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Development of New Antituberculosis Drugs (Hardcover, Illustrated Ed)
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Development of New Antituberculosis Drugs (Hardcover, Illustrated Ed)
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In the global war to control tuberculosis (TB), there are several
critical battles which must be waged and won if we are to make
significant progress. Broadly speaking, these battlefields may be
regarded as diagnosis, treatment and prevention. Within the arena
of treatment are various critical elements. Current drug regimens
require 6 months to achieve predictable cures; it is essential that
shorter regimens be developed to lessen non-adherence and to
improve affordability. To facilitate directly-observed therapy,
intermittent (less than daily) regimens have been employed. To
ensure favourable outcomes, including patients with AIDS,
thrice-weekly regimens are the current standard; reducing the
frequency of dosing to twice- or once-weekly may offer significant
advantages. Drug resistance to the current major medications, the
rifamycins and isoniazid, threatens to make tuberculosis
untreatable for rising numbers of patients in many regions of the
world. Finding new, effective agents is essential to ensure cures
for these cases and to halt transmission of multidrug-resistant
tuberculosis to others. Additional issues include reducing the side
effects and toxicity of anti-tuberculosis regimens and developing
regimens that can be given simultaneously with anti-retroviral
therapy without deleterious drug-drug interactions or unacceptable
toxicity. Finally, attention must be directed to the potential
utility of treating latent infection to prevent the evolution of
active disease. The current vaccine Bacille Calmette-Guerin (BCG),
while protecting infants and children against potentially lethal
forms of TB, has done little to control the incidence of
communicable adult pulmonary disease. Research is underway to
develop improved vaccines, but due to the prolonged period to
determine the efficacy of a TB vaccine (a minimum of 10 to 20
years) -- alternative strategies must be pursued. Furthermore, the
utility of a traditional vaccine would be sorely limited by the
fact that roughly two billion persons today harbour latent
tuberculosis infection. This huge reservoir of future disease would
not be eligible for a traditional pre-infection vaccine.
"Preventive therapy" with isoniazid has been shown to reduce the
subsequent risk of tuberculosis by about 70% in large, randomised
placebo-controlled clinical trials. However, this strategy is
limited by the requirement for extended duration of treatment (6 to
9 months), the risks of drug-induced hepatitis and rising rates of
resistance to isoniazid in many regions of the world where the TB
epidemic is most intense. Alternative means for the treatment of
latent tuberculosis infection should be given high priority. The
authors have assembled an outstanding panel of contributors to
address these issues. The topics herein have great relevance both
in the industrialised nations where contemporary medications and
strategies appear to have exacted their maximum benefits and for
the developing nations where this ancient scourge remains rampant.
This book will provide an impetus for authorities and organisations
devoted to the development of new drugs to address the
aforementioned growing problems of TB world-wide.
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