The genetic hypothesis for susceptibility to lepromatous leprosy

Summary Evidence for genetic influence of the host response to infection with Mycobacterium leprae is reviewed. A complex segregation analysis is performed on data for 91 families from Mactan, Philippines, in each of which at least one offspring developed lepromatous leprosy. The data are not found to be inconsistent with an autosomal recessive hypothesis for susceptibility to lepromatous leprosy. Heritability estimates in the range of 80% were calculated for sib-sib pairs under the multifactorial hypothesis for susceptibility. It is argued that the multifactorial hypothesis is more in keeping with available immunologic, epidemiologic, and demographic data than is the single gene hypothesis.     

Toxoplasma gondii antibody in patients of lepromatous leprosy

Sera from 140 lepromatous leprosy patients (test group) and 120 normal persons, who showed no clinical signs of acute or chronic toxoplasmosis (control group), were studied for the presence of Toxoplasma gondii antibody by indirect hemagglutination and indirect-immunofluorescent antibody tests. Both tests showed a high incidence of Toxoplasma antibody in the test group in comparison with the control group. IgM and IgG classes of antibody responses were observed in both the groups, which signified recent as well as past infections in them.     

Suppressor T lymphocytes from lepromatous leprosy skin lesions

The immune response in leprosy forms a spectrum with lepromatous leprosy patients exhibiting specific unresponsiveness to antigens of Mycobacterium leprae. This unresponsiveness is thought to be related to the prevalence of T8-positive lymphocyte in these lepromatous lesions. To analyze the immunoregulatory function of these T8 cells, we developed simple procedures to extract lymphocytes from skin biopsy specimens of patients with leprosy. These lymphocytes were sorted for T8 and T4 positive cells, and cell lines were established by expansion with interleukin 2 (IL 2) and irradiated feeder cells. All T8 positive lines tested were positive for IL 2 receptors and HLA-DR determinants. These lines were additionally assayed for lepromin-induced suppression of the normal peripheral blood lymphocyte Con A proliferative response. Thirteen of 32 lines from six lepromatous patients showed significant suppressor activity, whereas nine lines from six tuberculoid patients and one line from normal peripheral blood failed to show suppression (p less than 0.001). Taken together, the finding of M. leprae-triggered suppressor cells within lepromatous skin lesions may in part explain the M. leprae unresponsiveness of lepromatous leprosy patients.     

Laryngotracheobronchitis: 2 years' experience with racemic epinephrine.

A relatively new form of treatment of laryngotracheobronchitis, administration of racemic epinephrine by intermittent positive-pressure breathing, was begun in 1973 in the pediatric unit of a large community hospital. A review of 2 years'' experience with this treatment, compared with the experience of the 3 years prior to its introduction, has shown that it has reduced significantly the necessity for tracheostomy, to nearly zero, and the duration of hospital stay. A total of 119 children (33.15% of those admitted) received this treatment, the average number of treatments required being 1.8. There were no important complications of treatment and no deaths.     

Immunologic indices in a varying course of lepromatous leprosy

The study of the proliferative and regulatory functions of lymphocytes in patients with lepra of the lepromatous type has shown that at the active stage of the disease both the response of lymphocytes to mitogens and their suppressor functions are decreased. During the regression of the disease these characteristics are restored to the normal level only in patients with the relapse-free course of the disease, while patients with relapses in their medical history retain the low level of such characteristics. It is expedient to use these cell-mediated immunity characteristics as signs permitting the formation of risk groups of patients who may expect the relapse of the disease.     

Hydrogen sulfide poisoning: review of 5 years' experience.

The workforce of Alberta, a province rich in fossil fuel, faces an increasing risk of exposure to hydrogen sulfide (H2S). Basic knowledge of the population exposed during the years 1969 to 1973 inclusive was accumulated to identify the immediate medical and management problems. Data were recorded from three sources of records: the Workers'' Compensation Board of Alberta, the Alberta Hospital Services Commission and the provincial coroner''s office. There were 221 cases of exposure to H2S. The overall mortality was 6%; 5% of victims were dead on arrival at hospital. Admission to hospital was required for 65% of the victims arriving at a hospital emergency room (78% of the 221). Acute problems were coma, dysequilibrium and respiratory insufficiency with pulmonary edema. Increased attention to cardiopulmonary resuscitation at the exposure site and during transportation to hospital is necessary to reduce the mortality from H2S exposure. No long-term adverse effects were apparent in the survivors.     

Health surveillance of preschool children: four years' experience.

OBJECTIVES--To monitor the implementation of a programme of health surveillance for preschool children and measure its effect on child health. DESIGN--Regular reporting to primary care teams of their own performance, and determining the overall effect of the programme on children in the district. SETTING--All practices in Northumberland health district. SUBJECTS--All children of preschool age in Northumberland (3600 births each year). MAIN OUTCOME MEASURES--Proportion of eligible children immunised and screened for abnormalities. Age at diagnosis of congenital deafness, cerebral palsy, and special educational needs. RESULTS--Over 90% of eligible children were covered by the health surveillance scheme. Child health improved over the four years after the scheme was implemented. Uptake of immunisation against measles rose from 68% to 93% of eligible children, and the average age at which congenital deafness was diagnosed fell to 9 months. CONCLUSIONS--Maintaining the effectiveness of a surveillance programme and reporting this back to primary health care teams are processes which themselves improve health.     

Home peritoneal dialysis: 3 years' experience in Toronto.

From November 1972 to November 1975, 52 males and 39 females aged 11 to 71 years were trained for home peritoneal dialysis. Dialysis was performed through a permanent catheter 4 nights a week. The first 11 patients used the manual system, exchanging 2 / of dialysate solution every 50 to 60 minutes. Subsequently 73 patients used the automatic cycler and commercially available dialysate and 7 patients used Tenckhoff''s reverse osmosis peritoneal dialysis machine. The average duration of training was 15, 11.6 and 15 dialysis days, respectively, for the three methods. For the 83 patients followed up, the average duration of home dialysis was 8.3 months (range, 0.5 to 33 months); the total number of dialyses at home was 10 571. Ten received a transplant, 20 were transferred to hospital peritoneal dialysis or hemodialysis, 8 died and 48 continued with home dialysis. Twenty-three patients had a total of 33 episodes of peritonitis, an incidence of 27.7% among the patients in the program for up to 3 years or 0.3% among all the dialyses. By November 1975, 46 patients had returned to their predialysis lifestyle, 18 were working part-time, 10 were able to work but were not doing so, and 9 were unable to work or care for themselves.     

A student-centred,problem-based curriculum: 5 years' experience.

In 1987, the University of Sherbrooke''s school of medicine implemented a student-centred, problem-based learning (PBL) curriculum. The experience of the first 5 years is reviewed; program goals, the schedule of learning activities, the instructional format and assessment of student learning are described. The new program is more demanding of teachers and requires better faculty training in pedagogy. No new financial resources have been available. The preclinical reform has led to revision of the clerkship, where sessions on clinical reasoning are now based on the PBL philosophy. Student reactions to the program are reported. The Sherbrooke experience has demonstrated that it is both possible and feasible to shift from a traditional to a problem-based curriculum.     

Mechanisms of Mycobacterium leprae-specific T-cell deficiency in lepromatous leprosy

Patients suffering from lepromatous leprosy fail to develop an efficient cell-mediated immunity towards Mycobacterium leprae, the causative agent. The mechanism of such a specific T-cell tolerance to the bacillus remains a key question in the pathophysiology of leprosy. Macrophages do not show any intrinsic defect in phagocytizing and killing M. leprae or in presenting antigen to helper T-cells. On the other hand, M. leprae-reactive helper T-cells do persist in lepromatous patients, but their activation appears to prevented by active suppressor mechanisms, involving both suppressor T-cells and macrophages. The target of this specific suppression could be the interleukin 2-producing T-cell subset. A better molecular definition of M. leprae antigens, both by monoclonal antibodies and T-cell clones, should open new perspectives for further analysis of the regulation of immune responses to M. leprae.     

M. leprae and PPD-triggered T cell lines in tuberculoid and lepromatous leprosy

Proliferative responses of peripheral blood mononuclear cells (PBMC) to Mycobacterium leprae and bacillus Calmette Guerin-derived purified protein derivative (PPD) were studied in the presence or absence of interleukin 2 (IL 2) in high M. leprae responders (tuberculoid leprosy patients and healthy subjects) and low M. leprae responders (lepromatous leprosy patients). High responders in most cases developed a strong proliferative response to both antigens in the absence of IL 2. Additional IL 2 and restimulation with antigen plus autologous antigen-presenting cells (APC) allowed the derivation of antigen-specific T cell lines. The lines were assayed for proliferative responses to several mycobacterial antigens. Both PPD and M. leprae-triggered T cell lines exhibited a good proliferative response to either antigen and showed in addition a broad cross-reactivity with other mycobacteria, suggesting a preferential T cell response to epitopes shared by several mycobacterial species. Within the lepromatous group, 50% of the patients studied could mount a proliferative response to PPD antigen in the absence of IL 2, but none of them was able to do so with M. leprae antigen. The addition of IL 2 increased the number of positive responders to PPD in this group, and in some patients IL 2 was able to restore M. leprae reactivity as well, suggesting that IL 2 had overcome a suppressor mechanism. PPD and M. leprae-triggered T cell lines were obtained from these subjects (with IL 2 added from the beginning of the culture when required). M. leprae lines exhibited variable and unstable pattern of specificity, most lines exhibiting, at least transiently, a cross-reactive response to other mycobacteria, but some displaying only M. leprae-specific response. In contrast, PPD lines from these subjects consistently exhibited a good response to PPD, a lesser response to various other mycobacteria and no response to M. leprae, a pattern differing from that obtained with PPD lines of high M. leprae responders. Co-cultures of irradiated lepromatous PPD triggered T cell lines with fresh autologous PBMC non-specifically reduced the proliferative response of the latter to PPD, as well as to unrelated antigens. A similar suppression was also observed when PPD lines from one of the tuberculoid patients were assayed. PPD and M. leprae T cell lines from both high and low responders initially exhibited the same CD4+ CD8- phenotype. In all cases, antigenic specificity declined and could not be maintained after 5 to 8 wk of continuous culture, a change associated with the progressive appearance of CD8+ and Leu8+ cells.     

Phenoloxidase activity in organisms isolated from lepromatous and tuberculoid leprosy

Anaerobic corynebacteria (propionibacteria), isolated in pure culture from the plasma of a case of tuberculoid leprosy and from lepromata of cases of lepromatous leprosy, exhibited phenoloxidase activity such as that shown by Prabhakaran to be associated with leprosy bacilli harvested from patients suffering from leprosy. Several corynebacteria, mycobacteria, and nocardias similarly examined did not produce phenoloxidase.