LLIN evaluation in Uganda project (LLINEUP): The fabric integrity, chemical content and bioefficacy of long-lasting insecticidal nets treated with and without piperonyl butoxide across two years of operational use in Uganda

Frank Mechan; Agaba Katureebe; Violet Tuhaise; Martin Mugote; Ambrose Oruni; Ismail Onyige; Kawesa Bumali; Jonathan Thornton; Kilama Maxwell; Mary Kyohere; Moses R Kamya; Peter Mutungi; Simon P Kigozi; Adoke Yeka; Jimmy Opigo; Catherine Maiteki-Sebuguzi; Samuel Gonahasa; Janet Hemingway; Grant Dorsey; Lisa J Reimer; Sarah G Staedke; Martin J Donnelly; Amy Lynd

doi:10.1016/j.crpvbd.2022.100092

LLIN evaluation in Uganda project (LLINEUP): The fabric integrity, chemical content and bioefficacy of long-lasting insecticidal nets treated with and without piperonyl butoxide across two years of operational use in Uganda

Curr Res Parasitol Vector Borne Dis. 2022 May 25:2:100092. doi: 10.1016/j.crpvbd.2022.100092. eCollection 2022.

Authors

Frank Mechan¹, Agaba Katureebe², Violet Tuhaise², Martin Mugote², Ambrose Oruni¹, Ismail Onyige², Kawesa Bumali², Jonathan Thornton¹, Kilama Maxwell³, Mary Kyohere³, Moses R Kamya^{2

4}, Peter Mutungi², Simon P Kigozi², Adoke Yeka², Jimmy Opigo⁵, Catherine Maiteki-Sebuguzi², Samuel Gonahasa², Janet Hemingway¹, Grant Dorsey⁶, Lisa J Reimer¹, Sarah G Staedke^{2

7}, Martin J Donnelly¹, Amy Lynd¹

Affiliations

¹ Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK.
² Infectious Diseases Research Collaboration, Uganda.
³ Department of Medicine, Makerere University, Kampala, Uganda.
⁴ Makerere University - Johns Hopkins University (MUJHU) Research Collaboration, Kampala, Uganda.
⁵ National Malaria Control Division, Ministry of Health, Kampala, Uganda.
⁶ Department of Medicine, University of California, San Francisco, USA.
⁷ Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.

Abstract

Long-lasting insecticidal nets (LLINs) supplemented with the synergist piperonyl butoxide have been developed in response to growing pyrethroid resistance; however, their durability in the field remains poorly described. A pragmatic cluster-randomised trial was embedded into Uganda's 2017-2018 LLIN distribution to compare the durability of LLINs with and without PBO. A total of 104 clusters (health sub-districts) were included with each receiving one of four LLIN products, two with pyrethroid + PBO (Olyset Plus and PermaNet 3.0) and two pyrethroid-only (Olyset Net and PermaNet 2.0). Nets were sampled at baseline, 12 and 25 months post-distribution to assess physical condition, chemical content, and bioefficacy. Physical condition was quantified using proportionate Hole Index and chemical content measured using high-performance liquid chromatography. Bioefficacy was assessed with three-minute World Health Organisation (WHO) Cone and Wireball assays using pyrethroid-resistant Anopheles gambiae, with 1-h knockdown and 24-h mortality recorded. There was no difference in physical durability between LLIN products assessed (P = 0.644). The pyrethroid content of all products remained relatively stable across time-points but PBO content declined by 55% (P < 0.001) and 58% (P < 0.001) for Olyset Plus and PermaNet 3.0 respectively. Both PBO LLINs were highly effective against pyrethroid-resistant mosquitoes when new, knocking down all mosquitoes. However, bioefficacy declined over time with Olyset Plus knocking down 45.72% (95% CI: 22.84-68.62%, P = 0.021) and Permanent 3.0 knocking down 78.57% (95% CI: 63.57-93.58%, P < 0.001) after 25 months. Here we demonstrate that both Olyset Plus and PermaNet 3.0 are as durable as their pyrethroid-only equivalents and had superior bioefficacy against pyrethroid-resistant An. gambiae. However, the superiority of PBO-LLINs decreased with operational use, correlating with a reduction in total PBO content. This decline in bioefficacy after just two years is concerning and there is an urgent need to assess the durability of PBO LLINs in other settings.

Keywords: Bioefficacy; Durability; Insecticide; LLIN; Malaria; Piperonyl butoxide.