Typhoid Mary: One hundred years ago, she made humans realize for the first time that there are "asymptomatic infections"

Introduction

In February 1915[1], the weather in New York was very cold. Public health expert George A. Soper[2] was sitting in his warm office, reading reports on the war in Europe. Suddenly, the phone rang, and an anxious voice came from the receiver: "Sir, this is Sloane Hospital for Women. We may have typhoid fever!" Hearing the word typhoid, Soper shuddered. He hung up the phone and rushed to the hospital.

Photo: George Sober (1870-1948)

At Sloan Women's Hospital, more than 20 people were diagnosed with typhoid fever. The hospital suspected that a cook named Mary Brown was the source of infection because the patients had eaten the snacks she made. Hearing the name Mary, Sober was surprised: "It's not such a coincidence? She's also called Mary."

He then asked: "Where is she now?"

The hospital staff replied: "He's gone."

Sober asked, "What does she look like?"

The hospital staff replied: "Five feet six inches (1.68m) tall, blond hair, blue eyes, very strong."

Someone found Mary Brown's work documents and a letter and handed them to Sober. When Sober saw the handwriting of the person claiming to be Mary Brown, he immediately screamed: "She is not Mary Brown, she is Mary Malone, the horrible, long-missing Typhoid Mary. [3] Damn it, call the police immediately! Quick, not a second to waste. We must find her, otherwise New York will be in big trouble and many people will die!"

Who was Typhoid Mary? And why did she cause such a panic? Let me start with typhoid fever.

Horrible Typhoid

Now we know that typhoid fever is an intestinal infectious disease that is spread through contaminated water and food, and the transmission mode is similar to that of cholera. In human history, it is also a notorious infectious disease, but humans did not really understand it until the 19th century. Speaking of this, some students will definitely ask: Didn’t Zhang Zhongjing of my country write "Treatise on Febrile and Miscellaneous Diseases" a long time ago? Here I want to explain that this article describes the infectious disease "typhoid fever" in the concept of modern medicine, which is different from the concept of typhoid fever in ancient Chinese medicine.

Typhoid fever in traditional Chinese medicine is a general term for a large category of symptoms. The typhoid fever mentioned in this article is a specific infectious disease caused by microorganisms. When you get this disease, you will feel weak and have a loss of appetite at first, and your body temperature will gradually rise to 39-40℃. Then you will have symptoms such as hepatosplenomegaly, skin roseola, abdominal distension and pain, constipation or diarrhea, often accompanied by mental confusion, dullness or slow heartbeat, etc. In severe cases, you will have intestinal bleeding, intestinal perforation, toxic hepatitis, toxic myocarditis, etc. [4]. Many patients died from these symptoms, and they died in great pain. The mortality rate of typhoid fever is generally 8-15% [5], and in some areas it can reach 57%. The high mortality rate of typhoid fever even affected the military operations. During the American Civil War (1861-1865), the number of Northern Army deaths in combat was more than 90,000, but the number of deaths from typhoid fever and dysentery reached more than 80,000 [6]. Typhoid fever not only has a high mortality rate, but is also often prevalent. Between 1869 and 1875, 8,500 to 8,900 people died of typhoid fever in the UK each year. Even Queen Victoria’s husband, Prince Albert, died in agony from typhoid fever[7].

Image: Queen Victoria and Prince Albert Typhoid fever’s first “contact” with humans may have begun in ancient Greece in 430 BC. At that time, it was the Second Peloponnesian War, and the war was not favorable to Athens. In order to avoid the Spartan army, tens of thousands of farmers around Athens moved into the city. For a time, the city became extremely crowded, people and animals lived together, sewage flowed, and sanitary conditions were extremely poor, and the plague broke out. The ancient Greek historian Thucydides described a hellish scene: newcomers died like flies, the bodies of the dying were piled up on each other, and traditional funerals were cancelled. Corpses were stacked and burned, and patients had high fevers. Birds and animals were also infected and died... This is the famous "Athens Plague".

Photo: Michelle Sweets: The Great Plague of Athens

It is estimated that the plague killed one-third of the Athenians. However, there have been different opinions on what kind of infectious disease the plague was. Later scholars listed more than ten infectious diseases such as smallpox, plague, cholera, etc., but they felt that none of them was similar. [8] [9] It was not until 2006 that several Greek scientists found the remains of an 11-year-old girl in the mass grave of the great plague. They named the girl Myrtis. Myrtis's skull was well preserved. Scientists tested her teeth and found the DNA sequence of Salmonella typhi. [10] In fact, such evidence still cannot prove that the Athens plague was typhoid fever, but it at least shows that typhoid fever had contact with humans more than 2,400 years ago. However, for a long time afterwards, humans had limited knowledge of diseases and could not accurately identify them. They could only call typhoid fever and other infectious diseases "plague" in general.

Figure: Myrtle restored

It was not until 1829 that French doctor Pierre Bretonneau first named typhoid fever. If you are familiar with my series "Deadly Contagious Diseases", you must be familiar with the name Bretonneau. Yes, he is also the doctor who named "diphtheria". He also believed that typhoid fever was spread among the population through some "morbid seeds" [11]. It was not until the mid-to-late 19th century that people distinguished typhoid fever from typhus and knew that they were two different diseases. At that time, typhoid fever was a headache for people, and doctors were also trying to find ways to solve it. This heavy burden was taken up by William Bard, a pioneer in epidemiology.

Image: Pierre Bretonneau (1778-1862)
Water? Water! Water.

William Budd was born in 1811 in a medical family in Devon, England. His father was a doctor, and seven of his ten brothers became doctors. Budd studied medicine in France in his early years, and later obtained a doctorate from the University of Edinburgh. At that time, people did not have a correct understanding of the cause of typhoid fever. Some believed that the excrement of typhoid patients contained toxins, some believed that typhoid fever was transmitted through a certain medium, and some believed that typhoid fever was caused by malnutrition, dirty houses, etc. [12]. Budd wanted to understand this disease. His focus on research reached an almost crazy level. Even in the hot August, he would bring pigs that had ulcerated intestines and had been dead for three days to his home for dissection. In 1847, Budd found a typhoid patient in Richmond Terrace. Unlike ordinary doctors, Bud began to visit and investigate the surrounding areas. Bud found that there were 34 households in this area, 13 of which had people with fever, while the other 21 did not. Budd keenly noticed that the 13 households with fever used the same well, while the 21 households without fever used another well.[13] Does this mean that the onset of typhoid fever is related to water?

Image: William Bader (1811-1880)

In 1853, in the small town of Cowbridge in Wales, people held parties in the town's hotel for several consecutive nights. Unexpectedly, typhoid fever broke out. A total of 8 people died in this epidemic. So Bud started his investigation again. He interviewed the residents of the town again and again to learn the details of the epidemic, and finally he found a clue: the 8 dead had all drunk the same drink at the party-lemonade. But how did lemonade cause typhoid fever? Bud continued to track it down. It turned out that lemonade was made with well water, and near this well was the septic tank of the hotel. Can well water near the septic tank cause typhoid fever? Bud continued to investigate with this question, and finally found that a typhoid patient had stayed in that hotel shortly before the party. So, the feces of the typhoid patient contaminated the septic tank, and the well was too close to the septic tank and was also contaminated, so people who drank the well water would get sick. Does that mean that typhoid fever can be transmitted through contaminated water?

In 1866, Budd began investigating a typhoid outbreak in a farmhouse. Soon, residents near the farmhouse also contracted typhoid. This time, Budd discovered that the residents who later became ill and the farmhouse that first became ill all drew water and discharged water from the same river, and that the people who later became ill lived downstream of the farmhouse that first became ill. Now, the chain of evidence was complete. Combining his other research, Budd concluded that the feces discharged by typhoid patients contaminated the river water, and healthy people drank the contaminated river water and contracted typhoid. Typhoid is transmitted through fecal-oral transmission! So Budd proposed methods such as isolating patients, disinfecting feces and water with bleach, or boiling water before use to curb the spread of typhoid[14]. In 1873, his landmark work was published, titled Typhoid Fever.

William Bard's achievements in the field of infectious diseases were extraordinary. Without the intervention of bacteriology, he proved that diseases such as typhoid and cholera were contagious, and proposed the transmission routes and prevention methods of these diseases. It was not until 1880 that Karl Joseph Eberth discovered the pathogen of typhoid fever, Salmonella typhi, which is a gram-negative bacterium belonging to the genus Salmonella. Under a microscope, they look like short, thick sticks. They have flagella and can swim in water.

Figure: Salmonella typhi

Typhoid patients can excrete typhoid bacilli in their feces from the incubation period, becoming a source of typhoid infection. This is why typhoid is transmitted through the feces-oral route. Typhoid bacilli are relatively resistant and can survive low temperatures. They can survive in water for 2-3 weeks and in feces for 1-2 months. However, they are sensitive to chemical disinfectants. Boiling water can kill them, or heating to 60°C will kill them after 15 minutes. Therefore, pasteurization can kill typhoid bacilli. In order to combat infectious diseases such as typhoid and cholera, the world's major industrial countries gradually began to build sanitary facilities and improve water supply and drainage facilities in the late 19th century[15]. Later, chlorine was used to disinfect domestic water, so infectious diseases such as typhoid and cholera were reduced, especially in some wealthy areas with better conditions.

In 1896, British bacteriologist Almroth Wright invented the typhoid vaccine, and people finally gained an important weapon to fight typhoid. At that time, people thought that as long as they followed this method, disinfected well, and isolated patients, they could naturally avoid the spread of typhoid. But no one expected that typhoid would suddenly make a comeback in an extremely strange way, and it happened in the wealthy areas of the United States with good sanitary conditions. The "headless case" that occurred in the United States in the early 20th century refreshed people's understanding of infectious diseases.

Picture: Almroth Wright's Most Dangerous Cook

Long Island, New York, bordering the Atlantic Ocean, has beautiful scenery, charming beaches and lakes. It is an ideal resort for the rich in the United States, especially Oyster Bay on Long Island. Even US President Theodore Roosevelt liked to go there to cool off. In August 1906, banker Warren took his family and servants to Oyster Bay for vacation. But no one expected that typhoid fever would suddenly break out in such a well-equipped and tidy mansion. First, the little girl Margaret suddenly fell ill, and then Margaret's mother, maid, sister and gardener at home also fell ill. Among the 11 people in the mansion, 6 were infected with typhoid fever.

Picture: The wealthy area of ​​Oyster Bay The New York Health Department immediately intervened. They first tested the water used in the mansions, and found no problem, so they suspected that the local shellfish were contaminated, but after testing, they still found nothing. Finally, they tested the milk here, but still found no results. So where did the typhoid fever come from?

Until that winter, nothing was found. So public health expert Dr. George A. Soper took over and continued the investigation. Soper read all the investigation reports carefully and felt that the previous inspections were very rigorous and there were no problems. But typhoid fever could not happen for no reason. In order to find a breakthrough, he began to talk to everyone in the Warren family. Just as he was checking the number of people in the mansion, he discovered a detail: Mary Mallon, the cook of the Warren family, had resigned not long ago.

Mary went to work at the Warrens’ house on August 4, and the Warrens’ illness occurred between August 27 and September 3, which was consistent with the incubation period of typhoid fever! So Dr. Sober continued to ask Mary what food she had made. If the food could be cooked, it would not be easy to spread typhoid fever. Finally, Sober learned that shortly before the incident, Mary had made a very tempting dessert - fresh peach ice cream. It is impossible to heat ice cream and fresh peaches, and the cook Mary probably did not wash her hands during the production process. Thinking of this, Sober immediately continued to follow this clue [3]. He found the employment agency to inquire about Mary Malone’s situation, and the result surprised him.

Mary Malone was an immigrant from Ireland. She worked in eight families, and six of them had typhoid fever. However, what surprised Sober was that Mary herself was always healthy and had never been infected with typhoid fever. Could it be that people who were not sick could also spread typhoid fever? This was unbelievable to medical scientists at the time.

In March 1907, Sober finally found Mary, who was working at a house on Park Avenue in New York. Sure enough, when Sober found the house, he found that the family also had typhoid fever. Sober explained his purpose to Mary and hoped that Mary would cooperate with some examinations, but she refused. Mary even stabbed Sober's head with a fork. Fortunately, Sober ran away quickly and was not injured.

Mary's medical history

Nowadays, the COVID-19 pandemic has made us familiar with terms such as "asymptomatic infection" or "healthy carriers", but at that time, this was simply a fantasy. Mary insisted that she was healthy and refused to cooperate. Sober immediately reported the matter to the Health Bureau. After discussing with Sober, the Health Bureau felt that it might be better to send a female doctor to do the work, so they asked the gentle Dr. Josephine Baker to persuade Mary, but Mary still refused. So, the next day, Baker, with the assistance of three policemen, caught Mary after a five-hour search. Mary was abusing and resisting all the way. After arriving at the hospital, it was found that there were indeed a large number of typhoid bacilli in Mary's feces. In other words, although Mary was infected with typhoid bacilli, she did not get sick. Her body lived in peace with typhoid bacilli, but she kept excreting bacteria from her body. Mary was a "healthy carrier" with the ability to spread.

Photo: Josephine Baker

Sober explained to Mary: "When you go to the toilet, the bacteria in your body will get on your hands. If you don't wash your hands carefully, these bacteria will get on the food you touch. If these foods are not cooked, or if your hands touch them after they are cooked, others will be infected with typhoid fever if they eat them." But Mary refused to believe this. Not long after, Mary was transferred to North Brother Island for quarantine. [3] After this incident was reported by the media, the nickname "Typhoid Mary" spread. [16] Because of the media's exaggeration, Mary Malone was regarded as a scary woman with a shadow on her face who used human skulls as food in the minds of the American people. [17]

Two years later, in 1909, Mary filed a lawsuit in court, asking for her release, but the court did not support her. A year later, Mary promised the Health Bureau that she would no longer work as a cook, so the Health Bureau lifted Mary's isolation, but required Mary to contact the Health Bureau regularly and report her situation.

But not long after, Mary disappeared from the sight of the health department[18]. What no one expected was that five years later, in 1915, a typhoid fever outbreak suddenly occurred at the Sloan Women’s Hospital in New York, and more than 20 doctors, nurses, and care workers were infected. So the hospital invited Sobel, who had dealt with Mary Malone five years ago, to handle the case. After listening to people’s descriptions and checking the handwriting, Sobel immediately realized that the so-called “Mary Brown” was actually Mary Malone five years ago.

The New York police braved the freezing cold and tracked her down from New York to New Jersey, from New Jersey to Maine, and then from Maine back to Manhattan, and finally found her on Long Island. At the time, Mary was carrying a bowl of freshly made jelly to her friends when the police broke into her house and handcuffed and shackled her.[19] However, this time Mary did not resist and calmly followed the police.

Mary knew that she was sick but broke her promise, causing misfortune to others. This was condemnable, and she was sent to North Brother Island for isolation again. Until her death at the age of 69 in 1938, Mary never left North Brother Island again. She was isolated for 26 years. For Mary personally, this was her misfortune. But for the people of New York at that time, it was a blessing. Because with the medical conditions at that time, she was likely to cause a typhoid epidemic. However, thinking deeply, it was not Mary's fault to get sick. From a certain perspective, she finally safeguarded the interests of the majority of people in a self-sacrificing way (although forced) in the second half of her life and completed redemption. Starting with Mary, the term "healthy carrier" began to become familiar.

Photo: Mary's residence during isolation. Typhoid fever today

Typhoid fever was once one of the major infectious diseases in my country[20]. However, in earlier records, it was often recorded as "plague" along with other infectious diseases. Typhoid fever was once called "intestinal stasis"[21] in my country, and was also called "home destruction" by the people. Before liberation, typhoid fever was seen almost every year, causing a large number of deaths. In 1941, a typhoid fever outbreak occurred in Hunan, killing 620 people in Wugang County alone. After the founding of the People's Republic of China, with the improvement of environmental sanitation, the incidence of typhoid fever gradually decreased. After antibiotics entered the clinic, they became a powerful weapon against typhoid fever. Quinolones, cephalosporins, sulfonamides and other drugs can effectively treat typhoid fever. Now, typhoid fever has gradually faded from people's horizons in my country.

However, judging from the global situation, we still need to be vigilant. According to the World Health Organization, 11 million to 20 million people are infected with typhoid fever each year, of which 128,000 to 161,000 die. The risk is higher in people who lack safe drinking water and proper sanitation. Traveling to typhoid-endemic areas is still a potential risk, and typhoid vaccination should be carried out.
Looking back at the history of human struggle against typhoid fever, the story of Mary Malone left the deepest impression on me. It can be said that she posed a complex ethical dilemma for human beings: when the interests of a few people conflict with the interests of the majority, how should we choose?

If another Typhoid Mary appeared today, and she had done nothing wrong, do we have the right to isolate her for life?

The COVID-19 pandemic in 2020 has made everyone aware of "asymptomatic infections". In fact, every asymptomatic person is a "Typhoid Mary", but the latter is sometimes an insulting nickname. Starting this year, the entire human society will learn how to get along with countless "asymptomatic people", and a new medical ethics will be born under our witness. Although it is difficult for me to accurately predict how the citizens of each country will treat asymptomatic infections, one thing I am sure of is that we will no longer be as afraid as we were when we first faced "Typhoid Mary".

Image: Mary Malone's tomb

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Mao Lixia. Study on Typhoid Fever and Public Health Reform in 19th Century England[J]. History Teaching, 2020,(8): 52-59. https://kns.cnki.net/kcms/detail/detail.aspx?dbcode=CJFD&dbname=CJFDLASN2020&filename=LISI202008008&v=U2sTeXGBAjBi68wBu1LoIuJa1fii9Zrxqx9qOM%mmd2FOr fLB2W6GXh8PQ0hNBG1G%mmd2BBQO&uid=WEEvREcwSlJHSldTTEYzVDhUQ05ZSjZyZ2gvSkthe lU4WVJ2aHdRanVmcz0=$9A4hF_YAuvQ5obgVAqNKPCYcEjKensW4IQMovwHtwkF4VYPoHbKxJw

Robert Moorhead, MD FRACGP.William Budd and typhoid fever[J]. JR Soc Med. 2002 Nov; 95(11): 561–564.doi: 10.1258/jrsm.95.11.561. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1279260/

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Wang Jun, Wang Nishuang. What is a "patient": the "Typhoid Mary" incident and the shaping of the concept of "healthy carrier"[J]. Chinese Journal of Science and Technology History, 2020, 41(3):416-424 http://d.wanfangdata.com.cn/periodical/ChlQZXJpb2RpY2FsQ0hJTmV3UzIwMjAxMjI4Eg96Z2tqc2wyMDIwMDMwMTQaCDZ0MnRzbDdr

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959940/figure/F1/

Author's note: There are different descriptions about the time when Mary lost contact. Some sources say that Mary lost contact half a year later, while some sources say that she lost contact in 1913, but it is a fact that she lost contact for a long time.

https://web.archive.org/web/20101218233409/http://isbe.net/career/pdf/fcs_guide.pdf

Yin Huan, Gao Dongping, Lin Weiwei, Du Ranran. Research on the progress of infectious disease prevention and control in my country[J]. Journal of Medical Informatics, 2019, 40(8):1-8. https://d.wanfangdata.com.cn/periodical/ChlQZXJpb2RpY2FsQ0hJTmV3UzIwMjAxMjI4Eg95eHFiZ3oyMDE5MDgwMDEaCGF2eHVqYWNw

Zhang Taishan. Analysis of legal infectious diseases during the Republic of China period[J]. Chinese Journal of Medical History, 2007, 37(4): 215-217. https://d.wanfangdata.com.cn/periodical/ChlQZXJpb2RpY2FsQ0hJTmV3UzIwMjAxMjI4Eg96aHlzenoyMDA3MDQwMDYaCDN4MjI2dW1k