UN chief urges global fight against TB

By EDITH M. LEDERER
The U.N. secretary-general on Monday urged stepped-up action to stop the global tuberculosis epidemic that is killing 4,000 people every day.
In a message marking World TB Day, Ban Ki-moon said "the man-made multi-drug resistant strain and its even more lethal form, extensively drug-resistant TB, are both spreading."
"That is why the theme of this year's day is `I Am Stopping TB'," he said. "This is a fight that can be won only with the collective commitment of millions of individuals — donors and researchers, doctors and health care workers, patients and family members."
Tuberculosis is an infectious disease caused by bacteria that attack the lungs. It is spread through the air and typically requires six to 18 months of treatment. The extensively drug-resistant strain is virtually untreatable in poor countries.
In a report last week, the World Health Organization said the fight to control TB has slowed. It said the rate of new cases fell by less than 1 percent between 2005 and 2006, which WHO called "very modest."
"Thanks to a broad coalition of partners working to stop TB, the proportion of people who become ill with the disease is slowly falling," Ban said. "But this progress is not keeping pace with population growth, so more and more people are becoming infected with tuberculosis."
"World TB Day is an occasion to urge action to stop tuberculosis, a disease which still kills an appalling 4,000 people every day," he said.
In 2006, there were an estimated 9.2 million new tuberculosis cases and 1.5 million deaths, the WHO said. India and China report the most cases, followed by Indonesia, South Africa and Nigeria.

ICAAC: Mice Fare Better Than Men In Novel TB Regimen

CHICAGO, Sept. 19 -- When it comes to curing TB quickly, it may be better to be a mouse than a man.
Researchers have shown that a course of antibiotics that substitutes moxifloxacin (Avelox) for isoniazid (Nydrazid) in the standard tuberculosis regimen can dramatically shorten the time to a cure -- at least for mice with TB.
But the same approach doesn't seem to work as well in people, Susan Dorman, M.D., of Johns Hopkins, told attendees at the Interscience Conference on Anti-microbial Agents and Chemotherapy here.
In a large international study, there was a trend toward better performance with moxifloxacin but it wasn't statistically significant, Dr. Dorman said.
The study, organized by the CDC's Tuberculosis Trials Consortium, involved more than 400 patients with sputum-positive TB who were randomized to the gold standard TB regimen or to a regimen that used moxifloxacin instead of isoniazid.
The gold standard regimen includes rifampin (Rifadin), pyrazinamide, and ethambutol (Myambutol), as well as isoniazid.
A positive sputum culture means a patient is infectious and the time to convert the sputum culture from positive to negative is seen as a measure of how long a complete cure will take, Dr. Dorman said.
Eight weeks into her study, 60% of those in the moxifloxacin arm had negative sputum cultures, compared with 55% of those in the standard isoniazid arm. But that the difference was not statistically significant.
"It's a trend in the right direction," Dr. Dorman said, "but that's all."
She said that she and her colleagues are still analyzing data, but the result appears to be clear.
On the other hand, Dr. Dorman said, the new combination was safe and well tolerated, so it offers clinicians another treatment option.
"There's a discordance," said Jacques Grosset, M.D., also of Johns Hopkins and a leader in the search for new, shorter TB regimens. His research team has found that mice can be cured more rapidly by using moxifloxacin.
"I am surprised the result was not better than that," he said. But, he theorized, it's possibly because mice are easier to experiment on than people.
Dr. Grosset and colleagues argue that isoniazid is antagonistic to rifampin, one of the two major TB drugs, while moxifloxacin is not. In mice, he said, the substitution "significantly increased the bactericidal activity and reduced the time to culture conversion by two months."
But the idea of tweaking the standard regimen of TB treatment has some human evidence on its side.
In a smaller randomized trial in Brazil -- involving just 170 patients -- using moxifloxacin did speed up the culture conversion rate, reported Richard Chaisson, M.D., also of Johns Hopkins, and an investigator with Dr. Dorman on the larger trial.
But in that trial, the drug was substituted for ethambutol, rather than isoniazid and the culture conversion rate was 85% at eight weeks in the moxifloxacin arm, compared with 68% with ethambutol. The difference was significant at P=0.02.
Dr. Chaisson described the findings as "the most compelling evidence in nearly 25 years that a novel antibiotic drug combination works better than the current gold standard."
Dr. Dorman's study was supported by the CDC, the Global Alliance for TB Drug Development, and Bayer. Dr. Chaisson's work was supported by the FDA, the Global Alliance, and Bayer. Drs. Dorman, Grosset and Chaisson reported no financial conflicts.Primary source: ICAACSource reference: Grosset JHE et al. "Short-Course Treatment of Active TB with FDA Approved Agents: Predictions from Animal Models." Presentation 1961. Additional source: ICAACSource reference: Dorman S et al. "Moxifloxacin vs. Isoniazid in the First 2 Months of Treatment for Pulmonary Tuberculosis." Presentation L376b. Additional source: ICAACSource reference: Chaisson RE et al. "A Randomized, Placebo-Controlled Trial of Moxifloxacin vs. Ethambutol in the Initial Phase of Tuberculosis Therapy in Brazil." Presentation L736a

Studies: TB can be treated in few months

By MARILYNN MARCHIONE,

New research gives hope for successfully treating tuberculosis in a few months rather than the six months or more currently needed to beat the contagious lung disease, doctors reported Tuesday.
Adding the antibiotic moxifloxacin to the usual TB drugs shortened the time to cure to an estimated four months in a study in Brazil, Johns Hopkins University scientists reported at an American Society for Microbiology conference in Chicago.
A second study by Hopkins researchers cured mice of TB in 10 weeks instead of the usual six months with moxifloxacin plus the TB drug rifapentine at higher doses.
"It sounds fantastic," said Dr. Melvin Spigelman, research and development director for the nonprofit Global Alliance for TB Drug Development in New York. "The science is there" and just needs to be verified in larger studies, he said. The group will launch a 2,400-patient study later this year.
Also on Tuesday, the Seattle-based Bill & Melinda Gates Foundation announced its largest grants ever to fight TB — $280 million for research on vaccines, diagnostics and drugs.
"If everything goes well, it should be feasible to shorten treatment time," possibly even to ultra-short regimens of two weeks to a month, said Ken Duncan, the foundation's program director.
More than 8 million people worldwide develop TB each year and nearly 2 million die of it. The disease is mostly a problem in poor countries, but the recent case of Andrew Speaker, an Atlanta attorney who created an international health scare by traveling while he had a multidrug-resistant strain of TB, shows the danger in the United States as well.
Recently, a Mexican teenager was jailed in Georgia and threatened with deportation after refusing to take his recommended nine months of TB treatment. Similar cases have surfaced around the country.
Treatment now consists of three or four antibiotics taken daily for six months or more. But half of patients do not take all their pills, allowing resistant bacteria to grow and spread, said Dr. Jacques Grosset, the Hopkins researcher who led the study of several hundred mice.
The Brazil study involved about 170 men and women in Rio de Janeiro who had active TB. All were given three standard anti-TB drugs plus either moxifloxacin or an older drug, ethambutol.
After two months, 85 percent of those on moxifloxacin tested negative for the infection compared to 68 percent on ethambutol. The treatment advantage showed up in as little as two weeks.
"Based on what we know, if you get that big a difference at two months, you should be able to shorten the duration of treatment ... down to four," said Dr. Richard Chaisson, director of TB research at Hopkins.
In a third study of about 400 TB patients throughout Africa, 60 percent who received moxifloxacin plus three other drugs tested negative for TB at two months versus 55 percent given isoniazid and the other medications.
The federal government paid for the studies, and Bayer Healthcare AG donated moxifloxacin, which it sells as Avelox in the United States for short-term use against pneumonia and other respiratory illnesses. The pill costs $10 a day, but researchers said Bayer has promised to make it available in poor countries for less if it is approved to treat TB.
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On the Net:
Microbiology conference: http://www.icaac.org
Gates foundation: http://www.gatesfoundation.org

Obese people appear better protected from TB: study

Elderly people who are obese appear to have a lower risk of falling ill with tuberculosis compared to those who are underweight or of average weight, according to an extensive geriatric study in Hong Kong.
Although obesity has been linked to health problems such as hypertension, diabetes and cardiovascular disease, experts notice that among people suffering from the same ailments, those who are overweight tend to outlive those who are thin.
In the latest issue of the Archives of Internal Medicine, researchers in Hong Kong reported that elderly, obese people tend to be better protected from tuberculosis than slim people.
They studied a cohort of 42,116 people who registered in 18 geriatric health centers in 2000, and monitored them closely for a period of five years.
They were 65 years old and over, and were classified into five categories according to their body mass index (BMI).
Those who were underweight were six times more likely to fall sick with tuberculosis than those who were obese, while those who were of average weight were three times more likely, according to a member of the research team.
"This relationship is quite consistent, the heavier you are, the lower the risk," CC Leung, a consultant chest physician with the Department of Health in Hong Kong, said in an interview.
More than a third of the world's population is infected with TB and the infection rate is one every second. However, only one in 10 infected persons will develop symptoms and that usually happens when their immune systems are weak. Left untreated, TB, or Mycobacterium tuberculosis, kills half its victims.
Leung said studies should be done to establish the reasons for the apparent robustness of overweight people when it comes to TB, although it appears to be supported by a few theories.
"Our adipose (fatty) tissues not only control our metabolism, but also our endocrine and immunological systems. This is our conjecture, but it's not without basis. In our studies (in Hong Kong), in ICU wards, overweight people have lower death rates than thin people," Leung said. "We must find out why this is so."
Falling TB rates and the availability of food at more affordable prices in industrializing states in the late 18th and early 19th centuries may not be a mere coincidence, he added.
"The availability of food had a direct bearing on TB. And before we had a good TB cure, TB figures were already falling in places like Britain and Europe," he said.
The findings have important applications. Where resources are scarce, BMI may be used as a factor to help decide if a person should be screened or treated for tuberculosis.
"We have many latent infections, which we have to screen and decide whether to treat, which may bring side effects especially for the old. If BMI has such an important bearing, we may want to consider it when giving screening and treatment," he said.
"As for this thin fad, if a person's weight suddenly plunges, we have to be careful because it may raise chances of the person developing TB (if he is infected)," Leung added.

Experts Disagree on Whether TB Patient Needed to Be Isolated

WEDNESDAY, May 30 (HealthDay News) -- A leading tuberculosis expert believes U.S. health officials were right to quarantine a Georgia man with a dangerous form of the respiratory disease who took two trans-Atlantic flights, possibly infecting fellow passengers in the process.
But a second TB expert said the U.S. Centers for Disease Control and Prevention's decision to isolate the man in an Atlanta hospital was unwarranted, contending that the man is "minimally infectious."
Meanwhile, the man at the center of the controversy, who asked that his name be withheld due to the stigma associated with the disease, disputed federal and local health officials' claims that he traveled abroad in violation of their wishes. He said that while officials told him they preferred that he postpone his long-planned wedding in Greece and honeymoon, they did not prohibit him from flying. And the man knew he had tuberculosis but did not think he posed a health risk, according to published reports.
On Tuesday, CDC officials issued the first federal isolation order since 1963 to quarantine the man, who had been diagnosed with "extensively drug-resistant" TB, also called XDR-TB. This form of the disease resists many drugs used to treat the infection.
On May 12, the man flew from Atlanta to Paris, continued on to Prague, then took a return flight to Montreal, Canada, on May 24, before driving back into the United States.
The CDC has advised passengers who were on the two flights to get tested for tuberculosis, although they are thought to be at low risk of infection from the disease, agency officials said Wednesday.
"We believe that the patient's degree of infectiveness is limited," Dr. Martin Cetron, the CDC's director of the Division of Global Migration and Quarantine, said during an afternoon teleconference. Tests show the man was carrying a relatively low level of the tuberculosis bacteria, he said.
Cetron noted that on the flight from Atlanta to Paris, some 40 to 50 passengers who sat near the man were those most likely at risk. The man probably sat in row 51. The same is true for the 30 passengers who sat near the man on the flight from Prague to Montreal. On that flight the man sat in seat 12C.
However, Cetron said that the CDC and other health agencies in the United States and abroad would notify all passengers on both planes as well as passengers who flew with the patient on several shorter flights to and from Greece and Italy.
Dr. Tawanda Gumbo, an assistant professor of internal medicine at the University of Texas Southwestern Medical Center at Dallas and an infectious disease expert who specializes in TB and XDR-TB, believes that isolating the patient was the right thing to do.
"The best we can do right now is to make sure it doesn't spread. We don't want it to spread," Gumbo said, noting that tuberculosis can be very contagious. "You don't have to do anything, just breathe," he added.
It's very possible that passengers on both of the trans-Atlantic flights the patient took were infected, Gumbo said. "We know from the past that a single patient on an airplane can infect other people on the airplane," he said.
But Philip Alcabes, an epidemiologist and professor at New York City's Hunter College School of Health Sciences, said the man posed no public safety threat, and quarantine was "a maximum penalty for a minor medical problem."
"Pulling the trigger on a quarantine should be reserved for serious medical emergencies that pose a genuine health hazard to the general population," Alcabes said. "Doing so for this event only serves to trivialize the real quarantine call-to-action when it is finally needed. The man in question is obviously minimally infectious, as his wife has not been infected."
"Transmission in an airplane is very unlikely, owing to the intrinsic difficulty of transmitting TB and to the relatively high rate of filtration of airplane cabin air," Alcabes said.
"The CDC is making much of the fact that the man's TB strain is drug resistant," Alcabes added. "That is of some clinical relevance but of no public health importance. Drug-resistant strains are no more infectious than other strains. This TB is no more likely to be transmitted in this way than garden-variety TB would. Transmission is not impossible, but highly unlikely."
Dr. Howard Njoo, of the Public Health Agency of Canada, agreed with Alcabes' view that the man posed little risk to his fellow passengers, adding that modern jetliners are equipped with air filters designed to screen out infectious germs like the ones that cause tuberculosis.
"The risk of transmission is considered to be very low; however, we cannot say definitively that the risk is zero and therefore we are undertaking certain public health measures," Njoo told told CTV's Canada AM on Wednesday morning.
Meanwhile, Dr. Julie Gerberding, director of the CDC, said Wednesday that her agency was working closely with airlines to locate passengers who may have been exposed to the rare, dangerous strain of tuberculosis.
The infected man flew to Paris on May 12 aboard Air France Flight 385, then returned to Montreal on May 24 aboard Czech Air Flight 0104, before driving into the United States at Champlain, N.Y.
CDC officials said they were focusing on the trans-Atlantic flights because that's where people would have had the most exposure to the patient. But the risk of infection was considered low, the officials said.
As for the patient, the Atlanta-area man said he doesn't think he did anything wrong.
"I didn't want to put anybody at risk," he told The Atlanta Journal-Constitution in a telephone interview from Grady Memorial Hospital, with an armed sheriff's deputy outside his door.
The man, who said he has no symptoms and feels healthy, said he has met regularly for treatment with Fulton County, Ga., health officials since January. He said the local officials and the CDC knew he had drug-resistant TB before he left the United States, but they did not prevent him from leaving when he told them about his planned wedding in Greece, the newspaper said.
He questioned why no health officials told him to cancel his wedding before he left Atlanta -- and why the CDC waited until he was on his honeymoon in Rome to order him into isolation.
"The county health department knew I was going over to have a honeymoon. We had a meeting before I left," he told the newspaper.
"We headed off to Greece thinking everything's fine," he told the paper. He said he contacted the paper because he wanted to make sure his side of the story was heard.
He told the newspaper he did not report to Italian health officials because he was afraid that if he didn't get back to the United States, he wouldn't get the treatment he needed to survive.
"I'm a very well-educated, successful, intelligent person," he said. "This is insane to me that I have an armed guard outside my door when I've cooperated with everything other than the whole solitary confinement in Italy thing."
The man is not facing prosecution, health officials said, according to the Associated Press.
The man has plans to travel to Denver's National Jewish Hospital, which specializes in respiratory disorders, where he is to undergo an operation that would remove part of his infected lung.
Gumbo noted that such surgery is similar to older treatments for TB. "Before we had effective drugs, one on the options was surgery," he said. "When we run out of therapies there is really nothing else that could be done.
Extensively drug-resistant tuberculosis poses a growing threat because it is becoming more common throughout the world, Gumbo said. "It is being introduced into wider and wider populations," he said.

Resistant TB leaves few options

The highly dangerous form of tuberculosis that has infected a man now in quarantine resists almost all drugs used to treat TB, leaving only less effective options.
It's called "extensively drug-resistant tuberculosis," or XDR TB. It can't be cured by the two best first-line drugs, isoniazid and rifampin, or the best second-line medications.
That leaves options that are much less effective, according to the federal Centers for Disease Control and Prevention. Some programs have achieved cure rates for an estimated 30 percent of affected people, CDC says.
Success depends heavily on how resistant the germ is, how severe the disease is, and whether the patient's immune system is weakened, CDC says.
This form of TB is rare. Only 49 cases were reported in the United States between 1993 and 2006; 17 have been diagnosed since 2000. By contrast, the nation reported 13,767 ordinary TB cases last year alone, an all-time low.
The extremely resistant form can be caught from other people or develop from an ordinary case of TB. It generally appears in people who don't take their medicines regularly or don't take all of them; or those who develop active TB after having taken tuberculosis drugs in the past; or who are exposed to the germ from other people.
This dangerous form spreads the same way as ordinary TB. — when someone breathes in the germs from the air. TB germs can enter the air when an infected person coughs, sneezes, or even speaks. The germs can float for hours. TB is not spread by a handshake, sharing a glass or by kissing, the CDC says.