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Table of Contents    
Year : 2018  |  Volume : 66  |  Issue : 5  |  Page : 1288-1289

Zika virus and Guillain-Barré syndrome: Cause or association?

Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, India

Date of Web Publication17-Sep-2018

Correspondence Address:
Dr. Jayantee Kalita
Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow - 226 014, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.241382

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How to cite this article:
Kalita J, Misra UK. Zika virus and Guillain-Barré syndrome: Cause or association?. Neurol India 2018;66:1288-9

How to cite this URL:
Kalita J, Misra UK. Zika virus and Guillain-Barré syndrome: Cause or association?. Neurol India [serial online] 2018 [cited 2019 Feb 16];66:1288-9. Available from:

Guillain-Barré syndrome (GBS) is classically described as an immune-mediated acute inflammatory demyelinating polyradiculoneuropathy characterized by motor, sensory or autonomic dysfunction with albumin-cytological dissociation. In the last three decades, GBS has been projected as a multifaceted disease in its etiology, pathogenesis, phenotypic expression and prognosis. The list of GBS triggers has been increasing, especially with the emergence of new viral infections, such as dengue, chikungunya, Zika, H1N1, etc. Whether many of these organisms have an association or have a causal link is not confirmed. In an endemic area of viral infections such as Japanese encephalitis, dengue, chikungunya or Zika virus, the seroprevalence is very high; therefore, any disease may have a higher frequency of these infections. Experimental allergic neuritis and disseminated encephalomyelitis have shown transfer of immunological substance and occurrence of disease. A similar experimental study may establish the link.

After recognition of Zika virus, various neurological manifestations have been attributed to have a causal link. Zika virus belongs to the genus Flaviviridae and was first isolated in 1947 from a febrile Rhesus monkey in the Zika forest of Uganda.[1] In 1954, the first human Zika virus infection was reported from Nigeria. In 1962, the virus was isolated in human beings in Uganda.[2] Zika virus is a flavivirus, with a 40-50 nm in diameter enveloped, icosahedral virion containing a non-segmented, single-stranded, positive sense ribose nucleic acid (RNA) having 10,794 nucleotides.[3] Since 2007, Zika virus outbreaks have been reported outside Africa, including in South America, Central America, the Caribbean, Mexico and USA. Lately, outbreaks have also been reported from Asian countries. About 578,148 suspected cases of Zika virus infected individuals have been reported in 2016 in 45 countries and in territories of America.[4] It is an arthropod born disease transmitted by Aedes, Culex and Anopheles mosquitoes having a sylvatic and an urban life cycle. These mosquitoes are also widely prevalent in most of the South East Asia, making residents vulnerable to developing Zika virus infection. Like Japanese encephalitis, about 80% of Zika virus infected individuals remain asymptomatic. The symptomatic patients develop fever, an itchy maculopapular rash, conjunctival congestion, myalgia and arthralgia. Neurological manifestations of Zika virus may be due to direct viral invasion (meningoencephalitis) or immune-mediated injury, such as GBS, optic neuritis and acute transverse myelitis. Trans-placental transmission of Zika virus results in congenital malformations. It is important to differentiate direct viral infection of the nervous system from immune-mediated injury because the later may be benefited by corticosteroid treatment; whereas, corticosteroid in direct viral neurological manifestations may result in persistence of infection. The presence of viral RNA in the tissues and cerebrospinal fluid suggests direct viral injury rather than immune mediated injury.

GBS has been linked to Zika virus infection in the French outbreak, in which 41 out of 42 patients with GBS were positive for IgG and IgM antibody against Zika virus. However, 95% of these patients were also positive for dengue. Plaque reduction neutralization test was four times higher than dengue in one patient only.[5] In 2015-2016, studies from South America have reported an increased hospital admission of GBS patients compared to the pre-Zika era. In El Salvador, the number of GBS patients increased by two times, in Venezuela by 10 times, and in Brazil by about five times more than that prevalent in the pre-Zika era.[6] A recent study from Singapore, however, did not find an increase in GBS in the Zika virus epidemic.[7] Recently, the effect of Zika virus in producing GBS has been reported, based on 164651 Zika virus infected individuals; of them, 1513 developed GBS. On meta-analysis, the risk of developing GBS was 1.23% in patients who had zika virus infection (95% confidence interval 1.17-1.29).[8] In this issue of Neurology India, Baskar et al., have evaluated anti-Zika virus IgM antibody, anti C. Jejuni IgG antibody and antiganglioside IgG antibody in 90 patients with GBS. The anti-Zika IgM antibody was positive in 14 (15.5%) patients; and, 4 of these patients were also positive for dengue IgM antibody. C. Jejuni antibody was present in 46.6% and antiganglioside antibody in 62.2% patients.[9] Due to genetic similarities, the Zika virus antigen and antibody may cross react with other flaviviruses, such as dengue, West Nile and Japanese encephalitis. Quantitative polymerase chain reaction (PCR) may help in differentiating different flavivirus infections. Baskar et al., however, have not done the PCR study. The presence of Zika virus antibody in patients without Japanese encephalitis and dengue antibody, suggests circulating Zika virus in and around Pondicherry, which needs further study.

The causal link of Zika virus infection with GBS has been supported by the fact that a shorter latency (median 6 days) from the occurrence of Zika virus infection to the development of GBS has been observed. An immune-mediated injury following the occurrence of infection usually takes 2 to 4 weeks to develop. An increased immune response and molecular mimicry between a triggering agent and nerve antigen may result in involvement of the peripheral nerves and nerve roots. Many studies highlighting GBS as the causal link with Zika virus infection have reported. The presence of Zika virus RNA in the cerebrospinal fluid suggests a direct viral invasion. The study from France has revealed an autoimmune response against glycolipids, including the galactosides and the glycolipid complexes, in less than 50% patients. There was no competition of the GA1 antigen and Zika virus protein.[5] Another study has reported an overlap between Zika virus polyprotein and the human protein related to myelin and axon. Sural nerve biopsy of a patient with Zika virus GBS revealed demyelination as well as some axonal changes with mononuclear cell infiltration, simulating the nerve biopsy findings of patients suffering form the classical GBS.[10],[11],[12]

Flavivirus infection such as Japanese encephalitis virus and West Nile virus are known to produce polio like illness.[13] Dengue virus infection may also result in acute muscle dysfunction manifesting with myalgia and raised creatine kinase.[14],[15] It is important to look for Zika virus infection in India because of circulating mosquitoes and the congenial eco-geological environment. A possibility of anterior horn cell involvement or muscle dysfunction needs to be considered and should be evaluated in Zika virus infection over and above an immune mediated neurological syndrome.


We thank Mr. Shakti Kumar for the secretarial help rendered.

  References Top

Dick GW, Kitchen SF, Haddow AJ. Zika virus. (I). Isolations and serological specificity. Trans R Soc Trop Med Hyg 1952;46:509-20.  Back to cited text no. 1
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PAHO WHO (2016). Zika Cumulative Cases - 25 August 2016. Pan American Health Organization. World Health Organization. Avaliable from: =8424%3Acontents&Itemid=42090&lang=en. [Last accessed on 2018 Aug 14].  Back to cited text no. 4
Cao-Lormeau VM, Blake A, Mons S, Lastere S, Roche C, Vanhomwegen J, et al. Guillain-Barré syndrome outbreak associated with Zika virus infection in French Polynesia: A case-control study. Lancet 2016; 387:1531-9.  Back to cited text no. 5
da Silva IRF, Frontera JA, Bispo de Filippis AM, Nascimento OJMD; RIO-GBS-ZIKV. Research Group. Neurologic complications associated with the Zika virus in Brazilian adults. JAMA Neurol 2017;74(10):1190-8.  Back to cited text no. 6
Umapathi T, Kam YW, Ohnmar O, Ng BCJ, Ng Y, Premikha M, et al. The 2016 Singapore ZIKV outbreak did not cause a surge in Guillain-Barré syndrome. J Peripher Nerv Syst 2018 Aug 2.  Back to cited text no. 7
Barbi L, Coelho AVC, Alencar LCA, Crovella S. Prevalence of Guillain-Barré syndrome among Zika virus infected cases: A systematic review and meta-analysis. Braz J Infect Dis 2018;22:137-41.  Back to cited text no. 8
Baskar D, Amalnath D, Mandal J, Dhodapkar R, Vanathi K. Antibodies to Zika virus, Campylobacter jejuni, gangliosides in Guillain–Barre syndrome: A prospective single-center study from southern India. Neurol India 2018;66:1324-31.  Back to cited text no. 9
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Lucchese G, Kanduc D. Zika virus and autoimmunity: From microcephaly to Guillain-Barré syndrome, and beyond. Autoimmun Rev 2016;15:801-8.  Back to cited text no. 10
Hajra A, Bandyopadhyay D, Hajra SK. Zika virus: New interest in neurology. Neurol India 2016;64:1102-4.  Back to cited text no. 11
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Misra UK, Kalita J. Anterior horn cells are also involved in Japanese encephalitis. Acta Neurol Scand 1997;96:114-7.  Back to cited text no. 13
Kalita J, Misra UK, Mahadevan A, Shankar SK. Acute pure motor quadriplegia: Is it dengue myositis. Electromyogr Clin Neurophysiol 2005;45:357-61.  Back to cited text no. 14
Misra UK, Kalita J, Maurya PK, Kumar P, Shankar SK, Mahadevan A. Dengue-associated transient muscle dysfunction: Clinical, electromyography and histopathological changes. Infection 2012;40:125-30.  Back to cited text no. 15


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