Blastogenic response with autologous plasma and Mitsuda's reaction in leprosy patients and their unaffected sibs.

Many investigators have evaluated the influence of genetic constitution on the susceptibility to leprosy in studies linked to different types of research. To determine the possible existence of a family trait linked to the lymphoproliferation and to lepromin reactivity we studied the blastogenic response to phytohaemagglutinin, lepromin and M. leprae and the Mitsuda's reaction in leprosy patients and their unaffected sibs. Sixty-eight individuals were studied, 34 were leprosy patients (17 lepromatous and 17 tuberculoid leprosy) and the remaining were their sibs previously matched by sex and age. The indices of blastogenesis and lepromin reactivity were lower in lepromatous than in tuberculoid patients, that confirmed the immunological polarity of the two types of leprosy. Both the lymphoproliferation and Mitsuda's reaction results suggest different cell immune responses in leprosy patients and their unaffected sibs, so that the hypothesis of a family trait favouring the similarity of responses to these tests among sibs becomes unlikely.

Lymphocyte blastogenesis and lepromin reactivity in leprosy patients and their parents.

To determine whether there is an inherited familiar trait linked to the lymphocyte blastogenesis test (LTT), under stimulation with PHA, lepromin and Mycobacterium leprae in culture medium containing autologous plasma, this test was carried out in patients with the polar forms of leprosy and their parents. The lepromin reaction was also studied in the patients and their parents because, since the test is negative in lepromatous (L) patients and a greater proportion of negativity is detected among their relatives, it might be assumed that the lymphocytes of these individuals could have a lower tendency towards blastogenesis than lymphocytes of tuberculoid (T) patients and their relatives. Thirty individuals were studied, ten of them being leprosy patients (4 L and 6 T) and the remaining their parents; 115 LTT, including control and stimulated cultures, were performed. In the limited number of patients and parents studied, the results showed that mothers of either L or T patients displayed a similarly low response to the stimulants M. leprae and lepromin. The lepromin reaction was negative in all L patients and positive in 3 out of 8 parents, as well in all the T cases and their fathers. Fathers and their T descendants were lepromin positive and there was a certain relationship between this reactivity and blastogenesis. This might suggest a possible inherited familiar trait related to a relative degree of resistance. However, further evidences from studies with larger number of subjects are required to support this hypothesis.

Reflections on some aspects of leprosy among children in Brazil and in other countries.

The authors discuss the classification, clinical aspects, lepromin reactivity, and epidemiologic features of leprosy among children. The most frequent characteristics of each form of leprosy are described. Lepromatous leprosy is less frequent among children in countries of low endemicity and more frequent, even in the most advanced forms, in hyperendemic regions. Borderline forms are rare. In a large number of cases the initial manifestations are those of the indeterminate form and, in an even larger number of cases, of the tuberculoid pole. The evolution from indeterminate to the tuberculoid pole very frequently occurs in a few months or within less than one year. With respect to epidemiology, the authors consider the general frequency of leprosy among children and the frequency of each form of leprosy among children and adults. Data from surveys carried out in Brazil and other countries are presented. Children have a potential for the rapid development of immunoresistance and consequently of lepromin-positivity, and therefore only a few of them eventually develop lepromatous leprosy. This explains the low indices of lepromatous leprosy (approximately 5%) even in hyperendemic areas. Finally, they discuss the factors that may be responsible for the clinical manifestations of leprosy and their characteristics among children.

Indeterminate leprosy in a population survey and in the subsequent follow-ups of children in Burma.

The paper discusses various aspects of indeterminate (I) leprosy in the initial survey undertaken in the Burma BCG trial (69,242 inhabitants), and in the annual examinations of 28,220 children in the trial followed up over periods of five to eight years. Age-specific rates in the initial mass survey are presented. In total 1914 cases were detected (6.2% I, 76% T, 16% L and 1.8% B). Among the children in the BCG trial 768 cases were detected: 255 of them had the I form and their proportion (33%) was much higher than in the population survey. Of these 255 I cases only 4.3% had a negative or doubtful lepromin reaction. Two-thirds of these 255 cases evolved to the tuberculoid pole in less than one year. No L cases appeared in the trial population until ten and eleven years after the start of the trial. It is concluded that whereas a high proportion of indeterminate cases regress spontaneously or evolve towards the T pole, the indeterminate lepromin negative cases are important in the dynamics of the disease, because a proportion of them, if untreated, tend to envolve towards the L form. This stresses the importance of detection and treatment of I cases at an early stage in an effective strategy for controlling leprosy.

Alguns aspectos psicológicos, sociais e econômicos relacionados com a lepra / Some psychological, social and economical aspects related to leprosy

O A. considera certos aspectos psicológicos, sociais e econcômicos em relaçäo à história, manifestaçöes clínicas, evoluçäo dos conhecimentos e tratamento da moléstia. Eles resultariam principalmente da estigmatizaçäo do doente e familiares, e de sua rejeiçäo pela comunidade e até pelos próprios parentes. Estigma e atitude da populaçäo associam-se particularmente à ignorância sobre contagiosidade, aspecto e evoluçäo da doença, e atenuaram-se de modo acentuado, a partir do advento das sulfonas (1941) e de outras drogas. A ampliaçäo de conhecimentos e progresso no tratamento determinaram, em pouco menos de meio século, enfoque mais humano do problema e melhora considerável dos métodos de controle, com benefício enorme para doentes e familiares, e pronunciada reduçäo do impacto psicológico, social e econômico da moléstia

BCG vaccination of children against leprosy: fourteen-year findings of the trial in Burma.

The value of BCG vaccination in preventing leprosy among children was studied in an area of high leprosy endemicity in Burma through a controlled trial; one group of 13 066 children received BCG and another group of 13 176 served as controls. The overall protective effect of BCG, which was only about 20% over the 14-year period, was found to vary with the batch of vaccine, as well as age, sex, and contact status of the children. BCG protection was found to be independent of the initial tuberculin status of the children. The protective effect of BCG against the lepromatous type of leprosy could not be measured because of the low incidence. Protection was observed throughout the fourteen years of the study except for the first year. The results are compared with those of three other major BCG trials in leprosy. The trial has shown that BCG provides only a very modest level of protection and that BCG vaccination is not likely to be an important solution for leprosy control.

BCG vaccination of children against leprosy: fourteen-year findings of the trial in Burma

The value of BCG vaccination in preventing leprosy among children was studied in an area of high leprosy endemicity in Burma through a controlled trial; one group of 13066 children received BCG and another group of 13176 served as controls. The overall protective effect of BCG, which was only about 20% over the 14-year period, was found to vary with the batch of vaccine, as well as age, sex, and contacts status the children. The protective effect of BCG against the lepromatous type of leprosy could not be measured because of the low incidence. Protection was observed throught the fourteen years of the study except for the firts year. The results are compared with those of three other major BCG trials in leprosy. The trial has shown that BCG provides only a very modest level of protection and that BCG vaccination is not likely to be an important solution for leprosy control.

[Analysis of inter and intrapathologist concordance and discordance in a comparative study of the Madrid and Ridley-Jopling classifications of leprosy]. / Analyse de la concordance et de la discordance interet intrapathologistes dans une étude comparative des classifications de la lèpre de Madrid et de Ridley-Jopling.

Eighty-six patients of leprosy have been examined by three leprologists; they have been classified according to the Madrid classification and their lesions biopsied and sent to two pathologists for independent histopathological examination. The pathologists have not received any information regarding the cases. Firstly the "senior" pathologist (A) utilized the Madrid classification and the "junior" pathologist (B) the Ridley-Jopling classification. In a second phase, the "senior" pathologist utilized the Ridley-Jopling classification and the "junior" pathologist the Madrid classification. Both pathologists did not know their own previous histopathological diagnosis at the second phase. The analysis of concordance and discordance between the histopathological diagnosis of the two pathologists and for the same pathologist, on utilizing the two classifications, have elicited the following conclusions: 1. There has been more concordance between the two pathologists on utilizing the Madrid classification than the Ridley-Jopling classification for the lepromatous, borderline and tuberculoïd in reaction patients. 2. The comparison of the two classifications for each pathologist on "blindly" examination of the material, has shown more concordance for the "senior" pathologist than for the "junior" pathologist. 3. These observations have convoyed to the final conclusion that the Ridley-Jopling classification brings some difficulties to the pathologists with limited experience in leprology and therefore it should be utilized only by experienced pathologists. 4. This preliminary study shows the necessity of performing another one with larger number of patients, in the active phase, with larger number of pathologists, preferably from different countries, and by utilizing the same methodology of "blind" examination of the material.

Double blind trial on the effect of certain soluble cytoplasmic mycobacterial antigens on the late reactivity to lepromin.

Two hundred forty-four children between six months and 59 months of age from nursery schools and playgrounds in Ribeirão Preto, São Paulo, Brazil, were randomly allocated into five groups. These received: 1) intradermal BCG; 2) placebo; 3) antigen F, containing soluble cytoplasmic components of the mycobacteria Mycobacterium tuberculosis, M. aquae, and M. lepraemurium; 4) antigen G, containing soluble cytoplasmic components of M. piscium, and M. balnei, and 5) antigen H, containing soluble cytoplasmic components of M. leprae. BCG preinjected children had the highest proportion of positive late lepromin reactions. The injection of antigens F, G, or H had no effect on the late lepromin reactions. These findings contrasted with those observed in our earlier trial in which the injection of antigens X (containing soluble cytoplasmic components of the mycobacteria M. avium and M. gallinarum), Y (M. simiae, M. gallinarum, and M. avium), and Z (M. leprae, M. simiae, and M. borstelense) had caused significantly lower positive late lepromin reactions. By comparing the data of the present investigation with the findings of the first trial, it appears that the antigens obtained from M. borstelense and from either M. avium or M. gallinarum could have been instrumental in the impairment of lepromin activity observed in the first trial.

[Comparative analysis of the clinical diagnosis of hanseniasis and the histopathological examinations performed according to the criteria of the Madrid and Ridley-Jopling classifications]. / Análise comparativa entre o diagnóstico clínico da hanseníase e os exames histopatológicos realizados segundo os critérios da classificação de Madrid e a de Ridley-Jopling.

A comparative study of the Ridley-Jopling's (RJ) and of the Congress of Madrid's (CM) pathological criteria was made in the different clinical types and groups of hanseniasis. A concordance between both criteria was found in the Indeterminate group and in the regressive phases of the Virchowian (V), Tuberculoid (T) and Reactional tuberculoid (RT) types. Clinical RT was confirmed by pathology in 81.2% of the cases according to CM, whereas 46.2% were considered "Borderline" according to RJ. Out of the 48 clinically V patients, 17 (35.4%) were "Borderline" (BL-2, BL-1 and BB), but practically all were also pathologically V according to CM. It is concluded that there is no practical convenience in the establishment of histopathological sub-groups that do not perfectly agree with clinical criteria. The Authors stress the importance of the study of the plasmocytes in the V infiltrates, of the lymphocytes in all granulomas and of the differences in the involvement of the neural ends, specially between the T and V poles. The dyeing of lipids by the Sudan III is useful to perfectly characterize the V pole, recognize residual V structures, separate the sub-groups BT, BB and BL, help in the early diagnosis of V infiltrations and differentiate the edematous, diffuse, non-granular cytoplasmatic vacuolization of RT.

[Correlation between early (Fernandez) and late (Mitsuda) reactions in non-contact children and adolescents without manifestations of leprosy, tested with human lepromin and different concentrations of armadillo antigen in 3 double-blind trials]. / Corrélation entre les réactions précoces (Fernandez) et tardives (Mitsuda) chez des enfants et adolescents non-contacts et sans manifestations de lèpre, testés avec lépromine humaine et différentes concentrations de l'antigène du tatou en trois essais à double insu.

The authors carried out 3 double blind trials to determine the correlation between the early and the late lepromin reactions and to verify the practical and control values of the 48 hours or Fernandez reaction. Children and adolescents non-contacts were tested with human lepromin (40 x 10(6) bacilli/ml) and different concentrations of armadillo lepromin (160, 40, 20, 10, 5, 2,5, and 1 x 10(6) bacilli/ml). The conclusions are as follows: 1. The coefficients of correlation (r values) point out that the correlation between the two reactions is poor or almost null. 2. The negative or doubtful reactions, the most often observed, have no practical value because they are almost always followed by a positive Mitsuda reaction. 3. The positive Fernandez reaction was always followed by a positive Mitsuda reaction. Thus it has practical importance. However as the frequency of early positivity is low with human and armadillo lepromin of lower concentrations, recommended in routine testing, the 48 hours reading is unnecessary and without control value. It would represent a loss of time and money.