Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Rubin reports no financial relationships relevant to this field of study.

SYNOPSIS: Guillain-Barré syndrome associated with Zika virus is similar to non-Zika virus cases in terms of severity of illness and prognosis around long-term recovery and disability.

SOURCE: Dirlikov E, Major CG, Medina NA, et al. Clinical features of Guillain-Barré syndrome with vs without Zika virus infection, Puerto Rico, 2016. JAMA Neurol 2018;75:1089-1097.

Transmitted by mosquitoes, Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) that is related to other flaviviruses, including dengue, yellow fever, and West Nile. Approximately 20% of patients experience nonspecific manifestations of infection, including low-grade fever, rash, arthralgias, or conjunctivitis. More serious neurologic complications include congenital microcephaly, encephalitis, meningoencephalitis, transverse myelitis, and Guillain-Barré syndrome (GBS). Can GBS associated with ZIKV be differentiated from GBS that is not associated?

ZIKV disease was reported by the Department of Health, San Juan, Puerto Rico, in December 2015, with the first case of GBS in a patient with prior ZIKV infection confirmed in January 2016. In February 2016, public health surveillance was implemented to identify cases of GBS prospectively and test patients for ZIKV, dengue virus, and chikungunya virus. In October 2016, GBS case reporting was made compulsory. Between February and April 2017, all 57 nonspecialized hospitals and two rehabilitation centers in Puerto Rico provided lists of patients hospitalized in 2016 with a diagnostic code of GBS in their medical record. Confirmation of the diagnosis of GBS was performed by medical record review and encompassed clinical presentation, electrodiagnostic studies, cerebrospinal fluid analysis, and absence of an alternative neurologic diagnosis. Telephone interviews were conducted six months following illness onset to determine the extent of long-term disability using the modified Rankin scale, Overall Disability Sum score, and Facial Disability Index. A statistical analysis encompassed Pearson χ2 test, Fisher exact test, and χ2 partitioning to compare categorical variables, with the median two-sample test used to compare continuous variables. P < 0.05 was considered statistically significant.

Among 135 cases of suspected GBS reported by healthcare professionals in 2016, 98 (72.7%) were confirmed GBS, eight (5.9%) suspected GBS, and 29 (21.5%) non-GBS. Among 181 patients identified by diagnostic code, 100 (55.2%) already had been found through passive public health surveillance. Of the remainder, 25 (34.7%) were confirmed GBS cases, four (5.6%) were suspected GBS, and 43 (59.7%) were non-GBS. The researchers identified 123 confirmed GBS cases, of which 68 (55.3%) were male, with an overall median age of 54 years. ZIKV infection was confirmed in 66.4% of those tested (71 of 107).

Compared to GBS cases without evidence of ZIKV infection, ZIKV GBS cases were of similar age, although they more often were female. Antecedent illness was reported equally in both groups, but antecedent rash and arthralgia were more frequent in the ZIKV GBS group. Duration of hospitalization, medical complications, mortality rate, and frequency of intravenous immunoglobulin administration were similar in both groups, but those with ZIKV more often were admitted to the ICU and required mechanical ventilation, and were more likely to have facial weakness and paresthesiae, dysphagia, and shortness of breath. At clinical nadir, modified Rankin and Hughes Disability scores were comparable, as were median disability scores at six months, although ZIKV GBS patients reported long-term facial difficulties, including abnormal tearing and drinking from a cup, more often.

COMMENTARY

First isolated from a febrile macaque monkey in 1948 in the Zika forest of Uganda (hence its name), ZIKV was an unimportant human pathogen until a 2007 outbreak of what initially was thought to be dengue virus on the island of Yap in Micronesia. It turned out to be ZIKV confirmed by reverse transcriptase PCR. GBS cases then were reported in a 2013-2014 outbreak in French Polynesia, and ZIKV became hyperendemic in some South American areas in 2015. Transmitted by the bite of an infected Aedes species mosquito, humans and monkeys appear to be the only viable vertebral hosts for ZIKV, but it also may be transmitted perinatally, presumably through the placenta, as well as by a blood-borne route and via breast milk and semen.