Fight against malaria: investigating the impact of physical and insecticidal durability on epidemiological outcomes, as well as assessing community acceptability of, and preferences for dual-active ingredient long-lasting insecticidal nets in Tanzania

Since 2017, there has been a considerable scale-up of dual-active ingredient Long-Lasting Insecticidal Nets (LLINs) [dual-AI ITNs], gradually replacing the standard of care (pyrethroid-only LLINs) for the prevention of malaria transmitted by pyrethroid-resistant malaria vectors in Africa. As with other LLINs, dual-AI ITNs are likely to face challenges with their physical and insecticidal durability, which in turn, impacts net coverage and usage over time, ultimately affecting malaria control efforts. This thesis investigates the impact of physical and insecticidal durability on epidemiological outcomes, as well as assessing community acceptability of, and preferences for the dual AI LLINs namely: Royal Guard [containing pyriproxyfen and alpha(α)-cypermethrin], Interceptor G2 [chlorfenapyr and α-cypermethrin], and Olyset Plus [piperonyl-butoxide (PBO) and permethrin]. Data from two cluster-randomised controlled trials (RCTs) conducted in the rural districts of Muleba and Misungwi, Tanzania were used to assess the physical durability of dual-AI ITNs, the impact of LLIN damage on malaria infection, and perceptions of dual-AI LLIN compared to standard LLINs (pyrethroid-only nets) over the recommended lifespan of the net. Eleven cross-sectional surveys (six in Muleba & five in Misungwi) of 26,816 children aged 0.5-14 years (N=4,337 in Muleba & N=22,479 in Misungwi) from 14,433 households (N=1,779 in Muleba & N=12,654 in Misungwi) took place between January 2015 and February 2022. A total of 36 focus group discussions (FGDs) (N=17 in Muleba & N=19 in Misungwi) and 44 In-depth Interviews (N=14 in Muleba & N=30 in Misungwi) were conducted as part of qualitative data collection. The data showed that: • There was an association between fabric condition and malaria case incidence- though this differed by net type. For instance, in Olyset Plus and Interceptor G2 in poor condition, malaria incidence was lower than for intact/good pyrethroid-only LLINs during the first year after their distribution. However, this association was not present in the second year after their distribution, suggesting that the effectiveness of the dual-AI ITNs decreased with waning insecticide concentrations on nets over time. • The net attrition rate was very high in both trials with approximately 83% of the LLINs lost after 3 years, with a functional survival time far below the expected 3 years for all net types (1.6-1.9 years). Insecticidal content declined rapidly with only 3% of PBO and 45% of permethrin in Olyset Plus; 8% of chlorfenapyr and 28% of alpha- cypermethrin in Interceptor G2; and 27.8% of pyriproxyfen and 62% of alpha-cypermethrin remaining in the LLINs after 3 years. • Community-wide protection (benefits to others in the community not using nets) was found when community net use was above 40% across dual-AI study arms. Lower malaria risk was also observed in non-users living in villages with low usage of Interceptor G2 compared to high coverage of pyrethroid-only nets. • In both trials, LLIN effectiveness and perceived physical characteristics (fabric durability, fibers, texture) influenced opinions towards LLIN. The communities preferred polyester nets to polyethylene nets. Polyethylene LLINs were more prone to misuse than polyester nets, with higher misuse in Misungwi compared to Muleba. It was found that users of LLINs are much better protected than non-users regardless of net age, physical condition, or type. However, for better protection and upon the availability of resources, dual-AI ITNs should be considered as they provide superior protection to standard LLINs, even at low usage levels (Interceptor G2) or when they are torn (Interceptor G2 and Olyset Plus). For the sustainability of malaria control reliant on dual-AI ITNs, should be made more durable than the current ones which do not last for 3 years. Blue, rectangular, and pol- yester LLINs are preferred by the communities. While pilot studies to assess preferences before mass distribution could optimize outcomes, practical limitations in procurement timelines and availability of net types may make such studies infeasible for each campaign. Instead, integrating periodic evaluations of preferences within broader malaria control efforts may provide an actionable alternative. Despite challenges, findings suggest that dual-AI ITNs provide superior protection and are generally well-accepted. Recommendations for improving durability and aligning community preferences with net design are critical for sustaining malaria control efforts.