Today, this resilient and highly contagious bacterial infection continues to rage, virtually unchecked, throughout the developing world. TB kills 2 million people each year, and one-third of the world's population is estimated to be infected. It is the seventh-leading cause of death worldwide, behind heart disease, stroke, influenza and diarrheal infections.
Even in the United States, where the disease has been brought under tight control, American public health authorities are watchful for a resurgence. Officials have sweeping powers to quarantine TB's victims and force treatment, and the federal government has labeled tuberculosis an "emerging infectious disease threat" on the same order as influenza, yellow fever and hantavirus, and a potential weapon of bioterrorists.
But future historians of public health may mark the first decade of the 21st century as the turning point in humankind's struggle against the disease that killed Eleanor Roosevelt, Frederic Chopin and all five of the sisters Brontë. In Tacoma, Wash., a vaccine developed by the British pharmaceutical company Glaxo- SmithKline and a Seattle-based company called Corixa Corp. will be tested on 20 healthy volunteers starting this month. And in Winston-Salem, N.C., and St. Louis, a second vaccine begins tests this month in 30 volunteers uninfected by TB.
Alongside the proposed vaccines, expected to be more effective than the current version, a flood of research money has begun to yield new treatments for TB that promise to be easier to administer and more effective. That's important because many patients fail to complete the current treatment — a demanding regimen of four drugs, taken daily for six to 18 months. When treatment is spotty or incomplete, new forms of drug-resistant TB tend to develop, as happened in several frightening U.S. outbreaks during the 1990s.
Also in the pipeline are other potential vaccines that could prevent tuberculosis infection or head off disease after infection does occur. And researchers are devising more ways to detect tuberculosis infection before it begins to do damage.
Finally, the search for better ways to control tuberculosis has helped forge new kinds of partnerships among the U.S. government, academic researchers, pharmaceutical companies and philanthropic organizations. The goal, say those familiar with the broad fight against TB, is to relegate an age-old adversary to the history books.
"A highly effective vaccine, in combination with a good treatment, could actually eliminate the disease," says Jerald Sadoff, president of the Aeras Global TB Vaccine Foundation, a nonprofit organization that is carrying one of the two potential vaccines into the clinical trial phase and is laying plans for the vaccine's manufacture. "I think that could happen, and I hope it could happen in my lifetime."
A new vaccine — even if it's just a little better than the century-old vaccine still in use — could be the most efficient way to stem a global epidemic, to head off new strains of drug-resistant TB and to protect the U.S. (whose porous borders and high immigrant population make Americans vulnerable to health problems of the less developed world). Today, just over half of new TB cases diagnosed in the U.S. are among people born outside the country — and of the L.A. area's more than 1,000 cases, the foreign-born make up over 80%. Mexico is the most common birthplace of those sick with TB, followed by the Philippines, Vietnam, India and China.
"The central tactic in the U.S. fight against TB has to be improving the global situation," says Dr. Peter Small, a Stanford TB researcher serving as a program officer with the Bill & Melinda Gates Foundation, which is active in disease research. "Sixteen miles of steel wire on the Mexican border will do nothing" to reduce the threat, he adds. Small describes TB as a global disaster outside the U.S. and, within American borders, as a time bomb that has yet to be disarmed.
Active TB linked to HIV
In 2002, the U.S. death toll from TB was 749, with 15,075 new cases of the disease diagnosed — 3,169 of them in California. Beyond U.S. borders, TB's path of destruction is far more horrific. At the current rate of spread, TB is expected to cause 35 million deaths worldwide in the next 20 years.
In addition to its recent knack for evolving new strains that are tough to treat with existing antibiotics, the TB bacterium is opportunistic. Moreover, it has found new prey with the pandemic of HIV and AIDS. Although a healthy individual infected with TB has a 1-in-10 chance of becoming ill with the disease, HIV infection makes conversion to active TB 20 times likelier, and an AIDS diagnosis multiplies the probability by 170. TB has become the single largest cause of death of AIDS patients worldwide.
To create both vaccines now entering the human-testing phase, developers had to take account of the qualities that have made TB so irrepressible. The TB bacterium essentially tricks the human immune system by entering its cells and making itself at home, often for years. When TB comes to life and begins to multiply wildly, the immune system's normal defenses fail to recognize the bacterium as an unwelcome intruder.
Both of the test vaccines employ genetic engineering and recombinant DNA technology to flush the TB bacteria — or parts of them — out into the open so the immune system learns to recognize an attack and fight back.
The GSK-Corixa vaccine starts from scratch, plucking two key protein-making genes from the TB bacterium, fusing them onto a second harmless bacterium, and mixing the resulting organism into a broth of immunity boosters called "adjuvants."
The second vaccine, developed by UCLA infectious disease specialist Marcus Horwitz and moving into human trials under the sponsorship of Jerald Sadoff's Aeras Foundation, uses an existing vaccine known as BCG as the basis for its candidate. The older vaccine's effectiveness had waned after almost a century of use, so Horwitz and his team set out to improve it by snipping and splicing new genes into the DNA of the live TB bacterium that makes up the BCG vaccine. The added genes set in motion a complex chain of events that results in the mobilization of the immune system against TB.
Both trials are designed to test human subjects' ability to tolerate the vaccines without ill effect. They follow tests on animals, in which both vaccines conferred long-lasting immunity against TB at high rates. The tests now underway are the first step in a lengthy and expensive process of proving a new vaccine safe and effective in preventing disease in humans.