Rapid Responses to:

NEWS: Peter Moszynski Experts devise strategy to fight new TB strain BMJ 2006; 333: 566-b [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

TB - some interest at last

Alastair C Burtt   (16 September 2006)

Is there such a thing as a “mitotic accelerator” specific for tuberculosis?

John C Chambers   (16 September 2006)

TB - some interest at last 16 September 2006
Alastair C Burtt, Chief Executive Target Tuberculosis 82 Queen's Road, Brighton, BN1 3XE Send response to journal: Re: TB - some interest at last	I read Peter Moszynski's article "Experts devise strategy to fight new TB strain" (BMJ 2006;333:566 16 September)with great interest and a mixture of pessimism and optimism. My pessimism surrounds the whole concept of XDR TB. Now that this has emerged we are faced with a huge challenge. With no new TB drugs likely to be produced in the near future all of us who work in TB will face the problem of how to control its spead and effect a cure. People have warned of the dangers of giving scant attention to TB for years and now their worst fears seem to have been realised. My little ray of optimism comes from the attention that is now being given to TB in the light of the recent news about XDR TB. Let us hope that the interest will be sustained and will enter the consciousness of the public as well as experts so that TB is taken as seriously as HIV/AIDS, with which it is so inextricably linked. Target Tuberculosis is a British charity working with community based organisations overseas to try to prevent people catching TB and to ensure that treatment reaches patients. Alastair Burtt Chief Executive Target Tuberculosis aburtt@targettb.org.uk Competing interests: None declared
Is there such a thing as a “mitotic accelerator” specific for tuberculosis? 16 September 2006
John C Chambers, Macmillan Consultant and Medical Director Katharine House Hospice, East End, Adderbury, Oxon, OX17 3NL Send response to journal: Re: Is there such a thing as a “mitotic accelerator” specific for tuberculosis?	Part of the seven-point action plan to fight Mycobacteria tuberculosis (TB) is increased support for research and development of anti-tuberculous drugs. (1) Most bacterial infections are cured after days of antibiotic monotherapy, whereas several months of polytherapy are required for TB. Prolonged treatment is probably required because of the waxy outer coat and slow mitotic rate of this intramacrophage parasite. Compliance with lengthy multi-drug therapy is hard to achieve for many reasons, but compliance failure increases the risk of drug-resistant strains emerging. Whilst isoniazid is bacteriostatic for resting bacilli, it is bactericidal for rapidly dividing ones. It inhibits the synthesis of the long chain mycolic acids required for the waxy coats. Rifampicin inhibits RNA transcription and ethambutol, which is taken up most avidly by mycobacterial cultures in the exponential growth phase, blocks the ability of tubercle bacilli to build and maintain their waxy outer coats. Resistance develops rapidly to any of these drugs when used alone. (2) As isoniazid and ethambutol are particularly effective against rapidly dividing bacilli, and as RNA synthesis and waxy coat construction must be particularly crucial when new bacilli are being synthesised, it would seem likely that TB bacilli are most weakened by antibiotics and most vulnerable to successful macrophage attack whilst undergoing mitosis. Therefore, if one could guarantee absolute antibiotic compliance over a period of time, which is at least conceivable if appropriate depot injections were developed, then the introduction of a “mitotic accelerator” specific for TB to suitably antibiotic-primed patients could transform the treatment of TB by placing the bacilli in their most vulnerable state more frequently. Much shorter treatment courses with full compliance might ensue, which would greatly reduce the risk of drug- resistant tuberculosis into the bargain. Has such a thing as a “mitotic accelerator” specific for TB already been discovered or developed? If not, is it an idea worth exploring? Combined with the right antibiotics, it could potentially become one of the most important global developments in this emergent medical era of deliberate manipulation of gene regulation and expression. Equivalent products specific for particular lines of cancer cells could also hold promise. Many cells are more vulnerable to successful attack during mitosis so, having set a suitable trap, why not herd them into it? 1. Moszynski P. Experts devise strategy to fight new TB strain. BMJ 2006;333:566. 2. Dollery C, ed. Therapeutic Drugs, Second Edition. Edinburgh, Churchill Livingstone 1999. Competing interests: None declared