Aedes-borne Diseases, Chikungunya, Dengue, Zika
Conditions
Keywords
Targeted Indoor Residual Spraying, Children, Dengue virus (DENV), Chikungunya virus (CHIKV), Zika virus (ZIKV), Ae. aegypti mosquito
Brief summary
The objective of this trial is evaluate the efficacy of Targeted Indoor Residual Spraying (TIRS) in preventing symptomatic disease caused by Aedes-borne diseases (ABDs) in children 2 to 15 years of age in the city of Merida, Yucatan State, Mexico.
Detailed description
Contemporaneous urban vector control (truck-mounted ultra-low volume spraying, thermal fogging, larviciding) has failed to contain dengue epidemics and to prevent the global range expansion of Aedes-borne diseases (ABDs: dengue, chikungunya, zika). Part of the challenge in sustaining effective ABD control emerges from the remarkable paucity of evidence about the epidemiological impact of any vector control method. Furthermore, the classic deployment of interventions in response to clinical cases fails to account for the important contribution of out-of-home human mobility and asymptomatic infections. The trial will be conducted in the city of Merida extending ongoing longitudinal cohort to follow a population of 4,600 children 2-15 years old randomly allocated to receive either TIRS treatment or not. If efficacious, TIRS will drive a paradigm shift in Aedes control by: considering Ae. aegypti behavior to rationally guide insecticide applications; the change to preventive control (pre- ABD transmission season rather than in response to symptomatic cases); the use of third generation insecticides to which Ae. Aegypti is susceptible.
Interventions
OTHERTargeted Indoor Residual Spraying (TIRS)
Spraying of insecticide Actellic 300CS will start in May or June extending for 1 to 2 months. Residents will be asked to temporarily leave the house during treatment and wait half an hour to one hour for the product to dry before re-entering the house. Insecticide application will follow strict protocol developed by the Centers for Disease Control and Prevention (CDC), Emory University, and the Universidad Autónoma de Yucatán.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
Household Level Inclusion Criteria: * Household is located within the bounds of a study cluster (5x5 city-block clusters) * City block has at least 60% premises that are residential Individual Level Inclusion Criteria: * 2 or more and up to 15 years of age at the time of initial enrollment * Living in a house that consented to TIRS (for children in TIRS cluster)
Exclusion criteria
Household Level
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Symptomatic Participants Testing Positive for Aedes-borne Virus Infections That Are Laboratory Confirmed or Serologically | 18 months of active surveillance during high transmission seasons (each 6 months in duration) during 3 years (July through December in 2021, 2022, and 2023) | The number of symptomatic children with laboratory confirmed, by reverse transcription-polymerase chain reaction (RT-PCR) or immunoglobulin M/ immunoglobulin G (IgM/IgG) enzyme-linked immunosorbent assay (ELISA), Aedes-borne Viruses infections. The number of any Aedes-borne virus infection during three seasons of high transmission is described, as well as the number of Dengue virus (DENV), Chikungunya virus (CHIKV), Zika virus (ZIKV) and coinfections. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ae. Aegypti Mosquito Infection Rate With Aedes-borne Viruses (DENV, CHIKV and ZIKV) | Up to 6 months (mosquito pools were collected during the 6 months post TIRS spraying samplings in 2021) | Ae. aegypti mosquito infection rate with Aedes-borne Viruses (DENV, CHIKV and ZIKV) assessed by the number of positive RT-PCR tests. Infection is mosquitoes is analyzed by collecting binary data (a mosquito pool is either infected or not) and transforming that into minimum infection rates (MIR) with the calculation: (1/number of mosquitoes in the pool) times 1000. Households were randomly selected for testing; houses were eligible for testing if they were located within the central blocks and had at least one child enrolled in the study. |
| Ae. Aegypti Indoor Entomological Index of Adult Mosquito Abundance | Up to 36 months starting at the first TIRS application | The Ae. aegypti indoor entomological index of adult mosquito presence/abundance is calculated as the number of adult mosquitoes per house. Higher values mean that more mosquitoes are found within houses. |
| Ae. Aegypti Indoor Entomological Index of Female Mosquito Abundance | Up to 36 months starting at first TIRS application | The Ae. aegypti indoor entomological index of female mosquito presence/abundance is calculated as the number of female mosquitoes per house. Higher values mean that more mosquitoes are found within houses. |
| Number Positive Tests of Laboratory Confirmed Aedes-borne Viruses Infections By Season | Up to 36 months, during serosurvey seasons 2021-2022, 2022-2023, and 2023-2024 | Number of laboratory confirmed (IgG ELISA and neutralization testing) Aedes-borne Viruses (DENV, CHIKV and ZIKV) in annual surveillance samples. |
| Number of Households Where the Head of Household Would Recommend the Intervention | Post-intervention (up to 41 months and 26 days after the start of the intervention) | Acceptability of the intervention is determined through household surveys, for households that received the intervention. Acceptability is assessed as the number of households where the head of that household would recommend the intervention to others. |
| Number of Households With a Resident That Had a Reaction to the Insecticide | Post-intervention (up to 41 months and 26 days after the start of the intervention) | Safety of the intervention is assessed as the number of households receiving the TIRS intervention that had evidence of a household resident having a reaction possibly related to the insecticide, which was assessed and confirmed by study doctors. |
| Ae. Aegypti Indoor Entomological Index of Bloodfed Female Mosquito Abundance | Up to 36 months starting at first TIRS application | The Ae. aegypti indoor entomological index of bloodfed female mosquito presence/abundance is calculated as the number of bloodfed female mosquitoes per house. Higher values mean that more mosquitoes are found within houses. |
Countries
Mexico
Participant flow
Recruitment details
Participants are children from households in the study clusters in Merida, Yucatan, Mexico. Participant enrollment began November 3, 2020 and all follow-up assessments were completed by April 28, 2024.
Participants by arm
| Arm | Count |
|---|---|
| Targeted Indoor Residual Spraying (TIRS) Children residing in households located in Targeted Indoor Residual Spraying (TIRS) clusters that were offered the intervention. | 2,239 |
| Routine Aedes-borne Virus (ABV) Prevention and Control Children residing in households located in routine Aedes-borne virus (ABV) prevention and control clusters, without Targeted Indoor Residual Spraying (TIRS). | 2,222 |
| Total | 4,461 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Death | 1 | 2 |
| Overall Study | Lost to follow-up due to moving from the cluster | 327 | 393 |
| Overall Study | Withdrawal by study team | 6 | 12 |
| Overall Study | Withdrawal by Subject | 70 | 95 |
Baseline characteristics
| Characteristic | Total | Routine Aedes-borne Virus (ABV) Prevention and Control | Targeted Indoor Residual Spraying (TIRS) |
|---|---|---|---|
| Age, Categorical <=18 years | 4461 Participants | 2222 Participants | 2239 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4461 Participants | 2222 Participants | 2239 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Mexico | 4461 Participants | 2222 Participants | 2239 Participants |
| Sex: Female, Male Female | 2161 Participants | 1053 Participants | 1108 Participants |
| Sex: Female, Male Male | 2300 Participants | 1169 Participants | 1131 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 2,239 | 2 / 2,222 |
| other Total, other adverse events | 6 / 2,239 | 4 / 2,222 |
| serious Total, serious adverse events | 0 / 2,239 | 2 / 2,222 |
Outcome results
Primary
Number of Symptomatic Participants Testing Positive for Aedes-borne Virus Infections That Are Laboratory Confirmed or Serologically
The number of symptomatic children with laboratory confirmed, by reverse transcription-polymerase chain reaction (RT-PCR) or immunoglobulin M/ immunoglobulin G (IgM/IgG) enzyme-linked immunosorbent assay (ELISA), Aedes-borne Viruses infections. The number of any Aedes-borne virus infection during three seasons of high transmission is described, as well as the number of Dengue virus (DENV), Chikungunya virus (CHIKV), Zika virus (ZIKV) and coinfections.
Time frame: 18 months of active surveillance during high transmission seasons (each 6 months in duration) during 3 years (July through December in 2021, 2022, and 2023)
Population: This analysis includes symptomatic children who were tested for Andes-borne viruses during high transmission seasons.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Targeted Indoor Residual Spraying (TIRS) | Number of Symptomatic Participants Testing Positive for Aedes-borne Virus Infections That Are Laboratory Confirmed or Serologically | Number of Children Testing Positive for DENV | 151 Participants |
| Targeted Indoor Residual Spraying (TIRS) | Number of Symptomatic Participants Testing Positive for Aedes-borne Virus Infections That Are Laboratory Confirmed or Serologically | Number of Children Testing Positive for ZIKV | 39 Participants |
| Targeted Indoor Residual Spraying (TIRS) | Number of Symptomatic Participants Testing Positive for Aedes-borne Virus Infections That Are Laboratory Confirmed or Serologically | Number of Children Testing Positive for CHIKV | 1 Participants |
| Targeted Indoor Residual Spraying (TIRS) | Number of Symptomatic Participants Testing Positive for Aedes-borne Virus Infections That Are Laboratory Confirmed or Serologically | Number of Children Testing Positive for Coinfection | 22 Participants |
| Targeted Indoor Residual Spraying (TIRS) | Number of Symptomatic Participants Testing Positive for Aedes-borne Virus Infections That Are Laboratory Confirmed or Serologically | Number of Children Testing Positive for All Aedes-borne Viruses | 213 Participants |
| Routine Aedes-borne Virus (ABV) Prevention and Control | Number of Symptomatic Participants Testing Positive for Aedes-borne Virus Infections That Are Laboratory Confirmed or Serologically | Number of Children Testing Positive for Coinfection | 8 Participants |
| Routine Aedes-borne Virus (ABV) Prevention and Control | Number of Symptomatic Participants Testing Positive for Aedes-borne Virus Infections That Are Laboratory Confirmed or Serologically | Number of Children Testing Positive for All Aedes-borne Viruses | 209 Participants |
| Routine Aedes-borne Virus (ABV) Prevention and Control | Number of Symptomatic Participants Testing Positive for Aedes-borne Virus Infections That Are Laboratory Confirmed or Serologically | Number of Children Testing Positive for DENV | 146 Participants |
| Routine Aedes-borne Virus (ABV) Prevention and Control | Number of Symptomatic Participants Testing Positive for Aedes-borne Virus Infections That Are Laboratory Confirmed or Serologically | Number of Children Testing Positive for CHIKV | 0 Participants |
| Routine Aedes-borne Virus (ABV) Prevention and Control | Number of Symptomatic Participants Testing Positive for Aedes-borne Virus Infections That Are Laboratory Confirmed or Serologically | Number of Children Testing Positive for ZIKV | 55 Participants |
Secondary
Ae. Aegypti Indoor Entomological Index of Adult Mosquito Abundance
The Ae. aegypti indoor entomological index of adult mosquito presence/abundance is calculated as the number of adult mosquitoes per house. Higher values mean that more mosquitoes are found within houses.
Time frame: Up to 36 months starting at the first TIRS application
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Targeted Indoor Residual Spraying (TIRS) | Ae. Aegypti Indoor Entomological Index of Adult Mosquito Abundance | 0.61 mosquitoes/house | Standard Deviation 1.1 |
| Routine Aedes-borne Virus (ABV) Prevention and Control | Ae. Aegypti Indoor Entomological Index of Adult Mosquito Abundance | 1.39 mosquitoes/house | Standard Deviation 2.1 |
Secondary
Ae. Aegypti Indoor Entomological Index of Bloodfed Female Mosquito Abundance
The Ae. aegypti indoor entomological index of bloodfed female mosquito presence/abundance is calculated as the number of bloodfed female mosquitoes per house. Higher values mean that more mosquitoes are found within houses.
Time frame: Up to 36 months starting at first TIRS application
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Targeted Indoor Residual Spraying (TIRS) | Ae. Aegypti Indoor Entomological Index of Bloodfed Female Mosquito Abundance | 0.25 mosquitoes/house | Standard Deviation 0.92 |
| Routine Aedes-borne Virus (ABV) Prevention and Control | Ae. Aegypti Indoor Entomological Index of Bloodfed Female Mosquito Abundance | 0.53 mosquitoes/house | Standard Deviation 0.94 |
Secondary
Ae. Aegypti Indoor Entomological Index of Female Mosquito Abundance
The Ae. aegypti indoor entomological index of female mosquito presence/abundance is calculated as the number of female mosquitoes per house. Higher values mean that more mosquitoes are found within houses.
Time frame: Up to 36 months starting at first TIRS application
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Targeted Indoor Residual Spraying (TIRS) | Ae. Aegypti Indoor Entomological Index of Female Mosquito Abundance | 0.29 mosquitoes/house | Standard Deviation 0.9 |
| Routine Aedes-borne Virus (ABV) Prevention and Control | Ae. Aegypti Indoor Entomological Index of Female Mosquito Abundance | 0.65 mosquitoes/house | Standard Deviation 1.9 |
Secondary
Ae. Aegypti Mosquito Infection Rate With Aedes-borne Viruses (DENV, CHIKV and ZIKV)
Ae. aegypti mosquito infection rate with Aedes-borne Viruses (DENV, CHIKV and ZIKV) assessed by the number of positive RT-PCR tests. Infection is mosquitoes is analyzed by collecting binary data (a mosquito pool is either infected or not) and transforming that into minimum infection rates (MIR) with the calculation: (1/number of mosquitoes in the pool) times 1000. Households were randomly selected for testing; houses were eligible for testing if they were located within the central blocks and had at least one child enrolled in the study.
Time frame: Up to 6 months (mosquito pools were collected during the 6 months post TIRS spraying samplings in 2021)
Population: This analysis includes households where mosquito sampling occurred. Individual participants were not analyzed. Only households contributed data.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Targeted Indoor Residual Spraying (TIRS) | Ae. Aegypti Mosquito Infection Rate With Aedes-borne Viruses (DENV, CHIKV and ZIKV) | 0 Households samples |
| Routine Aedes-borne Virus (ABV) Prevention and Control | Ae. Aegypti Mosquito Infection Rate With Aedes-borne Viruses (DENV, CHIKV and ZIKV) | 0 Households samples |
Secondary
Number of Households Where the Head of Household Would Recommend the Intervention
Acceptability of the intervention is determined through household surveys, for households that received the intervention. Acceptability is assessed as the number of households where the head of that household would recommend the intervention to others.
Time frame: Post-intervention (up to 41 months and 26 days after the start of the intervention)
Population: This analysis includes households in TIRS clusters where the head of the household completed the household survey.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Targeted Indoor Residual Spraying (TIRS) | Number of Households Where the Head of Household Would Recommend the Intervention | 2160 Households |
Secondary
Number of Households With a Resident That Had a Reaction to the Insecticide
Safety of the intervention is assessed as the number of households receiving the TIRS intervention that had evidence of a household resident having a reaction possibly related to the insecticide, which was assessed and confirmed by study doctors.
Time frame: Post-intervention (up to 41 months and 26 days after the start of the intervention)
Population: This analysis includes households in TIRS clusters where the head of the household completed the household survey.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Targeted Indoor Residual Spraying (TIRS) | Number of Households With a Resident That Had a Reaction to the Insecticide | 2 Households |
Secondary
Number Positive Tests of Laboratory Confirmed Aedes-borne Viruses Infections By Season
Number of laboratory confirmed (IgG ELISA and neutralization testing) Aedes-borne Viruses (DENV, CHIKV and ZIKV) in annual surveillance samples.
Time frame: Up to 36 months, during serosurvey seasons 2021-2022, 2022-2023, and 2023-2024
Population: The population analyzed includes children living in study households where annual surveillance sampling for Aedes-borne viruses occurred.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Targeted Indoor Residual Spraying (TIRS) | Number Positive Tests of Laboratory Confirmed Aedes-borne Viruses Infections By Season | Number of Positive Tests for all Aedes-borne Viruses During 2021-2022 Season | 36 Number of Tests |
| Targeted Indoor Residual Spraying (TIRS) | Number Positive Tests of Laboratory Confirmed Aedes-borne Viruses Infections By Season | Number of Positive Tests for all Aedes-borne Viruses During 2022-2023 Season | 216 Number of Tests |
| Targeted Indoor Residual Spraying (TIRS) | Number Positive Tests of Laboratory Confirmed Aedes-borne Viruses Infections By Season | Number of Positive Tests for all Aedes-borne Viruses During 2023-2024 Season | 169 Number of Tests |
| Routine Aedes-borne Virus (ABV) Prevention and Control | Number Positive Tests of Laboratory Confirmed Aedes-borne Viruses Infections By Season | Number of Positive Tests for all Aedes-borne Viruses During 2021-2022 Season | 39 Number of Tests |
| Routine Aedes-borne Virus (ABV) Prevention and Control | Number Positive Tests of Laboratory Confirmed Aedes-borne Viruses Infections By Season | Number of Positive Tests for all Aedes-borne Viruses During 2022-2023 Season | 166 Number of Tests |
| Routine Aedes-borne Virus (ABV) Prevention and Control | Number Positive Tests of Laboratory Confirmed Aedes-borne Viruses Infections By Season | Number of Positive Tests for all Aedes-borne Viruses During 2023-2024 Season | 204 Number of Tests |