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Volume 23, Number 4—April 2017

Biologic Evidence Required for Zika Disease Enhancement by Dengue Antibodies

Scott B. HalsteadComments to Author 
Author affiliation: Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

Main Article


Case–control epidemiologic research protocol for assessing DENV antibody enhancement of Zika virus syndromes*

Zika virus PCR positive or serologically positive symptomatic persons (i.e., with febrile illness, Guillain-Barré syndrome or congenital Zika syndrome) of any age who have convalescent-phase serum samples available to test for DENV IgG by ELISA.
Serum samples from age-, sex-, residence-, and ethnicity-matched controls with blood drawn at about the same time as each index case-patient. Ratio: 4 controls to 1 index case-patient.
Laboratory studies
1. Convalescent-phase serum samples from case-patients are tested by indirect pan-DENV IgG ELISA. (A positive result indicates that the Zika virus infection occurred in a DENV-immune person.)
2. Control serum samples are tested for Zika virus neutralizing antibodies.
3. Control serum samples are tested for past DENV infections by using indirect pan-DENV IgG ELISA.
4. DENV IgG ELISA–positive serum samples from case-patients and controls are tested for DENV serotypes 1–4 neutralizing antibodies.
5. Frequency of prior DENV infections in symptomatic Zika virus case-patients is compared with frequency of DENV antibodies in Zika virus–immune controls. A statistically significant increase in past DENV infection indicates enhancement; a statistically significant reduction indicates protection.
6. All comparisons should be made separately and combined for persons of white and black† race.

*DENV, dengue virus.
†The powerful DENV disease resistance gene(s) in black sub-Saharan Africans might also protect against Zika virus diseases.

Main Article

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Page created: March 17, 2017
Page updated: March 17, 2017
Page reviewed: March 17, 2017
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