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PubMed1994

Study of nerve conduction velocity, somatosensory-evoked potential and late responses (H-reflex and F-wave) of posterior tibial nerve in leprosy.

The present study was conducted in 25 leprosy patients (of different age and sex) with or without clinical evidence of neuropathy. The diagnosis was confirmed by skin biopsy. A group of 15 age- and sex-matched, healthy persons also were studied for comparison and served as controls. Motor nerve conduction velocity (MNCV) was reduced in nine patients (36%) and sensory nerve conduction velocity (SNCV) was reduced in three patients (12%). Late responses (H-reflex and F-wave) were deranged in 16 patients (64%). Somatosensory evoked potential (SSEP) was deranged in 13 patients (52%). N7-N18 interpeak latency (PCT) was prolonged in two patients (8%); none showed prolongation of N18-N35 interpeak latency (CCT). We observed that nerve conduction velocity, late responses, and SSEPs were deranged in all types of leprosy, regardless of clinical evidence of neuropathy, and were more prominently affected in the tuberculoid (TT) type of leprosy. A study of late responses is more informative than conventional nerve conduction studies for the detection of early lesions of the nerves. The study of SSEP shows involvement of the peripheral part of the nervous system and complete sparing of the central part of the nervous system.

Adolescent↗
PubMed1993

Class-specific immunoglobulins and antibodies to mycobacterial sonicates and autoantigens in leprosy patients and contacts.

A comprehensive analysis of the humoral immune response in leprosy patients and contacts was undertaken. Class-specific antibodies to four mycobacterial sonicates, three autoantigens and three haptens were estimated by ELISA. It was found that IgG levels varied more extensively than IgM or IgA and that total serum IgG was significantly higher in lepromatous bacterial index positive (LL+ve) and negative LL-ve) leprosy patients than in tuberculoid (TT/BT) patients and controls. The high levels of anti-mycobacterial antibodies found in untreated LL+ve patients were significantly reduced in LL-ve patients after effective chemotherapy. Considerable amount of anti-mycobacterial IgG was also detected in TT/BT patients. Each serum when assayed against sonicates of Mycobacterium leprae, Mycobacterium tuberculosis, ICRC bacilli and BCG gave a similar antibody profile suggesting that these antibodies were directed predominantly against cross-reactive antigens. Up to 75% of LL patients and 35% of TT/BT patients were found to be positive for antibodies to histone, collagen and fibronectin. However, antibodies to several haptens were not detected in any of the patients and controls studied. Taken together, these results suggested that the amount of IgG antibodies is directly correlated with the antigenic load in the system, and that there is no evidence for polyclonal activation. It may be speculated that the regulatory mechanism of antibody production is severely deranged in lepromatous leprosy patients.

Antibodies, Bacterial↗
PubMed1999

Inhibition of apoptosis by ionomycin and zinc in peripheral blood mononuclear cells (PBMC) of leprosy patients.

PBMC from tuberculoid (BT/TT) and lepromatous leprosy (BL/LL) leprosy patients showed spontaneous apoptosis when cultured in the absence of mitogen for 24 h, which was inhibited by anti-tumour necrosis factor-alpha (TNF-alpha) antibodies. Apoptosis was also inhibited by ionomycin and zinc, which also increased IL-2 and decreased TNF-alpha production. The increase in IL-2 production suggests a mechanism whereby dietary supplements with zinc might alter the cell-mediated immunity response in leprosy patients.

Antibodies↗
PubMed2000

Granulomatous reaction to intradermal injection of lepromin (Mitsuda reaction) is linked to the human NRAMP1 gene in Vietnamese leprosy sibships.

The Mitsuda test, which measures the specific immune response against intradermally injected lepromin, has a high prognostic value for susceptibility or resistance to the lepromatous form of leprosy. A sib-pair linkage analysis between the Mitsuda response and the NRAMP1 gene was done among 20 nuclear families with leprosy (totaling 118 sibs) from Ho Chi Minh City, Vietnam. All family subjects were genotyped for several intragenic and flanking NRAMP1 markers, leading to the definition of a fully informative NRAMP1 haplotype. Significant linkage was observed between NRAMP1 and Mitsuda reaction when considered either as a quantitative (P<.002) or as a categorical (P=.001) trait. Separate analyses among healthy and affected sibs showed evidence for linkage in both subsamples, indicating that linkage between the Mitsuda reaction and NRAMP1 is independent of leprosy status. These results support the view that NRAMP1 plays a regulatory role for the development of acquired antimycobacterial immune responses as determined by in vivo Mitsuda test reaction.

Carrier Proteins↗
PubMed1990

Serum tumor necrosis factor levels and disease dissemination in leprosy and leishmaniasis.

It has been suggested that tumor necrosis factor alpha (TNF alpha) may serve as an important antigen-independent host defense mechanism against parasitic organisms. Sera from 66 patients with leishmaniasis and 68 patients with leprosy, all from Ethiopia, were tested for TNF alpha using an enzyme-linked immunoassay. Sera from patients with the multi-parasitic/bacillary type of disease (visceral or diffuse cutaneous leishmaniasis and lepromatous leprosy), known to be associated with absent or low specific T cell response, contained significantly higher TNF alpha titers than those of patients with pauci-parasitic/bacillary disease (localized cutaneous leishmaniasis and nonlepromatous leprosy). High titers of TNF alpha in the absence of a functioning T cell response do not appear to confer resistance against Leishmania aethiopica and Mycobacterium leprae.

Adolescent↗
PubMed1994

Identification of an antigenic domain on Mycobacterium leprae protein antigen 85B, which is specifically recognized by antibodies from patients with leprosy.

Sixty-three overlapping 15-oligomer peptides covering the 30-kDa protein antigen 85B of Mycobacterium leprae were tested by ELISA to identify epitopes recognized by human antibodies. Serum samples from patients with lepromatous leprosy (LL) reacted mainly with peptides comprising amino acid regions (AA) 206-230, 251-280, and 291-325. Sera of patients with active tuberculosis who responded to the native 30-kDa antigen did not recognize these peptides. The antibody-binding specificity to the defined B cell regions was evaluated in a blind study with 71 serum samples from patients and household contacts living in Ethiopia where leprosy is endemic. The peptide of AA 256-280 was recognized by 88% of LL patients, 15% of patients with tuberculoid leprosy, and none of the contacts. These findings suggest that there are major linear B cell epitopes on the M. leprae 30-kDa protein that are recognized by lepromin-negative LL patients, whereas lepromin-positive patients respond preferentially to conformational epitopes.

Amino Acid Sequence↗
PubMed2006

Mannan-binding lectin plasma levels in leprosy: deficiency confers protection against the lepromatous but not the tuberculoid forms.

Mannan-binding lectin (MBL) is an important component of the first-line defence against infections. Evidence has shown that MBL deficiency, reducing phagocytosis and internalization of intracellular pathogens may protect the host against intracellular infections such as leprosy. In this study, we speculated whether genetically determined low MBL serum levels confer protection against Mycobacterium leprae infection. One hundred and ninety-one patients with leprosy, presenting lepromatous (n = 118), tuberculoid (n = 31), dimorph (n = 30) and indeterminate (n = 12) clinical forms and 110 healthy controls matched with the patients according to sex, age and ethnic background were investigated. MBL concentrations were measured in a double-antibody enzyme immune assay and C-reactive protein (CRP) serum levels by nephelometry. A significant negative association of MBL low values (< 100 ng/ml) was observed with lepromatous patients when comparing with controls and tuberculoid patients [10/118, 8.47%versus 21/110, 19.09%P = 0.03 chi(2) with Yates' correction, odds ratio (OR) 0.39, confidence interval (CI) 0.18-0.88 and 8/31, 25.81%, P = 0.02, OR 0.27, CI 0.09-0.75, respectively]. There was no significant difference in the distribution of MBL levels between patients and controls or among the clinical forms. The concentration of CRP was significantly increased in the patients (P = 0.0002) and in the lepromatous form (P = 0.0001) when compared to controls. A weak positive correlation between MBL and CRP levels was observed in the patients (P = 0.010, R = 0.255). These data suggest a protective role for MBL deficiency against the development of the most severe and multi-bacillary form of leprosy.

Adult↗
PubMed2006

ML0405 and ML2331 are antigens of Mycobacterium leprae with potential for diagnosis of leprosy.

Despite the success of multidrug therapy in reducing the number of registered leprosy cases worldwide, evidence suggests that Mycobacterium leprae continues to be transmitted. A serological diagnostic test capable of identifying and allowing treatment of early-stage disease could reduce transmission and prevent the onset of the disability, a common complication of the disease in later stages. Serological diagnosis based on antibody recognition of phenolic glycolipid I (PGL-I) cannot reliably identify individuals with lower bacterial indices (BI). One strategy that might improve this situation is the provision of highly specific serological antigens that may be combined with PGL-I to improve the sensitivity of diagnosis. Using serological expression cloning with a serum pool of untreated lepromatous leprosy (LL) patients, we identified 14 strongly reactive M. leprae proteins, 5 of which were previously unstudied. We present results suggesting that two of these proteins, ML0405 and ML2331, demonstrate the ability to specifically identify LL/borderline lepromatous (BL) patients on the basis of immunoglobulin G (IgG) reactivity. In a household contact study, LL index cases were identified on the basis of this reactivity, while household contacts of these patients demonstrated undetectable reactivity. At a serum dilution of 1:800, suitable to reduce background PGL-I IgM reactivity, two BL patients with a BI of <4 showed anti-human polyvalent immunoglobulin G, A, and M reactivity measured with a combination of ML0405, ML2331, and natural disaccharide O-linked human serum albumin (NDOHSA) (synthetic PGL-I) that was markedly higher than IgM reactivity to NDOHSA alone. We suggest that ML0405 and ML2331 may have utility in serological leprosy diagnosis.

Antibodies, Bacterial↗
PubMed2000

Histological assessment of dermal nerve damage occurring during multidrug therapy for leprosy.

This is a prospective histomorphological assessment of dermal innervation in biopsies taken before and after multidrug therapy (MDT) from 41 leprosy patients: 35 borderline tuberculoid (BT), 3 borderline lepromatous (BL), 3 lepromatous (LL). Biopsies of the same lesions taken before commencement (diagnostic therapy) and at the end of therapy (check biopsy) were compared. Hematoxylin and eosin, immunoperoxidase stain for S-100 protein, and the Holmes' silver impregnation method for nerve cells and fibers were used. Skin biopsies were classified as having detectable or undetectable nerves. Of 35 patients with BT leprosy, 17 had no detectable nerves in their diagnostic biopsies; in the check biopsies of 13 of these 17, dermal nerves remained undetectable, in 2 they were S-100 positive but were Holmes negative. Identifiable dermal nerves were present in diagnostic biopsies from 18 patients; in the check biopsies 5 of these 18 had no detectable nerves while in the remaining 13 nerve branches could be detected. The study provides histological documentation of complete damage to dermal innervation in 62.85% (22/35) of patients with BT leprosy, of which 14.28% (5/35) occurred during MDT. Of the patients with detectable dermal innervation at the onset of MDT, 27.7% (5/18) suffered continuing damage during MDT.

Biopsy↗
PubMed2002

Lymphatics in leprosy: relationship to elastic fibres and observations following intra-lesional injections of colloidal carbon.

An investigation of skin lymphatics in leprosy has been undertaken. Examination of 62 skin biopsies from 31 patients with various classifications of leprosy has revealed dilated initial lymphatics within granulomas of lepromatous leprosy, but no significant abnormalities in non-lepromatous disease or in non-granulomatous skin. Colloidal carbon injected intra-lesionally failed to appear within granulomas, but could be seen in lymphatics in non-granulomatous dermis. Elastic fibres were also absent within granulomas. AFB were clearly identified within endothelial cells of initial lymphatics. We suggest lymphatic malfunction may be compartmental, existing only within the granulomas and not in the surrounding normal appearing dermis.

Carbon↗
PubMed1992

Preliminary study of cellular immunity to Mycobacterium leprae protein in contacts and leprosy patients.

Because of the good results obtained in the mononuclear cell (T lymphocyte) proliferative response in tuberculoid leprosy patients and family contacts and healthy Mitsuda-positive volunteers using Mycobacterium leprae soluble extract, we prepared different protein fractions from the soluble extract. We used the T-cell Western blot technique with separation by electrophoresis in SDS-polyacrylamide gels and transfer onto nitrocellulose membranes. Each unstained blot was converted into 18 fractions of antigen-bearing particles and tested with peripheral blood mononuclear cells from 21 individuals including Mitsuda-positive contacts, vaccinated lepromatous leprosy (LL) patients, borderline tuberculoid (BT) patients, and unvaccinated lepromatous patients. The stimulation index (SI) of the contacts was higher to the different fractions in comparison with the leprosy patients. They showed four peaks of stimulation to fractions 66-55, 45-29, 22-18, and 14 kDa. The second highest responders were BT patients, followed by vaccinated LL patients. The unvaccinated patients did not respond significantly to any of the fractions (SI less than 1).

Bacterial Proteins↗
PubMed1991

M. leprae- and BCG-induced chemiluminescence response of monocytes from leprosy patients and healthy subjects: effects of gamma-interferon and GM-CSF.

Mycobacterium leprae, in contrast to BCG, failed to trigger any chemiluminescence (CL) response in mononuclear cells from either leprosy patients or healthy subjects, a deficit not reversed by either interferon-gamma or GM-CSF. Chemiluminescence responses induced without mycobacteria or with BCG were found to be lower in leprosy patients than in controls. M. leprae were also less well phagocytosed than BCG. However, there was a significant difference in phagocytosis between healthy and tuberculoid leprosy subjects. Phagocytosis was not altered by the addition of either lymphokine, and no major differences between healthy subjects and patients were observed. Preincubating mononuclear cells with anti-mycobacteria antibodies (lepromatous patients' sera) did not increase the CL response nor the phagocytosis of M. leprae or BCG.

Antibodies, Bacterial↗
PubMed1991

Multibacillary leprosy presenting as a solitary skin lesion; report of three cases and its significance in control programs.

Three patients with solitary skin lesions showing the cardinal signs of leprosy were seen and clinically classified among the paucibacillary cases. Initially, they were treated with two drugs (rifampin and dapsone) as recommended by the WHO Expert Committee. On the first visit of their follow-up, they were seen to be histopathologically either in the borderline (BB) or borderline lepromatous (BL) group, and acid-fast bacilli were demonstrated in the sections. Later they were put on three drugs (rifampin, dapsone and clofazimine) as given for multibacillary cases, and therapeutically they also behaved like bacilliferous leprosy. Such cases are rare and the reasons for the occurrence are not clear. Further studies on the subtle relationship between the local host factors and the virulence of the organisms grown from these lesions may offer an explanation. In light of these cases and previous reports of even lepromatous leprosy presenting as a single skin lesion, field workers--including both medical and paramedical workers--should carefully perform and interpret slit-skin smears from clinically diagnosed paucibacillary cases so that such unusual presentations of the disease are treated appropriately and not missed.

Adolescent↗
PubMed1990

[Evaluation of 7 years of systematic surveys of leprosy in Morocco].

Between 1980 and 1987, 12 systematic surveys were made on a population of 254,979 people, of whom 236,868 were actually examined (92.61%). 422 suspected cases were identified i.e. a global detection rate of 1.66% of which only 241 reported to Aïn-Chock Hospital for further tests (55%). Out of these 241 suspected cases, 217 proved as having leprosy, i.e. a 90% correlation between the clinical suspicion and the biological identification. The 181 suspected cases who never reported to the hospital and the 16 leprosy patients whom we lost sight of constitute as a whole 46.68% of the suspected cases first identified. This shows an obvious lack of coordination between the local Authority and the medical service. The 185 confirmed cases of leprosy are shown in the table below and compared with those of the Central Statistical Office.

Adolescent↗
PubMed1990

Prospective immunological follow-up in household contacts of Mexican leprosy patients.

A 6-year prospective study of 79 household contacts of leprosy cases was made in order to correlate the development of the disease with their specific T-cell immunity, measured by the Mitsuda test, and levels of anti-Mycobacterium leprae antibodies determined in three consecutive observations with the FLA-ABS test. Overall in the contacts, 71.7% were Mitsuda positive and 93.6% showed seropositivity, without regard to their age, sex, or leprosy type of their index case. Households were divided into lower-risk and higher-risk groups according to either the paucibacillary or multibacillary character of their index case. The lower-risk group consisted of 19 contacts of 2 tuberculoid (TT) and 5 indeterminate cases. The higher-risk group was made up of 60 household contacts of 18 active lepromatous (LL) cases. All but two contacts in the former group had a positive Mitsuda reaction; the most common antibody titer was 1:160, with a tendency to stabilize or decrease over time. In the two Mitsuda-negative contacts, increased antibody levels were observed. In the higher-risk group, 61.6% were Mitsuda positive and showed a humoral profile similar to those Mitsuda positive in the lower-risk group. In most of the Mitsuda-negative LL contacts, the antibody levels remained constant or progressively increased, suggesting a high probability of active subclinical infection. This assumption was partially supported by the finding of a new borderline lepromatous (BL) leprosy case in the Mitsuda-negative LL contact group. Nevertheless, the contribution of the close and extensive contact with a multibacilliferous case as a risk factor was difficult to evaluate because of the small size of the sample studied.

Adolescent↗
PubMed1989

Dermatoglyphics in leprosy: (III) Creases of palm.

Palmar configurations of triradii and creases of 100 leprosy patients [50 lepromatous (BL/LL) and 50 tuberculoid (BT/LL)] were compared with those of 100 normal persons selected from families of these patients. The patterns of position of triradii were similar in controls and leprosy patients as such. But, the patterns in the two types of leprosy patients were different. As for palmar creases patterns, there was significant difference between those of controls and patients, double radial base crease occurring more often in patients. However, the differences between the two types of patients were not statistically significant.

Dermatoglyphics↗
PubMed1994

[How to detect neuropathy in leprosy].

In leprosy, the early detection of peripheral nerve damage is essential for the prevention of disability. To date, there is no consensus on what is the best clinical test to reveal such abnormalities. In this prospective study we examined the effectiveness of five clinical tests to assess radial cutaneous nerve (RCN) damage (the most frequently involved). Light touch was assessed by two nylon threads (based on the Semmes-Weinstein monofilaments testing technique) bent on the skin at a pressure of 0.5 (N. 4 nylon) and 0.2 gram (N. 5 nylon). Pinprick and cooling sensations were examined by a needle and a drop of ether. The nerve thickness was assessed by palpation. Sensory findings were then compared to sensory nerve conduction values of the RCN and a sensitivity analysis was performed. The patient group consisted of 108 consecutive new leprosy sufferers (138 RCN) who attended the Institut de Léprologie Appliquée de Dakar during one year. Diagnosis and classification were based on Ridley and Jopling's criteria (clinical examination, skin smears and biopsy). Normal values were determined among 22 healthy subjects (44 RCN). The best tests in term of sensitivity were palpation (.60), N. 5 nylon (.65) and N. 5 + palpation (.79). Their positive predictive values were .84 (palpation), .94 (N. 5 nylon) and .83 (N. 5 + palpation). The best tests in term of area under the curve were palpation (.66), N. 5 nylon (.71) and N. 5 + palpation (.78). The results remain the same for the lepromatous or tuberculoid leprosy patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1995

Leprosy in five human immunodeficiency virus-infected patients.

We present five cases of leprosy in five human immunodeficiency virus-positive individuals. The patients were five men between the ages of 18 and 45 years. The five patients presented with skin lesions; three patients with hypopigmented skin lesions, one with skin macules and a history of leprosy, and one with papular lesions. In one patient, there was bilateral "claw hands." Histologically, two cases were categorized as lepromatous leprosy, two as borderline tuberculoid, and one as borderline lepromatous. Follow-up information obtained in the five patients showed one patient had died, and the remaining four patients were alive and receiving antileprosy treatment.

Acquired Immunodeficiency Syndrome↗