Taming Wild Polio Virus

There was much attention devoted to recent changes in the global polio eradication campaign when it was announced that vaccination against type 2 polio virus will cease in April 2016. This change was prompted by the eradication of this strain of the virus from the planet, leaving just type 1 and 3 left. However, the removal of type 2 polio vaccines is likely a response to other issues as well.

Polio eradication is currently being accomplished using the live Sabin oral polio vaccine which has the capacity to cause vaccine-derived paralysis in rare cases. These vaccine derived paralysis cases are almost always the result of the type 2 vaccine strain and with wild type 2 polio virus no longer a threat, the risk-benefit analysis of continued vaccination against type 2 has become altered.

Overall I think this is a good development and will make polio eradication more likely and the vaccine more palatable to the population who, because of the rarity of polio, may fear the risks of vaccine-derived paralysis.  

Wild polio has found its last refuge in just 2 countries -- Afghanistan and Pakistan -- while vaccine derived paralysis has been noted in several countries. So long as the live vaccine is used, the risk of vaccine-derived paralysis will be present.

However, a larger issue which lies behind the entire program, is the lumping of cases of vaccine derived paralysis with wild polio cases, a practice that has always struck me as problematic, especially given the use of the Sabin vaccine (which is considerably cheaper than the inactivated Salk vaccine) for which the risk of such cases will always be non-zero. 

If planetary eradication will only be declared once polio vaccine-derived cases are gone, the world will be waiting considerably longer. Eradication of wild polio virus is the real goal we should be focused on.

Does the GSK Malaria Vaccine Change Things?

Many people might mistakenly believe that because of the development of the first licensed malaria vaccine, GSK's Mosquirix (RTS,S), its rollout and implementation will be a simple feat. However, this is far from the truth. As wily a pathogen as malaria -- which has killed half the humans that have ever lived -- shouldn't be expected to go down so quietly.

Make no mistake the RTS,S vaccine is an important step forward and its development, which represents the 1st licensed vaccine for a parasitic disease, will add to the armamentarium of anti-malaria control measures. The problem, however, is that the vaccine's efficacy after the required 4 doses is only 40%. 

More recent data shows that this 40% figure might slip lower when the malaria parasite's penchant for mutation is taken into account. In a study of over 4500 vaccinees, the efficacy of the vaccine slipped to about 33% when there was a mismatch between the malaria parasite's circumsporzoite C-terminal and the corresponding vaccine component giving rise to the idea of vaccine-resistant malaria. 

This puts malaria control personnel into a difficult situation. How does one allocate funds with a somewhat protective (but limited) vaccine in the mix? Should less emphasis be placed on indoor spraying? Bed nets? Will the vaccine instill false confidence in the population prompting them to be less compliant with insecticide treated bed nets which unequivocally work.

All are difficult questions that will require a lot of thought. 

Explaining American Biodefense

In lectures I give on biodefense, biological warfare, and bioterrorism I always include a discussion of General George Washington’s prescient action to variolate (no vaccine existed at that time) troops facing the British Empire who might seek to use smallpox as weapon.  That was the real beginning of biodefense in this nation and through the 2 and half centuries since, it has morphed and evolved substantially.

The University of Sydney's Frank L. Smith III’s American Biodefense is a great addition to the scholarly works on biodefense. In his book, Smith develops a powerful explanatory principle that explains the seeming paradox of civilian biodefense being much more extensive than military biodefense. What Smith convincingly shows is that organizational frames of reference set the context for how the Department of Defense (DoD) and the Department of Health and Human Services (HHS) successfully integrated biodefense into their respective missions.

The DoD, Smith argues, is dominated by a kinetic frame of reference that is best exemplified by guns, bombs, and missiles (i.e. things that are propelled through the environment and impact a target with immediate consequences). HHS, with its constituent agencies of the NIH and the CDC, by contrast use a biomedical frame of reference.

Smith shows that once certain thought leaders such as Nobel Laureate Joshua Lederberg and D.A. Henderson convincingly proved in the early 1990s how biodefense and emerging infectious diseases were inextricably intertwined, it provided a path for HHS to integrate biodefense activities into their mission—especially when the threat became more imminent in the late 1990s.

Smith, with ample evidence, illustrates that DoD’s kinetic framework led to the inaccurate lumping and stereotyping of chemical and biological weapons together. Such a package deal ignores crucial differences, compromising certain preparedness activities that must be fully informed by the specific threat faced (this is not meant to criticize all-hazards preparedness activities which exploit true commonalities between varied threats). Also, because of this inherent deficiency, when biodefense became an issue for military operations it often prompted a scramble for resources such as during Operation Desert Storm.

For those interested in the field of biodefense, Smith’s book provides an important explanation for how American biodefense came to be structured the way it is and a path for optimizing it in the future. As the threats have not diminished—and are arguably higher—incorporating Smith’s ideas will be an important component of enhancing preparedness and resiliency. 

Scraping Away the Mystery of Mold

My home institution's battle with Mucor mold infections is thankfully largely over and they are again safely transplanting organs into some of the sickest individuals in the world. The results of the CDC's investigation of the entire episode, which amounted to 4 infections (which may not even be more than would be expected in this type of patient population), are beginning to emerge and an important preliminary finding has been released.

According to press reports the 4 patients differed in their mode of acquisition of the mold. This is a noteworthy finding because it confirms that there was no point source for all the cases such as linens or bandages (previously linked to hospital-based Mucor cases).  It has been reported that 2 cases were inhalational, one was disseminated, and one was inoculated via the skin. As I have said on numerous occasions, mold is abundant in the environment and only poses a health risk to those that are immunocompromised. People can contract mold infections by inhaling spores, having the mold directly inoculated into a skin break, ingesting it (some outbreaks have been tied to contaminated infant feeding solutions), and injecting it into their veins. That these patient had differing modes of acquisition doesn't bear on the ultimate environmental source of the mold in the hospital, an important aspect of the investigation results yet to come.

I am currently attending a national infectious disease meeting and have listened to several lectures on mold rates in major hospitals and it is even more clear to me now that these 4 cases, though regrettable, are within the normal ranges to be expected at a major transplant center (despite what trial lawyers and rabble-rousers may believe). That my institution went through a Herculean process and basically had portions of their transplant list poached by a rival and declined organs during their unprecedented voluntary shut down, speaks to the high standards adhered to.

Station Eleven: Just Surviving a Cataclysmic Plague is Insufficient

Post-apocalyptic scenarios in which the world must recover from some catastrophic event are not new. Often, the catastrophic event is a massive infectious disease of some sort. What I find most interesting about this genre of fiction is what the author choses to place their selective focus on (because the nature of the cataclysm is of relatively little importance). 

Emily St. John Mandel's Station Eleven, which I read after seeing a recommendation by renowned HIV physician Paul Sax, is one such book that has attracted much attention. 

Set in a world emerging from the ravages of a recent pandemic of influenza--"The Georgia Flu"--Station Eleven weaves together past and present as seen through the experiences of several characters who were all connected to each other pre-pandemic. 

The pandemic, which was said to kill at an unfathomable and unrealistic rate of 99% with an equally implausible few hours of incubation, basically brought the world to a halt literally transforming all modern technology into relics for a museum.

What I find to be the best aspect of the novel is its portrayal of how various members of society respond to such a cataclysm. Do they carry on clinging to any remnant of society, descend into depression, hold out hope for a rebirth of civilization, become mindless acolytes to a "prophet", or go on living? What activities are important in such a society and which are superfluous? All of these facets of post-disaster life are important factors that actually have real-world counterparts and likely occurred in microcosm after major earthquakes, various tsunamis, as well as the West African Ebola outbreak.

The answers given to these questions, as exemplified by the characters in the novel, are, at once, both surprising and reassuring. In short, the book concretizes why, for humans, mere "survival is insufficient".