**4. Insecticides and malaria vector control**

scarcity of requisite skills, and minimal or lack of collaboration between health and other relevant sectors to effectively monitor and manage it [3]. Evidence of insecticide resistance operationally undermining malaria vector control is mounting and is resulting in policy changes [5]. Monitoring and management of resistant disease vectors is essential to limit the selection and spread of insecticide resistance and to maintain the effectiveness of vector control [6]. Nevertheless, substantial challenges for implementation exist at country level. Thus, countries are encouraged to implement pre-emptive insecticide resistance management (IRM) strategies against malaria vectors according to the Global Plan for IRM (GPIRM) [7]. While IVM and IRM are the recommended approaches for combating vector-borne diseases and preventing the spread of resistance respectively, operational experience for both strategies is limited to relatively few countries. However, IVM provides a potential platform that could be exploited for enhanced national strategic IRM planning and deployment. This chapter reviews the distribution, mechanisms, and resistance management strategies in malaria vectors including the challenges experienced in operational settings. A framework of policies and strategies to facilitate the implementation of the GPIRM using the IVM platform is also presented and accentuates coordinated response among stakeholders and political commit‐

ment for effective policy execution within the context of national health systems.

management (IVM), resistance patterns, and the impact in malaria vectors.

Mosquitoes belong to the family Culicidae in the order Diptera, class Insecta, phylum Arthropoda [12]. Culicidae is divided into three subfamilies Anophelinae, Culicinae, and

**3. Classification and distribution of malaria vectors**

Information sources for this review included all available data and accessible archived documentary records on malaria vectors and insecticide resistance. Structured literature searches of published, peer-reviewed sources using online scientific bibliographic databases were utilised to gather pertinent data. This was conducted via systematic literature search of Library catalogues and online electronic databases, particularly PubMed [8], the WHO Library Database [9], Google Scholar [10], the African Journals Online, the Armed Forces Pest Man‐ agement Board [11], and the research for life databases (AGORA, ARDi, HINARI, and OARE) were used to search for relevant literature. All digital electronic database searches for peerreviewed, published work used a combination of key search terms: 1) *Anopheles* malaria vectors complex and one of the following terms; 2) insecticide resistance; 3) resistance mechanisms; 4) resistance management; 5) impact of resistance; 6) malaria vector control; and 7) malaria epidemiology. Reference sections of all relevant articles were also reviewed to identify more literature. Additional non-peer reviewed literature were examined for information related to the subject. Articles that report biochemical and molecular tools for resistance monitoring were also retrieved. The inclusion criteria considered all manuscripts and publications in English language that report on selection of insecticide resistance in malaria vectors, causes and mechanisms of resistance, vector resistance and the epidemiology of malaria, integrated vector

**2. Literature search strategy**

156 Insecticides Resistance

The classes of insecticides most commonly used for contemporary malaria vector control include organochlorines, organophosphorus, carbamates, and pyrethroids [24]. The first synthetic organochlorine insecticide to be commercialised, DDT (dichlorodiphenyltrichloro‐ ethane), was central to the World Health Organisation (WHO)-led global malaria eradication campaign (1955–1969) [25]. Except in sub-Saharan Africa, this resulted in the elimination of the disease in North America, Europe, and parts of Asia [26]. While agricultural use of DDT has now ceased due to environmental persistence and reduced efficacy against resistant insects, extensive use for malaria control continues as a cost-effective and safe insecticide for indoor residual spraying (IRS). More recently, pyrethroids have been widely used for malaria control. They are the only class of insecticides recommended by the WHO for impregnation of long-lasting insecticidal bed nets (LLINs) [24] and are also available for IRS. Pyrethroids, such as permethrin and deltamethrin, and the pseudo-pyrethroid etofenprox, including DDT and its analogues, share a similar mode of action of targeting the sodium channels of the nerve membranes. Carbamates, such as bendiocarb, share the same mode of action as organophos‐ phates, such as pirimiphos methyl, malathion, and temephos, binding to acetylcholinesterase at the nerve junction [27]. Chlorfenapyr has a different mode of action involving disruption of oxidative phosphorylation and consequently the disruption of the conversion of ADP to ATP in mitochondria [28]. Although insecticides from different chemical classes are available as larvicides (e.g., temephos), the arsenal of insecticides recommended for IRS is limited to four classes only [29]. The selection of DDT resistance in malaria vectors resulted in the declining political and financial support for the Global Malaria Eradication Campaign launched by the WHO [30].

Vector control, personal protection, and community participation are the pillars of WHO strategies for insect-transmitted disease control. IVM has been advocated for as a recommend‐ ed approach for combating vector-borne diseases in the past decade [31]. IVM is defined as "a rational decision-making process for optimal use of resources for vector control". The objective of vector control is to reduce and/or interrupt transmission of malaria by preventing human contact with malaria-bearing mosquitoes, eliminating breeding sites, killing the mosquito larvae, or reducing the longevity of adult mosquitoes [30]. The use of IRS and LLINs are the mainstream contemporary malaria vector control interventions [32, 33]. The efficacy of these two methods has been evaluated in different epidemiological settings [34] at experimental field trial [35, 36] and community-wide levels [37, 38]. In reducing abundance and infectivity of malaria vectors, these tools reduce overall transmission and protect all individuals within a community [35], albeit with variation in responsiveness amongst vector populations. Present‐ ly, there is mounting evidence that combining IRS and insecticide treated nets (ITNs) affords enhanced protection to exposed populations compared to using one method alone [39]. As such, deployment of these interventions together in high malaria risk areas has been advocated [35, 40, 41]. Although these two interventions have been critical in providing community protection, the optimal policy for their co-implementation still remains to be determined. Moreover, the growing resistance of malaria vectors to available insecticides is a major cause for concern and an increasing threat to such essential and effective interventions [24, 42, 43].

In light of the inherent heterogeneity in the responsiveness of malaria vectors to control, the core interventions can be supplemented in specific locations by larval source management (LSM) strategies (e.g., larviciding, biological control, and environmental management) in the context of IVM [44, 45]. Larvivorous fishes or bacterial pathogens such as *Bacillus thuringien‐ sis israelensis* and *Bacillus sphaericus* are examples of biological agents that are used to kill larvae [46]. Temephos is the commonly used chemical larvicide. The environmental meth‐ ods to prevent malaria include elimination of breeding sites by drainage or by applying locally grown plants. With the selection of resistance, new insecticides, and novel ap‐ proaches to vector control must be developed. Effective and sustained malaria vector control requires clear commitment from national authorities, including long-term support from funding partners [47]. Several malaria control programmes have fragmentary empirical evidence to inform policy formulation for rational vector control. For this reason, malaria control programmes are encouraged to adopt the WHO-led IVM strategy [48], which should be an evidence-based decision making process that requires coherent monitoring and evaluation component [49]. This should include routine surveillance of resistance profiles of major malaria vectors and potential resistance mechanisms to facilitate informed decisions and policy changes, such as the incorporation of insecticide resistance management opera‐ tions into control programmes [29].
