Approach
Meningococcal infections classically present with abrupt onset of fever and malaise, progressing rapidly (within 24 hours) to signs and symptoms of sepsis and/or meningitis. Typically this is in infants under 1 year of age, adolescents, or young adults.[11][45]
A thorough history is important, focusing on place of employment, recent travel, place of residence, and a history of comorbidities such as immunoglobulin deficiency or asplenia, which are factors that indicate an increased risk of meningococcal infection.
Clinical evaluation
Many patients have a history of a recent mild respiratory illness. Early symptoms are nonspecific, including:
Fever
Irritability
Poor feeding or anorexia
Nausea and vomiting
Lethargy
Headache
Leg pain or generalized aches
These are followed rapidly by more obvious symptoms and signs of serious illness such as:
Thirst
Respiratory distress
Rash
Cold hands and feet
Altered consciousness
Photophobia
Hypotonia
Neck pain and stiffness
Seizures
Tachycardia
Hypotension
Shock.
Healthcare professionals should be aware that some of these classical signs of meningitis may not be present, and combinations of symptoms and signs may be more useful than individual clinical signs to identify serious disease.
In infants, a bulging fontanel and a characteristic high-pitched cry are characteristic signs of meningitis, particularly bacterial meningitis, though these are often absent.[40][45][46] Older adult patients with bacterial meningitis are more likely to present with altered consciousness, and less likely to develop headache and neck stiffness, than younger adult patients.[47]
Signs and features
A positive Kernig or Brudzinski sign indicates meningeal inflammation and is suggestive of meningitis but is present in a minority of patients. [47]
Distinguishing between meningococcal infections and less serious conditions is difficult in the early phases of infection, and it may be necessary to begin empiric antibiotic therapy while awaiting results of diagnostic tests. One study of meningococcemia in children identified signs of sepsis (cold hands and feet, leg pain, pallor or mottled skin, and, in young children, drowsiness and respiratory distress) as the most common indicators of serious illness.[40] Specific attention to these features, which typically develop in the first 12 hours of illness, may aid in the prompt recognition of meningococcal disease.
A rash is noted in 42% to 83% of patients, most commonly 4-18 hours after the initial symptoms of illness.[40][48] Typically the rash is a nonblanching petechial or purpuric exanthem, but a minority of patients may initially have nonspecific erythematous macular or maculopapular lesions. The rash may be less visible in patients with darker skin tones; soles of feet, palms of hands, and conjunctivae should be checked.
Although only a minority of patients with fever and a petechial rash will ultimately be found to have meningococcal infections, these findings should prompt the institution of empiric antibacterial therapy and investigations to exclude meningococcemia, unless an alternative diagnosis is likely.
Symptoms of meningitis typically develop 13-16 hours after the onset of illness and ultimately develop in 50% to 89% of patients.[40][48] Clinical symptoms may progress even after the institution of effective antibiotic therapy.[4][7][45]
Routine laboratory tests
Complete blood count and differential, electrolytes, glucose, calcium, magnesium, phosphate, and coagulation profile should be obtained.
All patients should have blood cultures. Isolation of Neisseria meningitidis from a normally sterile body site (blood, cerebrospinal fluid [CSF], joint, pleural fluid, pericardial fluid, or aspiration or biopsy of a purpuric lesion) is the definitive test for diagnosis of invasive meningococcal infections.[1][49]
Tests for rapid diagnosis
Rapid tests are most useful when it is desirable to individually tailor antibiotic therapy or if identification of a meningococcal infection has immediate public health implications, such as the need to provide antibacterial prophylaxis to close contacts.
A Gram stain of CSF, buffy coat suspension, or skin biopsy demonstrating gram-negative diplococci is suggestive of meningococcal infection in people with a compatible clinical illness. Biopsies of skin lesions typically demonstrate hemorrhagic vasculitis with a polymorphonuclear infiltrate. Gram-negative diplococci may be visible within vessel walls or intravascular thrombi. Detection of N meningitidis antigen in tissue specimens by immunochemical staining increases the sensitivity and specificity and should be ordered routinely if a biopsy has been taken.
Cerebrospinal fluid testing
CSF cultures should be considered in patients with signs and symptoms of meningitis. A lumbar puncture (LP) is contraindicated in patients with cardiovascular or respiratory instability, coagulopathy, or infection (including petechial or purpuric lesions) overlying the puncture site. Some experts recommend that LP be deferred in patients with classical presentations of meningococcal disease, as results of this test are unlikely to influence patient management.[50] However, clinical judgment is involved. Deferring an LP is prudent in a critically ill patient with a coagulopathy, but the information obtained by LP in a patient with milder disease may be very helpful in management and outweighs potential risks.
N meningitidis is isolated in up to 80% of people with clinically suspected meningococcal meningitis; therefore, a negative culture does not exclude infection.[51][52] CSF should also be sent for glucose and protein, cell count, and differential. The majority of patients with bacterial meningitis have a CSF glucose concentration of <45 mg/dL, or an absolute ratio of CSF to serum glucose concentrations of <0.4.[51] CSF protein is typically elevated. In rapidly progressive infections, values may be only slightly abnormal or normal. In bacterial meningitis, CSF cell counts are typically >100 cells/microliter, with a polymorphonuclear predominance.[47][51] In fulminant infections and in young infants, CSF cell counts may be only mildly elevated or normal. In early bacterial meningitis, there may be a transient pleocytosis.[53]
Testing in patients who have been treated empirically
Gram stain of normally sterile body fluids and tissues and antigen detection may still be useful in patients who are treated with antibiotics before cultures have been obtained. Positive blood cultures are reported in up to 86%, and positive CSF cultures in up to 80%, of cases of clinically suspected meningococcal infection.[51][52] Diagnostic yields are much lower in patients who have received antibiotics before cultures are obtained. Failure to isolate N meningitidis, therefore, does not reliably rule out meningococcal infection in people with a clinically compatible illness. Gram stains of CSF should be ordered if CSF is obtained.
The presence of group A, B, C, Y, and W-135 N meningitidis capsular polysaccharide antigen in CSF or serum may be detected by latex agglutination. These tests are useful in patients who receive antibiotic treatment before cultures are obtained, because antigen may persist in CSF for several days. The sensitivity of antigen detection ranges from 40% to 95%, but testing of serum or urine specimens is not recommended because of poor sensitivity and specificity.[49] The capsular polysaccharide of serogroup B N meningitidis and serotype K1 Escherichia coli is identical; therefore, neonatal meningitis caused by the latter organism may also produce a positive antigen detection test.
Polymerase chain reaction (PCR) amplification of N meningitidis DNA from blood and CSF is of particular value in patients who have received antibiotics before diagnostic samples are obtained. It is more rapid, sensitive, and specific than conventional microbiologic techniques.[54][55]
Focal infection tests
Cultures of non-CSF normally sterile body fluids (pericardial, pleural, synovial fluid) are indicated if focal meningococcal infection involving these areas is suspected: for example, when pericardial, pleural, or joint effusion is clinically apparent.
Nasopharyngeal cultures
Nasopharyngeal cultures are of limited usefulness in routine patient management. The isolation of N meningitidis from the nasopharynx of a patient with sepsis or meningitis is suggestive, but because nasopharyngeal colonization is common, it does not prove causality. Nasopharyngeal cultures may be helpful in identifying the serogroup of N meningitidis circulating in a community and whether immunization may be helpful in the prevention of secondary cases.
Diagnostic imaging
The role of imaging in the diagnosis of meningococcal infections is limited.
Computed tomography (CT)
CT of the head is commonly obtained prior to performing LP in patients with suspected bacterial meningitis (of any etiology) to exclude the presence of a focal intracranial lesion, although there is no conclusive evidence that LP increases the risk of cerebral herniation in this setting.[56] Although head CT is also frequently performed to exclude significantly elevated intracranial pressure, it is not a sensitive test for this purpose.[57] Most authorities feel that pre-LP head CT is indicated in patients with significant alterations of mental status, focal abnormalities on neurologic exam, papilledema, antecedent focal central nervous system disease, or immunocompromise.[53][56]
If head CT is requested prior to LP, antibiotics should be given immediately and not be delayed pending test results.
Other diagnostic imaging tests
Chest radiographs, joint films, or echocardiography are helpful in the diagnosis of meningococcal pneumonia and empyema, or hematogenous complications of meningococcemia such as septic arthritis and pericarditis.
A chest radiograph is indicated when pneumonia is clinically suspected (cough, dyspnea, tachypnea, chest pain, increased work of breathing, cyanosis, nasal flaring, intercostal or subcostal indrawing, grunting, decreased breath sounds, auscultatory crackles, pleural rub).
Bone and joint radiography is indicated when septic arthritis is suspected (joint erythema, swelling, warmth, pain, decreased range of motion, joint effusion).
Echocardiography is indicated when pericarditis is suspected (tachycardia, chest pain, muffled heart sounds, pericardial friction rub, poor peripheral perfusion, reduced arterial pulse pressure, pulsus paradoxus, increased cardiac size on chest radiography).
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