Prospects of global elimination of leprosy as a public health problem by the year 2000.
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Biomedical subjects
Publications and source records attributed to L M Bechelli.
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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.
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.
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.
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.
The morphology and ultrastructure of peripheral blood lymphocytes from patients with paracoccidioidomycosis (PCM) and from unaffected individuals (controls) were studied before and after Ficoll-Hypaque separation and at the end of culture, stimulated with phytohemagglutinin. Patient lymphocytes were cultured in medium with autologous plasma (from the patient himself) and with homologous plasma (from an unaffected donor), while donor lymphocytes were cultured in medium with plasma from a patient or with plasma from the donor himself. The Ficoll-Hypaque mixture caused no morphological or ultrastructural changes in the lymphocytes of patients or of unaffected donors. Patient lymphocytes cultured in medium with autologous plasma showed different degrees of cytoplasmic and nuclear alterations, such as organelle dissolution, vacuoles, amorphous masses, deformed nuclei, and absence of nucleoli. Lymphocytes from control individuals cultured in patient plasma also showed ultrastructural alterations, though they were less marked, and a reduced number of 'blasts'. Patient lymphocytes cultured in medium with homologous plasma (from a control individual) showed a morphology similar to that of lymphocytes from control individuals cultured in medium with their own plasma, although with a lower number of 'blasts'. On the basis of the results obtained using that methodology, we draw the following conclusions: separation by Ficoll-Hypaque does not seem to alter the ultrastructure of patient or donor lymphocytes; patients with diffuse PCM and more markedly impaired general condition can exhibit lymphocytes with morphological and ultrastructural alterations capable of affecting their biological systems and functionality.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine the correlation between the lymphocyte transformation test (LTT) with phytohemagglutinin (PHA) and the clinical forms of American leishmaniasis (AL), duration of the disease and reaction to leishmanin, the authors studied 12 patients and compared them to 25 unaffected individuals. The ulcerated cutaneous form of the disease was observed in 4 patients, the ulcero-nodular lymphangitic form in 1, the mucous cutaneous form with destruction of the nose in 6, and the verrucous form in 1. General patient condition was satisfactory and the Montenegro reaction macroscopically positive with infiltrations of 5-15 mm in diameter. The results revealed no evidence of immunodeficiency among patients. No correlation was observed between clinical forms, duration of the disease and Montenegro reaction and LTT results. LTT with PHA does not appear to be an adequate indicator of the cell immune system in AL cases.
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.
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The lymphocyte transformation test (LTT) by phytohemagglutinin was carried out on lymphocyte cultures from patients with paracoccidioidomycosis, in medium with autologous plasma (from the patient) or homologous plasma (from an unaffected individual), and lymphocyte cultures from unaffected and apparently normal individuals, in medium with autologous plasma (from the individual) or homologous plasma (from a patient with paracoccidioidomycosis). Blastogenesis was evaluated morphologically by 'blast' percentage, and the results analyzed according to clinical form of the disease and general condition of the patient. In the medium containing autologous plasma, percentages below the lower limit of the confidence interval for the distribution of the values for apparently normal individuals were encountered more frequently among patients with diffuse extrapulmonary paracoccidioidomycosis and in poor general condition. When the lymphocytes from patients with the disease were cultured in medium containing homologous plasma, blastogenesis increased in most cases. The lymphocytes of unaffected individuals exhibited a lower response more frequently when cultured in medium containing plasma from patients with the disease than when cultured in medium containing their own plasma. These results suggest that existence of factor(s) inhibiting blastogenesis in the plasma of these patients. In addition to such factor(s), an intrinsic lymphocyte defect may also occur in some patients, which might prevent a greater response to phytohemagglutinin even in homologous plasma. Smears of lymphocytes cultured in autologous plasma and obtained from patients, especially those with diffuse extrapulmonary disease and in regular or poor general condition, and smears from most of the controls whose lymphocytes were cultured in the plasma of these patients revealed deeply stained cells with altered morphology and considerably reduced in number.(ABSTRACT TRUNCATED AT 250 WORDS)
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.
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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.
A total of 9,955 schoolchildren aged 6-16 years have been examined in a tropical region. The prevalence of dermatosis varied from 21 to 87% in the municipalities surveyed. The most common dermatoses were pediculosis (prevalence 50%), nevi (16.8%), pityriasis versicolor (13.2%), pyoderma (12.2%), pityriasis alba (9.9%), dermatophytosis (6.2%), viral dermatosis (6.2%), scabies (3.0%) and acne vulgaris (2.7%). The prevalence of angular stomatitis, miliaria rubra, candidiasis, piedra nigra, keratosis pilaris, ephelides and geographic tongue is lower but still relatively high. Females had higher rates of pediculosis capitis and males higher prevalence of pityriasis alba. The prevalence of pityriasis versicolor, pigmented nevus and scabies was similar in males and females. Folliculitis, macular pigmented nevi and especially pityriasis versicolor tended to increase with age. Leprosy is hyperendemic in the surveyed area and its rate in the schoolchildren examined was 0.08%. Population movement (urbanization), socioeconomic situation, living conditions, promiscuity, and lack of hygiene may be the cause of such high prevalence and of association of two or more skin conditions. Climatic conditions might have enhanced the prevalence of certain dermatoses (pityriasis versicolor, dermatophytosis, piedra nigra, candidiasis, miliaria rubra).
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In the course of a WHO trial designed to evaluate the possible protective action of BCG vaccine against leprosy, a longitudinal epidemiological study of the whole population was carried out in an area of very high endemicity in Burma from 1964 to 1976. Two mass surveys of the whole population with an interval of 4 years and annual re-examination of the 28 000 children (0-14 years) in the BCG trial were carried out. The data collected yielded important information about general prevalence and yearly incidence of the disease as well as on sex, age, and classification of cases. The general prevalence rate declined from 32.6 per 1000 in the first survey to 25.2 per 1000 in the second. The number of cases among males was significantly higher than among females. Incidence rate among contacts of already known cases was 9.8 per 1000 person-years. The estimated yearly incidence among non-contacts was 5.9 per 1000. Prevalence rates reached a peak in the 20-39-year age group. The prevalence rate of multibacillary patients also reached a peak in the same age bracket. It is stressed that a further period of epidemiological surveillance will be essential in order to have a correct estimate of the expected number of new infections, especially multibacillary cases, in the 20-39-year group. The value of this information is considered unique for planning and programming of future control activities.
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