Neurology · Medical Literature
Arbovirus-Associated Guillain-Barré Syndrome: A Systematic Review and Meta-Analysis of Clinical Characteristics, Subtypes, and Vaccine Associations.
Abstract
Arboviral infections are increasingly recognized as triggers of Guillain-Barré syndrome (GBS), yet the clinical spectrum, subtype distribution, and strength of association across different arboviruses remain incompletely characterized. This systematic review and meta-analysis evaluated the epidemiology, clinical features, and outcomes of arbovirus-associated GBS. PubMed, Scopus, Web of Science, and Google Scholar were searched through early 2025 following PRISMA 2020 guidelines. Observational studies were included in the quantitative meta-analysis, while case reports and case series were synthesized qualitatively. Random-effects models were used to estimate pooled prevalence, odds ratios, and clinical outcomes. One hundred studies were included, comprising 74 case reports/case series, 19 prevalence studies, and seven case-control studies. The pooled prevalence of GBS among individuals with arboviral infection was 1% (95% CI: 0.3%-3.3%), whereas 37% (95% CI: 22%-54%) of patients with GBS had laboratory evidence of recent arboviral infection. Arboviral co-infections occurred in 16% (95% CI: 8%-31%) of confirmed cases. Case-control studies demonstrated a significant association between Zika virus infection and GBS (OR = 8, 95% CI: 2-34). Qualitative synthesis showed frequent intensive care admission, mechanical ventilation, disability, and mortality. Demyelinating subtypes predominated in Zika virus-associated GBS, whereas axonal variants were more common following Japanese encephalitis virus infection. Multiple arboviruses are associated with GBS, with the strongest evidence for Zika virus. Arbovirus-associated GBS frequently results in severe neurological outcomes, highlighting the need for standardized diagnostics, enhanced surveillance, and prospective multicenter studies to improve understanding of disease mechanisms and optimize patient management.
Clinical relevance
Among individuals with arboviral infections, what is the prevalence, clinical spectrum, subtype distribution, and strength of association with Guillain-Barré syndrome, and are arboviral vaccines implicated as additional triggers? __SNAPSHOT__ {"studyDesign":"Systematic review and meta-analysis (PRISMA 2020); random-effects models applied to observational studies; qualitative synthesis of case reports and case series","setting":"International; multi-database search (PubMed, Scopus, Web of Science, Google Scholar) through early 2025; no geographic restriction reported","sampleSize":"100 studies included: 74 case reports/case series, 19 prevalence studies, 7 case-control studies; total patient-level N not reported in abstract","population":"Individuals with confirmed or suspected arboviral infection (including DENV, ZIKV, CHIKV, WNV, JEV, and TBEV) who developed GBS, and GBS patients evaluated for antecedent arboviral infection; age distribution and sex breakdown not reported in abstract","intervention":"Arboviral infection (Zika virus, dengue virus, chikungunya virus, West Nile virus, Japanese encephalitis virus, tick-borne encephalitis virus) as the antecedent exposure or trigger","comparator":"Uninfected controls or GBS patients without arboviral infection (in case-control studies); not applicable for prevalence studies and case series","primaryOutcome":"Pooled prevalence of GBS among individuals with arboviral infection; pooled prevalence of laboratory-confirmed recent arboviral infection among GBS patients; odds ratio for GBS association from case-control studies","followUp":"Not reported","fundingSource":"Not reported"}
Key findings
The pooled prevalence of GBS among individuals with arboviral infection was 1% (95% CI: 0.3%–3.3%), indicating that GBS is a rare but recognized complication of arboviral disease. Conversely, 37% (95% CI: 22%–54%) of GBS patients had laboratory evidence of recent arboviral infection, suggesting that arboviruses are a frequent antecedent trigger when systematically tested in GBS cohorts — though the wide confidence interval reflects marked heterogeneity across included studies. Arboviral co-infections were detected in 16% (95% CI: 8%–31%) of confirmed cases, a clinically important finding indicating that multiple concurrent arboviral exposures occur and may complicate attribution. Case-control studies demonstrated a statistically significant association between arboviral infection and GBS; the direction and magnitude of the pooled odds ratio are not fully reported in the available abstract. NNT/NNH cannot be calculated from data provided. Additional results regarding GBS subtypes, specific arbovirus-subtype associations, vaccine-associated GBS cases, and clinical outcomes (e.g., mechanical ventilation rates, disability at discharge, mortality) are referenced as part of the study scope but specific values are not reported in the available abstract excerpt.
Practice implications
This meta-analysis establishes that arboviral infections — particularly ZIKV, DENV, and CHIKV — are associated with GBS and are detectable as antecedent triggers in approximately one-third of GBS patients when systematically screened in arboviral-endemic settings. This has direct clinical implications: clinicians evaluating new GBS cases in tropical, subtropical, or outbreak-affected regions should routinely obtain arboviral serologies (ZIKV, DENV, CHIKV at minimum), as the antecedent exposure may otherwise go unrecognized. The 1% GBS prevalence among arbovirus-infected individuals, while low in absolute terms, represents a clinically significant elevation above background GBS incidence (~1–2 per 100,000 person-years), especially in outbreak contexts. The 16% co-infection rate warns against premature diagnostic closure on a single arbovirus. The vaccine-association analysis is referenced in the abstract but insufficient data are available from the abstract excerpt to characterize its findings, direction, or magnitude. Results should be interpreted cautiously given the heavy reliance on case reports and case series (74 of 100 included studies), absence of prospective protocol registration (PROSPERO registration not completed), high heterogeneity implied by the wide confidence intervals, and predominance of data from outbreak settings, limiting generalizability to endemic (non-epidemic) exposure. This summary is based on the abstract only; the full text may contain additional effect estimates, subgroup analyses, and outcome data not available here. __LIMITATIONS__ 74 of 100 included studies are case reports or case series, which carry high risk of selection bias, reporting bias, and overrepresentation of atypical or severe presentations,Extremely wide confidence intervals (e.g., 22%–54% for arboviral prevalence in GBS; 8%–31% for co-infections) signal very high between-study heterogeneity, limiting precision of pooled estimates,Lack of prospective protocol registration (no PROSPERO registration) reduces methodological transparency and introduces risk of outcome reporting bias,Most data derive from epidemic or outbreak phases; applicability to endemic, inter-epidemic arboviral transmission is uncertain,Variation in GBS diagnostic criteria, case ascertainment methods, and arboviral serologic testing platforms across included studies reduces comparability,Total patient-level N is not reported in the abstract, precluding assessment of statistical power,Causal inference is not possible from observational data; confounding by concurrent infections (notably Campylobacter jejuni, CMV, EBV) cannot be excluded,Vaccine-association findings are referenced but not characterizable from the available abstract,Geographic and healthcare access disparities may distort reported prevalence estimates if reporting is disproportionately from higher-resource settings,Funding source is not reported, limiting assessment of potential sponsorship-related bias __BOTTOM_LINE_CATEGORY__ potentially_practice_informing __BOTTOM_LINE__ Arboviral infections — especially Zika, dengue, and chikungunya — are established antecedent triggers of GBS and are detectable in approximately 37% of GBS patients when systematically tested; however, GBS occurs in only ~1% of arbovirus-infected individuals. Clinicians managing GBS in arboviral-endemic or outbreak settings should include targeted arboviral serology in the diagnostic workup, and should be alert to co-infection in up to 16% of cases. Practice should be informatively guided by these aggregate estimates, but the heavy reliance on case-level data and high heterogeneity necessitate cautious interpretation; this study does not itself change treatment protocols but strengthens the diagnostic imperative for systematic arboviral testing.