They are the stuff of nightmares and scary movies, but animal diseases that cross the species barrier to wreak havoc among the human population – otherwise known as zoonoses - are very much part of the real world, too, as recent history demonstrates only too well.
COVID-19 wasn’t the first and will surely not be the last disease to develop a taste for human flesh. Here’s our pick of a deadly bunch…
Deadliest zoonotic diseases
Rabies
A proper horror show! Unlike COVID-19, rabies shows few signs of becoming less virulent over time. Indeed, it’s hard to imagine anything more virulent.
It starts with a bite from an infected dog and progresses horrifically once the virus has made its way to the central nervous system where it sets about changing its host’s behaviour to turn it into a virus delivery system for what little remains of its life. The fear of water and pain of swallowing induce the excessive production of saliva packed with virus particles, while the paranoia, confusion and mania promote aggression towards others. Paralysis and certain death follow in a matter of days.
Rabies is almost too virulent for its own good. Better, surely, to keep the host alive for longer to increase the opportunities for biting. Part of the reason for rabies’ crash-bang-wallop approach might be that a quick death is an unavoidable consequence of the changes the virus makes to its host’s nervous system. It might just not be possible to keep it alive for any length of time without turning off the very mechanism that allows the virus to spread.
Leprosy
Unlike rabies, leprosy (also known as Hansen's disease) reveals its horrors slowly and relentlessly.
The bacteria responsible for the disease are extremely slow-growing and may incubate in the body for years or even decades before symptoms appear. An early sign is often pale numb patches on the skin, which can spread slowly to the point that the sufferer has little sensation of pain, touch or temperature. And it may progress to muscle-wastage, blindness and deformities of the face and extremities that can lead to social stigmatisation.
Archaeological evidence of the disease dates back at least 4,000 years, but its evolutionary origins remain mysterious. Tantalisingly, nine-banded armadillos in the southern US harbour leprosy bacteria and will, very rarely, infect humans, which qualifies it as a zoonosis. The vast majority of cases, though, are the result of transmission between people, via respiratory droplets.
Chimpanzees and, in the UK, red squirrels, have also tested positive for the bacterium, but neither is known to infect people. Rather, it is thought that all these wild animal populations originally contracted the disease from humans - a phenomenon called ‘reverse zoonosis’.
Sleeping sickness
A scourge of sub-Saharan Africa, sleeping sickness (or African trypanosomiasis) is caused by a tiny, single-celled, eel-like parasite, called a trypanosome, which lives in mammalian blood, where it swims around by means of an undulating membrane along its length.
There are two closely related strains. One mostly infects cattle, antelope and warthogs but also spills over into human hosts. The other predominantly affects humans. Both are spread by blood-sucking tsetse flies.
Symptoms start with a painful sore at the site of the bite, followed by fever, muscle aches and distinctive swollen lymph nodes on the back of the neck. A second phase of the disease starts when the parasites pass into the brain, where they disrupt circuitry involved in regulating sleep, causing night-time insomnia and sleepiness during the day. These neurological tinkerings might help the trypanosomes disperse to new hosts. After all, a sleeping human is incapable of swatting away day-flying tsetse flies.
Over months or years, victims decline to the point of paralysis or coma and, without treatment, death is inevitable.
Historically, treatments have contained arsenic, which produces significant side-effects, although safer options are now being rolled out. Even then, people that do recover are likely to endure permanent brain damage.
Plague
The habitat of choice for the bacterium Yersinia pestis is the body of a rodent. But every once in a while, it leaves its comfort zone and starts killing people.
Few diseases have been as influential on the course of human history as the plague. which is transmitted by the bites of fleas - which are themselves spread by rats – and passed between people via body fluids. An epidemic in the 14th century, known as the Black Death, reduced Europe’s population by around 50 per cent. The event has been credited with disrupting Europe’s feudal system, setting the scene for the cultural revolutions of the Renaissance.
Bubonic plague causes grotesque pustulous swellings in the groin, neck and armpits and, if untreated, kills around 50 per cent of victims. Pneumonic plague infects the lungs, and is 100 per cent fatal. If it gets into the blood, it kills blocks of tissue and turns them black. Happily, all three types of infection respond to modern antibiotics.
Outbreaks still occur in Madagascar, Democratic Republic of the Congo, and Peru, and a fatal case of pneumonic plague, contracted from an infected animal carcass, was reported in Arizona in July 2025
Zika virus
Infectious diseases are most likely to cross the species barrier when the hosts are closely related. Little surprise that many zoonoses pass to humans from other mammals. Our closest relatives, the primates, are the original source of such delights as AIDS, MPox and Ebola.
Zika virus was first identified in a rhesus macaque in Uganda in 1947, during a study of yellow fever, and it was soon established that it was transmitted by mosquitoes. The first human cases were recorded in the 1950s, but it didn’t hit the headlines until 2015, when there was a major outbreak in Brazil.
While it usually produces a mild infection in adults, it can have devastating consequences when it affects pregnant women, inducing birth defects including a dramatic reduction in the size of the braincase (microcephaly) which results in significant malformations of the brain and profound life-long disability. Thousands of Zika-induced cases of microcephaly were recorded in 2015-2016, and the WHO declared it a Public Health Emergency of International Concern. However, cases plummeted in 2017, and have remained low, largely due to the spread of natural immunity throughout the human population.
Psittacosis
Not all zoonotic diseases originate in mammalian hosts. The ‘Great Parrot Fever Pandemic’ struck in 1929-30. It wasn’t big by pandemic stands. About 800 people contracted it, in the UK, USA, Argentina and Germany, and 100 of them died. Many casualties had had close contact with birds, and the outbreak was traced to the burgeoning global trade in South American and Australian parrots, which were much prized at the time for their feathers and company.
Psittacosis is a bacterial infection of parrots, pigeons, poultry and other birds that can be transmitted to people via the inhalation of dust from contaminated droppings or feathers. It starts with a flu-like illness that can lead to pneumonia and, rarely, necrotic skin lesions and multi-organ failure. Today, antibiotics have reduced the fatality rate to less than 1 per cent.
Anthrax
During World War II, British government scientists experimented with anthrax bombs designed to distribute spores over enemy territory. These tests were conducted on Gruinard Island on the west coast of Scotland, which was decontaminated only in the 1980s by removing the topsoil and spraying the ground with formaldehyde. In 2001, five people died after envelopes containing anthrax spores were posted to journalists and senators in the USA.
Primarily a disease of cattle, goats, horses and other grazing animals, anthrax is capable of infecting pretty much any mammal, given the chance, including humans. The bacterium responsible, Bacillus anthracis, disperses as spores, which are either inhaled or enter the body via wounds. Once inside, the bacteria release powerful toxins that destroy host tissues. Infections of the skin result in gruesome black ulcers. Lung infections are lethal in 95 per cent of untreated cases.
But anthrax has also had a constructive influence on civilisation. In 1876, Robert Koch’s work on the bacterium provided the first proof that specific micro-organisms cause particular diseases, a pivotal discovery in the development of the ‘germ theory of disease’ at a time when infections were still being explained away as imbalances between the humours.
Tick-borne encephalitis
This dangerous viral disease, spread by blood-sucking ticks, is on the march. Endemic historically across Central and Eastern Europe, southern Russia and northern Asia, tick-borne encephalitis (TBE) has been spreading northwards, westwards and further up mountains as rising temperatures open up new habitat. Two cases have recently been reported from the UK, in Yorkshire and Scotland.
Humans are incidental hosts of the parasite, which normally infects small mammals such as rodents and shrews. The virus attacks the central nervous system, causing swelling of the brain that is fatal in one or two per cent of cases. But the chances of contracting TBE from a single tick bite are extremely low. There is also an effective vaccine. 30-50 per cent of those that recover from the infection experience fatigue, cognitive dysfunction and other debilitating long-term effects for months or years.
Avian Influenza
More commonly known as ‘bird flu’, the H5N1 influenza virus has been knocking around since 1959, but it came to prominence in 1997 when it infected 18 people in Hong Kong, killing six of them. Since then, more than half a billion domestic birds have either succumbed to the virus or been slaughtered to contain it, but still it has spread to every continent except Australia.
Throughout the 2020s, a particularly virulent variant has been wreaking havoc on wild bird populations. In 2022, it reduced the world’s largest breeding colony of gannets, on Bass Rock in Scotland’s Firth of Forth, by 25 per cent.
Fewer than 1,000 cases have been documented in humans, most of them among people who work closely with farmed birds, but the mortality rate may be as high as 50 per cent. In a few cases, the virus has been transmitted between people, though not at a rate that would sustain a human pandemic – yet.
COVID-19
The majority of human infectious diseases – whether caused by bacteria, viruses or other parasites - could be described as zoonotic, having jumped to humans from animals at some point in history. Some, though, made the leap more recently than others.
The precise origin of the SARS-CoV-2 virus, which causes COVID-19, has not yet been pinned down. In the early days of the pandemic, it emerged that it is most similar to a group of coronaviruses that circulate among bats, but it remains unclear whether it infected humans directly or via an intermediate species that acted as a carrier (pangolins were early suspects, while raccoon dogs are also contenders). The possibility that the species gap was bridged by a leak from a virus research lab is also still on the table.
Either way, COVID-19 was most deadly when it first crossed the species barrier. Later variants were decreasingly virulent. This is a common scenario amongst zoonoses. A novel host has few defences against a parasite it has never encountered, so initially the infection can run riot. However, dead hosts are of little use to parasites, which tend to quickly evolve ways to keep their victims alive for as long as possible.