How's Your Microbiome?

Increasingly, awareness of a person's microbiome--the total population of bacteria that live within an individual, and their genetic material--has shaped how disease is approached. Not only are treatments that disrupt the microbiome beginning to be viewed as harmful, but also the idea that one's microbiome can be associated with specific conditions.

In the January issue of the Mayo Clinic Proceedings, an excellent review article provides a concise summary of the role of the microbiome in clinical diseases including:

• Clostridium difficile: probably the most paradigmatic example of microbiome alteration
• Irritable Bowel Syndrome
• Inflammatory Bowel Disease
• Obesity: a really fascinating phenomenon that will definitely be the focus of more research
• Allergic Disease
• Neuropsychiatric Diseases

The fact that in a human body the number of bacterial cells outnumber human cells (by a factor of 10) is impressive and will condition the current and future treatment of infectious diseases (as well as other illnesses).

Measles Made the Dark Ages Darker

Today, at the ASM Biodefense and Emerging Diseases Research Meeting I am attending, a speaker mentioned that measles first jumped into the human species about 1100 years ago, derived from the recently eradicated animal disease rinderpest.

While these facts weren't new to me, it prompted me to think about measles in the context of human history.

When measles made its zoonotic jump into the human species, life was harsh in the Western World.  The Roman Empire had fallen 400 years earlier and the Dark Ages followed. Roman Emperor Charlemagne's brief attempt at reunification of Europe had just failed with the partition of Europe into 3 distinct domains for each of his grandsons plunging Europe back into the dark for several hundred years more.

In this era, measles must have killed at a harrowing pace. 

It was only in the 1960s that the brilliant and legendary Nobel Prize winner John Enders developed the measles vaccine.

Today, thanks to Dr. Enders, life is lived generally free of the threat of measles. In fact, measles is one of the candidate diseases for eradication. However, Dr. Enders' heroic work may be for naught if suboptimal vaccination rates, linked to unwarranted fear of vaccines, allow this killer to again roam wild as it first did in the Dark Ages. 

Post-Lyme Syndrome: The Result of Altered Immunity, not Chronic Infection

One of the controversies in infectious diseases surrounds Lyme Disease. There is a large group of patients who, once adequately treated for the infection, continue to experience symptoms such as chronic pains, malaise, and related complaints. 

Although patients--and some clinicians--attribute this to ongoing replication of Borrelia burgdorferi, there is no evidence that a chronic form of infection amenable to antimicrobial therapy exists. A recent paper has shown that some Borrelia antigens may persist in a mouse model, but that does not mean long term antimicrobial therapy is warranted or beneficial in humans. The IDSA guidelines, which unfortunately continue to spark controversy, reflect this position.

Many infectious disease physicians believe that post-Lyme symptoms are the result of the specific immune constitution of individuals and, as such, prolonged antimicrobial therapy offers no benefit as clinical trials have shown.

A recent study, published in Clinical Infectious Diseases, attempted to assess if there are  immune differences in those that experience chronic Lyme symptoms. One of the fascinating results of this study was that, even prior to treatment, those that develop chronic Lyme symptoms have an altered polarity of their immune system when compared to those who suffer no chronic symptoms. Specifically, elevations of IL-23, a molecule which promotes the proliferation of Th 17 T cells, a specific class of immune cell linked to the development of autoimmune phenomena, were found to be associated with the development of chronic Lyme symptoms. One caveat: the study was conducted in Europe where B.afzelii is the culprit bacteria, which may limit its generalizability to the US setting.

The importance of this study is that it will, hopefully, dissuade those who demand chronic antimicrobial therapy from such requests while, at the same time, point the way towards fruitful areas of research that may yield effective treatment.

Apollo 18: Contagion on the Moon?

The movie Apollo 18, a sci-fi movie that portrays a horrific mission to the moon, addresses some important microbiological and infectious disease matters (albeit in a highly fictionalized manner). In the film, astronauts on a moon mission are infected/infested by an extraterrestrial pathogen.

The scenario of a contagious disease in space raises very difficult questions, some of which have been the subject of actual prior work in this field. Some fascinating questions include:

• Does being in space where sterilized food is consumed change one's microbiome to render one hypersusceptible to infection (either extraterrestrial or upon return to Earth)? The historical answers to this question and the possibility of astronauts being at a risk from a "fatal kiss" are discussed in the book Good Germs, Bad Germs.
• What would be the concept of operations in an extraterresterial infection (see Michael Crichton's The Andromeda Strain)?
• How does one handle a potentially contagious illness in an astronaut in space? 
• Is there bacterial life on other planets, asteroids, etc? Would they resemble earthly extremophile bacteria?

While movies such as this are pure fiction, they do serve to focus attention on the ubiquity of microbes and their ability to infect us in myriad scenarios. 

Starve the Flu, Have a Fever

An interesting new study published in the Proceedings of the Royal Society B (summarized in The New York Times) , using mathematical modeling tools, suggests that medications that reduce fever may amplify the ability of the virus to spread. 

Fever, as unpleasant and disabling as it is, serves two purposes with respect to infectious disease.

1. Usually, microbes are unable to reproduce at the higher temperature that characterizes fever.
2. The unpleasantness of fever often limits social contacts, starving the microbe of new hosts to infect. 

Consequently, when fever is controlled the propensity of the microbe--in this case influenza--is enhanced by 1-5%. Taken at a population level such a minor increment can translate into a substantial number of added cases. 

The results of the study while intriguing and logical, must be placed into context. Fever, though usually benign, can have serious consequences such as febrile seizures in children and increasing the metabolic demand, which could prove dangerous in someone with compromised cardiac or pulmonary function. 

Bottom line: Be cognizant that reducing fever helps the virus but may be a necessary action when the entire context of the patient is taken into account.