The Tracking Zebra Bulletin Newsletter

After a little bit of prodding, I've decided to add a newsletter to my blog's features. This newsletter -- I think I'll call it The Tracking Zebra Bulletin, will feature some highlights from the blog, some news stories I might have commented on, and other little features like speaking engagements, media appearances, and papers I publish. I anticipate this will be, on average, a weekly newsletter.

For those of you subscribe to the blog by email, that will still continue but you may want to subscribe to the email newsletter separately because it will have some content in addition to my blog posts. 

Here's the link.

Thanks for reading.

Gardasil: The iPhone of Vaccines

Today while scrolling through my Facebook feed a post caught my eye because it was about Gardasil, the revolutionary vaccine that has changed the face of myriad HPV-induced cancers. The post, which I would not click on, purported to detail a case of someone receiving the vaccine and developing leukemia. Looking through the comments, one stuck out. It explicitly called into question ever trusting pharmaceutical companies. It struck me as conspiratorial, arbitrary, and so misplaced. 

I, for the life of me, do not understand why there is any animus towards Gardasil -- it really is on the level of the polio vaccine in its importance to me (I also highly regard Cervarix, the other HPV vaccine). This vaccine, constructed through really cool processes involving viral like particles (VLP), has the capacity -- if adopted at high enough levels to eradicate HPV-caused cervical, vaginal, vulvar, penile, anal, and head/neck cancers. Not many other vaccines can do that. The evidence is already beginning to amount as the vaccine, first protective against 4 chief strains of HPV and now 9, has had the time to begin to impact rates of precancerous lesions as those who received the vaccine are now entering eras in their life (post sexual debut) when these changes first appear and are diagnosed. In New Mexico, for example, this is evident even with poor uptake.

There is very close to zero safety concern with this vaccine (see here and here) which should be as routine for boys and girls as all childhood immunizations are. However, I think the strong connection with HPV acquisition and sexual activity has caused some parents to balk for whatever reason (even physicians sometimes demur when including the HPV vaccine in the list of schedule vaccines at a given visit). It's odd to me that this objection comes up when hepatitis B vaccine is targeted against another a virus that can also be sexually transmitted and it is given soon after birth.

When you ask someone to articulate their opposition to Gardasil it is often something they are unable to give logical arguments and instead, at most, rattle off a litany of anecdotes they've heard or come across on the internet that are almost always wrong. The same type of people who claim the government has a "cure for cancer" locked up somewhere are the same type who shun an actual preventive cure for HPV-induced cancers. Consistency is not something that is the strong suit of the conspiracy-haunted mind.

Worse than anecdotal evidence, to me, is when they just arbitrarily assert that pharmaceutical companies are out to poison and kill everyone -- as if that would increase their profit or shareholder value. Such insults and attack on integrity not only insult the pharmaceutical company personnel who brought this product to market but also the scientists who meticulously devoted their lives to solving this problem (one of whom received a Nobel Prize).

In my estimation, Gardasil is technologically as important as the iPhone and it, and the individual minds that made it possible, should be lauded.

Diarrhea: Much More than Meets the Eye

On the 4th of July, people are invariably participating in cookouts and picnics eating lots of foods like hot dogs, potato salad, cheeseburgers, and the like while mixing with friends, family, and acquaintances. Invariably someone will get...diarrhea.

Diarrhea is a really meaty subject full of a lot of content that sits at the intersection of many fields. The diarrhea I like best is the kind related to infectious diseases. Infection-incited diarrhea is fascinating for a number of reasons including the role it plays in disseminating a microbe and the role it plays in expelling the microbe from a body desperately trying to eject it. 

A new study was recently published that provides new evidence of the pathogen-clearing role that diarrhea serves. In this study, using mice infection with the bacterium Citrobacter, it was shown that the infection prompts the secretion of the immune system molecule interleukin-22 (IL-22). IL-22, in turn, upregulates the production of a protein called claudin-2. This protein sort of loosens what are usually tight barriers between cells lining the intestine allowing more fluid and salt to make it into the intestinal lumen resulting in diarrhea, which expels the pathogen from the body. In elegant experiments it was shown that mice deficient in claudin-2 experienced worse symptoms suggesting that the IL-22/claudin-2 mechanism is an important component of host defense.

So, when the dreaded rumble presaging the deluge comes realize it's the result of the ingenuity of evolutionary immune mechanisms designed to help (and perhaps embarrass). 


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.