Sorologia Anti PGL-1 e risco de ocorrência de hanseníase em área de alta endemicidade do Estado de São Paulo: quatro anos de seguimento

Os testes sorológicos para diagnóstico de hanseníase, usando o glicolipídeo-fenólico-1 (PGL-1), considerado antígeno específico do M. leprae, têm aberto algumas possibilidades de estudo do comportamento epidemiológico desta doença. Algumas questões, como tempo de latência da doença, infecção subclínica e importância do contato intra-domiciliar (contatos) no controle da endemia, puderam ser melhor analisadas usando este instrumental. Este estudo teve por objetivo verificar a existência de associação entre a situação sorológica e a ocorrência de hanseníase. Foram seguidas, durante 4 anos, 6.520 pessoas com idade igual ou superior a 5 anos, submetidas no início do seguimento ao teste sorológico Anti PGL-1, pertencentes ao universo de 7.416 habitantes da área urbana de um município paulista caracterizado por elevada endemicidade de hanseníase. Foi identificado um grupo de 590 indivíduos soropositivos (9,0 %). Foram diagnosticados, no período, 82 casos novos de hanseníase, 26 no grupo de soropositivos (441 casos novos/10.000 indivíduos) e 48 no de soronegativos (81/10.000). Entre os que não fizeram sorologia, surgiram 8 casos novos (89/10.000). Procurou-se controlar, na análise, a condição de contato, dado que a taxa de soropositividade padronizada por idade e sexo era de 9,61% no grupo de contatos e 7,65% no de não-contatos. Tomando-se os não-contatos soronegativos como o grupo de não expostos, foram calculados os riscos relativos de adoecimento no período, a partir das taxas de detecção padronizadas por idade, resultando no seguinte: os contatos ID soropositivos apresentaram a taxa de 1.704/10.000, 27 vezes maior que a dos não-expostos, igual a 63/10.000; os não-contatos soropositivos e os contatos soronegativos apresentaram taxas, respectivamente, de 274 e 198/10.000, ambas maiores que as dos não-expostos e iguais entre si. A soropositividade associou-se à elevação de 8,6 vezes do risco de hanseníase entre os contatos e de 4,4 entre os não-contatos. Na situação epidemiológica estudada, caracterizada por elevada endemicidade de hanseníase, 50% dos casos novos surgiram entre os não-contatos soronegativos, ou seja, sem fonte de infecção conhecida. Portanto, o teste anti-PGL-1 usado revela-se, na prática, de pouca aplicabilidade. Resta estudar ainda o comportamento da sorologia anti-PGL-1 em áreas de média e baixa endemicidade para que se possa tirar conclusões mais consubstanciadas sobre sua utilidade no controle da endemia. Recomenda-se o aprofundamento das pesquisas sorológicas e de outras que aprimorem o diagnóstico precoce da infecção subclínica, inclusive para detecção de formas paucibacilares, para se ampliar as possibilidades de influir no controle endêmico.

Perfil de anticorpos anti-pgl-1 em indivíduos sadios de áreas endêmicas em hanseníase do estado do Pará, método de Elisa

No Brasil, a hanseníase ainda persiste com elevados coeficientes de detecção, inclusive em menores de quinze anos, em especial nas Regiões Norte, Nordeste e Centro-Oeste. Os resultados de estudos soroepidemiológicos para hanseníase, utilizando teste sorológico anti- PGL-1, pelo método Elisa, realizados no Estado do Pará onde os municípios em sua maioria alcançam patamares de elevadas endemicidade, podem ser comprometidos pela ausência de definição local de parâmetro que limite os níveis séricos de anticorpos específicos, IgM, anti- PGL-1 entre positivos e negativos; assim como, as avaliações e o seguimento de casos de pacientes reacionais e suspeitos de recidiva, ou de doentes e infectados sem sinais clínicos.Autores defendem a posição de que o ponto de corte (PC), entre positivos e negativos, deve ser encontrado a partir de uma população de doadores não contato de hanseníase da própria área de estudo para possibilitar comparabilidade. O objetivo do estudo foi descrever o comportamento sorológico dos níveis de anticorpos anti-PGL-1, método ELISA, em indivíduos sadios de áreas endêmicas em hanseníase no Estado do Pará, sua correlação com níveis de endêmicidade e fatores demográficos, e identificar PC para o teste. Estudo analítico transversal, população composta por doadores de sangue dos hemocentros do Estado do Pará. Amostra de 1.001 doadores de sangue não contato intradomiciliar de portadores de hanseníase, residentes em áreas de elevada endemicidade do Estado do Pará. Seleção dos participantes através de entrevista e ficha epidemiológica com variáveis independentes, como sexo, idade e cicatriz de BCG que foram correlacionadas com os níveis sorológicos de anti- PGL-1 encontrados na população do estudo. Resultados mostraram que não houve significância estatística entre sexo, idade, presença de cicatriz de BCG e os níveis de anti- PGL-1, usando PC ≥ 0,2. A média dos níveis de anti-PGL-1 foi notadamente baixa para áreas de hiperêndemicidade e muito alta endemicidade. As taxas de soropositividade e soroprevalência também foram consideradas baixas. Foram encontrados diferentes pontos de corte com a média geral dos níveis de anti-PGL-1, com a média por hemocentro e por municípios. A soropositividade obtida com PC ≥ 0,13 dobrou em valores absolutos de 15 para 36 em todas as três variáveis analisadas, apesar de não ter produzido resultados com significância estatística. Sugere-se a realização de mais estudos soroepidemiológicos utilizando ponto de corte mais baixo, como o encontrado neste estudo (0.13), para avaliar a influencia do mesmo na sensibilidade do teste, na soropositividade em contatos e não contatos de portadores de hanseníase, na descoberta de infecção subclínica e seguimentos dos casos.

Leprosy, a neglected disease that causes a wide variety of clinical conditions in tropical countries

Leprosy is an ancient disease that remains endemic and continues to be a major public health problem in some tropical countries, where it has been internationally recognized as being linked to the underdevelopment conditions. The natural course of the disease covers a wide variety of clinical conditions with systemic involvement. In this paper, we review the findings obtained in studies of the pathological mechanisms of leprosy, including a survey of the literature and of our own work. The understanding and control of the wide variety of clinical conditions should help improve patient care and thus prevent the onset of physical impairment and the stigma of the disease.

Anti-beta(1)-adrenergic receptor antibodies and heart failure: causation, not just correlation.

Antibodies specific for the beta(1)-adrenergic receptor are found in patients with chronic heart failure of various etiologies. From work presented in this issue of the JCI, we can now infer that these antibodies actually contribute to the pathogenesis of chronic heart failure. This commentary discusses mechanisms by which these antibodies may engender cardiomyopathy.

Recognition of Membrane-Bound Fusion-Peptide/MPER Complexes by the HIV-1 Neutralizing 2F5 Antibody : Implications for Anti-2F5 Immunogenicity

13 p.

A cocktail of thermally stable, chemically synthesized capture agents for the efficient detection of anti-gp41 antibodies from human sera and techniques

This thesis reports on a method to improve in vitro diagnostic assays that detect immune response, with specific application to HIV-1. The inherent polyclonal diversity of the humoral immune response was addressed by using sequential in situ click chemistry to develop a cocktail of peptide-based capture agents, the components of which were raised against different, representative anti-HIV antibodies that bind to a conserved epitope of the HIV-1 envelope protein gp41. The cocktail was used to detect anti-HIV-1 antibodies from a panel of sera collected from HIV-positive patients, with improved signal-to-noise ratio relative to the gold standard commercial recombinant protein antigen. The capture agents were stable when stored as a powder for two months at temperatures close to 60°C.

Development and standardization of solid phase assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). A report on the second phase of an international cooperative study on the standardization of ANCA assays

Anti-neutrophil cytoplasmic antibodies (ANCA) are diagnostic markers for systemic vasculitis. They are classically I detected by an indirect immunofluorescence test using normal donor neutrophils as substrate. This assay lacks antigenic specificity and is not quantitative. The 'EC/BCR Project for ANCA Assay Standardization' is an international collaboration study with the aim to develop and standardize solid phase assays for ANCA detection. In this part of the study the isolation and characterization of proteinase-3 and myeloperoxidase, the two main target molecules for ANCA, and the development and standardization of ELISAs with these antigens are described. Six laboratories successfully isolated purified proteinase-3 preparations that could be used. Three of these preparations, together with one myeloperoxidase preparation, were subsequently used for ANCA testing by ELISA. The ELISA technique was standardized in two rounds of testing in the 14 participating laboratories. The coefficient of variation of these new assays decreased from values of approx. 50% in the first round to approx. 20% in the second round. We conclude that purified proteinase-3 and myeloperoxidase can be used in standardized ELISAs for ANCA detection. Whether such procedures offer advantages over the IIF test will be determined in a prospective clinical study.

Favorable effect on acute and chronic graft-versus-host disease with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies for marrow transplantation from HLA-identical sibling donors for acquired aplastic anemia

Between August 1989 and November 2003, 33 patients at our center with acquired aplastic anemia underwent bone marrow transplantation (BMT) from HLA-identical sibling donors with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies (MoAb) for conditioning. The median age at BMT was 17 years (range, 4-46 years). Before BMT, 58% were heavily transfused (>50 transfusions), and 42% had previously experienced treatment failure with antithymocyte globulin-based immunosuppressive therapy. Unmanipulated bone marrow was used as the source of stem cells in all patients except 1. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine alone in 19 (58%) patients; 14 received anti-CD52 MoAb in addition to cyclosporine. The conditioning regimen was well tolerated without significant acute toxicity. Graft failure was seen in 8 patients (primary, n = 4; secondary, n = 4). Of those whose grafts failed, 4 survived long-term (complete autologous recovery, n = 2; rescue with previously stored marrow, n = 1; second allograft, n = 1). The cumulative incidence of graft failure and grade II to IV acute and chronic GVHD was 24%, 14%, and 4%, respectively. None developed extensive chronic GVHD. With a median follow-up of 59 months, the 5-year survival was 81% (95% confidence interval, 68%-96%). No unexpected early or late infectious or noninfectious complications were observed. We conclude that the conditioning regimen containing cyclophosphamide and anti-CD52 MoAb is well tolerated and effective for acquired aplastic anemia with HLA-matched sibling donors. The favorable effect on the incidence and severity of GVHD is noteworthy in this study and warrants further investigation.

Spectrum of Somatic Hypermutations and Implication on Antibody Function: Case of the anti HIV-1 antibody, b12

Thesis (Ph.D.)--University of Washington, 2015

Seroprevalence of anti-Leishmania spp. antibodies in rural dogs from the city of Monte Negro, State of Rondonia, Brazil

The present study assessed the prevalence of anti-Leishmania spp antibodies in dogs from the city of Monte Negro, State of Rondonia, Brazil ELISA (NE >= 3) and IFAT (>= 1 40) were used to evaluate 161 serum samples collected from rural dogs from Monte Negro Forty-five (27 9%) dogs were positive by ELISA tests and five (3 1%) were positive by IFAT The present study showed for the first time the frequency of exposure to Leishmania spp in dogs in the State of Rondonia, Amazon Region

Anti-Toxocara spp. antibodies in sheep from southeastern Brazil

The purpose of this study was to evaluate the frequency of anti-Toxocara antibodies in sheep from Presidente Prudente, southeastern Brazil. Serum samples were obtained from 365 sheep of diverse breeds and different ages. Samples were collected at a slaughterhouse and at farms located in Presidente Prudente. Three groups of animal of different ages were evaluated according to age: Group I: between 1 and 6 months old; Group II: between 7 and 10 months old; and Group III: between 11 and 15 months old. An ELISA test was carried out to detect anti-Toxocara antibodies (IgG) using the excretory-secretory antigens of Toxocara canis (TES) larvae. In total, 183 out of 365 animals (50.1%) were positive for anti-Toxocara antibodies. The frequency of antibody detection was directly proportional to the age of the animals (p<0.0001). indicating a relationship between infection and aging. In Group III, there was a higher prevalence in females (p = 0.0041). The relevance of these animals to the epidemiology of toxocariasis in pets and human should be considered. (C) 2011 Elsevier B.V. All rights reserved.

Detection of anti-Toxoplasma gondii antibodies in experimentally and naturally infected non-human primates by Indirect Fluorescence Assay (IFA) and indirect ELISA

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Seroprevalence of anti-Leishmania spp. antibodies in rural dogs from the city of Monte Negro, State of Rondônia, Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Occurrence of anti-Neospora caninum antibodies in Brazilian cervids kept in captivity

Neospora caninum is a coccidian parasite that causes disease in captive and domesticated animals and has been found in wild animals such as cervids. Sera from 150 cervids of the genus Mazama, were collected from 31 captive herds and 16 zoos from different Brazilian regions and analyzed by indirect fluorescent antibody test for anti-N. caninum antibodies. Positive reactions were found in 42% (63) of the samples and the titers varied from 50 to 51,200. of the 86 cervids from the captive herds, 38 (44.2%) had anti N. caninum antibodies and of the 64 samples from the zoo, 25 (39.1%) were positive. No significant difference (p > 0.05) was found for the occurrence values observed between the animals from captive herds and zoos as well as within the values documented for each one of the species analyzed. Therefore, the results indicate that the agent is prevalent from cervids in captivity in Brazil. (c) 2005 Elsevier B.V. All rights reserved.

Environmental effect on the occurrence of anti-Neospora caninum antibodies in pampas-deer (Ozotoceros bezoarticus)

Sera obtained from pampas-deer (Ozotoceros bezoarticus) captured in two different Brazilian environments were analyzed for the presence of anti-Neospora caninum antibodies by the indirect fluorescent antibody test (IFAT). Samples were collected from 23 animals from a savanna area in the National Park of Emas, in the state of Goias, Brazil. This area is surrounded by cultivated lands and allows very little contact between wild and domestic animals. Another batch of samples was collected from 16 animals from the Pantanal region, in the state of Mato Grosso, Brazil. This area is a flood plain where domestic animals have intensive contact with cervids. The 39 samples were analyzed (IFAT >= 1:50), and the values for the occurrences found in the animals from each region were compared by the test for comparison of two proportions. of the 39 cervids examined, 38.46% (15) had anti-N. caninum antibodies. Three (13%) of the 23 samples from the National Park of Emas. and 12 (75%) of the 16 samples from the Pantanal were positive, with significant differences between regions (p < 0.001). These results suggested that the presence of domestic animals, mainly dogs and cattle, may be responsible for the greater occurrence of N. caninum in the Pantanal cervids.Thus, as a recommendation of the Conservation Units that care for the pampas-deer, attention should be taken to carefully monitor the flow of diseases between the domestic animals and this species. (c) 2005 Elsevier B.V. All rights reserved.