Spatial Repellents for Aedes-borne Virus Control in Sri Lanka

Arbovirus Infections Clinical Trial

— AEGIS ABV  

Official title:

A Cluster Randomized, Placebo Control Trial to Evaluate the Efficacy of a Spatial Repellent (Mosquito ShieldTM) Against Aedes-borne Virus Infection Among Children ≥ 4-16 Years of Age in the Gampaha District, Sri Lanka

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05452447
• Other study ID #: 21-05-6629
• Status: Recruiting
• Phase: N/A
• Start date: March 2, 2023
• Est. completion date: August 2025

Study information

• Verified date: December 2023
• Source: University of Notre Dame
• Contact: John P Grieco, Ph.D.
• Phone: 5743617572
• Email: jgrieco[@]nd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to demonstrate and quantify the protective efficacy (PE) of a single SR product, in reducing DENV infection and active Aedes-borne virus (ABV) disease in human cohorts. The study design will be a prospective, cluster randomized controlled trial (cRCT). Although not a specific objective of this project, an overall goal is to allow for official recommendations (or not) from the World Health Organization (WHO) for the use of SRs in public health. A WHO global policy recommendation will establish evaluation systems of SR products to regulate efficacy evaluations, thereby increasing quality, overall use and a consequent reduction in disease.

Description:

The study will be a prospective, cRCT, participant and observer-blinded, placebo-controlled trial in a site endemic for ABV to measure the impact of a SR product on new ABV virus infections. Clusters of households, each cluster containing 110-120 residents testing negative for antibodies against DENV (seronegative) or positive to a single DENV infection (monotypic), will be selected from three MOH areas in the district of Gampaha: Negambo, Wattala, Kelaniya. All participating houses in each cluster will be monitored entomologically for adult Aedes aegypti surveys for 3 months before deployment of the SR intervention and monthly after the intervention is in place. Entomological surveys will include monitoring of indoor Ae. aegypti adult population densities and blood-fed status. DENV infection in study participants will be assessed by serologic testing of scheduled longitudinal blood samples (primary outcome) and passively by monitoring febrile persons for acute Dengue illness (secondary outcome). Seroconversion to DENV from baseline (pre-intervention) and follow-up (post-intervention) samples as well as ABV active disease rates will be compared between active intervention and placebo (control) clusters. Testing and confirmation of Zika virus (ZIKV) and Chikungunya virus (CHIKV) infection at baseline and during the intervention phase of the trial will be dependent on circulation history/detection in study area during study period. The spatial repellent (SR) will be a new formulation of transfluthrin. This active ingredient (AI) is widely used in mosquito coils and other household pest control products worldwide. The new formulation is a passive emanator that will release the AI over a period of up to four weeks, Mosquito ShieldTM. The emanator will consist of a pre-treated piece of cellulose acetate or other medium, which will be positioned within consenting households according to manufacturer specifications of 2 units/9m2. A placebo product of matched design with inert ingredients will be applied similarly. The Mosquito ShieldTM and placebo products for this study will be designed and provided by S.C. Johnson, INC. A Family Company.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 14430
• Est. completion date: August 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months and older

Eligibility

LONGITUDINAL SEROCONVERSION Individual Level

Inclusion Criteria:

• = 4 - 16 years of age
• Plans to stay in residence and/or study area for a minimum of 24 months
• Resident of household or frequent visitor (~20% of day hours in house / month)

Exclusion Criteria:

• < 4 and > 16 years of age
• Plans to leave residence and/or study area within next 24 months
• Temporary visitor to household (<20% of day hours in house/ month) FEBRILE SURVEILLANCE Household Level

Inclusion Criteria:

• Adult head of households agrees to census, health visits and logging resident symptoms when febrile (or in the case of suspected Zika in the absence of fever, presenting with rash, arthralgia, arthritis or non-purulent conjunctivitis).
• Individuals spend a minimum of 4hrs per week during the daytime hours or sleep in the house.

Exclusion Criteria:

• Adult head of households does not agree to census, health visits or logging symptoms of residents.
• Households where study personnel identify a security risk (i.e., site where drugs are sold, residents are always drunk or hostile).
• Sites where no residents spend time during the day (i.e. work 7d a week outside the home). FEBRILE SURVEILLANCE Individual Level

Inclusion Criteria:

• = 6mo of age.
• Fever at the time of presentation or report of feverishness within the previous 24 hours or presenting with a rash, arthralgia, arthritis or non-purulent conjunctivitis (suspicion of ZIKA determined by project physician)
• Individual who spends a minimum of 4 hours per week within the household or sleeps in the house.

Exclusion Criteria:

• < 6mo of age.
• No fever at time of presentation or report of feverishness within the previous 24 hours or not reporting with a rash, arthralgia, arthritis or non-purulent conjunctivitis
• Individuals who have spent less than 4 hours in the household during the week prior to illness. ENTOMOLOGICAL MONITORING Household Level

Inclusion Criteria:

• Adult head of household agrees to surveys.
• Properties where study personnel do not identify a security risk (i.e., site where drugs are sold, residents are always drunk or hostile).

Exclusion Criteria:

• Adult head of household does not agree to surveys.
• Properties where study personnel identify a security risk (i.e., site where drugs are sold, residents are always drunk or hostile). SPATIAL REPELLENT INTERVENTION Household Level

Inclusion Criteria:

• Adult head of households agrees to have intervention applied inside the home and to provide access to team member at 4-week intervals to change products.
• Properties where study personnel do not identify a security risk (i.e., site where drugs are sold, residents are always drunk or hostile).

Exclusion Criteria:

• Adult head of household does not agree to Mosquito ShieldTM deployment or study team access.
• Properties where study personnel identify a security risk (i.e., site where drugs are sold, residents are always drunk or hostile).

Related Conditions & MeSH terms

• Arbovirus Infections
• Infections

Intervention

Device:
• Transfluthrin
Passive emanator with formulated transfluthrin
• Placebo
Passive emanator with formulated inert ingredients

Locations

Country	Name	City	State
Sri Lanka	Epidemiology Unit, Ministry of Health	Colombo	West
Sri Lanka	Clinical Trials Unit	Ragama	West

Sponsors (7)

Lead Sponsor	Collaborator
University of Notre Dame	fhiClinical, Ministry of Health, Sri Lanka, RemediumOne, SC Johnson, A Family Company, University of Sri Jayewardenepura, Sri Lanka, University of Washington

Country where clinical trial is conducted

Sri Lanka, 

References & Publications (36)

Achee NL, Bangs MJ, Farlow R, Killeen GF, Lindsay S, Logan JG, Moore SJ, Rowland M, Sweeney K, Torr SJ, Zwiebel LJ, Grieco JP. Spatial repellents: from discovery and development to evidence-based validation. Malar J. 2012 May 14;11:164. doi: 10.1186/1475-2875-11-164. — View Citation

Achee NL, Sardelis MR, Dusfour I, Chauhan KR, Grieco JP. Characterization of spatial repellent, contact irritant, and toxicant chemical actions of standard vector control compounds. J Am Mosq Control Assoc. 2009 Jun;25(2):156-67. doi: 10.2987/08-5831.1. — View Citation

Ansari MZ, Shope RE, Malik S. Evaluation of vero cell lysate antigen for the ELISA of flaviviruses. J Clin Lab Anal. 1993;7(4):230-7. doi: 10.1002/jcla.1860070408. — View Citation

Comach G, Blair PJ, Sierra G, Guzman D, Soler M, de Quintana MC, Bracho-Labadie M, Camacho D, Russell KL, Olson JG, Kochel TJ. Dengue virus infections in a cohort of schoolchildren from Maracay, Venezuela: a 2-year prospective study. Vector Borne Zoonotic Dis. 2009 Feb;9(1):87-92. doi: 10.1089/vbz.2007.0213. Epub 2008 Sep 12. — View Citation

Erlanger TE, Keiser J, Utzinger J. Effect of dengue vector control interventions on entomological parameters in developing countries: a systematic review and meta-analysis. Med Vet Entomol. 2008 Sep;22(3):203-21. doi: 10.1111/j.1365-2915.2008.00740.x. — View Citation

Forshey BM, Morrison AC, Cruz C, Rocha C, Vilcarromero S, Guevara C, Camacho DE, Alava A, Madrid C, Beingolea L, Suarez V, Comach G, Kochel TJ. Dengue virus serotype 4, northeastern Peru, 2008. Emerg Infect Dis. 2009 Nov;15(11):1815-8. doi: 10.3201/eid1511.090663. Erratum In: Emerg Infect Dis. 2010 Jan;16(1):177. — View Citation

Getis A, Morrison AC, Gray K, Scott TW. Characteristics of the spatial pattern of the dengue vector, Aedes aegypti, in Iquitos, Peru. Am J Trop Med Hyg. 2003 Nov;69(5):494-505. — View Citation

Grieco JP, Achee NL, Andre RG, Roberts DR. A comparison study of house entering and exiting behavior of Anopheles vestitipennis (Diptera: Culicidae) using experimental huts sprayed with DDT or deltamethrin in the southern district of Toledo, Belize, C.A. J Vector Ecol. 2000 Jun;25(1):62-73. — View Citation

Grieco JP, Achee NL, Chareonviriyaphap T, Suwonkerd W, Chauhan K, Sardelis MR, Roberts DR. A new classification system for the actions of IRS chemicals traditionally used for malaria control. PLoS One. 2007 Aug 8;2(8):e716. doi: 10.1371/journal.pone.0000716. — View Citation

Grieco JP, Achee NL, Sardelis MR, Chauhan KR, Roberts DR. A novel high-throughput screening system to evaluate the behavioral response of adult mosquitoes to chemicals. J Am Mosq Control Assoc. 2005 Dec;21(4):404-11. doi: 10.2987/8756-971X(2006)21[404:ANHSST]2.0.CO;2. — View Citation

Gubler DJ. Aedes aegypti and Aedes aegypti-borne disease control in the 1990s: top down or bottom up. Charles Franklin Craig Lecture. Am J Trop Med Hyg. 1989 Jun;40(6):571-8. doi: 10.4269/ajtmh.1989.40.571. No abstract available. — View Citation

Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev. 1998 Jul;11(3):480-96. doi: 10.1128/CMR.11.3.480. — View Citation

Gubler DJ. Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century. Trends Microbiol. 2002 Feb;10(2):100-3. doi: 10.1016/s0966-842x(01)02288-0. — View Citation

Hapuarachchi HA, Bandara KB, Hapugoda MD, Williams S, Abeyewickreme W. Laboratory confirmation of dengue and chikungunya co-infection. Ceylon Med J. 2008 Sep;53(3):104-5. doi: 10.4038/cmj.v53i3.252. No abstract available. — View Citation

Hapuarachchi HC, Bandara KB, Sumanadasa SD, Hapugoda MD, Lai YL, Lee KS, Tan LK, Lin RT, Ng LF, Bucht G, Abeyewickreme W, Ng LC. Re-emergence of Chikungunya virus in South-east Asia: virological evidence from Sri Lanka and Singapore. J Gen Virol. 2010 Apr;91(Pt 4):1067-76. doi: 10.1099/vir.0.015743-0. Epub 2009 Dec 2. — View Citation

Hayes CG, Phillips IA, Callahan JD, Griebenow WF, Hyams KC, Wu SJ, Watts DM. The epidemiology of dengue virus infection among urban, jungle, and rural populations in the Amazon region of Peru. Am J Trop Med Hyg. 1996 Oct;55(4):459-63. doi: 10.4269/ajtmh.1996.55.459. — View Citation

Innis BL, Nisalak A, Nimmannitya S, Kusalerdchariya S, Chongswasdi V, Suntayakorn S, Puttisri P, Hoke CH. An enzyme-linked immunosorbent assay to characterize dengue infections where dengue and Japanese encephalitis co-circulate. Am J Trop Med Hyg. 1989 Apr;40(4):418-27. doi: 10.4269/ajtmh.1989.40.418. — View Citation

Kanakaratne N, Wahala WM, Messer WB, Tissera HA, Shahani A, Abeysinghe N, de-Silva AM, Gunasekera M. Severe dengue epidemics in Sri Lanka, 2003-2006. Emerg Infect Dis. 2009 Feb;15(2):192-9. doi: 10.3201/eid1502.080926. — View Citation

Kawada H, Maekawa Y, Takagi M. Field trial on the spatial repellency of metofluthrin-impregnated plastic strips for mosquitoes in shelters without walls (beruga) in Lombok, Indonesia. J Vector Ecol. 2005 Dec;30(2):181-5. — View Citation

Kawada H, Maekawa Y, Tsuda Y, Takagi M. Laboratory and field evaluation of spatial repellency with metofluthrin-impregnated paper strip against mosquitoes in Lombok Island, Indonesia. J Am Mosq Control Assoc. 2004 Sep;20(3):292-8. — View Citation

Kawada H, Maekawa Y, Tsuda Y, Takagi M. Trial of spatial repellency of metofluthrin-impregnated paper strip against Anopheles and Culex in shelters without walls in Lombok, Indonesia. J Am Mosq Control Assoc. 2004 Dec;20(4):434-7. Erratum In: J Am Mosq Control Assoc. 2005 Mar;21(1):105. — View Citation

Kochel TJ, Watts DM, Halstead SB, Hayes CG, Espinoza A, Felices V, Caceda R, Bautista CT, Montoya Y, Douglas S, Russell KL. Effect of dengue-1 antibodies on American dengue-2 viral infection and dengue haemorrhagic fever. Lancet. 2002 Jul 27;360(9329):310-2. doi: 10.1016/S0140-6736(02)09522-3. — View Citation

Kularatne SA, Gihan MC, Weerasinghe SC, Gunasena S. Concurrent outbreaks of Chikungunya and Dengue fever in Kandy, Sri Lanka, 2006-07: a comparative analysis of clinical and laboratory features. Postgrad Med J. 2009 Jul;85(1005):342-6. doi: 10.1136/pgmj.2007.066746. — View Citation

Kuno G. Review of the factors modulating dengue transmission. Epidemiol Rev. 1995;17(2):321-35. doi: 10.1093/oxfordjournals.epirev.a036196. No abstract available. — View Citation

Lanciotti RS, Calisher CH, Gubler DJ, Chang GJ, Vorndam AV. Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. J Clin Microbiol. 1992 Mar;30(3):545-51. doi: 10.1128/jcm.30.3.545-551.1992. — View Citation

Lucas JR, Shono Y, Iwasaki T, Ishiwatari T, Spero N, Benzon G. U.S. laboratory and field trials of metofluthrin (SumiOne) emanators for reducing mosquito biting outdoors. J Am Mosq Control Assoc. 2007 Mar;23(1):47-54. doi: 10.2987/8756-971X(2007)23[47:ULAFTO]2.0.CO;2. — View Citation

Messer WB, Vitarana UT, Sivananthan K, Elvtigala J, Preethimala LD, Ramesh R, Withana N, Gubler DJ, De Silva AM. Epidemiology of dengue in Sri Lanka before and after the emergence of epidemic dengue hemorrhagic fever. Am J Trop Med Hyg. 2002 Jun;66(6):765-73. doi: 10.4269/ajtmh.2002.66.765. — View Citation

Monath TP. Dengue: the risk to developed and developing countries. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2395-400. doi: 10.1073/pnas.91.7.2395. — View Citation

Morens DM, Halstead SB, Repik PM, Putvatana R, Raybourne N. Simplified plaque reduction neutralization assay for dengue viruses by semimicro methods in BHK-21 cells: comparison of the BHK suspension test with standard plaque reduction neutralization. J Clin Microbiol. 1985 Aug;22(2):250-4. doi: 10.1128/jcm.22.2.250-254.1985. — View Citation

Morrison AC, Astete H, Chapilliquen F, Ramirez-Prada C, Diaz G, Getis A, Gray K, Scott TW. Evaluation of a sampling methodology for rapid assessment of Aedes aegypti infestation levels in Iquitos, Peru. J Med Entomol. 2004 May;41(3):502-10. doi: 10.1603/0022-2585-41.3.502. — View Citation

Morrison AC, Gray K, Getis A, Astete H, Sihuincha M, Focks D, Watts D, Stancil JD, Olson JG, Blair P, Scott TW. Temporal and geographic patterns of Aedes aegypti (Diptera: Culicidae) production in Iquitos, Peru. J Med Entomol. 2004 Nov;41(6):1123-42. doi: 10.1603/0022-2585-41.6.1123. — View Citation

Morrison AC, Minnick SL, Rocha C, Forshey BM, Stoddard ST, Getis A, Focks DA, Russell KL, Olson JG, Blair PJ, Watts DM, Sihuincha M, Scott TW, Kochel TJ. Epidemiology of dengue virus in Iquitos, Peru 1999 to 2005: interepidemic and epidemic patterns of transmission. PLoS Negl Trop Dis. 2010 May 4;4(5):e670. doi: 10.1371/journal.pntd.0000670. — View Citation

Morrison AC, Zielinski-Gutierrez E, Scott TW, Rosenberg R. Defining challenges and proposing solutions for control of the virus vector Aedes aegypti. PLoS Med. 2008 Mar 18;5(3):e68. doi: 10.1371/journal.pmed.0050068. — View Citation

Munasinghe DR, Amarasekera PJ, Fernando CF. An epidemic of dengue-like fever in Ceylon (chikungunya--a clinical and haematological study. Ceylon Med J. 1966 Dec;11(4):129-42. No abstract available. — View Citation

Ogoma SB, Moore SJ, Maia MF. A systematic review of mosquito coils and passive emanators: defining recommendations for spatial repellency testing methodologies. Parasit Vectors. 2012 Dec 7;5:287. doi: 10.1186/1756-3305-5-287. — View Citation

Syafruddin D, Bangs MJ, Sidik D, Elyazar I, Asih PB, Chan K, Nurleila S, Nixon C, Hendarto J, Wahid I, Ishak H, Bogh C, Grieco JP, Achee NL, Baird JK. Impact of a spatial repellent on malaria incidence in two villages in Sumba, Indonesia. Am J Trop Med Hyg. 2014 Dec;91(6):1079-87. doi: 10.4269/ajtmh.13-0735. Epub 2014 Oct 13. — View Citation

* Note: There are 36 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse Events (AEs) and Serious Adverse Events (SAEs).	Measured by solicited and unsolicited reports from both the longitudinal cohort and febrile surveillance cohort during the trial period. Mean, minimum and maximum frequency and percentage of AEs and SAEs across clusters among enrolled subjects will be summarized by treatment arm.	24 months
Other	Incidence of Aedes-borne virus (ABV) infection in subjects residing in households within treatment clusters but without SR product.	Measured by comparing Aedes-borne virus infection rates between subjects residing in households with SR product in treatment clusters and subjects from the same clusters who did not agree to the SR application in their households but are receiving standard entomological surveillance and control procedures by the local ministry of health, as an indicator of community effect due to effect of product.	24 months
Other	Clinically apparent cases of Aedes-borne virus (ABV) disease in subjects residing in households within treatment clusters but without SR product.	Measured by comparing Aedes-borne virus disease case rates between subjects residing in households with SR product in households in treatment clusters and individuals from the same clusters who did not agree to the SR application in their households but are receiving standard entomological surveillance and control procedures by the local ministry of health, as an indicator of community effect due to effect of product.	24 months
Other	Adult female Aedes aegypti indoor abundance using Procopak mosquito aspiration in households within treatment clusters but without SR product.	Measured by comparing adult female Aedes aegypti indoor abundance in households with SR product in treatment clusters and households from the same clusters who did not agree to the SR application but are receiving standard entomological surveillance and control procedures by the local ministry of health, as an indicator of community effect to effect of product. Indoor mosquito collections in enrolled households once every 28 days during intervention	24 months
Other	Adult female Aedes aegypti blood fed rate using Procopak mosquito aspiration in households within treatment clusters but without SR product.	Measured by comparing adult female Aedes aegypti blood fed rate in households with SR product in treatment clusters and households from the same clusters who did not agree to the SR application but are receiving standard entomological surveillance and control procedures by the local ministry of health, as an indicator of community effect to effect of product. Samples from indoor mosquito collections in enrolled households once every 28 days during intervention.	24 months
Primary	Incidence of Aedes-borne virus (ABV) infection in the 'longitudinal cohort'.	The primary endpoint is the fraction of monotypic or seronegative individuals in the 'longitudinal cohort' who seroconvert to an arbovirus during the follow-up period post randomization with intervention. Here, the intervention follow-up period is 2 years after initial deployment of SR or placebo. There will be 3 blood samplings from longitudinal cohort participants for measure of seroconversion: one for baseline serostatus characterization (T0), a second at 12 months (T1) and a third at 24 months (T2) from time of initial placement of intervention.	24 months
Secondary	Clinically apparent cases of Aedes-borne virus (ABV) disease.	Clinically apparent is defined as an acute infection that causes overt symptoms (fever, rash, etc.) indicating virus circulation in the blood. For the longitudinal cohort participants, acute and convalescent blood sampling based on time of health facility visit when febrile throughout the intervention period. For other household members participating in febrile surveillance, case definition measured and reported whenever they visit designated health facilities throughout the intervention period.	24 months
Secondary	Adult female Aedes aegypti indoor abundance.	Measured by comparing adult female Aedes aegypti indoor abundance in households using Procopak mosquito aspiration with active and placebo product receiving standard entomological surveillance and control procedures by the local Ministry of Health, as an indicator for reduced mosquito house entry due to effect of product. Indoor mosquito collections in enrolled households once every 28 days during intervention.	24 months
Secondary	Adult female Aedes aegypti blood fed rate.	Measured by comparing adult female Aedes aegypti blood fed rate in households with active and placebo product receiving standard entomological surveillance and control procedures by the local Ministry of Health, as an indicator for reduced mosquito human contact due to effect of product. Direct mosquito abdominal observation by microscopy from samples taken by Procopak aspiration during indoor mosquito collections in enrolled households once every 28 days during intervention.	24 months
Secondary	Diversion of Aedes aegypti mosquitoes into untreated houses.	Measured by comparing adult female Aedes aegypti abundance using Procopak mosquito aspiration in untreated households adjacent to treatment clusters (with active product) to untreated households adjacent to placebo clusters as an indicator for mosquito diversion due to effect of product. Indoor mosquito collections in enrolled households once every 28 days during intervention.	24 months
Secondary	Overall incidence of Aedes-borne virus (ABV) infection.	Measured by the seroconversion rates of all children enrolled in the trial, independent of order of infection (i.e., including tertiary and quaternary infections). Based on blood samples taken for longitudinal seroconversion and febrile surveillance from time of initial placement of intervention.	24 months