Tuberculosis: forgotten but not gone

Microbiology Today UK scientists had an important role to play in the development of the first antibiotics for the treatment of tuberculosis in the mid-20th century. As we enter the second decade of the 21st century, the world is now confronted with the appearance of extremely drug-resistant strains. In this article in Microbiology Today (pdf) Stephen Gillespie asks what are UK scientists doing this time to help combat this serious threat?

It was not until the mid-1940s that specific antibiotic therapy became available when Selman Waks- man and Albert Schatz extracted a substance named streptomycin from a Streptomyces bacterium isolated from the soil. Shortly after this, a number of other antibiotics with activity against M. tuberculosis were described. The UK played an important role in developing effective treatment regimens. When streptomycin was first available, there was not enough for all of the patients who needed it, so the Medical Research Council team who had been asked to investigate the new drug decided that it was fair and ethical to develop a randomized placebo control trial of the new treatment. This was the first trial of this type ever performed, and the importance of its results made it the standard way of testing new drugs throughout the world. What the study revealed was that the patients receiving streptomycin fared much better initially, but at the end of 5 years the same number of patients had died. This was because the organisms infecting the streptomycin-treated patients had developed resistance. Fortunately, other drugs had been developed and could be combined with streptomycin; of these the most important was isoniazid. As new drugs became available, the Medical Research Council tuberculosis unit and their counterparts in the US Public Health Service trialled new agents in various combinations, incorporating rifampicin in the 1960s and, in the 1970s, rediscovering the value of pyrazinamide, which had previously been rejected due to toxicity. Each of the new regimens was shorter so that, by the time that the regimen that remains the international standard was finalized, treatment duration had reduced from 2 years to 6 months. In most European and North American countries, the combination of effective treatment, rising living standards and BCG vaccination resulted in the number of cases of tuberculosis falling to very low levels. In resource-poor countries, however, the number of cases did not fall in the same way. Also, for many countries in sub-Saharan Africa, the emergence of human immunodeficiency virus (HIV) was a catastrophe as the virus rendered the patients especially susceptible to TB. From the mid-1980s, the number of cases of TB increased rapidly across the continent.



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