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Study Finds Strong Evidence Of Link Between Zika Virus And Guillain-Barre


Scientists have discovered the strongest evidence yet that the Zika virus can cause Guillain-Barré syndrome, a rare but severe neurological disorder that kills 5 percent of people who develop it and leaves 20 percent permanently disabled. With Zika continuing to spread “explosively” throughout the Americas, affected countries are being told to make sure they have enough intensive care beds to deal with an increase of patients with Guillain-Barré.

In May 2015, Zika virus was found for the first time in the Western Hemisphere in northeastern Brazil. Since then, the virus has spread to dozens of countries throughout the Caribbean, Central America, South America, and–most recently–the United States, leading to millions of infections and a host of new concerns.

Many countries experiencing widespread Zika transmission have seen a subsequent spike in cases of Guillain-Barré, with the worst-hit regions like Colombia and Brazil reporting thousands of new cases of the rare neurological disease. However, the link between Zika infection and Guillain-Barré syndrome has been largely anecdotal — until now.

In a new study published in The Lancet, researchers led by Dr. Arnaud Fontanet of France’s Institut Pasteur analyzed data from a Zika outbreak in French Polynesia in 2013, when 32,000 suspected cases of the virus were reported in a period of about six months. During this same period, there was also an uptick in cases of Guillain-Barré. To assess the potential link, Dr. Fontanet’s team studied 42 cases of Guillain-Barré syndrome diagnosed in French Polynesia between October 2013 and April 2014, looking to see if there was any evidence that these patients had been exposed to Zika virus.

The results were overwhelming: researchers found that 98 percent of the Guillain-Barré patients–all but one–had antibodies to Zika, suggesting they had been infected with the virus, compared with only 56 percent of the individuals in a control group that did not have Guillain-Barré. Most of these patients (about 93 percent) showed evidence of recent Zika infection — within three months prior to developing Guillain-Barré syndrome. In addition, 88 percent of patients had experienced typical symptoms of Zika, including fever, rash and joint pain, usually about a week before developing Guillain-Barré.

The results suggest that Zika should be added to the list of infectious pathogens that can cause Guillain-Barré, the researchers write in The Lancet.

“This study provides the most compelling evidence to date of a causative link between Zika and Guillain-Barré syndrome,” said Dr. Jeremy Farrar, an infectious disease specialist and director of the Wellcome Trust global health charity, which helped fund the research. “The increase in reported cases of Guillain-Barré in Brazil and other South American countries seems to suggest that a similar situation may be occurring in the current outbreak.”

In addition to an increase in cases of the neurological syndrome, there has also been a surge in the incidence of microcephaly, a severe birth defect, in other areas with Zika outbreaks. According to a report by the World Health Organization released on Friday, eight countries or territories have seen increases in Guillain-Barre since 2015. In some of those areas, including Puerto Rico, Colombia and Venezuela, there’s evidence of Zika infection among Guillain-Barré patients.

“The scale of the crisis unfolding in Latin America has taken us all by surprise, and we should be prepared for further unforeseen complications of Zika virus infection to emerge in the coming weeks and months,” said Dr. Farrar.

To date, there have been 107 cases in the United States among U.S. travelers returning from Zika-infected areas, and at least one sexually-transmitted case. None of these resulted in Guillain-Barré, but that is not surprising considering the relative rarity of this syndrome, the researchers said.

But that could change, at least in parts of the United States.

Over 60 percent of the U.S. population now live in areas vulnerable to the seasonal transmission of Zika as mosquitoes have spread to more favorable environments, according to another recent study published in The Lancet, and global warming is expected to vastly increase the number of susceptible people, particularly in North America. As the weather warms this spring, experts say localized outbreaks within the U.S. are likely.

Based on the evidence presented in the new analysis, Dr. Fontanet said “high numbers of [Guillain-Barré] cases … might be expected in the coming months” in those countries where Zika is spreading explosively.

Why Guillain-Barré is so worrisome

In February, the World Health Organization declared Zika virus a “public health emergency of international concern” because of its suspected links to Guillain-Barré and microcephaly.

Although Guillain-Barre is very rare, affecting about one in 100,000 people in the United States, the study suggests that Zika could make it less rare. The researchers estimate, based on the rates of Zika and Guillain-Barré in French Polynesia, that one in 4,000 people infected with Zika could develop the neurological syndrome.

Guillain-Barré is an autoimmune disorder in which the body’s immune system attacks the nervous system. The disease typically affects axons, the parts of peripheral nerves that transmit nerve signals, or the myelin sheath covering the axons. The result is that patients, over the course of several weeks, experience tingling in their legs, then weakness in their legs and arms, and in some cases even paralysis. Even with proper medical care, it can take patients weeks to years to recover, and 30 percent of them still have weakness three years later.

In the current study, 74 percent of patients had muscle weakness, 64 percent had weakness specifically in facial muscles and 29 percent needed assistance (a respirator) to breathe. Breathing difficulties can be a fatal complication of the syndrome, although no patients in the study died.

Among the patients in the study, 57 percent were able to walk on their own within three months. There is no cure for the condition, but there are treatments that can reduce the symptoms, help recovery and treat complications.

The Guillain-Barré/infectious disease link

Although it is exactly not clear what causes Guillain-Barré, a number of viruses have been linked to the syndrome before Zika, such as influenza, Epstein-Barr, and other mosquito-borne viruses including dengue. Research also suggests that infections with the bacteria campylobacter could lead to Guillain-Barré in one to three in 4,000 cases.

It is thought that when the immune system responds to viral and bacterial infections, it makes antibodies that recognize them, but the antibodies also happen to recognize components of the nervous system. However, as the LA Times reports, evidence from this study indicates that something more serious may be going on in patients who develop Guillain-Barré linked to Zika infection:

Ominously, the scientists deconstructing the French Polynesian outbreak of Zika concluded that the mechanism by which Zika prompts Guillain-Barre syndrome may be different from any seen before. Polynesian patients with Guillain-Barre all had damage to the nerves’ ability to conduct electrical signals, which is typically seen when the immune system attacks the nervous system. But only a few carried certain biological markers that are the hallmark of Guillain-Barre.

That could mean, at least, that Zika prompts the immune system to attack nerves by some other means than have been seen in past cases of Guillain-Barre, the authors wrote. It could also mean that Zika has some more direct role in damaging the nerves, they added.

One of the main questions that remains to be answered is why Zika leads to the development of Guillain-Barré in certain patients, while causing only mild symptoms in most others.

“For the vast majority of people who develop Zika virus infection, Guillain-Barre syndrome isn’t something they need to be concerned about because the risk of it developing is small,” said study co-author Dr. Hugh Willison, a clinical neurologist at the University of Glasgow. “However, if you have a million people infected with Zika, you’re going to see a lot of cases of Guillain-Barre syndrome.”


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