Guillain–Barré syndrome linked to Zika virus infection
medwireNews: Researchers report strong biological evidence linking Zika virus (ZIKV) infection with Guillain–Barré syndrome, in particular the acute inflammatory demyelinating polyneuropathy (AIDP) form.
The findings support epidemiological data showing a substantial increase in Guillain–Barré syndrome cases during the ZIKV infection outbreak in Colombia, from about 20 to 90 cases per month, says the team in The New England Journal of Medicine.
They clinically evaluated 68 patients with Guillain–Barré syndrome at six Colombian hospitals and found that 66 (97%) had symptoms compatible with ZIKV infection that started a median of 7 days before the onset of the syndrome.
These symptoms were primarily fever (69%), rash (59%), headaches (34%), myalgias (34%), nonpurulent conjunctivitis (25%) and arthralgias (22%) and lasted for only a short time in most of the patients, at a median of 4 days.
The neurological symptoms of Guillain–Barré syndrome at presentation comprised ascending limb weakness (82%), paresthesias (76%) and facial palsy (23%) and for the 46 (68%) patients who underwent nerve-conduction and electrophysiological assessment, the AIDP form was confirmed in 78%.
Fluid samples from the urine, serum or cerebrospinal fluid of 42 patients were assessed for ZIKV infection using reverse transcriptase-polymerase chain reaction (RT-PCR) and 17 (40%) patients tested positive.
Most of the positive results (16 patients) were seen in urine samples, which seemed to remain sensitive to testing for longer than other fluid types. Indeed, generally there was a prolonged period of viruria, persisting for a median of 16.5 days and in one case up to 48 days after viral syndrome onset.
Carlos Pardo (Johns Hopkins University School of Medicine, Baltimore, Maryland, USA) and co-authors note that most (86%) of the 37 patients tested had evidence of a recent flavivirus infection and resulting immune response as evidenced by the presence of cross-reactive immunoglobulin (Ig)M or IgG antibodies, indicative of dengue virus.
This demonstrates one of the difficulties in diagnosing ZIKV infection, which has similar symptoms to that of dengue virus. But as the RT-PCR results were negative for this virus, the team suggests that these patients had previously been exposed to dengue virus and ZIKV infection was a secondary flavivirus infection.
For five patients with no detectable flavivirus antibodies, ZIKV infection is likely to have been the primary infection.
Based on laboratory testing, ZIKV infection was classified as definite in 17 patients, probable in 18 and suspected in 33.
The researchers also found that the Guillain–Barré syndrome associated with ZIKV infection more often followed the pattern of a parainfectious disorder rather than the classic postinfectious profile, in that almost half of the patients had a rapid onset of neurological symptoms without an asymptomatic period after ZIKV infection symptoms.
They speculate that this may be due to a hyperacute immune response to ZIKV infection, direct viral neuropathogenic mechanisms or initiation of immune molecular mimicry against nervous system antigens ahead of the clinical symptoms of viral infection.
Proving a causal relationship between ZIKV infection and Guillain–Barré syndrome is challenging, say Jennifer Frontera (Cleveland Clinic, Ohio, USA) and Ivan da Silva (Universidade Federal Fluminense, Niteroi, Brazil) in a related editorial.
“In keeping with Hill criteria for causality, the authors show a consistent, specific, temporal relationship which is analogous to relationships between ZIKV infection and the Guillain–Barré syndrome observed in other countries”, they comment.
By Lucy Piper
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