Biology of the mycobacterioses. The comparative epidemiology of leprosy and tuberculosis.
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Bacteria isolated from lesions of lepromatoid leprosy in the armadillo were studied in comparison with Mycobacterium leprae isolated directly from human lepromatous leprosy lesions. Three methods were used to show that the bacteria from the lesions of the armadillo were identical to those of the human lesions: (i) extraction of the bacteria with pyridine and subsequent staining with various techniques, (ii) the competence in clearing bacilli (CCB) test, and (iii) the Mitsuda test.
The immune responses to Mycobacterium leprae and other mycobacterial antigens were studied in 11 leprosy patients with concurrent human immunodeficiency virus type 1 (HIV-1) infection. Three patients manifested borderline lepromatous leprosy, and eight patients had borderline tuberculoid (BT) leprosy. Despite the low CD4+ T-cell count in the peripheral blood, no histologic or phenotypic change in the cellular infiltrate in either the lepromatous or tuberculoid lesions was observed when compared with HIV-1-negative patients. Lepromatous lesions contained heavily parasitized macrophages and few CD8+ T cells. Lesions from the patients with BT leprosy showed extensive CD4+ T-cell infiltration despite a significant reduction in CD4+ T-cell counts in the peripheral blood. No acid-fast bacilli were detected in the tuberculoid lesions. HIV-1 infection did not alter the lack of response in lepromatous leprosy to M. leprae antigens either in vitro or in vivo. In contrast, the skin test response to M. leprae antigens as well as the in vitro lymphoproliferative responses to mycobacterial antigens that are usually seen in patients with tuberculoid leprosy were abrogated in the BT HIV-1+ patients. However, production of gamma interferon in response to the same stimuli was preserved in most of the patients. Analysis of cytokine gene expression showed activation of additional cytokine genes in the unstimulated peripheral blood cells of patients with both leprosy and HIV-1 infections as compared with cells from patients with leprosy alone. These results suggest that granuloma formation in leprosy can be independent of the impaired CD4+ T-cell response of the HIV-1 infection. Furthermore, in HIV-1+ individuals with M. leprae infection, activation of cytokine genes is observed even when the circulating CD4+ T-cell count is significantly reduced.
From a series of 343 nerve biopsies taken by one clinician over a period of 12 years in Nepal, this paper describes the histopathological findings in 153 biopsies from 119 patients suffering from tuberculoid, borderline (dimorphous) or lepromatous leprosy, who were untreated at the time of first presentation and diagnosis. They were taken during the course of other studies, mainly concerned with the mode of transmission of leprosy, and which included biopsies of skin, dartos muscle, nasal mucous membrane and nipple, results of which have already been published. Examination of serial sections by light microscopy revealed a density of cellular infiltration in non-lepromatous cases, or of bacilli in macrophages and Schwann cells in lepromatous cases, which was marked in degree and usually widespread from one end of the biopsy to the other. Intraneural caseation was recorded in four patients with tuberculoid or borderline-tuberculoid leprosy, and many others in this part of the spectrum showed extensive disruption of perineurial and endoneurial structure. In lepromatous patients, the numbers of bacilli in the endoneurial area not infrequently exceeded one thousand per oil immersion field. Although well known to histopathologists familiar with this disease, it is considered that the significance of these findings, in patients presenting for the first time, is not well appreciated by those working in general medicine, neurology, epidemiology, or even in leprosy control.
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A comparison was made on the characteristics of the infiltrates, the number and distribution of CD1-positive epidermal Langerhans cells (LC) at the sites of skin reaction induced by autologous peripheral-blood-derived mononuclear cells (PBMC) in leprosy patients. Clinically and histologically, the skin reaction was well expressed in tuberculoid patients as compared to lepromatous patients, erythema nodosum leprosum (ENL) patients and contacts. The quantum of lymphocytes in the infiltrates was maximal in the tuberculoid patients and it was minimal in lepromatous and ENL patients. The number and distribution of LC in the tuberculoid patients was significantly higher in the PBMC-inoculated sites as compared to control sites over 24 h. In contrast, no difference in the number and distribution of LC was noticed in the lepromatous and ENL patients. These observations indicate that the lymphocytes of tuberculoid patients in contrast to lepromatous leprosy patients are capable of sustenance in the local micro-environments of the skin and an effective interaction may be possible between LC and PBMC.
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