Use of eculizumab (Soliris, Alexion Pharmaceuticals), a terminal complement inhibitor, is associated with a 1,000-fold to 2,000-fold increased incidence of meningococcal disease (1). Administration of meningococcal vaccines is recommended for patients receiving eculizumab before beginning treatment (2,3). Sixteen cases of meningococcal disease were identified in eculizumab recipients in the United States during 2008–2016; among these, 11 were caused by nongroupable Neisseria meningitidis. Fourteen patients had documentation of receipt of at least 1 dose of meningococcal vaccine before disease onset. Because eculizumab recipients remain at risk for meningococcal disease even after receipt of meningococcal vaccines, some health care providers in the United States as well as public health agencies in other countries recommend antimicrobial prophylaxis for the duration of eculizumab treatment; a lifelong course of treatment is expected for many patients. Heightened awareness, early care seeking, and rapid treatment of any symptoms consistent with meningococcal disease are essential for all patients receiving eculizumab treatment, regardless of meningococcal vaccination or antimicrobial prophylaxis status.

Eculizumab is licensed in the United States for treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome (2); both are rare, life-threatening illnesses. The Food and Drug Administration (FDA)–approved prescribing information includes a boxed warning regarding increased risk for meningococcal disease in eculizumab recipients (2). To mitigate the occurrence of and morbidity associated with meningococcal infections, FDA requires a Risk Evaluation and Mitigation Strategy (REMS) (http://www.solirisrems.com/) to educate health care providers and patients about the risk for and early signs of possible meningococcal infection and the need for immediate medical evaluation of signs and symptoms consistent with possible meningococcal infection. A key element of the Soliris REMS is ensuring that patients receive meningococcal vaccines.* The Advisory Committee on Immunization Practices recommends that eculizumab recipients receive both quadrivalent meningococcal conjugate (MenACWY) and serogroup B (MenB) meningococcal vaccines (3).

In February 2017, CDC requested that health departments review existing meningococcal disease case investigation records since 2007 to identify cases in eculizumab recipients; isolates or clinical specimens for identified cases were also requested for additional characterization. The requests were made through Epi-X (https://www.cdc.gov/epix/), CDC’s secure communications network for public health officials, and follow-up with each health department occurred through individual e-mail correspondence. Forty-seven state health departments and the health departments of New York City and the District of Columbia responded to CDC’s request for information. A search of the FDA Adverse Events Reporting System identified additional information on meningococcal vaccines received by patients identified through the Epi-X request.

CDC’s Bacterial Meningitis Laboratory performed slide agglutination,^† polymerase chain reaction (PCR) testing, and whole genome sequencing (WGS) on isolates to determine the serogroup (4); the serogroup for one clinical specimen with no isolate was determined by PCR. The serogroup results from slide agglutination (nongroupable) and WGS (serogroup C) differed for one isolate. For that isolate, the slide agglutination result (nongroupable) was used in analysis, because slide agglutination detects expression of the polysaccharide capsule, which is necessary for protection by MenACWY vaccines. Antimicrobial susceptibility testing also was performed.

In response to the Epi-X request, 16 meningococcal disease cases in eculizumab recipients were identified for the period 2008–2016 from 10 jurisdictions. The median patient age was 30 years (range = 16–83 years). All patients had meningococcemia; six also had evidence of meningitis. Patients were hospitalized for an average of 6.6 days (range = 1–14 days); one patient died (case-fatality ratio = 6%). Ten of the 16 patients were receiving eculizumab for paroxysmal nocturnal hemoglobinuria, five for atypical hemolytic uremic syndrome, and one for another condition, through a clinical trial.

Isolates from 14 patients were available for further characterization; a clinical specimen, but no isolate, was available for one patient; and for one patient no clinical specimen or isolate was available. Four cases were determined to be caused by serogroup Y and 11 by nongroupable N. meningitidis (Table 1). Antimicrobial susceptibility testing was performed on the 14 isolates (Table 2). One patient infected with a penicillin intermediate-susceptible strain had been prescribed penicillin prophylaxis, although the patient reported poor compliance. Further characterization of these isolates is ongoing.

Fourteen patients had documentation of receipt of MenACWY before disease onset (Table 1). Three of four meningococcal disease cases diagnosed after publication of the ACIP recommendations for use of MenB vaccine in persons at increased risk occurred in patients with documentation of receipt of 1 or more doses of MenB vaccine before disease onset. Three of four patients with serogroup Y disease had documentation of previous MenACWY receipt.