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Reactivity of a lecithin-free cardiolipin preparation (cardchol) in leprosy sera.

Previous experiments have shown that a mixture of cardiolipin and cholesterol in absolute ethanol (named "cardchol") might be used as an antigen in complement-fixation tests. The reactivity in the complement-fixation test of CWRM (an "ordinary" cardiolipin antigen) was compared with that of cardchol in several experiments, and it could be demonstrated that the reactivity of cardchol was especially pronounced in sera from false-positive reactors. In about 50% of such cases, quantitative determination of the antibody content showed that cardchol was more reactive than CWRM, whereas in syphilitic cases the reactivity of cardchol was inferior to that of CWRM. An exception was primary syphilis, which showed a reactivity level with cardchol equal to or even superior to that of CWRM.Examinations of a certain number of sera from leprosy patients had shown them to be highly reactive with cardchol and non-reactive or weakly reactive with CWRM; this observation is fully confirmed by examination of a larger number of leprosy sera, on which this paper reports. These sera were examined with a battery of tests using lipoidal antigens and with the TPI test. Testing with cardchol proved to give the highest reactivity with these sera, which were mostly non-treponemal.Subdivision of the material according to the clinical stage of leprosy showed that the highest reactivity of cardchol occurred in patients with lepromatous leprosy, particularly in those with leprosy of relatively short duration.Electrophoretic fractionation of these sera demonstrated that the substances reacting with cardchol were situated in the gamma-globulin or gamma- and beta-globulin serum fractions.

Antibodies↗

Protective effect of intradermal BCG against leprosy; a case-control study in central Brazil.

A case-control study was undertaken to evaluate the protective efficacy of intradermal BCG against leprosy in a high-endemic area of leprosy in central Brazil. Sixty-two cases and 186 controls were included in the study. Cases were all newly diagnosed leprosy patients under 16 years of age attending an outpatient health service, and all of them were schoolchildren. Three controls under 16 years old, frequency matched by sex and age group, were selected from schools geographically located in the area from which the cases came. The presence of BCG was negatively associated with leprosy, indicating a 5.3 risk of leprosy for those nonvaccinated and protective efficacy of 81%. Paucibacillary patients were more likely to have a BCG scar than multibacillary patients.

Adolescent↗

Chemoprophylaxis of leprosy with a single dose of 25 mg per kg rifampin in the southern Marquesas; results after four years.

In January-February 1988, a program of chemoprophylaxis for leprosy, using a single 25 mg/kg dose of rifampin, was conducted among 2786 (98.7%) inhabitants of the Southern Marquesas and 3144 South Marquesan "emigrants" and their families. Among the treated population, during the 4 years which followed the implementation of the program, two leprosy patients were detected, one of whom can be considered as a failure of chemoprophylaxis because she was not known by the leprosy control unit. During the same period (1988-1991), a decrease in detection rates for leprosy in the entire French Polynesian population has been observed, an event which makes the interpretation of these findings very difficult. Nevertheless, according to presently available data, the effectiveness of chemoprophylaxis with a single dose of 25 mg/kg rifampin is estimated to be about 40% to 50%. When considering not only the results of the present study but also the financial and logistic constraints raised by such a program, one is led to the conclusion that chemoprophylaxis, even with a single dose of rifampin, is not likely to become an effective component of leprosy control programs.

Adolescent↗

Nine-banded armadillo and leprosy research.

In this presentation an attempt has been made to describe the nine-banded armadillo as an animal model, probably the only one in which lepromatous leprosy similar to that found in humans can be experimentally produced. Some unique features of the physiology of the animal are mentioned. The pathology and the microbiology of leprosy in the armadillo are described in detail. The discovery of lepromatous leprosy in the wild armadillos in the southern parts of United States, the transmission of disease among them through trauma and thorn pricks and the pathogenesis of the disease are presented. The impact of leprosy in the wild animals may have on human leprosy is discussed.

Animals↗

Depressive status of leprosy patients in Bangladesh: association with self-perception of stigma.

Stigmatization by the general population and their negative attitudes towards leprosy negatively impacts on patients' mental health, and so too does patients' perception of that stigma. The objective of this present study is to assess the depressive status of leprosy patients, the patient perception of that stigma, and its association with their depressive status in Dhaka, Bangladesh. Subjects were 140 patients, and a selected comparison group of 135 local people without any chronic diseases. To evaluate depressive status, the Center for Epidemiologic Studies Depression scale (CES-D) Bengali version was applied. The patient group's depressive status was significantly more severe than that of the comparison group. Depressive status of those who answered affirmatively was significantly more severe than that of those who answered negatively for three responses to questions: 1) 'I have been physically attacked by people', 2) 'I feel people regard me as strange' and 3) 'I have been refused the purchase of something by a shopkeeper'. The results showed that the depressive status in leprosy patients was greater than that of the general public. Further, actual experiences of discrimination based on stigma associated with the depressive status of leprosy patients. Mental health care for patients, regulation of discriminatory action and education that would decrease social stigma among the general population, especially people who might often have contact with patients, seem necessary to improve the mental health of Bangladeshi leprosy patients.

Adolescent↗

Relationships between titers of antibodies immunoreacting against glycolipid antigens from Mycobacterium leprae and M. tuberculosis, the Mitsuda and Mantoux reactions, and bacteriological loads: implications in the pathogenesis, epidemiology and serodiagnosis of leprosy and tuberculosis.

Analysis of cell-mediated immunity [(CMI) as judged from the Mantoux, Fernandez, and Mitsuda reactions and the presence of granulomas in biopsy material] against humoral immunity (measurements of anti-PGL-I, PGL-Tb1, and SL-IV IgG and IgM antibody titers by ELISA) were performed in selected human populations. The investigations yielded data indicating that humoral (B-cell) responses preceded protective CMI in both tuberculosis and leprosy. The B-cell responses were unrelated to (unfavorable) cell-mediated delayed-type hypersensitivity (DTH). Notwithstanding the difficulty in inferring sequential events from studies in humans, it was shown that in humoral responses there was an initial rise of specific IgM immunoglobulins that switched afterward to IgG production during subclinical tuberculosis and leprosy infections. In patent tuberculosis disease the IgM-to-IgG switch was observed in the majority of patients; in patent leprosy disease the switch was impaired in the majority of patients. The clinical, immunological, and laboratory data indicated that the B-cell responses were suppressed as protective CMI was re-established in the patients during the protracted subclinical infection. According to the data, the diagnosis of subclinical tuberculosis and leprosy may be accomplished using ELISA. The yearly risk of tuberculosis in apparently healthy persons but with significant antibody titers was estimated at 44%; the yearly risk for leprosy has not yet been established. The clinical, epidemiologic, and diagnostic implications of these findings are discussed.

Antibodies, Bacterial↗

Oxidative stress and anti-oxidant status in leprosy patients.

Severe oxidative stress has been reported in leprosy patients because of malnutrition and poor immunity. The purpose of this study was to investigate the serum lipid peroxidation products, serum LDH and important free radical scavenging enzymes, i.e. superoxide dismutase (SOD), and catalase and anti-oxidant glutathione levels and total anti-oxidant status, in different types of leprosy patients. The subjects for this study were normal human volunteers (NHVs, n=14), paucibacillary leprosy patients (PB, n=18), untreated MB patients (MB1, n=18), MB patients under treatment (MB2, n=19), and MB patients released from treatment (RFT) (MB3, n=28). The levels of lipid peroxidation product, malondialdehyde (MDA), and LDH increased significantly (p<0.001) in MB (MB1, MB2, MB3) patients, and both gradually decreased with clinical improvement following MDT. The levels of SOD, catalase and glutathione, and the total anti-oxidant status decreased significantly in MB (MB1, MB2, MB3) patients (p<0.001), in comparison with NHVs. They gradually increased with clinical improvement with MDT. There was no significant variation of these parameters in PB leprosy patients in comparison with healthy volunteers. High free radical activity and low anti-oxidant levels observed in MB (MB1, MB2, MB3) leprosy patients indicate that there is an oxidative stress in MB cases, irrespective of the treatment status and suggest a suitable anti-oxidant therapy to prevent possible tissue injury.

Antioxidants↗

Childhood leprosy in eastern Nepal: a hospital-based study.

A hospital-based retrospective study on childhood leprosy was carried out at B.R. Koirala Institute of Health Sciences, Dharan, covering the period April 1998-April 2002. 20 (4.45%) leprosy patients were detected in children aged 6-14 years. The male:female ratio was 4:1. History of contact was found in 10% of the patients. The commonest type of leprosy was borderline tuberculoid leprosy (550%), followed by borderline lepromatous leprosy (301%). Most of the patients had more than one lesion. Nerve involvement and grade 2 deformity were noted in 55% and 20% of the patients respectively. Slit skin smear was positive in 30% of patients.

Adolescent↗

[Relapses after multibacillary leprosy treatment].

Leprosy relapses are mainly due to bacillary persistence and diamino-diphenyl-sulphone (DDS) monotherapy. Case histories were examined for 33 patients with lepromatous leprosy (LL), diagnosed 7-48 years before the relapse and treated only with DDS during 4 to 38 years. Twenty-eight patients received irregular non-supervised polychemotherapy (PCT) since 1983. Five patients received only DDS, and presented relapses 13-20 years after the treatment was stopped. Relapses were diagnosed by clinical methods, including the reappearance of lesions or presence of new anesthetic areas. All cases were confirmed by bacilloscopy, and a subset of 20 cases by skin biopsy. Four patients presented indeterminate leprosy (IL) and one patient borderline tuberculoid leprosy (BT) in the biopsy. The latter 5 demonstrated presence of intraneural bacilli; the remainder were LL. Two patients relapsed even with PCT treatment. The others were cured with supervised PCT. Predisposing factors for relapses were as follows: DDS monotherapy, irregular PCT with inadequate dosage, unsupervised treatment, treatment uncompliance, and inadequate relationship between the patient and the health staff. Inspections for relapse in leprosy is recommended for in all multibacillary patients that were treated with DDS. The clinical appearance of new lesions or new anesthetic zones, the bacilloscopy and skin biopsy, used together, are effective in establishing the presence of relapses.

Adult↗

Monitoring the size of the leprosy problem: which epidemiological indicators should we use?

The purpose of the study was to discuss the interpretation of epidemiological trends in leprosy, using currently available indicators. A number of leprosy-endemic countries and regions were chosen for which epidemiological data have been published for a period of at least 15 years. Using these examples, relative merit of the registered prevalence rate, the case detection rate, the children proportion among new cases and proportion of new cases with grade 2 disability will examined for interpreting the leprosy situation in these countries. Considerable drop of the registered prevalence rates (PR) were evident in all endemic countries. However, this decline was due largely to shortening of treatment and 'cleaning' of leprosy registers and has not been reflected in the annual case detection rates (CDR), except in a few countries. The proportion of new cases with grade 2 impairment had decreased substantially, which indicates earlier case finding. However, the proportion of children among new cases did not change much in the past decade. It is indicate that transmission is still continuing. We reiterate the conclusion of the ILA Technical Forum that the (annual) case detection rate is the most appropriate indicator for monitoring of leprosy situation in a given country or area. Two additional indicators that helped to interpret the CDR were the proportion of new cases with grade 2 impairments, reflecting the delay between occurrence and diagnosis of the disease, and the proportion of children among new cases, which is used as a proxy indicator for recent transmission.

Ethiopia↗

Prevention of leprosy using rifampicin as chemoprophylaxis.

An intervention study was implemented on five Indonesian islands highly endemic for leprosy to determine whether rifampicin can be used as chemoprophylaxis to prevent leprosy. The population was actively screened before the intervention and subsequently once a year for three years. In the control group, no chemoprophylaxis was given. In the contact group, chemoprophylaxis was only given to contacts of leprosy patients and in the blanket group to all eligible persons. The cohort consisted of 3,965 persons. The yearly incidence rate in the control group was 39/10,000; the cumulative incidence after three years was significantly lower in the blanket group (P = 0.031). No difference was found between the contact and the control groups (P = 0.93). Whether this apparent reduced leprosy incidence in the first three years in the blanket group is due to a delayed development of leprosy or a complete clearance of infection needs to be determined.

Case-Control Studies↗

Clinical manifestations, diagnosis and classification of leprosy.

Mycobacterium leprae, the causative organism of leprosy is slow-growing and the reason is its long incubation period of 2-4 years. Males are predominantly affected and deformity is produced in less than 2% of people affected with the disease. The disease manifests in the skin as macules, papules, nodules, plaques or infiltration. Hypopigmented or erythematous skin patches with definite sensory deficit is one of the clinical cardinal signs by which one can make a definite diagnosis. Demonstration of bacilli in the slit skin smear is the bacteriological cardinal sign used to make definite diagnosis of leprosy. Involvement of common cutaneous nerves with thickening and/or tenderness with its dysfunction is the second clinical cardinal sign used to diagnose leprosy. Diagnosis can be made by eliciting definite sensory deficit in the skin lesions (other than nodules and infiltration). In the absence of two clinical cardinal signs and when there is a strong suspicion of leprosy, slit skin smear should be taken from both ear lobes and one of the lesions for demonstration of acid-test bacilli. Clinical classification is based on characteristics like number of lesions, their margin, sensory deficit, satellite lesions, symmetry of lesions, central healing and scaling. Up to 5 lesions are grouped under paucibacillary and six and more are grouped under multibacillary leprosy.

Counseling↗

[2 infectious granulomatous diseases (leprosy and cutaneous and mucous leishmaniasis) by scintigraphic methods].

Leprosy is a multiform chronic infectious granulomatous disease caused by Mycobacterium leprae, that affects over 12 million people in the world. Cutaneous and mucous leishmaniasis (CML) is also a chronic granulomatous infectious disease, caused by Leishmania brasiliensis and transmitted to man by the mosquitoes of the Phlebotominae family. It is a worldwide spread disease. We studied one case of Borderline-wirchowian leprosy and 2 cases of CML with Gallium-67 (GA-67) scintigraphy. Ga-67 is a radiopharmaceutical known for its property of concentrating in inflammatory sites. In the leprosy patient, Ga-67 accumulated in the skin in a moderate, homogeneous and disseminated way (outlined skin); in the area of the face, the uptake was important and homogeneous (image in beard). Several internal organs accumulated Ga-67. As for the 2 CML patients, Ga-67 accumulated focally, in different degrees, in the affected anatomical areas. The leprosy patient was not under treatment and the 2 CML were under treatment (20 and 40 days, respectively). In the 3 cases, all affected areas accumulated Ga-67. Intensity differences of uptake may be explained both by different degrees of inflammatory processes (between leprosy and CML) and by treatment lasting. It is possible that Ga-67 scintigraphy may be useful for the evaluation of these 2 diseases extent and also for the therapy follow-up.

Adult↗

Epidemiological shift in leprosy in a rural district of central India following introduction of multi-drug therapy (April 1986 to March 1992 and April 1992 to March 2002).

This study compares the epidemiological pattern of leprosy in pre- (April 1986 to March 1992) and post- (April 1992 to March 2002) multi-drug therapy (MDT) periods by retrospective analysis of 3274 registered leprosy cases in the rural field area of Regional Leprosy Training & Research Institute (RLTRI), situated in Raipur district of Chattisgarh province of Central India. The area has high endemicity for leprosy. In the post-MDT period, prevalence rate (PR) came down to less than 1 in 10, while New Case Detection Rate (NCDR) remained almost static during the two periods. Of the total new registered cases, 30.1% were registered during the pre-MDT period and the remaining 69.9% during the post-MDT period. Comparison of key leprosy variables among new registered cases showed a 2-fold rise in the proportion of MB cases (14.8 versus 27.6%), 3.0% increase in proportion of child cases (15.3 versus 18.6%) and cases with deformity grade II (3.1 versus 5.9%) and 4.0% increase in female proportion (41.4 versus 45.7%) during the post-MDT period. A decline was noted in mean age of registration for both MB (6.4 years) and PB (5.7 years) groups in the post-MDT period. While comparing treatment and outcome related variables, a marked fall of 25.8 months was recorded in treatment duration in the post-MDT period. The defaulter rate came down by 45.0% and relapse rate by more than 12.0% during the same period. The study shows that MDT is effective operationally, but continued ongoing transmission of infection and delayed diagnosis needs corrective action.

Adolescent↗

A study on trend of relapse in leprosy and factors influencing relapse.

A retrospective analysis of data pertaining to the rural field operation area of the Central Leprosy Teaching and Research Institute, Chengalpattu, Tamil Nadu, was carried out to determine the magnitude of relapse after MDT and its significance with other variables. The study included 3248 leprosy patients who have successfully completed treatment during 1987-2003, of whom 2892 were PB and 356 MB cases. A total of 58 cases of relapse was reported which gives a crude cumulative relapse rate of 1.78% for the 16-year period of follow-up and the rates for PB and MB were 1.9% and 0.84% respectively. With respect to PB cases, 68% of relapses were reported in the first 3 years of RFT. The person-year relapse rate was highly significant with regard to the number of skin lesions (p<0.0002) and nerve involvement (p<0.0002). The person-year relapse rate did not differ significantly between PB and MB leprosy, male and female, and child and adult cases. RFT year cohort relapse rate reveals that the introduction of MB-MDT regimen for PB leprosy had resulted in the reduction of relapses among PB cases after 1998. The relapse rate with reference to the time gap after RFT reveals that relapse declines with passage of time after RFT. The risk of relapse was very low in both PB and MB leprosy which fact emphasizes that proper counselling about signs and symptoms of relapse during RFT is adequate to combat the problem. A majority of relapses occurred in the first three years after RFT. The number of skin lesions and involvement of nerves were the main risk factors for relapse.

Adult↗

Genetic markers and leprosy in South African negroes: Part II. Erythrocyte enzyme polymorphisms.

The phenotype frequencies of the erythrocyte enzyme polymorphisms acid phosphatase (aP), phosphoglucomutase loci 1 and 2 (PGM1 and PGM2), adenylate kinase (AK), adenosine desaminase (ADA), esterase D (EsD) and 6-phosphogluconate dehydrogenase (6-PGD) were determined on a sample of 234-248 South African Negroes with leprosy. These results were compared with data of 841--997 healthy Negro controls of similar geographical and ethnic origin, in order to determine whether or not any association exists between specific phenotypes and the manifestation of leprosy. A part of the data included in the present study were compared with the data of a similar comparative analysis on Mozambican Negroes. With regard to the polymorphisms aP, PGM1 and PGM2, the results derived from South Africa and Mozambique exhibit reverse patterns of deviations from the null hypothesis. From this it does not appear justified to postulate an association between these genetic markers and the occurrence of leprosy. For the enzyme polymorphisms ADA, AK and EsD (data are confined to South African Negroes only) the distribution of phenotypes between patients and controls was very similar. The differences were not statistically significant. However, observations on the 6-PGD polymorphism (data are confined to South African Negroes only) showed an excess of phenotype PGD A among leprosy patients as compared with controls. The difference was statistically highly significant. Further studies based on additional samples are required to substantiate whether or not the statistical outcome reflects a true association between this phenotype and leprosy.

Acid Phosphatase↗

Integration of leprosy control into general health care system: observations from a state with low endemicity.

The study was undertaken as part of operational research to assess the level of integration of leprosy services into general health care system in 24 low or moderately endemic states/union territories by the Ministry of Health and Family Welfare, Government of India. Himachal Pradesh was one of the nine randomly selected states for the study. Out of the 12 districts in the State, 2 were selected randomly for the study. In each of the selected districts, 8 health facilities (that included a district hospital, an urban hospital/urban health centre, an Employees' State Insurance Hospital, a community health centre and a primary health centre) and 9 sub-centres were surveyed. Selection was done randomly at each stage. Data were collected on training in leprosy of general health care staff, availability of drugs for MDT in the system and maintenance of leprosy records by the staff of the system. The study showed mixed results. About half (53.2%) of the existing medical officers, 83.9% of health supervisors and 96.8% of multi-purpose workers were trained in leprosy. But only 31.3% of medical officers were able to diagnose leprosy and most of them were relying on vertical staff and skin specialists for confirmation. MDT services were provided by 20% of rural and 66.7% of urban health facilities that were acting as treatment centres. None of the health facilities had 3 months' stock of all types of blister packs, as per the guidelines of the Government of India. None of the sub-centres was involved in MDT delivery. However, reporting as per SIS formats was universal. The study emphasized the need for training and better management of MDT drug stock.

Delivery of Health Care, Integrated↗

Leprosy blindness in Nepal.

Leprosy is a systemic disease with highest incidence of ocular complications and one of the important causes of blindness in the world. A comparative cross-sectional study was carried out to see the ocular involvement in leprosy leading to blindness in two groups of patients, one with the active disease and second already cured and thus released from treatment (RFT). Active cases attending Anandaban leprosy clinic, Patan hospital and RFT cases from Khokana leprosarium were included in the study consecutively. Total of 70 active cases and 101 RFT cases were evaluated during the study period. Active group of patients showed more of multibacillary type of disease than in RFT group. The prevalence of ocular manifestations was seen much higher among RFT cases accounting for 66.3% in contrast to active group where only 14.3% had ocular problems. Blindness was frequently seen in multibacillary (MB) leprosy patients in compare to paucibacillary (PB) disease in both the groups. However blindness frequency was seen more often among RFT cases accounting for 24% in compare to only 2.9% among active group. Causes of blindness were mainly corneal and cataract related disorders. Risk of blindness also increased with the increase in duration of illness. RFT group of leprosy patients are at higher risk of developing blindness than the active group thus eye care services should be more focused for this group. Having multibacillary type of disease could also be a risk for development of blindness.

Adult↗