It is somewhat taken to be an axiom that infectious diseases eventually taper in their ability to cause severe disease over time as they evolve to incite less physiological mayhem in the species they infect.
This is not an axiom but a complicated phenomenon that is very context dependent, the relevant context being the transmission mode of the pathogen, the teleology (or goal) of the pathogen, and what countermeasures the host species is deploying (either through evolution or consciously when it comes to humans). In this chapter, I am going to explore this concept and, by doing so, give you my second lens for looking at the pandemic, catastrophe, and extinction potential of any agent of infectious disease.
How Transmission Modes Matter
Thinking anthropomorphically, an infectious disease pathogen “wants” to flourish, complete its life cycle, and continue the propagation of its genetic lineage. To do so, it will need a suitable environment that is conducive to the completion of these tasks. Such an environment might be the gut of mosquito, the nasopharynx of a human, the digestive system of a cat, or even a combination of multiple hosts for different hosts for different life stages. Some pathogens do not need anything, but the conditions present in a pond, the detritus on the forest floor, or the soil. This last group is a special case I will discuss separately later in the chapter.
Pathogens, therefore, need to traverse the chasm from one host to another and, to do so, need to be carried from host A to a suitable place in host B via some medium. Suitable mediums and mechanisms include skin-to-skin contact, body fluids such as saliva, respiratory droplets, blood, sexual-activity related fluid, feces, nasal mucus, ingestion, via a tick or mosquito bite, or through exhaled air.
Additionally host A and host B need to be in close enough proximity or networked enough to be above a threshold degree for this to be successful.
Differing modes of transmission will lead to different proximity thresholds. For example, a pathogen like measles which spreads efficiently through the air just needs two humans to share the same air, even separated by a couple of hours. By contrast, Ebola requires close proximity for body fluids carrying viral particles to pass fairly directly from one human to another human. Certain other pathogens need humans to be in a network such as one that shares water sources, shares food sources, or shares an environment with the same pool of mosquitoes or ticks.
In general, a pathogen that requires people to be in close proximity to be transmitted by blood or body fluids is, in the modern world, going to be constrained in its spread. Additionally, the modern world can be thought of as very pathogen-proof (not foolproof of course) in the sense that modern sanitation, food handling processes, vector control measures against mosquitoes and ticks, and hand washing really make the terrain difficult for many pathogens.
What’s left for pandemic prone pathogens, as I concluded in the last chapter, are those that spread via the respiratory route either through respiratory droplets or via exhaled air. A pandemic pathogen not only needs to be able to spread, but it also has to spread prolifically, universally, and uncontainably. It has to easily overwhelm modern societal anti-infection measures. In short, it needs hosts in close proximity who are not apprised or unaffected by the respiratory droplets or contaminated air to which they are exposed.
Even though healthcare (or nosocomial) infections are a critical and devastating problem, they are not conducive to starting a global pandemic let alone something worse. This is because a hospitalized patient with a respiratory infection is, by definition, not in the most conducive environment to spread to the majority of the humans on the planet. A bedridden person, in the hospitalize or at home, is going to have less proximity to others and, because of the severity of the illness, is also likely to raise caution level of those that visit with the patient delimiting spread.
However, if a person is out and about performing their daily tasks— not changing the landscapes of their contacts with others because of unawareness of their illness, because the severity of the experienced infection insufficient to keep them home, and/or because the illness resembles an every-day baked in risk of daily living like stepping in a mud puddle, getting caught in the rain, or twisting one’s ankle stepping off of a curb, or transmitting or acquiring the common cold—transmission will be efficient and widespread.
Therefore, a pandemic prone pathogen is likely to be a respiratory virus that spreads efficiently between humans secondary to causing a spectrum of illness that is heavily weighted towards mild or clinically inapparent — yet contagious — manifestations.
A respiratory virus that causes fulminant symptoms too frequently is going to confine a significant portion of its transmissibility period to the bed-bound or hospitalized which is inefficient if a pandemic is the end game. It is also the case that fulminant symptoms occurring too frequently will eventually change enough of the behavior of humans to one that is more avoidant of individual risks.
The above is not meant to mean that a pandemic pathogen can’t evolve to be incrementally more dangerous to humans such as the delta variant of SARS-CoV-2 represents, but that a respiratory route-dependent pathogen cannot be on a path to kill all humans if it “wants” to be prolific and join the pantheon of pandemic pathogens.
It is important to recognize that in the above discussion and thought experiment I am confining myself to pandemic pathogens (in the modern era) and this does not apply to epidemic pathogens or outbreak pathogens. Recall the way the fecal-oral spread bacterium that causes cholera can evolve to more ferocity in certain situation when that is conducive to more extensive spread.
What about HIV?
An astute reader would be thinking that the above is skirting over probably the most devastating pandemic in our lifetimes — that of the Human Immunodeficiency Virus (HIV). HIV is the subject of a later chapter, but it is important to delineate some aspects its pandemicity now. HIV has killed at least 40 million people in the past 40 years, spread to every habitable niche of the planet, and infected around 100 million. Until around 1996 with the development of potent combination anti-retroviral therapy, it was essentially 100% fatal.
Why was HIV with its horrific case fatality ratio of 1.0 able to cause a still ongoing pandemic and defy what I take to be a general rule about pandemic-prone pathogens? It is a legitimate question to ask whether HIV qualifies as a pandemic because it differs from an unequivocal pandemic pathogen such as the 1918 influenza A virus, whose death toll exceeded 40 million plus in about year— not over 40 plus years.
Make no mistake, HIV has arguably been the most pressing infectious disease challenge in the past 100 years and its emergence was a seminal event in my profession. HIV was and remains a disruptive event that changed society indelibly (and probably eternally) when it comes to certain practices such as universal precautions, blood supply safety issues, safe sex, and safe injection drug use practices. However, the very attribute that allowed it to infect over 100 million humans is what makes it different than traditional pandemic pathogens (and also the same when viewed in a certain context) — its clinical latency or chronic period.
The time period after HIV initially infects someone, the occurrence of which will cause a severe flu-like illness, and when a person has overt symptoms due to the opportunistic infections that HIV predisposes to, involves a period of about a decade. We know that during this time, HIV is not biologically silent and physiologic damage is occurring, but it is often clinically silent..until enough damage is done that the immune system is so wrecked it cannot serve its purpose any longer and AIDS (Acquired Immunodeficiency Syndrome) ensues. Throughout this period of clinical silence a person is contagious to others via their blood and body fluids. This is why the virus spread around the world even before it was first noticed and continues to infect individuals who are asymptomatic and do not know their status. This asymptomatic period is what gave HIV its pandemic potential. However, the clinical latency and its blood/body fluid transmission mode also staggered cases temporally and did not overwhelm society (though some hospitals in the 1980s did have considerable burden of patients at once suffering from HIV) in the manner of 100 million cases occurring over a period of a year or two. Its slow silent spread gave HIV a prolific reach that other blood and body fluid infections could never attain but also did not cause a universal, all-at-once calamitous response or have the same velocity of risk that the 1918 influenza or COVID pandemics did. [A similar analysis could be applied to both hepatitis B and hepatitis C which followed similar trajectories but are even more silent and subtle, causing fatal liver disease and carcinoma over a period of multiple decades].
The Idea of a perfect pathogen
I have argued that pathogens have to “care” about what they do to their hosts if they want to spread. This is known as the host-density theorem: there must be enough density of hosts present for the pathogen to successively infect; if it kills too many it will extinguish itself. But what about a pathogen that just doesn’t care because finding itself in a human or some other species is a detour from its normal lifestyle, just a brief fling, a species to which the host density theorem does not apply? Think of a fungus, for example, that normally lives on the dying or dead vegetation in a pond. It, through whatever means, now finds itself in the body of a frog which summarily succumbs to the infection that ensues. In fact, imagine that this happens to every frog that happens upon the fungus. The fungus after killing the frog just leeches out if its body and goes back to its ordinary life cycle in the specific environment it is suited for. This type of pathogen can pose extinction level pandemic threats because of its non-relationship with the frog host, it is environmentally stable and can thrive irrespective of a frog being present or not. This is what is known as a sapronoticinfection and they are basically exclusively confined to the realm of fungi, and, in the case of humans, the environmental source can be removed or avoided, and anti-fungal therapies can be developed (many frogs are left without defenses of any sort as attested to the devastation their species has faced from the chytrid fungus). I have already discussed why I don’t think humans face this threat from fungi in an earlier chapter and will return to it again in a later chapter.
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The two lenses I employ prompt two questions for any outbreak and concretize why an extinction level event from an infectious disease in humans is not plausible. These questions are:
1. Is the etiologic agent a respiratory-borne pathogen?
2. Is it efficiently spreading?
If the answers are no, it is at most, capable of causing an epidemic and be regionally restricted. If the answers are yes, it will be pandemic capable. However, an efficiently spreading respiratory virus — the only pandemic prone pathogen according to my analysis — will fall far short of an extinction level event. To not fall short would contradict the prerequisite needed to be a pandemic pathogen: an efficient spreader requiring a wide spectrum of illness tilted towards the mild or asymptomatic.