Human catastrophe

Kathleen Moser has a speech ready for when people ask her what she does for a living. "When I tell people that I work with TB, over and over again, they say, 'Well, is that still around? What could you possibly do all day?'"

Moser, director of San Diego County's Tuberculosis Control Program, explains to surprised acquaintances again and again that TB is an airborne infectious disease that takes six months to two years of supervised therapy to cure. She tells them how she works to prevent and treat TB in San Diego County along with a staff of 60 people-eight of whom watch people take TB medicine all day long.

Once the world's leading cause of death, tuberculosis, or TB, still infects one in three people around the world.

Most of those infections, however, are latent TB, which does not make people sick. But one in 10 TB infections leads to the kind of wasting illness that gave the disease the name "consumption" in the 18th and 19th centuries.

Better public health care along with discovery of a cure made TB rates plummet in the 20th century. By the 1980s it appeared to be disappearing altogether. But the AIDS epidemic and the birth of drug-resistant strains of the disease set the stage for a worldwide resurgence.

Now, as a new kind of super drug-resistant TB threatens to go global, the World Health Organization (WHO) is calling on countries to dedicate billions of dollars to kill TB once and for all. As expensive as curing the world of TB is, the cost of doing anything less could prove much higher.

TB is the oldest known human disease. Archaeologists have found evidence of TB in Egyptian mummies. Bubonic plague, cholera, typhoid, and smallpox all have come and gone during TB's lifetime. When enough TB bacteria invade a person's lungs, the immune system attacks them by encasing them in a nodule of white blood and muscle cells. The nodule strangles the bacteria inside it along with any other living tissue. This lung damage may heal over time, but if TB is not treated it can lead to a slow death from bleeding in the lungs.

TB is the hippopotamus of infectious diseases; it moves slowly and has a thick, waxy cell wall, or skin. Its cells, called bacilli, divide only once a day. By comparison the common bacteria E. coli divides every 20 minutes. TB spreads from person to person in tiny droplets expelled in the coughs of infected people.

As an airborne contagion, the infection can silently cross ethnic and socioeconomic boundaries. But a person has to inhale many bacilli for hours at a time to acquire latent TB infection. Those bacilli have to multiply many times over to cause damage and become active TB. Doctors do not fully understand the relationship between latent TB, active TB, and the immune system, but active TB often develops in people who are immuno-compromised with diseases like HIV/AIDS.

For much of the 18th and 19th centuries, TB was the world's No. 1 killer. It thrived among the urban poor, who spent their lives on filthy factory floors and in cramped tenements.

"Everybody was exposed," said Andy Vernon, a physician in the Centers for Disease Control's TB Elimination Department. "There was no control. It would have been almost unusual for people to go through life without being exposed."

German physician Robert Koch identified the TB bacilli in 1882, but it took more than 60 years for science to discover drugs to treat the disease. In the meantime, doctors realized they could control the spread of the disease through isolation and quarantine. TB hospitals called sanitariums developed as places where the sick could retreat from society. By 1950, three years after the first TB drug was administered, the TB incidence rate in England, which kept records of TB infection, had declined by 66 percent in 50 years.

By the 1980s, TB had dropped off the radar screen of public health in the United States. The CDC stopped allocating a line item of its budget to TB. New York City cut its number of TB clinics from 24 to eight.

But TB had not disappeared. Just as TB bacilli can lie latent in a body, waiting for the right conditions to multiply and activate, TB in the United States was waiting for the right social conditions to mount another attack on the population. A combination of poor housing for immigrants and the homeless in urban centers and the rise of the HIV/AIDS epidemic fueled a resurgence of TB cases in the United States and around the world starting in 1985. Many patients had a new form of the disease that did not respond to the most common drugs.

"Multidrug-resistant TB tends to arise where wealth and poverty are mingled, where poor people get some treatment but not enough," journalist Tracy Kidder wrote in his biography of physician Paul Farmer, a now-famous advocate for proper TB treatment for the poor who founded the Boston-based global health agency Partners In Health. The New England Journal of Medicine stated that before 1989, fewer than half of patients who started TB treatment in New York City completed it. By 1992, TB incidence in New York had tripled, and one in five cases was drug-resistant.

Physicians have known about TB's propensity to drug resistance since the first successful TB drug, streptomycin, was administered in 1947 by England's Medical Research Council. Doctors there documented the "fall and rise" of TB in patients who would get better for a time but fall ill again. That was because not all the bacilli in the patients' bodies were susceptible to streptomycin. The first wave of treatment reduced the total number of bacilli, leaving those resistant to the drug. The remaining bacilli multiplied until the patients got sick again, but then the drug was useless against the resistant strain of TB.

Doctors quickly learned that one drug was not enough to cure TB. They also learned that the disappearance of symptoms did not mean TB was cured. Today, TB treatment requires six months of treatment with at least three drugs that each attack bacilli in different ways. The treatment works if patients take their medicine when, how, and for as long as they are supposed to take it. But many patients' devotion to their medication regimens wanes once their symptoms start to go away, usually after a month of therapy.

"If someone is very sick, they take their medicine," Moser said. "But if three months later they don't have a symptom at all, it's hard."

WHO and the CDC both recommend some form of supervision in all TB treatment. It is not enough to simply prescribe TB medication; a health-care worker must also watch patients swallow every dose. In that treatment model, called directly observed therapy, or DOTS, patients can come to a clinic for medicine or have it delivered to them by a health-care worker. Moser's program even includes video phones for workers to watch patients as they take their medicine.

"The best programs in the U.S. and in most of the world use directly observed therapy as standard of care," Vernon said.

In 2006 WHO released a plan for implementing DOTS in the corners of the world that need it most. The Global Plan to Stop TB focuses on 22 countries whose populations include 80 percent of the world's TB patients. The Global Plan aims to reduce the worldwide prevalence and death rate of TB by half by 2015.

Directly observed therapy programs require trained health-care workers and either a clean space for a clinic, transportation for getting to patients' homes, or both. Some TB-ravaged areas of the Third World are not even accessible by road. Places already exposed to shoddy TB treatment, particularly areas of Russia, need more than just directly observed therapy. Facilities to test strains of TB for drug susceptibility and access to good-quality, second-line drugs are a minimum for treating drug-resistant TB.

WHO estimates the plan will cost $56.1 billion. That amount is more than the gross domestic product of 10 of the 22 high-burden countries (view chart) targeted by the plan. WHO also predicts the plan could save 14 million lives, at a cost of only about $150 per year per life saved.

About half of the cost of the plan would go toward implementing DOTS and improving existing DOTS programs. The other half would be divided among treating drug-resistant TB, treating HIV/TB co-infection, and developing new TB tests, medicines, and vaccinations.

WHO would not directly implement the changes; it provides a blueprint for countries to follow. A worldwide partnership of private, public, and nonprofit organizations has committed funding and resources to the plan.

Moser oversees one of the programs that is a partner in the Global Plan to Stop TB. CureTB helps coordinate health care for patients who start TB treatment in the United States but move to Mexico before their therapy is finished. About 200 patients a year are referred to the program, which forwards the patients' treatment records to doctors who will take care of them in Mexico. CureTB started locally in San Diego but expanded to act as a communication hub for the United States.

The program began because public health officials treat TB patients who return to Mexico, "and we wonder what ever happened to the individual and hope they were able to tell doctors what medications they were on and hope they figured out where to go," Moser said.

CureTB is one of the Global Plan's many partners that receives no direct funding from WHO. The plan calls on the high-burden countries, especially those with developed economies like Russia and China, to fund many of the Stop TB activities themselves. The countries so far have committed to less than half the cost of the plan. Even less will be funded through the UN Global Fund, made famous by celebrity spokesperson Bono, and by private donations. The Bill and Melinda Gates Foundation has committed almost $900 million.

That leaves a funding gap of about $31 billion. WHO is calling on G8 countries to fund 40 percent of the gap and the affected countries to fund the remainder.

WHO officials justify the high price of the Global Plan by noting the much higher cost of inadequate TB treatment. The outbreak of drug-resistant TB in New York City in the late 1980s and early 1990s was estimated to have cost $1 billion to treat and had an 80 percent death rate.

A more recent outbreak of drug-resistant TB in South Africa was even deadlier. In 2005, the Church of Scotland Hospital in the KwaZulu-Natal province of South Africa reported some patients there were not responding to treatments they were given for multidrug-resistant TB, or MDR. Doctors later realized the patients had extensively drug-resistant TB, or XDR, which was resistant to the two most common, or "first-line," TB drugs and three of the six second-line drugs. Within a year, all but one of the more than 50 patients with XDR died in Kwazulu-Natal. All of the XDR patients who were tested were HIV-positive. Since then, South Africa has discovered XDR in all of its provinces.

The high death rate from XDR led doctors and journalists to call it "virtually untreatable." But Farmer, the physician whose life story is recounted in Tracy Kidder's book Mountains Beyond Mountains (Random House, 2003), says it's not too late to treat XDR. Patients who died in South Africa received only standard treatment for drug-sensitive TB. By the time test results confirmed that they had XDR-TB, all but one of the patients had died.

In March, Partners In Health announced it had received a $3 million grant from the Open Society Institute to develop a treatment model for XDR. It will start its work in Lesotho, a landlocked country within the borders of South Africa.

That same month the CDC released a report stating that there were 49 cases of XDR in the United States from 1993 to 2006. The report said the United States and global health organizations could target XDR by gathering more information about its incidence, prevalence, and causes.

WHO's Stop TB coordinator, Paul Nunn, in February called on nations to immediately fund the $650 million needed annually to combat drug-resistant TB with the Global Plan.

"If these resources are not found," Nunn told convention-goers in Geneva, "we face, over the next few years, the replacement of the current global epidemic of mostly drug-susceptible TB, with multi- or extensively drug-resistant disease, and the need to solve a human catastrophe, at vastly greater expense than if we address it now with all the skills and dedication of which we are actually capable."

SOURCE: WORLD HEALTH ORGANIZATION