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Erasing the World's Slow Stain: Strategies to Beat Multidrug-Resistant Tuberculosis

March 26, 2002

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Shelley's poetic casting of tuberculosis as a slow stain on the world, inspired by the death of John Keats, aptly characterizes the TB problem. TB ranks among the most important burdens on human health, not because the total number of cases is especially large (about 9 million/year worldwide, with incidence rates typically measured per 100,000 population), but because about one quarter of sufferers dies, most of them young adults. Globally, the number of TB cases is currently rising at 2 percent per year.

According to the authors, the perceived threat of drug-resistant TB is enormous. The biggest menace is multi-drug-resistant TB (MDR), caused by strains resistant to at least isoniazid and rifampicin. Among various readings of the evidence, the spread of MDR has been classified as a global pandemic; drug-resistant mycobacteria are said to be on the rampage, and MDR is thought to have become the norm.

The fraction of patients carrying MDR has escalated to levels that put TB control in jeopardy in some parts of the world. About 10 percent of new TB cases tested are carrying MDR strains in Estonia and Latvia. Management of TB is complicated by the very high expense and the toxicity of the drugs to treat MDR and by the fact that people with TB, including antibiotic-resistant TB, are becoming more mobile internationally.

The authors' goal is to describe the scale of the MDR problem, where it is focused, how it is changing, the importance of the link with HIV/AIDS, and the prospects for control.

  • Scale: In the year 2000, an estimated 273,000 of 8.7 million new TB cases (3.2%) were MDR. The highest MDR proportion among new cases has been found in Estonia (14%); Henan Province, China (11%); Latvia (9%); and Invanovo (9%) and Tomsk (7%) provinces in Russia. Measures of independent variables predictive of resistance in countries not surveyed indicate MDR rates of 10 percent or more in Yemen, Krygyzstan, Sudan, Pakistan, and Ukraine. Although resistance rates have become high in parts of Eastern Europe, there is little evidence that these rates were still growing during the 1990s. An estimated 70 percent of new MDR cases are in just 10 countries. MDR and resistance are more generally local rather than global problems. The majority of TB cases (85%) remain treatable using short-course chemotherapy (SCC) with cheap and safe first-line drugs.
  • Resistance: Resistance to a drug as defined by laboratory tests rarely implies total clinical inactivity. In a series of comparisons across six countries, on average 47 percent of MDR patients were cured by SCC, with 6- or 8-month treatment regimens with four drugs. The cure rates varied from 6 to 59 percent. There is a graded response by MDR to SCC, with the cure rate dependent on drug concentrations, the immunocompetence of the patients, their compliance and the number of drugs to which MDR strains are resistant.
  • The Link With HIV/AIDS: People who were infected with both M. tuberculosis and HIV are at progressively higher risk of developing TB as their immunity breaks down. Consequently, in those African countries presently suffering the largest epidemics of HIV, TB incidence has been increasing by 10 percent per year. Less clear is the relation between HIV and antibiotic resistance. There are a number of reasons why antibiotic resistance might be found more often among HIV-infected TB patients, and these include: the lower genetic fitness of MDR such that it would appear more often in immunosuppressed patients; TB infection among HIV-infected patients may be due to recent infection, where a higher fraction of recent infections are drug-resistant; the shared risk factors for infection with HIV and with TB (injection drug use and hospitalization) -- likely to be the most important factor; treatment failure due to a larger number of bacteria in immunosuppressed persons; HIV-infected TB patients may be subjected more often to functional monotherapy. Broadly speaking, there is no evidence that MDR is associated with HIV in cross-country comparisons. MDR appears to be uncommon in sub-Saharan Africa. There is no evidence that HIV exacerbates the spread of MDR.
  • Reproductive Fitness and the Spread of MDR: MDR is less fit than drug-sensitive TB. The best explanation for high local rates of MDR is that primary control has failed because patients have been subjected to many years of poor treatment. There is no strong evidence that disparate parts of the world with high resistance rates are encountering an MDR super bug with intrinsically high fitness.
  • Successes and Failure in the Management of Resistance: In comparisons across countries, the MDR rate among previously untreated cases is inversely correlated with treatment success under SCC. National control programs that have consistently cured a high proportion of patients for many years also report consistently low rates of resistance.
  • Investing in MDR Control: Although SCC appears to be successfully containing resistance in some parts of the world, it is happening with cure rates for MDR patients of no more than 60 percent. This is unsatisfactory. Second-line drugs must be part of the long-term solution and should be introduced sooner rather than later where MDR rates are very high. However, far more can be achieved with SCC.
  • Conclusion: According to the authors, "It is vital to remember that 97% of new TB cases are not MDR; most patients can be cured with first-line therapy, and yet most are still not receiving it. Putting in place the basic package for TB control remains the highest priority globally, to be followed by accurate drug susceptibility tests and the careful addition of second-line drugs.... In most parts of the world, there is time for a measured and targeted response."

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Adapted from:
Science
03.15.02; Vol. 295; P. 2042-2046; Christopher Dye; Brian G. Williams; Marcos A. Espinal; Mario C. Raviglione

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!



  
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This article was provided by CDC National Prevention Information Network. It is a part of the publication CDC HIV/Hepatitis/STD/TB Prevention News Update.
 
See Also
Tuberculosis (TB) Fact Sheet
Questions and Answers About Tuberculosis
More on Tuberculosis & HIV

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