A Brief Biological History of Quarantine

S captains speaking to health officers through a window. Doctors encouraging fastidious hygiene and social distancing. Schools closed. Politicians contesting public health measures. Newspapers pressured to stop publishing death counts. Travel bans. Disbelief and denial about infectious disease dangers. Arguments that quarantine measures are outdated, useless, and damaging to commerce. These vignettes could well describe events during the ongoing COVID19 pandemic. In fact, they reflect a glimpse of reactions to an epidemic of smallpox in the 1800s, the influenza pandemic of 1918, and the bubonic plague sweeping Europe in the fourteenth century. Quarantine measures such as these have long been recognized as a way to control the spread of disease. In a public health context, quarantine refers to the physical separation and restriction of movement of individuals who are not ill but may have been exposed to an infectious disease, to prevent its spread. As such, quarantine differs from isolation, which is applied to those already known to be sick. Over the centuries, quarantine and isolation have been applied thousands of times, and not only for humans. A survey of quarantine case studies in the fields of public health, biodiversity conservation, veterinary medicine, agriculture, and forestry provides fascinating insights into the extent to which this old practice still has a place in modern society.

S hip captains speaking to health officers through a window. Doctors encouraging fastidious hygiene and social distancing. Schools closed. Politicians contesting public health measures. Newspapers pressured to stop publishing death counts. Travel bans. Disbelief and denial about infectious disease dangers. Arguments that quarantine measures are outdated, useless, and damaging to commerce. These vignettes could well describe events during the ongoing COVID-19 pandemic. In fact, they reflect a glimpse of reactions to an epidemic of smallpox in the 1800s, the influenza pandemic of 1918, and the bubonic plague sweeping Europe in the fourteenth century.
Quarantine measures such as these have long been recognized as a way to control the spread of disease. In a public health context, quarantine refers to the physical separation and restriction of movement of individuals who are not ill but may have been exposed to an infectious disease, to prevent its spread. As such, quarantine differs from isolation, which is applied to those already known to be sick.
Over the centuries, quarantine and isolation have been applied thousands of times, and not only for humans. A survey of quarantine case studies in the fields of public health, biodiversity conservation, veterinary medicine, agriculture, and forestry provides fascinating insights into the extent to which this old practice still has a place in modern society.

Historical roots
Quarantine is an ancient concept. Many Bible passages cite a 7-day isolation for leprosy (Hansen's disease), for example. But the formalized use of quarantine in more modern times traces back to the 1300s in Mediterranean port cities. "Since the fourteenth century, quarantine has been the cornerstone of a coordinated disease-control strategy, " writes medical historian Eugenia Tognotti of the University of Sassari, in Italy, in a 2013 issue of Emerging Infectious Diseases.
In the 1300s, the concern was the bubonic plague, an extremely infectious disease. Effective treatments were unknown. Plague pandemics "appeared cyclically over many centuries and claimed millions of lives in Asia, the Middle East, the Mediterranean, and Europe, " write Zlata Blažina Tomić and Vesna Blažina in their 2015 book, Expelling the Plague: The Health Office and the Implementation of Quarantine in Dubrovnik, 1377-1533. Primarily a rodent infection transmitted by rat fleas carrying the plague bacteria Yersinia pestis, the disease spilled over to humans when the rats died, leaving blood-sucking fleas thirsty and eager for new hosts. On humans, the flea bites blackened. Swellings called buboes developed near lymph nodes, becoming painfully inflamed, eventually releasing toxins into the blood, causing neurological symptoms. Death occurred in hours or days, depending on virulence, with a 60% to 100% mortality rate. The mechanism of infection was not revealed until 1897, by researcher Paul-Louis Simond at the Pasteur Institute, in France. The Black Death wiped out at least a quarter of the population of Europe.
Trade routes carried the plague by sea along the Mediterranean coast and by land to the interior. Based on observation, Mediterranean cities, including Milan, Venice, and Dubrovnik, concluded that plague was a communicable disease and instituted control measures. Ships arriving in these port cities were required to anchor for 30 days to ensure they did not carry infection. That period was later extended to 40 days or longer; the word quarantine derives from the Italian quaranta giorni-40 days. In 1377, Dubrovnik, now in modern-day Croatia, enacted the world's first quarantine legislation.
At the Croatian Academy of Sciences Institute for Historical Studies, in Dubrovnik, Rina Kralj-Brassard has researched historical plague control measures. Dubrovnik's response to plague, she explains, was a compromise between a complete blockade of people and goods, as occurred in Mantua and Milan, versus unimpeded traffic irrespective of pestilence, a practice adopted in the Ottoman Empire. Dubrovnik, which traded with cities to the east and west, adopted plague control measures "designed to secure a fragile balance between profit making and the risk of great mortality, " she says. Dubrovnik's first permanent health office was established in 1390. City health officials, known as cazamorti, kept careful records of plague control expenditures, the names of those infected, and the locations of quarantine stations or lazarettos for isolating infected individuals. During outbreaks, lockdowns were sometimes enforced across whole neighborhoods.
Over time, much of the Mediterranean implemented a similar system, but their success in quelling plague was highly variable. Three key elements contributed to the relative success of Dubrovnik's quarantine measures, says Kralj-Brassard. The first was money. Dubrovnik was a wealthy city. The second was local health experts. Third was acceptance by locals, who became accustomed to following the measures. Anyone arriving in Dubrovnik suspected of having the plague was isolated immediately, says Kralj-Brassard, "and not only that person, but everybody that was in contact [with them]… and even the contacts of the contacts. " By the 1500s, in Dubrovnik, a system of contract tracing was already in place. Quarantine measures allowed the city to stay open safely. For this port city driven by commerce, "This was not just a health issue. It was a survival issue, " she says. Local ingenuity was proof of concept for quarantine measures we are all too familiar with today.
The psychological and sociological impacts of public health quarantine Quarantine, however, has had a dark side throughout history, Tognotti explains, with the potential to stigmatize individuals, families, or whole

In Australia, during an outbreak of the bubonic plague in 1900, sanitation workers went through impoverished areas, killing rats and disinfecting houses.
Photograph: John Degotardi Jr., Department of Public Works, Sydney, Australia. in the Journal of Public Health in April 2021, reviews quarantine acceptance and adherence. "Quarantine and isolation reduce [disease] transmission," Sopory says, "because we are preventing the pathogen from getting out of the host and infecting others." But there are harms too. "There are complexities involved with telling people they have to remain confined." Financial harm is one outcome, especially for those self-employed. Social isolation can also lead to negative psychological states of anxiety and stress.
"We are social beings. We need to connect, " says Lorie Laroche, a social worker who teaches the history of health care at the University of Ottawa. In times of crisis, such as a pandemic, when people need support, quarantine takes away one of our coping mechanisms. "We cannot function well long term without that connection, " says Laroche, noting that historical data on the "Spanish" flu suggests that, during and after quarantines, there was a negative impact on mental health and increased suicides.
Donna Stewart, chair of women's health at the University Health Network and the University of Toronto, led a team that studied psychosocial impacts on health care staff who were quarantined during the SARS outbreak in Toronto in 2003. She found that their fear, lack of control, anger, and frustration were accompanied by a professional dedication to their

A Board of Health quarantine poster warned that the premises were contaminated by smallpox. Image: National Library of Medicine. Quarantine and isolation can affect patients' mental health, including an increase in suicides. In 1918, the Bell System urged those in quarantine to stay connected over the telephone. Image: The Bell System.
patients. Stewart's study highlighted a range of supports that can allay anxiety during quarantine. Social interaction via electronic media or telephone, finding interesting pastimes, and having access to essential, accurate, and timely information are important in easing anxiety. "The whole issue of resilience and maintaining hope are things that leaders need to be aware of in their communications, " she adds.
When it comes to quarantine, "We know the harms exist," says Sopory. "We can't sweep them under the carpet." Policies, services, and communications to mitigate the harms of quarantine can include free professional virtual counseling and full or partial income replacement. For agencies that implement quarantine, Sopory's work suggests that quarantine messaging tailored to the individual, societal, or community level can lead to differing levels of resistance. Appealing to "the common good" at the societal level is often too abstract, he explains, with compliance and cooperation more likely when appealing to the good of one's community.

Quarantine in conservation:
Preventing spillover from humans to animals Quarantine reduces not only humanto-human disease transmission but also human-to-animal pathogen transmission, explains Kirsten Gilardi, executive director and chief veterinary officer at Gorilla Doctors, an organization that helps protect endangered mountain gorillas in Rwanda's Volcanoes National Park.
The world's mountain gorillasabout 1063 animals-are closely related to humans and vulnerable

Tourists wearing masks in Bwindi Impenetrable National Park, Uganda, as recommended by the International Union for the Conservation of Nature's best practices for great ape tourism (left). Fred Nizeyimana, field veterinarian for Gorilla Doctors, working in Uganda to conduct a visual health check. Photographs: Skyler Bishop for Gorilla Doctors.
to our diseases, including the highly infectious measles virus.
Most of the world's mountain gorillas are habituated to humans, which "lets us get close enough to do our work, " says Gilardi, including critical veterinary care for gorillas injured in poacher-set snares. But close human proximity puts mountain gorillas uniquely at risk. Mountain gorilla tourism came to a halt in March 2020, but, when it is functioning normally, "we have hundreds of people coming from all over the world to these parks every single day, " she says, with visitors eager to spend time near a gorilla group.
The International Union for Conservation of Nature best practice guidelines for great ape tourism recommends approaching no closer than 10 meters, self-monitoring for clinical illness, and wearing a mask when near the primates. Before a prolonged period of proximity to great apes for research, filming, or health monitoring, best practices recommend a 7-day quarantine, a duration shorter than preferred for diseases such as measles but one that is realistically achievable. Currently, Rwandan rangers, trackers, and guides get frequent COVID-19 tests.
Staff stay at a quarantine hotel until their test results return, then spend a month at their ranger control post to avoid social mixing while working close to mountain gorillas. "Rwanda has been strict but also very careful and thoughtful to minimize the risk of bringing the [SARS CoV-2] virus into the park," says Gilardi.
Thomas Gillespie, at Emory University, studies chimps at Gombe, in Tanzania. Quarantine is also part of life for field staff there. Field staff are scheduled for 2-week blocks of work, then family time, then quarantine, before the schedule repeats. Before work weeks, the staff stay close to Gombe but isolated enough that they can avoid the pressure or temptation to break their quarantine.
For our primate cousins, explains Gillespie, "most mortality events have been respiratory infections. " But his recent work demonstrates another route for pathogen infection: human fecal contamination, which has introduced antimicrobial-resistant pathogens to the chimps. His recent work suggests that streams are a source of contamination and urges increased awareness for researchers and park staff to "quarantine" their fecal material by packing it out, sanitizing their footwear, and wearing a different set of clothing inside and outside of the park. As for tourists as vectors of disease for great apes, that is suspected to be important but has been tricky to study.
Other veterinary, agricultural, and forestry-related quarantines In the 1800s and earlier, rabid stray dogs were not uncommon in Britain. But a control program eradicated rabies from the island nation by 1903. From 1897 to 2012, a strict universal quarantine was in place in the United Kingdom to prevent the reimportation of rabies, the quarantine length set to 6 months as the internationally recognized incubation period for the fatal viral disease. Caused by a biotype of the genus Lyssavirus, rabies is most often transmitted to humans by dog bites. According to World Health Organization data, rabies causes 59,000 premature human deaths each year, the majority in Asia.
Historically, in the United Kingdom, "Rabies has been hugely feared, " says Malcolm Bennett, zoonotic and emerging disease specialist at the University of Nottingham. Fear of rabies in the United Kingdom was fueled by government advertising campaigns of the 1970s, with airport posters of a

Gombe Ecohealth Project codirector Thomas Gillespie, and project manager and veterinarian Iddi Lipende, at Gombe National Park, Tanzania (left). Ferdinand, an adult male of the Kasakela chimpanzee community, feeding on figs after a rainstorm. Field staff self-quarantine before working near the chimps. Photographs: Ian Gilby.
ferocious-looking rabid dog attacking a terrified young girl with the title "Don't smuggle death. " Now, though, the United Kingdom's stance on the need for a rabies quarantine has radically changed. An updated epidemiological risk assessment, the emotional strain of a 6-month quarantine on pet owners, and the unpopularity from the perspective of animal health and welfare, combined with the availability of other scientific tools, have led to a shift in thinking and policy.
Vaccinations for rabies, initially developed by Louis Pasteur, are now combined with microchip identification for pets and antibody tests to ensure vaccine effectiveness. These, combined with a home-country waiting period before movement, facilitate greater mobility for companion animals. Pet owners in the United Kingdom can now take their animals on holiday to Europe under the United Kingdom's pet passport scheme. Similar policies are in place in other countries, including New Zealand, which has not used quarantine as a rabies mitigation measure since 2011, explains Peter Thomson, director of animal and plant health at Biosecurity New Zealand. The United States, however, has gone further than a quarantine for rabies, recently implementing an outright ban on dogs entering the United States from over 100 countries.
Although no longer in wide use for rabies, on arrival in New Zealand, all cats and dogs, except those from Australia, go into quarantine for a minimum of 10 days, explains Thomson. Mandatory pet quarantine helps prevent exotic ticks from entering New Zealand and gives veterinarians time to perform health inspections. "New Zealand is in the unique position of not having many pests and diseases that are found elsewhere in the world, " says Thomson. Pet quarantine aims to keep out exotics, such as the brown dog tick (Rhipicephalus sanguineus), a vector for canine ehrlichiosis. Horses (except those from Australia), zoo animals, and poultry hatching eggs also require quarantine on arrival to New Zealand. In many countries, on importation, animal products are sent to a transitional quarantine facility for inspection before release.
Rabies remains a global concern, and many nongovernmental organizations work with street dogs and vaccination campaigns. "We could virtually eliminate human rabies if we chose to do so, " says Rachael Tarlinton, veterinary virologist at the University of Nottingham.
Quarantine is one tool in a larger tool kit called biosecurity. "Quarantine is still a very useful and important tool today and one we've all become a lot more familiar with during the COVID pandemic, " says Jamie Rothenburger, a veterinary pathologist at the University

Public poster invoking fear and danger to warn against the risks of rabies imposed by animal smuggling into Britain. Image: Prepared for the Ministry of Agriculture Fisheries and Food by the Central Office of Information, Great Britain.
of Calgary. In poultry and hog production, one practice related to quarantine is all-in, all-out management, meaning all animals enter a facility at once. On maturity, all animals go to slaughter at the same time. Then, the empty barn is thoroughly cleaned and disinfected before a new population enters. In addition to disinfection, there is a gap in time so residual microbes die off. Linked to the concept of quarantine, all-in, all-out is "a really key biosecurity measure, " Rothenburger says. Another example is quarantine for horses. "Horses have their own flu, " explains Rothenburger, and when young horses go to the racetrack for the first time, "a lot of them get snotty noses and feel unwell, kind of like sending your child to daycare. " Australia, New Zealand, and Iceland are the only countries in the world without equine influenza. So horses taken to Australia for races must enter a postarrival quarantine for 14 days.
Quarantine is also effective for Lymantria dispar and other invasive pests that are an economic drain on the North American forest industry. Originally from Europe, L. dispar larvae voraciously consume over 500 plant species. Arriving in the late 1800s, the moths have munched their way across the northeastern United States and southern Canada. During severe outbreaks, caterpillars defoliate vast areas. "It's not really a tree killer, although trees will die if attacked repeatedly, " says Patrick Tobin. Having studied L. dispar for decades, he specializes in disturbance ecology at the University of Washington. L. dispar impact tree growth and are a nuisance in urban and suburban areas, so there is an incentive to curtail spread. One region particularly worried about the potential impact of L. dispar, given the caterpillar's penchant for oak trees, is the Ozarks, whose oaks are shipped to Scotland for scotch barrels.
Whereas public health quarantine refers to the isolation of exposed individuals who may or may not be infected, quarantine for L. dispar is akin to isolation. Regions of high population density are designated "quarantine areas," with measures implemented to avoid spread. The federal Slow the Spread program deploys grids of pheromone-baited traps to monitor local movement of L. dispar along the leading edge, determining optimal placement of quarantine areas. "It works really well, " says Tobin. It is possible because moths use sensitive sex pheromones, with males lured in by a female's species-specific perfume.
A few years ago, Tobin investigated where newly established Washington State populations of L. dispar originated and found industry a minor factor. Industry has been relatively easy and successful to manage when it comes to L. dispar quarantine because Christmas tree farms and tree nurseries, for example, get checked by state inspectors. It is a different matter for the general public. Tobin learned firsthand how well individual compliance with L. dispar quarantine worked when moving from the East Coast to Seattle.
"It's a funny story, " says Tobin. He is familiar with L. dispar legalities, and when movers arrived to pack his contents, Tobin handed them the quarantine-compliance paperwork. "They looked at me like, 'What the heck is this stuff?'" Most people, he learned, have no awareness of L. dispar quarantine requirements, "so, not surprisingly, a lot of our new colonies that pop up in Washington and Oregon are directly linked to a household move. " That is because, although female L. dispar lay egg masses mainly on trees, they also lay eggs on birdhouses, toy bulldozers in a sandbox, recreational vehicles, and outdoor furniture, according to Tobin's studies with Diana Kearns.
In the 1970s, Kearns was hired to put out L. dispar detection traps in Oregon. Now retired from the Oregon Department of Agriculture, she recalls only one year in which Oregon imposed a L. dispar quarantine: 1984. That year, a huge infestation was detected in Lane County. In the forested hills south of Eugene, "they caught 17,000 male L. dispar, " she says, spawning a huge eradication project that lasted four seasons. During that time, a quarantine was placed on Oregon by the US Department of Agriculture, with additional intrastate quarantines. A Bacillus spraying program was implemented. After 4 years, they were down to one moth.

Quarantines have been relatively successful for Lymantria dispar, unlike for many other invasive species. L. dispar defoliate forests and are a nuisance in residential areas in the Northeast United States and Canada. Photograph: J. E. Appleby, US Fish and Wildlife Service.
Quarantines have been relatively successful for L. dispar, unlike for many other invasives, says Tobin, because of the sensitive tool-pheromone-baited monitoring traps.
Animal use of "quarantine" Humans are not unique in implementing quarantine as an effective infectious disease mitigation measure. In March 2021, a team of scientists led by Sebastian Stockmaier published a review in Science of social distancing in nature. Animals, they document, exhibit a continuum of behaviors similar to quarantine, from passive self-isolation to enforced isolation by excluding infected individuals. Examples of passive self-isolation include social disinterest by vampire bats in grooming immune-challenged individuals and virus-infected bees sharing less food with nestmates. Avoidance of potentially infected individuals is seen in lobsters, Trinidadian guppies, mandrills, and termites. One famous example from human history is Typhoid Mary, explains Stockmaier, an asymptomatic typhoid fever spreader who did not want to be isolated by authorities. "There are obvious ethical concerns when it comes to quarantine enforced in the human realm, " he says, "but very similar behaviors have been shown in ants and bees, for instance. " Bees drag virus-infected individuals out of the nest.
Avoidance is widespread in animals too. "It's been shown in almost every taxon," he says. Stockmaier's colleague Nathalie Stroeymeyt used tiny digital tags to track the movements of individual ants within a colony. She discovered that if she introduced fungus-exposed individuals, other individuals increased their distance from each other, giving infected ants a wide berth.
But the enactment of quarantine measures in nature does not occur

The common vampire bat, Desmodus rotundus, is one of many species that try to exclude individuals that are ill or carry infection. Photograph: Uwe Schmidt, CC BY-SA 4.0.
across the board, as Stockmaier's coauthor Dana Hawley discovered for mongoose and house finches. "In those species, the diseases we were interested in are very visibly obvious," she says. Studying Mycobacterium mungi, a form of tuberculosis unique to banded mongoose, and pink eye disease Mycoplasmal conjunctivitis that causes a very active swelling of the eye in house finches, she did not find evidence of the avoidance of diseased individuals in either system. Does the ancient practice of quarantine still have a place in modern society? The answer, and not just for humans, is clearly yes. Seven centuries after Dubrovnik enacted a quarantine law, the separation of individuals with known exposure to disease remains a critical tool in an epidemiology toolbox. Quarantine is a blunt instrument for disease control. But its benefits are clear. Some of the worst outbreaks of human pathogens, including COVID-19, SARS, and bubonic plague, have involved the spread of poorly known emerging diseases for which no specific treatments were initially available. Performed effectively, the separation of individuals means the infection has nowhere to travel. Nevertheless, quarantine also exacts significant financial and social costs and complexity. Quarantine, carefully and ethically applied with appropriate supports, will remain an effective strategy to stem infectious disease, buying critical time for scientific efforts to develop more sophisticated treatments and vaccines.
Lesley Evans Ogden is a scientist turned storyteller. An internationally published freelance multimedia journalist based in Vancouver, Canada, she is forever following her curiosity to chase down the next fascinating and quirky story.
Say hello on Twitter@ljevanso