**11. Operational challenges of insecticide resistance management**

effectively than using a single class of insecticide [175, 176]. Temporal rotation over time of two, or preferably more, insecticide classes with different modes of action applied in an alternating sequence is also based on the assumption that an individual mosquito does not carry two resistant alleles [177]. Rotations are particularly effective if the resistance gene has an associated fitness cost [87] and assumes that if resistance to each insecticide is rare, then multiple resistances will be extremely rare [178]. The "mosaic" approach refers to applications of different compounds against the same insect in spatially segregated locations [55] and aim to preserve susceptibility by spatial restriction of insecticides [7]. Larger scale mosaics have been shown to be effective for the management of pyrethroid resistance in *An. albimanus* in Mexico [143, 179]. An alternative is simultaneous utilisation of a mixture of two or more insecticides of unrelated mode of action, the aim being that resistance will evolve more slowly to both insecticides than if either had been used on its own [180]. Unlike rotations, the effectiveness of mixtures is not directly related to the degree of fitness cost. Mixtures of insecticides require the expected frequency of resistant alleles at two different genetic loci to be low and that individual mosquitoes carrying both alleles are rare [181]. The other approach is through combinations of two vector control tools, such that a mosquito that survives contact with one (e.g., LLIN) is exposed to the other one (e.g., IRS) [182]. The success of combinations in effectively managing resistance depends on the ability to kill the vector despite the existence of resistance by using another intervention or insecticide [183]. However, caution should be exercised not to increase selection pressure by combining insecticides with same mode of

Ideally, insecticide resistance management should be undertaken using insecticide-based approaches in conjunction with other non-insecticidal vector control methods, in the context of IVM [3]. However, resistance surveillance is a fundamental step and insecticide suscepti‐ bility an indispensable resource of resistance management; it provides baseline data for program planning and insecticide selection before the commencement of control operations, facilitates detection of resistance at an early stage so that timely management can be imple‐ mented, and enables continuous monitoring of the effect of control strategies on resistance. Establishing international, multi-disciplinary technical working groups with a clear reporting system and defined responsibilities to facilitate data collation and rational policy transforma‐ tion is critical for optimal IRM strategies. This would require the presence of a multiplicity of partners with vested interest in insecticide resistance, demand close collaboration and sustained coordination of local and external technical experts, and require good stewardship for them to succeed. Availability of entomological resources provides an ideal opportunity to develop a rational IRM plan underpinned by entomological and epidemiological baseline data to facilitate tracking of spatial and temporal resistance profiles of malaria vectors and evalu‐ ating its impact on the efficacy of control interventions. There remains a paucity of evidence on the utility of conventional resistance management strategies (e.g., insecticide rotations, mosaics, mixtures, and combinations) in restoring the susceptibility of malaria vectors. There is also a need for well-designed assessments of the operational impact of combinations of insecticidal and non-insecticidal interventions, including larval source management ap‐

action (e.g., avoid pyrethroids for both IRS and LLINs) [86].

proaches [87].

168 Insecticides Resistance

The WHO has developed the GPIRM to help member states mitigate the development and spread of resistance [7]. However, countries continue to experience substantial constraints for effective deployment. First, there is limited country-level technical resource capacity to support entomological intervention monitoring and evaluation, minimal essential physical infrastructure and logistical resources to support implementation of the plan, including insufficient qualified vector control workforce. Second, gaps in availability of reliable routine monitoring data on vector bionomics, spatial distribution, insecticide resistance, underlying resistance mechanisms, including operational cost of insecticide resistance from epidemiolog‐ ically representative sites, makes decision-making on resistance management difficult. Third, deficiency in local financial support and sustainability that is threatened by donor dependency. Fourth, timely scale up has been constrained by paucity in coordinating in-country entomo‐ logical resources, coupled with scepticism surrounding scientific findings by some key national and international implementing and funding organisations. Fifth, skilled interna‐ tional technical assistance is a scarce resource that is overstretched. Sixth, there is limited data on malaria transmission and its correlation to epidemiological indices to guide the targeting of tools and monitoring of their impact. Seventh, poor data quality, management, and willingness to share data by different partners is usually nominal and remain a challenge to documenting insecticide resistance. Generally, there are limited resources and both human and institutional capacity to fill these gaps. However, the potential of IVM provides a window of opportunity that could be exploited for enhanced IRM activities.

Eight countries, Equatorial Guinea, Eritrea, Mozambique, Namibia, Rwanda, South Africa, United Republic of Tanzania, and Zambia, currently have plans of implementing the GPIRM, representing less than 10% of countries that need them. These plans are mainly reactive rather than proactive. Two examples of countries with well-developed plans are Bioko, Equatorial Guinea and Zambia [184]. Despite having good plans, the operational implementation of these plans remains challenging. In Bioko, large-scale LLIN distribution and island-wide pyreth‐ roid-based IRS were conducted before a switch to bendiocarb IRS for eight years, after the detection of kdr-based pyrethroid resistance. Despite kdr, there is evidence that pyrethroids remain operationally effective. Therefore a bendiocarb-deltamethrin annual rotation has been implemented. Pirimiphos-methyl remains a reserve option should this rotation fail, but was considered too expensive to include initially despite the greater treatment longevity. In Zambia, two major vectors (*Anopheles funestus* and *An. gambiae* sensus stricto) are resistant to carbamates and pyrethroids and pyrethroids alone, respectively. A mosaic pattern of insecti‐ cide use, driven by the prevalence of the different vectors has therefore been implemented. However, due to the increased cost, coverage has been reduced in a format that may adversely impact disease transmission. Widespread pyrethroid resistance is now a major problem. Getting new active ingredients to market quickly is imperative; large-scale randomised control trials over many years to document efficacy may be unrealistic given the urgency [184].
