Is there ever any good news without bad? Good and bad seem to be inextricably locked in a Hegelian dialectic, or perhaps Manichaean struggle would be a more accurate way of putting it. For example, tuberculosis became the captain of the men of death, the white plague, between the seventeenth and the nineteenth centuries. Then it began its long decline, accelerated by the discovery of the first effective anti-tuberculous drugs. Then, just as large numbers of people became more susceptible to tuberculosis because of the spread of the human immunodeficiency virus, the germ of tuberculosis developed resistance to the most effective drugs against it. It seemed that the disease might once more become what it had been not so very long before. But then, for the first time in 40 years, a new anti-tuberculous drug, bedaquiline, was developed by the pharmaceutical company Janssen. Good news has not retained the upper hand for very long, however. An article in a recent edition of the Lancet suggests that bedaquiline is not the answer to Mankind’s prayers, at least where tuberculosis is concerned. http://www.youtube.com/watch?v=A5Id3hD4m6A The drug was granted a licence with relative speed by the Food and Drug Administration, but other countries have not as yet followed suit. This is because the drug, though effective against the germ, has the tendency to kill not only the germ but the patient as well, and this is not the object of treatment. Small trials have shown that the mycobacterium of tuberculosis disappears from the sputum, and the culture of that sputum becomes negative after two months of incubation (usually taken as a sign of cure), more frequently in those people with drug-resistant TB who take it than in those who are treated by normal protocols for the disease, i.e., five so-called “second-line” drugs taken for a prolonged period. The sputum of 46.7 percent of those taking bedaquiline was negative for the germ at two months, compared with only 8.7 percent of the control group. So far so good.
Unfortunately, in one controlled clinical trial the death rate of patients taking the drug was six times higher than in the control group. This may well have been because of the drug’s severe side-effect profile, all the more serious because the half-life of the drug (the time taken for half of a dose to be eliminated from the body) is so long: nearly six months. This means that, when side effects develop, it is not enough — as it often is — to withdraw the drug. Once it’s in you, so to speak, it’s in you; and another problem is that there is no treatment for some of the worst side effects that it causes.
The question for the authors of the article was whether further clinical research on the drug was ethically justified, and whether other jurisdictions should license it. Drug-resistant TB is a serious condition, not only for the individuals who have it but for the public health, for its spread would be disastrous. Between 21 and 89 percent of cases have proved incurable for one reason or another, while 13 percent of those taking the drug in the trial above died. Suffice it to say that the answer to the authors’ question is not a straightforward one. One of the reasons patients with drug-resistant tuberculosis die is that they do not adhere to long and onerous treatment, taking five drugs a day for about eighteen months, or nine months after the germ has disappeared. Does death from non-compliance count as part of the death-rate of the disease or not, especially as compliance rates differ between countries and social groups? What seems at first a simple matter can soon make you dizzy with complication when you consider it closely. Only hard thought can give the answer, but even then it is not guaranteed to do so. **** images via shutterstock / Puwadol Jaturawutthichai / Burlingham
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