**2. New tools to fight malaria vectors in an IVM perspective**

To decrease the risk of vector-borne disease transmission and increase the effectiveness and sustainability of IVM in reducing mosquito populations, local features should be considered [29]. Therefore, guidelines were developed by the global vector control response (GVCR) including: (1) strengthening inter- and intra-sectoral action and collaboration; (2) enhance vector control surveillance and evaluation of interventions; (3) scale up and integrate tools and approaches; and (4) engage and mobilize communities. The goals of this initiative included increasing the effectiveness of reducing mosquito vectors for both capacity and capability as well as encouraging applied research and innovation [13].

The use of IVM aiming for optimum mosquito control contrasts with strategies used in the past that heavily relied on insecticide spraying. Current mosquito control strategies make use of every available tool. For that reason, regular assessments of local disease transmission dynamics and scientific-driven decision-making criteria are important for achieving effective vector-borne disease transmission reduction [27].

Several tools have been proposed to control vector mosquitoes, especially for the *Anopheles* genus [23, 30]. However, current malaria management programs widely rely on indoor residual spraying (IRS), and long-lasting insecticidal nets (LLINs) [5], contrasting with contemporary IVM guidelines. Moreover, residual transmission of malaria has been commonly found using both IRS and LLINs mosquito control strategies [31]. The presence of the insecticide can be translated as a powerful selective pressure, selecting mosquitoes that are able to avoid contact with it. Key shifts in mosquito behavior such as seeking for human hosts outdoors, avoiding contact with LLINs, and finding resting places outside houses decrease the effectiveness of long-lasting insecticidal strategies [32, 33]. The efficacy of LLINs and IRS can be increased if used together with new tools and guidelines available for controlling mosquito populations, as recommended by the Vector Control Advisory Group (VCAG). Some environments are also suited for using *Bacillus thuringiensis* serovar. *israelensis* (Bti) to manage breeding sites [34–38]. Moreover, promising new tools for mosquito control are being developed, the most notable being "eave tubes" and attractive toxic sugar baits (ATSB).

*Anopheles* (Diptera: Culicidae). There are five known species of *Plasmodium* that cause malaria in humans, *P. falciparum*, *P. vivax*, *P. ovale*, *P. malariae* and *P. knowlesi* [1–5]. Currently, 91 countries are endemic for malaria [6]. However, the African region is the most affected with 90% of the cases and 92% of deaths [7–9]. Added to that, malaria has a major impact on the economic development of these countries accounting for both direct and indirect medical costs, such as

In the past decade, two significant developments for malaria prevention and treatment were achieved. The first was the discovery of artemisinin, a very effective drug against *Plasmodium falciparum*; this molecule has been studied by the Chinese scientist Y. Tu [14–16]. The second was the development of the vaccine against *P. falciparum* (RTS,S/AS01), by GlaxoSmithKline Biologicals, the PATH Malaria Vaccine Initiative, supported by the Bill & Melinda Gates Foundation, and carried out at several African research centers [17, 18]. However, the vaccine

Importantly, new drugs and vaccines are needed to achieve further substantial decrease in the prevalence and incidence of malaria globally and address the increasingly resistance of *Plasmodium* to the drugs currently available such as chloroquine and artemisinin [20–22]. More importantly, effective and scientific-driven control strategies for reducing *Anopheles* vector densities remain the gold standard to prevent malaria transmission [23–25]. However, controlling mosquito populations is a difficult task and is unlikely to be achieved by employing only one tool, such as the use of insecticides commonly employed in the past [26, 27]. Now it is clear that local malaria elimination across different endemic environments will not be achieved with current vector control tools, but will require using several approaches together

To decrease the risk of vector-borne disease transmission and increase the effectiveness and sustainability of IVM in reducing mosquito populations, local features should be considered [29]. Therefore, guidelines were developed by the global vector control response (GVCR) including: (1) strengthening inter- and intra-sectoral action and collaboration; (2) enhance vector control surveillance and evaluation of interventions; (3) scale up and integrate tools and approaches; and (4) engage and mobilize communities. The goals of this initiative included increasing the effectiveness of reducing mosquito vectors for both capacity and capability as

The use of IVM aiming for optimum mosquito control contrasts with strategies used in the past that heavily relied on insecticide spraying. Current mosquito control strategies make use of every available tool. For that reason, regular assessments of local disease transmission dynamics and scientific-driven decision-making criteria are important for achieving effective

Several tools have been proposed to control vector mosquitoes, especially for the *Anopheles* genus [23, 30]. However, current malaria management programs widely rely on indoor

long-term disabilities and decrease in tourism [10–13].

388 Towards Malaria Elimination - A Leap Forward

only protected transiently the subjects against malaria [19].

in the form of integrated vector management (IVM) [28].

well as encouraging applied research and innovation [13].

vector-borne disease transmission reduction [27].

**2. New tools to fight malaria vectors in an IVM perspective**

Rural houses in African countries often are constructed with a gap between the walls and the roof to improve ventilation. *Anopheles* mosquitoes usually enter the houses exploiting this architectural structure exposing the residents to infective bites [39]. The "eave tubes" technology comprises the use of plastic tubes with adulticide-coated mesh under the roofline and the installation of a screen to close the remaining gap (**Figure 1**). When mosquitoes try to enter the house through the eaves, they come in contact with the insecticide and die. This technique is based on the attractive power that the human residents represent for the *Anopheles* mosquitoes comprising an "attract and kill" strategy (**Figure 2**) [40, 41]. The ATSB method is also found under the same strategy of "lure and kill"; it exploits the instinct of mosquitoes, both males and females to seek and feed on sugar sources [42, 43]. The ATBS can be deployed in bait stations or sprayed on plants and are co-formulated with low-risk toxic substances, such as boric acid [44–50]. Even though more studies and epidemiological field trials are required, "eaves tubes" and ATSB methods are leading new technologies for vector control that are highly effective, target-specific, and with minimal nontarget effects and contamination of the environment.

Several other modern strategies exploiting different approaches are being developed, including the use of cytoplasmic incompatibility caused by *Wolbachia* endosymbiotic bacteria. This

**Figure 1.** The "eave tubes" technology comprises the use of plastic tubes with adulticide-coated mesh under the roofline and the installation of a screen to close the remaining gap. (A) Graphic representation of a house without "eaves tubes" and (B) with "eaves tubes".

ovicidal and ovideterrent products are still scarce. This technology can provide rapid synthesis of toxic substances and mosquito repellents useful to manage mosquito populations, with minimal toxicity to humans. Even though mosquito control strategies relying on plant-based larvicides are a fast-growing research area, it is still in the preliminary phase of development and several steps should be taken into account, that is, (1) development, characterization, and optimization of potential botanical components suitable for nano-biosynthesis; (2) identification of potential toxic nanoparticles; (3) feasibility of utilization of plant-based industrial by-products as nano-mosquitocides; (4) field evaluation of the effectiveness of plant-based nanoparticles to control mosquito populations; and (5) effect of plant-based nanoparticles on

Newer Approaches for Malaria Vector Control and Challenges of Outdoor Transmission

http://dx.doi.org/10.5772/intechopen.75513

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Natural predators also have been used to control immature mosquitoes including cyclopoid copepods, *Toxorhynchites* mosquitoes, water bugs, backswimmers, tadpoles, and fishes [72–74]. The efficacy of mosquito predators may vary accordingly to different environmental settings and their impact on non-target aquatic species and difficulty in using multiple or artificial breeding containers should be considered for their use in control strategies [71, 75]. Another approach for controlling mosquitoes is based on endectocide ivermectin, a molecule that has been used for more than 30 years to control lymphatic filariasis. This molecule remains in the human bloodstream following a standard oral dose and can kill *Anopheles* mosquitoes that feed on the blood of medicated persons [76–79]. Controlling vector mosquito populations is a difficult task and so the addition of new technologies to be considered for IVM will help

Current strategies for malaria vector control used in most African countries still rely on LLINs and IRS, which generally are not sufficient to achieve successful malaria control and local elimination [13, 25, 84]. Even though LLINs and IRS are very effective for in-house reduction of malaria transmission, in endemic areas, it has been showed that insecticide-treated bed nets reduce malaria prevalence only by 13% [85–91]. Furthermore, due to the high abundance of mosquitoes, even low levels of *Plasmodium* transmission undermine efforts to reduce the prevalence of malaria, since human hosts are bitten multiple times increasing the chance of coming in contact with the parasite. The prevalence of *P. falciparum* is strongly related to the number of infective bites per person per year or annual entomological inoculation rates (EIRs), ranging from <1 to >500. Malaria prevalence is positively associated with high EIRs; however, even low annual EIRs (<5) can be associated with malaria prevalence levels of 40–60%. For a significant reduction in the prevalence of malaria, EIRs must be lower than 1 [92]. Vector control strategies implemented in Africa have so far been unable to achieve such low levels of

Besides, with the increase in the control efforts focused into indoor mosquitoes, the dynamics of malaria transmission is shifting from the highly endophilic to more exophilic outdoor-adapted species within the *Anopheles gambiae* complex [94–99]. In Asia, the main malaria vectors of the *Anopheles dirus* complex are exophagic and difficult to target with conventional control strategies [31]. Moreover, increasing resistance to insecticides renders LLINs and IRS less effective for controlling *Anopheles* populations. As well, even though larvicides are effective against immature mosquitoes, they are not recommended for application in rural areas [100–105].

improve the effectiveness of vector-borne disease transmission [80–83].

non-target species and environment [70, 71].

malaria transmission [93].

**Figure 2.** Attractive toxic sugar baits (ATSB) employing an "attract and kill" strategy. This technique consists of using natural attractants such as fruit or flower scent to lure mosquitoes to sugar feeding in a solution containing toxic substances that will lead to its death.

technique has been used to control *Aedes aegypti* and has achieved promising results [51]. Currently, it is undergoing field testing in Brazil and Colombia; however, further studies are needed to transfer this technology to other mosquito species since there are inherent risks for the release of mosquitoes infected with *Wolbachia*, and the result should be monitored for undesirable effects such as increased levels of West Nile virus infection observed in *Culex tarsalis* mosquitoes [52–54]. Other species of bacteria such as *Enterobacter* Esp\_Z and *Chromobacterium Csp\_P* have been used to inhibit the development of *Plasmodium* in mosquitoes such as *Anopheles stephensi* [55], by increasing the mosquito immune response to *Plasmodium* parasites [31, 56].

The release of irradiated sterile male mosquitoes that will seek and mate with wild females impairing the production of offspring (SIT) is once more being considered as a promising tool for controlling mosquitoes. However, its effectiveness is likely to be decreased by the presence of cryptic species and the presence of multiple *Anopheles* vectors. The same issue should be considered with the use of genetically modified mosquitoes carrying a lethal gene (RIDL), since this technique is species specific and may not be indicated to control outdoor malaria transmission. Genetically modified mosquito techniques based on impairing the *Plasmodium* life cycle inside the mosquito is still in preliminary phases of development and is not likely to be available in the near future [30, 57–61].

The above strategies can be used in the IVM context along with well-established control tools, such as selective microbial and plant-borne pesticides effective against immature mosquitoes, oviposition deterrents, insecticide-coated clothes and other surfaces for personal protection, spatial repellents reducing human-vector contact such as microencapsuled insecticide paint formulation, as well as synthetic and plant-borne repellents [23, 62–69].

The development of plant-based larvicides is of particular interest, and several plant species were successfully used for the synthesis of nano-mosquitocides; nonetheless, plant-based ovicidal and ovideterrent products are still scarce. This technology can provide rapid synthesis of toxic substances and mosquito repellents useful to manage mosquito populations, with minimal toxicity to humans. Even though mosquito control strategies relying on plant-based larvicides are a fast-growing research area, it is still in the preliminary phase of development and several steps should be taken into account, that is, (1) development, characterization, and optimization of potential botanical components suitable for nano-biosynthesis; (2) identification of potential toxic nanoparticles; (3) feasibility of utilization of plant-based industrial by-products as nano-mosquitocides; (4) field evaluation of the effectiveness of plant-based nanoparticles to control mosquito populations; and (5) effect of plant-based nanoparticles on non-target species and environment [70, 71].

Natural predators also have been used to control immature mosquitoes including cyclopoid copepods, *Toxorhynchites* mosquitoes, water bugs, backswimmers, tadpoles, and fishes [72–74]. The efficacy of mosquito predators may vary accordingly to different environmental settings and their impact on non-target aquatic species and difficulty in using multiple or artificial breeding containers should be considered for their use in control strategies [71, 75]. Another approach for controlling mosquitoes is based on endectocide ivermectin, a molecule that has been used for more than 30 years to control lymphatic filariasis. This molecule remains in the human bloodstream following a standard oral dose and can kill *Anopheles* mosquitoes that feed on the blood of medicated persons [76–79]. Controlling vector mosquito populations is a difficult task and so the addition of new technologies to be considered for IVM will help improve the effectiveness of vector-borne disease transmission [80–83].

technique has been used to control *Aedes aegypti* and has achieved promising results [51]. Currently, it is undergoing field testing in Brazil and Colombia; however, further studies are needed to transfer this technology to other mosquito species since there are inherent risks for the release of mosquitoes infected with *Wolbachia*, and the result should be monitored for undesirable effects such as increased levels of West Nile virus infection observed in *Culex tarsalis* mosquitoes [52–54]. Other species of bacteria such as *Enterobacter* Esp\_Z and *Chromobacterium Csp\_P* have been used to inhibit the development of *Plasmodium* in mosquitoes such as *Anopheles stephensi* [55], by increasing the mosquito immune response to

**Figure 2.** Attractive toxic sugar baits (ATSB) employing an "attract and kill" strategy. This technique consists of using natural attractants such as fruit or flower scent to lure mosquitoes to sugar feeding in a solution containing toxic

The release of irradiated sterile male mosquitoes that will seek and mate with wild females impairing the production of offspring (SIT) is once more being considered as a promising tool for controlling mosquitoes. However, its effectiveness is likely to be decreased by the presence of cryptic species and the presence of multiple *Anopheles* vectors. The same issue should be considered with the use of genetically modified mosquitoes carrying a lethal gene (RIDL), since this technique is species specific and may not be indicated to control outdoor malaria transmission. Genetically modified mosquito techniques based on impairing the *Plasmodium* life cycle inside the mosquito is still in preliminary phases of development and is not likely to

The above strategies can be used in the IVM context along with well-established control tools, such as selective microbial and plant-borne pesticides effective against immature mosquitoes, oviposition deterrents, insecticide-coated clothes and other surfaces for personal protection, spatial repellents reducing human-vector contact such as microencapsuled insec-

The development of plant-based larvicides is of particular interest, and several plant species were successfully used for the synthesis of nano-mosquitocides; nonetheless, plant-based

ticide paint formulation, as well as synthetic and plant-borne repellents [23, 62–69].

*Plasmodium* parasites [31, 56].

substances that will lead to its death.

390 Towards Malaria Elimination - A Leap Forward

be available in the near future [30, 57–61].

Current strategies for malaria vector control used in most African countries still rely on LLINs and IRS, which generally are not sufficient to achieve successful malaria control and local elimination [13, 25, 84]. Even though LLINs and IRS are very effective for in-house reduction of malaria transmission, in endemic areas, it has been showed that insecticide-treated bed nets reduce malaria prevalence only by 13% [85–91]. Furthermore, due to the high abundance of mosquitoes, even low levels of *Plasmodium* transmission undermine efforts to reduce the prevalence of malaria, since human hosts are bitten multiple times increasing the chance of coming in contact with the parasite. The prevalence of *P. falciparum* is strongly related to the number of infective bites per person per year or annual entomological inoculation rates (EIRs), ranging from <1 to >500. Malaria prevalence is positively associated with high EIRs; however, even low annual EIRs (<5) can be associated with malaria prevalence levels of 40–60%. For a significant reduction in the prevalence of malaria, EIRs must be lower than 1 [92]. Vector control strategies implemented in Africa have so far been unable to achieve such low levels of malaria transmission [93].

Besides, with the increase in the control efforts focused into indoor mosquitoes, the dynamics of malaria transmission is shifting from the highly endophilic to more exophilic outdoor-adapted species within the *Anopheles gambiae* complex [94–99]. In Asia, the main malaria vectors of the *Anopheles dirus* complex are exophagic and difficult to target with conventional control strategies [31]. Moreover, increasing resistance to insecticides renders LLINs and IRS less effective for controlling *Anopheles* populations. As well, even though larvicides are effective against immature mosquitoes, they are not recommended for application in rural areas [100–105].
