Zika Virus and Guillain-Barré Syndrome (GBS)

Zika virus infection is associated with a neurological condition called GBS (I’ve written more about what exactly GBS is here).

In this post, I’ll be exploring the connection between Zika and GBS.

What do we know about the relationship between Zika virus and GBS?

Although the link between Zika and GBS started out as speculation, the scientific community now agree that the Zika virus is a cause of GBS.

The initial suspicion arose after some astute doctors and researchers noticed that co-inciding with the arrival of the Zika virus, they were were seeing far greater numbers of GBS cases than usual.

Sure enough, the data on number of GBS patients rolled in, which showed there was a clear surge in the number of GBS cases. In fact, most countries reported between 2 and 10 times as many cases of GBS during the period of the Zika outbreak than they had experienced the previous year.

What’s more, the peak in the surge of GBS cases in each country occurred approximately two weeks after the peak of the Zika virus outbreak. This made sense because we know that the GBS complication tends to only occur around two weeks after people are infected by a virus.

zika gbs cases.png
Graph showing the number of cases of Zika virus and of GBS in Latin America. The emergence of Zika virus in the region (green line), co-incided with a dramatic increase in the numbers of GBS cases (blue bars) (source)

This alone might seem too much to be a coincidence, but the case was clinched by a group of researchers from French Polynesia. Every patient on the island who was affected by GBS during the Zika outbreak was carefully studied and, although it’s very difficult to prove a diagnosis of Zika virus retrospectively, good evidence was found that the majority had been infected with Zika shortly before the GBS symptoms started.

But scientists are notoriously pedantic and reluctant to claim that one thing is the cause of another until we have really good evidence! Researchers use a group of criteria, called the ‘Bradford Hill criteria’ when trying to determine whether there truly is a causative relationship between a disease and a potential trigger. The table below explains the research showing that Zika meets all of the ‘Bradford Hill Criteria’ for being a cause of GBS. With the conditions in the table met, scientists could stop arguing and be confident in officially declaring that Zika virus causes GBS!

Bradford-Hill Criteria What this means Evidence in the case of Zika and GBS
Temporality There must be evidence that Zika virus exposure comes before the development of GBS symptoms. On a country-wide level, the peak of the increase in GBS cases was around two weeks after the peak of the number of Zika virus cases.

The patients who had GBS usually reported having the symptoms of Zika infection around 1-2 weeks previously.

Biological plausibility There must be a reasonable hypothesis as to how/why Zika can cause GBS. We suspect Zika virus causes GBS through ‘molecular mimicry’, confusing the body’s immune system into attacking its own nerves, in a similar way to how many other infectious disease can cause GBS.
Strength of association GBS must be significantly more common among people with recent Zika infection than among people who haven’t had Zika. In the French Polynesia study, 100% (ALL!) of the patients with GBS had evidence of recent Zika infection, whereas just 56% of the background population had been exposed to the virus.
Exclusion of alternative explanations There are no other possible explanations for the recent rise in GBS cases. In the French Polynesia study, other infectious triggers of GBS (such as Campylobactor and CMV) were not found among the GBS patients.

An increase in other potential infectious causes of GBS hasn’t been found in any of the countries which have seen an increase in GBS cases.

Cessation When Zika transmission stops, there must be a decrease in the number of GBS cases. In in French Polynesia, in 4 other Central American countries and in one state in Brazil, reports of GBS decreased after Zika transmission slowed down or stopped.

There you go! Case closed!

I’m travelling to an area affected by Zika and worried about GBS. What’s the risk? Should I avoid travelling?

Based on the rates in French Polynesia, only about 1 in 4,000 people who get Zika virus will develop GBS.

This compares with a risk of between 1 in 1,500 and 1 in 4,000 for Campylobactor infection (a bacteria which causes diarrhoeal illness) and between 1 in 400 and 1 in 1,500 for CMV infection (a virus which is one of the other top causes of GBS).

Essentially, you’re more likely to get GBS after a bout of diarrhoea than because of the Zika virus. Most people don’t worry about food poisoning induced GBS, so you probably shouldn’t worry too much about Zika-induced GBS either.

So why the fuss over Zika and GBS?

This might be a relatively small risk of GBS for any individual with Zika, but the problem is that Zika is affecting people on such a huge scale.

The total number of people getting Zika virus is very high (around 50% of the population were affected in the outbreak in French Polynesia, as many as 90% in the outbreak in Yap) and this has meant there’s been a sharp increase in the number of GBS cases (between 2 and 10 times the normal annual totals in most Latin American countries).

This is putting a significant burden on the hospitals in the region, which are simply not equipped to deal with such an influx of patients requiring complex care, ITU support and whose only medical treatment (IVIg) is prohibitively expensive in under-resourced settings.

This may have left you wondering: if we already have evidence that Zika causes GBS and we also know roughly what the level of risk is, why do we need to study the disease any further?

I’ll be covering both of these in upcoming blog posts: the unanswered questions around Zika and GBS and why there is still need for further research.

~~~~~

References and further reading

WHO announcement that there was a consensus on Zika being a cause of GBS: WHO Zika Situation Report, March 2016.

A very comprehensive review, from a WHO working group, of all the lines of evidence linking Zika virus and GBS (also covers the evidence for links between Zika and microcephaly).

Data from 7 Latin American countries showing that GBS cases were 2-10 times what would usually be expected during the period of the Zika epidemic, and that the peak of GBS cases occurred shortly after the peak in Zika virus infections.

Since the important study by the group in French Polynesia, there was another similar large-scale study looking at all the patients with GBS admitted to 6 hospitals across Columbia which also showed that the majority had evidence of recent Zika virus infection.

There have since been even more  studies (smaller case-series and individual case reports) of patients whose blood tests and CSF analysis strongly suggest they were infected with Zika virus shortly before developing GBS. I won’t list them all here, instead I’ll point to a review article which summarises them quite nicely.

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