Cluster randomised controlled trial of double-dose azithromycin mass drug administration, facial cleanliness and fly control measures for trachoma control in Oromia, Ethiopia: the stronger SAFE trial protocol

Abstract

Introduction: Trachoma is caused by the bacterium Chlamydia trachomatis (Ct). The WHO recommends the SAFE strategy for trachoma elimination: Surgery for trichiasis, Antibiotics, Facial cleanliness and Environmental improvement. Multiple rounds of SAFE implementation have proven insufficient to eliminate trachoma in Ethiopia, where over 50% of the global trachoma burden remains. More effective antibiotic treatment schedules and transmission-suppressing approaches are needed. The aim of stronger SAFE is to evaluate the impact of a novel package of interventions to strengthen the A, F and E of SAFE on the prevalence of ocular Ct and trachoma in Oromia, Ethiopia.

Methods and analysis: 68 clusters were randomised in a 1:1:1:1 ratio to one of (1) standard A/standard F&E (standard SAFE), (2) standard A/enhanced F&E, (3) enhanced A/standard F&E or (4) enhanced A/enhanced F&E (stronger SAFE). Enhanced A includes two height-based doses of oral azithromycin (equivalent to 20 mg/kg) given as single doses 2 weeks apart, as mass drug administration, annually. Enhanced F&E includes fly control measures (permethrin-treated headwear and odour-baited traps) and face-washing hygiene behaviour change implemented at household level in selected communities. The interventions will be implemented and reinforced over 3 years.The primary outcome is the prevalence of ocular Ct by quantitative PCR in children aged 1-9 years at 36 months. A key secondary outcome is the prevalence of active (inflammatory) trachoma in the same children, assessed by validated trachoma graders and conjunctival photography. Laboratory technicians and photo-graders are masked to treatment allocation. Other important secondary analyses include process evaluations, assessment of behaviour change, fly indicators, adherence and coverage of interventions and a cost analysis.

Ethics and dissemination: Study protocols have been approved by the National Research Ethics Review Committee of the Ethiopian Ministry of Science and Higher Education and the London School of Hygiene & Tropical Medicine Ethics Committee. An independent data safety and monitoring board oversees the trial. Results will be disseminated through peer-reviewed publications, presentations and reports.

Trial registration number: ISRCTN40760473.

Keywords: Clinical Trial; Entomology; Epidemiology; Mass Drug Administration; OPHTHALMOLOGY; PUBLIC HEALTH.

Figure 1. Stronger SAFE trial schematic. Schematic showing 68 clusters randomised to 1 of 4 arms in a 1:1:1:1 ratio in a parallel-group cluster randomised controlled trial. Ct, Chlamydia trachomati; HH, households; TF, trachomatous inflammation-follicular; TI, trachomatous inflammation-inflammatory.

Figure 2. Repellent permethrin-treated headwear (PTH). A participant wearing a permethrin-treated scarf. The selected PTH is a commercial product made from 100% polyester, factory-treated with proprietary permethrin ((m-Phenoxybenzyl)-cis,trans-3-(2,2-dichlorovinyl)−2,2-dimethylcyclopropanecarboxylate, CAS number 52645-53-1) at a concentration of less than 1.25 g/m² fabric (this is equivalent to 0.125 mg/cm², the concentration that the US-Environmental Protection Agency considers to be safe for all ages) (InsectShield). Photograph with permission from Robinson et al.

Figure 3. Odour-baited trap (OBT) deployed to capture Musca sorbens in stronger SAFE. A homemade OBT trap, designed using locally available materials, constructed from a 5 L water bottle attached to a plastic bucket (cut to specification), baited with a commercially available lure (The Buzz).

Figure 4. Household WASH (Water, Sanitation, Hygiene) station employed in stronger SAFE. A simple wash station with a faucet, bar of soap and a soap dish were distributed to all households in the yolk. All residents of the cluster were invited to the community event and received components to build the wash station, and instructions for washing with soap (or soapy water). Reinforcement of the target behaviour and troubleshooting of barriers affecting WASH station function and use were conducted through family forums.

Figure 5. Hygiene behaviour change intervention developed for stronger SAFE. The hygiene behaviour change intervention was codeveloped with the community and is designed to be low-cost and sustainable, delivered by a team of implementers and health volunteers. The intervention comprises five main contact points over a month, with subsequent activities in the dry and rainy seasons each year.