Do escape mutants explain rapid increases in dengue case-fatality rates within epidemics?
M G Guzmán1, G Kourí, S B Halstead
1Institute of Tropical Medicine Pedro Kouri, Havana, Cuba. lupe@ipk.sld.cu
Lancet (London, England)
|June 24, 2000
Summary
During dengue epidemics, increased severe dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) cases were observed. This suggests prior dengue 1 virus immunity may enhance severe dengue 2 virus infections.
Area of Science:
- Virology
- Epidemiology
- Immunology
Background:
- Dengue virus outbreaks in Cuba in 1981 and 1997 showed increased proportions of severe dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) cases.
- Case-fatality rates for both dengue fever and DHF/DSS also increased during these epidemics.
Purpose of the Study:
- To explain the observed increases in severe dengue cases and mortality during Cuban epidemics.
- To investigate the role of cross-reactive antibodies from primary dengue 1 virus infections in exacerbating secondary dengue 2 virus infections.
Main Methods:
- The study proposes a hypothesis based on observed epidemiological data from Cuban dengue epidemics.
- It involves analyzing the immunological interactions between dengue virus serotypes and host antibody responses.
Main Results:
- Antibodies from primary dengue 1 virus infections may cross-react with dengue 2 viruses.
- These heterotypic antibodies can enhance, rather than neutralize, secondary dengue 2 virus infections in previously infected individuals.
- Dengue 2 virus strains replicating in dengue-1-immune hosts can escape neutralization, leading to severe disease upon subsequent infection.
Conclusions:
- Immunity to dengue 1 virus can paradoxically increase the risk of severe disease upon subsequent infection with dengue 2 virus.
- This phenomenon, known as original antigenic sin or antibody-dependent enhancement, contributes to the severity of dengue epidemics.
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