. Neisseria meningitidis

Neisseria meningitidis

Michele Estabrook

Neisseria meningitidis is a common commensal bacterium of the human upper respiratory tract. Colonization infrequently leads to disseminated disease, but the resulting meningitis and sepsis can be fulminant and rapidly fatal in healthy children and adults. Among survivors, 11% to 19% are left with disabilities such as neurological deficit, hearing loss, or limb amputation.^1,2 Despite advances in vaccine technology, N meningitidis remains a significant worldwide pathogen and the cause of epidemic meningitis.

EPIDEMIOLOGY

Humans are the only reservoir for N meningitidis, and approximately 10% of the general population are asymptomatic, nasopharyngeal carriers. Peak colonization rates of 24% to 37% occur in healthy adolescents and young adults.⁴ The colonization rate increases even more under conditions of crowding or during outbreaks and epidemics. The majority of these strains are not pathogenic, but carriage often results in protective, serum antibodies.^1-5 Even colonization with a virulent clone infrequently leads to disease, but when dissemination occurs, it is often in the first week after acquisition.^2,6 Baseline endemic disease can be punctuated with localized outbreaks or epidemics caused by virulent, genetically related (focal complex) strains.²

In the United States, the rate of meningococcal disease remained relatively stable at 0.9 to 1.5 cases per year per 100,000 population between 1960 and 1999.¹ The rate of disease then declined yearly until 2004 and has remained steady through 2006 at 0.3 cases per 100,000 population.⁹ The prevalence of serum bactericidal antibody is lowest in infants 6 to 24 months of age, and this window of susceptibility correlates with the peak incidence of meningococcal disease.¹⁰ Rates drop during childhood, and then a second, smaller peak occurs during adolescence and early adulthood.^1,9 The prevalence of meningococcal disease varies seasonally, with the highest attack rates occurring in the winter and early spring.

In the 1980s and early 1990s, most of the disease in the United States was due to serogroups B and C. Recently, group Y increased in prevalence and now accounts for about one third of the cases. Serogroup A is rarely found.^1,9 Epidemics have not occurred in the United States since World War II.

A multicenter surveillance study of invasive meningococcal disease in children identified 159 episodes between January 1, 2001, and March 15, 2005. The age distribution is shown in eFigure 275.2 . Sixty-six percent of the children were 5 years of age or younger.

Meningococcal disease occurs worldwide. Serogroups B and C cause most of the disease in industrialized nations, with an incidence of 1 to 3 per 100,000 population over the past 30 years. Serogroup A, and to a lesser extent C, predominate in developing countries, with a much higher incidence of 25 cases per 100,000 population.^1-3,5 eFigure 275.3 shows the global serogroup distribution of invasive meningococcal disease.⁵

Risk Factors

Antibody-induced, complement-mediated immune lysis is critical in host defense, and individuals who lack this ability are at increased risk. However, underlying immune defects account for only a small percentage of disease.¹ These include functional and anatomic asplenia as well as several genetic defects. X-linked properdin deficiency predisposes to fatal meningococcemia, and defects in the terminal complement components increase the risk for recurrent infections. Polymorphisms in genes encoding for mannose binding lectin, the Fcγ-receptor II (CD32) and III (CD16), plasminogen activator inhibitor (PAI-1), and Toll-like receptor 4 (TLR4) are associated with increased frequency or severity of disease.^2,3,5,11,16

Exposure to tobacco smoke, concurrent viral infection of the upper respiratory tract, household crowding, and chronic underlying illness all increase the risk of developing disseminated disease.^1,17

PATHOPHYSIOLOGY

N meningitidis are gram-negative, aerobic diplococci that grow well on enriched medium such as chocolate or Mueller-Hinton agar in an atmosphere of 5% to 10% carbon dioxide (eFig. 275.1 ). Organisms are divided into 13 serogroups based on the structure of their capsular polysaccharide, but only 6 (A, B, C, Y, W-135, and X) account for most of the disease, with groups A, B, C, and Y predominating. Molecular subtyping methods (multilocus enzyme electrophoresis, pulsed-field gel electrophoresis, or DNA sequence analysis) are useful for the characterization of outbreaks and the identification of disease-causing clones.^1,3

Meningococci are transmitted by aerosol or contact with secretions and colonize the respiratory mucosa. Focal spread can lead to respiratory tract infection, including pneumonia. Invasion through epithelial surfaces leads to bloodstream dissemination, allowing the bacteria to seed the meninges, pericardium, or large joints. The loss of protective maternal antibody renders the infant susceptible until endogenous antibody is induced by carriage of N meningitidis and Neisseria lactamica, a nonpathogenic species, as well as cross-reactive antibody induced by normal enteric organisms.^2,3,5,11,16

When meningococci enter the bloodstream, they can be cleared spontaneously, resulting in transient bacteremia, or they can result in overt disease. Endotoxin is released in the form of outer membrane vesicles and induces cytokine production, shock, and disseminated intravascular coagulation (see eFig. 275.4 ).

CLINICAL FEATURES

Meningococcal disease can manifest as several different clinical syndromes as summarized in Table 275-1. Meningitis without shock occurs in about 50% of cases (higher in developing countries) and is indistinguishable from other forms of purulent meningitis (see Chapter 231).

Bacteria are isolated from the blood in up to 75% of cases. This can present as occult bacteremia in young children being evaluated for fever without a source or as transient bacteremia associated with fever and a nonspecific rash. Meningococcal sepsis occurs in 5% to 10% of patients and is characterized by fever and petechial or purpuric rash (Fig. 275-1). This can progress to fulminant meningococcal septicemia (purpura fulminans). Patients present with severe, persistent shock with little or no signs of meningitis. The development of a profound inflammatory response leads to progressive circulatory collapse; severe coagulopathy; and impaired pulmonary, renal, and adrenal function. Disseminated intravascular coagulation results in thrombotic lesions in the skin, limbs, kidneys, adrenals (Waterhouse-Friderichsen syndrome), and choroid plexus and lungs: Multiorgan failure ensues. Vascular complications often lead to limb amputation and extensive skin loss^1,3 (eFig. 275.5 ).

Pneumonia occurs in 5% to 15% of patients with disseminated meningococcal disease and tends to occur in older children. Other, less common, respiratory tract infections include otitis media and epiglottitis. Focal infections occur less frequently and include septic arthritis, purulent pericarditis, conjunctivitis, urethritis, osteomyelitis, primary peritonitis, and endophthalmitis. Chronic meningococcemia is a rare manifestation that can last weeks to months and is characterized by prolonged intermittent fevers, rash, and arthralgias^1,3 (eFig. 275.6 ).