Meningococcal Infections¶
Chapter 160 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Meningococcal infections are caused by Neisseria meningitidis, primarily manifesting as asymptomatic nasopharyngeal colonization or invasive disease (meningitis, septicemia).
- Capsular groups A, B, C, W, X, Y, and W135 are critical for classification; the capsule is a key virulence factor resisting phagocytosis.
- Epidemics are common in sub-Saharan Africa (group A/C/W), with sporadic cases globally. Vaccination has significantly reduced disease burden.
- Clinical features include fever, rash (petechiae/purpura), meningitis signs, and septicemia. Early diagnosis is critical for mortality reduction.
- Management involves antibiotics (ceftriaxone, cefotaxime), supportive care, and vaccines (MenACWY, MenB) for prevention.
1. DEFINITION & OVERVIEW¶
Infection with Neisseria meningitidis typically presents as asymptomatic nasopharyngeal colonization. Invasive disease includes bacterial meningitis, septicemia, and other systemic manifestations.
Table 160-1: Structure of the Polysaccharide Capsule of Common Disease-Causing Meningococci¶
| CAPSULAR GROUP | CHEMICAL STRUCTURE | CURRENT DISEASE EPIDEMIOLOGY |
|---|---|---|
| A | 2-Acetamido-2-deoxy-D-mannopyran osyl phosphate | Epidemic disease mainly in sub-Saharan Africa; sporadic cases worldwide |
| B | a-2,8-N-acetylneuraminic acid | Sporadic disease and large outbreaks in the meningitis belt of Africa |
| C | a-2,9-O-acetylneuraminic acid | Small outbreaks and sporadic disease |
| W | 4-O-a-D-galactopyranosyl-N-acetyln euraminic acid | Sporadic disease; outbreaks associated with mass gatherings; epidemics in sub-Saharan Africa |
| X | (a1fi4) N-acetyl-D-glucosamine-1-p hosphate | Sporadic disease and large outbreaks in the meningitis belt of Africa |
1.1 Pathogenesis¶
N. meningitidis colonizes the nasopharynx, with capsule-mediated resistance to phagocytosis. Capsular groups (A, B, C, W, X, Y) determine virulence and disease severity. Capsule synthesis is regulated by phase variation and genetic factors.
1.2 Antigenic Variation¶
Outer-membrane proteins (PorA, PorB, FetA) and lipopolysaccharide (LPS) drive serotype diversity. Molecular typing (MLST, WGS) aids in tracking outbreaks and understanding transmission.
2. EPIDEMIOLOGY¶
Global incidence varies by region, with epidemics in sub-Saharan Africa (group A/C/W) and sporadic cases elsewhere. Risk factors include age (infants, adolescents), immunocompromise, and close contact.
Table 160-2: Common Causes of Petechial or Purpuric Rashes¶
| CAUSE |
|---|
| Enteroviruses |
| Influenza and other respiratory viruses |
| Measles virus |
| Epstein-Barr virus |
| Cytomegalovirus |
| Parvovirus |
| Deficiency of protein C or S |
| Platelet disorders |
| Henoch-Schönlein purpura |
| Pneumococcal, streptococcal, staphylococcal, or gram-negative bacterial sepsis |
2.1 Global Trends¶
Annual cases estimated at 500,000 globally, declining due to vaccination. Sub-Saharan Africa accounts for 80% of cases, with group A/C/W epidemics. Vaccination campaigns reduced group C disease in the UK and Africa.
2.2 Age Distribution¶
Peak incidence in infants (<1 year) and adolescents (15–25 years). Mortality rates up to 10% in untreated cases, with higher risk in young children and immunocompromised individuals.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
N. meningitidis is a gram-negative diplococcus with capsular polysaccharides determining serogroup. Capsule resistance to phagocytosis and LPS endotoxin drive systemic inflammation.
3.1 Capsular Structure¶
Capsule composition (e.g., polysaccharide A, B, C) influences virulence and immune evasion. Capsule-null strains are rarely invasive.
3.2 Molecular Mechanisms¶
Iron-regulated proteins (FetA, RmpM) and adhesins (Opa, PorA) enhance colonization. Complement deficiency (C5–9, factor D) increases susceptibility to invasive disease.
4. CLINICAL FEATURES¶
Presentations include meningitis (neck stiffness, fever), septicemia (purpuric rash, shock), and focal infections (arthritis, endocarditis). Early symptoms mimic viral illness.
4.1 Rash and Shock¶
Non-blanching purpuric rash (80% of cases) and hypovolemic shock are hallmark features. Purpura fulminans occurs in severe septicemia with ischemic skin necrosis.
4.2 Neurological Manifestations¶
Meningitis presents with headache, photophobia, altered consciousness. Infants may lack classic signs, presenting with irritability and bulging fontanelle.
5. DIFFERENTIAL DIAGNOSIS¶
Petechial/purpuric rashes may arise from viral infections, immune disorders, or other bacterial sepsis. Key differentials include viral exanthems, Henoch-Schönlein purpura, and disseminated intravascular coagulation.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis involves blood cultures, CSF analysis (elevated protein, low glucose), PCR, and antigen testing. Lumbar puncture is contraindicated in septicemia due to risk of herniation.
6.1 Laboratory Tests¶
Blood cultures (75% positivity), PCR (40% higher yield than cultures), and CSF analysis (elevated WBC, low glucose).
6.2 Imaging¶
CT scan before lumbar puncture in suspected raised ICP. MRI may detect cerebral edema or infarction in septicemia.
7. MANAGEMENT & TREATMENT¶
Immediate antibiotic therapy (ceftriaxone, cefotaxime, vancomycin) for suspected cases. Supportive care includes fluid resuscitation, vasopressors, and management of shock and coagulopathy.
7.1 Antibiotic Therapy¶
Third-generation cephalosporins (ceftriaxone 75–100 mg/kg/day) for meningitis/septicemia. Vancomycin added for suspected penicillin resistance. Duration: 7 days for meningitis, 3–5 days for septicemia.
7.2 Supportive Care¶
Aggressive fluid resuscitation, oxygen therapy, and monitoring for capillary leak syndrome. Activated protein C may reduce mortality in severe septicemia.
8. PROGNOSIS & COMPLICATIONS¶
Mortality up to 10% in untreated cases; 10% of survivors develop long-term complications (hearing loss, neurologic deficits). Amputations may be required for severe skin necrosis.
8.1 Long-Term Outcomes¶
Psychosocial sequelae (ADHD, learning disabilities) in survivors. Hearing loss (5%) and neurologic complications (7%) are common. Chronic meningococcemia may recur without treatment.
8.2 Complications¶
Renal failure, coagulopathy, and multiorgan failure in septicemia. Purpura fulminans leads to ischemic skin loss and amputation.
9. SPECIAL CONSIDERATIONS¶
Vaccination is critical for prevention. High-risk groups include adolescents, immunocompromised individuals, and travelers to endemic regions. Pregnancy and pediatric populations require tailored approaches.
9.1 Vaccination¶
MenACWY (conjugate) for adolescents (11–12 years), MenB vaccines (4CMenB, MenB-fHBP) for high-risk groups. WHO targets eradication by 2030 through global immunization.
9.2 Contact Management¶
Close contacts (household/kissing) receive prophylaxis (e.g., rifampin, ciprofloxacin). Secondary cases occur in 3% of sporadic cases, with highest risk within 1 year of index case.
10. KEY POINTS & CLINICAL PEARLS¶
- Capsular groups A, B, C, W, X, Y drive disease severity and vaccine targets. 2. Early recognition of rash, fever, and shock is critical for survival. 3. Vaccination (MenACWY, MenB) is the cornerstone of prevention. 4. Conjugate vaccines provide longer immunity than polysaccharides. 5. Prophylaxis for close contacts reduces secondary transmission.