Effectiveness of the Aedes aegypti Mosquito Vector Control Program in Southeast Asia – A Systematic Review

Background: Dengue is still a major vector-borne disease problem in the world. It is caused by infection with the Dengue virus, which can be spread through a vector in the form of the Aedes aegypti mosquito. One of the ways to reduce the incidence of dengue infection is by controlling vectors. Aim: This study aims to analyze the effectiveness of vector control of the Aedes aegypti mosquito on the dengue incidence in Southeast Asia. Methods and findings: This study was a systematic review that examines articles with experimental research designs and cluster randomized controlled trials. The scope of this research area is limited to Southeast Asian countries during 2012-2021. There are 333 articles obtained from two sources: PubMed and ScienceDirect, by using certain keywords. Furthermore, articles were selected based on inclusion and exclusion criteria, so that 31 articles were obtained. A total of 6 articles that met the inclusion criteria were then selected for further analysis. Three journals that discussed the output in the form of the Larva Density Index (LDI) showed a decrease with significant results. Two journals that discussed biological control ( Bacillus thuringiensis israelensis ) got significant results in decreasing Pupal Density (PD). The two journals on chemical control ( permethrin ) that discussed the outcome of the presence or absence of IgG seroconversion show insignificant results. Conclusion: All control methods are considered effective. However, among the three vector control methods studied, the control with Bacillus thuringiensis israelensis is the most effective method.

The criteria for searching research literature using the PICO (Population, Intervention, Comparison, and Outcome) method as shown in Table 1.The population characteristics used are people in Southeast Asia.It is with the intervention group that is considered as the dengue infection prevention program and the effectiveness of various dengue infection prevention programs as a comparison.The outcome is the dengue infection rate.

Data types and criteria
The following are the inclusion criteria used in Table 1.

Technique of data collection
The data collection in this systematic review was by taking six scientific research articles from English-language international journal publications in PDF format.The article searches were conducted using the PubMed and ScienceDirect search engines by the keywords dengue infection AND Southeast Asia AND dengue vector control AND Aedes aegypti.In the search for articles, the limitations of 2012 to 2021 were used.Based on the search results through search engines using the keywords in question, the articles were then selected based on the title and abstract.After being filtered again based on the inclusion and exclusion criteria, six articles were obtained that matched.The next process was grouping the data based on the variables that are going to be discussed.Furthermore, the data synthesis was conducted to obtain a systematic study related to the effectiveness of controlling the Aedes aegypti mosquito vector on the incidence of dengue infection in Southeast Asia (Figure 1).

Data analysis and synthesis
The data were analyzed qualitatively and descriptively.Afterward, examining how the effectiveness of controlling the Aedes aegypti mosquito vector affects the incidence of dengue infection in Southeast Asia.In this study, the data analysis will be formed in a table discussing the results of the answers to the research question that seeks to conclude the effectiveness of the control of the Aedes aegypti mosquito vector on the incidence of dengue infection in Southeast Asia according to the expected outcome.

RESULTS
There are 333 articles obtained from two sources: PubMed and ScienceDirect, by using certain keywords.For example, dengue infection AND Southeast Asia AND dengue vector control AND Aedes aegypti.Through a screening process based on the presence or absence of access, inclusion, and exclusion criteria.According to the evaluated parameters, the final results obtained were 6 articles.
Of the six articles, there are two studies discussing the effectiveness of permethrin as vector control, two studies that are discussing Mesocyclops, and two other studies discuss Bacillus thuringiensis israelensis (Bti).The outcome is the number of Aedes aegypti vectors with different forms of the dependent variable.As shown in Table 2, five journals provide an output in the form of the number of Aedes aegypti mosquitoes, four of which stated that they had a significant result in that there was a decrease in the number of mosquitoes after the intervention using permethrin by Kittayapong et  Of the four journals that both studied biological control, only three of them are two studies on Mesocyclops and one study on Bacillus thuringiensis (by Bohari et al.).Those studies discuss the outcome in the form of the Larva Density Index or LDI.However, only the administration of Bacillus thuringiensis shows a significant reduction in LDI.Those studies also showed that the intervention of Bacillus thuringiensis show a significant reduction in Pupal Density (PD) after the treatment.
Another articles on vector control in the form of chemical control using permethrin also discussed about the presence or absence of dengue IgG seroconversion after the intervention.However, both studies show insignificant results.There is one article in each that provides output in the form of House Index (HI) and Breteau Index (BI).Yet, both are accompanied by Container Index (CI) numbers.Only research by Bohari et al. includes the calculation of Ovitrap Index (OI) with significant results and Incidence Rate (IR).The journal compares the results before and after the intervention, as well as between the intervention group and the control group.Z-7L = 0,26 ± 0,11a (pre-treatment) and 0b (posttreatment).Z-5 = 0,19 ± 0,09a(pre-treatment) and 0,09 ± 0,03a (posttreatment).a,b show Significant Difference (p<0,05).

DISCUSSION
Dengue is an infectious disease caused by the dengue virus and is transmitted by mosquitoes of the Aedes genus. 11Until now, dengue is still a major health problem that can cause morbidity and economic burden, especially in tropical and subtropical countries. 12,13arious prevention efforts are carried out to reduce and overcome the incidence of dengue infection in the world, one of which is by controlling the vector.Various prevention efforts are conducted to reduce and overcome the incidence of dengue infection in the world.One of them is by controlling the vector.The control of vectors based on the mechanism can be grouped into environmental management, chemical control, and biological control. 1

Permethrin
Permethrin, based on its chemical structure, is a type I pyrethroid insecticide, which can be used as a chemical vector control.Pyrethroids have an insecticidal effect by intervening with voltage-gated sodium channels (VGSC) on vector neuron membranes, binding open channels, and preventing re-closure., thereby prolonging the potential action causing the vector to experience paralysis or knock-down, resulting in vector mortality. 14In addition to having an insecticidal effect, pyrethroids have a spatial repellent effect and contact irritant effect, as well as excito-repellency, which is the reason for the use of pyrethroid insecticides such as permethrin for clothing. 15The results of a study conducted by Pattamaporn Kittayapong et al. (2017) and Tsunoda et al. (2013) showed that permethrin was effective in reducing the number of Aedes mosquito vectors, although it was applied with 2 application methods and 2 different research locations.Kittayapong et al. impregnated permethrin in school uniforms in Thailand and was shown to reduce the incidence of dengue and the number of Aedes aegypti mosquitoes caught in the classroom compared to control schools. 16,17anwhile, Tsunoda et al. in Vietnam impregnated 2% permethrin in mosquito nets (Olyset® Net) and reduced the Container Index (CI), House Index (HI), the percentage of positive containers for immature Aedes mosquitoes (p<0.05), and the dengue seroconversion rate was lower than the control area. 17This Olyset® Net has previously been developed as a mosquito net for protection against the bite of the malaria mosquito vector and reduced the prevalence of malaria by 45.7% in India. 18Olyset® Net (permethrin 2%) reduces mosquito landing effort and increases flight time, thereby preventing female mosquitoes from laying eggs in containers installed with Olyset® Net.The use of permethrin on clothing may cause side effects.It is seen in the study by Kittayapong et al. (2017), where a number of students experienced mild skin irritation.Hence, they had to be withdrawn from the study. 16According to Marlie Hartley (2010), the use of permethrin can cause allergic dermatitis in individuals who have allergies to chrysanthemums, ragweed plants, or turpentine, although this is rare.
In addition to possible side effects, the knock-down value (after 1 hour) and mortality (after 24 hours) in mosquitoes decrease rapidly after 4 washes, and the efficacy of permethrin is calculated to be below 20% after 20 washes. 16veral findings also reported the possibility of mosquito resistance to pyrethroids which underlies a recent study to develop Olyset® Net containing only 2% permethrin and combining it with other substances.

Mesocyclops
Mesocyclops is used as a form of biological mosquito control that is non-toxic and inexpensive because it has a high reproductive capacity. 21esocyclops works by preying on the larvae of Aedes aegypti so that it can break the life cycle of the mosquito. 22The results of a study conducted by Nam and colleagues (2012) 23 with community-based Mesocyclops intervention showed a significant decrease in the number of Aedes aegypti mosquitoes with an average decrease of 98.8%.
In 4 of the 5 communities, no incidence of dengue is found after the serological analysis.The results of this study are in line with the results of research by Tran et al. (2015) 24 on 100 randomly selected households in the community.It was found that the Mesocyclops intervention program reduced larval density by more than 98% during the program intervention period conducted by the government.However, in the last period of program intervention by the government, there was an increase in larval density and the number of Aedes aegypti mosquitoes, as well as a decrease in the number of Mesocyclops after the transfer of program responsibility to the community.This can happen due to a lack of public knowledge about effective methods of mosquito control management with Mesocyclops, considering that limited food and poor care will inhibit Mesocyclops populations.Although no incidence of dengue occurred, this cannot be said to be related to a decrease in the number of Mesocyclops and an increase in the number of Aedes aegypti mosquitoes.This is because many other factors affect the incidence of dengue, such as weather, dengue virulence, the immunological status of patients, and population density. 24Both studies were conducted community-based in Vietnam in different locations and time periods.The intervention of the two studies was carried out by inserting Mesocyclops as a biological agent into water containers.Based on these two studies, Mesocyclops proved to be effective as a biologic agent in dengue vector control.

Bacillus thuringiensis israelensis (Bti)
Of the six journals reviewed, there are two journals that discuss biological vector control using the bacterium Bacillus thuringiensis israelensis (Bti).Bacillus thuringiensis (Bti) will form parasporal crystals composed of protoxin proteins.These protein crystals are toxic when eaten by mosquito larvae, bind to intestinal epithelial cells, and cause holes in the intestines so that the larvae die. 25Bti has been used as mosquito control for more than 30 years and has been shown to be non-toxic to humans and other animals.Based on a study conducted by Setha and colleagues (2016) in Cambodia and Bohari et al. (2020)  in Malaysia, it showed that containers or containers treated with Bti during treatment and post-treatment experienced a decrease in the number of pupae, and even the number of pupae became less.None at all compared to containers or containers that were not treated with Bti (p<0.05). 26,27cording to Setha and colleagues (2016), 26 treatment with Bti strain AM65-52 at 8g/1000L, the same dose used in the previous study, can significantly suppress the formation of Ae aegypti pupae (p<0.05).In addition to suppressing the formation of pupae, according to research conducted by Setha et al. (2016) 26 , Bti also reduced the number of Ae aegypti mosquitoes counted during treatment and post-treatment (p <0.05).Meanwhile, the research conducted by Bohari and colleagues (2020) 27 in 2015 showed the results that Bti treatment proved effective in reducing the AI (Aedes Index), larval density index (LDI) (p <0.05), ovitrap index ( OI) (p<0.05), and Incidence Rate (IR) compared to areas that did not receive Bti treatment.Bohari and colleagues (2020) also investigated the use of Bti with the wide spray method, which turned out to be able to reach larval habitats that are difficult to detect.An evaluation confirmed that Bti droplets were able to penetrate barriers and settle in water containers among dense vegetation, as well as on the first level of buildings up to 5 meters above the ground.The Bti solution with a concentration of 125 grams/12 liters is said to be efficacious for 21 days after treatment.From these two studies, it can be concluded that Bti is the most effective in controlling vectors, as stated by the CDC in 2017.

CONCLUSION
According to the results of six studies review, it can be concluded that all control methods studied were effective in controlling Aedes aegypti as a dengue vector.The researchers review two studies that discussed chemical control, namely permethrin, and four studies that discussed biological control, namely Mesocyclops and Bacillus thuringiensis israelensis.Among the three vector control methods studied, the control with Bacillus thuringiensis israelensis was the most effective method.Further studies are needed on the advantages and disadvantages of each vector control method.In addition, adjustments are also needed to existing environmental and community conditions so that vector control methods can be more effective.
al., Mesocyclops by Nam et al., and Bti by Setha.et al. and Bohari et al.

Table 1 : Inclusion and exclusion criteria. Figure 1: Diagram of preferred reporting items for systematic review and meta-analysis (PRISMA) 971 Pharmacognosy Journal, Vol
15, Issue 5, Sep-Oct, 2023 Sulistiawati, et al.Effectiveness of the Aedes aegypti Mosquito Vector Control Program in Southeast Asia -A Systematic Review

No Title Author Location Design, Number of Samples, Time, and Period Intervension Outcome of measurement Outcome
Percentage of immature Aedes mosquitoes, HI, CI, and dengue seroconversion rate (IgG antidengue ELISA)Percentage immature mosquito: lower positive after treatment (trial) compared to with area control.After 2 post month treatment, area treatment with Olyset® Net experience drop significant and lower compared to area control (value p<0.001,OR area treatment 0.7 and OR control area 1.0).moon girl Dec and Feb when combined, that in the area treatment has percentage positive container lower than area control (value x2 test 6.38 and value P <0.05).Container Index (CI): gradually decreased on October-February (trial) compared to with CI area control, except 'concrete tank cylinder' on the moon February.House Index (HI): before treatment, HI trial area more Tall compared to area control.After treatment, HI area decreased trial last October increase gradually month December-February.HI control area continues to increase August-February.Seroprevalence of anti-dengue IgG: in healthy residents of the trial and control areas did not differ significantly.Mesocyclops: In > 50-liter containers increased from 12.77 ± 8.39 to 75.69 ± 9.17% during period 15-45 months.Dengue incident: There was no incidence of dengue in 4 out of 5 communities by serological analysis.