RESUMO
INTRODUCTION: Autologous tumor cell vaccines rely on the concept of preserving an individual's own tumorigenic makeup, expressing its unique set of tumor-associated antigens as well as antigenic elements from the surrounding stroma. These autologous tumor characteristics are usually presented with an immune adjuvant in the hopes of enhancing an immune response. METHODS: The autologous vaccine we used was composed of tumor cells combined with BCG and formalin. Animal safety and toxicity were evaluated using mice tumors for the immunotherapy. A small number of patients with advanced stage breast cancer were recruited for an uncontrolled study, using the vaccine solely or combined with chemotherapy/radiotherapy. RESULTS: The immunotherapy had shown to be safe in mice and humans. Upon a 5-year follow-up, the survival rate was 60 % for the combined treatment. CONCLUSIONS: The data suggest that the combined treatment could be a feasible and safe therapeutic strategy. However, further controlled studies should be conducted.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Neoplasias da Mama/terapia , Vacinas Anticâncer/uso terapêutico , Mycobacterium bovis/imunologia , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/mortalidade , Vacinas Anticâncer/imunologia , Quimiorradioterapia , Cricetinae , Feminino , Cobaias , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Taxa de SobrevidaRESUMO
American cutaneous leishmaniasis is an endemic anthropozoonosis that exhibits a broad spectrum of clinical presentations. Intermediate/borderline disseminated cutaneous leishmaniasis is a distinct clinical condition that comprises cutaneous disease of a chronic nature, usually occurring as multiple lesions with or without mucosal involvement. The disease is usually caused by parasites of the subgenus Viannia, frequently occurs in context of an underlying disease, and is often resistant to standard antileishmanial therapy. We report a case that was refractory to standard therapy and other second-line drugs, but resolved after treatment with fluconazole, and review the use of fluconazole as a second-line drug in children.
Assuntos
Antifúngicos/uso terapêutico , Fluconazol/uso terapêutico , Leishmania braziliensis , Leishmaniose Cutânea/tratamento farmacológico , Criança , Feminino , Humanos , Leishmaniose Cutânea/parasitologia , Resultado do TratamentoRESUMO
Although curable, leprosy requires better diagnostic and prognostic tools to accompany therapeutic strategies. We evaluated the serum samples of leprosy patients from Venezuela and Brazil for reactivity against the specific recombinant proteins, ML0405 and ML2331, and the LID-1 fusion protein that incorporates both of these antigens. Antigen-specific IgG was highest in lepromatous leprosy patients (LL) and decreased across the disease spectrum, such that only a small subset of true tuberculoid patients (TT) tested positive. The impact of multidrug therapy (MDT) on these antibody responses was also examined. Several years after treatment, the vast majority of Venezuelan patients did not possess circulating anti-LID-1, anti-ML0405, and anti-ML2331 IgG, and the seropositivity of the remaining cases could be attributed to irregular treatment. At discharge, the magnitude and proportion of positive responses of Brazilian patients against the proteins and phenolic glycolipid (PGL)-I were lower for most of the clinical forms. The monthly examination of IgG levels in LL patient sera after MDT initiation indicated that these responses are significantly reduced during treatment. Thus, responses against these antigens positively correlate with bacillary load, clinical forms, and operational classification at diagnosis. Our data indicate that these responses could be employed as an auxiliary tool for the assessment of treatment efficacy and disease relapse.
Assuntos
Anticorpos Antibacterianos/sangue , Monitoramento de Medicamentos/métodos , Imunoglobulina G/sangue , Hanseníase/diagnóstico , Antibacterianos/uso terapêutico , Antígenos de Bactérias , Brasil , Humanos , Hanseníase/tratamento farmacológico , Estudos Longitudinais , Proteínas Recombinantes , Recidiva , Fatores de Tempo , Resultado do Tratamento , VenezuelaRESUMO
BACKGROUND: Diffuse cutaneous leishmaniasis (DCL), although rare, is profoundly incapacitating. At present there is no successful treatment for this progressive protozoan infection, which is associated with the absence of specific cell-mediated immunity (CMI) to Leishmania. This disease shares features with visceral leishmaniasis (VL), including specific CMI inactivity during active disease and a heavy parasitic burden, but VL responds well to treatment. Miltefosine is the first orally administered drug which has shown efficacy in the treatment of VL; it has not been adequately evaluated in the treatment of DCL. OBJECTIVES: To evaluate the efficacy of miltefosine in the treatment of DCL, using clinical, parasitological, histopathological and immunological criteria. METHODS: Sixteen patients with DCL were treated with miltefosine, 2.0-2.5 mg kg(-1) daily, for variable periods of time (75-218 days). Patients were hospitalized for the first month and evaluated every 2 weeks until the termination of treatment with routine laboratory chemistry, percentage clinical improvement, presence of parasites in skin smears, growth of parasites in culture medium and in hamsters, histopathological characteristics of the granulomas, adverse side-effects, and reactivity to leishmanin skin test antigen. Further cycles of treatment were given in some of these patients, particularly after suspension of treatment was followed by relapse. RESULTS: Patients showed dramatic clinical improvement and reduction in the parasite burden by day 15 after the initiation of treatment, which continued while treatment was maintained. By day 45, 15 patients showed 80-90% clinical improvement. Nevertheless, suspension of treatment was followed by the development of new lesions in all but one patient. Inoculation in hamsters was observed to be the most sensitive technique to detect persisting parasites. Adverse events were very mild. CONCLUSIONS: Miltefosine produced a dramatic clinical and parasitological response in patients with DCL and improvement continued during drug administration, but with a single exception all patients presented new lesions after suspension of treatment. There was no histological or skin test evidence to suggest the development of CMI during treatment, which may be an indispensable criterion for the evaluation of potentially effective drugs against DCL.
Assuntos
Antiprotozoários/uso terapêutico , Leishmaniose Tegumentar Difusa/tratamento farmacológico , Fosforilcolina/análogos & derivados , Adolescente , Adulto , Criança , Pré-Escolar , Resistência a Medicamentos , Feminino , Humanos , Leishmaniose Tegumentar Difusa/imunologia , Leishmaniose Tegumentar Difusa/parasitologia , Masculino , Pessoa de Meia-Idade , Fosforilcolina/uso terapêutico , Qualidade de Vida/psicologia , Recidiva , Falha de TratamentoRESUMO
We have evaluated biopsies from patients with atypical nodular and typical ulcerated lesions of cutaneous leishmaniasis, from leishmanin reactions and skin from normal individuals from Nicaragua, Honduras and Guatemala for the presence of inorganic particles using confocal microscopy with a polarised light source and conventional histopathological techniques. Analysis by semiquantitative confocal microscopy permitted the demonstration of significantly larger numbers of particles in atypical lesions. Silica and aluminium, important components of these particles, were less abundant in particles from normal skin. The histology of these atypical lesions, characterised by 'naked' sarcoidal granulomas with epithelioid differentiation but very few lymphocytes, was very similar to the histological reaction observed after 14 days in persisting inflammation at leishmanin skin test sites. The presence of these unusual lesions in areas of Central American countries characterised by the presence of large amounts of volcanic ash, as well the unexpectedly low prevalence of leprosy in Central America, suggest that environmental factors may contribute significantly to the frequency and clinical manifestations of these infections. Among possible environmental features, the presence of inorganic particles with immunomodulatory properties in the skin may be a significant factor.
Assuntos
Corpos Estranhos/diagnóstico , Leishmaniose Cutânea/imunologia , Hanseníase/imunologia , Pele , Alumínio/análise , América Central/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Corpos Estranhos/imunologia , Granuloma de Corpo Estranho/etiologia , Granuloma de Corpo Estranho/patologia , Humanos , Leishmaniose Cutânea/epidemiologia , Hanseníase/epidemiologia , Dióxido de Silício/análise , Erupções Vulcânicas/efeitos adversos , Erupções Vulcânicas/análiseRESUMO
Biopsies of 71 cases of atypical cutaneous leishmaniasis from Costa Rican patients were evaluated by histopathological procedures and attempts were made to culture Leishmania from nine biopsies. Leishmanin skin tests were carried out in 31 patients and 112 healthy individuals. Additional biopsies from 19 patients from Nicaragua were evaluated by routine histopathology. Ten biopsies were studied by confocal and nine by scanning electron microscopy. Inorganic material was analysed using an electron probe for microanalysis. Leishmania parasites were isolated from only two biopsies, but 90.3% of the patients from Costa Rica were leishmanin-positive, as were 27.7% of healthy individuals. Routine histopathological studies revealed naked granulomas formed by differentiated macrophages. Abundant inorganic material was observed in sections examined by confocal microscopy. Electron probe analysis revealed that silica and aluminium were the predominant elements in large particles. We postulate that the presence of this inorganic material, possibly of volcanic origin, in the skin may modulate the immunological response to Leishmania and may inhibit visceralization in the cases caused by Leishmania chagasi.
Assuntos
Leishmaniose Cutânea/patologia , Adolescente , Adulto , Alumínio/análise , Animais , Costa Rica/epidemiologia , Exposição Ambiental/efeitos adversos , Feminino , Granuloma/patologia , Humanos , Leishmania/isolamento & purificação , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/parasitologia , Masculino , Nicarágua/epidemiologia , Dióxido de Silício/análise , Pele/metabolismo , Pele/patologia , Testes CutâneosRESUMO
This study was aimed at investigating alternate methods for serodiagnosis of tuberculosis (TB), which are needed because bacteriologic diagnosis of childhood TB is difficult. A selection of 80 serum and saliva samples were tested from Warao indigenous children under 15 years of age; 34 high TB suspects (28 positive and 6 negative for the tuberculin skin test, TST) and 46 healthy contact children (32 positive and 14 negative for the TST). Several enzyme-linked immunosorbent assay (ELISA) serological tests were developed to test for Mycobacterium tuberculosis-specific antibodies, including serum IgA, IgG, IgE, and secretory IgA (sIgA) in saliva against 3 specific antigens (PPD, HSP60, 38 kDa). Of these, 2 antigens, PPD and 38 kDa, showed significantly higher reactivity. The sensitivity and specificity of these tests for diagnosis remained limited, between 26.5% and 38.2%, and 77.4% and 97%, respectively. Of all the samples studied and combinations realized between all isotypes and antigens combined with 3 isotypes (anti-PPD IgG, IgE, and anti-38kDa sIgA) managed to detect the largest number of patients, showing an improved sensitivity level of 64.7%, although specificity levels dropped to 81.8%. These results were compared with the Omega diagnostics commercial kit results. The commercial kits showed significantly lower reactivity (sensitivity of 20% and 13.33% to Myco G and Complex Plus, respectively) and a specificity of 100%. This study shows that in indigenous populations of Venezuela, where invasive procedures cannot be used to select samples but evaluation with a chest X-ray for radiological studies is available, the combination of 3 specific isotypes may be a useful tool to increase diagnostic accuracy with pulmonary TB in this population, when used together with clinical and epidemiological criteria.
Assuntos
Anticorpos Antibacterianos/imunologia , Imunoglobulinas/análise , Indígenas Sul-Americanos , Mycobacterium tuberculosis/imunologia , Tuberculose/diagnóstico , Adolescente , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulinas/imunologia , Lactente , Masculino , Sensibilidade e Especificidade , Teste Tuberculínico/métodos , Tuberculose/epidemiologia , Tuberculose/imunologia , Venezuela/epidemiologiaRESUMO
This study was aimed at investigating alternate methods for serodiagnosis of tuberculosis (TB), which are needed because bacteriologic diagnosis of childhood TB is difficult. A selection of 80 serum and saliva samples were tested from Warao indigenous children under 15 years of age; 34 high TB suspects (28 positive and 6 negative for the tuberculin skin test, TST) and 46 healthy contact children (32 positive and 14 negative for the TST). Several enzyme-linked immunosorbent assay (ELISA) serological tests were developed to test for Mycobacterium tuberculosis-specific antibodies, including serum IgA, IgG, IgE, and secretory IgA (sIgA) in saliva against 3 specific antigens (PPD, HSP60, 38 kDa). Of these, 2 antigens, PPD and 38 kDa, showed significantly higher reactivity. The sensitivity and specificity of these tests for diagnosis remained limited, between 26.5 percent and 38.2 percent, and 77.4 percent and 97 percent, respectively. Of all the samples studied and combinations realized between all isotypes and antigens combined with 3 isotypes (anti-PPD IgG, IgE, and anti-38kDa sIgA) managed to detect the largest number of patients, showing an improved sensitivity level of 64.7 percent, although specificity levels dropped to 81.8 percent. These results were compared with the Omega diagnostics commercial kit results. The commercial kits showed significantly lower reactivity (sensitivity of 20 percent and 13.33 percent to Myco G and Complex Plus, respectively) and a specificity of 100 percent. This study shows that in indigenous populations of Venezuela, where invasive procedures cannot be used to select samples but evaluation with a chest X-ray for radiological studies is available, the combination of 3 specific isotypes may be a useful tool to increase diagnostic accuracy with pulmonary TB in this population, when used together with clinical and epidemiological criteria.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Anticorpos Antibacterianos , Imunoglobulinas , Tuberculose , Estudos de Casos e Controles , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Indígenas Sul-Americanos , Sensibilidade e Especificidade , Teste Tuberculínico , VenezuelaRESUMO
Of a total of 11532 Venezuelan patients with American cutaneous leishmaniasis (ACL) receiving immunotherapy with a combined vaccine containing heat-killed Leishmania promastigotes and bacille Calmette-Guerin (BCG) during the period 1990-99, we evaluated 5341 from 4 widely separated geographical states. Clinical healing varied from 91.2 to 98.7%, with an average of 95.7%. Adverse reactions were mild and limited to those associated with BCG vaccination alone. Immunotherapy failures in 143 patients included 54.5% with typical localized ulcers and 45.5% with non-mucosal intermediate cutaneous leishmaniasis (ICL). Less than 2% of the patients in this study had lesions suggestive of ICL. The disproportionately large number of immunotherapy failures in the ICL group suggests that it should not be used as monotherapy in this group. Weaker reactivity to purified protein derivative in immunotherapy failures, while not statistically significant in the small group reported here, suggests the possibility that these patients develop a relatively torpid immune response. The high percentage of clinical cures achieved with immunotherapy, associated with few secondary effects and low cost, support the use of immunotherapy in the routine treatment of localized ACL.
Assuntos
Vacina BCG/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Vacinas Protozoárias/uso terapêutico , Animais , Humanos , Leishmania mexicana/imunologia , Leishmaniose Cutânea/imunologia , Testes Cutâneos , Falha de Tratamento , Resultado do Tratamento , Vacinas Combinadas/uso terapêuticoRESUMO
The American cutaneous forms of leishmaniasis include immune-responder individuals with localised cutaneous leishmaniasis (LCL) and non-responder individuals with diffuse cutaneous leishmaniasis (DCL). Patients with intermediate or chronic cutaneous leishmaniasis (ICL) have increased morbidity due to the length of their illness, atypical forms and areas of compromise. In the present study, we evaluated the expression of the leukocyte antigens (CD4, CD8, CLA: cutaneous lymphocyte antigen, CD69, CD83 and CD1a) and cytokines (IFN-gamma, IL-4, IL-10 and TGF-beta 1) in the lesions of patients with ICL (n = 18) using an immunocytochemical procedure. ICL results were compared with the information for LCL (n = 19) and DCL (n = 4). The numbers of CD4+ and CD8+ T cells in ICL were similar to those of LCL lesions, but significantly different (P < or = 0.05) from DCL lesions. LCL lesions have about half the numbers of early activated CD69+ cells as ICL, but most are CLA+ skin homing memory T cells, whereas ICL lesions have the highest number of CD69+ T cells, but about one-third of these cells expressed CLA. This suggests that the granuloma of ICL patients contains many activated T cells that are unprimed to cutaneous-launched antigens, thus contributing to an aberrant immune response. In contrast, DCL granulomas presented the lowest numbers of activated CD69+ and CLA+ cells, associated with the characteristic tolerogenic state of these patients. The immunolocalisation of cytokines showed a mixed cytokine pattern in ICL lesions with many positive cells for IL-10, TGF-beta 1, IL-4 and IFN-gamma, with a preponderance of the first two, and different from the prevalent Th1 and Th2 responses associated with LCL and DCL lesions, respectively. CD1a+ Langerhans cells were decreased (P < or = 0.05) in both ICL (271 +/- 15 cells/mm2) and DCL (245 +/- 19 cells/mm2) as compared to LCL (527 +/- 54 cells/mm2) epidermis. The percentage of IL-10+ epidermal Langerhans cells in ICL (33.69), from the total CD1a+ population, was higher than in LCL (17.45). In addition, fewer CD83+ primed Langerhans cells were present in ICL epidermis. The diminished participation of epidermal Langerhans cells, causing a defective signalling by the epidermis, in ICL lesions may account for the tissue-damaging state observed in these patients.
Assuntos
Citocinas/metabolismo , Leishmaniose Cutânea/fisiopatologia , Leucócitos/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T , Antígenos de Neoplasias , Doença Crônica , Humanos , Imunofenotipagem , Leishmaniose Cutânea/patologia , Leishmaniose Tegumentar Difusa/patologia , Leishmaniose Tegumentar Difusa/fisiopatologia , Leishmaniose Mucocutânea/patologia , Leishmaniose Mucocutânea/fisiopatologia , Glicoproteínas de Membrana/análiseRESUMO
An increase in the incidence of human visceral leishmaniasis (HVL) has been detected in recent years on Margarita Island, located off the NE coast of Venezuela. Recent studies have revealed reactivity to rK39 antigen (Leishmania chagasi) in 20% of 541 sera from domestic dogs in endemic communities; PCR reactions were positive using primers for the L. donovani complex. Here we report that isolates from human and canine infection, identified by isoenzyme analysis, correspond to L. infantum, zymodeme MON-1. This appears to be the first isolation and identification of an isolate from HVL on Margarita Island and demonstrates the presence of this zymodeme in the canine population.
Assuntos
Doenças do Cão/epidemiologia , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/veterinária , Animais , Antígenos de Protozoários/sangue , Doenças do Cão/parasitologia , Cães , Humanos , Incidência , Isoenzimas/análise , Leishmania donovani/enzimologia , Leishmania donovani/isolamento & purificação , Leishmania infantum/enzimologia , Leishmaniose Visceral/parasitologia , Reação em Cadeia da Polimerase , Prevalência , Venezuela/epidemiologiaRESUMO
Los contactos intradomiciliarios de pacientes con lepra representan una población con riesgo de infección . El uso combinado de pruebas cutáneas y ELISA revela el grado de sensibilización, la capacidad de respuesta inmunológica y casos subclínicos de la enfermedad. Con base en lo anteriormente expuesto y con la finalidad de justificar el uso de estas pruebas, de rutina en otros contactos, se entrevistó el evaluó clínicamente a 211 contactos intradomiciliarios, de 32 casos de lepra registrados. Se colocó a los contactos lepramina intradérmica y se determinó niveles de anticuerpos específicos contra M. leprae (prueba de ELISA con PGL-1). De la población evaluada, 99.88 por ciento presentó reacción de Fernández negativa y 2/3 de ella presentó una reacción de Mitsuda positiva. Sólo 30.85 por ciento constituyó un grupo de riesgo por presentar reacción de Mitsuda negativa. Al correlacionar las pruebas cutáneas con el ELISA se mostró que ninguno presentaba lepra en fase subclínica y que un sólo caso de ELISA débilmente positivo resultó ser una infección pasada autolimitada. No se justifica usar todas las pruebas inmunológicas, en todos los contactos. Se recomienda usar pruebas cutáneas para detectar grupos de riesgo y para orientar quimiprofilaxis, reservado el uso del ELISA sólo para grupos de riesgo demostrado.
Assuntos
Humanos , Masculino , Adolescente , Adulto , Feminino , Controle de Infecções/métodos , Quimioterapia Combinada , Hanseníase/diagnóstico , Hanseníase/patologia , Mycobacterium leprae/patogenicidade , Controle de Doenças Transmissíveis/organização & administração , Ensaio de Imunoadsorção Enzimática/métodos , Visita Domiciliar , Testes Cutâneos/métodosRESUMO
In this retrospective study we asses the molecular epidemiological situation of Tuberculosis of the city of Caracas, Venezuela in the year 1994, applying IS6110 DNA Fingerprinting of clinical isolates. Fingerprinting of Mycobacterium tuberculosis strains of sixty-four patients TB patients from all the 5 districts of the city revealed fifty-one distinct IS6110 patterns. Isolates from 20 patients (30%) had fingerprints that were shared with at least one other patient. Based on this sampling we conclude that at least a third of the tuberculosis cases in Caracas in the year 1994 were the result of recent and ongoing transmission, indicating micro-epidemics in the town.
Assuntos
Técnicas de Tipagem Bacteriana/métodos , Impressões Digitais de DNA , Mycobacterium tuberculosis/genética , Tuberculose/epidemiologia , DNA Bacteriano/genética , Humanos , Estudos Retrospectivos , Venezuela/epidemiologiaRESUMO
The frequency of American visceral leishmaniasis affecting humans on Margarita Island, Venezuela, has increased in recent years, and infected dogs appear to constitute the principal source of infection. ELISA tests with Leishmania donovani promastigotes and rK39 antigen from L. chagasi in serum from 541 dogs were positive in 33.1% and 21.6% of the samples, respectively. A second blood sample taken from 50 animals after 8-10 months revealed an increase from 24% to 40% of ELISA positivity to both antigens, suggesting high susceptibility and transmission in the canine population. Among 42 serologically positive dogs, 33% of which showed clinical signs of disease, 79% were positive in polymerase chain reactions using primers specific for the L. donovani complex. Control measures including epidemiological hypersurveillance, the humane sacrifice of infected dogs, and rapid diagnosis and treatment of human cases have been initiated.
Assuntos
Doenças do Cão/epidemiologia , Leishmaniose Visceral/veterinária , Animais , Doenças do Cão/parasitologia , Cães , Ensaio de Imunoadsorção Enzimática/métodos , Leishmaniose Visceral/epidemiologia , Reação em Cadeia da Polimerase/métodos , Venezuela/epidemiologiaRESUMO
La lucha antileprosa se incia en Venezuela en el siglo XIX, y se refuerza a comienzos del siglo XX. Con la creación del Ministerio de Sanidad en 1936 se inicia el servicio de lucha antileprosa y en 1946 se crea la División de Lepra, que se convertirá después en el Departamento de Dermatología, el cual actualmente forma parte del Instituto de Biomedicina, que es organismo rector de esta actividad a nivel estatal, y cuyas actividades a nivel operativo se realizan a través de los 31 servicios regionales de Dermatología Sanitaria. En 1985 se inició la aplicación de la poliquimioterapia supervisada como tratamiento de elección. La evolución de la lepra en Venezuela desde 1946 se caracteriza por un aumento de la detección y la prevalencia en los años inmediatos a esta fecha, con un descenso posterior desde la década del 60, estabilizándose la deteción desde inicios de la década del 80, con tasas alrededor de 0'25 (algo más de 500 casos) por 10.000 habitantes por año. Para este período de ha mantenido el descenso de la prevalencia, la cual mostró cambios bruscos en 1982 y 1995, por actuatualización de los registros. En nivel de eliminación de la lepra como problema de salud (de acuerdo al criterio de la OMS de una tasa de prevalencia inferior a uno ano por 10.000 habitantes), se alcanzó en Venezuela en 1997. En las entidadades federales, soleamente cuatro de las 23 (Apure, Barinas, Dojedes y Portuguesa) mantienen tasas de prevalencia por encima del nivel de eliminación. Dado el hecho de haber alcanzado el nivel de eliminación, manteniéndose relaticamente estables el número de casos nuevos y la tasa de detección, se propone que el criterio para clasificar a un país como "en fase de eliminación) sea más estricto e incluya, además de la tasa de prevaelncia, datos relativos a la detección de casos. El tipo clínico predominante es el multibacilar. Las tasas de detección por edade muestran un aumento gradual al avanzar en edad. La racón masculino/femenino se mantiene alrededor de 2. Un 10% de los casos presentaron algún grado de discapacidad, aunque discreta en la mayoría de los casos. Existe un porcentaje de casos nacidos en el ixterior que es superior a la proporción de población con esta característica en el país. La mayor proporción de casos proviene del área urbana, especialmente de las zonas marginales, aun cuando las tasas son mayores para la zona...
Assuntos
Hanseníase/história , Hanseníase/prevenção & controle , Venezuela/epidemiologia , Venezuela/etnologiaRESUMO
Humoral immune responses were studied in 24 leprosy patients treated with multidrug therapy (MDT) and 16 contacts. The patients were monitored for 2 to 3 years with repeated determination of IgG antibody levels directed to different mycobacterial proteins (Mycobacterium tuberculosis, Mt70; M. bovis, Mb65; M. leprae, Ml36, 28, 18, 10 kDa, and the complete protein M. leprae extract, MLSA). All recombinant antigens were used at 5 micrograms/ml concentration and the complete soluble M. leprae extract at 2 micrograms/ml. The results shown in this study reveal a clear decline in IgG antibodies directed toward mycobacterial proteins in the 12 multibacillary (MB) patients when they were submitted to MDT. Initially we found strong reactivity toward complete cytosolic protein and M. leprae membrane protein. The most reactive recombinant proteins in MB patients were Ml10, Ml36, Mt70 kDa and, finally, Ml18 kDa when compared to the paucibacillary (PB) group. After treatment was completed all lepromatous and borderline lepromatous patients showed low or undetectable levels as compared with their initial values before starting treatment.
Assuntos
Anticorpos Antibacterianos/sangue , Hanseníase/tratamento farmacológico , Hanseníase/imunologia , Mycobacterium/imunologia , Adulto , Busca de Comunicante , Feminino , Seguimentos , Humanos , Imunoglobulina G/sangue , Hanseníase/epidemiologia , Hanseníase Dimorfa/imunologia , Hanseníase Virchowiana/imunologia , Masculino , Mycobacterium bovis/imunologia , Mycobacterium leprae/imunologia , Mycobacterium tuberculosis/imunologiaRESUMO
Multibacillary (MB) leprosy patients treated with multidrug therapy (MDT) or MDT + immunotherapy (IMT) with BCG + heat-killed Mycobacterium leprae were tested annually for their ability to proliferate in vitro to the mycobacterial antigens BCG, M. leprae soluble extract, and intact M. leprae. IgM antibody responses to phenolic glycolipid I (PGL-I) were measured, as well as serum nitrite levels in patients' sera, before, during and after treatment. Patients who received only MDT did not present cellular reactivity to intact M. leprae antigens, in contrast to the results obtained with BCG, which elicited reactivity at time zero, that increased after treatment. Regarding PGL-I antibody variations in relation to the initial value, we observed a statistically significant marked decrease at the end of 2 years which continued to fall in successive evaluations. MB patients showed high initial serum nitrite concentrations which dropped drastically with treatment. This decay was apparently associated with the bacillary load present in these patients. The group submitted to IMT + MDT showed high and long-lasting T-cell responses to mycobacterial antigens in a significant number of initially unresponsive MB patients. There was a marked increase to M. leprae soluble extract and BCG, as well as a more variable response to whole bacilli. The antibody levels in this group of patients are sustained for a somewhat longer period and decreased more slowly during the 5-year follow up.