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When a researcher’s scrawling of the letter O was misinterpreted as a zero in reference to a HIV patient in the early 1980s, the provocative term “patient zero” was born.
It triggered a wave of events in which the patient, Gaëtan Dugas, a French-Canadian flight attendant, was erroneously blamed for bringing the human immunodeficiency virus, or HIV, to the United States.
Decades passed before research, published in the journal Nature last month, cleared Dugas’ name and provided strong evidence that the virus emerged in the United States from a pre-existing Caribbean epidemic in or around 1970.
Though Dugas’ disturbing saga has been put to rest, the term “patient zero” lives on, and continues to create confusion and curiosity about how disease spreads.
“Zero is a capacious word,” Richard McKay, a historian at the University of Cambridge in England and a co-author of the Nature study, said last month. “It could mean nothing, but it can also mean the absolute beginning.”
Super-spreaders vs. super-shedders
“Patient zero” is still frequently used to describe index cases – the first documented cases of a disease observed or reported to health officials.
Many scientists and public health officials are loath to identify those patients and avoid the term “patient zero” altogether, said Thomas Friedrich, an associate professor of pathobiological sciences at the University of Wisconsin-Madison School of Veterinary Medicine.
“Identifying one person as the patient zero, on the one hand may give an incorrect impression about how the disease emerges in the first place and, on the other hand, insinuate that somebody should be blamed for this outbreak, when that’s not really appropriate,” Friedrich said. “Nonetheless, it’s important scientifically and for people and public health to understand index cases so that we know how diseases are coming into a community and how to stop their spread.”
Some scientists argue that it’s equally important to analyze primary cases – the person or animal that first brings a bacterium or virus into a population. For many infectious-disease pandemics, the primary case will never be known, said Dr. Ian Lipkin, a professor of epidemiology and director of the Center for Infection and Immunity at Columbia University in New York.
“It is not uncommon for infectious agents to percolate in the environment for years or even decades without detection,” Lipkin said, adding that an agent could enter the human population in more than just one person.
And even after an infectious agent crosses into the human population, some people are more capable of spreading it than others, he noted.
“So it may make more sense to talk in terms of super-spreaders than patient zeroes,” Lipkin said. “Super-spreaders may travel or engage in certain types of behaviors … that result in transmission to large numbers of people.”
For instance, even though Dugas wasn’t the patient zero of HIV, he still may have served as a super-spreader, Lipkin said.
Still others might be super-shedders, individuals who shed many more types of the virus into the environment – and not just through person-to-person contact – than others.
Whether they were truly patient zero, super-spreaders or super-shedders, here are the stories of six people who may have played a role in the spread of deadly diseases in the 20th and 21st centuries.
The real Typhoid Mary
One of the first-known examples of super-spreading, and maybe even super-shedding, was Mary Mallon.
She became known as Typhoid Mary, said Dr. Richard Stein, a research scientist at New York University School of Medicine and adjunct assistant professor at City University of New York, who wrote the book “Super-Spreading in Infectious Diseases.”
“I’m still not sure whether she was only a super-spreader or whether she was also a super-shedder or possibly both,” Stein said.
Mallon, an Irish-born cook, appeared healthy as she prepared meals for the families she worked for in the early 1900s in New York. Soon after her meals were served, members of the households where she worked developed typhoid fever, a life-threatening illness caused by the bacterium Salmonella typhi.
As more households where she worked developed typhoid fever, Mallon was soon identified as something of a patient zero, even though she never developed the symptoms.
“There are these individuals, like so-called Typhoid Mary, who for one reason or another may be infected with a pathogen and not have that many symptoms but can shed that pathogen in a way that makes it infectious to other people,” Friedrich said.
Mallon was forced into quarantine on two occasions for a total of 26 years, during which she unsuccessfully sued the New York department of health, saying she didn’t feel sick and therefore could not infect other people. She died in 1938.
No one really knows whether Mallon was the true patient zero in the typhoid case or simply a super-spreader or super-shedder. After all, naming a patient zero remains tricky.
“I can’t even think of a time when we’ve actually known an index case,” said Dr. Bertram Jacobs, director and professor of virology at Arizona State University’s School of Life Sciences. The closest we can come is probably the SARS epidemic, he said.
The spread of SARS
Scientists have traced a serious super-spreading event during the 2003 global outbreak of SARS to one doctor and one night that he spent in a Hong Kong hotel, according to a World Health Organization bulletin (PDF).
Dr. Liu Jianlun, a 64-year-old medical doctor from southern China’s Guangdong province, was ill during his stay at the hotel and may have transferred the virus to at least 16 other guests staying on the same floor, according to the bulletin. Coincidentally, Liu stayed in room 911 on the ninth floor of the Metropole Hotel.
“You wouldn’t call him ‘patient zero,’ but if you consider his impact in terms of the outbreak, he was critical in the spread of the disease,” said Lipkin, who received the International Science and Technology Cooperation Award this year for assisting the WHO and the People’s Republic of China during the height of the SARS outbreak.
The other hotel guests who were exposed to the virus probably traveled to other countries after being infected. In less than four months, about 4,000 cases and 550 deaths from SARS could be traced to Liu’s stay in Hong Kong.
How was Liu infected with SARS to begin with? The hospital where he worked treated SARS, and Liu might have come into contact with the virus through a patient.
In Guangdong, it was believed that a farmer first developed SARS after coming in contact with the virus through an animal. Such diseases that are spread from animals are called zoonotic.
“For many zoonotic infectious diseases, the first step involves the species jump, and then if the virus is able to be transmitted directly among humans and no longer needs the animal reservoir for this, it has the potential to unleash an epidemic,” Stein said. “I think that, exploring this from a global perspective, that very first patient would be patient zero.”
’Contagion’ in real life
“In the process of adapting from one species to the next, you have the spread of disease,” Lipkin said, who served as senior technical adviser during the production of the 2011 medical thriller “Contagion.” Some of the scenes in the film mirror his memories of Beijing when he assisted in managing the SARS outbreak, Lipkin said. In the film, a fictional deadly virus sweeps the world after migrating from a dead pig to a chef that handles it.
About 60% of all existing human infectious diseases are zoonotic, said Stein, the research scientist at New York University. In other words, there are numerous microorganisms in nature that infect animals – and some of these same microorganisms infect humans.
“It was predicted that by 2020, about 10 to 40 new viruses might emerge in humans,” Stein said, citing a 2008 study published in the journal Proceedings of the Royal Society B.