Leprosy In India Research Articles

P1-384 Inverse sampling to estimate disease burden of leprosy in India: a pilot study

Background and ObjectiveLeprosy continues to be an important public health problem. The magnitude of the disease is often expressed by the number of cases registered by the system. Estimation of...

Ancient Skeletal Evidence for Leprosy in India (2000 B.C.)

BackgroundLeprosy is a chronic infectious disease caused by Mycobacterium leprae that affects almost 250,000 people worldwide. The timing of first infection, geographic origin, and pattern of transmission of the disease are still under investigation. Comparative genomics research has suggested M. leprae evolved either in East Africa or South Asia during the Late Pleistocene before spreading to Europe and the rest of the World. The earliest widely accepted evidence for leprosy is in Asian texts dated to 600 B.C.Methodology/Principal FindingsWe report an analysis of pathological conditions in skeletal remains from the second millennium B.C. in India. A middle aged adult male skeleton demonstrates pathological changes in the rhinomaxillary region, degenerative joint disease, infectious involvement of the tibia (periostitis), and injury to the peripheral skeleton. The presence and patterning of lesions was subject to a process of differential diagnosis for leprosy including treponemal disease, leishmaniasis, tuberculosis, osteomyelitis, and non-specific infection.Conclusions/SignificanceResults indicate that lepromatous leprosy was present in India by 2000 B.C. This evidence represents the oldest documented skeletal evidence for the disease. Our results indicate that Vedic burial traditions in cases of leprosy were present in northwest India prior to the first millennium B.C. Our results also support translations of early Vedic scriptures as the first textual reference to leprosy. The presence of leprosy in skeletal material dated to the post-urban phase of the Indus Age suggests that if M. leprae evolved in Africa, the disease migrated to India before the Late Holocene, possibly during the third millennium B.C. at a time when there was substantial interaction among the Indus Civilization, Mesopotamia, and Egypt. This evidence should be impetus to look for additional skeletal and molecular evidence of leprosy in India and Africa to confirm the African origin of the disease.

Skeletal Evidence for Leprosy in India by the Second Millenium B.C.

AbstractLeprosy is a chronic infectious disease caused by Mycobacterium leprae that affects almost 500,000 people worldwide^1^. The timing of first infection, geographic origin, and pattern of transmission of the disease are unknown^1-3^. Comparative genomics research has recently suggested M. leprae evolved in East Africa or South Asia before spreading to Europe and the rest of the World^4-5^. The earliest accepted textual evidence indicates that leprosy existed in India by at least 600 B.C. and was known in Europe by 400 B.C.^6-7^. The earliest skeletal evidence was dated 300-200 B.C. in Egypt^8^ and Thailand^9^. Here, we report the presence of lepromatous leprosy in skeletal remains from Balathal, a Chalcolithic site (2300-1550 B.C.) in India^10-11^. A middle aged adult male skeleton demonstrates manifestations of facies leprosa and rhinomaxillary syndrome, degenerative joint disease, infectious involvement of the tibia (periostitis), and injury to the peripheral skeleton, often the result of skin anaesthesia. Paleopathological analysis indicates that lepromatous leprosy was present in India by 1800 B.C., a result which supports some translations of the Atharva Veda that reference leprosy and its treatment in hymns composed before the first millennium B.C.^12^. The presence of leprosy in Chalcolithic India suggests M. leprae may have been transmitted during the second or third millennium B.C., at a time when there was substantial interaction between South Asia, West Asia, and Northeastern Africa^13^. This evidence should be impetus to look for additional skeletal and molecular evidence of leprosy in human remains from this time period in India and Africa to confirm the origin of the disease.

Treatment of leprosy in India

Introduction of multi-drug therapy (MDT) into the National Leprosy Eradication Program (NLEP) of India has brought a decline in both the burden of the disease and the detection of new cases in the country. Despite this success, MDT has had many problems like remarkable relapse rate, non-adherence to the MDT and the emergence of drug resistance associated with it. Moreover, there is no new MDT regimen at present, which could solve all these problems. The current situation suggests that we should look for alternative solutions in the delivery of leprosy-related services. With the introduction of Accredited Social Health Activists under the National Rural Health Mission, there is an opportunity to control some of these problems associated with MDT. Besides, District Nucleus should take initiatives and actively participate in establishment of coordination between departments of Health, Social welfare and justice, education and various non-governmental agencies working in the field of leprosy and disability in order to deliver the best of services to the persons affected by leprosy.

The Stigmatization of Leprosy in India and Its Impact on Future Approaches to Elimination and Control

Traditionally, India holds the unenviable position of the origin of leprosy. The disease is thought to have then spread, via trade and war, to China, Egypt, and the Middle East, and later to Europe and the Americas. From antiquity to modernity, Indian society treated leprosy singularly with respect to custom and law, a response shaped by both scientific knowledge and cultural attitudes. India's future challenges in leprosy control include multiple systems of medicine, stigma, and educational knowledge gaps. By looking through the historical window of leprosy in India, we propose that continued success in elimination and control requires a holistic approach addressing these issues (Image 1).

DERMATOLOGISTS AND LEPROSY IN INDIA

DERMATOLOGISTS AND LEPROSY IN INDIA

Current epidemiology of leprosy in India

Current epidemiology of leprosy in India

Evaluation of leprosy patients with 1 to 5 skin lesions with relevance to their grouping into paucibacillary or multibacillary disease

Patients with 1 to 5 skin lesions are arbitrarily categorized as belonging to the paucibacillary (PB) group for treatment purposes. With the decreasing prevalence of leprosy in India and modifications in leprosy program, the relevance of this grouping needs further study. To study a group of leprosy patients with 1 to 5 skin lesions and compare the clinical parameters with histopathological findings and bacteriological status of the skin and nerve to evaluate the relevance of this grouping. Seventy seven patients of leprosy with 1 to 5 skin lesions were included in the study. The number of skin lesions was recorded. Slit skin smears (SSS) and skin biopsies were taken in all patients and nerve biopsy was performed in 19 of them. The biopsies were evaluated for the type of pathology and AFB status. In these 77 patients (single skin lesions, 42; two lesions, 18; three lesions, 10; four lesions, 5; and five lesions, 2 patients) the clinical classification was indeterminate leprosy (IL) in 4, tuberculoid leprosy (TT) in 4 patients and borderline tuberculoid leprosy (BT) in 69 patients. Skin smears were positive only in 1 patient. The histological diagnoses in the skin were IL in 13, TT in 3, BT in 48 and borderline lepromatous (BL) in 4 patients. Acid-fast bacilli (AFB) were found in 14 out of 77 skin biopsies. Of the 19 nerve biopsies, 17 showed histological features of BT leprosy; of these, 12 demonstrated AFB on Fite staining. The bacillary index of granuloma (BIG) ranged from 1+ to 2+. The clinico-histopathogical correlation was 63% in the BT group, with 4 patients of this group showing features of BL on histopathology. When the presence of AFB was assessed, the percentage of positivity was 1.3% in SSS, 18% in skin biopsies and 63% in nerve biopsies. Our results point to the non-homogeneous nature of this group of leprosy patients with 1 to 5 skin lesions, with varied bacteriological and histopathological features. The significance of MB type findings on histopathology in patients grouped as PB leprosy should be resolved so that these patients may be given the drug therapy and the duration of therapy they warrant.

Elimination of leprosy in India: Response by authors

Elimination of leprosy in India: Response by authors

Pure neuritic leprosy in India: an appraisal.

Pure neuritic leprosy (PNL) constitutes a significant proportion of all cases in India, however, this form of disease has not been fully recognized and investigated and there is little information in the existing literature. To study the epidemiological characteristics of PNL in India. A retrospective analysis of leprosy clinic records for the period 1993 to 2003 was undertaken. Detailed demographic profiles and clinical findings were noted from the predesigned clinic proforma. A slit-skin smear for acid-fast baclli (AFB) was done in all cases from the area of sensory loss. A skin biopsy was done from the area of sensory impairment to study histopathological changes. Further investigations such as nerve conduction velocity studies (NCV), fine needle aspiration cytology (FNAC), or nerve biopsy (superficial nerve twigs) were done if indicated in patients whenever there was difficulty in clinical diagnosis. Of the total 1542 leprosy patients seen over this period, 65 (4.2%) had PNL. Males were more commonly affected than females (2.6:1.). The majority of patients 40/65(61.5%) were aged between 15 and 35 yrs. Predominant presenting symptoms were paresthesia, pain, sensory/motor deficit, and trophic changes. A majority of the patients 39/65 (60.0%) presented with involvement of 2 or more nerves in the same extremity. Mononeuritis was seen in 26 (40%) patients. The nerves most often involved were the right ulnar nerve in the upper extremity, and the right common peroneal nerve in the lower limb. In general, the nerves of the upper extremity were more commonly involved than in the lower limbs (67 vs. 55). Motor deformities such as claw hand and foot drop were present in 13/75 (20%) and 7/65 (10.8%) patients, respectively. Slit-skin smears were negative in all patients, and skin histopathology from the area of sensory loss revealed non-specific inflammation in the dermis in a majority of patients, with perineural inflammation in a few. All patients were treated with multi-drug therapy (MDT); patients with >/=2 peripheral nerve trunk involvements were treated with WHO MDT MB regimen, while others were administered WHO MDT PB regimen. Follow-up for up to 2 yrs was available in only 32/65 (49.2%) patients, none of whom developed any skin lesions during this period. PNL is a distinct subset of disease frequently seen in India. There is need to pay more attention to this form of leprosy and diagnose and treat patients earlier to prevent deformities and sequelae of nerve damage.

Genome-wide scans for leprosy and tuberculosis susceptibility genes in Brazilians.

Genome-wide scans were conducted for tuberculosis and leprosy per se in Brazil. At stage 1, 405 markers (10 cM map) were typed in 16 (178 individuals) tuberculosis and 21 (173 individuals) leprosy families. Nonparametric multipoint analysis detected 8 and 9 chromosomal regions respectively with provisional evidence (P<0.05) for linkage. At stage 2, 58 markers from positive regions were typed in a second set of 22 (176 individuals) tuberculosis families, with 22 additional markers typed in all families; 42 positive markers in 50 (192 individuals) new leprosy families, and 30 additional markers in all families. Three regions (10q26.13, 11q12.3, 20p12.1) retained suggestive evidence (peak LOD scores 1.31, 1.85, 1.78; P=0.007, 0.0018, 0.0021) for linkage to tuberculosis, 3 regions (6p21.32, 17q22, 20p13) to leprosy (HLA-DQA, 3.23, P=5.8 x 10(-5); D17S1868, 2.38, P=0.0005; D20S889, 1.51, P=0.004). The peak at D20S889 for leprosy is 3.5 Mb distal to that reported at D20S115 for leprosy in India. (151 words).

“WITHOUT THE CAMP”: LEPROSY AND NINETEENTH-CENTURY WRITING

FOUCAULT WAS PROBABLY RIGHT WHEN he argued in the first chapter of Madness and Civilization that the asylum replaced the lazar house at the end of the Middle Ages, but he exaggerated in claiming that leprosy had disappeared from the western world. The decline of leprosy in early modern Europe did not mean that fear of it vanished or that Europe lost all contact with the disease. From the sixteenth century it became involved in the debate about the origin of syphilis, which at first was widely believed to be a new form of leprosy. A later, converse theory claimed that leprosy was a common terminal stage of syphilis, particularly in hot climates (Leprosy in India 353). This was given circulation and respectability at the turn of the nineteenth century by William Jones when he wrote that “The Persian, or venereal, fire generally ends in this malady” (qtd. in Crook and Guiton 91). The Collected Works of this distinguished Orientalist were published in 1799 and widely discussed. Britain’s steady colonial expansion in the late eighteenth century had brought renewed contact with leprosy and the consequent fear of its reintroduction into Europe. Although the disease had remained available to writers as a figure for horror throughout the early modern period, it was to take on renewed force in the century or so following the publication of Lyrical Ballads (1798).

A major susceptibility locus for leprosy in India maps to chromosome 10p13.

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is prevalent in India, where about half of the world's estimated 800,000 cases occur. A role for the genetics of the host in variable susceptibility to leprosy has been indicated by familial clustering, twin studies, complex segregation analyses and human leukocyte antigen (HLA) association studies. We report here a genetic linkage scan of the genomes of 224 families from South India, containing 245 independent affected sibpairs with leprosy, mainly of the paucibacillary type. In a two-stage genome screen using 396 microsatellite markers, we found significant linkage (maximum lod score (MLS) = 4.09, P < 2x10-5) on chromosome 10p13 for a series of neighboring microsatellite markers, providing evidence for a major locus for this prevalent infectious disease. Thus, despite the polygenic nature of infectious disease susceptibility, some major, non-HLA-linked loci exist that may be mapped through obtainable numbers of affected sibling pairs.

T‐Cell Responses to Fractionated Antigens of Mycobacterium w, a Candidate Anti‐Leprosy Vaccine, in Leprosy Patients

Mycobacterium w, an atypical cultivable mycobacterium, is undergoing phase III clinical trials as a vaccine against leprosy in India. It has brought about lepromin conversion and histopathological upgradation in a significant number of patients studied so far. It is important to identify antigens of M. w that trigger T-cell responses in leprosy patients vaccinated with this organism. In the present study the peripheral T-cell repertoire of 12 M. w-vaccinated leprosy patients, 10 unimmunized leprosy patients, 8 tuberculoid and 5 healthy contacts was analysed with fractionated antigens of M. w. The lepromatous leprosy patients who are in general anergic to antigens of M. leprae did not respond to antigens of M. w. However, peripheral blood mononuclear cells obtained from leprosy patients who had been vaccinated with M. w responded to many antigens. These responses were frequently directed against low molecular weight entities of 14-45 kDa. T cells from tuberculoid leprosy patients and healthy contacts also responded predominantly to a number of low molecular weight antigens of M. w. The study also identified an immunodominant 28-31 kDa antigenic fraction carrying T- as well as B-cell activating determinants.

An approach to study in vitro the expression of HLA-encoded genetic factors predisposing to tuberculoid leprosy.

The existence of HLA-encoded genetic factors controlling susceptibility to tuberculoid leprosy in humans has been firmly established. Furthermore HLA-DR2 has been recognized as a marker for tuberculoid leprosy in India. At this moment, however, the gene products involved and the mechanism by which they confer susceptibility to tuberculoid leprosy remain only speculative. In an attempt to detect in vitro the expression of these HLA-encoded factors, we studied 12 tuberculoid leprosy patients and 22 healthy family members in a lymphocyte transformation test (LTT). All individuals were derived from multi-case Indian families, previously reported to show the presence of HLA-linked susceptibility genes. Although the responder-status of the healthy contact siblings was shown to behave independently from the fact whether they were HLA-identical with the patient-siblings or not, some evidence for in vitro expression of HLA-DR2 associated factors could be obtained. Nevertheless, it is concluded that the standard LTT seems not to be a test-system of first choice to detect the in vitro expression of the genes under study.

The epidemiological situation of leprosy in India.

The epidemiological situation of leprosy in India.

Leprosy in India and Ceylon

Leprosy in India and Ceylon

Leprosy in India and Ceylon

Leprosy in India and Ceylon

Methods of Campaign against Leprosy in India (ABRIDGED.)

Methods of Campaign against Leprosy in India (ABRIDGED.)

ON LEPROSY AND ELEPHANTIASIS IN SOUTH AFRICA AND INDIA.

ON LEPROSY AND ELEPHANTIASIS IN SOUTH AFRICA AND INDIA.