New vector control tools
Existed vector control intervention tools which are limited by the aforementioned problems are a top concern and necessitate the development of alternative effective tools. Moreover, timely approval and deployment of these new tools in the public domain are needed, so as to make them relevant under realistic timelines. In order to increase access to safe, high-quality, effective vector control products (VCPs), WHO works in close cooperation with national regulatory agencies and partner organisations to ensure that quality VCPs are available to those who need them. The WHO PQT/VCP assesses VCPs and public health pesticide active ingredients to determine that they can be used safely and effectively and are manufactured to a high-quality standard. This is carried out by assessing product dossiers and inspecting manufacturing sites. Given below are the new vector control tools, which have the potential to be used as public health interventions against VBDs:
Next-generation insecticide-treated nets
ITNs treated with a pyrethroid insecticide alone (effective for 20 washes and 3 years of use in the field) are currently referred to as LLINs.46 The LLINs played a key role in reducing malaria by more than half a billion in Africa between 2000 and 2015.47 To overcome the issue of the development of insecticide resistance in malaria vectors globally, WHO has approved the use of ‘new types of nets’ with insecticide mixtures or synergists. Pyrethroid-treated LLINs are standard, while others are considered ‘new types’.48 Notable examples include PermaNet V.3.0 with deltamethrin and piperonyl butoxide (PBO), and veeralin with alphacyphermethrin and PBO. The new-generation ITNs with PBO show enhanced efficacy in contrast to pyrethroid-only impregnated nets.49 Another insecticide mixture used in ITNs approved by PQ VC is alpha-cypermethrin with chlorfenapyr and alpha-cypermethrin with pyriproxyfen. Pyrethroid and pyrrole chlorfenapyr-impregnated nets have shown improved killing of the resistant vectors in comparison to nets with only pyrethroids in experimental hut studies.50 In India, synthetic pyrethroid LLINs are in use by the national programme, while PBO nets have recently recieved approval for public health use51. Demonstration of advantage of PBO nets over synthetic pyrethroid nets and subsequent adoption of PBO nets by NCVBDC could pave the way for their application against resistant An. culicifacies.
New molecules/formulations for indoor residual spraying
The emergence of resistance to DDT and synthetic pyrethroids has prompted the exploration of alternative insecticides for use in IRS. In a trial conducted for IRS using Fludora Fusion (a mixture of deltamethrin and clothianidin), enhanced and prolonged mortality of wild pyrethroid-resistant malaria vectors was observed for up to 7–10 months, primarily attributed to clothianidin component. The pyrethroid component in the mixture also led to substantial early exiting of mosquitoes from treated huts.52 Another study in Gujarat, India, using Fludora Fusion WP-SB (clothianidin and 62.5 deltamethrin), reported equal or better efficacy compared with deltamethrin and bendiocarb alone against pyrethroid-resistant malaria vector population.53 In Tanzania, IRS with SumiShield 50 WG (Clothianidin 50%, w/w) was found effective against insecticide-resistant An. arabiensis mosquito vectors. In Karnataka, India, IRS with SumiShield 50 WG demonstrated effectiveness for up to 6 months against pyrethroid-resistant An. culicifacies.54 A small-scale field study in Tanzania evaluated the effectiveness of IRS against malaria-carrying mosquitoes. It reported a prolonged residual efficacy using deltamethrin 62.5 SC-PE compared with DDT 75% water-dispersible powder.55 Deltamethrin 62.5 polymer-enhanced suspension concentrate also exhibited prolonged effectiveness, up to 5 months, compared with deltamethrin 2.5%.56 The WHO PQVC list includes clothianidin, both as a separate moiety and in combination with deltamethrin, for IRS application. These new IRS formulations are much needed intervention tools in India, especially in the management of insecticide-resistant malaria vector species and longer residual efficacy.
New molecules/formulation for larvicides
Three major types of larval control agents, that is, (a) microbial larvicides (eg, Bacterial Larvicides; Bacillus thuringiensis israelensis (Bti) and B. sphaericus (Bs)), (b) insect growth inhibitors (pyriproxyfen, diflubenzuron) and (c) chemical insecticide (mainly temephos)) are used for vector control. The microbial larvicides, currently available are characterised by short and declining residual activity, necessitating frequent reapplication, which adds to the total cost of the control interventions. To overcome the bottlenecks of the conventionally used microbial larvicides, newer and more efficient larvicidal formulations have been developed that release effective levels of its active ingredients at the water surface with prolonged residual activities. Large-scale intervention in western Kenya showed that a single application of the formulations of Bti and Bs showed a reduction of 60%–80% of the pupal production with a prolonged activity for almost 10 weeks with no impact on non-targeted organisms.57–59 ICMR-Vector Control Research Centre isolated indigeneous Bti ‘VCRC B 17’ and developed it as a bacterial biolarivicide for use in public health programme. It is also identified as Indian standard reference strain to compare the quality of other Bti products in India. Trials of long-lasting larvicide formulations of Bti in India should be carried out to ensure the availability of newer efficient formulations in the instance of the development of resistance against the currently used larvicides.
Attractive toxic sugar baits
Attractive toxic sugar baits (ATSB) strategy is based on the exploitation of the predilection of mosquitoes towards sugars. An important characteristic of ATSB is that it targets both female and male mosquitoes and minimises insecticide resistance due to the use of toxicants with different modes of action. It has been reported that ATSB has been effective in reducing the densities of mosquitoes (Anopheles, Aedes and Culex) and sand fly vectors.60–62 In a field trial conducted in Mali, An. gambiae densities were reduced to 90% with a single outdoor application of boric acid-based ATSB.61 In a laboratory trial conducted in India, An. culicifacies, An. stephensi and Ae. aegypti experienced >90% mortality with 2% boric acid-based toxic sugar bait.63 The impact of ATSB might be exponential in conjunction with LLINs as mosquitoes deprived of blood meals take more and larger sugar meals.64 65 Furthermore, biolarvicide B. spharicus has been used in ATSB to suppress larval populations of An. sergentii in Jordan.66 In India, the use of ATSB strategies may be efficient under urban conditions where the availability of flowering plants is scarce limiting the feeding opportunities for mosquito populations. Apart from urban areas, regions with patchy vegetation such as Rajasthan and Gujarat can be ideal areas for ATSB strategy, due to the limited availability of natural sugar sources in these patchy vegetation. For rural vectors, the strategy employed by N'do et al in which can be of great use in which Bti sugar patches were attached to bed nets, which resulted in the killing of insecticide-resistant mosquitoes landing on the bed nets.67 The Indian Council of Medical Research has developed a standardised methodology for testing ATSB in both laboratory and field settings (www.icmr.nic.in). This methodology will prove beneficial for researchers and the insecticide industry to test the ATSB in a robust scientific way.
Ivermectin-like endectocides
Endectocides are drugs that have both ecto and endo parasiticidal activity. Ivermectin is the most commonly recommended endectocide for vector control purposes. The application of ivermectin has multiple advantages including efficacy against both endophagic and exophagic vectors, minimal chance of insecticide resistance due to different modes of action, kills mosquitoes as well as the malaria parasite. In Africa’s endemic regions, ivermectin trials have been carried out and have been reported with encouraging outcomes.68 According to Mekuriaw et al’s study, mosquitoes that fed on blood treated with ivermectin displayed a higher mortality rate compared with the control group.69 Further research has shown that administering standard veterinary doses of ivermectin to cattle results in a significant decrease in the survival rates of An. epiroticus and An. dirus.70 In India, ivermectin as sugar bait was found effective against resistant An. culicifacies and An. stephensi.71 Ivermectin is already in use in the LF control programme of India. Before its use in the vector control programme, trials of ivermectin should be conducted against different vectors followed by preclinical and clinical trials in humans as well as cattle.68 Drug administration of ivermectin in malaria-persistent areas either to cattle or humans might help control the disease transmission.
Insecticidal paints
Insecticidal paint is one of the innovative vector control strategies that involves microencapsulated insecticides embedded within the paint matrix. Unlike IRS, insecticidal paints do not require skilled/trained personnel or logistical planning. Application of insecticidal paints resulted in ≥90% mortality of An. gambiae mosquitoes both under laboratory and field conditions.72 73 Acharya et al also reported insecticidal activity for an insecticidal paint formulation against Ae. aegypti in a study conducted in India, where a 94% knockdown and 90% mortality with a residual efficacy of almost 18 months was observed.74 In another laboratory trial involving insecticide paint formulations, significant behavioural avoidance was observed in vectors of dengue, malaria and filariasis.75 India may consider further development and evaluation of the insecticidal paints due to their ease of application, efficacy against insecticide-resistant vectors and targeted approach before possible adoption by the national programme.
Tools for animal shelters
An. culicifacies, An. stephensi and An. fluviatilis mosquitoes are responsible for transmitting the majority of malaria cases in India, which rest in cattle sheds and feed on both cattle and humans. The densities of these mosquitoes can be reduced either by spraying cattle shelters or by applying insecticide topically on cattle.76 A community-level randomised controlled trial reported from Pakistan study on highly zoophilic mosquitoes showed a drastic reduction in the malaria incidence with the topical application of insecticides.77 Another study reported from India showed that the IRS in houses and cattle sheds yielded a higher reduction in malaria cases in comparison to individual treatments.78 The use of deltamethrin-treated ITNs in covering the pigsties was found to be effective in deterring mosquitoes away from the pigs, which act as the amplifying host of the JE virus, thereby curtailing the bridge of contact with the reservoir.79 As the topical application of insecticide to each cattle can be impractical, IRS or application of insecticidal paint on walls of cattle sheds might be used in controlling the vector populations.
Insecticide-treated wearables and materials
Insecticide-treated materials/wearables include clothing, bed nets or other personal items treated with insecticides. When individuals use or wear these treated materials outdoors, they create a protective barrier that repels or kills mosquitoes on contact. This is particularly effective in preventing outdoor mosquito bites, reducing the risk of VBDs like malaria. Insecticide-treated clothing and fabrics have been employed as personal protective wearables, particularly in military and recreational settings, as a means of safeguarding against insect bites.80 81 The insecticide-treated clothing can be an easy-to-use tool for protecting against vectors and can easily be integrated into everyday routines at work or educational spaces such as industrial/defence/school.81 Insecticide-treated materials or wearables and spatial repellents serve as valuable tools in addressing outdoor mosquito biting. Permethrin, a synthetic pyrethroid, is a prevalent ingredient employed in fabrics, while alternative compounds, such as deltamethrin, cyfluthrin, bifenthrin, KBR3023 and DEET (N, N-diethyl-3-methylbenz-amide), have also been tested.80 A modelling study by Massad et al reported that impregnating school uniforms with insecticide can lower dengue incidence in school children by at least 6%–55%.82 Another report by Banks et al highlighted that insecticide-impregnated clothing could provide around 0%–75% and 0%–79% protection against malaria and leishmaniasis, respectively.80 In a field trial of deltamethrin-treated curtains, a significant reduction (87.9%–93.7%) of An. stephensi and Ae. aegypti was reported in India.83 Therefore, these insecticide-treated clothing or hammocks can be a good option for protection from indoor and outdoor biting mosquitoes. Moreover, these might be useful for migratory populations and armed force personnel who are at risk of vector bites.
Spatial Repellents (SRs)
Spacial reppellents offer protection against blood-seeking vectors, such as mosquitoes, by releasing airborne chemicals.1 SRs deter mosquitoes from entering a defined space, such as a room or outdoor area. This technology is beneficial for outdoor settings where conventional methods like bed nets may be impractical. SRs provide a localised solution to protect individuals in specific areas from mosquito bites. Various chemicals have been reported to show insect-repelling properties. Metofluthrin and transfluthrin, which are volatile pyrethroids, as well as terpenoids derived from plants, and volatile organic compounds present on human skin, and organic compounds released by skin bacteria, such as 1-methyl piperazine, exhibit properties of spatial insect repellents. SRs might be useful in protection from vector bites when (1) vector biting is outdoors, (2) when LLINs are irregularly used or not used at all, (3) when vectors are restricted from resting or have limited resting time on indoor surfaces treated with insecticide and (4) when IRS or LLINs are neither accessible nor practical, SRs may be an added advantage in reducing VBDs.84 85 Several trials have been conducted to demonstrate the efficacy of SR products against malaria and other disease vectors.86–89 In a randomised household trial carried out in China evaluating mosquito coils, it was observed that coils alone could provide 77% protective efficacy against P. falciparum using 0.03% transfluthrin coils.86 A field study in Indonesia using metofluthrin as a SR in mosquito coils resulted in a 52% increase in malaria protection.88 Therefore, the application of SRs can help minimise vector bites, resulting in the containment of the VBDs. SRs will be useful to migratory people and armed force personnel in India due to their regular movements outdoors making them receptive to vector bites.