Rational Use of Antibiotics: Nearly A Hundred Years War

When I discuss antibiotic resistance, a point I am sure to make is that these compounds are to be treated like precious commodities. In the modern era, that strikes many people as odd because they have taken countless courses of different antibiotics and have always recovered. There always seems to be a new antibiotic released that their PCP may try them on if their symptoms are particularly recalcitrant to the first course. Medicine will always develop new antibiotics, they assume. 

Last week, I had the pleasure of listening to Harvard University's Dr. Scott Podolsky discuss the topic of antibiotics, not from the usual perspective that is focused on a prophecy of a post-antibiotic era (a valid concern), but from a historical perspective. Such a perspective allows one to place antibiotics and their overuse into a much larger context that is informed by an understanding of how antibiotics rose to such prominence that today prescriptions for them are literally demanded of physicians.

In his talk, part of C.F. Reynolds Medical History Society's annual lecture series at the University of Pittsburgh, Dr. Podolsky highlighted an important of the pre-antibiotic era that is often overlooked--and may hold the key to combating infectious diseases more rationally in the future: serum therapy. Serum therapy was a means of using products manufactured by the immune system against specific microbes in another individual.  It was the opposite of broad-spectrum and was largely supplanted by the much simpler use of broad-spectrum antibiotics. Today, we have anti-serum therapies for diseases like botulism and tetanus. But, there is a lot of effort to develop modernized serums, aka monoclonal antibodies, which we saw used experimentally against Ebola in the form of ZMapp and which already exist for anthrax and RSV. Moving back to specific therapies is a sure means to not only delimit antibiotic resistance but to avoid the collateral damage to the microbiome that is probably just as important.

Another aspect of Dr. Podolsky's talk I found fascinating was the prescience of those at the dawn of the antibiotic age, such as the first president of the Infectious Diseases Society of America (IDSA) Dr. Maxwell Finland, who realized the dangers of injudicious use of antibiotics and established early principles for antibiotic stewardship.

One of the themes from Dr. Podolsky's lecture that resonated with me was that the current debates on rational use of antibiotics we are in reaches back several decades and understanding the terms of the debate, at its inception, is an important and over-looked task. Thanks to Dr. Podolsky for doing the intellectual work needed to make these facts easily accessible and able to be integrated into the modern context.

Would Gerbils Obey the Pied Piper?

Rats are considered an unavoidable bane of urban life and have been generally associated with filth, disease, and pestilence. One of the most ominous events--The Black Death and the following European plague outbreaks--they have been linked to may not actually have involved them (they would blame it on the fleas anyway).

A new study suggests another rodent might have been to blame: the gerbil (actually the great gerbil from Asia). In this study, Schmid and colleagues looked at climatological data contained in tree rings in Europe and Asia (the traditional home of plague) to determine if such conditions were conducive to rat populations. The study attempts to unravel a few paradoxes regarding plague in Europe: what was the rodent reservoir that allowed plague to persist there (which disappeared in the late 19th century when plague outbreaks tapered off) and was plague something that seeded Europe at the time of The Black Death and persisted in rodent populations there? 

What the evidence presented in this paper suggests is that tree ring data in Europe from the time of known plague outbreaks do not support a climate suitable for rat populations to thrive. However, tree ring data from Asia do show a correlation with a climate conducive to gerbil population booms followed by  busts, forcing resident fleas to look for alternate hosts (i.e. humans and other animals, including rats). This finding is at odds with the traditional view that attributes the presence of plague in an infected European rat reservoir.

The authors speculate that repeated introductions of plague to Europe from Asia occurred to produce each plague outbreak--a finding that may absolve the rat of its role in perpetuating Europe's plague outbreaks. 

This study shouldn't dissuade people from having gerbils as pets as it is not applicable to captive gerbils. Similarly, it shouldn't encourage people to have rats as pets (don't forget about rat bite fever). 

What the study does do, at least for me, is provide another great concretization of how infectious diseases affect and are effected by absolutely everything: animal population, international trade, seasons, and, in the case of the Black Death, perhaps the structure of Western society. 

Looking at the Roots of My Immunity

Normal people look on Ancestry.com to find out things about their history. I, being the infectious disease obsessed nerd that I am, dig out my immunization book to look at which vaccines I received.

My parents are both doctors are kept pretty good records on my immunizations which made my task a little easier. Looking at the little blue book that holds the secrets of my early immunologic experiences, I was shocked by how few vaccines were available in 1975, when I was born, versus now. There was no rotavirus, HiB, Prevnar, varicella, meningococcal, hepatitis B, hepatitis A, or HPV vaccine. What does that leave? DTwP (now unfortunately replaced by DTaP, oral polio (now replaced with the inactivated Salk injection form), and measles/mumps/rubella.  I also received the cholera vaccine (no longer available in the US) for travel-related reasons.

Looking at the relative paucity of the vaccines I received I have the opposite reaction than many anti-vaccine advocates who reminisce for an era with less vaccines. I, on the other hand, which I was more vaccinated because I had to suffer through rotavirus (I’m pretty sure on an ominous notation of me having diarrhea in March of 1977 was the result of this virus), chickenpox (in 8th grade!), and dodged the bullets of invasive infections with type B H.influenzae and pneumococcus.

Another interesting thing I learned is that I received the measles, mumps, and rubella vaccines as individual injections. The MMR vaccine was introduced in 1971 and its uptake may not have been universal for some time. I was a person who only received one dose of these vaccines as the recommendation for a 2nd dose wasn’t made until 1989.

Interestingly, as a medical student in 2000 I was required to have my titers checked against measles and rubella and was found to not have adequate protection against rubella and received the MMR at that time. Then, 5 years later, the titers to all three components of the vaccine were checked and this time my mumps titers were found to be low and I got another MMR.

I wonder why my titers against rubella and mumps were low and I speculate that maybe I received the old killed mumps vaccine which was inferior to the live-attenuated version that replaced it. But that can’t be the whole story because I didn’t develop adequate mumps titers after receiving the MMR in 2000. As for rubella, I’m not sure. So in the end, I received 2 MMRs, in spite of receiving the monovalent vaccines I received as a child, just like the children of today.

As an adult, I treat vaccines like the precious commodities they are. To that end, I have gotten typhoid, hepatitis A, meningococcus, hepatitis B, and hepatitis A vaccines. Even when it comes to the sub-par influenza vaccine, I go out of my way for it—standing in line for the pandemic H1N1 vaccine at a local school and travelling around to find the quadrivalent vaccine in its first year of limited availability.

In the almost 40 years since I went through my routine childhood immunizations what were once breakthrough vaccines have now become routine.  So many infectious diseases remain for which no vaccine is commercially available. To name but a few: HIV, hepatitis C, malaria, MERS, SARS, Ebola, and West Nile Virus.  As science and medicine continue their reason-inspired march, routinizing of the cutting-edge will be the norm. 

A Measlely Journey Through Social Media

Last night and today I was immersed in an interesting social media adventure that, at once, concretized the good, the bad, and the ugly of the medium.

As everyone knows, the U.S. is in the midst of a measles outbreak that has logged 141 cases so far in 2015. Pennsylvania, fortunately, has only had one case but it is only a matter of time before more accrue.

I am a member of a Facebook group whose mission is to improve vaccination rates in the state and seek an end to the philosophical exemption to school vaccination.  Last night, a message on the page alerted members that a mayor of a Pittsburgh suburb had announced on his publicly visible Facebook page that his fully vaccinated son was diagnosed with measles. Such an announcement set off a storm of questions in my and others’ mind including:

·      How was the diagnosis made?

·      How sick was the child?

·      What was his exposure history?

·      Were appropriate public health interventions taking place?

There had been no formal announcement of a case--possible, probable, or confirmed—from public health authorities as there had been with other instances.

The next day the mayor publicly tweeted and posted on Facebook that the diagnosis was made at an urgent care center without any laboratory testing.

This immediately triggered several more thoughts centered on stand-alone urgent care centers  (i.e. those not affiliated with a hospital). In general, I support these facilities and many excellent health care providers work at them. However, one shortcoming that I have noted is that they are not particularly well integrated into the public health emergency apparatus as they tend not to be part of health care emergency coalitions (unless they are owned by a hospital system)—a fact my colleagues and I noted in a paper focused on Hurricane Sandy.

Even a suspect measles case--let alone telling a patient they have measles—no matter how unlikely it is, should trigger notification of appropriate public health authorities because of the need for appropriate testing (PCR), isolation, a contact investigation, school notification, and the need to administer post-exposure prophylaxis to those not vaccinated.

The mayor’s follow-up tweet and postings confirmed what I thought when he wrote that measles was highly unlikely.

The lesson to me is that responsible health care providers, in all settings, need to take the right actions at the point-of-care and communicate the level of diagnostic certainty and appropriate protective actions needed to the patient who.

Social media has immense power for improving infectious disease management but can only be harnessed if its content is based on sound information.

One Bourbon, One Virus, One Tick

To me the allure of infectious diseases is that you never know what is around the next corner. Because we live in a world teeming with microbes--many of which are undiscovered--hearing about a novel infectious disease is not unexpected but is always exciting.

Much of the cutting edge research in infectious disease centers on pathogen discovery. In this quest certain places, animals, and humans are more fertile than others. For example, bush meat hunters and abattoir workers are frequent targets for emerging infections because these individuals live on the human-animal interface. Similarly, looking for pathogens that infect primate species is also fruitful because of the close evolutionary relationship between humans and other primates.

In recent decades and years, however, several new infectious diseases have been linked to ticks. Lyme Disease is probably the most well-known but more recently diseases such as the Heartland Virus, STARI, a novel cause of Ehrlichiosis, and SFTS virus have come to light. 

Ticks have an intimate relationship with humans because they gain direct access to our bloodstream during their blood meal, giving the microbes they harbor unrivaled access.

The latest microbe to capture the headlines is the interestingly named Bourbon Virus. This virus, responsible for the death of a man in Kansas, is tick-borne as well and its discovery is the direct result of improved diagnostic capabilities and the increasing recognition that it is important to not allow unexplained infectious disease syndromes to remain undiagnosed, points I made to USA Today. 

It's not clear at this point how widespread this virus is in humans and ticks or how frequently severe disease results, but all are important questions to be answered.