Editor—The recurrence of tuberculous disease emphasises the failure of antimycobacterial treatment based on isoniazid to eradicate latent Mycobacterium tuberculosis infection. We present the follow up of a patient originally reported on in 1953 as a survivor of advanced tuberculous meningitis.1 The original case heralded the remarkable impact of isoniazid in the treatment of tuberculosis.
The genomes of M tuberculosis and its human host have recently been sequenced.2 The scientific tools are now at hand to decipher the molecular mechanisms by which the organism achieves clinical latency and to devise new therapeutic strategies to eliminate these reservoirs of infection.
In 1952 the patient was a nursing student and presented with life threatening tuberculous meningitis that had failed to respond to treatment, including intrathecal streptomycin. Treatment with newly available isoniazid resulted in complete neurological recovery. A second course of four drug antituberculous chemotherapy was given for 12 months in 1986 because of spinal tuberculosis. In 2000 she presented with fevers and a sacral ulcer associated with ischial osteomyelitis. Microbiological studies of draining fluid yielded a diagnosis of tuberculosis. Antituberculous chemotherapy was given for a third time, and the ulcer healed completely.
The central paradigm in the pathogenesis of M tuberculosis infection is the maintenance of latency in its human reservoir. The recurrence of the infection in this patient despite two courses of antituberculous treatment over 50 years shows the clinical consequences of such latency. It emphasises the fact that current antituberculous chemotherapy targets metabolically active mycobacteria and is ineffective against latent organisms.
Recent work has identified unique enzymatic pathways, such as the glyoxylate shunt enzyme isocitrate lyase, that are critical to the survival of latent M tuberculosis.3 Specific treatment targeting such pathways may provide the key to the final eradication of M tuberculosis.4
References
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