Implementing OECD GLP principles for the evaluation of novel vector control tools: a case study with two novel LLINs, SafeNet® and SafeNet NF®.

BACKGROUND: To sustain high universal Long-Lasting Insecticidal Nets (LLINs) coverage, affordable nets that provide equivalent or better protection than standard LLINs, are required. Test facilities evaluating new LLINs require compliance to Good Laboratory Practice (GLP) standards to ensure the quality and integrity of test data. Following GLP principles allows for the reconstruction of activities during the conduct of a study and minimizes duplication of efficacy testing. This case study evaluated the efficacy of two LLINs: SafeNet NF® and SafeNet® LLIN. METHODS: The study was conducted according to GLP principles and followed World Health Organization guidelines for evaluating LLINs. The LLINs were assessed in experimental huts against wild, pyrethroid-resistant Anopheles arabiensis mosquitoes. Nets were either unwashed or washed 20 times and artificially holed to simulate a used torn net. Blood-feeding inhibition and mortality were compared with a positive control (Interceptor® LLIN) and an untreated net. RESULTS: Mosquito entry in the huts was reduced compared to negative control for the unwashed SafeNet NF, washed Safenet LLIN and the positive control arms. Similar exiting rates were found for all the treatment arms. Significant blood-feeding inhibition was only found for the positive control, both when washed and unwashed. All insecticide treatments induced significantly higher mortality compared to an untreated net. Compared to the positive control, the washed and unwashed SafeNet NF® resulted in similar mortality. For the SafeNet® LLINs the unwashed net had an equivalent performance, but the mortality for the washed net was significantly lower than the positive control. Internal audits of the study confirmed that all critical phases complied with Standard Operating Procedures (SOPs) and the study plan. The external audit confirmed that the study complied with GLP standards. CONCLUSIONS: SafeNet NF® and SafeNet® LLIN offered equivalent protection to the positive control (Interceptor® LLIN). However, further research is needed to investigate the durability, acceptability, and residual efficacy of these nets in the community. This study demonstrated that GLP-compliant evaluation of LLINs can be successfully conducted by African research institutions.

Three-dimensional rendering of trabecular bone microarchitecture using a probabilistic approach.

In the past, researchers have attempted to model trabecular bone using computational techniques. However, only a few of these models are visually similar, but not representative of the microstructural characteristics of real trabecular bones. In this study, we hypothesized that probabilistic modeling approaches could be used to generate representative digital models that capture the microstructural features of real trabecular bones. To test this hypothesis, we proposed a novel mathematical framework to build the digital models and compared the digital models to real bone specimens. First, an initial three-dimensional cellular structure was generated using Voronoi tessellation, with the faces and edges of the Voronoi cells considered as a pool of potential trabecular plates and rods, respectively. Then, inverse Monte Carlo simulations were performed to select, delete, or reassign plates and rods until the underlying size, orientation, and spatial distributions of the plates and rods converged to the target distributions obtained from real trabecular bone microstructures. Next, digital graphics techniques were used to define the thickness of trabecular plates and the diameter of trabecular rods, followed by writing the model into a Standard Tessellation Language file and then smoothing the model surfaces for a more natural appearance. To verify the efficacy of the digital model in capturing the microstructural features of real trabecular bones, forty-six digital models with a large variation in microstructural features were generated based on the target distributions obtained from trabecular bone specimens of twelve human cadaveric femurs. Then, the histomorphological parameters of the digital models were compared with those of the real trabecular bone specimens. The results indicate that the digital models are capable of capturing major microstructural features of the trabecular bone samples, thus proving the hypothesis that the proposed probabilistic modeling approach could render real trabecular bone microstructures.

Evaluation of a national universal coverage campaign of long-lasting insecticidal nets in a rural district in north-west Tanzania.

BACKGROUND: Insecticide-treated nets (ITN) are one of the most effective measures for preventing malaria. Mass distribution campaigns are being used to rapidly increase net coverage in at-risk populations. This study had two purposes: to evaluate the impact of a universal coverage campaign (UCC) of long-lasting insecticidal nets (LLINs) on LLIN ownership and usage, and to identify factors that may be associated with inadequate coverage. METHODS: In 2011 two cross-sectional household surveys were conducted in 50 clusters in Muleba district, north-west Tanzania. Prior to the UCC 3,246 households were surveyed and 2,499 afterwards. Data on bed net ownership and usage, demographics of household members and household characteristics including factors related to socio-economic status were gathered, using an adapted version of the standard Malaria Indicator Survey. Specific questions relating to the UCC process were asked. RESULTS: The proportion of households with at least one ITN increased from 62.6% (95% Confidence Interval (CI) = 60.9-64.2) before the UCC to 90.8% (95% CI = 89.0-92.3) afterwards. ITN usage in all residents rose from 40.8% to 55.7%. After the UCC 58.4% (95% CI = 54.7-62.1) of households had sufficient ITNs to cover all their sleeping places. Households with children under five years (OR = 2.4, 95% CI = 1.9-2.9) and small households (OR = 1.9, 95% CI = 1.5-2.4) were most likely to reach universal coverage. Poverty was not associated with net coverage. Eighty percent of households surveyed received LLINs from the campaign. CONCLUSIONS: The UCC in Muleba district of Tanzania was equitable, greatly improving LLIN ownership and, more moderately, usage. However, the goal of universal coverage in terms of the adequate provision of nets was not achieved. Multiple, continuous delivery systems and education activities are required to maintain and improve bed net ownership and usage.