Clandestine Diarrhea & Inadequate Chlorination: The Perfect Storm

Possibly lost amongst many other pressing infectious disease issues such as yellow fever, Zika, and antibiotic resistance was a report released by CDC assessing public swimming pools. The bombshell contained in the report is the finding that 80% of pools have been closed for safety violations. While I believe that many of these safety violations might be the result of bureaucratic intricacies and pose no danger, those that deal with diminished chlorine, for example, are likely serious as they potentially can allow dangerous microbes to pass from one swimmer to another. Rotavirus, E.coli O157, and cryptosporidium are pathogens that can find a poorly disinfected pool hospitable. 

While it is unequivocally important to highlight the appropriate disinfection procedures that must be followed for optimal safety, it is not a good state of affairs when people have to be warned not to swim in a public pool if they have diarrhea. A floating turd, which I have seen on multiple occasions (in fact it's how, as a child taking swimming lessons at the YMCA, I first learned what the word feces meant), is an identifiable hazard that can be easily seen, avoided, and remedied. Diarrhea, to unaware swimmers, to use threat analysis terms is an unknown unknown. 

Why people with diarrhea think it's OK to merge their "stream" with that of the pool's I will never know.


Will Dengue Unravel the Mystery of Zika?

One of the puzzles about Zika virus and its newly discovered penchant to cause fetal anomalies is understanding why these facts about Zika are being noticed now given relatively large outbreaks of the virus that occurred in Micronesia and French Polynesia. In those outbreaks, complications such as Guillain-Barre Syndrome were noted but not microcephaly was noted (French Polynesia recently reported 8 microcephaly cases from their outbreak).

One tantalizing hypothesis which is gaining evidence is the role of preexisting dengue antibodies. Dengue, a flavivirus like Zika, has the ability to cause severe disease by employing preexisting antibodies to one strain to enhance infection with another. This phenomenon is known as antibody-dependent enhancement and was discovered by Dr. Scott Halstead who, early on, thought this was playing a role with Zika.  

Now, evidence is beginning to be presented that shows that this may be more than a hypothesis. A pre-publication paper published by researchers at Florida Gulf Coast University illustrates that dengue monoclonal antibodies and immune sera both have the potential to enhance Zika infection in a cell culture model. 

These preliminary findings were pathbreaking in their own right but yesterday at the Cura Zika symposium at the University of Pittsburgh's School of Public Health a leading Zika researcher at the institute presenting some extremely important data on this phenomenon that deserve a wide audience.

Dr. Ernesto Marquez, working out of Recife, presented data illustrating that in Brazil -- as opposed to Southeast Asia and other other areas in which dengue and Zika co-circulate --monotypic infection is much more common. What this means is that Recife women are more likely to have been infected with just 1 (out of 4 strains) of dengue than in Thailand where multi-typic infection is the norm. DENV-3 is the 

What Marquez noted in his data was the almost unique association of DENV-3 to enhance infection. There is much more to this presentation and much nuance to how these antibodies work (for example, their quantity) so I suggest watching it online. It is a great example of how scientific analysis proceeds. 

The obvious policy question that comes to mind is how would the dengue vaccine, approved for use in Brazil, Mexico, and the Philippines, interact with Zika? Would it foster antibody dependent enhancement? Or would it be protective? Other questions to answer would involve looking at case-control data between dengue-naive and non-naive pregnant women who are infected and assessing how their clinical courses may differ. 

Nonetheless, science is advancing quite rapidly on this fascinating virus. 

Can I Check Your Inflammatory Reflex?

The realms of infectious disease and critical care medicine intersect at a place called sepsis. Sepsis is what our grandmothers called "blood poisoning" and what our ancestors before that believed was caused by evil "humors" in the body. As one of about 113 physicians with dual training in both infectious disease and critical care medicine, this disease entity is one I find extremely fascinating for obvious reasons. A good way to think of sepsis, is as the final common pathway for many infections as they increase in severity. 

Sepsis recently underwent a notable change in definition that improved the utility of the concept by reflecting state-of-the-art scientific principles. The fundamental basic definition of sepsis is dsyregulated host response to infection. When I first saw the new definition, which I found to have much more clarity than prior versions, I didn't parse every word out. However, after reading Clifford Deutschman's analysis, I am reminded of how important definitions are both for what they include and also for what they exclude.

The definition of sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. What Deutschman's piece highlights is the fact that the definition stipulates only a host response -- not which part of the host. Most people, rightly, think of the dysregulated response as largely immunologic but, like many physiological phenomenon, there's more to the story. He also goes on to point to the answer to the question of what other systems are involved. 

Tracking down his references one finds that it is the nervous system that is involved. A tantalizing aspect of this involvement is something known as "the inflammatory reflex" (sounds like a media term for an attribute of Donald Trump) as elucidated by Kevin Tracey.

This reflex involves the vagus nerve directly communicating with the immune system. This communication is two way with infection triggering "sickness behavior" such as anorexia, social withdrawal, and sleepiness. On the other side, T-cells of the immune system are influenced in order to diminish inflammation, which though essential can sometimes be overwhelming. 

The details of this interaction are endlessley fascinating and open up whole areas for intervention. Equally fascinating is understanding the evolutionary role of this pathway, which predates the immune system proper as it is present in the simple organism C.elegans which does not have immune cells. Sickness behavior is interesting in its own right and one can see how such behavior might delimit contagion and conserve metabolic resources needed to weather the infectious storm--a really cool thing to contemplate.


Flu: Always Trying to Avoid Partying like It's 1918

That a 57 year old man died from influenza should come as no surprise, even if that man is named Prince. While it is not confirmed that Prince actually succumbed to true influenza—people use the word “flu” for a variety of conditions--his tragic loss should serve as a reminder that influenza is not a benign illness but a major infectious disease killer responsible for the deaths of thousands of Americans yearly.  Just hours before Prince’s death was announced to the world, a friend of mine was baffled over the death of a young police officer in my own county from influenza.

People die from influenza when it progresses to severe pneumonia blocking the ability of the lungs to deliver oxygen to the bloodstream. This phenomenon can occur with primary viral pneumonia caused by influenza or via a secondary bacterial pneumonia. Also, those with severe illness who are hospitalized are at risk for downstream complications of that hospitalization such as kidney failure or pulmonary embolism, for example.

As of this writing it is unclear what the circumstances of Prince’s death were and the nature of his illness, but it is said he was battling flu for weeks leading me to speculate he may have had a secondary complication of some sort.

While this year’s flu season has been late-peaking and relatively benign (thanks, in part, to a well-matched flu vaccine), there have been many severe cases around the nation. In its latest weekly report (covering through April 9) on flu the CDC relates that 7.5% of deaths reported in the 122 Cities Mortality Reporting System were due to pneumonia/influenza – above the threshold value expected for this time of year. Additionally, 10 pediatric deaths were reported for that same week.

This is what it sounds like when flu kills.

Zika and Causality: A Crucial Threshold Crossed

Today a major milestone was achieved with Zika virus: the establishment of a causal relationship between the virus and fetal abnormalities such as microcephaly. By now the world has been acting, appropriately, as if this was the case based on highly suggestive data. However, seeing the fidelity to causality in making the definitive case was heartening.

As philosopher Leonard Peikoff writes: 

“The explicit identification of causality (by the Greeks) was an enormous intellectual achievement; it represented the beginning of a scientific outlook on existence, as against the prescientific view of the world as a realm of miracles or of chance.”

Causality is the hallmark of science--no appeals to correlations, suggestions, faith, "optics", or notion can supplant the need for causality. The CDC's New England Journal paper announcing the linkage does so with absolute deference to causality as exemplified by Shephard's Criteria.

Shephard's Criteria delineate what is required to establish the teratogenicity -- fetal malformation causation -- of a substance and Zika now unequivocally meets that threshold. With this development, the greenest light possible has been given to scientists to determine how to combat the virus.

Seeing such fealty paid to causality in an era when, unfortunately, logic is regarded as superfluous is remarkable.