Tuberculosis: are we making it incurable?

Tuberculosis (TB) is most probably the disease that has caused more damage to the human species throughout its history in terms of number of patients and, above all, death toll. There have been thousands of years spent fighting against Mycobacterium tuberculosis in which the human species could only rely on the efficiency of the immune system [1]. We must recall its importance as, in the pre-antibiotic era, the immune system alone could ensure important achievements such as: 1) only 50% of the people exposed to M. tuberculosis contract the infection [2]); 2) only 10% of those infected progress to active disease; and 3) up to 30% of patients with advanced TB disease heal spontaneously (fig. 1) [3, 4]. In spite of this, the fate of TB patients in the pre-chemotherapy period was very bleak, with a mortality of .50% within 5 years after the onset of disease [3, 4]. For centuries, several empirical treatments were attempted to trying to change this fateful prognosis. Additionally, sanatoriums were built throughout the world for many decades (fig. 2). However, all these interventions were not really effective, and none of them contributed significantly to improve the doom of TB patients [4]. Then, fortunately, their fate changed dramatically with the advent of the antibiotic era. The two decades from the discovery of streptomycin in 1943 to that of rifampicin in 1963 changed a devastating disease into a relatively easy to cure one. Not only were up to 11 different drugs with activity against M. tuberculosis discovered (streptomycin, p-aminosalicylate (PAS), thiacetazone, isoniazid (H), pyrazinamide, cycloserine, kanamycin, ethionamide, ethambutol, capreomycin and rifampicin (R)), but, based on multiple randomised clinical trials, the basic fundamentals of TB treatment were also established [4, 5]. Probably the most essential of these was the need to combine at least two to three drugs to which the patient was sensitive, as M. tuberculosis can develop resistance to single drugs.