DNA-mediated immunization in a transgenic mouse model of the hepatitis B surface antigen chronic carrier state.

Transgenic mice expressing the sequences coding for the envelope proteins of the hepatitis B virus (HBV) in the liver have been used as a model of the HBV chronic carrier state. We evaluated the possibility of inducing a specific immune response to the viral envelope antigens and thus potentially controlling chronic HBV infection. Using HBV-specific DNA-mediated immunization in this transgenic model, we show that the immune response induced after a single intramuscular injection of DNA resulted in the complete clearance of circulating hepatitis B surface antigen and in the long-term control of transgene expression in hepatocytes. This response does not involve a detectable cytopathic effect in the liver. Adoptive transfer of fractionated primed spleen cells from DNA-immunized mice shows that T cells are responsible for the down-regulation of HBV mRNA in the liver of transgenic mice. To our knowledge, this is the first demonstration of a potential immunotherapeutic application of DNA-mediated immunization against an infectious disease and raises the possibility of designing more effective ways of treating HBV chronic carriers.

Persistent high frequency of human immunodeficiency virus-specific cytotoxic T cells in peripheral blood of infected donors.

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTLs) are thought to play a major role in the immune response to HIV infection. The HIV-specific CTL response is much stronger than previously documented in an infectious disease, yet estimates of CTL frequency derived from limiting-dilution analysis (LDA) are relatively low and comparable to other viral infections. Here we show that individual CTL clones specific for peptides from HIV gag and pol gene products are present at high levels in the peripheral blood of three infected patients and that individual CTL clones may represent between 0.2% and 1% of T cells. Previous LDA in one donor had shown a frequency of CTL precursors of 1/8000, suggesting that LDA may underestimate CTL effector frequency. In some donors individual CTL clones persisted in vivo for at least 5 years. In contrast, in one patient there was a switch in CTL usage suggesting that different populations of CTLs can be recruited during infection. These data imply strong stimulation of CTLs, potentially leading some clones to exhaustion.

Switch from a type 2 to a type 1 T helper cell response and cure of established Leishmania major infection in mice is induced by combined therapy with interleukin 12 and Pentostam.

Successful treatment in allergic, autoimmune, and infectious diseases often requires altering the nature of a detrimental immune response mediated by a particular CD4+ T helper (Th) cell subset. While several factors contribute to the development of CD4+ Th1 and Th2 cells, the requirements for switching an established response are not understood. Here we use infection with Leishmania major as a model to investigate those requirements. We report that treatment with interleukin 12 (IL-12), in combination with the antimony-based leishmanicidal drug Pentostam, induces healing in L. major-infected mice and that healing is associated with a switch from a Th2 to a Th1 response. The data suggest that decreasing antigen levels may be required for IL-12 to inhibit a Th2 response and enhance a Th1 response. These observations are important for treatment of nonhealing forms of human leishmaniasis and also demonstrate that in a chronic infectious disease an inappropriate Th2 response can be switched to an effective Th1 response.

Tuberculostáticos potenciais planejados com base na estrutura de maltosiltransferase (GlgE) de mycobacterium tuberculosis. Estudo da síntese por meio de micro-ondas

A tuberculose (TB) é uma doença infectocontagiosa, causada por micobactérias do complexo Mycobacterium, principalmente, o M. tuberculosis. Praticamente extinta em países desenvolvidos, antigamente denominados Países de Primeiro Mundo, a tuberculose voltou a ter foco mundial dada a sua crescente taxa de incidência e mortalidade. Segundo a Organização Mundial de Saúde, a TB, hoje, figura como principal causa de morte por doenças infectocontagiosas em todo mundo, com a incidência de 8,6 milhões de novos casos ao ano e cerca de 1,5 milhões de mortes. O principal desafio no tratamento da tuberculose é a multirresistência de M. tuberculosis frente aos fármacos disponíveis. Sendo assim, a busca de novos fármacos antituberculose e o estudo de novos alvos são necessários para superar essa situação. Frente à necessidade de exploração de novos alvos e ante a indicação da maltosiltransferase (GlgE) como novo alvo potencialmente promissor contra M. tuberculosis, este projeto pretendeu viabilizar a síntese de análogos da glicose (análoga do substrato natural da GlgE, a maltose 1-fosfato) por meio de rotas sintéticas que fazem uso do micro-ondas. Essas rotas sintéticas seguem os princípios da click chemistry, que são reações químicas modulares, cujas condições reacionais são simples e resultam em produtos de fácil purificação. O presente trabalho também visou à comparação entre o método convencional de síntese de triazóis e aquele que utiliza o micro-ondas, no que se refere aos os tempos de reação, às condições reacionais e aos rendimentos com derivados sintetizados no Laboratório de Planejamento e Síntese de Quimioterápicos Potencialmente Ativos em Doenças Negligenciadas (LAPEN). Entretanto, não obteve-se sucesso na etapa final da rota sintética, a glicosilação. Nos demais métodos sintéticos o micro-ondas mostrou-se uma valiosa ferramenta para obtenção dos compostos triazólicos.

Análise espacial da leishmaniose visceral canina no município de Panorama, São Paulo, Brasil

A leishmaniose visceral é uma zoonose de grande importância para a saúde pública, com ampla distribuição geográfica e epidemiologia complexa. Apesar de diversas estratégias de controle, a doença continua se expandindo, tendo o cão como principal reservatório. Levando em consideração que análises espaciais são úteis para compreender melhor a dinâmica da doença, avaliar fatores de risco e complementar os programas de prevenção e controle, o presente estudo teve como objetivo caracterizar a distribuição da leishmaniose visceral canina e relacionar sua dinâmica com características ou feições espaciais no município de Panorama (SP). A partir de dados secundários coletados em um inquérito sorológico entre agosto de 2012 e janeiro de 2013, 986 cães foram classificados como positivos e negativos de acordo com o protocolo oficial do Ministério da Saúde. Posteriormente uma análise espacial foi conduzida, compreendendo desde a visualização dos dados até a elaboração de um mapa de risco relativo, passando por análises de cluster global (função K) e local (varredura espacial). Para avaliar uma possível relação entre o cluster detectado com a vegetação na área de estudo, calculou-se o Índice de Vegetação por Diferença Normalizada (NDVI). A prevalência da doença encontrada na população de cães estudada foi de 20,3% (200/986). A visualização espacial demonstrou que tanto animais positivos quanto negativos estavam distribuídos por toda a área de estudo. O mapa de intensidade dos animais positivos apontou duas localidades de possíveis clusters, quando comparado ao mapa de intensidade dos animais negativos. As análises de cluster confirmaram a presença de um aglomerado e um cluster foi detectado na região central do município, com um risco relativo de 2,63 (p=0,01). A variação espacial do risco relativo na área de estudo foi mapeada e também identificou a mesma região como área significativa de alto risco (p<0,05). Não foram observadas diferenças no padrão de vegetação comparando as áreas interna e externa ao cluster. Sendo assim, novos estudos devem ser realizados com o intuito de compreender outros fatores de risco que possam ter levado à ocorrência do cluster descrito. A prevalência, a localização do cluster espacial e o mapa de risco relativo fornecem subsídios para direcionamento de esforços do Setor de Vigilância Epidemiológica de Panorama para áreas de alto risco, o que pode poupar recursos e aperfeiçoar o controle da leishmaniose visceral no município.

La transición sanitaria en España desde 1900 a 1990

Fundamento: El concepto de transición sanitaria trata de explicar, desde un enfoque plural, los cambios en las condiciones de salud que contribuyeron al descenso de la mortalidad que acompaño a la transición demográfica. El objetivo de este trabajo es analizar la transición sanitaria en España a lo largo del presente siglo ( 1900- 1990). Método: El estudio de los distinto componentes de la transición sanitaria (transición epidemiológica, transición de riesgos y transición de la atención sanitaria) se ha basado en las series históricas disponibles procedentes de los Movimientos Naturales de la Población, Anuarios Estadísticas y Censos de viviendas. Resultados: La evolución de las tasas de mortalidad general y mortalidad infantil refleja una tendencia descendente que se manifiesta a lo largo de todo el periodo: la mortalidad general se ha reducido un 70%. mientras que la infantil lo ha hecho en un 96%. Respecto a la esperanza de vida al nacer, la ganancia ha sido de 43 años entre 1900 (35 años) y 1990 (77 años), lo que en términos relativos supone un aumento del 130%. Conclusiones: El nuevo perfil epidemiológico que fue emergiendo durante el período considerado, aparece relacionado con mejoras en las infraestructuras sanitarias, con el aumento del gasto y de las prestaciones sanitarias. pero también con la aparición de nuevos problemas de salud relacionados con las condiciones de trabajo, el crecimiento masivo del medio urbano (a partir, sobre todo, de la década de los 60) o las modificaciones en los patrones de vida.

Diagnóstico da tuberculose pulmonar no adulto nos países de baixo rendimento : será o XPERT® MTB/RIF a escolha correcta?

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Recurrent bacteremia with Streptococcus dysgalactiae: a case-control study.

Beta-hemolytic streptococci of groups C and G, designated as Streptococcus dysgalactiae (SD), can cause severe and recurring invasive infections. In this case-control study, we aimed to identify clinical and molecular risk factors for recurrence of SD bacteremia. Twenty-two cases of recurrent SD bacteremia were identified, and median time between episodes was 6 months. The most frequent clinical manifestation was skin and soft tissue infection. Cases and 92 controls, with single-episode SD bacteremia, showed similar demographics, had similar Charlson comorbidity scores, and had similar clinical presentations. Thirty-day fatality was 13% among controls, whereas none of 22 cases died. In 19 cases (86%), the same emm type was encountered in both episodes. SD isolates from recurrent episodes and from single episodes had a similar emm type distribution. Thus, we did not identify clinical risk factors for recurrences. The high proportion of identical emm types in recurrent episodes indicates a host-specific colonization.

Genotypic Resistance Tests Sequences Reveal the Role of Marginalized Populations in HIV-1 Transmission in Switzerland.

Targeting hard-to-reach/marginalized populations is essential for preventing HIV-transmission. A unique opportunity to identify such populations in Switzerland is provided by a database of all genotypic-resistance-tests from Switzerland, including both sequences from the Swiss HIV Cohort Study (SHCS) and non-cohort sequences. A phylogenetic tree was built using 11,127 SHCS and 2,875 Swiss non-SHCS sequences. Demographics were imputed for non-SHCS patients using a phylogenetic proximity approach. Factors associated with non-cohort outbreaks were determined using logistic regression. Non-B subtype (univariable odds-ratio (OR): 1.9; 95% confidence interval (CI): 1.8-2.1), female gender (OR: 1.6; 95% CI: 1.4-1.7), black ethnicity (OR: 1.9; 95% CI: 1.7-2.1) and heterosexual transmission group (OR:1.8; 95% CI: 1.6-2.0), were all associated with underrepresentation in the SHCS. We found 344 purely non-SHCS transmission clusters, however, these outbreaks were small (median 2, maximum 7 patients) with a strong overlap with the SHCS'. 65% of non-SHCS sequences were part of clusters composed of >= 50% SHCS sequences. Our data suggests that marginalized-populations are underrepresented in the SHCS. However, the limited size of outbreaks among non-SHCS patients in-care implies that no major HIV outbreak in Switzerland was missed by the SHCS surveillance. This study demonstrates the potential of sequence data to assess and extend the scope of infectious-disease surveillance.

Laws relating to agriculture,

p. 464-536: Bureau of Animal Industry act and amendments; Meat importation act ... Infectious disease of livestock and poultry ... Bang's disease or tubercular cattle.

The Kitasato archives of experimental medicine.

Chemical abstracts

Athanasii Kircheri e Soc. Iesu Scrutinium physico-medicum contagiosæ luis, quæ pestis dicitur : quo origo, causæ, signa, prognostica pestis, nec non insolentes malignantis naturæ effectus, qui statis temporibus, cælestium influxuum virtute & efficacia, tum in elementis, tum in epidemijs hominum animantiumque morbis elucescunt, vnà cum appropriatis remediorum antidotis nouâ doctrinâ in lucem eruuntur.

"Errores": p. [15] (3rd group).

Cases of animal rabies by county and species, California.

Description based on: Jan. 1, 1972-Dec. 31, 1972; title from caption.

Tracing Hybrid Collectives of Illness, War, and Medicine in Twentieth- and Twenty-First Century Narratives of Illness

Thesis (Ph.D.)--University of Washington, 2016-06

Does terrestrial epidemiology apply to marine systems?

Most of epidemiological theory has been developed for terrestrial systems, but the significance of disease in the ocean is now being recognized. However, the extent to which terrestrial epidemiology can be directly transferred to marine systems is uncertain. Many broad types of disease-causing organism occur both on land and in the sea, and it is clear that some emergent disease problems in marine environments are caused by pathogens moving from terrestrial to marine systems. However, marine systems are qualitatively different from terrestrial environments, and these differences affect the application of modelling and management approaches that have been developed for terrestrial systems. Phyla and body plans are more diverse in marine environments and marine organisms have different life histories and probably different disease transmission modes than many of their terrestrial counterparts. Marine populations are typically more open than terrestrial ones, with the potential for long-distance dispersal of larvae. Potentially, this might enable unusually rapid propagation of epidemics in marine systems, and there are several examples of this. Taken together, these differences will require the development of new approaches to modelling and control of infectious disease in the ocean.