Volume 23, Number 4—April 2017
Perspective
Biologic Evidence Required for Zika Disease Enhancement by Dengue Antibodies
Scott B. Halstead
Table
Case–control epidemiologic research protocol for assessing DENV antibody enhancement of Zika virus syndromes*
| Category |
Description |
|---|---|
| Case-patients |
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. |
| Controls |
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.
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