eMedicine Specialties > Neurology > Neurological Infections

Meningococcal Meningitis

Author: Francisco de Assis Aquino Gondim, MD, MSc, PhD, Professor Adjunto II, Departments of Physiology and Pharmacology, Neurology Residency Program Director, Faculdade de Medicina, Universidade Federal do Ceará, Brazil
Coauthor(s): Manish K Singh, MD, Assistant Professor, Department of Neurology, Teaching Faculty for Pain Management and Neurology Residency Program, Hahnemann University Hospital, Drexel College of Medicine; Medical Director, Neurology and Pain Management, Jersey Institute of Neuroscience; Sidney E Croul, MD, Director of Neuropathology, Professor, Department of Pathology and Laboratory Medicine, Medical College of Pennsylvania Hahnemann University
Contributor Information and Disclosures

Updated: Aug 11, 2009

Introduction

Background

Meningococcal meningitis (International Classification of Disease-9 [ICD-9] code: 036.0) has been recognized as a serious problem for almost 200 years. It was first identified definitely by Vieusseux in Geneva in 1805. The causative organism, Neisseria meningitidis, was isolated first in 1887.

Meningococcal disease still is associated with a high mortality rate and persistent neurological defects, particularly among infants and young children.

The first successful treatment of meningitis with intravenous and intrathecal penicillin was reported in 1944, and the first clinical trials using high doses of intravenous penicillin as monotherapy for the treatment of meningitis were reported in 1950. Since then, penicillin has remained the drug of choice for the treatment of meningococcal meningitis.1

For related information, see eMedicine article Meningococcal Infections.

Pathophysiology

N meningitidis is a gram-negative, aerobic, encapsulated diplococcus that grows best on enriched media such as Mueller-Hinton or chocolate agar, at 37° and in an atmosphere of 5-10% carbon dioxide.

Meningococci comprise numerous serogroups that are based on the composition of their polysaccharide capsular antigens. They differ in their agglutination reactions to sera directed against polysaccharide antigens. At least 13 serogroups have been described: A, B, C, D, E, H, I, K, L, W-135, X, Y, and Z. Serogroups B and C have caused most cases of meningococcal meningitis in the United States since the end of World War II; before that, group A was more prevalent. More than 99% of meningococcal infections are caused by serogroups A, B, C, 29E, or W-135.

The natural habitat and reservoir for meningococci is the mucosal surfaces of the human nasopharynx and, to a lesser extent, the urogenital tract and anal canal. Approximately 5-10% of adults are asymptomatic nasopharyngeal carriers, but that number increases to as many as 60-80% of members of closed populations (eg, military recruits in camps).

The modes of infection include direct contact or respiratory droplets from the nose and throat of infected people. Meningococcal disease most likely occurs within a few days of acquisition of a new strain, before the development of specific serum antibodies.

The incubation period averages 3-4 days (range 1-10 days), which is the period of communicability. Bacteria can be found for 2-4 days in the nose and pharynx and for up to 24 hours after starting antibiotics. Treatment with penicillin may not eradicate the bacteria from the nasopharyngeal carriers.

After adherence to the nasopharyngeal mucosa, meningococci are transported to membrane-bound phagocytic vacuoles. Within 24 hours, they can be seen in the submucosa, close to vessels and local immune cells. In most cases, meningococcal colonization of mucosal surfaces leads to subclinical infection or mild symptoms. In approximately 10-20% of cases, N meningitidis enters the bloodstream. In the vascular compartment, they may be killed by bactericidal antibodies, complement, and phagocytic cells or may multiply, initiating the bacteremic phase. Organisms replicate rapidly.

Systemic disease appears with the development of meningococcemia and usually precedes meningitis by 24-48 hours. This can lead to systemic infection in the form of bacteremia, metastatic infection that commonly involves the meninges (see Media file 3), or severe systemic infection with circulatory collapse and disseminated intravascular coagulation (DIC). Meningococcemia leads to diffuse vascular injury, which is characterized by endothelial necrosis, intraluminal thrombosis, and perivascular hemorrhage.

Grossly purulent exudate is seen in the leptomeni...

Grossly purulent exudate is seen in the leptomeninges.

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Grossly purulent exudate is seen in the leptomeni...

Grossly purulent exudate is seen in the leptomeninges.


Invasive disease depends on host factors. Infants are protected from meningococcal disease for the first few months of life by transferred maternal antibodies and low rate of meningococcal acquisition. Subsequently, susceptibility peaks at age 6-12 months and decreases again after colonization of closely related nonpathogenic bacteria such as Neisseria lactamica that have surface antigens in common with virulent strains. Colonization with N meningitidis gradually replaces the nonpathogenic bacteria and induces antibodies to the infecting strain, thus reinforcing natural immunity. Invasive disease occurs if no protective bactericidal antibodies are mounted against the infecting strain.

Meningococci that elaborate a capsule can lead to invasive disease. The capsule protects them from desiccation and from host immune mechanisms. Adhesins and endotoxins also enhance their pathogenic potential. Dysfunctional properdin (ie, component of the alternative pathway of complement), HIV infection, functional or anatomical asplenia, and congenital complement deficiencies also predispose individuals to meningococcal disease.

Individuals acquire the infection if they are exposed to virulent bacteria and have no protective bactericidal antibodies. Smoking and concurrent viral infection of the upper respiratory tract diminish the integrity of the respiratory mucosa and increase the likelihood of invasive disease. Crowding living conditions also facilitate disease spread, since individuals from different areas have different strains of meningococci. The risk of invasive disease is higher in the first few days after exposure to a new strain.

Frequency

United States

Since 1960, the incidence has been stable, at approximately 0.9-1.5 cases per 100,000 people per year. Most cases occur during winter and early spring. In the United States, increased frequency of serogroups B and Y meningococci has been noted since 1990. The frequency of localized outbreaks has increased since 1991.2,3

International

Serogroups A, B, and C are responsible for most cases of meningococcal disease throughout the world.

In Europe and the Americas, serogroup B is the predominant agent causing meningococcal disease, followed in frequency by serogroup C. Historically, serogroup A was the main cause of epidemic meningococcal disease globally, and serogroup A is still the predominant cause of meningococcal meningitis in Africa and Asia.

In the African "meningitis belt" (a region of savanna that extends from Ethiopia in the east to Senegal in the west), this disease frequently occurs in epidemics during the hot and dry weather (December to March).

The recent meningococcal meningitis pandemic, which began in 1996, has resulted so far in approximately 300,000 cases being reported to the World Health Organization (WHO).

Mortality/Morbidity

Morbidity and mortality rates from the disease remain high. Apart from epidemics, at least 1.2 million cases of bacterial meningitis are estimated to occur every year; 135,000 of them are fatal. Approximately 500,000 of these cases and 50,000 of the deaths are due to meningococci.

  • Even when the disease is diagnosed early and adequate therapy is instituted, the case-fatality rate ranges from 5-10% and may exceed 40% in patients with meningococcal sepsis. In a review of 493 episodes of bacterial meningitis in adults, the overall case-fatality rate was 25%. In another study, patients with meningococcal meningitis had a case-fatality rate of 7.5%.4
  • In developing countries, the mortality rate from bacterial meningitis is often higher (20-40%) than in developed countries.
  • Among those who survive the meningococcal disease, 10-20% experience neurological sequelae.
  • A 2008 published cohort study from Netherlands (the Meningitis Cohort Study) revealed a 7% mortality and unfavorable outcome in 12% of the cases.5

Race

In one study conducted in the United States, the incidence of meningococcal disease was slightly higher among African Americans (1.5 cases per 100,000 people) than whites (1.1 cases per 100,000 people).

Sex

In one study conducted in the United States, males accounted for 55% of total cases of meningococcal meningitis.

Age

Meningococcal meningitis most commonly affects individuals aged between 3 years and adolescence. It rarely occurs in individuals older than 50 years.

Clinical

History

  • In a 2008 published cohort study from Netherlands (the Meningitis Cohort Study), only 70% of the patients had the classic triad of fever, neck stiffness, and change in mental status. If the presence of rash was added, 89% of the patients had 2 of the 4 features.5
  • Meningococcal meningitis is characterized by acute onset of intense headache, fever, nausea, vomiting, photophobia, and stiff neck.
  • Lethargy or drowsiness frequently is reported. Stupor or coma is less common. If coma is present, the prognosis is poor.
  • Patients also may complain of skin rash, which usually points to disease progression.
  • The clinical pattern of bacterial meningitis is quite different in young children: Bacterial meningitis usually presents as a subacute infection that progresses over several days.
    • Irritability is a common presenting feature, and headache and neck stiffness may not be present. Projectile vomiting may occur.
    • Seizures occur in 40% of children with meningitis, typically during the first few days. The majority of seizures have a focal onset.
    • In infants, the illness may have an insidious onset; stiff neck may be absent. In children, even when the combination of convulsive status epilepticus and fever is present, the classic signs and symptoms of acute bacterial meningitis may not be present.6

Physical

  • Neurological signs include nuchal rigidity, lethargy, delirium, coma, or convulsions.
    • Most adult patients have an altered mental state, clinical signs of nuchal rigidity (eg, Kernig sign, Brudzinski sign), and fever.
    • Elderly patients are prone to have an altered mental state and a prolonged course with fever.
  • Patients older than 30 years were noted to have petechiae (62%) less frequently than younger patients (81%).
  • A more severe but less common form of meningococcal disease is meningococcal septicemia, which is characterized by rapid circulatory collapse and a hemorrhagic rash.
  • The Waterhouse-Friderichsen syndrome may develop in 10-20% of children with meningococcal infection. This syndrome is characterized by large petechial hemorrhages in the skin and mucous membranes, fever, septic shock, and DIC.
  • A petechial or purpuric rash usually is found on the trunk, legs, mucous membranes, and conjunctivae. Occasionally, it is on the palms and soles. The rash may progress to purpura fulminans, when it usually is associated with multiorgan failure (ie, Waterhouse-Friderichsen syndrome).

More on Meningococcal Meningitis

Overview: Meningococcal Meningitis
Differential Diagnoses & Workup: Meningococcal Meningitis
Treatment & Medication: Meningococcal Meningitis
Follow-up: Meningococcal Meningitis
Multimedia: Meningococcal Meningitis
References
Further Reading
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Keywords

Neisseria meningitidis, N meningitidis, meningococcal disease, meningococci, meningococcal infections, Neisseria lactamica, N lactamica, bacterial meningitis, Waterhouse-Friderichsen syndrome, meningococcal septicemia

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Contributor Information and Disclosures

Author

Francisco de Assis Aquino Gondim, MD, MSc, PhD, Professor Adjunto II, Departments of Physiology and Pharmacology, Neurology Residency Program Director, Faculdade de Medicina, Universidade Federal do Ceará, Brazil
Francisco de Assis Aquino Gondim, MD, MSc, PhD is a member of the following medical societies: American Academy of Neurology and Movement Disorders Society
Disclosure: Boehringer-Ingelheim Honoraria Speaking and teaching

Coauthor(s)

Manish K Singh, MD, Assistant Professor, Department of Neurology, Teaching Faculty for Pain Management and Neurology Residency Program, Hahnemann University Hospital, Drexel College of Medicine; Medical Director, Neurology and Pain Management, Jersey Institute of Neuroscience
Manish K Singh, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American Association of Physicians of Indian Origin, American Headache Society, American Medical Association, and American Society of Regional Anesthesia and Pain Medicine
Disclosure: Nothing to disclose.

Sidney E Croul, MD, Director of Neuropathology, Professor, Department of Pathology and Laboratory Medicine, Medical College of Pennsylvania Hahnemann University
Sidney E Croul, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuropathologists, and Society for Neuroscience
Disclosure: Nothing to disclose.

Medical Editor

Norman C Reynolds Jr, MD, Neurologist, Veterans Affairs Medical Center of Milwaukee; Professor Medical College of Wisconsin (retired)
Norman C Reynolds Jr, MD is a member of the following medical societies: American Academy of Neurology, Association of Military Surgeons of the US, Movement Disorders Society, Sigma Xi, and Society for Neuroscience
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University
Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Paraplegia Society, and National Multiple Sclerosis Society
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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