Chapter 8: Meningococcal Disease

Authors: Amy Rubis, MPH; Sarah Schillie, MD, MPH, MBA

Key points

This chapter provides general guidance for vaccine-preventable disease surveillance, describing the disease background/epidemiology, case investigation and reporting/notification, disease case definitions, and activities for enhancing surveillance, case investigation, and outbreak control for meningococcal disease.

Disease Description

Meningococcal disease is a serious and potentially life-threatening infection caused by the bacterium Neisseria meningitidis. N. meningitidis can be classified into 12 serogroups based on its capsular polysaccharide; serogroups A, B, C, W, X, and Y are the primary causes of meningococcal disease worldwide.

Signs and symptoms of meningococcal disease include sudden onset of high fever, neck stiffness, confusion, nausea, vomiting, lethargy, and/or petechial or purpuric rash. Without prompt and appropriate treatment, the infection can progress rapidly and result in death.

Background

Epidemiology

The incidence of meningococcal disease steadily declined in the United States from the late 1990s through 2020–2021, when the incidence of meningococcal disease reached a low of 0.06–0.07 cases per 100,000 population. However, cases of meningococcal disease have increased sharply since 2021 and now exceed pre-COVID-19 pandemic levels. In 2023, the preliminary incidence of meningococcal disease was 0.13 cases per 100,000 population. Meningococcal disease incidence varies by age and is highest in infants less than 1 year of age, and is particularly high in those younger than 6 months of age.12

Historically, serogroup B accounted for about 40% of cases in the United States, with serogroups C, W, and Y, as well as infections due to nongroupable (non-encapsulated) meningococci each causing a smaller proportion of cases overall.13 In 2022 and 2023, serogroup Y drove the increase in incidence and accounted for a larger proportion of cases.4 The relative distribution of serogroups varies by age; serogroup B causes about 40% of cases in children and young adults less than 25 years of age, while serogroups C, W, Y cause about 80% of all cases of meningococcal disease among persons age 25 years and older.3 Although serogroup A was responsible for most large meningococcal disease outbreaks during the first half of the twentieth century, serogroup A no longer circulates in the United States.567 During 2013–2018, 10 outbreaks of serogroup B meningococcal disease occurred on college campuses, resulting in 39 cases and 2 deaths (range, 2–9 cases per outbreak).8 An additional 2022 serogroup B outbreak in a college resulted in 2 cases and no deaths.[CDC Unpublished data] In addition, outbreaks of serogroup C meningococcal disease have been reported among men who have sex with men (MSM) in major metropolitan areas.910 Outbreaks have recently occurred among other populations, including persons experiencing homelessness (PEH) and in association with travel to the Kingdom of Saudia Arabia.[CDC Unpublished data,1112]

Meningococcal disease incidence historically had a cyclical pattern, with peaks in incidence occurring every 7–10 years. However, the declining incidence of meningococcal disease observed over the last 20 years does not reflect the previously observed cyclical periodicity of disease. Although it occurs year-round, meningococcal disease has a seasonal pattern with peak incidence in the United States in later winter and early spring.113

Natural history

Humans are the only natural reservoir for N. meningitidis. Meningococci are gram-negative, aerobic diplococci that can attach to the surface of mucosal cells of the nasopharynx. In the nasopharynx, the bacteria multiply, bind to specific receptors, and are taken up by epithelial cells, which transport the meningococci across the mucosal epithelium. In a small number of persons, the bacteria penetrate the mucosa and gain access to the bloodstream, resulting in systemic disease.

Meningococcal bacteria can be transmitted from person-to-person through direct contact with large droplet respiratory secretions or saliva. Asymptomatic carriers as well as persons with invasive disease can serve as the source of transmission.

Carriage

Asymptomatic nasopharyngeal carriage of N. meningitidis is common; approximately 5%–10% of the population are asymptomatic nasopharyngeal carriers of N. meningitidis at any given time.14 The frequency of carriage, like that of invasive disease, varies by age. In the Americas and western Europe, adolescents and young adults have the highest rates of meningococcal carriage.14 Although asymptomatic carriage of both pathogenic and nonpathogenic N. meningitidis is common, few carriers develop invasive disease. For most people, carriage is an immunizing process that results in a systemic, serogroup-specific protective antibody response.13

Risk factors

Risk factors for meningococcal disease include organism, host, and environmental factors. Persons with anatomic or functional asplenia, persistent complement component deficiencies (e.g., C3, C5–C9, properdin, factor D, factor H), human immunodeficiency virus (HIV), and those who are receiving complement inhibitors such as eculizumab (Soliris®, Alexion Pharmaceuticals) or ravulizumab (Ultomiris®, Alexion Pharmaceuticals) are at increased risk for meningococcal disease.315

Crowded living conditions can facilitate respiratory droplet transmission of meningococci. College freshmen residing in residence halls have been shown to be at greater risk of acquiring meningococcal disease compared to college students not living in residence halls.1617 Active or passive smoking and recent upper respiratory tract infections also increase risk of disease.18 Historically, Black individuals and persons of low socioeconomic status have been found to be at higher risk for meningococcal disease than White individuals and persons of high socioeconomic status; however, in 2010–2021 these differences had diminished.119 In 2022 and 2023, the increase in serogroup Y incidence disproportionately affected Black individuals, leading to a newly increasing disparity in incidence among Black persons compared to other racial groups in these years.4

Meningococcal disease is more commonly diagnosed among infants, adolescents, young adults 16–23 years of age, and adults 65 years and older compared to other age groups. Infants less than 1 year of age have the highest incidence of meningococcal disease; the majority of cases in infants occur during the first 6 months of life.12

Those who have close contact with patients with meningococcal disease, such as household members, are at substantially increased risk for acquiring carriage and disease.20 Rates of secondary disease are also elevated among daycare and preschool contacts of patients with meningococcal disease.21

Clinical characteristics

Diagnosing meningococcal disease is often challenging because its initial clinical manifestations are similar to more common but less serious illnesses. However, meningococcal disease can progress rapidly and therefore a rapid, accurate diagnosis is critical.

The common clinical presentations of meningococcal disease include meningitis, bacteremia, and bacteremic pneumonia. Meningitis is observed in approximately 50% of invasive cases and is characterized by abrupt onset of fever, headache, and stiff neck.1 These clinical features may be accompanied by nausea, vomiting, photophobia, and altered mental status. In infants, symptoms may have a slower onset, signs may be nonspecific, and neck stiffness may not be present. Approximately 30% of meningococcal disease cases present as bacteremia without meningitis.1 A portion of these cases will present as meningococcemia, the most severe manifestation of meningococcal bacteremia.19 Signs of meningococcemia include sudden onset of fever and a characteristic petechial or purpuric rash, which may progress to purpura fulminans. The clinical course can include hypotension, acute adrenal hemorrhage, multiorgan failure, shock, and death. Patients with severe meningococcemia often respond poorly to treatment, and death can occur within hours of onset. Bacteremic pneumonia occurs in approximately 15% of cases and occurs most frequently in older persons.1 Diagnosing meningococcal pneumonia is difficult because isolation of the organism from sputum does not distinguish persons who are carriers from those with pneumonia caused by the organism.22

Less common manifestations of meningococcal disease include myocarditis, endocarditis or pericarditis, arthritis, or non-invasive infections such as conjunctivitis or urethritis. Non-invasive meningococcal infections are not reportable; therefore, the incidence of these infections is not known. Descriptions of the epidemiology and risk factors for meningococcal disease throughout this chapter refer exclusively to invasive meningococcal disease cases.

The use of antibiotics has dramatically reduced mortality due to meningococcal disease, but even with prompt and appropriate antimicrobial treatment the case-fatality ratio remains 10%–15%, and may be as high as 40% among patients with meningococcemia.13 Of those who survive invasive disease, 10%–20% experience sequelae, including limb loss from gangrene, extensive skin scarring, neurosensory hearing loss, mild to moderate cognitive defects, or seizure disorders.

Treatment

Because of the risks of severe morbidity and death, effective antibiotics should be administered promptly to patients suspected of having meningococcal disease. Multiple antimicrobial agents may be effective against N. meningitidis. Empirical therapy for suspected meningococcal disease should include an extended-spectrum cephalosporin, such as cefotaxime or ceftriaxone. Once the microbiologic diagnosis is established, definitive treatment can be continued with an extended-spectrum cephalosporin (cefotaxime or ceftriaxone). Alternatively, if susceptibility of the meningococcal isolate to penicillin is confirmed, treatment can be switched to penicillin G or ampicillin.19 Ceftriaxone clears nasopharyngeal carriage effectively after 1 dose; if antimicrobial agents other than ceftriaxone or cefotaxime are used for the treatment of meningococcal disease, eradication of nasopharyngeal carriage with rifampin (4 doses over 2 days) or a single dose of either ciprofloxacin or ceftriaxone are recommended prior to discharge from the hospital.

Chemoprophylaxis

Close contacts of persons with meningococcal disease should receive antimicrobial chemoprophylaxis, regardless of vaccination status, because they are at increased risk for infection.23 Close contacts include: 1) household members, 2) childcare center contacts, and 3) anyone else directly exposed to an infected patient's oral secretions (e.g., via kissing, mouth-to-mouth resuscitation, endotracheal intubation, or endotracheal tube management) in the 7 days before symptom onset. Health care personnel should receive chemoprophylaxis if they were managing an airway or exposed to respiratory secretions of a patient with meningococcal disease.

When a meningococcal disease case is identified in a person who has traveled by air, jurisdictions should contact the Port Health Station who will determine if a contact investigation is warranted. Chemoprophylaxis is recommended for passengers seated directly next to a patient during airline flights lasting more than 8 hours, or passengers seated within one seat in any direction from a patient on a flight of any duration if the patient was coughing or vomiting during the flight.

Chemoprophylaxis is not recommended for close contacts of patients with evidence of N. meningitidis only in non-sterile sites such as an oropharyngeal swab, endotracheal secretions, or conjunctival swab. Furthermore, there is no indication to treat persons who are asymptomatic nasopharyngeal carriers who have no known close contact with a meningococcal disease patient.

Risk of secondary disease among close contacts is highest during the first few days after the onset of disease, which requires that chemoprophylaxis be administered as soon as possible. If given more than 14 days after the onset of disease, chemoprophylaxis is probably of limited or no benefit.23 Oropharyngeal or nasopharyngeal cultures are not useful in determining the need for chemoprophylaxis and may unnecessarily delay the use of effective preventive measures.

Rifampin, ceftriaxone, and ciprofloxacin have typically been 90%–95% effective in reducing nasopharyngeal carriage of N. meningitidis and may be acceptable antimicrobial agents for chemoprophylaxis (Table 1). However, the number of cases caused by ciprofloxacin-resistant N. meningitidis strains has increased in recent years and public health staff should update prophylaxis practices as needed based on detection of ciprofloxacin-resistant cases (Table 2).2425 Although azithromycin is not recommended for use as a first-line chemoprophylaxis agent, azithromycin has been recommended for chemoprophylaxis in circumstances of sustained ciprofloxacin resistance in a community. Use of azithromycin as a single oral dose has been shown to be effective for eradication of nasopharyngeal carriage based on limited evidence and can be used where ciprofloxacin resistance has been detected.2627

Table 1. Recommended chemoprophylaxis regimens for close contacts of persons with invasive meningococcal disease

Recommended chemoprophylaxis regimens for close contacts and persons with invasive meningococcal disease
Drug Age Dose Duration Efficacy (%) Cautions
Rifampin <1 month 5 mg/kg, orally, every 12 hours 2 days Discussion with an expert for infants <1 month
≥1 month 10 mg/kg (maximum 600 mg), orally, every 12 hours 2 days 90–95 Can interfere with efficacy of oral contraceptives and some seizure prevention and anticoagulant medications; may stain soft contact lenses.

Not recommended for pregnant women.
Ceftriaxone <15 years 125 mg, intramuscularly Single dose 90–95 To decrease pain at injection site, dilute with 1% lidocaine.
≥15 years 250 mg, intramuscularly Single dose 90–95
Ciprofloxacina ≥1 month 20mg/kg (maximum 500 mg), orally Single dose 90-95 Not recommended for pregnant women.
Azithromycin 10 mg/kg
(maximum 500 mg)		 Single dose 90 Not recommended routinely. Equivalent to rifampin for eradication of N. meningitidis from nasopharynx in one study

Source:23

aUse only if fluoroquinolone-resistant strains of N. meningitidis have not been identified in the community.

Table 2. Implementation guidance for health departments for preferentially considering antibiotics other than ciprofloxacin for invasive meningococcal disease prophylaxis

  • Discontinue use of ciprofloxacin as prophylaxis for close contacts when both of the following threshold criteria have been met in the catchment area* during a rolling 12-month period:
    • Two or more invasive meningococcal disease cases caused by ciprofloxacin-resistant strains have been reported, and
    • Cases caused by ciprofloxacin-resistant strains account for ≥20% of all reported invasive meningococcal disease cases.
  • Prescribe rifampin, ceftriaxone, or azithromycin instead of ciprofloxacin as prophylaxis when the threshold criteria have been reached.
  • Implement updated prophylaxis guidance in all counties within the catchment area.
  • Maintain updated prophylaxis guidance until a full 24 months have passed without any invasive meningococcal disease cases caused by ciprofloxacin-resistant strains having been reported in the catchment area.

*The catchment area should be a single contiguous area that contains all counties reporting ciprofloxacin-resistant cases. Jurisdictions should include surrounding counties, if warranted, based on population mixing patterns

Source:24

Importance of Rapid Case Identification

Immediate recognition and treatment of meningococcal disease is critical. Persons with suspected meningococcal disease should be treated promptly without waiting for laboratory confirmation. All suspected, probable, and confirmed meningococcal disease cases should be promptly reported to the appropriate health department to ensure that proper prevention and control measures can be implemented.

Importance of Surveillance

High-quality epidemiologic surveillance data along with collection of invasive meningococcal isolates from a broad and representative population are crucial to inform prevention and control strategies for meningococcal disease in the United States. These data are used to monitor disease trends, characterize risk factors for and severe outcomes of disease, guide vaccine policy, monitor vaccine impact, and inform development of new vaccines.

Case Definition

The following case definition has been approved by the Council of State and Territorial Epidemiologists (CSTE) and was published in 2014.28

Confirmed case:

  • Detection of N. meningitidis-specific nucleic acid in a specimen obtained from a normally sterile site (e.g., blood or cerebrospinal fluid [CSF]), using a validated polymerase chain reaction (PCR) assay; or
  • Isolation of N. meningitidis
    • from a normally sterile body site (e.g., blood or CSF, or less commonly, synovial, pleural, or pericardial fluid); or
    • from purpuric lesions.

Probable case:

  • Detection of N. meningitidis antigen
    • in formalin-fixed tissue by immunohistochemistry (IHC); or
    • in CSF by latex agglutination.

Suspected case:

  • Clinical purpura fulminans in the absence of a positive blood culture; or
  • Gram-negative diplococci, not yet identified, isolated from a normally sterile body site (e.g., blood or CSF).

Laboratory Testing

Rapid and reliable laboratory results are critical for prompt diagnosis and implementation of appropriate prevention and control measures. Refer to the CDC web page Laboratory Information and Chapter 22 for specific information on specimen collection, identifying N. meningitidis, and determining N. meningitidis serogroups.

Specimen collection

Specimen collection and shipping are important steps in obtaining laboratory diagnosis or confirmation for vaccine-preventable diseases. Guidelines have been published for specimen collection and handling for microbiologic agents.29 Information is also available by using CDC laboratories as support for reference and disease surveillance;3031 this includes:

  • A central website for requesting lab testing, which includes the CDC Infectious Diseases Laboratories Test Directory, that not only contains a list of orderable tests for that institution but also detailed information on appropriate specimen types, collection methods, specimen volume, and points of contacts.
    • Meningococcal disease diagnostic testing: refer to test order CDC-10219 and use the 50.34 form required for submitting specimens to CDC or see Appendix 23, Form # CDC 50.34.
    • Surveillance only testing: refer to test order CDC-10220 for shipping instructions and requirements.
    • Note that meningococcal isolates/specimens are classified as a category B infectious substance.
  • Information on general requirements for shipment of etiologic agents (Appendix 24 Cdc-pdf)—although written to guide specimen submission to CDC, this information may be applicable to submission of specimens to other laboratories.

Reporting and Case Notification

Case reporting within a jurisdiction

Each state and territory (jurisdiction) has regulations and laws governing the reporting of diseases and conditions of public health importance.32 These regulations and laws list the diseases that are to be reported, and describe those persons or institutions responsible for reporting, such as health care providers, hospitals, laboratories, schools, daycare and childcare facilities, and other institutions. Detailed information on reportable conditions in each jurisdiction is available through CSTE.33

Case notification to CDC

Notification for suspect, probable, and confirmed cases of meningococcal disease should be sent to CDC using the event code 10150 in the National Notifiable Diseases Surveillance System (NNDSS).34 Case information should be reported through the NNDSS via the National Electronic Telecommunications System for Surveillance (NETSS), or the National Electronic Disease Surveillance System (NEDSS) within 14 days of the initial report to the jurisdiction or local health department. The jurisdiction in which the patient usually resides at the time of diagnosis should submit the case notification to CDC. Of note, for college students this typically means that the jurisdiction in which the student attends school is responsible for reporting the case, not necessarily the jurisdiction of the student's legal residence [12 pages].35 Case notifications should not be delayed because of incomplete information or lack of confirmation; data can be updated electronically as more information becomes available.

Vaccination

For specific information about meningococcal vaccination, refer to The Pink Book, which provides general recommendations, including vaccine use and scheduling, immunization strategies for providers, vaccine content, adverse events and reactions, vaccine storage and handling, and contraindications and precautions.

Enhancing Surveillance

Active population-based and laboratory-based surveillance

CDC coordinates active, population- and laboratory-based surveillance for invasive meningococcal disease as part of the Active Bacterial Core surveillance (ABCs) system, through the Emerging Infections Program (EIP). ABCs operates in 10 sites that collect data from all patients from whom N. meningitidis was isolated or detected by PCR from a normally sterile body site. This surveillance program allows for collection of detailed information on meningococcal cases, including extensive information on underlying medical conditions.

In addition, CDC has implemented Enhanced Meningococcal Disease Surveillance (EMDS) through the Epidemiology and Laboratory Capacity (ELC) Vaccine-Preventable Diseases (VPD) surveillance project. Through this initiative, data on key variables for monitoring meningococcal disease epidemiology and vaccine policy decisions, along with meningococcal isolates, are routinely collected from most state and territorial (jurisdiction) health departments. The Enhanced Meningococcal Disease Surveillance Worksheet is included in Appendix 9 to serve as a guide for data collection for key variables. Reports on the enhanced meningococcal surveillance data are published online annually.

Streamlining reporting using electronic methods

Use of data from sources such as electronic medical records, electronic case reporting,36373839404142 and clinical laboratory information management systems (LIMS) can significantly improve reporting speed, enhance data quality, and reduce workload.

Case Investigation

All reports of suspected meningococcal disease should be investigated immediately. A critical component of case investigation is ensuring that all close contacts (see definitions) receive appropriate chemoprophylaxis as soon as possible to eradicate nasopharyngeal carriage of meningococci and prevent secondary disease (see Chemoprophylaxis, above). CDC is available to assist with epidemiologic and laboratory investigations during outbreaks.

Outbreaks

Approximately 95% of meningococcal disease cases in the United States are sporadic; the other 5% are associated with outbreaks.43 Guidance on the control of meningococcal disease outbreaks can be found on the CDC Meningococcal Outbreaks web page.

Resources

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National Center for Immunization and Respiratory Diseases (NCIRD)
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