Meningococci are gram-negative aerobic cocci that belong to the family Neisseriaceae. There are 13 serogroups; 6 serogroups (A, B, C, W135, X, and Y) cause most human disease.
Worldwide, the incidence of endemic meningococcal disease is 0.5 to 5/100,000, with an increased number of cases during winter and spring in temperate climates. Local outbreaks occur most frequently in sub-Saharan Africa between Gambia and Senegal in the west and Ethiopia, Eritrea, and northern Kenya in the east; this area is known as the sub-Saharan (African) meningitis belt, which includes 26 countries. In major African epidemics (which were often caused by serogroup A), attack rates ranged from 100 to 800/100,000 and affected up to 200,000 people each year. After widespread use of the meningococcal A vaccine in the African meningitis belt, serogroup A has been replaced by other meningococcal serogroups and by Streptococcus pneumoniae.
In the US, the annual incidence ranges from 0.12 to 1.1/100,000. Over the past 20 years, incidence of meningococcal disease has declined annually. Most cases are sporadic, typically in children < 2 years of age; < 2% occur in outbreaks. Outbreaks tend to occur in semiclosed communities (eg, military recruit camps, college dormitories, schools, day care centers) and often involve patients aged 5 to 19 years. Serogroups B, C, and Y are the most frequent causes of disease in the US; each serogroup accounts for about one third of reported cases. Serogroup A is rare in the US.
Diseases Caused by Meningococci
Over 90% of meningococcal infections involve
Infections of lungs, joints, respiratory passageways, genitourinary organs, eyes, endocardium, and pericardium are less common.
N. meningitidis has been reported to cause urethritis, but, recently, incidence of meningococcal urethritis has been increasing in heterosexual men and in men who have sex with men. These men frequently reported oral sex; N. meningitidis colonizes the nasopharynx. N. meningitidis may also cause proctitis Proctitis Proctitis is inflammation of the rectal mucosa, which may result from infection, inflammatory bowel disease, or radiation. Symptoms are rectal discomfort and bleeding. Diagnosis is by sigmoidoscopy... read more , primarily in men who have sex with men.
Pathophysiology of Meningococcal Diseases
Meningococci can colonize the nasopharynx of asymptomatic carriers. A combination of factors is probably responsible for transition from carrier state to invasive disease. Despite documented high rates of colonization (5 to 40% of healthy people), which may be transient, brief, or prolonged, transition to invasive disease is rare (< 1%) and occurs primarily in previously uninfected patients. Transmission usually occurs via direct contact with respiratory secretions or by inhalation of large-droplet nuclei from a nasopharyngeal carrier. Nasopharyngeal carriage rates are highest in adolescents and young adults, who serve as reservoirs for transmission of N. meningitidis. Carrier rates rise dramatically during epidemics.
After invading the body, N. meningitidis causes meningitis and severe bacteremia in children and adults, resulting in profound vascular effects. Infection can rapidly become fulminant. The case-fatality rate is 4 to 6% for meningitis alone, compared with up to 40% for meningococcemia with septic shock. Of patients who recover, 10 to 20% have serious sequelae, such as permanent hearing loss, intellectual disability, or loss of phalanges or limbs.
The most frequently infected are
Children aged 6 months to 3 years
Other high-risk groups include
College freshmen living in dormitories
Travelers to places where meningococcal disease is common (eg, certain countries in Africa and in Saudi Arabia during the Hajj)
People with functional or anatomic asplenia or a complement deficiency
People treated with eculizumab or ravulizumab
Microbiologists working with N. meningitidis isolates
Infection or vaccination confers serogroup-specific immunity.
Incidence of meningococcal disease is higher in people with AIDS than in the general adult population. Antecedent viral infection, household crowding, chronic underlying illness, and both active and passive smoking are associated with increased risk of meningococcal disease ( 1 Pathophysiology reference Meningococci (Neisseria meningitidis) are gram-negative cocci that cause meningitis and meningococcemia. Symptoms, usually severe, include headache, nausea, vomiting, photophobia, lethargy... read more ).
Symptoms and Signs of Meningococcal Diseases
Patients with meningitis Acute Bacterial Meningitis Acute bacterial meningitis is rapidly progressive bacterial infection of the meninges and subarachnoid space. Findings typically include headache, fever, and nuchal rigidity. Diagnosis is by... read more frequently report fever, headache, and stiff neck. Other symptoms include nausea, vomiting, photophobia, and lethargy. A maculopapular or hemorrhagic petechial rash often appears soon after disease onset. Meningeal signs are often apparent during physical examination.
Fulminant meningococcemia syndromes include Waterhouse-Friderichsen syndrome (septicemia, profound shock, cutaneous purpura, adrenal hemorrhage), sepsis with multiple organ failure, shock, and disseminated intravascular coagulation. A rare, chronic meningococcemia causes recurrent mild symptoms (mostly joint and cutaneous).
Diagnosis of Meningococcal Diseases
Gram stain and culture
Neisseria are small, gram-negative cocci readily identified with Gram stain and by other standard bacteriologic identification methods. Serologic methods, such as latex agglutination and coagglutination tests, allow rapid presumptive diagnosis of N. meningitidis in blood, cerebrospinal fluid, synovial fluid, and urine. However, both positive and negative results should be confirmed by culture.
Polymerase chain reaction testing of cerebrospinal fluid, blood, and other normally sterile sites for N. meningitidis is more sensitive and specific than culture and may be useful when prior antibiotic administration interferes with isolating the organism.
Treatment of Meningococcal Diseases
While awaiting definitive identification of the causal organism, immunocompetent adults suspected of having meningococcal infection are given a 3rd-generation cephalosporin (eg, cefotaxime 2 g IV every 6 hours, ceftriaxone 2 g IV every 12 hours) or meropenem (2 g IV every 8 hours) plus vancomycin 30 to 60 mg/kg IV every 8 to 12 hours. In immunocompromised patients and patients > 50 years, coverage for Listeria monocytogenes should be considered by adding ampicillin 2 g IV every 4 hours. The fluoroquinolone antibiotic, moxifloxacin, is an alternative in patients allergic to penicillin and cephalosporins.
Once N. meningitidis has been definitively identified, the preferred treatment is one of the following:
Ceftriaxone 2 g IV every 12 hours
Penicillin 4 million units IV every 4 hours
In many countries, penicillin G is still the first-choice for invasive meningococcal disease. However, because many countries, including the US, have increasing incidence of isolates with reduced susceptibility to penicillin, those countries typically give initial treatment with a 3rd-generation cephalosporin, such as ceftriaxone or cefotaxime. Also, when penicillin is used, follow-up treatment with ceftriaxone, ciprofloxacin, or rifampin is necessary to eliminate nasopharyngeal carriage. Recently, 2 isolates in Costa Rica and 6 in India have been reported to be resistant to both penicillin and 3rd-generation cephalosporins.
Corticosteroids decrease the incidence of neurologic complications in children and adults with suspected bacterial meningitis due to Haemophilus influenzae type b or S. pneumoniae. The evidence is less clear when N. meningitidis is the cause. However, high-dose corticosteroids worsen the outcome in meningococcal shock without meningitis and should not be used in such cases; however, low-dose corticosteroids can be used in patients with inadequate adrenal function. When corticosteroids are used, they should be given with or before the first dose of antibiotics. Dexamethasone 0.15 mg/kg IV every 6 hours in children (10 mg every 6 hours in adults) is given for 4 days.
Prevention of Meningococcal Diseases
Close contacts of people with meningococcal disease are at increased risk of acquiring disease and should receive a prophylactic antibiotic. Options include
Rifampin 600 mg (for children > 1 month, 10 mg/kg; for children < 1 month, 5 mg/kg) orally every 12 hours for 4 doses
Ceftriaxone 250 mg (for children < 15 years, 125 mg) IM for 1 dose
In adults, a fluoroquinolone (ciprofloxacin or levofloxacin 500 mg or ofloxacin 400 mg) orally for 1 dose
Azithromycin is not routinely recommended, but a recent study showed that a single 500-mg dose was equivalent to rifampin for chemoprophylaxis and so could be an alternative for patients with contraindications to recommended drugs.
Ciprofloxacin-resistant meningococcal disease is rare but has been reported in several countries (Greece, England, Wales, Australia, Spain, Argentina, France, India) and in 2 US states (North Dakota, Minnesota). When choosing an antibiotic for postexposure prophylaxis, clinicians should consider reports of local ciprofloxacin-resistant meningococci.
See Meningococcal Vaccine Meningococcal Vaccine The meningococcal serogroups that most often cause meningococcal disease in the US are serogroups B, C, and Y. Serogroups A and W cause disease outside the US. Current vaccines are directed... read more for more information, including indications Indications The meningococcal serogroups that most often cause meningococcal disease in the US are serogroups B, C, and Y. Serogroups A and W cause disease outside the US. Current vaccines are directed... read more , contraindications and precautions Contraindications and Precautions The meningococcal serogroups that most often cause meningococcal disease in the US are serogroups B, C, and Y. Serogroups A and W cause disease outside the US. Current vaccines are directed... read more , dosing and administration Dose and Administration The meningococcal serogroups that most often cause meningococcal disease in the US are serogroups B, C, and Y. Serogroups A and W cause disease outside the US. Current vaccines are directed... read more , and adverse effects Adverse Effects The meningococcal serogroups that most often cause meningococcal disease in the US are serogroups B, C, and Y. Serogroups A and W cause disease outside the US. Current vaccines are directed... read more . See also the vaccine schedules for children and adults from the Centers for Disease Control and Prevention (CDC) and meningococcal vaccine recommendations from the Advisory Committee on Immunization Practices (ACIP).
There are several meningococcal vaccines:
2 quadrivalent conjugate vaccines (MenACWY-D and MenACWY-CRM) that protect against 4 of the 6 common pathogenic serogroups of meningococcus (all but B and X)
A bivalent conjugate vaccine that protects against serogroups C and Y that is available only in combination with tetanus toxoid and Haemophilus influenzae type b vaccine (Hib-MenCY-TT) is available for infants at increased risk of meningococcal disease (see also infant meningococcal vaccination recommendations from the ACIP)
A quadrivalent polysaccharide vaccine (MPSV4) for use in selected patients ≥ 56 years
2 monovalent vaccines against serogroup B (MenB-4C and MenB-FHbp)
All children should receive MenACWY-D or MenACWY-CRM at age 11 or 12 years, with a booster dose at age 16 years (see also the routine childhood vaccination schedule Childhood Vaccination Schedule Vaccination follows a schedule recommended by the Centers for Disease Control and Prevention (CDC), the American Academy of Pediatrics, the American Academy of Family Physicians, and the American... read more ). Either of these vaccines is also recommended for adults who are at increased risk.
MenB is recommended for people ≥ 10 years who are at increased risk of serogroup B meningococcal disease.
Over 90% of meningococcal infections involve meningitis or meningococcemia.
An asymptomatic nasopharyngeal carrier state is common; transmission usually occurs via direct contact with respiratory secretions from a carrier.
In the US, most cases are sporadic, typically in children < 2 years of age, but outbreaks can occur, primarily in semiclosed communities (eg, military recruit camps, dormitories, day care centers) and often involve patients aged 5 to 19 years.
Treat with ceftriaxone or penicillin; add dexamethasone for patients with meningitis.
Give close contacts a prophylactic antibiotic.
Vaccinate all children starting at age 11 or 12 years, and selectively vaccinate high-risk younger children and other high-risk people.
The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
See the following government sites for comprehensive, updated vaccination information:
Centers for Disease Control and Prevention: Vaccine schedule for children 18 years of age or younger
Centers for Disease Control and Prevention: Vaccine schedule for adults
Centers for Disease Control and Prevention: Meningococcal vaccination recommendations for infants
Advisory Committee on Immunization Practices: Meningococcal vaccine recommendations
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