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Role of target groups in integrated leprosy programmes.

The introduction of integrated leprosy services into the primary health care set-up has taken away active case-detection in the community and is replaced by passive reporting by the suspected, afflicted individuals. This can only be made operative effectively with intensive IEC activities in the community. A research study involving school-children (219,000) in leprosy work achieved spectacular success in new case-detection, effective monitoring, completion of MDT and coverage of a large number of individuals (750,000). The results evaluated on a representative sample of 20,000 school students (pre- and post-test), showed over 90% success in creating awareness about the cause of the disease, its symptoms, curability by fixed duration MDT and better attitudes and perceptions of the community towards leprosy-affected individuals. It is emphasised that, in view of the experience gained from the study, other more cohesive and disciplined target groups, such as scouts and guides, NCC cadets, NSS volunteers, should be identified for leprosy work throughout the country in a planned and coordinated manner in order to implement and sustain leprosy eradication activities in the near-elimination and post-elimination phases.

Adolescent↗

Genetics of host response in leprosy.

In this review, we discuss recently accumulated data, analysing genetic influence on leprosy outcome. Most leprosy-related epidemiological studies are based on the comparison of frequencies of genetic markers in case-control designs using candidate genes, mainly on immunological pathways. Genomic scans using family-based designs also identified some chromosome regions to be tested for association with leprosy. The results have suggested that different genes are implicated in resistance/susceptibility to leprosy, such as tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-10, vitamin D receptor (VDR), and parkin, although some of the results obtained in different populations are controversial. In spite of the recent advances in genomics and genetic epidemiology we have experienced, the results must be confirmed using better designed epidemiological studies to directly pinpoint the genes responsible for leprosy outcome. Furthermore, there is a clear requirement of functional/biological data in order to validate epidemiological findings. In this way, these genetic markers could be used to screen high-risk populations introducing gene testing as diagnostic and prognostic tools to interrupt the chain of transmission and prevent neurological damage.

Cytokines↗

Studies of human leprosy lesions in situ using suction-induced blisters: cell changes with IgM antibody to PGL-1 and interleukin-2 receptor in clinical subgroups of erythema nodosum leprosum.

To examine the immunopathogenesis of type 2 erythema nodosum leprosum (ENL) reactions in leprosy, we studied cellular and soluble immunologic components of skin lesions in 57 patients with reactions (19 acute ENL and 38 chronic ENL), 61 active patients without reactions, and 33 control patients whose leprosy had been treated and cured. Cells, IgM antibody to PGL-1 and Tac peptide levels were obtained from fluid aspirated from blisters induced by suction directly over representative skin lesions. During ENL reactions: a) the lesions in chronic ENL showed a decreased number of CD8+ (T-suppressor) cells and increased helper/suppressor ratio as compared to those in acute ENL and non-reactional leprosy; b) Tac peptide and IgM antibody to PGL-1 levels were elevated in the chronic ENL lesions; c) and systemic administration of corticosteroids appeared to cause a reduction in the intralesional CD4+ cell population and IgM antibody to PGL-1 but did not change CD8+ cell population and the levels of Tac peptide in the lesions. The elevated levels of Tac peptide were localized in the skin lesions while increased levels of IgM anti-PGL-1 seemed to be filtered from the peripheral blood. We conclude that spontaneous lymphocyte activation in situ, primarily of decreased CD8+ and relatively increased CD4+ cells, are important features of chronic, recurrent ENL reactions and may be an intermittent or cyclic phenomenon during the reaction. Understanding the mechanisms of these spontaneous changes in immunity in leprosy will enlarge our knowledge of reactions and of the underlying determinants of delayed type hypersensitivity and cell-mediated immunity in leprosy, which in turn will allow us to realize the potential for artificially manipulating these responses as proposed with vaccines or immunotherapy.

Adolescent↗

Detection of M. leprae-specific antigens with dot-ELISA in urine and nasal samples from leprosy patients.

One-hundred-two urine and nasal samples collected from leprosy patients of different classifications of disease were studied for the presence of Mycobacterium leprae antigens, including phenolic glycolipid-I (PGL-I). Lipids were extracted from the urine samples, and nasal washings were concentrated and used as such in the dot-ELISA. Two types of primary antibodies, a polyclonal antibody obtained from lepromatous (LL) leprosy patients' pooled and absorbed sera and an anti-PGL-I monoclonal antibody, were used for the detection of M. leprae antigens from these samples. The polyclonal sera detected 23% to 36% of the paucibacillary (PB) and 100% of the multibacillary (MB) leprosy cases from the urine samples. Corresponding values for nasal detection were 10% to 18% for PB and 100% for MB cases. The monoclonal antibody against PGL-I could not detect tuberculoid (TT) leprosy cases. From the urine samples, however, 16% of the borderline tuberculoid (BT), 25% of the borderline (BB), 80% of the borderline lepromatous (BL), and 100% of the LL leprosy cases were detectable. It was interesting to note that PB, skin-smear negative cases were detectable from urine examination. The specificity and sensitivity of the test is discussed in relation to the crossreacting antigens.

Adolescent↗

Post-kala-azar dermal leishmaniasis simulating leprosy. (A case report).

The case of a 40 years male suffering from post-kala-azar dermal leishmaniasis simulating nodular lepromatous leprosy is reported. In countries where leprosy is endemic, other diseases are not infrequently taken to be leprosy (Schaller, 1971). Dermal leishmaniasis is a common cause of confusion in countries where the condition is endemic (Browne, 1964). Dharmendra and Chatterji (1940) discussed in detail the question of differential diagnosis between Leprosy and Dermal Leishmaniasis. The present communication is concerned with a patient suffering from post-kala-azar dermal leishmaniasis whose skin lesions simulated nodular lepromatous leprosy.

Adult↗

Lepromatous leprosy in Saudi female from central region.

Leprosy is an uncommon disease in Saudi population. Lepromatous leprosy is a most contagious form of leprosy. Erythema nodosum leprosum is an unusual complication of leprosy. We report an unusual case of leprosy from the central region of Saudi Arabia presenting as erythema nodosum leprosum.

Aged↗

[Intensification of the fight against leprosy using early and systematic polychemotherapy].

The latest epidemiologic enquiries realized in West Africa and Central Africa have shown that real prevalence of leprosy is far greater, at least twice the number of patients than are actually listed in the medical records. This data proves that the fight against leprosy is highly inefficient and stresses the partial failure of the anti-hansenian strategy that has been adopted for over 10 years in this area, in spite of the use of rifampicin in multidrug therapy which would normally cure leprosy. Therefore we suggest that the fight against leprosy should be re-organised and reinforced in high endemic areas. The anti-hansenian programmes should be carried out by specific services composed of mobile and specialised teams whose task would be to aim for the early detection and continual testing for new cases. Only with this kind of organisation can chemotherapy be administered at the beginning, therefore arresting the disease before it reaches the multi-neuritis stage. This strategy offers great epidemiologic and economic advantages and would also give hope and dignity to the patients assured of a permanent cure. Leprosy would then be classed as a disease "just like any other".

Africa, Central↗

Studies of human leprosy lesions in situ using suction-induced blisters. 2. Cell changes and soluble interleukin 2 receptor (Tac peptide) in reversal reactions.

To examine the pathogenesis of type 1 (reversal) reactions in leprosy, we studied cellular and soluble immunologic components of skin lesions in 10 patients with reactions, 24 active patients without reactions, and 33 control patients whose leprosy had been treated and cured. Cells and Tac-peptide levels were obtained from fluid aspirated from blisters induced by suction directly over representative skin lesions. During reversal reactions: a) the lesions contained an increased number and percentage of CD4+ (T-helper) cells; b) Tac-peptide levels were elevated in half of the lesions; c) the increases in Tac peptide and CD4+ cells were directly correlated; and d) systemic administration of corticosteroids appeared to cause a reduction in the intralesional CD4+ cell population. These findings were localized to the skin, and do not represent simple filtration of these components from the peripheral blood. We conclude that spontaneous lymphocyte activation in situ, primarily of CD4+ cells, is an important feature of reversal reactions, and may be an intermittent or cyclic phenomenon during the reaction. Findings in active patients without reactions are consistent with the hypothesis that differing states of immunologic equilibrium have been established in different portions of the leprosy spectrum. In reversal reactions we may, therefore, be examining immunologic processes set in motion when a pre-existing equilibrium has been upset by spontaneous, natural events. The mechanism of such spontaneous changes in immunity in leprosy is of considerable interest, not only to understand the reaction, but also to examine the underlying determinants of delayed-type hypersensitivity and cell-mediated immunity in leprosy and the potential for artificially manipulating these responses, as proposed with vaccines or immunotherapy.

Adult↗

Significance of nail changes in leprosy: a clinical review of 357 cases.

Leprosy can cause many nail changes, which have been observed in up to 64% of infected patients. The manifestations of leprosy (clinical, bacteriologic, and histological) are profoundly affected by the patient's immunological status, which also determines the prognosis. Nail changes in leprosy can be caused by neuropathy and trauma, vascular impairment, infections, and miscellaneous changes. Often more than one factor will be important. Paradoxically, nail changes in tuberculoid and lepromatous patients are similar, despite wide differences in pathology. This may be because etiological factors common to both are implicated. Factors only associated with lepromatous disease are invasion of the bones of terminal phalanges by lepromatous granulomas and endarteritis occurring during type 2 lepra reactions. Otherwise, the only difference from tuberculoid leprosy is the time of onset and the symmetry of lesions. Lepromatous patients develop nail changes late in the course of disease. The presentation is usually bilaterally symmetrical. However, these changes are not specific to leprosy, and may be observed in other peripheral neuropathies.

Bacterial Infections↗

Antigens of Mycobacterium leprae in the cerebrospinal fluid of leprosy patients: detection by monoclonal-antibody-based sandwich immunoradiometric assay and avidin/biotin immunoblotting.

Mycobacterium leprae antigens could be detected in the cerebrospinal fluid (CSF) of patients with leprosy, using a monoclonal-antibody-based sandwich immunoradiometric assay (SIRMA). Antigens of 12 kD, 35 kD and 30-40 kD were detected using ML06, ML04, and ML34 monoclonal antibodies, respectively. The 30-40-kD polysaccharide antigen, although present in larger amounts in M. leprae than the 12-kD and 35-kD protein antigens, was found in the CSF of comparatively fewer subjects. The antigen capture assay has been found sensitive to the level of nanograms. Avidin-biotin-based immunoblotting using pooled leprosy sera detected a larger number of antigens than using anti-M. leprae antisera raised in rabbits. The immunoblotting of CSF samples revealed about three antigens in the region of 100-160 kD and three more in the region of 45-60 kD as probed by leprosy sera. This study has for the first time revealed the presence of M. leprae antigens in the CSF of leprosy patients and the probable involvement of the central nervous system in leprosy.

Antibodies, Monoclonal↗

Is HIV infection a risk factor for leprosy?

A case control study was undertaken during 1988 and 1989 within the framework of the LEPRA Evaluation Project (LEP)/Karonga Prevention Trail (KPT) in Karonga District, northern Malawi, to investigate whether HIV infection is a risk factor for clinical leprosy. Cases were newly ascertained, biopsy-confirmed, incident leprosy patients older than 14 years of age. Controls were selected from the computer data base on over 170,000 people who form the basis of LEP/KPT. They were matched for sex, age, and area of residence. HIV seropositivity rates were 1.8% (2/112) for incident leprosy cases and 2.4% (24/1011) for controls. The Mantel Haenszel odds ratio is 0.6 (95% confidence interval 0.1-3.3). Thus, no evidence for an association between HIV infection and leprosy incidence has been observed in this population. In a parallel investigation, an odds ratio of 7.4% (95% confidence interval 3.3-16.7) was found for 102 microscopy- and/or culture-confirmed, incident pulmonary tuberculosis cases in the same population during 1989, a result similar to those obtained elsewhere in Africa. Among leprosy relapses, 16.7% (2/12) were HIV positive.

Adult↗

Ocular leprosy in nine-banded armadillos following intrastromal inoculation.

Leprosy shows a higher percentage of ocular involvement than any other systemic infection. In humans, the cornea is the first ocular tissue affected. Our previous studies in armadillos with naturally acquired and experimental disseminated leprosy showed that 44% had corneal infection. Mycobacterium leprae is found in armadillo burrows in Louisiana, U.S.A., and ocular abrasions may be the portal of entry for these organisms in wild armadillos. To test the cornea as a route of infection, we injected eight armadillos intrastromally with 2 x 10(6) M. leprae in 1 microliters. Two and 4 months later, the armadillos were sacrificed and their eyes processed for light- and electron-microscopy. After 2 months, M. leprae were found in histiocytes mainly in the corneal limbus, sclera and bulbar conjunctiva. At 4 months, however, there was a visible corneal leproma in one animal. Microscopically, it was found to be a histiocytic granuloma with heavy M. leprae invasion. In addition, cells were seen in the anterior chamber. Leprosy is endemic in regions where other corneal infections which compromise the epithelial barrier property are prevalent and where leprosy bacilli are found in the environment. The entry of leprosy bacilli into the cornea may produce lesions which spread posteriorly in the eye.

Animals↗

Non-pruritic eczemas as presenting manifestation of leprosy.

Three patients who presented with eczemas as manifestation of leprosy are described. One of them having lepromatous leprosy had extensive areas of acquired ichthyosis. He developed asteatotic eczema on the legs. The pathophysiologic mechanisms for the development of ichthyosis and asteatotic eczema in this patient are briefly discussed. The second patient, with tuberculoid leprosy, presented with allergic contact eczema due to neomycin which he had applied over the plaque for scaling and crusting. The third patient, also with tuberculoid leprosy, presented with features of nummular eczema. Dryness of the skin that resulted from leprosy had led to the development of nummular eczema in this case. One peculiarity noted in all these eczemas was that they were non-pruritic.

Adult↗

Thyroid function in leprosy.

Thyroid function tests were carried out in 43 cases of leprosy. The study subjects included cases of tuberculoid, borderline and lepromatous leprosy and those with lepra reaction. The parameters studied included serum cholesterol, protein bound Iodine, serum T3 level and serum T4 levels. The levels of serum cholesterol and protein bound Iodine were normal in all the four groups of leprosy patients. However, the mean serum T3 and T4 were low in all the four groups. The difference in the levels of serum T3 was statistically significant only in the lepra reaction group. The levels of T4 were statistically significantly decreased in borderline leprosy, lepromatous leprosy and in lepra reaction.

Adolescent↗

Pattern of drug compliance in leprosy patients attending urban centres--a longitudinal study.

The pattern of drug compliance in 485 leprosy patients attending urban leprosy centres in Bombay was studied for 2 years. The study subjects included 113 patients with paucibacillary leprosy under dapsone monotherapy, 241 patients with paucibacillary leprosy under multidrug therapy and 131 patients with multibacillary leprosy under multidrug therapy. Their urine samples had been checked at least 6 times during the 2 years by DDS tile test at the time of their clinic attendance. The urine test results were not disclosed to the patients, but patients showing negative results were counselled about the need for regular drug intake. 35% of the patients were "Regular through out", 13% were "Irregular through out" and the other 52% who "Tended to be irregular" in their drug intake became "Regular" after counselling. Regularity in drug compliance was better in patients on multidrug therapy than in those on monotherapy. It is suggested that periodic testing of urine for checking for regularity of drug intake and subsequent counselling of patients should be made a routine practice to maintain drug compliance at a high level.

Dapsone↗

Is leprosy bacillus a chemo-autotrophic nocardioform organism?

Numerous attempts at in vitro cultivation of the leprosy bacillus have all proved to be unsuccessful. Recently, we have repeatedly isolated chemo-autotrophic nocardioform (CAN) organisms in pure culture from multibacillary cases of leprosy. We find that these resemble the leprosy bacillus in many respects and suggest that the leprosy bacillus may be closer to the genus Nocardia than to Mycobacterium, and that it may be a chemo-autotroph, requiring only simple sources of carbon and nitrogen for its growth. This is in contrast to most other human pathogens, which are heterotrophs requiring complex sources of carbon and nitrogen for their growth. This could offer a possible explanation for the repeated failure at in vitro cultivation of the leprosy bacillus.

Humans↗

Vaccination and skin test studies on the children of leprosy patients.

In an attempt to achieve maximal skin-test positivity to leprosin A in children of leprosy patients living in Baba Baghi Leprosy Sanatorium in Iranian Azerbaijan, two new vaccines have been employed. Children without scars of previous BCG and without response to leprosin A were given a vaccine containing 10(8) viable units of BCG Glaxo plus 10(7) killed Mycobacterium vaccae per dose (vaccine B). Children with BCG Pasteur (Teheran) scars but without response to leprosin A were given a vaccine containing 10(8) killed M. vaccae alone (vaccine D). Eight years later skin testing was repeated, and both new vaccines were found to have significantly increased the numbers of children responding to leprosin A above the level that would have been expected had they received BCG Pasteur alone. This increase was due in large part to increases in the proportions of individuals responding to group i (common mycobacterial) antigens, and known as category 1 responders. The use of suspensions of killed M. vaccae in conjunction with BCG may represent a considerable advance in inducing protection from multibacillary leprosy in close contacts of leprosy patients if leprosin A positivity is truly a correlate of protective immunity. A comparison, using the same criteria, with the other proposed vaccines for leprosy would be very interesting.

Antigens, Bacterial↗

Immunoepidemiological studies on subclinical infection among leprosy household contacts in Thailand.

Three-thousand-fourteen leprosy house-hold contacts in Thailand were surveyed by their personal history, physical examination, and immunological tests. The results were compared with those obtained from villagers in leprosy-endemic and nonendemic areas. The percentages of young people, students, children and grandchildren of the patient, the contacts of multibacillary leprosy cases, long duration of contact, BCG vaccination, FLA-ABS and Dharmendra's lepromin-positive responders were significantly higher in the household contacts than those in the villagers. The percentages of neural and dermal symptoms were not significantly different between the household contacts and the villagers in the endemic area, but the percentages were higher than those of the villagers in the nonendemic area. A PPD skin test was more frequently negative in the former two groups than in the latter. Both FLA-ABS and lepromin tests showed a significant correlation with the age of the contacts, their occupations, blood relation to the patient, the duration of contact, BCG vaccination, dermal signs such as an ill-defined plaque or macule with or without sensory loss, but did not correlate with sex, type of leprosy in the patient, or other skin diseases. The FLA-ABS test in the house-hold contacts and the villagers in an endemic area showed a significant correlation with the neural signs, such as enlargement of the peripheral nerve without sensory loss. These suspicious dermal and neural signs and symptoms were therefore considered signs of Mycobacterium leprae infection. The FLA-ABS test was sufficiently sensitive for detecting this infection and did not correlate with the lepromin or PPD skin tests. FLA-ABS-positive but lepromin-negative responders were found in 33.5% of the house-hold contacts. They were considered to be a high-risk group who may develop clinical leprosy. Nearly half of them were treated with dapsone or BCG according to the results of the PPD skin test. Follow up of these contacts, together with the remaining contacts without treatment, is in progress.

Adolescent↗