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Dengue virus serotypes 1 to 4 (DENV1 to-4) and Zika virus (ZIKV) are closely related mosquito-borne flaviviruses with high global burdens. Risk of symptomatic DENV2 infection and severe disease was elevated by one prior ZIKV infection, one prior DENV infection, or one prior DENV infection followed by one ZIKV infection, compared with being flavivirus-naïve. By contrast, multiple prior DENV infections reduced dengue risk. Further, although high preexisting anti-DENV antibody titers protected against DENV1, DENV3, and ZIKV disease, intermediate titers induced by previous ZIKV or DENV infection enhanced future risk of DENV2 disease and severity, as well as DENV3 severity.
Dengue epidemics often overwhelm health care systems as medical staff respond to life threatening manifestations of severe dengue disease, including vascular leak syndrome and shock. ZIKV spread across the Pacific and Americas in 2013 to 2017 and caused rare but devastating clinical outcomes, including congenital microcephaly and Guillain-Barré syndrome in adults. These two viruses are closely related mosquito-borne flaviviruses with a significant burden to global public health. A study about prospective pediatric cohorts in Nicaragua that experienced sequential DENV1 to -3 (2004 to 2015), Zika (2016 to 2017), and DENV2 (2018 to 2020) epidemics aimed to find out whether immune interactions among dengue virus serotypes 1 to 4 (DENV1 to -4) extend to the closely related Zika virus (ZIKV)，with the following results.
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Fig 1. Dengue and Zika cases, DENV-Ab and ZIKV-Ab titers, and infection histories in the PDCS (2004 to 2020).
A prior DENV infection is an established risk factor for future symptomatic and severe dengue during infection with a different serotype. A first DENV or ZIKV infection induces antibodies that limit disease upon reinfection with the same virus but also generates nonprotective antibodies that bind other viruses. DENV cross-reactive antibodies can facilitate heterologous DENV infection of myeloid cells by means of antibody-dependent enhancement (ADE) and can increase dengue disease severity in humans. In addition, emerging evidence suggests that prior DENV infection may not enhance noncongenital Zika disease, and there is a certain precaution against Zika virus. In contrast, anti-ZIKV antibodies increased DENV2 infection, viral output, and migration of myeloid cells in skin explants to the same degree as anti-DENV3 antibodies.
A history of ZIKV infection was also a significant risk factor for severe dengue disease. The probability of experiencing dengue with warning signs or severe dengue (DwWS/SD) was significantly elevated for individuals with one ZIKV infection, or one prior DENV infection followed by one ZIKV infection compared with flavivirus-naïve children. The risk of dengue hemorrhagic fever or dengue shock syndrome was also unusually high and was significantly greater for children with one prior ZIKV infection and one DENV and one ZIKV infection compared with flavivirus-naïve children. These relationships held for individual manifestations of severe dengue disease. In contrast, multiple prior DENV infections did not enhance dengue disease severity.
Immunecorrelate analyses in natural infection and vaccine studies have shown that high preexisting neutralizing antibody titers protect against DENV1 and DENV3 but not necessarily DENV2. In the pre-Zika era, children with intermediate preexisting DENV-Ab titers also had increased probability of symptomatic or severe dengue disease caused by DENV2. In the post-Zika era, the magnitude of the enhancement effect is greater due to the higher incidence of dengue fever in 2019-2020. By contrast, high preexisting DENV-Abs had a protective effect against symptomatic DENV1 and DENV3 Infections.
| Target | Cat. No. | Product Name | Size | Application | Detection Sample | |
| ZIKV | DEIABL43 | Zika Virus IgM ELISA Kit | 96T | Quantitative, qualitative | seum, plasma | Inquiry |
| DEIAJX001 | Human Anti-ZIKV NS1(Zika Virus Non-structural Protein) IgG ELSIA Kit | 96T | Quantitative | Serum and other biological fluids | Inquiry |
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