Drink Up! Volunteers Swallow Bacteria That Causes Typhoid

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If somebody asked you to drink a solution filled with live bacteria that can cause typhoid, you'd probably say ... no.

But more than 100 healthy adults visited an Oxford clinic within the past two years to take a gulp of faith. They swallowed a swig of bacteria to help scientists test a new vaccine for fighting typhoid, a disease spread through contaminated food or water and affecting 21 million people per year, particularly in south Asia and sub-Saharan Africa. As a result of those trials, researchers were able to prove that a new typhoid vaccine is the most effective yet, according to a study led by the Oxford Vaccine Group in The Lancet.

"I think they did a beautiful job," says Myron Levine, the University of Maryland School of Medicine's associate dean for Global Health, Vaccinology and Infectious Diseases, who was not involved with the study. "Unless you have experience trying to do this kind of study, you can't fully appreciate how hard it is to bring participants in and get them to do the challenge."

This study is not the first to rely on healthy volunteers willing to expose themselves to serious diseases. In 1959, scientists at the University of Maryland began inoculating volunteers and exposing them to typhoid. The model worked; over 16 years, researchers recruited almost 1,900 volunteers and published numerous studies about resistance to the disease, including proving the efficacy of a typhoid oral vaccine. But the researchers recruited among prison inmates, prompting a lawsuit from the American Civil Liberties Union, which charged that the prisoners were coerced into participating. The suit was unsuccessful because the ACLU could not prove its case. Nonetheless, the Prison Volunteer Research Unit at the University of Maryland closed in 1974.

The model of human guinea pigs, however, has endured. Inoculating healthy volunteers and exposing them to disease has a couple of advantages, according to Andrew Pollard, director of the Oxford Vaccine Group and lead author of the recent paper. In more traditional field studies, researchers must vaccinate a large group of people and hope the participants naturally come into contact with the targeted disease in order to test the vaccine's effectiveness. But there's no guarantee participants will be exposed to the disease. What's more, people living in an area where a disease is prevalent might have some immunity already.

By contrast, giving healthy volunteers typhoid bacteria concoctions in a place like the United Kingdom, where typhoid is incredibly rare, virtually guarantees participants with no preexisting immunity from exposure to typhoid. "It's a really important way of trying to establish efficacy early in the development of vaccines," says Pollard.

To recruit roughly 100 participants, Pollard's group reached out to tens of thousands of people through social media, radio advertisements and website posts. Pollard says the team made sure participants understood the nature of the study before they enrolled. The researchers divided the participants into three groups, each of which received a different vaccine: the new typhoid vaccine, launched in 2013, a more commonly used typhoid vaccine prescribed for travelers or a control vaccine that did not offer any resistance to typhoid.

One month later, the participants swallowed a mixture of typhoid-causing bacteria and sodium bicarbonate to weaken their stomach acid. (Stomach acid can help humans resist typhoid.) For the next two weeks, the participants visited an outpatient clinic daily to be checked for signs of typhoid. Those who developed typhoid were immediately treated at no personal expense, generally through antibiotics.

Roughly half of the participants who received the new vaccine did not contract typhoid. Those results are more promising than they sound, according to Pollard, because the study's participants are exposed to typhoid under conditions that are more favorable to the disease than would normally be the case.

"We make it very hard for the vaccine," Pollard explains. "We give very big doses of typhoid, and we neutralize acid in the stomach to make it easier for the typhoid to cause infection." Extrapolating from the volunteer rates, the researchers suggest the vaccine would have an effectiveness rate of 87 percent.

The new vaccine has two important advantages over preexisting typhoid vaccines. It's the first to be effective in infants, a particularly vulnerable group for typhoid. And researchers believe it provides protection for a longer period than previous typhoid vaccines —potentially up to five years as opposed to a couple of years.

Both Pollard and Levine say they hope the new study will prove useful to the World Health Organization, which is meeting in October to determine whether to recommend the new vaccine as part of a strategy to combat typhoid. Levine says he hopes the experiment's model can next be applied to paratyphoid, a disease caused by a similar bacterium to the one causing typhoid.

That means recruiting more healthy volunteers to guzzle bacteria-laden cocktails. And to do that, it's helpful to understand why people join such studies in the first place, especially for diseases that don't directly affect the country where they live. To answer that question, Pollard's group surveyed participants to learn their motivations.

Participants are reimbursed for travel and lost income during their participation, but Pollard was surprised to hear that money was not the driving factor. "We've asked if people would still participate if hypothetically the amount of money paid were reduced, and we never had anyone say 'no,' " says Pollard. "What comes through very clearly in these surveys is that these people or their relatives have had health difficulties of their own. They want to give back to science."

Natalie Jacewicz is a freelance writer and law school student. Follow her @NatalieJacewicz.