Immunoprophylactic trial with combined Mycobacterium Leprae/BCG vaccine against leprosy: preliminary results

Convit, J; Sampson, Celsa; Zúñiga, Marco; Plata, J.; Silva, J.; Molina, Juan; Pinardi, M. E.; Salgado, Antonio; Smith, P. G.; Bloom, Barry R.

doi:10.1016/0140-6736(92)91056-e

Cited by 96 publications

(41 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Attempts to produce leprosy vaccines have been limited to the use of proteins extracted from various mycobacteria in the laboratory setting and, until relatively recently, to the use of whole bacteria in the field setting (7,14,18). It has been argued, paradoxically, that MB leprosy contacts are both at an increased risk of developing leprosy and protected from leprosy.…”

Section: Discussionmentioning

confidence: 99%

“…This has impaired the ability to produce antigens for research purposes, and until recently, studies of antigen-specific immune responses during the course of the disease have been limited to using crude bacterial extracts or a few single M. leprae antigens purified from animal extracts (10,18,27). Partial vaccination against M. leprae can be achieved with other mycobacteria, but a defined subunit vaccine for leprosy is lacking (7,14). Following the recent completion of the M. leprae genome and other mycobacterial genomes (5,12), molecular biology and bioinformatic tools have revealed M. leprae-specific antigens that may be used for leprosy diagnosis or vaccination.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Antigen-Specific T-Cell Responses of Leprosy Patients

Duthie

Goto

Ireton

et al. 2008

Clin Vaccine Immunol

View full text Add to dashboard Cite

The identification of human T-cell antigens of Mycobacterium leprae could improve treatment and help to disrupt the transmission of leprosy by directing diagnosis and vaccine programs. This study screened a panel of M. leprae recombinant proteins for T-cell recall responses, measured by gamma interferon (IFN-␥) production, among leprosy patients. After initial studies using peripheral blood mononuclear cells from leprosy patients, we transitioned our studies to simple whole-blood assays (WBA), which are more applicable in field or clinical settings. T-cell responses generated in WBA using blood from individuals in Goiânia, Brazil, demonstrated that several M. leprae antigens (ML0276, ML0840, ML1623, ML2044, and 46f) elicited >0.5 IU/ml IFN-␥, and these proteins were classified as immunogenic and leprosy specific. Several of these individual antigens were recognized by cells from >60% of Brazilian paucibacillary (PB) leprosy patients, and ML0276, ML0840, ML1623, and 46f complemented each other such that 82% of PB patients had strong (>1.25 IU/ml IFN-␥) responses to at least one of these proteins. These proteins were also recognized by cells from a significant proportion of the household contacts of multibacillary leprosy patients, but in contrast, few responses were observed in active tuberculosis patients or healthy control groups from areas of endemicity. Our results indicate several potential candidate antigens which may be useful for either leprosy diagnosis or vaccination and demonstrate the utility of leprosy WBA that can be applied broadly in clinical or field settings.Leprosy is a chronic disease with a wide range of clinical outcomes. Leprosy patients are predominantly diagnosed by the appearance of disease signs, but they can also be characterized by the physical and histological attributes of skin or nerve lesions or by their immune response to crude Mycobacterium leprae antigens (25). Individuals infected with M. leprae exhibit wide-ranging immunity. One end of this immunologic spectrum comprises paucibacillary (PB) leprosy patients, who have strong cellular immunity in the form of a Th1-type response characterized by antigen-specific gamma interferon (IFN-␥) secretion. This response controls bacterial growth and limits dissemination, typically resulting in a few small and localized lesions. At the other end of the spectrum, multibacillary (MB) patients have poor cellular immunity but potent humoral immunity. Responses of MB patients do not control bacterial growth, and infection becomes systemic, typically resulting in disseminated lesions and significant nerve function impairment. Identifying antigens that are the target of the cellular immune response could direct the development of a defined leprosy vaccine.Despite vigorous efforts, conditions that permit the in vitro culture of M. leprae bacilli have not yet been identified. This has impaired the ability to produce antigens for research purposes, and until recently, studies of antigen-specific immune responses during the course of the disease hav...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Antigen-Specific T-Cell Responses of Leprosy Patients

Duthie

Goto

Ireton

et al. 2008

Clin Vaccine Immunol

View full text Add to dashboard Cite

show abstract

“…The presence of BCG scars has been associated with some protection against the development of the disease. It has been suggested that two or more BCG scars may reduce the incidence of the disease, especially the MB forms (6,7,19).…”

mentioning

confidence: 99%

“…Bacillus Calmette-Guérin (BCG) vaccination has been extensively applied to humans, and the use of its intradermal injection for leprosy prevention has been proposed (18), but results are controversial (2,3,6,7,15). Many reports have confirmed its interference with the Mitsuda response, stimulating positivity (10,11,27).…”

mentioning

confidence: 99%

Risk and Protective Factors for Leprosy Development Determined by Epidemiological Surveillance of Household Contacts

Goulart

Souza

Marques

et al. 2008

Clin Vaccine Immunol

100

View full text Add to dashboard Cite

Household contacts of leprosy patients are the group with the highest risk of developing the disease, and although many risk or prevention factors have been identified, they have not been employed in leprosymonitoring programs. This investigation aimed to establish the relative risks or the preventive effects of the presence of BCG vaccination, the Mitsuda test, and the ML-Flow assay. Household contacts (1,396) were monitored for a 5-year period. Twenty-eight contacts (2%) developed leprosy and had their clinical and operational classifications established. All immunological tests were performed, and intradermal BCG vaccination was given after the BCG scar count. Of the affected contacts, 75% developed the disease in the first year, and 71.4% were classified as having paucibacillary forms. Contacts of lepromatous leprosy patients presented a 3.8-fold-higher risk of developing leprosy. BCG vaccination and the Mitsuda test showed a protective effect against leprosy of 0.27 (at least one scar) and 0.16 (>7 mm), respectively, and the positive ML-Flow test indicated a relative risk approximately sixfold higher for occurrence of the disease. All unfavorable combinations of two and three assays generated significant risk values that ranged from 5.76 to 24.47, with the highest risk given by the combination of no BCG scar, negative Mitsuda test, and positive ML-Flow test. We suggest that the BCG vaccination may be given to stimulate Mitsuda test positivity, reducing the patient's risk of developing multibacillary forms. The high significance of these tests may have a great impact on programs to monitor contacts and should be used to improve early detection and treatment.

show abstract

“…El estado actual de los conocimientos sobre la utilización de vacunas contra la lepra (10)(11)(12)(13)(14) no ha permitido emprender aún acciones de prevención primaria. Sin embargo, la consideración de la lepra como problema de salud pública y la introducción de la poliquimioterapia cambiaron diametralmente la imagen sombría que ofrecía la lucha contra la enfermedad en años recientes (9).…”

Section: Introductionunclassified

La eliminación de la lepra de las Américas: situación actual y perspectivas

Lombardi¹,

Martolli²,

Silva³

et al. 1998

Rev Panam Salud Publica

View full text Add to dashboard Cite

RESUMENEn la actualidad, la lepra es una enfermedad curable (1-5) como resultado de los avances de la quimioterapia y, especialmente, de la utilización desde 1981 de la poliquimioterapia recomendada por la OMS (6, 7). En los últimos 15 años, la experiencia acumulada con este esquema terapéutico (que consiste en la administración de tres medicamentos -rifampicina, clofazimina y dapsona-para tratar los casos multibacilares o paucibacilares de acuerdo con la clasificación operacional de la lepra recomendada por la OMS (8)) ha mostrado que este tratamiento es muy efectivo para curar la enfermedad; es aceptado por la mayoría de los pacientes; tiene efectos secundarios mínimos, y previene la aparición de cepas de Mycobacterium leprae resistentes a los medicamentos (9).El estado actual de los conocimientos sobre la utilización de vacunas contra la lepra (10-14) no ha permitido emprender aún acciones de prevención primaria. Sin embargo, la consideración de la lepra como problema de salud pública y la introducción de la poliquimioterapia cambiaron diametralmente la imagen sombría que ofrecía la lucha contra la enfermedad en años recientes (9). El perfil epidemiológico de la lepra cambió notablemente en la mayoría de los países endémicos (1, 2) y su eliminación se convirtió en una meta factible (7, 15). En 1991, la Asamblea Mundial de la Salud aprobó la resolución relativa a la eliminación de la lepra como problema de salud pública a nivel mundial y nacional en el año 2000 (1, 2). Esta decisión histórica de la comunidad internacional ha tenido una enorme repercusión, ha despertado el interés de los países en el control de la enfermedad y ha contribuido a aumentar el número de pacientes tratados con poliquimioterapia (16). Por otra parte, el término "eliminación", incluido en la definición de la meta, ha creado cierta confusión (16,17). La eliminación no debe ser confundida con la erradicación, por cuanto esta última supone la interrupción completa de la transmisión, la reducción a cero de la incidencia y la desaparición total del agente causal (9) o, en otras palabras, la supresión de toda fuente de infección o infestación, de tal manera que, aunRev Panam Salud Publica/Pan Am J Public Health 4(3), 1998 149 1 Las solicitudes de separatas han de dirigirse a este autor a la siguiente dirección postal: Organización

show abstract

Immunoprophylactic trial with combined Mycobacterium Leprae/BCG vaccine against leprosy: preliminary results

Cited by 96 publications

References 2 publications

Antigen-Specific T-Cell Responses of Leprosy Patients

Antigen-Specific T-Cell Responses of Leprosy Patients

Risk and Protective Factors for Leprosy Development Determined by Epidemiological Surveillance of Household Contacts

La eliminación de la lepra de las Américas: situación actual y perspectivas

Contact Info

Product

Resources

About