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.

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.