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Pathology of iris in leprosy.

AIM: The histopathological features of the iris in leprosy were studied by light microscopy. METHOD: Formalin fixed and paraffin embedded iris tissue excised during cataract surgery from 20 leprosy patients were sectioned and studied with haematoxylin and eosin stain and modified Fite Faraco's stain for acid fast bacilli (AFB). RESULTS: Chronic inflammatory reactions were seen in the iris of 11 patients, seven of whom did not have any clinically demonstrable evidence of iridocyclitis. Smooth muscle disruption and destruction were seen in two specimens. AFB were found in the iris tissue of a polar lepromatous patient whose skin smears were negative for AFB and who had completed the WHO recommended antileprosy multidrug therapy (MDT). CONCLUSION: Histopathology discloses far more silent chronic iridocyclitis in leprosy patients than are diagnosed clinically. AFB can persist in the iris tissue even after completion of MDT. Smooth muscle disruption and destruction, a cause of the miotic pupil in leprosy has been conclusively demonstrated histopathologically.

Adult↗

Subclinical infection in leprosy.

Lymphocyte transformation has been used to study the immune response to Mycobacterium leprae among contacts and non-contacts of leprosy patients. Of 26 subjects living in a leprosy endemic area for less than two months none responded to M. leprae; 24% of subjects who had lived in an endemic area for more than a year gave a positive response to M. leprae; more than 50% of individuals with occupational contact of leprosy for more than a year responded; and about 50% of contacts of tuberculoid and treated lepromatous patients responded to M. leprae, while only 22% (4/18) of contacts of lepromatous patients treated for less than six months responded.It seems that leprosy is more highly infectious than is indicated by the prevalence of the disease and that a subclinical infection commonly follows exposure to M. leprae. The relatively low response found in contacts of active lepromatous patients suggests that in these contacts "superexposure" to M. leprae can bring about a decrease in host resistance.

Ethiopia↗

The Treponema pallidum haemagglutination (TPHA) test in biological false positive and leprosy sera.

The Treponema pallidum haemagglutination (TPHA) test was carried out on 274 sera known to show biological false positive reactions to reagin tests for syphilis. The Treponema pallidum immunization (TPI) and fluorescent treponemal antibody absorption (FTA-ABS) tests were non-reactive on all these sera. Thirty-one or 11.3% showed reactive results in the TPHA test. Sera from 267 people who had lepromatous leprosy were also tested in the TPHA test. Fourteen sera were reactive in the TPHA, TPI, and FTA-ABS tests and were from people who had both syphilis and leprosy. Biological false positive reactions were shown by 26 of the leprosy sera, of which three or 11.5% were also reactive in the TPHA test. A further four sera in the leprosy group were reactive only in the TPHA test. The possible cause of false reactive TPHA test results is discussed. It was concluded that where reagin and TPHA tests are reactive in a person who has no history or clinical signs of syphilis, the serum should be referred for TPI and FTA-ABS testing.

Antibodies, Bacterial↗

Leprosy in peripheral nerves: histopathological findings in 119 untreated patients in Nepal.

From a series of 343 nerve biopsies taken by one clinician over a period of 12 years in Nepal, this paper describes the histopathological findings in 153 biopsies from 119 patients suffering from tuberculoid, borderline (dimorphous) or lepromatous leprosy, who were untreated at the time of first presentation and diagnosis. They were taken during the course of other studies, mainly concerned with the mode of transmission of leprosy, and which included biopsies of skin, dartos muscle, nasal mucous membrane and nipple, results of which have already been published. Examination of serial sections by light microscopy revealed a density of cellular infiltration in non-lepromatous cases, or of bacilli in macrophages and Schwann cells in lepromatous cases, which was marked in degree and usually widespread from one end of the biopsy to the other. Intraneural caseation was recorded in four patients with tuberculoid or borderline-tuberculoid leprosy, and many others in this part of the spectrum showed extensive disruption of perineurial and endoneurial structure. In lepromatous patients, the numbers of bacilli in the endoneurial area not infrequently exceeded one thousand per oil immersion field. Although well known to histopathologists familiar with this disease, it is considered that the significance of these findings, in patients presenting for the first time, is not well appreciated by those working in general medicine, neurology, epidemiology, or even in leprosy control.

Female↗

The patient as a starting point for health education in leprosy control.

The current strategy for leprosy control remains the early diagnosis and effective treatment of leprosy patients with multi-drug therapy (MDT), together with the prevention and/or limitation of disabilities. This paper proposes patients-centred health education strategies that may help in the goal of eliminating leprosy as a public health problem by the year 2000, in leprosy endemic countries like Nigeria.

Attitude to Health↗

Blindness in leprosy patients of Kaduna State, Northern Nigeria.

We examined the eyes of 311 leprosy patients to determine the prevalence of blindness and impaired vision, and the causes of blindness in leprosy patients in Northern Nigeria. There was impaired vision or blindness in 74 eyes. Both eyes were affected in 5.1% of patients while 2.9% were totally blind. Leprosy alone was responsible for total blindness in 1.3% of patients, while other ocular diseases contributed to blindness in 1.6%. Exposure keratitis (21.3%), corneal opacities (13.5%) and chronic uveitis (10.1%) were the commonest leprotic cause of blindness. Primary care and early intervention could help prevent blindness in many of these patients. Primary eye care should therefore be given a prominent position in the training of carers of leprosy patients.

Blindness↗

Immunogold labeling method for Mycobacterium leprae-specific phenolic glycolipid in glutaraldehyde-osmium-fixed and Araldite-embedded leprosy lesions.

Phenolic glycolipid (PGL)-I, a Mycobacterium leprae-specific antigen currently used for serodiagnosis of preclinical leprosy, has thus far not been localized subcellularly in leprosy bacilli and their host cells. In this study, we developed an immunogold-labeling technique for qualitative identification of PGL-I sites in glutaraldehyde-osmium-fixed and Araldite-embedded M. leprae and host macrophages in human skin biopsies. Such "hard-fixed," plastic-embedded skin and nerve biopsies from patients with varying cell-mediated immunity to leprosy are amply available worldwide. Our method involves etching of plastic sections with H2O2, incubation with swine serum to eliminate nonspecific labeling, and long (22 hr) incubation at room temperature with monoclonal antibodies to PGL-I. Gold labeling was seen predominantly on cell walls of M. leprae, in vacuolar spaces of bacillated phagolysosomes, and occasionally on the cytoplasm and cell membrane of M. leprae. Host macrophage cytoplasm was labeled very infrequently. This technique allows studies on possibly persisting antigenic PGL-I in multibacillary leprosy patients during or after multidrug therapy. The method may also prove useful for subcellular localization of specific bacterial lipids in other mycobacterial diseases, including tuberculosis.

Antigens, Bacterial↗

Update on leprosy.

Leprosy, a result of infection by Mycobacterium leprae, is a leading cause of peripheral neuropathy. The World Health Organization aimed to eliminate leprosy as a public health problem by 2000, but this has not been attained. Patients with leprosy continue to present in the UK. The diagnosis of leprosy is frequently not considered, with resultant pathological and psychological problems for patients.

Clofazimine↗

Pure neuritic leprosy in India: an appraisal.

BACKGROUND: Pure neuritic leprosy (PNL) constitutes a significant proportion of all cases in India, however, this form of disease has not been fully recognized and investigated and there is little information in the existing literature. OBJECTIVE: To study the epidemiological characteristics of PNL in India. MATERIALS AND METHODS: A retrospective analysis of leprosy clinic records for the period 1993 to 2003 was undertaken. Detailed demographic profiles and clinical findings were noted from the predesigned clinic proforma. A slit-skin smear for acid-fast baclli (AFB) was done in all cases from the area of sensory loss. A skin biopsy was done from the area of sensory impairment to study histopathological changes. Further investigations such as nerve conduction velocity studies (NCV), fine needle aspiration cytology (FNAC), or nerve biopsy (superficial nerve twigs) were done if indicated in patients whenever there was difficulty in clinical diagnosis. RESULTS: Of the total 1542 leprosy patients seen over this period, 65 (4.2%) had PNL. Males were more commonly affected than females (2.6:1.). The majority of patients 40/65(61.5%) were aged between 15 and 35 yrs. Predominant presenting symptoms were paresthesia, pain, sensory/motor deficit, and trophic changes. A majority of the patients 39/65 (60.0%) presented with involvement of 2 or more nerves in the same extremity. Mononeuritis was seen in 26 (40%) patients. The nerves most often involved were the right ulnar nerve in the upper extremity, and the right common peroneal nerve in the lower limb. In general, the nerves of the upper extremity were more commonly involved than in the lower limbs (67 vs. 55). Motor deformities such as claw hand and foot drop were present in 13/75 (20%) and 7/65 (10.8%) patients, respectively. Slit-skin smears were negative in all patients, and skin histopathology from the area of sensory loss revealed non-specific inflammation in the dermis in a majority of patients, with perineural inflammation in a few. All patients were treated with multi-drug therapy (MDT); patients with >/=2 peripheral nerve trunk involvements were treated with WHO MDT MB regimen, while others were administered WHO MDT PB regimen. Follow-up for up to 2 yrs was available in only 32/65 (49.2%) patients, none of whom developed any skin lesions during this period. CONCLUSION: PNL is a distinct subset of disease frequently seen in India. There is need to pay more attention to this form of leprosy and diagnose and treat patients earlier to prevent deformities and sequelae of nerve damage.

Adolescent↗

Leprosy patients with lepromatous disease have an up-regulated IL-8 response that is unlinked to TNF-alpha responses.

Tumor necrosis factor (TNF-alpha) in conjunction with interferon-gamma (IFN-gamma) plays an important role in lymphocyte recruitment and granuloma formation in mycobacterial diseases. Lepromatous leprosy infections are typically associated with low to absent T cell responses and the absence of INF-gamma secretion. Chemokines such as IL-8, MCP-1, and MIP-1beta, have also been shown to recruit neutrophils and lymphocytes to the site of mycobacterial infections. We have studied IL-8 expression in relation to TNF-alpha and TGF-beta in monocytes from lepromatous patients (LL) as compared with healthy endemic controls. In endemic controls, no spontaneous expression of IL-8, TNF-alpha, and TGF-beta was observed, but BCG and M. leprae induced activation of all three cytokines. Lepromatous leprosy monocytes spontaneously expressed high levels of IL-8 and TGF-beta but negligible levels of TNF-alpha. A further increase in IL-8 secretion or gene expression by BCG or M. leprae was not significant. BCG, but not M. leprae, was able to stimulate TNF-alpha activation in lepromatous leprosy subjects. TGF-beta responses in LL were parallel to those of IL-8. This suggests a vigorous and active ongoing IL-8 response in lepromatous disease that is independent of TNF-alpha activation. Therefore, in the absence of IFN-gamma and TNF-alpha activation, IL-8 may assume a pivotal role in cell recruitment in leprosy patients with disseminated mycobacterial infections.

Adult↗

Epidemiological characteristics of leprosy reactions: 15 years experience from north India.

A retrospective analysis of patient's leprosy clinic records at PGIMER, Chandigarh, India for the period 1983 to 1998 was undertaken to study the frequency, time of onset, and risk factors for leprosy reactions. Of the 2600 cases analyzed, 1494 were multibacillary and 1106 had paucibacillary disease. Presentation with reaction was common with 30.9% of our patients having reactions at the time of first visit. The incidence of reversal reaction (RR) was highest during 6 to 12 months after starting multi-drug therapy (MDT), thereafter declining gradually. Late RR occurred in 9.5% of all cases and was noted up to 7 years after treatment. Female gender, widespread disease, and multibacillary disease were identified as risk factors for RR. Erythema nodosum leprosum (ENL) reactions were noted to occur mostly during second or third year after starting MDT. Of the total number of patients who experienced ENL, 64.3% had recurrent episodes which continued for up to 8 years after the start of treatment. Lepromatous leprosy, female gender, and high Bacterial Index (>/=3) were recognized as risk factors for developing ENL. Occurrence of recurrent and late reactions, even though of mild severity, highlights the importance of recognizing and treating them promptly to prevent or reduce morbidity, complications, and further deterioration in the disability status. Although it is hoped that leprosy will have been eliminated at all levels by 2005, the recognition and management of these reactions will continue to be the most essential/significant task in the post elimination era.

Adult↗

Leprosy reactions: humoral and cellular immune responses to M. leprae, 65kDa, 28kDa, and 18 kDa antigens.

This study examines the immune responses against some stress proteins of Mycobacterium leprae in leprosy patients with and without leprosy reactions. Leprosy patients showed a higher level of antibodies to all antigens compared to healthy controls. The antibody response to 18kDa antigen was significantly higher in patients with Type 1 reaction compared to those of TT or borderline patients without Type 1 reaction, or those with Type 2 reaction. Borderline (BT/BL), lepromatous (LL) and patients with reactions (Type 1 and Type 2) had higher levels of antibodies to M. leprae soluble extract (MLSE) and 65kDa than those of the tuberculoid (TT) group. LL, borderline patients, and patients with Type 1 reaction had a higher level of antibody to 28kDa than those of healthy controls. However, no significant differences could be observed in antibody response to these antigens (MLSE, 65kDa, and 28kDa) between patients with reaction and without reaction. A significant proportion of TT/BT patients showed positive lymphoproliferative response to MLSE compared to BL/LL patients. In addition, the lymphoproliferative response to MLSE was significantly greater in patients with Type 1 reaction compared to patients without reaction. No difference in proliferative response to 65kDa could be observed in any of these groups. The finding of high levels of antibodies against stress proteins in patients with Type 1 reactions, especially to 18 kDa antigen, along with a heightened lymphoproliferative response to MLSE is suggestive of a coexistence of cell mediated and humoral immunity in leprosy patients during Type 1 reactions. On the other hand, in Type 2 reactions no significant role of stress proteins could be demonstrated except a heightened lymphoproliferative response to the 28 kDa antigen.

Antibodies, Bacterial↗

Axonal spherical bodies in the peripheral nerves of leprosy patients.

Spherical bodies, roughly 10 micro m in diameter, which have not been reported before, were found in the peripheral nerve axons of specimens collected during post-mortem examination of leprosy patients. These bodies were found in the fascicles of all peripheral nerves of the extremities examined (median, radial, ulnar, peroneal and sciatic nerves). Their incidence was not related to the type of leprosy. The area immediately below the thickened perineurium, a feature associated with leprosy, often showed a large number of spherical bodies. When observed under a transmission electron microscope, the spherical lesions often showed a lamellar structure, although some of them were amorphous. No structure resembling organelles was seen within the bodies. Observation with the merge technique showed a clearly lamellar structure in most of the spherical bodies. These bodies and the surrounding myelin sheaths were partially polarized. The axonal spherical bodies observed in our study seem to represent lesions gradually formed due to glycoprotein denaturation over long periods of time and to be associated with leprosy-caused thickening of the perineurium of peripheral nerves.

Aged↗

Linkage of leprosy susceptibility to Parkinson's disease genes.

In early 2003, an international team of scientists conducted a genome scan in Vietnamese multiplex leprosy families and found that susceptibility to leprosy was significantly linked to region q25 on the long arm of chromosome 6. Further confirmation of the chromosome 6 locus was provided by high-resolution linkage mapping in simplex leprosy families. Now, in a continuation of these findings, the team has pinpointed the chromosome 6 susceptibility locus to the 5' regulatory promoter region shared by both the Parkinson's disease gene PARK2 and its co-regulated gene PACRG. The surprising discovery has important implications for the understanding of leprosy pathogenesis and for the strategy of genetic analysis of infectious diseases.

Chromosomes, Human, Pair 6↗

Neuropathic pain in leprosy.

Neuropathic pain appears to be much more common in leprosy than has been generally appreciated. Emphasis in leprosy control programs has been on the distribution of multi-drug therapy, on early and better detection, and on the prevention of disability related to anesthetic limbs. Most have thus been inattentive to the problem of neuropathic pain in leprosy patients. Neuropathic pain does not respond to the usual analgesics employed for reactions, for example, and so it is important that those treating leprosy patients give this problem the special attention it requires, both in diagnosis and in treatment.

Humans↗

Susceptibility to leprosy may be conditioned by an interaction between the NRAMP1 promoter polymorphisms and the lepromin response.

Controversial results have been achieved by attempting to associate the NRAMP1 gene with Mycobacterium leprae susceptibility as well as with the Mitsuda reaction, which represents a specific immune response to M. leprae. This study evaluated this association as well as the interaction of the polymorphism (GT)(n) in the promoter region of the NRAMP1 gene with a specific immune response to M. leprae measured by the intradermal Mitsuda test in leprosy patients and in non-consanguineous household contacts. The study aimed to evaluate the association of this gene polymorphism with resistance or susceptibility to the disease, and/or with clinical forms of the disease, in a population in an endemic area served by the State Reference Center in Sanitary Dermatology and Leprosy, Federal University of Uberlandia, MG, Brazil. Leprosy patients (90) were diagnosed according to Ridley and Jopling criteria and they grouped into multibacillary (MB) and paucibacillary (PB) patients. The control group consisted of 61 non-consanguineous contacts. NRAMP1 promoter genotypes were obtained through amplification by the polymerase chain reaction (PCR) followed by the detection through the low ionic-strength single strand conformational polymorphism (LIS-SSCP) electrophoretic technique. There were no significant differences in the allelic and genotypic frequencies for alleles 2, 3, and 4 in relation to the Mitsuda test among patients and household contacts, nor between those with MB and PB forms. However, individuals with a negative lepromin response associated with genotypes 22 and 23 presented a 7- and 8-fold greater chance of developing leprosy, respectively. Therefore, the NRAMP1 gene promoter polymorphism exhibited an interaction with the lepromin response, suggesting that allele 2 of the NRAMP1 promoter is an independent genetic factor that predisposes cells to enable pathogen survival, probably due to its low efficiency in iron transport. However, establishment of the infection and disease development may be conditioned by other immunological and genetic factors.

Alleles↗

Using the blink reflex as measured by electromyogram to assess cranial nerve involvement in people affected by leprosy.

Damage to the peripheral nervous system is particularly frequent in leprosy patients. Trigeminal and facial nerves are among the most commonly affected. The aim of our study was to evaluate the efficacy of the blink reflex as a method for diagnosis of cranial nerve involvement in people affected by leprosy. We studied 37 affected people (mean age: 38 yrs, 20 female and 17 male) and 35 age-matched healthy subjects (mean age: 34 yrs, 20 female and 15 male). Blink reflexes were obtained after unilateral electrical stimulation of the supraorbital nerve for quantitative analysis of 3 responses, early ipsilateral phasic component (R1), late ipsilateral tonic component (R2i), and late contralateral tonic component (R2c). Nerve conduction parameters were studied in all subjects. The latencies of both the ipsilateral early phasic component (R1) and bilateral late tonic components (R2i and R2c) in people affected by leprosy were significantly prolonged compared with the controls. Out of 37 people affected by leprosy, 22 (59%) showed abnormalities R1 latency, 28 (75%) R2i latency and 31 (83%) R2c latency. No correlation was observed between prolonged latencies and duration of the disease. We conclude that blink reflex testing, which can be easily and rapidly performed in an EMG laboratory using standard equipment, can provide useful and objective information for the diagnosis of cranial nerve lesions and for the determination of the degree thereof.

Adult↗

[Phacoemulsification with intraocular lens implantation in leprosy patients: case control study].

PURPOSE: To check the complications of cataract surgery with intraocular lens implantation in leprosy patients by the phacoemulsification technique, and to compare these results, with a control group. METHODS: The used method was a case control study, where 31 eyes from leprosy patients were submitted to cataract surgery, from June 1999 to January 2003, called Case Group. On the other hand, 31 eyes of healthy patients were selected for the Control Group. The comparison between the groups was performed using Fisher's exact test. The used program was EPI INFO 6.04. RESULTS: Sphincter tear was the only postoperative complication higher in the leprosy group (p=0.024). The other alterations did not show statistic differences (p>0.05). Visual acuity improvement was the same in both groups. CONCLUSIONS: This study showed that the visual acuity and complications after cataract surgery with intraocular lens are the same in leprosy patients and healthy ones.

Adult↗