Ancient Mesopotamian lawmakers wrote penalties for owners of rabid dogs around 1930 BC. In 1918, an influenza virus that likely originated in birds or pigs killed an estimated 50 million people, more than the combat deaths of World War I. In the 1920s, HIV-1 crossed from chimpanzees to humans in Central Africa through bushmeat hunting. Pathogens have been crossing from animals to humans for as long as the two have shared space, and the history of these spillover events is also a history of how we learned to fight back.
More than 60% of known human infectious diseases can be spread from animals, and roughly 75% of emerging infectious diseases have animal origins (CDC). Familiar examples include influenza, rabies, HIV and, most recently, COVID-19, all arising from complex interactions between humans, animals and the environment, amplified by habitat loss, agricultural intensification and global travel. Yet for every spillover that makes headlines, many others are contained through routine surveillance, hygiene and vaccination before they reach a second host.
A Brief History of Zoonotic Spillover
Rabies offers one of the clearest long-term case studies. Recognised for millennia as a fatal consequence of a bite from a “mad” dog, it was transformed by Louis Pasteur’s vaccine in 1885 from a near-certain death sentence into a preventable disease. That pattern, a devastating zoonotic pathogen met by human ingenuity, has repeated itself across centuries.
The Black Death (caused by the bacterium Yersinia pestis, not a virus, but frequently referenced in zoonotic discussions) killed an estimated 25 to 50 million people across Eurasia in roughly seven years, demonstrating how trade routes and urban crowding amplify pathogen spread. The 1918 influenza pandemic showed the same dynamic on a global scale, and within decades HIV-1 had become one of the defining public health crises of the 20th century.
Coronaviruses: Three Spillovers in Two Decades
SARS-CoV-1 emerged in 2002. Early epidemiological data pointed to a zoonotic origin: 33% of the first detected cases were animal or food handlers, and many asymptomatic workers in Guangdong’s wet markets carried circulating antibodies. The virus infected approximately 8,000 people and killed 774 before public health measures, primarily case isolation, contact tracing and increased testing, brought it under control.
MERS (Middle East Respiratory Syndrome) was first identified in Saudi Arabia in 2012. The virus likely originated in bats, with dromedary camels acting as the primary intermediate host for human infections. As of March 2026, MERS has caused 2,647 confirmed cases and 959 deaths worldwide (ECDC).
SARS-CoV-2, the virus behind COVID-19, led to a global pandemic from late 2019. Among the earliest confirmed patients, 49% had contact with the Huanan Seafood Market in Wuhan. A separate full-length genome study showed 96.2% sequence similarity to the bat coronavirus RaTG13. Together, these findings pointed strongly to a zoonotic origin. The pandemic claimed millions of lives, but it also drove the fastest vaccine development programme in history and a step change in global genomic surveillance capacity.
The Science Behind Spillover
Spillover is not random. It requires a reservoir host, an exposure route, and a virus capable of adapting to human biology.
Reservoir hosts. Many zoonotic viruses persist in bats and rodents, where they cause little or no disease. Bats in particular have evolved immune features linked to the metabolic demands of flight: enhanced DNA damage repair, high baseline interferon levels, and dampened inflammatory responses, all of which allow them to tolerate viral loads that would be lethal in other mammals.
Exposure routes. Transmission to humans can be direct (handling infected animals), vector-borne (mosquitoes carrying Zika or West Nile virus), or environmental (contaminated food or water). Deforestation and habitat loss force wildlife into closer contact with humans and livestock, increasing the probability of exposure. Climate change extends vector ranges: warmer winters and longer transmission seasons have helped Culex mosquitoes, the carriers of West Nile virus, spread across North America since 1999.
Biological barriers. For an animal virus to infect humans, it must attach to human cell receptors, a step at which most animal viruses fail. Influenza, for example, had to shift from avian-type sialic acid receptors to human-type via mutations in haemagglutinin before it could efficiently infect human airways. Most RNA viruses mutate rapidly because their polymerases lack proofreading, and this error rate occasionally produces variants that can cross the species barrier. The 2009 H1N1 pandemic began in a pig co-infected with avian, swine and human influenza strains; reassortment produced a virus capable of efficient human-to-human transmission, eventually causing an estimated 151,000 to 575,000 deaths worldwide in just over a year.
Dead-end infections. The vast majority of spillover events go nowhere. The pathogen infects one individual, fails to transmit efficiently between humans, and dies out. Sustained outbreaks are the exception, not the rule.
Notable Zoonotic Viruses
Rabies. WHO estimates approximately 59,000 human deaths from rabies each year, with 99% of cases transmitted through dog bites. India accounts for roughly 35% of the global burden. The disease is 100% preventable through dog vaccination, and mass vaccination campaigns are central to the WHO/FAO/WOAH target of zero dog-mediated human rabies deaths by 2030.
Influenza. Zoonotic influenza strains drive both seasonal epidemics and pandemics. Avian influenza (H5N1) has infected humans intermittently since 1997, with case fatality rates up to 50% (clade dependent) but limited human-to-human spread. The 1957 Asian Flu (H2N2) and 1968 Hong Kong Flu (H3N2) each killed over a million people, but seasonal and pandemic vaccines now exist to reduce impact.
Nipah and Hendra. These closely related paramyxoviruses circulate in fruit bats. Nipah was first identified in 1998 in Malaysia, where deforestation pushed fruit bats into closer contact with pig farms, creating a bat-to-pig-to-human transmission chain. Nipah carries a case fatality ratio of 40 to 75% and recurs periodically in Bangladesh and India. In January 2026, two confirmed cases in healthcare workers in West Bengal were contained through rapid isolation, contact tracing of 196 individuals (all negative), and enhanced surveillance (WHO). Prevention in endemic areas focuses on avoiding consumption of raw date palm sap, which can be contaminated by bat secretions.
Viruses Under Surveillance
Several viruses are being monitored closely as of 2026, though none currently pose an imminent pandemic threat.
Influenza D. Common in cattle, with occasional subclinical infections in farmworkers, but no efficient human-to-human transmission has been documented.
Canine coronavirus HuPn-2018. Linked to respiratory infections in Southeast Asia with zoonotic potential, but further biological adaptation would be required for widespread human transmission.
Oropouche virus. Transmitted by biting midges and mosquitoes, expanding beyond the Americas due to climate shifts. It causes febrile illness but rarely fatalities. WHO is recommending accelerated development of vaccines and diagnostics.
Mpox. Cases outside Africa signalled broader geographic spread through travel, but trends are currently decreasing. A vaccine is available for high-risk groups, and WHO continues to monitor.
Prevention and Preparedness
Prevention is built on the “One Health” framework, which integrates human, animal and environmental health. The approach is coordinated by FAO, UNEP, WHO and the World Organisation for Animal Health (WOAH), who launched the One Health Joint Plan of Action (2022-2026) with six priority areas including zoonotic risk reduction and antimicrobial resistance. Surveillance systems such as GLEWS+ (the Global Early Warning and Response System for Major Animal Diseases, including Zoonoses) detect early spillover signals, while the WHO’s Global Outbreak Alert and Response Network (GOARN), established in 2000, mobilises rapid response teams to contain outbreaks.
At the individual level, practical measures include hand washing after animal contact, thorough cooking of meat, and avoiding consumption of wild animals. At the structural level, protecting habitats, regulating wildlife trade, and improving farm biosecurity all reduce spillover risk. Initiatives like the SMART Antiviral Prize, which offers USD 100 million for broad-spectrum compounds targeting Togaviridae and/or Flaviviridae (including Dengue, Zika and West Nile virus), are accelerating the development of treatments that could be deployed against novel zoonotic threats before they escalate.
Preparedness also means stockpiling antivirals, maintaining rapid diagnostic capacity, and sustaining the international data-sharing frameworks that proved essential during COVID-19. The Pandemic Agreement, negotiated through the WHO and reaching a milestone in 2025, aims to strengthen these mechanisms further.
The Path Ahead
Zoonotic spillover is a fact of biology, not a sign of inevitability. AI-driven surveillance systems are improving our ability to detect outbreaks early. Genomic sequencing can now characterise a novel virus within days of its identification. mRNA vaccine platforms, proven during COVID-19, can be adapted to new targets faster than any previous technology.
The risks are real, and they grow with deforestation, urbanisation and climate change. But the tools grow faster. Every outbreak, however costly, has expanded the knowledge and infrastructure available for the next one. The goal is not to eliminate zoonotic risk entirely, which is not possible while humans and animals share ecosystems, but to detect, contain and treat spillovers before they become pandemics.
How VRS Can Help
Many of the viruses discussed here, including influenza, coronaviruses, and paramyxoviruses, are part of our active testing portfolio. At VRS, we offer antiviral drug screening and neutralisation assays across a wide panel of viruses in our containment level 2 and 3 laboratories. Whether you are developing antivirals, testing surface treatments against zoonotic pathogens, or screening vaccine candidates, get in touch to discuss how we can support your work.
Blog by Paul Griffin
Supported by Reckon Better
References
- Centers for Disease Control and Prevention. Zoonotic Diseases. https://www.cdc.gov/one-health/about/zoonotic-diseases.html
- World Health Organization. Rabies: Epidemiology and Burden. https://www.who.int/teams/control-of-neglected-tropical-diseases/rabies/epidemiology-and-burden
- European Centre for Disease Prevention and Control. MERS-CoV Situation Update, March 2026. https://www.ecdc.europa.eu/en/middle-east-respiratory-syndrome-coronavirus-mers-cov-situation-update
- Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270-273. doi: 10.1038/s41586-020-2012-7
- World Health Organization. Nipah Virus Disease, India. Disease Outbreak News, 30 January 2026. https://www.who.int/emergencies/disease-outbreak-news/item/2026-DON593
- FAO, UNEP, WHO, WOAH. One Health Joint Plan of Action (2022-2026). https://www.who.int/publications/i/item/9789240059139
