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Patterns of ocular morbidity and blindness in leprosy--a three centre study in Eastern India.

BACKGROUND: Eye disease and visual impairment due to leprosy are not uncommon, but their prevalence and the risk factors for such pathology have yet to be fully characterized. METHODS: An observational study of leprosy-affected individuals in the community, in three districts in Eastern India was performed to determine the prevalence of ocular morbidity and blindness. The subjects were chosen by stratified random sampling, according to stage of treatment, or stage of post-treatment surveillance. Each subject underwent ophthalmic examination according to a standard pro-forma. RESULTS: Thirty-three out of 1137 (2.9%) subjects were blind according to the WHO classification, and 232/1137 (20.7%) had moderate visual impairment. The prevalence of blindness and visual impairment was greatest in one centre, Jhalda. Multivariate Logistic Regression analysis showed that longer duration of disease, more advanced treatment stage and older age were independently associated with blindness. One hundred and forty-one cases (28%) in Muzaffarpur, 95 cases (63%) in Saldoha and 378 cases (78%) in Jhalda had active or treated multibacillary leprosy. DISCUSSION: The prevalence of blindness in leprosy varies in different population groups, with differing patterns of leprosy-related ocular morbidity, blindness and disease type evident even in different areas of the same region. Leprosy screening and surveillance programmes should include ocular examination as part of routine screening, particularly in individuals with a history of multi-bacillary disease. Individuals with known sight- threatening pathology should undergo continued active follow up. Local epidemiological studies would enable appropriate programme planning and efficient allocation of resources.

Adult↗

Trends in leprosy over fifty years in Gudiyatham Taluk, Vellore, Tamil Nadu.

This paper presents epidemiological trends over a fifty-year period observed in a defined population served by the Schieffelin Leprosy Research and Training Centre (SLR & TC), Karigiri, Vellore District in Tamil Nadu. It covers three distinct periods, namely, the pre-MDT era with dapsone monotherapy, the MDT era under a vertical leprosy control programme and the MDT era after leprosy control services were integrated into the general health services. Prevalence rates have declined steadily from 125 per 10,000 population at the time of introduction of MDT in 1982 to 5 per 10,000 at the time of integration in 1997 to less than 1 per 10,000 in 2005. The new case-detection rate was 5.4 per 10,000 when the field programme started in 1962, and held steady at 15-20 per 10,000 between 1970 and 1980. It then showed a gradual fall from 10.8 per 10,000 in 1985 to 3.9 at the time of integration, and continued to fall in the post-integration period and was 0.8 per 10,000 in 2005. The mean age at detection showed a gradual increase from 23.4 years in the dapsone era to 31.2 years in the post-integration period. The male: female ratio showed a preponderance of males almost throughout the reference period. While polar types of leprosy (TT & LL) were common in the dapsone era, more of borderline leprosy (BT & BL) cases was seen more recently. MB rates that were high initially, declined steadily during monotherapy and stabilized between 10% and 12% during the vertical MDT programme and is showing an increase in the post-integration-period. The proportion of cases with Grade 2 disability at registration showed a gradual decline during the monotherapy period, remained relatively unchanged at 8%-10% during the the MDT period, and showed a sharp rise in the immediate post-integration period before falling. Analysis of trends of leprosy in a well-defined geographical population over a fifty-year period gives useful information on how the disease has evolved over the years. It provides opportunities to explore the reasons for the changes observed, though one has to be cautious while interpreting such data due to changes in definition, the play of operational factors, and changes in policies and strategies.

Adult↗

Lepromatous leprosy: a review and case report.

Leprosy is a contagious and chronic systemic granulomatous disease caused by Mycobacterium leprae (Hansen s bacillus). It is transmitted from person to person and has a long incubation period (between two and six years). The disease presents polar clinical forms (the multibacillary lepromatous leprosy and the paucibacillary tuberculoid leprosy), as well as other intermediate forms with hybrid characteristics. Oral manifestations usually appear in lepromatous leprosy and occur in 20-60% of cases. They may take the form of multiple nodules (lepromas) that progress to necrosis and ulceration. The ulcers are slow to heal, and produce atrophic scarring or even tissue destruction. The lesions are usually located on the hard and soft palate, in the uvula, on the underside of the tongue, and on the lips and gums. There may also be destruction of the anterior maxilla and loss of teeth. The diagnosis, based on clinical suspicion, is confirmed through bacteriological and histopathological analyses, as well as by means of the lepromin test (intradermal reaction that is usually negative in lepromatous leprosy form and positive in the tuberculoid form). The differential diagnosis includes systemic lupus erythematosus, sarcoidosis, cutaneous leishmaniasis and other skin diseases, tertiary syphilis, lymphomas, systemic mycosis, traumatic lesions and malignant neoplasias, among other disorders. Treatment is difficult as it must be continued for long periods, requires several drugs with adverse effects and proves very expensive, particularly for less developed countries. The most commonly used drugs are dapsone, rifampicin and clofazimine. Quinolones, such as ofloxacin and pefloxacin, as well as some macrolides, such as clarithromycin and minocyclin, are also effective. The present case report describes a patient with lepromatous leprosy acquired within a contagious family setting during childhood and adolescence.

Aged↗

Hypogonadism in male Leprosy patients--a study from rural Uttar pradesh.

Hypogonadism in male patients with Leprosy is common and may identify patients with future risk for bone loss and osteoporosis. In the present study, we evaluated gonadal function in 71 male patients with Leprosy both clinically and by estimation of serum testosterone levels. The patients belonged to selected rural areas of Uttar pradesh, with majority aged less than 50 yrs (74.6%), Hindus (66.7%), illiterate (60.9%), and of low socioeconomic status (58% with per capita income < Rs.500 per month). Most patients had multibacillary Leprosy (83.1%), duration less than 2 years (75.4%) and had received antileprosy drugs for less than a year (95.6 %). Seven patients (9.9%) had clinical features of hypogonadism such as gynaecomastia, decreased sexual hair and infertility. Serum testosterone levels, estimated in 31 of the patients, revealed low values in 25.8% (8/31) patients (Mean 4.65+/-3.37 ng/ml). Age, duration of Leprosy and socioeconomic status but not type of Leprosy or treatment duration affected hypogonadism significantly. The results of the present study indicate a high frequency of hypogonadism among rural male Leprosy patients that warrants routine screening to identify patients at risk for osteoporosis and possible prevention with testosterone replacement therapy.

Adolescent↗

Nine-banded armadillo (Dasypus novemcinctus) as an animal model for leprosy.

Dr. Dharmendra was one of the most distinguished leprologists of our time. He loved India so much that he offered his entire life to fight leprosy, a major health problem in India. He realized the great need in this much neglected field of medicine and willingly gave his utmost, whatever be the cost. He served in the field of leprosy with great distinction and he earned the respect of his fellow workers from all over the world. He made outstanding contributions to the study of leprosy, the identification and isolation of the active principle in the lepromin reagent, the use of lepromin test for identifying persons susceptible to leprosy, the use of an antileprosy drug as a means of chemoprophylaxis, the nurturing of the Indian Journal of Leprosy and developing it as one of the foremost leprosy journals, are a few of his major contributions. He received many well deserved national and international honours and awards. I first met Dr. Dharmendra in 1956 and feel privileged to have known him and to be associated with him all these years. I am honored to be asked to contribute this paper for a publication meant to pay tribute to his memory.

Animals↗

Comparative evaluation of enzyme immunoassays based on synthetic glycoconjugates and phenolic glycolipid-I for immunodiagnosis of leprosy.

Enzyme immunoassays (EIAs) based on synthetic glycoconjugates containing the terminal monosaccharide (M-BGG) or disaccharide (ND-BSA) residue of the trisaccharide component of phenolic glycolipid-I (PGL-I), for immunodiagnosis of leprosy are described. The results of the assays were compared with that of the EIA using PGL-I. All the three assays were highly specific for leprosy. The per cent positivity of active lepromatous leprosy (LL) patients with M-BGG was 78.05 in comparison to 85.36 with ND-BSA and 82.11 with PGL-I. Similarly, the positivity of tuberculoid (TT) leprosy patients in M-BGG assay was lower than that in EIAs using ND-BSA or PGL-I. However, the difference in the positivity of individual category of leprosy patients in the three EIAs was not statistically significant. The correlation between absorbance values of leprosy sera in EIAs based on M-BGG and PGL-I, as well as that in assays using ND-BSA and PGL-I was statistically significant.

Antigens, Bacterial↗

Experiences with Mycobacterium leprae soluble antigens in a leprosy endemic population.

Rees and Convit antigens prepared from armadillo-derived Mycobacterium leprae were used for skin testing in two leprosy endemic villages to understand their use in the epidemiology of leprosy. In all, 2602 individuals comprising 202 patients with leprosy detected in a prevalence survey, 476 household contacts and 1924 persons residing in non-case households were tested with two antigens. There was a strong and positive correlation (r = 0.85) between reactions to the Rees and Convit antigens. The distribution of reactions was bimodal and considering reactions of 12 mm or more as 'positive', the positivity rate steeply increased with the increase in age. However, the distributions of reactions to these antigens in patients with leprosy, their household contacts and persons living in non-case households were very similar. These results indicate that Rees and Convit antigens are not useful in the identification of M. leprae infection or in the confirmation of leprosy diagnosis in a leprosy endemic population with a high prevalence of nonspecific sensitivity.

Adolescent↗

Quantitation of IgM antibodies to the M. leprae synthetic disaccharide can predict early bacterial multiplication in leprosy.

Quantitative enzyme-linked immunosorbent assays detecting IgM to the soluble Mycobacterium leprae crude sonicate (CD75) and the synthetic disaccharide antigen coupled to bovine serum albumin (ND-BSA) were assessed for their ability to determine early infection in families/household contacts of leprosy patients and employees of a leprosy center working in close contact with leprosy patients. Although IgM to both antigens (CD75 and ND-BSA) correlated with the bacterial index (BI) assessed histologically on skin-biopsy samples, the level of IgM antibodies to ND-BSA was a much more sensitive indicator of low bacterial loads. A 4.4-fold difference in antibody levels was observed between the mean group levels of endemic controls (N = 116) and tuberculoid leprosy patients with a BI of 0 (N = 88), increasing to sevenfold in tuberculoid leprosy patients with a BI of 1 (N = 20). Using a statistical cut off with endemic controls (mean + 2 S.D.), household/family contacts showed 30% seropositivity (N = 180) as compared to staff contacts who showed 17% seropositivity (N = 55). Percent seropositivity in family contacts was not related to the type of leprosy of the index case (lepromatous vs. tuberculoid) or the duration of treatment of the index case. Age of the individual in the family contact group had a significant influence on seropositivity. These results support the hypothesis that, in this community, factors other than the viable bacterial load of the index case, such as genetic susceptibility, may be influencing the high rate of seropositivity in family contacts. IgM ND-BSA antibodies seem to provide a good indicator of low antigenic loads and could prove to be useful in detecting subclinical infection before the onset of disease. Follow-up studies of these seropositive individuals are in progress to understand the relationship between seropositivity and the progress of clinical disease.

Antibodies, Bacterial↗

Inter-observer agreement and clinical diagnosis of leprosy for prophylaxis studies.

Clinical diagnosis is still the most useful tool for detecting early cases of leprosy in field research. In prophylaxis studies accuracy of clinical diagnosis of leprosy is important during intake as well as for measuring efficacy of the intervention. This paper reports our observations regarding the extent of inter-observer variations in clinical diagnosis of leprosy and its implications for a prophylaxis study. Information on 225 suspects and cases of leprosy, each examined independently by three senior workers after initial standardization, was used for this purpose. Agreement among the examiners regarding the presence of skin patch, thickened nerve trunk and sensory deficit was fairly high (Kappa = 0.7). Agreement on the presence of infiltration in a skin patch was not satisfactory (Kappa = 0.4-0.5). It was observed that in clinical diagnosis of leprosy, presence of skin patch and sensory deficit, as well as thickened nerve trunk and related anaesthesia were correlated observations. The influence of inter-observer variations on defining leprosy problem in the community can be quite large. The paper suggests some ways of overcoming the problem.

Adult↗

A study on nutrition, growth and development of a high-risk group of children of urban leprosy patients.

This paper describes a cross-sectional study of the physical development of a high-risk group of 182 socially deprived healthy children of leprosy patients ranging from preschool age to early teens. They were rescued at the age of 4 years from the distress of leprosy colonies where they were born, and brought up in Government Homes (Preventorium) under better environmental conditions. Of them 135 children could be followed clinically for 10 years for the development of childhood leprosy. Another 94 children of leprosy patients living with their parents were included for comparison. A group of 158 normal children of similar economic status and age group were included as controls. It was observed that, although better environment, food and training were provided in the Preventorium, so that the children could be brought into the national mainstream, nevertheless 5 children developed an indeterminate type of leprosy during the course of 10 years. This is the first report of growth and development of children of leprosy patients from the Indian sub-continent.

Adolescent↗

Clinical significance of changes in serum proteins, immunoglobulins, and autoantibodies in leprosy.

Changes in the level of acute phase reactants such as C-reactive protein (CRP), serum globulins, and autoantibodies have been reported previously in patients with leprosy, particularly at the lepromatous end of the spectrum. The clinical significance of these findings was investigated by comparing the same parameters of humoral immune function in populations of Australian Aboriginals with stable treated leprosy and relevant contact groups including a) noninfected European sporadic contacts and b) healthy Aboriginal relatives of patients with confirmed leprosy. Raised levels of CRP and immunoglobulins and the higher frequency of autoantibodies seen in leprosy patients compared with sporadic contacts are probably related to differences in the incidence of nonleprous infection rather than to leprosy per se. Comparable results were obtained in the leprosy patients and their family contacts. The data highlight the need to use antigen-specific assays for determining the significance of changes in acute phase reactants and for distinguishing between the primary and secondary effects of Mycobacterium leprae infection.

Alpha-Globulins↗

Productivity loss due to deformity from leprosy in India.

The productivity loss in India due to deformity from leprosy was assessed in a random sample of 550 leprosy patients from a rural and an urban area in the state of Tamil Nadu. Logistic and log-linear regression analyses on these leprosy patients showed that elimination of deformity would: a) raise the probability of gainful employment from 42.2% to 77.6%; b) increase annual earnings per patient gainfully employed from Rs 2948 to Rs 6469; and c) raise overall earnings for all patients from Rs 1259 to Rs 5023 per year. The earnings of 550 control subjects (adult family members of the leprosy patients) were consistent with these predictions. Extrapolation to all of India's estimated 645,000 leprosy patients with deformity suggests that elimination of deformity would raise productivity by +130 million per year. The authors conclude that the development and evaluation of programs to eliminate deformity from leprosy deserve high priority.

Disability Evaluation↗

Diabetic status in leprosy.

The diabetic status of the local Jhansi patients (120 cases) was established before and after antileprosy treatment. Control studies were performed in normal healthy subjects (50 persons) without family history of diabetes mellitus. Random normals showed an incidence of diabetes only 2%, while leprosy patients (94 males and 26 females) had incidence of diabetic status of 14.2%. The highest incidence (19.3%) of diabetes was in lepromatous leprosy and lowest incidence (6.4%) in tuberculoid leprosy patients. Repeated studies in leprosy after treatment showed not only clinical improvement for leprosy but also disappearance of the chemical and latent diabetes mellitus and lowering of blood sugar levels in manifest diabetes mellitus. Incidentally it was noted that 'diabetic status' was worse among males (82.3%) and with advancing age. Association and improvement of diabetic status with specific treatment would tentatively suggest that Mycobacterium leprae lesions are not confined to skin alone but somehow also related to carbohydrate metabolism. A careful management of the chemical and latent diabetes may help in clinical management of leprosy too.

Adolescent↗

Vaccination and skin test studies on children living in villages with differing endemicity for leprosy and tuberculosis.

The purpose of this study carried out in Iranian Azerbaijan was to determine the pattern of skin-test positivity to mycobacterial antigens in children living in the valley, and to assess the effect on this of a series of vaccines against mycobacterial disease. Set up in 1978, 1707 tuberculin-negative children without scars of previous BCG vaccination were vaccinated with BCG Glaxo alone (vaccine A) or with the addition of a suspension of killed Mycobacterium vaccae (vaccine B). One hundred children were vaccinated with BCG Glaxo plus a suspension of M. leprae (vaccine C). Eight to 10 years later about half of the children were found for follow up. At this time further children were skin tested, and the results obtained were related to whether or not they had scars of vaccination with BCG Pasteur (Teheran) given by the local health authorities. Between setting up the study and the first follow up, cases of leprosy or tuberculosis had occurred in some of the villages, although not among those we had vaccinated. Differences between the effects of the vaccines were only found in villages with cases of leprosy. In these villages positivity to leprosin A was significantly greater after vaccine B (49%) than after vaccine A (36%; p less than 0.04). The results for scrofulin and vaccine were the same after both vaccines, and significantly lower than in the villages without cases of leprosy. The general reduction in skin-test positivity in the villages with leprosy cases was mainly due to a loss of category 1 responders to group i, common mycobacterial, antigens. It was concluded that where casual contact with cases of leprosy occurs the combination of BCG with killed M. vaccae is likely to be a better vaccine for leprosy than is BCG alone. Although few children received the combination with M. leprae, the results obtained were not particularly promising.

Adolescent↗

Undernutrition in lepromatous leprosy. V. Severe nutritional deficit in lepromatous patients co-infected with pulmonary tuberculosis.

We have compared the nutritional status of patients with lepromatous leprosy coinfected with pulmonary tuberculosis (18 cases) with that of lepromatous leprosy (239 cases) and of pulmonary tuberculosis (21 cases) and with that of healthy controls. There was a severe weight loss and reduction of skinfold thickness in the patients with pulmonary tuberculosis as well as in lepromatous patients with associated pulmonary tuberculosis, but not in patients with lepromatous leprosy. Levels in sera of diet-dependent proteins, such as albumin, prealbumin and retinol binding protein, were significantly decreased in all three groups of patients; on the other hand, levels of the diet-independent proteins, such as the immunoglobulins, were raised in all the groups, particularly in the pulmonary tuberculosis patients as compared with healthy controls. Serum transferrin levels were decreased only in the tuberculosis patients with or without lepromatous leprosy, but not in patients with leprosy alone. While haemoglobin levels decreased in all patient groups, serum iron concentrations were reduced most in lepromatous patients concomitantly infected with pulmonary tuberculosis. Serum ferritin levels increased in the sera of pulmonary tuberculosis and lepromatous leprosy patients, but was severely reduced in lepromatous patients with associated pulmonary tuberculosis. Mean serum zinc and calcium levels were decreased in all three groups of patients, while the serum copper concentration was increased in all of them compared with healthy controls. Also, inorganic phosphorus was elevated in tuberculosis and lepromatous patients coinfected with pulmonary tuberculosis, but not in lepromatous patients. Serum calcitonin levels were increased in all patient groups indicating an inverse correlation between serum calcium and calcitonin levels. This is the first comparative report describing the status of macro- and micronutrients in two most important mycobacterial diseases of the third world countries.

Adolescent↗

Leprosy as a zoonosis: an update.

Naturally-acquired leprosy has been reported in nine-banded armadillos captured in the southern United States, a chimpanzee from Sierra Leone, and in two "sooty" mangabey monkeys from Nigeria. A significant prevalence of leprosy in wild armadillos establishes this animal as a reservoir of M. leprae, and exposure to armadillos has been implicated as a source of leprosy in humans. Current evidence suggests that leprosy is a zoonosis in certain nonhuman primate species. Control and eradication programs for leprosy should take into consideration the possible influence of extra-human sources of M. leprae, especially zoonotic leprosy.

Animals↗

Antibodies to a synthetic analog of phenolic glycolipid-I of Mycobacterium leprae in healthy household contacts of patients with leprosy.

Fifty-four household contacts of lepromatous patients, 39 household contacts of tuberculoid patients, and 99 control persons were examined with an enzyme-linked immunosorbent assay for their antibody responses to phenolic glycolipid-I (PGL-I) of Mycobacterium leprae using a synthetic analog (PGL-ISA) with the same terminal sugar epitope, namely, O-(3, 6-di-O-methyl-beta-D-glucopyranosyl)-(1----4)-O-(alpha-L-rhamnopyranosyl )-(1----9)-oxynonanoyl-BSA. This study was conducted in the Gurage area of Ethiopia in 15 households with a leprosy patient and 15 matched control households. Household contacts with more than 1 year of exposure to a lepromatous patient had antibodies to PGL-ISA significantly more often (19 of 34 persons) than did household contacts with less than 1 year of exposure to a lepromatous patient (4 of 20 persons), household contacts of tuberculoid patients (8 of 39 persons), and persons without exposure to leprosy in the household (33 of 99 persons). No significant association was found between the prevalence of antibodies to PGL-ISA in the household contacts and disease activity in the lepromatous index patients at the time of examination; nor was there a significant association between antibody responses and age or sex of the contacts. The increased prevalence of antibodies to M. leprae antigen in healthy persons with more than 1 year of contact with a lepromatous patient provides further evidence that subclinical infection in leprosy is common, and is related to the type of leprosy in the index patient. The fact that antibodies to PGL-ISA were detected in one third of the persons without household exposure to leprosy emphasizes the necessity to always include comparable controls from the same endemic area in studies of leprosy contacts.

Adolescent↗

Detection of major genes for susceptibility to leprosy and its subtypes in a Caribbean island: Desirade island.

To determine the nature of the genetic component controlling susceptibility to leprosy and its subtypes, complex segregation analysis, by means of the POINTER strategy, was performed on 27 multigenerational pedigrees from Desirade, a Caribbean island where leprosy is highly prevalent. The results are consistent with the presence of a recessive or codominant major gene controlling susceptibility to leprosy per se and nonlepromatous leprosy, respectively. Under the major-gene model, tests of homogeneity to check for internal consistency of the sample and to compare subsamples according to an epidemiological criterion, the place of residence of the probands, were conducted; results of none of these tests were significant. However, we have noted that information on 3 generations (nuclear families with a pointer to the sibship) is of major importance for detecting major gene(s). Besides, the discrepancy in the results obtained in separate analyses of the family subsamples defined by the place of residence of the probands is discussed in terms of possible genetic and/or environmental differences. Referring to experimental data and previous studies, we suggest that the gene for susceptibility to leprosy per se and that for susceptibility to nonlepromatous leprosy might be different, acting at successive stages of the immune response to infection with Mycobacterium leprae.

Disease Susceptibility↗