By Brian R. Moyer
The word “Zika” has been escalating in the press, in the medical community, and in government public health circles. The nonscientist sees this as an infection like Ebola and senses a dire outcome. In truth, the eruption of the Zika virus as a “threat” is a new epidemiologic observation. Typically, only one in five Zika-infected individuals may actually feel “ill” with malaise, fever, and other manifestations, according to the Centers for Disease Control. The reason we see such a wave of anxiety is the only recently “proven” relationship of the viral infection to fetal abnormalities such as microcephaly. In Brazil, the epicenter of the crisis, microcephaly was appearing at a rate of about 125 cases per year, and there have now been 4,700 cases in the past year. In children with microcephaly, the affected brain is not just small; it’s small with malformations of the cerebral cortex and with calcifications. The rise in the malady was coincident with the Zika infection rate, and the relationship is now confirmed.
Zika is a flavivirus. Several other human-pathogenic flaviviruses include yellow fever, dengue, Japanese encephalitis, West Nile, and tick-borne encephalitis viruses, and they all have a significant public health impact in different parts of the world. Zika is now a Western hemisphere threat. Dengue fever has been the most serious threat, and a vaccine for this flavivirus has been hampered by the theoretical risk of vaccine-related adverse events such as immune enhancement of infection and the requirement to induce a long-lasting protective immune response against all four dengue serotypes simultaneously. A Zika vaccine may have the same issues. Dengue vaccines are in development with only one success currently moving forward to phase 3 clinical trials (a chimeric dengue-yellow fever live-attenuated vaccine). It is not clear whether Zika requires such chimeric engineering.
Will a vaccine for the mother protect the unborn? And what about sexual transmission of Zika now shown in a Dallas, Texas, case and others. This portends serious problems where a woman can be infected even when not in an endemic area, have an infection that does not manifest overt symptoms, becomes pregnant, and not even know that the child is at risk for fetal abnormalities. The timing of infection in pregnancy is also important. In the thalidomide era, the drug was used in the first trimester for nausea and morning sickness, and the consequence of phocomelia (absent/malformed limbs) was apparently related to fetal drug exposure around the 17th week of gestation. Exposure before or after this time window minimized the effect. Not so for Zika, but the spectrum of issues changes. While exposure in utero in early pregnancy can lead to microcephaly, exposure later in pregnancy or in the continuum of gestation can seriously alter the brain connectivity, and there is a relationship to Guillain-Barre syndrome and potentially to other neurologic problems.
This is a serious state of affairs for world public health. How can we manage blood supplies? Is there a diagnostic to identify infected donated blood? How will we develop an effective vaccine? Can it be done quickly with the northern hemisphere summer months coming now? And what about the Rio Olympics? What will be done for the potentially thousands of microcephalic children who manage to survive and the other, yet to be identified, neurologic deficits from in utero or even possibly postpartum infections that can alter neural architecture?
I personally am looking forward to the 2016 AAPS National Biotechnology Conference in Boston, where there will be the symposium The Zika Virus: The Threat, Vaccine Challenges, and World Response, which may shed some light on these questions. I hope you can join us there!