Share this article on:

Meningococcal Disease: Early recognition is vital to patient outcomes

Mertz, Lori CNP

doi: 10.1097/01.NPR.0000398844.35575.51
Feature: INFECTIOUS DISEASE: CE Connection

Since the development of vaccines to prevent Haemophilus influenzae type b and Streptococcus pneumoniae, Neisseria meningitidis is the leading cause of bacterial meningitis in the United States. Education of healthcare professionals to improve identification and provide immediate treatment of patients with symptoms consistent with meningococcal disease will result in improved outcomes.

Lori Mertz is a nurse practitioner at UH Neurological Institute, University Hospitals Case Medical Center, Cleveland, Ohio.

The author has disclosed that she has no financial relationship related to this article.



Meningococcal disease is a severe and devastating disease leading to morbidity and death worldwide. An estimated 1,400 to 2,800 cases of meningococcal disease occur in the United States each year.1

Meningococcal disease is caused by Neisseria meningitidis (N. meningitidis). Since the development of conjugate vaccines and the reductions in incidence of Streptococcus pneumoniae and Haemophilus influenzae type B (Hib), N. meningitidis has become the most frequent cause of meningitis in the United States. Annually, there are as many as 500,000 estimated cases of meningococcal disease worldwide with a death rate of approximately 50,000 to 135,000 each year.2

Back to Top | Article Outline


N. meningitidis is a Gram-negative aerobic diplococcus, and its strains are classified into 13 serogroups. Six of the serogroups—A, B, C, W-135, X, and Y—are associated with more than 90% of systemic disease throughout the world. Serogroups are determined by the immunologic response of the outer membrane, which is composed of a polysaccharide capsule. Meningococci can be encapsulated or unencapsulated.3 Unencapsulated strains of N. meningitidis are not protected from the body's immune response and rarely cause systemic disease.4 Encapsulated strains are associated with disease virulence as the capsule offers protection from phagocytic destruction, as well as other immune-mediated processes.3 They also help with transmission and colonization of meningococcus.

Capsular switching, a mechanism that allows N. meningitidis to change its capsular phenotype through horizontal gene transfer, is responsible for the meningococcal strains that have caused disease in the United States. Horizontal gene transfer allows the organism to acquire large DNA sequences from other strains or species and is presumed to occur when an individual is colonized in the pharynx with two or more meningococcal strains.5 Neisseria species contain protruding surface proteins known as pili. These structures facilitate adhesion by interacting with the nonciliated cells of the respiratory tract of the host.6

Other factors that contribute to the virulence of strains of N. meningitidis are rapid doubling time (30 to 45 minutes), an ability to sustain genetic diversity by facilitating the uptake of foreign DNA, and presence of endotoxins that result in inflammatory signaling, sepsis, and meningitis.2,6,7

Back to Top | Article Outline


Although the first described outbreak occurred in Switzerland in 1805, the most frequent incidence of disease occurs in sub-Saharan Africa (also known as the "Meningitis Belt"), China, and Russia.3,8,9 Serogroup A is responsible for epidemics in these regions, as well as in the United States during the first half of the 20th century; however, it is no longer implicated as a cause for disease in the United States and Europe.

According to the CDC Advisory Committee on Immunization Practices, the United States experiences 0.5 to 1.1 meningococcal disease cases per 100,000 individuals each year.1 Serogoups B, C, and Y contribute equally to the majority of disease in the United States today.8 Serogroup B disease is more prevalent in young children and toddlers and may produce prolonged outbreaks with considerable morbidity and mortality.2,3,8 In infants less than 1 year of age, Serogroup B causes more than 50% of cases. Serogroups B and C are responsible for most meningococcal disease in developed countries.9

The highest rates of disease are in children less than 2 years of age, and elevated rates of meningococcal disease in young children are attributed to declining maternal antibodies.3 For those older than 11 years of age, serogroups C, Y, and W-135 are the causative organisms in 75% of cases.1 Outbreaks of serogroup W-135 have been associated with the Hajj pilgrimage (the Islamic pilgrimage to Mecca and Medina in Saudi Arabia) in 1987, 2000, and 2001,when U.S. residents returned.10 Serogroup C is responsible for a larger proportion of cases in adolescents and young adults, and group Y has caused increasing numbers of cases in the United States and Israel.2,8

From 1998 to 2007, infants younger than 1 year had the highest rate of meningococcal disease at 5.38 per 100,000 population with a second peak incidence of disease in adolescents ages 14 to 17 years at 0.74 per 100,000 population. College freshmen living in a dormitory environment have a rate of disease of 5.1 per 100,000 population.8

Individuals age 65 years and older have the highest fatality rate at 23.2%, while infants have a case fatality rate of approximately 7% and adolescents' fatality rate is approximately 20%.4,11 A peaked incidence of case fatality in adolescents is attributed to the increased likelihood that adolescents will present with meningococcemia or septic shock.4

Morbidity rates in meningococcal disease survivors are 11% to 19% and include neurologic sequelae such as cognitive impairment, mental retardation, spasticity, seizures, and hearing loss.8,12,13 Additional morbidity may be related to postnecrotic complications of disseminated intravascular coagulation (DIC), including amputation and renal impairment.14

Back to Top | Article Outline

Populations at risk

N. meningitidis normally resides in the upper respiratory tract of humans. It is estimated that 0.6% to 34.5% of the general population are carriers; that is, they have N. meningitidis within the upper respiratory tract.8 Transmission occurs through the inhalation of the large droplet of meningococcus in respiratory secretions or saliva and can result in colonization or invasive disease.3

Meningococcal carriage can last days to months and induces an immunologic response that results in immunity for the majority of the population by young adulthood.15 It is affected by age, intimate contact, crowded environments such as dormitories and bars, and active or passive tobacco or marijuana smoking. One epidemiologic study showed rave-style club and bar attendance to be possible risk factors for invasive meningococcal disease.16 Other data have shown that spacing between beds and chairs of less than 3 feet contributes to the risk of disease and carriage.8

Meningococcal carriage rates increase gradually after birth (2% of children younger than 5 years of age), and reach peaks in teenage years (individuals ages 15 to 24 are 13 times more likely to be carriers than children under age 15).8 Rates may be elevated in institutional settings such as university dormitories (7% to 37%), or in military recruits (may be as high as 36% to 71%).3 Rates have been noted to rise among freshman undergraduates during the first few months of school, especially for those living on campus.6,8,15 In addition, Blacks and individuals of low socioeconomic status in the United States are at a higher risk.1

Additional predisposing factors to carriage and meningococcal disease include upper respiratory coinfections such as Mycoplasma, influenza and other respiratory viral infections, and trauma induced by dust and low humidity or drying of the mucosal surfaces that may damage the upper respiratory tract.2,8,15 Individuals with functional asplenia and immune disorders, such as nephrotic syndrome, hypogammaglobulinemia, HIV/AIDS, and complement and antibody deficiencies, are at increased risk for N. meningitidis infection.3,6,15

Back to Top | Article Outline

Clinical presentation

N. meningitidis can be a rapidly fatal disease. Clinical presentation is dependent on the patient's immune response and is influenced by age, disruption of physiologic barriers, and immunocompromising medical conditions.17

Specific clinical features of presentation may vary in outbreaks of meningococcal disease. The classic symptoms of acute meningitis are headache, fever, and nuchal rigidity. Approximately 50% of those with meningococcal disease will present with these symptoms, but up to 30% of patients with invasive disease will present without signs of sepsis or meningitis.8 Hemorrhagic skin lesions may be present in 28% to 77% of patients who present with disease. Lesions may be most prevalent over the limbs, but may be scattered over the body and sometimes on mucous membranes or sclera (see Infection with N. meningitidis). The petechiae associated with meningococcemia may be larger and bluer than petechiae from other disease and are nonblanching (they do not lose color when touched or pressed). Biopsies of these lesions show meningococci.3 The classic hemorrhagic rash is seen more often in those older than 1 year of age.8 Patients may present with complaints of leg pain, abnormal skin color, cold hands or feet, and thirst.18

Meningococcal meningitis without septicemia usually has a lower serum concentration of meningococci (less than 103/mL) and meningococcal endotoxin (less than 3 endotoxin units/mL [EU/mL]) but has elevated cerebrospinal fluid (CSF) level concentrations.3 Levels of bacteria in CSF are higher than those in plasma in these patients. This leads to a compartmentalized inflammatory response in the subarachnoid space, while the systemic vascular inflammatory response is limited.3 The ability of N. meningitidis to invade the meninges is related to virulence factors that allow the bacteria to escape the immune system, multiply in the blood, and react closely with the endothelial defense of the blood-brain barrier. Only a few types of bacteria are able to invade the meninges, one of which is N. meningitidis.19

Figure. I

Figure. I

Meningococcal septicemia may present with severe, persistent shock that may last up to 24 hours or until death and has classic symptoms of fever and a petechial or purpuric rash.3,8 Meningococcal septicemia is a result of rapid proliferation of meningococci in the plasma with very high bacterial concentrations (105 to 108/mL) and meningococcal endotoxin (101 to 103 EU/mL).3 The rapid bacterial growth causes an intravascular inflammatory response that leads to circulatory collapse with severe coagulopathies, DIC, and thrombotic lesions in organs and limbs, which can result in multisystem organ failure or amputation (see Meningococcemia). Meningococcal infection can result in pneumonia, conjunctivitis, pericardial infection, and arthritis, and patients can develop impaired renal, adrenal, and pulmonary function. Vascular complications can leave patients severely handicapped.3 Meningococcal septicemia occurs in about 5% to 20% of patients, and it has a mortality from 20% to 80%.8

Neonates and infants may not present with the classic clinical findings. They may present with nonspecific symptoms such as fever, lethargy, irritability, respiratory distress, vomiting, diarrhea, or bulging fontanel. Because their immature immune system results in less frequent presentation with meningismus, seizures, and coma than adults, the American Academy of Pediatrics recommend a lumbar puncture be performed on any child who presents with febrile seizure and meningeal signs, any infant between 6 and 12 months in whom Hib and Streptococci pneumonia vaccine status is deficient or unknown, or as an option in any child who presents with febrile seizure who has been pretreated with antibiotics (,17



Symptoms in children may be nonspecific such as fever, headache, loss of appetite, nausea, and vomiting, which may make initial diagnosis difficult, especially for clinicians who see few cases of meningococcal disease. Nonspecific symptoms may be present for 4 hours in young children and as long as 8 hours in adolescents before specific symptoms were recognized. One study in the United Kingdom found the first specific clinical feature in all age groups was signs of circulatory collapse—leg pain, abdominal skin color, and cold hands and feet.18 These may be due to changes in peripheral circulation and are rarely reported by parents to a primary care provider and, therefore, may have a significant diagnostic value.18 The Scottish Intercollegiate Guidelines Network advises urgent treatment and hospital admission for an ill child with purpuric rash in any distribution or petechial rash beyond the distribution of the superior vena cava. Recommendations also include reevaluation of children with nonspecific presentation within 4 to 6 hours when meningococcal disease cannot be excluded.20

Back to Top | Article Outline


The gold standard test for diagnosis of N. meningitidis is culture from a normally sterile body fluid.8 The administration of antibiotics should not be delayed if lumbar puncture cannot be immediately performed, and blood cultures should be obtained and appropriate adjunctive treatment begun.21 The polymerase chain reaction (PCR) test has been used to amplify DNA to detect the presence of the bacteria and is useful for individuals pretreated with antibiotics.8,21 While there is a reduction in positive CSF cultures after antibiotic administration, one study showed no significant reduction in positive PCR results.8

Findings from lumbar puncture and CSF studies demonstrate that the indications for bacterial meningitis may include elevated CSF opening pressure, an elevated white blood cell count of 100 to 10,000/mm3, elevated protein, and CSF-to-plasma glucose ratio below 0.60.17 Although Gram stain of CSF fluid is rapid, inexpensive, and highly specific, the yield of Gram stain of CSF correlates with CSF bacterial load and type of bacteria present. N. meningitidis may yield positive results in 75% of cases. Gram stain specimen yield may be approximately 20% lower in patients who have received antibiotic therapy.21

Patients with meningococcal meningitis and mild meningococcemia usually have a significant leukocytosis and left shift (increased number of immature neutrophils). An inverse relationship is noted between severity of sepsis and the peripheral white blood cell count due to adherence of neutrophils to endothelial cells in the peripheral vasculature. This process results in the release of toxins, further damaging the endothelial surface.3

Back to Top | Article Outline

Imaging for meningitis

Imaging studies may be requested prior to lumbar puncture to rule out increased ICP (patients may have increased ICP because of inflammation of the meninges and capillary leak that contribute to cerebral edema). Contrasted computed tomography scans should be normal in most cases of uncomplicated meningitis; contrasted magnetic resonance images are normal in 50% of cases.22 Imaging features of meningitis may include pial enhancement, brain edema, widened extra-axial CSF spaces, or enhancement of the subarachnoid spaces due to leakage of contrast through inflamed capillary walls. These changes may be seen on fluid-attenuated inversion recovery (FLAIR) images, which do not require contrast, but changes are nonspecific. A mild hydrocephalus may be seen in most patients with meningitis and, in some patients, the hydrocephalus may not return to normal. Most hydrocephalus due to meningitis is nonobstructing or communicating hydrocephalus due to blockage of CSF resorption by accumulation of exudates.22

A recent study showed gadolinium-enhanced FLAIR may be useful in detecting early meningitis. Of 27 patients who presented to an ED with symptoms of meningitis, all 12 patients diagnosed with meningitis by CSF analysis demonstrated abnormal meningeal enhancement on gadolinium-enhanced FLAIR images.17

Back to Top | Article Outline


Early recognition allows for immediate antibiotic therapy, which is a definitive treatment for meningococcal disease. Case fatalities from systemic meningococcal disease were as high as 70% to 90% before antibiotics were used, but antibiotic therapy has reduced the fatality rate to approximately 10%.7 Doubling time of bacteria may be 30 to 45 minutes, and antibiotic treatment of N. meningitidis does not induce release of meningococcal endotoxin. Because of the combination of these factors, many countries advocate prehospital antibiotic treatment.3

Recommendations by the Infectious Disease Society of America recommend third-generation cephalosporins such as ceftriaxone or cefotaxime, with penicillin G or ampicillin, and chloramphenicol, a fluoroquinolone, or aztreonam as alternative therapies.23

Targeted therapy should be based on Gram stain analysis; if lumbar puncture is delayed, empirical therapy may be initiated by administering vancomycin plus a third-generation cephalosporin, ceftriaxone, or cefotaxime. However, the FDA issued an alert in 2007 because of concerns regarding calcium chelation in vivo; therefore, ceftriaxone can no longer be administered within 48 hours of the completion of infusions containing calcium.24

Recommendations for specific therapy based on pathogens are penicillin G or ampicillin, if penicillin minimum inhibitory concentration (MIC) less than 0.1 mcg/mL; or a third-generation cephalosporin (ceftriaxone or cefotaxime), if penicillin MIC 0.1 to 1.0 mcg/mL, with alternative therapies of chloramphenicol, a fluoroquinolone, or meropenem.23 If antibiotic therapy is begun prior to hospital admission, penicillin G, ceftriaxone, or cefotaxime should be administered via I.V. or I.M. in adults. In pediatric patients, antibiotics should be administered I.V. or intraosseously by butterfly. While I.M. administration is least preferred in children due to compromised blood flow and absorption, it is preferable to no antibiotics.25

Patients should be placed in droplet precaution isolation until 24 hours of antibiotic therapy has been completed.14 In addition to antibiotic therapy, treatments for meningococcal disease include administering fluids to treat hypovolemia as a result of vascular permeability and leakage of fluid into the extravascular space. Untreated hypovolemia may lead to circulatory collapse and multiorgan failure. Colloids or crystalloids may be used to restore circulating volume. Electrolyte replacement through a central venous catheter assists in maintaining myocardial function and tissue oxygenation. Inotropic agents improve cardiac output and assist tissue perfusion and oxygenation while increasing intravascular volume with fluids.

Patients with signs of significantly increased ICP may be treated with mannitol. Patients also presenting with shock require treatment to maintain adequate blood pressure and cerebral perfusion, including endotracheal intubation and respiratory support to manage the PaCO2 and to assist in reducing ICP.24 Seizure management should be aggressive to avoid additional increases in ICP.24

DIC is common in severe meningococcal disease, and patients may exhibit a prolonged international normalized ratio/prothrombin time (INR/PT) and activated partial thromboplastin time (aPTT) as well as reduced platelet and fibrinogen levels with increased concentrations of fibrin degradation products. Patients may display simultaneous symptoms of bleeding and thrombosis. Replacement of clotting factors, platelets, and fibrinogen may result in escalating the prothrombotic process. Platelets should be given only for persistent bleeding after fresh frozen plasma has been administered in patients with profound thrombocytopenia.24

Patients who develop fulminant meningococcal septicemia may develop adrenal hemorrhage (Waterhouse-Friderichsen syndrome).8 Inadequate adrenal function may result in the need for supplemental low-dose corticosteroids.4 Corticosteroids may be used in children with refractory shock, but there is no consensus for use in patients with meningococcal septicemia.14 The literature suggests initial administration of adjunctive dexamethasone in adults with meningitis of unknown etiology at presentation because data exist for adjunctive dexamethasone in patients with pneumococcal meningitis. Dexamethasone should be discontinued unless CSF Gram stain is positive for Gram-positive diplococci or blood or CSF cultures are positive for S. pneumoniae.23

Back to Top | Article Outline


Chemoprophylaxis should be initiated within 24 hours of the identification of the index case to individuals who had close contact with an index case of meningococcal disease from 1 week prior to the onset of symptoms until 24 hours after the index case receives treatment. Chemoprophylaxis after 2 weeks of onset of illness in the index patient is of little benefit. Definition of close contacts includes household members, child-care center contacts, and persons directly exposed to the index case's oral secretions by kissing, mouth-to-mouth resuscitation, endotracheal intubation, or endotracheal tube management. For travelers, anyone with direct contact with respiratory secretions of an index patient or anyone seated next to an index patient on a plane for 8 hours or more should receive chemoprophylaxis. The risk of exposure for household members is 500 to 800 times greater than the general population.1 Early prophylaxis is recommended because the highest risk of illness is within the first 48 hours after the onset of disease in the index case.24

The goal of chemoprophylaxis is to eliminate nasopharyngeal carriage. It should be administered regardless of immunization status as vaccines do not provide 100% protection and immunity may diminish over time.8 Certain antibiotics are 90% to 95% effective in reducing nasopharyngeal colonization, and include rifampin, ciprofloxacin, and ceftriaxone (see Chemoprophylaxis against N. meningitidis). In certain counties in the United States, the CDC suggests that ceftriaxone, rifampin, or azithromycin be used due to ciprofloxacin–resistant N. meningitidis.8 Further data are needed regarding the effectiveness of azithromycin in eradication of nasal carriage. Patients with meningococcal disease who have been treated with agents other than ceftriaxone or third-generation cephalosporins may not have eradicated nasopharyngeal carriage of N. meningitidis. Patients should also receive chemoprophylaxis for eradication of carriage before being discharged from the hospital. Chemoprophylaxis is not recommended for control of epidemics due to cost, difficulty administering simultaneously to large populations, adverse effects, and potential for resistant organisms.1 Vaccination is not of value for immediate protection after close contact with an infected individual because protective antibody levels are not achieved for 7 to 10 days after immunization.15

Table. C

Table. C

Back to Top | Article Outline


Vaccination is the best strategy for prevention and control of meningococcal disease. The meningococcal vaccine, Menomune (MPSV4), contains antigens from A, C, Y, and W-135 serogroups and has been available since 1981. The polysaccharide vaccine stimulates a B-cell immune response, does not result in long-term immunologic response, and has no effect on nasal carriage. As a disadvantage, polysaccharide vaccines are usually ineffective in infants, produce a poor immunologic response in children under the age of 2 years, and are thought to have an immunologic duration of 3 to 5 years.8 In addition to a short duration of immunologic responsiveness, antibodies of children younger than 6 years of age decrease over time and, even though antibodies may be found up to 10 years after immunization in healthy adults, these antibodies' ability to neutralize disease may decrease. The vaccine is also unable to provide herd immunity and induces a hyporesponsiveness, which means redosing an individual with a booster dose results in an antibody response of less than half the amount of an individual receiving his or her first vaccine dose. However, the tetravalent polysaccharide vaccine rarely causes adverse reactions, and can protect high-risk individuals during outbreaks.26 These vaccines have been used extensively in mass vaccination programs and administered to international travelers.

In 2005, a quadrivalent meningococcal conjugate vaccine, Menactra (MCV4), was licensed for use. This vaccine contains the same antigens as the polysaccharide vaccine conjugated to 48 mcg of diphtheria toxoid. Menactra elicits an initial antibody response similar to Menomune, and revaccination will result in a rise in antibody levels. It is likely that Menactra will be more durable and will reduce nasopharyngeal carriage of N. meningitidis, reducing transmission by herd immunity similar to effects of serogroup C conjugate vaccination in the United Kingdom.15

Vaccination with Menactra is recommended for children ages 11 to 12 at preadolescent health screening visits and others between 11 and 55 years who have increased risk for meningococcal disease. In October 2010, the Advisory Committee on Immunization Practices, which advises the CDC, voted 6 to 5 to add a booster vaccine dose for Menactra at age 16 for children immunized at ages 11 to 12 years or 5 years after initial vaccine for teenagers vaccinated at ages 13 to 15. The booster dose was suggested due to waning immunity among older teens during high-risk years.27 Vaccination with Menactra is also advised for travelers visiting parts of sub-Saharan Africa and required by the Saudi Arabia government for all travelers to Mecca during the annual Hajj. Routine vaccination among adults ages 20 to 55 years is not recommended because rates of meningococcal disease are low in this age group. However, persons who wish to decrease their risk may choose to be vaccinated. In 2007, the vaccine was approved for children as young as 2 years. As of April 22, 2011, Menactra is now approved for children as young as 9 months.28

Use of Menomune is recommended in children ages 2 to 10 and adults older than 55 years who are at increased risk for meningococcal disease. Routine vaccination of children younger than 2 years is not recommended because it is ineffective and provides limited protection. Individuals with HIV may be at increased risk for meningococcal disease and may elect vaccination with Menactra, although the efficacy in this population is unknown. Revaccination may be indicated for children first vaccinated when younger than 4 years and for persons vaccinated with Menomune who remain at risk of infection. Menactra is recommended for revaccination of individuals ages 11 to 55 years.1

Vaccination may be administered to persons with mild acute illness but should be deferred in moderate or severe illness. Vaccination is contraindicated in individuals with allergic reaction to any component of the vaccine, allergy to diphtheria toxoid, or allergy to dry natural rubber latex. Because both Menactra and Menomune are inactivated vaccines, they are safe to administer to individuals who are immunocompromised. There are no data available on the safety of Menactra during pregnancy.1 Menactra and Menomune can be administered concurrently with other vaccines, but they must be at different anatomic sites. Adverse reactions for both vaccines are similar but with local adverse reactions more common with patients receiving Menactra, attributed to the diphtheria toxoid contained in the vaccine. Guillain-Barré syndrome (GBS) has been associated with Menactra; therefore, individuals with a history of GBS, or their parents, should not receive the vaccine. Menomune is an alternative to short-term vaccination for this population.1 Rates of GBS in this population appear to be similar to the expected incidence of the disease.15 In 2011, the FDA approved the vaccine Menveo to prevent meningococcal disease in individuals ages 2 through 55 years. The vaccine contains the antigens from A, C, Y, and W-135 serogroups. It is contraindicated in individuals with allergic reaction to any component of the vaccine and postmarking data suggest an increased risk of GBS.29

There is currently no vaccine for serogroup B meningococcus. A serogroup B vaccine is under development but has been challenging because the anti-serogroup B polysaccharide antibodies cross-react with the central nervous system.26 Scientists in New Zealand developed a serogroup B outer-membrane vesicle vaccine to treat a single clone that accounted for 85% of cases in 2000. Vaccination was estimated at 80% effectiveness in fully immunized children, but no data are available on meningococcal carriage among vaccinated individuals or incidence of disease among those not vaccinated.5

Serogroup A meningococcus is responsible for outbreaks of meningitis in Africa's "meningitis belt." A polysaccharide group A vaccine is available and used for emergency vaccination during outbreaks of group A meningococcal disease. The vaccine does not provide long-term immunity in individuals older than age 5, and the efficacy in young children is unknown. Clinical trials are underway for a serogroup A conjugate vaccine to help eradicate meningococcal epidemics in Africa by giving long-term protection and decreasing nasal carriage resulting in herd immunity.30

Back to Top | Article Outline


Early clinical recognition and treatment are imperative to reducing morbidity and mortality of meningococcal disease. Education of healthcare professionals to improve identification and provide immediate treatment of patients with symptoms consistent with meningococcal disease will result in improved outcomes. Furthermore, campaigns to improve public awareness and increase policy makers' knowledge of the benefits of vaccination are integral to eradication of meningococcal disease.

Back to Top | Article Outline


1. Centers for Disease Control and Prevention: Morbidity and Mortality Weekly Review .
2. Reisinger KS, Black S, Stoddard JJ. Optimizing protection against meningococcal disease. Clin Pediatr. 2010;49(6):586–597.
3. Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet. 2007;369(9580):2196–2210.
4. Hershey JH, Hitchcock W. Epidemiology and meningococcal serogroup distribution in the United States. Clin Pediatr. 2010;49(6):519–524.
5. Harrison LH. Epidemiological profile of meningococcal disease in the United States. Clin Infect Dis. 2010;50(suppl 2):S37-S44.
6. Virji M. Pathogenic neisseriae: surface modulation, pathogenesis and infection control. Nature Rev. 2009;7(4):274–286.
7. Stephens DS. Conquering the meningococcus. FEMS Microbiol Rev. 2007;31(1):3–14.
8. Brigham KS, Sandora TJ. Neisseria meningitidis: epidemiology, treatment and prevention in adolescents. Curr Opin Pediatr. 2009;21(4):437–443.
9. Makwana N, Riordan FA. Bacterial meningitis: the impact on vaccination. CNS Drugs. 2007;21(5):355–366.
10. Chen LH, Wilson ME. The role of the traveler in emerging infections and magnitude of travel. Med Clin North Am. 2008;92(6):1409–1432.
11. Cohn AC, MacNeil JR, Harrison LH, et al. Changes in Neisseria meningitidis disease epidemiology in the United States, 1998–2007: implications for prevention of meningococcal disease. Clin Infect Dis. 2010;50(2):184–191.
12. Hoogman M, van de Beek D, Weisfelt M, de Gans J, Schmand B. Cognitive outcome in adults after bacterial meningitis. J Neurol Neurosurg Psychiatry. 2007;78(10):1092–1096.
13. Kutz JW, Simon LM, Chennupati SK, Giannoni CM, Manolidis S. Clinical predictors for hearing loss in children with bacterial meningitis. Arch Otolaryngol Head Neck Surg 2006;132(9):941–945.
14. Baumer JH. Guideline review: management of invasive meningococcal disease, SIGN. Arch Dis Child Educ Pract Ed. 2009;94(2):46–49.
15. Gardner P. Prevention of meningococcal disease. N Eng J Med. 2006;355(14):1466–1473.
16. Honish L, Soskolne C, Senthilselvan A, Houston S. Modifiable risk factors for invasive meningococcal disease during an Edmonton, Alberta, outbreak, 1999–2002. Can J Public Health. 2008;99(1):46–51.
17. Lin AL, Safdieh JE. The evaluation and management of bacterial meningitis current practice and emerging developments. Neurologist. 2010;16(3):143–151.
18. Thompson MJ, Ninis N, Perera R, et al. Clinical recognition of meningococcal disease in children and adolescents. Lancet. 2006;367(9508):397–403.
19. Join-Lambert O, Morand PC, Carbonelle E, et al. Mechanisms of meningeal invasion by a bacterial extracellular pathogen, the example of Neisseria meningitidis. Prog Neurobiol. 2010;91(2):130–139.
20. Theilen U, Wilson L, Wilson G, et al. Guidelines: management of invasive meningococcal disease in children and you people: summary of SIGN guidelines. BMJ. 2008;336(7657):1367–1370.
21. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39(9):1267–1284.
22. Hughes DC, Raghavan A, Mordekar SR, Griffiths PD, Connolly DJ. Role of imaging in the diagnosis of acute bacterial meningitis and its complications. Postgrad Med J. 2010;86(1018):478–485.
23. Infectious Diseases Society of America: Infections by organ system .
24. Cathis K, Levin M, Faust SN. Drug use in acute meningococcal disease. Arch Dis Child Educ Pract Ed. 2008;93(5):151–158.
25. Rajapaksa S, Starr M. Meningococcal sepsis. Aust Fam Physician. 2010;30(5):276–278.
26. Price AA. Meningococcal vaccines. Curr Pharm Des. 2007;13(19):2009–2014.
27. Reuters. UPDATE 1-CDC panel votes to add meningitis booster dose .
28. FDA. FDA approves the first vaccine to prevent meningococcal disease in infants and toddlers. 2011 .
29. Novartis. Menveo. Full Prescribing Information. 2011 .
30. Riordan A. The implications of vaccines for prevention of bacterial meningitis. Curr Opin Neurol. 2010;23(3):319–324.

bacterial meningitis; meningococcal disease; Neisseria meningitidis

© 2011 Lippincott Williams & Wilkins, Inc.