Does distance to healthcare facility affect care-seeking for TB-related symptoms in Tanzania?

BACKGROUND: In high TB burden countries, delayed diagnosis remains a big challenge in TB control. The objective of this study is to assess the role of distance between residence and healthcare facility (HCF) on care-seeking among individuals with symptoms associated with pulmonary TB in Tanzania.METHODS: In this cross-sectional study, using data from a national TB survey, coordinates of 300 (residential) sites within 62 clusters were obtained through Google searches and average distances to HCF were calculated per cluster. Univariable and multivariable logistic regression analyses were conducted, with care-seeking behaviour being the primary outcome variable.RESULTS: Distance from residence to HCF had no effect on care-seeking behaviour of individuals with TB-related symptoms in this study (OR 1.00, 95% CI 1.00-1.00). Over 85% of HCFs where care has been sought lack TB diagnostic capacity, mostly comprising dispensaries with staff less educated in TB-related symptoms.CONCLUSION: Care-seeking behaviour among individuals with TB-related symptoms in Tanzania was not found to be associated with distance to HCF. First-line diagnostics should be improved 1) by equipping local dispensaries with basic TB diagnostic capacity, and 2) by educating staff of local dispensaries more thoroughly about basic TB symptoms and the importance of swift referrals.

An open source physiologically based kinetic model for the chicken (Gallus gallus domesticus): Calibration and validation for the prediction residues in tissues and eggs.

Xenobiotics from anthropogenic and natural origin enter animal feed and human food as regulated compounds, environmental contaminants or as part of components of the diet. After dietary exposure, a chemical is absorbed and distributed systematically to a range of organs and tissues, metabolised, and excreted. Physiologically based kinetic (PBK) models have been developed to estimate internal concentrations from external doses. In this study, a generic multi-compartment PBK model was developed for chicken. The PBK model was implemented for seven compounds (with log Kow range -1.37-6.2) to quantitatively link external dose and internal dose for risk assessment of chemicals. Global sensitivity analysis was performed for a hydrophilic and a lipophilic compound to identify the most sensitive parameters in the PBK model. Model predictions were compared to measured data according to dataset-specific exposure scenarios. Globally, 71% of the model predictions were within a 3-fold change of the measured data for chicken and only 7% of the PBK predictions were outside a 10-fold change. While most model input parameters still rely on in vivo experiments, in vitro data were also used as model input to predict internal concentration of the coccidiostat monensin. Future developments of generic PBK models in chicken and other species of relevance to animal health risk assessment are discussed.

Generic physiologically based kinetic modelling for farm animals: Part II. Predicting tissue concentrations of chemicals in swine, cattle, and sheep.

The development of three generic multi-compartment physiologically based kinetic (PBK) models is described for farm animal species, i.e. cattle, sheep, and swine. The PBK models allow one to quantitatively link external dose and internal dose for risk assessment of chemicals relevant to food and feed safety. Model performance is illustrated by predicting tissue concentrations of melamine and oxytetracycline and validated through comparison with measured data. Overall, model predictions were reliable with 71% of predictions within a 3-fold of the measured data for all three species and only 6% of predictions were outside a 10-fold of the measured data. Predictions within a 3-fold change were best for cattle, followed by sheep, and swine (82%, 76%, and 63%). Global sensitivity analysis was performed to identify the most sensitive parameters in the PBK model. The sensitivity analysis showed that body weight and cardiac output were the most sensitive parameters. Since interspecies differences in metabolism impact on the fate of a wide range of chemicals, a key step forward is the introduction of species-specific information on transporters and metabolism including expression and activities.

Generic physiologically based kinetic modelling for farm animals: Part I. Data collection of physiological parameters in swine, cattle and sheep.

Physiologically based kinetic (PBK) models for farm animals are of growing interest in food and feed safety with key applications for regulated compounds including quantification of tissue concentrations, kinetic parameters and the setting of safe exposure levels on an internal dose basis. The development and application of these models requires data for physiological, anatomical and chemical specific parameters. Here, we present the results of a structured data collection of anatomical and physiological parameters in three key farm animal species (swine, cattle and sheep). We performed an extensive literature search and meta-analyses to quantify intra-species variability and associated uncertainty of the parameters. Parameters were collected for organ weights and blood flows in all available breeds from 110 scientific publications, of which 29, 48 and 33 for cattle, sheep, and swine, respectively. Organ weights were available in literature for all three species. Blood flow parameter values were available for all organs in sheep but were scarcer in swine and cattle. Furthermore, the parameter values showed a large intra-species variation. Overall, the parameter values and associated variability provide reference values which can be used as input for generic PBK models in these species.

Physiologically based kinetic models for farm animals: Critical review of published models and future perspectives for their use in chemical risk assessment.

Physiologically based kinetic (PBK) models in the 10 most common species of farm animals were identified through an extensive literature search. This resulted in 39 PBK models, mostly for pharmaceuticals. The models were critically assessed using the WHO criteria for model evaluation, i.e. 1) purpose, 2) structure and mathematical representation, 3) computer implementation, 4) parameterisation, 5) performance, and 6) documentation. Overall, most models were calibrated and validated with published data (92% and 67% respectively) but only a fraction of model codes were published along with the manuscript (28%) and local sensitivity analysis was performed without considering global sensitivity analysis. Hence, the reliability of these PBK models is hard to assess and their potential for use in chemical risk assessment is limited. In a risk assessment context, future PBK models for farm animals should include a more generic and flexible model structure, use input parameters independent on calibration and include assessment tools to assess model performance. Development and application of PBK models for farm animal species would furthermore benefit from the setup of structured databases providing data on physiological and chemical-specific parameters as well as enzyme expression and activities to support the development of species-specific QIVIVE models.

Cumulative risk assessment of chemical exposures in urban environments.

We performed a cumulative risk assessment for people living in a hypothetical urban environment, called Urbania. The main aims of the study were to demonstrate how a cumulative risk assessment for a middle-sized European city can be performed and to identify the bottlenecks in terms of data availability and knowledge gaps. The assessment focused on five air pollutants (i.e., PM10, benzene, toluene, nonane and naphthalene) and six food pesticides (i.e., acetamiprid, carbendazim, chlorpyrifos, diazinon, imidacloprid and permethrin). Exposure predictions showed that PM10, benzene and naphthalene exposure frequently exceeded the standards, and that the indoor environment contributed more than the outdoor environment. Effect predictions showed that mixture and interaction effects were generally limited. However, model calculations indicated potential synergistic effects between naphthalene and benzene and between chlorpyrifos, diazinon and toluene. PM10 dominated the health impact expressed in Disability Adjusted Life Years (DALYs). We conclude that measures to reduce the health impact of environmental pollution should focus on the improvement of indoor air quality and the reduction of PM10 emissions. Cumulative risk assessment can be improved by (1) the development of person-oriented exposure models that can simulate the cumulative exposure history of individuals, (2) a better mechanistic understanding of the effects of cumulative stressors, and (3) the development of instruments to prioritize stressors for inclusion in cumulative risk assessments.