A rabid bite and its consequence: Turning wind and water into greatest fears

A dog sticking its head out of a window with a sign reading "Beware of dog" above its head

Even the fearless few would meet their match, cowering in terror at just wind and water, when infected with Rabies. Image credit: Don Agnello via Unsplash


An animal’s bite has roused fear for most of history. In Mesopotamia in the eighteenth-century BC, chants known as “dog incantations” were carved into stone tablets. They warned of a dog’s salivary component that behaves like poison, casting death sentences upon any recipients of a bite. The cause of these deaths is now known as a disease called rabies, which is still heralded as a global threat, claiming almost 59,000 lives globally each year.  

The salivary component impressively speculated thousands of years ago is now known as the rabies virus (RABV), an infective agent consisting of not much more than ribonucleic acids (RNA) and protein. RABV is classified as a lyssavirus—a class of viruses comprising seven neurotropic species that carry RNA as their genetic material. As neurotropic viruses, RABV can infect the central nervous system, which consists of the brain and spinal cord. Lyssaviruses are an ode to Lyssa, the Greek Goddess of fury and madness. This forebodes the horrors that those infected will ultimately endure.

The rabies virus has an incubation period in humans, where carriers of RABV do not experience symptoms, of around 1-3 months. Generic signs of illness, however, appear following this period, such as fever and pain at the bite or scratch. The most unsettling symptoms of rabies appear during the 2-10 day-long acute phase of illness, as patients become incapacitated by a fear of wind and water. These phenomena are known as “aerophobia” and “hydrophobia”, respectively. These infected individuals are not truly afraid of these innocuous elements. Rather, they are betrayed by their bodies and, consequently, their minds.

These infected individuals are not truly afraid of these innocuous elements. Rather, they are betrayed by their bodies and, consequently, their minds.

Programmed rhythm

Both swallowing and breathing are orchestrated by neural circuits in the brain called Central Pattern Generators (CPGs). These maintain vital rhythmicity, allowing our bodies to function as if automated, coordinating the two processes so they do not interfere with one another. This is why it feels near-impossible to swallow whilst inhaling.

As RABV is neurotropic, it infects the specific regions of the brain where CPGs are found, for example, regions called the brain stem respiratory neurones and the dorsal respiratory or swallowing groups. As a result, the delicate timing of the muscle contractions that allow swallowing to occur is disrupted. This cycle is replaced by painful spasms in the throat and larynx, often called the voice box.

Consequently, the simple act of swallowing, so easily taken for granted, becomes impossible. The accompanying painful spasms cause those infected with RABV to appear terrified of drinking water, or any liquid for that matter. In fact, in the late stages of the disease, the mere thought of water can cause excruciating muscle spasms in sufferers. A similar phenomenon is observed when those infected encounter a gust of wind—this is termed “aerophobia”. Here, damage caused by RABV to the CPGs that control breathing responds in the same way to air as they do water. As a result, wind causes excruciating spasms, as if fire was burning through the skin.

Cunning RABV

There has been great speculation surrounding the molecular mechanism by which RABV damages neurones in both the brain stem respiratory neurones and the dorsal respiratory/swallowing groups. The currently accepted mechanism involves a phosphoprotein found in RABV, called “RABV P”. This protein is modified by the addition of a negatively charged chemical group containing one phosphorus atom and three oxygen atoms.

RABV P wreaks havoc within neurones, as it interacts with “complex I”—a protein found in the mitochondria with a vital role in oxidative phosphorylation. This reaction converts the physical energy of movements within the mitochondria to the chemical energy of a molecule called ATP, used to power virtually every process that occurs within us.

RABV P exacerbates complex I’s activity, producing high levels of dangerous reactive oxygen species (ROS). These induce “oxidative stress”, where there is an imbalance between the accumulation of ROS and the ability of tissues to detoxify them. Oxidative stress has a plethora of negative implications for neurones, such as DNA and protein damage, and the breakdown of cellular tissues—effects that percolate across brain regions and infiltrate the final moments of individuals infected by RABV. 

A purpose for fear

It seems as if only a deep-rooted evil could drive viruses to inflict such ghastly ends unto their hosts. But viruses are not driven by desire or ill-intention. They are purely evolutionarily driven in their behaviour—they have no goal, just an innate drive conferred to them by the nature of the universe that pushes them, in many cases, to be “better” infective agents.

(Viruses) are purely evolutionarily driven in their behaviour—they have no goal, just an innate drive conferred to them by the nature of the universe that pushes them, in many cases, to be “better” infective agents.

New viruses are “evolutionarily useless” if they cannot facilitate transmission to the next host; their goal is to continue their ancestors’ infectious rampage. To ensure this, viruses biologically manipulate the host so that they engage in behaviours that optimise the virus’ spread. The common cold, for example, infects cells lining the respiratory tract and causes coughing. This launches projectiles, called aerosols, of saliva and mucous, which cause infection in a new host once inhaled. This forces chains of infection that facilitate the continuous replication of new viruses.

RABV is no exception. Though it may seem like a last-ditch attempt at cruelty inflicted upon individuals already enduring immense suffering, there is a method to RABV’s madness. As a virus that spreads through saliva entering a bite, it is optimally transmitted when sufficient amounts of saliva are produced and when the salivary concentration of RABV is high.

This brings us back to hydrophobia and aerophobia. These phenomena allow RABV to fulfil these sinister objectives. Hydrophobia prevents sufferers from hydrating themselves sufficiently, dwindling the water content of the saliva. With less water in the saliva, RABV concentrations soar, facilitating optimal transmission.

Similarly, aerophobia forces the host to avoid winds, gusts, and breezes at all costs. This keeps their faces, and importantly their mouths, from drying out, maximising saliva production. This causes the characteristic foaming at the mouth often seen in portrayals of rabies. Once infected, sufferers of rabies have no choice but to do the very last things they would consciously want to—drink no water and avoid air.

What is there to do when you long to live, but your body “longs” for the virus to?

What is there to do when you long to live, but your body “longs” for the virus to?

Odds hard to beat

There have been 30 individuals recorded to have survived a rabies infection following the onset of symptoms. It is clear that the odds of overcoming a RABV infection without immediate intervention are considered slim to none. In fact, these chances are so slim that, despite these 30 recorded survivors, rabies is still referred to as a 100% fatal disease once symptoms appear. If the disease has progressed to the point of hydrophobia and aerophobia, death seems practically inevitable. Despite a 100% fatality rate, rabies is 100% preventable through post-exposure prophylaxis (PEP) given on the day of exposure, three vaccinations over the following two weeks, and community awareness.

PEP involves washing the wound with soap and water for 15 minutes and assessment of the need for rabies biologicals, such as rabies immunoglobin or monoclonal antibodies. These immunity-based interventions can artificially mimic immune responses against RABV that may act to clear early infection. PEP also involves engagement with patients and families to clarify any misconceptions surrounding rabies, ensuring compliance with protective measures, and improving community awareness. Vaccinations have also been developed against rabies, but there are issues of access and supply, especially considering the high global burden of rabies.

Rousing fears of being infected, but also rousing fear upon infection, rabies truly is a disease of terror.

Rabies, a global killer, is a threat that can be placated with careful community efforts and preventative biological interventions. These interventions have the potential to confer great deals of protection but are still lacking in many ways, such as access and supply. In addition to this, aerophobia and hydrophobia both reveal a sinister evolutionary push towards consistent viral transmission. Rousing fears of being infected, but also rousing fear upon infection, rabies truly is a disease of terror.