Contribution of Hfq to gene regulation and virulence in Histophilus somni.

Histophilus somni is one of the predominant bacterial pathogens responsible for bovine respiratory and systemic diseases in cattle. Despite the identification of numerous H. somni virulence factors, little is known about the regulation of such factors. The post-transcriptional regulatory protein Hfq may play a crucial role in regulation of components that affect bacterial virulence. The contribution of Hfq to H. somni phenotype and virulence was investigated following creation of an hfq deletion mutant of H. somni strain 2336 (designated H. somni 2336Δhfq). A comparative analysis of the mutant to the wild-type strain was carried out by examining protein and carbohydrate phenotype, RNA sequence, intracellular survival in bovine monocytes, serum susceptibility, and virulence studies in mouse and calf models. H. somni 2336Δhfq exhibited a truncated lipooligosaccharide (LOS) structure, with loss of sialylation. The mutant demonstrated increased susceptibility to intracellular and serum-mediated killing compared to the wild-type strain. Transcriptomic analysis displayed significant differential expression of 832 upregulated genes and 809 downregulated genes in H. somni 2336Δhfq compared to H. somni strain 2336, including significant downregulation of lsgB and licA, which contribute to LOS oligosaccharide synthesis and sialylation. A substantial number of differentially expressed genes were associated with polysaccharide synthesis and other proteins that could influence virulence. The H. somni 2336Δhfq mutant strain was attenuated in a mouse septicemia model and somewhat attenuated in a calf intrabronchial challenge model. H. somni was recovered less frequently from nasopharyngeal swabs, endotracheal aspirates, and lung tissues of calves challenged with H. somni 2336Δhfq compared to the wild-type strain, and the percentage of abnormal lung tissue in calves challenged with H. somni 2336Δhfq was lower than in calves challenged with the wild-type strain. In conclusion, our results support that Hfq accounts for the regulation of H. somni virulence factors.

[The Pan American Health Organization's Revolving Fund for access to vaccines: 43 years responding to the regional immunization programO Fundo Rotativo para Acesso a Vacinas da Organização Pan-Americana da Saúde: 43 anos respondendo ao Programa Regional de Imunizações]. / El Fondo Rotatorio para el acceso a las vacunas de la Organización Panamericana de la Salud: 43 años respondiendo al programa regional de inmunizaciones.

The Pan American Health Organization's Revolving Fund for Access to Vaccines (the Revolving Fund) is a shared pool of funds for the procurement of vaccines, syringes, and cold-chain equipment for the Member States of the Organization. With a view to evaluating the results obtained during the Revolving Fund's operation and analyzing its contributions to achievements in immunization, a review was conducted of historical documents and grey literature related to the Fund's history and current processes, as well as data from platforms fed by countries' annual reports, with reference to growth indicators, burden of vaccine-preventable diseases, introduction of new vaccines in the Region of the Americas, and lessons learned. In its 43 years of operation, the Revolving Fund has grown and contributed to the introduction of new vaccines, and the Region has made rapid progress in the field of immunization. However, several countries and territories in the Region have not yet introduced certain vaccines due to their high cost and the economic impact of sustainably administering them. The requirement to obtain the lowest possible price and to set a uniform price for all participating Member States has been instrumental in the Revolving Fund's contribution to the vaccination goals of national immunization programs, and for timely planning of demand, accompanied by technical advice. An interprogrammatic approach and the planning of auxiliary inputs are key to the success of the programs. Pandemic preparedness, regional vaccine production, and the protection of national budgets for sustainable procurement of high-cost vaccines are current and future challenges.

O Fundo Rotativo para Acesso a Vacinas (FR) da Organização Pan-Americana de Saúde é um fundo comum de capital e compra conjunta de vacinas, seringas e equipamento da cadeia de frio para os Estados Membros da Organização. Com o objetivo de avaliar os resultados obtidos durante sua operação e analisar sua contribuição para os êxitos da imunização, procedeu-se a uma revisão de documentos históricos e da literatura cinzenta relacionados à história do FR e revisaram-se os processos atuais, os dados de plataformas alimentadas pelos relatórios anuais dos países, os indicadores de crescimento, a carga de doenças imunopreveníveis, a introdução de novas vacinas na Região das Américas e as lições aprendidas. Constatou-se que, em seus 43 anos de operação, o FR cresceu e contribuiu para a introdução de novas vacinas e a região avançou com rapidez no campo da imunização. Entretanto, vários países e territórios da região ainda não introduziram determinadas vacinas em razão dos altos preços e do impacto econômico de manter sua administração. A cláusula do menor preço disponível e do preço uniforme para todos os Estados Membros participantes foi fundamental para a contribuição do FR para as metas de vacinação dos programas nacionais de imunização, bem como para o planejamento oportuno da demanda acompanhado pela assessoria técnica. A abordagem interprogramática e o planejamento de insumos auxiliares são necessários para o êxito dos programas. A preparação para pandemias, a produção regional de vacinas e a proteção dos orçamentos nacionais para a compra de vacinas de alto custo e sua sustentabilidade ainda constituem desafios atuais e futuros.

El Fondo Rotatorio para el acceso a las vacunas de la Organización Panamericana de la Salud: 43 años respondiendo al programa regional de inmunizaciones

[RESUMEN]. El Fondo Rotatorio para el acceso a las vacunas (FR) de la Organización Panamericana de la Salud es un fondo común de capital y compra mancomunada de vacunas, jeringas y equipo de cadena de frío para los Estados Miembros de la Organización. Con el objetivo de evaluar los resultados obtenidos durante su funcio- namiento y analizar su contribución a los logros de inmunización, se llevó a cabo una revisión de documentos históricos y literatura gris relacionados con la historia del FR, y se revisaron los procesos actuales, los datos de plataformas alimentadas por los informes anuales de los países, los indicadores de crecimiento, la carga de enfermedades prevenibles por vacunación, la introducción de nuevas vacunas en la Región de las Amé- ricas, y lecciones aprendidas. Se encontró que, en sus 43 años de funcionamiento, el FR ha crecido y ha contribuido a la introducción de nuevas vacunas, y que la Región ha avanzado de manera acelerada en el ámbito de las inmunizaciones. Sin embargo, varios países y territorios de la Región todavía no han introducido ciertas vacunas debido a sus altos precios y al impacto económico del mantenimiento de su administración. La cláusula del precio más bajo posible y del precio uniforme para todos los Estados Miembros participantes ha sido fundamental para la contribución del FR a las metas de vacunación de los programas nacionales de inmunización, así como para la planeación oportuna de la demanda acompañada por la asesoría técnica. El abordaje interprogramático y la planeación de insumos auxiliares son necesarios para el éxito de los progra- mas. La preparación ante pandemias, la producción regional de vacunas y la protección de presupuestos nacionales para la compra de vacunas de alto costo y su sostenibilidad constituyen aún retos en el presente y el futuro.

[ABSTRACT]. The Pan American Health Organization’s Revolving Fund for Access to Vaccines (the Revolving Fund) is a shared pool of funds for the procurement of vaccines, syringes, and cold-chain equipment for the Member States of the Organization. With a view to evaluating the results obtained during the Revolving Fund’s operation and analyzing its contributions to achievements in immunization, a review was conducted of historical docu- ments and grey literature related to the Fund’s history and current processes, as well as data from platforms fed by countries’ annual reports, with reference to growth indicators, burden of vaccine-preventable diseases, introduction of new vaccines in the Region of the Americas, and lessons learned. In its 43 years of operation, the Revolving Fund has grown and contributed to the introduction of new vaccines, and the Region has made rapid progress in the field of immunization. However, several countries and territories in the Region have not yet introduced certain vaccines due to their high cost and the economic impact of sustainably administe- ring them. The requirement to obtain the lowest possible price and to set a uniform price for all participating Member States has been instrumental in the Revolving Fund’s contribution to the vaccination goals of national immunization programs, and for timely planning of demand, accompanied by technical advice. An interpro- grammatic approach and the planning of auxiliary inputs are key to the success of the programs. Pandemic preparedness, regional vaccine production, and the protection of national budgets for sustainable procure- ment of high-cost vaccines are current and future challenges.

[RESUMO]. O Fundo Rotativo para Acesso a Vacinas (FR) da Organização Pan-Americana de Saúde é um fundo comum de capital e compra conjunta de vacinas, seringas e equipamento da cadeia de frio para os Estados Membros da Organização. Com o objetivo de avaliar os resultados obtidos durante sua operação e analisar sua con- tribuição para os êxitos da imunização, procedeu-se a uma revisão de documentos históricos e da literatura cinzenta relacionados à história do FR e revisaram-se os processos atuais, os dados de plataformas alimenta- das pelos relatórios anuais dos países, os indicadores de crescimento, a carga de doenças imunopreveníveis, a introdução de novas vacinas na Região das Américas e as lições aprendidas. Constatou-se que, em seus 43 anos de operação, o FR cresceu e contribuiu para a introdução de novas vacinas e a região avançou com rapidez no campo da imunização. Entretanto, vários países e territórios da região ainda não introduziram determinadas vacinas em razão dos altos preços e do impacto econômico de manter sua administração. A cláusula do menor preço disponível e do preço uniforme para todos os Estados Membros participantes foi fundamental para a contribuição do FR para as metas de vacinação dos programas nacionais de imunização, bem como para o planejamento oportuno da demanda acompanhado pela assessoria técnica. A aborda- gem interprogramática e o planejamento de insumos auxiliares são necessários para o êxito dos programas. A preparação para pandemias, a produção regional de vacinas e a proteção dos orçamentos nacionais para a compra de vacinas de alto custo e sua sustentabilidade ainda constituem desafios atuais e futuros.

Species-agnostic polymeric formulations for inhalable messenger RNA delivery to the lung.

Messenger RNA has now been used to vaccinate millions of people. However, the diversity of pulmonary pathologies, including infections, genetic disorders, asthma and others, reveals the lung as an important organ to directly target for future RNA therapeutics and preventatives. Here we report the screening of 166 polymeric nanoparticle formulations for functional delivery to the lungs, obtained from a combinatorial synthesis approach combined with a low-dead-volume nose-only inhalation system for mice. We identify P76, a poly-ß-amino-thio-ester polymer, that exhibits increased expression over formulations lacking the thiol component, delivery to different animal species with varying RNA cargos and low toxicity. P76 allows for dose sparing when delivering an mRNA-expressed Cas13a-mediated treatment in a SARS-CoV-2 challenge model, resulting in similar efficacy to a 20-fold higher dose of a neutralizing antibody. Overall, the combinatorial synthesis approach allowed for the discovery of promising polymeric formulations for future RNA pharmaceutical development for the lungs.

El Fondo Rotatorio para el acceso a las vacunas de la Organización Panamericana de la Salud: 43 años respondiendo al programa regional de inmunizaciones / The Pan American Health Organization's Revolving Fund for access to vaccines: 43 years responding to the regional immunization program / O Fundo Rotativo para Acesso a Vacinas da Organização Pan-Americana da Saúde: 43 anos respondendo ao Programa Regional de Imunizações

RESUMEN El Fondo Rotatorio para el acceso a las vacunas (FR) de la Organización Panamericana de la Salud es un fondo común de capital y compra mancomunada de vacunas, jeringas y equipo de cadena de frío para los Estados Miembros de la Organización. Con el objetivo de evaluar los resultados obtenidos durante su funcionamiento y analizar su contribución a los logros de inmunización, se llevó a cabo una revisión de documentos históricos y literatura gris relacionados con la historia del FR, y se revisaron los procesos actuales, los datos de plataformas alimentadas por los informes anuales de los países, los indicadores de crecimiento, la carga de enfermedades prevenibles por vacunación, la introducción de nuevas vacunas en la Región de las Américas, y lecciones aprendidas. Se encontró que, en sus 43 años de funcionamiento, el FR ha crecido y ha contribuido a la introducción de nuevas vacunas, y que la Región ha avanzado de manera acelerada en el ámbito de las inmunizaciones. Sin embargo, varios países y territorios de la Región todavía no han introducido ciertas vacunas debido a sus altos precios y al impacto económico del mantenimiento de su administración. La cláusula del precio más bajo posible y del precio uniforme para todos los Estados Miembros participantes ha sido fundamental para la contribución del FR a las metas de vacunación de los programas nacionales de inmunización, así como para la planeación oportuna de la demanda acompañada por la asesoría técnica. El abordaje interprogramático y la planeación de insumos auxiliares son necesarios para el éxito de los programas. La preparación ante pandemias, la producción regional de vacunas y la protección de presupuestos nacionales para la compra de vacunas de alto costo y su sostenibilidad constituyen aún retos en el presente y el futuro.

ABSTRACT The Pan American Health Organization's Revolving Fund for Access to Vaccines (the Revolving Fund) is a shared pool of funds for the procurement of vaccines, syringes, and cold-chain equipment for the Member States of the Organization. With a view to evaluating the results obtained during the Revolving Fund's operation and analyzing its contributions to achievements in immunization, a review was conducted of historical documents and grey literature related to the Fund's history and current processes, as well as data from platforms fed by countries' annual reports, with reference to growth indicators, burden of vaccine-preventable diseases, introduction of new vaccines in the Region of the Americas, and lessons learned. In its 43 years of operation, the Revolving Fund has grown and contributed to the introduction of new vaccines, and the Region has made rapid progress in the field of immunization. However, several countries and territories in the Region have not yet introduced certain vaccines due to their high cost and the economic impact of sustainably administering them. The requirement to obtain the lowest possible price and to set a uniform price for all participating Member States has been instrumental in the Revolving Fund's contribution to the vaccination goals of national immunization programs, and for timely planning of demand, accompanied by technical advice. An interprogrammatic approach and the planning of auxiliary inputs are key to the success of the programs. Pandemic preparedness, regional vaccine production, and the protection of national budgets for sustainable procurement of high-cost vaccines are current and future challenges.

RESUMO O Fundo Rotativo para Acesso a Vacinas (FR) da Organização Pan-Americana de Saúde é um fundo comum de capital e compra conjunta de vacinas, seringas e equipamento da cadeia de frio para os Estados Membros da Organização. Com o objetivo de avaliar os resultados obtidos durante sua operação e analisar sua contribuição para os êxitos da imunização, procedeu-se a uma revisão de documentos históricos e da literatura cinzenta relacionados à história do FR e revisaram-se os processos atuais, os dados de plataformas alimentadas pelos relatórios anuais dos países, os indicadores de crescimento, a carga de doenças imunopreveníveis, a introdução de novas vacinas na Região das Américas e as lições aprendidas. Constatou-se que, em seus 43 anos de operação, o FR cresceu e contribuiu para a introdução de novas vacinas e a região avançou com rapidez no campo da imunização. Entretanto, vários países e territórios da região ainda não introduziram determinadas vacinas em razão dos altos preços e do impacto econômico de manter sua administração. A cláusula do menor preço disponível e do preço uniforme para todos os Estados Membros participantes foi fundamental para a contribuição do FR para as metas de vacinação dos programas nacionais de imunização, bem como para o planejamento oportuno da demanda acompanhado pela assessoria técnica. A abordagem interprogramática e o planejamento de insumos auxiliares são necessários para o êxito dos programas. A preparação para pandemias, a produção regional de vacinas e a proteção dos orçamentos nacionais para a compra de vacinas de alto custo e sua sustentabilidade ainda constituem desafios atuais e futuros.

Experiencia en el cuadro clínico, diagnóstico y tratamiento de COVID-19 / Experience in the clinical picture, diagnosis and treatment of COVID-19 / Experiência no quadro clínico, diagnóstico e tratamento da COVID-19

Resumen: Introducción: La infección por SARS-CoV-2 en Wuhan, China, ocasionó una pandemia de tal magnitud que ha provocado la muerte por neumonía a causa de enfermedad infecciosa por coronavirus 19 (COVID-19) de millones de personas. Nos dimos a la tarea de recolectar todas las características de los pacientes que estuvieron hospitalizados por esta enfermedad en nuestra UCI adultos. Material y métodos: Se realizó un estudio de tipo analítico, descriptivo, observacional y retrospectivo en pacientes con diagnóstico de COVID-19 ingresados en la Unidad de Cuidados Intensivos (UCI) del Hospital Ángeles Clínica Londres en la Ciudad de México, evaluados en el periodo del 23 de marzo de 2020 al 10 de mayo de 2020. Se revisaron los expedientes y se tomaron los datos de los mismos, se describieron variables de tipo demográfico, factores de riesgo, signos y síntomas, tratamiento médico y atención respiratoria. Se revisaron escalas de mortalidad SAPS III, APACHE II, SOFA y CALL-score. Se formaron dos grupos con y sin mortalidad realizándose análisis bivariado y multivariado de las variables significativas. El análisis estadístico se efectuó con el programa SPSS 25. Resultados: En el periodo considerado, 25 expedientes cumplieron con los criterios de inclusión, de ellos la demografía y factores de riesgo, 18 (72%) correspondieron a hombres y siete (38%) a mujeres con una mortalidad de 10 (40%). Los factores de riesgo más frecuentes fueron diabetes mellitus (DM) en siete (38%) pacientes, hipertensión arterial (HAS) en seis (24%), obesidad en cuatro (16%), enfermedad pulmonar obstructiva crónica (EPOC) en uno (4%), tabaquismo en 11 (44%) y alcoholismo en siete (28%). Se encontraron diferencias estadísticamente significativas en los grupos sin mortalidad y con mortalidad, 15 y 10 pacientes, respectivamente, observando las siguientes significancias: glucosa 105 mg/dL (percentil [PE 88]) versus 171 mg/dL (PE 125) p = 0.012, urea 33 mg/dL (PE 22) versus 95 mg/dL (PE 57) p = 0.03, BUN 15.3 mg/dL (PE 11) versus 44.2 mg/dL (PE 26.28) p = 0.04, TGO 32 U/L (PE 24.4) versus 58 U/L (PE 43.8) p = 0.010, DHL 239 U/L (PE 198) 454 U/L (PE 260) p = 0.003, triglicéridos 148 mg/dL (PE 120) versus 187.5 mg/dL (PE 165) p = 0.002, CPK 70 U/L (PE 35) versus 81 U/L (PE 78.25) p = 0.003, ferritina 446 mg/L (PE 238) versus 1,030 mg/L (PE 665) p = 0.007. Se realizó un análisis bivariado con regresión logística binaria, con la variable mortalidad dicotómica, no resultando significativa con esta prueba. Conclusiones: Se entiende que ninguna variable es predominantemente importante para explicar la mortalidad y que se recurre a muchos factores que se conjugan para explicar este desenlace, uno de éstos es la severidad misma del problema respiratorio en que se encuentre el paciente.

Abstract: Introduction: The SARS-CoV-2 infection in Wuhan, China caused a pandemic of such magnitude that it has caused the death of millions of people from pneumonia due to infectious disease caused by coronavirus 19 (COVID-19). We took on the task of collecting all the characteristics of the patients who were hospitalized for this disease in our Adult Intensive Care Unit. Material and methods: An analytical, descriptive, observational and retrospective study was carried out in patients with a diagnosis of COVID-19 admitted to the Intensive Care Unit (ICU) of the Hospital Ángeles Clínica Londres in Mexico City, evaluated in the period of March 23 from 2020 to May 10, 2020. The files were reviewed and the data taken from them, demographic variables, risk factors, signs and symptoms, medical treatment and respiratory care were described. SAPS III, APACHE II, SOFA and CALL-score mortality scales were reviewed. Two groups were formed with and without mortality, performing bivariate and multivariate analyzes of the significant variables. Statistical analysis was performed with the SPSS 25 program. Results: In the period considered, 25 files met the inclusion criteria for them: demographics and risk factors were 18 (72%) corresponding to men and seven (38%) to women. With a mortality of 10 (40%). The most frequent risk factors are diabetes mellitus (DM) in seven (38%), arterial hypertension (SAH) six (24%), obesity four (16%), chronic obstructive pulmonary disease (COPD) one (4%), smoking 11 (44%) and alcoholism seven (28%). Statistically significant differences were found in the groups without mortality and with mortality 15 and 10 patients respectively, observing the following significance: glucose 105 mg/dL (percentil [PE] 88) versus 171 mg/dL (PE 125) p = 0.012, urea 33 mg/dL (PE 22) versus 95 mg/dL (PE 57) p = 0.03, BUN 15.3 mg/dL (PE 11) versus 44.2 mg/dL (PE 26.28) p = 0.04, TGO 32 U/L (PE 24.4) versus 58 U/L (PE 43.8) p = 0.010, DHL 239 U/L (PE 198) 454 U/L (PE 260) p = 0.003, triglycerides 148 mg/dL (PE 120) versus 187.5 mg/dL (PE 165) p = 0.002, CPK 70 U/L (PE 35) versus 81 U/L (PE 78.25) p = 0.003, ferritin 446 mg/L (PE 238) versus 1,030 mg/L (PE 665) p = 0.007. A bivariate analysis with binary logistic regression was performed, with the dichotomous mortality variable, not resulting in this significant test. Conclusions: It is understood that no variable is predominantly important to explain mortality and that many factors are involved that are combined to explain this outcome, one of these being the same severity of the respiratory problem in which the patient is.

Resumo: Introdução: A infecção por SARS-CoV-2 em Wuhan China causou uma pandemia de tal magnitude que causou a morte de milhões de pessoas por pneumonia devido a doença infecciosa causada pelo coronavírus 19 (COVID-19). Assumimos a tarefa de coletar todas as características dos pacientes internados por essa doença em nossa unidade de terapia intensiva adulto. Material e métodos: Realizou-se um estudo analítico, descritivo, observacional e retrospectivo em pacientes com diagnóstico de COVID-19 internados na Unidade de Terapia Intensiva (UTI) do Hospital Ángeles Clínica Londres na Cidade do México, validado para o período de 23 de março de 2020 a 10 de maio de 2020. Os prontuários médicos foram revisados e seus dados coletados, as variáveis do tipo demográficas foram descritas, fatores de risco, sinais e sintomas, tratamento médico e cuidados respiratórios. Foram revisadas as escalas de mortalidade SAPS III, APACHE II, SOFA e CALL-score. Dois grupos foram formados com e sem mortalidade, realizando análises bivariadas e multivariadas das variáveis significativas. A análise estatística foi realizada com o programa SPSS 25. Resultados: No período considerado, 25 prontuários atenderam aos critérios de inclusão para os mesmos: dados demográficos e fatores de risco foram 18 (72%) correspondentes a homens e 7 (38%) a mulheres. Com mortalidade de 10 (40%). Os fatores de risco mais frequentes são diabetes mellitus (DM) em 7 (38%), hipertensão arterial (HAS) 6 (24%), obesidade 4 (16%), doença pulmonar obstrutiva crônica (DPOC) 1 (4%), tabagismo 11 (44%) e alcoolismo 7 (28%). Encontrou-se diferenças estatisticamente significativas nos grupos sem mortalidade e com mortalidade de 15 e 10 pacientes respectivamente, observando a seguinte significância: glicose 105 mg/dL (percentil [PE] 88) versus 171 mg/dL (PE 125) p = 0.012, uréia 33 mg/L (PE 22) versus 95 mg/L (PE 57) p = 0.03, BUN 15.3 mg/L (PE 11) versus 44.2 mg/L (PE 26.28) p = 0.04, TGO 32 U/L (PE 24.4) versus 58 U/L (PE 43.8) p = 0.010, DHL 239 U/L (PE 198) 454 (PE 260) p = 0.003, triglicerídeos 148 mg/dL (PE 120) versus 187.5 mg/dL (PE 165) p = 0.002, CPK 70 U/L (PE 35) versus 81 U/L (PE 78.25) p = 0.003, ferritina 446 mg/L (PE 238) versus 1030 mg/L (PE 665) p = 0.007. Realizou-se análise bivariada com regressão logística binária, com a variável mortalidade dicotômica, não resultando em teste significativo. Conclusões: Entende-se que nenhuma variável é predominantemente importante para explicar a mortalidade e que usamos muitos fatores que se conjugam para explicar esse desfecho, sendo um deles a mesma gravidade do problema respiratório em que o paciente se encontra.

Overcoming challenges to sustainable immunization financing: early experiences from GAVI graduating countries.

Over the 5-year period ending in 2018, 16 countries with a combined birth cohort of over 6 million infants requiring life-saving immunizations are scheduled to transition (graduate) from outside financial and technical support for a number of their essential vaccines. This support has been provided over the past decade by the GAVI Alliance. Will these 16 countries be able to continue to sustain these vaccination efforts? To address this issue, GAVI and its partners are supporting transition planning, entailing country assessments of readiness to graduate and intensive dialogue with national officials to ensure a smooth transition process. This approach was piloted in Bhutan, Republic of Congo, Georgia, Moldova and Mongolia in 2012. The pilot showed that graduating countries are highly heterogeneous in their capacity to assume responsibility for their immunization programmes. Although all possess certain strengths, each country displayed weaknesses in some of the following areas: budgeting for vaccine purchase, national procurement practices, performance of national regulatory agencies, and technical capacity for vaccine planning and advocacy. The 2012 pilot experience further demonstrated the value of transition planning processes and tools. As a result, GAVI has decided to continue with transition planning in 2013 and beyond. As the graduation process advances, GAVI and graduating countries should continue to contribute to global collective thinking about how developing countries can successfully end their dependence on donor aid and achieve self-sufficiency.

Projections of costs, financing, and additional resource requirements for low- and lower middle-income country immunization programs over the decade, 2011-2020.

The Decade of Vaccines Global Vaccine Action Plan has outlined a set of ambitious goals to broaden the impact and reach of immunization across the globe. A projections exercise has been undertaken to assess the costs, financing availability, and additional resource requirements to achieve these goals through the delivery of vaccines against 19 diseases across 94 low- and middle-income countries for the period 2011-2020. The exercise draws upon data from existing published and unpublished global forecasts, country immunization plans, and costing studies. A combination of an ingredients-based approach and use of approximations based on past spending has been used to generate vaccine and non-vaccine delivery costs for routine programs, as well as supplementary immunization activities (SIAs). Financing projections focused primarily on support from governments and the GAVI Alliance. Cost and financing projections are presented in constant 2010 US dollars (US$). Cumulative total costs for the decade are projected to be US$57.5 billion, with 85% for routine programs and the remaining 15% for SIAs. Delivery costs account for 54% of total cumulative costs, and vaccine costs make up the remainder. A conservative estimate of total financing for immunization programs is projected to be $34.3 billion over the decade, with country governments financing 65%. These projections imply a cumulative funding gap of $23.2 billion. About 57% of the total resources required to close the funding gap are needed just to maintain existing programs and scale up other currently available vaccines (i.e., before adding in the additional costs of vaccines still in development). Efforts to mobilize additional resources, manage program costs, and establish mutual accountability between countries and development partners will all be necessary to ensure the goals of the Decade of Vaccines are achieved. Establishing or building on existing mechanisms to more comprehensively track resources and commitments for immunization will help facilitate these efforts.

An analysis of how the GAVI alliance and low- and middle-income countries can share costs of new vaccines.

Immunization is one of the "best buys" in global health. However, for the poorest countries, even modest expenditures may be out of reach. The GAVI Alliance is a public-private partnership created to help the poorest countries introduce new vaccines. Since 2008 GAVI has required that countries cover a share of the cost of vaccines introduced with GAVI support. To determine how much countries can contribute to the cost of vaccines--without displacing spending on other essential programs--we analyzed their fiscal capacity to contribute to the purchase of vaccines over the coming decade. For low-income countries, external financing will be required to purchase vaccines supported by GAVI, so co-financing needs to be modest. Relatively better-off "intermediate" countries could support initially modest but gradually increasing co-financing levels. The countries soon to graduate from GAVI can generally afford to follow a rapid path to self-sufficiency. Co-financing for these countries needs to ramp up so that national budgets fully cover the costs of the new generation of vaccines once GAVI support ends.

Evaluación de la inmunidad específica celular en pacientes estadio III de cáncer de mama / Evaluation of the specific cellular inmunity in patients with breast cancer, stage III

Individuos que presentan procesos neoplásicos y sometidos a stress, cirugía y terapia inmunosupresora prolongada, presentan una marcada inmunodeficiencia en la función de los linfocitos T. En este trabajo se analizaron cuatro pacientes con Ca de mama en estadio III (UICC) sometidas a idéntico esquema terapéutico: biopsia, cobaltoterapia, quimioterapia y mastectomía. Se evaluó la inmunidad específica celular por análisis de rosetas E (RE), E activas (REa), EA (REA), linfocitos T4+, T8+ e índice T4/T8 en muestras tomadas durante 3 o 4 etapas de evolución. Los resultados mostraron en 3 pacientes (1, 2 y 4) que la muestra prebiopsia presentaba valores de RE, REa inferiores a lo normal, con un curso semejante; alza en la II muestra (prerradiación) y una marcada disminución en la III muestra (premastectomía). En sólo 1/3 de estas pacientes se analizó una IV muestra (postmastectomía), que mostró una recuperación en todos los parámetros analizados. Dos tercios presentaron también una disminución de rosetas EA. El índice T4/T8 en las pacientes 1, 2 y 4 estuvo dentro del rango normal; no obstante el paciente 3 mostró un aumento de la población T supresora, lo que disminuyo el índice T4/T8. L cuarta paciente (N-3) mostró resultados diferentes a las 3 anteriores, con valores disminuídos sólo en la II muestra