Diagnosing TB in developing countries

SciDev.Net's TV Padma reports that tuberculosis experts are looking to India to develop affordable TB-testing kits. An estimated four million cases of the disease go undetected, and two million TB patients die every year. India has increased its efforts at finding and treating cases of the disease, but diagnostics still present a challenge, Padma explains:

TB tests come in a range. Latent infections can show up as a reaction when the protein, tuberculin, is injected under the skin. Blood tests may reveal immune molecules (gamma interferon) produced by the body to protect against the bacterium.

A surer test is the chest X-ray where white spots indicate infection. Microscopic examination offers further confirmation, though this method picks up less than 70 per cent of infections, dipping as low as 35 per cent in some settings and in patients co-infected with HIV.

TB is reliably confirmed when sputum samples are cultured in a laboratory with nutrients, but this technique takes two to four weeks, is costly and calls for technical training.

Last year, WHO endorsed an accurate two-hour test using DNA technology, but this is yet unaffordable in developing countries where the bulk of cases occur.

Padma outlines some of the challenges of developing a test that can be widely used in developing countries:

But, developing newer, cheaper and quicker test kits is not easy. For one thing, there is little consensus on benchmarks. Observed WHO's Puneet Dewan: "The tools on the table are all compromises between accuracy, simplicity, cost and time."

McInsey India's benchmarks include 90 per cent sensitivity and specificity; results within 24 hours; use of urine or blood samples rather than sputum; instruments that are compatible with tropical environments, portability and ruggedness.

A key criterion on the list is that the cost to the patient should be under US$ 1.2 per test.

In a New Yorker piece published last year, Michael Specter explores the challenges of diagnosing and treating TB in India. He begins with a visit to a woman named Runi, a mother of 16 who lives in a slum in the Indian city of Patma. Runi visited a private medical clinic after developing a painful cough and let "someone who called himself a doctor" draw and examine her blood; he told her she had TB. But the test she received wasn't one that can distinguish between latent and active infections. Specter explains the implications:

In India, China, and Africa, at least two billion people have latent infections. Yet every day thousands are told, mistakenly, that they are sick and need treatment. That's what happened to Runi. Soon after she received her diagnosis, Runi began a regimen of powerful (and toxic) drugs provided by the public-health service, and she stuck to the program for the required six months. Not long after finishing, however, she started to feel worse than she ever had before. "This is the tragedy of our TB-control program,'' Shamim Mannan said as we watched Runi's children play. Mannan, who is from Assam, a few hundred miles from Patna, serves as the Indian government's chief TB consultant in the region.

"Officially, she is cured,'' he said. "But how would we know? She took a test that showed she had the antibody for TB in her blood. So do I. So do five hundred million Indians." As Runi stooped to gather fuel for the stove, she began to cough, lightly at first and then with alarming force. Every cough sounded as if somebody had shattered a pane of glass.

"Now she really is sick,'' he continued, explaining that Runi's TB was no longer dormant, and that taking drugs when they are not necessary often makes them ineffective when they are. "This is what happens when tests mislead us. She will need the drugs again. If they don't work properly, she will be in real trouble. She has almost certainly infected some of her children. That makes everything harder, more expensive, more painful.''

Specter not only makes clear the importance of better diagnostics for TB, but explores some of the dysfunction in India's healthcare system, which leaves many poor patients paying for shoddy care outside of the official health system. The problems are daunting, but the last section of the article has a hopeful reminder:

The uncertainties and dangers of diagnosis remain the greatest obstacle to successful TB treatment, in India and throughout the developing world. For that to change, investments from international aid organizations and from private companies will be necessary. That may seem unlikely, but it has happened before, most notably with AIDS drugs. In the nineteen-eighties, when AZT became the first effective treatment for H.I.V., the annual cost for each patient was ten thousand dollars. People in the West, who were rich or lucky enough to have good insurance, could afford it. In countries that struggle to provide basic immunizations against diseases like measles, though, AIDS treatments were a fantasy. Then various groups, including the Clinton Foundation, the Gates Foundation, and the Global Fund to Fight AIDS, Tuberculosis and Malaria, joined together to push for lower prices. Generic manufacturers, led by Cipla, the Mumbai-based pharmaceutical giant, began to churn out highly effective medicine at a small fraction of what it cost in the United States. Political pressure mounted, officials of the World Health Organization joined the call for cheaper AIDS medications, and today the governments of poor countries like India can buy those drugs for an annual price of less than a hundred dollars per patient. These drugs are normally distributed in bulk, through international AIDS organizations.

A similar effort will be required to lower the cost of diagnosing tuberculosis. There will also have to be a transformation in how TB medicine is regulated. That may seem like an insurmountable barrier, but, with the proper incentives, the system could work. Again, one can look to the history with AIDS medicines for a model. Because Cipla and other Indian pharmaceutical companies are frequently inspected by international regulators--such as the U.S. Food and Drug Administration--governments are willing to buy their products. That's one reason that Indian firms have become the most important manufacturers of generic AIDS medicines in the world.

If India becomes a major player in the production of affordable TB diagnostics, its economy could improve along with its TB prevalence rate.