FluBlok: Not Your Father's Flu Vaccine

There are very good reasons why many infectious disease experts spend a lot of time focused on the threat of influenza. This virus is a known pandemic threat and has producing such devastating phenomenon at regular intervals throughout human history. 

Our chief means of defense against this threat -- as it is with almost all infectious disease threats -- is vaccination. However, as I and many others have written, we largely battle flu with a vaccine technology from the 1940s that has many limitations and at best is possibly about 60% protective and its worst not so protective at all.

Influenza is a tricky virus and has the capacity to drift, shift, mutate, and reassort in a manner that renders vaccines obsolete and requires an intensive process of regular reformulation (because we do not have a universal evergreen flu vaccine). This process is further complicated because the vaccine is grown in chicken eggs -- a cumbersome process that not only is dependent on a supply of chicken eggs but can itself mutate the vaccine strain during growth further handicapping the vaccine.

One solution to this problem is to move out of chicken eggs altogether and to cell lines -- something that is the norm for many other vaccines. To date, however, only one totally cell-based vaccine is available (there is another partial cell-based vaccine as well which relies on an egg derived viral reference strains that is then grown in MDCK cells): Flublok, a recombinant vaccine grown in insect cells through a baculovirus vector.

It's no secret that I am a huge fan of this vaccine, insisted on receiving it this season, recommend it to my friends, and even got to tour their vaccine plant. The value of FluBlok is not only that it frees flu vaccine production from the tyranny of eggs from a production standpoint, but that its recombinant nature results in a better vaccine. A recent study, published in The New England Journal of Medicine, illustrates this latter point. 

During the 2014-2015 influenza season -- a season  characterized by influenza A/H3N2 dominance and vaccine mismatch-- a randomized clinical trial was conducted on 9000 individuals aged 50 years of age and older. Participants were randomized to quadrivalent FluBlok vs. a standard quadrivalent GSK flu vaccine. The primary endpoint was PCR confirmed influenza-like illness.

Fully 30% less participants randomized to FluBlok experienced PCR-positive influenza reaching statistical superiority. In subgroup analysis, this appeared to be derived from enhanced protection against influenza A. Since no influenza A/H1N1 was detected in the study, the result was driven from enhanced efficacy against A/H3N2 -- a usually more severe strain of seasonal flu. No safety concerns arose.

This trial is very significant and should help physicians and the public understand that moving away from eggs in vaccine production will have many important effects including rapid scale up, flexibility in plugging in new strains of flu and other viruses (e.g. Zika), and no susceptibility to egg supply shocks (a real concern during an avian flu outbreak that could make chicken egg supplies dwindle), less mutation of vaccine strains induced by adaptation to egg growth, and -- as this trial illustrates -- better protection during seasonal flu.

Eat Shit and...Ride

I can't count how many times I have said that understanding the mysteries of the microbiome will unlock the secrets to many physiological and pathophysiological process. The latest example of the microbiome's explanatory power regards the athletic prowess of elite cyclists. In a new unpublished study, that is getting a crapload of press, the microbiomes of elite and amateur cyclists were compared and, not surprisingly, differences were found. Particularly intriguing was the presence of the anaerobic bacteria Prevotella in half of the elite cyclists and none of the amateurs. An archae (Methanobrevibacter archaea) -- a disparate branch of life from eukaryotes (us) and prokayrotes (bacteria) was also more likely to be present.

This study is thought provoking and has many implications and it will be important for this to be thoroughly vetted through the peer-review process -- as studies on rugby players have. It will also be essential to untangle this correlation to try and determine causation -- is the microbiome difference related to the enhanced performance of athlete or the result of their diet, their exercise regimen, their genetics, or some other factor. If the microbiome is causative, poop doping could become a real phenomenon for enhancing athletic prowess (it already has promise in weight management and treatment of Clostridium difficile infection).

Though it's not quite time to follow athletes into the port-a-John, the promise of microbiome research is definitely making poop exponentially more appetizing each day.

The Ebola Inferno: A Review of Dr. Hatch's Memoir

I just finished another Ebola memoir by an American doctor who battled the virus during the West African outbreak. Inferno: A Doctor's Ebola Story by UMass's Dr. Steven Hatch is much more than patient vignettes and is really an intimate window into how an academic infectious disease physician fared against a deadly virus. 

Dr. Hatch's book moves from his first pre-Ebola visit to Liberia in which he was tasked with building medical capacity in a country ravaged by a recent civil war to his return to the country in the midst of the Ebola outbreak.

It is now almost cliche to say that the usual measures didn't work in Liberia because of the populace's distrust of the government and that one-size-fits-all solutions don't exist. Dr. Hatch unpacks that statement by weaving into this narrative an important discussion of the origins of Liberia and the civil war. As Dr. Hatch demonstrates, both of these factors distinctly shaped the response to the virus as did the Christianity and animistic beliefs of the population. 

Another aspect of the book that bears highlighting is Dr. Hatch's unfortunate navigation of the myriad details regarding his return to the panic-stricken US and the inanity of bureaucracies that were responsive less to science than to pandering politicians. 

I highly recommend the book.

Face to Face with Ebola: A Review of Dr. Kent Brantly's Memoir

Remembering the height of the worldwide Ebola pandemonium in 2014 is instructive 3 year later. All the names, dates, controversies and places from that era have long faded from headlines and the memories of the general public. Even I, who was keeping up with Ebola on an almost minute-by-minute basis, sometimes forget the intensity of the outbreak and continual media coverage. 

One of the first explosions of worldwide media occurred, of course, with the infection of American family medicine physician and medical missionary Dr. Brantly in Liberia. His infection, his transport back to the US, and his receipt of experimental therapeutics were unprecedented in the history of Ebola. The opposition to his transport to Atlanta was also unprecedented, disturbing, and shocking. 

I was one of those who vociferously argued for Dr. Brantly's evacuation to the US where he received state-of-the art treatment and recovered. Because of those efforts I made in the media at the time I was honored to be in the same room with him during a White House event. But I had no real familiarity with his personal experiences in Liberia and with Ebola.

I recently read Dr. Brantly and his wife's memoir of the experience Called for Life: How Loving Our Neighbor Led us into the Heart of the Ebola Epidemic. This book, written in 2015, is not only a gripping and poignant account of the Brantlys experiences with the outbreak but also how they coped with Dr. Brantly's infection.

The book weaves together the Brantly's decisions to enter the medical field and the career choices they made with the narrative of the Ebola outbreak. Many of the observations included are, by now, familiar (e.g. the unique challenges of containing Ebola in an urban populated area that emerged from civil war, the angry mobs, and the overall logistical challenges. However, to me, the value of the book is chiefly Dr. Brantly's recounted of his own personal experience with Ebola.

A few important points he makes merit emphasis:

• The initial negative Ebola test which required repeating given lack of sensitivity at early infection
• The necessity of ruling out malaria and initially treating for malaria empirically
• The voluminous diarrhea and ensuing electrolyte abnormalities of Ebola and the absoulte need to correct them
• The role of experimental agents and the challenges with administering them in a resource-challenged environment 

My favorite part of the book is Dr. Brantly's recounting of the  appearance of a top Ebola virologist outside his window in Liberia to discuss experimental treatments with him. 

Reading this family physician's account of his successful battle with the deadly Ebola virus is well worth it.

Confronting Our Deadliest Enemy

The world of infectious disease changes almost daily and with the well-overdue newstream-like enhanced focus on emerging infectious diseases the field has basically transformed. Emerging infectious diseases did not, however, supplant other concerns such as bioterrorism, dual use research, endemic infections, and antimicrobial resistance. All of these topics are now the bread-and-butter of infectious disease. A new book by Professor Michael Osterholm, a renowned leader in the field, is a must read for those with an interest (advanced or novice) in the field.

Deadliest Enemy: Our War Against Killer Germs is a comprehensive expertly-guided tour that spans all the major issues, outbreaks, and controversies in the field that have occurred over the past several decades. While many of these incidents are familiar, the value of the book is getting Professor Osterholm's analysis and opinion which provide deep insights and platforms for further thinking on the issues

Chapters topics span toxic shock syndrome to gain-of-function research and everything in between. Some particular standouts, to me, where Professor Osterholm's very personal battle with Lacrosse encephalitis, his discussion of MERS, his treatment of the economics of vaccine, his four-tiered threat matrix analysis (pathogens of pandemic potential, pathogens of critical regional importance, bioterrorism, and endemic infections), his "Crisis Agenda", and his unrivalled analysis and solution to influenza vaccine shortcomings.

In his decades long career, Professor Osterholm has been at the forefront of the field and led myriad investigations and influenced policy at the highest level and his book is an important distillation that I highly recommend.