A Non-Inferiority Evaluation of YAHE 4.0, an Alphacypermethrin-PBO Insecticide-Treated Net Against Pyrethroid Resistant Anopheles arabiensis in Experimental Huts in Moshi, North-Eastern Tanzania

A new generation of insecticide-treated nets (ITNs) that incorporate the synergist piperonyl butoxide (PBO) has been shown to restore susceptibility to pyrethroids where P450 enzymes are the primary mechanism conferring the resistance. The present study evaluated the efficacy of YAHE 4.0, a PBO ITN, against wild free-flying Anopheles arabiensis in experimental huts in Lower Moshi, north-eastern Tanzania. It is the first evaluation of YAHE 4.0 in the country. Bio-efficacy evaluations, including susceptibility tests and cone bioassays, were conducted using the standard WHO guidelines. DuraNet Plus, a WHO-recommended PBO ITN, and Interceptor ITNs served as active and standard comparators, respectively. Unwashed and 20 times washed nets were subjected to experimental hut trials. Multiple logistic regression was employed to analyse experimental hut trial data. The results of the susceptibility testing showed that the An. arabiensis population of Lower Moshi was resistant to pyrethroids, but susceptible to organophosphates. Particularly, low mortality was recorded for cyhalothrin (2%) and alpha-cypermethrin (38%). Mortality rates to alpha-cypermethrin pirimiphos-methyl were 38% and 100%, respectively. The non-inferiority of YAHE 4.0 to DuraNet Plus ITN in terms of mortality and blood feeding was determined according to the WHO guidelines. The results for pooled unwashed and 20 times washed ITNs showed that YAHE 4.0 was superior to Interceptor ITN (adjusted odds ratio, AOR = 1.33; 95% CI = 1.04–1.69; non-inferiority margin, NIM = 0.68; p-value = 0.023) and non-inferior to DuraNet Plus (AOR = 1.02; 95% CI = 0.78–1.35; NIM = 0.72; p-value = 0.867) in terms of mortality. In terms of blood feeding inhibition for pooled unwashed and 20× washed ITNs, YAHE 4.0 was superior to both Interceptor ITN (AOR = 0.80; 95% CI = 0.64–1.00; NIM = 1.35; p-value = 0.049) and DuraNet Plus (AOR = 0.67; 95% CI = 0.52–0.86; NIM = 1.33; p-value = 0.002). Chemical analysis showed higher wash retention of active ingredients in YAHE 4.0 LLIN (88.9% for PBO and 94.9% for alpha-cypermethrin) compared to DuraNet Plus LLIN (89.2% for PBO and 90.5% for alphaypermethrin) before the hut trial. YAHE 4.0 LLIN demonstrated superior entomological efficacy and wash durability to DuraNet Plus and Interceptor LLINs, and fulfilled WHO non-inferiority criteria for mosquito mortality and blood-feeding inhibition. Therefore, YAHE 4.0 LLIN should be considered as an addition to the current list of pyrethroid-PBO nets used for control of pyrethroid-resistant vector populations with P450 enzymes as the main mechanism conferring resistance.