One Nation Under Vaccines (I wish): My Review of Vaccine Nation

The relationship the general public has had with vaccines over the past several decades has is not simple. The trajectory of vaccination began with just a single vaccine protecting against a single disease--that of Jenner's for smallpox in the late 1700s--and now every American child is protected against 16, if up-to-date on recommended vaccines (which I hope they all become). When I was a child, I was able to be protected against only 7 of what became routine in 2015.

There are, of course, more vaccines that are not routinely administered though easily available. These include vaccines against smallpox, anthrax, rabies, yellow fever, Japanese encephalitis, typhoid, and adenovirus.

What may be puzzling to many is how diseases get specifically targeted for control via vaccination and how members of the "sweet 16" came to be. A new book by Emory historian Elena Conis entitled Vaccine Nation: America's Changing Relationship with Immunization provides a lot of context and history that is not well appreciated. 

The most important aspect of the book, to me, is the theme that as society matures and medicine progresses what is a tolerable risk changes. New contexts condition how risk is objectively evaluated by individuals. Thus when there was no measles vaccines, measles was an accepted risk. However, when a safe and effective vaccine was available the risk became unacceptable.

Not all diseases are as a straightforward as measles, but the general conceptual model is the same. In many cases, the ability to live a life devoid of a "nuisance" infection may have played a role. For example, mumps--in which complications occur at a low rate--the convenience of living a life free of mumps and the ensuing need to be cared for by parents who must stay home from work (not to mention the national security implications of having soldiers sidelined by the virus which is more severe in adults). This point is moot in the current context when the mumps vaccine is exclusively (and conveniently) bundled with measles and rubella.

Risk goes the other way as well. When smallpox was nearly eradicated from the planet, the US stopped vaccinating against it (1972) because the scientifically-established risk from the vaccine outweighed the risk of contracting the illness for the general public. Similarly, when polio was nearly eliminated from the Americas there was a switch in the US from the Sabin live vaccine to the Salk inactivated vaccine to remove the risk of vaccine-derived polio from the vaccine strain.

Professor Conis provides much vivid material surrounding the debates and decisions that played a role in the rise of such vaccines as ones against measles, mumps, rubella, hepatitis B and HPV.

She also, in a very clinical way, looks at the various facets of the anti-vaccine movement finding its roots in other social movements which espoused certain philosophies that derided the scientific method, logic, and objective evidence in favor of some other "method".

The book also usefully immerses the reader in the politics that followed the introduction of the polio vaccine in the 1950s. This political atmosphere led to a growing government role in specifically funding vaccination activities of the states through various laws that developed new programs beginning in the Eisenhower administration and culminating in the Clinton administration's Vaccines for Children program.

With this book, Professor Conis has made a great contribution to the literature on the social aspects of vaccination and as a dyed-in-the-wool unapologetic vaccine advocate I think it is required reading.

P.S. Get your flu shot

Buffalo Wings Clipped by E.coli-tainted Celery

A new outbreak of the potentially deadly O157:H7 strain of E.coli linked to celery from California's Taylor Farm Pacific has spread to 18 states and involves over 150,000 products. This bacteria calls the calf's GI tract home but can proliferate in almost any food substance it contaminates.

That this outbreak, from a single type of food, involves such a wide swath of products is illustrative of the worse aspects of food-borne outbreaks: their dissemination. Also, the fact that one need only ingest about 100 bacteria to become ill heightens the risk. Celery is a component of many other pre-packaged products including sandwiches, salads, stuffing, and vegetable mixes. That's why this outbreak has touched major corporations such as Target, Walmart, and Starbucks. Tracing the ultimate fate of all the contaminated celery is extremely cumbersome and wide-ranging. 

This strain of E.coli, which is classified as a Shiga toxin-producing E.coli (STEC),  is not as benign as other food-borne infections for it has the capacity to cause kidney failure via a toxin it secretes in up to 10% of cases, especially children. This complication is known as hemolytic uremic syndrome (HUS) and it has occurred in 2 of the 19 individuals infected during this outbreak. Though there are no deaths have been reported in this latest outbreak, 12% of those with HUS progress to death or become dialysis-dependent. Antibiotics are ineffective and, in fact, can heighten the chance of HUS occurring as toxin secretion increases when the bacteria is under stress. Treatment is largely supportive though some experimental treatments are in trials.

So for those dieters, buffalo wing eaters, and rabbits who chew on celery, maybe try a pickle instead.

Hold Your Fire -- It's Just a Mitochondria, it's One of Us

One of the most intricate and fascinating aspects of physiology is the immune and inflammatory response and how it is triggered. At a 10,000 foot level, the immune system is triggered by the presence of some sign of an invading organism. Such a sign could come from, for example, detecting its genetic material through special receptors known as toll-like receptors (TLRs). 

One such receptor, TLR-9, is used to detect foreign DNA sequences. These sequences, which are rare in vertebrates, are considered to be pathogen-associated molecular patterns (PAMPs). Once this process is started the result is systemic inflammation in order to quell the infection.

However, not all systemic inflammatory reactions are due to a microbial pathogen. The ICU is literally full of people who are exhibiting systemic inflammatory response syndrome (SIRS) but without a clinical infection. Trauma and post-surgical patients are two common examples. In these settings it is thought that tissue damage leads to the release of damage-associated molecular patterns (DAMPs), and not PAMPs, triggering the inflammation. A new paper from the Medical University of Vienna, elegantly provides more information to help unravel this process.

Within our cells are special structures that basically serve as the power plant, generating energy from oxygen: the mitochondria. Mitochondria are special amongst our cellular organelles as they were once free-living bacteria that entered into a symbiotic relationship with the evolutionary precursors to our cells and now live within our cells. As such, they retain their own genetic material which is, for all intents and purposes, bacterial. 

Prior studies have demonstrated that mitochondrial DNA (mtDNA) levels correlate with illness severity in certain conditions such as trauma. In this fascinating study, this was taken one step further as the levels of circulating mtDNA as well as TLR-9 expression were measured in ICU patients. The findings show that high levels of mtDNA, when coupled with high TLR-9 expression, were found to correlate with mortality. 

The study will likely lead to interest directed at medications to block TLR-9's effect but even without such an application the whole process is very interesting to ponder: little bacterial creatures that live within our cells and are essential for life leak their DNA into our blood when we are sick or hurt and, because of their ancestry, our body (quite understandbly) mistakes for a bacterial invasion and launches an attack which could be fatal for us. 

So cool.

I am Thankful for Jonas Salk

To the general public, Pittsburgh is the land of sports superstars but to me it will always be the land of Dr. Jonas Salk. It was here that he developed the polio vaccine taming a virus that struck fear in the population. 

Reading the excellent new biography of Salk, Jonas Salk: A Life by Dr. Charlotte Jacobs, reinforced that conclusion. I have read several books about polio and the race for the vaccine but none focused exclusively on Dr. Salk. To me the strength of Dr. Jacobs' book is that it doesn't just end with the conquering of polio but spends much time on Dr. Salk's post-polio life. 

One might think that once he received the deserved acclaim from the development of the vaccine that all would be smooth-sailing for Dr. Salk. However, that wasn't totally the case. The trials and tribulations that Dr. Salk endured trying to establish and maintain the institution that still bears his name is a case in point.

The most intriguing part of the book is Dr. Salk's battle with HIV, which occurred in the last years of his life. At this time, Dr. Salk had closed his laboratory and was focused more on philosophy and the humanities than medicine per se. However, this man -- who believed he was destined to be a benefactor of humanity -- delved back into the field and developed an approach to a vaccine. As Dr. Jacobs writes, "When the desperate need for an AIDS vaccine became apparent, Salk found a raison d’être.”

The approach he favored was that of a therapeutic, as opposed to preventative, vaccine in which the vaccine would be administered to those already infected with HIV with the hope that it might boost immune responses to the virus. If successful, such a vaccine would provide a "functional cure" for HIV. Needless to say and not surprising, such an approach, with some modernization, is still alive.

I read biographies not just for their historical value, but for inspiration. In that vein, my favorite passage from the book is this (from the last pages):

“...he held strong convictions. Certain about the merit of the things he had done, the things he wanted to do, he rarely expressed self-doubt. Connected to this, he was unrelenting, repeating his view over and over, never seeming piqued or tired. Once he determined a course of action, he would not waver from it. His persistence exasperated those on the receiving end.”

As I write this on the eve of Thanksgiving -- a holiday that celebrates the abundance made possible by productivity -- I am thankful for Dr. Jonas Salk whose work to rid the world of polio not only saved countless lives and raised the standard of living of the entire race but provides inspiration.

Thank you Dr. Salk.

Giving the Rectal Thermometer its Due

One of the cardinal features of many infectious diseases is the presence of fever. Fever, usually defined as a temperature exceeding 38.3 degrees Centigrade (100.94 degrees Fahrenheit), is a defense mechanism employed to stifle the growth of microbes who prefer to grow at lower temperatures and augment the immune system which heightens its activities at higher temperatures. 

Fever also has a major diagnostic role as it is used to discriminate between those who are more ill and those who are less ill. Fever is also part of the criteria for employing the concept "systemic inflammatory response syndrome" to a patient--which can trigger an extensive evaluation for an inciting infection.

With that context, it becomes clear that accurately determining if fever is present in a patient is an important task. Sometimes fever can be obvious and felt directly by touch, however tactile temperature taking is fraught with error therefore thermometers are employed. While it is well known that peripheral temperatures obtained in the mouth, ear, arm pit or forehead can be inaccurate and subject to manipulation (think of the school child who sticks a thermometer in a hot liquid before putting it in his mouth) they generally are the primary means of temperature assessment employed in healthcare settings. The gold standard of temperature measurement is more invasive and would involve measuring the temperature of the blood, the bladder, the esophagus, or the rectum directly. 

Rectal temperatures, being the least invasive of the three, is employed variably to determine temperatures. Usually small children and critically ill adults may have their temperature measured in this manner. A new study, however, provides evidence that this form of temperature measurement should be employed more liberally if accurate temperature measurement will make a difference in clinical management. 

In this study, which was a systematic review and meta-analysis, 75 studies were pooled and revealed that peripheral thermometers level of agreement with central thermometers was unacceptable and could be off by 1-2 degrees Centigrade at extreme temperatures (higher or lower). The sensitivity for detecting fever, furthermore, was just 64%--not too much better than flipping a coin. Specificity, meaning the reliability of a peripheral thermometer's detection of a febrile range temperature, was good at 96%. Translation: if your oral thermometer detects a fever, it is likely a real fever but if it reads normal, fever may still be present. 

To me, the results of this study should lower the threshold for obtaining a rectal temperature in those patients in whom the result would change management (after a peripheral temperature is reported as normal). This does not mean that every parent or grandparent should subject children to routine rectal temperature measurement because in that setting -- an ill-appearing child -- temperature adds little to the treatment (fluids, acetaminophen, ibuprofen). The other implication is the need to better calibrate peripheral thermometers prior to use and the need for innovation in this market to spare all our rectums.