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Effect of preincubation on the proliferative response to antigen by cells from leprosy patients and healthy controls.

One of the postulated mechanisms contributing to the selective T-cell hyporesponsiveness in patients with leprosy is receptor blockade, the characteristic feature of which is reversibility following preincubation of cells in vitro. To test this hypothesis, peripheral blood mononuclear cells (PBMC) obtained from 17 leprosy patients and 10 healthy Mantoux-positive and -negative controls were cultured freshly or after a period of preincubation in serum-containing medium, and the proliferative responses to Mycobacterium leprae, BCG, and streptokinase-streptodornase (SKSD) were measured. On the basis of the response to M. leprae, the leprosy patients could be divided into low, intermediate and high responders. Preincubation for 2-16 hr resulted in enhanced proliferation by cells from moderate responders, but not from low or high responders. Although the effect was serum dependent, it was neither antigen specific nor was it confined to cells from leprosy patients. Thus, an increase in response to both the crossreactive and unrelated antigens BCG and SKSD occurred, and the same trend was observed when cells from healthy controls were preincubated in serum-containing medium. Furthermore, cells from different individuals displayed varying responses to different antigens following preincubation, suggesting that the effect of this step was neither confined to isolated individuals nor to particular antigens. The addition of pronase to the preincubation step did not further enhance the response to antigen over and above that obtained with preincubation alone. It was therefore concluded that the enhanced proliferative response to antigen following preincubation was an in vitro phenomenon dependent upon the culture conditions employed, was not specific to leprosy, and was not related to receptor blockade.

Antigens, Bacterial↗

Impact of MDT on incidence rates of leprosy among household contacts. Part 1. Baseline data.

This preliminary study from Gudiyatham Taluk, the leprosy control area of the Schieffelin Leprosy Research & Training Centre, investigated the incidence rates of leprosy among household contacts during the period 1970-1985. The incidence rates of leprosy among the household contacts prior to and during the initiation of multi-drug therapy are presented here. The overall incidence rate among the household contacts was 4 per 1000 person-years at risk. Contacts of multibacillary and paucibacillary cases had a relative risk of 3-6 times and 2-4 times the risk of leprosy in the general population, respectively. The incidence rates among children were higher than adults; the peak age-specific incidence rate was between 5-9 years, and nearly one third of the primary cases were children. These findings are presented and the methodological issues discussed.

Age Factors↗

Studies on social medicine and leprosy in east China.

Leprosy is a disease in which the social, economic, cultural and environmental factors play an important role in occurrence, spread, control, eradication and rehabilitation. Eliminating the unfavourable factors hindering leprosy control can make achieving the goal of basic eradication of leprosy in China before the end of this century possible. For this reason, since 1984 we have carried out systematic studies of the social aspects of leprosy in Baoying County, a former high-endemic area in Jiangsu Province of East China, where the endemicity of leprosy is nearing full control.

Adolescent↗

The leprosy bacillus: a microbe-dependent microbe.

Since the discovery of the leprosy bacillus, cultivable mycobacteria were regularly found in lepratic tissues of humans and armadillos. Unpublished data indicate that Professor Hugo Preisz isolated and collected several cultures of unidentified cultivable strains of mycobacteria from leprosy sufferers. Recent findings suggest that Mycobacterium leprae is a microbe-dependent, mycobactin-deficient microorganism. The author proposes the concept that secondary mycobacteria found in leprosy cases are ethilogical cofactors in the pathogenesis of leprosy. Since secondary mycobacteria are rich in mycobactin, it is suggested that they provide the essential mycobactin for growth multiplication and virulence for the mycobactin deficient leprosy bacilli. The implications of this concept are discussed.

Bacteriological Techniques↗

BCG vaccination of children against leprosy: fourteen-year findings of the trial in Burma.

The value of BCG vaccination in preventing leprosy among children was studied in an area of high leprosy endemicity in Burma through a controlled trial; one group of 13 066 children received BCG and another group of 13 176 served as controls. The overall protective effect of BCG, which was only about 20% over the 14-year period, was found to vary with the batch of vaccine, as well as age, sex, and contact status of the children. BCG protection was found to be independent of the initial tuberculin status of the children. The protective effect of BCG against the lepromatous type of leprosy could not be measured because of the low incidence. Protection was observed throughout the fourteen years of the study except for the first year. The results are compared with those of three other major BCG trials in leprosy. The trial has shown that BCG provides only a very modest level of protection and that BCG vaccination is not likely to be an important solution for leprosy control.

Adolescent↗

A study of cell-mediated immunity and histocompatibility antigens in leprosy patients in Iran.

Fifty-six male and 14 female leprosy patients, aged 11-62, were studied for cell-mediated immunity (CMI) and histocompatibility antigens. Healthy blood donors were used as normal controls. All patients were receiving antileprosy drugs. T and B cells were detected by E and EAC rosette formation technics, and the leukocyte migration test (LMT) was done in the presence of PHA. HLA antigens were defined by a modified N.I.H. lymphocytotoxicity test in order to type 48 patients and 100 controls. There was a significant difference (p less than 0.01) in the number of T cells between tuberculoid and lepromatous forms of the disease as compared to normal controls. We did not observe any differences in EAC rosette cells. It should be noted that the migration index is significantly higher in controls than in leprosy patients for PHA. There are no significant differences in the distribution of the A locus antigens between leprosy patients and controls, although a higher percentage of A-11 was obtained in leprosy patients. A slight elevation of B5 antigen was observed but these results are preliminary and our information regarding the B locus is incomplete. Thus, it is difficult to establish any precise relationship between HLA antigen and leprosy at this stage.

Adolescent↗

In vitro modulation of lymphocyte responses to phytohaemagglutinin by plasma in mother and baby at the time of birth. Increased lymphocyte responses in babies of mothers with lepromatous leprosy.

Peripheral blood lymphocytes from nineteen healthy mothers, mothers with borderline tuberculoid leprosy and fourteen mothers with borderline or polar lepromatous leprosy, and their newborn babies, were stimulated in vitro with phytohaemagglutinin (PHA). The responses in medium supplemented by serum from a pool of healthy non-pregnant individuals were compared with responses in medium supplemented by plasma from the mothers or from their babies, to assay for the presence of non-specific effects on T-cell responses. It was found that plasma from the mothers at the time of labour profoundly suppressed their own lymphocyte responses to PHA. However, the lymphocyte responses of healthy mothers were not significantly suppressed when cultivated in the presence of plasma from the babies, indicating that the suppressive factor(s) of normal pregnancy did not pass the placental barrier. Plasma from mothers with leprosy had a greater inhibitory effect on their babies' lymphocytes than plasma from healthy mothers. This raises the possibility that plasma from leprosy patients contains suppressive factors other than those associated with pregnancy. Babies of lepromatous leprosy mothers, who might have been exposed to mycobacterial antigens in utero, had higher PHA responses than the other babies, possibly due to a compensatory reaction to early stresses in the immune system.

Female↗

Leprosy situation in Thailand.

The prevalence rate of leprosy in Thailand was approximately 5 per 1,000 in 1953. Specialized leprosy control programme was first launched in 1956 in Khon-Kaen Province and gradually expanded to cover the whole country in 1972. After successful control, it has been partially integrated in provincial health services in 1971 and fully integrated into primary health care system in 1976. Effective case finding in combination with chemotherapy using WHO multidrug therapy regimen and health education have brought about a decline in the prevalence of the disease to only 0.537 per 1,000 in 1987. However, the estimated prevalence rate by random survey is approximately twice the number of registered cases. Reduction in number of lepromatous leprosy patients, particularly the new cases, decrease in number of patients with deformities caused by leprosy and increased number of patients who voluntarily came to attend at the treatment centres imply the successful control at a certain level. It is then justified to aim at the goal of eradication of leprosy by combination of chemotherapy, immunotherapy and immunoprophylaxis with antileprosy vaccines in the future.

Drug Therapy, Combination↗

Study of serum zinc level in leprosy.

Serum Zinc level was estimated in different types of leprosy by 'Dithiazone extraction' method in 75 leprosy patients comprising 15 each of Tuberculoid-Tuberculoid (TT); Borderline Tuberculoid (BT); Borderline Borderline (BB); Borderline Lepromatous (BL) and Lepromatous Lepromatous (LL). These findings were evaluated in comparison to 15 normal subjects serving as controls. Serum zinc level was observed to be significantly low in all types of leprosy except tuberculoid leprosy (TT). No significant difference was observed in serum zinc levels before and after 90 days of dapsone Therapy. The findings of our study are of considerable importance as zinc deficiency can be one of the factors involved in non-specific suppression of cell mediated Immunity (CMI) in lepromatous leprosy.

Adult↗

Estimation of high density lipoprotein cholesterol in the diagnosis of lepromatous leprosy.

A high incidence of increased plasma level of high density lipoprotein cholesterol (HDL-C) has been reported in cases of lepromatous leprosy. HDL-C levels were estimated in 96 (50 under treatment and 46 untreated) lepromatous leprosy patients and 84 randomly selected matched control patients suffering from other skin diseases attending skin out-patients department. HDL-C estimations were performed for the diagnosis of lepromatous leprosy in patients aged below 60 years, taking plasma HDL-C levels as 28-71 mg./dl. in men and 34-91 mg./dl. in women, as range of normal values. The study revealed that HDL-C levels in lepromatous leprosy group were raised and significantly different when compared with control group (t = 35.1668 and P less than 0.001). The sensitivity of the test was very high, 97.9 per cent (94/96), but specificity was low 80.95 per cent (68/84). False positive and false negative results were 19.04 per cent (16/84) and 2.08 per cent (2/96) respectively. It is opined that a negative test will be mainly useful in excluding diagnosis of lepromatous leprosy.

Adult↗

Healing time in untreated paucibacillary leprosy: a cross-sectional study.

The healing time of leprosy lesions in 117 paucibacillary (PB) cases who took no antileprosy treatment was estimated to be 2.03 +/- 0.10 (mean +/- S.E.) years in a leprosy hyperendemic area. This healing time does not appear to be influenced by epidemiological characteristics of the patients such as age, sex, intrafamilial leprosy contact status, number and site of leprosy lesions, etc. It was also observed that the rate of healing and downgrading among the total untreated cases was 22.4% and 0.57%, respectively, per year. About 39% of the total untreated PB leprosy cases healed within a period of 2 years. The scientific implication of this observation is discussed.

Adult↗

Antigens of Mycobacterium leprae identified by immunoprecipitation with sera from leprosy and tuberculosis patients.

Mycobacterial antigens which react with human B lymphocytes were investigated by immunoprecipitation of radiolabelled sonicates of Mycobacterium leprae and M. bovis (BCG) with sera from patients with leprosy and tuberculosis in the presence of Staphylococcus aureus. SDS-PAGE analysis of the immunoprecipitates demonstrated that dense bands of Mr 12,000 (12K), 15K, 27K, 32-33K, 36K and 48K were the major antigens of M. leprae recognized by antibodies in lepromatous leprosy sera. Of these, only the 15-16K band reacted significantly with sera from patients with tuberculoid leprosy and tuberculosis. Other antigens including the T cell immunogens of Mr 18K and 70K reacted with some of the BL/LL sera tested. There were differences in the pattern of antigens precipitated from BCG sonicate by leprosy sera with the 65K antigen and a high molecular weight band (greater than 94K) being readily detected. These results differ in part to these obtained by probing immunoblots of M. leprae sonicate with leprosy sera. Factors contributing to these differences are discussed.

Antigens, Bacterial↗

Assessment of the immune deficit in leprosy patients and the effect of recombinant IL-2 in vitro.

Although the mechanism of immunologic unresponsiveness in lepromatous leprosy remains unknown, it has been shown that interleukin-2 (IL-2) production is defective in these patients. Peripheral blood mononuclear cells (PBMC) were isolated from treated (less than 16 months) and untreated leprosy patients as well as household contacts; age, sex, ethnically matched control subjects; and laboratory staff. PBMC were cultured for 6 days with sonicated Mycobacterium leprae (1-10 micrograms/ml), Dharmendra lepromin (1:10), or phenolic glycolipid-I (PGL-I) (0.05-5.0 micrograms/ml) in medium supplemented with various concentrations of recombinant IL-2 (rIL-2) or cultured for 3 days with one of the three mycobacterial antigens in the presence of concanavalin A (ConA). TT/BT patients and household control subjects had a robust response to M. leprae and lepromin, but were unresponsive to PGL-I delivered in liposomes. PBMC from LL patients did not respond to any of the three antigen preparations. rIL-2 induced proliferation of PBMC both in leprosy patients and control subjects regardless of the presence or absence of the three leprosy antigen preparations. This antigen nonspecific augmentation of proliferation by the wide range of doses of rIL-2 employed makes difficult the interpretation of the enhanced thymidine incorporation noted when rIL-2 is added in the presence of antigen to cultures of lymphocytes from LL patients. Our studies are at variance with reports that leprosy antigens, specifically PGL-I, induce immunological suppression, in that mycobacterial antigens did not cause significant suppression of the ConA-induced proliferations of PBMC from patients.

Adolescent↗

Comparison between autoantibodies in malaria and leprosy with lupus.

Sera from 16 patients with falciparum malaria, 16 patients with vivax malaria and 31 patients with leprosy were tested for autoantibodies to intracellular proteins and nucleic acids. Precipitating antibodies to soluble protein extracts were not detected in any serum. Sera from malaria patients showed prominent immunofluorescence staining of the HEP2 nuclear membrane as well as frequent 75% (24/32) and intense Western blot reactivity. In contrast, only 20% and 36% of patients with leprosy had positive immunofluorescence or positive immunoblots respectively, and reactivity was weak in most cases. Neither the malaria nor leprosy sera contained autoantibodies with specificities similar to the characteristic lupus autoantibodies such as double stranded DNA (dsDNA), Ro/SSA, La/SSB, Sm, RNP and P proteins. Low levels of antibodies to single stranded (ssDNA) were however found in 11 (34%) malaria sera and in seven (23%) leprosy sera. Thirteen percent of patients with leprosy had anti-histone antibodies. These findings demonstrate considerable differences in the capacity of infectious agents to induce autoantibodies and also the infrequency with which autoantibodies characteristic of idiopathic systemic lupus erythematosus are induced.

Adolescent↗

Diagnostic efficacy of cutaneous nerve biopsy in primary neuritic leprosy.

The role of nerve biopsy in the diagnosis of primary neuritic leprosy was evaluated in a study of 77 patients who had symptoms of peripheral neuropathy without hypopigmented patches, positive skin smears, or a skin biopsy consistent with leprosy. A biopsy of a representative cutaneous nerve near the site of the neurological deficit was taken for histopathological examination and acid-fast staining. Nearly half of the patients had leprosy confirmed by nerve biopsy, and the entire spectrum of leprosy was represented. No significant relationship was seen by age or sex or type of neuropathy. The duration of symptoms did not correlate with the severity of nerve damage as seen histologically. The probability of false-positive or false-negative results is discussed in light of clinical management. Being a relatively simple office procedure, a cutaneous nerve biopsy is strongly recommended as an important diagnostic tool, particularly for primary neuritic leprosy.

Adolescent↗

Tetanus in leprosy patients: report of five cases.

It has long been noted that tetanus is rare in leprosy patients. Five cases of tetanus are reported in leprosy patients in Addis Ababa, Ethiopia. Although natural immunity to tetanus occurs and this appears to be higher in leprosy patients than in the general population, it is not completely protective. Further research on the relationship between tetanus and leprosy is indicated. Although firm epidemiologic data are lacking, it is prudent to give leprosy patients at least one dose of tetanus toxoid.

Adult↗

Histoid leprosy in Singapore.

Histoid leprosy is a rare variant of lepromatous leprosy. This is the first documented case of histoid leprosy in Singapore. The patient was diagnosed as borderline leprosy in 1973, remained untreated and progressed to lepromatous leprosy. The characteristic histoid lesions were firm pruriginous nodules on the dorsum of his feet. The histology showed a pseudocapsulated tumour with fibroblasts and histiocytes filled with lepra bacilli. Electron microscopy showed fibroblasts, macrophages with bacilli and plasmacytoid cells with active endoplasmic reticulum. He was found to be dapsone-resistant and the lesions cleared with clorphazimine. Immunological defects were not detected.

Aged↗

Leprosy in the Union Territory of Delhi.

One hundred and seventy seven patients of leprosy residing in Delhi comprised 16.4% of the total Urban Leprosy Centre attendance in a three-year retrospective study with a M:F ratio of 3:1. The average age at onset of disease was 28.75% years and childhood leprosy was only 6.78%. The cases of pauci- and multibacillary leprosy were almost evenly distributed. Borderline leprosy (including BT, BB & BL of Ridley-Jopling classification) comprised the largest single group with 51.42%, followed by Lepromatous with 21.47%. In 90% cases the high probability of acquiring infection during period of stay in the city and the involvement of lower age-group are pointers towards the endemic nature of the disease in the region.

Age Factors↗