The non-inferiority efficacy of Piperonyl-butoxide Yorkool® G3 Insecticide treated nets in the experimental huts in Tanzania

Abstract

Background Non-inferiority trials are recommended by the World Health Organization (WHO) to demonstrate that health products show comparable efficacy. 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 need to determine the efficacy of other pyrethroid-PBO nets to ensure timely market availability of nets and so 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. Method The trial of the two pyrethroid-PBO ITNs was conducted in experimental huts in Lupiro, Tanzania, using a randomised double-blind 7 x 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 resistant Anopheles arabiensis. Using the non-inferiority approach, the efficacy (mosquito mortality at 24 hours and 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. Results The experimental hut trial demonstrated the non-inferiority of Yorkool® G3 to Olyset® Plus based on mortality [51% vs 39%, respectively, OR 1.68 (95% CI: 1.50–1.88)], given that lower 95% CI exceeded 0.74 (delta of 39%). Blood feeding inhibition was high for all treated ITNs (> 90%). 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). Conclusion 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 insecticide resistant An. arabiensis mosquitoes. Yorkool® G3 ITNs are therefore potential tools for the control of metabolic insecticide resistant malaria vectors.