How To Survive A Plague: Much More Than a How-To Guide

Even for someone in infectious disease it is very hard, in 2017, to appreciate the enormity of the emergence of HIV in the United States in the early 1980s. HIV, a prototypical emerging infectious disease, has been transformed from one for which no treatments were available pre-1987 to one in which medical students are overwhelmed with trying to learn the various drugs that can be used against it (in the developed world).  The diagnosis of HIV is no longer the equivalent of a uniform death sentence (although I just witnessed an HIV patient die from an overwhelming infection this past Saturday).

It is well recognized that this transformation occurred with a full-throttled research agenda that delivered new drugs, new diagnostics, and pathbreaking identifications in immunology and virology culminating in the awarding of a Noble Prize. What isn't well recognized is the intransigent efforts of HIV activists to not allow this disease to become victim to bureaucratic inertia (or worse). This story is masterfully told by David France in How to Survive a Plague: The Inside Story of How Citizens and Science Tamed AIDS, a comprehensive narrative based on France's award-winning documentary of the same name. 

The book is a personal tour of those plague years in which little to nothing was known about the virus when death and despair was the norm. In this dismal context, a group of citizen activists, many of whom were literally fighting for their lives flourished alongside a select cadre of scientists and physicians who attacked this problem with the full force of their intellects. France's book weaves all these tales together and shows how these tandem tracks converged and diverged while all involved were navigating in a largely inhospital political environment.

In its chronicling of the origins and rise of AmFAR, ACT UP, GMHC, TAG, and many other organizations that sprang into action to face the pandemic, the book illustrates just how impactful citizen activists were. Their success was not just in raising awareness but was instrumental in drug development and treatment guideline promulgation.

That these early People with AIDS fought so valiantly, many to death, for their lives through every avenue, whether open or closed is heroic and admirable. The innovative solutions such as "buyers' clubs" that made experimental therapies available are one example. The best representation of this heroism, to me, was their refusal to let bureaucratic regulations stand in way of their lives. Their actions, particularly with the FDA, fundamentally altered the way things had been usually done. Such lessons could directly impact on current fights against modern infectious disease threats such as antibiotic resistant bacteria and emerging infectious diseases.

The book is full of powerful anecdotes and poignant incidents that should never be forgotten and now won't be.

A Very Short Introduction to the Coolest Subject on Earth -- A Review of Wayne and Bolker's Infectious Disease: A Very Short Introduction

I often give lectures on the whole breadth of the discipline of infectious diseases and am often stymied by just what to include, what to merely mention, and what to exclude. Given this difficult task that I often encounter I was very interested to to read Infectious Disease: A Very Short Introduction. This book, part of the extensive "A Very Short Introduction series of books, is written by University of Florida biologist Marta Wayne and McMaster University mathematics, statistics, and biology professor Ben Bolker. 

The book is a short read aimed at the novice but definitely appealing to those with expert knowledge, primarily because of the choice of the topics they included and the facets they chose to highlight. The combination of a biologist and a biological modeler as co-authors is very strong strength of the book.

Some of the highlights to me include the discussion of the proposed value, conceptually, of models of infection. Specifically, I found the discussion of the encounter filter (does a microbe have access to a host?) and the compatibility filter (does the microbe have the ability to productively infect a host?) to be illuminating and an important way to gauge the effectiveness of various countermeasures. 

Other important concepts discussed include genotype frequency, HIV template switching, fascinating comparisons of the genetic diversity of HIV and influenza, the predator-prey relationship of cholera and its phages, and the natural "cholera bomb".

To me one of the most valuable chapters dealt not with a human disease but with a disease of amphibians: the chytrid fungus. This chapter is full of important information that illustrates how an emergence of a disease might occur, how it might progress, and how it might be controlled. Particularly illuminating is the juxtaposition of the novel and endemic pathogen hypotheses.

I highly recommend this little but very valuable book to those both casually interested in infectious as well as those obsessively interested in the field (like me).

We're Not in Kansas Anymore: Space Bacteria

Since the inception of the space program, studying the physiological changes that occur to astronauts has been a major endeavor. In the early days of the space program, there was even a major interest in the role of infectious diseases. Not only were concerns raised regarding astronauts bringing back an alien infection but also concerns regarding returned astronauts being hyper-susceptible to earth microbes. What is also extremely fascinating to me is the effect of space on microbes. A recent piece in The Wall Street Journal contained exciting information in that regard.

It had been well known that space has some sort of salutary effect on microorganisms as evidenced by the proliferation of fungus  on Mir. What this article details are several new facets of the space-microbe interaction:

• More resistance
• Faster replication
• Heightened infectivity

Additionally, the microbiome of astronauts changes in space which may play some role in heightened respiratory illnesses and other ailments they suffer from. I also wonder what role the microbiome, with its role in inflammation and myriad disease processes, may have play in the four to five-fold increased cardiovascular death rates seen in astronauts who completed deep space missions vs. astronauts who only participated in low Earth orbit missions. 

I suspect that radiation might be the cause behind these phenomena because, without the protection of the atmosphere and magnetosphere of the Earth, organisms are bombarded with higher levels of radiation which can have pleiotropic effects including the inducing of genetic mutations. These mutations, especially in rapidly reproducing bacteria, may speed evolutionary processes and lead to the attributes. The role of changing gravitational forces, which all organisms on Earth evolved in the midst of, likely also has some influence as well. I wonder what the selection pressure is in space that favors the development of the particularly scary characteristics listed above.

Just another reason why infectious disease is the coolest thing ever.

Integrating Molecular Biology with Infectious Disease: A Review of the Infectious Microbe

Just a quick post on a useful little book I recently finished: The Infectious Microbe. This book, by the late Wesleyan University professor William Firshein, is a short, concise overview of the field of medical microbiology and infectious disease aimed at the intelligent general reader. The book delivers on this aim and, unlike many other introductory books in this field, successfully integrates the concepts of molecular biology with medical microbiology, epidemiology, and clinical infectious diseases that is at once accessible to the novice reader while providing a good review (with some additional new insights) to the expert reader. 

The book covers several specific infectious diseases including HIV, Helicobacter pylori, influenza, and tuberculosis. There is also a chapter devoted to emerging infectious disease and, surprisingly but encouragingly, one devoted to biofilms -- a very important concept to understand in the modern era of infectious diseases and infections tied to prosthetic material.

Professor Firshein laudably ends the book with the topic of bioterrorism -- an area that many academics shy away from for various reasons. Firshein correctly emphasizes the urgent need to prepare for these types of events and appropriately calls attention to the deficiencies in our current preparations. As the late professor writes:

"Clearly, if our nation is to meet the horror of a bioterror attack, all the parts of the state and federal government have to cooperate and do much more than they are doing now. There is a terrible danger, and we would be absolutely delinquent in letting these problems continue to fester."

 We, including the new administration, would do well to heed his words.

VX: 2 Letters that Spell Death

The assassination of Kim Jong-un's half brother Kim Jong-nam was reportedly carried out in Malaysia using VX, a nerve agent that has been well-characterized as a potent chemical weapon for decades. The delivery mechanism was allegedly via skin exposure as the assassin rubbed the substance into Kim Jong-nam's face.

VX belongs to a class of banned chemical warfare agents that includes sarin, well known after its use in the Aum Shinrikyo (they also experimented with VX) Tokyo Subway attacks in the 1990s, and all of these agents act to interfere with neurotransmission -- the way nerves speak to each other and to muscles. Specifically, these agents increase the amount of the neurotransmitter acetylcholine leading to predictable effects that medical students always memorize. Salivation, lacrimation, urination, diarrhea, vomiting, small pupils (miosis), and a slow heart rate are all part of what is known as a cholinergic syndrome. If not reversed, it is fatal. 

The most potent of nerve agents, just 10 milligrams of this tasteless odorless liquid is enough to prove fatal.

Atropine, a very commonly used medication in hospitals, is one of the antidotes that can reverse the symptoms. This is given in conjunction with another medication called pralidoxime. 

This event underscores that  chemical -- and likely biological weapons -- remain major threats and rogue nations, where individual rights are non-existent, remain a threat that merit preparing for. During the coming days, it will be critical to confirm the manner of death of Kim Jong-nam.