Data from: Single-dose oral ciprofloxacin prophylaxis as a response to a meningococcal meningitis epidemic in the African meningitis belt: a three-arm, open-label, cluster-randomized trial

Background: Antibiotic 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
findings: In 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.
Conclusions: Village-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.

背景：非洲脑膜炎带（African meningitis belt）暴发流行性脑脊髓膜炎期间，不推荐对病例接触者实施抗生素预防。本研究针对脑膜炎奈瑟菌性脑膜炎暴发场景，评估了单剂量口服环丙沙星分别用于家庭接触者预防与全村范围内分发时，对总攻击率（attack rate, AR）的干预效果。
方法与结果：本研究为一项三臂、开放标签整群随机试验（cluster-randomized trial），开展于尼日尔马达鲁纳法县的流行性脑脊髓膜炎暴发期间。将上报疑似病例的村庄按1:1:1比例随机分配至三组：标准护理对照组、病例上报后24小时内为家庭接触者给予单剂量口服环丙沙星的家庭预防组、首例病例上报后72小时内开展全村环丙沙星分发的全村预防组。本研究的主要结局为纳入研究后疑似脑膜炎的总攻击率。同时随机抽取20个参与村庄，用于监测干预前后耐环丙沙星与产超广谱β-内酰胺酶（extended-spectrum beta-lactamase, ESBL）肠杆菌科（Enterobacteriaceae）粪便携带率的变化。
2017年4月22日至5月18日，本研究共纳入49个村庄：对照组17个、家庭预防组17个、全村预防组15个。指数病例上报后，研究中共记录248例病例。对照组攻击率为451/10万人，家庭预防组为386/10万人（与对照组行t检验，p=0.68），全村预防组为190/10万人（与对照组行t检验，p=0.032）。家庭预防组与对照组的校正后攻击率比为0.94（95%置信区间CI：0.52~1.73，p=0.85）；全村预防组与对照组的校正后攻击率比为0.40（95%CI：0.19~0.87，p=0.022）。本研究未报告任何不良事件。基线时，耐环丙沙星肠杆菌科粪便携带率为95%，产ESBL肠杆菌科粪便携带率＞90%，干预后该携带率无显著变化。本研究的局限性之一为用于确诊的脑脊液样本量较少。
结论：病例上报后72小时内开展单剂量口服环丙沙星全村分发，可降低脑膜炎总攻击率。环丙沙星药物分发可作为未来脑膜炎暴发应对的有效手段，但仍需开展进一步研究，以评估其保护时长、城市环境中的应用有效性，以及其对抗菌药物耐药性模式的潜在影响。