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V. Disease Pathogenesis

V. Disease Pathogenesis. Risk Factors Reported for DHF. Virus strain Pre-existing anti-dengue antibody previous infection maternal antibodies in infants Host genetics Age. Risk Factors for DHF (continued). Higher risk in secondary infections

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V. Disease Pathogenesis

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  1. V. Disease Pathogenesis

  2. Risk Factors Reported for DHF • Virus strain • Pre-existing anti-dengue antibody • previous infection • maternal antibodies in infants • Host genetics • Age

  3. Risk Factors for DHF (continued) • Higher risk in secondary infections • Higher risk in locations with two or more serotypes circulating simultaneously at high levels (hyperendemic transmission)

  4. Increased Probability of DHF Hyperendemicity Increased circulation of viruses Increased probability of secondary infection Increased probability of occurrence of virulent strains Increased probability of immune enhancement Increased probability of DHF Gubler & Trent, 1994

  5. Hypothesis on Pathogenesisof DHF (Part 1) • Persons who have experienced a dengue infection develop serum antibodies that can neutralize the dengue virus of that same (homologous) serotype

  6. 1 1 1 1 1 Homologous Antibodies Form Non-infectious Complexes Dengue 1 virus Neutralizing antibody to Dengue 1 virus Non-neutralizing antibody Complex formed by neutralizing antibody and virus

  7. Hypothesis on Pathogenesisof DHF (Part 2) • In a subsequent infection, the pre-existing heterologous antibodies form complexes with the new infecting virus serotype, but do not neutralize the new virus

  8. 2 2 2 2 2 2 Heterologous Antibodies Form Infectious Complexes Dengue 2 virus Non-neutralizing antibody to Dengue 1 virus Complex formed by non-neutralizing antibody and virus

  9. Hypothesis on Pathogenesisof DHF (Part 3) • Antibody-dependent enhancement is the process in which certain strains of dengue virus, complexed with non-neutralizing antibodies, can enter a greater proportion of cells of the mononuclear lineage, thus increasing virus production

  10. 2 2 2 2 2 2 2 2 2 2 2 2 Heterologous Complexes Enter More Monocytes, Where Virus Replicates Dengue 2 virus Non-neutralizing antibody Complex formed by non-neutralizing antibody and Dengue 2 virus

  11. Hypothesis on Pathogenesisof DHF (Part 4) • Infected monocytes release vasoactive mediators, resulting in increased vascular permeability and hemorrhagic manifestations that characterize DHF and DSS

  12. Viral Risk Factorsfor DHF Pathogenesis • Virus strain (genotype) • Epidemic potential: viremia level, infectivity • Virus serotype • DHF risk is greatest for DEN-2, followed by DEN-3, DEN-4 and DEN-1

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