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Soluble tumor necrosis factor alpha receptors in sera from leprosy patients.

Serum levels of soluble tumor necrosis factor alpha receptor I (sTNF-RI) were elevated in patients with lepromatous (LL) reactional-state type II leprosy, and sTNF-RII levels were increased in patients with full tuberculoid (TT) or LL type II leprosy. The sTNF-R in sera from patients with type II leprosy, but not other forms of leprosy, inhibited recombinant TNF cytolytic activities in vitro. This suggests that sTNF-R regulatory activities are partially impaired in patients with leprosy.

Adult↗

Ocular complications in newly diagnosed borderline lepromatous and lepromatous leprosy patients: baseline profile of the Indian cohort.

AIM: To describe ocular manifestations in newly diagnosed borderline lepromatous (BL) and lepromatous leprosy (LL) patients in India. METHODS: Ocular complications, at enrolment, occurring in all new borderline lepromatous and lepromatous leprosy patients detected by active case finding within the geographically defined leprosy endemic area of the Gudiyattam Taluk in India from 1991 to 1997 who consented to ocular examinations every 6 months, during and 5 years after treatment with multidrug therapy (MDT), were studied. RESULTS: Orbicularis oculi weakness (4.62%), lagophthalmos (4.20%), ectropion (0.42%), trichiasis (0.84%), blocked nasolacrimal ducts (1.68%), pterygium (11.34%), impaired corneal sensation (53%), corneal opacity (10.5%), corneal nerve beading (1.68%), punctate keratitis (1.26%), keratic precipitates (4.62%), iris atrophy (1.68%), and cataract (12.6%) were ocular complications seen in the 301 lepromatous patients at enrolment. 4.6% had blind eyes. Increasing age was associated with ocular complications. 80% of patients were skin smear acid fast bacilli (AFB) positive. The LL/BL ratio was 1:6.4. 71% had some limb deformity. 44% had only leprosy related ocular complications (LROC), 28% had only general ocular complications (GOC) while 14% had both LROC and GOC. Ocular complications were significantly related to leg deformities. Corneal nerve beading was seen most in LL patients (100%) having high bacterial content. Lagophthalmos and muscle weakness were associated with reversal reactions. CONCLUSIONS: Corneal nerve beading occurs in LL patients with high bacillary count. Patients with reversal reaction are more likely to present with orbicularis oculi weakness and lagophthalmos. Leprosy related ocular complications and general ocular complications are significant problems in newly diagnosed lepromatous patients. Elderly, deformed, skin smear positive, lepromatous patients are associated with increased ocular morbidity and form a group that require acceptable and accessible eye care.

Adolescent↗

Polymorphism of the 5' flanking region of the IL-12 receptor beta2 gene partially determines the clinical types of leprosy through impaired transcriptional activity.

BACKGROUND: Individual differences in T cell responsiveness to interleukin 12 (IL-12), resulting from inherited factors, may be responsible for differences in the intensity of cell mediated immune (CMI) responses in patients with leprosy, a disease with a wide clinical spectrum. AIM: Polymorphisms in the 5' flanking region of the IL12RB2 gene were analysed to determine potential immunogenetic factors affecting CMI responses, using leprosy as a model. METHODS: Polymorphisms in the 5' flanking region of IL12RB2 were examined using direct sequencing techniques, and allele frequencies between patients with lepromatous leprosy and patients with tuberculoid leprosy were compared. The effect of these single nucleotide polymorphisms (SNPs) on IL12RB2 expression was estimated using the dual luciferase reporter gene assay in Jurkat T cells. RESULTS: Several SNPs, including -1035A>G, -1023A>G, -650delG, and -465A>G, were detected within the 5' flanking region of IL12RB2. The frequency of haplotype 1 (-1035A, -1023A, -650G, -464A) was high in the general Japanese population, but was significantly lower in lepromatous patients compared with tuberculoid patients and healthy controls. Reporter gene assays using Jurkat T cells revealed that all haplotypes carrying one or more SNP exhibited a lower transcriptional activity compared with haplotype 1. CONCLUSION: SNPs within the 5' flanking region of IL12RB2 affect the degree of expression of this gene and may be implicated in individual differences in CMI responsiveness to mycobacterial antigens, leading to lepromatous or tuberculoid leprosy.

5' Flanking Region↗

Active surveillance of leprosy contacts in country with low prevalence rate.

For advanced control of leprosy in Pakistan where the World Health Organization leprosy elimination goal was achieved in 1996, we conducted surveillance of Mycobacterium leprae-seropositive patients and their contacts and drug resistant strains of M. leprae. We measured anti-PGL-I antibody level in sera from leprosy patients and their contacts for early detection of M. leprae infection. Out of 34 leprosy patients undergoing treatment, 4 lepromatous leprosy patients were antibody positive, and 6.8 to 23.7 percent of occupational or household contacts were seropositive. Furthermore, three cases (1.2%) had a high antibody titer. For surveillance of drug resistant strains of M. leprae, dapsone and rifampin were targeted. Four out of 18 polymerase chain reaction (PCR) positive samples had mutation in folP gene, and among 10 PCR positive samples, one had a mutation in the rpoB gene. These results indicate that serological analysis of patient contacts might be useful to find out high risk individuals, and there are M. leprae strains resistant to chemotherapeutic agents in Pakistan.

Adult↗

A study on the methods for early serological diagnosis of leprosy and their potential use.

This is a serial study. In this series we have established 12 methods for the early serological diagnosis of leprosy, including the FLA-ABS test, ELISAs with artificial products (ND-O-, ND-P-, NT-O-, NT-P-BSA; PGL-I, whole M. leprae and M. smegmatis), monoclonal antibody specific binding assay (McAb/SBA), latex agglutination test (LAT), and MLPA. These methods were compared with each other on a large scale in leprosy patients and in the field. The results indicate that 1) Excellent results were obtained when ELISAs were conducted with skim milk or egg albumin as the blocking agent and by using blood from earlobes instead of from venipuncture. 2) According to the four "S" standard (sensitivity, specificity, simplicity and speed), among the 12 methods the ND-O-BSA-ELISA (ND-ELISA) is the best and the MLPA is more suitable for use in the field because it is simple and rapid. 3) In the ND-ELISA, the increase or decrease of the OD value has a positive correlation with the BI, and the order of positive rates was a) in various types of leprosy: LL > BL > BB > BT > TT; b) in household contacts (HC), random population (RP), normal controls in endemic areas (ENC) and normal controls in nonendemic areas (NNC): HC > RP > ENC > NNC. 4) In a population with subclinical M. leprae infection, the highest risk group was between the ages of 15 and 25 and had an increase or a persistence of high OD values prior to onset of disease. 5) OD values gradually decreased over time following treatment and these declines paralleled declines in the BI. 6) In cases cured with dapsone therapy, there was an increase or a persistence of high OD values in ND-ELISA prior to the onset of a leprosy relapse. In conclusion, we have compared and evaluated 12 immuno-assays and have shown that the ND-ELISA is the most practical one for use in investigating sero-immunological epidemiology, subclinical infection with M. leprae, early detection of disease, monitoring of antimicrobial therapy, and even for the prediction of leprosy relapse.

Antibodies, Bacterial↗

Leprosy and hepatitis B virus markers: incidence of HBsAg and HBeAg in Somalian patients.

Serum samples from 222 Somalian patients, 135 with the lepromatous form of leprosy and 87 with the tuberculoid form of the disease, were examined for the presence of the surface antigen (HBsAg), the "e" antigen (HBeAg), and their corresponding antibodies (anti-HBs and anti-e). HBsAg was present in 24.4% of the LL cases and in 11.5% of the TT patients while anti-HBs was found respectively in 46.6% and 58.6%. The e-antigen was not found in any case of leprosy; anti-e was detected in 8.1% of the LL patients and in 3.5% of the TT cases. The rate of HBV seropositivity (HBsAg plus anti-HBs) was the same in the LL patients (71.1%) and in the TT patients (70.1%) and that could reflect the conditions of life in their closed community. The analysis of results obtained in Somalia has shown the presence of a difference in the distribution of HBsAg among leprosy patients, with an increased antigenemia in the lepromatous form which was statistically significant (p less than 0.05). No differences, however, were found between the leprosy patients and healthy controls. These observations seem to indicate that patients with lepromatous leprosy do not have an increased susceptibility to infection by hepatitis B virus.

Adolescent↗

Cold fingers in leprosy.

Under conditions of maximal thermoregulatory peripheral dilatation, most healthy subjects (both Indian and European) showed raised blood flow in the fingertips (measured by laser Doppler flowmetry) where the skin temperature is only slightly lower than the core body temperature. Most borderline lepromatous (BL) leprosy patients had much colder fingers and the blood flow was slow: borderline tuberculoid (BT) patients had skin temperatures similar to those seen in healthy subjects, but their fingertip blood flow was reduced relative to that in control subjects. The occurrence of cold fingers and slow blood flow was clearly associated with evidence of sensory impairment to light touch, pressure and temperature. Slower fingertip blood flow was strongly associated with impairment of vasomotor control in this anatomical region, suggesting that both may be a consequence of leprosy peripheral neuropathy, at least in patients with early leprosy, but it is likely that leprosy arteriopathy may contribute to the lowered peripheral perfusion in advanced cases. It is suggested that the simple clinical sign of cold fingers may be of value in the preliminary assessment of patients presenting at any leprosy control clinic in the tropics.

Adult↗

Leprosy in HIV infection: a study of three cases.

The course of leprosy in patients with HIV infection has been a controversial issue for a long time. It is still a matter of debate whether the HIV status of an individual has any impact on the natural history of leprosy and response to anti-leprosy treatment. We report here three HIV-positive leprosy cases (two BT and one BB) along with their CD4 counts and HIV staging with anti-leprosy therapeutic response. Both BT cases responded well to conventional WHO MDT (PB) for 6 months, whereas the BB case relapsed 3 months after completion of MDT (MB) for one year. However, he became inactive again following a further one-year course of MDT (MB).

Adult↗

[Leprosy: identification of an isolated case].

Leprosy is an infrequent disease in Spain. 4,714 cases of leprosy was registered in the last national census (1979). The disease is still common in certain regions, such as Levant, Andalusia, Extremadura, Canary Island and Galicia. Lepromatous type is more frequent, a typical hallmark of endemies with low activity or characterized by regression. We report a patient affected of borderline lepromatous leprosy with the following characteristics: 1) the only known case in his locality, 2) lack of reaction after the treatment, and 3) due to its clinic, histological, and bacteriological characteristics was quite difficult to determine the leprosy's type. Even though the leprosy is an infrequent disease, it can be seen in everyday's practice, so that the internist and specialist. Have to know the disease in order to make an early diagnosis and to treat the patient effectively.

Humans↗

[Leprosy. Pathogenesis--classification--diagnosis--treatment].

Leprosy (hanseniasis) is caused by chronic infection with Mycobacterium leprae (M. leprae). The disease involves primarily the superficial peripheral nerves and the skin, but almost any organ can be affected. The clinical features vary and are determined by the host's immune response to the infection. A distinction is made between multibacillary and paucibacillary forms of leprosy. The multibacillary forms are lepromatous, borderline-lepromatous and borderline-borderline leprosy; the paucibacillary forms are tuberculoid and borderline-tuberculoid leprosy. The clinical features and the histological picture depend on the patient's immune response. Because effective chemotherapy has become available, leprosy can now be cured, and frightening disabilities are therefore preventable.

Diagnosis, Differential↗

Comparison of IgM, IgG and IgA responses to M.leprae specific antigens in leprosy.

Antibodies of IgM, IgG and IgA classes against M.leprae specific antigens (PGL-I, ND-O-BSA, and NT-O-BSA) were determined in the sera of 80 leprosy patients (28 untreated, 34 treated lepromatous and 18 tuberculoid), 25 tuberculosis patients and 33 normal individuals of Northern Thailand. No strong distinction in reactivity could be found between the three antigens. The IgM antibody assay yielded more positive results than assays for IgG and IgA. It was found that the positivity rates of IgM antibodies to all three antigens were highest in untreated lepromatous leprosy (82%). In tuberculoid leprosy, the positivity rates of IgM, IgG and IgA to the antigens were more variable, ranging from 22 to 50 percent. Patients with tuberculosis and normal individuals did not produce IgM antibodies against the antigens. The results suggested that the determination of IgM against the three antigens is a more sensitive and specific test for active leprosy than those of IgG and IgA. The relationship between the duration of treatment and IgM antibody levels in lepromatous leprosy (LL) was studied. Untreated LL patients had significantly higher IgM and IgA antibody levels than treated patients. There was no difference in IgG antibody levels between the two groups, and the levels of both groups were higher than normal controls. Serial determination of IgM antibodies in 7 LL patients revealed that treatment was strongly associated with progressive decrease in IgM antibody levels against all three antigens.

Antigens, Bacterial↗

Lipid composition of the stratum corneum of the sole in patients with leprosy.

Several reports support the view that changes of composition of the stratum corneum (SC) lipids may be the cause of impaired barrier function which, in turn, gives rise to xerosis and ichthyotic skin in leprosy. Many reports about abnormalities of serum lipids and cutaneous manifestations, such as xerosis and ichthyotic changes in leprosy, led us to the idea that the composition of SC lipids in patients with leprosy may be different from that in normal subjects. However, the many studies done in the past do not sufficiently account for this. To investigate the composition of SC lipids in patients with leprosy, thin-layer chromatography (TLC) was undertaken. Extraction of the SC lipids with a methanolchloroform-H2O mixture (4:2:1.6, v/v/v, Bligh-Dyer solvent) was carried out after shaving of the SC from the sole. TLC was performed and the composition of lipids was quantitated by photodensitometry. Our study revealed that the composition of SC lipids in the anesthetic lesions of leprosy patients was higher in cholesterol sulfate and triglycerides and lower in sphingolipids and cholesterol esters than that of normal subjects.

Aged↗

Calcium metabolism and its regulating hormones in patients with leprosy.

Calcium metabolism was studied in 47 patients with borderline or lepromatous leprosy. Total and ionized calcium, phosphorus, creatinine, total alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxy vitamin D [25(OH)D], and 1,25-dihydroxy vitamin D [1,25(OH)2D] were measured in serum; calcium and total hydroxyproline were determined in urine. Total subperiosteal diameter and medullar cavity diameter were measured on an X-ray of the hand of all patients. Average values were within normal ranges for all of the biochemical determinations. Total serum calcium was moderately below the normal range in eight patients but ionized calcium levels were within the normal ranges in all of the patients. Four patients, all of them with lepromatous leprosy, had levels of 1,25(OH)2D higher than normal but none of them was hypercalcemic and PTH levels were within normal range. Although all values were within the normal ranges, lepromatous leprosy patients had lower total calcium, higher alkaline phosphatase, and higher urinary hydroxyproline than borderline leprosy patients (9.1 +/- 0.4 vs 9.4 +/- 0.3 mg%, p < 0.001; 10.3 +/- 2.9 vs 7.4 +/- 2.3 King-Armstrong units, p < 0.02 and 27.2 +/- 12 vs 19.4 +/- 5.6 mg/24 hr, p < 0.02, respectively). No differences were found between patients and controls in the average micrometric measurements of the second metacarpal bone but significant osteopenia was found in 19% of the patients. The main finding of the present study in a representative sample of leprosy patients is that the average total serum calcium was in the lowest limit of the normal range, but the ionized serum calcium was in the middle of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Audiovestibular involvement in leprosy.

100 leprosy patients were studied for audiovestibular involvement. Conductive hearing loss was detected in 6 cases of BT leprosy, all of them having coincidental chronic middle ear infection. Sensori-neural hearing loss was detected in 10 cases, of which 6 had LL, 2 BT and 2 pure neuritic type of disease respectively. All the cases of lepromatous leprosy having sensorineural hearing loss had evidence of ENL reaction. Vestibular involvement was not detected in any of the cases. Evaluation of audiovestibular function was also carried out in 50 fresh cases of leprosy and after 3 months, 6 months and 1 year of multidrug therapy to ascertain any ototoxic side effects of antileprosy drugs. No audiovestibular dysfunction was detected in these patients at any time during follow-up.

Adult↗

[Leprosy in The Netherlands in the period 1970-1991].

OBJECTIVE: To inventory the changes in leprosy epidemiology in the Netherlands. DESIGN: Retrospective. SETTING: Academic Medical Centre (Amsterdam) and University Hospital Dijkzigt (Rotterdam), the Netherlands. METHOD: The medical records of all new leprosy patients in the period 1970-1991 were analysed. RESULTS: Between 1970 and 1991, 622 new leprosy patients were registered; 371 men (59.6%) and 251 women (40.4%). Most patients came from Surinam (73.3%) and Indonesia (7.2%). The mean time lapse between onset and treatment in the Netherlands was 10.1 years. Switching from monotherapy to combination therapy (1979) had no effect on the incidence of reversal reactions (cellular hypersensitivity in immunologically unstable patients), but did affect the incidence of erythema nodosum leprosum during the treatment. CONCLUSION: Leprosy in the Netherlands is an important disease, mainly from Surinam. The main advantage of combination therapy is the shortened duration of treatment. The treatment of choice is the one recommended by the WHO, the combination therapy with rifampicin administration once a month, because of the few adverse effects.

Adult↗

Effect of drug treatment on electroneurological measures of peripheral nerve function in leprosy patients.

OBJECTIVE: To investigate whether drug treatment improves the electroneurological measures of affected peripheral nerve function in leprosy patients. DESIGN: Clinical status of patients determined on the first visit by an investigator administered, pre-designed questionnaire, followed by measurement of motor conduction velocity (MCV) and distal latency (DL) of ulnar, median, common peroneal and posterior tibial nerves bilaterally in patients referred consecutively from the dermatology unit and leprosy clinic, Teaching Hospital, Galle. MCV and DL measurements were repeated after 6 to 12 months of treatment. SETTING: Department of Physiology, Faculty of Medicine, University of Ruhuna, Galle. SUBJECTS: 24 diagnosed leprosy patients; tuberculoid, lepromatous and borderline in clinical type. INTERVENTIONS: Based on clinical typing. Tuberculoid (paucibacillary) type rifampicin 600 mg monthly and dapsone 100 mg daily for six months. Lepromatous and borderline (multibacillary) type rifampicin 600 mg and clofazimine 300 mg monthly and dapsone 100 mg and clofazimine 50 mg daily for 24 months. RESULTS: DL in all 4 nerves and MCV in 3 nerves tested were significantly different (p > 0.001) to those for the normal population and remained so after 6 to 12 months of treatment. The DL in the ulnar nerve showed significant improvement (p < 0.05) after treatment. When analysed in each patient individually, before and after treatment, the MCV showed an improvement in 48 to 72% of patients and the DL in 41 to 59%, but differences were not significant. CONCLUSIONS: Electroneurological recovery (return to normal state) of the affected peripheral nerves of leprosy patients does not occur after 6 to 12 months of drug treatment. The significant (p < 0.05) improvement (becoming better) of ulnar nerve DL indicates that, if at all, electroneurologically detectable improvement of nerve function occurs in the early stages of nerve damage, and that it may take longer than one year after starting treatment.

Adolescent↗

Ultrasonographic findings in the livers of patients with lepromatous leprosy.

Abdominal ultrasonography, including assessment of the liver, spleen, pancreas, great abdominal vessels, and kidneys, was carried out in seven patients with lepromatous leprosy, six patients with tuberculoid leprosy, and 32 healthy Congolese controls. Abnormal ultrasound findings were predominantly detected in the livers of patients with lepromatous leprosy and included an inhomogeneous echo texture of the hepatic parenchyma in all cases. Furthermore, six patients revealed echo-dense, partly irregular areas up to 1.5 cm X 3 cm in size distributed throughout the liver. These were associated with shadowing and were considered to contain calcium. No abnormal findings were encountered in controls or in patients with tuberculoid leprosy except for one patient with tuberculoid leprosy who had a rounded caudal liver edge. The sizes and volumes of liver, spleen, and kidneys were not different in the three groups.

Adolescent↗

Prevalence of antibodies to hepatitis C virus among patients with leprosy in several African countries and the Yemen.

The prevalence of anti-HCV was determined in 1,309 leprosy patients and a control group of 1,469 subjects from 6 sub-Saharan African countries and the Yemen. Sera found positive by an initial second generation ELISA were subjected to 3 additional confirmatory tests. The anti-HCV prevalence in leprosy patients (7.1%) was significantly higher than in the control group (2.6%). HCV seroprevalence increased with age in both the control and leprosy groups. No statistically significant difference could be found between anti-HCV prevalence and the several clinical forms of leprosy among patients. The results of this study indicate a high degree of exposure or chronic carriage of hepatitis C among leprosy patients.

Adult↗