Meningococcal Disease

Infectious Agent

Neisseria meningitidis is a gram-negative diplococcus. Meningococci are classified into serogroups on the basis of the composition of the capsular polysaccharide. The 6 major meningococcal serogroups associated with disease are A, B, C, W, X, and Y.

Transmission

Spread through respiratory secretions; requires close contact. Both asymptomatic carriers and people with overt meningococcal disease can serve as sources of infection. Asymptomatic carriage is transient and typically affects approximately 5%–10% of the population at any given time.

Epidemiology

N. meningitidis is found worldwide, but the highest incidence occurs in the “meningitis belt” of sub-Saharan Africa (Map 4-10). Meningococcal disease is hyperendemic to this region, and periodic epidemics during the dry season (December–June) reach up to 1,000 cases per 100,000 population. By contrast, rates of disease in the United States, Europe, Australia, and South America range from 0.12 to 3 cases per 100,000 population per year.

Map 4-10.Areas with frequent epidemics of meningococcal meningitis
Map 4-10.Areas with frequent epidemics of meningococcal meningitis

Disease data source: World Health Organization. International Travel and Health. Geneva, Switzerland: 2015.

Although meningococcal outbreaks can occur anywhere in the world, they are most common in the African meningitis belt, and large-scale epidemics occur every 5–12 years. Historically, outbreaks in the meningitis belt were primarily due to serogroup A. However, with the introduction of a monovalent serogroup A meningococcal conjugate vaccine (MenAfriVac) in the region starting in 2010, recent meningococcal outbreaks in the meningitis belt have primarily been due to serogroups C and W, although serogroup X outbreaks are also reported.

Outside the meningitis belt, infants and adolescents have the highest rates of disease. In meningitis belt countries, high rates of disease are seen in people up to age 30 years, and the highest rates are in children and adolescents aged 5– 14 years. Risk for travelers is highest in people visiting meningitis belt countries who have prolonged contact with local populations during an epidemic. The Hajj pilgrimage to Saudi Arabia has also been associated with outbreaks of meningococcal disease in returning pilgrims and their contacts.

Clinical Presentation

Meningococcal disease generally occurs 1–10 days after exposure and presents as meningitis in ≥50% of cases. Meningococcal meningitis is characterized by sudden onset of headache, fever, and stiffness of the neck, sometimes accompanied by nausea, vomiting, photophobia, or altered mental status. Approximately 40% of people with meningococcal disease present with meningococcal sepsis, known as meningococcemia. Symptoms of meningococcemia can include abrupt onset of fever, chills, vomiting, diarrhea, and a petechial or purpuric rash, which may progress to purpura fulminans. Meningococcemia often involves hypotension, acute adrenal hemorrhage, and multiorgan failure. Among infants and children aged <2 years, meningococcal disease may have nonspecific symptoms. Neck stiffness, usually seen in people with meningitis, may be absent in this age group. Meningococcal disease is rapidly progressive and has a case-fatality ratio of 10%–20%, even with antibiotic treatment. Without rapid treatment, fatality ratios can be much higher.

Diagnosis

Early diagnosis and treatment are critical. A lumbar puncture should be done to examine the cerebrospinal fluid (CSF) and perform a Gram stain. If possible, the lumbar puncture should be done before starting antibiotic therapy to ensure that bacteria, if present, can be cultured from CSF; however, lumbar puncture should not delay antibiotic treatment. In general, diagnosis is made by isolating N. meningitidis from a normally sterile body site (such as blood or CSF) through culture or by detection of N. meningitidis –specific nucleic acid by PCR.

The signs and symptoms of meningococcal meningitis are similar to those of other causes of bacterial meningitis, such as Haemophilus influenzae and Streptococcus pneumoniae . The causative organism should be identified so that the correct antibiotics can be used for treatment and prophylaxis. Meningococcal disease is nationally notifiable in the United States and should be immediately reported to the state or local health department.

Treatment

Meningococcal disease can be rapidly fatal and should always be viewed as a medical emergency. Antibiotic treatment must be started early in the course of the disease, and empirically when suspected and prior to the diagnostic test results. Several antibiotic choices are available, including third-generation cephalosporins.

Prevention

Vaccine

Four meningococcal vaccines are licensed and available in the United States. Refer to Table 4-14 for more information about available meningococcal vaccines. Approximately 7–10 days are required after vaccination for the development of protective antibody levels.

Table 4-14. Meningococcal vaccines licensed and available in the United States

Vaccine

Trade Name (Manufacturer)

Age of Vaccine Initiation

Dose

Route

Interval Since First Dose

Booster

Meningococcal (serogroups A, C, W, and Y) oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM) 1

Menveo (GSK)

2 mo

0.5 mL

IM

0, 2, 4, 10 mo

If at continued risk 3

7–23 mo

0.5 mL

IM

0, 3 mo (2nd dose administered in 2nd year of life)

≥ 2 y

0.5 mL

IM

1 dose 2

Meningococcal (serogroups A, C, W, and Y) polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-D) 1

Menactra (Sanofi Pasteur)

9–23 mo

0.5 mL

IM

0, 3 mo

If at continued risk 3

≥ 2 y

0.5 mL

IM

1 dose 2

Meningococcal serogroup B vaccine (MenB-FHbp)

Trumenba (Pfizer)

10–25 y

0.5 mL

IM

0, 1–2, 6 mo or 0, 6 mo (depending on indication) 4

None

Meningococcal serogroup B vaccine (MenB-4C)

Bexsero (GSK)

10–25 y

0.5 mL

IM

0, ≥1 mo

None

Abbreviations: IM, intramuscular; SC, subcutaneous.

1 If an infant is receiving the vaccine before travel, 2 doses may be administered as early as 8 weeks apart.

2 For people with HIV, anatomic or functional asplenia, and people with persistent complement component deficiencies (C3, C5-9, properdin, factor D, factor H, or people taking eculizumab [Soliris]) should receive a 2-dose primary series 8–12 weeks apart.

3 Revaccination with meningococcal conjugate vaccine (MenACWY-D or MenACWY-CRM) is recommended after 3 years for children who received their last dose at <7 years of age. Revaccination with meningococcal conjugate vaccine is recommended after 5 years for people who received their last dose at ≥7 years of age, and every 5 years thereafter for people who are at continued risk.

4 In April 2016, FDA approved updates to the prescribing information for MenB-FHbp to allow for the administration of either a 3-dose schedule (0, 1–2, 6 months) or a 2-dose schedule (0, 6 months). The 3-dose schedule is preferred for groups at increased risk where more rapid protection is desired.

Routine Immunization

The Advisory Committee on Immunization Practices (ACIP) recommends routine administration of a quadrivalent meningococcal conjugate vaccine (MenACWY) for all people aged 11–18 years. A single dose of vaccine should be administered at age 11 or 12 years, and a booster dose should be administered at age 16 years. Routine immunization with MenACWY is not recommended for other age groups in the United States, with the exception of people at increased risk for meningococcal disease. Those at increased risk for meningococcal disease include people who have a persistent complement component deficiency (C3, C5-9, properdin, factor D, factor H, or people who are taking eculizumab [Soliris]), people who have functional or anatomic asplenia, or people with HIV. Vaccine, product, number of doses, and booster dose recommendations are based on age and risk factors and are described in detail for each risk group in the 2013 ACIP Meningococcal Disease Recommendations (www.cdc.gov/mmwr/preview/mmwrhtml/rr6202a1.htm) and additional ACIP policy notes (www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/mening.html).

Adolescents and young adults aged 16–23 years may also be vaccinated with a serogroup B meningococcal (MenB) vaccine series to provide short-term protection against most strains of serogroup B meningococcal disease. The preferred age for MenB vaccination is 16–18 years. ACIP also recommends routine use of MenB vaccine for people aged ≥10 years who are at increased risk for meningococcal disease, including people who have persistent complement component deficiency and people who have functional or anatomic asplenia. ACIP recommendations for MenB vaccines can be found at www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/mening.html.

Immunization for Travelers

ACIP recommends that travelers aged ≥2 months who visit or reside in parts of sub-Saharan Africa known as the “meningitis belt” (see Map 4-10) during the dry season (December–June) receive vaccination with a MenACWY vaccine before travel. Advisories for travelers to other countries are issued when outbreaks of meningococcal disease are recognized (see the CDC Travelers’ Health website at www.cdc.gov/travel).

For infants aged <9 months, MenACWY-CRM (Menveo) is the only licensed and available meningococcal vaccine. In children initiating vaccination at 2 months of age, MenACWY-CRM should be administered as a 4-dose series at 2, 4, 6, and 12 months of age. In children initiating vaccination at 7– 23 months of age, MenACWY-CRM should be administered as a 2-dose series, with the second dose administered at ≥12 months of age and ≥3 months after the first dose, although it can be administered as early as 8 weeks after the first dose to precede travel.

For travelers initiating vaccination at ≥9 months (i.e., 9 months through 55 years), either MenACWY-CRM or MenACWY-D (Menactra) may be used. For travelers 9–23 months of age who receive MenACWY-D, 2 doses should be administered, with the second dose administered ≥3 months after the first dose, although it can be administered as early as 8 weeks after the first dose to precede travel. For most people aged ≥2 years, 1 dose of a MenACWY vaccine (MenACWY-CRM or MenACWY-D) is recommended before travel.

Additional dosing instructions for people with HIV, asplenia, or persistent complement component deficiencies are available in the 2013 ACIP Meningococcal Disease Recommendations (www.cdc.gov/mmwr/preview/mmwrhtml/rr6202a1.htm). Although not licensed for use in adults aged ≥56 years, MenACWY is the recommended vaccine for people in this age group, as the quadrivalent meningococcal polysaccharide vaccine (MPSV4) is no longer available in the United States.

Travelers to the Kingdom of Saudi Arabia (KSA) for Umrah or Hajj are required to provide documentation of quadrivalent vaccine at least 10 days and no more than 3 years before arrival for polysaccharide vaccine and no more than 5 years before arrival for conjugate vaccine (see www.moh.gov.sa/en/Hajj/Pages/HealthRegulations.aspx). Visa requirements should be confirmed with the KSA embassy. Although the KSA Ministry of Health currently advises against travel to Hajj for pregnant women or children, these groups should receive meningococcal vaccination according to licensed indications for their age if they travel.

International travelers at risk for meningococcal disease who were previously vaccinated with a quadrivalent vaccine should receive a booster dose. For children who completed the primary dose or series at <7 years of age, a booster dose of MenACWY should be administered after 3 years and repeated every 5 years thereafter if they live in or travel to a hyperendemic area. For people who received the primary dose or series at ≥7 years of age, a booster dose should be administered after 5 years and every 5 years thereafter if they live in or travel to a hyperendemic area.

MenB vaccine is not recommended for people who live in or travel to meningitis belt countries, as serogroup B disease is extremely rare in this region. MenB vaccine is not routinely recommended for travel to other regions of the world unless an outbreak of serogroup B disease has been reported.

A monovalent serogroup A meningococcal conjugate vaccine (MenAfriVac) has been introduced into meningitis belt countries since 2010 through mass vaccination campaigns and the routine childhood immunization schedule. This vaccine is not available in the United States for travelers and is not recommended in place of MenACWY vaccine for travelers who will be living in meningitis belt countries as it does not protect against serogroups C, W, and Y. In some countries outside the meningitis belt, meningococcal vaccination (such as monovalent conjugate C vaccine or MenB vaccine) may be recommended as part of the routine immunization program for infants. Infants residing in these countries may consider meningococcal vaccination according to the routine immunization recommendations of that country.

Vaccine Safety and Adverse Reactions

Low-grade fevers and local reactions, such as injection-site pain, arm swelling, and pain that limits movement of the injected arm, are side effects seen after MenACWY vaccine. Symptoms are generally mild to moderate and resolve within 48–72 hours. Severe adverse events, such as high fever, chills, joint pain, rash, or seizures are rare (<5% of vaccinees).

Although no clinical trials of meningococcal vaccines have been conducted in pregnant or lactating women, postlicensure safety data have not identified any serious safety concerns to the mother or fetus. Pregnancy or lactation should not preclude vaccination with MenACWY if indicated.

Precautions and Contraindications

People with moderate or severe acute illness should defer vaccination until their condition improves. Vaccination is contraindicated for people who have a severe allergic reaction to any component of the vaccines. All meningococcal vaccines are inactivated and may be given to immunosuppressed people.

Antibiotic Chemoprophylaxis

In the United States and most industrialized countries, antibiotic chemoprophylaxis is recommended for close contacts of a patient with invasive meningococcal disease to prevent secondary cases. Chemoprophylaxis ideally should be initiated within 24 hours after the index patient is identified; prophylaxis given >2 weeks after exposure has little value. Antibiotics used for prophylaxis include ciprofloxacin, rifampin, and ceftriaxone. Ceftriaxone is recommended for pregnant women.

CDC website: www.cdc.gov/meningococcal

Bibliography

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Authors

Sarah A. Mbaeyi, Lucy A. McNamara