Power calculation for mosquito bioassays: Quantifying variability in the WHO tube bioassay and developing sample size guidance for the PBO synergism assay using a Shiny application.

Gates Open Research Pub Date : 2024-09-12 eCollection Date: 2024-01-01 DOI:10.12688/gatesopenres.16123.1
Frank Mechan, Giorgio Praulins, Jack Gillespie, Katherine Gleave, Annabel Murphy-Fegan, Daniel P McDermott, David Weetman, Rosemary Susan Lees
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Abstract

Background: The WHO tube bioassay is a method for exposing mosquitos to determine susceptibility to insecticides, with mortality to discriminating doses <98% indicating possible resistance and <90% confirming resistance. This bioassay is also used for synergism testing to assess if susceptibility is restored by pre-exposure to the synergist piperonyl butoxide.

Methods: Here we perform testing with pyrethroid-susceptible and pyrethroid-resistant An. gambiae to quantify the variability of the WHO tube bioassay and identify its sources. These estimates of within and between day variability are then used to evaluate the power of the bioassay to detect a mortality difference between pyrethroid-only and pyrethroid-PBO.

Results: We show that approximately two-thirds of variation occurs between days, with the pyrethroid-susceptible strain twice as variable as the pyrethroid-resistant strain. The total number of mosquitoes in the tube and their bodyweight contributes to approximately 10% of this variability. Changes in temperature and humidity, within a climate-controlled insectary, didn't impact mortality. Using a simulation-based framework, we show that the current synergism guidelines, using a 4x4 design, can reliably detect a difference between 90% and 100% mortality (>90% power). However, as the mortality of either group gets closer to 50%, a 10% difference between groups is more difficult to reliably detect. In the worst-case scenario where the mortality of either group is 50%, the mortality difference must be >22.5% to be detected with 80% power. We provide an R shiny application to assess power for other comparisons.

Conclusions: Our findings indicate that detecting synergism with the WHO tube assay is more difficult than assumed by the current WHO guidelines. Additionally, we demonstrate the value of using a Shiny application to make the outputs of simulation-based power analysis readily available to end-users, allowing them to determine the number of tubes needed to detect a given mortality difference.

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蚊子生物测定的功率计算:使用 Shiny 应用程序量化世卫组织试管生物测定的变异性,并为 PBO 增效测定制定样本量指南。
背景:方法:在这里,我们用对拟除虫菊酯敏感的冈比亚蚊和对拟除虫菊酯抗性的冈比亚蚊进行测试,以量化世卫组织管式生物测定的变异性并确定其来源。然后利用这些日内和日间变异性估计值来评估生物测定法检测纯拟除虫菊酯和拟除虫菊酯-PBO死亡率差异的能力:结果:我们发现,大约三分之二的变化发生在日间,除虫菊酯易感株系的变化是除虫菊酯抗性株系的两倍。管中蚊子的总数及其体重约占这一变化的 10%。在气候可控的昆虫室内,温度和湿度的变化不会影响死亡率。通过基于模拟的框架,我们表明,采用 4x4 设计的现行协同作用准则可以可靠地检测出 90% 和 100% 死亡率之间的差异(功率大于 90%)。然而,当任何一组的死亡率接近 50%时,组间 10% 的差异就更难被可靠地检测到。在任何一组死亡率为 50%的最坏情况下,死亡率差异必须大于 22.5%,才能以 80% 的功率检测出来。我们提供了一个R闪亮应用程序,用于评估其他比较的功率:我们的研究结果表明,使用世卫组织试管测定法检测协同作用比世卫组织现行指南假设的要困难得多。此外,我们还展示了使用 Shiny 应用程序的价值,该应用程序可随时向最终用户提供基于模拟的功率分析输出结果,使他们能够确定检测特定死亡率差异所需的试管数量。
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来源期刊
Gates Open Research
Gates Open Research Immunology and Microbiology-Immunology and Microbiology (miscellaneous)
CiteScore
3.60
自引率
0.00%
发文量
90
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