Bio-efficacy of field aged novel class of long-lasting insecticidal nets, against pyrethroid-resistant malaria vectors in Tanzania: A series of experimental hut trials

New classes of long-lasting insecticidal nets (LLINs) incorporating two insecticides, or an insecticide and a synergist, are recommended by the World Health Organization (WHO) to prevent malaria transmitted by mosquito vectors resistant to pyrethroid and other common insecticide classes. This study was nested in a large-scale cluster-randomized controlled trial conducted in Tanzania. A series of experimental hut trials (EHTs) aimed to evaluate the bio-efficacy of trial LLINs on the mosquito indicators most pertinent to malaria transmission over 3 years of use in the community. The aim was to evaluate nets subjected to a broader range of household factors than WHO standardized washing. The following field collected LLINs were assessed: 1/OlysetTM Plus (combining piperonyl butoxide synergist and permethrin), 2/Interceptor® G2 (chlorfenapyr and alpha-cypermethrin), 3/Royal Guard® (pyriproxyfen and alpha-cypermethrin), 4/Interceptor® (alpha-cypermethrin only), 5/a new Interceptor®, and 6/an untreated net. Thirty nets of each type were withdrawn from the community at 12, 24 and 36 months after distribution and used for the EHTs. Pre-specified outcomes were 72-hour mortality for Interceptor® G2, 24-hour mortality for OlysetTM Plus, and fertility based on egg development stage for Royal Guard®. Overall; Interceptor® G2 LLINs induced higher 72-hour mortality compared to standard LLINs of the same age up to 12 months (44% vs 21%), OR: 3.5, 95% CI: 1.9 – 6.6, p-value < 0.001 and 24-hour mortality was only significantly higher in OlysetTM Plus when new (OR: 13.6, 95%CI: 4.4 – 41.3, p-value < 0.001) compared to standard LLINs but not at 12 months (17% vs 13%; OR: 2.1, 95% CI: 1.0 – 4.3; p-value = 0.112). A small non-significant effect of pyriproxyfen on Anopheles fertility was observed for Royal Guard® up to 12 months (75% vs 98%, OR: 1.1, 95% CI: 0.0 – 24.9, p-value = 0.951). There was no evidence of a difference in the main outcomes for any of the new class of LLINs at 24 and 36 months compared to standard LLINs. Interceptor® G2 LLINs showed superior bio-efficacy compared to standard LLINs for only up to 12 months and the effect of OlysetTM Plus was observed when new for all species and 12 months for An. gambiae s.l. only. The pyriproxyfen component of Royal Guard® had a short and limited effect on fertility ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This study was funded by the Department of Health and Social Care, the Department for International Development, the Medical Research Council and Wellcome. Bill and Melinda Gate foundation through IVCC. The funder has no any role in this study. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study has received ethical approval from the Medical Research Coordinating Committee (MRCC) of the National Institute for Medical Research (NIMR), Kilimanjaro Christian Medical University College (KCMUCO), and the London School of Hygiene and Tropical Medicine (LSHTM) (LSHTM Ethics Ref: 16524). The study use animals (guinea pigs) with animal ethical approval reference: 2019-14 obtained from LSHTM AWERB for National Institute for Medical Research Mwanza centre. This study was conducted according to the Declaration of Helsinki and the International Guidelines for Ethical Review of Epidemiological Studies. Although there is minimum impact of these nets to volunteers, safety was monitored by trial investigators; any adverse events were reported and severity was monitored by clinician. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data will be available upon publication. All data for this study are store in data repository and the access will be given for the particular dataset. Currently, there is still additional data analysis ongoing, and we are unable to share the data at the time of the review but data will be made available at the end of the project in the LSHTM repository.