Abstract
BackgroundAntibiotic prophylaxis for contacts of meningitis cases is not recommended during outbreaks in the African meningitis belt. We assessed the effectiveness of single-dose oral ciprofloxacin administered to household contacts and in village-wide distributions on the overall attack rate (AR) in an outbreak of meningococcal meningitis.Methods and findingsIn this 3-arm, open-label, cluster-randomized trial during a meningococcal meningitis outbreak in Madarounfa District, Niger, villages notifying a suspected case were randomly assigned (1:1:1) to standard care (the control arm), single-dose oral ciprofloxacin for household contacts within 24 hours of case notification, or village-wide distribution of ciprofloxacin within 72 hours of first case notification. The primary outcome was the overall AR of suspected meningitis after inclusion. A random sample of 20 participating villages was enrolled to document any changes in fecal carriage prevalence of ciprofloxacin-resistant and extended-spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae before and after the intervention. Between April 22 and May 18, 2017, 49 villages were included: 17 to the control arm, 17 to household prophylaxis, and 15 to village-wide prophylaxis. A total of 248 cases were notified in the study after the index cases. The AR was 451 per 100,000 persons in the control arm, 386 per 100,000 persons in the household prophylaxis arm (t test versus control p = 0.68), and 190 per 100,000 persons in the village-wide prophylaxis arm (t test versus control p = 0.032). The adjusted AR ratio between the household prophylaxis arm and the control arm was 0.94 (95% CI 0.52–1.73, p = 0.85), and the adjusted AR ratio between the village-wide prophylaxis arm and the control arm was 0.40 (95% CI 0.19‒0.87, p = 0.022). No adverse events were notified. Baseline carriage prevalence of ciprofloxacin-resistant Enterobacteriaceae was 95% and of ESBL-producing Enterobacteriaceae was >90%, and did not change post-intervention. One limitation of the study was the small number of cerebrospinal fluid samples sent for confirmatory testing.ConclusionsVillage-wide distribution of single-dose oral ciprofloxacin within 72 hours of case notification reduced overall meningitis AR. Distributions of ciprofloxacin could be an effective tool in future meningitis outbreak responses, but further studies investigating length of protection, effectiveness in urban settings, and potential impact on antimicrobial resistance patterns should be carried out.Trial registrationClinicalTrials.gov NCT02724046
Highlights
Cyclical, seasonal epidemics of meningococcal meningitis have been described for at least the past century in a region of sub-Saharan Africa called the “meningitis belt” [1]
Distributions of ciprofloxacin could be an effective tool in future meningitis outbreak responses, but further studies investigating length of protection, effectiveness in urban settings, and potential impact on antimicrobial resistance patterns should be carried out
The trial began on April 22, 2017, and over the course of the epidemic, 50 villages in a total of 5 health area (HA) were enrolled (Figs 1 and 2); 1 village was enrolled in error
Summary
Seasonal epidemics of meningococcal meningitis have been described for at least the past century in a region of sub-Saharan Africa called the “meningitis belt” [1]. Epidemics of all 3 of these serogroups have been reported in Niger [3,4,5]. In 2013 and 2014, localized epidemics of meningitis due to a novel strain of N. meningitidis serogroup C (NmC) occurred in northwestern Nigeria, the first outbreaks of NmC described in Africa since 2 small outbreaks in the 1970s [7]. In 2015, over 15,000 cases, predominantly of NmC, were reported in Niger and Nigeria [8]. The emergence of this strain is seen as a natural evolutionary occurrence in the population of N. meningitidis, as opposed to PsA-TT-related serogroup replacement [9]. We assessed the effectiveness of single-dose oral ciprofloxacin administered to household contacts and in village-wide distributions on the overall attack rate (AR) in an outbreak of meningococcal meningitis
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