Friday, October 21, 2016

NEJM: Guillain–Barré Syndrome Associated with Zika Infection - Colombia

Credit WHO Zika SitRep 10/20/16


According to the latest WHO Zika SitRep:

19 countries and territories have reported an increased incidence of GBS and/or laboratory confirmation of a Zika virus infection among GBS cases (Table 4). Puerto Rico, which has previously reported GBS cases with confirmed Zika virus infections, has reported an increase in incidence of GBS cases in the last week. 

While this temporal-geographic link between Zika and GBS has been on our radar for  2 1/2 years (see 2014's Eurosurveillance: Zika Virus Infection Complicated By Guillain-Barré Syndrome), proof of GBS's causation by Zika infection is still lacking. 

Part of the problem is that the onset and diagnosis of GBS often occurs 1 to 2 weeks (or longer) after infection with the Zika virus, when many conventional Zika testing methods are no longer able to detect the virus. 

The co-circulation of Dengue and Chikungunya - which can produce similar symptoms - also clouds the issue.  A patient recalling a recent fever-rash-like illness is suggestive of Zika, but far from exclusive to it. 

There is also evidence that other arbovirus infections (WNV, Dengue, CHKV, etc.) may occasionally spark the onset of GBS as well (see Guillain-Barre syndrome: The Other Zika Concern).

And if things were complicated enough, there is evidence to suggest that concurrent or sequential flavivirus (Dengue, Zika, etc.) infection may increase the severity of an  individual's illness through a process called ADE (see PLoS Currents: Another In Vitro Study Suggests Previous Dengue Exposure May Exacerbate Zika Severity).

It is against this `noisy' background that researchers must work to connect recent Zika infection with the rare neurological complication of Guillain-Barré Syndrome.  All of which is why the CDC's Zika-GBS website states:

Current CDC research suggests that GBS is strongly associated with Zika; however, only a small proportion of people with recent Zika virus infection get GBS.

Adding to our understanding of this association today is the following study appearing in the NEJM that used RT-PCR testing of urine samples to help extend the detection time for prior Zika infection, and help bolster the case for a Zika-GBS link.

The full article is available at the link below, as well as an accompanying editorial (HERE).  Follow the links to read:

Original Article
Guillain–Barré Syndrome Associated with Zika Virus Infection in Colombia

Beatriz Parra, Ph.D., Jairo Lizarazo, M.D., Jorge A. Jiménez-Arango, M.D., Andrés F. Zea-Vera, M.D., Ph.D., Guillermo González-Manrique, M.D., José Vargas, M.D., Jorge A. Angarita, M.D., Gonzalo Zuñiga, M.D., Reydmar Lopez-Gonzalez, M.D., Cindy L. Beltran, M.D., Karen H. Rizcala, M.D., Maria T. Morales, M.D., Oscar Pacheco, M.D., Martha L. Ospina, M.D., Anupama Kumar, M.B., B.S., David R. Cornblath, M.D., Laura S. Muñoz, M.D., Lyda Osorio, M.D., Ph.D., Paula Barreras, M.D., and Carlos A. Pardo, M.D.
N Engl J Med 2016; 375:1513-1523October 20, 2016DOI: 10.1056/NEJMoa1605564


Zika virus (ZIKV) infection has been linked to the Guillain–Barré syndrome. From November 2015 through March 2016, clusters of cases of the Guillain–Barré syndrome were observed during the outbreak of ZIKV infection in Colombia. We characterized the clinical features of cases of Guillain–Barré syndrome in the context of this ZIKV infection outbreak and investigated their relationship with ZIKV infection.


A total of 68 patients with the Guillain–Barré syndrome at six Colombian hospitals were evaluated clinically, and virologic studies were completed for 42 of the patients. We performed reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays for ZIKV in blood, cerebrospinal fluid, and urine, as well as antiflavivirus antibody assays.


A total of 66 patients (97%) had symptoms compatible with ZIKV infection before the onset of the Guillain–Barré syndrome. The median period between the onset of symptoms of ZIKV infection and symptoms of the Guillain–Barré syndrome was 7 days (interquartile range, 3 to 10). Among the 68 patients with the Guillain–Barré syndrome, 50% were found to have bilateral facial paralysis on examination. Among 46 patients in whom nerve-conduction studies and electromyography were performed, the results in 36 patients (78%) were consistent with the acute inflammatory demyelinating polyneuropathy subtype of the Guillain–Barré syndrome. Among the 42 patients who had samples tested for ZIKV by RT-PCR, the results were positive in 17 patients (40%). Most of the positive RT-PCR results were in urine samples (in 16 of the 17 patients with positive RT-PCR results), although 3 samples of cerebrospinal fluid were also positive. In 18 of 42 patients (43%) with the Guillain–Barré syndrome who underwent laboratory testing, the presence of ZIKV infection was supported by clinical and immunologic findings. In 20 of these 42 patients (48%), the Guillain–Barré syndrome had a parainfectious onset. All patients tested were negative for dengue virus infection as assessed by RT-PCR.


The evidence of ZIKV infection documented by RT-PCR among patients with the Guillain–Barré syndrome during the outbreak of ZIKV infection in Colombia lends support to the role of the infection in the development of the Guillain–Barré syndrome. (Funded by the Bart McLean Fund for Neuroimmunology Research and others.)

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