Epidemic cerebrospinal meningitis, also known as "meningococcal meningitis," is an acute purulent meningitis caused by Neisseria meningitidis. It is one of the common acute infectious diseases observed during winter and spring. Its clinical manifestations typically include sudden high fever, headache, vomiting, petechiae and ecchymosis on the skin and mucosa, positive meningeal irritation signs, and purulent changes in cerebrospinal fluid. In severe cases, manifestations may include septic shock and damage to the brain parenchyma.
Pathogen
Neisseria meningitidis, commonly referred to as "meningococcus," belongs to the genus Neisseria. It is a Gram-negative bacterium, kidney-shaped, typically appearing in pairs, and characterized by the presence of a capsule and pili. It is non-motile and obligately aerobic. Based on the specific antigens of its capsular polysaccharide, the bacterium can be divided into 13 serogroups: A, B, C, D, H, I, K, L, X, Y, Z, 29E, and W135. Among these, serogroups A, B, and C are the primary pathogenic strains, with serogroup C being the most virulent.
The bacterium produces autolytic enzymes, and cultures often die after more than 48 hours. Its resistance to external factors is weak; it is susceptible to heat, desiccation, cold, and standard disinfectants. Immediate inoculation of blood or cerebrospinal fluid specimens at the bedside helps improve positive detection rates.
Epidemiology
Carriers of Neisseria meningitidis and infected children act as sources of transmission, with carriers playing a more critical role in the spread of the disease. The primary mode of transmission is through respiratory droplets, making crowded living conditions, poor ventilation, and densely populated areas conducive to disease spread. Infants and young children may become infected through close contact.
Susceptibility to infection is widespread among people, and those who recover typically develop long-lasting immunity to the specific serogroup of bacteria. The disease is more common in winter and spring. Since the widespread implementation of the serogroup A meningococcal vaccine, the incidence rate of meningococcal meningitis has been steadily declining.
Pathogenesis
The likelihood of disease development and its severity depend on the bacterial load, virulence, and the patient’s immune status.
The primary pathogenic factor is the release of bacterial endotoxins. Endotoxins induce a systemic Schwartzman reaction, activate the complement system, and increase the release of inflammatory mediators, causing circulatory disorders and shock. Among bacterial endotoxins, meningococcal endotoxins are particularly potent in activating the coagulation system, leading to disseminated intravascular coagulation (DIC) and secondary fibrinolysis in the early stages of shock. These processes exacerbate microcirculation disorders, bleeding, and shock, eventually resulting in multi-organ failure.
Meningococci invade the meninges and enter the cerebrospinal fluid, releasing endotoxins that trigger purulent inflammation of the meninges and spinal membranes and increase intracranial pressure. This leads to symptoms such as seizures and coma. Severe cerebral edema may result in brain herniation, which can lead to rapid mortality.
Pathology
In the septicemic stage, vascular damage constitutes the predominant pathological change, featuring inflammation, necrosis, and thrombosis of the vascular walls. Hemorrhage around affected vessels may lead to petechiae or ecchymosis on the skin and mucosa.
During the meningitic stage, pathological changes are primarily observed in the leptomeninges on the surface of the cerebral hemispheres and at the cranial base. Early-stage inflammation includes meningeal congestion, edema, and focal hemorrhage, which elevate intracranial pressure. In the later stages, extensive fibrin exudation and infiltration by neutrophils result in cerebrospinal fluid becoming turbid or purulent.
Inflammatory lesions at the cranial base may cause damage to corresponding cranial nerves and, in severe cases, involve the brain parenchyma. In fulminant meningococcal meningitis, the septic shock subtype is marked by diffuse coagulation and thrombosis in the blood vessels of the skin and internal organs, with adrenal hemorrhage and necrosis being the most severe complication. The mixed form features concurrent damage to the adrenal glands, meninges, and brain parenchyma.
Clinical Manifestations
The incubation period ranges from 1 to 10 days, typically lasting 2 to 3 days. Based on clinical presentation, four types can be identified:
Common Type
This is the most prevalent form, accounting for over 90% of all cases.
Prodromal Stage (Upper Respiratory Infection Stage)
Typical symptoms include mild fever, sore throat, cough, nasal congestion, and other upper respiratory symptoms lasting 1 to 2 days.
Septicemic Stage
This stage is typically characterized by abrupt onset with fever, accompanied by chills, headache, and lethargy. Infants may exhibit crying, irritability, feeding refusal, and convulsions. Older children may report headache, generalized pain, or joint pain affecting one or a few joints. A key clinical sign is the presence of petechiae or ecchymosis on the skin and mucosa, ranging from 1–2 mm to 1–2 cm in size. These lesions initially appear bright red but quickly turn purplish-red, often with central necrosis or blistering. Splenomegaly may occur in some cases. After 1–2 days, progression into the meningitic stage occurs.
Meningitic Stage
Symptoms associated with sepsis and skin petechiae or ecchymosis persist, and the involvement of the central nervous system becomes prominent. Clinical features include irritability, projectile vomiting, intense headache, and more severe manifestations such as delirium, coma, and convulsions, along with positive meningeal irritation signs. In infants, due to open cranial sutures and fontanelles, clinical manifestations may be atypical, such as irritability, shrill crying, feeding refusal, vomiting, diarrhea, coughing, convulsions, and bulging of the fontanelle, with less apparent meningeal signs. The recovery stage usually begins 2–5 days later.
Recovery Stage
Following treatment, body temperature gradually normalizes, skin petechiae and ecchymosis fade, and large ecchymotic areas with necrosis at the center develop ulcers or scabs that ultimately heal. Neurological examination returns to normal, and other symptoms improve. Recovery generally occurs within 1–3 weeks.
Fulminant Type
A small number of children experience an extremely rapid onset and progression, which poses significant danger to life if not promptly treated. Clinically, three subtypes are identified:
Shock Subtype
This subtype is characterized by septic shock and widespread hemorrhagic lesions on the skin and mucosa. Symptoms include sudden onset, followed within hours by hypotension, impaired consciousness, and potentially seizures. Extensive petechiae and ecchymosis rapidly coalesce, and patients may appear pale with poor peripheral circulation, weak and rapid pulse, and unmeasurable blood pressure. Meningeal irritation signs may be absent. In some cases, severe shock is observed with fewer petechial or ecchymotic lesions.
Meningoencephalitic Subtype
This subtype primarily involves damage to the meninges and brain parenchyma. Severe central nervous system symptoms can appear within 1–2 days, such as consciousness impairment, coma, recurrent convulsions, positive pyramidal tract signs, pupil abnormalities, and irregular respiration indicative of brain herniation.
Mixed Subtype
This is the most severe form, combining features of the previous two subtypes simultaneously or sequentially, with high mortality rates.
Mild Type
This type is more common during the later stages of an outbreak. Symptoms may include low-grade fever, sore throat, and mild headache resembling upper respiratory infections, with scattered fine petechiae on the skin and mucosa but no ecchymosis or meningeal irritation signs. Cerebrospinal fluid findings are generally normal.
Chronic Septicemia Type
This rare form primarily occurs in adults, with a course lasting several weeks to months. Manifestations include intermittent fever, petechiae or rash on the skin, and joint pain. General health remains relatively good, although some individuals may exhibit splenomegaly.
Complications
Complications include subdural effusion, hydrocephalus, and cranial nerve damage resulting in oculomotor nerve paralysis, deafness, or blindness. Long-term sequelae, such as psychiatric disorders, epilepsy, and limb paralysis, may also occur. Permanent skin and limb damage can result from ischemic necrosis.
Laboratory Findings
Complete Blood Count (CBC)
Peripheral white blood cell counts are significantly elevated, often exceeding 20 × 109/L, with neutrophils as the predominant subtype. However, some individuals may have normal or reduced white cell counts. Progressive thrombocytopenia may occur in cases complicated by DIC.
Cerebrospinal Fluid (CSF) Examination
Typical findings include elevated pressure, turbidity, a white cell count exceeding 1,000 × 106/L predominantly composed of neutrophils, significantly reduced glucose levels, and elevated protein levels. During the shock stage, CSF cell counts may remain normal or slightly elevated.
Coagulation Tests
Dynamic monitoring may reveal evidence of DIC during the shock stage, including prolonged prothrombin time, reduced fibrinogen levels, and elevated FDP (fibrin degradation products).
Pathogen Identification
Microscopic Examination
Samples of exudate from skin petechiae or ecchymosis, or centrifuged CSF deposits, can be stained using Gram stain and examined microscopically. Detection rates are often over 50%.
Bacterial Culture
Positive results may be obtained from throat swabs during the prodromal stage, blood cultures during the shock stage, or CSF cultures during the meningitic stage. Antimicrobial susceptibility testing can be performed. Specimen collection is recommended before initiating antimicrobial therapy, with careful attention to specimen temperature and prompt submission.
Immunological Testing
Tests such as latex agglutination can detect meningococcal-specific antigens in CSF, serum, or urine. ELISA-based detection of specific IgG in paired acute and recovery phase sera is useful for diagnosis, with a four-fold or greater rise in antibody titers indicating infection.
Nucleic Acid Testing
PCR can be used to detect meningococcal-specific DNA fragments in serum or CSF samples.
Diagnosis and Differential Diagnosis
A clinical diagnosis can be established based on the major clinical characteristics, such as the occurrence of illness in winter or spring or in endemic areas, sudden onset of high fever, headache, vomiting, petechiae and ecchymosis on the skin and mucosa, and meningeal irritation signs, along with typical changes observed in complete blood counts and cerebrospinal fluid (CSF). Laboratory findings, including positive smears from petechiae, ecchymosis, or CSF, as well as positive blood or CSF cultures, or immunological tests, further support pathogen identification.
This condition requires differentiation from the following diseases:
Other Purulent Meningitis
Non-epidemic in nature, typically lacks petechiae and ecchymosis, and rarely involves disseminated intravascular coagulation (DIC). Differentiation can be made using etiological tests on CSF or blood samples.
Tuberculous Meningitis
This features a gradual onset with symptoms of tuberculosis-related toxicity, such as low-grade fever, night sweats, and weight loss. The CSF often appears cloudy and may form a thin film upon standing. Cell counts are generally between (50–500) × 109/L, predominantly lymphocytes. Glucose and chloride levels are markedly reduced, while protein levels are significantly elevated. Acid-fast bacilli can be detected through CSF sedimentation and acid-fast staining of the thin film.
Viral Encephalitis
This typically presents with less pronounced toxemia-like symptoms and lacks petechiae and ecchymosis. The CSF is clear, with cell counts usually below 500 × 106/L. Glucose and chloride levels remain normal, while protein levels show only mild elevation. Bacterial culture results are negative.
Infectious Form of Bacterial Dysentery
This is associated with acute onset, which may include high fever, convulsions, coma, shock, or respiratory failure. CSF findings are normal. Stool analysis often reveals numerous pus cells and red blood cells, and Shigella species can be isolated through stool culture.
Other Conditions
Attention should also be given to differentiating this disease from sepsis caused by other pathogens, thrombocytopenic purpura, and allergic purpura.
Treatment
Treatment for the Common Type of Meningococcal Meningitis
General Management
Emphasis is placed on early diagnosis, inpatient isolation, maintaining skin cleanliness to prevent infection of petechiae and ecchymosis, ensuring adequate fluid and electrolyte balance, maintaining airway patency, and preventing complications.
Pathogen-Directed Therapy
The principle is to administer sufficient doses of antimicrobial agents that are effective and capable of crossing the blood-brain barrier at an early stage. Currently, meningococcal resistance to sulfonamides is significant, and the minimum inhibitory concentration for penicillin has risen.
- Penicillin G: High doses can achieve effective therapeutic concentrations in cerebrospinal fluid. The pediatric dose is 200,000–400,000 U per kilogram per day, divided into four intravenous infusions, over a course of 5–7 days.
- Cephalosporins: Third-generation cephalosporins have strong antibacterial activity and readily cross the blood-brain barrier. Cefotaxime at 200 mg per kilogram per day or ceftriaxone at 100 mg per kilogram per day can be administered intravenously for 5–7 days.
- Chloramphenicol: This drug easily penetrates the blood-brain barrier and displays good antibacterial activity against meningococci. The dosage is 30–50 mg per kilogram per day, divided into 3–4 intravenous infusions over 3–5 days, but not exceeding 7 days. Close monitoring of blood counts is required during treatment to detect bone marrow suppression as a side effect.
Treatment for Fulminant Meningococcal Meningitis
Shock Subtype
Early administration of effective antimicrobial agents with the use of third-generation cephalosporins as previously described is crucial.
Rapid Correction of Shock
Measures include:
- Expansion of blood volume and correction of acidosis: Physiological saline at 10–20 ml/kg is commonly given as a rapid intravenous bolus over 10–20 minutes during the first hour. If circulation does not improve significantly, this can be repeated 1–2 times, with a total volume not exceeding 40–60 ml/kg. Hemodynamic stability, tissue perfusion improvement, and oxygen balance restoration should be achieved within the first 6 hours of resuscitation. Blood glucose should remain within the normal range.
- Vasoactive drugs: Used after fluid volume expansion and correction of acidosis. Commonly used agents include anisodamine (654-2), which relieves microvascular spasms. The dose is 0.5–1 mg/kg, administered by intravenous injection every 10–15 minutes until the limbs become warm and blood pressure rises. Once improvement is observed, the dose is gradually reduced and the interval extended until discontinuation is achieved. Sudden discontinuation should be avoided. Dopamine or norepinephrine can also be considered.
Glucocorticoids
These may help correct septic shock, reduce toxemia, and lower intracranial pressure. Dexamethasone at 0.6 mg per kilogram per day may be administered in two doses for up to 3 days.
Treatment for DIC
Heparin is administered when progressive and coalescent petechiae or ecchymosis are observed, along with a significant reduction in platelets. The dosage is 0.5–1 mg/kg, mixed into 100 ml of 10% glucose solution and given by intravenous infusion every 4–6 hours. Most cases require just one or two doses for efficacy before discontinuation. Overuse of heparin can result in extensive fresh bleeding and significantly prolonged APTT, necessitating immediate discontinuation. Protamine sulfate should then be administered at a dose equivalent to the last heparin infusion for neutralization.
Once the hypercoagulable state is corrected, fresh plasma, fibrinogen, or prothrombin complex should be infused to replenish depleted coagulation factors.
Protection of Vital Organs
Respiratory failure may require mechanical ventilation. Extracorporeal membrane oxygenation (ECMO) may be needed for refractory heart failure. Hemofiltration or dialysis may be utilized for managing toxin clearance and hepatic or renal failure.
Meningoencephalitic Subtype
Measures include:
- Early use of effective antimicrobial agents as described for the shock subtype.
- Reduction of cerebral edema and prevention of cerebral herniation: Cerebral edema requires close monitoring and active dehydration therapy to prevent brain herniation. Mannitol at 20% is commonly used at a dose of 1 g/kg, with a second dose administered 30 minutes later for severe intracranial hypertension. The medication is administered every 4–6 hours as needed, depending on the clinical situation.
- Use of glucocorticoids: Follows the same protocol as for the shock subtype.
- Management of respiratory failure: Involves maintaining airway patency and, when necessary, endotracheal intubation with mechanical ventilation.
- Management of hyperthermia and convulsions: Includes timely use of physical or pharmacological cooling measures and early administration of sedatives. Sub-hibernation therapy may also be considered when necessary.
Mixed Subtype
This subtype involves a complex and critical condition, requiring simultaneous management of shock and cerebral edema. Treatment priorities depend on the specifics of the clinical presentation, with both aspects addressed.
Prevention
Control of Disease Transmission
Early identification of cases, with respiratory isolation until 3 days after symptoms have resolved or at least 7 days from the onset of illness, is crucial. Close contacts require medical observation for 7 days. Indoor environments should be well-ventilated. Crowded public places should be avoided, and masks are recommended during endemic seasons.
Vaccination
Vaccination is an effective method for preventing meningococcal meningitis. Available vaccines include the group A meningococcal vaccine and the AC conjugate meningococcal vaccine.
Chemoprophylaxis
Close contacts may receive preventive medication. Options include:
- Trimethoprim-sulfamethoxazole: 50–100 mg per kilogram per day.
- Rifampin: 10 mg per kilogram per day for 3 consecutive days.