**9. Resistance and vector control**

Insecticide resistance has been perceived to have the potential to undermine efforts to control vector-borne diseases including malaria [151, 152]. However, the impact of resistance on the ability of malaria control intervention to reduce disease transmission is poorly understood [153]. Insecticide resistance triggers a chain reaction that through deteriorated efficacy leads to vector control failure and disease control failure may be expected [153]. Evidence linking the potential of ITNs increasing phenotypic resistance and kdr frequency [154, 155] that threaten to compromise their effectiveness exists [86]. However, whether these various forms of resistance have an impact on the effectiveness of ITNs in malaria control remains a topic of debate among policy makers and researchers [60]. Conclusive evidence of insecticide resist‐ ance impacting on the efficacy of vector control interventions in decreasing disease transmis‐ sion is by large still absent. However, minimal evidence of an effect of resistance on entomological indicators having an impact on disease transmission exist [60]. The number of studies aimed at evaluating the operational significance of insecticide resistance on epidemio‐ logical outcomes of malaria remains nominal. This could be ascribed to multiple confounding factors capable of complicating the interpretation of data. The most available evidence is laboratory or experimental huts-based and harnessing entomological outcomes to assess the impact resistance on mosquito biting rates, blood feeding rates, or insect mortality [153]. Conflicting findings on the impact of resistance on vectorial capacity has been reported with some results indicating an increasing effect [156–160] while others present decreasing out‐ comes [159, 160].

Mostly, the impact of pyrethroid resistance is not clearly observable in entomological and epidemiological terms. For instance, in areas with detected kdr resistance the distribution of LLINs has been shown to successfully reduce malaria transmission [161]. Insecticide resistance has only been directly implicated in operational control failure of pyrethroids in *An. funestus* in South Africa [162]. In 1996, pyrethroid resistance compromised malaria control in KwaZulu Natal following a switch of IRS insecticides from using DDT to deltamethrin [163]. The reintroduction of IRS with DDT controlled the pyrethroid resistant *An. funestus* population and malaria cases dropped by 91% [164]. In Bioko Island, IRS with pyrethroid had no impact on kdr-mediated resistant *An. gambiae* population, but had significant impact on transmission index and malaria cases [39, 42]. After switching to IRS with a carbamate, the mosquito population declined [42]. In Burundi, programmatic IRS with pyrethroids and ITNs markedly reduced Anopheles density by 82% and transmission intensity by 90% and occurrence of clinical episodes by 43% in children despite high kdr frequencies in *An. gambiae* s.s. [40, 165]. In Côte d'Ivoire, ITN-randomised controlled trials demonstrated a significant reduction on the entomological inoculation rate (55%) [166] and on malaria incidence in children <5 (56%) [167] despite the presence of kdr-based pyrethroid resistance.

The current information gathered across Africa indicates that there is rapid loss of efficacy of most pyrethroids against malarial vectors [109, 168]. In Malawi, pyrethroid resistance did not trigger an operationally significant epidemiological impact on malaria parasite prevalence in children [114]. To compromise insecticide vector control, the level of resistance must be high enough to adversely affect disease transmission [169]. Despite the observed decline of vector abundance after the use of the pyrethroid derivatives [170, 171], the reported loss of efficacy of these widely used insecticides should be taken as a major threat for potential resurgence of malarial transmission in areas where gains have already been achieved against malaria vectors [172]. In many cases, vector control may not be affected by the level of resistance but enhanced surveillance and monitoring would be required [56]. This has refocused attention on the production of chemicals that are efficient and cost-effective [161]. The impact of resistance on the ability of the vector to transmit malaria is underexplored due to the scanty published literature available. However, most studies use kdr alleles frequency as a proxy for resistance due to the lack of molecular markers for alternative resistance mechanisms. This can be misleading if metabolic or other resistance mechanisms are the predominant drivers of the phenomenon. There is a need for additional attention to investigate on evolution and devel‐ opment of resistance to insecticides by disease vectors and consequently the epidemiological impacts of malaria and other vector-borne diseases [153].
