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Hiding place for mycobacteria

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I suspect that in many of our minds “the literature” begins at about the time we entered medical school. This may, of course, mean that much useful research is ignored. A fascinating example of the value of knowing about findings from a previous era has been provided by work on the location of latent tubercle bacilli (R Hernández-Pando and colleagues.Lancet2000;356:2133–8).  In 1927, E L Opie and J D Aronson reported transmitting tuberculosis to guinea pigs from less than 10% of old tuberculous lung lesions but from almost 50% of specimens of apparently unaffected lung, suggesting that the bacilli in latent tuberculosis might live in normal lung tissue rather than, as is often supposed, in old, encapsulated lesions. The recentLancet report has described similar findings using DNA technology.  They used in situ and conventional PCR to examine apparently normal postmortem lung tissue from one experimental and two control groups: 47 people who had died in tuberculosis endemic areas (13 in Ethiopia and 34 in Mexico) but had not had tuberculosis (experimental group), six who had died in Norway and had not had tuberculosis (negative controls), and six who had died in Ethiopia of tuberculosis (positive controls). All of the negative controls proved negative and all of the positive controls positive on PCR testing of macroscopically normal lung tissue for M tuberculosis DNA. In the experimental group, however, the tests were positive in 15 cases (five of 13 in Ethiopia, and 10 of 34 in Mexico). (Eight of the Mexican subjects were children of 16 years or less and six of those had positive PCR tests.) None of the tissue samples showed histological evidence of tuberculosis. The mycobacterial DNA was located within alveolar and interstitial macrophages, type II pneumocytes, endothelial cells, and fibroblasts.  The presence of mycobacterial DNA does not, of course, prove the presence of living organisms and the method used would detect BCG DNA as well as that from infective M tuberculosis (see commentary, Ibid:2113–4). Nevertheless, if latent mycobacteria do reside in normal lung cells, rather than in old encapsulated lesions, fresh thoughts about the elimination of latent infection may be needed.

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