Interruption of Onchocerca volvulus transmission in Northern Venezuela.

BACKGROUND: Onchocerciasis is caused by Onchocerca volvulus and transmitted by Simulium species (black flies). In the Americas, the infection has been previously described in 13 discrete regional foci distributed among six countries (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela) where more than 370,000 people are currently considered at risk. Since 2001, disease control in Venezuela has relied on the mass drug administration to the at-risk communities. This report provides empirical evidence of interruption of Onchocerca volvulus transmission by Simulium metallicum in 510 endemic communities from two Northern foci of Venezuela, after 10-12 years of 6-monthly Mectizan (ivermectin) treatment to all the eligible residents. METHODS: In-depth entomologic and epidemiologic surveys were serially conducted from 2001-2012 in selected (sentinel and extra-sentinel) communities from the North-central (NC) and North-east (NE) onchocerciasis foci of Venezuela in order to monitor the impact of ivermectin treatment. RESULTS: From 2007-2009, entomological indicators in both foci confirmed that 0 out of 112,637 S. metallicum females examined by PCR contained L3 infection in insect heads. The upper bound of the 95% confidence intervals of the infective rate of the vector reached values below 1% by 2009 (NC) and 2012 (NE). Additionally, after 14 (NC) and 22 (NE) rounds of treatment, the seasonal transmission potential (±UL CIs) of S. metallicum was under the critical threshold of 20 L3 per person per season. Serological analysis in school children < 15 years-old demonstrated that 0 out of 6,590 individuals were harboring antibodies to Ov-16. Finally, epidemiological surveys made during 2010 (NC) and 2012 (NE) showed no evidence of microfilariae in the skin and eyes of the population. CONCLUSIONS: These results meet the WHO criteria for absence of parasite transmission and disease morbidity in these endemic areas which represent 91% of the population previously at-risk in the country. Consequently, the two Northern foci are currently under post-treatment onchocerciasis surveillance status in Venezuela.

Serologic follow-up of IgG responses against recombinant mycobacterial proteins ML0405, ML2331 and LID-1 in a leprosy hyperendemic area in Venezuela

Leprosy is a slowly evolving disease that occurs mainly in adults. In this study, the Mamaría Village, state of Portuguesa was selected because it had one of the highest prevalence rates (13.25%) of leprosy cases in 1997. Between 1998-2004, 20.2% of the 89 cases registered in this village were less than 15 years old and 61.8% were males. Pau-cibacillary (PB) lesions were the predominant clinical forms identified, although also multibacillary (MB) forms were found. Additionally, 76% of the patients were bacteriologically negative. At the time of diagnosis, 75% of the patients presented with grade 0 disabilities, 23% with grade 1 and 2% with grade 2. Serum samples were collected from 18 PB and 15 MB patients, in addition to 14 family contacts, at the beginning and end of treatment. All the groups were re-evaluated during a three-year period (2008-2011). The proteins used for evaluation were ML0405, ML2331 and LID-1. These mycobacterial proteins were highly specific for Mycobacterium leprae and the IgG responses decreased in both MB and PB patients during multidrug treatment. Our results suggest that these antigens could be used as markers for successful treatment of non-reactional lepromatous patients.

Cojedes: a leprosy hyperendemic state.

BACKGROUND: Leprosy is a chronic infectious disease produced by Mycobacterium leprae. In 1997 Venezuela reached the goal of elimination of leprosy as a public health problem (according to the World Health Organization a prevalence rate of ≤ 1/10,000 inhabitants), but five states still had prevalence rates over that goal. For this study we selected Cojedes State, where prevalence rates remain over the elimination goal. OBJECTIVE: Evaluate the real leprosy situation in high-prevalence areas of Cojedes State. MATERIALS AND METHODS: Seven communities of Cojedes State were selected because they had the highest historic prevalence, as well as the highest prevalence in the year to be studied (1997). RESULTS: A rank correlation using Spearman's test comparing historical prevalence rates (1946-1996) and detection rates (1998-2004) gave a statistically significant P < 0.05 value. Diagnosed leprosy cases were as follows: age: 3.2% under 15 years old; sex: male/female rates between 60% and 91.66% males. The highest number of cases were paucibacillary forms: indeterminate leprosy (33.07%) and borderline tuberculoid leprosy (32.28%); tuberculoid leprosy (7.00%); and multibacillary cases (lepromatous leprosy, LL) were only 2.36%. Bacteriologically, 18.52 patients were M. leprae positive. At the moment of diagnosis, 96.6% showed no disabilities, 3.4% showed grade I disabilities, and there were no grade II or III disabilities. CONCLUSION: This study confirms that several communities in Cojedes State have extremely high leprosy rates.

Serologic follow-up of IgG responses against recombinant mycobacterial proteins ML0405, ML2331 and LID-1 in a leprosy hyperendemic area in Venezuela.

Leprosy is a slowly evolving disease that occurs mainly in adults. In this study, the Mamaría Village, state of Portuguesa was selected because it had one of the highest prevalence rates (13.25%) of leprosy cases in 1997. Between 1998-2004, 20.2% of the 89 cases registered in this village were less than 15 years old and 61.8% were males. Paucibacillary (PB) lesions were the predominant clinical forms identified, although also multibacillary (MB) forms were found. Additionally, 76% of the patients were bacteriologically negative. At the time of diagnosis, 75% of the patients presented with grade 0 disabilities, 23% with grade 1 and 2% with grade 2. Serum samples were collected from 18 PB and 15 MB patients, in addition to 14 family contacts, at the beginning and end of treatment. All the groups were re-evaluated during a three-year period (2008-2011). The proteins used for evaluation were ML0405, ML2331 and LID-1. These mycobacterial proteins were highly specific for Mycobacterium leprae and the IgG responses decreased in both MB and PB patients during multidrug treatment. Our results suggest that these antigens could be used as markers for successful treatment of non-reactional lepromatous patients.

Immunological correlates of cure in the first American Cutaneous Leishmaniasis patient treated by immunotherapy in Argentina: A case report. / Correlatos inmunológicos de curación en el primer paciente con Leishmaniasis Cutánea Americana tratado con inmunoterapia en Argentina: Reporte de un caso

A patient with localized cutaneous leishmaniasis due to Leishmania (Leishmania) amazonensis infection was treated with an antigen containing heat-killed L. (L.) amazonensis promastigotes plus BCG. Expression of T-cell differentiation, memory and senescence receptors markers were analyzed on T cell subpopulations, in order to establish the correlation between the percentages of expression of these receptors and his clinical status, at different stages of his follow up. The following case reports on the achievement of a successful clinical outcome with complete resolution after receiving immunotherapy. A thorough clinical and immunological follow up supporting the healing process of this patient’s lesion is presented in detail.

Un paciente con leishmaniasis cutánea localizada producida por Leishmania (Leishmania) amazonensis fue tratado con un antígeno compuesto por promastigotes de L. (L.) amazonensis muertos por calor combinado con BCG. Se analizó la expresión de distintos receptores de diferenciación, de memoria y de senescencia en las subpoblaciones de células T, con el fin de establecer una relación entre los porcentajes de expresión de dichos receptores y la clínica del paciente en diferentes momentos del seguimiento. Se reporta en este caso un resultado exitoso, con resolución completa de la lesión después de recibir la inmunoterapia, y se presenta en detalle un seguimiento clínico e inmunológico completo durante el proceso de curación.

Reactividad serológica y celular frente a proteínas micobacterianas en la enfermedad de Hansen / No disponible

Se diseñó un estudio para evaluar la reactividad inmunológica frente a diferentes preparaciones proteicas micobacterianas utilizando pruebas serológicas y de inmunidad celular. Para el estudio fueron incluidos pacientes con manifestaciones clínicas de lepra predominantemente de la forma multibacilar. El 58% correspondía a la forma clínica de Lepra Lepromatosa (LL) n=81, el 29% a la forma Borderline Lepromatosa (BL) n=41 y 10% a Borderline Bordeline (BB) n=14. Sólo el 3% fueron pacientes Borderline Tuberculoide (BT): 74% masculino y 26% femenino. El fenómeno reaccional más frecuente fue de tipo eritema nodoso leproso (ENL). Las proteínas micobacterianas ensayadas fueron: antígenos proteicos crudos totales de Mycobacterium leprae (MISA), Mycobacterium bovis (MbSA y MbSA de excreción), antígeno proteico de excreción parcialmente purificado con una movilidad relativa de 30 kDa (MI30) y proteínas recombinantes de Mycobacterium (Mt70, Mb 65, MI 36, 28, 18 y 10 KDa) encontrándose que las proteínas recombinantes (MI 10KDa, MI36 kDa) a mayor carga bacilar presentaban una mayor reactividad serológica estadísticamente significativa (p=0.0051 y 0.050 respectivamente). La proteína de 30 kDa) a mayor carga bacilar presentaban una mayor reactividad serológica estadísticamente significativa (p=0.0051 y 0.0050 respectivamente). La proteína de 30 kDa fue predominantemente reconocida por anticuerpos de los pacientes multibacilares. Los resultados demuestran que el promedio de los valores de anticuerpos en pacientes no reaccionales fueron superiores en presencia de proteínas completas (MbSA y MbSA de exreción) en comparación con el grupo de pacientes que presentaron fenómenos reaccionales (p=0.000567 y 0.000061 respectivamente). Este mismo comportamiento se observó frente a las proteínas micobacterianas individuales (30kDA, 10kDa y 36 kDa). La respuesta proliferativa de los linfocitos T en los pacientes multibacilares reaccionales y no reaccionales frente a las proteínas micobacterianas (MISA, ML 10kDa, MbSA, MbSA de excreción) fue negativa en ambos grupos (AU)

The study was designed for evaluating immunological reactivity to various mycobacterial protein preparations using serological and cell-mediated immunological test in patients with clinical leprosy signs, predominantly, with the multibacillary forms. Al patients wer adults with ages between 20 and 39 years. Fifty eight (n=81) percent corresponded to Lepromatous Leprsy (LL), 29% (n=41) to Borderline Lepromatuous Leprosy (BL) and 10% (n=14) to Borderline Borderline Leprosy (BB); only 3% were Bordeline Tuberculoid (BT) patients: 74% males and 26% females. The most frequent reactional phenomenon was of the Erythema Nodosum (ENL) type. The mycobacterial proteins tested were: total crude Mycobacterium leprae antigens (MISA); Mycobacterium bovis (MbSA and excretion MbSA); partially purified excretion protein antigen, with a 30KDa relative movility (Ml30); and recombinant M. leprae protein (Mt70, Mb 65, Ml36, 28, 18 and 10kDa). Two of the recombinant proteints (M110 and Ml36 kDA) presented a statiseally significant higher serological reactivity, directly related with a larger bacillary load (p=0.0051 and 0.050 respectively). The 30kDa protein was predominantly recognized by antibodies from multibacillary patients. Results show that mean antibody values were higher in non reactional patients when tested against complete proteins (MbSA and ex MbSA) when compared with the group of patients who presented reactional phenomena (p=0.000567 and 0.000061, respectively). Comparing reactional with non reactional patients, it was seen that mean antibody values against complete proteins (MbSA and ex MbSA) were higher in non reactional individual (p=0.000567 and 0.000061, respectively). This same behavior occurred towards individual mycobacyterial proteins (30, 10 and 36 kDa). The T lymphocyte prolyphetative response in reactional and non reactional patients towards mycobacterial proteins (MISA, Ml 10 kDA, MbSA, ex MbSA) was negative (AU)

Immunological correlates of cure in the first American cutaneous leishmaniasis patient treated by immunotherapy in Argentina. A case report.

A patient with localized cutaneous leishmaniasis due to Leishmania (Leishmania) amazonensis infection was treated with an antigen containing heat-killed L. (L.) amazonensis promastigotes plus BCG. Expression of T-cell differentiation, memory and senescence receptors markers were analyzed on T cell subpopulations, in order to establish the correlation between the percentages of expression of these receptors and his clinical status, at different stages of his follow up. The following case reports on the achievement of a successful clinical outcome with complete resolution after receiving immunotherapy. A thorough clinical and immunological follow up supporting the healing process of this patient's lesion is presented in detail.

Citocinas reguladoras (IL-10 y TGF-B) en pacientes con leishmaniasis cutánea Americana / Regulatory cytokines (IL-10 and TGF-B) in American cutaneous leishmaniasis patients

La leishmaniasis cutánea Americana (LCA) presenta un espectro clínico e inmunológico, donde las formas intermedias se asocian con respuestas celulares exacerbadas frente a Leishmania spp., que pueden reflejar defectos de inmunoregulación. Debido a que la IL-10 y el TGF-β son algunos de los factores importantes en modular la respuesta inmunitaria, nos propusimos establecer si existen alteraciones en su producción entre las diferentes manifestaciones de la leishmaniasis cutánea. Se estudiaron individuos con leishmaniasis cutánea: localizada (LCL n=20), mucocutánea (LCM n=14), intermedia (LCI n=20), difusa (LCD n=12) y 22 voluntarios sanos. La IL-10 se determino por citometría de flujo y el TGF-β por ELISA en muestras de plasma y en sobrenadantes de cultivos linfocitarios de pacientes y controles, estimulados "in vitro" con L. braziliensis. Se evidenció una baja producción de IL-10 en los pacientes con LCI respecto a los LCM y LCD. Mientras que en plasma, no se observaron variaciones en la concentración de esta citocina entre los diferentes grupos. En contraste, el TGF-β estuvo incrementado significativamente en concentración y frecuencia de individuos respondedores en todos los grupos de pacientes respecto a los controles, siendo más elevado en los pacientes LCM asociado con un Odds Ratio muy elevado (87). Luego de estimulación con L. braziliensis, los pacientes con LCM continúan mostrando una mayor producción de TGF-β que los pacientes con LCI y LCD. En general, nuestros resultados sugieren que la IL-10 y el TGF-β pudiesen estar mediando supresión en los pacientes con LCD y una inadecuada inmunoregulación en los pacientes con LCI por el escaso nivel de estas. En los pacientes LCM, ambas citocinas fallan en modular la respuesta exacerbada presente en ellos. Otros mecanismos de regulación deben de ser investigados en futuros estudios.

American cutaneous Leishmaniasis shows a clinical and immunological spectrum, where intermediate forms are associated with exacerbated cell responses against Leishmania spp., which may reflect defective immunoregulation. Since IL-10 and TGF-β modulate the immune response, we aimed to establish whether there are changes in its production between the different manifestations of cutaneous leishmaniasis. We studied individuals with cutaneous leishmaniasis: localized (LCL n = 20), mucocutaneous (MCL n = 14), intermediate (ICL n = 14), diffuse (LCD n = 12) and twenty two healthy subjects. The IL-10 was determined by flow cytometry and TGF-β by ELISA in plasma and in supernatants of lymphocyte cultures from patients and controls stimulated in vitro with L. braziliensis. The results showed a low production of IL-10 in patients with intermediate or chronic leishmaniasis compared to MCL and DCL patients. There were no changes in plasma concentration of this cytokine among the different groups. In contrast, the TGF-ß was significantly increased in concentration and frequency of respondents in all groups of patients compared to controls, being higher in MCL patients associated with an elevated odds ratio (87). After stimulation with L. braziliensis, the MCL patients continue to show increased production of TGF-β compared to ICL and LCD patients. Overall, our results suggest that IL-10 and TGF-β could be mediating suppression in DCL patients and an inadequate or defective regulation in ICL patients by the low level of these cytokines. In MCL patients, both cytokines fail to modulate their exacerbated response. Other regulatory mechanisms must be investigated in future studies.

Leishmaniasis cutánea americana en Venezuela: un análisis clínico epidemiológico a nivel nacional y por entidad federal, 1988-2007 / American cutaneous leishmaniasis in Venezuela: a clinical and epidemiological analysis at a national level and by federal entity, 1988-2007

Se describen las características epidemiológicas generales, junto a algunos aspectos clínico-inmunológicos, de las diferentes formas clínicas de leishmaniasis cutánea en Venezuela. Esto se logró a través de un estudio descriptivo retrospectivo de la base de datos del registro nacional de leishmaniasis en el Instituto de Biomedicina. La información fue analizada con EpiInfo 3.5.1, SPSS 11.0 y Excel. 47.762 casos de las diferentes formas clínicas de leishmaniasis cutánea fueron diagnosticados en el periodo 1988-2007, esto es 2.388 casos por año, con una tasa promedio anual de 10,5 por 100.000 habitantes. Predomina en sexo masculino con una razón de masculinidad que oscila entre 1,2 y 1,8. Casos en todas las edades, con predominio en el grupo de 15 a 24 años, edad promedio de 28 años. En cuanto a la ocupación 24,58 % corresponde a personas del sector agropecuario, seguido de estudiantes (21,40%) y Oficios del Hogar (18,47%). Se han registrado casos en todas las entidades federales, observándose regiones como los estados andinos (Trujillo y Mérida) con tasas superiores a 30 por 100.000 habitantes. La distribución según forma clínica fue: 97,94% (46.778) leishmaniasis cutánea localizada; 0,72% (346) leishmaniasis cutánea intermedia; 1,11% (531) leishmaniasis cutánea mucosa y 0,22% (107) leishmaniasis cutánea difusa. Las características clínicas e inmunológicas estudiadas variaron de acuerdo con las diferentes formas clínicas descritas. En conclusión, se hace una descripción clínico-epidemiológica de la leishmaniasis cutánea americana en Venezuela en base a los datos del registro de casos del Programa Nacional de Control de la Leishmaniasis. Esto sirve de apoyo al desarrollo de futuras investigaciones y para la mejora del propio registro con los consecuentes beneficios que ello puede traer al programa de control.

The general epidemiological characteristics are described, together with some clinical and immunological aspects of the different clinical forms of cutaneous leishmaniasis in Venezuela. This was accomplished through a descriptive retrospective study of the leishmaniasis national registry database of the Institute of Biomedicine. The information was analyzed with EpiInfo 3.5.1, SPSS 11.0 and Excel. 47,762 cases of different clinical forms of cutaneous leishmaniasis were diagnosed during the period 1988-2007, i.e. 2,388 cases per year, with an average annual rate of 10.5 per 100,000 inhabitants. It is predominant in males, with a sex ratio of between 1.2 and 1.8. There are cases in all ages, with predominance in the 15 to 24 years group, average age 28 years. In terms of occupation, 24.58% are people of the agricultural sector, followed by students (21.40%) and housewives (18.47%). Cases have been registered in all the federal entities, observing regions such as the Andean States (Trujillo and Merida) with rates above 30 per 100,000 inhabitants. Distribution according to clinical form was: 97.94% (46,778) localized cutaneous leishmaniasis; 0.72% (346) intermediate cutaneous leishmaniasis, 1.11% (531) mucocutaneous leishmaniasis and 0.22% (107) diffused cutaneous leishmaniasis. The clinical and immunological characteristics examined varied according to the different clinical forms described. In conclusion, a clinical and epidemiological description is made of the American cutaneous leishmaniasis in Venezuela, based on the data of the register of cases of the Leishmaniasis Control National Program. This serves to support the development of future research and improve the register with the consequent benefits is can bring to the control program.

Reactividad serológica y celular frente a proteínas micobacterianas en la enfermedad de Hansen / Serological and cellular reactivity to mycobacterial proteins in Hansen´s disease

Se diseñó un estudio para evaluar la reactividad inmunológica frente a diferentes preparaciones proteicas micobacterianas utilizando pruebas serológicas y de inmunidad celular. Para el estudio fueron incluídos pacientes con manifestaciones clínicas de lepra predominantemente de la forma multibacilar. Todos los pacientes fueron adultos con edad comprendida entre 20 y 39 años. El 58 por ciento correspondía a la forma clínica de Lepra Lepromatosa (LL) n= 81, el 29 por ciento a la forma Borderline Lepromatosa (BL) n=41 y 10 por ciento a Borderline Borderline (BB) n=14. Solo el 3 por ciento fueron pacientes Borderline Tuberculoide (BT): 74 por ciento masculino y 26 por ciento femenino. El fenómeno reaccional más frecuente fue del tipo eritema nodoso leproso (ENL). Las proteínas micobacterianas ensayadas fueron: antígenos proteicos crudos totales de Mycobacterium leprae (MlSA), Mycobacterium bovis (MbSA y MbSA de excreción), antígeno proteico de excreción parcialmente purificado con una movilidad relativa de 30 kDa (Ml 30) y proteínas recombinantes de Mycobacterium (Mt70, Mb 65, Ml 36, 28, 18 y 10 kDa) encontrandose que las proteínas recombinantes (Ml10 kDa, Ml 36 kDa) a mayor carga bacilar presentaban una mayor reactividad serológica estadísticamente significativa (p= 0,0051 y 0,050 respectivamente). La proteína de 30 kDa fue predominantemente reconocida por anticuerpos de los pacientes multibacilares. Los resultados demuestran que el promedio de los valores de anticuerpos en pacientes no reaccionales fueron superiores en presencia de proteínas completas (MbSA y MbSA de exc) en comparación con el grupo de pacientes que presentaron fenómenos reaccionales (p=0,000567 y 0,000061 respectivamente) Este mismo comportamiento se observó frente a las proteínas micobacterianas individuales (30 kDa, 10 kDa y 36 kDa). La respuesta proliferativa de los linfocitos T en los pacientes multibacilares reaccionales y no reaccionales frente a las proteínas micobacterianas...

The study was designed for evaluating immunological reactivity to various mycobacterial protein preparations using serological and cell-mediated immunological tests in patients with clinical leprosy signs, predominantly, with the multibacillary forms. All patients were adults with ages between 20 and 30 years. Fifty eight (n= 81) percent corresponded to Lepromatous Leprosy (LL), 29 percent (n= 41) to Borderline Lepromatous Leprosy (BL) and 10 percent (n=41) to Borderline Borderline Leprosy (BB); only 3 percent were Borderline Tuberculoid (BT) patients: 74 percent males and 26 percent females. The most frequent reactional phenomenon was of the Erythema Nodosum (ENL) type. The mycobacterial proteins tested were: total crude Mycobacterium leprae antigens (MISA); Mycobacterium bovis (MbSA and excretion MbSA); partially purified excretion protein antigen, with a 30kDa relative movility (Ml30); and recombinant M. leprae proteins (Mt70, Mb 65, Ml 36, 28, 18 and 10 kDa). Two of the recombinant proteins (Ml10 and Ml 36 kDa) presented a statiscally significant higher serological reactivity, directly related with a larger bacillary load (p= 0.0051 and 0.050 respectively). The 30 kDa protein was predominantly recognized by antibodies from multibacillary patients. Results show that mean antibody values were higher in non reactional patients when tested against complete proteins (MbSA and ex MbSA) when compared with the group of patients who presented reactional phenomena (p= 0.000567 and 0.000061, respectively). Comparing reactional with non reactional patients, it was seen that mean antibody values against complete proteins (MbSA and ex MbSA) were higher in non reactional individuals (p= 0.000567 and 0.000061, respectively). This same behavior occurred towards individual mycobacterial proteins (30, 10 and 36 kDa). The T lymphocyte prolypherative response in reactional and non reactional patients towards mycobacterial proteins (MlSA, Ml 10 kDa, MbSA...

[Serological and cellular reactivity to mycobacterial proteins in Hansen's disease]. / Reactividad serológica y celular frente a proteínas micobacterianas en la enfermedad de Hansen.

The study was designed for evaluating immunological reactivity to various mycobacterial protein preparations using serological and cell-mediated immunological tests in patients with clinical leprosy signs, predominantly, with the multibacillary forms. All patients were adults with ages between 20 and 30 years. Fifty eight (n = 81) percent corresponded to Lepromatous Leprosy (LL), 29% (n = 41) to Borderline Lepromatous Leprosy (BL) and 10% (n = 41) to Borderline Borderline Leprosy (BB); only 3% were Borderline Tuberculoid (BT) patients: 74% males and 26% females. The most frequent reactional phenomenon was of the Erythema Nodosum (ENL) type. The mycobacterial proteins tested were: total crude Mycobacterium leprae antigens (MISA); Mycobacterium bovis (MbSA and excretion MbSA); partially purified excretion protein antigen, with a 30 kDa relative movility (Ml30); and recombinant M. leprae proteins (Mt70, Mb 65, Ml 36, 28, 18 and 10 kDa). Two of the recombinant proteins (Ml10 and Ml 36 kDa) presented a statiscally significant higher serological reactivity, directly related with a larger bacillary load (p = 0.0051 and 0.050 respectively). The 30 kDa protein was predominantly recognized by antibodies from multibacillary patients. Results show that mean antibody values were higher in non reactional patients when tested against complete proteins (MbSA and ex MbSA) when compared with the group of patients who presented reactional phenomena (p = 0.000567 and 0.000061, respectively). Comparing reactional with non reactional patients, it was seen that mean antibody values against complete proteins (MbSA and ex MbSA) were higher in non reactional individuals (p = 0.000567 and 0.000061, respectively). This same behavior occurred towards individual mycobacterial proteins (30, 10 and 36 kDa). The T lymphocyte prolypherative response in reactional and non reactional patients towards mycobacterial proteins (MlSA, Ml 10 kDa, MbSA, ex MbSA) was negative.

Respuesta inmunitaria de la enfermedad de Hansen: revisión / Immune response of Hansen´s disease: review

La enfermedad de Hansen presenta un amplio espectro de manifestaciones clínicas e histopatológicas, las cuales son un reflejo de la naturaleza de la respuesta inmunológica del individuo ante diversos componentes del Mycobacterium leprae. El sistema inmunológico, integrado por la existencia de una inmunidad innata y adaptativa, ofrece protección frente a infecciones de diversas etiologías, entre ellas las bacterianas. Por supuesto las bacterias han logrado desarrollar múltiples estrategias para evadir las defensas del hospedador, que se basan en mecanismos algunos muy complejos y otros más simples, pero con una sola finalidad de “resistir” el ataque del hospedador y lograr sobrevivir. Estudios realizados en la enfermedad de Hansen han podido determinar los diferentes componentes que puedan estar actuando tanto en la inmunidad innata cómo en la adquirida. En este trabajo se trata de resumir algunos estudios recientes en la enfermedad de Hansen con mayor énfasis en el área de inmunología, sin dejar de considerar que toda enfermedad debe estar muy ligada a otros aspectos tan igual de importantes cómo son los sociales, ambientales y otros de muy difícil resolución en un laboratorio.

Hansen’s disease presents a wide spectrum of clinical and histopathological manifestations that reflect the nature of the immunological response of the host towards diverse Mycobacterium leprae components. The immunological system, composed by both innate and adaptive immunology, offers protection towards infections of various etiologies, among them bacterial. Bacteria, of course, have developed multiple strategies for evading host defenses, based on either very complex or simple mechanisms, but with a single purpose: to “resist” host attacks and to be able to survive. We have tried to summarize some recent studies in Hansen’s disease, with more emphasis in the inmunology area. We think that in the future, all illnesses should also be very strongly related to other important aspects such as the social, environmental and economic, and whose development is not solved in a laboratory.

Antibody response in children infected with Giardia intestinalis before and after treatment with Secnidazole.

We examined 364 school children for intestinal parasites in a sub-urban zone of Caracas, Venezuela. Giardia intestinalis was the most prevalent parasite in stool samples from 34 children. Levels of IgA and IgG antibodies to G. intestinalis were assessed by enzyme-linked immunosorbent assay and Western blot before and after treatment with secnidazole. All patients were cured with a reduction of IgA antibody levels in 26 of 34 children and a reduction in IgG-specific antibody levels in 18 of 34 children. Serum of infected patients reacted with proteins of 14 kD to 137 kD. Some patients did not show a change in IgA serum reactivity for parasite proteins by Western blot after treatment. Seventeen children showed reduction of the reactivity or disappearance of protein reactivity (mainly the 14-kD, 122-kD, and 137-kD proteins). Antibody response was not related to clinical status, but quantitative and qualitative serum antibody response against G. intestinalis infection could be used to assess levels of new protein markers that decrease or disappear with successful chemotherapy.

[Immune response of Hansen's disease. Review]. / Respuesta inmunitaria de la enfermedad de Hansen. Revisión.

Hansen's disease presents a wide spectrum of clinical and histopathological manifestations that reflect the nature of the immunological response of the host towards diverse Mycobacterium leprae components. The immunological system, composed by both innate and adaptive immunology, offers protection towards infections of various etiologies, among them bacterial. Bacteria, of course, have developed multiple strategies for evading host defenses, based on either very complex or simple mechanisms, but with a single purpose: to "resist" host attacks and to be able to survive. We have tried to summarize some recent studies in Hansen's disease, with more emphasis in the inmunology area. We think that in the future, all illnesses should also be very strongly related to other important aspects such as the social, environmental and economic, and whose development is not solved in a laboratory.

The effect of Bacille Calmette-Guérin vaccine on tuberculin reactivity in indigenous children from communities with high prevalence of tuberculosis.

The Bacille Calmette-Guérin (BCG) vaccine is the most widely used vaccine in the world, however it may cause problems for the appropriate interpretation of the tuberculin skin test (TST). We assessed the diagnostic value of latent infection in vaccinated and unvaccinated indigenous children from communities that have a very high prevalence of adult tuberculosis (TB). A total of 997 children under 15 years old and classified in age groups (0-1.9, 2-5, 6-9 and 10-15 years old) were randomly selected and given TSTs using the Mantoux technique. TST induration values of vaccinated children (n=724) were compared with those of children unvaccinated (n=273). BCG vaccination was not an important cause of false-positive TST, except in communities with a low prevalence of active TB. In conclusion, the results suggested that a history of BCG vaccination on TST+ response after 10 years of vaccination was statistically insignificant but whether at earlier age TST+ reflects most probably the degree of exposure to TB cases than BCG vaccination should be clarified in the future.

Treatment of diffuse cutaneous leishmaniasis with miltefosine: a case report.

BACKGROUND: A 31-year-old man who has suffered since age 3 from diffuse cutaneous leishmaniasis (DCL), a disease with profound physical and psychosocial repercussions and no effective treatment at present, was treated with miltefosine. METHODS: The patient was treated for 120 days, 100 mg/day for 1 week, then 150 mg/day subsequently. RESULTS: Lesions were free of parasites at 43 days, and no signs of infiltration were present at day 76. No adverse side effects were observed. CONCLUSIONS: The dramatic clinical effect of miltefosine in this patient appears to fully justify further evaluation of this experimental therapy in DCL.

[Some immunological aspects in the reaccional states of Hansen disease]. / Ciertos aspectos inmunológicos en los estados reaccionales en la enfermedad de Hansen. Revisión.

The crucial clinical problem in leprosy is represented by episodes of intense inflammation that produce nerve damage. When Mycobacterium leprae has been eliminated by means of antibiotics, the death of the bacteria is not a complete solution to the damage caused in nerves. Two of the more frequent immunopathological phenomena in Hansen's disease are Type I, reactions, known as Reversal Reactions (RR), and Type II reactions, of which the most frequent and well known are those called Erythema Nodosum Leprosum (ENL). Type II reactions have been defined as an immunologic complication in multibacillary patients. Both types of reactions are accompanied mainly by the increase of pro-inflammatory cytokines TNF-alpha, IL-1, IL-2, IL-4, IL-6, IL-8, INF-gamma, IL-10, IL-12, among others. In a retrospective analysis of a population of 150 patients of the Central Service of Dermatology, Institute of Biomedicine, where these patients were subjected to Multidrug Therapy (MDT) and MDT + inmunotherapy (IMT), both groups presented type II reactions, but the group that additionally received inmunotherapy also presented type I reactions. In the group of patients that presented ENL, it appeared to be associated with the large amount of bacilli in their lesions.

Ciertos aspectos inmunológicos en los estados reaccionales en la enfermedad de Hansen: revisión / Some immunological aspects in the reaccional states of Hansen disease: review

El problema clínico crucial en la lepra son los episodios de inflamación aguda que conllevan a daño de los nervios. Aun cuando el Mycobacterium leprae ha sido eliminado mediante el uso de antibióticos, la muerte de la bacteria no es una solución completa al daño ocasionado en los nervios. Dos de los fenómenos inmunopatológicos más frecuentes son: Reacciones tipo I conocidas como reacciones de reversión (RR) y las Reacciones tipo II, como eritema nodoso leproso (ENL). Estas reacciones tipo II se han definido como: una complicación inmunológica en los pacientes multibacilares. Ambos tipos de reacciones están acompañadas por el incremento de citocinas pro-inflamatorias principalmente TNF-a, IL-1, IL-2, IL-4, IL-6, IL-8, INF-g, IL-10, IL-12, entre otras. En un análisis retrospectivo realizado en una población de 150 pacientes del Servicio Central de Dermatología del Instituto de Biomedicina sometidos a terapia multidroga (PQT) y PQT + inmunoterapia, ambos grupos presentaron fenómenos reaccionales tipo II, sólo el grupo que adicionalmente recibió inmunoterapia presentó además reacciones del tipo I. El grupo de pacientes que presentaron ENL estuvo asociado con presencia de gran cantidad de bacilos en las lesiones