Assessing the impact of housing improvement and ivermectin administration to cattle on malaria transmission in southwest Ethiopia: A study protocol for a community-based cluster randomized control trial

Introduction The transmission of malaria and other infectious diseases can be linked to housing conditions. For malaria, poor housing conditions can result in higher indoor transmission rates compared to improved houses. The current study aims to introduce a new approach known as the push-pull strategy. This strategy involves screening houses to prevent mosquitoes from entering the houses and administering ivermectin to cattle to kill mosquitoes in the household compound. With this approach, we anticipate reducing mosquito bites and, subsequently, malaria incidence. Methods This study is a cluster randomized control trial in malaria-endemic Kebeles (villages the smallest administrative unit) near the southern Rift Valley Lakes in the Gamo Zone of Ethiopia. The trial is open-labeled and four-armed with 60 clusters. The unit of randomization is a cluster (Limat Budin with 30 to 35 households) with an equal number of households in each arm. Each cluster will receive one of the following interventions: house screening (n=15), ivermectin cattle treatment (n=15), a combination of house screening and ivermectin cattle treatment (n=15), or no intervention (control arm, only a standard malaria prevention intervention; n=15). All clusters will continue with the essential malaria interventions such as bed nets and, according to the Ministry of Health policy. A total of 1912 households with 9060 individuals will be included in the study. The study's primary outcome is determining malaria incidence among all age groups in the intervention groups compared to the control arm. Over two years, we will screen study participants every four months to measure epidemiologic and serologic endpoints. Additionally, we will conduct bimonthly entomological assessments in 480 households with equal numbers in each arm for two years. All household members will undergo malaria testing using microscopy, with results confirmed through molecular methods to determine malaria prevalence and incidence. Children under five will also be tested for anemia with the Hemocue 301+ analyzer. We will use serological markers and entomological indices to estimate the human exposure to parasites and mosquito bites. Furthermore, we will evaluate the interventions durability, community acceptance, cost-effectiveness and it effect on household poverty reduction. We will perform an intention-to-treat analysis for cluster-level analysis. Discussion This is the first randomized control trial to assess the effectiveness of the push-pull strategy in controlling malaria in Ethiopia. This innovative approach aims to decrease the number of malaria-carrying mosquitoes indoors and outdoors, reduce human exposure to mosquito bites and parasites, and ultimately lower malaria incidence. Moreover, this strategy has the potential to ease the burden of malaria illness and aid in reducing household poverty. Ethics The trial has been approved by the Institutional Research Ethics Review Board (IRB/1423/2023) and the Animal Ethics Review Committee (AMU/AREC/12/2015) of Arba Minch University. Dissemination The study findings will be disseminated through presentations at national and international conferences, sharing information with study participants and stakeholders, and publications in peer-reviewed journals. Additionally, policymakers will be informed of the results and possibly incorporate them into the national malaria control toolbox. Trial registration The study is registered in the Pan African Clinical Trial Registry (PACTR202306667462566). ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial The study is registered in the Pan African Clinical Trial Registry: PACTR202306667462566 ### Funding Statement The Norwegian Programme for Capacity Development in Higher Education and Research for Development (grant number QZA-21/0162) funds the South Ethiopia Network of Universities in Public Health (SENUPH II). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The trial has been approved by the Institutional Research Ethics Review Board (IRB/1423/2023) and the Animal Ethics Review Committee (AMU/AREC/12/2015) of Arba Minch University I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes After the study ends, study protocols, all publications, and data will be archived and made publicly available, and each of these items will have a Digital Object Identifier [DOI]. In collaboration with the Data Centre, efforts will be made to ensure that data is provided and organized in a format that is accessible. Only anonymized data will be made publicly available. In the case of household survey data, we will follow standard protocols for anonymization