Evaluation of live-attenuated Salmonella vaccines expressing Campylobacter antigens for control of C. jejuni in poultry

Campylobacter jejuni is a zoonotic bacterial pathogen of worldwide importance. It is estimated that 460,000 human infections occur in the United Kingdom per annum and these involve acute enteritis and may be complicated by severe systemic sequelae. Such infections are frequently associated with the consumption of contaminated poultry meat and strategies to control C. jejuni in poultry are expected to limit pathogen entry into the food chain and the incidence of human disease. Toward this aim, a total of 840 Light Sussex chickens were used to evaluate a Salmonella enterica serovar Typhimurium ΔaroA vaccine expressing the C. jejuni amino acid binding protein CjaA as a plasmid-borne fusion to the C-terminus of fragment C of tetanus toxin. Chickens were given the vaccine at 1-day-old and two weeks later by oral gavage, then challenged after a further two weeks with C. jejuni. Across six biological replicates, statistically significant reductions in caecal C. jejuni of c. 1.4 log10 colony-forming units/g were observed at three and four weeks post-challenge relative to age-matched unvaccinated birds. Protection was associated with the induction of CjaA-specific serum IgY and biliary IgA. Protection was not observed using a vaccine strain containing the empty plasmid. Vaccination with recombinant CjaA subcutaneously at the same intervals significantly reduced the caecal load of C. jejuni at three and four weeks post-challenge. Taken together these data imply that responses directed against CjaA, rather than competitive or cross-protective effects mediated by the carrier, confer protection. The impact of varying parameters on the efficacy of the S. Typhimurium ΔaroA vaccine expressing TetC-CjaA was also tested. Delaying the age at primary vaccination had little impact on protection or humoral responses to CjaA. The use of the parent strain as carrier or changing the attenuating mutation of the carrier to ΔspaS or ΔssaU enhanced the protective effect, consistent with increased invasion and persistence of the vaccine strains relative to the ΔaroA mutant. Expression in the ΔaroA strain of a TetC fusion to Peb1A, but not TetC fusions to GlnH or ChuA, elicited protection against intestinal colonisation by C. jejuni that was comparable to that observed with the TetC-CjaA fusion. Our data are rendered highly relevant by use of the target host in large numbers and support the potential of CjaA- and Peb1A-based vaccines for control of C. jejuni in poultry. © 2009 Elsevier Ltd. All rights reserved.

Aquaculture Asia, Vol.13, No.1, pp.1-56, January-March 2008

Developing guidelines for sustainable freshwater aquaculture planning in Vietnam. Aquaculture production, certification and trade: Challenges and opportunities for the small-scale farmer in Asia. The successful development of backyard hatcheries for crustaceans in Thailand. Alternate carp species for diversification in freshwater aquaculture in India. Genetic and reproduction technologies for enhanced aquaculture and fisheries management of Murray cod. Effluent and disease management in traditional practices of shrimp farming: A case study on the west coast of Sabah, Malaysia. Status of sahar domestication and its development in the Himalayan Region of Nepal. Vaccination benefits highlighted as Schering-Plough reinforces commitment to Asian aquaculture. Comparative advantage analysis of shrimp production in Asia. Strategies to improve livelihood of the rural poor: A case study in two small reservoirs in Binh Phuoc Province, Vietnam. Cambodian Government ban on snakehead farming enforced. Marine finfish aquaculture developments at ‘Indonesian Aquaculture 2007’. Production update – marine finfish aquaculture in the Asia-Pacific region. Body size of rotifers from estuaries in North Sulawesi. NACA Newsletter.

Dynamics of pneumococcal nasopharyngeal carriage in healthy children attending a day care center in northern Spain. Influence of detection techniques on the results

8 p.

Dynamics of Streptococcus pneumoniae Serotypes Causing Acute Otitis Media Isolated from Children with Spontaneous Middle-Ear Drainage over a 12-Year Period (1999–2010) in a Region of Northern Spain

10 p.

Malaria Vaccine Adjuvants: Latest Update and Challenges in Preclinical and Clinical Research

There is no malaria vaccine currently available, and the most advanced candidate has recently reported a modest 30% efficacy against clinical malaria. Although many efforts have been dedicated to achieve this goal, the research was mainly directed to identify antigenic targets. Nevertheless, the latest progresses on understanding how immune system works and the data recovered from vaccination studies have conferred to the vaccine formulation its deserved relevance. Additionally to the antigen nature, the manner in which it is presented (delivery adjuvants) as well as the immunostimulatory effect of the formulation components (immunostimulants) modulates the immune response elicited. Protective immunity against malaria requires the induction of humoral, antibody-dependent cellular inhibition (ADCI) and effector and memory cell responses. This review summarizes the status of adjuvants that have been or are being employed in the malaria vaccine development, focusing on the pharmaceutical and immunological aspects, as well as on their immunization outcomings at clinical and preclinical stages.

Distribución de "coxiella burnetii" en los rumiantes domésticos y en la fauna silvestre de la Comunidad Atutónoma Vasca. Evaluacióndel efecto del tratamiento antibiótico y de la vacunación en el control de la fiebre Q en rebaños ovinos naturalmente infectados

243 p. : il.

Vacunas profilácticas frente al VPH

Actualmente sólo existen dos vacunas disponibles para la prevención primaria frente al virus del papiloma humano, Gardasil® y Cervarix®. Ambas vacunas ofrecen una alta protección contra los genotipos 16 y 18 del papillomavirus, que son los responsables de más del 70% de los cánceres de cérvix, segunda causa de mortalidad por cáncer a nivel mundial en mujeres. Además, Gardasil®, ofrece una protección del 99% para las mujeres y del 89,4% para los hombre, frente a los genotipos 6 y 11 del virus, responsables del 90% de las verrugas genitales. Uno de los principales obstáculos para su uso generalizado es su elevado coste, por ello, los ensayos clínicos se dirigen a conseguir una inmunogenicidad eficaz con el menor número de dosis. Cervarix® se comercializa en Europa con una pauta de dos dosis en niñas de 9 a 14 años, con una inmunogenicidad de 48 meses. Gardasil® ha sido autorizada para su comercialización para una pauta de dos dosis en niñas/os de 9 a 13 años, con una imunogenicidad de 36 meses. Ambas vacunas han despertado una gran controversia en los últimos tiempos, por este motivo se están realizando continuos estudios de control que, hasta la fecha, avalan su seguridad. La falta de información sobre las vacunas, los escasos programas de sensibilización y las dudas sobre su seguridad han dificultado su aceptación. El papel de la enfermera es clave en este aspecto para fomentar la vacunación, a través de actividades dirigidas hacía la promoción y prevención frente al virus del papiloma humano.

The nutritional status of pre-school children, Kainji Lake communities, Nigeria: a baseline survey

This survey was carried out to provide the Kainji Lake Fisheries Promotion Project (KLFPP), whose overall goal is the improvement of the standard of living of fishing communities around Kainji Lake, Nigeria, and an increase in the availability of fish to consumers, with nutritional status baseline data for long-term monitoring and evaluation of the overall project goal. In a cross-sectional survey, baseline anthropometric data was collected from 768 children, aged 3-60 months in 389 fisherfolk households around the southern sector of Kainji Lake, Nigeria. In addition, data was collected on the nutritional status and fertility of the mothers, vaccination coverage of children and child survival indicators. For control purposes, 576 children and 292 mothers from non-fishing households around Kainji Lake were likewise covered by the survey. A standardised questionnaire was used to collect relevant information, while anthropometric measurements were made using appropriate equipment. Data compilation and analysis was carried out with DATAEASE registered and EPI-INFO registered software, using NCHS reference data for the analysis of anthropometric measurements. The prevalence of stunted children in fishing households was high at 40%, while the prevalence of wasted and underweight children was likewise high at 10% and 29% respectively. Children from non-fishing households had a marginally lower prevalence of stunting, wasting and underweight with 37%, 7% and 25 % respectively, although these differences were not statistically significant. Considering the fact that the survey was carried out during a period of relative food abundance, the prevalence of wasting and underweight children is likely to be much higher during periods of food shortage. The prevalence of stunting, wasting and underweight was relatively high for children aged 3 to 23 months, suggesting an increased risk of malnutrition during this period, most likely associated with inadequate weaning practices. The prevalence of malnourishment amongst women of child-bearing age was relatively high, irrespective of occupation of the household, with an average of 11% undernourished and 6% wasted. Vaccination coverage was very low while infant and child mortality were extremely high with about 1 in 5 children dying before their fifth birthday. Based on the ethical obligation to maximise the potential benefits of the survey, recommendations for activities to improve community nutrition and health were made for communication to relevant authorities. (PDF contains 52 pages)

The nutritional status of pre-school children, Kainji Lake communities, Nigeria: a follow-up survey

This survey was carried out to provide the Kainji Lake Fisheries Promotion Project (KLFPP), whose overall goal is the improvement of the standard of living of fishing communities around Kainji Lake, Nigeria, managing the fisheries on a sustainable basis, with follow-up data for long-term monitoring and evaluation of the overall project goal. A similar survey, conducted in 1996, provided the baseline against which data from the current survey was evaluated. In a cross-sectional survey, anthropometric data was collected from 576 children aged 3-60 months in 282 fisherfolk households around the southern sector of Kainji Lake, Nigeria. In addition, data was collected on the nutritional status and fertility of the mothers, vaccination coverage of children and child survival indicators. For control purposes, 374 children and 181 mothers from non-fishing households around Kainji Lake were likewise covered by the survey. A standardised questionnaire was used to collect relevant data, while anthropometric measurements were made using appropriate equipment. Data compilation and analysis was carried out with a specially designed Microsoft Access application, using NCHS reference data for the analysis of anthropometric measurements. Statistical significance testing was done using EPI-INFO" software. The results of the follow-up survey indicate a slight increase in the percentage of stunted pre-school children in fishing households around Kainji Lake, from 40% in 1996 to 41% in 1999. This increase is however not statistically significant (p= 0.704). Over the same period, the percentage of stunted children in non-fishing households increased from 37% to 39% (p= 0.540), which is also not statistically significant. Likewise, there were no statistically significant differences between the 1996 and 1999 results for the prevalence of either wasted or underweight children in fishing households. The same applies to children from non-fishing households. In addition, vaccination coverage remains very low while infant and child mortality rates continue to be extremely high with about 1 in 5 children dying before their fifth birthday. There has been no perceptible and lasting improvement in the standard of living of fishing households over the course of the second project phase as indicated by the persistently high prevalence of stunting. The situation is the same for the control group, indicating that for the region as a whole, a number of factors beyond the immediate influence of the project continue to negatively impact on the standard of living. The results also show that the project activities have not had any negative long-term effect on the nutritional status of the beneficiaries. (PDF contains 44 pages)

Impacto da campanha de vacinação para influenza em uma empresa

A influenza é uma das doenças respiratórias agudas mais prevalentes e importante causa de absenteísmo e presenteísmo. Entretanto, a eficácia vacinal para influenza pode alcançar 80% quando há elevada correspondência entre cepas vacinais e circulantes. Por este motivo, a empresa há anos promove campanha de vacinação, contudo, sem estimar sua efetividade (eficácia na redução da carga da doença) e o impacto econômico (produtividade) para o aprimoramento de sua política de saúde ocupacional. Considerou-se que a efetividade da campanha seria determinada pela eficácia vacinal previamente demonstrada em estudos randomizados, pelo grau de acurácia diagnóstica ou de triagem dos casos, pelo nível de adesão do profissional de saúde ao registro no prontuário e do paciente ao informar a ocorrência dos sintomas e pela cobertura vacinal alcançada. Com os objetivos de avaliar a efetividade e impacto econômico da campanha de vacinação para influenza, optou-se por um desenho estudo observacional de coorte histórico com características de estudo de intervenção baseado em dados históricos da campanha de 2008 e informações individuais sobre a frequência de sintomas respiratórios e absenteísmo, idade, gênero, função (administrativa e operacional) e renda, comorbidades relevantes e tabagismo, obtidas mediante revisão de prontuário dos 12 meses subsequentes, comparadas entre os grupos de vacinados e não-vacinados (qui-quadrado e test t) e analisadas por regressão logística, e estimada a fração prevenível (proporção de episódios potenciais de influenza evitados pela vacinação). Foram analisados os prontuários de 2.425 trabalhadores (1.651 não-vacinados e 754 vacinados) correspondendo à cobertura de 31,1%. A prevalência de influenza observada foi de 10,4% e a vacinação foi efetiva entre os trabalhadores (RR=0,51; IC95% 39-67), quando considerados os sintomas de alta probabilidade de influenza. A fração prevenível foi 0,09 (9 casos evitados a cada 100 trabalhadores vacinados). A campanha de vacinação foi mais efetiva e provocou maior impacto econômico entre os trabalhadores em regime operacional.

Avaliações econômicas do uso da vacina contra o Papilomavírus Humano (HPV) em meninas adolescentes: uma revisão sistemática

O câncer de colo do útero persiste como um importante problema de saúde em todo o mundo, em particular nos países em desenvolvimento. Duas vacinas contra o papilomavirus humano (HPV) encontram-se atualmente disponíveis e aprovadas para uso em meninas adolescentes, antes do início da vida sexual: uma bivalente, contra os sorotipos 16 e 18 e outra quadrivalente, contra os sorotipos 6, 11, 16 e 18. Estes imunobiológicos têm por objetivo induzir uma imunidade contra o papilomavírus e, desta forma, atuar na prevenção primária do câncer do colo de útero. As avaliações econômicas podem ser um elemento que auxiliem nos processos de tomada de decisão sobre a incorporação da vacina em programas de imunização nacionais. Estas avaliações foram o objeto central deste trabalho, que teve como objetivo sintetizar as evidências procedentes de uma revisão sistemática da literatura de estudos de avaliação econômica da utilização da vacina contra o HPV em meninas adolescentes e pré-adolescentes. Foi realizada uma busca na literatura nas bases MEDLINE (via Pubmed), LILACS (via Bireme) e National Health Service Economic Evaluation Database (NHS EED) ate junho de 2010. Dois avaliadores, de forma independente, selecionaram estudos de avaliação econômica completa, que tivessem como foco a imunização para HPV em mulheres com as vacinas comercialmente disponíveis direcionada à população adolescente. Após a busca, 188 títulos foram identificados; destes, 39 estudos preencheram os critérios de elegibilidade e foram incluídos na revisão. Por tratar-se de uma revisão de avaliações econômicas, não foi realizada uma medida de síntese dos valores de relação incremental entre custos e efetividade. Os 39 artigos incluídos envolveram 51 avaliações econômicas em 26 países. Predominaram estudos de custo-utilidade (51%). Do ponto de vista da perspectiva da análise, predominou o dos sistemas de saúde (76,4%). A maioria dos trabalhos (94,9%) elegeu meninas, com idade entre 9 e 12 anos, como sua população alvo e desenvolveu simulações considerando imunidade para toda a vida (84,6%). Os modelos utilizados nos estudos foram do tipo Markov em 25 análises, de transmissão dinâmica em 11 e híbridos em 3. As análises de sensibilidade revelaram um conjunto de elementos de incerteza, uma parte significativa dos quais relacionados a aspectos vacinais: custos da vacina, duração da imunidade, necessidade de doses de reforço, eficácia vacinal e cobertura do programa. Estes elementos configuram uma área de especial atenção para futuros modelos que venham a ser desenvolvidos no Brasil para análises econômicas da vacinação contra o HPV.

Fatores associados ao aleitamento materno exclusivo em Juiz de Fora, MG

Este trabalho teve como objetivos identificar e analisar fatores associados ao aleitamento materno exclusivo, com significância estatística, em crianças menores de quatro meses residentes em Juiz de Fora, Minas Gerais. Fornece informações básicas para planejamento de política de amamentação neste município, estudando fatores influentes no desmame e criando Banco de Dados em Aleitamento Materno no Centro de Computação do Núcleo de Assessoria Técnica aos Estudos em Saúde da Universidade Federal de Juiz de Fora, disponível pára uso público. Compara os resultado desta pesquisa aos de outras cidades brasileiras com estudo de metodologia semelhante. Para atingir os objetivos propostos foi realizada pela autora desta tese uma pesquisa no período de 10 de agosto a 13 de setembro de 2002, época da campanha de vacinação na cidade, em uma amostra por conglomerado, tendo sido entrevistadas 1859 pessoas, sendo 625 mães e acompanhantes de crianças menores de 4 meses, em 24 postos de vacinação. A terminologia empregada deu-se de acordo com a recomendação da OMS (1991). Aplicou-se um questionário por intermédio de 268 entrevistadores voluntários, previamente treinados, incluindo estudantes da área de saúde. A pesquisa fez parte de um estudo multicêntrico em conjunto com o Núcleo de Pesquisas Epidemiológicas em Nutrição e Saúde da Universidade de São Paulo e do Núcleo de Investigação em Saúde da Mulher e da Criança, Instituto de Saúde, Secretaria Estadual de Saúde de São Paulo denominado Avaliação das práticas alimentares no primeiro ano de vida em dias nacionais de vacinação. A análise dos dados foi processada utilizando-se o programa Statiscal Package for The Social Sciences (SPSS) e os resultados foram descritos utilizando-se o teste do qui-quadrado para verificar a significância estatística da associação dos fatores independentes com o fator de desfecho aleitamento materno exclusivo. Para estudar possíveis fatores de confusão foi aplicada a técnica de análise de regressão logística. A pesquisa evidenciou que a prevalência de Aleitamento Materno Exclusivo aos 4 meses é baixa, sendo que esta é menor que as taxas da maioria das capitais brasileiras, com exceção de Cuiabá. Os hábitos de usar chupetas e mamadeiras são muito freqüentes no município. Os fatores de risco para interrupção do aleitamento materno exclusivo até os quatro meses encontrados foram: primiparidade, nascimento em hospital público ou público-privado, não disponibilidade para amamentar, uso de chupetas ou mamadeiras. A maioria das crianças inicia a amamentação no primeiro dia de vida em casa mas não de forma exclusiva. À medida que a idade aumenta, o índice de amamentação vai diminuindo progressivamente, indicando a necessidade urgente de programas de apoio e incentivo ao aleitamento materno, em especial de sua forma exclusiva, bem como de promoção do mesmo no município. Deve ser dada ênfase nesta atenção às mulheres primíparas e àquelas mulheres cujos partos ocorreram em hospitais públicos ou públicos-privados, que não tenham disponibilidade para amamentar e que utilizam mamadeiras ou chupetas para seus filhos.

Robust Sliding Control of SEIR Epidemic Models

This paper is aimed at designing a robust vaccination strategy capable of eradicating an infectious disease from a population regardless of the potential uncertainty in the parameters defining the disease. For this purpose, a control theoretic approach based on a sliding-mode control law is used. Initially, the controller is designed assuming certain knowledge of an upper-bound of the uncertainty signal. Afterwards, this condition is removed while an adaptive sliding control system is designed. The closed-loop properties are proved mathematically in the nonadaptive and adaptive cases. Furthermore, the usual sign function appearing in the sliding-mode control is substituted by the saturation function in order to prevent chattering. In addition, the properties achieved by the closed-loop system under this variation are also stated and proved analytically. The closed-loop system is able to attain the control objective regardless of the parametric uncertainties of the model and the lack of a priori knowledge on the system.

Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles

Self-amplifying RNA or RNA replicon is a form of nucleic acid-based vaccine derived from either positive-strand or negative-strand RNA viruses. The gene sequences encoding structural proteins in these RNA viruses are replaced by mRNA encoding antigens of interest as well as by RNA polymerase for replication and transcription. This kind of vaccine has been successfully assayed with many different antigens as vaccines candidates, and has been shown to be potent in several animal species, including mice, nonhuman primates, and humans. A key challenge to realizing the broad potential of self-amplifying vaccines is the need for safe and effective delivery methods. Ideally, an RNA nanocarrier should provide protection from blood nucleases and extended blood circulation, which ultimately would increase the possibility of reaching the target tissue. The delivery system must then be internalized by the target cell and, upon receptor-mediated endocytosis, must be able to escape from the endosomal compartment into the cell cytoplasm, where the RNA machinery is located, while avoiding degradation by lysosomal enzymes. Further, delivery systems for systemic administration ought to be well tolerated upon administration. They should be safe, enabling the multiadministration treatment modalities required for improved clinical outcomes and, from a developmental point of view, production of large batches with reproducible specifications is also desirable. In this review, the concept of self-amplifying RNA vaccines and the most promising lipid-based delivery systems are discussed.

On the Stability and Equilibrium Points of Multistaged SI (n) R Epidemic Models

This paper relies on the concept of next generation matrix defined ad hoc for a new proposed extended SEIR model referred to as SI(n)R-model to study its stability. The model includes n successive stages of infectious subpopulations, each one acting at the exposed subpopulation of the next infectious stage in a cascade global disposal where each infectious population acts as the exposed subpopulation of the next infectious stage. The model also has internal delays which characterize the time intervals of the coupling of the susceptible dynamics with the infectious populations of the various cascade infectious stages. Since the susceptible subpopulation is common, and then unique, to all the infectious stages, its coupled dynamic action on each of those stages is modeled with an increasing delay as the infectious stage index increases from 1 to n. The physical interpretation of the model is that the dynamics of the disease exhibits different stages in which the infectivity and the mortality rates vary as the individual numbers go through the process of recovery, each stage with a characteristic average time.