infections--triggered by the astute mind of a critical care physician--led to rapid action to safeguard patients on the part of the hospital. 

My institution is not just any transplant hospital--it is arguably THE most storied, most innovative, and most aggressive transplant institution on the planet performing nearly 400 transplants a year, including the rarely obtainable small bowel transplant. In short, pathbreaking work in transplantation has occurred here for decades and the human race is better off because of it. For example, transplant candidates that have no where left to turn come to Pittsburgh and are successfully transplanted. From pioneering work transplanting livers into HIV+ patients to transplantation of lungs into cystic fibrosis patients infected with a particularly nasty bacteria, my institution breaks the mold (no pun intended)--much like the city in which it is located in has.

This unfortunate and tragic outbreak has prompted the hospital to take many bold and unprecedented steps that include closing a major ICU, literally breaking down walls, a voluntary halting of transplantation, changing anti-fungal prophylactic guidelines, leaving no etiologic stone unturned, hiring world renown experts to join our own world experts, and even creating a blog to provide a level of transparency and public communication rarely seen.

These actions speak to the integrity and honor of the system and its leadership, whom I have extreme confidence in.

To me (and any intellectually honest observer), this is indisputable. 

This leads me to discuss another facet of my institution: the unjust persecution it continually faces from the state government, the press, unions, and many other parties.

For years, the health system has been locked in a battle with the state government which has sought to interfere--time and again--with its business practices. It has been damned for the very practices that have made it immensely successful, a boon for the economy of the state, and a destination for patients from all over the world. 

Just a few examples of the state's dictatorial meddling should suffice to sketch out a picture that shows the state's snarling attitude toward value creation. In recent months, the state government blocked the merger with an ailing hospital that has been forced to curtail services because it so desperately needs rescuing. The state would rather see a hospital continue to ail rather than be healed by merger. Additionally, the state has forced the health system to enter into absurd agreements with a direct competitor--a matter that the state Supreme Court has now taken up. The current executive branch of the state's attacks are so blatant that no less than the leader of the state senate called the governor biased against the system. These and many other actions and statements are nothing short of  a nihilistic desire to destroy the system on behalf of a power-lusting executive branch of the state government. It may attempt to hide its vicious motives behind platitudes regarding "consumer protection," as voiced by our state secretary of health, but their intentions are clear. I have spoken out against this envy-laden attack by the state many times and will continue to do so (despite bullying and even a piece of rotting meat sent to my doorstep).

The fact remains that no matter how much the governor and his cabinet seek to bully the health system and its employees, they cannot change the facts of reality. These facts unequivocally demonstrate the prowess of this system in delivering care, fostering innovation, and providing nothing short of life changing medicine. 

Getting this transplantation program back on line safely is not just a priority for the region, but the world. I am completely confident it will happen as soon as is possible.

 

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.

 

 

 

The World is Short One Astute Clinician

It's almost a cliche in my field to speak of the "astute clinician" -- the physician of unborrowed vision who sees something amiss to which others are blind. They find the needles in the haystacks, the outliers, the one aberrancy among homogeneity. Behind every outbreak, you will always find one of this rare breed of physician.

Every infectious disease story has a hero like this and there is news today that one of the best recent examples of this pantheon of infectious disease doctors has died: Dr. Deborah Asnis. 

While Dr. Asnis might not be known to the general American public, the work she did surely is. Dr. Asinis was the first physician in the US to alert public health authorities that something unusual was happening in Queens in 1999. in particular, Dr. Asnis noted an unusual cluster of encephalitis cases some of which had polio-like features. Fast-forward through a major investigation led by Dr. Marcie Layton (another astute clinician) and extraordinary veterinarians and at the end it was announced that West Nile Virus had made its first foray to this side of the planet.  

Were it not for her brilliant identifications it is unclear how long it would have taken for public health authorities to realize what was occurring, delaying mosquito control efforts and physician awareness.

I never formally met Dr. Asnis but I recall atleast one occasion passing her at a meeting and glancing at her name badge. As someone who devours stories of outbreaks and knew of her work, I was star struck. The infectious disease world is a little less astute without her.

Having Too Many Vaccines: We Should be So Lucky

At last night’s Republican’s presidential candidate debate the vaccine issue arose. I believe that infectious diseases are worth talking about in these types of forums because the government has an important role in keeping its citizens safe from infectious disease. However, when vaccines are discussed by presidential candidates the exchange often proceeds as if there actually is a question about their benefit.

Often, the media continually dangles these red meat questions in front of candidates who apparently care less for the truth than they do pandering to people whose votes I would never want. Last night Donald Trump delivered answers that were concerning (I thought it was cool that the Washington Post dug out an old quote from me on the topic for their coverage).

While Dr. Carson explicitly—and thankfully—rejected the false notion of any link between autism spectrum disorder and vaccines, he did give credence to the idea that there are too many vaccines administered in too short a time with which Mr. Trump agreed.

Make no mistake, Dr. Carson is a world-class pediatric neurosurgeon who has advanced his field immeasurably and, as a physician, I deeply respect his unequivocal achievements. However, on the issue of too many vaccines over too short a period, the evidence clearly does not support Dr. Carson's position--though his statement regarding the relative importance of certain vaccines based on the severity of the disease they intend to prevent is valid (and why vaccines such as the influenza vaccine are not mandated by government schools).

While it is true that the vaccination schedule has become increasingly more extensive and that is something I am thankful for. We now have vaccines against human papillomavirus, pneumococcus, hemophilus, rotavirus, varicella, and meningooccus—diseases that children, and adults, no longer have to fear. I actually wish there were more vaccines to administer to children and to adults.

It must be remembered, however, that though there are more vaccines routinely administered they are of such purity that the load on the immune system of all of them combined is less than what was in the once routinely administered smallpox vaccines. Moreover, a child’s immune system is literally bombarded with foreign invaders, foreign materials, and myriad challenges that our current high purity vaccines pale by comparison.

The immunization schedule is not divined from tea leaves, it is made after rigorous deliberation by medical professionals who weigh mountains of data on immunogenicity, safety, and epidemiology. Vaccines have transformed our children into bionic $20 billion men and women and, until more diseases meet the fate of smallpox, the more vaccines the better.

Mold Outbreaks in Hospitals: Rare and Containable

Hospital based outbreaks of infectious disease are nothing new and have haunted hospitals for hundreds of years. Indeed horrific outbreaks of childbed fever in Austria were what prompted the revolutionary studies of Semmelweis on the power of simple hand-washing.

While hospitals have modernized and are often associated with that particular sterile smell--when I was child I loved to sniff my mom's lab coat--they are chock full of microbes waiting to pounce. MRSA, norovirus, C.diff, VRE, Legionella, Acinetobacter, ESBLs, and CRE abound in hospitals and cause over 800,000 healthcare-associated infections annually with 75,000 of those ending in death. 

As I often say, we live in a world of microbes and they are literally everywhere -- including hospitals, no matter how clean and no matter how modern. News of mold being present in a hospital in Pittsburgh (on which I am on staff) may seem alarming, but it is not unprecedented as hospitals are part of our microbe-laden planet.

Molds are types of fungi (see graphic) that grow in a certain manner, forming hyphae or little branches. Yeast, the other type of fungi, grow in a different manner forming buds. Some fungi are dimorphic and can switch between the two forms. The most famous mold is probably Penicillium from which penicillin was derived, changing the trajectory of medicine forever. Molds can be found in your fridge, in your basement (the medically unimportant "black molds"), and basically everywhere you look -- if you see them on your favorite cheese you can often just separate that portion of the cheese and the rest will be perfectly edible. 

Other medically important molds include Aspergillus, Scedosporium, Fusarium, and Exserohilum. This last was recently in headlines after a nationwide outbreak of fungal meningitis occurred after steroid vials were contaminated during manufacture. 

Mold infections can range from infection to the lung to disseminated infection throughout the body--an often fatal event. Symptoms such as difficulty breathing and skin lesions can be present either as result of dissemination from the blood or from direct infection of a skin breach (e.g. after the Joplin tornadoes individual impaled with debris developed Mucor infections). Each mold has its own specific predilections and associated clinical course, some more severe than others, and some more amenable than others to anti-fungal treatments.

Healthcare-based outbreaks of molds are a rarity but have occurred. Some recent cases include:

Mold infections are not the usual nosocomial infection and often can only infect those with a high degree of immune system compromise. Because of that fact these infections are thankfully fairly delimited but, because of the overall condition of those susceptible to such infections, can prove to be very severe, as seen in the outbreaks mentioned above. The general public or hospital staff has nothing to fear from these occurrences.

The large scale of the steroid injection fungal meningitis outbreak is the exception that proves the rule as its mechanism of entry into the body involved a major assist in breaching the major component of the immune system: the skin. 

Hospitals are constantly vigilant for patient safety from molds and other microbes, and though there is variation in the ability of individual hospitals to deal with such situations, I am completely confident that this latest situation is being handled expertly.