Interferon Gamma: A Social Lubricant that Packs a Pathogen Punch

I've written before about the extremely fascinating link between the immune and nervous system, hypothesizing about such interactions having a role in "sickness behavior". Such behavior may cause someone ill to not feel up to participating in social interaction thus delimiting spread of a potential contagious disease. 

There is no doubt that social interaction fosters the spread of infection. In fact, the rise of large settlements (proto-cities) changed the infectious milieu our ancestors faced as the transitioned away from a nomadic hunter-gatherer lifestyles. In cities, social interaction is the norm and it presents a constant challenge to the immune system as it faces a heightened exposure to microbes from other humans, some of which can be deleterious if allowed to proliferate.

So if social interaction is unavoidable, how does one protect oneself. Vaccinations, hand hygiene, social distancing, and cough etiquette are all fairly recent developments. Before these technologies, humans had to cope on their own and those evolutionarily endowed with a coping mechanism would be favored. 

New research published in Nature, helps flesh out this "inflammatory reflex" a little more. A group at the University of Virginia has discovered that the molecule interferon gamma -- a well characterized means organisms use to fend off pathogens -- is intimately linked with social behavior. To oversimplify, when one is in a social context interferon gamma increases so as to protect one from the microbes one will face from others. When the molecule is blocked in mice, social interaction decreases.

The implications of this research are far reaching and may lead to further investigation of how interferon gamma may influence pathological social deficits.

Zika: An Increasingly Frustrating Unknown Unknown

The last few days in Zika-land have been quite calamitous. Major changes in how the disease is conceived occurred. The first revolves around the sexual transmission of the virus from female to male. While male to female and male to male transmission had been known to take place for some time, female to male transmission was not really thought to occur though the virus has been found in the female genital tract and prolonged maternal viremia has been noted. This case, which occurred in NYC, illustrates that such transmission events are possible, though may be more rare than male to female transmission events. HIV, for example, is about half as likely to jump from female to male as it is from male to female.

The other big Zika news involves transmission of the virus in Utah from a fatal case to one of his caregivers. There is much to learn about this incident and it is difficult to hypothesize in such a context but several facts are known: the deceased had an extraordinary level of virus in his blood, the caregiver did not have sexual contact with the patient, mosquitoes in Utah are not known to harbor the virus, and the deceased was diagnosed with Zika post-mortem. 

This case, in my estimate, likely represents a chance transmission event that was facilitated by an extraordinary case of Zika in which the patient died (from Zika or from underlying illnesses) and possibly unique characteristics of the caregiver. It is unclear how generalizable this case may be but the mechanism as to how the caregiver was infected does carry important implications for the trajectory of the virus including the requisite infection control measures needed in the face of a virus that is present in multiple body fluids (blood, urine, semen, saliva).

Zika, more and more, is becoming an unknown unknown.

A Snapshot of a Storm -- A Review of Zika: The Emerging Epidemic by Donald McNeil

It is a difficult task to write a book about an ongoing event in which what are believed to be facts are regularly found out to not be so when truths are constantly modified by new contexts. Such is the case with the current Zika epidemic and the task that The New York Times' stellar global health reporter Donald McNeil Jr. took on with his newly released book Zika: The Emerging Epidemic. McNeil superbly executed his task.

This short book is an expertly written guided tour of not only the ongoing epidemic and its vicissitudes, but also the history of this once relegated virus. Throught the work, McNeil covers unfolding events play-by-play, something that is extremely useful to those who, unlike me, do not follow outbreaks like sports games (it is useful to those who do as well). McNeil delves into the controversy that truly existed regarding the causal role of Zika in the development of microcephaly prior to the virus's meeting of the definitive Shepard's Criteria.

One of the chief values of the book, to me (beside the fact his reference 160 is to the work of my colleagues and me), is that McNeil provides a much needed exploration of the issues surrounding the recommendations, issued by some countries, for women in Zika-laden areas to delay pregnancy and the hesitancy of others to not follow suit for various reasons.

This book is must reading for those following the Zika outbreak, those wanting to learn about it, and those wanting to immerse oneself in excellent scientific writing. 


Taking HIV "Treatment is Prevention" to New Heights

Somewhat missing from the headlines in recent days is a landmark HIV study the solidifies the concept that treatment is prevention. The back story to that important catch phrase is that, in the recent past, there was a real policy debate over where emphasis should be placed: on treatment or on prevention. One's answer to that question would have multiple cascading effects on which anti-HIV strategies were planned, evaluated, and promoted. 

All that changed with the publication of HPTN 052 which demonstrated a 96% reduction in sexual transmission of HIV in mostly hetorosexual serodiscordant couples when the HIV-infected member was on HIV therapy. This trial was revolutionary in that it showed that the HIV treatment vs. prevention debate rested on a false dichotomy. Its results changed the way HIV prevention was viewed and provided yet another reason to initative therapy as soon as possible in the HIV infected. Caveats to the generalizability of this study existed however and included the high number of heterosexual couples and a high use of condoms (94%). Despite these caveats, HPTN 052 was pathbreaking.

Buttressing and expanding HPTN 025 is the PARTNER study, recently published in JAMA. This study's aim was to assess the ability of antiretroviral therapy on the transmission of HIV in serodiscordant couples who regularly engaged in condomless sex. The results, which solidify the treatment as prevention, paradigm are stunning.

The trial included about 2/3 heterosexual couples and 1/3 men-who-have-sex with men (MSM) couples. Condom-less sex occurred between couples a median of 37 times per year. Strikingly, just 11 transmission events occurred with nearly 60,000 condom-less sex acts. The thing about the 11 HIV infections was they were not genetically linked to the other study partner, meaning these infections derived from an additional partner not in the study--a great example of the exception proving the rule. 

This study shows just how potent antiretroviral therapy is. It is not only life-saving for those who take it but extremely effective at extinguishing contagiousness. As we wait for a vaccine, antiretroviral therapy (treatment as well as pre-exposure prophylaxis) is the cornerstone to keeping HIV contained.

Is 21st Century Civilization Immune? A Review of the Novel Immunity

Taylor Antrim's Immunity, a novel set in a post-pandemic world, provides an interesting view of how such a world could look, operate, and devolve. Even as a work of fiction, there are aspects of Antrim's insights--some of with which I agree, some with which I disagree--that merit discussion in their own right.

In the universe of Immunity, the TX virus, a genetic recombinant of influenza and Lassa Fever that emerged in Texas, has circled the globe in a murderous spree. By killing 4% of the world's population the pandemic threw the governments of the world into a quarantine-laden panic. At the time of the events depicted in the novel, the pandemic is over but occasional flare-ups continue to occur, prompting draconian controls, in the name of "public health", on the population. The plot of the novel centers on a young former socialite who has is struggling to flourish in this setting that is rife with unsavory individuals and public health "police" who are ready to pounce with just one errant cough or elevated temperature reading on the ubiquitous thermal scanners that this world is rife with.

The unsavory characters range from the protagonist's conspiracy-minded father (who is eerily reminiscent of people who I debated during the West African Ebola outbreak), to "propagators" who purposely try to infect unsuspecting citizens by coughing on them, to the overtly exploitative who find a perverse pleasure in sacrificing others to their whims. The various strands of the events in Immunity culminate in an intersection of biotechnology and surveillance that leaves the reader wondering what really happened and what will happen next. 

What I take to be the theme of Immunity is what is worthy of discussion. Antrim's point seems to be on stressing how the well-off are not only the first to be granted immunity through biotechnology but that they are, in a higher sense, immune from the vicissitudes of the rumblings in the infectious disease world. Through hyperbolic characters, Antrim shows that the realm of the rich and famous is easily adaptable to a world in which a deadly virus has destroyed the lives of everyone else. I suspect Antrim is making a political point about the relative resiliency of various socioeconomic segments of the population and is using the TX virus as a background. However, the fact that the world still turns after 4% of the population has died is itself a fact that highlights species-level resiliency that transcends socioeconomics.

My own thoughts on this theme are somewhat different. Humans today live in a civilization that is itself largely immune from the challenges of outbreaks that occurred just 50 years ago. Today, worldwide extreme poverty -- in real terms -- is at its lowest. Smallpox has been vanquished with polio and guinea worm about to follow suit. Even Ebola, because of major advances that have occurred in the basic understanding of the clinical illness as well as in vaccine technology since the last outbreak, has been substantially defanged.

In many ways civilization's progress can be roughly gauged by the conquest of various infectious diseases. This species-wide resilience humans possess (which I discussed in my recent Atlantic piece) is the result of both the immune systems and the fruits of humans minds that have largely rendered nature's beasts, in all their shapes and sizes, threats from a bygone era...if we are willing to confront them with the appropriate response.