Typhoid Mary and the global rise in typhoid cases today

Tiny Matters

Typhoid fever is a disease that, in the United States, is synonymous with Mary Mallon—a woman better known as Typhoid Mary, who infected New Yorkers with typhoid in the early 1900s. But typhoid is not just a thing of the past. Across the globe every single year, it kills over 100,000 people. And over the last few years, even in countries like the US where typhoid hasn’t been a concern for generations, the number of reported cases is climbing. So why is typhoid making a comeback? And what are scientists doing to stop it?

Transcript of this Episode

Sam Jones: In 1884, a teenager by the name of Mary Mallon emigrated from her home country of Ireland to the United States. And, not too long after arriving, she started working as a cook for  wealthy New Yorkers.

In 1906, Mary was hired at a wealthy banker’s summer house on Long Island. Soon after, people staying at the house came down with typhoid fever.

Deboki Chakravarti: Typhoid fever is caused by bacteria and typically spreads through water and food. And the symptoms are really serious. A person infected with typhoid fever can run a temperature of around 104 degrees fahrenheit for days on end, while also usually suffering from super intense stomach pain and a whole list of other unpleasant symptoms. In the most extreme cases, typhoid fever can cause internal bleeding and death. And, back in the early 1900s, it killed 2 to 3 people out of every 10 infected.

Sam: So after the typhoid outbreak at this swanky Long Island home, a man named George Soper was hired to try to figure out where it came from. Soper was a sanitary engineer, so his job was to look at waste removal in communities, with the goal of keeping drinking water safe. His first inclination was that these people got typhoid from local freshwater clams. The bacteria that causes typhoid fever is found in human feces, so he figured the water the clams were growing in could have been contaminated with sewage. When it turned out that wasn’t the case, Soper started digging deeper. That led him to a trail of wealthy families who had also been infected with typhoid. And there was a common denominator in all of those outbreaks: Mary Mallon.

Welcome to Tiny Matters, I’m Sam Jones.

Deboki: And I’m Deboki Chakravarti. Today on the show, Sam and I are covering typhoid fever: a disease that, in the United States at least, is synonymous with Mary Mallon—a woman better known as Typhoid Mary.

If you live in the US, you’ve probably only heard typhoid talked about as a thing of the past, but it’s not. Across the globe, every single year, tens of millions of people are infected and over 100,000 of those people die. And over the last few years, even in countries like the US, where typhoid hasn’t been a concern for generations, the number of reported cases is climbing.

So in this episode we’re asking, “Why is typhoid making a comeback? And what are scientists doing to stop it?”

Sam: Back in 1907, sanitary engineer George Soper figured out that this was not Mary’s first typhoid rodeo. She had worked as a cook for at least eight other families before showing up in the home on Long Island. Seven of those eight families had also experienced a typhoid outbreak, some family members had even died.

And through all of it, Mary was fine—never critically ill, never spiking a 104 degree fever. How was that possible?

Deboki: Mary Mallon was asymptomatic.

Jeongmin Song: An asymptomatic carrier is actually a real concern for typhoid fever. They don't have any symptoms. Usually the individual doesn't know they got infected.

Deboki: That’s Jeongmin Song, a professor of microbiology and immunology at Cornell University.

When I hear the word “asymptomatic” my brain goes right to COVID-19. Maybe yours does too. The concept is the same—if someone is asymptomatic it means they’ve been infected with a virus or bacteria or whatever other microbe and they feel fine. But the microbe stays in their system and can still be passed on to other people, who might get really sick. In fact, 1 to 6 percent of people infected with the bacterium that causes typhoid fever become asymptomatic carriers, just like Mary Mallon.

Sam: Who, by the way, was not the first person to get or spread typhoid. Not by a long shot. Typhoid has been around for millennia. I mean, it’s thought to have been what caused the “plague of Athens”—an epidemic in 430 BCE that many believe killed the Athenian leader Pericles along with a third of the city’s population.

So now let’s talk about the bacterium that causes typhoid fever: Salmonella Typhi.

Deboki: There are so many types of Salmonella bacteria out there that do not cause typhoid fever and also don’t live in humans, but are instead passed from other animals to us. Like the Salmonella spread through raw or poorly processed meat, eggs, fruits, and veggies—the one that causes grocery store recalls and gives millions of people food poisoning each year. That’s typically Salmonella enterica serotype Enteritidis and Salmonella enterica serotype Typhimurium.

Sam: The serotype of a bacteria is based on the molecules on its surface. There are over 2,600 Salmonella serotypes, but the one that causes typhoid fever is Salmonella enterica serotype Typhi. To keep things simple for this episode, we’re just going to call it Salmonella Typhi or Typhi bacteria.

Deboki: So say you’ve had food or water that’s contaminated with Typhi bacteria. That bacteria first travels to your stomach, and if it survives all that stomach acid, it heads to your intestines where it can hang out for a week or so. From there it can get into the tissue lining your gut and then make its way to your bloodstream, where it can travel pretty much anywhere, including your organs, even your bones.

Symptoms normally start 6 to 30 days after someone is exposed. The two major symptoms of typhoid are a rash and, of course, a fever. And without treatment, most people will also experience gastrointestinal bleeding, which can lead to sepsis. Typhoid can also cause swelling in the brain, heart, spleen, liver…it’s just really, really awful.
Sam: There are still a lot of unanswered questions about how Salmonella Typhi causes all of these symptoms but scientists do know that a toxin it produces—called typhoid toxin—plays a really big role. Typhoid toxin is made up of a combination of proteins. A couple of years back, Jeongmin and her lab discovered that one of those proteins will locate immune cells by zeroing in on specific sugars sticking off of them. Then the other proteins that make up the typhoid toxin will help it enter the cells and damage them.

Deboki: If someone gets diagnosed with typhoid, they’re treated with antibiotics. But this is becoming less of a guaranteed cure, and we’ll get to why in a minute.

Luckily there are ways to prevent getting typhoid. If someone lives in or is traveling to a place where typhoid fever is endemic, meaning it’s pretty common, then they might be vaccinated for it. There are two widely available vaccines: one is injected and uses a piece of the bacteria, and the other is a tablet taken orally and is made of a weakened form of the bacteria. Over the last few years, scientists have shifted their focus to another type of vaccine, called a conjugate vaccine.

Sam: Conjugate vaccines combine a piece of the thing you’re vaccinating against—like something sticking off the typhoid bacteria’s surface—with an additional molecule that triggers a bigger response from your immune system. The goal is to help you build stronger, longer-lasting immunity.

That being said, all of the vaccines currently available for typhoid… could be better.

Jeongmin: Similar to other vaccines, typhoid vaccines are not one hundred percent effective. Depending on the individual, you know, 50 to 80% vaccine efficacy has been reported.

Deboki: So the vaccines have reduced cases globally, but there are still upwards of 100,000 people dying of typhoid each year. A lot of the victims are very young kids and babies. And that’s partly because the vaccines available are not given to patients under a certain age or they’re even less effective in young kids. Helping kids was a big motivator for Jeongmin to study typhoid.

Jeongmin: I want to do something meaningful. Since I was trained as a microbiologist I was thinking about, you know, what bacteria pathogen actually causes deadly disease and one of the pathogens was Salmonella Typhi. And I found that these innocent children in developing countries are actually one of the primary targets mostly affected by typhoid fever.

Sam: Jeongmin and her lab are really focused on the typhoid bacteria and the toxin it produces. She wants to understand how typhoid toxin gets into our cells and destroys them, and how our immune system responds. Because knowing all of that could help researchers create a more effective vaccine and target typhoid bacteria that are resistant to current antibiotics.

For years, antibiotics like penicillin did the trick. But now, the bacteria has mutated so much that even newer antibiotics are failing.

Without a really effective vaccine or effective antibiotics, we’re not all that better off than people were in the time of Mary Mallon. Okay, maybe that’s a little dramatic—medical care has advanced a lot since 1907. Thank goodness. But still—this is pretty bad.

Jeongmin: Antibiotic resistance—that is actually a really big concern. In a typhoid fever endemic country, nearly all Salmonella Typhi isolated from those countries are extensively drug resistant Salmonella Typhi strains, meaning that most of all antibiotics available are not really, you know, working. In addition, typhoid fever patients infected with extensively drug-resistant Salmonella Typhi are reported in many developed countries, including the United States.

Deboki: Jeongmin and her lab are also analyzing different Salmonella Typhi strains to predict how certain genetic changes might make them more or less susceptible to current vaccines and antibiotics. They’re particularly interested in strains circulating in endemic countries.

Sam: One country where typhoid is endemic is Malawi. Malawi’s in Sub-Saharan Africa, sandwiched between Zambia, Mozambique and Tanzania. Microbiologist Chisomo Msefula has been studying typhoid there for well over a decade. Today he’s a professor at the Kamuzu University of Health Sciences. And he told us that, for a while, the number of cases in Malawi were relatively low—every year, from 1997 to 2010 there were around 40 cases of typhoid fever per every hundred thousand people.

Chisomo: But then suddenly in 2011, there were 67 cases. And then I think two years later we had 800 cases of typhoid. The status of typhoid has changed over the years where we used to get typhoid that was sensitive to most of the antibiotics, but then this large surge of cases ended up with typhoid that was resistant to the three common antibiotics that you’d easily find for treating typhoid.

Deboki: In addition to antibiotic resistance, Chisomo told us that a rise in cases could be caused by new Salmonella Typhi strains introduced from other countries. The typhoid strains that have come to Malawi more recently are pretty similar to those that have been circulating in South and Southeast Asia for years.

Sam: In the last couple of years, the number of typhoid cases has been between 400 and 500 per 100,000 people. And although 400 or 500 is considered a large number of cases, Chisomo thinks the number is a lot higher. He says that many of the current diagnostic tools for figuring out if patients have typhoid fever are only around 50% sensitive, so there could be a lot of cases that are going undetected which, again, adds to the bacteria’s spread.

Deboki: Having more sensitive, accurate diagnostics won’t just help prevent the spread of typhoid fever—they’ll more accurately separate the patients with typhoid from those who have a disease with similar symptoms, like yellow or dengue fever or malaria, and ensure that all patients can receive appropriate treatment and aren’t accidentally treated for the wrong disease.

Chisomo: So apart from the lack of proper diagnostics—typhoid is being reported mostly in countries that are low income. So it's related to having clean water, proper sanitation and hygiene. So those are things that are actually hard to come by for a size of the population within our setting. But also when you’re implementing some of these prevention or control measures—if it's linked to sanitation or hygiene, I mean these are matters that are beyond the scientists, it’s socioeconomic. You are looking at a problem that you want to address, but then it also needs to be addressed by looking at a larger—the larger picture.
Sam: Chisomo is realistic about the barriers that exist beyond the science that might make it harder to get the vaccine to places where people are more at risk for typhoid, where there aren’t proper latrines or consistently clean water. It’s an important reminder of how intertwined science and society are.

Deboki: And it’s a reminder to people who may be in a place like the US—where Sam and I are—that just because a disease isn’t very common where you live doesn’t mean it still isn’t really deadly in parts of the world that may not have the same resources to control it. And remember, typhoid wasn’t all that common in Malawi, either, until the last decade.

Sam: There is, however, a bright spot on the horizon. Over the last 2 years in Malawi, researchers have been trialing a new typhoid conjugate vaccine. 28,000 children in Malawi’s capital took part in the study, and they ranged in age from 9 months to 12 years old. And the vaccine was found to be both safe and effective which is a huge deal.

Chisomo: The good news is that they found efficacy of over 80%. We are moving towards a phase where we have a vaccine that targets not just two years and above, we can even go lower, but also the efficacy is higher than the vaccine that was there before. So we are at a phase, I think, where we might be seeing the vaccine rolled out this year. It's just a matter of implementing it properly, getting the messages out there, making sure that we're not getting any challenges in terms of what we've seen with COVID misinformation and other things, but I think we're on the right track.

Sam: So now let’s travel back to 1907. Sanitary engineer George Soper had put together that Mary might be behind the Long Island summer home outbreak, and many other typhoid outbreaks before it. So he went to confront her. She was already at the next residence where she was, again, working as a cook.

Deboki: He showed up and asked for some feces and urine samples…

Sam:...as one does. Not off putting at all.

Deboki: Right. Well the story goes that Mallon was not pleased at all and ran at Soper with a carving fork.

Sam: Yikes, but also what’s a carving fork?

Deboki: Good question. A carving fork is that 2-pronged fork you’ve probably seen used by someone cutting a Thanksgiving turkey.

Sam: Ok, got it. Still yikes. Please continue.

Deboki: So then a public health worker was sent to get samples. Her name was Josephine Baker, and she’d actually become the first woman to earn a doctorate in public health. She was also chased away by Mallon. But Baker came back, this time with five policemen in tow, and Mallon was finally taken to the hospital where she tested positive for Salmonella Typhi. She was then quarantined in a small house on the hospital grounds.

Sam: Remember, Mary Mallon was asymptomatic so she felt fine and did not believe people when they were telling her she was sick. Historians and scientists have written about how Mallon, in all likelihood, did not understand the concept of being a carrier. So when she was told that she could be cured by getting her gallbladder removed, because it’s an organ where Salmonella Typhi is known to hang out, she refused. And, shortly after, a popular newspaper of the time—the New York American—dubbed her Typhoid Mary.

Deboki: And Mallon was angry. So angry that she sued the New York City Department of Health and the case made it to the Supreme Court, her lawyer arguing that she had been imprisoned without due process. The court said no, they wouldn’t release her on the grounds of needing to protect the community against the spread of typhoid fever. But the next year New York City had a new health commissioner and he agreed to release her if she would stop working as a cook.

Sam: Fast forward 5 years later, in 1915, and 25 people at Sloane Maternity Hospital come down with typhoid fever. George Soper was again called to investigate and figured out that the cook who went by “Mrs. Brown,” was actually Mary Mallon.

Deboki: And that was the final straw. Mary Mallon was sent to an island off the coast of New York and quarantined there until she died of a stroke 25 years later.

Sam: Mary Mallon’s story is one where, at least for me, I constantly find myself saying “lady, come on, are you serious? Like they told you that you have typhoid and cannot be a cook because people could die and you’re still cooking and infecting people.” But on the other hand, it’s just all so incredibly sad. The whole asymptomatic thing was probably not explained well. And I think today we’re so tuned into that concept because of COVID but maybe Mary Mallon had never heard that term before and thought it was complete nonsense and just wanted to cook because she was apparently a good cook.

Deboki: Yeah it’s definitely one of those stories that’s kind of infuriating when you hear about it because there were people who got really sick that wouldn’t have if Mary Mallon took her diagnosis seriously. But, at the same time, the communication seemed so bad. Plus, by the time she died over 400 other asymptomatic carriers of Salmonella Typhi had been identified in New York and, based on what I’ve found, none of them had been given an embarrassing name or had their face plastered in the paper or were locked away on an island for the rest of their life.  

Sam: So that is the interesting, super depressing story of Mary Mallon. And I think it’s fair to say that it’s also a reminder of the importance of effectively communicating medicine and other science to people. Just a closing, totally unbiased, thought.

Deboki: Completely unbiased.

Thanks for listening to Tiny Matters, a production of the American Chemical Society, a non-profit scientific organization based in Washington, DC. Tiny Matters is hosted by me, Deboki Chakravarti, and Sam Jones who is also our executive producer and audio editor.

Sam: This week’s script was edited by Andrew Sobey and was fact-checked by Michelle Boucher. The Tiny Matters theme and episode sound design are by Michael Simonelli, and our artwork was created by Derek Bressler. Thanks to Chisomo Msefula and Jeongmin Song for chatting with us.

Deboki: If you haven’t rated and reviewed us on Apple Podcasts, Spotify, Stitcher, Audible, or wherever else you listen, please do!

Sam: Also, if there are some tiny things that you think matter and that you’d love us to explore in an episode, shoot us an email: tinymatters@acs.org.

Deboki: We’ll see you next time.


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