Where the Wild Things Are: Polio and Vaccine-Derived Polio are Distinct Issues

One of my major pet peeves with infectious disease reporting is the conflation of polio with vaccine-derived polio. While both conditions can be severe and paralyzing, there's an important distinction that is missing from headlines announcing the "return of polio." 

Vaccine-derived polio is a known and expected risk so long as the Sabin oral polio vaccine is used. The Sabin oral polio vaccine has many advantages that have favored its use: it's given orally (no needles), it's cheaper, and it's "live". This last is important since the vaccine is given orally and replicates in the GI tract -- just like the untamed wild strain of polio -- it more closely mimics natural infection. It is also shed in the stool and others are, in effect, vaccinated upon exposure. On the contrary, the injectable Salk vaccine does not prevent viral spread as the vaccinated are protected against paralytic polio but are still able to be infected with the wild virus, but only in their intestine, and are able to pass the virus along.

However, these advantages are a double-edged sword as the virus, which has been weakened, can mutate its way back to its original virulence level and paralyze someone (vaccine-associated paralytic polio, VAPP) In rare circumstances, the altered vaccine virus can circulate and cause outbreaks as a circulating vaccine-derived poliovirus (cVDPV) -- this last usually requires recombination with a non-polio enterovirus. Usually the impact of cVDPVs is delimited because of population immunity. This paper provides a great overview of the phenomenon. 

The risk of VAPP, in the US, became too much to bear and the US slowly changed recommendations and moved to an all injectable Salk regimen several years ago. The global eradication program will eventually phase out the oral vaccine as well.

What is missed by the recent headlines is the fact that so long as oral polio vaccine is used there will always be a risk of VAPP and the emergence of cVDPVs. I think that the eradication of polio should be restricted to the eradication of the wild virus -- something my mentor and smallpox eradicator DA Henderson insisted upon. cVDPVs and wild polio are distinct problems. Wild polio continues to spread in only two countries: Pakistan and Afghanistan, where a dozen cases have occurred so far this year. cVDPV outbreaks in the DRC, Somalia, and Papua New Guinea are important problems but should not, in my opinion, be considered on the same level as wild polio virus infections. 

Antibiotic Resistant Infections Kill More than Car Accidents: A Review of Superbugs

I often say that the biggest infectious disease problem humans face is that of antimicrobial resistance. I am not alone in this assessment and today there are myriad books describing  this problem and its many facets. However, a recent book I read on this topic, Superbugs: An Arms Race Against Bacteria, provides a unique lens to view the problem: economics. Below I give a short overview of the prime value I took from this book.

Superbugs is a book that stems from a high level review of antimicrobial resistance commissioned by then UK prime minister David Cameron and is written, not by scientific subject matter experts, but by economists and policymakers (Jim O'Neill, William Hall, and Anthony McDonell).

I think it is not difficult for anyone to see that a drug-resistant infection will be, on average, more expensive to treat than a drug-sensitive one. This cost disparity exists for several reasons that include the expense of switching therapy to a an appropriate regimen, the expense of isolation of patients with drug resistant infections, and the increased severity of illness because time to appropriate antibiotic therapy is delayed. 

The book is divided into two parts that focus, respectively, on the problem and solutions to drug resistance. To me, the chief value of the book is the authors attempt to quantify the problem of antimicrobial resistance because as they note a whole different audience -- beyond the health one -- is more receptive to a quantitative analysis. Several of their estimates are worth noting.

• 1.5 million people die of antimicrobial resistant infections annually (more than die i automobile accidents)
• Total worldwide costs (direct and lost productivity) are approximately $864 billio

The book provides a comprehensive overview of the economic challenges inherent with antibiotics: namely, stewardship programs that diminish revenue from new antibiotics, low prices of antibiotics vs. other pharmaceuticals, and the ability to substitute antibiotics.

One of the most valuable portions of the book, to me, is their discussion of diagnostic tests. Much of inappropriate antibiotic prescribing is done for viral infections. It is thus obvious that by employing diagnostic tests to determine whether a patient's symptoms are caused by a virus or a bacteria and which virus it might be could curtail injudicious antibiotic prescribing (and provide valuable epidemiological information) however they are seldom employed despite their availability. Superbugs delves into the dilemma that has stifled the routine use of diagnostics for infectious disease contrasting it the use of advanced diagnostics tests that are standard of care for cancer. 

Chief amongst these obstacles, as they note and I have experienced first hand, is the hospital siloing of costs. Because a multiplex point-of-care molecular diagnostic test deployed during an office visit for bronchitis is more than the entire cost of the visit plus the inappropriate antibiotic prescription that will likely result, testing is foregone. But economics is not only about the seen, but also the unseen, and taking a wider perspective allows one to realize that the costs of antimicrobial resistance driven by the inappropriate prescribing outweighs the cost of running a diagnostic test. 

The book concludes with policy recommendations to solve what the authors believe to be a tractable problem that are informed by a thorough analysis of the problem that are familiar to those that follow this issue and include increasing awareness, increased R&D, and the inclusion of all relevant parties (including agriculture). 

I recommend Superbugs to those who would like an up-to-date holistic analysis of a pressing public-- and individual -- health threat.