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Better Tests Needed to Control Tuberculosis

A disease that seems like it should belong to some past century is doing just fine in this one, as the World Health Organization reports a slowdown in progress against tuberculosis.

In some countries, the disease is coming back. In others, it is taking on new and more deadly forms, especially when it is linked to another epidemic — AIDS. And in poor countries, many people don't even find out that they have TB until it's too late to treat them — and too late to protect others from infection.

In 2002, as part of a Yale Fellowship, Dr. Neil Ghandi traveled to rural Tugela Ferry in the province of KwaZulu Natal, South Africa, a region where two epidemics — TB and HIV — are killing people. A project there was introducing new medicines for people infected with both diseases.


"The majority of our patients responded very well to both the TB and the HIV medicines — gained weight, really became very healthy — and we were very pleased by that," Ghandi says. "But there were a handful of patients who didn't respond. And those were the ones who really made us think that there may be something else going on here."

He suspected that they might have a resistant strain of TB but had no way of knowing.

"The way TB was being diagnosed there was just by doing microscopy — the same technique that was used for the past 100 years when Robert Koch first discovered TB."

The patient coughs up sputum. It's smeared on a slide and examined under a microscope. But it's not a very effective way to diagnose TB. The bacteria cannot always be seen under a microscope.

And when AIDS patients get infected with the TB bacteria, the least amount of bacteria is enough to make them sick. But finding those bacteria under a microscope is especially difficult. The end result is that microscopy detects only 60 percent of all TB cases.


Dr. Giorgio Roscigno is the head of the Foundation for Innovative New Diagnostics, which is trying to come up with simple and affordable technologies for detecting TB. He says in poor countries, a patient can be sick with TB for up to five months before the disease is detected.

"During that period, he might have gone to a pharmacist, to a sort of traditional healer, he might have spent a lot of money going up and down in the public health system," Roscigno says. "But most importantly, he might have already infected most of his family, his co-workers and many other people that would have shared a bus or a taxi with him."

In rural South Africa, Ghandi had to send his sputum specimens to a laboratory in a city three hours away so he could find out which drugs would work.

"It took six to eight weeks for us to get our results back. That delay was a costly delay because in most cases most of our patients died during that time."

When TB bacteria are so few in number that they can't be detected under a microscope, an even more time-consuming culture can be used. The bacteria are grown on a plate in a solid gelatin-like substance until they're visible — a process that can take up to two months.

Most poor countries have neither the laboratories nor the trained workers to carry out even solid cultures.

In the U.S., the standard practice is a more complex test procedure. Instead of solid cultures, a liquid culture makes the bacteria grow faster. Until recently, Roscigno says, it was not recommended that developing countries try to do that, with facilities and safeguards being practically nonexistent.

"The argument has been that liquid culture is much more complicated to perform," he says. "The technology needs special safety in the laboratory, like negative pressure to absorb all this microbacteria in the air, and you don't want the workers to be infected while they are doing the tests."

And yet Roscigno's foundation established a TB hospital in Maseru, Lesotho, with a laboratory and trained workers who conduct such tests.

Dr. Peter Small of the Bill and Melinda Gates Foundation says the real solution for developing countries is a test that takes minutes to do. It identifies the DNA of the TB bacteria.

"Rather than either waiting until there are enough bacteria in a patient's sputum that you can see it under the microscope, or rather than waiting the four to six weeks until you can actually see the bacteria in a petri dish, very sensitive and very specific molecular techniques can be applied to detect the presence of a very few bacteria in any patient's specimen," Small says.

Roscigno says there's one form of the test that holds a lot of promise because it is so simple — much like a coffee dispenser: "You put your sputum into the cartridge, you put the cartridge into the machine, press a button, wait 120 minutes and you get the results" that tell you whether the patient has TB and whether it is a resistant strain.

If the patient is infected with HIV, it also can tell you how fast the AIDS virus is reproducing in the patient's blood.

The machine is currently being used to detect anthrax in the U.S., in post office mail sorting centers. It's expensive — $20,000 to $50,000. But with billions now being proposed by the U.S. and other donors for TB research and treatment abroad, Small believes a test like that should be used.

"If you told me that you had a test that was going to cost a dollar, I would say great. But if you told me that you had a test that was going to take out the confusion that perpetuates this epidemic and it cost $20, I would say great, let's go find the money," Small says.

Considering that millions of people with TB go undiagnosed and infect others, Small thinks health officials should invest in developing new tests, as well.

"The test that we really need would be in the local equivalent of Mom's medicine cabinet. We're a long way from that."

Until then, he says, all existing options — some incremental, some bold — need to be tried.

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