This study examines the constructions of leprosy in Colombia from the late nineteenth century to the 1930s. In the nineteenth century Colombian physicians constructed leprosy as highly infectious and threatening and adopted rigid segregation of “lepers” to prevent its propagation. At the same time, medicine was becoming a profession in Colombia, and physicians used leprosy to build their cultural and scientific authority. In order to assert their power, doctors exaggerated the number of leprosy sufferers, and unfolded a nationalist rhetoric. Colombian isolation policies had their roots in Spanish medieval traditions and in international examples. Colombian physicians were aware of European scientific developments. In the 1870s, the Norwegian physician Gerhard A. Hansen postulated what later came to be known as Mycobacterium leprae as the causative agent of leprosy. In 1897, the first international conference on leprosy declared leprosy a disease produced by Hansen’s bacillus. Meanwhile, Westerners discovered leprosy in their colonial territories during their imperialist expansion of the late nineteenth century. They developed a racialist image of leprosy as a disease afflicting inferior peoples, and instituted an international movement to build leprosaria in which to isolate patients. Colombian doctors also adopted a colonialist attitude towards their own leprous population. In the early twentieth century, the Colombian government, took charge of leprosaria, imposing severe regulations related to compulsory isolation. The state and the physicians treated leprosy as a disease apart, reinforcing prejudices of medieval origin. They tried to transform the town-lazarettos, which had been built by patients themselves in the 1870s, into colonies exclusively for lepers. Patients actively resisted the medicalization of leprosy, and non-leprous people remained within the lazarettos during this period. In the 1930s, the medical rhetoric started to change. As a result of improvements in leprosy therapy, doctors began to regard leprosy as a curable disease and to reject compulsory isolation for patients in all stages of infection. The physicians’ emphasis shifted from isolation to prevention and research. Scientific prevailed over social reform, and physicians and the government gave priority to searching for a vaccine instead of improving the general living conditions of the population. / Ph. D.

Yes / Goal setting is a fundamental practice in the effective management of healthcare services worldwide. This study investigated the extent to which leprosy goal formulation in Nigeria is logical and SMART. Method: Document review of baseline problems, goal statements and goal attainments for 2016 in six leprosy projects using a customised logical framework matrix. Results: A total of 15 main problems, 6 aims, 19 objectives and 42 indicators were found. The goals were problem-based and logically linked, with a pattern of a single aim per project, multiple objectives per aim, and multiple indicators per objective. Goal statements specified only impact in 5/6 aims, and only outcome and terminal timeframe in 17/19 (89.5%) objectives. Only one objective stated all four SMART components of outcome, indicator, target and timeframe. While three (7.1%) indicators and two (10.5%) objectives were measurable, no target was attainable. Discussion: Goal-setting frameworks for leprosy projects should be problem based and logical according to best practice. That most leprosy objectives were not completely SMART is similar to the reported structure of objectives published by other health organisations globally.

No / Goal-setting is indispensable for effective healthcare management. Yet, literature evidence suggests many organisations worldwide do not know how to formulate ‘SMART’ goals. Evidence of how existing theories work in practice is scarce, and the practices in low-income countries are unknown. Therefore, this research explored how leprosy project goals were formulated to describe the theoretical practice framework of A leprosy-focused organisation in Nigeria. Using a case-study design, ten managers were interviewed individually concerning their goal-setting knowledge, experience and perspective; and documented goals of six projects were reviewed. A five-step constructionist thematic data analysis generated eleven theoretical frameworks from the concepts of the emergent core themes of ‘stakeholders’, ‘strategies’ and ‘statements.’ Further theorisation reduced them to one general framework. This revealed organisational goal-setting practice as a four-stage centre-led, top-down, beneficiary-focused and problem-based process. The stages were national preparation, baseline needs-survey, centralised goal formulation and nationalised planning. The outcome was the formulation of assigned, ‘non-SMART’ objective statements, which are then used for planning projects. Other theoretical models constructed included a Goal Effects Cycle, ‘SMARTA’ goal attributes and hierarchical criteria for differentiating goal-types. A theory developed from the goal-setting practice postulates that: ‘Assigned non-SMART goal formulation directly results from centralised goal-setting practice and is the predictor of unrealistic project planning.’ Therefore, I propose that goal statements will be ‘SMARTA’ and plans, more realistic and relevant if goal-setting is done collaboratively by all stakeholders at all stages of the process. Also, ‘Change-Beneficiary-Indicator-Target-Timeframe’ and ‘Change-Beneficiary-Location-Timeframe’ frameworks are recommended as templates for writing SMART objectives and aims respectively.

No / This study compares associations between demographic profiles, long bone lengths, bone mineral content, and frequencies of stress indicators in the preadult populations of two medieval skeletal assemblages from Denmark. One is from a leprosarium, and thus probably represents a disadvantaged group (Næstved). The other comes from a normal, and in comparison rather privileged, medieval community (Æbelholt). Previous studies of the adult population indicated differences between the two skeletal collections with regard to mortality, dental size, and metabolic and specific infectious disease. The two samples were analyzed against the view known as the osteological paradox (Wood et al. [1992] Curr. Anthropol. 33:343-370), according to which skeletons displaying pathological modification are likely to represent the healthier individuals of a population, whereas those without lesions would have died without acquiring modifications as a result of a depressed immune response. Results reveal that older age groups among the preadults from Næstved are shorter and have less bone mineral content than their peers from Æbelholt. On average, the Næstved children have a higher prevalence of stress indicators, and in some cases display skeletal signs of leprosy. This is likely a result of the combination of compromised health and social disadvantage, thus supporting a more traditional interpretation. The study provides insights into the health of children from two different biocultural settings of medieval Danish society and illustrates the importance of comparing samples of single age groups.

Yes / We examined six skeletons from mediaeval contexts from two sites in England for the presence of Mycobacterium leprae DNA, each of the skeletons displaying osteological indicators of leprosy. Polymerase chain reactions directed at the species-specific RLEP multicopy sequence produced positive results with three skeletons, these being among those with the clearest osteological signs of leprosy. Following in-solution hybridization capture, sufficient sequence reads were obtained to cover >70% of the M. leprae genomes from these three skeletons, with a mean read depth of 4–10×. Two skeletons from a mediaeval hospital in Chichester, UK, dating to the 14th–17th centuries AD, contained M. leprae strains of subtype 3I, which has previously been reported in mediaeval England. The third skeleton, from a churchyard cemetery at Raunds Furnells, UK, dating to the 10th to mid-12th centuries AD, carried subtype 3K, which has been recorded at 7th–13th century AD sites in Turkey, Hungary and Denmark, but not previously in Britain. We suggest that travellers to the Holy Land might have been responsible for the transmission of subtype 3K from southeast Europe to Britain. / Funded by a studentship awarded by Majlis Amanah Rakyat (MARA) to A.K. and by the University of Bradford and the University of Manchester.

Submitted by Nuzia Santos (nuzia@cpqrr.fiocruz.br) on 2016-07-07T12:38:57Z No. of bitstreams: 1 Jairo Campos de Carvalho Avaliação da produção de óxido nítrico, citocinas e expressão de receptores Toll em leucócitos do sangue periférico de pacientes com reações hansênicas e formas clínicas da hanseníase 2016.pdf: 2181484 bytes, checksum: d0a59c438a72ba1abbf03a31f901d434 (MD5) / Approved for entry into archive by Nuzia Santos (nuzia@cpqrr.fiocruz.br) on 2016-07-07T12:39:08Z (GMT) No. of bitstreams: 1 Jairo Campos de Carvalho Avaliação da produção de óxido nítrico, citocinas e expressão de receptores Toll em leucócitos do sangue periférico de pacientes com reações hansênicas e formas clínicas da hanseníase 2016.pdf: 2181484 bytes, checksum: d0a59c438a72ba1abbf03a31f901d434 (MD5) / Made available in DSpace on 2016-07-07T12:39:09Z (GMT). No. of bitstreams: 1 Jairo Campos de Carvalho Avaliação da produção de óxido nítrico, citocinas e expressão de receptores Toll em leucócitos do sangue periférico de pacientes com reações hansênicas e formas clínicas da hanseníase 2016.pdf: 2181484 bytes, checksum: d0a59c438a72ba1abbf03a31f901d434 (MD5) Previous issue date: 2016 / Made available in DSpace on 2016-07-08T18:46:22Z (GMT). No. of bitstreams: 3 Jairo Campos de Carvalho Avalia??o da produ??o de ?xido n?trico, citocinas e express?o de receptores Toll em leuc?citos do sangue perif?rico de pacientes com rea??es hans?nicas e formas cl?nicas da hansen?ase 2016.pdf.txt: 165886 bytes, checksum: 99c9bf145630a298a5981d91ce0b9e67 (MD5) Jairo Campos de Carvalho Avalia??o da produ??o de ?xido n?trico, citocinas e express?o de receptores Toll em leuc?citos do sangue perif?rico de pacientes com rea??es hans?nicas e formas cl?nicas da hansen?ase 2016.pdf: 2181484 bytes, checksum: d0a59c438a72ba1abbf03a31f901d434 (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) Previous issue date: 2016 / Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil / O objetivo deste estudo foi identificar biomarcadores associados com as distintas formas/manifestações da hanseníase. Características fenotípicas (TLR2; TLR4; HLA-DR) e funcionais (NO-DAF-2T; IL-8;TNF-α; IL-4; IL-10;TGF- β) da imunidade inata (Neutrofilos-NEU; Monocitos-MON) e adaptiva (CD4+; CD8+T-cells) foram avaliadas ex vivo e sob estímulo de M. leprae in vitro (*). A população do estudo incluiu indivíduos com as forma Tuberculóide (DD/DT/T); Virchowiano (DV/V); reação hansênica Tipo-1; reação hansênica Tipo-2 e indivíduos saudáveis controle (NI). A análise dos dados demonstrou que independente da forma clínica, pacientes com hanseníase apresentaram baixo NEU TLR4+ e MON TGF-β+, enquanto DV/V apresentou alto MON HLA-DR+. Ambos DD/DT/T e DV/V apresentou aumento de CD4+IL-10+, mas não somente DV/V apresentou aumento de CD8+TLR2+ e IL-10. Pacientes com reação Tipo-1 exibiram, no geral, uma baixa na regulação de TLR na imunidade inata e adaptativa (NEU: MON TLR2+ e NEU: CD4+TLR4+). Foi observada uma alta regulação de CD4+: CD8+IL-10+ nos indivíduos com reação hansênica, mas somente pacientes com reação do Tipo-2 mostrou aumento em MON IL-10+. Assinaturas de biomarcadores específicos para M. leprae (*) revelaram uma expansão das características fenotípicas e funcionais nos pacientes com hanseníase com aumento de *MON NO-DAF-2T+ em DD/DT/T e alta regulação de *NEU TLR2+ e *CD8+IL-10+ em DV/V. Foi evidenciado diminuição na expressão dos principais biomarcadores dos pacientes com reação hansênica particularmente na imunidade adaptativa. Um resumo dos dados trabalhados indicou que MON IL-10+ e *NEU TLR4+ podem ser considerados como biomarcadores universais da hanseníase juntamente com MON TGF-β+; *MON TNF-α+; *CD4+TGF-β+; *CD8+TLR2+; *CD8+TNF-α+; *CD8+IL-4+; *CD8+TGF-β+ como um ensaio clínico relacionado com as características da hanseníase e *CD4+ como biomarcadores de reação hansênica. MON HLA-DR+; *CD8+IL-10+ foram biomarcadores polo seletivo para DV/V, NEU TLR2+; NEU TLR4+; CD4+TLR4+; *NEU NO-DAF-2T+; *MON TLR2+; *MON HLA-DR+; *CD4+TLR2+; *CD4+TLR4+; *CD8+ para reação hansênica Tipo-1 e MONIL-10+; *CD8+IL-8+ para Tipo-2. Em conclusão, este estudo mostrou a existência de diferenças em marcadores imunológicas entre as formas/manifestações da hanseníase que poderão ser futuramente aplicados como biomarcadores para estudos clínicos. / The aim of this study was to identify biomarkers associated with distinct clinical forms/manifestations of leprosy. Phenotypic (TLR2;TLR4;HLA-DR) and fuctional features (NO-DAF-2T;IL-8;TNF-α;IL-4;IL-10;TGF-β) of innate (Neutrophils- NEU;Monocytes-MON) and adaptive (CD4+;CD8+T-cells) immunity were evaluated at ex vivo and upon M. leprae stimuli in vitro (*). Study population included tuberculoid-(BB/BT/T); lepromatous-(BL/L); Type-1; Type-2 and healthy controls-(NI). Data analysis demonstrated that regardless of clinical forms, leprosy patients presented lower NEUTLR4+ and MONTGF-β+, while BL/L displayed higher MONHLA-DR+. Both BB/BT/T and BL/L showed enhanced CD4+IL-10+, but only BL/L presented increased CD8+TLR2+ and IL- 10. Type-1 patients displayed an overall downregulation of TLR in innate/adaptive immunity (NEU:MONTLR2+ and NEU:CD4+TLR4+). An overall upregulation of CD4+:CD8+IL-10+ was observed in leprosy reactions, but only Type-2 patients displayed enhanced MONIL-10+. M. leprae-specific (*) biomarker signatures revealed an expansion of phenotypic and functional features in leprosy patients with enhanced *MONNO-DAF-2T+ in BB/BT/T and upregulation of *NEUTLR2+ and *CD8+IL-10+ in BL/L. Evident was the shrinkage of most biomarkers in leprosy reaction patients particularly in the adaptive immunity. A summary of data mining indicated MONIL-10+ and *NEUTLR4+ as universal leprosy biomarkers along with MONTGF- β+;*MONTNF-α+;*CD4+TGF-β+;*CD8+TLR2+;*CD8+TNF-α+;*CD8+IL- 4+;*CD8+TGF-β+ as clinical-related leprosy features and *CD4+ as leprosy reaction biomarker. MONHLA-DR+;*CD8+IL-10+ were pole-selective biomarkers for BL/L, NEUTLR2+;NEUTLR4+;CD4+TLR4+;*NEUNO-DAF- 2T+;*MONTLR2+;*MONHLA-DR+;*CD4+TLR2+;*CD4+TLR4+; *CD8+ for Type-1 and MONIL-10+;*CD8+IL-8+ for Type-2. In conclusion, this study provided insights into the immunological features of leprosy forms/manifestations applicable as novel biomarkers for clinical studies.

Leprosy is a chronic, infectious-contagious disease caused by the Mycobacterium leprae bacillus. This is transmitted by airway and infects phagocytic cells of the skin and the Schwann cells of the peripheral nerves. Despite clinical treatment, patients may present with inflammatory complications such as leprosy reactions and lesions on peripheral nerves which may progress to physical disability. The disease may present different profiles of immune responses that are related to its clinical manifestations. Although it is known about the immune response in leprosy and the influence of hormones in the evolution of infections, there is still no understanding to generate markers that can define the most serious clinical forms and inflammatory complications of the disease. Therefore, this work aimed to identify immunological and hormonal aspects associated with the clinical presentation and complications of leprosy. The methodology included a cross-sectional study comparing groups based on the collection of clinical data and serum markers (immunological and hormonal) of healthy contact controls and patients with leprosy. In addition, a cohort study was carried out with monthly follow up and up to one year after clinical discharge in order to evaluate the occurrence of reactional episodes and/or physical disability. Serum levels of hormones (adrenocorticotrophic- ACTH, cortisol, Insulin-like growth factor type 1-IGF-1 and testosterone) and cytokines (INF-ɣ, IL-12p70, IL-17A, IL1-β, IL-10 and TNF-ɣ was related to clinical forms (indeterminate-IL, tuberculoid-TT, boderline-BL and lepromatous- LL), operational classification (paucibacillary-PB and multibacillary-MB), presence of reactional episodes and physical disability. There was a higher proportion of MB men (54.3%). MB patients also had a higher frequency of reaction episodes (44.4%) and physical disability (76.5%) when compared to patients with PB. As regards the presence of circulating hormones, high levels of ACTH were found in MB (24.2 ±13.1 ng/ml, p= 0.002) and PB (23.5 ± 14.9 ng/ml, p = 0.007) when compared whit controls (11.9 ± 12.3 ng/ml). High levels of cortisol were also detected in TT patients (12.1 ± 4.7 μg/dl) compared to controls (8.4 ± 2.7 μg/dl, p = 0.003), BL (9.02 ± 4 , 8 μg/dL, p = 0.004) and LL (8.9 ± 2.7 μg/dL, p = 0.03). Patients who had leprosy before treatment had lower levels of ACTH (19.7 ± 10.3 ng/ml) and cortisol (8.5±3.9 ng/ml; p= 0.04) when compared with the patients without reaction. A positive correlation was observed when correlating ACTH and cortisol between the hormones (CI: 0.35-0.65, r= 0.52, p <0.0001). Higher IGF-1 levels were obtained in IL patients (6.5 ± 6.4 ng/ml) than in the other forms (TT 3.03 ± 3.5 ng/ml; BL 3.1 ± 4.5 ng/ml; LL 3.6 ± 2.5 ng/ml). Patients with physical disabilities (grades 1 and 2) have lower levels of IGF-1 (2.8 ± 1.6 ng/ml) compared to those without this limitation (grade 0: 4.5 ± 2,7 ng/ml, p= 0.007). High testosterone levels were found in men over 50 years of age and MB (6.58 ± 3.2 ng/ml) when compared to PB men (4.21 ± 2.3 ng/ml) and controls (4.26 ± 0,8 ng/ml). Regarding the evaluation of immunological markers, all the cytokines evaluated were increased in the patients, in comparison to the controls, highlighting INF-ɣ (79.02 ± 26.9 pg/ml), IL-10 (156.4 ± 53 pg/ml) and TNF-α (463.3±160.6 pg/ml) that were elevated in the LL forms. Regarding IL-17A, patients with TT presented higher levels (49.2±10.5 pg/ml) when compared to patients with LL (40.7 ± 4.6 pg/ml). IL1-β was elevated in IL forms (62.9 ± 16.3 pg/ml) when compared to more severe forms of the disease and controls. Finally, the increase in INF-ɣ (97.1 ± 44.5 pg/ml, p= 0.02) and TNF-α (407.3 ± 82.08 pg/ml, p= 0.04) was related in MB patients to the occurrence of reaction episode. The latter was also higher in patients with physical disability (354.3 ± 92.2 pg/ml, p= 0.04). The hormonal and immunological markers support the hypothesis that the interaction between leprosy and the neuroendocrine and immunological systems play an important role in the natural course of M. leprae infection. Reduced concentrations of cortisol and IGF-1, high testosterone concentrations related to the worst clinical outcome suggest that these hormones are important modulators of the inflammatory episode and supports future therapeutical studies as well as the attempt of prophylactic treatment. In addition, IL-17 and IL-1β cytokines act to control bacillus multiplication. The cytokines IFN-ɣ and TNF-α were associated with the presence of a reaction suggesting a deleterious effect on the lesion. / A Hanseníase é uma doença crônica, infecto-contagiosa, causada pelo bacilo Mycobacterium leprae. Este é transmitido por via aérea superior e infecta células fagocíticas da pele e as células de Schwann dos nervos periféricos. Apesar do tratamento clínico, os pacientes podem apresentar complicações inflamatórias como as reações hansênicas e lesões em nervos periféricos o que pode evoluir para incapacidade física. A doença pode apresentar diferentes perfis de respostas imunológicas que estão relacionadas com as suas manifestações clínicas. Embora se conheça sobre a resposta imune na hanseníase e da influencia hormônal na evolução de infecções, ainda não há entendimento para gerar marcadores que possam definir as formas clínicas mais graves e complicações inflamatórias da doença. Diante disso, esse trabalho objetivou identificar aspectos imunológicos e hormonais associados à apresentação clínica e complicações da hanseníase. A metodologia incluiu um estudo transversal de comparação de grupos baseado na coleta de dados clínicos e marcadores séricos (imunológicos e hormonais) de controles contactantes sadios e pacientes com hanseníase. Além disso foi realizado um estudo de coorte com acompanhamento mensal e até um ano após a alta clínica a fim de avaliar o surgimento de episódios reacionais e/ou incapacidade física. Foram realizadas dosagem séricas de hormônios (adenocorticotrófico-ACTH, cortisol, fator de crescimento semelhante à insulina tipo 1- IGF-1 e testosterona) e de citocinas (INF-ɣ, IL-12p70, IL-17A, IL1-β, IL-10 e TNF-α) e, em seguida, relacionados às formas clínicas (Indeterminada- HI, Tuberculóide- HT, Dimorfa- HD e Virchowiana- HV), classificação operacional (Paucibacilar-PB e Multibacilar-MB), presença de episódios reacionais e incapacidade física. Os resultados encontraram maior proporção de homens MB (54,3%). Os pacientes MB também apresentaram maior frequência de episódios reacional (44,4%) e incapacidade física (76,5%) em comparação aos pacientes PB. Quanto à presença de hormônios circulantes foi encontrado níveis elevados de ACTH em MB (24,2±13,1 ng/ml; p= 0,002) e PB (23,5±14,9 ng/ml; p= 0,007) quando comparados aos controles (11,9±12,3 ng/ml). Concentrações elevadas de cortisol também foram detectados nos pacientes HT (12,1±4,7 μg/dl) em relação aos controles (8,4±2,7 μg/dl, p= 0,003), HD (9,02±4,8 μg/dl; p= 0,004) e os HV (8,9±2,7 μg/dl; p= 0,03). Os pacientes que apresentaram reação hansênica antes do tratamento tiveram níveis mais baixos de ACTH (19,7±10,3 ng/ml) e cortisol (8,5±3,9 ng/ml; p= 0,04) quando comparados com os pacientes sem reação. Também foi observado correlação positiva entre ACTH e cortisol (IC: 0,35-0,65; r=0,52; p<0,0001). Foram obtidos níveis mais altos de IGF-1 nos pacientes HI (6,5±6,4 ng/ml) que nas demais formas (HT 3,03±3,5 ng/ml; HD 3,1±4,5 ng/ml; HV 3,6±2,5 ng/ml). Os pacientes com incapacidades físicas (graus 1 e 2) apresentam concentrações mais baixas de IGF-1 (2,8±1,6 ng/ml) quando comparados aos que não apresentam essa limitação (grau 0: 4,5±2,7 ng/ml; p= 0,007). Níveis elevados de testosterona foram encontrados em homens acima de 50 anos e MB (6,58± 3,2 ng/ml) quando comparado aos homens PB (4,21± 2,3 ng/ml) e com os controles (4,26± 0,8 ng/ml). Em relação à avaliação de marcadores imunológicos todas as citocinas avaliadas estiveram aumentadas nos pacientes, em relação aos controles, destacando INF-ɣ (79,02 ± 26,9 pg/ml), IL-10 (156,4 ± 53 pg/ml) e TNF-α (463,3 ± 160,6 pg/ml) que estavam elevadas nas HV. Em relação à IL-17A, os pacientes com HT apresentaram níveis mais elevados (49,2 ± 10,5 pg/ml) quando comparados aos valores de pacientes com HV (40,7 ± 4,6 pg/ml). Já a IL1-β esteve elevada formas HI (62,9 ± 16,3 pg/ml) quando comparada às formas mais graves da doença e aos controles. Por fim o aumento em INF-ɣ (97,1 ± 44,5 pg/ml, p= 0,02) e TNF-α (407,3 ± 82,08 pg/ml, p= 0,04) esteve relacionado, nos pacientes MB, à ocorrência de episódio reacional. E esta última, também, mais elevada nos pacientes com incapacidade física (354,3 ± 92,2 pg/ml, p= 0,04). Os marcadores hormonais e imunológicos acima descritos suportam a hipótese de que a interação entre a hanseníase e os sistemas neuroendócrinos e imunológicos desempenham um papel importante no curso natural da infecção pelo M. Leprae. Concentrações reduzidas de cortisol e IGF-1, altas concentrações de testosterona relacionadas ao pior desfecho clínico sugerem esses hormônios sejam importantes moduladores do episódio inflamatório e dá suporte estudos terapeuticos futuros bem como a tentativa de tratamento profilático. Além disso, as citocinas IL-17 e IL-1β atuam no controle da multiplicação do bacilo. Já as citocinas IFN- ɣ e TNF-α foram associadas a presença de reação sugerindo um efeito deletério na lesão.

Leprosy is a chronic, infectious-contagious disease caused by the Mycobacterium leprae bacillus. This is transmitted by airway and infects phagocytic cells of the skin and the Schwann cells of the peripheral nerves. Despite clinical treatment, patients may present with inflammatory complications such as leprosy reactions and lesions on peripheral nerves which may progress to physical disability. The disease may present different profiles of immune responses that are related to its clinical manifestations. Although it is known about the immune response in leprosy and the influence of hormones in the evolution of infections, there is still no understanding to generate markers that can define the most serious clinical forms and inflammatory complications of the disease. Therefore, this work aimed to identify immunological and hormonal aspects associated with the clinical presentation and complications of leprosy. The methodology included a cross-sectional study comparing groups based on the collection of clinical data and serum markers (immunological and hormonal) of healthy contact controls and patients with leprosy. In addition, a cohort study was carried out with monthly follow up and up to one year after clinical discharge in order to evaluate the occurrence of reactional episodes and/or physical disability. Serum levels of hormones (adrenocorticotrophic- ACTH, cortisol, Insulin-like growth factor type 1-IGF-1 and testosterone) and cytokines (INF-ɣ, IL-12p70, IL-17A, IL1-β, IL-10 and TNF-ɣ was related to clinical forms (indeterminate-IL, tuberculoid-TT, boderline-BL and lepromatous- LL), operational classification (paucibacillary-PB and multibacillary-MB), presence of reactional episodes and physical disability. There was a higher proportion of MB men (54.3%). MB patients also had a higher frequency of reaction episodes (44.4%) and physical disability (76.5%) when compared to patients with PB. As regards the presence of circulating hormones, high levels of ACTH were found in MB (24.2 ±13.1 ng/ml, p= 0.002) and PB (23.5 ± 14.9 ng/ml, p = 0.007) when compared whit controls (11.9 ± 12.3 ng/ml). High levels of cortisol were also detected in TT patients (12.1 ± 4.7 μg/dl) compared to controls (8.4 ± 2.7 μg/dl, p = 0.003), BL (9.02 ± 4 , 8 μg/dL, p = 0.004) and LL (8.9 ± 2.7 μg/dL, p = 0.03). Patients who had leprosy before treatment had lower levels of ACTH (19.7 ± 10.3 ng/ml) and cortisol (8.5±3.9 ng/ml; p= 0.04) when compared with the patients without reaction. A positive correlation was observed when correlating ACTH and cortisol between the hormones (CI: 0.35-0.65, r= 0.52, p <0.0001). Higher IGF-1 levels were obtained in IL patients (6.5 ± 6.4 ng/ml) than in the other forms (TT 3.03 ± 3.5 ng/ml; BL 3.1 ± 4.5 ng/ml; LL 3.6 ± 2.5 ng/ml). Patients with physical disabilities (grades 1 and 2) have lower levels of IGF-1 (2.8 ± 1.6 ng/ml) compared to those without this limitation (grade 0: 4.5 ± 2,7 ng/ml, p= 0.007). High testosterone levels were found in men over 50 years of age and MB (6.58 ± 3.2 ng/ml) when compared to PB men (4.21 ± 2.3 ng/ml) and controls (4.26 ± 0,8 ng/ml). Regarding the evaluation of immunological markers, all the cytokines evaluated were increased in the patients, in comparison to the controls, highlighting INF-ɣ (79.02 ± 26.9 pg/ml), IL-10 (156.4 ± 53 pg/ml) and TNF-α (463.3±160.6 pg/ml) that were elevated in the LL forms. Regarding IL-17A, patients with TT presented higher levels (49.2±10.5 pg/ml) when compared to patients with LL (40.7 ± 4.6 pg/ml). IL1-β was elevated in IL forms (62.9 ± 16.3 pg/ml) when compared to more severe forms of the disease and controls. Finally, the increase in INF-ɣ (97.1 ± 44.5 pg/ml, p= 0.02) and TNF-α (407.3 ± 82.08 pg/ml, p= 0.04) was related in MB patients to the occurrence of reaction episode. The latter was also higher in patients with physical disability (354.3 ± 92.2 pg/ml, p= 0.04). The hormonal and immunological markers support the hypothesis that the interaction between leprosy and the neuroendocrine and immunological systems play an important role in the natural course of M. leprae infection. Reduced concentrations of cortisol and IGF-1, high testosterone concentrations related to the worst clinical outcome suggest that these hormones are important modulators of the inflammatory episode and supports future therapeutical studies as well as the attempt of prophylactic treatment. In addition, IL-17 and IL-1β cytokines act to control bacillus multiplication. The cytokines IFN-ɣ and TNF-α were associated with the presence of a reaction suggesting a deleterious effect on the lesion. / A Hanseníase é uma doença crônica, infecto-contagiosa, causada pelo bacilo Mycobacterium leprae. Este é transmitido por via aérea superior e infecta células fagocíticas da pele e as células de Schwann dos nervos periféricos. Apesar do tratamento clínico, os pacientes podem apresentar complicações inflamatórias como as reações hansênicas e lesões em nervos periféricos o que pode evoluir para incapacidade física. A doença pode apresentar diferentes perfis de respostas imunológicas que estão relacionadas com as suas manifestações clínicas. Embora se conheça sobre a resposta imune na hanseníase e da influencia hormônal na evolução de infecções, ainda não há entendimento para gerar marcadores que possam definir as formas clínicas mais graves e complicações inflamatórias da doença. Diante disso, esse trabalho objetivou identificar aspectos imunológicos e hormonais associados à apresentação clínica e complicações da hanseníase. A metodologia incluiu um estudo transversal de comparação de grupos baseado na coleta de dados clínicos e marcadores séricos (imunológicos e hormonais) de controles contactantes sadios e pacientes com hanseníase. Além disso foi realizado um estudo de coorte com acompanhamento mensal e até um ano após a alta clínica a fim de avaliar o surgimento de episódios reacionais e/ou incapacidade física. Foram realizadas dosagem séricas de hormônios (adenocorticotrófico-ACTH, cortisol, fator de crescimento semelhante à insulina tipo 1- IGF-1 e testosterona) e de citocinas (INF-ɣ, IL-12p70, IL-17A, IL1-β, IL-10 e TNF-α) e, em seguida, relacionados às formas clínicas (Indeterminada- HI, Tuberculóide- HT, Dimorfa- HD e Virchowiana- HV), classificação operacional (Paucibacilar-PB e Multibacilar-MB), presença de episódios reacionais e incapacidade física. Os resultados encontraram maior proporção de homens MB (54,3%). Os pacientes MB também apresentaram maior frequência de episódios reacional (44,4%) e incapacidade física (76,5%) em comparação aos pacientes PB. Quanto à presença de hormônios circulantes foi encontrado níveis elevados de ACTH em MB (24,2±13,1 ng/ml; p= 0,002) e PB (23,5±14,9 ng/ml; p= 0,007) quando comparados aos controles (11,9±12,3 ng/ml). Concentrações elevadas de cortisol também foram detectados nos pacientes HT (12,1±4,7 μg/dl) em relação aos controles (8,4±2,7 μg/dl, p= 0,003), HD (9,02±4,8 μg/dl; p= 0,004) e os HV (8,9±2,7 μg/dl; p= 0,03). Os pacientes que apresentaram reação hansênica antes do tratamento tiveram níveis mais baixos de ACTH (19,7±10,3 ng/ml) e cortisol (8,5±3,9 ng/ml; p= 0,04) quando comparados com os pacientes sem reação. Também foi observado correlação positiva entre ACTH e cortisol (IC: 0,35-0,65; r=0,52; p<0,0001). Foram obtidos níveis mais altos de IGF-1 nos pacientes HI (6,5±6,4 ng/ml) que nas demais formas (HT 3,03±3,5 ng/ml; HD 3,1±4,5 ng/ml; HV 3,6±2,5 ng/ml). Os pacientes com incapacidades físicas (graus 1 e 2) apresentam concentrações mais baixas de IGF-1 (2,8±1,6 ng/ml) quando comparados aos que não apresentam essa limitação (grau 0: 4,5±2,7 ng/ml; p= 0,007). Níveis elevados de testosterona foram encontrados em homens acima de 50 anos e MB (6,58± 3,2 ng/ml) quando comparado aos homens PB (4,21± 2,3 ng/ml) e com os controles (4,26± 0,8 ng/ml). Em relação à avaliação de marcadores imunológicos todas as citocinas avaliadas estiveram aumentadas nos pacientes, em relação aos controles, destacando INF-ɣ (79,02 ± 26,9 pg/ml), IL-10 (156,4 ± 53 pg/ml) e TNF-α (463,3 ± 160,6 pg/ml) que estavam elevadas nas HV. Em relação à IL-17A, os pacientes com HT apresentaram níveis mais elevados (49,2 ± 10,5 pg/ml) quando comparados aos valores de pacientes com HV (40,7 ± 4,6 pg/ml). Já a IL1-β esteve elevada formas HI (62,9 ± 16,3 pg/ml) quando comparada às formas mais graves da doença e aos controles. Por fim o aumento em INF-ɣ (97,1 ± 44,5 pg/ml, p= 0,02) e TNF-α (407,3 ± 82,08 pg/ml, p= 0,04) esteve relacionado, nos pacientes MB, à ocorrência de episódio reacional. E esta última, também, mais elevada nos pacientes com incapacidade física (354,3 ± 92,2 pg/ml, p= 0,04). Os marcadores hormonais e imunológicos acima descritos suportam a hipótese de que a interação entre a hanseníase e os sistemas neuroendócrinos e imunológicos desempenham um papel importante no curso natural da infecção pelo M. Leprae. Concentrações reduzidas de cortisol e IGF-1, altas concentrações de testosterona relacionadas ao pior desfecho clínico sugerem esses hormônios sejam importantes moduladores do episódio inflamatório e dá suporte estudos terapeuticos futuros bem como a tentativa de tratamento profilático. Além disso, as citocinas IL-17 e IL-1β atuam no controle da multiplicação do bacilo. Já as citocinas IFN- ɣ e TNF-α foram associadas a presença de reação sugerindo um efeito deletério na lesão.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-05-05T11:55:53Z No. of bitstreams: 2 Tese - Michele Dias da Silva Oliveira - 2017.pdf: 5624248 bytes, checksum: a79ee7794bc5b6cb101cc52adb44a0a5 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-05-05T11:56:14Z (GMT) No. of bitstreams: 2 Tese - Michele Dias da Silva Oliveira - 2017.pdf: 5624248 bytes, checksum: a79ee7794bc5b6cb101cc52adb44a0a5 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-05-05T11:56:15Z (GMT). No. of bitstreams: 2 Tese - Michele Dias da Silva Oliveira - 2017.pdf: 5624248 bytes, checksum: a79ee7794bc5b6cb101cc52adb44a0a5 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-02-10 / Introduction: To take care of people with leprosy, nurses make diagnostic and therapeutic judgments, which must be expressed through special terminology of the profession of theoretical nursing models. Therefore, the International Classification for Nursing Practice usage - CIPE® for the construction of a terminological subset aimed at people with leprosy is necessary to train nurse clinical practice. Objective: To create a terminological subset of nursing diagnoses, results and interventions for the care of people with leprosy, using CIPE® in clinical practice. Method: This is a methodological research study with two phases: one exploratory and the other, a field study. In the exploratory phase, three stages were used to perform terminological research and cross mapping between the terms extracted from Health Ministry publications, related to leprosy and those contained in CIPE® version 2015. In field phase: 1 - Nursing consultation based on Orem's self-care theory with elaboration of nursing diagnosis, results and interventions; 2 - Nursing diagnosis statements validation by three specialists; 3 - Cross mapping of diagnostic statements, results and nursing interventions with CIPE® and the database of terms extracted from the Health Ministry publications; 4 - Creation of the terminology subset of CIPE® to assist people with leprosy. Results: In exploratory phase, 1,041 terms were extracted from the Ministry of Health publications related to leprosy, from which 300 (28.80%) were equal to constant terms in the CIPE® axes; 51 (4.86%) were similar; 49 (4.68%) were larger; 172 (16.45%) were more restricted and 469 (45.00%) were different from the terms of that classification. In field phase, nursing consultations have been carried out on 24 people with leprosy, resulting in 81 nursing diagnoses / results and 303 nursing interventions. In the statements analysis of diagnosis / results and nursing interventions, 564 primitive terms have been evaluated: 342 (61%) were considered constant (equal term, similar, similar more restricted and Similar) in CIPE® and 222 (39.4%) different from CIPE®. From pre-coordinated terms, 384 were evaluated, from which 275 (72%) were considered constant (equal term, similar, more similar, similar and broader) and 109 (28.4%) different from pre-coordinated ICNP terms. Conclusions: The methodology used in this research made it possible to create a terminological subset based on Dorothea Orem self-care theory and CIPE®, and it can be used in clinical practice in nursing care to people with leprosy, in a systematized way, using the steps of nursing process and assisting in the teaching and creation of electronic medical records. In addition, from the results found in this study, it was noticed the need to expand CIPE® in order to better contemplate the phenomena of nursing practice in the care of people with leprosy. / Introdução: No atendimento a pessoas com hanseníase os enfermeiros realizam julgamentos diagnósticos e terapêuticos, que devem ser expressos por meio de terminologia especial da profissão a luz de modelos teóricos de enfermagem. Portanto, o uso da Classificação Internacional para a Prática de Enfermagem- CIPE® para a construção de um subconjunto terminológico voltado para pessoas com hanseníase faz-se necessário para instrumentalizar a prática clínica do enfermeiro. Objetivo: Construir um subconjunto terminológico de diagnósticos, resultados e intervenções de enfermagem para o atendimento de pessoas com hanseníase, utilizando a CIPE® na prática clínica. Método: Trata-se de um estudo de pesquisa metodológica com duas fases: uma exploratória e a outra, estudo de campo. Na fase exploratória, foram utilizadas três etapas para a realização da pesquisa terminológica e mapeamento cruzado entre os termos extraídos das publicações do Ministério da Saúde, relacionados à hanseníase e os contidos na CIPE® versão 2015. Na fase de campo empregou-se: 1- Consulta de enfermagem baseada na teoria de Autocuidado de Orem com elaboração de enunciados de diagnósticos, resultados e intervenções de enfermagem; 2- Validação dos enunciados de diagnóstico de enfermagem por três especialistas; 3- Mapeamento cruzado de enunciados de diagnóstico, resultados e intervenções de enfermagem com a CIPE® e com o banco de termos extraídos das publicações do Ministério da Saúde; 4- Construção do subconjunto terminológico da CIPE® para atendimento de pessoas com hanseníase. Resultados: Na fase exploratória foram extraídos 1.041 termos das publicações do Ministério da Saúde relacionados a hanseníase, dos quais 300 (28,80 %) eram iguais a termos constantes nos eixos da CIPE®; 51 (4,86%) eram semelhantes; 49 (4,68%) eram mais amplos; 172 (16,45%) eram mais restritos e 469 (45,00%) eram diferentes dos termos daquela classificação. Na fase de campo foram realizadas consultas de enfermagem a 24 pessoas com hanseníase, resultando em 81 diagnósticos/resultados de enfermagem e 303 intervenções de enfermagem. Na análise dos enunciados de diagnósticos/resultados e intervenções de enfermagem, quanto à similaridade e abrangência aos conceitos da CIPE®, foram avaliados 564 termos primitivos, desses: 342 (61%) foram considerados constantes (termo igual, semelhante, semelhante mais restrito e semelhante mais amplo) na CIPE® e 222 (39,4%) como diferentes da CIPE®. Dos termos pré coordenados, 384 foram avaliados, sendo 275 (72 %) considerados constantes (termo igual, semelhante, semelhante mais restrito e semelhante mais amplo) e 109 (28,4%) diferentes dos termos pré coordenados da CIPE® e em relação ao banco de termos extraídos das publicações do Ministério da Saúde. Conclusões: A metodologia utilizada nesta pesquisa possibilitou a construção de um subconjunto terminológico com base na teoria de autocuidado de Dorothea Orem e a CIPE®, podendo ser utilizada na prática clínica de enfermagem no atendimento a pessoas com hanseníase, de uma forma sistematizada, utilizando as etapas do processo de enfermagem e auxiliar no ensino e na construção de prontuários eletrônicos. Ademais, a partir dos resultados encontrados neste estudo, percebeu-se a necessidade de ampliação da CIPE® de modo a contemplar melhor os fenômenos da prática de enfermagem no atendimento a pessoas com hanseníase.

Doctorat en philosophie et lettres / info:eu-repo/semantics/nonPublished