Preventing malaria | South Ethiopia Network of Universities in Public Health (Senuph

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

Preprint research protocol

Massebo, Fekadu, Betelihem Jima, Nigatu Eligo, Feven Wudneh, Mohammed Seid, Daniel Woldeyes, Biniam Wondale, Teklu Wegayehu, and Bernt Lindtjørn. “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.” medRxiv (2023): 2023.12.01.23299280. https://doi.org/10.1101/2023.12.01.23299280. https://www.medrxiv.org/content/medrxiv/early/2023/12/01/2023.12.01.23299280.full.pdf.

Introduction
The transmission of infectious diseases is related to housing conditions, with higher indoor transmission in poor housing conditions than in improved houses. The current study aims to introduce a novel push-pull approach to divert malaria mosquitoes to cattle through household screening and kill them by administering ivermectin. We, therefore, hypothesised that a push-pull strategy (house screening and ivermectin administration to cattle) could make a measurable change in reducing malaria.

Objective: The primary objective of this intervention is to determine whether house screening and ivermectin administration to cattle belonging to the household reduce malaria incidence among all age groups compared to conventional malaria control tools.

The secondary objectives of the trial are:

To determine whether house screening and ivermectin cattle treatment reduce the density of host-seeking and resting malaria vectors.
To determine whether house screening and ivermectin cattle treatment reduce malaria parasitemia among all age groups.
To assess whether house screening and ivermectin cattle treatment reduce gametocyte carriage rates among all age groups.
To assess the effect of house screening and ivermectin cattle treatment on the human blood index of malaria mosquitoes
To assess whether house screening and ivermectin cattle treatment reduce the gametocyte positivity rate in freshly fed mosquitoes.
To assess the night-time mosquito biting and human activities in intervention and control arms
Using serological markers to determine whether house screening and ivermectin cattle treatment reduce human exposure to malaria mosquito bites.
To assess the effect of house screening and ivermectin cattle treatment on malaria seroconversion rate among children under five years
To determine the effect of house screening and ivermectin cattle treatment on the spatiotemporal distribution of malaria
To assess the impact of house screening and ivermectin cattle treatment on bed net use rate
To assess the community acceptance of house screening and ivermectin cattle treatment malaria intervention
To determine the durability of the house screening intervention
To determine the incremental cost and cost-effectiveness of house screening and ivermectin cattle treatment against malaria compared to control arms.
To evaluate the impact of house screening and ivermectin cattle treatment against malaria on the reduction of multidimensional poverty at the household level

Methods: This is a four-arm, open-labelled, cluster randomised control trial with 60 clusters in malaria endemic Kebeles (= villages) close to the southern Rift Valley Lakes in Gamo zone, Ethiopia. The unit of randomisation will be a cluster (with 30-35 households). A computer-generated sequence will do it in blocks of four clusters in each village in the ratio 1:1:1:1. Thus, clusters will receive intervention comprising house screening (n =15), ivermectin cattle treatment (n =15), and a combination of house screening and ivermectin cattle treatment (n =15) and the control arm (n =15) will continue with the essential malaria interventions as recommended by the Ministry of health. A total of 1912 households (9060 individuals) will be included. The primary outcome variable of the study will be the incidence of malaria among all age groups in intervention groups compared with the control arm. Epidemiologic and serologic endpoints will be measured by screening study participants every four months for two years. A bimonthly entomological assessment will be done in 480 households with equal numbers in each arm for two years. All household members will be screened for malaria using a rapid diagnostic technique.

Further confirmation of results will be done by microscopy and molecular technique. We measure the prevalence, incidence, and human exposure to mosquito bites and malaria parasites by focusing on serological markers and the entomological indices of malaria. The durability, community acceptance and cost-effectiveness of the interventions will be assessed. Multidimensional household poverty reduction due to malaria intervention will be assessed. Intention-to-treat analysis will be performed for cluster-level analysis of outcome variables using R-statistical software. The spatiotemporal distribution clustering of malaria will be done by using ARC-View GIS. Multilevel mixed-effect regression analysis will be used to compare outcome variables between intervention and control clusters by considering the clustering effect.

Discussion: This is the first randomised control trial to assess the novel push-pull malaria control strategy. We hypothesise that this novel push-pull control strategy can make a measurable change in malaria incidence, the indoor and outdoor density of malaria vectors and human exposure and reduce household poverty.

Ethics: The institutional and national review boards approved the trial.

Dissemination: The findings will be presented in the consortium at national and international conferences to promote the intervention to be considered in the package of the malaria control toolbox. The results will also be communicated with the stakeholders; data will be available for the policymaker’s decision and published in peer-reviewed Journals.

Researchers include: The lead researcher is Dr Fekadu Massebo. The PhD students are Betelihem Jima, Nigatu Eligo, Bereket Tadesse, Feven Wudneh, Mohammed Seid, and Amsale Tekle. Researchers include Dr Daniel Woldeyes, Dr Biniam Wondale, Teklu Wegayehu, Bernt Lindtjørn

Trial registration: Registration for the trial is at The Pan African Clinical Trials Registry (PACTR) with registration number PACTR202306667462566

Keywords/phrases: Push-pull, House screening, Ivermectin administration, Malaria incidence, Entomological indicators, Malaria clustering, Serological biomarkers, Cost-effectiveness, Gamo zone, Ethiopia