Background
Early-biting, outdoor-biting and pyrethroid resistant malaria vectors cannot be adequately controlled using the current primary interventions, namely long-lasting insecticide-treated bed nets (LLINs) and indoor residual spraying (IRS) [
1‐
3]. To address these challenges and accelerate ongoing efforts for malaria control and elimination, complementary tools that are affordable, easy-to-use and scalable are urgently needed [
4,
5]. Fortunately, there have been recent advances on various individual products, which can address outdoor-biting, though these still require further assessment and optimization [
4]. To maximize benefits, these complementary tools should also be effective at both household and community-level, and readily scalable across multiple socio-economic groups.
A recent review of evidence on proposed complementary vector control interventions identified seven tools for which there is at least some evidence of community-level evaluation of malaria parasite reduction [
6]. These included insecticide-treated clothing and blankets, insecticide-treated hammocks, insecticide-treated livestock, larval source management, mosquito-proofed housing, spatial repellents and topical repellents. The authors emphasized that larval source management and topical repellents had the most advanced evidence, but also that the topical repellents were unlikely to offer wide-spread community-level protection [
6]. Indeed, personal protection measures with topical repellents or insecticidal clothing may effectively prevent outdoor-bites, but mosquitoes can move from protected to unprotected individuals [
7]. These approaches are also affected by poor compliance among users [
8], as well as inadequate supply and access.
Spatial repellent products, which protect multiple persons over wide areas, present a viable alternative with minimal diversionary effects [
9] while also providing significant community-wide benefits against malaria infections. In one study in Indonesia, where metofluthrin-based coils were provided to households, malaria parasite prevalence was reduced by 52% among users, compared to non-users [
10]. Separately, in China, where mosquito coils treated with 0.03% transfluthrin were provided either alone or in combination with LLINs, malaria parasite prevalence was reduced by between 77% and 94% [
11]. However, overall evidence remains inconclusive and findings of this China study particularly had very large confidence intervals because of very low number of cases, therefore, reducing the strength of the evidence [
11]. Indeed, a recent Cochrane review on this subject concluded that although some studies have found a protective effect, it remains unclear if spatial repellents are effective at reducing the risk of malaria infection, and that further well-designed studies must be conducted in order to improve the certainty of evidence [
12].
A major challenge observed in the two trials above was that they both relied on mosquito-coils, which required daily replacement and high user compliance. Fortunately, new formats are now available for dispensing spatial repellents without application on human skin or burning coils, thereby minimizing challenges associated with compliance. For example, in previous studies where transfluthrin was applied to hessian strips and used outdoors, at least 80% bite prevention was observed consistently over 6 months without any sign of mosquito diversion to non-users within an 80 m radius [
13]. These area-wide mosquito repellent formats offer protection in form of passively-dispensed vapours, without any external energy for vaporization, and could be highly applicable in low-income or remote communities [
14]. With regard to transfluthrin, which is one of the most widely used spatial repellent compounds, hessian-based fabrics have particularly demonstrated a high level of retention for the insecticides, and can maintain efficacy for up to half a year [
13,
14]. In east Africa, the transfluthrin-treated hessian is also highly acceptable by the rural communities and can be produced locally, making such approaches even more applicable for low-income rural communities [
15].
Another vector control intervention considered readily applicable for low-income households, and which could be highly complementary to LLINs and IRS is improved housing. Despite ongoing economic transitions, millions of people in rural and peri-urban Africa still live in poorly-constructed houses with unscreened windows and open eave spaces. These gaps and spaces let in
Anopheles mosquitoes, and represent a significant gap in malaria vector control beyond the times when LLINs are effective [
16,
17]. Since majority of malaria transmission in Africa still occurs indoors [
18], house improvement initiatives, such as screening doors, windows and eave-spaces are among the best for curbing mosquito-borne disease transmission [
17,
19]. Indeed, various interventions targeting these spaces already exist. Examples include blocking the eave spaces [
19], using insecticidal eave-baffles and window screens [
20], and deploying eave-tubes [
21]. However, these methods will only target endophilic and endophagic vector populations, leaving the people outdoors exposed to exophagic and exophilic mosquitoes when they are performing various outdoor activities, such as cooking, storytelling and fetching water [
22]. Indeed, in many African communities, families spend long evening hours outdoors performing various activities [
23,
24], and sometime even entire nights outdoors, due to factors such as high temperatures indoors and small size of houses.
In this current study, a new approach, hereafter called eave ribbons (ER) is presented which: (a) exploits the eave spaces being the preferred entryway for
Anopheles mosquitoes, (b) improves delivery of spatial repellents such as transfluthrin, (c) does not require frequent retreatments or high-levels of user-compliance, (d) does not restrict human movements, and (e) provides significant protection from indoor-biting to outdoor-biting mosquitoes for potentially long durations without requiring any electricity. This approach is an adaptation from the previously tested transfluthrin-treated hessian fabric [
13,
15,
25]. The new format can be easily fitted onto the eave spaces around human houses. Because of its simplicity, the eave ribbon technology provides a readily-scalable option for using effective spatial repellents against common malaria vectors even in poorly-constructed houses in rural and remote communities.
Discussion
Spatial repellents are considered potential alternatives for malaria vector control and could be applicable alongside existing interventions such as LLINs and IRS. However, there have been challenges associated with low compliance rates [
8], poor delivery formats that cannot be readily scaled-up, high costs and lack of effective spatial repellent compounds with suitable safety profiles. The work presented here was an attempt to address most of these challenges by developing a low-cost, easy-to-use and highly scalable format that is applicable for even poorly-constructed houses in remote communities. A format previously tested by Ogoma et al. and demonstrated to provide long-lasting protection up to 6 months [
14] or more [
13] was adopted. Using the same hessian fabric, simple eave ribbons were created that can be fitted alongside any house type without necessarily covering eave spaces.
This study has demonstrated that the approach can confer protection against indoor and outdoor bites of the major malaria vector
An. arabiensis in both semi-field and field settings. Targeting the eaves with treated ribbons reduced indoor mosquitoes substantially while also protecting individuals outdoors in the peri-domestic area. This means the technology could be highly suitable for communities where people spend significant amounts of time outdoors before eventually going indoors to sleep under their bed nets. Previous studies targeting eaves with insecticidal treatments were able to demonstrate reduction of indoor densities and biting risks, but did not show any benefits against outdoor densities or biting risk [
20]. Similarly, eave screening measures have been widely used to limit malaria vector densities indoors in multiple countries and even demonstrated to reduce malaria incidence [
17,
41,
42]. The approach developed here uses spatial repellent treated fabrics along the eaves of houses, thereby preventing entry through repellency, while also providing protection to people in the nearby environment. Other additional advantages here would be that: (a) it protects multiple people at the same time, (b) it does not require direct application of the repellents on human skin and (c) by hanging the products high up close to the eaves, it prevents human contact with the treated surfaces.
A major determinant of the overall efficacy of this approach was the concentration of transfluthrin used. While this study was primarily designed to demonstrate potential of this approach of using eave ribbons, it will be important that future developments of the technology focus also on finding appropriate active ingredients and doses that are both effective and safe. In this study various dosses were assessed and observed high levels of protection even with doses as low as 0.02% transfluthrin, equivalent to 0.25 g/m
2. Eave ribbons treated with 5%, 1.5% and 0.2% transfluthrin all achieved near complete protection, i.e. > 99% against both indoor and outdoor biting mosquitoes, while the ones treated with 0.02% provided between 56 and 72% protection in the semi-field. These results corroborate the previous studies, which demonstrated that treated hessian strips can offer more than 75% protection against outdoor mosquito bites for long-periods [
13].
With regard to indoor mosquito bite prevention, the current study findings also match the previous work which involved window-screening and eave-baffles treated with combination of insecticides, and which also offered significant biting protections indoors [
20]. However in those previous studies, and also in other experiments to evaluate related technologies such as eave tubes [
21], no effects outdoors were expected and were therefore not measured. In this current study however, the untreated eave ribbons installed along the eave-spaces of the huts did not reduce mosquito densities indoors by more than one-third, and only marginally increased outdoor biting risk, though neither of these effects were statistically significant relative to controls. This demonstrates that biting prevention offered by the ribbons was due primarily to the spatial repellent treatment as opposed to the physical barrier effect.
Whereas it may be more directly beneficial to just fully screen the houses, the eave ribbons approach enables protection for even poorly-constructed houses with multiple other openings on walls and eaves, but which can still be protected without full screening. This way, the technology is more readily scalable even to very low income households and even in housing structures considered not amenable to screening or other technologies such as eave tubes [
21] or eave baffles [
20]. In an ongoing study in Tanzania, the technology is currently being evaluated for protection of migratory rice farmers who typically dwell in temporary semi-open shanty-like structures for long period of time (sometime up to 6 months) while tending to their crops (Kyeba Johnson Swai; Personal Communication). While house screening, IRS or LLINS may not be readily applicable for such migratory farming households [
32] the eave ribbons approach would be directly applicable. The technology could potentially also be applicable to other itinerant populations e.g. pastoralists, fishermen and forest workers.
Both personal and household protections offered by the eave ribbons are crucial not only in south-eastern Tanzania, but more generally in context of community life in many rural malaria-endemic developing countries. In such settings, early in the evening and mornings, significant proportions of individuals are usually active within the peri-domestic area, performing various activities e.g. cooking, storytelling, washing dishes and performing other domestic activities that put them at risk of being bitten by disease transmitting mosquitoes if not protected [
22,
24,
32]. It can be expected that technologies such as the one tested here would offer protection to multiple family members outdoors. In the different study when the treated hessian strips were used outdoors, there was sufficient biting protection within a 5 m radius [
13], which was also the case for the treated eave ribbons when fitted along the eave-spaces of the hut shown to offer protection to human at peri-domestic areas.
The levels of protective efficacy demonstrated by the treated eave ribbons in this study, could potentially be further improved by adding odour-baited traps or lure and kill technologies so as to achieve high levels of communal level protection beyond the household and personal protection currently observed. Indeed, this has already been demonstrated in small-scale in push–pull approaches [
43,
44]. A study by Menger et al. demonstrated that such push–pull effects may however be greater at community level than in the peri-domestic areas [
43], most likely because of the traps, when placed near houses lure the mosquitoes to the area, potentially increasing risk in the peridomestic space, and but the trapped mosquitoes are killed, thereby reducing overall risk at community level overtime. It is particularly interesting that the Menger et al. study also applied a form of eave wrappings similar to the eave ribbons used here, though using a different fabric. It is clear therefore that this approach, though originally tested as a component of push–pull could be a highly effective stand-alone product for personal and household level protection (Table
2).
In the field settings the eave-ribbons offered significant protection of more than 80% against
An. arabiensis mosquito bites for both outdoors and more than 90% indoors. This corroborates results obtained in the semi-field system. Additionally, there was more than 30% reduction in
An. arabiensis mosquitoes found resting on the walls of the huts with the eave ribbons compared to huts without the ribbons (control). However, for
An. funestus, also a major malaria vector, the ribbons offered only modest protection of approximately 40% both indoors and outdoors. This too is in line with a previous study, which involved using the transfluthrin actively dispensed at the peri-domestic areas in a push–pull approach whereby the approach did not significantly reduce
An. funestus biting and it increased possibility of mosquito diversion effect [
44]. The unresponsiveness of
An. funestus towards the eave-ribbons might be due to strong levels of insecticide resistance [
36] and possibly the strong anthropophilic tendencies of this species [
45]. The eave-ribbons also reduced secondary malaria vectors biting risk by approximately 55% at both indoor and outdoor, which is crucial as these vectors can also play a role in contribute malaria transmission [
46]. However, the ribbons offered minimal biting protections of less than 40% from the non-malaria vectors such as
Culex species, which are mostly nuisance biters but can also transmit other mosquito-borne infections like filaria worms and arboviruses.
Although, the eave-ribbons have demonstrated significant protection in this study, this intervention faces a challenge of low temperatures which hinder the vaporization of the transfluthrin (spatial repellents) hence lowering its efficacy in cold evenings and nights or generally in cold climates. In the field evaluation of the push–pull system, average nightly temperatures of 22.9 °C and 73% relative humidity were recorded, at which there was still substantial protection. It has been shown that conditions significantly below room temperature can reduce the biting protection offered by the treated materials such as sisal strips and sisal decorative materials [
13,
15]. The intervention is, therefore, mostly useful for the tropical and sub-tropical countries. However, this temperature effect is not considered a major barrier simply because mosquito-borne illnesses are also more prevalent in hot temperate climates than in cold climates. The need for this technology therefore diminishes with diminishing temperatures, and the fabric will retain the active ingredient until temperatures rise, which would be coincident to the time when biting risk also rises. One limitation with this study was that the exact amount of transfluthrin adsorbed into the hessian fibres was not determined. Future developments of this technology could benefit from microencapsulation techniques and also assessment techniques that measure exact doses in the treatments and also the actual decay rates over time at different temperatures.
For these prototypes tested here, only 7 US dollars was needed to make and install the sets of treated eave-ribbons per experimental hut, possibly accommodating four people. This is just under the cost of bed nets, which cost up to 5 USD (including manufacturing and distribution costs), and can protect a maximum of two people only indoors (with no protection to people who are active outdoor before getting indoors to sleep). Thus, the eave ribbon technology, if developed further could offer an effective, scalable and low-cost complementary tool to be used alongside LLINs and IRS even in low income communities.