A True Doomsday Pathogen?

Today, while rounding on infectious disease patients, I came face to face with a deadly killer for which I had no treatment to offer.

It wasn't Ebola. 

This killer lurks within the US, can spread person to person with ease, and can cause whole hospital units to shut down.

Its name: XDR Acinetobacter.

Because many of the infections this pathogen causes occur in elderly chronically Ill nursing home patient, it doesn't grab headlines. It should for it is a harbinger of the future if antimicrobial resistance continues and current strategies in the treatment of infectious diseases, reliant almost exclusively on broad spectrum antimicrobials, are not rethought.

So while more flashy diseases may turn heads, the serial killer in the shadows continues its work.

Would You Like Some Mycobacteria with Your Tramp Stamp?

People often forget that one of the most crucial components of the immune system is the skin. Though it is less intricate and flashy as antibodies, complement, neutrophils, lymphocytes, and, one of my favorites, natural kill cells, the skin is an essential barrier that stymies many pathogens.

This fact is why Band-Aids are important. 

Anything that causes a breach in the skin--be it a laceration, an IV, or a puncture--is the equivalent of leaving the door open to pathogens. 

One ornate welcome mat recently in the news is the tattoo. Tattoos, when applied with dirty needles, have been associated with hepatitis C infections but a recent advisory was issued warning of the possibility of infection from certain bacterially-contaminated  tattoo inks. In particular, non-tuberculous mycobacterial infections are the main risk. It is thought that dilution of inks with tap water introduces bacterial contamination. Mycobacterial infections are particularly hard to diagnose and often require prolonged courses of treatment. 

I once heard the expression "peeing on the birthday cake" and it seems to be a particularly apt way to describe what the inconsiderate Mycobacteria are doing to people's tattoos. 

HIV, Ebola, & Wild Child Emerging Infectious Diseases

I was asked a really interesting question on a recent TV interview. I was asked about what lessons from HIV can be applied to Ebola. That I think about HIV a lot might seem strange given that it is now a completely treatable "chronic" infectious disease and not an explosive mysterious emerging infection. 

But, HIV had its wild-child phase and it is the arguably the most successful emerging infectious disease ever. 

HIV-1 spilled into humans from chimpanzees around the dawn of the 20th century, probably in Cameroon, and at first was likely a disease of bush-meat hunters and their close contacts who contracted the virus when butchering chimpanzees. Once industrialization connected these once remote areas to each other HIV-1 found a means to propagate amongst humans through sexual contact and the disease exploded. 

The disease trickled on, accruing victims without notice. I always think if infectious disease physicians would have noted this trickle of patients before it became a worldwide epidemic decades later, it could have been contained (to some degree). 

There's a story I've heard about a physician, Dr. Bila Kapita, recognizing the presence of the AIDS-defining illness Kaposi's Sarcoma in Kinshasa in 1975 and noting its presence in prior hospital records. I think this anecdote illustrates that if you look hard enough, you can find low-level "viral chatter" transpiring. 

Ebola is similar in many respects. These explosive outbreaks represent stuttered forays into the human population and burn out because the virus is not efficiently transmitted between humans. 

Studying these stuttered starts of emerging pathogens is what it means to be "tracking zebra".

Demystifying the ZMapp "Miracle" Cure for Ebola

Like everyone I am very excited about the prospect of Mapp Biopharmaceutical's innovative tobacco-based monoclonal antibody product, ZMapp, dministered to both individuals with Ebola who were subsequently transported to Atlanta. One of these patients is ambulatory and the other is able to eat--encouraging signs of recovery.

Monoclonal antibodies are a promising new technology used in host of illnesses and provide an elegant means to avert the use of antibiotics by using a rationally-designed targeted treatment. I spent a lot of thinking about monoclonal antibodies working as a team member on this project (in which we even interviewed Mapp's Larry Zeitlen). Currently, the only FDA-approved monoclonal antibodies for infectious diseases are for RSV and anthrax.

There have been reports labeling these drugs as a "miracle cure" with near instantaneous effects. I believe that people should be cautious, as NIAID director Dr. Anthony Fauci noted, about such interpretations for a number of reasons that include:

• The small number of humans (2) that have received the drug--were these two already going to recover without this medication and was ZMapp administered on the cusp of convalescence?
• The presence of confounding effects: Atleast one patient received convalescent sera prior to ZMapp, a treatment that likely has some efficacy on its own.
• The lack of published data from these patients on such biomarkers as viral load, liver function tests, blood clotting times, etc.

In short, much excitement is justified and this drug has proven to be highly efficacious in non-human primates. However, I think that more data is clearly needed to establish causation with respect to the course of illness in these two patients (and I am confident it will emerge as more individuals are administered this treatment). But I, for one, am cheering the use of monoclonal antibodies for the treatment of an infectious disease. 

In the Year 2036...Hepatitis C Will be Rare

I've written before about how the advent of new therapies for hepatitis C, with their promise of increased cure rates and compliance, could change the face of hepatitis C. Now, some of my colleagues at the University of Pittsburgh Graduate School of Public Health (led by Mina Kabiri) have shown just that with mathematical modeling in an important paper published in the Annals of Internal Medicine. 

As this viral infection, which exists in the over 3 million individuals,  progresses and  viral damage accrues, cirrhosis and need for transplantation will ensue. Hepatitis C is currently the leading cause of liver transplantation, liver cancer, and end stage liver disease. Anything that can diminish the disease burden of hepatitis C would be a huge boon. 

Kabiri and coauthors constructed a mathematical model that simulated the US hepatitis C population from the years of 2001 through 2050. Varied treatments were placed into the model based on what the standard of care treatment was in a given year, culminating with our modern regimens. 

The major finding of this study is that, using current treatment regimens coupled to universal screening, hepatitis C could become rare by 2036!

This study really provides a substantial quantitative basis to justify the excitement over newer hepatitis C regimens--regimens I believe are truly priceless, pathbreaking, and have the ability to alter the landscape of disease.