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As discussed above, the most common form of infection with N. meningitidis is asymptomatic carriage of the organism in the nasopharynx. Despite the location of infection in the upper airway, meningococcal pharyngitis is rarely reported; however, upper respiratory tract symptoms are common prior to presentation with invasive disease. It is not clear whether these symptoms relate to preceding viral infection (which may promote meningococcal acquisition) or to meningococcal acquisition itself. After acquiring the organism, susceptible individuals develop disease manifestations in 1–10 days (usually <4 days, although colonization for 11 weeks has been documented).
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Along the spectrum of presentations of meningococcal disease, the most common clinical syndromes are meningitis and meningococcal septicemia. In fulminant cases, death may occur within hours of the first symptoms. Occult bacteremia is also recognized and, if untreated, progresses in two-thirds of cases to focal infection, including meningitis or septicemia. Meningococcal disease may also present as pneumonia, pyogenic arthritis or osteomyelitis, purulent pericarditis, endoph-thalmitis, conjunctivitis, primary peritonitis, or (rarely) urethritis. Perhaps because it is difficult to diagnose, pneumococcal pneumonia is not commonly reported but is associated with serogroups Y, W, and Z and appears most often to affect individuals >10 years of age.
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A nonblanching rash (petechial or purpuric) develops in >80% of cases of meningococcal disease; however, the rash is often absent early in the illness. Usually initially blanching in nature (macules, maculopapules, or urticaria) and indistinguishable from more common viral rashes, the rash of meningococcal infection becomes petechial or frankly purpuric over the hours after onset. In the most severe cases, large purpuric lesions develop (purpura fulminans). Some patients (including those with overwhelming sepsis) may have no rash. While petechial rash and fever are important signs of meningococcal disease, fewer than 10% of children (and, in some clinical settings, fewer than 1% of patients) with this presentation are found to have meningococcal disease. Most patients presenting with a petechial or purpuric rash have a viral infection (Table 180-2). The skin lesions exhibit widespread endothelial necrosis and occlusion of small vessels in the dermis and subcutaneous tissues, with a neutrophilic infiltrate.
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Meningococcal meningitis commonly presents as nonspecific manifestations, including fever, vomiting, and (especially in infants and young children) irritability, and is indistinguishable from other forms of bacterial meningitis unless there is an associated petechial or purpuric rash, which occurs in two-thirds of cases. Headache is rarely reported in early childhood but is more common in later childhood and adulthood. When headache is present, the following features, in association with fever or a history of fever, are suggestive of bacterial meningitis: neck stiffness, photophobia, decreased level of consciousness, seizures or status epilepticus, and focal neurologic signs. Classic signs of meningitis, such as neck stiffness and photophobia, are often absent in infants and young children with bacterial meningitis, who more usually present with fever and irritability and may have a bulging fontanelle.
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While 30–50% of patients present with a meningitis syndrome alone, up to 40% of meningitis patients also present with some features of septicemia. Most deaths from meningococcal meningitis alone (i.e., without septicemia) are associated with raised intracranial pressure presenting as a reduced level of consciousness, relative bradycardia and hypertension, focal neurologic signs, abnormal posturing, and signs of brainstem involvement—e.g., unequal, dilated, or poorly reactive pupils; abnormal eye movement; and impaired corneal responses (Chap. 328).
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Meningococcal septicemia alone accounts for up to 20% of cases of meningococcal disease. The condition may progress from early nonspecific symptoms to death within hours. Mortality rates among children with this syndrome have been high (25–40%), but early aggressive management (as discussed below) may reduce the figure to <10%. Early symptoms are nonspecific and suggest an influenza-like illness with fever, headache, and myalgia accompanied by vomiting and abdominal pain. As discussed above, the rash, if present, may appear to be viral early in the course until petechiae or purpuric lesions develop. Purpura fulminans occurs in severe cases, with multiple large purpuric lesions and signs of peripheral ischemia. Surveys of patients have indicated that limb pain, pallor (including a mottled appearance and cyanosis), and cold hands and feet may be prominent. Shock is manifested by tachycardia, poor peripheral perfusion, tachypnea, and oliguria. Decreased cerebral perfusion leads to confusion, agitation, or decreased level of consciousness. With progressive shock, multiorgan failure ensues; hypotension is a late sign in children, who more commonly present with compensated shock (tachycardia, poor peripheral perfusion, and normal blood pressure). Poor outcome is associated with an absence of meningism, hypotension, young age, coma, relatively low temperature (<38°C), leukopenia, and thrombocytopenia. Spontaneous hemorrhage (pulmonary, gastric, or cerebral) may result from consumption of coagulation factors and thrombocytopenia.
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Chronic Meningococcemia
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Chronic meningococcemia, which is rarely recognized, presents as repeated episodes of petechial rash associated with fever, joint pain, features of arthritis, and splenomegaly that may progress to acute meningococcal septicemia if untreated. During the relapsing course, bacteremia characteristically clears without treatment and then recurs. The differential diagnosis includes bacterial endocarditis, acute rheumatic fever, Henoch-Schönlein purpura, infectious mononucleosis, disseminated gonococcal infection, and immune-mediated vasculitis. This condition has been associated with complement deficiencies in some cases and with inadequate sulfonamide therapy in others.
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A study from the Netherlands found that half of isolates from patients with chronic meningococcemia had an underacylated lipid A (part of the surface LPS molecule) due to an lpxL1 gene mutation, which markedly reduces the inflammatory response to endotoxin.
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Postmeningococcal Reactive Disease
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In a small proportion of patients, an immune complex disease develops ~4–10 days after the onset of meningococcal disease, with manifestations that include a maculopapular or vasculitic rash (2% of cases), arthritis (up to 8% of cases), iritis (1%), pericarditis, and/or polyserositis associated with fever. The immune complexes involve meningococcal polysaccharide antigen and result in immunoglobulin and complement deposition with an inflammatory infiltrate. These features resolve spontaneously without sequelae. It is important to recognize this condition since a new onset of fever and rash can lead to concerns about relapse of meningococcal disease and unnecessarily prolonged antibiotic treatment.