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PubMed1991

Blastogenic response with autologous plasma and Mitsuda's reaction in leprosy patients and their unaffected sibs.

Many investigators have evaluated the influence of genetic constitution on the susceptibility to leprosy in studies linked to different types of research. To determine the possible existence of a family trait linked to the lymphoproliferation and to lepromin reactivity we studied the blastogenic response to phytohaemagglutinin, lepromin and M. leprae and the Mitsuda's reaction in leprosy patients and their unaffected sibs. Sixty-eight individuals were studied, 34 were leprosy patients (17 lepromatous and 17 tuberculoid leprosy) and the remaining were their sibs previously matched by sex and age. The indices of blastogenesis and lepromin reactivity were lower in lepromatous than in tuberculoid patients, that confirmed the immunological polarity of the two types of leprosy. Both the lymphoproliferation and Mitsuda's reaction results suggest different cell immune responses in leprosy patients and their unaffected sibs, so that the hypothesis of a family trait favouring the similarity of responses to these tests among sibs becomes unlikely.

Antigens, Bacterial↗
PubMed1989

Evaluation of humoral immunity on leprosy patients in Taiwan: a preliminary report.

Twenty-four tuberculoid (T)-type and 31 lepromatous (L)-type leprosy patients from Taiwan Provincial Lo-Sheng Leprosarium were enrolled in this study. Twenty-six age- and sex- matched normal subjects were also studied as a control group. The evaluation of their general and specific humoral immunity included B-cell subpopulations, 3 major classes of immunoglobulin (G, A and M) and antibodies in the IgG class against lepromin suspension and Bacillus Calmette-Guerin (BCG) sonicate. T-type patients showed a larger B-cell percentage than L-type patients (p less than 0.01). In general, patients with leprosy, both T and L types, had higher serum immunoglobulin levels than the control group. T-type patients showed greater antibody levels than the control group (p less than 0.05 for anti-lepromin and p less than 0.0001 for anti-BCG). L-type patients demonstrated a higher anti-BCG IgG level than the control group (p less than 0.0001). The level of anti-BCG IgG was more frequently above the cutoff level than that of anti-lepromin IgG in leprosy patients (p less than 0.01 for T, p less than 0.005 for L). In conclusion, humoral immunity is not impaired in leprosy patients. Discrepancies for T- and L-type patients among B-cell subpopulation, serum immunoglobulin levels and specific antibody levels reflect different aspects of cell-mediated immunity impairment. Though leprosy patients had elevated anti-BCG IgG levels, it is impossible to differentiate L- and T-type patients; specific antigens are needed for serodiagnosis of leprosy patients in Taiwan.

Adult↗
PubMed1988

A bacteriological assessment of multibacillary cases in leprosy colonies after 4 1/2 years of multidrug therapy.

In this presentation we have devised a novel way of calculating the total bacterial quantum in 100 (78 LL and 22 BL) multibacillary leprosy patients living in leprosy colonies. The calculation is based on Ridley's logarithmic scale. We have also attempted to assess the reduction in the bacterial quantum as a result of intervention through multidrug therapy (MDT). 53% of the patients rendered bacteriologically negative within two years of treatment of MDT and 94% at 54th pulse dose i.e. at 54th month. The bacterial quantum in human source as leprosy patients was calculated thus--Average BI of the group X Number of patients in each group X Multiplication factor devised as per Ridley's Bacterial Index (BI). By applying this purely arithmetic formula, it was found that 99.8% of the bacterial load is harboured in leprosy patients having BI more than 3. The introduction of MDT initiated the reduction in total bacterial quantum "based on above arithmetic scale" was achieved very fast i.e., from 100% to 5% at 12 months and to 0.4% at 24 months. We believe that if one wants to achieve leprosy control through a reduction in total bacterial quantum within a specific period, leprosy cases with BI more than 3 should be treated on priority basis.

Colony Count, Microbial↗
PubMed1995

CD26 expression in leprosy and other granulomatous diseases correlates with the production of interferon-gamma.

BACKGROUND: Leprosy represents a spectrum of clinical manifestations that reflect the immune response to antigens of Mycobacterium leprae. The tuberculoid form of leprosy, which is characterized by an organized development of granulomas, has recently been correlated with a Th1-like immune response. The lepromatous form of leprosy, with a characteristic lack of cellular immunity, has been correlated with a Th2-like immune response to mycobacterial antigens. Dipeptidylpeptidase IV (CD26) is an ectopeptidase that is expressed in various tissues; in the hemopoietic system, it is predominantly expressed by T cells. EXPERIMENTAL DESIGN: We stained frozen sections of skin biopsies obtained from patients with different forms of leprosy, sarcoidosis, and Piringer's lymphadenitis. Sections were stained for interferon-gamma (IFN-gamma) and CD26 with the alkaline phosphatase anti-alkaline phosphatase technique and in two-color stainings by immunofluorescence. RESULTS: We found strong signals for IFN-gamma and for CD26 in all investigated cases of tuberculoid leprosy. In contrast, in all biopsies taken from patients with lepromatous leprosy, we found no or very weak signals for these antigens. By immunofluorescence double-labeling, we could show that IFN-gamma and CD26 were expressed by the identical cell population. We confirmed this correlation of CD26 expression and IFN-gamma production in other granulomatous inflammatory reactions such as sarcoidosis and Piringer's lymphadenitis. CONCLUSIONS: From our results, we conclude that a high expression of CD26 may be suggestive of Th1-like immune reactions.

Dipeptidyl Peptidase 4↗
PubMed1993

Damage and regeneration of peripheral nerves in advanced treated leprosy.

Despite the rapidly falling prevalence of leprosy, the disability and handicap resulting from loss of protective sensation, due to irreversible nerve damage, will remain a huge medical problem for many years. To elucidate the location and consequences of permanent nerve damage in treated leprosy, a prospective study involving nine patients who underwent leg amputation was conducted. Full-length nerves dissected from amputated legs were studied with histological and immunohistochemical methods. Our main findings were that: in both lepromatous and tuberculoid leprosy nerve damage increased distally, culminating in total destruction of dermal nerves and sensory nerve endings; after the therapy-related decrease of inflammation large-scale nerve regeneration took place; and that regenerating axons persisted for decades and in tuberculoid leprosy they might reach the subcutaneous fat of the plantar skin. We conclude that nerve regeneration was blocked by fibrous replacement of the distal-most nerves and nerve endings, and that the theoretical basis of nerve grafting in leprosy is in need of further clarification. In some patients, autologous transplantation of skin flaps, probably irrespective of the duration of loss of sensation, might help in regaining protective sensation.

Adult↗
PubMed1989

Leprosy in children: correlation of clinical, histopathological, bacteriological and immunological parameters.

The study of leprosy in children has indicated an incidence of 10% amongst leprosy patients attending the clinic. The duration of the disease was usually less than 2 years. The expression of leprosy in this group was either a macule and/or a plaque. Classification was, therefore, different and conforms to indeterminate (I), borderline tuberculoid (BT) and borderline (BB) leprosy. Only occasionally were other clinical variants seen. The bacteriology was largely unproductive by slit-skin smears. The lepromin (Mitsuda) responses were positive in BT and unpredictable in BB patients. Epicutaneous responses to sensitization with dinitrochlorobenzene (DNCB) paralleled responses to lepromin. Microscopic pathology was of very little help. The correlation of these parameters was only 50-60% indicating that the diagnosis of leprosy should primarily be based on clinical features.

Adolescent↗
PubMedDate not supplied

Correlation of serum lipids and lipoproteins in leprosy.

Serum lipids and lipoproteins were assessed in sixty leprosy and forty age and sex matched healthy controls. The study subjects included cases of LL with reactions, LL without reactions, BL with reactions, BL without reactions, BT and TT types of leprosy. The levels of serum phospholipids, triglycerides, total cholesterol, LDL and VLDL fractions were significantly decreased in leprosy patients compared to control subjects. The levels of serum HDL cholesterol and HDL fraction were significantly elevated in leprosy patients. Maximum elevation in serum HDL cholesterol level and HDL fraction and maximum reduction in the levels of serum phospholipids, triglycerides, total cholesterol and LDL and VLDL fractions were observed in lepromatous leprosy (LL) patients with reactions.

Cholesterol↗
PubMed1991

Effect of BCG on the risk of leprosy in an endemic area: a case control study.

The effect of BCG on the risk of leprosy was measured using a case-control design in an area endemic for the disease. In this study, 397 newly diagnosed cases and 669 controls matched for age, sex and locality were selected from a defined population. Information on exposure to BCG, contact with another case of leprosy, and relevant socioeconomic variables were obtained from the subjects. Having infectious (multibacillary) and noninfectious (paucibacillary) contacts in the household increased the risk of disease 11.7 times (p less than 0.001) and 2.7 times (p less than 0.001), respectively. Overall, the protection offered by BCG was not significant (odds ratio = 0.8; p = 0.17). However, BCG appeared to increase the risk for indeterminate leprosy (adjusted odds ratio = 2.7; p = 0.09) while protecting against borderline disease (adjusted odds ratio = 0.39; p = 0.03). It is possible that BCG causes a shift in the overall cell-mediated immune response, thus increasing the risk for milder and transient forms of leprosy while protecting against more serious forms. These findings may have important implications for the design and interpretation of vaccine trials. Namely, trials should be designed to measure the protective efficacy of vaccines against the more serious forms of leprosy, which have the greatest public health significance.

Adolescent↗
PubMedDate not supplied

Glucose tolerance test in leprosy.

Glucose tolerance test was carried out in 43 cases of leprosy. They included cases of tuberculoid, borderline, lepromatous leprosy and those with lepra reaction. It was observed that normal curve was common in tuberculoid leprosy. Flat glucose tolerance curve was observed in borderline and lepromatous leprosy. However, the diabetic curve was common in Lepra reaction. Fasting blood sugar was low in lepromatous leprosy and it tended to be marginally high in lepra reaction. Normal GTT response was observed in those with duration of disease between 0-6 months, flat curves in those with duration of disease between 7-12 months while diabetic curve was more common in those with disease duration of more than 2 years.

Adolescent↗
PubMed1993

Lymphocyte proliferation, IFN-gamma production and limiting dilution analysis of T-cell responses to ICRC and Mycobacterium leprae antigens in leprosy patients.

Lymphocyte proliferative responses and interferon-gamma (IFN-gamma) production after stimulation with antigens of ICRC, Mycobacterium leprae, and purified protein derivative (PPD) were assessed in leprosy patients and healthy donors. The patients studied were newly diagnosed as having lepromatous leprosy (LL), multidrug therapy (MDT) responders (MDT-R LL), MDT nonresponders (MDT-NR LL), borderline lepromatous (BL), and borderline tuberculoid/tuberculoid (BT/TT) leprosy. The tuberculoid leprosy patients showed increased lymphocyte proliferation and IFN-gamma production in response to stimulation with ICRC, M. leprae, and PPD antigens compared to other groups of LL patients and healthy donors. Although lymphocytes from LL patients showed low responses to ICRC and M. leprae antigens, their responses to PPD were not grossly affected. MDT-R LL patients showed higher lymphocyte proliferative responses and IFN-gamma production after stimulation with ICRC and PPD but not with M. leprae antigens. Tuberculoid leprosy patients showed higher T-cell frequencies to ICRC and M. leprae antigens compared to MDT-R LL and MDT-NR LL patients. The increased lymphocyte proliferative responses to ICRC observed in the MDT-R LL patients was reflected in the increased T-cell frequency to ICRC compared to M. leprae.

Antigens, Bacterial↗
PubMed1996

Double jeopardy: women and leprosy in India.

This article presents evidence from two states of India, Bihar and Maharashtra, on the process of "dehabilitation" among male and female leprosy patients, and suggests gender-sensitive interventions to address existing problems in leprosy control. While the study investigated a wide range of gender differences in the impact of leprosy, this article focuses on only two-marriage and family reactions. Important gender differences were apparent in the impact of the disease. While both men and women were negatively affected in terms of their family and marital lives, women suffered more isolation and rejection. Psychologically, women appeared more vulnerable because they were deprived of personal contact with others in the domestic environment where they were accustomed to receiving their greatest emotional rewards. Women reported that indifference to them by other family members, or seeming negation of their presence, caused them the greatest suffering. This underscores the importance of providing information to both leprosy patients and their families about the disease and its treatment, including the possibility of cure with MDT (multi-drug therapy) and of counselling family members about their crucial role in helping patients cope and recover. This support is even more critical for women, who often lack access to the variety of outside advice and assistance available to men. The evidence presented in the article demonstrates the importance of analysing leprosy from a gender perspective, not only because this approach helps to inform our understanding of the determinants and consequences of the disease, but also because it provides new insights for improved disease control.

Adolescent↗
PubMed1997

Humoral and cellular immune reactivity to recombinant M. leprae antigens in HLA-typed leprosy patients and healthy controls.

In our search for Mycobacterium leprae antigens that might specifically induce immunity or immunopathology, we have tested both humoral and cellular immune reactivity against purified recombinant M. leprae antigens in 29 paucibacillary (PB), 26 multibacillary (MB) leprosy patients, and 47 matched healthy contacts. The following M. leprae antigens were tested: 2L-1 (65L-1, GroEl-1), 2L-2 (65L-2, GroEl-2), 4L (SoDA), 43L, 10L (B) and 25L (Sra). The individuals were also typed for HLAD-RB1 and DQB1 in order to see whether leprosy status and/or immune reactivity to these antigens might be associated with certain HLA types. We also tested sera from another 48 patients before, during and after multidrug therapy (MDT) to study the relationship between antibody reactivity to recombinant M. leprae antigens and MDT. Antibody titers to the four recombinant M. leprae antigens tested and to D-BSA were higher in MB patients compared to PB patients and healthy controls, and declined with treatment. From a diagnostic or monitoring point of view none of the recombinant antigens seemed to be an improvement over D-BSA, mainly due to the lower sensitivity. IgG subclasses were measured in positive sera of untreated patients. These were mainly of the IgG1 and IgG3 subclasses, but subclass diversity was also observed and antigen dependent: all four subclasses could be detected against 10L (B), only IgG1 and IgG3 against 43L and only IgG1 against 25L and 2L-1. Cellular immune reactivity against the purified recombinant M. leprae antigens was measured in a lymphocyte stimulation test (LST). As for M. leprae, there was an inverse correlation between antibody and T-cell reactivity. However, the number of LST responders to recombinant antigens was much lower than to M. leprae. The 43L antigen was recognized most often (19%-24% of individuals tested) and more often than the 10L (B) antigen (10%-12%). No clear correlation was observed with leprosy type or protection and, in general, M. leprae nonresponders were also negative with recombinant antigens. Finally, we confirmed that HLA-DRB1*02 is associated with leprosy in this population, and we observed an association between DQB1*0601 and lepromatous leprosy. The number of positive individuals was too small to allow a meaningful analysis of the relationship between HLA type and immune reactivity. Although these data do not allow a conclusion as to one of these purified recombinant antigens being either protection or disease related, the antigen-dependent IgG subclass diversity warrants further study on antigen-specific qualitative differences in immune reactivity that may be relevant for the outcome of an infection with M. leprae.

Antibody Formation↗
PubMed1986

Naturally acquired leprosy in the nine-banded armadillo: a decade of experience 1975-1985.

A decade has passed since our first report of naturally acquired leprosy in the nine-banded armadillo. Our studies and those of others during this period confirm the identification of the etiologic agent as Mycobacterium leprae. Confirmation is based on the results of histopathologic examination and microbiologic evaluations that included attempts to culture the organism, flourescent antibody studies, mycolic acid analysis, and DNA determinations demonstrating complete relatedness between the natural agent and M. leprae. Surveys involving large numbers of animals demonstrate a significant prevalence of the disease in armadillos captured in Louisiana and Texas. The discovery of naturally acquired leprosy in a chimpanzee in 1977 and a sooty mangabey monkey in 1979 reinforce the concept of leprosy as a zoonosis. Extensive contact with armadillos has been implicated by other observers in seven patients with leprosy in Texas. We believe the prevalence of leprosy in wild armadillos requires that they be considered a source of infection in patients from geographic areas where leprosy and armadillos co-exist.

Animals↗
PubMed1975

The histopathology of lepromatous leprosy in the nose.

On the basis of clinical, histological and bacteriological assessments, 31 patients in Central India were selected and classified as having active but early lepromatous leprosy and 4 patients as having early borderline leprosy. From the nose of each patient an average of 4 biopsies were taken from particular sites of the septum and turbinates either by punch biopsy or dissection with a scalpel. The nasal tissues from all the lepromatous patients contained many acid-fast bacilli; no bacilli or abnormalities were seen in nasal tissues from the borderline patients. The histopathology of these highly bacilliferous tissues is described. Bacilli were universally seen in macrophages, but they were also seen in blood monocytes and polymorphs, fibroblasts, squamous and pseudo-columnar epithelium, keratin, peri- and endo-neurial cells of tiny nerve bundles, erectile tissue, vascular plain muscle, perivascular histiocytes and frequently and abundantly in the cytoplasm of endothelial lining cells of lymphatics and of small blood vessels and free within the lumina of these vessels. Five basic mechanisms of escape of bacilli from the submucosa on to the surface, and thus into the external environment, are described. Secondary infection, in the presence of an expansile lepromatous infiltrate, together with simple trauma to the surface epithelium, are the main factors in the discharge of bacilli. These histopathological observations are consistent with the findings from other recent studies on the nose in leprosy regarding (1) the large numbers of morphologically intact and viable Myco. leprae excreted in the nasal mucus of lepromatous patients; (2) the clinical changes observed in the nose of such patients, and (3) the similar nasal involvement and excretion of Myco. leprae from the nose of mice inoculated with leprosy bacilli of human origin. Of particular interest was the frequency and intensity of bacilli within the endothelial lining cells of small blood and lymph vessels and the presence of bacilli free within the lumina of these vessels or within monocytes and polymorphs. The possible dynamic significance of these observations in the pathogenesis of leprosy is discussed. The significance of all these observations in relation to (1) the spread of leprosy; (2) local factors in the nose which might favour the growth of Myco. leprae, and (3) the nose as a portal of entry, are discussed.

Biopsy↗
PubMed1978

Surface markers on lymphocytes and cells of the mononuclear phagocyte series in skin sections in leprosy.

E, EA and EAC rosetting techniques and Ig fluorescence were used in a study of receptor sites in cryostat sections of lesions through the spectrum of leprosy, and for comparison in some other mycobacterial and granulomatous lesions. Anti-C3, and trypsin were used as blocking agents. Lymphocytes in borderline lepromatous leprosy produced EA adherence and IgG fluorescence indicating B type cells. Lymphocytes in tuberculoid leprosy produced neither E or EA adherence and no fluorescence; these cells were presumed to be T cells. EAC and EA adherence was more marked in areas of macrophage infiltration, where there were few lymphocytes, than over the lympocytes themselves. Two distinct patterns emerged: (i) EA binding together with IgG fluorescence was seen in active lepromatous leprosy and could be localised to the surface of individual macrophages, and (ii) EAC binding together with IgM fluorescence was seen in the granuloma of tuberculoid leprosy and sarcoidosis, but could not be definitely related to cell surface; rather it was diffusely spread over the whole granuloma; EAC adherence was diminished by anti-C3 serum. Trypsin removed EA binding completely, but only diminished EAC adherence. It is suggested that the EA pattern indicates immunoglobulin receptors on macrophage and lymphocyte surfaces: and that the EAC binding (which is stronger than EA) involves C3 and IgM receptors at extracellular sites as well as C3 receptor sites on epithelioid cell surfaces. EA and EAC binding were enhanced in borderline tuberculoid leprosy in reaction and erythema nodosum leprosum, suggesting that immunoglobulin and complement receptor sites increase in number with enhanced hypersensitivity.

Cell Membrane↗
PubMed1989

Changes in nerves and neuropeptides in skin from 100 leprosy patients investigated by immunocytochemistry.

The cutaneous innervation is now known to contain neuropeptides including substance P (SP) and calcitonin gene-related peptide (CGRP) in sensory nerves, and vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY), principally in autonomic nerves. Skin biopsies from 100 leprosy patients and equivalent areas from 50 non-leprosy controls were fixed in p-benzoquinone solution for immunofluorescence staining and in Bouin's fluid for classification of leprosy type. Antisera to the neural markers, neurofilaments, and protein gene product 9.5 (PGP 9.5), and to neuropeptides were used. Cutaneous nerves and nerve endings immunoreactive for neuropeptides, neurofilaments, and PGP 9.5 were seen in all non-leprous control cases. In leprosy, PGP 9.5- and neurofilament-immunoreactive nerve fibres were seen in all 14 cases of the indeterminate (early) type and in the majority (33/43) of lepromatous cases, but in a smaller proportion (15/43) of tuberculoid cases. Neuropeptide immunoreactivity was seen in only 2/14 of the indeterminate leprosy specimens and was completely absent in other types. This early disappearance may be of diagnostic significance. Thus, cutaneous sensory and autonomic dysfunctions in leprosy are well reflected by changes in nerve fibres and neuropeptides.

Calcitonin↗
PubMed1993

Vasomotor reflexes in the fingertip skin of patients with type 1 diabetes mellitus and leprosy.

Fingertip skin blood flow was measured by laser Doppler flowmetry (as LDflux) under environmental conditions promoting vasodilation in Scottish patients with diabetes mellitus and Indian patients with leprosy. The reflex control of fingertip blood flow was assessed by measuring the reduction in LDflux induced by deep inspiratory gasp (IG) and cold challenge (CC) of immersing the contralateral hand in cold water. The uncomplicated diabetic patients showed normal vasomotor reflexes and an increased, though non significant, LDflux level (p < 0.06). The patients with diabetic neuropathy had resting LDflux levels significantly less than the uncomplicated group and also had substantial impairment of both IG and CC reflexes. Those with retinopathy (but no clinically apparent neuropathy) had LDflux within the normal range, but they showed minor evidence of impairment of the vasomotor reflexes. The uncomplicated newly registered leprosy patients had reduced LDflux and substantial impairment of CC reflexes. These changes were more marked in newly registered leprosy patients with clinical evidence of neuropathy. Leprosy patients with long-standing neuropathy requiring orthopaedic treatment had LDfluxes so greatly reduced that measurement of vasomotor reflexes was not practicable. The CC reflex was more severely affected than the IG reflex and more frequently absent in leprosy patients, possibly because of associated sensory neuropathy affecting the afferent limb of this response. Thus laser Doppler flowmetry can detect impairment of reflex control of fingertip blood flow in both diabetes mellitus and leprosy, but there are functional differences in the pattern of autonomic impairment between the diseases, suggesting differences in the pathogenesis of nerve damage.

Adult↗
PubMed2000

Leprosy and the anesthesiologist.

PURPOSE: To discuss particular aspects of leprosy (complications treatment, special population) that have implications for anesthetic management in leprous patients scheduled for surgery. SOURCE: MEDLINE and manual searches of relevant literature. Multiple MEDLINE searches (from 1966 onwards) were done, using LEPROSY as a common Medical Subject Heading (MeSH). Other headings used were: anesthesia, surgery, cardiovascular system, respiratory system, eye, skin, nervous system, genitalia, pathology, psychology and pregnancy. A large number of references were retrieved, but only 18 of them were relevant to our topic. Others were obtained by manual search and cross referencing. PRINCIPAL FINDINGS: Leprosy, especially lepromatous leprosy, is a systemic disease, affecting many organs and systems of the body, e.g., cardiovascular (cardiac dysautonomia), respiratory (impaired cough response, nasal obstruction), hepatobiliary (hepatitis), renal (nephritis), ocular (anesthesia), hematological (reduced red, white and platelet count) and osseous systems (bone resorption). CONCLUSION: Investigation of the systems likely to be affected by leprosy (e.g., complete hemogram, liver, lung and kidney function tests, Valsalva response, assessment of ocular anesthesia) should form part of a preanesthetic check up in patients with leprosy.

Anesthesia↗