Impact of Wolbachia Deployment on Arboviral Disease Incidence in Medellin and Bello, Colombia

Study Overview
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Brief Summary
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Study setting: Medellin and Bello municipalities, Colombia Health condition(s) studied: Dengue, Zika and chikungunya virus infection Intervention: Deployment of Wolbachia-infected Aedes aegypti mosquitoes in Medellin and Bello. Study design: An interrupted time-series analysis utilising routine disease surveillance data collected by the Medellín and Bello Health Secretariats, which aims to compare incidence of dengue, chikungunya and Zika pre- and post-Wolbachia release. A test-negative study using an incident case-control design, which aims to quantify the reduction in disease incidence among people living within a Wolbachia-treated zone compared with an untreated zone that has a similar dengue risk profile at baseline.

Detailed Description
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Selection and enrolment of participants: Enrolment of patients will commence after completion of Wolbachia releases in the early zones. Study processes for enrolling patients presenting with febrile illness will be established at a network of primary health care facilities that serve the population who reside in the study area. Trained research staff will be employed to assist with study processes in each site. Participants will be enrolled from within the population of patients (aged ≥3 years old) presenting with undifferentiated fever of 1-4 days' duration. All patients meeting the inclusion criteria will be eligible for enrolment and will be asked to provide written informed consent before participating in the study. Recruitment procedures: All eligible participants meeting study inclusion criteria will be invited to enroll continuously throughout the study period. Recruitment will occur during normal clinic hours. Participants will be managed according to standard clinical practice by the attending physicians. Recruitment rates in each clinic and across the study site as a whole will be monitored weekly, including a review of the screening logs to identify the proportion of eligible participants who did not consent to participate. The field coordinator will make regular visits to low-enrolling clinics to identify clinic-based, patient-based or other causes for low recruitment, and put measures in place to address these. Screening: All patients presenting with febrile illness will be screened against the study inclusion criteria by trained staff. All eligible febrile individuals will be recorded in a screening log and invited to participate. Participation status (consent/decline) will be recorded against each participant in the log. Informed consent: Written informed consent will be sought from participants (or their guardian where the participant is a minor) by trained local staff, after explaining the study objectives, processes, data, and sample collection, and the participant has had an opportunity to ask questions. A verbal explanation of the written Explanatory Statement will be provided to all participants in the local language. In addition, participants aged between 7 and 17 years will be invited to sign an assent form indicating they understand the research and agree to participate. Data and sample collection procedures Data collection: A unique identifier will be assigned to each participant at enrollment. Basic demographic details, eligibility against the inclusion criteria and illness onset date will be recorded in a standardized case report form.

Official Title
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World Mosquito Program - Colombia (WMP-COLOMBIA): The Impact of City-wide Deployment of Wolbachia-infected Mosquitoes on Arboviral Disease Incidence in Medellin and Bello, Colombia

Conditions
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Dengue, Chikungunya Virus Infection, Zika Virus Infection

Intervention / Treatment
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* Biological: Wolbachia-carrying Ae.aegypti mosquitoes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fever (either self-reported or objectively measured, e.g. axillary temperature ≥38oC, with a date of onset between 1-4 days prior to the day of presentation. Aged ≥3 years old. Lived (i.e. slept) in the study area every night (or day) for the 10 days preceding illness onset. Exclusion Criteria: Localising features suggestive of a specific diagnosis e.g. severe diarrhea, otitis, pneumonia Prior enrollment in the study within the previous 4 weeks.

Ages Eligible for Study
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Minimum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Early-release<br>Resident in areas that receive early Wolbachia deployments. | Biological: Wolbachia-carrying Ae.aegypti mosquitoes<br>* Wolbachia-infected Ae. aegypti mosquito eggs and adults sequentially deployed into Medellin and Bello, Colombia. Deployments cease once Wolbachia prevalence has reached a predetermined frequency (usually ≥60%).<br>|
| Late-release<br>Resident in areas that receive late Wolbachia deployments. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dengue cases notified to surveillance system | Incidence of dengue cases (suspected, epidemiological link, and IgM positive for dengue) notified to the disease surveillance system | 5 years | 
| Virologically-confirmed dengue | Virologically-confirmed dengue virus infection in patients reporting febrile illness recruited from health clinics. Participants are classified as dengue cases if plasma samples collected 1-4 days after onset of fever test positive for dengue virus NS1 antigen or dengue virus nucleic acid by RT-qPCR. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IgM test positive for dengue | Number of cases who were IgM test positive for dengue | 5 years | 
| Severe dengue cases | Incidence of severe dengue cases reported to the surveillance system, by release zone and overall. | 5 years | 
| Zika cases notified to surveillance system | Incidence of Zika cases reported to the surveillance system. | 5 years | 
| Chikungunya cases notified to surveillance system | Incidence of chikungunya cases reported to the surveillance system. | 5 years | 
| Spatial analysis | The spatial distribution of notified dengue cases with geolocated primary address available, before and after Wolbachia deployment | 5 years | 
| Virologically-confirmed chikungunya infection | Virologically-confirmed chikungunya virus infection in patients reporting febrile illness recruited from health clinics. Participants are classified as chikungunya cases if plasma samples collected 1-4 days after onset of fever test positive for chikungunya virus NS1 antigen or chikungunya virus nucleic acid by RT-qPCR. | 2 years | 
| Virologically-confirmed Zika infection | Virologically-confirmed Zika virus infection in patients reporting febrile illness recruited from health clinics. Participants are classified as Zika cases if plasma samples collected 1-4 days after onset of fever test positive for Zika virus NS1 antigen or Zika virus nucleic acid by RT-qPCR. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Wolbachia, Colombia, Dengue, Zika, Chikungunya, Arboviral diseases, Disease surveillance