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Chapter 8 : Mycobacteria: Leprosy, a Battle Turned; Tuberculosis, a Battle Raging; Paratuberculosis, a Battle Ignored

Authors: R. J. Greenstein1, T. Gillis2, D. S. Scollard3, S. T. Brown4
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Affiliations: 1: Veterans Affairs Medical Center, Department of Surgery, Bronx, NY 10468; 2: Laboratory Research Branch at Louisiana State University, National Hansen’s Disease Programs, Baton Rouge, LA 70803; 3: Laboratory Research Branch at Louisiana State University, National Hansen’s Disease Programs, Baton Rouge, LA 70803; 4: Veterans Affairs Medical Center, Department of Medicine, Bronx, NY 10468
Content Type: Monograph
Publication Year: 2009

Category: Clinical Microbiology

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Abstract:

This chapter addresses three mycobacterial organisms that have entirely different profiles: , , and subsp. Several trends continue to gravely threaten progress toward further global reductions in tuberculosis (TB). Of the 85 species within the genus , members of the 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 and , 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 nor 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 genome with that of and more recently with those of other mycobacterial species have made it possible to assign potential gene function to many of 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.

Citation: Greenstein R, Gillis T, Scollard D, Brown S. 2009. Mycobacteria: Leprosy, a Battle Turned; Tuberculosis, a Battle Raging; Paratuberculosis, a Battle Ignored, p 135-167. In Fratamico P, Smith J, Brogden K (ed), Sequelae and Long-Term Consequences of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555815486.ch8
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Mycobacteria: Leprosy, a Battle Turned; Tuberculosis, a Battle Raging; Paratuberculosis, a Battle Ignored
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Citation: Greenstein R, Gillis T, Scollard D, Brown S. 2009. Mycobacteria: Leprosy, a Battle Turned; Tuberculosis, a Battle Raging; Paratuberculosis, a Battle Ignored, p 135-167. In Fratamico P, Smith J, Brogden K (ed), Sequelae and Long-Term Consequences of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555815486.ch8
/content/10.1128/9781555815486.ch08.ch08fig01
Figure 1.
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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10.1128/9781555815486/ch8fig1.gif
Image of Figure 1.
Figure 1.

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.

Citation: Greenstein R, Gillis T, Scollard D, Brown S. 2009. Mycobacteria: Leprosy, a Battle Turned; Tuberculosis, a Battle Raging; Paratuberculosis, a Battle Ignored, p 135-167. In Fratamico P, Smith J, Brogden K (ed), Sequelae and Long-Term Consequences of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555815486.ch8
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Figure 2.
Salicylic acid and derivatives.
10.1128/9781555815486/ch8fig2_thmb.gif
10.1128/9781555815486/ch8fig2.gif
Image of Figure 2.
Figure 2.

Salicylic acid and derivatives.

Citation: Greenstein R, Gillis T, Scollard D, Brown S. 2009. Mycobacteria: Leprosy, a Battle Turned; Tuberculosis, a Battle Raging; Paratuberculosis, a Battle Ignored, p 135-167. In Fratamico P, Smith J, Brogden K (ed), Sequelae and Long-Term Consequences of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555815486.ch8
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Figure 3.
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 . 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. Philip Brachman and Elias Abrutyn (ed.), , 3rd ed. Springer, in press.]
10.1128/9781555815486/ch8fig3_thmb.gif
10.1128/9781555815486/ch8fig3.gif
Image of Figure 3.
Figure 3.

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 . 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. Philip Brachman and Elias Abrutyn (ed.), , 3rd ed. Springer, in press.]

Citation: Greenstein R, Gillis T, Scollard D, Brown S. 2009. Mycobacteria: Leprosy, a Battle Turned; Tuberculosis, a Battle Raging; Paratuberculosis, a Battle Ignored, p 135-167. In Fratamico P, Smith J, Brogden K (ed), Sequelae and Long-Term Consequences of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555815486.ch8
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