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The present study is of quantitative histology in immunologically intact mice inoculated with M. leprae. Total twelve sciatic nerves are studied. The fibres are grouped as large, medium and small sized fibres. Initially there is loss of small size fibres. At later stages there is involvement of all sized fibres and ultimately Wallerian type of degeneration sets in. The process of regeneration is more active than that of human leprosy of tuberculoid type. This study adds a new dimension in understanding the pathogenesis of leprosy.

Macrophages from lepromatous patients after phagocytosis of M. leprae showed alteration in their surface property as determined by their ability to express Fc receptors. The same macrophages without intracellular M. leprae show normal Fc receptors. The lepromatous macrophages also show very poor interaction with lymphocytes in the presence of M. leprae while they are able to interact with lymphocytes when exposed to other antigens. These observations along with earlier ones on macrophage defects have indicated a probable reason for defective cell mediated immunity (CMI) in lepromatous leprosy patients. There appears to be a defective macrophage population in lepromatous patients that is unable to process M. leprae antigens and initiate the CMI response.

Schwann cells that contain M. leprae fail to incorporate DNA precursor, indicating blockage of DNA synthesis. Such a block could lead to no proliferation of Schwann cells, an essential requirement for successful association with axons and consequent myelination.

Our previous studies have demonstrated a defective macrophage response to M. leprae in lepromatous leprosy patients. In the present study we report the restoration of Fc receptor and HLA-DR antigen expression as well as antigen specific macrophage-lymphocyte interaction on treatment with levamisole in vitro. These results indicate that levamisole activates the macrophages which in turn results in an improved cell mediated immune response in lepromatous leprosy. This may also be applicable in other disease situations.

Neonatal dorsal root ganglia were cultivated in vitro by the technique of Murray. Within a week bundles of organized nerve fibers containing proliferating Schwann cells in different phases of axon association and fibroblast cells destined to become peri- or endoneural cells were obtained, peri- or endoneural cells were obtained. Many of these nerve fibers were myelinated within 3-4 weeks. Such 1 or 2 week old cultures were inoculated with M. leprae, and bacilli were found in the cytoplasm of Schwann cells and fibroblasts, demonstrating that these cells are phagocytic in nature and that it is possible to infect them with M. leprae, Schwann cells, mostly in the free or early association phase, engulfed the bacilli, and this affected their further interaction with the axons and subsequent myelin synthesis.

The project at Mandwa was designed to study the problems of health in rural India and the delivery of health care by the existing public and private health systems. The results demonstrate the important role of socioeconomic and political factors not only in vital areas such as nutrition, water supply, sanitation, and housing, but also in the delivery of health services. The private sector showed a predominantly curative and monetary orientation, while the public sector demonstrated a lack of accountability to the people it was designed to serve. Under these conditions, an attempt was made to test the possibility of training local women in self-help with a minimal supportive service. The results reveal that adequate knowledge and technology exist for most of the prevalent problems of health and illness in developing countries, and that semiliterate villagers have the capacity to use these effectively if they are provided in a simple manner. This experiment also demonstrates the opposition from local vested interests to any change of the status quo, even in the relatively noncontroversial field of health.

When macrophages from lepromatous leprosy patients are exposed to M. leprae, the macrophages show reduced protein synthesis. Such a phenomenon is not seen with macrophages from tuberculoid patients or normal individuals. M. leprae phagocytized by Schwann cells affect the incorporation of DNA precursor in the cells, leading to failure of Schwann cell association with axons in in vitro cultures. These 2 observations form a basis of proposing that basic biochemical events take place when M. leprae are associated with host cells, which in turn can be amplified to physiologically functional defects.

Pure neuritic leprosy is a well accepted clinical entity. In the absence of skin lesions there is a greater possibility of missing the diagnosis of leprosy due particularly to a wide variety of pure neural manifestations that may mimic other peripheral neuropathies. Histopathological studies of pure neuritic leprosy have received less attention for ethical reasons and limitations of surgery. Classification of pure neuritic leprosy poses problems since the histological spectrum (e.g. Ridley-Jopling scale) is based chiefly on the skin picture. Review of the past literature shows conflicting reports about comparability of the skin and nerve pictures. This paper presents clinical and histopathological observations on twelve patients of pure neuritic leprosy, the interesting observations being that all the patients showed lepromin positivity and a narrower histological spectrum, ranging from TT to BB only.

An attempt was made to establish an animal model for analysing the cellular immune alterations following thermal injury and to correlate the results with those obtained in humans. A standard burn involving 20 per cent of the body surface area was established in C57 black mice (b1). The results revealed a loss of total T cells until post-burn day 10 and an increase in B cells only during post-burn day 1. The lymphocyte proliferative response to PHA was elevated with the appearance of null cells on post-burn day 10. This observation revealed a generalized depression in the immune responses which was significant until post-burn day 10. However, the results were not comparable with the human studies.

The index branch of the radial cutaneous nerve has been demonstrated as a constant nerve which can readily biopsied under local anesthesia and yields a nerve which is of suitable size for quantitative and qualitative studies both by light and electron microscopy. It supplies a limited but constant area where the sensory loss does not disturb the patient. Definite ultrastructural changes have been demonstrated in the clinically normal nerves of leprosy patients. These nerves have also revealed a loss in the small myelinated and unmyelinated fibers, which correlated with the common clinical findings of the absence of sweating and dissociated sensory loss in this disease. Gross damage has been encountered in nerves which showed only early signs of clinical damage even with refined methods of sensory testing. These nerves would have passed as normal on routine testing by No. 5 nylon. Regeneration of small fibers was noted following loss of large size fibers. Nerve conduction velocity may be a useful tool in early diagnosis.

In patients sustaining thermal injury, a sequential study was formulated to evaluate Fc and complement receptor expression of polymorphonuclear cells (PMN). Additionally, the role of factors in burn sera and maturity of PMN cells in the circulation were studied. The salient features of the study were: Marked reduction in Fc receptor expression by the 5th day of injury in both survivors and non-survivors. Thereafter levels gradually increased in survivors, though they were still below the normal range. In non-survivors, the depression was severe and persistent. In contrast to Fc receptor expression, complement receptor integrity was not grossly affected in both survivors and non-survivors. Burn sera collected from survivors on the 5th and 13th post-burn day showed reduction in Fc receptor expression of normal PMN cells, whereas sera obtained a month after the injury exhibited no inhibitory effect. Non-survivors sera inhibited Fc receptor expression of normal PMN cells on 5th, 13th and 21st post-burn days. The appearance, increase and disappearance of immature PMN cells in the circulation was correlated with the clinical progress of the patient. Mechanisms involved in the aberrations and its implications are discussed.

Although leprosy, a chronic disease caused by M. leprae, primarily affects skin and peripheral nerves, pathological changes and granulomas have been observed in lymph nodes which are: (a) present in tuberculoid lymph nodes in the absence of acid-fact bacilli and (b) persistent in lepromatous patients even after prolonged treatment. We detected substantial amounts of mycobacterial antigen in 16 leprous lymph nodes using anti-BCG by the peroxidase anti-peroxidase method. The load and distribution of antigen varied along the spectrum and with the duration of treatment. Tuberculoid and long-term treated lepromatous lymph nodes had a similar distribution of antigen in clusters of cells giving a 'speckled' appearance. The untreated lepromatous had a 'diffuse' staining of antigen in foamy histiocytes whereas lepromatous lesions with a lower bacillary load had a mixed pattern of 'diffuse' and 'speckled'. Antigen was also detected in a number of plasma cells along the spectrum but predominantly in lepromatous lymph nodes. Our observations indicate that: (a) antigen exists in lymph nodes despite prolonged chemotherapy which may be responsible for the persistent granuloma and (b) antigen is not confined to any particular anatomical compartment of the lymph node.

Cellular immune response was studied longitudinally for a period of 1 month in a group of 51 patients sustaining burns between 20 and 55 per cent of their body surface area. The results indicated lymphocytopenia and significant depression in the total T cells in all the patients. T cells showed a significant rise in their levels in those patients who showed clinical improvement. Further, the loss of expression of 'E' receptor correlated with the lowering of the protein-synthesizing capacity of the mononuclear cells. The functional integrity of the lymphocytes also showed an inability to recognize and stimulate normal alloantigens in an MLR reaction. Investigation of the mechanisms responsible for immunosuppression revealed the generation of T suppressor activity.

Since the resolution of neural lesions and subsequent nerve damage in leprosy must inevitably involve the participation of immune cells sensitized to Mycobacteria, we have used the dissociated Schwann cell culture model to study the relationship between M. leprae-infected Schwann cells and sensitized immune cells. Our earlier study on light and ultrastructural observations showed that on infection with M. leprae, the cytomorphology of Schwann cells remains unaffected, while degenerative changes suggestive of apoptosis are seen in extraneous lymphocytes which are subsequently phagocytosed by the Schwann cells. We now present additional evidence confirming that the phagocytosis of splenic cells by Schwann cells is indeed a two-step process. The first involves M. leprae-dependent cytotoxicity to splenic cells. This is followed by phagocytosis of these cells, which is a secondary and M. leprae-independent phenomenon. This finding has implications particularly on the weak inflammatory response observed in nerve lesions of a majority of lepromatous patients.

A patient recorded to be suffering from tuberculoid leprosy since 1973 and on regular Dapsone monotherapy for about nine years developed asymmetrical, erythematous, subcutaneous, nodular swellings restricted chiefly to the extensor aspects of lower limbs two months after discontinuation of Dapsone therapy. During the course of Dapsone treatment, the patient had developed similar swellings twice previously each time when he stopped the drug for about a month. The swellings disappeared on commencement of Dapsone Treatment. This has been reconfirmed under our supervision. The biopsy of one of the lesions revealed panniculitis with vasculitis. The original diagnosis of leprosy was probably invalid.

Sensory and mixed nerve conduction studies were performed on the distal segments of the radial, sural, median and ulnar nerves of leprosy patients from the entire spectrum of the disease. The values obtained were compared with those of age matched normal controls. All the clinically involved nerves, and about 30% of the clinically normal patient nerves showed a delayed conduction velocity. The conduction velocity difference was most significant (P less than 0.001) for the cutaneous branch of the radial, and sural nerves as compared to the ulnar and median. Five patients nerves that were clinically normal and showed a normal conduction velocity when tested in vivo, were biopsies and studied in vitro to determine the type of early nerve damage. C and A delta fibre involvement was found in all these nerves. It is concluded that leprosy is a diffuse neuropathy and there is early detectable nerve involvement even in clinically normal nerves of leprosy patients.