Zika Virus Update

by Guy McKhann, M.D.

March 24, 2016

This is a column from Dana's print publication, Brain in the News.

One cannot pick up a newspaper without seeing a comment on the Zika virus, likely one that warns pregnant women of potential infection and a damaged fetal brain. This virus was first identified in 1947. Like many new infectious agents, it sort of slumbered in remote parts of the world until the last two or three years, when there has been a dramatic increase of illness in South America, particularly Brazil. For most people, the Zika virus is not a very significant illness—its effects range from no symptoms to a mild illness with fever, joint pain, muscle pain, and a rash. It reminds me of the epidemics of polio: Most infected people didn’t even know that they were infected, but a small percentage had a paralyzing illness.

With Zika there are two manifestations that involve the nervous system. The first, and the one that has garnered the most attention, is damage to the developing fetal brain in pregnant women. The second is the appearance of a paralyzing disease, Guillain-Barre Syndrome (GBS) some time after the signs of infection.

If a mother is infected relatively early in the pregnancy (before the 20th week), the virus passes from the mother to the fetus, infecting the brain and leading to major abnormalities in brain growth and development. The head and brain are smaller than normal, a condition known as microcephaly. These children do not necessarily die, so there is not a lot of pathological information. An autopsy of a late-term aborted fetus showed the brain was only three percent of its expected weight. The surface of the brain normally develops ridges (gyri); this brain was quite smooth. On histological examination, the nerve cells were reduced and not in their normal layers. Most importantly, the Zika virus was cultured from the brain. This autopsy provides evidence that the virus can cause microcephaly. In Brazil, where the virus is rampant, doctors have recorded 1.5 million Zika infections and 3,500 cases of microcephaly in the past year. The reported incidence of microcephaly is about 20 times the expected rate. It is not clear what the virus does to the fetal brain when the mother is infected during later stages of pregnancy. There is evidence that the brain does not grow and develop normally, but information from autopsies of these “later” brains is needed.

Recent evidence indicates that the Zika virus is neurotropic, meaning that it selectively damages nerve cells. When added to primitive nerve cells growing in a dish, the virus selectively infects and kills nerve cells at an early stage of development.

The second neurological problem is not associated with pregnancy, and can occur at any age after infection with the virus. Sometime after infection, when the person has seemingly recovered, a sudden paralysis occurs, often over just a few days. Subjects can progress to a total paralysis, including losing functions like swallowing and breathing, and require respiratory support. This illness is also seen after other infections and is known as Guillain-Barre Syndrome. It is self-limited (you can’t catch it from a person who has it) and most patients gradually recover. This appears to be a rare association with the Zika virus, but the true incidence is not known.

With this background, I would like to propose some suggestions for tackling this problem:

Develop reliable tests to determine if a person has, or has had, infection with the Zika virus. Such tests will be useful in following patients as well as in larger population studies.

Limit the mosquito vector. The virus is spread by the bite of the Aedes aegypti, a daytime active bug. The virus gets into the bug’s gut and replicates, and then gets into its blood. If a pregnant woman is bitten, the virus can invade and cross the placenta, coursing through the fetus to the fetal brain. Beyond the traditional methods of mosquito control such as use of screens, spraying, anti-mosquito lotions, and covering body surfaces, there are two possible new approaches to eradicating mosquitoes, both using genetic modifications. In the first, male mosquitoes are genetically modified so that their offspring die. This approach is being tried for the first time on an island in the Florida Keys and in Puerto Rico, where the virus has started to appear. If successful, one should see a gradual reduction in living Aedes mosquitoes. A second approach is to genetically modify the Aedes bug so that the mechanisms allowing the virus to live in its gut are no longer effective in doing so. This approach is still in the development phase. A note of caution: The Aedes aegypti is not the only possible vector, so eliminating it may not eliminate the problem.

Develop a vaccine to the Zika virus. This approach has worked spectacularly well in German measles (rubella), another virus that causes fetal brain developmental abnormalities. We do not see this rubella-related problem today.

The Zika virus has not hit the United States mainland or Europe yet, but it will. Just look at how fast it spread in Brazil. It is a very rapidly expanding problem, on that I will revisit in a few months.