É provável que a mudança climática afete a natureza, destino e transporte de elementos patogênicos/químicos no ambiente . Avaliamos as implicações das mudanças climáticas em mudanças na exposição humana a elementos patogênicos/químicos nos sistemas agrícolas no Reino Unido e discutimos os efeitos sobre os impactos à saúde, usando a contribuição de especialistas e literatura; efeitos à saúde da exposição a elementos patogênicos/químicos provenientes da agricultura; introdução de elementos químicos/patogênicos e caminhos de exposição humana a elementos patogênicos/químicos nos sistemas agrícolas. Definimos a base de evidência para efeitos de saúde de elementos químicos/patogênicos no ambiente agrícola; determinamos as possíveis implicações da mudança climática na introdução de elementos químicos/patogênicos nos sistemas agrícolas; e exploramos os efeitos da mudança climática no transporte ambiental e destino de diversos contaminantes. Consolidamos dados para avaliar as implicações das mudanças climáticas em relação à exposição humana indireta a elementos patogênicos/químicos nos sistemas agrícolas e recomendamos futuras pesquisas e mudanças políticas para administrar aumentos adversos nos riscos.

Climate change is likely to affect the nature of pathogens/ chemicals in the environment and their fate and transport. We assess the implications of climate change for changes in human exposures to pathogens/chemicals in agricultural systems in the UK and discuss the effects on health impacts, using expert input and literature on climate change; health effects from exposure to pathogens/chemicals arising from agriculture; inputs of chemicals/pathogens to agricultural systems; and human exposure pathways for pathogens/chemicals in agricultural systems. We established the evidence base for health effects of chemicals/pathogens in the agricultural environment; determined the potential implications of climate change on chemical/pathogen inputs in agricultural systems; and explored the effects of climate change on environmental transport and fate of various contaminants. We merged data to assess the implications of climate change in terms of indirect human exposure to pathogens/chemicals in agricultural systems, and defined recommendations on future research and policy changes to manage adverse increases in risks.

É provável que a mudança climática afete a natureza, destino e transporte de elementos patogênicos/químicos no ambiente . Avaliamos as implicações das mudanças climáticas em mudanças na exposição humana a elementos patogênicos/químicos nos sistemas agrícolas no Reino Unido e discutimos os efeitos sobre os impactos à saúde, usando a contribuição de especialistas e literatura; efeitos à saúde da exposição a elementos patogênicos/químicos provenientes da agricultura; introdução de elementos químicos/patogênicos e caminhos de exposição humana a elementos patogênicos/químicos nos sistemas agrícolas. Definimos a base de evidência para efeitos de saúde de elementos químicos/patogênicos no ambiente agrícola; determinamos as possíveis implicações da mudança climática na introdução de elementos químicos/patogênicos nos sistemas agrícolas; e exploramos os efeitos da mudança climática no transporte ambiental e destino de diversos contaminantes. Consolidamos dados para avaliar as implicações das mudanças climáticas em relação à exposição humana indireta a elementos patogênicos/químicos nos sistemas agrícolas e recomendamos futuras pesquisas e mudanças políticas para administrar aumentos adversos nos riscos.

Climate change is likely to affect the nature of pathogens/ chemicals in the environment and their fate and transport. We assess the implications of climate change for changes in human exposures to pathogens/chemicals in agricultural systems in the UK and discuss the effects on health impacts, using expert input and literature on climate change; health effects from exposure to pathogens/chemicals arising from agriculture; inputs of chemicals/pathogens to agricultural systems; and human exposure pathways for pathogens/chemicals in agricultural systems. We established the evidence base for health effects of chemicals/pathogens in the agricultural environment; determined the potential implications of climate change on chemical/pathogen inputs in agricultural systems; and explored the effects of climate change on environmental transport and fate of various contaminants. We merged data to assess the implications of climate change in terms of indirect human exposure to pathogens/chemicals in agricultural systems, and defined recommendations on future research and policy changes to manage adverse increases in risks.

OBJECTIVE:The Guanacaste study ("Guanacaste Project," or GP), was designed to investigate the role of human papillomavirus (HPV) infection and its cofactors in the development of cervical neoplasia and to evaluate new cervical cancer screening technologies. The follow-up phase of the GP was designed to study why a small proportion of women infected with HPV develop cervical intraepithelial neoplasia grade 2 (CIN 2), CIN 3, or cancer (these three together are globally referred to as > CIN 2, that is, CIN 2 or worse). The purpose of this article is to describe this prospective study in detail and to present the preliminary findings regarding the incidence of cervical neoplasia. METHODS: A cohort of 10 049 randomly selected women from 18 to 97 years old from Guanacaste, a province in northwestern Costa Rica, was intensively screened in 1993-1994 and then followed up for seven years after being enrolled. A questionnaire for demographic and risk factors was administered, and a pelvic examination was performed on sexually active women at each follow-up visit in order to obtain samples for screening tests and for research purposes. The final diagnosis given at the end of the enrollment phase categorized women into several groups according to the perceived risk of their developing either high-grade precursors of cancer or cancer. These groups were followed up at different intervals according to the risk of developing > CIN 2. The most active follow-up (every 6-12 months) was concentrated on the women most likely to develop > CIN 2, based on cytology (n= 492). The remainder of the cohort was followed either annually (n= 2 574) or after five to seven years of passive follow-up (n= 3 926). All women with possibly severe lesions detected by any technique were referred to colposcopy for further evaluation and treatment, and they were also censored from the study. Lesions >CIN 2 served as both the censoring outcome and our surrogate for cancer risk. RESULTS: Participation during follow-up was high (near 90%). Suspected > CIN 2 by any screening technique censored 4.6% of women. Most of the women censored because of suspected > CIN 2 came from the large group perceived at entry as being at low risk of developing > CIN 2, but the greatest rates of progression to > CIN 2 were observed among women perceived at entry to be at highest risk of >CIN 2, based on their cytology, virology, or sexual behavior. CONCLUSIONS: The GP is the largest population-based longitudinal cohort for the study of HPV and cervical neoplasia in the world, and its results will hopefully let us soon plan future worldwide prevention strategies. Research projects such as this one require the long-term commitment of a large multidisciplinary team and ample financial resources. The intensive effort and expertise applied in all aspects of this study were key factors in its success as a model of cooperative, interdisciplinary cancer research in Latin America. Quality control played an important role at all times during the study and made it possible to adapt new diagnostic and screening technology to Guanacaste. The systematic follow-up of a population-based group of close to 10 000 women in Guanacaste should permit careful, time-dependent evaluation of factors postulated to be linked to the development of cervical cancer as well as the evaluation of clinical markers of disease progression. The study results that have already been published have validated sensitive screening techniques and have also promoted the use of more affordable screening techniques in resource-poor, developing countries. The GP has also contributed to building knowledge for the search for vaccines against HPV as part of the effort to develop an effective tool to reduce the incidence and mortality of cervical cancer worldwide.

OBJETIVOS: El estudio de cohorte de Guanacaste, o Proyecto Epidemiológico Guanacaste, fue diseñado para investigar el papel que desempeñan la infección por el virus del papiloma humano (VPH) y sus cofactores en el desarrollo de neoplasias cervicouterinas y para evaluar nuevas tecnologías de tamizaje del cáncer del cuello de útero. La fase de seguimiento de este proyecto se diseñó para analizar por qué una pequeña parte de las mujeres infectadas por el VPH desarrollan neoplasias intraepiteliales cervicouterinas (NIC) grados 2 y 3, o cáncer (que en lo adelante se llamarán en conjunto > NIC 2, es decir, NIC 2 o peor). El propósito de este artículo es describir en detalle ese estudio prospectivo y presentar los resultados preliminares relacionados con la incidencia de neoplasias cervicouterinas. MÉTODOS: Se realizó el tamizaje intensivo de una cohorte de 10 049 mujeres de 18 a 97 años de edad seleccionadas aleatoriamente en Guanacaste, provincia del noroeste de Costa Rica, en 1993-1994 con un seguimiento ulterior de siete años. A las participantes se les aplicó un cuestionario para conocer sus características demográficas y sus factores de riesgo, y a las sexualmente activas se les realizó además un examen pélvico en cada una de las visitas de seguimiento, a fin de obtener muestras para las pruebas de tamizaje y la investigación. El diagnóstico obtenido al final de la fase de captación permitió clasificar a las mujeres en varios grupos de acuerdo con el riesgo que presentaban de desarrollar cáncer o alguno de sus precursores de alto grado. Estos grupos tuvieron seguimientos a intervalos diferentes, según su riesgo de desarrollar > NIC 2. El seguimiento más activo (cada 6-12 meses) se concentró en las mujeres con mayores probabilidades de desarrollar > NIC 2, según los resultados citológicos (n = 492). Las mujeres restantes recibieron visitas de seguimiento anualmente (n = 2 574) o después de cinco a siete años de seguimiento pasivo (n = 3 926). A todas las mujeres en quienes se detectaron lesiones que pudieran ser graves, por cualquiera de las técnicas empleadas, se les remitió a una evaluación ulterior mediante colposcopia y a tratamiento médico, y se retiraron del estudio. Las lesiones > NIC 2 se utilizaron como criterio para la salida del estudio y como indicadores indirectos del riesgo de cáncer. RESULTADOS: La participación durante la fase de seguimiento fue alta (cercana al 90%). Cualquier indicio de > NIC 2, según cualquiera de las técnicas de tamizaje, fue motivo para eliminar a 4,6% de las mujeres participantes. La mayor parte de estas mujeres procedían del grupo que al inicio del estudio parecía tener un riesgo bajo de desarrollar > NIC 2, pero el mayor riesgo absoluto de progresión a > NIC 2 a partir de lesiones intraepiteliales escamosas de bajo grado se observó entre las mujeres que al incorporarse al estudio parecían estar en mayor riesgo de > NIC 2 según los resultados citológicos y virológicos y su comportamiento sexual. CONCLUSIONES: El Proyecto Epidemiológico Guanacaste es el estudio de cohorte de base poblacional de neoplasia cervicouterina más grande del mundo y se espera que sus resultados permitan elaborar en un futuro cercano estrategias preventivas en todo el mundo. Proyectos de investigación como este requieren del compromiso a largo plazo de un numeroso equipo multidisciplinario y de considerables recursos financieros. El intenso esfuerzo y la gran pericia demostrados en todas las facetas de este estudio constituyeron factores clave que explican su éxito como modelo de investigación cooperativa interdisciplinaria sobre el cáncer en América Latina. El control de la calidad desempeñó un papel importante en todas las etapas de la investigación y permitió adaptar las nuevas tecnologías de diagnóstico y tamizaje a las condiciones de Guanacaste. El seguimiento sistemático de un grupo poblacional de aproximadamente 10 000 mujeres de Guanacaste debe permitir una evaluación cuidadosa y cronológica de los factores que diversos autores han asociado con el desarrollo de cáncer cervicouterino, así como la evaluación de marcadores clínicos de la progresión de esta enfermedad. En los resultados publicados de este estudio se definen las técnicas de tamizaje más sensibles y se promueve la utilización de técnicas de tamizaje más asequibles para países en desarrollo y con pocos recursos. Este proyecto también ha aportado información útil para la búsqueda de vacunas contra los VPH, como parte de las iniciativas dirigidas a desarrollar vías eficaces para reducir la incidencia del cáncer cervicouterino y la mortalidad que ocasiona en todo el mundo.