For the past 25 years, UCSF scientist Philip Hopewell has been helping the City and County of San Francisco control tuberculosis (TB).
At the same time, Hopewell has been using his laboratories at San Francisco General Hospital to conduct research that is helping physicians around the world fight the disease. Recently, he and colleagues from other institutions spent a year drafting a document for the World Health Organization (WHO) defining the essential elements of care for TB.
TB is a life-threatening bacterial infection that predominantly affects the lungs. It has plagued humans for millennia. Even 5,000-year-old Egyptian mummies show signs of infection. The disease is also widespread: the WHO estimates that 2 billion people - one-third of the human population - are currently infected, and over 1.5 million people die every year from the disease. The infection can lie dormant for years before advancing into the full-blown disease. It can be cured with drugs that cost about $18 per patient, according to the WHO.
The rate of TB infection in the United States and most other developed countries is lower than that in the rest of the world, mostly because industrialized countries have the resources to make sure people undergo the drug regimen that controls TB. "Most of the cases we get in San Francisco are in immigrants," Hopewell says.
The WHO consensus document on treatment is an attempt to influence physicians in individual practice around the world. "Individual physicians are not focused in a programmatic way to think about TB from a public health perspective," Hopewell says. "Doctors have to realize that with TB, they are not just treating individual patients; they are taking on a public health role."
Taking on a public health role means, for instance, guarding against transmission to others and watching for the spread of TB. It also means making extensive efforts to ensure that patients take the required drug regimen exactly as prescribed. Failure to do so can lead to rise of bacteria that are drug-resistant.
The WHO document that Hopewell helped write is now circulating among governmental and nongovernmental organizations for comment, he says. He hopes that it will soon be approved by the WHO.
Hopewell's work at UCSF has taken him far beyond clinical treatment of TB to research on the biology of the pathogen itself. Hopewell and his colleagues have made surprising discoveries by investigating the genetics of the TB bacillus. By doing genetic fingerprinting, Hopewell can look at genetic differences between TB bacilli taken from different patients and tell how the disease spreads, he says.
One result of these studies was the discovery that the progression of the disease is often much more rapid than previously suspected. "We used to think that about 5 percent of those newly infected with TB would get the disease within the year, another 5 percent would get sick in the next year, and the rest would start to show symptoms sometime, perhaps many years after that," Hopewell says. "We now know that a high percentage of those newly infected get the disease fairly rapidly."
A close analysis of TB genetics may also offer ideas for new TB drugs or show how some strains are acquiring resistance to medication. One study, for instance, showed that the same bacterial protein that "turned on" a TB drug and made it effective also made the TB less pathogenic, Hopewell says. So if a TB strain adapts to medication by halting the production of that protein, it simultaneously becomes resistant to the drug and much more dangerous.
Such genetic changes and adaptations are going on all the time, Hopewell says. He is now looking at how strains of TB specialize and adapt to a given environment. And since their favored environment is the human lung, adaptation may mean changing to better work with a population's predominant genetic mix. At a slower rate, human populations evolve to be resistant to the effects of the bacillus. "It's really an example of coevolution between humans and TB," he says.
Such in-depth understanding may be a critical part of worldwide efforts to control TB, Hopewell says.
Photo by Chris T. Anderson
Source: Christopher Vaughan
