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Giant nerve abscesses in leprosy.

Two leprosy patients with neuritis caused by giant abscesses involving almost the entire ulnar nerve are described. One patient, who also had skin lesions, was diagnosed histopathologically as having borderline tuberculoid leprosy both on skin and nerve biopsy, and the other, with only nerve involvement, belonged to the pure neuritic group. The lepromin test was strongly positive (with a vesicular reaction in one patient) and lymphocyte transformation to Mycobacterium leprae antigen was raised. These lesions can be easily mistaken for a peripheral nerve tumour in places where leprosy is uncommon. A brief account of the management of nerve abscess in leprosy is given.

Abscess↗

T-cell responses to fractionated antigens of Mycobacterium w, a candidate anti-leprosy vaccine, in leprosy patients.

Mycobacterium w, an atypical cultivable mycobacterium, is undergoing phase III clinical trials as a vaccine against leprosy in India. It has brought about lepromin conversion and histopathological upgradation in a significant number of patients studied so far. It is important to identify antigens of M. w that trigger T-cell responses in leprosy patients vaccinated with this organism. In the present study the peripheral T-cell repertoire of 12 M. w-vaccinated leprosy patients, 10 unimmunized leprosy patients, 8 tuberculoid and 5 healthy contacts was analysed with fractionated antigens of M. w. The lepromatous leprosy patients who are in general anergic to antigens of M. leprae did not respond to antigens of M. w. However, peripheral blood mononuclear cells obtained from leprosy patients who had been vaccinated with M. w responded to many antigens. These responses were frequently directed against low molecular weight entities of 14-45 kDa. T cells from tuberculoid leprosy patients and healthy contacts also responded predominantly to a number of low molecular weight antigens of M. w. The study also identified an immunodominant 28-31 kDa antigenic fraction carrying T- as well as B-cell activating determinants.

Antigens, Bacterial↗

Preliminary study of a Mycobacterium leprae bacterin vaccine in a human volunteer population in a nonendemic area.

Seventeen volunteers who had never resided in areas with significant transmission of leprosy (Hansen's disease) were inoculated intradermally with 1.5 X 10(8) killed, purified armadillo-derived Mycobacterium leprae in a standardized preparation being tested for possible vaccine use. The peak of local skin responses, consisting of induration with or without ulceration similar to the post-lepromin Mitsuda reaction, occurred between the 21st and 28th days after injection. The maximum mean induration diameter was 17.2 mm, the minimum, 6.1 mm. Sera tested with the ELISA technique revealed no humoral response to either the sonicated bacilli, M. leprae-specific phenolic glycolipid I antigen, or three semi-synthetic analogues reactive with lepromatous patients' sera. The dose of M. leprae inoculated appeared to be safe and without unacceptable reactions at the injection site. One volunteer developed a generalized skin rash parallel to the local reaction, but the relationship of the former to the inoculation was unclear.

Adult↗

Treatment of paucibacillary leprosy.

BACKGROUND: When multidrug therapy was introduced a decade ago to shorten the duration of treatment, paucibacillary leprosy was advocated 6 months of treatment. The diagnosis is based mainly on clinical and histopathologic examination, negative slit-skin smear examination, and positive lepromin test. METHODS: The case records of 508 paucibacillary leprosy patients attending our urban leprosy center have been analyzed with reference to regularity of therapy, response to multidrug regimen, follow-up, and relapse. RESULTS: The incidence of paucibacillary leprosy was found to be 37%. Defaulter rate was 45%. Nine percent of the cases attended the center with deformities emphasizing the need for corrective surgery and early case detection to prevent them. CONCLUSIONS: The main problem that we faced was the optimum duration of treatment, which is as yet an unsettled question. The opinions of other workers have been given, and a slight modification in current WHO regimen has been suggested without significantly affecting the cost of therapy.

Drug Therapy, Combination↗

Reversal reaction in patients with lepromatous leprosy after transplantation of human fetal thymic grafts.

An attempt has been made to reconstitute impaired cell-mediated immunity in 1 patient with indeterminate, 4 patients with borderline and 2 patients with polar lepromatous leprosy by grafting three thymus glands obtained from human fetuses of 14--19 weeks gestation. Most of these patients had severe ulcerative erythema nodosum leprosum (ENL) and were intolerant to dapsone. After thymus transplantation these patients were followed for 1 1/2 years. During this period, all conventional chemotherapy had been withdrawn. In most cases, there was dramatic improvement of the clinical condition, resolution of skin lesions, subsidence of ENL, clearance of bacteria from skin and reconstitution of several immunologic deficits; but late lepromin reactivity returned in none, which indicated permanent lose of resistance to Mycobacterium leprae.

Adult↗

An attempt at passive transfer of immunity to leprosy patients by transfusion of allogeneic lymphocytes, inactivated with mitomycin C.

An attempt was made to repair cell-mediated immunity in 7 patients suffering from lepromatous leprosy and severe erythema nodosum leprosum by intravenous infusion of 400 million allogeneic blood lymphocytes on 3 occasions. The lymphocytes were obtained from lepromin and tuberculin-positive subjects and were inactivated in vitro by treatment with mitomycin C. Immunotherapy with inactivated lymphocytes only modified the severity of erythema nodosum leprosum, without altering other aspects of the disease.

Blood Transfusion↗

Peripheral nerve biopsies in the diagnosis of leprosy in Aboriginal patients from the Northern Territory of Australia.

In the 12 years from 1964 to 1976, 171 peripheral nerve biopsies were taken from 81 Aboriginal patients in the Northern Territory of Australia, in whom a diagnosis of leprosy was either known or strongly suspected. Sixty-eight biopsy samples were from 19 patients known to have leprosy, and who were under assessment for nerve grafting, results of which have already been published. We describe here the histopathological findings in the remaining 62 patients, in whom a diagnosis of leprosy was suspected on clinical grounds, backed in many cases by abnormalities of nerve conduction. Forty-one patients (66%) had abnormal histopathological findings in the nerve biopsy sample, 19 (31%) showing definite evidence of leprosy. Several patients with enlarged peripheral nerves, in whom the biopsy findings did not confine leprosy, remain under observation; their future investigation will include lymphocyte transformation tests and testing with refined lepromin, together with repeat nerve biopsy, where ethical and feasible. The clinical and epidemiological data suggest that a previous, and perhaps self-healing, form of leprosy may account for the neurological findings.

Abscess↗

Stigma variations: observations on suppressor T cells and leprosy.

Few areas of immunology have been so controversial as that of suppressor T cells. Studies of T cell clones derived from patients with infectious diseases, including leprosy, and allergies have allowed the delineation of functional human T cell subsets. Both CD4 and CD8 cells can be discriminated into subsets that are differentiated by their functions and patterns of lymphokines. Type 1 CD4 cells reactive with lepromin and PPD produce IFN-gamma and IL-2 predominantly, while Type 2 CD4 clones, specific for tetanus toxoid, produce IL-4 and IL-5. Type 1 CD8 cytotoxic T lymphocytes produce predominantly IFN-gamma and IL-2. T suppressor clones derived from immunologically unresponsive lepromatous leprosy patients are antigen-specific, CD8 cells, HLA-DQ restricted, and produce predominantly IL-4, and were designated Type 2 CD8 cells. Several models for peripheral tolerance based on distinct functional T cell subsets are discussed. Previous models of T cell suppression in the mouse and the reciprocal relationship between humoral and cell-mediated immunity in general are reinterpreted in light of such T cell subset interactions.

Animals↗

Antibodies to the phenolic glycolipid-1 antigen for epidemiologic investigations of enzootic leprosy in armadillos (Dasypus novemcinctus).

Other than man, nine-banded armadillos (Dasypus novemcinctus) are the only known natural hosts of leprosy with high rates of disease. The origin, range and risk of their infection is not yet clear and a better description of the rate of leprosy over the armadillo's range is needed. Both histopathological examination of armadillo ear tissues and serologic screening for IgM antibodies to the phenolic glycolipid-1 (PGL-1) antigen of Mycobacterium leprae are good relative indices of enzootic prevalence. A survey of 216 armadillos from Louisiana and Florida detected infection only among Louisiana animals. Average antibody prevalence (12.5%) was five times higher than the fully disseminated disease rate described histopathologically (2.7%). The differences in antibody and histopathological prevalence are due to the sensitivity of the methods for detecting early infection. Histopathological examinations describe an advanced disease. The higher antibody prevalence of wild armadillos is not likely to be the result of false positive serologies from self-healing infections or other casual encounters with M. leprae as might be mimicked by lepromin injection. The environmental reservoir of M. leprae represented by infected armadillos is greater than could be previously estimated.

Animals↗

Serodiagnosis of leprosy in patients' contacts by enzyme-linked immunosorbent assay.

Serum samples from 3336 contacts of leprosy patients were tested for antiphenolic glycolipid I antibodies by enzyme-linked immunosorbent assay with the albumin coupled synthetic disaccharide antigen. The overall positivity rate was 9.3%. No significant differences were seen between a group of household contacts of lepromatous patients and those of the other types of the disease. The proportion of ELISA positives was slightly higher in the relatives as compared to workplace contacts and neighbours but significantly different only between the two former (p less than 0.05). Among those contacts with absorbance values higher than 0.100, 5 new leprosy patients were diagnosed, 2 of them with positive skin smears. A sixth contact was detected with a very high absorbance value in whom no single skin lesion was found but whose lepromin reaction was 0 mm and the skin smear showed a bacteriological index of 3+.

Antibodies, Bacterial↗

Neuritic leprosy: epidemiology and therapeutic responsiveness.

We studied epidemiology, progression and therapeutic responsiveness in 62 cases of neuritic leprosy. Numbness was the main presenting symptom. Mononeuritis involving the ulnar nerve, followed by the common peroneal nerve was the commonest presentation. The lepromin test was positive in 34 cases while a slit-skin smear was negative in all cases. We treated 20 of these cases with dapsone monotherapy and 5 cases (25%) developed a skin lesion after an average duration of 3 months' treatment. We treated 42 cases with a combination of dapsone and rifampicin, and 3 cases (7%) developed a skin lesion after an average duration of 2-6 months. The subsequent diagnosis in cases developing skin lesions was borderline--lepromatous in 1 case, borderline-tuberculoid in 4 cases, tuberculoid in 2 cases and indeterminate in 1 case.

Adult↗

Serological reactivity to a synthetic analog of phenolic glycolipid I and early detection of leprosy in an area of low endemicity.

A total of 23,863 individuals living in an area of low endemicity for leprosy were tested by enzyme-linked immunosorbent assay with a semisynthetic analogue of the phenolic glycolipid I antigen of Mycobacterium leprae. The proportion found positive was 3.86% which was significantly higher than that in a sample of a population known to be free of leprosy. Clinical examinations as well as Mitsuda and skin smear tests were organized for those defined as seropositive. The proportion of individuals with lepromin reactions of less than 3 mm increased 18.9% per serological interval as antibodies rose though it was not statistically significant. As a result of the clinical and bacteriological examinations, 2 cases with clinical signs and heavy bacillary load were found, whereas acid-fast bacilli were demonstrated in 2 other individuals without clinical manifestations of leprosy. The usefulness of the system for control purposes is discussed.

Adolescent↗

Lymphostimulatory and delayed-type hypersensitivity responses to a candidate leprosy vaccine strain: Mycobacterium habana.

Lymphostimulatory and delayed-type hypersensitivity (DTH) immune responses to a candidate antileprosy vaccine Mycobacterium habana have been quantified in inbred AKR mice. M. habana vaccine in three physical states, live, heat-killed and gamma-irradiated, was given intradermally to separate groups of mice and after 28 days these mice were given subcutaneous challenge with heat-killed M. leprae and heat-killed M. habana in the left hind footpad. Live BCG vaccine alone and in combination with gamma-irradiated M. habana were also compared similarly. A sufficient degree of DTH response was generated in mice by M. habana vaccine in all physical forms against two challenge antigens (lepromin and habanin). The BCG combination with M. habana did not increase the DTH response indicating internal adjuvanticity endowed in M. habana. The active hypersensitivity of immunized mice was transferable to syngeneic mice by the transfer of sensitized cells from the donor to the recipient mice intravenously. M. leprae-infected Rhesus monkey PBMC have shown comparable stimulatory response with M. habana (sonicate), and M. leprae (sonicate) antigens. The possibility of developing M. habana as a candidate antileprosy vaccine is discussed.

Animals↗

Reactional states and neuritis in multibacillary leprosy patients following MDT with/without immunotherapy with Mycobacterium w antileprosy vaccine.

A vaccine based on autoclaved Mycobacterium w was administered, in addition to standard multidrug therapy (MDT), to 157 untreated, bacteriologically positive, lepromin negative multibacillary leprosy patients, supported by a well matched control group of 147 patients with similar type of disease, who received a placebo injection in addition to MDT. The MDT was given for a minimum period of 2 years and continued until skin smear negativity, while the vaccine/placebo was given at 3-monthly intervals up to a maximum of eight doses. The incidence of type 2 reaction and neuritis during treatment and follow-up showed no statistically significant difference in the vaccine and placebo groups. The incidence of type 1 reaction (mild in most cases), however, was higher in the vaccine group (P = 0.041, relative risk ratio 1.79), considering LL, BL and BB leprosy types together, and considerably higher (P = 0.009) in LL type, probably because of confounding due to higher number of patients with previous history of reaction in this group. The occurrence of reactions and neuritis in terms of single or multiple episodes was similar in the vaccine and placebo groups. The association of neuritis and reactions, as well as their timing of occurrence (during MDT or follow-up), was also similar in the two groups, with more than 90% of occurrences taking place during MDT. The incidence of reversal reaction was significantly higher among the males in the vaccine group (34.5% versus 8.3%, P = 0.019). Patients with high initial BI (4.1-6.0) showed higher incidence of reactions (70.3%) as compared to those with medium (2.1-4.0) and low (0.3-2.0) BI where the reactions were observed with a frequency of 56.1% and 38.8%, respectively. However, unlike reactions, neuritis incidence did not seem to be affected by initial BI to the same extent in the vaccine group, with frequencies of 35.3%, 36.3% and 25.9% in the three mentioned BI ranges. Overall, the vaccine did not precipitate reactional states and neuritis over and above that observed with MDT alone.

Bacterial Vaccines↗

Prophylaxis--scope and limitations.

Attempts to prevent leprosy by one or another prophylactic method began with the use of dapsone as a chemoprophylaxis. Following early, small-scale studies, which were promising, large-scale studies with dapsone and acedapsone, both among contacts and in the general population, demonstrated that it is possible to prevent the occurrence of leprosy to a modest extent. With regard to immunoprophylaxis, BCG had long been considered a possibility, particularly in view of its potential to convert the skin test reaction to lepromin. Over the years, major, large-scale field trials of BCG had been carried out in Uganda, Burma, Papua New Guinea and India. All of the studies demonstrated that BCG was capable of preventing leprosy. However, protective efficacy varied from around 20% to greater than 80%. Killed Mycobacterium leprae mixed with BCG has also given varying results. Other vaccines based on cultivable mycobacteria have also been tried, and at least one of them appears promising. An approach to prophylaxis must take into account (a) the level of risk addressed and the perception of risk by the community; (b) the level of efficacy of the method of prophylaxis; (c) the possibility of easily identifying high-risk groups; (d) the operational feasibility; and (e) the focus of the prophylaxis, whether the individual or the community, or both. However, in view of the enormous progress being made towards elimination of leprosy by the widespread application of MDT, prophylaxis is becoming less and less relevant and less and less cost-effective, except in very special situations.

Bacterial Vaccines↗

Fine needle aspiration cytology (FNAC) of nerves in leprosy.

Leprosy is primarily a disease of the peripheral nerves and a technique that is simpler than nerve biopsy is required to evaluate nerve involvement, especially in pure neuritic (PN) leprosy. This study was designed to evaluate the role of FNAC of the nerve in the diagnosis and classification of leprosy. A prospective study was carried out on 25 patients with clinically active leprosy and at least one thickened peripheral sensory nerve. Nerve aspirates were evaluated by May-Grunwald-Giemsa and Fite's staining. Lepromin test, slit skin smears (SSS), skin biopsies (except PN cases) and nerve biopsies were performed and compared with FNAC. FNAC of nerve from 23 cases (92%) yielded diagnostic aspirates. Acid fast bacilli were observed in six cases by FNAC. FNAC and nerve pathology were equally comparable with the other parameters evaluated. Based on the results, cytological criteria were developed for interpreting nerve aspirates and the cases were classified as paucibacillary (18), BB (2), BL (2), LL (1) and non-diagnostic (2). All PN cases showed diagnostic paucibacillary type cytology. FNAC of the nerve yields diagnostic aspirates in leprosy comparable with nerve pathology and the proposed cytological criteria may be useful in classification of nerve aspirates.

Adult↗

[Aspects of cutaneous sarcoidosis in Brazil].

This study collects all cases of sarcoidosis with cutaneous involvement referred to in the Brazilian literature. Only 40 cases could be found confirming the rarity of the disease in Brazil. With regard to these cases the following aspects of the disease were studied: age, incidence, race and sex distribution, origin of patients, clinical forms, systemic involvement, behaviour of the intradermic reactions and histopathology. Some characteristics could be established: 1) Females are most frequently affected than males. 2) No racial differences were noticed as far as the caucasian and the negroid are concerned. 3) The onset of the disease occurred between 16 and 69 years of age (mean age 37). 4) All patients originated from the south-central region of the country. 5) The most frequent cutaneous forms were associations of papulous lesions, nodular lesion and plaques. 6) Besides the skin, involvement of lymph nodes, bones, liver, eyes, spleen, salivary glands, heart, bowels and the facial nerve could be found. Heerfordt syndrome (uneoparotidic fever) was seen only once. Death occurred twice. 7) Kveim test was positive in all 11 cases in which it was done. Tuberculin and lepromin tests resulted in weak reaction or its complete absence. 8) All cases were confirmed by histopathology. Eight of the forty biopsies were reexamined by the authors themselves.

Adolescent↗

Stimulating effect of leucine on the growth of M. leprae.

M-Y 16j agar slant was prepared by modifying M-Y 14b which has hitherto been used most widely in our experiments by increasing the amount of Na pantothenate and adding leucine, and the growth stimulating effect was investigated referring to the foregoing subculture experiments. The results revealed that the growth of M. leprae was stimulated remarkably in the primary isolation quite similarly to the subculture. This seemed to be resulted from stimulated biosynthesis of fatty acids by the leucine metabolism. The authors are greatly indebted to the World Health Organization and the Comité Exécutif International pour l'Assistance aux Lépreux for their financial support and to Dr. S. Ishihara, the Director of the National Suruga Leprosarium, for his kind supply of the materials to be cultured and for the lepromin test in leprosy patients carried out by himself. The main point of this study was presented to the 50th Annual Meeting of the Japanese Leprosy Association.

Agar↗