Experts devise strategy to fight new TB strain
BMJ 2006; 333 doi: https://doi.org/10.1136/bmj.333.7568.566-b (Published 14 September 2006) Cite this as: BMJ 2006;333:566
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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
Competing interests: No competing interests
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
Competing interests: No competing interests