The Chimp and The River: The Origin Story of HIV

When I think of the prototypical infectious disease -- the one that illustrates everything perfectly and makes all the "right" moves -- HIV is what always comes to mind. This prolific killer emerged and sparked a pandemic that killed 40 million humans to date. Like any good serial killer, the origin story is important and fascinating not just because it gives us a morbid pleasure to see the first forays the virus made into killing but it underscores the essentials of how any emerging infectious disease establishes itself, transitioning from epidemic to endemic.

I have read many book on different facets of HIV and, for the most part, have found value in all of them. The latest HIV book I read, The Chimp and The River: How AIDS Emerged from an African Forest by David Quammen, wasn't a "new" book in the strict sense but an adaptation of a part of his earlier must-read book Spillover. Though the material in this book wasn't new to me, its stand alone presentation did something to make it much more real to me -- or it could be just be the benefits of a good 2nd reading.

The book's aim is to focus on just one aspect of HIV: how, when, where, and why it spilled into humans. Quammen's ability to tell an Indiana Jones-style detective adventure story is completely captivating to me and, even though I know where the story is going to lead from familiarity with the scientific research, his version is much better than the often dry scientific papers I read.

Integrating the cut-hunter hypothesis for HIV's initial spillovers into humans (and before that spillovers from monkeys to chimpanzees) with the trajectory of the global pandemic is a tough task that is expertly executed in this short book. Many important facts such as how many times HIV has spilled-over into humans (about a dozen, one for each strain of HIV-1 and HIV-2), the 2 monkey species chimerism of the HIV-1 progenitor SIVcpz, and the wedge of Cameroon where it all began are covered with great and memorable detail.

I highly recommend this book and hope that as the HIV story continues to unravel, Quammen's expert narrative of the phenomen will continue as well. 

Mucor, Negative-Pressure Rooms, and the Immunosuppressed

Today the Centers for Disease Control released the long-awaited report on the Mucor mold infections that occurred in the ICU at my home institution. The findings did not contain any major findings that were not well known prior to the report. However, the report is important, nonetheless, as it highlights the ubiquity of mold in the environment and illustrates how immunosuppressed patients are exquisitely--and almost exclusively--at risk.

To recap, there were 3 probable and 1 suspect infection that occurred with mold of the Mucor variety in transplant patients. Of the 4 cases, three were fatal and three occurred in the same ICU room. This type of mold is important given its high mortality rate which is a largely a result of the type of patients it infects (i.e. the immunosuppressed). 

The most important part of the CDC report is the case-control study they conducted. Case control studies are very important at delineating risks and eliminating noise in the quest for a definitive answer to the phenomenon under study.

In this case-control study, the room that 3 of the 4 patients stayed in was found to be the only significant factor that distinguished cases from the controls studied. This result puts to rest any other factor that may have been at play such as contaminated linens, for example.

What was special about this room, according to the CDC report,  was that it was a negative-pressure room which, by design, draws air in (these are the room we use for contagious tuberculosis patients to prevent infectious air from leaking out of the room). Could the negative-pressure have drawn fungal spores in? The room was also located near the exit of the ICU providing a route for spores from visitors's clothes, shoes, and elsewhere outside the to gain some proximity to the negative-pressure room.

It is important to remember that these mold infections, unfortunate and tragic, likely do not represent a major statistical aberration over what would be expected at a major transplant center that cares for some of the sickest patients in the world. FYI, my mother just had surgery at the hospital and I didn't bat an eye over her risk for infection with Mucor.

The report's recommendations to not use negative-pressure rooms for immunosuppressed patients (unless needed), to change some of the geography, and maintain vigilance for future occurrences are valid. 

What are the Barriers to Bioweapons? A review of Sonia Ben Ouargham-Gormley's Important Book

Rapid advances in science which have simplified the skill set needed to perform what once were sophisticated experiments coupled with the ubiquity of biological agents in the environment comprise the standard narrative regarding the risk of of biological weapons development. The threat of these banned weapons as assessed through the lens of the standard narrative led to the dire prediction in 2008 by The WMD Commission that an attack using, most likely, a biological weapon would occur by 2013. 

This is a narrative I have presented countless times when lecturing on the topic. I do add in that a lot of tacit knowledge, an identification made by Kathleen Vogel in her book, is needed as biological weapons manufacturing, even on small scales, is not as easy as making crystal meth. Almost invariably, I am asked by an audience member why, if this process is so easy,  a large-scale biological attack has not occurred. I don't usually give an answer that I myself find satisfactory.

However, I never appreciated how potentially limiting the "standard narrative" is to how the world approaches counter threat activities and how I answer the above question. George Mason University's Sonia Ben Ouargham-Gormley's 2014 book Barriers to Bioweapons: The Challenges of Expertise and Organization for Weapons Development convincingly illustrates how a new conceptualization -- inductively derived from the experiences of the US, Soviet, Iraq, South African, and Aum Shinrikyo biological weapons programs -- of the risk provides a new path to positively augment current counter threat activities and answers the question frequently posed to me.

Throughout this book Professor Ben Ouargham-Gormley challenges the premise that the formative stage of a bioweapons program is the most crucial to the acquisition of biological weapons capacity. She argues that the formative stage, which involves the acquisition of biological material and technology, is not nearly as important as the sustenance phase of a program in which the actual production, scale-up, and viable weaponization occur. Nuclear counterproliferation, she further argues, is much more suited to a focus on the formative stage and this paradigm is not wholly applicable to the biological realm.

As she writes,“in the bioweapons field, expertise and knowledge—and the conditions under which scientific work occurs—are significantly greater barriers to weapons development than are procurement of biomaterials, scientific documents, and equipment.”

The quick retort to her might be that the deadly anthrax attacks of 2001, the almost monthly reports of someone home-brewing the assassination tool ricin, and the continual "white powder incidents" demonstrate that the threat of biological weapons at any scale is dangerous enough to provoke calamity and fear. Additionally, Project Bacchus, in which 1 kilogram of an anthrax simulant was made from off-the-shelf materials in a 2 year US government project shows what is possible. These points are definitely true but miss the point of this work as they are not the exact subject of the book nor the intended focus of much of our preparedness activities, the large breadth and scope of which are aimed at larger scale use of biological weapons. Similarly, it is not that her thesis is that no large scale bioweapon production could ever occur, but that it is most likely to occur in a certain contexts.

Professor Ben Ouargham-Gormley provides ample evidence for her thesis from several known biological weapons programs, concretizing that even in the most adept programs difficulties arose because of suboptimal organizational and managerial practices. The book heavily documents such practices and provides much evidence, as well as many important anecdotes involving Soviet bioweapons scientists as well as the infamous Iraqi scientists Dr. Germ and "Chemical Sally".

My understanding of the topic has been greatly deepened by this work and this scholarly treatment of a vital national security issue is a welcome addition to the field.

Pregnancy as an Ebola Potentiator: Trying to Understand the Liberian cluster

One of the most recent mysteries of Ebola is the recent re-establishment of the disease in Liberia, which had rid itself of the disease months earlier. This cluster of 3 infections was puzzling as the index case was a 15 year old boy who had no known contact with Ebola patients.

Further investigation revealed that the boy's mother had antibodies to the virus yet was never noted to be an Ebola case -- she likely represented the rare occurrence of a minimally symptomatic Ebola patient. Her uncle had succumbed to Ebola in July 2014 and likely passed it silently to his sister.

So what happened in the ensuing 4 months? One hypothesis is the mother became pregnant. Pregnancy is a well-known to be associated with diminished immune system function (e.g. pregnancy and severe influenza) and possibly lurking remnants of Ebola, freed from total immune surveillance, begin to stir again and reached levels sufficient to infect the boy. This asymptomatic shedding of Ebola has been reported in other pregnant women who, in most circumstances, are considered at higher risk for severe Ebola. The mother, with her antibodies and her genetics (which protected her the first time), had no outward symptoms.

When the origin of this transmission is hopefully definitively established through genetic sequencing of the viruses, it will provide much insight into the residual risk of transmission that there may be from Ebola survivors. While it is known that sexual transmission from males is possible up to 6 months from recovery, the other Ebola sanctuaries (Dr. Ian Crozier's eye, Nurse Pauline Cafferkey's central nervous system) have not yet been linked to transmission. Another important question will revolve on understanding just who has subclinical infection and who has persistent virus.

Elucidating these risks in more detail will influence how Ebola vaccination is used to protect those not just in contact with active cases, but those in contact with recovered  cases.

One Nation Under Vaccines (I wish): My Review of Vaccine Nation

The relationship the general public has had with vaccines over the past several decades has is not simple. The trajectory of vaccination began with just a single vaccine protecting against a single disease--that of Jenner's for smallpox in the late 1700s--and now every American child is protected against 16, if up-to-date on recommended vaccines (which I hope they all become). When I was a child, I was able to be protected against only 7 of what became routine in 2015.

There are, of course, more vaccines that are not routinely administered though easily available. These include vaccines against smallpox, anthrax, rabies, yellow fever, Japanese encephalitis, typhoid, and adenovirus.

What may be puzzling to many is how diseases get specifically targeted for control via vaccination and how members of the "sweet 16" came to be. A new book by Emory historian Elena Conis entitled Vaccine Nation: America's Changing Relationship with Immunization provides a lot of context and history that is not well appreciated. 

The most important aspect of the book, to me, is the theme that as society matures and medicine progresses what is a tolerable risk changes. New contexts condition how risk is objectively evaluated by individuals. Thus when there was no measles vaccines, measles was an accepted risk. However, when a safe and effective vaccine was available the risk became unacceptable.

Not all diseases are as a straightforward as measles, but the general conceptual model is the same. In many cases, the ability to live a life devoid of a "nuisance" infection may have played a role. For example, mumps--in which complications occur at a low rate--the convenience of living a life free of mumps and the ensuing need to be cared for by parents who must stay home from work (not to mention the national security implications of having soldiers sidelined by the virus which is more severe in adults). This point is moot in the current context when the mumps vaccine is exclusively (and conveniently) bundled with measles and rubella.

Risk goes the other way as well. When smallpox was nearly eradicated from the planet, the US stopped vaccinating against it (1972) because the scientifically-established risk from the vaccine outweighed the risk of contracting the illness for the general public. Similarly, when polio was nearly eliminated from the Americas there was a switch in the US from the Sabin live vaccine to the Salk inactivated vaccine to remove the risk of vaccine-derived polio from the vaccine strain.

Professor Conis provides much vivid material surrounding the debates and decisions that played a role in the rise of such vaccines as ones against measles, mumps, rubella, hepatitis B and HPV.

She also, in a very clinical way, looks at the various facets of the anti-vaccine movement finding its roots in other social movements which espoused certain philosophies that derided the scientific method, logic, and objective evidence in favor of some other "method".

The book also usefully immerses the reader in the politics that followed the introduction of the polio vaccine in the 1950s. This political atmosphere led to a growing government role in specifically funding vaccination activities of the states through various laws that developed new programs beginning in the Eisenhower administration and culminating in the Clinton administration's Vaccines for Children program.

With this book, Professor Conis has made a great contribution to the literature on the social aspects of vaccination and as a dyed-in-the-wool unapologetic vaccine advocate I think it is required reading.

P.S. Get your flu shot