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PubMed1986

Natural killer (NK) cell activity and reversal reaction in leprosy.

Two studies were conducted to assess natural killer (NK) cell activity in leprosy patients and healthy Ethiopian controls. The first study tested 26 untreated leprosy patients across the spectrum of the disease. It was found that lepromatous leprosy and all untreated, nonreactional patients had lower NK activity than healthy controls. However, patients presenting with reversal reaction (RR) had NK activity within the normal range. Heterogeneity was particularly marked in the NK activity of borderline patients. In the second study, NK cell activity was assessed in treated borderline tuberculoid leprosy (BT) patients. There were 30 patients with a history of RR and 27 BT patients without such a history (NR). All patients had had at least 3 years of dapsone treatment and 6 months of multidrug therapy. There were 26 control subjects. NK activity was higher in controls than in patients only at one effector:target (E:T) ratio tested, but NK cells from the BT patient group appeared to be more "aggressive" in that there was significantly (p less than 0.001) less reduction of activity with dilution of effector cells. There were no significant differences in NK activity between RR and NR patients. The NK activity of NR patients was positively correlated with the size of induration of the lepromin response. We conclude that higher NK activity in acute RR would appear to be a consequence rather than a cause of reversal reactions.

Cytotoxicity, Immunologic↗

PubMed1985

Leprosy in a mangabey monkey--naturally acquired infection.

Naturally acquired leprosy was detected in an otherwise normal "sooty" mangabey monkey (Cercocebus atys). This animal was imported from West Africa in 1975 and developed clinical symptoms of leprosy in 1979. Histopathologic findings were those of subpolar-lepromatous to borderline-lepromatous leprosy in the Ridley-Jopling classification. The disease was progressive, with crippling neuropathic deformities of the hands and feet. The disease regressed under specific therapy. The etiologic agent was identified as Mycobacterium leprae by the following criteria: invasion of nerves of host, staining properties, electron microscopic findings, noncultivable on mycobacteriologic media, DOPA-oxidase positive, lepromin reactivity, infection patterns in mice and armadillos, sensitivity to sulfone, and DNA homology. We believe the animal acquired the disease from a patient with active leprosy. The mangabey monkey offers promise as a primate model for leprosy, and adds a third reported species to animals with naturally acquired leprosy.

Animals↗

PubMed1985

A single skin lesion--an unusual presentation of lepromatous leprosy.

Lepromatous leprosy presenting as a solitary lesion with a high bacterial count is a rare occurrence. Such a case has been followed at the National Hansen's Disease Center, Carville, Louisiana, U.S.A., since 1977. The lesion was located on the left elbow and had been present for about nine months. The bacterial index in the lesion was 5+ and the morphological index was 0%, but slit-skin smears elsewhere were negative. The histopathology of the lesion was that of subpolar lepromatous leprosy, and the lepromin skin test was negative. Growth of the organism in the mouse foot pad was characteristic of Mycobacterium leprae, and the patient's response to dapsone monotherapy has been excellent. Therefore, this patient with a single skin lesion has lepromatous leprosy histologically, immunologically, and bacteriologically. This case illustrates the importance of slit-skin scrapings and biopsy in new cases with unusual lesions and, secondly, suggests that there are factors yet undetermined which play a significant role in determining host response to M. leprae.

Biopsy↗

PubMed1970

BCG vaccination of children against leprosy. Preliminary findings of the WHO-controlled trial in Burma.

The use of BCG vaccine in the prevention of leprosy has been one of the most important subjects of investigation in the field of leprology in the last 25 years. The action of the vaccine was for many years investigated by determining its effect on the lepromin reaction. Field studies were later considered essential to determine whether BCG vaccination would be useful to leprosy contacts, to the child population probably exposed to infection, or to persons persistently lepromin-negative.The interest of the World Health Organization in this matter began in 1952 and, following the recommendations of certain advisory committees, it was decided to institute a field trial in Singu township in Burma. The main purpose of the investigation was to observe, in a highly endemic area, the protective effect, if any, of BCG vaccine against leprosy in the child population not exposed to Mycobacterium leprae at home but possibly exposed to the infection elsewhere.Field operations began at the end of August 1964 and the preliminary findings obtained up to the end of June 1968 relate to 3 annual re-examinations. So far, from the material studied, it appears that, under the conditions prevailing in Singu township, no significant effect of BCG vaccine can be seen within a period of 3 years. When children in both trial groups are followed-up for much longer periods, mainly children aged 0-4 years at intake, it is possible that a significant difference may emerge. However, to be operationally desirable, a merely significant difference is not enough; the protective effect of BCG should be substantial to warrant its large-scale use as an immunization procedure against leprosy.

Adolescent↗

PubMed1973

BCG vaccination of children against leprosy: seven-year findings of the controlled WHO trial in Burma.

A controlled study of the efficacy of BCG vaccination for the prevention of leprosy began in Burma at the end of August 1964. This paper presents the findings after 7 years-i.e., the results of 6 annual follow-up examinations up to the end of June 1971. The incidence rate in BCG-vaccinated children 0-4 years of age at intake was lower than that in children in the control group. The protection conferred by BCG was relatively low (44%) and applied only to early cases of leprosy, the great majority tuberculoid cases. BCG vaccination did not protect household contacts or children 5-14 years of age who were not exposed in the household. This reduction must be interpreted in the light of several factors: form of leprosy, bacterial status, lepromin reactivity, evolution of cases, and level of endemicity. Consequently it does not seem probable that the reduction in incidence would substantially affect the pattern or trend of the disease in an area similar to that where the study is being carried out; the probability would be much lower if not nil in regions of relatively low endemicity (1-2 per 1 000 or less).

Adolescent↗

PubMed1973

Some epidemiological data on leprosy collected in a mass survey in Burma.

In the WHO Leprosy BCG Trial in Burma a mass survey was undertaken to determine whether children had been exposed to patients with leprosy and, if so, the form of the index case. This paper presents the most important epidemiological data collected in this survey. The prevalence rate was 31.6 per 1 000. It seems that even if the prevalence rate is very high the L rate does not increase accordingly. The high T rates in areas of high endemicity seem to be related mainly to the degree of spreading of leprosy, even to persons who react to lepromin. Comparison of the results with data available for the area before the survey was made shows that 87% of the L cases had already been detected and that 54% of the T cases had not. There was a tendency for high L rates to be associated with high prevalence rates. The results do not suggest that any particular age group has greater susceptibility or resistance; the prevalence rates seemed to be related mainly to the age when exposure occurred. A higher prevalence of leprosy in males started to appear in the 10-14-year age group, and after the age of 15 the difference became impressive. Biological, socio-economic, and environmental factors seem to be responsible for the level of endemicity, which does not seem to be essentially or primarily related to ethnic origin.

Adolescent↗

PubMed1966

An epidemiologist's view of leprosy.

While leprosy has been studied exhaustively by leprologists, it is only recently that persons in other disciplines have given this disease the attention it deserves. Various methods for its prevention and control are now being advocated and tested in the field, and it appears reasonable for an epidemiologist to review the bases of current theories and to examine the evidence for existing hypotheses. This has been done by a review of some of the more recent literature. The conclusion is reached that the anergic, or factor N, hypothesis that has been evolved to relate the lepromin test to the findings in clinical leprosy appears to be the most promising, and that, if this hypothesis can be substantiated, it is unlikely that BCG vaccination can be a very useful tool for prevention. Many possibilities exist for epidemiological and laboratory research into this disease, which in many ways appears to be unique.

Epidemiologic Methods↗

PubMedDate not supplied

Hepatic lesions in asymptomatic children of leprosy patients.

Forty-two asymptomatic children of leprosy patients were studied for possible hepatic lesions. Hepatic lesions were observed in 47% while acid-fast bacilli in the liver were found in 9.5%. The most frequent lesions encountered included granuloma in 9.5%, focal areas of necrosis in 14%, portal triaditis in 17%, and Kupffer cell hyperplasia in 33%. Occasionally more than one lesion was observed in a biopsy. No correlation with the occurrence of the various hepatic lesions could be made with a history of BCG vaccination or results of skin tests done with tuberculin and lepromin.

Adolescent↗

PubMed1983

Leprosy in Vietnamese refugees: a case report.

A 41-year-old Vietnamese refugee was found to have tuberculoid leprosy. Dapsone treatment cleared her skin lesion, but did not remove the paraesthesia in the right ulnar nerve. Immunological investigations revealed a strongly positive lepromin test and a significant change in the ratio of T-y and T-mu lymphocytes in peripheral blood. The incidence of leprosy in Vietnamese refugees in Scandinavia is discussed.

Adult↗

PubMed1983

Suppressor cell activity and phenotypes in the blood or tissues of patients with leprosy.

Suppressor cell activity has been demonstrated in the peripheral blood of patients with leprosy. Cells bearing the suppressor/cytotoxic phenotype have been enumerated in both peripheral blood and tissues, and microanatomical differences in tissue distribution have been observed. This first generation of studies has been characterized by considerable disagreement, a not unusual circumstance in the study of leprosy. In the case of blood suppressor cell activity, there appears to be no doubt as to its existence, but much uncertainty regarding its distribution. Concerning peripheral blood phenotypic suppressor cells, the observed differences in lepromatous and ENL patients may well reflect differences in methods used. Concerning phenotypic suppressor cells in tissue, there is no agreement as to their numbers or microanatomical distribution across the spectrum of leprosy or in its reaction states. Although these observational differences make firm conclusions impossible, this first generation of studies has provided new ways of considering old problems. For example, lepromin unresponsiveness might be a consequence of active cellular suppression. Differences in the numbers (or percentages) of the suppressor phenotype in blood or tissues of lepromatous patients with or without ENL reopens the door to the possibility of cell-mediated immune mechanisms in the pathogenesis of ENL. The identification of defective suppressor cells as important in the pathogenesis of hypergammaglobulinaemia is of interest in and of itself, but also gives rise to the possibility that other kinds of phenomena may be a consequence of defective or effete suppressor mechanisms. The observation of microanatomical differences in the distribution of the suppressor phenotype in tuberculoid and lepromatous leprosy indicates that effective or ineffective immunity might be a sequela of particular interactions between the suppressor/cytotoxic and helper/inducer phenotypes, and that these interactions merit further study. These new perspectives may be subject to experimental testing by the next generation of studies, which will surely include the techniques of clonal expansion and limiting dilution, as well as the study of interleukins 1 and 2.

Humans↗

PubMed1981

Studies on T cell subsets and functions in leprosy.

T cell subsets and T cell functions were explored in 31 leprosy patients with the following methods: determination of the percentages of the different T cell subpopulations defined by monoclonal antibodies directed at total T cells, helper T cells and suppressor/cytotoxic T cells; measurement of the in vitro proliferative responses to mitogens; study of the concanavalin A-induced suppressive activity, assessed on MLC; measurement of delayed-type hypersensitivity by skin testing. The confrontation between immunological lepromatous patients without type-2 reaction (erythema nodosum leprosum), (2) lepromatous patients without ENL (erythema nodosum leprosum), (2) lepromatous patients was recent ENL and (3) tuberculoid patients. Unexpectedly, groups 1 and 3, although differing strongly in their clinical status and their sensitivity to lepromin (absent in group 1 and strong in group 3), showed a similar immunological profile with a normal percentage of T cells and a normal distribution of T cells among the major T cell subset contrasting with a moderate decrease of proliferative responses to mitogens and impaired delayed-type hypersensitivity reactions. Concanavalin A-induced suppressive activity was type-2 reaction) strongly differed from both other groups, showing striking abnormalities other groups, showing striking abnormalities of the repartition of the T cell subsets, with increased percentages of helper T cells and decreased percentages of suppressor T cells, and elevated proliferative responses to mitogens. Concanavalin A-induced suppressive activity was reduced in most patients of this group. It is suggested that this imbalance between T cell subsets contributes to the occurrence of ENL reactions in lepromatous patients.

Adolescent↗

PubMedDate not supplied

Immunochemical analysis of soluble antigens of Mycobacterium lepraemurium.

Soluble antigens obtained from purified M. lepraemurium were identified by SDS polyacrylamide gel electrophoresis as three different proteins, M-W 1 X 10(4), 1 X 10(5), and 4 X 10(6), and two polysaccharide-polypeptides. Three antigens were found to react with anti-M. leprae antiserum; a single antigen proved to be immunologically related to M. tuberculosis, M. similae, M. balnei and a few other mycobacteria, but not to Eubacteriales and fungi, as examined by immunoelectrophoresis. In the dermal hypersensitivity assay, the guinea pigs sensitized with soluble antigens of M. lepraemurium only responded to the antigens of M. lepraemurium, M. leprae and partly to M. scrofulaceum, but not to other antigens, including lepromin and leprous serum globulins.

Actinomycetales↗

PubMed1983

A clinico-pathological study of primary neuritic leprosy.

Normally neural involvement in leprosy is an ascending neuritis from the nerve involvement in the dermal lesions. However, in some cases neural involvement is seen in the absence of any dermal lesions. In some of these pure neuritic cases, dermal lesions appear sometime later. It is, therefore, more appropriate to designate such cases as 'primary neuritic' cases. This study is aimed at diagnosing primary neuritic leprosy among patients presenting with only neuritic symptoms. An attempt is also made to classify primary neuritic leprosy on a clinical and histopathological basis. During the period 1979-80, 30 patients reported to the out patient department of Schieffelin Leprosy Research and Training Centre, Karigiri with complaints of neuritic origin. In addition to clinical examination and routine skin smears, investigations such as skin, nerve and nasal biopsies, nerve conduction velocity and lepromin testing were carried out where feasible. 17 of these patients were diagnosed as primary neuritic leprosy and in 7 patients other neurological conditions were diagnosed. The remaining 6 patients were kept under observation and have not shown evidence of leprosy during a two year period of following-up. It is interesting that 4 of the 17 primary neuritic cases developed patches during follow-up period of two years. In the final analysis 7 patients (41.2%) were classified into the lepromatous group and 10 patients (58.8%) in the non-lepromatous group (Table-6). This classification will have a bearing on duration of treatment and for their subsequent release from control.

Adult↗

PubMed1980

[Transfer factor in diffuse cutaneous leishmaniasis. Experience with one case].

Transfer factor was administered in one case of Diffuse Cutaneous Leishmaniasis ("DCL") with minimal therapeutical results after two courses of ten doses each. The patient was 34-year-old white man, born in the State of Pará --Amazon-- region, goldwasher, his disease started 9 years ago and consisted of disseminated papular and nodular lesions, some of them secondarily ulcerated and more closely clustered over the knees elbows and dorsa of the hands. Physical examination was normal except for the skin lesions and a perforation of the nasal septum. Some intradermal tests (Paracoccidiodin, Lepromin and PPD) were positive while the Montenegro (leishmanin) reaction was negative. Increased levels of IgG and IgM were found; IgA was normal even after the treatment. Transfer Factor was obtained from leishmanin positive and PPD strong reactors and the method of preparation is described. By the end of the first ten-doses course, lesions were reduced to dark atrophic residual macules but the histological sections displayed a surprising amount of parasites, predicting unavoidable relapse. For the second series, as the patient refused to be given Amphotericin B he was treated with hot baths and levamisole was administered in a 150 mg daily dosage and 45 days cycles. The leishmanin intradermal test did not became positive after the treatment and this fact is discussed.

Adult↗

PubMed1976

Defective leukotaxis in patients with lepromatous leprosy.

Serums from patients with lepromatous leprosy show a high incidence of a chemotactic inhibitor. This inhibitor acts directly on leukotactic factors (bacterial chemotactic factor, C3 fragment, and C5 fragment) to render the factors irreversibly inactive. Functionally, the inhibitor acts as a chemotactic factor inactivator. While normal serum shows no inhibitory activity under the conditions employed, inhibitory activity causing more than 30 per cent reduction of the bacterial chemotactic factor was found in the serums from 14 of 19 patients with lepromatous leprosy. Although exceptions were noted, a correlation was found between the presence of the inhibitor and depressed skin reactivity to a series of antigens (Lepromin, Trichophytin, Candida, PPD, and mumps antigen) used for elicitation of delayed-type hypersensitivity reactions. The presence in leprosy serums of this inhibitor may be responsible, at least in part, for some of the defects of cellular inflammatory responses in patients with lepromatous leprosy.

Chemotaxis↗

PubMed1993

Water soluble complex of palmitic acid in media for cultivation of leprosy-derived psychrophilic mycobacteria from Mycobacterium leprae infected tissues.

Palmitic acid and palmitates were transformed into water soluble complexes with crystalline heptakis-2,6-di-0-methyl-beta-cyclodextrin. This formulation was incorporated into liquid and solid chemically well-defined media. The fatty acid served as C and energy source, ammonium thioglycolate as the sole source of N with the SH group as further source of energy. Minute amount of dimethyl-sulfoxide added was used for its known effect on cell membrane permeability. The media were inoculated with host grown Mycobacterium leprae cells isolated from human, armadillo and Nu mice foot pad lepromata. No growth occurred in the liquid medium at 22 or 32 degrees C, but cultures and subcultures of acid fast rods were grown at 10 degrees C. Bacilli in the cultures were solid, strongly acid fast rods, growing in clumps like globi. Growth on the semisolid media was visible as smooth round colonies, of white to ivory in colour, slowly expanding flatly at the periphery of the colony on the agar surface. Colonies developed within 2-3 weeks and reached maximum size at 50-80 days depending on the size of inoculum. Subcultures grow faster and more abundantly with adaptation to the media. No growth was seen without the water soluble complexes of palmitic acid or palmitates in the media. The free fatty acid or its salts had an equal growth supporting effect. Identical psychrophilic cultures were obtained from 7 out of 9 armadillo, 12 out of 12 Nu mice and 1 out of 2 human lepromata. None of the cultures grow on Loewenstein, Dubos or 7H9 media at 10 degrees C, 20 degrees C or 32 degrees C, respectively. The tested 4th to 7th subcultures of the strains were strongly positive for phenolic glycolipid-1. Heat killed suspensions of up to 7th subcultures gave negative late skin reaction in all of 16 LL cases. In 19 I, B and T cases the late skin reactions were all similar to that obtained with authentic human lepromin.

Animals↗

PubMed1993

Fixed duration MDT in paucibacillary leprosy (classical and modified).

We analyzed the records of 1022 patients of paucibacillary leprosy who had received either 6 doses of WHO-MDT alone (" classical" MDT, 668 patients) or had post-MDT dapsone for at least 6 months ("modified" MDT, 354 patients). The duration of posttherapy surveillance ranged from 6 months to 7 years (mean 20.4 months). We found that the incidence of unfavorable events was significantly higher with the classical regimen when patients were graded as active at the end of the fixed duration regimen, especially when patients with > 2 lesions were considered. In the patients who were graded as inactive at the end of 6 doses, there was a slight excess of unfavorable events in the modified regimen, although not statistically significant. No correlation was found between unfavorable events and the regularity of treatment or the lepromin status. Overall, the incidence of adverse events was higher in patients with multiple lesions, and more than 90% of the adverse events occurred during the first 2 years of follow up. It is felt that 6 doses of MDT is adequate in the majority of patients who have few lesions or who have become inactive at the end of the treatment period. However, caution should be exercised in those with multiple lesions or in those considered active at the end of 6 doses.

Dapsone↗

PubMed1993

Pilot study to determine acceptability and ability of heat-killed Mycobacterium leprae plus BCG (HKML+BCG) vaccine to induce skin test conversion.

Although local reactions, including erythema, induration and ulcers, appeared in every patient after the injection of the combined HKML+BCG vaccine, they were accepted by the patients. There was no tendency for the local reaction to become aggravated after repeated vaccination. However, systemic reactions, mainly iridocyclitis and complaint of numbness of the fingers and toes, became quite common after the 5th vaccination and therefore significantly reduced the acceptability of vaccine by injection. It seems that repeated vaccination might activate the iridocyclitis, but the relationship between the complaint of numbness and vaccination has not been well established. Neither typical ENL nor reversal reaction had been observed throughout the trial. A significant proportion of patients converted to SMLA positivity after repeated vaccination. However, it seems the positive status was not stable as many of them reverted to negative after the following vaccination. After the 7th vaccination, the positive conversion rate to SMLA-I was 45% and to SMLA-II was 35%. After the 8th vaccination, 66.7% of patients converted to Mitsuda reaction positive, which has been confirmed by histopathological examination. Nevertheless, further follow-up is required in order to determine whether or not such conversion will be of a long duration. The reactions to SMLA-I and SMLA-II were associated but only correlated at a moderate level. Overall, the positive conversion rate to SMLA-I was significantly higher than that to SMLA-II after repeated vaccination. Neither the early reaction nor the late (Mitsuda) reaction of the lepromin test were correlated to either SMLA reaction. The repeated vaccination of HKML+BCG vaccine did not affect the weakly-positive anti-PGL-1 Mycobacterium leprae antibody level seen in the skin-smear negative lepromatous patients participating in this study.

Adult↗