The goal of this clinical trial is to test whether In2Care EaveTubes (ETs) as a stand-alone tool can reduce malaria in an area where transmission is driven by insecticide-resistant Anopheles gambiae. Children who live in homes with ETs will be monitored for malaria infection and compared to children living in homes without ETs in Côte d'Ivoire where there is universal coverage of long lasting insecticide nets and pyrethroid resistance is high.

In2Care EaveTubes (ETs) are an inexpensive, new vector control product under World Health Organization (WHO) evaluation informed by mosquito ecology to efficiently target malaria vectors. By installing ETs in the walls of the house at eave level that funnel the natural airflow, mosquitoes are drawn in by the same heat and odor cues that typically attract them through the eaves. Once inside an ET, mosquitoes come into contact with insecticide-treated netting placed inside the ET.

The aim of this study is to test whether ETs as stand-alone tool have an effect on the epidemiology of malaria in villages where houses have been modified with the ET intervention. This prospective 2-arm cluster randomized control trial based on a WHO Vector Control Advisory Group approved protocol will include 17 intervention clusters and 17 control clusters. Both arms will have pyrethroid-treated bednets. Based on the population census, 55 households per cluster with eligible children will be randomly selected for recruitment into the active detection cohorts. In the intervention arm, we will enroll eligible children who reside in ET-treated houses. In the control arm, we will enroll children residing in villages without ET-treated houses. The intervention and control cohorts will be followed for 4 months for baseline covariate measurements and 24 months of a clinical follow up period. During case detection visits, blood samples will be taken from all febrile children and tested for malaria infection with rapid diagnostic tests. To assess the impact of the ET on mosquito density, entomological measurements will be conducted monthly in 20 clusters (10 ET, 10 Control) in 10 randomly selected households per cluster. To estimate the infectiousness of malaria vectors, sporozoite rates will be measured in subsets of the collected mosquito samples.

Village Level Inclusion Criteria:

• ≥ 80% of Households (HHs) must be suitable for EaveTube(ET) installation.
• ≥70% of HHs willing to have ETs installed.
• No participation in the previous Screening + ETs cluster randomized control trial (cRCT).
• Received standard pyrethroid-only long lasting insecticide nets(LLINs) (Permanet 2.0).
• 100-300 HHs per village.
• ≥2 km apart from another village.

Village Level Exclusion Criteria:

• < 80% of HHs suitable for ET installation.
• <70% of HHs willing to have ETs installed.
• Villages being treated by indoor residual spray (IRS) and/or new generation bed net campaigns.
• Participation in previous Screening + ET cRCT.
• <100 and >300 households per village.
• <2 km from another village.

Household Level Inclusion Criteria

• HHs must be suitable for ET installation.
• Provision of consent from heads of HH.

Household Level Exclusion Criteria

• HH not suitable for ET installation (e.g. houses with poor quality thatch roofing or very large eaves or wall gaps, houses in substantial disrepair, unfinished houses under construction, poorly constructed houses, ).
• No provision of consent from heads of HH.

Individual Level Inclusion Criteria

• Children aged ≥ 6 months to < 8 years old at time of enrollment (so all participants are under 10 years old for the duration of clinical follow-up).
• Provision of written, informed consent by parents/care givers.
• Children must reside in villages enrolled in the study and in ETs-treated HHs.
• Hemoglobin at baseline of >7 mg/dL.

Individual Level Exclusion Criteria

• Children aged < 6 months or ≥ 8 years old at time of enrollment.
• No provision of written, informed consent by parents/care givers for child participation.
• Expected to be non-resident during a significant part of the transmission season.
• Hemoglobin at baseline of ≤7 mg/dL, have a known chronic disease, or who have signs of clinical decompensation.
• Participation in another clinical trial investigating a drug, vaccine, medical device or procedure.

Given the nature of the intervention, it is impossible to conduct this study in a fully blinded manner but those parts of the data collection that can be blinded will be. Observer bias will be reduced where feasible. All laboratory work will be blinded. Mosquito collector bias will be reduced by using standard light traps which do not rely on the ability of the fieldworker to collect specimens. Trap catches will not be examined and analyzed by those who collected them but by different technicians who will not know the trap location. We will use codes to identify any clinical samples. Electronic records will not carry the name of the research participants, only an alphanumeric code. Primary analysis by the project statistician will be conducted on blinded data (e.g. arms designated as treatment A & B or something similar). Datasets will only be unblinded once they have been locked.