RESUMO
Molecular karyotype and kDNA restriction analyses were utilized to examine the genetic heterogeneity and plasticity of the Leishmania (Viannia) guyanensis strain WHI/BR/78/M5313, composed of metastatic and non-metastatic populations. Cloning revealed that the strain was constituted by multiple closely related populations that were distinguishable by restriction fragment polymorphisms in kDNA. Size polymorphisms in molecular karyotype were not detected. Passage of clones in hamsters and recovery of parasites from cutaneous metastatic lesions yielded evidence of further genetic heterogeneity among some of the progeny populations. Overall, six kDNA minicircle restriction patterns or schizodemes were observed among clones, subclones and progeny. Although the possibility that population heterogeneity was not resolved by cloning cannot be ruled out, subcloning and kDNA restriction analysis to determine whether the putative clones consisted of homogeneous populations showed the schizodeme of subclones of 3 out of 4 clones to be identical to the clone of origin, while a subclone of the fourth had a co-efficient of similarity of 0.95. Metastasis did not segregate with a particular schizodeme: all six restriction profiles were represented among populations isolated from metastatic lesions and some clones with the same restriction profile did not produce metastatic lesions. The strain from which the clones, subclones and progeny were derived had a kDNA restriction pattern identical to the most prevalent schizodeme (38%) among these subpopulations. This finding together with the reappearance of the repertoire of schizodemes found among clones in the populations recovered from metastatic lesions in hamsters inoculated with a single clone, suggest that sequence polymorphisms in kDNA can emerge during infection.
Assuntos
Leishmania guyanensis/genética , Leishmaniose Mucocutânea/parasitologia , Polimorfismo Genético , Animais , Cricetinae , DNA de Cinetoplasto/genética , Modelos Animais de Doenças , Variação Genética , Genótipo , Masculino , Mesocricetus , Polimorfismo de Fragmento de RestriçãoRESUMO
Leishmanin skin test (LST) antigens prepared from Leishmania braziliensis panamensis were compared with respect to sensitivity, specificity, and side effects. Within the dose range 0.5-3.0 x 10(5) promastigotes of L. b. panamensis and 10 x 10(5) promastigotes of combined L. amazonensis and L. b. panamensis, specificity in healthy controls was nearly 100% for all antigens. Sensitivity increased minimally with increasing dose. Lot-to-lot differences were small. Side effects, such as vesiculation and ulceration at the site of LST application increased with antigen dose. Storage under harsh conditions decreased LST potency but not sensitivity while storage at 2-8 degrees C affected neither potency nor sensitivity. Eighty-five percent of parasitologically diagnosed, LST-positive cases of leishmaniasis remained LST-positive when retested six months to three years later. The LST did not sensitive 19 healthy controls who were skin tested twice or thrice.
Assuntos
Antígenos de Protozoários , Leishmania braziliensis/imunologia , Leishmania mexicana/imunologia , Leishmaniose/diagnóstico , Testes Cutâneos/normas , Adulto , Animais , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/normas , Criança , Cricetinae , Relação Dose-Resposta Imunológica , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Humanos , Hipersensibilidade Tardia , Leishmaniose/epidemiologia , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
Skin biopsies from 221 parasitologically confirmed cases of tegumentary leishmaniasis caused by Leishmania braziliensis spp. were evaluated with respect to histopathology, the qualitative and quantitative nature of the cellular infiltrate, and the presence of Leishmania amastigotes. These variables were cross correlated with the Leishmania-specific immune response, clinical presentation, and response to treatment. Physical evidence of prior leishmanial lesions was associated with the absence of amastigotes (P less than or equal to 0.001) and the presence of giant (P = 0.03) and epitheloid cells (P = 0.03) in the biopsy of the active lesion. The presence of amastigotes was inversely related to the duration of the lesion (P less than or equal to 0.001) and the presence of eosinophils (P less than or equal to 0.01), whereas the presence of adenopathy (P = 0.01), necrosis (P = 0.001), histiocytes (P = 0.001), and increased serum antibody titer (P = 0.02) were directly associated with the presence of amastigotes. The lymphocyte transformation response was correlated with the presence of granulomas (P = 0.001), but showed no correlation with cutaneous delayed type hypersensitivity. The presence of epithelioid (P = 0.04) and giant cells (P = 0.03) was associated with less drug being required to achieve healing. In contrast, necrosis was associated with a greater amount of drug to achieve healing (P = 0.05). The observed correlations between tissue responses and immune and clinical parameters provide further evidence for the role of antibody and other soluble mediators of the cellular immune response in the evolution of disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Leishmania braziliensis/isolamento & purificação , Leishmaniose Cutânea/patologia , Pele/patologia , Animais , Anticorpos Antiprotozoários/sangue , Biópsia , Estudos de Coortes , Imunofluorescência , Granuloma/patologia , Humanos , Imunidade Celular , Leishmania braziliensis/imunologia , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Ativação Linfocitária , Necrose , Pele/parasitologia , Testes CutâneosRESUMO
Phenotypic characterization of 511 strains of Leishmania, subgenus Viannia, isolated from Colombian patients was conducted based on electrophoretic polymorphisms of 13 isoenzymes. Ninety-one Colombian strains of L. braziliensis were the most heterogeneous, constituting seven zymodemes while 397 L. panamensis and 22 L. guyanensis strains yielded five and three zymodemes, respectively. Phosphogluconate dehydrogenase, nucleoside hydrolase, and superoxide dismutase were the most polymorphic enzymes in this collection of strains, and together with glucose-6-phosphate dehydrogenase, allowed the discrimination of the three aforementioned species. Hierarchical cluster analysis of the zymodemes using Jaccard's coefficient of similarities revealed two clusters, one constituted by L. braziliensis zymodemes, and another by three subgroups consisting of zymodemes of L. panamensis closely related to the species reference strain, another consisting of L. guyanensis zymodemes, and a third group distinguished by new electromorphs of proline iminopeptidase and aspartate aminotransferase that reacted with the L. panamensis-specific monoclonal antibody B-11. Multiple zymodemes of L. panamensis and L. guyanensis were found to be sympatrically transmitted in foci along the Pacific coast. Leishmania braziliensis variants were ubiquitous throughout the territory of Colombia; L. panamensis was prevalent in the western region and L. guyanensis was prevalent in the Orinoco and Amazon river basins in the eastern half of the country. Distinct zymodemes of L. panamensis predominated in the northern and southern regions of the Pacific coast. Nine zymodemes of all three species were isolated from mucosal lesions. Zymodeme 1.1 of L. braziliensis had the highest frequency of mucosal involvement (10% of the cases), and disease caused by this zymodeme had the longest mean time of evolution (31 months; P = 0.002). In addition to being useful in describing epidemiologic relationships, the intraspecific heterogeneity of strains of the Viannia subgenus within and among foci can be used to understand such fundamental questions as the pathogenicity of different populations of parasites, and the induction of cross-protection against related parasites.
Assuntos
Isoenzimas/análise , Leishmania/classificação , Leishmaniose/epidemiologia , Animais , Análise por Conglomerados , Colômbia/epidemiologia , Água Doce , Geografia , Humanos , Isoenzimas/genética , Leishmania/enzimologia , Leishmania/genética , Leishmaniose/parasitologia , Leishmaniose/transmissão , Fenótipo , Polimorfismo GenéticoRESUMO
During natural infections, Leishmania is in contact with a variety of mononuclear phagocytic cells in different tissues, including resident macrophages and monocytes mobilized to the site of infection from the bone marrow and blood circulation. Because the functional capabilities of fully differentiated macrophages and blood monocytes differ, the outcome of infection by Leishmania may depend upon the stage of differentiation of the host cells. To address this question, we evaluated Leishmania panamensis infection of (1) the human promonocytic/histiocytic cell line U-937 before and after induction of differentiation by phorbol myristate acetate; (2) fresh human peripheral blood monocytes; and (3) macrophages derived from monocytes by differentiation in vitro. Based on the percentage of cells infected and the number of parasites per cell, macrophages derived from monocytes or by induction of differentiation of U-937 cells were significantly more permissive to infection by stationary-phase L. (Viannia) panamensis promastigotes than monocytes. Increasing time and maturation in culture prior to exposure to infective promastigotes was associated with the increased permissiveness of differentiated macrophages to infection (P<0.05). The percentage of cells infected and number of amastigotes per cell increased with time postinfection for both monocytes and macrophages but remained significantly greater for macrophages. The increased expression of CD68, CD16, and lysozyme, and decreased expression of peroxidase by macrophages cultured for 5 days in vitro compared with fresh monocytes, whether adherent or in suspension, supported the distinct maturation status of these cells.
Assuntos
Leishmania guyanensis/fisiologia , Macrófagos/parasitologia , Monócitos/parasitologia , Animais , Diferenciação Celular , Células Cultivadas , Cricetinae , Meios de Cultura , Humanos , Leishmania guyanensis/crescimento & desenvolvimento , Macrófagos/citologia , Monócitos/citologia , Fatores de TempoRESUMO
Metastatic disease is a major concern of dermal leishmaniasis caused by Leishmania of the Viannia subgenus. The golden hamster provides an experimental model of systemic dissemination and cutaneous metastasis of Leishmania Viannia. We have exploited this model to examine the expression of parasite virulence in cloned populations derived from a strain of L. guyanensis previously shown to be highly metastatic in the hamster. Metastatic capacity manifested as dissemination throughout the lymphoid organs; cachexia and secondary cutaneous lesions were found to differ among clones, yielding a spectrum of virulence. The metastatic phenotype of clonal populations was stable over 5 sequential passages in hamsters. In addition, the low or high propensity to disseminate and produce cutaneous metastatic lesions was reproduced. Capacity to disseminate from the inoculation site was conserved following subcloning of metastatic clones that had been passaged in culture for several generations; clinical manifestations, cachexia, and cutaneous metastatic lesions were variably expressed. Dissemination of parasites and cachexia were significantly related (P = 0.004). Overall, cachexia was an earlier manifestation of dissemination than cutaneous metastases (P < 0.001). The reproducible expression of virulence phenotypes by discrete populations of Leishmania in the golden hamster provides an experimental model for clinically relevant expression of virulence in human leishmaniasis.
Assuntos
Leishmania guyanensis/patogenicidade , Leishmaniose Mucocutânea/parasitologia , Animais , Medula Óssea/parasitologia , Cricetinae , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Leishmaniose Mucocutânea/patologia , Linfonodos/parasitologia , Masculino , Mesocricetus , Fenótipo , Inoculações Seriadas , Pele/parasitologia , Baço/parasitologia , VirulênciaRESUMO
OBJECTIVES: To identify existing programs serving 11- to 15-year-olds that aim to improve adolescent health in the areas of Health & Well-being, Fitness, Family & Peer Relationships, School Environment, Smoking, Alcohol Use, and Violence and to assess the utility of readily available resources in providing detailed program information. METHODS: In Phase 1, publicly available program databases were searched to identify potential programs serving the target population. In Phase 2, an in-depth search of a limited sample of programs meeting the content and age criteria was performed to identify program descriptors. RESULTS: Over 1,000 program names were identified in Phase 1. Information regarding programs is becoming more readily available through the internet; however, the program information that was publicly available only begins to draw the picture. Phase 2 revealed that a broad array of efforts are underway in all seven content areas, but found information on the program descriptors to be limited. CONCLUSIONS: Investment in programming is not enough; an upfront investment in communication and information sharing is critical in order to maximize the resources dedicated to the improvement of adolescent health. A well-publicized centralized program repository offered in conjunction with technical assistance would provide an efficient mechanism for this information sharing. We further suggest that the inherent gap between research and practice can be lessened by building a new body of practice knowledge. This would require improved program data collection by programs, the incorporation of program participation information in national surveys and enhanced evaluation efforts.
Assuntos
Serviços de Saúde do Adolescente/provisão & distribuição , Bases de Dados Factuais/estatística & dados numéricos , Promoção da Saúde/provisão & distribuição , Disseminação de Informação , Serviços de Informação/provisão & distribuição , Internet/estatística & dados numéricos , Desenvolvimento de Programas/estatística & dados numéricos , Adolescente , Serviços de Saúde do Adolescente/organização & administração , Criança , Relações Familiares , Financiamento Governamental , Academias de Ginástica , Promoção da Saúde/organização & administração , Humanos , Serviços de Saúde Mental , Serviços de Saúde Escolar , Centros de Tratamento de Abuso de Substâncias , Estados Unidos , United States Dept. of Health and Human ServicesRESUMO
Paraflagellar rod proteins (PFR) are a potent immunogen against experimental Trypanosoma cruzi infection. PFR are highly conserved among kinetoplastid parasites. We therefore evaluated the immunogenicity of the Leishmania mexicana pfr-2 gene and protein product in the hamster model of American cutaneous leishmaniasis. Immunization with pfr-2 DNA-induced specific antibody, confirming immunogenicity. Subsequent challenge with 10,000 and 500 stationary phase L. mexicana promastigotes respectively, resulted in delayed appearance of lesions, and significant reduction in lesions post infection in male hamsters, yet exacerbated lesions in female hamsters. Immunization with recombinant PFR-2 protein (rPFR-2) prevented lesion development in female hamsters challenged with L. panamensis, but was ineffective against L. mexicana. Nevertheless, prime boost immunization of female hamsters with rPFR and pfr-2 DNA significantly reduced lesion size following challenge with 500 L. mexicana promastigotes, supporting the relevance of PFR-2 as a potential vaccine constituent.
Assuntos
Leishmania mexicana/imunologia , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/prevenção & controle , Proteínas de Protozoários/administração & dosagem , Proteínas de Protozoários/imunologia , Vacinas Protozoárias/imunologia , Vacinas de DNA/imunologia , Animais , Cricetinae , Feminino , Células HeLa , Humanos , Masculino , Vacinas Protozoárias/administração & dosagem , Fatores Sexuais , Vacinas de DNA/administração & dosagemRESUMO
PURPOSE: To describe lessons learned from the Centers for Disease Control and Prevention's Community Coalition Partnership Program (CCPP) about building a community's capacity to prevent teen pregnancy through strengthening of partnerships, mobilization of community resources, and changes in the number and quality of community programs. METHODS: A multi-component post-test-only evaluation. In-person interviews (n = 364) were conducted with a sample of CCPP project staff, evaluators, and community and agency members from each of the 13 CCPP communities. RESULTS: All partnerships reported that new groups worked together to address teen pregnancy prevention; however, more time, effort, and resources than anticipated were spent engaging these groups and strengthening their partnerships. Respondents reported increases in community awareness of the problem of teen pregnancy and the willingness to discuss the issue. As a result of partnerships' activities, knowledge and skills related to addressing teen pregnancy improved among partnership members, but respondents were concerned that the broader community did not share these gains. To a lesser extent, respondents reported that partners worked together to reduce duplication and fill gaps in services either through increased collaboration and/or differentiation of activities. Respondents from most of the partnerships also reported new programs were developed as a result of the project; however, in several partnerships, only a few programs were developed in their community. Many respondents doubted whether the limited mobilization of resources during the program would translate into increased agency and community capacity. CONCLUSIONS: Overall, increased partner skills, program improvements, and new programs did not appear to be sufficient to affect community capacity. Research is needed to identify the pathways between changes in community capacity and in individual-level behavior that might result in the avoidance or reduction of teen pregnancy.
Assuntos
Centers for Disease Control and Prevention, U.S. , Planejamento em Saúde Comunitária , Gravidez na Adolescência/prevenção & controle , Adolescente , Coleta de Dados , Estudos de Viabilidade , Feminino , Humanos , Entrevistas como Assunto , Modelos Teóricos , Gravidez , Inquéritos e Questionários , Estados UnidosRESUMO
PURPOSE: To describe the models created by the 13 communities in the Centers for Disease Control and Prevention's Community Coalition Partnership Program (CCPP), and the relationship between key organizational features of the coalitions and the perception by coalition members of interim and community-wide outcomes. METHODS: This study relied on three sources of data: interviews conducted on site with a sample of coalition staff, evaluators, and members (n = 364); a written survey administered after the site visit to those interviewed (n = 216) asking about perceived outcomes and changes between the beginning and end of the project; and a coalition member survey mailed to all coalition members at all sites (n = 341) focusing on perceptions of coalition functioning, outcomes, and satisfaction. RESULTS: A variety of coalition models were developed. Respondents were positive in their assessments of how their coalitions operated even though few were sustained. The coalitions for which members perceived more positive outcomes were better established at the outset of the grant, led by paid staff, and had an area-wide focus, a steering committee, and a hub that was not a community-based organization. Coalitions composed primarily of neighborhood members were difficult to maintain. CONCLUSIONS: Despite members' high ratings, by the end of the funding period most coalitions were no longer functioning. It may be that coalitions are useful but not as permanent structures in communities. Grassroots and individual members not affiliated with an agency may require meaningful incentives to sustain participation. Because maturity of the coalition at the start of the project was a good predictor of sustainability, time should be spent verifying the stage of coalition development before funding.
Assuntos
Centers for Disease Control and Prevention, U.S. , Planejamento em Saúde Comunitária , Gravidez na Adolescência/prevenção & controle , Adolescente , Planejamento em Saúde Comunitária/organização & administração , Planejamento em Saúde Comunitária/normas , Coleta de Dados , Feminino , Seguimentos , Humanos , Entrevistas como Assunto , Liderança , Modelos Organizacionais , Gravidez , Fatores de Tempo , Estados UnidosRESUMO
Leishmania-specific immunoglobulin subclass response was evaluated in 133 patients infected with Leishmania braziliensis. The indirect immunofluorescent antibody test (IFAT) was employed with amastigotes of L. mexicana amazonensis as antigen. Among the 133 sera obtained at consultation for diagnosis of active lesions, IgM was detected in 54 following absorption with Staphylococcus aureus Cowan strain I, and in 5 sera prior to absorption. IgM reactive with Leishmania antigen was only found in sera from patients whose lesions had evolved over the past two months or less. Leishmania-specific IgG was detected in all sera prior to absorption. Sera obtained at the time of recurrence or after complete healing of lesions presented only specific IgG. The combined use of the Montenegro skin test and specific IgM increased the sensitivity of immunodiagnostic methods in patients with lesions of less than 2 months duration. Normal control volunteers were negative for specific IgM and unreactive to Montenegro skin testing. Among 16 patients with non-leishmanial lesions, 3 with sporotrichosis showed IgG reactive with Leishmania; none, including 4 with lesions of less than two months duration, showed specific IgM. We conclude that in patients infected with L. braziliensis the presence of specific IgG and IgM is associated with the time of lesion evolution and the primary or recurrent nature of the lesions. In addition, the combined use of IgM titer and Montenegro reactivity is of potential utility in the diagnosis of early lesions.
Assuntos
Isotipos de Imunoglobulinas/imunologia , Leishmania braziliensis/imunologia , Leishmaniose Cutânea/imunologia , Animais , Anticorpos Antiprotozoários/análise , Imunofluorescência , Humanos , Testes IntradérmicosRESUMO
Mechanisms of constitutive and acquired susceptibility/resistance to Leishmania Viannia panamensis (L. (V ) p.) were investigated in endemically exposed human populations presenting either recurrent disease (putative susceptible) or subclinical infection (clinically resistant). Cutaneous delayed type hypersensitivity response to leishmanin was significantly lower among individuals experiencing recurrent leishmaniasis than among those whose skin test converted without developing the disease. Monocyte derived macrophages from individuals with recurrent disease were more permissive in vitro to the entry of parasites than macrophages from subclinically infected individuals. In vitro proliferation of CD4 and CD8 T lymphocytes in response to intracellular amastigotes was significantly lower among individuals with a history of recurrent disease compared with subclinically infected individuals. Linear regression analyses revealed a strong direct relationship between the production of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 by peripheral blood mononuclear cells (PBMC) from resistant (subclinically infected) individuals and no correlation in the production of these cytokines by PBMC from individuals who experienced recurrent disease. The results provide evidence of differences in the innate and acquired responses to Leishmania according to the outcome of the natural infection. These findings support the feasibility of identifying the immunological bases of innate and acquired resistance through studies in naturally exposed human populations.
Assuntos
Doenças Endêmicas , Leishmania guyanensis/imunologia , Leishmaniose Mucocutânea/imunologia , Adolescente , Adulto , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/parasitologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/parasitologia , Células Cultivadas , Suscetibilidade a Doenças/imunologia , Feminino , Humanos , Hipersensibilidade Tardia/imunologia , Imunidade Inata/imunologia , Interferon gama/biossíntese , Interferon gama/farmacologia , Interleucina-10/biossíntese , Leishmaniose Mucocutânea/epidemiologia , Macrófagos/citologia , Macrófagos/parasitologia , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/parasitologia , Proteínas Recombinantes , Recidiva , Fatores de Risco , Trítio , Fator de Necrose Tumoral alfa/biossínteseRESUMO
The indirect immunoperoxidase method was evaluated in 265 biopsies with the purpose of increasing the sensitivity of the diagnostic histopathology of tegumentary lesions caused by subspecies of the Leishmania braziliensis complex. A diagnosis of leishmaniasis was established by parasitological methods (181) or clinical criteria (12) in 193 patients (72.8%). In the latter group of confirmed cases standard histochemistry and immunoperoxidase were compared with direct examination of tissue scraping and culture of lesion aspirates. The detection and localization of amastigotes was more efficient using the immunoperoxidase method (61.3%) than conventional histopathology with hematoxilin and eosin (34.6%) or direct examination of tissue scraping (43.9%). However, culture of lesion aspirates was the most sensitive procedure (89.8%). The efficiency of the immunoperoxidase method was greater in recent lesions, being positive in 75% of cases with less than 3 months evolution, while 55.6%, 37.5%, and 21.1% of cases with lesion evolution of 3-5.9, 6-11, and 12 months or greater, respectively, were positive. The combined use of the direct examination of lesion scraping and immunoperoxidase applied to histological sections of the biopsy from the lesion border allowed an etiologic diagnosis of 72% of confirmed cases. Cross-reactivity was observed with Paracoccidioides braziliensis but not with Mycobacterium leprae, Sporothrix schenckii, or Histoplasma capsulatum.
Assuntos
Leishmaniose Mucocutânea/diagnóstico , Leishmaniose/diagnóstico , Humanos , Técnicas Imunoenzimáticas , Testes Intradérmicos , Leishmaniose/patologia , Leishmaniose Mucocutânea/patologia , Mucosa Nasal/parasitologia , Pele/parasitologiaRESUMO
This prospective study measured the incidence of Leishmania infection, by Leishmanin skin test (LST) conversion, and leishmaniasis, by new acquisition of lesions, in a Leishmania braziliensis endemic area of Colombia, during 7243 person-years. The incidence rate of infection and leishmaniasis varied greatly by village, ranging from 2.8 to 23.0/100 person-years and 0.0 to 20.4/1000 person-years, respectively. Adult males experienced greater rates of both infection and leishmaniasis. Most primary infections (91%) were subclinical initially. Typical scars were predictive of subsequent leishmaniases both for persons initially LST-reactive (risk ratio = 11.3, P = .003) and for those initially nonreactive (risk ratio = 3.2, P = .02). Only one-third of the diagnosed leishmaniasis cases (24/77) were due to newly acquired infections in naive hosts. The relative contribution of existing lesions, recurrences, and new infections to the burden of disease should be considered in the planning of leishmaniasis control programs.
Assuntos
Leishmania braziliensis , Leishmaniose Cutânea/epidemiologia , Adolescente , Adulto , Fatores Etários , Animais , Antígenos de Protozoários/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Colômbia/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Leishmaniose Cutânea/diagnóstico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Estudos Prospectivos , Sistema Respiratório/patologia , População Rural , Fatores Sexuais , Pele/patologia , Testes Cutâneos , Fatores de TempoRESUMO
Through a longitudinal, active surveillance for Leishmania (Viannia) braziliensis and Leishmania (Viannia) panamensis infection and lesions on the Pacific Coast of Colombia, risk factors for infection (leishmanin skin test conversion), leishmanial lesions, and pathogenicity were examined. Risk factor information was obtained prior to and independently of case ascertainment. Similar factors were associated with acquisition of infection and of leishmaniasis, including male sex, age > 10 years, and farming occupation. The behaviors of entering the forest after sunset, hunting, and lumbering were most strongly associated with Leishmania infection independently of age, sex, and farming occupation. Environmental conditions associated with infection, including tall trees near the home, home located > 15 m from the nearest neighbor, and floor and roof made of open material, were less strong predictors of risk. Pathogenicity, the risk of lesion given a new infection, was reduced in those > 30 years of age and those entering the forest frequently.
Assuntos
Leishmania braziliensis/patogenicidade , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/epidemiologia , Adolescente , Adulto , Fatores Etários , Agricultura , Animais , Criança , Colômbia/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Exposição Ocupacional , Fatores de Risco , Assunção de Riscos , População Rural , Fatores SexuaisRESUMO
Multivariate analyses of clinical presentation, subspecies identity of the causal organism, and the Leishmania-specific immune response parameters (indirect fluorescent antibody test [IFAT], cutaneous delayed type hypersensitivity [DTH], and in vitro lymphocyte transformation [LT]) of 441 patients with tegumentary leishmaniasis were used to examine the human host-parasite interaction in L. braziliensis infection. Mucocutaneous disease (P less than .002) and L. braziliensis braziliensis infection (P less than .001) were independently associated with significantly higher IFAT titers and cutaneous DTH than were cutaneous disease or L. braziliensis panamensis infection. Lesion size was also correlated with IFAT titer (P. less than .001). Although time of lesion evolution was highly correlated with all parameters, differences associated with subspecies and disease form were independent of lesion duration (three-way analysis of variance). In contrast with the cutaneous DTH response, the in vitro lymphocyte proliferative response to Leishmania antigen did not correlate with disease form and only weakly with infecting subspecies when time of evolution and subspecies were controlled. The association of mucosal disease presentation with a particular subspecies and the independent correlation of both variables with heightened IFAT titers and cutaneous DTH to Leishmania antigen supports the possibility of immune mechanisms of pathogenesis in human tegumentary leishmaniasis.
Assuntos
Anticorpos Antiprotozoários/biossíntese , Leishmania braziliensis/imunologia , Leishmania/imunologia , Leishmaniose Mucocutânea/parasitologia , Leishmaniose/parasitologia , Análise de Variância , Animais , Antígenos de Protozoários/imunologia , Relação Dose-Resposta Imunológica , Imunofluorescência , Interações Hospedeiro-Parasita , Humanos , Hipersensibilidade Tardia , Soros Imunes/imunologia , Imunidade Celular , Cinética , Leishmaniose/imunologia , Leishmaniose Mucocutânea/imunologia , Ativação Linfocitária , Análise de RegressãoRESUMO
OBJECTIVE: This study analyzes the major clinical characteristics of patients with active leprosy in relation to the in vitro immune response to the T-lymphocyte activator anti-CD3. METHODS: Thirty-eight patients with an established diagnosis of leprosy were classified according to the Ridley and Jopling table. Peripheral blood mononuclear cells from both lepromatous leprosy (LL) and tuberculoid leprosy (TL) patients and healthy controls were used to evaluate lymphocyte proliferation; immunoenzymatic assays were used to evaluate cytokine production (IL-1, IL-2, IL-4, IL-6, IL-10, IFN-gamma). RESULTS: Peripheral blood mononuclear cells from both LL and TL patients displayed blastogenic responses to anti-CD3. The cytokines IL-1 beta, IL-6, IL-10, and IFN-gamma were detected in culture supernatants. Endogenous production of IL-1 beta was significantly higher in cell cultures from patients with the lepromatous form of the disease compared to those with tuberculoid leprosy. Production of IL-6 in response to anti-CD3 was observed in a significantly higher proportion of LL than TL patients (P = 0.0025). Gamma-interferon production did not differ between TL and LL, but a direct correlation was observed between time of multidrug treatment and IFN production in vitro (P = 0.016). Interleukin-10 was detected in culture supernatants of lymphocytes activated by anti-CD3 from both patient groups, but not from healthy controls. CONCLUSIONS: The findings of this study suggest that patients with the two distinct forms of leprosy are capable of responding to a polyclonal T-lymphocyte stimulus such as anti-CD3 and provide evidence suggestive of alterations in the immune responses mediated by cytokines that may contribute to the spectrum of disease and response to treatment.
Assuntos
Citocinas/sangue , Hanseníase Virchowiana/imunologia , Hanseníase Tuberculoide/imunologia , Adulto , Feminino , Humanos , Técnicas Imunoenzimáticas , Interferon gama/sangue , Interleucina-1/sangue , Interleucina-10/sangue , Interleucina-2/sangue , Interleucina-4/sangue , Interleucina-6/sangue , Hanseníase Virchowiana/sangue , Hanseníase Tuberculoide/sangue , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Muromonab-CD3/imunologia , Neutrófilos/imunologiaRESUMO
Advanced stages of mycobacterial diseases such as leprosy and tuberculosis are characterized by a loss of T-cell function. The basis of this T-cell dysfunction is not well understood. The present report demonstrates major alterations in the expression of signal transduction molecules in T cells of leprosy patients. These alterations were most frequently observed in lepromatous leprosy (LL) patients. Of 29 LL patients, 69% had decreased T-cell receptor zeta-chain expression, 48% had decreased p56(lck) tyrosine kinase, and 63% had a loss of nuclear transcription factor NF-kappaB p65. An electrophoretic mobility shift assay with the gamma interferon core promoter region revealed a loss of the Th1 DNA-binding pattern in LL patients. In contrast, tuberculoid leprosy patients had only minor signal transduction alterations. These novel findings might improve our understanding of the T-cell dysfunction observed in leprosy and other infectious diseases and consequently might lead to better immunologic evaluation of patients.
Assuntos
Hanseníase/metabolismo , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Proteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Linfócitos T/metabolismo , Adulto , Citocinas/biossíntese , DNA/metabolismo , Feminino , Humanos , MasculinoRESUMO
Se considera el impacto que tiene en la mente del paciente y del analista, una situación de vida a la que concurre la posibilidad de coexistencia de verdades contradictorias. Se plantea que la realidad compleja de la transexualidad, cuestiona principios lógicos que suelen fundamentar nuestro pensamiento psicoanalítico. Se postula que las comprensiones dinámicas de las neosexualidades obligan a la consideración de modelos flexibles para enfrentarlas y se concluye, a partir del trabajo con el paciente Markithox, que la complejidad de estas realidades resulta más aprehensible si nos ubicamos en un vértice en el que se asume más decididamente la posibilidad de que la vida no sólo pueda ser verdadera o falsa sucesivamente, sino que también, simultáneamente, verdadera y falsa.
The impact on the patient and analysts mind of a life situation that attends the possible coexistence of contradictory truths is discussed. From the complex reality of transsexuality, the logical principles on which psychoanalytical thinking is often based are put into question. It is propose that the dynamic understanding of neosexualities force us to consider flexible models of approach. Finally, from the work with the patient Markithox, it is conclude that the complexity of these realities becomes easier to apprehend if we strongly assume the possibility that life may not only be either true or false, but simultaneously true and false.
Assuntos
Humanos , Masculino , Adolescente , Transtornos Parafílicos/psicologia , Transexualidade , Transtornos Sexuais e da Identidade de Gênero/psicologia , Identidade de Gênero , Psicanálise , SexualidadeRESUMO
Entre los casos de Pancreatitis Aguda Idiopática (PAI), una de las causas más frecuentes, es la presencia de microlitiasis, etiología que se observa más frecuentemente en países donde la colelitiasis es más común. Es conocido que la presencia de microlitiasis en la vesícula biliar puede ser difícil de demostrar con los métodos habituales de imágenes. Se ha descrito que el análisis microscópico de la bilis (estudio de cristales), después de la estimulación duodenal, con el objeto de observar microcristales de colesterol, contribuye a la confirmación del diagnóstico en estos casos, en un porcentaje de alrededor del 75 por ciento (dos terceras partes) de casos de PAI. En el presente artículo, se describe la metodología recomendable para el estudio de sedimento biliar (SB) y de cristales en la bilis.