Memories and history of Hansens disease in Brazil told by witnesses (1960-2000)

Este trabalho é um resultado preliminar de pesquisa sobre a memória e história da hanseníase, deseenvolvida pela Fundação Oswaldo Cruz (Fiocruz) e Universidade Federal do Rio de Janeiro (UFRJ), através de depoimentos de quem padeceu da doença ou atuou contra ela. Apresenta as opções metodológicas adotadas pelos autores, um sucinto histórico da hanseníase no Brasil e dados a respeito do estágio em que se encontra a pesquisa, com extratos de depoimentos que constituem o acervo gerado. Na década de 1980 houve avanços, como a adoção do tratamento através da poliquimioterapia, que provocou a redução do índice de prevalência da doença, que passou de 16,3 casos por dez mil habitantes em 1985, para 4,57 casos para dez mil habitantes em 2000, em nosso país. A gênese e as atividades do Movimento de Reintegração das Pessoas Atingidas pela Hanseníase (Morban) são reveladas pelos testemunhos de Thomas Frist, cientista social norte-americano que trabalhou no Brasil nas décadas de 1970 e 1980, período de reestruturação das antigas colônias, e pelo de Cristiano Torres, ex-paciente, com passagens por preventórios e leprosários no Pará, personagem atuante, inclusive na proposição de políticas de controle da hanseníase

Distinct patterns of microvasculature in the cutaneous lesions of leprosy.

This work is an investigation on the microvasculature of the cutaneous infiltrates of leprosy with the immunohistochemical staining of endothelial cells in cutaneous biopsies. Anti-Factor VIII-related antigen antibody (anti-FVIII-ra) and Ulex Europaeus-1 lectin (UEA-1) binding were utilized as endothelial cell markers. Thirty-nine patients grouped according to the Ridley-Jopling classification (14 borderline tuberculoid, 18 borderline lepromatous, 6 lepromatous, and 1 indeterminate leprosy) were selected for this study. Two microvascular architectural patterns could be clearly distinguished: lepromatous lesions presented a dense and tortuous mesh of microvessels among the Mycobacterium leprae-glutted macrophages; whereas the microvessels in the tuberculoid lesions were restricted to the periphery of the granulomas and were not seen among the central epithelioid cells. We were able to distinguish three basic morphological kinds of infiltrate distribution related to the microvessels: micronodules, cords and macronodules. Intensifications of the FVIII-ra immunoreactivity and UEA-1 binding capacity were observed in the endothelial cells of microvessels involved by the inflammatory infiltrate. A distinct cytokine expression profile at the leprosy poles and the role of mast cells in angiogenesis were speculated as factors contributing to these distinct patterns. Growth of the lesion and systemic dissemination of M. leprae in the bipolar spectrum of leprosy may hypothetically be influenced by the vascular-infiltrate relationship. The detection of angiogenesis in the cutaneous lesions of leprosy may bring about alternate and/or additional strategies for leprosy treatment.

Dermal extracellular matrix in cutaneous leprosy lesions.

Thirty-eight biopsies of cutaneous lesions from leprosy patients [borderline tuberculoid (BT) 14, borderline lepromatous (BL) 18, lepromatous (LL) 6] were processed for staining of some extracellular matrix (ECM) components (collagen, proteoglycans, elastic fibers and fibronectin). Specific histological staining and the indirect immunofluorescence method with antibodies to collagen and fibronectin were utilized. The ECM of the normal dermis was strikingly modified in the inflammatory infiltrate. By Gomori's reticulin and anti-fibronectin immunostaining, replacement of the dense interlaced collagen fibers with a reticular mesh was observed in the infiltrate. The immunoreactivity obtained with anti-type I and anti-type III collagens showed positive fibrils and a lumpy pattern in the lepromatous and tuberculoid lesions with a higher amount in the lepromatous lesions. The lack of clear-cut boundaries between the normal dermis and the inflammatory infiltrate in the lepromatous (BL, LL) lesions was correlated with the blurred limits of the clinical lesions of this pole of the leprosy spectrum. Absence of elastic fibers in the infiltrate was a constant finding, and fuchsin-positive microfibrils were found in some infiltrates. The clear zone of lepromatous lesions was devoid of oxytalan fibers. Elaunin fiber rings around sweat gland acini were present even when the leprosy infiltrate was seen enveloping them. The original ECM is replaced by a newly assembled one, which is suited for the dynamic nature of the inflammatory process. The trophic effects of the ECM upon the cutaneous epithelial structures are modified so that atrophy and late degeneration ensues. These ECM modifications contribute, therefore, to the biological alterations of the skin functions in leprosy.

Reactional states in multibacillary Hansen disease patients during multidrug therapy.

It is well known that reactions are commonplace occurrences during the course of leprosy disease. Stigmatization may even be attributable to reactions which are also responsible for the worsening of neural lesions. A cohort of 162 newly-diagnosed baciloscopically positive patients from the Leprosy Care Outpatient Clinic of the Oswaldo Cruz Foundation (FIOCRUZ) was selected for this study. While 46% of the multibacillary (MB) patients submitted to the 24 fixed-dose multidrug therapy (MDT) regimen suffered reactions during treatment, it was found that all MBs were susceptible and that constant attention and care were required at all times. Fourteen per cent were classified as BB, 52% as BL, and 33% as LL. None of the variables under study, such as, sex, age, clinical form, length of illness, length of dermatological lesions, baciloscopic index (BI), or degree of disability proved to be associate with reaction among the patients studied. Reversal Reaction (RR) occurred in 45%, and Erythema Nodosum Leprosum (ENL) occurred in 55%. Among BB patients who developed reactions (15 patients), 93% presented RR; while among the LL patients who developed reactions (34 patients), 91% presented ENL. Likewise, ENL was very frequent among those with disseminate lesions, while RR was most often observed in patients with segmentary lesions. RR was also most likely to occur during the initial months of treatment. It was demonstrated that the recurrence rate of ENL was significantly higher than that of RR. Neither grade of disability nor BI was shown to be associated with RR and ENL reaction. However, the RR rate was significantly higher among patients showing BI < 3, while ENL predominated among those patients with BI > 3.

Use of the polymerase chain reaction in the diagnosis of leprosy.

One of the main limitations for successful epidemiological control of leprosy is the lack of a method for its diagnosis in subclinical cases. Because of the long incubation period of the disease, liberation and spread of Mycobacterium leprae during subclinical stages-principally in cases of untreated multibacillary forms of leprosy-constitute the main source of infection. This report describes the use of the polymerase chain reaction (PCR) for the detection of M. leprae in different types of tissue samples (blood, lymph, nasal secretion and hair) from an individual who was suspected of having leprosy. Although no conclusive diagnosis could be made by traditional diagnostic methods, the individual was found to be infected with M. leprae after amplification of the bacterial DNA.

Borderline--tuberculoid leprosy: clinical and immunological heterogeneity.

The authors analysed some immunological criteria in leprosy patients diagnosed as borderline tuberculoid by the presentation of different grades of skin lesions as well as different grades of nerve involvement. Only 50% of the patients presented a single skin lesion and 58% had none or only one affected nerve. Nineteen patients (39.6%) showed a positive lepromin reaction (induration > or = 5 mm). Patients with a positive skin test had a greater number of skin lesions when compared with patients with a negative lepromin test. Fifty-seven percent of the patients were found to be positive using a lymphoproliferation test (LTT) in response to Mycobacterium leprae antigens. Positive LTT results did not correlate with the number of skin lesions, but patients unresponsive to LTT had a lesser extent of nerve involvement. Four out of 18 patients (22%) released high IFN gamma levels in PBMC culture stimulated by M. leprae. (mean U/ml +/- SD = 142 +/- 72). All of these 4 patients presented only one skin lesion, although three of them had more than one affected nerve. Nineteen out of 21 patients (90.5%) showed no anti-PGL-1 antibodies in their serum. The low levels of anti-PGL-1 antibodies among these patients confirmed their tuberculoid background even in those with multiple skin lesions. These findings seem to attribute an important role to IFN gamma in restraining the spreading of the infection in the skin, but IFN gamma may have an opposite effect on the nerves. The potential pathological effects of IFN gamma during the delayed type of hypersensitivity can be related to its ability to synergise with other inflammatory cytokines such as TNF alpha, IL-1 beta, and others.

Two multidrug fixed-dosage treatment regimens with multibacillary leprosy patients.

This study compares the clinical, bacilloscopic, and histopathological evolution of 140 patients classified as having multibacillary leprosy with no previous specific treatment who were submitted to two multidrug treatment regimens with a fixed dose. Regimen I-Group 1: 70 cases received 600 mg rifampicin (RMP) + 100 mg dapsone (DDS) daily for three consecutive months followed by 100 mg DDS daily, self-administered doses for 21 months. Regimen II-Group II: 70 cases received 600 mg RMP + 300 mg clofazimine (CLO) once a month under supervision plus self-administered doses of 50 mg CLO + 100 mg DDS daily for 24 months. The bacilloscopic, histopathological and neuromotor evaluation parameters showed no statistically meaningful differences (P > 0.05) between the two groups except for reaction frequency (P < 0.05) in that group II patients presented the least number of reactional episodes during the treatment and in the dermatological examination at discharge. Follow-up after treatment was carried out for a consecutive four year period. During routine clinical examination one case submitted to regimen I developed nodular skin lesion over the right arm. Skin biopsy was done for histopathological examination and mouse foot-pad experiment by Shepard technique. The drug susceptibility test with DDS and RPM showed that M. leprae strain isolated was susceptible to both the drugs.

Evaluation of PCR mediated DNA amplification in non-invasive biological specimens for subclinical detection of Mycobacterium leprae.

DNA from Mycobacterium leprae, present in non-invasive clinical samples from leprosy patients, such as nasal secretion and hair bulbs, was submitted to amplification by the polymerase chain reaction using a M. leprae-specific repetitive sequence as a target. After optimization of sample processing and of the PCR conditions, we were able to detect DNA from M. leprae in both types of clinical samples, even from paucibacillary leprosy patients. The use of hair bulbs and nasal secretion as clinical samples for screening of household contacts and for the evaluation of a risk population, or for the follow-up of patients under chemotherapy, and monitoring of bacterial load is discussed.

Use of the anti-PGL-I antibody ELISA and the Mitsuda reaction in early diagnosis of leprosy.

Cutaneous reaction to the Mitsuda antigen and anti-PGL-I IgM antibodies (ELISA) were determined in 134 leprosy patients, 290 household contacts, 52 healthy controls and 43 tuberculous individuals. The multibacillary patients did not develop cell-mediated immunity (CMI), although they presented high levels of IgM (absorbance at 492 nm greater than 0.5). The paucibacillary patients presented CMI, although in varying degrees, and IgM levels did not exceed 0.5 absorbance units. Most of the contacts (107) showed a Mitsuda-positive test, and 25 of them were anti-PGL-I IgM seropositive (absorbance less than 0.5 but greater than 0.22), although none became ill during the two-year follow-up. Of the 17 Mitsuda-negative contacts, two exhibited an immunological status of lepromatous leprosy (negative Mitsuda test and positive serology; absorbance greater than 0.5) and became ill (one borderline lepromatous and one indeterminate leprosy). These results show that the immunological status of lepromatous leprosy can appear prior to clinical symptoms, and thus serology for anti-PGL-I IgM together with the Mitsuda test can be useful in an active search for new preclinical cases among high risk populations.

The dot-ELISA test for the detection of anti-PGL-1 IgM in leprosy patients and their contacts.

1. Since dot-ELISA has recently been reported to be a sensitive, simple and fast method, we have compared it with the conventional microplate ELISA method. Sera of 124 leprosy patients, 136 household and professional contacts, and 92 controls were tested for antibodies against a Mycobacterium leprae antigen using dot-ELISA on nitrocellulose membrane filters and microplate ELISA. 2. The sensitivity of the two techniques was similar for multibacillary patients, but dot-ELISA was less sensitive for paucibacillary patients although it was more specific (100%) than ELISA (93.4%). 3. Of 21 household contacts that gave a response by ELISA, 3 were also positive by dot-ELISA; one of these 3 developed indeterminate leprosy 12 months later and the other was diagnosed as borderline lepromatous after 28 months. 4. These data indicate that dot-ELISA has a high specificity and can be a useful tool in field evaluation.

Use of the anti-PGL-I antibody ELISA and the Mitsuda reaction in early diagnosis of leprosy

Cutaneous reaction to the Mitsuda antigen and anti-PGL-I IgM antibodies (ELISA) were determined in 134 leprosy patients, 290 household contacts, 52 healthy controls and 43 tuberculous individuals. The multibacillary patients did nort developed cell-mediated immunity (CMI), although they presented high levels of IgM (absorbance at 492 m > 0.5). The paucibacillatry patients presented CMI, although in varying degrees, and IgM levels did not exceed 0.5 absorbance units. Most of the contacts (107) showed a Mitsuda-postive test, and 25 of then were anti-PGL-I IgM seropositive (absorbance < 0.5 but > 0.22), although none became ill during the twoyear follow-up. Of the 17 Mitsuda-negative contacts, two wxhibited an immunological status of lepromatous leprosy (negative Mitsuda test and positive serology; absorvance > 0.05) and became ill (one borderline lepromatous and one indeterminate leprosy). These results show that the immunological status of lepromatous leprosy can appear prior to clinical symptoms, and thus serology for anti-PGL-I IgM together with the Mitsuda test can be useful in an activbe search for new preclinical cases among high risk populations

The dot-ELISA test for the detection of anti-PGL-1 IgM in leprosy patients and their contacts

Since dot-ELISA has recently been reported to be a sensitive, simple and method, we have compared it with the conventional microplate ELISA method. Sera of 124 leprosy patients, 136 household and professional contacts, and 92 controls were tested for a antibodies against a Mycobacterium leprae antigen using dot-ELISA on nitrocellulose membrane filters and microplate ELISA. The sensitive of the techniques was similar for multibacillary patients, but dot-ELISA was less sensitive for paucibacillary patients although it was more specific (100%) than ELISA (93,4%). Of 21 household contacts that gave a response by ELISA, 3 were also positive by dot-ELISA; one of these 3 developed indeterminate leprosy 12 months later and the other was diagnosed as borderline lepromatous after 28 months. These data indicate that dot-ELISA has a high spedificity and can be a useful tool in field evaluation

Effect of treatment on immune responsiveness in lepromatous leprosy patients.

This study was performed in order to analyse whether the immune unresponsiveness to Mycobacterium leprae, largely seen in lepromatous patients, persisted after discharge from treatment. Lymphoproliferation and skin tests were performed using two mycobacterial antigens (M. leprae and BCG) in three groups of lepromatous patients grouped by treatment status. Forty-seven per cent of the lepromatous patients tested acquired reactivity to M. leprae after long-term treatment.

IgM immunoglobulins reacting with the phenolic glycolipid-1 antigen from Mycobacterium leprae in sera of leprosy patients and their contacts

For the first time in Brazil it was investigated the occurrence of IgM anti-PGL-1 in the sera of household contacts of leprozy patients using the ELISA methodology. The sera of the multipatients. It was observed a high subclinical infection incidence among household contacts (19.4%). The percentage of leprosy development was 5% (1/21) among the seropositive contact group. This finding suggests that serology could be useful as prognostic test, but for better definition is necessary to tet a population from endemic area for long period time

IgM immunoglobulins reacting with the phenolic glycolipid-1 antigen from Mycobacterium leprae in sera of leprosy patients and their contacts.

For the first time in Brazil it was investigated the occurrence of IgM anti-PGL-1 in the sera of household contacts of leprosy patients using the ELISA methodology. The sera of the multibacillary patients showed significantly more immuno-reactivity than from the paucibacillary patients. It was observed a high subclinical infection incidence among household contacts (19.4%). The percentage of leprosy development was 5% (1/21) among the seropositive contact group. This finding suggests that serology could be useful as prognostic test, but for better definition is necessary to test a population from endemic area for long period time.

[Secondary sulfone resistance--presentation of a case of leprosy-Oswaldo Cruz Foundation, Rio de Janeiro-Brazil]. / Sulfono resistência secundária--relato de um caso setor de hanseníase-Fundação "Oswaldo Cruz", Rio de Janeiro-Brasil.

Report on a case of dapsone resistance in a BL patient with clinical diagnosis and laboratory confirmation. The resistance appeared after 17 years of dapsone treatment, and the laboratory tests revealed total resistance to all the tested dapsone concentrations. The case reported occurred in the city of Rio de Janeiro (Brazil) which presents a leprosy prevalence of 1.79/1,000.

Estudo dos dermatoglifos digitais em portadores de hanseniase. / Digital dermatoglyphics in leprosy

Foram analisadas 100 alteracoes nas impressoes digitais de hansenianos controlados no Ambulatorio Souza Araujo.Comparamos as impressoes digitais de cada paciente com as individuais arquivadas no Instituto de Identificacao Felix Pacheco, tomadas na epoca da identificacao civil.Os resultados obtidos sugerem o uso da tecnica de tomada de impressoes digitais como mais uma forma de se observar a evolucao clinica do paciente, atraves da regressao ou manutencao das alteracoes durante o tratamento e como possivel metodo de triagem, descobrindo portador real ou potencial da doenca