Eave ribbons treated with transfluthrin can protect both users and non-users against malaria vectors

Vector control is the frontline malaria prevention strategy across Africa today. Insecticide-treated nets (ITNs) and house spraying with residual insecticides (IRS) alone contributed 81% of all gains accrued against malaria between 2000 and 2015 [1]. In Tanzania, effective vector control interventions contributed to a 50% reduction in malaria prevalence between 2008 and 2017 [2, 3], and the country is now pursuing an ambitious new strategy to reduce malaria prevalence below 1% by 2020 [4]. Today, ITNs and IRS continue to be the main interventions deployed against malaria vectors, however gaps in protection can remain due to various challenges, notably insecticide resistance [5], sub-optimal ITN access and use [6], high net attrition rates [7], and high levels of exposure to malaria vectors occurring outdoors or indoors before bed time [8, 9].

To complement these current strategies and advance efforts towards malaria elimination, complementary new tools are urgently required. In recent years, substantial effort has been put into creating an expanded vector control toolbox [10]. Some of these are techniques widely used in historical times with great success and are being brought back to the fore, such as larval source management [11] and mosquito-proof housing [12]. Others are the commodity-based approaches, such as insecticide-treated hammocks [13], insecticide-treated clothing [14], topical repellents [15], insecticides propagated by mosquitoes, i.e. auto dissemination [16], eave tubes combined with house screening [17], insecticide-treated livestock [18], entomopathogenic fungi [19], attractive targeted sugar baits [20], odour-baited mosquito traps [21], targeted spraying of mosquito swarms [22] and spatial repellent based technologies [23, 24]. Unfortunately, none of these so far have proven as scalable as ITNs in low-income communities. Moreover, many still require high user compliance, which particularly hinders interventions such as topical repellents [25].

Spatial repellents are increasingly being proposed as a leading contender in the complementary vector control toolbox, especially since they can protect multiple persons at the same time and often function at sub-lethal doses [23]. Another advantage is that recent advances have demonstrated new delivery formats that require no electricity, remain effective over several months and have multiple modes of action against mosquitoes, including bite prevention, feeding inhibition and lethality [26‐29]. In one example, hessian-based strips treated with transfluthrin prevented at least 75% of outdoor-biting by Anopheles arabiensis, Culex and Mansonia mosquitoes for at least 1 year [29]. Combinations of these spatial repellent products and odour-baited mosquito traps have also been evaluated, against indoor and outdoor-biting mosquitoes [30‐33].

Mmbando et al. [32] recently described a related application, i.e. eave ribbons, which are simple hessian ribbons treated with spatial repellents and wrapped around eaves of houses (without completely blocking the eave-spaces) to prevent outdoor-biting and indoor-biting mosquitoes over long periods of time. In the initial studies, they demonstrated high levels of protection in semi-field settings against laboratory-reared mosquitoes and also in experimental hut studies against field mosquitoes in rural Tanzania. It was concluded that this technology, pending further development and validation, has potential to complement current tools, as it is simple, low-cost, highly-scalable and easy-to-use; making it suitable even for poorly-constructed houses and low-income groups [31].

In a follow up study [31], Mmbando et al. evaluated different configurations of a push–pull system consisting of the transfluthrin-treated eave ribbons and odour-baited traps. Here, they concluded that efficacy of push–pull was mainly due to the spatial repellent component, and that adding odour-baited traps only slightly improved personal protection, but excessive trap densities increased exposure outdoors [31].

This current study addressed two important questions that remained unanswered regarding the eave ribbon technology. First, whether the eave ribbons at different intervention coverages, could effectively provide both personal and communal protection without diverting mosquitoes from users to non-users, as previously shown with transfluthrin-based mosquito coils under incomplete coverage situations [34]. Second, whether the personal and communal protection could be improved through different configurations of the push–pull systems, such as using indoor traps instead of outdoor traps as previously used [31], or placing the ribbons and traps in different houses instead of the same house as previously tested [30, 31, 35, 36]. For purposes of this study, a commercially-available UV–LED trap recently demonstrated as effective for trapping Tanzanian Anopheles and Culex mosquitoes was used as the intervention trap of choice alongside the eave ribbons [37].

This study assessed whether transfluthrin-treated eave ribbons, previously demonstrated to protect against both indoor-biting and outdoor-biting mosquitoes in semi-field and experimental hut studies [31, 32], could effectively protect both users and non-users without diverting mosquitoes from users to non-users. Another question addressed was whether the protection offered by these ribbons, either at personal or communal level could be improved by adding mosquito traps to form push–pull, and by different configurations of such push–pull systems. Two main differences in the configurations were as follows: (a) this current study used indoor intervention traps instead of outdoor traps as previously used [31], and (b) this study included one configuration with spatial repellents and traps in different houses and a another with both interventions placed in the same house as previously tested [30‐33, 36]. Overall, the studies lasted more than 450 hut nights, during which mosquito trapping was done indoors and outdoors, totalling more than 900 trap nights.

The most important finding was that transfluthrin-treated eave ribbons can protect both users and non-users. Besides, the protection afforded to the non-users peaked when the intervention was delivered at high coverages. In the tests where four of the five huts had the intervention, and the sentinel hut (i.e. non-user) did not, the eave ribbons provided 83% and 62% protection indoors and outdoors respectively to users, plus 57% and 48% protection indoors and outdoors to the non-user. Separately, in the experiment where coverage was varied from 0 to 100%, protection for users remained constant after 20% coverage while protection for non-users increased correspondingly with intervention coverage, peaking once 4/5 (80%) of huts had received the eave ribbons. Protection for users was consistently higher indoors than outdoors, possibly due to: (1) surface area of the transfluthrin treated eave ribbons relative to the indoor space, (2) the preference of candidate vector species, An. arabiensis to bite more outdoors than indoors [44], (3) sub-lethal effect of transfluthrin, which may disrupt host-seeking behaviour of mosquitoes entering the huts [28], and (4) the barrier effect of eave ribbons, however minimal [32]. The findings regarding personal protection to users corroborate those from the previous studies which tested the efficacy of the transfluthrin treated eave-ribbons at both semi-field and field settings [32, 33]. However, the findings relating to non-users represent the first report of such additional benefits associated with the eave ribbons technology.

An earlier study by Maia et al. [34] suggested that under conditions of incomplete coverage, transfluthrin-based products, in this case mosquito coils, provided personal protection to users, but could potentially divert mosquitoes to other users. In this current study, there was no increase in exposure to the non-users, possibly because the intervention also killed substantial proportions of the mosquitoes exposed in those huts, and which would have otherwise been diverted to the non-users. Consistently, 100% of mosquitoes held inside the huts with transfluthrin-treated eave ribbons, died within 24 h of observation. Such levels of mortality indicate not only diminished likelihood of diversion of mosquitoes, but also suggest increased communal protection. However, it will be important to validate these findings in field settings where malaria mosquitoes are resistant to pyrethroids, and where such mortality may be reduced. Preliminary findings from rural south-eastern Tanzanian villages suggest that transfluthrin vapours remain substantially toxic to An. arabiensis, Anopheles funestus and Culex mosquito populations, which are known to be resistant against pyrethroids and carbamates (Mmbando et al., unpublished). The first experimental hut study with eave ribbons in rural Tanzania also showed significant repellency against all these mosquito species despite being pyrethroid resistant. Nonetheless, this must be investigated in detail to guide future potential application of the eave ribbons technology.

These findings add to the body of evidence that spatial repellent eave ribbons can provide protection against malaria vectors both indoors and outdoors in the peri-domestic space. The benefits extend beyond personal or household protection, and are accruable also non-users. Studies of night time human activities and sleeping patterns highlight the importance of interventions that can protect people during times when ITN use is not feasible, including when they are outdoors or indoors before going to sleep. Spending time outdoors near the home during evening hours, is common in many parts of sub-Saharan Africa [8], particularly in rural communities [8]. This includes activities such as cooking and other household chores, resting, and socializing in the hours before bed [8, 9, 45]. Spatial repellent eave ribbons offer a potentially viable solution for protecting people during these times and can offer protection to groups of people without requiring high levels of individual compliance.

Mosclean traps (pull component) alone resulted in increased risk of exposure to indoor mosquito bites in both the huts with taps and the sentinel hut without traps. Besides, it offered only minimal protection against mosquito bites outdoors. This trap, which has UV–LED and a photocatalytic CO₂ generator as the main lures, was recently shown to be highly attractive and therefore effective for trapping mosquitoes indoors [37]. It could have therefore increased the overall densities indoors as measured by the CDC-light trap in the same huts. This also indicates that Mosclean may be attracting large densities of the mosquitoes to the vicinity, but it does not trap all the mosquitoes. In past experiments where CO₂ baited traps were placed outdoors at the peri-domestic area, the traps provided only marginal protection against An. arabiensis indoors, but increased biting risk to volunteers sitting outdoors [31]. An interesting observation however was that when the huts with the traps were near huts with transfluthrin-treated eave ribbons, the risk of mosquito bites was substantially lower than when all the huts had traps (Figs. 5, 6). The protective efficacy of the eave ribbons was, therefore, more obvious than that of the Mosclean traps at the scale of these studies. Mass trapping of mosquitoes generally has cumulative benefits, which could not be detected in this study since new batches of mosquitoes were released nightly.

Using the traps together with eave ribbons, whether in same houses or in different houses achieved less protection for non-users compared to eave ribbons alone (Table 1). For users, the protection achieved was similar to that obtained with just eave ribbons alone. The change from standard push–pull system to push–pull mosaic resulted in modest improvements in protection indoors or outdoors for the non-user, but these gains were still lower than what was achievable by transfluthrin-treated eave ribbons alone (Table 1). Moreover, in the push–pull mosaic design, the specific user huts that had Mosclean traps achieved lower percentage protection both indoors and outdoors than huts fitted with eave ribbons. The motivation for push–pull mosaic, as opposed to standard push–pull where huts are assigned both traps and repellents, had been to minimize any antagonistic effects between the two interventions at hut level, and also reduce costs and complexity of the overall application package. A related observation was that actual mosquito catches by the Mosclean traps themselves were halved upon introduction of eave ribbons, suggesting any value of these devices for removal trapping would be compromised by the spatial repellents.

Considering the complexities associated with using traps, especially those that require baits, Mmbando et al. [31] suggested that once high coverage with transfluthrin-treated eave ribbons is achieved, it may be best to not add traps at all. Nevertheless, since traps remove large numbers of mosquitoes from circulation, it is still theoretically possible that large-scale deployment may deliver communal level benefits overtime, as previously simulated by Okumu et al. [21]. Such cumulative impacts were also demonstrated in a trial of odour-baited trap in western Kenya, which achieved significant reductions in densities of An. funestus mosquitoes, and subsequently reduced malaria incidence by 40.8% and prevalence by 28.9% [46]. The potential benefits of traps, used alone or in combination with transfluthrin-treated eave ribbon, could however not be detected at the scale of this current study.

Most Anopheles traps have been developed for surveillance, and their applications as mass-trapping interventions remain circumstantial, often dependent on the type of lure used and the density of traps relative to human and animal hosts. In this study, Mosclean trap was selected and used as an intervention based on a previous study [37], where the trap was demonstrated to catch more mosquitoes than other commonly used traps such as CDC-light traps, BG-sentinel, and Suna traps.

One limitation of this study is that it was conducted in semi-field settings under controlled environment and using laboratory-reared mosquitoes. Second, the sentinel hut remained the same throughout the tests, and therefore lacked the natural variability associated with actual field settings. Lastly, the study used untreated mosquito nets for primary protection in all the huts instead of insecticide-treated bed nets (ITNs). The method for assessing exposure also did not consider the exposure to bites that occur when people are indoors but not yet under their nets. Instead the method used assumed that people went to bed as soon as they were indoors. Field validation of the findings may therefore be necessary, in different geographical locations, with different vector species composition. Preferably such studies should be in areas with pyrethroid resistant mosquitoes so that both the mortality and repellency effect, and any other effects of the intervention can be validated. An alternative validation strategy could be mathematical simulations, such as previously done for odour-baited traps [21]. Future research is needed to establish public health impact and inform successful execution of the technology.

Eave ribbons treated with protect both users and non-users against malaria mosquitoes. The benefits to the non-users is highest where coverage of eave ribbons exceeds 80%. Besides, most of the gains accrued by the non-users was in form of outdoor protection, even though percentage overall protection for both users and non-users was higher indoors. The mosquito-killing property of transfluthrin can magnify the communal benefits by limiting unwanted diversion to non-users, but should be validated in field trials against pyrethroid-resistant vectors. The potential of the UV–LED traps as an intervention alone or alongside eave ribbons was however undetectable at the scale of this study. Overall, these findings extend the evidence that transfluthrin-treated eave ribbons could potentially complement ITNs. This study highlights the potential for eave ribbons to protect people in peri-domestic space before sleeping hours when ITN use is not feasible.