Animal models for early leprosy.
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Biomedical subjects
Publications and source records attributed to C K Job.
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1. Much of the nerve destruction in leprosy takes place during the reactive phase, both during ENL reaction and RR. 2. The high risk patients expected to develop RR are borderline patients with generalized lesions (more than 10 skin lesions) and those presenting with three or more thickened nerve trunks. 3. In RR there is a sudden enhancement of already existing DTH to M. leprae and its antigens resulting in the release of excessive quantities of TNF alpha, INF gamma, and IL-2. The triggering mechanisms of this phenomenon is poorly understood. 4. The already existing granulomas suddenly increase considerably in size due to oedema and rapid influx of lymphocytes, Langhan's and foreign body giant cells. Fragments of M. leprae are also present in the granuloma of some patients. 5. In RR, the acute granulomatous inflammation can produce destruction of nerves even to the extent of causing caseous necrosis of the nerve tissue and irreversible paralysis. The swelling of the nerves due to sudden increase in inflammatory cells and oedema within an unyielding perineurium produce ischaemia and transient paralysis. 6. With prompt administration of anti-inflammatory drugs, paralysis recovers quickly, if it is of ischaemic origin; but will not recover if the Schwann cells and other nerve tissues are destroyed as a result of the immune granuloma. 7. A course of corticosteroids for six months along with anti-leprosy therapy is suggested in high risk patients as a preventive measure. 8. Further the serious problem of continuing nerve damage after clinical cure should be urgently tackled.
Eleven lepromatous leprosy (LL) patients with a bacterial index (BI) of three and above who had undergone two years of multidrug therapy (MDT) and yet had positive skin smears at the end of treatment were chosen for this study. Biopsies from the skin and lymphnodes were histopathologically evaluated for the presence of granulomas and M. leprae. M. leprae isolated from the skin and lymphnodes were inoculated into the foot-pads of normal mice to test their viability. On histopathological examination of the biopsy specimens, it was found that granulomas and M. leprae were present in the skin and lymphnode biopsies of all patients except two, in whom, although granulomas persisted, M. leprae were not found in skin biopsy specimens. No growth was obtained in the foot-pads of mice inoculated with organisms isolated from skin and lymphnode biopsies of all 11 patients indicating a near complete bacterial kill. That would account for the extremely low relapse rates reported until now in LL patients who had undergne two years of MDT.
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Thirty paucibacillary (PB) patients were given multidrug therapy (MDT) PB regimen for six months and were examined clinically and histopathologically before therapy, at six months and 12 months after therapy; and in four patients, at 18 to 23 months after MDT. Histopathological activity was present in 50% and 25% of patients after six months and 12 months respectively after MDT. At 18 to 23 months, the four patients continued to have active lesions both clinically and histopathologically. On the basis of this study it is found that fixed duration of MDT is effective in a large majority of patients especially those with indeterminate leprosy. However, there is "delayed resolution" in a significant number of patients which in a few instances may turn out to be "treatment failures". Therefore, a regular follow up of high risk patients for at least two years and if possible, five years, with freedom to intervene with additional anti-inflammatory or antileprosy therapy as desired, is recommended.
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The pseudocholinesterase levels and the nature of the enzyme as shown by the dibucaine number (D.N.) were estimated in 720 controls and 420 lepromatous leprosy patients, and 301 tuberculoid leprosy patients. There was no statistical difference in the esterase levels between leprosy patients and normal controls. But the distribution of D.N. was significantly different in the leprosy patients compared to the normal population studied. The D.N. below 40 indicates the samples with the atypical pseudocholinesterase--the presence of which is genetically determined. The distribution of samples with D.N. below 40 was significantly higher in the lepromatous leprosy patients compared to the normal population or tuberculoid leprosy patients. It is proposed that since there is a greater incidence of the atypical enzyme in lepromatous leprosy cases, the presence of this enzyme or the deficiency of the typical enzyme may make a person more susceptible to leprosy.