Meningococcal Infections¶

Chapter 160 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 160

Key Clinical Points¶

Asymptomatic nasopharyngeal colonization is common in adolescents and adults.
Invasive disease presents as meningitis or septicemia; mortality from septicemia can be reduced to <10% with early management.
Capsular groups A, B, C, W, X, and Y account for the majority of invasive cases.
Complement deficiency (C5–9, properdin, factor D) increases infection risk by up to 600-fold.
Empirical treatment requires third-generation cephalosporins (ceftriaxone 75–100 mg/kg/day or cefotaxime 200 mg/kg/day).
Purpura fulminans indicates severe disease with peripheral ischemia and coagulopathy.
Chronic meningococcemia presents with recurrent petechial rash, fever, and arthritis.
Postmeningococcal reactive disease is an immune-complex mediated condition occurring 4–10 days post-infection.
Conjugate vaccines (e.g., MenACWY) are necessary to induce T-cell help and memory B-cell production.
Petechial rash is a hallmark of septicemia but is absent in approximately 20% of cases.

1. DEFINITION & OVERVIEW¶

• Pathogen: Neisseria meningitidis is a gram-negative diplococcus that colonizes humans exclusively. • Colonization: Asymptomatic colonization in the nasopharynx of healthy adolescents and adults. • Invasive Disease: Occurs rarely; presents as bacterial meningitis or septicemia. Other manifestations include occult bacteremia, pneumonia, septic arthritis, conjunctivitis, and chronic meningococcemia. • Related Species: N. gonorrhoeae (pathogen); N. lactamica and N. flavescens (commensals). • Biochemistry: Catalase- and oxidase-positive; utilizes glucose and maltose for acid production.

2. EPIDEMIOLOGY¶

• Global Incidence: ~500,000 cases/year; declining trends due to immunization programs. • Mortality Rate: ~10% overall. • Disease Patterns: Includes epidemics (sub-Saharan Africa), outbreaks (closed communities), hyperendemicity, and sporadic cases. • Serogroup Distribution: ◦ Group A: Dominates the African meningitis belt. ◦ Groups C/W/X: Common in Europe and North America. ◦ ST11 clone: A capsular group C/W strain driving recent outbreaks. • US Trends: Incidence fell from 1.2/100k (1997) to 0.06/100k (2021). • Peak Age Groups: Infants (<1 year) and adolescents (15–25 years).

2.1 Age Distribution & Risk Factors¶

• Carriage Rates: ~25% in adolescents/young adults; <10% in adults. • Risk Factors for Carriage/Disease: Overcrowding, smoking, and viral infections. • Complement Deficiency: ◦ Components: C5–9, properdin, factor D. ◦ Risk Increase: 600-fold increased risk of infection. ◦ Prevalence: Found in 0.3% of all cases but 7–20% of W/X/Y/Z/E infections. • Genetic Factors: MBL deficiency, TLR4 polymorphisms, and FcγR variants.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

• Capsule: Essential for survival; determines serogroup (A–W). ◦ Function: Resists phagocytosis and aids transmission. • Outer Membrane: Contains Lipopolysaccharide (LPS/endotoxin) and proteins such as PorA, Opa, and FetA. • Iron Acquisition: Critical via transferrin-binding proteins. • Inflammatory Cascade: Endotoxin binds CD14/TLR4 → release of TNF-α, IL-6, and PAI-1. • Systemic Effects: ◦ Endothelial injury → capillary leak syndrome, thrombosis (purpura fulminans), and shock. ◦ Organ dysfunction: Resulting from hypovolemia, myocardial depression, and coagulopathy.

3.1 Capsular Groups¶

• Major Serogroups: A, B, C, W, X, Y (most invasive cases). ◦ Group D: Variant of group C. ◦ Capsule-null strains: Lack capsule genes; rarely invasive. ◦ Hyperinvasive clones: May span multiple serogroups.

3.2 Pathogenesis¶

• Colonization: Adhesins (Opa, pili) bind epithelial mucosa. • Immune Evasion: IgA1 protease reduces mucosal IgA interference. • Invasion Timing: Rare; usually occurs within days of acquiring an invasive strain. ◦ Note: Prolonged colonization precedes invasion in <5% of cases.

4. CLINICAL FEATURES¶

• General Prevalence: 30–50% present with meningitis alone; 40% have septicemia features. • Meningitis Presentation: ◦ Infants: Fever, vomiting, irritability. ◦ Older Children/Adults: Fever, headache. ◦ Note: Neck stiffness and photophobia are often absent in infants. Bulging fontanelle may be present. • Septicemia Features: ◦ Rash: Nonblanching petechial/purpuric rash (>80% cases) develops hours after onset. ◦ Severity: Purpura fulminans indicates severe disease with peripheral ischemia. • Chronic Meningococcemia: Recurrent petechial rash, fever, joint pain, splenomegaly. ◦ Mechanism: Bacteremia clears spontaneously then recurs. • Postmeningococcal Reactive Disease: Immune complex disease 4–10 days post-infection. ◦ Symptoms: Maculopapular rash (2%), arthritis (8%), iritis (1%), pericarditis, polyserositis.

4.1 Septicemia Severity¶

• Progression: Fulminant cases may die within hours of symptoms. • Mortality: 25–40% in children → reduced to <10% with early management. • Skin Lesions: Show endothelial necrosis and neutrophil infiltration.

5. DIFFERENTIAL DIAGNOSIS¶

• Meningococcal Septicemia: ◦ Viral infections (similar rash). ◦ Other bacterial sepsis. • Chronic Meningococcemia: ◦ Endocarditis. ◦ Henoch-Schönlein purpura (HSP). ◦ Disseminated gonococcal infection. ◦ Immune-mediated vasculitis. • Postmeningococcal Reactive Disease: ◦ Autoimmune arthritis. ◦ Infectious mononucleosis.

6. INVESTIGATIONS & DIAGNOSIS¶

CSF Analysis: Evaluate for pleocytosis, low glucose, and elevated protein.
Microbiology:
Blood cultures to identify N. meningitidis.
PCR for N. meningitidis.
Serology: Determine capsular groups.
Imaging (CT/MRI): Perform if complications are suspected (e.g., cerebral edema).
Molecular Typing: Antigen gene sequencing to identify specific strains.

7. MANAGEMENT & TREATMENT¶

Empirical Antibiotic Therapy:
Ceftriaxone: 75–100 mg/kg/day IV (every 24 hours).
Cefotaxime: 200 mg/kg/day IV.
Adjunctive Therapy:
Dexamethasone: 0.15 mg/kg IV every 6 hours (for meningitis).
Supportive Care:
Fluid Resuscitation: Normal saline 10–20 mL/kg/hr initially.
Vasopressors: Norepinephrine (0.1–2 μg/kg/min).
Anticoagulation: Heparin infusion (target aPTT 1.5–2× control) for purpura fulminans.
Vaccination:
MenACWY (routine).
MenB (infants in UK since 2015).
Prophylaxis for Hajj pilgrims; mass vaccination during outbreaks.

7.1 Antibiotic Therapy¶

7.2 Supportive Care¶

• Fluid Resuscitation: Normal saline 10–20 mL/kg/hr initially. ◦ Vasopressors: Norepinephrine (0.1–2 μg/kg/min). ◦ Anticoagulation: Heparin infusion (target aPTT 1.5–2× control) for purpura fulminans.

7.3 Adjunctive Therapy¶

8. PROGNOSIS & COMPLICATIONS¶

• Mortality: ◦ Septicemia: 25–40% → <10% with early management. • Complications: - Hearing loss, seizures, cerebral palsy. - Purpura fulminans, limb infarction. - Acute kidney injury (AKI). • Long-term Sequelae: ~10–20% of survivors have neurological deficits.

9. SPECIAL CONSIDERATIONS¶

• Complement Deficiency Screening: Recommended in cases of recurrent infections with non-B serogroups. • Travel Medicine: Prophylaxis for Hajj pilgrims. • Outbreak Management: Mass vaccination with MenACWY.

10. KEY PEARLS & CLINICAL TRAPS¶

• Petechial Rash Prevalence: A hallmark of septicemia but absent in 20% of cases. • Dexamethasone Timing: Early administration reduces mortality in meningitis. • Strain Dynamics: ST11 clone drives recent outbreaks. • Clinical Trap: Viral infections mimic meningococcal rash; avoid unnecessary antibiotic use for postmeningoccal reactive disease (which resolves spontaneously).

Reference Tables¶

TABLE 160-1 Structure of the Polysaccharide Capsule of Common Disease-Causing Meningococci¶

Harrison's 22e, p.1244

MENINGOCOCCAL CAPSULAR GROUP	CHEMICAL STRUCTURE OF OLIGOSACCHARIDE	CURRENT DISEASE EPIDEMIOLOGY
A	2-Acetamido-2-deoxy- D-mannopyranosyl phosphate	Epidemic disease mainly in sub-Saharan Africa; sporadic cases worldwide
	α-2,8-N- acetylneuraminic acid
C	α-2,9-O-acetylneuraminic acid	Small outbreaks and sporadic disease
	4-O-α-D-glucopyranosyl- N-acetylneuraminic acid
W	4-O-α-D- galactopyranosyl-N- acetylneuraminic acid	Sporadic disease; outbreaks of disease associated with mass gatherings; epidemics in sub- Saharan Africa
	(α1→4) N-acetyl- D-glucosamine-1- phosphate
160	Meningococcal Infections Manish Sadarangani, Andrew J. Pollard

TABLE 160-2 Common Causes of Petechial or Purpuric Rashes Enteroviruses Influenza and other respiratory viruses Measles…¶

Harrison's 22e, p.1248

Enteroviruses
Influenza and other respiratory viruses
Measles virus
Epstein-Barr virus
Cytomegalovirus
Parvovirus
Deficiency of protein C or S (including post-varicella protein S deficiency)
Platelet disorders (e.g., idiopathic thrombocytopenic purpura, drug effects, bone
marrow infiltration)
Henoch-Schönlein purpura, connective tissue disorders, trauma (including
nonaccidental injuries in children)
Pneumococcal, streptococcal, staphylococcal, or gram-negative bacterial
sepsis