Meningococcal Meningitis

Individuals acquire meningococcal infections if they are exposed to virulent bacteria and have no protective bactericidal antibodies.

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, the bacterium may be killed by bactericidal antibodies, complement, and phagocytic cells, or it 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, or severe systemic infection with circulatory collapse and DIC. Meningococcemia leads to diffuse vascular injury, which is characterized by endothelial necrosis, intraluminal thrombosis, and perivascular hemorrhage.

Risk factors

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 predispose individuals to meningococcal disease.

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.

Frequency and serogroup incidence in the United States

Since 1960, the incidence of meningococcal meningitis in the United States has been stable, at approximately 0.9-1.5 cases per 100,000 people per year. Most cases occur during winter and early spring.

Serogroups B and C have caused most cases of meningococcal meningitis in the United States since World War II. An increased frequency of serogroup B and Y meningococci has been noted since 1990. The frequency of localized outbreaks has increased since 1991. ^{[2, 3]}

Global disease distribution

As previously mentioned, 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 it 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 meningococcal meningitis pandemic that began in 1996 has resulted so far in approximately 300,000 cases being reported to the World Health Organization (WHO).

Morbidity and mortality in meningococcal meningitis

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.

Early complications of bacterial meningitis include seizures, raised intracranial pressure (seen in the image below), cerebral venous thrombosis, sagittal sinus thrombosis, and hydrocephalus. The risk of cerebral herniation from acute meningitis is about 6-8%.

In fulminant meningococcemia, severe disseminated intravascular coagulation (DIC) may develop, leading to hemorrhagic diathesis with bleeding into the lungs, urinary tract, and gastrointestinal tract. Ischemic complications of DIC also are common.

Infrequent suppurative complications include septic arthritis, purulent pericarditis, endophthalmitis, and pneumonia. Of survivors, 10% developed allergic complications manifested as cutaneous vasculitis or arthritis.

Late complications may include communicating hydrocephalus (which can present with gait difficulty, mental status changes, and incontinence) and hearing loss. ^[4]

In one study, 27% of survivors experienced 1 or more suppurative, allergic, or neurologic complications, including hearing loss, cutaneous vasculitis, and arthritis.

Hearing loss, noted in 9% of children, occurred significantly more often in patients with marked leukocytosis or leukopenia or with cerebrospinal fluid (CSF) leukocytosis greater than 10 X 10⁹/L.

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.

Even when the disease is diagnosed early and adequate therapy is instituted, the case-fatality rate in meningococcal meningitis ranges from 5-10%; it 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%. ^[5]

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 neurologic sequelae.

A cohort study from Netherlands (the Meningitis Cohort Study) revealed a 7% mortality rate and an unfavorable outcome in 12% of the cases. ^[6]

Race predilection

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

Sex predilection

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

Age predilection

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

The prognosis for meningococcal meningitis is fair if the patient does not have focal neurologic deficits and is not stuporous or comatose. The prognosis for meningococcal disease is poor when the infection has a septicemic component. Most patients with meningococcal meningitis recover completely if appropriate antibiotic therapy is instituted promptly.

Thrombocytopenia, a lowered coagulation index, moderate anemia (hemoglobin < 11 g/dL), an obtunded mental state, and a history of convulsions were reported to be poor prognostic factors.

In one study, only anemia was correlated independently with fatality; the results suggested that anemia should be considered an important prognostic marker in the acute phase of meningococcal meningitis.

Advise any household contacts and close respiratory contacts that chemoprophylaxis agents are available to eliminate the carrier state and prevent the spread of infection. ^[7]