What are the most likely triggers for Guillain-Barre syndrome, specifically among Campylobacter (C.) jejuni enteritis, cytomegalovirus, Epstein-Barr virus, Human Immunodeficiency Virus (HIV), and mycoplasma infection?

Most Likely Triggers for Guillain-Barré Syndrome

Campylobacter jejuni enteritis is the most common trigger for Guillain-Barré syndrome (GBS), followed by cytomegalovirus and Epstein-Barr virus infections. 1, 2

Primary Infectious Triggers for GBS

Strongly Associated Triggers

• Campylobacter jejuni

  • Responsible for approximately 30-32% of GBS cases worldwide 2, 3
  • Higher prevalence (60-70%) in Bangladesh, China, and Curaçao 4
  • Typically causes the axonal subtype of GBS (AMAN) 1
  • Associated with more severe disease course 2
  • Molecular mechanism: molecular mimicry between C. jejuni lipo-oligosaccharides and human nerve gangliosides 1

• Cytomegalovirus (CMV)

  • Accounts for approximately 13% of GBS cases 3
  • Usually triggers the demyelinating form of GBS (AIDP) 1
  • Associated with antibodies to ganglioside GM2 3
  • Typically presents with severe motor-sensory deficits 3

• Epstein-Barr virus (EBV)

  • Responsible for about 10% of GBS cases 3
  • Associated with the demyelinating form of GBS 1

• Mycoplasma pneumoniae

  • Accounts for approximately 5% of GBS cases 3
  • Pathophysiological mechanism similar to C. jejuni but less extensively investigated 1

Less Common Triggers

• HIV infection

  • More commonly reported in sub-Saharan Africa 1
  • Causal relationship established but less frequent

• Zika virus

  • Strong association demonstrated during outbreaks 1
  • Approximately 2 in 10,000 infected individuals develop GBS 1

• Other viral agents

  • Hepatitis viruses (A, B, C, E) 5
  • Influenza virus 3
  • Herpes simplex virus 3
  • Varicella zoster virus 3

• Other bacterial agents

  • Haemophilus influenzae 1, 3
  • Escherichia coli (rare cases) 6

Pathophysiological Mechanisms

1. Molecular Mimicry

   • Most established in C. jejuni infections
   • Cross-reactive antibodies target peripheral nerve components due to structural similarities between pathogen and nerve tissue 2
   • In AMAN: antibodies target gangliosides GM1, GM1b, GD1a, and GalNAc-GD1a on motor axolemma 5
   • In AIDP: exact target molecules not yet identified 5

2. Risk Factors for Developing GBS After Infection

   • Only 1 in 1,000-5,000 patients with C. jejuni infection develop GBS 1
   • Genetic factors: polymorphisms in TNF and MBL2 genes 1
   • Nutritional status may influence susceptibility 1
   • Specific bacterial strain characteristics (e.g., carbohydrate mimicry in C. jejuni) 1

Clinical Patterns Based on Triggering Agent

• C. jejuni-associated GBS

  • Predominantly axonal subtype (AMAN)
  • More severe pure motor form 3
  • Associated with anti-GM1 and anti-GD1b ganglioside antibodies 3

• CMV-associated GBS

  • Predominantly demyelinating subtype (AIDP)
  • Severe motor-sensory deficits 3
  • Associated with anti-GM2 ganglioside antibodies 3

Geographic Variations

• Axonal GBS (AMAN): More common in East Asia, associated with higher rates of C. jejuni infection 5
• Demyelinating GBS (AIDP): Predominant form in Europe and North America 5
• Regional variations in triggers: Higher rates of gastroenteritis-associated GBS in India and Bangladesh (36-47%) 4

Important Clinical Considerations

• Despite strong associations, the overall risk of developing GBS after infection remains very small 1
• The specific infectious trigger may help predict the clinical course and prognosis
• Recognition of these associations is crucial for early diagnosis and appropriate management
• Public health interventions targeting C. jejuni (particularly in poultry) can reduce GBS incidence, as demonstrated in New Zealand 4