Lepromatous Lesions Research Articles

The cutaneous infiltrates of leprosy: cellular characteristics and the predominant T-cell phenotypes.

We report on the characteristics of cells in the cutaneous lesions and blood of 21 patients with lepromatous, tuberculoid, and intermediate forms of leprosy. A large proportion of the infiltrates in lepromatous lesions consist of macrophages heavily parasitized with Mycobacterium leprae. The T cells in the lesions are devoid of OKT4/Leu 3a-positive ("helper") cells and consist almost exclusively of OKT8/Leu 2a-positive ("suppressor") populations. In contrast, the tuberculoid infiltrates contain well-organized epithelioid and giant-cell granulomas and only remnants of bacilli, and the predominant T cell is from the OKT4/Leu 3a-positive subset. In both tuberculoid and lepromatous infiltrates, T cells and macrophages expressed HLA-DR antigen. No marked alteration in the distribution of blood T-cell phenotypes was noted. We conclude that there is a marked difference between T-cell subsets in lepromatous and tuberculoid infiltrates, which may influence the microbicidal activity of macrophages in the lesions.

Borderline leprosy. Study on new borderline cases in Japan (author's transl)

This reports results of the clinical, bacteriological, immunological and histological studies on 18 new borderline cases in Japan. These cases were clinically classified as BT (6 cases), BT/BB (2), BB (1), BB/BL (1), BL (7) and B (1). The maximum score of B.I. in these cases failed into two main groups, i.e., a group of B.I. 0 and that of B.I. 5-6. Results of the late lepromin reaction test were weak positive in 8 cases, doubtful in 4 and negative in 5. In 3 cases, lepromin test was done on both the inside and outside of their annular skin lesion, and there was no significant difference between them in all cases tested. The test by FLA-ABS method revealed significantly higher titers in BL group than in BT and BT/BB groups. Among 7 cases clinically diagnosed as BL, 5 cases were histologically classified as LL. Other one case showed different features in biopsy specimens of two different lesions.Epitheloid cell granuloma in the foamy cell infiltration was observed in 6 cases. The granuloma varied from BT to BL with varying degrees of lymphocytic infiltration and appearance of giant cells. These changes were interpreted as those resulted from some acquired delayed hypersensitivity against Mycobac. leprae antigens which developed after lepromatous lesions were established. These findings are unusual in the new patient, and the changes observed were tentatively termed in this report as "reaction from L" because Ridley and Jopling's classification was not applicable in these cases. While "Madrid" classification has officially been adopted in Japan since 1979, several propositions on the classification in Japan are made in an attempt to prevent confusion in clinical and statistical studies on this disease.

Growth inhibitory activity of deoxyribonucleic acid-containing factor(s) isolated from lepromatous lesions.

Deoxyribonucleic acid-containing factor(s) isolated from Mycobacterium leprae suspensions obtained from lepromas of nine patients showed growth inhibitory activity against Micrococcus and both orange-red-pigmented and coccoid mutants of mycobacteria. No growth inhibition was observed for parent mycobacterial species, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus epidermidis.

Immunological Problems in Leprosy Research

This Memorandum reviews the present status of knowledge of the immunology of leprosy, with particular attention to developments since the publication of a similar review in 1970. The different types of lepromin reaction and their significance in healthy contacts and in patients with tuberculoid and lepromatous leprosy are discussed. The immunological responsiveness of patients with leprosy is also considered, with special attention to in vitro methods for evaluating this response. Part 2 of the Memorandum will cover possible mechanisms of altered immune response in leprosy (including a tentative scheme to explain the possible genesis of the lepromatous lesion); genetic, nutritional, and hormonal factors; the possibility of vaccination; attempts at immunotherapy; and areas in which further research is needed. A detailed protocol for evaluating the effect of transfer factor in leprosy will be included as an annex.

Application of Nyka's method for the staining of mycobacteria in leprous skin sections.

Biopsy specimens from 20 leprosy patients have been studied. Adjacent sections were in each case both stained by the ordinary Ziehl‐Neelsen method and after oxidation with periodic acid (Nyka's method). Sections from tuberculoid, indeterminate and lepromatous lesions all revealed an increased number of acid fast bacilli after oxidation. In ten examinations of tuberculoid and indeterminate cases the increase observed was in average four‐fold. It is concluded that there is a considerable higher number of bacilli present in leprous tissue than revealed by the ordinary Ziehl‐Neelsen method.

Ocular leprosy in Uganda.

Leprosy has been noted to cause more ocular complications than any other systemic bacterial disease (Mendonsa de Barros, 1946). Before the advent of sulphone treatment almost every leprosy patient sooner or later developed an ocular complication (Prendergast, 1940; MendonSa de Barros, I946), but modern treatment has reduced the incidence of ocular complications judging from the more recent reports (Holmes, I957; Chatterjee and Chaudhury, I964; McLaren, Shaw, and Dalley, I96I; Crawford, 1969; Ticho and Ben Sira, I970). Nevertheless, leprosy still causes much morbidity in all countries where it is endemic. The incidence of the ocular complications of leprosy varies from one country to another, because of differences in the availability of and the amenability of the people to modern treatment, the stage of the disease at which treatment is commenced, and the relative frequency of the main clinical types of the disease. Where there is more lepromatous than tuberculoid leprosy, the incidence of ocular complications tends to be higher (Chatterjee and Chaudhury, I964). The range of the age of the people screened may also lead to variation, as the proportion of ocular involvement increases with age. Furthermore, there also seem to be regional variations, since it has been noted that lepromatous ocular lesions are more common in temperate than in tropical areas (Doull, I959). The ocular complications ofleprosy in Uganda have not been reported before. Although the incidence of the various ocular lesions broadly follows the general pattern, the data from this survey lends support to findings from other parts ofAfrica, that certain eye lesions are uncommon in this region.

Some cytochemical and cytophysiological properties of the cells from tuberculoid and lepromatous lesions.

Some cytochemical and cytophysiological properties of the cells from tuberculoid and lepromatous lesions.

Tissue mast cells.

WHILE examining the histology of tuberculoid and lepromatous skin lesions of leprosy, we noted that there were many cells containing acid-fast granules in the cytoplasm, around the granulomatous collections, in the connective tissue and in relation to small capillaries in both types of the disease. These granules were spherical, and stained somewhat paler red than the acid-fast Myco. leprae with the Fite-Faraco modification of Ziehl-Neelsen stain using Harris's haematoxylin as counter-stain. These cells were rounded, oval, stellate or spindle-shaped with oval, rounded or bean-shaped nucleus. The cell membrane was indistinct, and in some cells the granules appeared extracellular.

ELECTRON MICROSCOPE STUDY OF MYCOBACTERIUM LEPRAE AND ITS ENVIRONMENT IN A VESICULAR LEPROUS LESION

Imaeda, Tamotsu (Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela) and Jacinto Convit. Electron microscope study of Mycobacterium leprae and its environment in a vesicular leprous lesion. J. Bacteriol. 83:43-52. 1962.-Biopsied specimens of a borderline leprosy lesion were observed with the electron microscope. In this lesion, the majority of Mycobacterium leprae were laden with cytoplasmic components. The bacilli were separated from the cytoplasm of host cells by an enclosing membrane, thus differing from the environment of well-developed lepra cells in lepromatous lesions. The cell wall is composed of a moderately dense layer. A diffuse layer is discernible outside the cell wall, separated from it by a low density space. It is suggested that the cell wall is further coated by a low density layer, although the nature of the outermost diffuse layer has not yet been determined. The plasma membrane consists of a double layer, i.e., dense inner and outer layers separated by a low density space. The outer layer is closely adjacent to the cell wall. In the region where the outer layer of the plasma membrane enters the cytoplasm and is transformed into a complex membranous structure, the inner layer encloses this membranous configuration. Together they form the intracytoplasmic membrane system. In the bacterial cytoplasm, moderately dense, presumably polyphosphate bodies are apparent. As neither these bodies nor the intracytoplasmic membrane system are visible in the degenerating bacilli, it seems probable that these two components represent indicators of the state of bacillary activity.

Electron microscopic study of the ultra-thin sections of leprous peripheral nerves.

1. Ultra-thin sections of great auricular nerves from one lepromatous and three tuberculoid cases of leprosy were made and examined with electron microscope. 2. In a lepromatous great auricular nerve, we have found My. leprae in axons, degenerated myelin sheaths, “Bungnersche Bander” and also in lepra cells of the nerve interstitium. 3. My. leprae were found in “Bungnersche Bander” only in one of the three tuberculoid cases. 4. It is most probable that My. leprae invade primarily axons of the peripheral nerves, and then, axons and myelin sheaths are destroyed byWallerian degeneration. My. leprae settle for a long period in the cytoplasm ofSchwann cells which had already changed into “Bugnersche Bander”. 5. The endoneurial lepra cells of the lepromatous nerve lesions do not destroy the neuralemmal collagen fibers andSchwann cell surface membrane, and for this reason “Bungnersche Bander” remain unchanged in the lepromatous nerve lesions. On the contrary, the epithelioid cells of the tuberculoid nerve lesions destroy the neurilemmal collagen fibers andSchwann cell surface membrane, and break the structure of “Bungersche Bander”. This destruction of the nerve parenchyma causes the profound necrosis of the nerve trunk of tuberculoid leprosy.

Electron microscopy of the leprosy bacillus: A study of submicroscopical structure

Summary This paper reports a preliminary study of the leprosy bacillus with the electron microscope. The submicroscopical structure of the intact bacillus is compared with the results of ultra-thin sectioning. Material from 6 patients with lepromatous lesions and from 3 patients suffering from the tuberculoid or macular type of leprosy was obtained at the leprosarium at Oicha in the Belgian Congo. Tissue juices were embedded in agar and fixed in osmic acid. They were transported to England by air in 70 per cent alcohol, and then embedded in methacrylate. Punch biopsies were prepared in the same way. The leprosy bacilli in the tissue juices were observed to occur as isolated filaments and rods, and as groups of organisms or ‘globi’. Their submicroscopical structure is described and compared with that of the tubercle bacillus. Tissue cells were present in the juices and the appearance of intracellular bacilli is described. The results obtained with the electron microscope are compared with observations made by earlier workers with stained preparations and the various theories arising from them are discussed.

癩菌と末梢神経

The relationship between M. leprae and peripheral nerves has been studied since the beginning of the scientific research of leprosy by many workers, especially from histo-pathological point of view.In this paper we present the data of our experimental studies concerning the affinity of M. leprae to peripheral nerves. We have studied this problem by the following experiments and observations, i. e. "Intraneural inoculation of acid-fast bacilli, " "Tissue culture of leprous peripheral nerves" and "Biomicroscopy of leprous corneal nerves" etc.1) Intraneural inoculation of acid-fast bacilli.We inoculated M. leprae, M. leprae murium, Tubercle bacillus (human, bovine and avian types), B. C. G., M. ulcerans, Smegma bacillus in sciatic nerves of rabbits, guinea-pigs, rats and monkey, and examined histo-pathologically the affinity of these acid-fast bacilli to the peripheral nerves of these mammalians.We have found that acid-fast bacilli multiply in peripheral nerves of susceptible animals, especially in the endoneurial cells. For instance, M. leprae murium causes intraneural leprom in the sciatic nerves of rats, when inoculated directly in these nerves. Tubercle bacillus multiplies in the sciatic nerves of susceptible animals, and makes tuberculous lesions in these nerves. M. leprae does not multiply in. the peripheral nerves of monkey, rat, guinea-pig and rabbit. The most strong lipoid degeneration was observed in the lesions of intraneural inoculation of M. leprae into rabbits. Strong calcification occurs very often, when smegma bacillus is inoculated into the sciatic nerves of rabbits.2) Tissue culture of the leprous peripheral nerves.We have cultured 14 biopsy specimen of leprous peripheral nerves in vitro, and examined the possibility of multiplication of M. leprae in the growing cells.Endoneural fibroblasts are most frequently seen in the tissue culture of lepromatous nerves, on the contrary tuberculoid nerves show scanty cell growth in vitro. Sometimes small number of M. leprae was found in the growing cells, but we could not conclude from such finding the multiplication of M. leprae in vitro. The growth of Schwann cells as observed frequently in the tissue culture of normal peripheral nerves was rarely encountered in the culture of leprous nerves. This fact is perhaps related to the deficiency of nerve regeneration in leprosy cases.3) Biomicroscopy of leprous corneal nerves.We have examined biomicroscopically the corneal nerves of leprosy patients and confirmed the "beaded corneal effect" in both lepromatous and tuberculoid cases. This finding indicated the affinity of M. leprae to the peripheral nerves of both polar types of leprosy.We have also examined the corneal nerves of rabbits by polarizing microscope and found that there is a thin bi-refringent layer over the axon even in the so-called amyelinated portion of corneal nerves.4) Histo-chemical study of leprous peripheral nerves.In the tuberculoid nerves both acid and alkaline-phosphatase were found histochemically, and in case of lepromatous nerve lesions we have found acid phosphatase, but no alkaline phosphatase was confirmed. We think alkaline phosphatase in tuberculoid nerve lesions might play a role in the calcification of tuberculoid nerve lesions.5) Study of the nerve regeneration in leprous nerves.We examined the nerve stump of re-amputated legs of leprosy cases with polarizing microscope, and found that this microscope is very convenient to trace the remaining myelin sheath in the highly degenerated nerves.6) Summary and conclusion.M. leprae has an affinity to the axon in both lepromatous and tuberculoid leprosy, and after reaching peripheral nerves, it causes different lesions according to the tissue resistance of the individual toward this microbe.

Tentativas de transmissão da lepra ao homem, por meio de Triatomídeos infectados em doentes lepromatosos: (nota prévia)

The A.A. started a new series of experiments upon the transmission of Leprosy to man by means of one of the more widespread hematophagi of the hinterland of Brazil, the Triatomidae. Two species of these insects were found naturally infected with Hansen's bacillus in huts of lepers in the interior of the State of Minas Gerais and one of the writers (S.A.) upon feeding the same insects on lepromatous cases could obtain two strains of acid-fast bacilli cultures smearing Lowenstein medium with the intestinal contains of the same. The first phase of the experiments lasted five months and the results, partially positive, are here describe. More than one hundred Triatomidae (Triatoma infestans and Panstrongylus megistus) bred in the Institute Oswaldo Cruz and fed in normal pigeons until convenient growth were put on lepromatous lesions, which they sucked many times, and them after one or more days they were put to be fed on selected regions of the skin of four negativated cases of leprosy. The arguments in favour and against the possibility of obtaining new lesions of leprosy in such burnet out patients were discussed. The A.A. are not authorized to draw any definite conclusions, but the few facts registered are worth of divulgation, in orther that other workers send their suggestions. Three out of the four volunteers showed moderate local reactions between 1 to 4 days after being sucked by the infected insectes. After five months experiments subcutanous lymph were obtained from the points where the insects have bitten. A very few acid-fast bacilli were found in such material. The patients, being kept in separation from infectious cases, will be followed up during months or a year in order to be detected any suspicious experimental lesions of leprosy.

Resultados comparativos das reações intra-dermicas com antígenos de bacilos ácido-alcool-resistentes (Leprolinas "Souza-Araújo") e emulsão de lepromas (Lepromina): (Primeira Nota)

Em 20 portadores de Lepra, internados na Colônia de São Roque, Paraná, 13 dos quais eram da forma lepromatosa e os 7 restantes da forma nervosa pura ou tuberculoide, o autor estudou a reação intradérmica de antigenos bacilares (Leprolinas Souza-Araujo 1, 1a, 3, 5, 5a), comparativamente com as reações produzidas, ao mesmo tempo, com antígeno lepromatoso (Emulsão de lepromas, lepromina). Observou o seguinte: 1.° - Que a lepromina, comportou-se como habitualmente, isto é, negativa nos lepromatosos e ositiva nos nervosos e tuberculoides e sempre mais intensa ao fim da quarta semana. 2.° - Que as leprolinas provocam reações, que o autor não conclui serem positivas ou negativas no sentido imunológico da expressão em virtude de estar estudando-as neste sentido, nos leprotomatosos e tuberculoides, mas, sempre mais intensas entre a 1.ª e 2.ª semanas, diminuindo de intensidade na 3.ª e desaparecendo ou quase desaparecendo ao fim da quarta semana: nódulos, nódulos-eritema, ulcerações. 3.° - Que nestas reações houve destruição de tecidos, pois a presença tardia de cicatrizes, mesmo quando não houve ulceração, mostra êste fato. 4.° - Que as inoculações das lepromina, não trouxeram nenhum inconveniente a saúde dos paciente; embora um deles tenha apresentado nos primeiros dias leve reação geral; outro, intensa fusão de suas lesões nodulars de lepra e, dois outros, a chamada Reação leprótica.