Advances in leprosy immunology and the field application: A gap to bridge.

Advances concerning the hosts' immune response to Mycobacterium leprae infection have focused on elucidating the immune pathomechanisms involved, with the hope that predictive diagnostic and prognostic parameters (biomarkers) for field use would emerge; however, improvements in our understanding of the immunologic responses to this complex disease have, to date, somewhat failed to provide the effective and robust methods for improving its predictive diagnosis in the field situation, particularly in those patients suffering from paucibacillary disease. In this contribution we have attempted to review some of the advances both in the immunology and immunopathology of leprosy, and also highlight the limited clusters of immune parameters that are now available. Most importantly, we point out the limitations that still prevail in the provision of effective biomarkers in the field situation for either: (1) the diagnosis of indeterminate disease, (2) predictive diagnosis of individuals developing reactional states, (3) monitoring efficacy of treatment, or (4) monitoring treatment of reactional states.

Advances in leprosy immunology and the field application: a gap to bridge

Advances concerning the hosts' immune response to Mycobacterium leprae infection have focused on elucidating the immune pathomechanisms involved, with the hope that predictive diagnostic and prognostic parameters (biomarkers) for field use would emerge; however, improvements in our understanding of the immunologic responses to this complex disease have, to date, somewhat failed to provide the effective and robust methods for improving its predictive diagnosis in the field situation, particularly in those patients suffering from paucibacillary disease. In this contribution we have attempted to review some of the advances both in the immunology and immunopathology of leprosy, and also highlight the limited clusters of immune parameters that are now available. Most importantly, we point out the limitations that still prevail in the provision of effective biomarkers in the field situation for either: (1) the diagnosis of indeterminate disease, (2) predictive diagnosis of individuals developing reactional states, (3) monitoring efficacy of treatment, or (4) monitoring treatment of reactional states.

Granulomatous Reactivation during the Course of a Leprosy Infection: Reaction or Relapse

Leprosy is a chronic granulomatous infectious disease and is still endemic in many parts of the world. It causes disabilities which are the consequence of nerve damage. This damage is in most cases the result of immunological reactions...

Leprosy in transplant recipients: report of a case after liver transplantation and reviewof the literature

Leprosy still is an important public health problem in several parts of the world including Brazil...

Guidelines on the role of skin care in the management of mobile populations.

The Task Force for Skin Care for All: Community Dermatology, when seeking to collate evidence for capacity to benefit, wanted to know how best to manage mobile populations. The task force met where there is most experience at a time of maximum migration to the Mediterranean islands and to Italy from Somalia, Sudan, Cote d'Ivoire, Tunisia, and Libya. Members attended the workshop hosted by Aldo Morrone at the San Gallicano Hospital, Rome, Italy. Issues discussed were the size of the problem, ethics and legality, potential value of the migrant, dermatologist as carer, challenges met by interpretation, good listening, and transcultural mediation. The experiences of the National Institute for Health Migration and Poverty at the San Gallicano Hospital in Rome, Ethiopia, Malta, and Lampedusa were key to the development of guidelines on cultural competence.

Granulomatous reactivation during the course of a leprosy infection: reaction or relapse.

BACKGROUND: Leprosy is a chronic granulomatous infectious disease and is still endemic in many parts of the world. It causes disabilities which are the consequence of nerve damage. This damage is in most cases the result of immunological reactions. OBJECTIVES: To investigate the differences between a type 1 leprosy (reversal) reaction and relapse on using histopathology. METHODS: The histopathological changes in 167 biopsies from 66 leprosy patients were studied. The patients were selected when their sequential biopsies demonstrated either different patterns or maintained the same pattern of granulomatous reaction over more than two years during or after the treatment of leprosy. RESULTS: In 57 of the patients studied, a reactivation was seen which coincided with a decrease in the bacteriological index (BI), suggesting that this reactivation (reversal reaction or type 1 leprosy reaction) coincides with an effective capacity for bacteriological clearance. In nine patients, an increase of the bacteriologic index (IB) or persistence of solid bacilli occurred during the reactivation, indicating proliferative activity, suggestive of a relapse. The histopathological aspects of the granulomas were similar in both groups. CONCLUSION: Bacterioscopy provided the only means to differentiate a reversal reaction from a relapse in patients with granulomatous reactivation. The type 1 leprosy reaction may be considered as a part effective immune reconstitution (reversal, upgrading reaction) or as a mere hypersensitivity reaction (downgrading reaction) in a relapse.

Utility of measuring serum levels of anti-PGL-I antibody, neopterin and C-reactive protein in monitoring leprosy patients during multi-drug treatment and reactions

Objective: To verify the validity of measuring the levels of Mycobacterium leprae‐specific anti‐phenolic glycolipid (PGL)‐I antibody, neopterin, a product of activated macrophages, and C‐reactive protein (CRP), an acute phase protein, in serial serum samples from patients for monitoring the leprosy spectrum and reactions during the course of multi‐drug treatment (MDT).Methods: Twenty‐five untreated leprosy patients, 15 multi‐bacillary (MB) and 10 paucibacillary (PB), participated. Eight patients developed reversal reaction and five developed erythema nodosum leprosum (ENL) during follow‐up. The bacterial index (BI) in slit‐skin smears was determined at diagnosis and blood samples collected by venipuncture at diagnosis and after 2, 4, 6 and 12 months of MDT. PGL‐I antibody and neopterin were measured by enzyme‐linked immunosorbent assay, whereas the CRP levels were measured by the latex agglutination method. Results: The levels of PGL‐I antibodies and neopterin were higher in the sera of MB than PB patients, which correlated with the patients’ BI. The serum levels of CRP did not differ significantly between the MB and PB patients. The serum levels of PGL‐I and neopterin were no higher in reactional patients than non‐reactional patients prone to such reactions. However, ENL patients had higher serum CRP levels than non‐reactional MB patients. The serum PGL‐I antibody levels declined significantly during MDT, in contrast to neopterin and CRP levels. Conclusion: Measuring the serum levels of PGL‐I antibodies and neopterin appeared to be useful in distinguishing MB from PB patients, whereas monitoring the levels of PGL‐I antibodies appeared to be useful in monitoring MB patients on MDT. Measuring serum CRP, although not useful in monitoring the patients, has limited significance in detecting ENL reactional patients

Duración del tratamiento para la reacción de reversión: una revisión. Volver al pasado

En este trabajo, se revisa la información existente sobre la duración de los tratamientos con prednisolona. Basándose en esta información y apoyado por la literatura y las propias observaciones del autor, se puede llegar a la conclusión de que Ias leprorreacciones tipo 1 deben tratarse con prednisolona durante un período más prolongado que Ias 12 semanas actuales aconsejadas por la OMS. El trabajo también advierte sobre la afectacion neural silente que puede presentarse cuando la prednisolona es discontinuada precozmente (AU)

Treatment duration of reversal reaction: a reappraisal. Back to the past.

In this paper, earlier data on the length of prednisolone treatment are re-examined. Based on those data and supported by the literature and the author's own observations, it can be concluded that type I leprosy reaction should be treated with prednisolone for a longer period than the 12 weeks, advised by the WHO. The paper also warns against silent nerve damage that may occur when prednisolone is discontinued early.

Identification and characterization of the ESAT-6 homologue of Mycobacterium leprae and T-cell cross-reactivity with Mycobacterium tuberculosis.

In this paper we describe identification and characterization of Mycobacterium leprae ESAT-6 (L-ESAT-6), the homologue of M. tuberculosis ESAT-6 (T-ESAT-6). T-ESAT-6 is expressed by all pathogenic strains belonging to the M. tuberculosis complex but is absent from virtually all other mycobacterial species, and it is a promising antigen for immunodiagnosis of tuberculosis (TB). Therefore, we analyzed whether L-ESAT-6 is a similarly powerful tool for the study of leprosy by examining T-cell responses against L-ESAT-6 in leprosy patients, TB patients, and exposed or nonexposed healthy controls from areas where leprosy and TB are endemic and areas where they are not endemic. L-ESAT-6 was recognized by T cells from leprosy patients, TB patients, individuals who had contact with TB patients, and healthy individuals from an area where TB and leprosy are endemic but not by T cells from individuals who were not exposed to M. tuberculosis and M. leprae. Moreover, leprosy patients who were not responsive to M. leprae failed to respond to L-ESAT-6. A very similar pattern was obtained with T-ESAT-6. These results show that L-ESAT-6 is a potent M. leprae antigen that stimulates T-cell-dependent gamma interferon production in a large proportion of individuals exposed to M. leprae. Moreover, our results suggest that there is significant cross-reactivity between T-ESAT-6 and L-ESAT-6, which has implications for the use of ESAT-6 as tool for diagnosis of leprosy and TB in areas where both diseases are endemic.

Factors influencing the development of leprosy: an overview

The clinical manifestations of leprosy vary, seemingly depending on the host's immune response. Mode and route of infection, such as skin versus nasal mucosa, insect bites, sexual and gastroenteral transmission, together with genetic factors that may contribute to the outcome of the infection, including HLA, Lewis factor, Nramp1 and more subtle inherited alterations, are discussed. It is theorized that a balance between host responses elicited by different routes of infection and size and spacing of inocula is responsible for the clinical and immunological manifestations of the disease. Genetic factors and contact with environmental microorganisms may modulate these responses. The final result, resistance, delayed-type hypersensitivity, tolerance, disease or no disease, spectrum and reactions, is most likely reached via the orchestration of the induced cyto- and chemokines.

Environmental mycobacteria may induce recognition of auto-antigens: circumstantial evidence using maternal and cord blood

Background: It was assumed that the recognition of auto-antigens induced by environmental and infective micro-organisms may be involved in the clinical presentation of leprosy and a number of auto-imune diseases. Methodes: Serum antibodies to epidermal antigens in the blood of 21 healthy mothers and in the cordblood of their new-bor were compared using immunoblotting before and after absortion of the sera with mycobacteria (M. marinum, M. tuberculosis, M. kansaii). Results: Sera of the mothers caontained a higher antibody titre than that of their rspective babies. The pattern of bands for IgG was the same, for IgM the sera of 14 mothers showed more bandsthan that of their off-spring. Absorption with the mycobacteria, especially M. tuberculosis resulted in the partial or total disappearance of some bands. Conclusion: The results of this study provide some supportive evidence for the above-mentioned assumption. The observation that M. tuberculosis was the most effective in the absorption experiment may be because of the BCG vaccination all the mothers had received in infancy

Factors influencing the development of leprosy: an overview

The clinical manifestations of leprosy vary, seemingly depending on the host's immune response. Mode and route of infection, such as skin versus nasal mucosa, insect bites, sexual and gastroenteral transmission, together with genetic factors that may contribute to the outcome of the infection, including HLA, Lewis factor, Nramp1 and more subtle inherited alterations, are discussed. It is theorized that a balance between host responses elicited by different routes of infection and size and spacing of inocula is responsible for the clinical and immunological manifestations of the disease. Genetic factors and contact with environmental microorganisms may modulate these responses. The final result, resistance, delayed-type hypersensitivity, tolerance, disease or no disease, spectrum and reactions, is most likely reached via the orchestration of the induced cyto- and chemokines

Hanseníase e HIV: uma análise / Leprosy an HIV: an analysis

Após a introduçäo do HIV, o número de pacientes com tuberculose aumentou e muitos deles, infectados com o HIV, sofrem de tuberculose. Em outras infecçöes micobacterianas, também foi demonstrada uma incidência aumentada nos pacientes infectados com HIV, mas näo na hanseníase. Muitos pesquisadores têm observado isso, mas os resultados têm sido conflitantes. Nos pacientes com HIV, contudo nunca foi encontrado um aumento maior na prevalência da hnaseníase e nem um aumento significativo de soroprevalência para o HIV entre os pacientes com hanseníase. Na África, durante os últimos 30 anos, tem sido vista uma contínua queda na incidência da hanseníase. Contudo, em anos recentes, esse declínio parece ter feito uma parada e, em algumas áreas, foi observado até um aumento dessa incidência. O autor considera que o Mycobacterium leprae näo causa a doença em pacientes já infectados com HIV, posto que o Mycobacterium leprae é virtualmente näo toxico e necessita uma imunidade mediada poe células (CMI) mais ou menos funcionante para causar a doença clínica