Métodos alternativos como parte de las nuevas tendencias en el control de calidad de vacunas / Alternative methods as part of the new trends in vaccine quality control

El control de calidad de las vacunas resulta fundamental para las actividades de producción, liberación lote a lote y comercialización de las vacunas. Sin embargo, en la actualidad este es un proceso que por su concepción es lento y costoso debido a que se apoya en la realización de extensas pruebas en animales para demostrar la potencia y seguridad de estos productos biológicos. El desarrollo de métodos alternativos inspirados en el principio de las 3Rs (Reducción, Refinamiento y Reemplazo) constituye una tendencia que debe impactar de manera muy significativa en la reducción de los tiempos de liberación y el costo del proceso de control de calidad de vacunas en los próximos años. En particular la sustitución de las pruebas de potencia y toxicidad in vivo por procedimientos alternativos más relevantes, rápidos, exactos, reproducibles, robustos y baratos, que incluyen la serología, la cuantificación directa de antígeno, los ensayos en cultivos celulares y el enfoque a consistencia, por solo mencionar algunos; implica un cambio de paradigma, con indiscutibles repercusiones éticas, logísticas, económicas y científico-técnicas, para el aseguramiento de los parámetros de calidad de los inmunobiológicos con el mejor balance costo-beneficio: las vacunas. Los fundamentos técnicos de estos métodos alternativos, sus ventajas y nivel de implementación a nivel internacional, así como sus principales limitaciones, son abordados en este trabajo(AU)

Vaccine quality control is crucial for the manufacturing, lot release and commercialization activities worldwide. However, the current process is by-design too slow and expensive because is based on large animal assays for assuring the potency and safety of these important biological products. The development of 3Rs alternative methods (Reduction, Refinement and Replacement) is a trend able to significantly reduce the releasing times and costs of the vaccine quality control processes in the next few years. Particularly, the replacement of the animals-based potency and toxicity assays by alternative procedures more relevant, fast, accurate, reproducible and cheap, including serology, direct antigen quantification, cell culture tests and the Consistency Approach, for just mentioning some of them, implies a paradigm shift, with undisputable ethical, logistical, economic, scientific and technical repercussions for ensuring the vaccine quality parameters. Theoretical basements, advantages and implementation levels of the alternatives methods as well as their main limitations are presented in this paper(AU)

Assessment on the ownership and use of mosquito nets in Mozambique / Avaliação sobre a posse e uso de redes mosquiteiras em Moçambique

ABSTRACT OBJECTIVE To assess the ownership and use of mosquito nets in 2014, in Mozambique. METHODS This observational and cross-sectional study assessed, in February and March 2015, 69 districts (nine of 11 provinces of Mozambique) that have benefited from the mass distribution of mosquito nets. The Lot Quality Assurance Sampling methodology was used. Each locality was denominated supervision area. The Lot Quality Assurance Sampling opts for a minimum of 19 households (in this case, we decided for a minimum of 100 households per district) from each supervision area to assess an indicator (in this case, two indicators were assessed: ownership and use of mosquito nets). Two questions guided the research: a) received a mosquito net; b) used a mosquito net the night before. RESULTS A total of 6,725 households were assessed. Eighty three percent of them had received mosquito nets in the campaign. Of the 6,232 respondents, 82.0% said they used mosquito nets the night before. The districts of the provinces with low coverage of ownership and use were Tete (69.5% and 60.0%, respectively), Zambezia (79.0% and 60.0%, respectively), and Gaza (81.6% and 70.7%, respectively). The largest coverage of ownership and use were observed in the districts of Nampula (96.7% and 93.8%, respectively) and Niassa (86.0% and 85.4% respectively). CONCLUSIONS In the districts assessed, the progression of ownership and use of mosquito nets is satisfactory. Nampula and Niassa are the only provinces where ownership and use are at desired levels.

RESUMO OBJECTIVO Avaliar a posse e o uso das redes mosquiteiras no ano de 2014 em Moçambique. MÉTODOS Este estudo observacional transversal avaliou, em fevereiro e março de 2015, 68 distritos (nove das 11 províncias de Moçambique) que se beneficiaram da distribuição de redes em massa. Usou-se a metodologia Lot Quality Assurance Sampling. Cada localidade foi designada de área de supervisão. O Lot Quality Assurance Sampling opta por um mínimo de 19 agregados familiares (neste caso decidiu-se um mínimo de 100 agregados familiares por distrito) de cada área de supervisão, a fim de avaliar um indicador (neste caso dois indicadores foram avaliados: posse e uso de redes mosquiteiras). Duas perguntas nortearam a pesquisa: a) recebeu rede; b) usou rede na noite anterior. RESULTADOS Foram avaliados 6.725 agregados familiares . Desses, 83,0% tinham recebido redes na campanha. Dos 6.232 inqueridos, 82,0% disseram que usaram na noite anterior. As províncias com distritos com menores coberturas de posse e uso foram Tete (69,5% e 60,0%, respectivamente), Zambézia (79,0% e 60,0%, respectivamente) e Gaza (81,6% e 70,7%, respectivamente). As maiores coberturas de posse e uso foram observadas nos distritos de Nampula (96,7% e 93,8%, respectivamente) e Niassa (86,0% e 85,4%, respectivamente). CONCLUSÕES Nos distritos avaliados, a progressão para a posse e uso de redes mosquiteiras é satisfatória. Nampula e Niassa são as únicas províncias onde a posse e o uso estão em níveis desejados.

Validation on the elimination of neonatal tetanus programs through Lot Quality Assurance-Cluster Sample Survey in China / 中华流行病学杂志

<p><b>OBJECTIVE</b>Field surveys were performed under WHO recommended validation procedures, using the Lot Quality Assurance-Cluster Sample(LQA-CS)method to validate the elimination status regarding neonatal tetanus in China.</p><p><b>METHODS</b>LQA-CS surveys were conducted in two areas under the highest risk of neonatal tetanus-Jiangmen prefecture in Guangdong and Hechi in Guangxi. Random sampling method was conducted on 96 survey clusters in each prefecture with 12 eligible live births(live birth born one year before the survey)for each cluster, by trained investigators.</p><p><b>RESULTS</b>There were 1 153 eligible live births from 23 465 families surveyed in Jiangmen and 1 152 eligible live births from 21 623 families being studied in Hechi. All the indices on quality control were strictly followed. There was no neonatal tetanus case which met the criteria of neonatal elimination found in either of the areas. Data showed that neonatal tetanus had been eliminated in both Jiangmen and Hechi cities.</p><p><b>CONCLUSION</b>Since both Jiangmen and Hechi were cities having the highest-risk in China, it was most likely that neonatal tetanus had also been eliminated in other prefectures at lower risk. Elimination programs on MNT was therefore considered validate in China when the study was carried out. However, the achievements needed to be maintained.</p>

Atributos eco-estéticos del paisaje urbano / The uban landscaape eco-aesthetic attribuess

Este artículo presenta una síntesis teórico-conceptual sobre los aspectos relevantes de las dimensiones ecológica y estética que definen los atributos del paisaje urbano. La ciudad como producto y creación, tiene sus características, elementos, cualidades y relaciones, que pueden ser percibidos e interpretados a la luz de quien observa, con lo cual, su definición abarca el análisis objetivo y subjetivo. La ecología aporta la perspectiva sistémica de la dinámica urbana observada en la interacción de sus factores naturales y socioculturales; la estética abarca la percepción desde el contacto visual con los elementos del paisaje a las sensaciones, sentimientos y condiciones que influyen en la interpretación. La naturaleza multidimensional basada en la concepción eco-estética de los atributos del paisaje urbano,es una base fundamental para determinar los indicadores de análisis de la calidad visual, orientada a la práctica del diseño urbano.

This article presents a theoretical and conceptual synthesis on relevant aspects of the ecological and aesthetic dimensions that define the urban landscape attributes. The city, as product and creation, has its characteristics, elements, qualities and relationships that can be perceived and interpreted under the light of the viewer, so that its definition embraces both an objective and a subjective analysis. Ecology provides a systemic perspective of the urban dynamics observed in the interaction of its natural and social-cultural factors; aesthetics encompasses perception from the visual contact, with the elements of the landscape, to sensations, feelings and conditions that influence the interpretation. The multidimensional nature based on the eco-aesthetics conception of the urban landscape attributes is a fundamental base to determine the analysis indicators of visual quality oriented to the , urban design practice.

Aplicação do conceito do erro total na validação do ensaio de potência da vacina oral contra a poliomielite / Use of the total error approach for validating the potency assay for oral poliomyelitis vaccine

Esta pesquisa foi realizada utilizando-se uma abordagem alternativa na validação do ensaio de potênciada vacina oral contra a poliomielite para traçar o perfil deste ensaio, levando-se em conta a grande variabilidade de ensaios biológicos. Foram adotadas duas abordagens para a validação do ensaio: a abordagem Clássica da “International Conference on Harmonization” aplicada aos ensaios biológicos e a abordagem do Conceito do Erro Total. As principais características avaliadas no estudo de validação, por se tratar de um ensaio quantitativo, foram a veracidade, a precisão e a exatidão. Foram ainda avaliadas: a adequação do ensaio aos critérios de aceitação preconizados pelo Food and Drug Administration (EUA) para validação, adotando-se a variação máxima aceita de 20 por cento, a reprodutibilidade do ensaio em uma abordagem prática, com o uso das variâncias entre os resultados de potência de 39 lotes da vacina (do mesmo produtor) obtidos no INCQS e no laboratório produtor, por amostra, para calcular o Coeficiente de Variação geométrico geral. Foi também determinada a Incerteza de Medição do Teste. O ensaio apresentou veracidade e precisão satisfatórias, o que demonstrou sua Exatidão satisfatória para a intenção de uso nas duas abordagens de validação.

Using Lot Quality Assurance Sampling Methodology to Evaluate the uThukela District Child Survival Project of KwaZulu-Natal

Health services programmes and interventions require objective measures on coverage and quality to ensure that managers have the evidence to adopt and expand health interventions effectively and efficiently. Over the past 15 years; the uThukela District Child Survival Project of South Africa achieved this through regular two- to three-year project evaluations using cluster sampling. Results of these surveys have improved the ability of Child Survival Projects to identify priorities; define objectives based on data; and measure progress towards these objectives. However; the inability to disaggregate information to composite Supervision Areas (SAs) was a limitation. Lot quality assurance sampling (LQAS) was adopted as an improved method based on its ability to assess performance in disaggregated units within a study population and to reliably compare coverage and health status indicators for routine monitoring of child survival activities. This study assessed the feasibility and reliability of LQAS to evaluate the Child Survival Project and compare the results of a rapid manual analysis with a secondary electronic analysis of the same data. The accuracy of the manual analysis was comparable and provides evidence that LQAS and rapid manual analysis can be used to evaluate intervention programmes; particularly in settings of limited electronic technology and expertise

A community based approach to improve health care seeking for newborn danger signs in rural wardha, India.

OBJECTIVE: To find out the effect of community mobilization and health education effort on health care seeking behavior of families with sick newborns, and to explore the rationale behind the changed health care seeking behaviors of mothers in a rural Indian community. METHODS: In the present community based participatory intervention, a triangulated research design of quantitative (survey) and qualitative (Focus group discussions, FGDs) method was undertaken for needs assessment in year 2004. In community mobilization, women's self help groups; Kishori Panchayat (KP, forum of adolescent girls), Kisan Vikas Manch (Farmers' club) and Village Coordination Committees (VCC) were formed in the study area. The trained social worker facilitated VCCs to develop village health plans to act upon their priority maternal and child health issues. The pregnant women and group members were given health education. The Lot Quality Assurance Sampling (LQAS) technique was used to monitor awareness regarding newborn danger signs among pregnant women. In year 2007, a triangulation of quantitative survey and a qualitative study (free list and pile sort exercise) was undertaken to find out changes in health care seeking behaviors of mothers. RESULTS: There was significant improvement in mothers' knowledge regarding newborn danger signs. About half of the mothers got information from CLICS doot (female community health worker). The monitoring over three years period showed encouraging trend in level of awareness among pregnant women. After three years, the proportion of mothers giving no treatment/home remedy for newborn danger signs declined significantly. However, there was significant improvement in mothers' health care seeking from private health care providers for sick newborns. CONCLUSION: The present approach improved mothers' knowledge regarding newborn danger signs and improved their health care seeking behavior for newborn danger signs at community level. Due to lack of faith in government health services, women preferred to seek care from private providers.

MLC leaf position and dynalog file accuracy QA procedure using the EPID

A main concern about the IMRT dose validation tool using Monte Carlo [MC] simulation and R and V-system/Dynalog file is the potential inconsistency between the actual leaf-end positions and those recorded by the Dynalog file. The present study investigates a method to validate the accuracy of the Dynalog tiles using amorphous silicon electronic portal imaging device [aSi-EPID] images. A computer program was developed to detect the MLC segmented field edges in EPID images [l024x768 pixels, pixel size: 0.392 mm], Standard reference MLC segmented fields were designed and leaf-end positions were measured accurately. EPID images for these reference MLC fields were recorded and the leaf-end positions were calculated as the locations where the image intensity is 50% of the maximum. Small corrections were made to minimize the effect of scattered photons [background]. Daily EPII] images of the same MLC segmented fields were compared to the original images and to check the accuracy of the Dynalog files. A daily QA tool was developed to check the accuracy of the Dynalog file and MLC leaf end positions as part of the comprehensive IMRT-QA procedure. This ensures the accuracy of the MC based patient-specific IMRT dose verification using the information recorded in the Reeord and Verify system/Dynalog files