Cheap shots — typhoid vaccine shows broad coverage

A new trial suggests that a shot confers immunity across age groups for three years.

An inexpensive vaccine against typhoid fever offers protection across age groups and is particularly effective in preschool-age children, a large trial in India finds. The same study shows that vaccinating half the people in a neighborhood confers significant protection throughout its population, researchers report in the July 23 New England Journal of Medicine.

TYPHOID’S REACH This map depicts areas where typhoid is endemic, or naturally recurring. A large study in India shows that vaccination against typhoid fever can limit the disease’s spread in entire neighborhoods, even among people who aren’t vaccinated. (Map sources: CDC/WHO) Janel Kiley

Despite the availability of two approved vaccines, many countries have lagged in their efforts to confront typhoid, which strikes 21 million people each year and causes 200,000 to 600,000 deaths worldwide.

In the new study, an international team took an unusual approach to gauge the public health effect of one of the vaccines. In late 2004, the researchers vaccinated more than 37,000 people in the slums of Calcutta. People in some neighborhoods received an injection of a typhoid vaccine called Vi, while half the people in other neighborhoods, serving as a control sample, received hepatitis A vaccinations.

The scientists vaccinated roughly half of the people in each neighborhood and arranged for clinics and hospitals to track any subsequent cases of fever that might be typhoid.

After two years, the researchers found that people who had received the typhoid vaccine had 61 percent fewer cases of the disease than did those who got the hepatitis shot. In children ages 2 to 5, a high-risk group, there were 80 percent fewer cases, says study coauthor John Clemens, a physician at the International Vaccine Institute and Seoul National University in South Korea. 

Unvaccinated neighbors and relatives of people receiving the typhoid vaccine gained some protection, too. There were 57 percent fewer cases of typhoid overall in neighborhoods in which half of the people received the typhoid shot compared with neighborhoods where people got the hepatitis shot. That drop was not solely attributable to fewer cases among people who had been vaccinated.

“I find this plausible,” says pediatrician and vaccine researcher Myron Levine of the University of Maryland School of Medicine in Baltimore. Researchers have seen similar indirect protection with pneumococcal vaccines, he says. “It makes sense that this could happen with typhoid.”

Scientists call this indirect coverage “herd immunity” or “community immunity.” By vaccinating some people, pathogens have fewer targets to infect. Since typhoid is typically spread by feces-contaminated food and water, having fewer sick people spreading the microbes lessens overall disease risk.

The new study was funded by the Bill and Melinda Gates Foundation, and the vaccines were donated by GlaxoSmithKline. The Vi vaccine uses a polysaccharide molecule found on the typhoid microbe to impart a degree of immunity that lasts three years. It doesn’t work in those under age 2, but it is inexpensive — as little as 50 cents per dose. It’s also no longer patent protected, Clemens notes.

Regulators approved the Vi vaccine for use more than a decade ago, as well as another vaccine that requires several oral doses but engenders longer-lasting immunity. Still, the nature of typhoid has limited the use of both vaccines, Clemens says. For example, lab tests needed to confirm typhoid are often unavailable in parts of developing countries, he says. That leaves many cases undetected and may lead governments to underestimate typhoid’s prevalence.

What’s more, Clemens says, “typhoid rarely causes explosive, highly publicized epidemics, but tends to cause steady endemic disease that is less well recognized.”

“We believe that this study will strengthen the case for vaccinating against typhoid,” he says.

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