Abstract
New strategies for meningococcal meningitis outbreak response are needed. Village-wide ciprofloxacin prophylaxis is promising but needs further study.
INTRODUCTION
Vaccine supply against newly-emerged serogroup C meningococcus is limited. New epidemic response strategies are therefore needed in the African meningitis belt. We conducted a three-arm, open-label
cluster-randomized trial of single-dose ciprofloxacin prophylaxis as an epidemic response. (ClinicalTrials.gov number NCT02724046).
METHODS
Villages notifying a suspected meningitis case were randomly assigned (1:1:1) to standard care, single-dose oral ciprofloxacin for household contacts <24h after case notification, or village-wide distribution of ciprofloxacin <72h after first case notification. Dosing was age-based and directly-observed. The primary outcome was the overall attack rate (AR) after inclusion of the village. A random sample of 400 participants
in 20 villages was enrolled to describe any changes in fecal carriage prevalence of ciprofloxacin-resistant Enterobacteriaceae before and after intervention.
RESULTS
Between April 22 and May 18, 2017, 49 villages (total population 71 308) were included and randomly assigned; 17 to the control arm, 17 to household prophylaxis, and 15 to village-wide prophylaxis.
A total of 248 cases were notified. The AR were 451 per 100 000 persons in the control arm; 386 per 100 000 persons in the household prophylaxis arm (p=0.68); and 190 per 100 000 persons in the village-wide prophylaxis arm (p=0.032). After controlling for whether the village was included after
the first rainfall, the adjusted AR ratio between the village-wide prophylaxis arm and the control arm was 0.40 ([0.19‒0.87], p=0.022). Baseline carriage prevalence of ciprofloxacin-resistant Enterobacteriaceae was 95% in the control arm and the village-wide prophylaxis arm and did not change postintervention.
CONCLUSIONS
Village-wide distribution of single-dose oral ciprofloxacin within 72 hours of case notification reduced overall meningitis AR. This novel strategy is promising as a meningitis epidemic response. Further studies should be
carried out in different settings to confirm effectiveness and duration of protection and to investigate the impact on antimicrobial resistance.
