Diffuse (anergic) cutaneous leishmaniasis responding to amphotericin B.

American cutaneous leishmaniasis is an important endemic zoonotic disease in the New World that comprises a spectrum of clinical manifestations. Diffuse cutaneous leishmaniasis (DCL) is a rare form of the disease characterized by antigen-specific immunodeficiency that often presents with multiple disfiguring non-ulcerated confluent nodules or plaques that involve large areas of the skin, resembling lepromatous leprosy. Relapse is invariable in advanced stages, despite aggressive chemotherapy, and a plethora of drugs has been tested with unchanging results. We report on a severe an exceptional case that resolved after treatment with amphotericin B, a drug considered only mildly effective, and discuss the therapeutic approach to this disease.

Extensive chromoblastomycosis caused by Fonsecaea pedrosoi successfully treated with a combination of amphotericin B and itraconazole.

Chromoblastomycosis is a chronic infection caused by dematiaceous (dark-colored) fungi which affect the skin and subcutaneous tissues, and is characterized by a wide variety of clinical and dermatological features including papillomatous, verrucous and vegetating lesions. Although it has been described world-wide, most cases originate in tropical and sub-tropical areas. In general, present treatments of the disease are unsatisfactory as one of the most common etiologic agents, Fonsecaea pedrosoi is difficult to manage from a therapeutic point of view. We report a case of extensive chromoblastomycosis of 22 years duration caused by F. pedrosoi and review the clinical course, diagnosis and management of this disease.

Immunotherapy of american cutaneous leishmaniasis in Venezuela during the period 1990-99.

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.

Serologic response to mycobacterial proteins in hansen's patients during multidrug treatment.

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.

A follow-up study of multibacillary Hansen's disease patients treated with multidrug therapy (MDT) or MDT + immunotherapy (IMT).

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.

A longitudinal study of immunologic reactivity in leprosy patients treated with immunotherapy.

More than 150 leprosy patients treated with multidrug therapy (MDT) plus immunotherapy (IMT) with a mixture of heat-killed Mycobacterium leprae plus live BCG were studied in relation to humoral and cell-mediated immune responses. Many previously had received prolonged sulfone monotherapy. Patients received 2 to 10 doses of IMT in a period of 1 to 3 years, depending upon their clinical form of leprosy. The patients were followed up for 5 to 10 years with repeated determinations of antibody levels to phenolic glycolipid-I; lymphoproliferative (LTT) responses to soluble extract of M. leprae, to whole bacilli and to BCG, skin-test responses and bacterial indexes (BIs). After MDT plus IMT there was a statistically significant decrease of antibody levels in the multibacillary (MB) group. The BI decreased proportionally to the ELISA results. LTT increased to M. leprae antigens, especially to soluble extract, in a high percentage of these patients (34% of LL patients positive). Lepromin positivity in MB patients increased from 5% initially positive to 75% at the cut-off during this follow up. These results show substantial early and persistent cell-mediated reactivity to M. leprae in many MB patients treated with MDT-IMT, confirming and expanding previously published data.

Leprosy in women: characteristics and repercussions.

"Health is often measured in terms of low mortality; nevertheless, merely being alive is not a measure of the quality of life" H. Méndez Castellanos. Physiological, socioeconomic and cultural factors play important roles in the response of women to Mycobacterium leprae and in the impact of leprosy on their lives. They appear to develop stronger immunological responses to M. leprae than men, as suggested by lower incidence and less severe clinical forms of disease in most areas of the world, as well as stronger reactions of cell-mediated immunity after prophylactic vaccination. Genetic factors and physiological status including pregnancy, intercurrent infection and malnutrition might be among the factors which modulate this response. Women in leprosy-endemic areas of the world, with few exceptions, suffer from marked economic and social dependency and inferiority which can only be heightened by the social stigma associated with leprosy. Nevertheless, they bear an enormous responsibility for the health of their families, often as head of the household, and they often possess a unique capacity to influence community opinion. With the introduction of multidrug therapy, leprosy control throughout the world is no longer an unrealistic goal. Active vaccination may constitute the other factor necessary for eventual eradication of the disease. The incorporation of women at all levels into active roles in health care programs may constitute one of the decisive factors in the success or failure of leprosy control.

Preliminary study of cellular immunity to Mycobacterium leprae protein in contacts and leprosy patients.

Because of the good results obtained in the mononuclear cell (T lymphocyte) proliferative response in tuberculoid leprosy patients and family contacts and healthy Mitsuda-positive volunteers using Mycobacterium leprae soluble extract, we prepared different protein fractions from the soluble extract. We used the T-cell Western blot technique with separation by electrophoresis in SDS-polyacrylamide gels and transfer onto nitrocellulose membranes. Each unstained blot was converted into 18 fractions of antigen-bearing particles and tested with peripheral blood mononuclear cells from 21 individuals including Mitsuda-positive contacts, vaccinated lepromatous leprosy (LL) patients, borderline tuberculoid (BT) patients, and unvaccinated lepromatous patients. The stimulation index (SI) of the contacts was higher to the different fractions in comparison with the leprosy patients. They showed four peaks of stimulation to fractions 66-55, 45-29, 22-18, and 14 kDa. The second highest responders were BT patients, followed by vaccinated LL patients. The unvaccinated patients did not respond significantly to any of the fractions (SI less than 1).

Leukocyte subsets in the granulomatous response produced after inoculation with Mycobacterium leprae-BCG in lepromatous patients.

Leukocyte subsets present in the granulomatous response produced after the inoculation of a mixture of Mycobacterium leprae and BCG in lepromatous leprosy patients were characterized in situ using monoclonal antibodies and an immunoperoxidase technique. The granuloma produced after M. leprae-BCG inoculation showed a distribution pattern similar to tuberculoid granulomas. T lymphocytes bearing the CD8 phenotype (T cytotoxic/suppressor) were sequestered to the periphery of the epithelioid tubercles and T helper-inducer CD4+ lymphocytes were distributed throughout the infiltrate. Langerhans cells CD1+ were increased in the epidermis, and in dermis they were localized mainly in the mantle surrounding the granuloma. Most of the dermal infiltrate produced after the inoculation or M. leprae-BCG expresses the HLA-DR antigen. Similarly, most keratinocytes were also positive to this MHC antigen. The granulomatous response to BCG was similar to the inoculation of a mixture of M. leprae-BCG, however acid-fast bacilla were still present. The inoculation of M. leprae produced a macrophage granuloma with no clearing of the bacilla which resembles the lepromatous leprosy granuloma.

Immunosuppression and cellular immunity reactions in leprosy patients treated with a mixture of Mycobacterium leprae and BCG.

Suppressor reactivity was studied in a group of leprosy patients before and after immunotherapy with a mixture of Mycobacterium leprae and BCG. The treatment increases the responses in lymphocyte transformation tests to levels which are comparable to those observed in BT-TT patients and reduces suppressor activity. The soluble extract of M. leprae appears to be more sensitive than purified intact bacilli in the lymphocyte transformation tests, but this preparation did not induce suppressor reactivity with the regularity observed when using a Dharmendra preparation.

La citoestructura de Mycobacterium leprae en pellet y vacuolas fagocíticas del nódulo hanseniano activo / Structure of Mycobacterium leprae in pellet and phagocitic vacuoles of active hansen node

Se hace estudio ultraestructural del bacilo de Hansen a 20.000 x en pellet y en vacuola del nódulo hanseniano activo. Se observa su pared celular, membrana plasmática mesosoma y nucleoide. En su citoestructura no se diferencia de otras bacterias ya sean éstas Gram positivas o Gram negativas. Solo las diferencia su ácido resistencia la cual le da sus características tintoriales especiales

New projections in the development of a vaccination model using two microorganisms and its application in leishmaniasis and leprosy

Conventional vaccination is oriented toward the prevention of disease in individuals capable of developing normal immune responses. A new model of vaccination employing two microorganisms has been described for the correction of variable degrees of antigen-specifit deficiency in the development of effective cell-mediated immunity in two diseases, leprosy and cutaneous leishmaniasis, both of which are characterized by a spectrum of clinical manifestations. A schematic representation of the immunologic defect in the severe and progressive forms of these diseases and a possible mechanism for its correction using this vaccine model are presented. Immunotherapeutic and immunoprophylactic applications of the model are described, with particular reference to recent experience in the immunotherapy of localized cutaneous leishmaniasis. The efficacy, virtual absence of secondary effects, ease of administration and low cost of this therapeutic modality indicate that it offers an important option or field use in endemic of leishmaniasis

IgE in leprosy; effect of a Mycobacterium leprae-BCG vaccine.

Since some previous studies have reported elevated total serum IgE levels in leprosy, that may be associated with the existence of a state of generalized T cell anergy, we undertook a carefully controlled study of this immunoglobulin in such patients before and after treatment with a Mycobacterium leprae-BCG vaccine. We found, firstly, that lepromatous leprosy patients suffering active disease had only a moderate elevation of IgE levels that was not statistically significant when compared to appropriate controls. In addition, multiple injections of the vaccine did not cause alterations in the concentration of this immunoglobulin. We were, therefore, unable to confirm the possible existence of a generalized immunodeficiency in lepromatous leprosy that could cause hyper-production of IgE.