How to Tame a Virus- A Review of *Paralyzed with Fear: The Story of Polio*

Polio is an infectious disease that holds a special allure for Pittsburghers. It was here that Jonas Salk conducted the research that led to his famous vaccine, forever changing the relationship between humans and this virus. I often imagine what it must have been like to witness Dr. Salk's triumphant return to Pittsburgh--police escort and all--after the vaccine was shown to be efficacious. Dr. Salk's achievement, however, is not something that stands alone; it is part of a pantheon of scientific advances (not the least of which includes Albert Sabin's version of the vaccine). 

There have been many books written about this virus, Jonas Salk, and other aspects of the fight to rid the world of this virus. One such book cost me a considerable amount of money (and is now available for $3.50). 

I recently completed one of the newer additions to this growing library: Gareth William's Paralyzed with Fear: The Story of Polio. 

I really enjoyed this book primarily because it provided a broad, historical, inductively-based scientific approach to the topic. Instead of providing a simple chronological listing of the landmark achievements that led to the control of polio, Dr. Williams employed an approach that places the reader on the trail of scientific inquiry that painstakingly led scientists, step-by-step (and down some unfortunate blind alleys), to higher rungs in the ladder of knowledge which culminated in Eckard Wimmer's synthesis--from scratch--of polio in 2002. 

Some highlights of the book include: a description of the well-known rivalry between Sabin and Salk (which included a particularly nasty bit of correspondence in which Sabin wrote to Salk that "love and kisses were being saved up" for him); DA Henderson's discovery of vaccine-associated paralytic polio (VAPP) linked to the Sabin vaccine in the 1960s; the anti-vaccine movement's opposition to the vaccine; a thorough discussion of the discredited hypothesis of the polio vaccine being the origin of HIV; speculation that FDR may have actually had Guillan-Barre Syndrome (not polio); the "fear campaign" designed to spur public concern in the US over this disease, which was never as big a threat to US public health as other diseases; and countless other anecdotes that make for good reading.

As of today polio eradication remains a daunting task with 89 cases occurring in 9 countries this year, 2 of which are new to the list from 2013. Nigeria, Afghanistan, and Pakistan are the 3 most important heads of this hydra that must be decapitated if eradication is to succeed. It remains to be seen whether this eradication will be successful but one thing is certain: the polio vaccine and the individuals who created it, or whose work led to its creation, have thoroughly destroyed the ability of this virus to wage war on mankind. It only remains for humans to allow the destruction to be total.

Six Little Monkeys Aren't Jumping Any Longer

I just read about the death of 6 recently arrived tamarin monkeys at the Oregon Zoo. While I am by no means a veterinarian, the mysterious death of lower primates should make every infectious disease physician's ears perk up. 

The reason why unexplained outbreaks--epizootics--in lower primates are so important stems from the fact that if a pathogen is able to infect a monkey or chimpanzee, there is a good chance that it has the ability to infect humans, as all primates are genetically similar. 

In fact, preventing these diseases from spilling over--a concept made popular by David Quammen's book--into humans has become a major focus of interest in the emerging infectious diseases world. 

Integral to this paradigm is the simple concept of "One Health," a viewpoint that recognizes that  physicians and veterinarians have many of the same goals and that situational awareness of diseases of interest occurring in animal populations is crucially important to the task of safeguarding human health from infectious disease threats. Monitoring sentinel animal populations such as primates, bats, and poultry for infectious diseases can provide clues allowing some degree of predicting the pathogens on the cusp of jumping into humans to be possible. Similarly, monitoring human populations that have exposure to these species, such as bushmeat hunters and poultry workers, can provide early evidence of cross-species infections before a wider outbreak occurs. In fact, such monitoring would likely have shown HIV in its early years as an agent almost exclusively infecting bushmeat hunters and bushmeat preparers.  

While these monkeys, who were in quarantine because of their recent arrival, may have died from something common and not on par with the events detailed in Hot Zone, their deaths cannot be taken lightly and the cause should be determined. As a non-veteranarian it is difficulty to speculate on causes of death, but ruling out an infectious disease is paramount. 

Update: Seems like travel-related shock may have been the etiology.

Distracting Injuries & Complex Pathologies in my A/C

My air conditioner broke. Twice. Within one week.

What could that have to do with medicine and infectious disease? A lot, if you are as obsessed with these topics as I am. 

What I had a hard time understanding was how the HVAC repairman fixed the air conditioner on one day only to have it malfunction a few days later. To blame were two different components. After the first repair, since everything seemed to be working, there was no impetus to check for further issues in the system. A few days later, those other "issues" manifested and I was left with a sweltering condo. 

In medicine there is something known as a distracting injury. For example, if someone breaks her leg in a fall the pain may be so intense that the individual doesn't realize that her neck also hurts. So, physicians are encouraged to discount the patient's denial of pain in one body part if a distracting injury is present in another. In effect, my air conditioner had a distracting injury that the repairman exclusively focused upon, blinding him to the other issue. 

I also recalled something one of my favorite attendings said to me when I was an infectious disease fellow. It was her admonition that complex patients--such as the severely immunosuppressed--can have more than one pathophysiological process occurring within them.

Was my air conditioner immunosuppressed? 

The Ever-sharpening Spear Aimed at HIV

It's hard to keep track of the various strategies being employed to functionally cure HIV and their relative merits. A new book titled, Cured: How the Berlin Patients Defeated HIV and Forever Changed Medical Science by Nathalie Holt, does a great job at detailing these approaches and their histories.

The book weaves together the paths of the two Berlin patients, Timothy Ray Brown and his predecessor Christian Hahn, who experienced functional cures of their HIV infections. While the story of Timothy Ray Brown is familiar to many in this field (receipt of a bone marrow transplant for leukemia from a donor who possessed the HIV resistance mutation CCR5Δ32), Christian Hahn's story is equally fascinating.

Hahn was placed on anti-HIV therapy soon after infection and his regimen included an unusual drug, hydroxyurea, with unique properties. After stopping therapy Hahn did not have any viral rebound. Debates over whether it was the timing of therapy, the use of hydroxyurea, or another factor ensued. In the end, Hahn was found to harbor a protective genetic signature HLA-B*57 that can control HIV replication.

The book also covers other cure approaches such as that employed with the Visconti Cohort, the "Mississippi Baby" (and her offspring, the "Long Beach Baby"), and the failed approach taken with the "Boston Patients" who underwent non-CCR5Δ32 bone marrow transplants. See this great amFAR graphic for a guided tour of these cure approaches. 

I highly recommend this book to those interested in getting a glimpse of the cutting-edge science being employed in this Herculean effort. 

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.