Typhoid fever.
Simply put, it’s a bacterial infection that comes largely from contaminated food, water,
or sewage.
But it’s not just a fever, typhoid can tear holes in your intestines and infect many other
organs in your body.
Oh, and it’s uniquely evolving to become more and more drug resistant.
Typhoid fever is caused by a salmonella bacteria, but not the salmonella you’re probably thinking of.
So the salmonella typhi bacteria is different from the salmonella that you might see in
the U.S., which is the foodborne salmonellosis.
I'm Anita Zaidi and I'm the director for the Bill and Melinda Gates Foundation’s Enteric
and Diarrheal Disease team and the vaccine development and surveillance team.
One of my reasons that I was very attracted to working at the foundation was there was
an interest in working on diseases of the poor.
And Typhoid was one of the problems that I thought I could solve.
So while salmonellosis is transmitted via infected animals and it consumed usually on raw
meat or eggs.
Typhoid is different in that it only infects humans.
But it is pretty good at surviving outside its human host until it gets picked up
again, like by someone drinking contaminated water.
So what happens when, let's say that you drink 100,000 organisms of salmonella?
First it goes to your stomach, right?
And over there, if you're a healthy person and you have lots of stomach gastric acid,
which healthy people should have. Most people will actually, the stomach acid will kill those salmonella
and you won't get sick.
But children, and some adults, who don't produce a lot of stomach acid have a higher susceptibility
of getting a typhoid infection.
If the typhoid bacteria aren’t killed by stomach acid like they should be, they travel
to the terminal part of the small intestine and enter the cells lining the intestines.
This provokes a massive immune response.
What happens is the inflammatory response is unconstrained, or too much, and it punctures
a hole in the intestine where the inflammation, inflammatory response is happening.
So basically ulcerates, if that's a good way of thinking about it.
Like a pustule almost think about it, right?
When you get a pustule and that pustule bursts, that's what happens inside the intestine because
you have all of those white cells together eating away the tissue.
Now your bowel contents are coming out in your abdomen and then that makes people very,
very sick.
From here they get into lymphoid tissue underlying the enterocytes, called Peyer’s patches
and then into the bloodstream and spread widely to many organs of the body, especially the liver,
spleen, and bone marrow.
They also re-enter the intestine through the bile draining from the liver into the gallbladder
and then upper intestine so they can be excreted in feces and spread to other people.
In some cases, the typhoid bacteria cause ulceration of the Peyer’s patches all the way through
to the outer lining of the terminal ileum resulting in a perforation of the small intestine,
a very dangerous condition that can kill unless repair can happen through open abdominal surgery.
The bacteria spreads ferociously to other organs like the brain, heart, and pancreas.
Inflammation then occurring in these areas can cause pancreatitis, meningitis, and a
whole host of other problems.
These are the most serious complications of typhoid and they happen after already being
sick for 2-3 weeks..
Leading up to this, the patient feels extreme fatigue set in and a fever that can gradually
increase to dangerously high levels.
Other symptoms include headache, muscle aches, loss of appetite, diarrhea, and a rash.
Diarrhea flushes the salmonella typhi out of its human host and back into the sewage system.
From here, the bacteria can spread rapidly in areas with poor sanitation.
This is what’s known as the fecal-oral route of transmission.
So you start having fever and slowly the fever gets worse and worse and worse over time because
the organism makes you sick slowly.
Instead of very fast.
So if a bug gets in you and it kills you very fast, it can't be spread.
But typhi is very clever.
So what it does, it doesn't kill you fast.
It kills you slowly.
And by that time you already spread the infection to other people.
It's a survival tactic for typhi.
Throughout the process, the bacteria evades the immune system by living inside of human cells.
And since it can live inside macrophage cells in the bloodstream and tissues, it can evade
the immune system for some time.
The good news is typhoid can be treated with antibiotics.
The bad news is that some drugs that were highly effective in the past can no longer
combat the more evolved strains of salmonella typhi.
These are what are known as “Extensively Drug-Resistant” or XDR.
Now, there's very few drugs that are left to treat it, if you have the XDR type of typhoid.
… Which is why it was so important to have vaccines for typhoid.
And so until recently we did have some vaccines, but those vaccines worked only in older people.
So older than six years old.
Some of the really exciting work on typhoid has been around actually developing
what we call a conjugate vaccine.
The protein-carbohydrate conjugation makes the vaccine work for very young children,
as their immune systems aren’t fully developed to handle carbohydrate antigens by themselves.
In a small number of cases after someone has recovered from typhoid, the bacteria will
live on, hiding out in their gallbladder.
These people are known as carriers and can infect the people around them.
And that's the story of the famous Typhoid Mary who wasn't sick, but actually had a really
high infection burden of salmonella typhi and she was a cook in New York.
And so whichever family she would go and work for, there would be an outbreak of typhoid,
and eventually they had to put her in confinement so that she couldn't spread the infection anymore.