The Normal Heart Illustrates Normal Principles of Epidemic Management

I just watched HBO's The Normal Heart, a star-studded movie based on Larry Kramer's play of the same name. (Incidentally, in 2001 the HIV and Hepatitis B-positive Kramer received a liver transplant at my institution, UPMC, which had been pioneeringly transplanting HIV-positive patients since 1997.) The setting of the movie is the early days of the HIV epidemic and its plot revolves around the actions taken to increase awareness of this nascent epidemic. 

For those in infectious diseases, the story of how HIV and AIDS rose in the public consciousness is not new. In my own case, I remember learning about this disease in the early 1980s from my mother, a pulmonary medicine physician in a small town outside of Pittsburgh. She recounted to me a chilling story of having no nurse to help her perform a bronchoscopy on a dying AIDS patient with Pneumocystis pneumonia. She used a paramedic.

Watching this movie now, given the context of my own interest in emerging infectious disease, a few aspects really struck me. 

Social Network Analysis is Crucial

In any outbreak of a novel infectious disease--from HIV to MERS--it is vitally important to understand how people are getting infected. Old-fashioned detective work is usually how this is done. In the modern age, electronic social networking tools like Facebook and Twitter might make the activity more technology-driven but the principle remains the same. In the movie, the polio-afflicted character portrayed by Julia Roberts realizes that many of her patients are all sexual partners of each other and anticipates that they will all infect each other. Understanding the epidemiology and dynamics of infection through social network analysis often provides brilliant insight into the factors driving an epidemic.

Public Health Communications

During outbreaks there is an almost an unquenchable need for those at risk of infection to know how to protect themselves. During the early stages of an outbreak, misinformation may provoke anxiety, false security, or lead to incorrect actions to be taken. The Normal Heart effectively dramatizes the fact that when HIV was thought to be sexually transmitted, that and other information had to be disseminated. The Gay Men's Health Crisis served in that role.

Sentinel Populations Provide Early Warning

Outbreaks affect populations disproportionately. Not all elements of a population may be at risk. For example, veterinarians are at higher risk for rabies than the general population. Similarly, with HIV, men who have sex with men, injection drug users, and hemophiliacs were groups that were at higher risk because of the higher rates they were exposed to blood and body fluids. Currently, sentinel populations of interest include bushmeat hunters (novel viruses) and poultry farmers (avian influenza) and situational awareness of the illnesses these groups are afflicted with can potentially provide an early warning that a novel virus is spilling into the human population. 

The Normal Heart is primarily a movie about the social politics of the early AIDS epidemic and the intransigence of those trying to draw attention to what has risen to become the current #1 infectious disease killer. However, for those interested in more the movie provides some insight into how a disease emerges and the reactions of those caught in the midst of the ongoing war between man and microbe.

Another Victim of Antibiotic Resistance

This past week I was informed that a patient whom I had treated died. This patient was suffering from a multitude of cancer-related problems that, when coupled with an infection, were too much to overcome. The patient's infectious problems weren't the stuff of movies nor was he infected with something with an ominous name. However, his death is a lesson in what the practice of infectious disease entails today and will increasingly entail in the future.

My patient died with an enterococcal bloodstream infection. Because of characteristics it possessed, this puny bacterium proved too difficult to treat. While enterococcus is not a bacterium that most people know about, some may have heard of its more troublesome form: VRE. 

VRE is the acronym for vancomycin-resistant enterococci, a form of the bacterium not killed by the workhorse antibiotic vancomycin. When infections with VRE occur we usually have several other options to try. This VRE with which I was battling wasn't just any VRE though, it was resistant to the next drug we tried as well, daptomycin. And, because this was a serious bloodstream infection that had secondarily infected his heart valves, drugs like linezolid--which only inhibit enterococcal growth and don't kill it--would be expected to fail as well given the nature of the infection (it did). Novel combinations of antibiotics (ceftaroline + daptomycin) were also attempted and failed.

In the end, I turned back to an old but painful friend, Synercid. This antibiotic which was the first targeted to VRE enjoyed a brief 15 minutes of fame until it was supplanted by linezolid and daptomycin. This fame ended when it was realized that hours of pain, in the form of joint aches, were the result of Synercid administration. I warned the patient and he bravely bared the aches and pains. Initially, I had hope as he initially cleared his blood of the bacteria but later surveillance cultures revealed that it had not actually been vanquished. No surgical options were available as cancer had diminished the patient's immune system as well as the ability of his blood to clot.

This enterococcus was one bad bug for which there was no drug and it cost a man his life.

Antibiotic resistance has real victims.

Unsolved "MERSteries"

The announcement of the 2nd domestic MERS case today is not surprising and doesn't represent a major change in the pattern of cases. This case, like the one before it, is in a traveling healthcare worker and its detection reinforces the importance of astute clinicians armed with the knowledge and tools to detect emerging viruses.

However, in light of this case, lingering questions should be revisited given the smoldering nature of this 2 year plus outbreak.

Do super spreaders exist?

The most dramatic feature of SARS was the existence of super spreaders. These Typhoid Mary like individuals were responsible for much of the global spread of SARS. With MERS however, evidence of super spreaders has not been definitively established although events suggestive of such spread exist. For example, in Abu Dhabi there is an case patient who may have been responsible for secondary spread to 27 additional cases. It is unclear, according to the WHO (at this time), whether these were all linked transmission events or from non-human sources. Additionally, the Al Hasa outbreak detailed in the NEJM is also suggestive. 

I think that for all infectious diseases, super spreaders likely play a major role and MERS will turn out to be no different. 

Is This a Public Health Emergency of International Concern?

The International Health Regulations provide WHO with a mechanism to declare a public health emergency of international concern (PHEIC) when events reach a certain threshold. The WHO is convening a meeting tomorrow to determine whether MERS meets that criteria. I think this is a difficult decision because, in a way, MERS has met this criteria over the last 2 years and nothing fundamentally different has occurred (granted the uptick in cases). Prior meetings have not resulted in such declarations.  However, a PHEIC declaration may provide an impetus to countries with cases to provide more information about cases and the means by which they were infected. 

Little Pink Houses and MERS in Indiana

The just revealed news of an imported MERS (Middle East Respiratory Syndrome) case in Indiana--the first in the US--is not surprising. 

MERS has been simmering for 2 years and importations have occurred to several countries, including the UK. 

In this case, an infected healthcare worker (not surprisingly) traveled from Riyadh to London and on to Chicago. The patient then boarded a bus to Indiana.  

Although MERS has a case fatality rate of 30%, this patient appears to be not critically ill. Important actions in the coming days will include searching for secondary cases.

This case illustrates 2 important things:

1. It's a small world and infections on one side of the globe can appear on the other with no border restriction string enough to stop it. 

2. Astute clinicians are crucial. From what I've read, the patient's travel history tipped off physicians who ordered the appropriate tests. 

MERS occurring in the US was something that was expected and planned for--remember 8 SARS cases occurred in the US as well.

To Catch a Virus You Need A Special Mitt

I just finished the book To Catch a Virus. This book is focused on the developments in diagnostic virology that have shaped the way modern medicine confronts viral infections. What is most attractive about this book is that it details the discovery in a chronological fashion stressing the conceptual links between discoveries. For example, the development of PCR testing is handled in a manner in which one is able to see the progression from Oswald Avery to Kary Mullis without difficulty. Additionally, the book stresses the inductions made by various investigators providing a treasure trove of material for historians and philosophers of science. I highly recommend the book.