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Re: Norman - TB

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This free paper gives a nice overview of how Mitchison developed the

hypothesis of nonreplicating Mtb subsets in human TB, and thus

explained why multi-month therapy was necessary to prevent clinical

relapse. It is most valuble for its description of how Mitchisons

hypothesis was verified.

Lesions from humans treated with multi-drug therapy were cultured.

Culture of open lesions rapidly grew Mtb with some acquired resistance

to the treatment drugs. Culture of closed lesions (where hypoxia

causes Mtb dormancy) produced Mtb only after months of incubation, and

said Mtb had no resistance, demonstrating that they belonged to a

subset of the bacterial population which had faced little mortality

during treatment. The best explanation for this (well-supported by

work in vitro) is phenotypic resistance due to a nonreplicating status.

http://gasp.med.harvard.edu/micro200/Rubin/TB%20persistence%

20review.pdf

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I think it's pretty well known that in CF (cystic fibrosis) that low

dose Zith keeps the bacteria in a non- replicating colony.

I've often wondered if some of the improvements on low dose abx is

exactly that - meaning the offending chronic bacteria is a species

that CAN be held in check by low dose.

Barb

>

> This free paper gives a nice overview of how Mitchison developed

the

> hypothesis of nonreplicating Mtb subsets in human TB, and thus

> explained why multi-month therapy was necessary to prevent clinical

> relapse. It is most valuble for its description of how Mitchisons

> hypothesis was verified.

>

> Lesions from humans treated with multi-drug therapy were cultured.

> Culture of open lesions rapidly grew Mtb with some acquired

resistance

> to the treatment drugs. Culture of closed lesions (where hypoxia

> causes Mtb dormancy) produced Mtb only after months of incubation,

and

> said Mtb had no resistance, demonstrating that they belonged to a

> subset of the bacterial population which had faced little mortality

> during treatment. The best explanation for this (well-supported by

> work in vitro) is phenotypic resistance due to a nonreplicating

status.

>

> http://gasp.med.harvard.edu/micro200/Rubin/TB%20persistence%

> 20review.pdf

>

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