International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association最新文献

Emergence of drug resistant strains of Mycobacterium leprae was reported soon after the introduction of dapsone (diamino-diphenyl sulphone, DDS) for leprosy treatment (6, 10, 11). Three cases of multidrug-resistant strains of M. leprae have been reported recently (2, 8, 9, 13). In order to prevent multiple drug resistant strains of M. leprae from developing, current leprosy control strategies are based on early detection of cases and treatment with multidrug therapy (MDT) as recommended by the World Health Organization (WHO). We report here the identification of a multidrug-resistant strain of M. leprae from a patient who received inadequate therapy for leprosy. The drug resistant profile of the isolated strain was confirmed by the mouse footpad method and the identification of mutations in genes previously shown to be associated with resistance to each drug was made.

Nodular leprosy of childhood (NL) is a benign clinical variant of tuberculoid leprosy that affects breast-feeding infants and children that remained in a highly infected environment. The lesions resolve with complete healing and NL has been considered a manifestation of allergy and congenital immunity to Mycobacteria leprae. We studied the tissue reaction, Mycobacterial antigen frequency, and the lymphocyte subsets (CD45RO+, CD4+, CD8+, B, NK), dendritic cells (epidermal CD1a+ cells and S100+ dermal dendrocytes), and macrophages in skin lesions of a clinically well characterized NL group (N = 11). Results were compared to children (N = 23) and adults (N = 24) with classical tuberculoid leprosy. NL lesion histopathology was characterized by dense granulomatous inflammatory reaction, with a greater number of confluent tubercles when compared to the other groups. Neural compromise was seen in all biopsies. The frequency of Mycobacterium antigen was similar in all groups. The population of CD45RO+, CD4+ and CD8+ T lymphocytes, natural killer cells, B lymphocytes, CD1a+ epidermal cells, and macrophages of NL lesions did not differ from the other groups. The number of S100+ dermal dendritic cells of the NL group was smaller than that of the adult group, although it did not differ from the other group of children. Except for the confluent tubercules, our data could not disclose any other difference in the tissue reaction of NL, in spite of its peculiar clinical features and evolution when compared with the classical tuberculoid leprosy. The localization of NL lesions may be the result of the intimate skin contact with lepromatous parents or relatives, in areas such as cheeks, arms, buttocks, and limbs, and the innoculation of M. leprae into skin may strongly stimulate cell mediated immunity (CMI) against the bacilli. These circumstances might explain the good CMI response leading to high resistance, stability, and auto-resolution of nodular leprosy of childhood.

Footpad lesions of 3 nude mice infected by Mycobacterium leprae were studied at 9, 12, and 14 months after inoculation with light and electron microscope. The lesions were somewhat similar to those found in nodules in polar lepromatous leprosy. Striated muscles rather than nerves were the preferred site of the growth of M. leprae. Yet, M. leprae were identified in Schwann cells and endothelial cells, singly and in clumps. M. leprae filled macrophages, and free M. leprae were found in large numbers in the endoneurium without producing any significant demyelination.

A literature review was conducted to review work done to date on measuring stigma related to leprosy. References were obtained through a PubMed (Medline) search and through examining relevant bibliographies. Twelve papers were selected that addressed the issue of measurement of stigma and that contained a sample of the instrument used. Three unpublished studies were also included in the review. Studies that attempt to measure stigma can be broadly categorized in two groups, a) studies that assess the effects of stigma on the person affected, and b) surveys that assess community attitudes and/or practices. The study and questionnaire characteristics of the studies in both categories are described and compared. The studies reviewed indicate that leprosy stigma is still a global phenomenon, occurring in both endemic and non-endemic countries. The consequences of stigma affect individuals as well as the effectiveness of leprosy control activities. Despite enormous cultural diversity, the areas of life affected are remarkably similar. They included mobility, interpersonal relationships, marriage, employment, leisure activities, and attendance at social and religious functions. This suggests that development of a standard stigma scale for leprosy may be possible. Data obtained with such an instrument would useful in situational analysis, advocacy work, monitoring and evaluation of interventions against stigma, and research to better understand stigma and its determinants.

Eighty six adult female patients with multibacillary leprosy were included to study the sex hormone profile LH, FSH, and prolactin, as well as their gynecological events like menstrual function and fertility status. A third of the patients gave a history of irregularity of periods. The mean levels of LH and FSH were significantly higher in patients with multibacilary leprosy vis-à-vis the controls. Of the 24 married women with irregularity of periods, 12 (50%) were infertile. Seven of these patients had elevated levels of FSH and LH, almost reaching castration levels.

Leprosy patients lack specific cellular immunity against Mycobacterium leprae, but other immunological functions are thought to be preserved. However, in a leprosy sanatorium in South Japan between 1982 and 2000, we found that the average age at death of cured lepromatous leprosy patients was about 5 yrs younger than that of cured tuberculoid patients; [male/lepromatous, 76.0 +/- 10.0 yrs old vs. male/tuberculoid, 79.7 +/- 9.4 yrs old, p = 0.026], and [female/lepromatous, 78.0 +/- 10.5 vs. female/tuberculoid, 85.3 +/- 9.8, p = 0.0001]. This trend was also observed in autopsy records of two other leprosy sanatoria in Japan. In a prospective study based on their age in 1982, among females in the age group between 60 and 69, lepromatous patients (75.3 +/- 6.0 yrs) died earlier than tuberculoid patients (81.0 +/- 5.1 yrs) (p < 0.01). These findings suggest that lepromatous patients have higher risk of death even in a post-chemotherapy era.

In order for these findings to have practical significance in terms of leprosy control and prevention, it will be necessary to extend the linkage of chromosome 6q25 to another region endemic for leprosy. Replicative findings would likely mean that the chromosome 6q25 susceptibility gene is a variant of a common gene that promotes susceptibility to infection per se. Identification of the gene variant will hopefully reveal insight about transmission and disease incidence--the longstanding enigmas of leprosy. Whether a more effective, universal MDT treatment or another type of prevention (either vaccine or environmental) could be based on this knowledge, is an exciting prospect to contemplate.