A TASTE FOR TYPHOID
Experimental vaccine requires test subjects to ingest live bacteria — but it works,
“I was curious.” That is how James Duggan, an Oxford University medical student, explains why he agreed to swallow a big dose of live typhoid bacteria.
“This may sound odd,” he continued, “but as a medical student, it’s quite interesting to go through the process of being very ill. It does help to create empathy for your patients.”
Duggan, 33, was not on a self-destructive sympathy bender. Like more than 100 other residents of Oxford, England, he was taking part in a trial of a new typhoid vaccine.
Typhoid fever, caused by the bacteria Salmonella typhi and spread in food and water, kills almost 200,000 victims a year — many of them young children — in Africa, Asia and Latin America. Survivors may suffer perforated intestines, heart problems and other complications.
The experimental vaccine was a big success. The trial’s results were published recently in the Lancet: the vaccine turned out to be 87-per-cent effective.
It is the only effective vaccine that is also safe for infants, and already it is made cheaply and used widely in India. The Oxford Vaccine Group, which ran the trial, and the Bill & Melinda Gates Foundation, which paid for it, hope the World Health Organization will endorse the vaccine soon.
“These are great results,” said Dr. Anita Zaidi, the foundation’s director of diarrheal diseases. “And challenge tests are a great way to short-circuit the process of proving it works.
“If we’d done this in the field, we would have had to follow children for three or four years.”
So-called challenge tests involve giving subjects an experimental vaccine and then deliberately infecting them with the disease to see if it protects them.
These tests can only be done with illnesses — such as cholera or malaria — that can be rapidly and completely cured, or with diseases — such as seasonal flu — that usually do not damage healthy adults.
Still, there was a good chance that the participants in Oxford would be unpleasantly sick with typhoid fever for several days until their antibiotics kicked in.
So what would motivate dozens of well-educated Britons to swallow a vial full of the germs that made Typhoid Mary famous? In interviews, they gave various reasons.
Some, like Duggan, were curious. Some wanted to help poor people. And some mostly wanted the cash.
Participants who followed all the steps, which included recording their temperatures online, making daily clinic visits and providing regular blood and stool samples, received about $4,000. They all said they understood the risks.
Typhoid got its fearsome reputa- tion in the preantibiotic age, but these days it usually can be driven out of the body with common antibiotics, such as ciprofloxacin or azithromycin.
All participants had to be healthy adults, ages 18-60, with ultrasound scans proving their gallbladders were stone-free.
(The bacteria can persist for decades by clinging to gallstones — which is probably how Typhoid Mary, working as a cook in grand houses and a maternity hospital, infected so many people between 1900 and 1915 without ever feeling ill herself.)
Different participants had very different experiences.
Duggan was sick for three days with flu-like symptoms: “proper flu, where you don’t want to get out of bed,” he said. His temperature rose to 38.8 C and he had joint pains and a bad headache.
Once a blood culture proved he had typhoid, he got antibiotics right away; he was not released from treatment until three typhoid-free blood and stool samples proved he was out of danger.
He later was told that he had been in the trial’s placebo arm and had received a meningitis vaccine instead. (Modern ethics boards frown on useless “sugar pill” placebos.)
Nick J. Crang, 24, a graduate student in proteomics, also got the placebo. But somehow he never got sick, even after two typhoid challenges a year apart.
“It turns out I’ve got innate immunity to typhoid,” he said.
So does he feel superhuman? “No, I’m the lab rat who’s screwing with the figures.”
He did give extra blood samples to researchers curious about his immune system.
Faye Francis, a 42-year-old psychiatric nurse, said she felt “happy to be doing something that could help millions of poor people who haven’t got antibiotics.”
“But I won’t lie,” she added. “The money was a big part of it.”
She used it to take her husband and three children on a vacation in Cornwall “and buy a few bits for the car and the house.”
Her mother was not happy. “She said, ‘That’s ridiculous — don’t think about the money, think about your health!’ ” Francis said. “And people were telling me horror stories about things they’d seen on TV. So I didn’t go on about it to my parents after that.”
She got sick and “felt rotten for about a week” with a 38.3 C fever, headache and nausea.
“But I still went to work,” she said. “I felt a bit guilty about not going when I had an illness I’d given myself.”
Because her job is to distribute medicine on home visits, no patients were endangered, she said. (Duggan, the medical student, was also quick to say that he took part during a period when he was not assigned to hospital rounds.)
“And you’re not allowed to handle food, so my husband did all the cooking,” Francis said.
During the worst week, “you feel sorry for yourself and you say ‘I’m never doing that again,’ ” she said. “And then it’s like childbirth — you get amnesia, and you do it again. I’ve just signed up for a second trial.”