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PubMedDate not supplied

Serum zinc, copper, magnesium, proteins and superoxide dismutase in leprosy patients on multidrug therapy--a follow-up study.

Serum zinc, copper, magnesium, total proteins and albumin-globulin fractions and superoxide dismutase (SOD) were estimated in 80 untreated patients with TT/BT/BL/LL type of leprosy and in 40 controls. The investigations were repeated on day 30, 60 and 120 after starting multidrug therapy (MDT-WHO) on the patients. Serum zinc was significantly lowered in all types of leprosy on days 0 and 30. Serum copper was significantly raised in all types of leprosy. This was not significant in BT/TT cases on 60, 120 days. There was a correlation between serum zinc and copper levels and the severity and type of leprosy. The lowering of serum magnesium values were not significant. With therapy, there was a shift of all the three elements towards normal values. Serum total proteins reduction was not significant. Serum albumin was significantly lowered in all types of leprosy. Serum globulin was significantly raised in all types of leprosy. This rise in TT/BT was not significant on day 60 and 120 after starting treatment. Serum SOD was significantly reduced in all the untreated cases. It gradually increased with the clinical improvement under MDT.

Blood Proteins↗
PubMed1996

Leprosy in Hawaii; the end of an epidemic.

Two different patterns of leprosy have occurred in Hawaii. First is the continuing influx of infected people among immigrants from several leprosy-endemic areas. The number of new cases among their descendents has tended to abate within one generation after arrival in Hawaii. The most recent example of this has occurred in Asians arriving since immigration laws were liberalized in 1965, followed by a rise of imported leprosy, peaking in 1970-1980, then falling. The second pattern was an explosive epidemic among native Hawaiians, rising to its peak in the 1890s, then slowly subsiding, and now approaching zero. It appears that official disease-control efforts (physical isolation and/or early multidrug treatment) cannot fully explain the ending of the epidemic in Hawaii, in spite of the continuing importation of M. leprae. It is suggested that the influence of changing socioeconomic factors (nutrition, crowding, genetics) has been of importance, particularly among the Hawaiians, who have undergone profound foreign influence (both positive and negative) during the 150-year history of this epidemic. The late Dr. Ma Haide was responsible for leprosy control in China, where leprosy is also fading away, but not simultaneously in all subpopulations. He summarized his view by saying, "Leprosy lingers longest among the poorest" (personal communication). This statement appears to hold true for Hawaii, also.

Disease Outbreaks↗
PubMed1996

[Leprosy differential diagnosis in 1996].

Due to a decrease in the prevalence of leprosy, discussion of its differential diagnosis assumes increasing importance. Research on the early diagnosis of leprosy, before the onset of nervous lesions, the appearance (or improved definition) of certain diseases and the expansion of intercontinental migration are some of the factors which have induced changes in the conditions of leprosy diagnosis. The most frequent and most sensitive differential diagnosis of leprosy have been reviewed: hypochromic diseases, tropical infections diseases, systemic diseases, deforming diseases, cutaneous lymphoma and AIDS. The difficulties posed by forms of leprosy revealed by reactional manifestations are stressed. Today, as in previous times, positive and differential diagnosis of leprosy is based on the following simple practices: study of lesion, sensitivity, bacilloscopy and the examination of the peripheral nervous system. Cutaneous histology is the complementary reference examination.

Diagnosis, Differential↗
PubMed1997

Immunotherapy of lepromin-negative borderline leprosy patients with low-dose Convit vaccine as an adjunct to multidrug therapy; a six-year follow-up study in Calcutta.

The present report, which describes management of lepromin-negative borderline leprosy patients with low-dose Convit vaccine, is an extension of our earlier study on the treatment of lepromatous leprosy patients with low-dose Convit vaccine as an adjunct to multidrug therapy (MDT). The test Group I, consisting of 50 lepromin-negative, borderline leprosy patients, were given low-dose Convit vaccine plus MDT. The control group II consisted of 25 lepromin-negative, borderline leprosy patients given BCG vaccination plus MDT and 25 lepromin-negative, borderline leprosy patients given killed Mycobacterium leprae (human) vaccine plus MDT. The control group III consisted of 50 lepromin-positive, borderline leprosy patients not given any immunostimulation but given only MDT. Depending upon the lepromin unresponsiveness, the patients were given one to four inoculations of the various antileprosy vaccines and were followed up every 3 months for 2 years for clinical, bacteriological and immunological outcome. All patients belonging to the test and control groups showed clinical cure and bacteriological negativity within 2 years. However, immunologic potentiation, assessed by lepromin testing and the leukocyte migration inhibition test (LMIT), was better in the test patients receiving low-dose Convit vaccine plus MDT than in the control patients receiving BCG vaccine plus MDT or killed M. leprae vaccine plus MDT or MDT alone. But the capacity of clearance bacteria (CCB) test from the lepromin granuloma showed poor bacterial clearance in the test patients. However, there was no relapse during 6 years of follow up. Two mid-borderline (BB) patients had severe reversal reactions with lagophthalmos and wrist drop during immunotherapy despite being given low-dose Convit vaccine.

Adult↗
PubMed1997

Prevalence of HIV1 in leprosy patients in Rio de Janeiro, Brazil.

The purpose of this study was to learn if HIV1 infection was associated with leprosy in Rio de Janeiro, Brazil by comparing the prevalence rates of 1.016 leprosy patients tested on a voluntary basis and 78.482 blood donors. A cross-sectional survey of anti-HIV1 antibodies was conducted in Rio de Janeiro, from 1990 to 1992 for this purpose. HIV1 prevalence found among leprosy patients was (3 cases) 2.9 per 1000, and among blood donors was (282 cases) 3.8 per 1000. Such difference was not significant (OR = 0.79; p = 0.69). Since HIV1 cases were only found among male leprosy patients, further analysis excluded females. Male leprosy patients showed a slightly higher prevalence of HIV1 than blood donors before and after age adjustment. However, this result was not statistically significant (adjusted odds ratio = 1.38, 95% CI 0.35-4.5; p = 0.83). These data do not provide evidence that leprosy and HIV1 infection are associated in the State of Rio de Janeiro. This is consistent with similar investigations conducted elsewhere.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Profile of leprosy in children: past and present.

The profile of leprosy in children currently seen in a referral hospital is compared with that of children with leprosy admitted in the 1970s. Children with leprosy under the age of 15 years in 1974 and 1979 comprised one group (Group I) while those during 1989 and 1994 constituted the second group (Group II) The variables studied included age, sex, type of leprosy, deformity and contact status. Multidrug therapy (MDT) was introduced in the treatment of leprosy in 1982. The probable change it has made in the presentation of leprosy in children is discussed.

Adolescent↗
PubMed1998

Effectiveness of bacillus Calmette-Guerin (BCG) vaccination in the prevention of leprosy; a case-finding control study in Nagpur, India.

A hospital-based, pair-matched, casecontrol study was carried out at Government Medical College Hospital in Nagpur in central India to estimate the effectiveness of BCG vaccination in the prevention of leprosy. The study included 314 incidence cases of leprosy [diagnosed by World Health Organization (WHO) criteria] below the age of 32 years. Each case was pair matched with one control for age, sex and socioeconomic status. Controls were selected from subjects attending this hospital for conditions other than tuberculosis and leprosy. A significant protective association between BCG and leprosy was observed (OR 0.29, 95% CI 0.21-0.41). The vaccine effectiveness (VE) was estimated to be 71% (95% CI 59-79). The BCG effectiveness against multibacillary and paucibacillary leprosy was 79% (95% CI 60-89) and 67% (95% CI 45-78), respectively. It was more effective during the first decade of life (VE 74%; 95% CI 38-90), among females (VE 82%; 95% CI 64-90), and in the lower socioeconomic strata (VE 75%; 95% CI 32-92). The prevented fraction was calculated to be 51% (95% CI 38-62). In conclusion, this study has identified a beneficial role of BCG vaccination in the prevention of leprosy in central India.

Adolescent↗
PubMed1998

Assessment of anti-PGL-I as a prognostic marker of leprosy reaction.

The anti-phenolic glycolipid-I (PGL-I) assay as currently applied for leprosy is conceived as an early marker of asymptomatic infection, early disease diagnosis and cure monitoring. Its use as a prognostic marker of reaction is still a matter of controversy. We conducted a case-control study to investigate whether IgM and IgG anti-PGL-I antibodies could discriminate patients at increased risk of developing reactions. Eligible cases were untreated leprosy patients at the onset of type 1 and type 2 reactions recruited from among 600 concurrent, newly detected, untreated leprosy patients attending an outpatient clinic in central Brazil. For the patients with reaction, approximately the same number of leprosy cases without reaction matched as to bacterial index (BI), age and gender were randomly selected. Individuals without clinical leprosy were evaluated as healthy controls. Sera from type 1 reaction (N = 43) and type 2 reaction (N = 26) patients were tested by an ELISA using PGL-I synthetic disaccharide-BSA antigen and 1:300 sera dilution (cut-off point > or = 0.2 OD). Antibody profiles were evaluated by exploratory data analysis and reverse cumulative distribution curves. The IgG anti-PGL-I response did not have a defined pattern, being detected only at low levels. Our results indicate that leprosy patients, independently of their reactional status, produce high levels of IgM anti-PGL-I, demonstrating a strong correlation between the magnitude of antibody response and the BI. Patients with a higher BI were at least 3.4 times more prone to produce an antibody response compared to healthy controls.

Adult↗
PubMed1999

Association of vitamin D receptor genotype with leprosy type.

Host genetic factors including major histocompatibility complex (MHC) polymorphisms influence both susceptibility to leprosy per se and also to leprosy type. Non-MHC genes may play an important role, but such genes remain undefined. The influence of two non-MHC candidate genes was assessed in a case-control study of Bengali leprosy patients from Calcutta. Recent studies have implicated variation in the vitamin D receptor (VDR) gene in susceptibility to several diseases, including osteoporosis and pulmonary tuberculosis. In this population, homozygotes for the alternate alleles of the VDR polymorphism are associated, respectively, with lepromatous and tuberculoid leprosy. The NRAMP1 (natural resistance associated macrophage protein 1) gene may influence human mycobacterial disease susceptibility based on studies with the murine homologue Nramp1. However, no significant association was found between NRAMP1 and leprosy susceptibility. This study suggests that the VDR polymorphism may influence susceptibility to some diseases by affecting the type and the strength of the host immune response.

Alleles↗
PubMed2004

High expression of myeloid-related proteins 8 and 14 characterizes an inflammatorily active but ineffective response of macrophages during leprosy.

Macrophages are decisive cells for the course of leprosy as they phagocytose Mycobacterium leprae and have the potential to influence the specific immune response. Expression and release of the myeloid-related protein (MRP) 8 and MRP14 (S100A8 and S100A9) characterize a proinflammatory subtype of macrophage that is prominent in, for example, murine infection with lack of a T helper 1 cell response and in certain highly active chronic inflammations of mice and humans. We investigated cutaneous biopsies of the different forms of leprosy (41 untreated patients) including leprosy reaction type 1 (reversal reaction) and type 2 (erythema nodosum leprosum) (n = 18) for expression of MRP8 and MRP14 by subtypes of macrophages. Concomitantly we determined serum levels of MRP8 and MRP14 by sandwich enzyme-linked immunosorbent assay. Expression of MRP8 and MRP14 by CD68-positive macrophages was low in tuberculoid leprosy and rose significantly in borderline tuberculoid leprosy and especially in multibacillary forms, there being expressed by mycobacteria-loaded foam cells. A significant rise of MRP8 and MRP14 expression also occurred in lepra reactions compared to the corresponding non-reactional forms. In type 2 reactions this additional increase was associated with a significant elevation of serum levels. In type 1 it was associated with expression of MRP8 and MRP14 by epitheloid and giant cells, which so far were considered not to express both proteins. In conclusion, we present evidence that the two prominent proteins MRP8 and MRP14 can be re-expressed in vivo by tissue macrophages in chronic infection, that their increased expression is characteristic for a macrophage subtype associated with high inflammatory but low antimycobacterial activity in the absence of a T helper 1 response, and that their significant rise in serum during erythema nodosum leprosum bears diagnostic and pathophysiological relevance.

Adolescent↗
PubMed2004

Clinico-pathological study of 12 cases of patients with leprosy admitted to Sina Hospital, Hamadan, Iran, from 1991 to 2000.

BACKGROUND: Leprosy is considered a chronic disabling condition. Many clinical and immunological aspects of the disease remain ill defined. AIM: The study of clinico-pathological and laboratory findings of patients with leprosy admitted to Sina Hospital, Hamadan, Iran, from 1991 to 2000. METHODS AND PATIENTS: This is a descriptive retrospective cross-sectional study. The statistical community comprised all patients diagnosed leprosy. This diagnosis was clinical and confirmed through pathology (skin-biopsy) and laboratory (peripheral smear) measures. RESULTS: In this study, the disease was more common in males than females with a mean age of 48.5 +/- 16.2 years. Most of the patients were more than 40 years old. Among 12 patients in this study, six cases were urban and six cases were rural. Six cases were living in Hamadan province and two cases migrated to Hamadan province (one of them from Afghanistan and the other from Kurdestan). Clinical diagnosis was confirmed by pathology in 11 cases, but in one case the clinical diagnosis did not match the pathology. In four cases the clinical diagnosis did not match the peripheral smear. Eight cases were admitted just once. Four cases had a history of recurrence and readmission (two patients had one time recurrence and the other two patients had two recurrences). There was no difference in the clinical findings between first presentation and recurrence. From the point of complication and disability, extremity disability was more common than eye disability. Increased severity of complications was found in patients with a delayed diagnosis and incomplete treatment. CONCLUSION: This study showed that a rapid and correct diagnosis and complete treatment was necessary for prevention of complication and disability in patients with leprosy. Also the accuracy of pathology (skin biopsy) in the diagnosis exceeded the peripheral smear. Skin biopsy is recommended to confirm the diagnosis in all cases of leprosy. In the absence of pathology, patients must be considered as multibacillary patients and treated as such.

Adolescent↗
PubMed2006

Use of protein microarrays to define the humoral immune response in leprosy patients and identification of disease-state-specific antigenic profiles.

Although the global prevalence of leprosy has decreased over the last few decades due to an effective multidrug regimen, large numbers of new cases are still being reported, raising questions as to the ability to identify patients likely to spread disease and the effects of chemotherapy on the overall incidence of leprosy. This can partially be attributed to the lack of diagnostic markers for different clinical states of the disease and the consequent implementation of differential, optimal drug therapeutic strategies. Accordingly, comparative bioinformatics and Mycobacterium leprae protein microarrays were applied to investigate whether leprosy patients with different clinical forms of the disease can be categorized based on differential humoral immune response patterns. Evaluation of sera from 20 clinically diagnosed leprosy patients using native protein and recombinant protein microarrays revealed unique disease-specific, humoral reactivity patterns. Statistical analysis of the serological patterns yielded distinct groups that correlated with phenolic glycolipid I reactivity and clinical diagnosis, thus demonstrating that leprosy patients, including those diagnosed with the paucibacillary, tuberculoid form of disease, can be classified based on humoral reactivity to a subset of M. leprae protein antigens produced in recombinant form.

Antibodies, Bacterial↗
PubMed2000

High dose prednisolone treatment of leprosy patients undergoing reactions is associated with a rapid decrease in urinary nitric oxide metabolites and clinical improvement.

Evidence is accumulating that nitric oxide (NO) produced by macrophages has a role in the pathogenesis of reactions in leprosy. We followed the urinary levels of the metabolites of NO [nitrite (NO2-) and nitrate (NO3-)] and the clinical response to prednisolone treatment in leprosy patients (n = 9) admitted to ALERT leprosy hospital Addis Ababa, Ethiopia, because of reversal reaction (RR) or erythema nodosum leprosum (ENL). In untreated reactional leprosy patients, the levels of urinary NO metabolites (1645 +/- 454 microM, n = 9, ENL = 4, RR = 5) decreased significantly 2 weeks after high dose prednisolone treatment (1075 +/- 414 microM, P < 0.05), and remained stable 4 (895 +/- 385 microM, P < 0.02) and 6 weeks following treatment initiation (1048 +/- 452 microM, P < 0.02). This decrease was also present when the reactional patients were subdivided according to the type of reaction (ENL, RR) and coincided with a clinical improvement. In patients showing a poor clinical response to steroids, no or minor effects on the urinary NO metabolite levels were observed. We conclude that there is a correlation between the decrease in urinary NO metabolites and a favourable clinical response after high dose prednisolone treatment of reactional leprosy patients.

Adolescent↗
PubMed1989

Hepatic morphology in reactional states of leprosy.

Liver function tests and liver biopsies were studied in 23 leprosy patients in reaction and 10 without reaction. The liver biopsies in leprosy patients with reaction showed exudative lesions, epithelioid and tuberculoid granulomas, and foam-cell granulomas. Portal vasculitis was encountered in a few cases. Neutrophilic infiltration into the foam-cell granulomas was seen in a few cases of lepromatous (LL) leprosy with reaction. In six cases of borderline (BL, BB and BT) leprosy with reaction, a spectrum of lesions bearing footprints of exudative lesions were seen evolving into epithelioid-cell granulomas. Foam-cell granulomas and tuberculoid and epithelioid granulomas along with exudative lesions were encountered in two cases on individual biopsy strips. An altered albumin-to-globulin ratio was the chief functional derangement observed in these cases. The spectrum of changes observed in borderline leprosy with reaction could be discrete steps in the evolution of upgrading reaction.

Adolescent↗
PubMedDate not supplied

Semen biochemistry of leprosy patients.

Studies have been made on the semen of three categories (borderline, borderline tuberculoid and lepromatous) of leprosy patients to evaluate the seminal biochemical constituents viz. fructose, glycerylphosphorylcholine and acid phosphatase besides the physical properties viz. volume, pH, liquefaction time, sperm density and sperm motility. In all categories of leprosy patients, seminal pH, liquefaction time and sperm density underwent significant decline. The decline in the seminal volume and sperm motility was significant only in borderline leprosy. It was observed that seminal glycerylphosphorylcholine (GPC) concentration and acid phosphatase activity declined in all categories of leprosy patients but GPC showed a significant decline only in borderline tuberculoid and acid phosphatase declined significantly only in borderline and lepromatous leprosy.

Acid Phosphatase↗
PubMed1993

IL-6 production in response to purified mycobacterial heat-shock proteins and to antigen 85 in leprosy.

IL-6 production was examined in PBMC cultures from healthy leprosy contacts and from leprosy patients stimulated with the purified mycobacterial 18-, 65-, and 70-kDa heat-shock proteins (hsp) and the secreted fibronectin-binding antigen 85 (Ag85). In lepromin-negative contacts, the 70-kDa hsp was the only antigen capable of eliciting significant IL-6 production. In lepromin-positive contacts, Ag85, the 65- and the 70-kDa hsp induced substantial IL-6 titers. IL-6 levels induced with the 70-kDa antigen were about fourfold higher than with the 65-kDa hsp or with Ag85. The 18-kDa antigen did not induce any IL-6 in these healthy contacts. PBMC from tuberculoid leprosy patients produced even more elevated levels of IL-6, and PBMC from lepromatous leprosy patients produced extremely high levels of IL-6. All antigens were capable of inducing IL-6 in leprosy patients. Highest levels were found in cultures stimulated with the 65-kDa hsp, and lowest levels were in cultures stimulated with the 18-kDa hsp.

Antigens, Bacterial↗
PubMed2001

Expression of inducible nitric oxide synthase and nitrotyrosine in borderline leprosy lesions.

BACKGROUND: In the response to T-helper cell (Th1)-type cytokines and interactions with pathogens, high levels of nitric oxide (NO) are produced by activated macrophages expressing the inducible NO synthase (iNOS). The role and importance of reactive nitrogen intermediates (RNIs) such as NO and peroxynitrite in the host response to diseases caused by intracellular pathogens such as Mycobacterium leprae and M. tuberculosis is unclear. OBJECTIVES: The aim of this study was to investigate the presence of local production of NO and peroxynitrite in borderline leprosy by using antibodies against iNOS and the product of peroxynitrite, nitrotyrosine (NT). METHODS: We detected the presence of iNOS and NT in skin biopsies from borderline leprosy patients, with and without reversal reaction (RR), by immunohistochemistry (n = 26). RESULTS: In general, the granulomas from borderline leprosy lesions with and without RR showed high and specific expression of iNOS and NT. Moreover, strong immunoreactivity to iNOS and NT was observed in granulomas surrounding and infiltrating dermal nerves. The expression of iNOS and NT was also strong in keratinocytes, fibroblasts and endothelial cells in close relation to the granulomatous reaction. In contrast, normal human skin showed no expression of iNOS and NT in these cells. CONCLUSIONS: We conclude that iNOS and NT are expressed in granulomas from borderline leprosy patients with and without RR and propose that RNIs might be involved in the nerve damage following RR in leprosy.

Biopsy↗
PubMed1992

Detection of antibodies to human nerve antigens in sera from leprosy patients by ELISA.

Anti-neural antibodies have been implicated to play a role in the pathogenesis of nerve damage in leprosy patients. To find the relationship between anti-neural antibodies and clinical findings, we attempted to detect antibodies against neurofilament-enriched proteins by ELISA in sera from leprosy patients. Of 289 sera from leprosy patients, 74 (25.6%) had significant anti-neural antibodies; in contrast, 1 (5.0%) of 20 tuberculosis patients and 11 (7.1%) of 154 controls were seroreactive to nerve antigen. When clinical types were considered, a significant level of anti-neural IgG antibodies was detectable in 53 (30.1%) of 176 sera from lepromatous patients compared with 21 (18.6%) of 113 sera from tuberculoid patients, indicating that lepromatous patients were more likely to be seropositive to nerve antigens in ELISA. Some of the ELISA-reactive sera showed antibody reactivity with 38-kD, 40-kD and 43-kD nerve antigens in Western blotting analysis. There was no apparent correlation between seroreactivity to nerve antigens and bacterial load in leprosy patients. Although there was no statistical significance, anti-neural antibodies were detectable more often among the patients on chemotherapy than the untreated and among the patients with erythema nodosum leprosum than without. The results, therefore, suggest that anti-neural antibodies are elicited during the course of leprosy and may be associated with the extensiveness of nerve involvement in the patients.

Animals↗