IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-γ production

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP) located in the first intron of the human IFN-γ gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL) and also the influence of this SNP in the secretion of IFN-γ <it>in vitro</it>.</p> <p>Methods</p> <p>Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML) and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-γ gene was carried out by Amplification Refractory Mutational System (ARMS-PCR). <it>Leishmania</it>-induced IFN-γ production on peripheral blood mononuclear cell (PBMC) culture supernatants was assessed by ELISA.</p> <p>Results</p> <p>There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-γ than TA/TT genotypes. In mucosal cases, high and low IFN-γ producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers.</p> <p>Conclusion</p> <p>Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-α and IL-10 are also involved thus interfering with IFN-γ secretion.</p

Tuberculosis control: decentralization, local planning and management specificities

The goal was to analyze, according to the perception of health managers, the practices that guide tuberculosis control actions in cities in the metropolitan region of João Pessoa - PB, Brazil. This qualitative study involved eight professionals in management functions. Testimonies were collected through semi-structured interviews between May and June 2009 and organized through content analysis. Despite the acknowledged benefits of tuberculosis control action decentralization, local planning indicates the predominance of a bureaucratic model that is restricted to negotiation and supplies. Local programming is centered on the coordinator, which shows a command line and vertical management that lead to the fragmentation of the work process. Management action should follow an innovative and transformative route that surpasses bureaucratic barriers and faces the biggest challenge it is proposed: to balance professional interrelations with a view to improving health work performance.Se buscó analizar, según la percepción de los gestores de salud, las prácticas que orientan las acciones de control de la tuberculosis en municipios de la región metropolitana de Joao Pesoa, estado de Paraíba. Se trata de un estudio cualitativo que envolvió ocho profesionales que ejercían cargos de gestión. Las declaraciones fueron recolectadas por medio de entrevistas semiestructuradas, entre mayo y julio de 2009, y organizadas mediante análisis de contenido. A pesar de que se reconozcan los beneficios de la descentralización de las acciones de control de la tuberculosis, la planificación local señala la predominancia del modelo burocrático restricto a negociación y suministro de insumos. La programación local se centra en la figura del coordinador, retratando una línea de comando y gestión vertical que induce a la fragmentación del proceso de trabajo. La tarea de administrar debe explorar un camino innovador y transformador, que ultrapase las barreras burocráticas y alcance el mayor desafío que le es impuesto: equilibrar las interrelaciones profesionales con la finalidad de perfeccionar el desempeño del trabajo en salud.Buscou-se analisar, segundo a percepção dos gestores de saúde, as práticas que norteiam as ações de controle da tuberculose, em municípios da região metropolitana de João Pessoa, PB. Trata-se de estudo qualitativo que envolveu oito profissionais que exerciam cargos de gestão. Os depoimentos foram coletados por meio de entrevista semiestruturada, entre maio e julho de 2009, e organizados mediante análise de conteúdo. Embora se reconheça os benefícios da descentralização das ações de controle da tuberculose, o planejamento local sinaliza a predominância de modelo burocrático restrito à negociação e provisão de insumos. A programação local centra-se na figura do coordenador, retratando uma linha de comando e gestão vertical que induzem à fragmentação do processo de trabalho. A tarefa de gerenciar deve trilhar caminho inovador e transformador que ultrapasse as barreiras burocráticas e alcance o maior desafio que lhe é imposto: equilibrar as inter-relações profissionais no intuito de aperfeiçoar o desempenho do trabalho em saúde