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Category: Clinical Microbiology
Mycobacteria: Leprosy, a Battle Turned; Tuberculosis, a Battle Raging; Paratuberculosis, a Battle Ignored, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555815486/9781555814304_Chap08-1.gif /docserver/preview/fulltext/10.1128/9781555815486/9781555814304_Chap08-2.gifAbstract:
This chapter addresses three mycobacterial organisms that have entirely different profiles: Mycobacterium leprae, Mycobacterium tuberculosis, and Mycobacterium avium subsp. Several trends continue to gravely threaten progress toward further global reductions in tuberculosis (TB). Of the 85 species within the genus Mycobacterium, members of the Mycobacterium tuberculosis complex have evolved as one of the preeminent pathogens of man. The clinical course of TB can be roughly divided into three phases: primary infection, latent TB, and chronic active TB. Additionally, for both M. leprae and M. tuberculosis, multiple-drug therapy (MDT) is usually considered obligatory, to prevent the emergence of resistant mycobacterial strains. The other two components of this chapter enunciate in detail that even with the most intensive MDT regimes, neither M. leprae nor M. tuberculosis is eradicated. A provocative study has reported that mycobacterial antigen activation of toll-like receptors 2 (TLR2) on monocytes from tuberculoid leprosy patients induced differentiation into cells bearing the dendritic cell-specific intercellular adhesion molecule grabbing nonintegrin MPH and CD1b+ DC. Biopsies of lepromatous lesions reveal acute inflammation, with focal infiltrates of polymorphs, superimposed upon the chronic inflammation and high mycobacterial load of lepromatous (LL-BL) leprosy. Initial comparisons of M. leprae’s genome with that of M. tuberculosis and more recently with those of other mycobacterial species have made it possible to assign potential gene function to many of M. leprae’s genes. Additionally, an appropriately designed potent vaccine should protect against many, if not all, drug-resistant mutants of the infectious agent, an inevitability in leprosy that cannot be minimized.
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The cycle of TB infection and opportunities to interrupt it. Solid arrows indicate the path of various stages in the cycle of TB infection. Dashed lines indicate opportunities to interrupt the cycle of infection. Numbers refer to the most important corresponding control methods used to interrupt the cycle of infection. 1, public health and epidemiological measures; 2, multidrug treatment of active disease; 3, single-drug treatment of asymptomatic infection; 4, immunologic enhancement, including vaccination.
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The immunopathologic spectrum of leprosy. Representative sections of human skin biopsy specimens illustrate the full spectrum of inflammation seen in leprosy. Well-organized granulomatous inflammation characterizes polar TT lesions; the perimeter of the epithelioid center of a granuloma is outlined by the arrowheads. In borderline tuberculoid (BT) lesions, the granulomas are less well organized but still contain typical features, such as giant multi-nucleated cells (arrow). BB lesions contain both well-formed granulomas (bottom of BB panel) and disorganized areas (top of panel). Disorganization becomes more pronounced and foamy histiocytes become more prominent in BL lesions, and polar LL lesions are composed of the completely disorganized sheets of foamy MPH. Most patients are classified in the broad borderline region. As indicated in the diagram, the number of bacilli present in lesions (solid line) varies from rare in TT lesions to abundant in LL ones. This is inversely related to the patient’s degree of CMI to M. leprae. The open arrows indicate the portions of the spectrum in which patients are at risk for T1R or T2R, reversal or ENL leprosy reactions, respectively. [Modified from Frankel, R. I., and D. M. Scollard. Leprosy. In Philip Brachman and Elias Abrutyn (ed.), Bacterial Infections of Humans, 3rd ed. Springer, in press.]