Meningococcal Infection: Etiology and Epidemiology

• Meningococcal infection is an anthroponotic disease transmitted by airborne droplets.
• It manifests as bacteriocarrier state, nasopharyngitis, meningococcemia, or purulent meningitis.
• Less frequently, it can damage other organs and systems.

Etiology

• The causative agents are meningococci (Neisseria meningitidis), which are gram-negative bacteria.
• They are diplococci belonging to the Neisseriaceae family in the Neisseria genus, and are strict aerobes.
• Meningococcal polysaccharide capsules are subdivided into serogroups: A, B, C, X, Y, Z, W-135, 29-E, K, H, L, and I.
• Six serogroups are pathogenic for humans: A, B, C, W, Y, and X.

Epidemiology

• Source of the disease includes meningococcal carriers and patients with nasopharyngitis.
• Routes of transmission include airborne, contact, and household.
• The entrance gate is the mucous membrane of the upper respiratory tract.
• Incubation period lasts 2–10 days, typically 2–3 days.
• Morbidity structure: Meningococcal carriage - 40-43% generally and 70-100% during epidemics, Meningococcal nasopharyngitis - 3-5%, Meningococcemia - 36-43%, Meningitis - 10-25%, Mixed form - 47-55%.
• Meningococcal infection shows seasonality, peaking in winter-spring, coinciding with rises in ARVI and influenza with 28–30 year intervals between epidemic rises.

Immunity

• Specific agglutinins, precipitins, bactericidal antibodies, and opsonins form after clinically pronounced infections or after long-term carrier status.
• Hemagglutinin titers increase and peak with generalized forms by the 5th day.
• Antibody titers decrease after the 4th week, and their duration of preservation is not known.

Pathogenesis

• Meningococcus enters the nasopharyngeal mucosa (nasopharyngeal stage) and reproduces.
• In 10-15% of cases with decreased resistance, secretory IgA deficiency leads to inflammation of the nasopharyngeal mucosa, causing meningococcal nasopharyngitis.
• Meningococcus can cross the blood-brain barrier, damaging the meninges and brain matter, causing purulent meningitis or meningoencephalitis.
• The main role in severe forms plays a systemic inflammatory response (SIRR), developing due to bacteremia and toxinemia.

Classification of MI

• Localized forms: meningococcal carriage, acute nasopharyngitis.
• Generalized forms: meningococcemia (typical, fulminant, chronic), meningitis, meningoencephalitis, mixed (meningitis and meningococcemia).
• Rare forms: meningococcal endocarditis, meningococcal arthritis (synovitis), polyarthritis, meningococcal pneumonia, meningococcal iridocyclitis.

Syndromes:

• Intoxication
• Nasopharyngitis syndrome
• Meningeal syndrome
• Exanthema syndrome
• Joint Syndrome

Intoxication

• The disease starts with a sudden increase in body temperature to 39-40°C and above, accompanied by chills, lethargy, headache, decreased appetite, and vomiting.
• Children over 3 years often complain of limb and abdomen pain.
• It is characterized by a 2 hump character of fever.
• It has a short-term effect from the initiation of antibiotic therapy followed by its repeated rise, and a short-term temperature decrease by 1-2 after introduction of "lytic" mixtures.

Nasopharyngitis Syndrome

• Manifested by nasal congestion, sore throat, flushing, and swelling of the posterior pharyngeal wall with lymphoid formation hypertrophy.
• Includes swelling of lateral ridges and small amount of mucus.
• Hyperemia has a bluish tint.

Meningeal Syndrome

• Manifested by a combination of cerebral symptoms of consciousness and behavior violation and actual meningeal symptoms (irritation of meningeal membranes due to CSF overproduction).
• General cerebral symptoms include intense bursting headache, hyperesthesia, repeated vomiting, and impaired behavior and consciousness.
• Infants experience sharp anxiety, unmotivated “brain” cry, tremor of hands and chin, profuse regurgitation, hyperesthesia, and head tilting backwards.

Meningeal Syndrome Symptoms

• Bulging of the fontanelle, discrepancy of sagittal and coronary sutures, and increased head circumference with expansion of the venous network.
• Retraction of the fontanelle is a sign of intracranial hypotension.
• Older children complain of severe bursting headache, recurrent "fountain" vomiting not related to food, particularly in the morning or at night.
• General hyperesthesia (cutaneous, muscular, optical, acoustic).
• Consciousness disorders show changes in arousal, stunning, stupor, and coma.
• Includes stiff neck muscles, Meningeal posture (“gun trigger” or “pointing dog” posture), Kernig's Sign, Brudzinsky's Sign, and Lower Brudzinsky's Sign.

Exanthema Syndrome

• Hemorrhagic rash of sizes and shapes, from small-point petechiae to extensive hemorrhages, appear on the skin hours after onset.
• Hemorrhagic rash has irregularly shaped elements, is dense to the touch, and protrudes.
• The number of rash elements varies.
• The rash is often localized to the buttocks, back thighs, shins, eyelids and sclera, and less often on the face.

Pathogenesis of rash (stellate, hemorrhagic)

• Changes in hemocoagulation develop.
• Generalized intravascular coagulation of blood occurs.
• Bacterial blood clots form in small arterioles.
• Leads to development of consumption coagulopathy.
• Hemorrhages are present in the skin.

Meningococcemia

• Meningococcemia presents acutely with a temperature increase to high values.
• Chills, repeated vomiting, and severe headache are present.
• Severe cases feature a piercing scream, loss of consciousness, and convulsions.
• Symptoms worsen within 1-2 days.
• A hemorrhagic rash, hemorrhages in the sclera, conjunctiva, and mucous membranes most abundant on the legs and buttocks show up at the end of the first or start of the second day.
• Joint damage in the form of synovitis or arthritis is possible.
• Uveitis and iridocyclochorioiditis develop in the vascular membrane of the eyes.
• Uveitis causes the vascular membrane color to change to brown (rusty).

Meningococcemia General Details

• General blood test reveals high leukocytosis, neutrophil shift, aneosinophilia, and increased ESR.
• There are mild, moderate and severe forms.
• Disease proceeds in waves that include periods of both improvement and deterioration.
• Clinically presents as acute swelling of the brain manifested by a sharp headache, convulsions, loss of consciousness, psychomotor agitation, and repeated vomiting.
• Infringement of the medulla oblongata due to wedging of the brain into the large occipital foramen may cause oliguria up to anuria and decompensated metabolic acidosis.
• The clinical form can pathogenetically be seen as infectious-toxic shock caused by massive bacteremia with microorganism and toxinemia decomposition.

Joint Syndrome

• Postmeningococcal arthritis is infectious and allergic, found in 15-22% of children with HMI on days 6-10.
• Affects both small and large joints.
• Symptoms: joint pain, movement limitation, possible skin hyperemia, fluctuation, and increased joint volume.
• Joint swelling and hyperemia disappear after 2-4 days, and soreness goes away after 3-6 days of treatment.
• The function of the joint is fully restored.

Meningococcal Diagnostics

• General blood analysis, blood chemistry, cerebrospinal fluid examination, PCR, serodiagnostics, magnetic resonance imaging, CT scan, electroencephalography, and electromyography.

Meningococcal Diagnostics Tests

• Rash elements that don't fade under pressure and are visible through glass indicate meningococcal rash.
• Rash elements that change color and fade indicate that the rash is not meningococcal.
• Spinal punctures collect transparent or slightly opalescent fluids and cause pleocytosis with 50 to 200 lymphocyte cells.
• Bacteriological examinations of cerebrospinal fluids and blood smears are preformed.
• RRGA and IFA (serological) examinations are also preformed.

Differential Diagnosis

• Influenza with hemorrhagic syndrome, measles, rubella, other meningitis with changes in CSF.

Treatment

• Use antibiotics, such as those of the beta-lactam group like benzylpenicillin and cephalosporins.
• Localized forms can be treated with rifampicin and azithromycin.
• It is recommended to carry out etiotropic therapy of general forms via parenteral drug administration only.
• Use maximum doses of antibiotics with consideration for their permeability through the blood-brain barrier.
• Antibacterial drugs should generally be applied at the prehospital stage in cases with strong suspicion of meningococcal infection and hemorrhagic rash, while ensuring vascular access.
• Recommended: infusion therapy with isotonic glucose-salt and colloidal solutions to maintain/replenish blood volume, acid-base balance, and correct metabolic disorders.
• With cerebral edema: osmotic diuretics.
• Include antioxidant, antihypoxic, metabolic, neuroprotective, and nootropic preparations of pathogenetic therapy for children with generalized MI.
• Symptomatic treatment consists of anticonvulsants and antipyretics.
• Surgical treatment is recommended for patients with massive skin and soft tissue lesions.

Prevention

• Rifampicin is often used after contacting a patient with an invasive meningococcal infection.
• Rifampicin is also recommended for nasopharyngeal eradication of Neisseria meningitidis in carriers.
• After hospitalization of a patient with HMI, quarantine the outbreak for 10 days.
• Examine those who were in close contact with the sick for acute nasopharyngitis.
• Prescribe a bacteriological exam to the identified patients with acute nasopharyngitis before the appointment of appropriate treatment.

Specific prevention is done by preventive vaccination

• Indications include children from 1 to 8 years old.
• Also includes first-year students of secondary and higher institutions in teams from different regions.