Ciprofloxacin for contacts of cases of meningococcal meningitis as an epidemic response: study protocol for a cluster-randomized trial.

BACKGROUND: Epidemics of meningococcal meningitis are common in the "African meningitis belt." Current response strategies include reactive vaccination campaigns, which are often organized too late to have maximal impact. A novel strain of Neisseria meningitidis serogroup C has been circulating in recent years, and vaccine supplies are limited. An evaluation of chemoprophylaxis with single-dose ciprofloxacin for household contacts of meningitis cases has therefore been recommended.

METHODS/DESIGN: A three-arm cluster-randomized trial has been designed for implementation during a meningococcal meningitis epidemic in a health district in Niger in which at least two Health Zones (HZs) have met the weekly epidemic threshold. The primary outcome is the incidence (attack rate) of meningitis during the epidemic. Villages will be randomized in a 1:1:1 ratio to one of three different arms: standard care, household-level prophylaxis, or village-wide prophylaxis. After study launch, when a case of meningococcal meningitis is identified in an HZ, the first reported case from a village will trigger the inclusion and randomization of the village. Household-level prophylaxis with single-dose ciprofloxacin will be offered in the home to all household members within 24 hours of the notification of the case, and village-wide distributions will occur within 72 hours of the notification of the case. The sample size necessary to detect differences between each of the two intervention arms and the standard care arm will be set after 4 weeks of data collection, in order to quantify multiple variables that could be particular to a given area. The primary analysis will compare attack rates at the end of the epidemic in each of the three arms. A nested sub-study will assess the effects of ciprofloxacin prophylaxis on the prevalence of ciprofloxacin-resistant enterobacteriaceae. A total of 200 participants in the standard care arm and 200 in the village-wide prophylaxis arm will provide stool samples at days 0, 7, and 28 following their village's inclusion in the study.

DISCUSSION: An innovative trial is proposed for implementation during an epidemic that will assess the impact of a novel strategy for meningitis outbreak response. In parallel, we will describe potential negative effects of the intervention.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02724046 . Registered on 15 March 2016. Last updated on 13 June 2017.