Histological studies in primary neuritic leprosy: changes in the apparently normal skin.

The visually normal skin of 196 patients diagnosed clinically to have primary neuritic leprosy was studied histologically to determine whether there were any specific changes due to the disease in this site. Histological changes due to leprosy were seen in 32.1% of the patients, and included, indeterminate leprosy in 19.4%, borderline tuberculoid leprosy in 6.6% and borderline lepromatous leprosy in 6.1%. The remaining biopsies showed mild non-specific dermal inflammation, mild nerve changes or no significant lesion. The nerve inflammation and/or granulomas were mostly in the deep dermal nerves or neurovascular complexes. This study shows that there is a cutaneous component to primary neuritic leprosy and the disease is not totally confined to nerves. The absence of visible hypopigmented patches in these patients is probably related to the deep location of the dermal inflammation.

Histological studies in primary neuritic leprosy: changes in the nasal mucosa.

The nasal mucosae of 39 cases of primary neuritic leprosy (PNL) registered at Karigiri were studied histologically to determine nasal mucosal involvement in PNL and its relevance to the pathogenesis of the disease. Specific changes of leprosy were seen in 20 (51%) biopsies, ranging from macrophage granulomas with acid fast bacilli, to epithelioid granulomas and nerve inflammation. The remaining biopsies revealed chronic inflammatory changes of the mucosa or mild non-specific nerve changes. These findings show that there are widespread effects of the disease even in PNL patients in whom the disease is believed to be confined to the peripheral nerves. The findings also show that early leprosy involvement can be found in the nasal mucosa even before lesions become apparent in the skin or other parts of the body. The nasal mucosa could be one of the sites for the primary lesion in leprosy. Clinical and histological examination of the nasal mucosa may be useful and important in the early diagnosis of leprosy and especially in contacts.

Computerized mathematical model of M. leprae population dynamics during multiple drug therapy.

A computerized mathematical model of M. leprae populations during multiple drug therapy (MDT) was constructed. Relevant published information available to date was fed into it, and reasoned assumptions were made. From the model, it seems likely that MDT steadily selects bacteria resistant to the most powerful of the three drugs used: unless the individual bactericidal potencies of the drugs balance one another. If the drugs used have differing potencies, cure probably hinges on treatment being continued until all metabolically active bacteria are killed. Withdrawal of treatment before that could lead to relapse with bacteria resistant to the most powerful of the drugs used.

The mouse footpad test--sensitive to small proportions of drug-resistant bacilli in a sample of M. leprae.

In experiments at the Radda Barnen Research Laboratories of the SLR & TC Karigiri, the mouse footpad test was demonstrated to detect DDS-resistant M.leprae even if as few as 0.1% (1 in 1000) of the M. leprae tested were DDS-resistant. The mouse footpad test appears to be sensitive to minute proportions of drug-resistant bacilli in samples of M. leprae tested.

An ultrastructural study of the response of traumatized rabbit tibial nerve to epineurial infection with Mycobacterium leprae.

Crushed rabbit tibial nerves were inoculated with a suspension of living Mycobacterium leprae at and just distal to the site of nerve trauma. The resulting changes occurring over a period of time from 40 min to 72 hr post-inoculation were studied electron microscopically. Bacilli were seen in perineurial cells and in macrophages that had infiltrated the perineurium adjacent to epineurial deposits of M. leprae. It is suggested that trauma may weaken the perineurial barrier and facilitate the transperineurial passage of phagocytes, some of which may be laden with M. leprae, and may thus be a means whereby M. leprae enter the endoneurium of peripheral nerves.

Reactional states in the nasal mucosa: a clinical and histopathological study.

Twenty leprosy patients in the reactive phase of the disease were studied clinically and histologically for evidence of reactive lesions in the nasal mucosa. Ten of 14 patients with erythema nodosum leprosum (ENL) showed characteristic polymorphonuclear leukocytic infiltration and two patients showed vasculitis. The histological changes of reversal reactions in the nasal mucosa, one with upgrading reaction and the other with downgrading reaction, are reported.

An ultrastructural study of dermal nerves in early human leprosy.

Skin biopsies from the cutaneous lesions of seven patients with indeterminate, BT, BL, and LL leprosy of less than 1 year's duration were examined by light and electron microscopy. Inflammatory cells, which marked the location of Mycobacterium leprae in bacilliferous cases (BL and LL) were most frequently and consistently found in relation to dermal blood vessels, neurovascular bundles, nerves, arrector pili muscles, and skin adnexa. The number of bacilli and inflammatory cells in the epineurium was in great excess of those in the perineurium and endoneurium. Perineurial infiltration by lymphocytes and bacillated macrophages was seen to occur through gaps between the constituent cells of a loosened and sometimes proliferated perineurium. Bacillation of Schwann cells and associated inflammation in the endoneurium was minimal. M. leprae were identified in endothelial cells, arrector pili muscles, macrophages and Schwann cells. At this stage, inflammatory destruction of nerve fibers was not encountered. It is concluded that M. leprae which are extruded from the circulation into the epineurium (or perineurium) may be carried in inflammatory cells across the perineurium which is loosened and rendered permeable to inflammatory cells as a consequence of chronic inflammation in the adjacent epineurium. This is suggested as a very probable route for M. leprae to enter nerves.

The significance of dapsone (DDS)-resistant Mycobacterium leprae in untreated patients.

In a stable rural population of South India, 18 consecutive untreated persons newly discovered to have leprosy with a Bacterial Index (BI) greater than or equal to 2+ were tested for Mycobacterium leprae resistant to dapsone (DDS) by the mouse foot pad test. Of 12 successful tests, five detected resistant M. leprae. Known contact with a treated patient in the ten years preceding the diagnosis of leprosy was not found to increase the risk of DDS-resistant M. leprae occurring in an untreated, newly diagnosed patient. This data is consistent with the bulk of evidence in the field of bacteriology, which makes it seem unlikely that treated patients are the only source, or even the major source, of resistant M. leprae in untreated patients. Bacterial mutants resistant to a drug have been shown to precede initial use of the drug. Tests for drug-resistant bacteria in untreated patients before a drug is widely used in a community are likely to be important for subsequent evaluation of resistance to the drug in that community.

Response to dapsone (DDS) monotherapy in leprosy patients of Gudiyatham Taluk, South India: comparison between the 1960s and the 1970s.

At the Schieffelin Leprosy Research and Training Centre, Karagiri, India, 148 lepromatous (LL) and borderline lepromatous (BL) leprosy patients registered for treatment in the years 1971 to 1973 were found to respond as well to dapsone (DDS) monotherapy as 391 LL and BL patients registered in 1964 to 1966, as indicated by clearance of Mycobacterium leprae from skin smears during the initial seven years of therapy in each patient. Apparently, the efficacy of DDS monotherapy has not been progressively diminishing since the introduction of DDS monotherapy into the area.