While the worries that the Zika virus will cause severe birth defects if it infects pregnant woman have grabbed most of the headlines, this week researchers reported more evidence that an encounter with the virus can also leave some people temporarily paralyzed: On Monday, The Lancet published the first systematic study of a possible link between the virus and Guillain-Barré syndrome. The data add support to the theory that the recent increase in cases of sudden paralysis across Latin America is due to the spreading Zika outbreak. Science answers some key questions about the syndrome.
I’ve never heard of Guillain-Barré syndrome. What is it?
Guillain-Barré syndrome (GBS) is an unusual reaction to several kinds of infection, which leaves people immobile to varying degrees. A few days or weeks after a person has recovered from their initial symptoms, they experience sudden numbness and weakness in their limbs, which can progress to the point where they are partially or completely paralyzed. People usually recover sensation and movement over a period of weeks or months, but many suffer lasting effects, including limb weakness and lingering tingling sensations. The syndrome was first described 100 years ago, in 1916, by French doctors Georges Guillain, Jean-Alexandre Barré, and André Strohl.
What causes it?
Scientists think that GBS develops when the body’s immune response to a bacterial or viral infection goes awry and attacks the nervous system.
Why would the body do that?
Such autoimmune attacks can happen as a result of so-called “molecular mimicry,” when part of a virus or bacterium resembles part of a human cell. The antibodies that develop to recognize and fight the pathogen can, accidentally, trigger attacks on the body’s own cells. In the case of GBS, the immune molecules target nerve cells. In one well-studied example, the bacteria called Campylobacter jejuni, a common cause of food poisoning, carries a lipid molecule on its outer coat that resembles so-called gangliosides, molecules that help human nerve cells recognize and communicate with each other. In some cases, the antibodies that develop to help fight off the bacteria also signal the immune system to attack the body’s own cells that bear gangliosides.
Researchers don’t yet know why or how Zika might prompt such an attack on nerve cells. In the Lancet paper this week, a team reports that antibodies from the blood of GBS patients in French Polynesia do not react as strongly as expected to some of the molecular targets often associated with GBS. One of the paper’s co-authors, Hugh Willison, who studies GBS at the University of Glasgow in Scotland, says it’s possible that something more subtle is happening: Like other viruses, the one that causes Zika hijacks a cell’s own replication machinery to make new copies of itself, which then break out of the dying cell and infect neighboring cells. When the viruses emerge, they sometimes carry with them lipids that are made by the cells they have infected. Evidence is building that the Zika virus often targets nerve cells. It’s possible that emerging virus particles display nerve-specific lipid compounds. If the immune system develops antibodies to those, that could trigger GBS.
How is GBS treated?
There are two main treatments for GBS. Doctors can give patients immunoglobulin, a mix of antibodies from healthy donors, which can block the rogue antibodies. Or they can treat patients with plasma exchange, in which the body’s red blood cells are separated from the plasma (which carries the antibodies and other immune cells) and then returned without the plasma. (The body replaces the removed plasma.) As patients recover, physical therapy helps them regain strength and mobility.
Paralysis sounds scary. Is it life-threatening?
In severe cases, GBS can interfere with a person’s ability to breathe, and doctors estimate that about 5% of cases are fatal. Most patients recover, although it can be a long process. After 6 months, 80% of patients can walk again without assistance. After 1 year, about 60% have returned to full strength. Some patients take years to fully recover.
How sure are we that Zika is causing GBS?
Doctors in several countries have noticed over the last 2 years that during Zika outbreaks, the number of cases of GBS increases. (Doctors across Latin America have recorded hundreds of cases in recent months.) The Lancet paper is the first case-controlled study that looks carefully at how often infection with the Zika virus might lead to GBS. Researchers studied 42 cases of GBS that occurred during the Zika outbreak that hit French Polynesia 2 years ago. They found evidence in the patients’ blood for antibodies that react to Zika virus. But because it is difficult for antibody tests to distinguish between past infections with Zika and dengue, which is also common in French Polynesia, the study still leaves some open questions. Clearer answers should emerge from ongoing studies during the current Zika outbreak. Researchers are also trying to determine if certain genes or other factors might make some Zika patients more likely to develop GBS.
Have there been other clusters of GBS?
GBS is usually a rare and apparently random occurrence. However, there have been famous clusters: In 1976, a flu vaccine is thought to have triggered several dozen cases. In China in the 1970s, 80s, and early 90s, seasonal outbreaks of GBS left hundreds of children paralyzed every spring and summer. Chinese doctors were puzzled by these seemingly random clusters of the syndrome, in what was initially described as “Chinese Paralytic Syndrome.”
Guy McKhann of Johns Hopkins University in Baltimore, Maryland, began research on what was to become known as AMAN (acute motor axonal neuropathy)—a type of GBS—in 1990 while on a visit to Beijing pediatric hospitals. He described seeing dozens of children suffering from Guillain-Barré syndrome, which he at first presumed must have been polio. GBS does not normally occur in clusters, so he and other American researchers made an agreement to work with a team of Chinese counterparts, including Li Chunyan, a neurological researcher affiliated with a medical hospital in Hebei province, to find what was causing the outbreaks. Through dozens of nerve biopsies, they did discover a key difference in AMAN from traditional GBS in that the attack focuses on the nerve axon, rather than the surrounding myelin. The clusters created de facto GBS specialists in rural China. “We had so many cases every year, the local doctors became experts in treating Guillain Barré,” Li recalled.
Through a painstaking process of elimination and animal testing, they found their culprit in chickens. Heavy spring rains washed chicken waste from outdoor coops into village streams where children drank and played. The waste was contaminated with Campylobacter jejuni, and many of the children fell ill. Upon learning the results, local governments undertook massive public education campaigns that focused on clean drinking water and proper waste disposal and by the mid-1990s, the AMAN outbreaks in China were quelled.
Can GBS be prevented?
No one knows how to prevent GBS, other than to prevent the initial infections that seem to trigger it. In China, the seasonal outbreaks ended once researchers realized where those infections were coming from. Cases in places where Zika disease has waned have returned to the usual low levels.