Enhancing protection against vector-borne diseases in forcibly displaced communities: evaluating the efficacy of spatial repellents for cutaneous leishmaniasis control in North-East Syria

Enhancing protection against vector-borne diseases in forcibly displaced communities: evaluating the efficacy of spatial repellents for cutaneous leishmaniasis control in North-East Syria | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Enhancing protection against vector-borne diseases in forcibly displaced communities: evaluating the efficacy of spatial repellents for cutaneous leishmaniasis control in North-East Syria Richard Allan, Ramona Scherrer, Ozge Erisoz Kasap, Laura Paris, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6664771/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Jul, 2025 Read the published version in BMC Medicine → Version 1 posted 13 You are reading this latest preprint version Abstract Background In Syria, 14 years after the outbreak of civil war, 16.7 million people have been forced to flee their homes and 7.2 million remain internally displaced in 2025. Breakdown in waste management caused by aerial bombardment has created ideal conditions for cutaneous leishmaniasis (CL) transmission, vectored by phlebotomine sandflies. Displaced populations reside in flimsy shelters where conventional vector control tools are operationally unfeasible. A small, lightweight, portable transfluthrin-based spatial repellent (Mosquito Shield™) has been developed which may circumvent some of these logistical issues and provide improved protection from vector-borne diseases in harsh environments. Methods A two-arm, non-randomized cluster trial was undertaken in Ar-Raqqa governorate, North-East Syria, to evaluate the efficacy of Mosquito Shield™ in reducing CL case incidence and sand fly densities in shelters. Weekly epidemiological monitoring was performed by MENTOR Initiative mobile clinics and supported health facilities. Entomological monitoring was performed fortnightly using indoor U.S. Centers for Disease Control and Prevention light traps in 40 randomly selected households per study arm. Phlebotomine sandflies were morphologically identified; a sub-set were analysed for molecular species confirmation, bloodmeal preferences and pyrethroid resistance. Household surveys and focus group discussions were used to assess intervention feasibility, acceptability and uptake. Results Assuming a 2-month diagnosis cut-off, the CL incidence rate was 9.9 and 5.2 per 1,000 in the control and the intervention arms, respectively; Mosquito Shield™ demonstrated a significant impact on rate of CL infection in all ages (incidence rate ratio; IRR: 0.52 [95% CI: 0.37–0.74]; p < 0.0001). Mosquito Shield™ demonstrated a significant impact on all female sand fly density (IRR: 0.22 [95% CI: 0.14–0.33]; p < 0.0001) and blood-fed female sand fly density (IRR: 0.21 [95% CI: 0.11–0.40]; p < 0.0001). Mosquito Shield™ was received positively and perceived to be easy to use, to protect from CL, sandflies and other insect bites and required minimal behaviour change. Conclusions Trial findings provide the first demonstrable impact of spatial repellents on CL transmission, strengthening the growing evidence basis for the effectiveness of this intervention against multiple vector species and their associated pathogens. Study results strongly support the deployment of spatial repellents to control CL in humanitarian crises. Trial registration ClinicalTrials.gov, NCT06917040. Conflict internally displaced persons cutaneous leishmaniasis temporary shelter vector control spatial repellents Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Around 80% of the world’s population are at risk from vector-borne diseases (VBDs), which kill more than a million people each year [ 1 ]. However, the majority of these deaths and immeasurable suffering occur in countries devastated by conflict or natural disaster driven humanitarian crises [ 2 ]. The number of armed conflicts and extreme weather events has multiplied dramatically since the end of the Cold War [ 3 , 4 ]. These disproportionately affect regions of the world that are endemic for VBDs and displace more people globally than at any other time in history. Currently, there are 114 ongoing armed conflicts worldwide [ 5 ]; there are 35 armed conflicts across 12 countries in sub-Saharan Africa, 21 in Asia, 6 in Latin America and 7 in Europe [ 5 ]. Forty-five of these are in the Middle East and North Africa, of which Syria continues to be one of the worst affected, 14 years after the outbreak of civil war; 16.7 million people have been forced to flee their homes and 7.2 million remain internally displaced in 2025 [ 6 , 7 ]. As of June 2024, worldwide, a staggering 122.6 million people have been forced from their homes on unimaginable journeys, often without shelter for long periods, followed by years living in camps or poor urban squalor [ 8 , 9 ]. Around 305 million people, including the displaced and many of the communities that host them, are dependent upon humanitarian assistance for their very survival [ 10 ]. These are the most vulnerable to infectious diseases and malnutrition, have the least access to emergency services and are the most likely to die [ 11 , 12 ]. Mosquitoes are overwhelmingly the most important disease vector in most humanitarian crises, where they transmit malaria, dengue fever, yellow fever, chikungunya, Zika virus and West Nile virus. Syria is a notable exception, where leishmaniasis, an endemic parasitic disease transmitted by sandflies, was historically centred around just a few foci, but now predominates. This disease has escalated to epidemic levels across the north of the country in parallel with the onset of mass urban destruction and population displacement following the outbreak of war in 2011. If not diagnosed and treated effectively, the cutaneous form can result in permanent severe scaring, disfigurement and stigmatisation, and sometimes death. The visceral form, though less common, if untreated, usually results in death [ 13 – 15 ]. Mosquitoes, sandflies and other blood-feeding arthropods require regular vertebrate blood for oogenesis [ 16 ]. Their blood feeding preferences often correlate with common human behaviour patterns, defined time frames and contexts when people are most accessible and vulnerable to attack. Such arthropod behaviour, however, also presents unique opportunities to deploy appropriate control tools to reduce the risk of disease transmission and abate the vector population. For decades, malaria has dominated the global public health agenda and naturally also entomological research. This has driven understanding of mosquito behaviours and extraordinary achievements in disease control since 2000, by scaling up access to two core malaria interventions, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), alongside significant advances in diagnostics, therapeutics and vaccines to reduce malaria in stable settings [ 17 ]. The success of LLINs and IRS has been in targeting the predominantly indoor, nocturnal blood feeding behaviour of many of the most effective mosquito vector species; behaviour and vulnerability to control largely shared by phlebotomine sandflies, the vectors of leishmaniasis. However, the more challenging needs of displaced and conflict affected populations have exposed the limitations of these two key vector control tools in tackling both diseases [ 2 , 18 , 19 ]. In conflict settings, people may be displaced for years, living under temporary shelter or in damaged buildings shared with multiple families. Standard LLINs generally do not last very long and rapidly fall apart in such harsh conditions [ 20 ]. LLINs are bulky, slow and expensive to transport, limiting them operationally. The different shapes and sizes of temporary shelters used by displaced people, render LLINs a very poor tool choice ergonomically. While IRS is a somewhat more versatile format for targeting insecticides to a diversity of different shelter formats, it requires mobilization and training of specialist teams, as well as significant logistical and operational campaign infrastructure that may take too long to establish or be excessively risky in many conflict settings [ 18 , 19 ]. Sustained aerial bombardment of cities and towns across northern Syria has caused a vast scale of destruction and the breakdown of municipal waste management services. This has created ideal conditions for the proliferation of Phlebotomus (Ph.) papatasi and Ph. sergenti sandflies [ 21 ] and transmission of Leishmania tropica , and L. major , the causative agents of cutaneous leishmaniasis (CL) [ 13 , 15 , 22 , 23 ]. The extraordinary scale of destruction and forced population movement has inevitably resulted in sustaining epidemic levels of disease transmission and the onward transmission of CL into previously non endemic areas and across international borders [ 24 ]. The 7.8 magnitude earthquake that struck on 6th February 2023 caused further devastation in North-West Syria and South-East Turkey [ 25 ]. This exacerbated the risk posed by leishmaniasis and further exposed the limitations of IRS and LLINs used at scale from 2013 to 2024 to protect people across northern Syria by The MENTOR Initiative, an international non-governmental organisation (NGO) [ 13 ]. Recognising the inherent operational shortcomings of IRS and LLINs, there is an urgent need to evaluate novel vector control tools that are light weight, highly portable and easily implementable in humanitarian crises, especially in displaced populations residing in flimsy temporary shelters with exposure to the elements. Spatial repellents interrupt human-vector contact by eliciting a range of behaviours in insect vectors, including movement away from chemical stimuli, interference with host detection, attraction inhibition, and/or reduced feeding response, thereby providing protection from daytime, early evening and night-time biting. Spatial repellents can provide protection in enclosed/semi-enclosed and peri-domestic spaces and increase coverage of vector control compared to traditional methods [ 26 – 28 ]. Mosquito Shield™ is a commercially manufactured spatial repellent emanator containing transfluthrin. Transfluthrin is a fast-acting volatile pyrethroid with low persistency, which can either act by inducing vector mortality or via sublethal toxicity, causing repellency and thereby reduction in host-vector contact. The chemical passively releases into the air, creating a vapor space, and interacts with vector odour receptors, causing irritation; vectors do not need to directly contact an insecticidal-surface, but rather the continual release of transfluthrin builds a protective atmosphere in enclosed or semi-enclosed spaces [ 29 , 30 ]. Prior to this current study, transfluthrin emanators have demonstrated significant protective efficacy (PE) from malaria in a cluster-randomized controlled trial (cRCT) in Indonesia [ 30 ], reduction in Aedes -borne viruses in Peru [ 31 ] and decrease in malaria case incidence in Kenya [ 32 ]. This study was the first to evaluate the feasibility, acceptability and PE of the spatial repellent emanator Mosquito Shield™, as an alternative vector control tool for the control of sandflies and CL amongst displaced and conflict affected populations in North-East Syria. Methods Study design and setting The aim of this study was to determine the efficacy of Mosquito Shield™ as a CL control tool in active conflict zones amongst internally displaced persons (IDPs) living in temporary shelter camps. The primary trial objective was to evaluate the PE of Mosquito Shield™ against CL case incidence in all ages during 1 year of follow-up. The secondary trial objectives were to evaluate the impact of Mosquito Shield™ on phlebotomine sand fly population density inside shelters during 9 months of follow-up and to assess the acceptability of Mosquito Shield™ as a CL control tool, in a context where LLINs and IRS are operationally unfeasible. This study was conducted between February 2021 and April 2022 in Ar-Raqqa governorate, an area of North-East Syria hosting IDPs, living in organised camps composed of temporary shelters made from heavy duty tarpaulins or factory-made family tents, supplied by the United Nations High Commissioner for Refugees (UNHCR). Camp residents originated from the neighbouring governorates of Hama, Homs and Deir-ez-Zor, and from the northern regions Tell Abiad, Ein Issa and Suluk [ 33 ]. The study setting was chosen based on increasing CL cases during the war and the accessibility of the region. The CL vector species in this area were Ph. papatasi and Ph. sergenti [ 21 ], both responsible for transmitting L. tropica and L. major [ 15 ]. To test the efficacy of Mosquito Shield™ in reducing CL case incidence among IDPs and sand fly density in temporary shelters, a two-arm, non-randomized cluster trial was undertaken in Ar-Raqqa governorate, North-East Syria (Fig. 1). Eligibility and allocation Initially 23 clusters, each housing IDPs, were identified in Ar-Raqqa governorate, North-East Syria. Seventeen clusters were excluded because they did not meet study inclusion criteria or were unsafe to access. Eligibility criteria for clusters were a known history of CL, comparable shelter type (all distributed by UNHCR), water access, latrine resources and environmental conditions, accessibility by road, a minimum distance of 5 km between clusters, and adequate security levels. Global Positioning System (GPS) data of this governorate were plotted as open circles at 1:80,000 and examined for formal and informal camps housing IDPs in relatively isolated locations. Google Maps satellite view was searched for major population centres and if a camp was less than 5 km away, the camp was excluded. If a camp was less than 5 km away from a neighbouring camp, it was also excluded to ensure no risk of intervention contamination. Six camps were eligible and selected to achieve a minimum of 6,951 individuals per study arm. Two camps were allocated Mosquito Shield™ in all temporary shelters, and 4 camps were allocated as control clusters (Fig. 2). The rationale for this pragmatic study design considered: (i) security and camp accessibility concerns for weekly post-intervention monitoring; and (ii) perceived discontentment, regarding intervention allocation, if control and intervention camps were neighbouring. Intervention arm The study intervention was Mosquito Shield™ (S.C. Johnson & Son, Racine, WI, USA). The active ingredient is transfluthrin (C 15 H 12 Cl 2 F 4 O 2, 110 mg / Mosquito Shield™, EPA Reg. number 432–1588) and it releases on a controlled basis over a 1-month period (1 emanator in rooms up to 18 m 2 / 2 emanators per 9 m). The study population of the intervention arm, in camps Tawihena and Mahmoudli, was provided with Mosquito Shield™ for 9 months between April and December 2021 (Fig. 3A). Mosquito Shield™ was distributed directly to households every month, together with nails and string for installation and pictogram instructions in the local language describing the correct intervention usage, including how to open Mosquito Shield™, the number of Mosquito Shield™ to be installed per room, and duration of Mosquito Shield™ usage (30 days) prior to replacement (Fig. 3C). Shelter occupants were shown how to install and replace Mosquito Shield™ and they attached Mosquito Shield™ to the wall surface above head level with the impregnated side pointing towards the room (Fig. 3A) and replaced them when distributed each month. Control arm The study population of both the control (Royan, Sahlat Al Banat and Tel Elsamen camps) and intervention arms received information, education and communication (IEC) campaigns by the MENTOR Initiative study team, reinforced with brochures and posters throughout the study period (Fig. 3B). The standardized IEC messages included information on the transmission of CL, the prevention of CL, clinical symptoms, correct treatment seeking practices and where to seek treatment. All camps had free access to diagnostic and treatment services for CL during the study period as encouraged by the IEC campaigns, either via MENTOR Initiative mobile clinics or via nearby MENTOR Initiative supported health facilities. Passive treatment seeking was reinforced by active identification and referral of suspected CL cases by the MENTOR Initiative study team when conducting entomological surveillance activities at the household level. Epidemiological monitoring Epidemiological monitoring was conducted for 1 year between April 2021 and April 2022, due to the long incubation time of CL (2–8 months between infection and onset of symptoms) [ 34 ]. All patients were clinically assessed in MENTOR Initiative mobile clinics (once or twice weekly each month) or by MENTOR Initiative supported health facilities (diagnosis and treatment provided 2 days per week), according to the comprehensive WHO standardized clinical guideline [ 34 ]. Clinically confirmed patients, based on direct parasitological observation in skin scrapings, were treated with sodium stibogluconate (20 mg Sb 5+ / kg per day for 21 days), according to the WHO treatment protocol [ 34 ]. Data on newly diagnosed patients per month was collected in both study arms, including the date of diagnosis, the estimated date when clinical symptoms started, sex, age, and the date of movement into the camp. Each patient was provided with a card, and each CL case was assigned a unique identifier to track treatment and clinical prognosis, including treatment failure and relapse. Standard operating procedures were in place to minimize the risk of re-registration of the same patient. Entomological monitoring For the entomological monitoring, U.S. Centers for Disease Control and Prevention (CDC) light traps were set up in 40 randomly selected households per study arm every fortnight. Entomological monitoring was performed by camp residents, trained by the MENTOR Initiative. CDC light traps were installed 1-1.5 m from the ground in the morning, turned on at sunset and collected the following morning. Baseline assessment was conducted between February and March 2021, followed by fortnightly entomological monitoring from April to December 2021 (2 trap nights per month). All CDC light traps were exclusively used inside camp shelters due to security considerations. Entomological monitoring was conducted in both intervention camps and 3 control camps (Tel Elsamen, Sahlat Al Banat and Khayala) due to operational constraints; Khayala camp was included for entomological monitoring, performed by camp residents, but not epidemiological monitoring because of security concerns for safe access by external mobile clinics. Laboratory analysis Sand flies collected from CDC light traps were frozen at -20°C. Entomological identification of sand flies was undertaken using magnifying glasses. The number of males / females were recorded per trap, and females were further classified as blood-fed / non-blood-fed. All females were preserved in Eppendorf tubes containing 100% (v/v) ethanol and refrigerated at 4°C. A random subset of entomological samples per camp were transported for further analysis to the University of Hacettepe in Ankara, Turkey. Preserved sand flies were morphologically analyzed to confirm species identification using dichotomous keys available for Old World sand flies [ 35 – 39 ]. The head and the last 2–3 abdominal segments of each specimen were dissected, cleared in Marc-André solution and mounted in a drop of Swan solution. The thorax and the rest of the abdominal segments of each specimen were stored in 70% (v/v) ethanol for molecular analyses. Genomic DNA from individual female sandflies was extracted using the Qiagen DNeasy Blood and Tissue Kit, according to the manufacturer’s instructions, and stored at − 20°C. To identify host preferences of blood-fed female specimens, a ~ 340bp region of mammalian 12S rRNA gene was amplified using the Mam12S-340F and Mam12S-340R primers, according to [ 40 ]. Polymerase chain reaction (PCR) reactions were conducted in 50µl final volume and contained 2µl template DNA, 10X NH 4 buffer, 4µl of 2.5mM dNTPs, 2µl of each primer (10 pmol/µl), 2µl of 25mM MgCl 2 and 0.4µl of Taq polymerase. Reaction conditions were an initial denaturation step at 94°C for 2 minutes; 35 cycles of 94°C for 30 seconds, 45°C for 30 seconds, and 72°C for 45 seconds; and a final extension of 72°C for 5 minutes. To detect the presence of the knock-down resistance ( kdr ) mutation, L1014F, indicative of pyrethroid resistance, a ~ 360bp region of the voltage-gated sodium channel ( vgsc ) that included the codon 1014, was amplified using the Vssc8F and Vssc1bR primers [ 41 ]. PCR reactions were conducted in 50µl final volume and contained 2µl template DNA, 10X NH 4 buffer, 3µl of 2.5mM dNTPs, 2µl of each primer (10 pmol/µl), 2µl of 25mM MgCl 2 and 0.25µl of Taq polymerase. Reaction conditions were an initial denaturation step at 95°C for 5 minutes; 36 cycles of 94°C for 45 seconds, 51°C for 50 seconds, and 72°C for 50 seconds; and a final extension of 72°C for 7 minutes [ 42 ]. To confirm species identification of Sergentomyia (S.) clydei (n = 1) and Sergentomyia dreyfussi (n = 3), a ~ 650bp barcoding region of cytochrome oxidase 1 ( cox1 ) was amplified using the universal LCO1490 and HCO2198 primers [ 43 ]. PCR reactions were conducted in 50µl final volume and contained 2µl template DNA, 10X NH 4 buffer, 3µl of 2.5mM dNTPs, 2µl of each primer (10pmol/µl), 2µl of 25mM MgCl 2 and 0.25µl of Taq polymerase. Reaction conditions were an initial denaturation step at 95°C for 5 minutes; 34 cycles of 95°C for 30 seconds, 48°C for 30 seconds, and 72°C for 45 seconds; and a final extension of 72°C for 10 minutes. Amplification products for all PCRs were visualized on 2% stained agarose gels. The purified PCR products were sequenced in both directions using the same primer pairs for the amplification reactions at BM Labosis Company, Ankara, Turkey. Raw sequences were aligned and edited using the ClustalW Multiple Alignment algorithm implemented in BioEdit v7.2.5 [ 44 ]. 12S rRNA mammalian sequences were compared with reference sequences in NCBI GenBank using the the Basic Local Alignment Search Tool (BLAST) ( http://www.ncbi.nlm.nih.gov/BLAST ) algorithm. Barcoded Se. clydei and Se. dreyfussi showed 97.74–98.59% and 95.58–96.18% homology with reference sequences in NCBI GenBank, respectively (Reference Accession Numbers: Se. clydei : KJ481134 and OR671496; and Se. dreyfussi : MT644236 and KJ481106). Vgsc sequence data were compared with reference wild type and mutant sand fly sequences available in NCBI GenBank, to screen for common kdr mutations at codon 1014. To assess the presence of Leishmania in sand fly specimens, monospecific pools were prepared by transferring 2–11 female sand flies into Roche Magna Lyzer™ tubes. The reference strain Le. tropica MHOM/PS/2001/ISL590 was used as a positive control, while body parts from male sand flies were used as negative controls. Homogenization was performed using the Roche Magna Lyser™ (Mannheim, Germany) at 7,000 rpm for 90 seconds. The resulting homogenates were resuspended in 200µl of Qiagen® tissue lysis buffer and incubated overnight at 56°C. Following incubation, genomic DNA was extracted using the Roche High Pure PCR Template Preparation Kit (Mannheim, Germany), with the final elution step carried out in 50µl of elution buffer to maximize DNA yield. Amplification of total genomic DNA was conducted using LITSR and L5.8S primers under PCR conditions previously described by [ 45 ]. PCR products were visualized on a 1.2% agarose gel. Positive amplicons were purified and subsequently sequenced commercially (MedSanTek, Istanbul, Turkey). Raw sequence data were analyzed using Geneious R8 software, and identity confirmation was performed via comparison with GenBank entries using BLAST. The minimum infection rate (MIR) was calculated using the formula: (number of positive pools / total number of specimens tested) × 100, as described by [ 46 ]. Intervention feasibility, acceptability and uptake monitoring Mosquito Shield™ feasibility, acceptability and uptake was monitored in 40 randomly selected shelters each month in the intervention arm, using a cross-sectional survey from June – December 2021. The total number of Mosquito Shield™ emanators distributed per household during the trial was recorded by the study team. At the end of the study period (April 2022), a focus group discussion (FGD) was conducted in Mahmoudli camp with women (n = 7) and a FGD was conducted in Tawihena camp with men (n = 7), to determine context-specific modifiers of intervention community acceptance, usage, perceived benefits, accessibility and affordability. Study variables The epidemiological endpoints were the CL incidence rate ratio (IRR) between intervention and control arms and the PE of Mosquito Shield™. The entomological endpoints were the IRR between intervention and control arms for female phlebotomine sand fly density (all physiological status), blood-fed female phlebotomine sand fly density and density of both sexes of phlebotomine sandflies. The intervention feasibility, acceptability and uptake endpoints were the proportion of the surveyed study population retaining Mosquito Shield™ for 1-month post-distribution, perceived reduction of insect numbers and insect bites in the household, and the acceptability of Mosquito Shield™. Sample size Assuming a CL incidence of 10 cases per 1,000 individuals, a coefficient of variation (CV) of 0.69 (MENTOR Initiative, unpublished data), to detect a 50% reduction in CL in the intervention arm compared to the control arm, with 80% power at the 5% significance level, a sample size of 6,951 individuals per study arm was required [ 47 , 48 ]. Entomological sampling followed a standardized protocol using previously evaluated methods by the MENTOR Initiative in the study setting [ 49 , 50 ]. Statistical analysis Analysis of the CL incidence rate included all newly diagnosed patients who were infected in the study camps after the first Mosquito Shield™ distribution. The analysis considered two different incubation times or diagnosis cut-offs: at 2 months post-intervention (from June 2021 – April 2022) and at 4 months post-intervention (from August 2021 – April 2022). Incidence rates were calculated using the average population during the study period. Poisson regression was carried out with CL cases as response and the study arm as an explanatory variable, reporting IRR. PE was calculated as (1-IRR)x100. Differences in the density of female phlebotomine sandflies, female blood-fed phlebotomine sandflies and both sexes of phlebotomine sand fly were analysed using mixed effects negative binomial regression, with study arm as a fixed effect and collection month, household and camp as random effects. No sub-analysis was performed per species due to low sample sizes of the minority species present. An alpha level of p = 0.05 was used for significance testing. No missing data were reported. All statistical analyses were performed using STATA/SE 17.0. Data were visualized in RStudio v2024.12.1 + 563 [ 51 ]. Results The total population during the study period (April 2021–2022) was 18,404, residing across intervention (11,430) and control (6,974) camps. Camps were balanced with regards to shelter and housing source and type; epidemiological data were collected by MENTOR Initiative supported health facilities and mobile clinics (Table 1 ). In the intervention arm a total of 90,782 Mosquito Shield™ emanators were distributed during the study across 2,153 shelters, with a mean of 5.7 Mosquito Shield™ units (standard deviation (SD) ± 0.016) distributed per house. Table 1 Characteristic of the study camps. Camp name Study arm IDP origins Camp management Camp population Shelter type / material MENTOR Initiative mobile clinic MENTOR Initiative supported health facility Khayala camp Control Hama, Homs Community leader Informal IDP settlement UNHCR tents / plastic sheets No Yes Royan camp Control Hama, Homs Community leader Informal IDP settlement UNHCR tents / plastic sheets No Yes Sahlat Al Banat camp Control Hama, Homs, Deir Ezzor Community leader Informal IDP settlement UNHCR tents / plastic sheets Yes Yes Tel Elsamen camp Control Tal Abyad, Ras Al Ain Blumont (NGO) Informal IDP settlement UNHCR tents / plastic sheets Yes Yes Tawihena camp Intervention Hama, Homs, Deir Ezzor Blumont (NGO) Formal IDP settlement UNHCR tents / plastic sheets No Yes Mahmoudli camp Intervention Hama, Homs, Deir Ezzor Blumont (NGO) Formal IDP settlement UNHCR tents / plastic sheets No Yes Epidemiological impact Assuming a 2-month diagnosis cut-off, a total of 128 cases of CL were reported at the MENTOR Initiative mobile clinics and supported health facilities from June 2021 – April 2022. The mean age was 21.5 years (SD ± 15.11) and 48% of the cases were female. The incidence rate of CL was 9.9 and 5.2 per 1,000 in the control and the intervention arms, respectively (Table 2 and Supplementary Table S1 ). Mosquito Shield™ demonstrated a significant impact on rate of CL infection in all ages (IRR: 0.52 [95% CI: 0.37–0.74]; p < 0.0001); thus, the PE of Mosquito Shield™ was 48%. The median number of months to develop CL infection from the beginning of the study was 7.43 (SD ± 2.30) and 8.16 (SD ± 2.12) in the intervention and control arms, respectively. Table 2 Incidence of cutaneous leishmaniasis from June 2021 – April 2022 (using 2-months diagnosis cut-off). Population December 2020 – before intervention † Population March 2022 – after intervention † Average population during the study follow-up (Dec 2020 to March 2022) New cases of leishmaniasis during the study follow-up (June 2021 to April 2022) Incidence rate per 1,000 IRR [95% CI; p-value] Control arm 5,412 8,536 6,974 69 9.9 Intervention arm 11,060 11,800 11,430 59 5.2 0.52 [0.37–0.74]; p < 0.0001 Total study population 16,472 20,336 18,404 128 7.0 † Data from The MENTOR Initiative records. Assuming a 4-month diagnosis cut-off, a total of 115 cases of CL were reported at the MENTOR Initiative mobile clinics and supported health facilities from August – April 2022. The mean age was 21.6 years (SD ± 15.4) and 44% of the cases were female. The incidence rate of CL was 8.6 and 4.8 per 1,000 in the control and intervention arms, respectively (Supplementary Table S2). Mosquito Shield™ demonstrated a significant impact on rate of CL infection in all ages (IRR: 0.56 [95% CI: 0.39–0.81]; p = 0.002); thus, the PE of Mosquito Shield™ was 44%. Entomological impact A total of 928 sandflies were collected across 80 shelters (40 per study arm) from April – December 2021, using indoor CDC light traps (Table 3 and Supplementary Table S3). By comparison, no sandflies were collected from either trial arm during baseline (February – March 2021). Post-intervention, Mosquito Shield™ demonstrated a significant impact on all female phlebotomine sand fly density (IRR: 0.22 [95% CI: 0.14–0.33]; p < 0.0001) and blood-fed female phlebotomine sand fly density (IRR: 0.21 [95% CI: 0.11–0.40]; p < 0.0001) (Fig. 5). The peak in female sand fly density was July – September 2021, corresponding to a rise in CL cases in October 2021 – January 2022. An intervention effect was also evident when considering both sexes of phlebotomine sandflies (IRR: 0.20 [95% CI: 0.14–0.29]; p < 0.0001). The major vector species was Ph. papatasi (96.3%; 894/928), followed by Se. dentata (3.1%; 29/928), Se. dreyfussi (0.3%; 3/928); individual S. cyldei and Ph. sergenti were also collected (Supplementary Table S4). DNA barcoding was successful for Se. clydei and Se. dreyfussi , confirming the first report of both species in Syria. Bloodmeal analysis indicated that Ph. papatasi fed predominantly on humans (75%), followed by Ovis aries (12.5%) and Capra spp. (6.25%) (Supplementary Table S5). The vgsc -L1014F- kdr mutation was not detected in any sand fly sample screened from any camp (n = 25). One pool of Ph. papatasi from Khayala tested positive for Leishmania ; sequence analysis identified the species as Le. tropica . The MIR was estimated as 0.13% for Ph. papatasi . Table 3 Density of sandflies collected with indoor CDC light traps from April – December 2021. Study arm and location Number of households with light traps Total number of sandflies Number of female sandflies (%) Number of blood-fed female sandflies (%) Mean of sandflies per household collection (SD) Female sand fly density IRR [95% CI; p-value] Control 40 776 463 (59.7) 126 (27.2) 2.2 (5.1) Intervention 40 152 101 (66.4) 24 (23.8) 0.4 (1.3) 0.22 [0.14–0.33]; p < 0.0001 Total 80 928 564 (60.8) 150 (26.6) 1.3 (3.8) Intervention feasibility, acceptability and uptake Among 280 households where Mosquito Shield™ feasibility, acceptability and uptake was assessed, the mean age of the respondent was 41.5 years old (SD ± 1.07), most were male (75.7%; 212/280) and received no (40.7%; 114/280) or primary school education (35.7%; 100/280). Eighty-six per cent (241/280) of households reported that Mosquito Shield™ was very easy to use with no problems; 11.1% (21/280) reported it was easy, experiencing one or two problems. The instructional pictogram was considered very easy to understand by 91.4% (256/280) of respondents. Seventy-two per cent (203/280) of participants reported still using at least 1 Mosquito Shield™ after distribution, of which 97.1% (203/280) were placed at the correct height, 92.8% (194/280) were positioned in the correct orientation and 84.7% (177/280) were correctly spaced. Of the 27.5% (77/280) households which had stopped using Mosquito Shield™, the main reasons were: it kept falling down (33.8%; 26/77), it was not perceived to be effective (37.7%; 29/77), health / side effect concerns (23.4%; 18/77), the participant did not like the intervention (31.2%; 24/77) or it was expired (18.2%; 14/77). Forty-one per cent (116/280) of households had used alternate installation materials for Mosquito Shield™, including sewing with needle and thread (48.3%; 56/116), wire (41.4%; 48/116) or pins (6.9%; 8/116). Mosquito Shield™ was well received by study participants, with 54.2% (149/275) reporting that the intervention provided protection from insects; and 49.6% (139/280) and 52.5% (147/280) observing a decrease in perceived number of indoor insects or insect bites, respectively. Seventy-eight per cent (218/280) of respondents would use Mosquito Shield™ again; the easiest outlets identified for intervention distribution were NGOs / camp management / community leaders (72.5%; 203/280), the local market (14.3%; 40/280) or bakeries (11.1%; 31/280). At the end of the study period (April 2022) two FGDs were conducted with either women (n = 7) or men (n = 7) separately in Mahmoudli and Tawihena camps, respectively. Responses from both sexes were similar. In general, Mosquito Shield™ was perceived to be easy to use, to protect from CL, sandflies and other insect bites, require no behaviour change, be small, compact and lightweight with no side effects or smell. Additionally, respondents saved money because the intervention and access to healthcare was free, and they did not need to purchase other vector control tools. Participant recommendations to improve Mosquito Shield™ included decreasing the number of emanators required per room (to reduce plastic and logistical efforts), increasing the effectiveness for longer and improving its appearance. Regarding accessibility, women, younger, healthy and employed people and registered IDPs were perceived to have greater access to the intervention compared to older, disabled, illiterate or uneducated people with lower awareness of CL. Future access could be improved by identification of these individuals by camp management / community leaders / NGOs and by targeted distribution of the intervention free of charge directly to their homes. Participants suggested that the price of Mosquito Shield™ be adapted to the economic circumstances, be cheaper (or potentially free) in IDP camps than in urban settings and cost maximum US $ 0.2 per emanator. Unregistered IDPs, women without income and unemployed people were recognised as those who might be unable to afford the intervention; distribution for free by camp management / community leaders / NGOs, as part of other humanitarian aid and/or the provision of incentives were proposed mechanisms to mitigate financial barriers. Discussion Humanitarian crises are exceptional circumstances which critically threaten the health, safety, security and well-being of populations. Those forced to flee their homes and reside in temporary shelters or shared housing, are often exposed to hematophagous disease vectors and experience other co-morbidities and contributing factors, including anaemia, malnutrition, violence and trauma, and are therefore more likely to suffer ill health and die [ 12 , 52 – 54 ]. In areas of intense VBD transmission, related morbidity and mortality rates escalate in the early weeks of humanitarian crises, remaining high until the implementation of effective vector control [ 12 , 52 – 54 ]. Conventional vector control interventions, most of which were developed to interrupt malaria transmission, are predicated on living in a suitable housing or shelter structure, which can support a hanging LLIN, or insecticidal treatment of an interior wall surface; these methods are largely insufficient in some crises, suffering from both biological and operational constraints [ 55 ]. Vector control tools with robust epidemiological evidence are even more scarce for leishmaniasis in both stable and emergency settings [ 56 , 57 ]. Spatial repellents are a new vector control tool class that have several key characteristics rendering them highly suitable for use during humanitarian crises, particularly in remote, unsafe and inaccessible areas, or in very mobile populations that move with little forewarning. They are light weight, portable, and easily implementable, requiring minimal behavioural change. Furthermore, spatial repellents cannot be repurposed for any other function and remain viable when kept in storage for long time periods, allowing for intervention stockpiling in strategic locations for rapid deployment during crisis onset. In this trial, Mosquito Shield™ demonstrated a significant reduction in CL transmission during 1-year of follow-up in refugee camps in North-East Syria, with an estimated PE of 44–48%. These observations strongly align with previous evaluations of the same intervention, which reported a PE of 40.9% against malaria primarily transmitted by Anopheles (An.) vagus and An. sundaicus in Indonesia [ 30 ], a PE of 29.5% against malaria transmitted by An. gambiae sensu strictu, An. arabiensis and An. funestus in Kenya [ 32 ] and a PE of 34.1% from dengue and Zika viruses transmitted by Aedes (Ae.) aegypti in Peru [ 31 ]. Epidemiological observations were supported by a significant reduction in female Phlebotomine sand fly density (the majority of which were pyrethroid-susceptible, anthropophagic Ph. papatasi ), irrespective of physiological status (i.e. unfed, gravid or blood-fed) and density of both sexes of phlebotomine sandflies. These entomological effects were consistent with the mode of action of spatial repellents, i.e. deterrence from house entry and interference with human biting. By comparison to previous studies, the evidence for an impact of spatial repellents on entomological indices has been mixed. In Kenya and Indonesia, spatial repellents exerted no observable reduction in Anopheline vector populations [ 30 , 32 ], while in Peru, the abundance and blood-feeding rates of Ae. aegypti were reduced by 28.6% and 12.4%, respectively [ 31 ]. Other community-level evaluations of spatial repellents have reported promising results against pyrethroid-resistant An. arabiensis in Tanzania and An. gambiae sensu lato in Benin [ 58 , 59 ]. This discordance in entomological data has been attributed to relative differences in vector species feeding, host preferences and resting behaviours, underpowered trial designs and trapping techniques [ 30 , 32 , 60 ]. While evaluations of user acceptability and feasibility of spatial repellents have been more limited, trial results are also consistent with those from Cambodia, Peru and Thailand, where spatial repellents were well received by community members, who acknowledged the need for new vector control strategies and were willing to pay for them [ 61 , 62 ]. In this setting, Mosquito Shield™ was perceived to be easy to use, to protect from CL, sandflies and other insect bites, require minimal behaviour change, and have no side effects or smell. Feedback from study participants, particularly for longer lasting emanators, has already been addressed in more recent iterations of this intervention, which have recently demonstrated efficacy against mosquito vectors for 1 year in Phase II trials in Tanzania [ 63 ]. Study findings should be interpreted in the context of the following limitations. Several pragmatic operational considerations largely determined trial design. Participants presented for CL diagnosis and treatment at MENTOR Initiative supported mobile clinics and health facilities, rather than being enrolled into a prospective cohort, due to logistical and financial constraints. Without detection of asymptomatic cases, CL incidence may have been underestimated in this context. Importantly, camp populations were stable and balanced for biological factors which modify risk of symptomatic disease, including immunocompetency, malnutrition, host genetics, and major circulating parasite strains and vector species [ 64 ], supporting overall trial interventional effect. Study entomological indices relied exclusively on indoor measurements of host-seeking phlebotomine sandflies; due to volatile security levels throughout the study, matched outdoor trapping per shelter was not feasible but would warrant inclusion in future trials to assess the extent of repellency to the peri-domestic space. Finally, camps were not randomized to trial arm to avoid inciting perceived discontentment regarding intervention allocation, if control and intervention camps were adjacent. In unstable settings where resources are extremely limited and interventions are provided to householders for self-installation, this would have introduced the potential for cross-cluster contamination. Conclusions In 2025, the UN estimates that 305 million people will need humanitarian aid [ 10 ], and by 2030, two-thirds of the world’s extreme poor will reside in areas of fragility, conflict and violence, with the latter driving 80% of all humanitarian needs [ 65 ]. It is imperative that novel vector control tools, appropriate for the humanitarian emergency context, continue to be developed to tackle disease transmission among forcibly displaced populations at their most vulnerable. Combined trial epidemiological and entomological findings provide the first demonstrable impact of spatial repellents on CL incidence and phlebotomine sand fly density; strengthening the growing evidence basis for the effectiveness of this intervention against multiple vector species and their associated pathogens [ 30 – 32 ], and expanding the toolbox of efficacious vector control interventions for crisis settings. Abbreviations BLAST Basic local alignment search tool CDC Centres for Disease Control and Prevention cRCT Cluster randomised controlled trial CV Coefficient of variation CL Cutaneous Leishmaniasis FGD Focus group discussion GPS Global positioning system KDR Knock-down resistance IEC Information, education, communication IDP Internally Displaced People IRR Incidence rate ratio IRS Indoor residual spraying LOESS Locally estimated scatterplot smoothing LLIN Long lasting insecticidal net NGO Non-governmental organisation SD Standard deviation PCR Polymerase chain reaction UNHCR United Nations High Commission for Refugees VBD Vector borne disease VGSC Voltage gated sodium channels Declarations Ethics approval and consent to participate Ethical review and approval for the study in Northeast Syria was granted by the Ministry of Health of the governorate Ar-Raqqa, the Humanitarian Organizations Affairs of Tabqa, and the Department of Development and Humanitarian Affairs of Atareb (reference number: MNTSYR012021). Verbal informed consent was obtained from each enrolled participant who presented for CL diagnosis and treatment at MENTOR mobile clinics or MENTOR supported health facilities, and the head of households which participated in the entomological monitoring. Consent for publication Not applicable. Availability of data and materials Study data are available from the corresponding author upon reasonable request. Nucleotide sequence data are available from NCBI GenBank under the accession numbers PV454695 – PV454697, PV528669 – PV528704, PV564661 and PV564643. Competing interests The authors declare no competing interests. Funding This work was supported by Grand Challenges Canada. Grand Challenges Canada is funded by the Government of Canada and is dedicated to supporting Bold Ideas with Big Impact ® . Authors’ contributions RA conceived and designed the study with TS and OW. RS, OEK, LP, HL, ZA, MK, AY and BA acquired the study data. LAM undertook the analysis of study data with OEK, BA, RS, SEQ, and RA. RA, LAM, and RS interpreted the data. RA and LAM wrote the manuscript and prepared the figures. All authors read and approved the final manuscript. Authors’ information Please send correspondence to RA OBE MSc PhD at [email protected] Acknowledgements We would like to acknowledge the extraordinary dedication of the many MENTOR Initiative staff and health workers delivering essential prevention and health services in conflict-affected areas of northern Syria. We would also like to thank the North-East Syria health authorities, and other humanitarian aid organisations working in partnership to meet the needs of the most vulnerable communities in hard-to-reach areas of the country. References Organization WH. Global vector control response 2017–2030. World Health Organization: Geneva, Switzerland; 2017. Allan RJ. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6664771","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":458005330,"identity":"8a941b04-4a58-4ada-9102-2bde2dc299f3","order_by":0,"name":"Richard Allan","email":"data:image/png;base64,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","orcid":"","institution":"The MENTOR Initiative","correspondingAuthor":true,"prefix":"","firstName":"Richard","middleName":"","lastName":"Allan","suffix":""},{"id":458005331,"identity":"06f34d9c-375e-4ebe-8395-715d1f676d6b","order_by":1,"name":"Ramona Scherrer","email":"","orcid":"","institution":"The MENTOR Initiative","correspondingAuthor":false,"prefix":"","firstName":"Ramona","middleName":"","lastName":"Scherrer","suffix":""},{"id":458005332,"identity":"55e7b8b2-9677-406f-8ecf-d683635f4d62","order_by":2,"name":"Ozge Erisoz Kasap","email":"","orcid":"","institution":"VERG Laboratories, Hacettepe University","correspondingAuthor":false,"prefix":"","firstName":"Ozge","middleName":"Erisoz","lastName":"Kasap","suffix":""},{"id":458005333,"identity":"f124eca8-c2ca-47ea-ae0c-92fe778216e5","order_by":3,"name":"Laura Paris","email":"","orcid":"","institution":"The MENTOR Initiative","correspondingAuthor":false,"prefix":"","firstName":"Laura","middleName":"","lastName":"Paris","suffix":""},{"id":458005334,"identity":"6b837eda-668c-4b1c-b76f-29364795e270","order_by":4,"name":"Thomas Stewart","email":"","orcid":"","institution":"The MENTOR Initiative","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"","lastName":"Stewart","suffix":""},{"id":458005336,"identity":"6150b7f6-6df1-44b0-b36a-2cc0e8394b98","order_by":5,"name":"Hendrik Sauskojus","email":"","orcid":"","institution":"The MENTOR Initiative","correspondingAuthor":false,"prefix":"","firstName":"Hendrik","middleName":"","lastName":"Sauskojus","suffix":""},{"id":458005338,"identity":"4ff5fe50-1b07-4d61-9f4f-12d4ec3565ac","order_by":6,"name":"Olivia Wetherill","email":"","orcid":"","institution":"The MENTOR Initiative","correspondingAuthor":false,"prefix":"","firstName":"Olivia","middleName":"","lastName":"Wetherill","suffix":""},{"id":458005340,"identity":"5f6e4b38-e89d-455d-8b2b-faaf59b89312","order_by":7,"name":"Sara Estecha-Querol","email":"","orcid":"","institution":"The MENTOR Initiative","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Estecha-Querol","suffix":""},{"id":458005342,"identity":"78f65977-9da9-4979-a91f-ba1d17d8ff50","order_by":8,"name":"Zaid Alkhalaf","email":"","orcid":"","institution":"The MENTOR Initiative","correspondingAuthor":false,"prefix":"","firstName":"Zaid","middleName":"","lastName":"Alkhalaf","suffix":""},{"id":458005344,"identity":"1f54adb4-8d35-4340-aebf-3e8969510275","order_by":9,"name":"Mehmet Karakus","email":"","orcid":"","institution":"University of Health Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mehmet","middleName":"","lastName":"Karakus","suffix":""},{"id":458005345,"identity":"ad87b092-9298-48bc-b0dd-e83a0047f8fd","order_by":10,"name":"Ayda Yilmaz","email":"","orcid":"","institution":"VERG Laboratories, Hacettepe University","correspondingAuthor":false,"prefix":"","firstName":"Ayda","middleName":"","lastName":"Yilmaz","suffix":""},{"id":458005346,"identity":"4ff98f90-17bd-4920-b321-d5e9824e942c","order_by":11,"name":"Bülent Alten","email":"","orcid":"","institution":"VERG Laboratories, Hacettepe University","correspondingAuthor":false,"prefix":"","firstName":"Bülent","middleName":"","lastName":"Alten","suffix":""},{"id":458005347,"identity":"f62060ce-7916-4578-98a7-49ac203dbd14","order_by":12,"name":"Louisa A. Messenger","email":"","orcid":"","institution":"University of Nevada","correspondingAuthor":false,"prefix":"","firstName":"Louisa","middleName":"A.","lastName":"Messenger","suffix":""}],"badges":[],"createdAt":"2025-05-14 13:38:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6664771/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6664771/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12916-025-04244-2","type":"published","date":"2025-07-03T15:57:20+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83145652,"identity":"7900631e-a9b8-4f2f-8ce2-c0d5314803d0","added_by":"auto","created_at":"2025-05-20 13:00:01","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":272169,"visible":true,"origin":"","legend":"\u003cp\u003eTrial profile.\u003c/p\u003e","description":"","filename":"Figure1300dpl.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6664771/v1/688563279e9b37a2c1b14284.jpg"},{"id":83145660,"identity":"9c0a8bd1-19ca-4bc7-977d-5f9a106412f9","added_by":"auto","created_at":"2025-05-20 13:00:01","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":554934,"visible":true,"origin":"","legend":"\u003cp\u003eGeographical location of study camps in Ar-Raqqa governorate, North-East Syria. Intervention and control camps are shown in red and blue, respectively. Green line in upper left indicates 5 km.\u003c/p\u003e","description":"","filename":"Figure2300dpi.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6664771/v1/412051676008f2bff5d83454.jpg"},{"id":83146454,"identity":"2de1f9cd-7e7b-4bb4-8655-9e8010d628d2","added_by":"auto","created_at":"2025-05-20 13:08:01","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":363524,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA: \u003c/strong\u003eInstallation of Mosquito Shield\u003csup\u003eTM\u003c/sup\u003e in the intervention arm; \u003cstrong\u003eB:\u003c/strong\u003e Poster used in the information, education and communication campaign in Sahlat Al Banat camp (control arm), Ar-Raqqa governorate, North-East Syria; and \u003cstrong\u003eC:\u003c/strong\u003e pictogram instructions for correct Mosquito Shield\u003csup\u003eTM\u003c/sup\u003e usage.\u0026nbsp;\u003c/p\u003e","description":"","filename":"Figure3300dpi.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6664771/v1/d8e980feac4135d0b8bc3019.jpg"},{"id":83148509,"identity":"d2d5dbc3-f539-4429-989e-68e3e5acf646","added_by":"auto","created_at":"2025-05-20 13:24:07","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":173075,"visible":true,"origin":"","legend":"\u003cp\u003eCutaneous leishmaniasis incidence rate per 1,000 person-months for control and intervention arms, using 2 months diagnosis cut-off (June 2021 – April 2022). Vertical bars indicate 95% confidence intervals.\u003c/p\u003e","description":"","filename":"Figure4300dpi.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6664771/v1/d77866d15ba7b3acc0e4be84.jpg"},{"id":83147348,"identity":"b3a433f0-b143-4c3f-8ee1-89f93a57be4f","added_by":"auto","created_at":"2025-05-20 13:16:01","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":144862,"visible":true,"origin":"","legend":"\u003cp\u003eMonthly female phlebotomine sand fly density for control and intervention arms (April – December 2021). Points indicate CDC light trap occurrence, while smoothed lines are estimated trend using locally estimated scatterplot smoothing (LOESS), with shaded 95% confidence intervals.\u003c/p\u003e","description":"","filename":"Figure5300dpi.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6664771/v1/d803948a593197b91506c8fa.jpg"},{"id":86178958,"identity":"f532a83c-7a59-4f2b-b12d-41a49a9b86ff","added_by":"auto","created_at":"2025-07-07 16:12:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2810655,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6664771/v1/f15d5c00-deae-43e3-bcd5-1b13e0ce3ad1.pdf"},{"id":83145653,"identity":"78c683bd-f08e-434e-a1bd-659f00474a34","added_by":"auto","created_at":"2025-05-20 13:00:01","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":34089,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile14052025.docx","url":"https://assets-eu.researchsquare.com/files/rs-6664771/v1/cd0577442443bc80113dee6a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Enhancing protection against vector-borne diseases in forcibly displaced communities: evaluating the efficacy of spatial repellents for cutaneous leishmaniasis control in North-East Syria","fulltext":[{"header":"Background","content":"\u003cp\u003eAround 80% of the world\u0026rsquo;s population are at risk from vector-borne diseases (VBDs), which kill more than a million people each year [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, the majority of these deaths and immeasurable suffering occur in countries devastated by conflict or natural disaster driven humanitarian crises [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The number of armed conflicts and extreme weather events has multiplied dramatically since the end of the Cold War [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. These disproportionately affect regions of the world that are endemic for VBDs and displace more people globally than at any other time in history. Currently, there are 114 ongoing armed conflicts worldwide [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]; there are 35 armed conflicts across 12 countries in sub-Saharan Africa, 21 in Asia, 6 in Latin America and 7 in Europe [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Forty-five of these are in the Middle East and North Africa, of which Syria continues to be one of the worst affected, 14 years after the outbreak of civil war; 16.7\u0026nbsp;million people have been forced to flee their homes and 7.2\u0026nbsp;million remain internally displaced in 2025 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. As of June 2024, worldwide, a staggering 122.6\u0026nbsp;million people have been forced from their homes on unimaginable journeys, often without shelter for long periods, followed by years living in camps or poor urban squalor [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Around 305\u0026nbsp;million people, including the displaced and many of the communities that host them, are dependent upon humanitarian assistance for their very survival [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. These are the most vulnerable to infectious diseases and malnutrition, have the least access to emergency services and are the most likely to die [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMosquitoes are overwhelmingly the most important disease vector in most humanitarian crises, where they transmit malaria, dengue fever, yellow fever, chikungunya, Zika virus and West Nile virus. Syria is a notable exception, where leishmaniasis, an endemic parasitic disease transmitted by sandflies, was historically centred around just a few foci, but now predominates. This disease has escalated to epidemic levels across the north of the country in parallel with the onset of mass urban destruction and population displacement following the outbreak of war in 2011. If not diagnosed and treated effectively, the cutaneous form can result in permanent severe scaring, disfigurement and stigmatisation, and sometimes death. The visceral form, though less common, if untreated, usually results in death [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMosquitoes, sandflies and other blood-feeding arthropods require regular vertebrate blood for oogenesis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Their blood feeding preferences often correlate with common human behaviour patterns, defined time frames and contexts when people are most accessible and vulnerable to attack. Such arthropod behaviour, however, also presents unique opportunities to deploy appropriate control tools to reduce the risk of disease transmission and abate the vector population. For decades, malaria has dominated the global public health agenda and naturally also entomological research. This has driven understanding of mosquito behaviours and extraordinary achievements in disease control since 2000, by scaling up access to two core malaria interventions, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), alongside significant advances in diagnostics, therapeutics and vaccines to reduce malaria in stable settings [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The success of LLINs and IRS has been in targeting the predominantly indoor, nocturnal blood feeding behaviour of many of the most effective mosquito vector species; behaviour and vulnerability to control largely shared by phlebotomine sandflies, the vectors of leishmaniasis. However, the more challenging needs of displaced and conflict affected populations have exposed the limitations of these two key vector control tools in tackling both diseases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In conflict settings, people may be displaced for years, living under temporary shelter or in damaged buildings shared with multiple families. Standard LLINs generally do not last very long and rapidly fall apart in such harsh conditions [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. LLINs are bulky, slow and expensive to transport, limiting them operationally. The different shapes and sizes of temporary shelters used by displaced people, render LLINs a very poor tool choice ergonomically. While IRS is a somewhat more versatile format for targeting insecticides to a diversity of different shelter formats, it requires mobilization and training of specialist teams, as well as significant logistical and operational campaign infrastructure that may take too long to establish or be excessively risky in many conflict settings [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSustained aerial bombardment of cities and towns across northern Syria has caused a vast scale of destruction and the breakdown of municipal waste management services. This has created ideal conditions for the proliferation of \u003cem\u003ePhlebotomus (Ph.) papatasi\u003c/em\u003e and \u003cem\u003ePh. sergenti\u003c/em\u003e sandflies [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and transmission of \u003cem\u003eLeishmania tropica\u003c/em\u003e, and \u003cem\u003eL. major\u003c/em\u003e, the causative agents of cutaneous leishmaniasis (CL) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The extraordinary scale of destruction and forced population movement has inevitably resulted in sustaining epidemic levels of disease transmission and the onward transmission of CL into previously non endemic areas and across international borders [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The 7.8 magnitude earthquake that struck on 6th February 2023 caused further devastation in North-West Syria and South-East Turkey [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. This exacerbated the risk posed by leishmaniasis and further exposed the limitations of IRS and LLINs used at scale from 2013 to 2024 to protect people across northern Syria by The MENTOR Initiative, an international non-governmental organisation (NGO) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecognising the inherent operational shortcomings of IRS and LLINs, there is an urgent need to evaluate novel vector control tools that are light weight, highly portable and easily implementable in humanitarian crises, especially in displaced populations residing in flimsy temporary shelters with exposure to the elements. Spatial repellents interrupt human-vector contact by eliciting a range of behaviours in insect vectors, including movement away from chemical stimuli, interference with host detection, attraction inhibition, and/or reduced feeding response, thereby providing protection from daytime, early evening and night-time biting. Spatial repellents can provide protection in enclosed/semi-enclosed and peri-domestic spaces and increase coverage of vector control compared to traditional methods [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Mosquito Shield\u0026trade; is a commercially manufactured spatial repellent emanator containing transfluthrin. Transfluthrin is a fast-acting volatile pyrethroid with low persistency, which can either act by inducing vector mortality or via sublethal toxicity, causing repellency and thereby reduction in host-vector contact. The chemical passively releases into the air, creating a vapor space, and interacts with vector odour receptors, causing irritation; vectors do not need to directly contact an insecticidal-surface, but rather the continual release of transfluthrin builds a protective atmosphere in enclosed or semi-enclosed spaces [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrior to this current study, transfluthrin emanators have demonstrated significant protective efficacy (PE) from malaria in a cluster-randomized controlled trial (cRCT) in Indonesia [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], reduction in \u003cem\u003eAedes\u003c/em\u003e-borne viruses in Peru [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] and decrease in malaria case incidence in Kenya [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. This study was the first to evaluate the feasibility, acceptability and PE of the spatial repellent emanator Mosquito Shield\u0026trade;, as an alternative vector control tool for the control of sandflies and CL amongst displaced and conflict affected populations in North-East Syria.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and setting\u003c/h2\u003e \u003cp\u003eThe aim of this study was to determine the efficacy of Mosquito Shield\u0026trade; as a CL control tool in active conflict zones amongst internally displaced persons (IDPs) living in temporary shelter camps. The primary trial objective was to evaluate the PE of Mosquito Shield\u0026trade; against CL case incidence in all ages during 1 year of follow-up. The secondary trial objectives were to evaluate the impact of Mosquito Shield\u0026trade; on phlebotomine sand fly population density inside shelters during 9 months of follow-up and to assess the acceptability of Mosquito Shield\u0026trade; as a CL control tool, in a context where LLINs and IRS are operationally unfeasible.\u003c/p\u003e \u003cp\u003eThis study was conducted between February 2021 and April 2022 in Ar-Raqqa governorate, an area of North-East Syria hosting IDPs, living in organised camps composed of temporary shelters made from heavy duty tarpaulins or factory-made family tents, supplied by the United Nations High Commissioner for Refugees (UNHCR). Camp residents originated from the neighbouring governorates of Hama, Homs and Deir-ez-Zor, and from the northern regions Tell Abiad, Ein Issa and Suluk [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. The study setting was chosen based on increasing CL cases during the war and the accessibility of the region. The CL vector species in this area were \u003cem\u003ePh. papatasi\u003c/em\u003e and \u003cem\u003ePh. sergenti\u003c/em\u003e [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], both responsible for transmitting \u003cem\u003eL. tropica\u003c/em\u003e and \u003cem\u003eL. major\u003c/em\u003e [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo test the efficacy of Mosquito Shield\u0026trade; in reducing CL case incidence among IDPs and sand fly density in temporary shelters, a two-arm, non-randomized cluster trial was undertaken in Ar-Raqqa governorate, North-East Syria (Fig.\u0026nbsp;1).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEligibility and allocation\u003c/h3\u003e\n\u003cp\u003eInitially 23 clusters, each housing IDPs, were identified in Ar-Raqqa governorate, North-East Syria. Seventeen clusters were excluded because they did not meet study inclusion criteria or were unsafe to access. Eligibility criteria for clusters were a known history of CL, comparable shelter type (all distributed by UNHCR), water access, latrine resources and environmental conditions, accessibility by road, a minimum distance of 5 km between clusters, and adequate security levels. Global Positioning System (GPS) data of this governorate were plotted as open circles at 1:80,000 and examined for formal and informal camps housing IDPs in relatively isolated locations. Google Maps satellite view was searched for major population centres and if a camp was less than 5 km away, the camp was excluded. If a camp was less than 5 km away from a neighbouring camp, it was also excluded to ensure no risk of intervention contamination. Six camps were eligible and selected to achieve a minimum of 6,951 individuals per study arm. Two camps were allocated Mosquito Shield\u0026trade; in all temporary shelters, and 4 camps were allocated as control clusters (Fig.\u0026nbsp;2). The rationale for this pragmatic study design considered: (i) security and camp accessibility concerns for weekly post-intervention monitoring; and (ii) perceived discontentment, regarding intervention allocation, if control and intervention camps were neighbouring.\u003c/p\u003e \n\u003ch3\u003eIntervention arm\u003c/h3\u003e\n\u003cp\u003eThe study intervention was Mosquito Shield\u0026trade; (S.C. Johnson \u0026amp; Son, Racine, WI, USA). The active ingredient is transfluthrin (C\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e12\u003c/sub\u003eCl\u003csub\u003e2\u003c/sub\u003eF\u003csub\u003e4\u003c/sub\u003eO\u003csub\u003e2,\u003c/sub\u003e 110 mg / Mosquito Shield\u0026trade;, EPA Reg. number 432\u0026ndash;1588) and it releases on a controlled basis over a 1-month period (1 emanator in rooms up to 18 m\u003csup\u003e2\u003c/sup\u003e / 2 emanators per 9 m). The study population of the intervention arm, in camps Tawihena and Mahmoudli, was provided with Mosquito Shield\u0026trade; for 9 months between April and December 2021 (Fig.\u0026nbsp;3A). Mosquito Shield\u0026trade; was distributed directly to households every month, together with nails and string for installation and pictogram instructions in the local language describing the correct intervention usage, including how to open Mosquito Shield\u0026trade;, the number of Mosquito Shield\u0026trade; to be installed per room, and duration of Mosquito Shield\u0026trade; usage (30 days) prior to replacement (Fig.\u0026nbsp;3C). Shelter occupants were shown how to install and replace Mosquito Shield\u0026trade; and they attached Mosquito Shield\u0026trade; to the wall surface above head level with the impregnated side pointing towards the room (Fig.\u0026nbsp;3A) and replaced them when distributed each month.\u003c/p\u003e\n\u003ch3\u003eControl arm\u003c/h3\u003e\n\u003cp\u003eThe study population of both the control (Royan, Sahlat Al Banat and Tel Elsamen camps) and intervention arms received information, education and communication (IEC) campaigns by the MENTOR Initiative study team, reinforced with brochures and posters throughout the study period (Fig.\u0026nbsp;3B). The standardized IEC messages included information on the transmission of CL, the prevention of CL, clinical symptoms, correct treatment seeking practices and where to seek treatment. All camps had free access to diagnostic and treatment services for CL during the study period as encouraged by the IEC campaigns, either via MENTOR Initiative mobile clinics or via nearby MENTOR Initiative supported health facilities. Passive treatment seeking was reinforced by active identification and referral of suspected CL cases by the MENTOR Initiative study team when conducting entomological surveillance activities at the household level.\u003c/p\u003e\n\u003ch3\u003eEpidemiological monitoring\u003c/h3\u003e\n\u003cp\u003eEpidemiological monitoring was conducted for 1 year between April 2021 and April 2022, due to the long incubation time of CL (2\u0026ndash;8 months between infection and onset of symptoms) [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. All patients were clinically assessed in MENTOR Initiative mobile clinics (once or twice weekly each month) or by MENTOR Initiative supported health facilities (diagnosis and treatment provided 2 days per week), according to the comprehensive WHO standardized clinical guideline [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Clinically confirmed patients, based on direct parasitological observation in skin scrapings, were treated with sodium stibogluconate (20 mg Sb\u003csup\u003e5+\u003c/sup\u003e / kg per day for 21 days), according to the WHO treatment protocol [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Data on newly diagnosed patients per month was collected in both study arms, including the date of diagnosis, the estimated date when clinical symptoms started, sex, age, and the date of movement into the camp. Each patient was provided with a card, and each CL case was assigned a unique identifier to track treatment and clinical prognosis, including treatment failure and relapse. Standard operating procedures were in place to minimize the risk of re-registration of the same patient.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEntomological monitoring\u003c/h2\u003e \u003cp\u003eFor the entomological monitoring, U.S. Centers for Disease Control and Prevention (CDC) light traps were set up in 40 randomly selected households per study arm every fortnight. Entomological monitoring was performed by camp residents, trained by the MENTOR Initiative. CDC light traps were installed 1-1.5 m from the ground in the morning, turned on at sunset and collected the following morning. Baseline assessment was conducted between February and March 2021, followed by fortnightly entomological monitoring from April to December 2021 (2 trap nights per month). All CDC light traps were exclusively used inside camp shelters due to security considerations. Entomological monitoring was conducted in both intervention camps and 3 control camps (Tel Elsamen, Sahlat Al Banat and Khayala) due to operational constraints; Khayala camp was included for entomological monitoring, performed by camp residents, but not epidemiological monitoring because of security concerns for safe access by external mobile clinics.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eLaboratory analysis\u003c/h3\u003e\n\u003cp\u003eSand flies collected from CDC light traps were frozen at -20\u0026deg;C. Entomological identification of sand flies was undertaken using magnifying glasses. The number of males / females were recorded per trap, and females were further classified as blood-fed / non-blood-fed. All females were preserved in Eppendorf tubes containing 100% (v/v) ethanol and refrigerated at 4\u0026deg;C. A random subset of entomological samples per camp were transported for further analysis to the University of Hacettepe in Ankara, Turkey. Preserved sand flies were morphologically analyzed to confirm species identification using dichotomous keys available for Old World sand flies [\u003cspan additionalcitationids=\"CR36 CR37 CR38\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. The head and the last 2\u0026ndash;3 abdominal segments of each specimen were dissected, cleared in Marc-Andr\u0026eacute; solution and mounted in a drop of Swan solution. The thorax and the rest of the abdominal segments of each specimen were stored in 70% (v/v) ethanol for molecular analyses.\u003c/p\u003e \u003cp\u003eGenomic DNA from individual female sandflies was extracted using the Qiagen DNeasy Blood and Tissue Kit, according to the manufacturer\u0026rsquo;s instructions, and stored at \u0026minus;\u0026thinsp;20\u0026deg;C. To identify host preferences of blood-fed female specimens, a\u0026thinsp;~\u0026thinsp;340bp region of mammalian 12S rRNA gene was amplified using the Mam12S-340F and Mam12S-340R primers, according to [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Polymerase chain reaction (PCR) reactions were conducted in 50\u0026micro;l final volume and contained 2\u0026micro;l template DNA, 10X NH\u003csub\u003e4\u003c/sub\u003e buffer, 4\u0026micro;l of 2.5mM dNTPs, 2\u0026micro;l of each primer (10 pmol/\u0026micro;l), 2\u0026micro;l of 25mM MgCl\u003csub\u003e2\u003c/sub\u003e and 0.4\u0026micro;l of \u003cem\u003eTaq\u003c/em\u003e polymerase. Reaction conditions were an initial denaturation step at 94\u0026deg;C for 2 minutes; 35 cycles of 94\u0026deg;C for 30 seconds, 45\u0026deg;C for 30 seconds, and 72\u0026deg;C for 45 seconds; and a final extension of 72\u0026deg;C for 5 minutes. To detect the presence of the knock-down resistance (\u003cem\u003ekdr\u003c/em\u003e) mutation, L1014F, indicative of pyrethroid resistance, a\u0026thinsp;~\u0026thinsp;360bp region of the voltage-gated sodium channel (\u003cem\u003evgsc\u003c/em\u003e) that included the codon 1014, was amplified using the Vssc8F and Vssc1bR primers [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. PCR reactions were conducted in 50\u0026micro;l final volume and contained 2\u0026micro;l template DNA, 10X NH\u003csub\u003e4\u003c/sub\u003e buffer, 3\u0026micro;l of 2.5mM dNTPs, 2\u0026micro;l of each primer (10 pmol/\u0026micro;l), 2\u0026micro;l of 25mM MgCl\u003csub\u003e2\u003c/sub\u003e and 0.25\u0026micro;l of \u003cem\u003eTaq\u003c/em\u003e polymerase. Reaction conditions were an initial denaturation step at 95\u0026deg;C for 5 minutes; 36 cycles of 94\u0026deg;C for 45 seconds, 51\u0026deg;C for 50 seconds, and 72\u0026deg;C for 50 seconds; and a final extension of 72\u0026deg;C for 7 minutes [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. To confirm species identification of \u003cem\u003eSergentomyia (S.) clydei\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1) and \u003cem\u003eSergentomyia dreyfussi\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;3), a\u0026thinsp;~\u0026thinsp;650bp barcoding region of cytochrome oxidase 1 (\u003cem\u003ecox1\u003c/em\u003e) was amplified using the universal LCO1490 and HCO2198 primers [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. PCR reactions were conducted in 50\u0026micro;l final volume and contained 2\u0026micro;l template DNA, 10X NH\u003csub\u003e4\u003c/sub\u003e buffer, 3\u0026micro;l of 2.5mM dNTPs, 2\u0026micro;l of each primer (10pmol/\u0026micro;l), 2\u0026micro;l of 25mM MgCl\u003csub\u003e2\u003c/sub\u003e and 0.25\u0026micro;l of \u003cem\u003eTaq\u003c/em\u003e polymerase. Reaction conditions were an initial denaturation step at 95\u0026deg;C for 5 minutes; 34 cycles of 95\u0026deg;C for 30 seconds, 48\u0026deg;C for 30 seconds, and 72\u0026deg;C for 45 seconds; and a final extension of 72\u0026deg;C for 10 minutes.\u003c/p\u003e \u003cp\u003eAmplification products for all PCRs were visualized on 2% stained agarose gels. The purified PCR products were sequenced in both directions using the same primer pairs for the amplification reactions at BM Labosis Company, Ankara, Turkey. Raw sequences were aligned and edited using the ClustalW Multiple Alignment algorithm implemented in BioEdit v7.2.5 [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. 12S rRNA mammalian sequences were compared with reference sequences in NCBI GenBank using the the Basic Local Alignment Search Tool (BLAST) (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.ncbi.nlm.nih.gov/BLAST\u003c/span\u003e\u003cspan address=\"http://www.ncbi.nlm.nih.gov/BLAST\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) algorithm. Barcoded \u003cem\u003eSe. clydei\u003c/em\u003e and \u003cem\u003eSe. dreyfussi\u003c/em\u003e showed 97.74\u0026ndash;98.59% and 95.58\u0026ndash;96.18% homology with reference sequences in NCBI GenBank, respectively (Reference Accession Numbers: \u003cem\u003eSe. clydei\u003c/em\u003e: KJ481134 and OR671496; and \u003cem\u003eSe. dreyfussi\u003c/em\u003e: MT644236 and KJ481106). \u003cem\u003eVgsc\u003c/em\u003e sequence data were compared with reference wild type and mutant sand fly sequences available in NCBI GenBank, to screen for common \u003cem\u003ekdr\u003c/em\u003e mutations at codon 1014.\u003c/p\u003e \u003cp\u003eTo assess the presence of \u003cem\u003eLeishmania\u003c/em\u003e in sand fly specimens, monospecific pools were prepared by transferring 2\u0026ndash;11 female sand flies into Roche Magna Lyzer\u0026trade; tubes. The reference strain \u003cem\u003eLe. tropica\u003c/em\u003e MHOM/PS/2001/ISL590 was used as a positive control, while body parts from male sand flies were used as negative controls. Homogenization was performed using the Roche Magna Lyser\u0026trade; (Mannheim, Germany) at 7,000 rpm for 90 seconds. The resulting homogenates were resuspended in 200\u0026micro;l of Qiagen\u0026reg; tissue lysis buffer and incubated overnight at 56\u0026deg;C. Following incubation, genomic DNA was extracted using the Roche High Pure PCR Template Preparation Kit (Mannheim, Germany), with the final elution step carried out in 50\u0026micro;l of elution buffer to maximize DNA yield. Amplification of total genomic DNA was conducted using LITSR and L5.8S primers under PCR conditions previously described by [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. PCR products were visualized on a 1.2% agarose gel. Positive amplicons were purified and subsequently sequenced commercially (MedSanTek, Istanbul, Turkey). Raw sequence data were analyzed using Geneious R8 software, and identity confirmation was performed via comparison with GenBank entries using BLAST. The minimum infection rate (MIR) was calculated using the formula: (number of positive pools / total number of specimens tested) \u0026times; 100, as described by [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eIntervention feasibility, acceptability and uptake monitoring\u003c/h3\u003e\n\u003cp\u003eMosquito Shield\u0026trade; feasibility, acceptability and uptake was monitored in 40 randomly selected shelters each month in the intervention arm, using a cross-sectional survey from June \u0026ndash; December 2021. The total number of Mosquito Shield\u0026trade; emanators distributed per household during the trial was recorded by the study team. At the end of the study period (April 2022), a focus group discussion (FGD) was conducted in Mahmoudli camp with women (n\u0026thinsp;=\u0026thinsp;7) and a FGD was conducted in Tawihena camp with men (n\u0026thinsp;=\u0026thinsp;7), to determine context-specific modifiers of intervention community acceptance, usage, perceived benefits, accessibility and affordability.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStudy variables\u003c/h2\u003e \u003cp\u003eThe epidemiological endpoints were the CL incidence rate ratio (IRR) between intervention and control arms and the PE of Mosquito Shield\u0026trade;. The entomological endpoints were the IRR between intervention and control arms for female phlebotomine sand fly density (all physiological status), blood-fed female phlebotomine sand fly density and density of both sexes of phlebotomine sandflies. The intervention feasibility, acceptability and uptake endpoints were the proportion of the surveyed study population retaining Mosquito Shield\u0026trade; for 1-month post-distribution, perceived reduction of insect numbers and insect bites in the household, and the acceptability of Mosquito Shield\u0026trade;.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSample size\u003c/h2\u003e \u003cp\u003eAssuming a CL incidence of 10 cases per 1,000 individuals, a coefficient of variation (CV) of 0.69 (MENTOR Initiative, unpublished data), to detect a 50% reduction in CL in the intervention arm compared to the control arm, with 80% power at the 5% significance level, a sample size of 6,951 individuals per study arm was required [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. Entomological sampling followed a standardized protocol using previously evaluated methods by the MENTOR Initiative in the study setting [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAnalysis of the CL incidence rate included all newly diagnosed patients who were infected in the study camps after the first Mosquito Shield\u0026trade; distribution. The analysis considered two different incubation times or diagnosis cut-offs: at 2 months post-intervention (from June 2021 \u0026ndash; April 2022) and at 4 months post-intervention (from August 2021 \u0026ndash; April 2022). Incidence rates were calculated using the average population during the study period. Poisson regression was carried out with CL cases as response and the study arm as an explanatory variable, reporting IRR. PE was calculated as (1-IRR)x100. Differences in the density of female phlebotomine sandflies, female blood-fed phlebotomine sandflies and both sexes of phlebotomine sand fly were analysed using mixed effects negative binomial regression, with study arm as a fixed effect and collection month, household and camp as random effects. No sub-analysis was performed per species due to low sample sizes of the minority species present. An alpha level of p\u0026thinsp;=\u0026thinsp;0.05 was used for significance testing. No missing data were reported. All statistical analyses were performed using STATA/SE 17.0. Data were visualized in RStudio v2024.12.1\u0026thinsp;+\u0026thinsp;563 [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe total population during the study period (April 2021\u0026ndash;2022) was 18,404, residing across intervention (11,430) and control (6,974) camps. Camps were balanced with regards to shelter and housing source and type; epidemiological data were collected by MENTOR Initiative supported health facilities and mobile clinics (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In the intervention arm a total of 90,782 Mosquito Shield\u0026trade; emanators were distributed during the study across 2,153 shelters, with a mean of 5.7 Mosquito Shield\u0026trade; units (standard deviation (SD)\u0026thinsp;\u0026plusmn;\u0026thinsp;0.016) distributed per house.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristic of the study camps.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCamp name\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudy arm\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIDP origins\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCamp management\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCamp population\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eShelter type / material\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMENTOR Initiative mobile clinic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMENTOR Initiative supported health facility\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKhayala camp\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHama, Homs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCommunity leader\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInformal IDP settlement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUNHCR tents / plastic sheets\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRoyan camp\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHama, Homs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCommunity leader\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInformal IDP settlement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUNHCR tents / plastic sheets\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSahlat Al Banat camp\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHama, Homs, Deir Ezzor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCommunity leader\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInformal IDP settlement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUNHCR tents / plastic sheets\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTel Elsamen camp\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTal Abyad, Ras Al Ain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBlumont (NGO)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInformal IDP settlement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUNHCR tents / plastic sheets\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTawihena camp\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHama, Homs, Deir Ezzor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBlumont (NGO)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFormal IDP settlement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUNHCR tents / plastic sheets\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMahmoudli camp\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHama, Homs, Deir Ezzor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBlumont (NGO)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFormal IDP settlement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUNHCR tents / plastic sheets\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eEpidemiological impact\u003c/h2\u003e \u003cp\u003eAssuming a 2-month diagnosis cut-off, a total of 128 cases of CL were reported at the MENTOR Initiative mobile clinics and supported health facilities from June 2021 \u0026ndash; April 2022. The mean age was 21.5 years (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;15.11) and 48% of the cases were female. The incidence rate of CL was 9.9 and 5.2 per 1,000 in the control and the intervention arms, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). Mosquito Shield\u0026trade; demonstrated a significant impact on rate of CL infection in all ages (IRR: 0.52 [95% CI: 0.37\u0026ndash;0.74]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001); thus, the PE of Mosquito Shield\u0026trade; was 48%. The median number of months to develop CL infection from the beginning of the study was 7.43 (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;2.30) and 8.16 (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;2.12) in the intervention and control arms, respectively.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIncidence of cutaneous leishmaniasis from June 2021 \u0026ndash; April 2022 (using 2-months diagnosis cut-off).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePopulation December 2020 \u0026ndash; before intervention\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePopulation March 2022 \u0026ndash; after intervention\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAverage population during the study follow-up (Dec 2020 to March 2022)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNew cases of leishmaniasis during the study follow-up (June 2021 to April 2022)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIncidence rate per 1,000\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIRR [95% CI; p-value]\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eControl arm\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5,412\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8,536\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6,974\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e9.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntervention arm\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11,060\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11,800\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11,430\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.52 [0.37\u0026ndash;0.74]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal study population\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16,472\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20,336\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18,404\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e7.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003e\u0026dagger;\u003c/sup\u003eData from The MENTOR Initiative records.\u003c/p\u003e \u003cp\u003eAssuming a 4-month diagnosis cut-off, a total of 115 cases of CL were reported at the MENTOR Initiative mobile clinics and supported health facilities from August \u0026ndash; April 2022. The mean age was 21.6 years (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;15.4) and 44% of the cases were female. The incidence rate of CL was 8.6 and 4.8 per 1,000 in the control and intervention arms, respectively (Supplementary Table S2). Mosquito Shield\u0026trade; demonstrated a significant impact on rate of CL infection in all ages (IRR: 0.56 [95% CI: 0.39\u0026ndash;0.81]; p\u0026thinsp;=\u0026thinsp;0.002); thus, the PE of Mosquito Shield\u0026trade; was 44%.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eEntomological impact\u003c/h2\u003e \u003cp\u003eA total of 928 sandflies were collected across 80 shelters (40 per study arm) from April \u0026ndash; December 2021, using indoor CDC light traps (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Supplementary Table S3). By comparison, no sandflies were collected from either trial arm during baseline (February \u0026ndash; March 2021). Post-intervention, Mosquito Shield\u0026trade; demonstrated a significant impact on all female phlebotomine sand fly density (IRR: 0.22 [95% CI: 0.14\u0026ndash;0.33]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and blood-fed female phlebotomine sand fly density (IRR: 0.21 [95% CI: 0.11\u0026ndash;0.40]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig.\u0026nbsp;5). The peak in female sand fly density was July \u0026ndash; September 2021, corresponding to a rise in CL cases in October 2021 \u0026ndash; January 2022. An intervention effect was also evident when considering both sexes of phlebotomine sandflies (IRR: 0.20 [95% CI: 0.14\u0026ndash;0.29]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e \u003cp\u003eThe major vector species was \u003cem\u003ePh. papatasi\u003c/em\u003e (96.3%; 894/928), followed by \u003cem\u003eSe. dentata\u003c/em\u003e (3.1%; 29/928), \u003cem\u003eSe. dreyfussi\u003c/em\u003e (0.3%; 3/928); individual \u003cem\u003eS. cyldei\u003c/em\u003e and \u003cem\u003ePh. sergenti\u003c/em\u003e were also collected (Supplementary Table S4). DNA barcoding was successful for \u003cem\u003eSe. clydei\u003c/em\u003e and \u003cem\u003eSe. dreyfussi\u003c/em\u003e, confirming the first report of both species in Syria.\u003c/p\u003e \u003cp\u003eBloodmeal analysis indicated that \u003cem\u003ePh. papatasi\u003c/em\u003e fed predominantly on humans (75%), followed by \u003cem\u003eOvis aries\u003c/em\u003e (12.5%) and \u003cem\u003eCapra\u003c/em\u003e spp. (6.25%) (Supplementary Table S5). The \u003cem\u003evgsc\u003c/em\u003e-L1014F-\u003cem\u003ekdr\u003c/em\u003e mutation was not detected in any sand fly sample screened from any camp (n\u0026thinsp;=\u0026thinsp;25). One pool of \u003cem\u003ePh. papatasi\u003c/em\u003e from Khayala tested positive for \u003cem\u003eLeishmania\u003c/em\u003e; sequence analysis identified the species as \u003cem\u003eLe. tropica\u003c/em\u003e. The MIR was estimated as 0.13% for \u003cem\u003ePh. papatasi\u003c/em\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDensity of sandflies collected with indoor CDC light traps from April \u003cem\u003e\u0026ndash;\u003c/em\u003e December 2021.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy arm and location\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of households with light traps\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTotal number of sandflies\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNumber of female sandflies (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNumber of blood-fed female sandflies (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMean of sandflies per household collection (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFemale sand fly density IRR [95% CI; p-value]\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eControl\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e776\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e463 (59.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e126 (27.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.2 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntervention\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e101 (66.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e24 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.4 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.22 [0.14\u0026ndash;0.33]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e928\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e564 (60.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e150 (26.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.3 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eIntervention feasibility, acceptability and uptake\u003c/h2\u003e \u003cp\u003eAmong 280 households where Mosquito Shield\u0026trade; feasibility, acceptability and uptake was assessed, the mean age of the respondent was 41.5 years old (SD\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07), most were male (75.7%; 212/280) and received no (40.7%; 114/280) or primary school education (35.7%; 100/280). Eighty-six per cent (241/280) of households reported that Mosquito Shield\u0026trade; was very easy to use with no problems; 11.1% (21/280) reported it was easy, experiencing one or two problems. The instructional pictogram was considered very easy to understand by 91.4% (256/280) of respondents. Seventy-two per cent (203/280) of participants reported still using at least 1 Mosquito Shield\u0026trade; after distribution, of which 97.1% (203/280) were placed at the correct height, 92.8% (194/280) were positioned in the correct orientation and 84.7% (177/280) were correctly spaced. Of the 27.5% (77/280) households which had stopped using Mosquito Shield\u0026trade;, the main reasons were: it kept falling down (33.8%; 26/77), it was not perceived to be effective (37.7%; 29/77), health / side effect concerns (23.4%; 18/77), the participant did not like the intervention (31.2%; 24/77) or it was expired (18.2%; 14/77). Forty-one per cent (116/280) of households had used alternate installation materials for Mosquito Shield\u0026trade;, including sewing with needle and thread (48.3%; 56/116), wire (41.4%; 48/116) or pins (6.9%; 8/116). Mosquito Shield\u0026trade; was well received by study participants, with 54.2% (149/275) reporting that the intervention provided protection from insects; and 49.6% (139/280) and 52.5% (147/280) observing a decrease in perceived number of indoor insects or insect bites, respectively. Seventy-eight per cent (218/280) of respondents would use Mosquito Shield\u0026trade; again; the easiest outlets identified for intervention distribution were NGOs / camp management / community leaders (72.5%; 203/280), the local market (14.3%; 40/280) or bakeries (11.1%; 31/280).\u003c/p\u003e \u003cp\u003eAt the end of the study period (April 2022) two FGDs were conducted with either women (n\u0026thinsp;=\u0026thinsp;7) or men (n\u0026thinsp;=\u0026thinsp;7) separately in Mahmoudli and Tawihena camps, respectively. Responses from both sexes were similar. In general, Mosquito Shield\u0026trade; was perceived to be easy to use, to protect from CL, sandflies and other insect bites, require no behaviour change, be small, compact and lightweight with no side effects or smell. Additionally, respondents saved money because the intervention and access to healthcare was free, and they did not need to purchase other vector control tools. Participant recommendations to improve Mosquito Shield\u0026trade; included decreasing the number of emanators required per room (to reduce plastic and logistical efforts), increasing the effectiveness for longer and improving its appearance. Regarding accessibility, women, younger, healthy and employed people and registered IDPs were perceived to have greater access to the intervention compared to older, disabled, illiterate or uneducated people with lower awareness of CL. Future access could be improved by identification of these individuals by camp management / community leaders / NGOs and by targeted distribution of the intervention free of charge directly to their homes. Participants suggested that the price of Mosquito Shield\u0026trade; be adapted to the economic circumstances, be cheaper (or potentially free) in IDP camps than in urban settings and cost maximum US \u003cspan\u003e$\u003c/span\u003e0.2 per emanator. Unregistered IDPs, women without income and unemployed people were recognised as those who might be unable to afford the intervention; distribution for free by camp management / community leaders / NGOs, as part of other humanitarian aid and/or the provision of incentives were proposed mechanisms to mitigate financial barriers.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eHumanitarian crises are exceptional circumstances which critically threaten the health, safety, security and well-being of populations. Those forced to flee their homes and reside in temporary shelters or shared housing, are often exposed to hematophagous disease vectors and experience other co-morbidities and contributing factors, including anaemia, malnutrition, violence and trauma, and are therefore more likely to suffer ill health and die [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR53\" citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. In areas of intense VBD transmission, related morbidity and mortality rates escalate in the early weeks of humanitarian crises, remaining high until the implementation of effective vector control [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR53\" citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. Conventional vector control interventions, most of which were developed to interrupt malaria transmission, are predicated on living in a suitable housing or shelter structure, which can support a hanging LLIN, or insecticidal treatment of an interior wall surface; these methods are largely insufficient in some crises, suffering from both biological and operational constraints [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. Vector control tools with robust epidemiological evidence are even more scarce for leishmaniasis in both stable and emergency settings [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSpatial repellents are a new vector control tool class that have several key characteristics rendering them highly suitable for use during humanitarian crises, particularly in remote, unsafe and inaccessible areas, or in very mobile populations that move with little forewarning. They are light weight, portable, and easily implementable, requiring minimal behavioural change. Furthermore, spatial repellents cannot be repurposed for any other function and remain viable when kept in storage for long time periods, allowing for intervention stockpiling in strategic locations for rapid deployment during crisis onset. In this trial, Mosquito Shield\u0026trade; demonstrated a significant reduction in CL transmission during 1-year of follow-up in refugee camps in North-East Syria, with an estimated PE of 44\u0026ndash;48%. These observations strongly align with previous evaluations of the same intervention, which reported a PE of 40.9% against malaria primarily transmitted by \u003cem\u003eAnopheles (An.) vagus\u003c/em\u003e and \u003cem\u003eAn. sundaicus\u003c/em\u003e in Indonesia [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], a PE of 29.5% against malaria transmitted by \u003cem\u003eAn. gambiae\u003c/em\u003e sensu strictu, \u003cem\u003eAn. arabiensis\u003c/em\u003e and \u003cem\u003eAn. funestus\u003c/em\u003e in Kenya [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] and a PE of 34.1% from dengue and Zika viruses transmitted by \u003cem\u003eAedes (Ae.) aegypti\u003c/em\u003e in Peru [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEpidemiological observations were supported by a significant reduction in female Phlebotomine sand fly density (the majority of which were pyrethroid-susceptible, anthropophagic \u003cem\u003ePh. papatasi\u003c/em\u003e), irrespective of physiological status (i.e. unfed, gravid or blood-fed) and density of both sexes of phlebotomine sandflies. These entomological effects were consistent with the mode of action of spatial repellents, i.e. deterrence from house entry and interference with human biting. By comparison to previous studies, the evidence for an impact of spatial repellents on entomological indices has been mixed. In Kenya and Indonesia, spatial repellents exerted no observable reduction in Anopheline vector populations [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], while in Peru, the abundance and blood-feeding rates of \u003cem\u003eAe. aegypti\u003c/em\u003e were reduced by 28.6% and 12.4%, respectively [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Other community-level evaluations of spatial repellents have reported promising results against pyrethroid-resistant \u003cem\u003eAn. arabiensis\u003c/em\u003e in Tanzania and \u003cem\u003eAn. gambiae\u003c/em\u003e sensu lato in Benin [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. This discordance in entomological data has been attributed to relative differences in vector species feeding, host preferences and resting behaviours, underpowered trial designs and trapping techniques [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile evaluations of user acceptability and feasibility of spatial repellents have been more limited, trial results are also consistent with those from Cambodia, Peru and Thailand, where spatial repellents were well received by community members, who acknowledged the need for new vector control strategies and were willing to pay for them [\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e, \u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e]. In this setting, Mosquito Shield\u0026trade; was perceived to be easy to use, to protect from CL, sandflies and other insect bites, require minimal behaviour change, and have no side effects or smell. Feedback from study participants, particularly for longer lasting emanators, has already been addressed in more recent iterations of this intervention, which have recently demonstrated efficacy against mosquito vectors for 1 year in Phase II trials in Tanzania [\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudy findings should be interpreted in the context of the following limitations. Several pragmatic operational considerations largely determined trial design. Participants presented for CL diagnosis and treatment at MENTOR Initiative supported mobile clinics and health facilities, rather than being enrolled into a prospective cohort, due to logistical and financial constraints. Without detection of asymptomatic cases, CL incidence may have been underestimated in this context. Importantly, camp populations were stable and balanced for biological factors which modify risk of symptomatic disease, including immunocompetency, malnutrition, host genetics, and major circulating parasite strains and vector species [\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e], supporting overall trial interventional effect. Study entomological indices relied exclusively on indoor measurements of host-seeking phlebotomine sandflies; due to volatile security levels throughout the study, matched outdoor trapping per shelter was not feasible but would warrant inclusion in future trials to assess the extent of repellency to the peri-domestic space. Finally, camps were not randomized to trial arm to avoid inciting perceived discontentment regarding intervention allocation, if control and intervention camps were adjacent. In unstable settings where resources are extremely limited and interventions are provided to householders for self-installation, this would have introduced the potential for cross-cluster contamination.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn 2025, the UN estimates that 305\u0026nbsp;million people will need humanitarian aid [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and by 2030, two-thirds of the world\u0026rsquo;s extreme poor will reside in areas of fragility, conflict and violence, with the latter driving 80% of all humanitarian needs [\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e]. It is imperative that novel vector control tools, appropriate for the humanitarian emergency context, continue to be developed to tackle disease transmission among forcibly displaced populations at their most vulnerable. Combined trial epidemiological and entomological findings provide the first demonstrable impact of spatial repellents on CL incidence and phlebotomine sand fly density; strengthening the growing evidence basis for the effectiveness of this intervention against multiple vector species and their associated pathogens [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], and expanding the toolbox of efficacious vector control interventions for crisis settings.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBLAST\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBasic local alignment search tool\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCDC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCentres for Disease Control and Prevention\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ecRCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCluster randomised controlled trial\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCoefficient of variation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCutaneous Leishmaniasis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFGD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFocus group discussion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGPS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlobal positioning system\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKDR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKnock-down resistance\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIEC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInformation, education, communication\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIDP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternally Displaced People\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIRR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIncidence rate ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIRS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIndoor residual spraying\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLOESS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLocally estimated scatterplot smoothing\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLLIN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLong lasting insecticidal net\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNGO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNon-governmental organisation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePolymerase chain reaction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUNHCR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUnited Nations High Commission for Refugees\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVBD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVector borne disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVGSC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVoltage gated sodium channels\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical review and approval for the study in Northeast Syria was granted by the Ministry of Health of the governorate Ar-Raqqa, the Humanitarian Organizations Affairs \u0026nbsp;of Tabqa, and the Department of Development and Humanitarian Affairs of Atareb (reference number: MNTSYR012021). Verbal informed consent was obtained from each enrolled participant who presented for CL diagnosis and treatment at MENTOR mobile clinics or MENTOR supported health facilities, and the head of households which participated in the entomological monitoring.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy data are available from the corresponding author upon reasonable request. Nucleotide sequence data are available from NCBI GenBank under the accession numbers PV454695 \u0026ndash; PV454697, PV528669 \u0026ndash; PV528704, PV564661 and PV564643.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Grand Challenges Canada. Grand Challenges Canada is funded by the Government of Canada and is dedicated to supporting Bold Ideas with Big Impact\u003csup\u003e\u0026reg;\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRA conceived and designed the study with TS and OW. RS, OEK, LP, HL, ZA, MK, AY and BA acquired the study data. LAM undertook the analysis of study data with OEK, BA, RS, SEQ, and RA. RA, LAM, and RS interpreted the data. RA and LAM wrote the manuscript and prepared the figures. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePlease send correspondence to RA OBE MSc PhD at [email protected]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to acknowledge the extraordinary dedication of the many MENTOR Initiative staff and health workers delivering essential prevention and health services in conflict-affected areas of northern Syria. We would also like to thank the North-East Syria health authorities, and other humanitarian aid organisations working in partnership to meet the needs of the most vulnerable communities in hard-to-reach areas of the country.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOrganization WH. Global vector control response 2017\u0026ndash;2030. World Health Organization: Geneva, Switzerland; 2017.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAllan RJ. \u003cem\u003ePractical new approaches to delivering biologically rational vector control in the context of conflict displacement, extreme weather events and other natural disasters\u003c/em\u003e, in \u003cem\u003eUniversity College Cork\u003c/em\u003e. 2024, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://hdl.handle.net/10468/16365\u003c/span\u003e\u003cspan address=\"https://hdl.handle.net/10468/16365\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e: Cork, Ireland.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRustad SA. \u003cem\u003eConflict Trends: A Global Overview, 1946\u0026ndash;2023.\u003c/em\u003e PRIO Paper. Oslo: PRIO; 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e(UNDRR), C.F.R.o.t.E.o.D.C.U.N.O.F.D.R.R., \u003cem\u003eThe human cost of disasters: an overview of the last 20 years (2000\u0026ndash;2019)\u003c/em\u003e. 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAcademy G. \u003cem\u003eToday\u0026rsquo;s Armed Conflicts\u003c/em\u003e. 2025; Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://geneva-academy.ch/galleries/today-s-armed-conflicts\u003c/span\u003e\u003cspan address=\"https://geneva-academy.ch/galleries/today-s-armed-conflicts\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRefugees UN. H.C.f. \u003cem\u003eSyria Situation\u003c/em\u003e. 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Parasitol Int. 2021;81:102229.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBank TW. \u003cem\u003eFragility conflict and violence\u003c/em\u003e 2021; Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.worldbank.org/en/topic/fragilityconflictviolence/overview\u003c/span\u003e\u003cspan address=\"https://www.worldbank.org/en/topic/fragilityconflictviolence/overview\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmed","sideBox":"Learn more about [BMC Medicine](http://bmcmedicine.biomedcentral.com/)","snPcode":"12916","submissionUrl":"https://submission.nature.com/new-submission/12916/3","title":"BMC Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Conflict, internally displaced persons, cutaneous leishmaniasis, temporary shelter, vector control, spatial repellents","lastPublishedDoi":"10.21203/rs.3.rs-6664771/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6664771/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIn Syria, 14 years after the outbreak of civil war, 16.7\u0026nbsp;million people have been forced to flee their homes and 7.2\u0026nbsp;million remain internally displaced in 2025. Breakdown in waste management caused by aerial bombardment has created ideal conditions for cutaneous leishmaniasis (CL) transmission, vectored by phlebotomine sandflies. Displaced populations reside in flimsy shelters where conventional vector control tools are operationally unfeasible. A small, lightweight, portable transfluthrin-based spatial repellent (Mosquito Shield\u0026trade;) has been developed which may circumvent some of these logistical issues and provide improved protection from vector-borne diseases in harsh environments.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA two-arm, non-randomized cluster trial was undertaken in Ar-Raqqa governorate, North-East Syria, to evaluate the efficacy of Mosquito Shield\u0026trade; in reducing CL case incidence and sand fly densities in shelters. Weekly epidemiological monitoring was performed by MENTOR Initiative mobile clinics and supported health facilities. Entomological monitoring was performed fortnightly using indoor U.S. Centers for Disease Control and Prevention light traps in 40 randomly selected households per study arm. Phlebotomine sandflies were morphologically identified; a sub-set were analysed for molecular species confirmation, bloodmeal preferences and pyrethroid resistance. Household surveys and focus group discussions were used to assess intervention feasibility, acceptability and uptake.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAssuming a 2-month diagnosis cut-off, the CL incidence rate was 9.9 and 5.2 per 1,000 in the control and the intervention arms, respectively; Mosquito Shield\u0026trade; demonstrated a significant impact on rate of CL infection in all ages (incidence rate ratio; IRR: 0.52 [95% CI: 0.37\u0026ndash;0.74]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Mosquito Shield\u0026trade; demonstrated a significant impact on all female sand fly density (IRR: 0.22 [95% CI: 0.14\u0026ndash;0.33]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and blood-fed female sand fly density (IRR: 0.21 [95% CI: 0.11\u0026ndash;0.40]; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Mosquito Shield\u0026trade; was received positively and perceived to be easy to use, to protect from CL, sandflies and other insect bites and required minimal behaviour change.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eTrial findings provide the first demonstrable impact of spatial repellents on CL transmission, strengthening the growing evidence basis for the effectiveness of this intervention against multiple vector species and their associated pathogens. Study results strongly support the deployment of spatial repellents to control CL in humanitarian crises.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e \u003cp\u003eClinicalTrials.gov, NCT06917040.\u003c/p\u003e","manuscriptTitle":"Enhancing protection against vector-borne diseases in forcibly displaced communities: evaluating the efficacy of spatial repellents for cutaneous leishmaniasis control in North-East Syria","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-20 12:59:56","doi":"10.21203/rs.3.rs-6664771/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-27T10:29:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-26T08:48:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-26T01:44:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"283875760909220517543677117926133227463","date":"2025-05-22T08:12:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"163350046560503485897534504286030762550","date":"2025-05-17T12:56:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"76141995885369444133694690099312401462","date":"2025-05-17T12:45:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"63180090952684060392091349686056626251","date":"2025-05-15T19:30:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"118334222850733590383661090286700614253","date":"2025-05-15T16:30:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"138123928455859376376292189306513067660","date":"2025-05-15T13:14:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-15T12:42:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-15T08:22:35+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-15T08:09:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Medicine","date":"2025-05-14T13:36:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmed","sideBox":"Learn more about [BMC Medicine](http://bmcmedicine.biomedcentral.com/)","snPcode":"12916","submissionUrl":"https://submission.nature.com/new-submission/12916/3","title":"BMC Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ad23bdef-ea8f-45c3-8213-d414de8f1041","owner":[],"postedDate":"May 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-07T16:01:20+00:00","versionOfRecord":{"articleIdentity":"rs-6664771","link":"https://doi.org/10.1186/s12916-025-04244-2","journal":{"identity":"bmc-medicine","isVorOnly":false,"title":"BMC Medicine"},"publishedOn":"2025-07-03 15:57:20","publishedOnDateReadable":"July 3rd, 2025"},"versionCreatedAt":"2025-05-20 12:59:56","video":"","vorDoi":"10.1186/s12916-025-04244-2","vorDoiUrl":"https://doi.org/10.1186/s12916-025-04244-2","workflowStages":[]},"version":"v1","identity":"rs-6664771","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6664771","identity":"rs-6664771","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}