Thursday, January 21, 2016

Exploring The Zika - Guillain-Barré Connection


The exact cause of Guillain-Barré Syndrome - a rare immune disorder that damages nerve cells, and can cause muscle weakness and sometimes paralysis - is unknown, but it often follows a viral or bacterial illness.

In the United States between 3,000 and 6,000 cases are reported every year.  Most people recover fully, but some may have lingering neurological damage.

Not quite two years ago (Feb 2014), in Zika, Dengue & Unusual Rates Of Guillain Barre Syndrome In French Polynesia, we saw the first hint that a relatively obscure, and previously thought to be mild virus - Zika - might be causing neurological symptoms following an outbreak in the South Pacific.

Unlike Dengue, or even Chikungunya, little had been written about the Zika virus, although in 2009 the CDC’s EID Journal carried a report called Zika Virus Outside Africa by Edward B. Hayes that explored the virus's arrival in Yap Island where 70% of the population was affected.

While most cases had reported relatively mild symptoms, the author cautioned that until the West Nile Virus began causing neuroinvasive symptoms in Romania and North America, it too was considered a fairly innocuous viral infection.

In February of 2014, a report came from Le Centre d’Hygiène et de Salubrité Publique  (CHSP) in French Polynesia Bulletins health surveillance in French Polynesia and related documents which reported of 41 Guillain-Barré syndrome (GBS) and 26 cases of other neurological complications they believed linked to the ongoing Zika/Dengue outbreak which had started in 2013.
The expected incidence of GBS is 1 to 2 cases per 100,000 population per year . With a population of 275,000, one would expect fewer than 10 cases per year in that sized population. 

A month later, in Eurosurveillance: Zika Virus Infection Complicated By Guillain-Barré Syndrome, we looked at a report that calculated a 20 fold increase in GBS after the arrival of Zika in French Polynesia.   The authors wrote:
Since the beginning of this epidemic, and as up to 8,200 cases of ZIKA infection have already been reported of a 268,000 total population, the incidence of GBS has been multiplied by 20 in French Polynesia (data not shown), raising the assumption of a potential implication of ZIKA.

Since these islands were seeing a concurrent Dengue outbreak there was speculation that co-infection by Dengue and Zika  - or sequential arboviral immune stimulation - might predispose one to more severe illness. 

Adding some credence to this notion, with dengue, it is usually a person's second infection that causes severe illness, while the first infection is usually mild.

The prevailing theory is that the host’s immune system - which already has neutralizing antibodies to the first DENV infection - mistakenly identifies the second DENV infection as being the same strain.

Rather than creating new neutralizing antibodies to fight the infection, it deploys its existing cross reactive, but non-neutralizing (read: ineffective) antibodies to the field of battle.

Sometimes called OAS or Original Antigenic Sin, this is the immunological equivalent of taking a knife to a gun fight.

Since many populations now seeing  Zika have long dealt with Dengue, or Chikungunya - or both - teasing out the cause or causes of increased neurological side effects (including microcephaly) isn't going to be easy.

It is worth noting that a there is now a suspected link between GBS and Chikungunya infection as well (see Eurosurveillance Increase in cases of Guillain-Barré syndrome during a Chikungunya outbreak, French Polynesia, 2014 to 2015).

Earlier this week PAHO released an updated epidemiological report on Zika, and mentioned the Polynesian increase in GBS, along with increased reports in Brazil and El Salvador (see PAHO: Epidemiological Update On Zika - Jan 17th) where they wrote:

Currently, similar situations are being investigated in other countries of the Americas. These findings are consistent with a temporal and spatial link between Zika virus circulation and the increase of GBS. Although the etiopathogenesis and associated risk factors have not yet been well established, Member States should implement surveillance systems to detect unusual increases in cases and prepare health services for patients care with neurological conditions.

Today the World Health Organization published the following statement on the increase in GBS in El Salvador.

Guillain-Barré syndrome – El Salvador

Disease Outbreak News
21 January 2016 

The National IHR Focal Point of El Salvador has notified PAHO/WHO of an unusual increase of Guillain-Barré Syndrome (GBS) in the country. In El Salvador, the annual average number of GBS is 169; however, from 1 December 2015 to 6 January 2016, 46 GBS were recorded, including 2 deaths. 

Of the 46 GBS cases, 25 (54%) are male and 35 (76%) are 30 years old or older. All cases were hospitalized and treated with plasma exchange or intravenous immunoglobulin. One of the two deceased patients had a history of multiple underlying chronic diseases. Out of the 22 patients whose information was available, 12 (54%) presented with febrile rash illness in the 15 days prior to the onset of symptoms consistent with GBS.

Investigations are ongoing to determine the cause of infection and acquire further details about the laboratory diagnosis. Possible associations between GBS and Zika virus infection are also being investigated. Since the confirmation of the first case of Zika virus infection in November 2015 until 31 December 2015, Salvadoran health authorities reported 3,836 suspected cases of Zika virus infection.

(Continue . . . )

Unlike microcephalic births, which are a lagging indicator, GBS symptoms usually appear within days or weeks of acute infection, and therefore may give us a more immediate read on the progress and severity Zika's spread.

Despite all of this, it is not at all a certainty that Zika - or even a combination of Zika and other viral infections (concurrent or sequential) - is responsible for this apparent increased incidence of GBS.

The evidence, however - while not conclusive - continues to mount.

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