Vector Control Product Testing Unit (VCPTU) Ifakara Health Institute, Environmental Health, and Ecological Sciences, P.O. Box 74, Bagamoyo, Tanzania.
Vector Biology Unit, Department of Epidemiology and Public Health, Swiss Tropical & Public Health Institute, Kreuzstrasse 2, 4123, Allschwill, Basel, Switzerland.
Malar J. 2024 Oct 16;23(1):309. doi: 10.1186/s12936-024-05130-7.
Non-inferiority trials are recommended by the World Health Organization (WHO) to demonstrate that health products show comparable efficacy to that of existing standard of care. As part of the WHO Global Malaria Programme (GMP) process of assessment of malaria vector control products, a second-in-class insecticide-treated net (ITN) must be shown to be non-inferior to a first-in-class product based on mosquito mortality. The public health impact of the first-in-class pyrethroid-piperonyl butoxide (PBO) ITN, Olyset Plus, has been demonstrated in epidemiological trials in areas with insecticide-resistant mosquitoes, but there is a need to determine the efficacy of other pyrethroid-PBO nets to ensure timely market availability of nets in order to increase access to ITNs. The non-inferiority of a deltamethrin-PBO ITN Yorkool G3 was evaluated entomologically against Olyset Plus in experimental huts in Tanzania, following WHO guidelines for non-inferiority trials.
The trial of the two pyrethroid-PBO ITNs was conducted in experimental huts in Lupiro, Tanzania, using a randomized 7 × 7 Latin square block design. The study ran for 49 nights in 14 huts assessing the mosquito mortality and blood-feeding of wild, free-flying, pyrethroid-resistant Anopheles arabiensis. Using the non-inferiority approach, the comparative efficacy (primary endpoint was mosquito mortality at 24 h and secondary endpoint was blood-feeding) of unwashed and 20 times field-washed pyrethroid-PBO Yorkool G3 ITNs, were compared with the first-in-class product Olyset Plus and against a pyrethroid-only ITN, PermaNet 2.0 ITNs, as a standard comparator.
The experimental hut trial demonstrated non-inferiority and superiority of Yorkool G3 to Olyset Plus based on mosquito mortality [51% vs. 39%, OR 1.68 (95% CI 1.50-1.88)], given that lower 95% CI exceeded 0.74 (delta of 39%) and the margin of no difference (1). Blood-feeding inhibition was high for all treated ITNs (> 90%) and Yorkool® G3 was non-inferior to Olyset® Plus [4% vs. 2%, OR 1.81 (95% CI 1.46-2.39)], given that upper 95% CI was less than 4.85 (delta of 4%). The pyrethroid-PBO ITNs were superior to the pyrethroid-only net, PermaNet 2.0, as determined by both the proportion of mortality and blood-feeding of mosquitoes (p-value < 0.05).
Yorkool G3 ITNs demonstrated non-inferiority to the first-in-class Olyset® Plus and superiority over the standard pyrethroid-only ITN, PermaNet 2.0 as measured by mortality and blood-feeding inhibition of wild pyrethroid-resistant An. arabiensis mosquitoes. Yorkool G3 ITNs are potential tools for the control of metabolic insecticide-resistant malaria vectors, and their market availability will contribute to the cost-effective selection of ITNs by malaria control programmes to improve population access to ITNs.
世界卫生组织（WHO）建议进行非劣效性试验，以证明卫生产品与现有标准护理具有相当的疗效。作为世界卫生组织全球疟疾规划（GMP）评估疟疾媒介控制产品过程的一部分，必须证明第二类杀虫剂处理蚊帐（ITN）在基于蚊虫死亡率方面不劣于第一类产品。第一类拟除虫菊酯-胡椒基丁醚（PBO）ITN，Olyset Plus 的公共卫生影响已在具有抗杀虫剂蚊子的流行病学试验中得到证实，但需要确定其他拟除虫菊酯-PBO 网的功效，以确保及时提供市场上的蚊帐，以增加对 ITN 的获取。根据世界卫生组织非劣效性试验指南，在坦桑尼亚卢皮罗的实验小屋里，对一种氯菊酯-PBO ITN Yorkool G3 进行了与 Olyset Plus 的昆虫学非劣效性评估。
在坦桑尼亚 Lupiro 的实验小屋里，使用随机 7×7 拉丁方设计进行了两种拟除虫菊酯-PBO ITN 的试验。该研究在 14 个小屋里进行了 49 个夜晚的研究，评估了野生、自由飞行、对拟除虫菊酯具有抗药性的疟蚊的死亡率和血液摄入。使用非劣效性方法，对未清洗和经过 20 次田间清洗的拟除虫菊酯-PBO Yorkool G3 ITN 的比较疗效（主要终点为 24 小时的蚊虫死亡率，次要终点为血液摄入）与第一类产品 Olyset Plus 进行了比较，并与仅含拟除虫菊酯的 PermaNet 2.0 ITN 进行了比较，作为标准对照。
实验小屋里的试验表明，Yorkool G3 在蚊虫死亡率方面具有非劣效性和优于 Olyset Plus 的优势[51%对 39%，OR 1.68（95%CI 1.50-1.88)]，因为较低的 95%CI 超过 0.74（39%的差值）和无差异的差距（1）。所有处理过的 ITN 的血液摄入抑制率都很高（>90%），并且 Yorkool® G3 与 Olyset® Plus 的非劣效性[4%对 2%，OR 1.81（95%CI 1.46-2.39)]，因为上 95%CI 小于 4.85（4%的差值）。拟除虫菊酯-PBO ITN 优于仅含拟除虫菊酯的网 PermaNet 2.0，这是由死亡率和蚊子血液摄入决定的（p 值<0.05）。
Yorkool G3 ITN 在野生抗拟除虫菊酯的疟蚊的死亡率和血液摄入抑制方面，与第一类 Olyset® Plus 相比具有非劣效性，与标准的仅含拟除虫菊酯的 ITN PermaNet 2.0 相比具有优势。Yorkool G3 ITN 是控制代谢性抗杀虫剂疟疾媒介的潜在工具，其市场供应将有助于疟疾控制规划以具有成本效益的方式选择 ITN，以提高人口对 ITN 的获取。
