The Gut microbiota is crucial for regulating immune responses in autoimmune neuropathies like Guillain–Barré syndrome (GBS). Yet, its influence on disease course and recovery remains unclear. This study examined gut microbiota dysbiosis in 57 GBS patients and 57 age- and gender-matched healthy controls, following 32 patients for six months to identify microbial signatures associated with disease onset and clinical progression. Gut microbiota profile was obtained through 16S rRNA sequencing (V4-region) and processed using Qiime2-Dada2. Alpha/beta diversity matrices and linear discriminant analysis were applied. Acute-GBS showed significantly altered microbial composition compared to controls, with elevated Enterococcus, Streptococcus, Bacteroides, Ruminococcues-gnavus-group, Lachnoclostridium, taxa, along with reduced Prevotella, Alloprevotella, Megasphaera, Dialister, and Agathobacter. Severe GBS correlated with lower Prevotella, Agathobacter, Subdoligranulum, Dialister, and elevated Enterococcus abundance. At six-months, Streptococcus, Agathobacter, and Eubacterium hallii trended toward normalization, while Enterococcus, Clostridium sensu stricto-1, Romboutsia, Dialistes, Alloprevotella, and Prevotella remained persistently altered. Patients with good 6-months outcomes exhibited reduced Bacteroides, Weissella, UCG-002 and increased Lactobacillus, Ruminococcus gauvreauii, Blautia, Collinsella, and Megasphaera. These findings identify distinct gut microbial signatures associated with GBS onset and clinical course, highlighting their potential as exploratory microbiome-associated biomarkers linked with prognosis that require further validation.
Guillain-Barré syndrome is an acute polyradiculoneuropathy in which preceding infections often elicit the production of antibodies that target peripheral nerve antigens, principally gangliosides. Anti-ganglioside antibodies are thought to play a key role in the clinical diversity of the disease and can be helpful in clinical practice. Extensive research into clinical associations of individual anti-ganglioside antibody specificities has been performed. Recent research has highlighted glycolipid complexes, glycolipid combinations that may alter antibody binding, as targets. In this study, we investigated antibody reactivity patterns to glycolipids and glycolipid complexes using combinatorial array, in relation to clinical features in Guillain-Barré syndrome. In total, 1413 patients from the observational International Guillain-Barré syndrome Outcome Study (0-91 years, 60.3% male) and 1061 controls (healthy, family, infectious, vaccination, other neurological disease) were included. Acute-phase sera from patients were screened for IgM, IgG, and IgA reactivity against 15 glycolipids and one phospholipid and their heteromeric complexes, similarly to archived control sera. Antibody specificities and reactivity patterns were analysed in relation to clinical features. Of all patients, 1309 (92.6%) were positive for at least one anti-glycolipid (complex) antibody. Anti-GM1 and anti-GQ1b (complex) antibodies best distinguished motor Guillain-Barré syndrome and Miller Fisher syndrome from controls, with antibodies to glycolipid complexes outperforming antibodies to single glycolipids. Three models consisting of anti-glycolipid (complex) antibodies distinguished patients with Guillain-Barré syndrome, the motor variant, and Miller Fisher syndrome from controls with high sensitivity and specificity, performing better than antibodies to single glycolipids used in clinical practice. Seven patient clusters with particular antibody reactivity patterns were identified. These clusters were distinguished by geographical region, clinical variants, preceding Campylobacter jejuni infection, electrophysiological subtypes, the Medical Research Council sum score at study entry, and the ability to walk 10 m unaided at 26 weeks. Two patient clusters with distinct anti-GM1 (complex) reactivity (broad versus restricted) differed in frequency of the axonal subtype. In cumulative incidence analyses, 15 anti-glycolipid (complex) antibodies were associated with the time required to regain the ability to walk 10 m unaided. After adjustment for known prognostic factors, IgG anti-GQ1b:GM4, GQ1b:PS and GQ1b:Sulfatide remained associated with faster recovery. Addition of anti-glycolipid antibodies to clinical prognostic models slightly improved their discriminative capacity, though insufficiently to improve the models. Measurement of anti-glycolipid antibodies by combinatorial array increases the diagnostic yield compared to assaying single glycolipids, identifies clinically relevant antibody reactivity patterns to glycolipids and glycolipid complexes, and may be useful in outcome prediction in Guillain-Barré syndrome.
Guillain-Barré syndrome (GBS) is a rare immune-mediated polyradiculoneuropathy. Patients typically develop rapidly progressive weakness and sensory deficits that can result in complete paralysis requiring mechanical ventilation. GBS is usually a monophasic disease in which an aberrant immune response to an infection or other trigger damages the peripheral nerves. For example, in patients with preceding Campylobacter jejuni infection, molecular mimicry causes a cross-reactive antibody response to nerve gangliosides. Diagnosis is based on clinical features, supported by cerebrospinal fluid analysis and nerve conduction studies. Effective treatments include plasma exchange and intravenous immunoglobulins. However, ~20% of patients who received treatment are unable to walk after 6 months and ~5% die as a consequence of GBS. Important knowledge gaps in GBS include its pathogenesis, especially after viral infections. In addition, there is a lack of specific biomarkers to improve the diagnosis, monitor the disease activity, and predict the clinical course and outcome of GBS. Major challenges for the future include finding more effective and personalized treatments, which are affordable in low-income and middle-income countries, and preparation for outbreaks of infections as potential triggers for GBS.
Guillain–Barré syndrome (GBS) is a rare immune-mediated polyradiculoneuropathy. Patients typically develop rapidly progressive weakness and sensory deficits that can result in complete paralysis requiring mechanical ventilation. GBS is usually a monophasic disease in which an aberrant immune response to an infection or other trigger damages the peripheral nerves. For example, in patients with preceding Campylobacter jejuni infection, molecular mimicry causes a cross-reactive antibody response to nerve gangliosides. Diagnosis is based on clinical features, supported by cerebrospinal fluid analysis and nerve conduction studies. Effective treatments include plasma exchange and intravenous immunoglobulins. However, ~20% of patients who received treatment are unable to walk after 6 months and ~5% die as a consequence of GBS. Important knowledge gaps in GBS include its pathogenesis, especially after viral infections. In addition, there is a lack of specific biomarkers to improve the diagnosis, monitor the disease activity, and predict the clinical course and outcome of GBS. Major challenges for the future include finding more effective and personalized treatments, which are affordable in low-income and middle-income countries, and preparation for outbreaks of infections as potential triggers for GBS. Guillain–Barré syndrome is an acute immune-mediated polyneuropathy that can occur following infections or other rare triggers. In this Primer, Leonhard and colleagues summarize the epidemiology, mechanisms and diagnosis of this disease and discuss its management, patient quality of life and open research questions.
Rabies is one of the oldest and deadliest disease in the world and causes a significant number of deaths. Over 95% of all human deaths from rabies occur in Asia and Africa. Bangladesh is endemic to rabies. Since the National Rabies Elimination Program was successfully implemented in 2010, Bangladesh has achieved considerable strides in preventing human mortality from rabies. Rabies post-exposure prophylaxis (PEP) is widely used and very effective. However, occasional incidences of rabies in individuals who have initiated or completed PEP have been documented.In this observational cohort study, a total of 45 clinically diagnosed rabies patients, irrespective of age and gender, from 33 different districts of Bangladesh were studied. A detailed clinico-demographic profile, including post-exposure prophylaxis received before the development of rabies, was recorded. RT-PCR for rabies was done on the saliva samples of all patients. An MRI, EEG, and CSF viral panel was also done for patients who were RT-PCR negative.From January 2022 to June 2023, 45 clinically diagnosed rabies cases were admitted to IDH. Two of them were PCR-positive. The median age of the patients was 11 years (IQR 5–40 years). 37 (82.2%) were males. Dogs were the most commonly accused animal (86.5%). The median time from exposure to the development of rabies symptoms was 37 days (IQR 22–60 days, range 07–240 days). The median duration of illness was 5 days (IQR: 3–7 days). All of the patients had severe exposure. Only 5 (11%) patients received complete WHO-recommended post-exposure prophylaxis (PEP). 20 (45%) patients received only the rabies vaccine (incomplete PEP) without a wound wash or RIG. All the patients received supportive management. In addition to that, three patients were given intrathecal RIG at 40 U/kg/dose for two doses seven days apart. Out of three patients, two survived for more than two months. One patient is still alive after six months with significant morbidity.There is no cure for rabies; however, appropriate animal bite management by trained medical personnel with WHO-recommended PEP is the only way to achieve the goal of a rabies-free world.
Leonhard et al. analyzed the pattern of preceding infections in a large cohort of 768 patients with Guillain-Barré syndrome (GBS) from 19 countries spread over 5 continents.1 To some extent, this study is biased because the majority of the patients were from temperate regions and testing for preceding infections was limited to only 5 microorganisms ( Campylobacter jejuni , hepatitis E virus, Mycoplasma pneumoniae , cytomegalovirus, and Epstein-Barr virus). The burden of infections varies significantly across tropical and temperate regions, with arboviral infections being quite prevalent in the tropics. Dengue, chikungunya, Japanese encephalitis, and zika have consistently been associated with GBS.2-4
BACKGROUND AND AIMS:Considerable variation in clinical practice for management of Guillain-Barré syndrome (GBS) has been observed worldwide. Diagnosis and treatment are challenging in low- and middle-income countries (LMIC) due to lack of facilities and treatment availability. We aimed to evaluate current clinical practice and limitations and to provide recommendation for GBS management in low-resource settings. METHODS:We conducted an explanatory-sequential mixed-methods survey among neurologists and internists working in tertiary and secondary government hospitals in Bangladesh. There were two phases: (1) quantitative (cross-sectional survey to evaluate clinical practice and limitations); (2) qualitative (key informant interview to explain certain clinical practice and provide recommendations for GBS management in LMIC). Data were analyzed by frequencies, χ2 test and thematic analysis. RESULTS:Among 159 physicians (65 neurologists and 94 internists), 11% and 8% physicians used Brighton and NINDS criteria respectively to diagnose GBS. Specific treatment protocols of GBS were used by 12% physicians. Overcrowding of patients, inadequate diagnostic facilities, high costs of standard therapy, and inadequate logistics and trained personnel for intensive care unit and rehabilitation services were considered major challenges for GBS management. In qualitative part, respondents recommended regular training for the physicians, development of cost-effective treatment strategies and appropriate patients' referral and management guideline considering existing limitations in health service delivery and socio-economic status of the country. INTERPRETATION:Current study design and recommendations might be applied for other LMIC. Such data can assist policymakers to identify areas requiring urgent attention and take required action to improve GBS management in LMIC.
Background and Objectives The clinical course and outcome of the Guillain-Barré syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity. Methods We used prospective data from the first 1,500 patients included in IGOS, aged ≥6 years and unable to walk independently. We evaluated whether the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using 2 measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC) and (2) calibration: observed vs predicted probability of being unable to walk independently. To improve the model predictions, we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors. Results For validation of mEGOS at entry, 809 patients were eligible (Europe/North America [n = 677], Asia [n = 76], other [n = 56]), and 671 for validation of mEGOS at week 1 (Europe/North America [n = 563], Asia [n = 65], other [n = 43]). AUC values were >0.7 in all regional subgroups. In the Europe/North America subgroup, observed outcomes were worse than predicted; in Asia, observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort. Discussion mEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in patients with GBS, also in countries outside the Netherlands. We developed a region-specific version of mEGOS for patients from Europe/North America. Classification of Evidence This study provides Class II evidence that the mEGOS accurately predicts the inability to walk unaided at 4 and 26 weeks in patients with GBS. Trial Registration Information NCT01582763.
Background and Objectives The clinical course and outcome of the Guillain-Barre syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity. Methods We used prospective data from the first 1,500 patients included in IGOS, aged >= 6 years and unable to walk independently. We evaluated whether the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using 2 measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC) and (2) calibration: observed vs predicted probability of being unable to walk independently. To improve the model predictions, we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors. Results For validation of mEGOS at entry, 809 patients were eligible (Europe/North America [n = 677], Asia [n = 76], other [n = 56]), and 671 for validation of mEGOS at week 1 (Europe/North America [n = 563], Asia [n = 65], other [n = 43]). AUC values were >0.7 in all regional subgroups. In the Europe/North America subgroup, observed outcomes were worse than predicted; in Asia, observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort. Discussion mEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in patients with GBS, also in countries outside the Netherlands. We developed a region-specific version of mEGOS for patients from Europe/North America. Classification of Evidence This study provides Class II evidence that the mEGOS accurately predicts the inability to walk unaided at 4 and 26 weeks in patients with GBS.
Objective To investigate features of Guillain-Barré syndrome (GBS) following SARS-CoV-2 vaccines and evaluate for a causal link between the two.Methods We captured cases of GBS after SARS-CoV-2 vaccination through a national, open-access, online surveillance system. For each case, the certainty of GBS was graded using the Brighton criteria, and the relationship to the vaccine was examined using modified WHO Causality Assessment criteria. We compared age distribution of cases with that of prepandemic GBS cases and clinical features with the International GBS Outcome Study (IGOS).Results Between 1 January and 30 June 2021, we received 67 reports of GBS following the ChAdOx1 vaccine (65 first doses) and three reports following the BNT162b2 vaccine (all first doses). The causal association with the vaccine was classified as probable for 56 (80%, all ChAdOx1), possible for 12 (17%, 10 ChAdOx1) and unlikely for two (3%, 1 ChAdOx1). A greater proportion of cases occurred in the 50–59 age group in comparison with prepandemic GBS. Most common clinical variants were sensorimotor GBS (n=55; 79%) and facial diplegia with paraesthesias (n=10; 14%). 10% (n=7/69) of patients reported an antecedent infection, compared with 77% (n=502/652) of the IGOS cohort (p<0.00001). Facial weakness (63% (n=44/70) vs 36% (n=220/620); p<0.00001) and sensory dysfunction (93% (n=63/68) vs 69% (n=408/588); p=0.00005) were more common but disease severity and outcomes were similar to the IGOS study.Interpretation Most reports of GBS followed the first dose of ChAdOx1 vaccine. While our study cannot confirm or refute causation, this observation, together with the absence of alternative aetiologies, different than expected age distribution and the presence of unusual clinical features support a causal link. Clinicians and surveillance bodies should remain vigilant to the possibility of this very rare adverse event and its atypical variants.
In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barre syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies. The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization. Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016]. The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12-22). Patients with SARS-CoV-2 infection shared uniform neurological features, similar to those previously described in other post-viral GBS patients. The frequency (22%) of a preceding SARS-CoV-2 infection in our study population was higher than estimates of the contemporaneous background prevalence of SARS-CoV-2, which may be a result of recruitment bias during the pandemic, but could also indicate that GBS may rarely follow a recent SARS-CoV-2 infection. Consistent with previous studies, we found no increase in patient recruitment during the pandemic for our ongoing International GBS Outcome Study compared to previous years, making a strong relationship of GBS with SARS-CoV-2 unlikely. A case-control study is required to determine if there is a causative link or not.
ABSTRACT Global health research partnerships with institutions from high-income countries and low- and middle-income countries are one of the European Commission’s flagship programmes. Here, we report on the ZikaPLAN research consortium funded by the European Commission with the primary goal of addressing the urgent knowledge gaps related to the Zika epidemic and the secondary goal of building up research capacity and establishing a Latin American-European research network for emerging vector-borne diseases. Five years of collaborative research effort have led to a better understanding of the full clinical spectrum of congenital Zika syndrome in children and the neurological complications of Zika virus infections in adults and helped explore the origins and trajectory of Zika virus transmission. Individual-level data from ZikaPLAN`s cohort studies were shared for joint analyses as part of the Zika Brazilian Cohorts Consortium, the European Commission-funded Zika Cohorts Vertical Transmission Study Group, and the World Health Organization-led Zika Virus Individual Participant Data Consortium. Furthermore, the legacy of ZikaPLAN includes new tools for birth defect surveillance and a Latin American birth defect surveillance network, an enhanced Guillain-Barre Syndrome research collaboration, a de-centralized evaluation platform for diagnostic assays, a global vector control hub, and the REDe network with freely available training resources to enhance global research capacity in vector-borne diseases.
A síndrome de Guillain–Barré (SGB) é uma doença imunomediada rara, mas potencialmente fatal, dos nervos periféricos e das raízes nervosas, que é geralmente desencadeada por infecções. A incidência da SGB pode, portanto, aumentar durante surtos de doenças infecciosas, como foi observado durante a epidemia do vírus Zika em 2013 na Polinésia Francesa e em 2015 na América Latina. O diagnóstico e manejo da SGB podem ser complicados visto que sua apresentação clínica e o curso da doença são heterogêneos e não existem atualmente diretrizes clínicas internacionais disponíveis. Para auxiliar os médicos, especialmente em um cenário de surto, desenvolvemos uma diretriz globalmente aplicável para o diagnóstico e manejo da SGB. A diretriz se baseia no consenso de especialistas e na literatura atual e tem uma estrutura de dez etapas para facilitar seu uso na prática clínica. Primeiro fornecemos uma introdução aos critérios diagnósticos, às variantes clínicas e aos diagnósticos diferenciais da SGB. A seguir, as dez etapas abrangem o reconhecimento e o diagnóstico precoces da SGB, a internação na unidade de terapia intensiva, a indicação e seleção do tratamento, o monitoramento e tratamento da progressão da doença, o prognóstico do curso e resultado clínico e o manejo das complicações e sequelas.
Background Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barre syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barre syndrome with a predicted poor outcome. Methods In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (>= 12 years) with Guillain-Barre syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of >= 6) according to the modified Erasmus Guillain-Barre syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7-9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barre syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis. Findings Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barre syndrome disability score at 4 weeks was 1.4 (95% CI 0.6-3.3; p=0.45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13-24 weeks after randomisation). Interpretation Our study does not provide evidence that patients with Guillain-Barre syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barre syndrome. Funding Prinses Beatrix Spierfonds and Sanquin Plasma Products. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
The epidemiology, clinical characteristics, management and outcome of Guillain-Barré syndrome (GBS) differ between low-income and middle-income countries (LMIC) and high-income countries (HIC). At present, limited data are available on GBS in LMIC and the true incidence of GBS in many LMIC remains unknown. Increased understanding of GBS in LMIC is needed because poor hygiene and high exposure to infections render populations in LMIC vulnerable to GBS outbreaks. Furthermore, insufficient diagnostic and health-care facilities in LMIC contribute to delayed diagnosis in patients with severe presentations of GBS. In addition, the lack of national clinical guidelines and absence of affordable, effective treatments contribute to worse outcomes and higher mortality in LMIC than HIC. Systematic population-based surveillance studies, cohort and case-control studies are required to understand the incidence and risk factors for GBS. Novel, targeted and cost-effective treatment strategies need to be developed in the context of health system challenges in LMIC. To ensure integrative rehabilitation services in LMIC, existing prognostic models must be validated, and responsive outcome measures that are cross-culturally applicable must be developed. Therefore, fundamental and applied research to improve the clinical management of GBS in LMIC should become a critical focus of future research programmes.
Global health research partnerships with institutions from high-income countries and low- and middle-income countries are one of the European Commission's flagship programmes. Here, we report on the ZikaPLAN research consortium funded by the European Commission with the primary goal of addressing the urgent knowledge gaps related to the Zika epidemic and the secondary goal of building up research capacity and establishing a Latin American-European research network for emerging vector-borne diseases. Five years of collaborative research effort have led to a better understanding of the full clinical spectrum of congenital Zika syndrome in children and the neurological complications of Zika virus infections in adults and helped explore the origins and trajectory of Zika virus transmission. Individual-level data from ZikaPLAN`s cohort studies were shared for joint analyses as part of the Zika Brazilian Cohorts Consortium, the European Commission-funded Zika Cohorts Vertical Transmission Study Group, and the World Health Organization-led Zika Virus Individual Participant Data Consortium. Furthermore, the legacy of ZikaPLAN includes new tools for birth defect surveillance and a Latin American birth defect surveillance network, an enhanced Guillain-Barre Syndrome research collaboration, a de-centralized evaluation platform for diagnostic assays, a global vector control hub, and the REDe network with freely available training resources to enhance global research capacity in vector-borne diseases.
Objective To identify the clinical phenotypes and infectious triggers in the 2019 Peruvian Guillain-Barré syndrome (GBS) outbreak. Methods We prospectively collected clinical and neurophysiologic data of patients with GBS admitted to a tertiary hospital in Lima, Peru, between May and August 2019. Molecular, immunologic, and microbiological methods were used to identify causative infectious agents. Sera from 41 controls were compared with cases for antibodies to Campylobacter jejuni and gangliosides. Genomic analysis was performed on 4 C jejuni isolates. Results The 49 included patients had a median age of 44 years (interquartile range [IQR] 30–54 years), and 28 (57%) were male. Thirty-two (65%) had symptoms of a preceding infection: 24 (49%) diarrhea and 13 (27%) upper respiratory tract infection. The median time between infectious to neurologic symptoms was 3 days (IQR 2–9 days). Eighty percent had a pure motor form of GBS, 21 (43%) had the axonal electrophysiologic subtype, and 18% the demyelinating subtype. Evidence of recent C jejuni infection was found in 28/43 (65%). No evidence of recent arbovirus infection was found. Twenty-three cases vs 11 controls (OR 3.3, confidence interval [CI] 95% 1.2–9.2, p < 0.01) had IgM and/or IgA antibodies against C jejuni. Anti-GM1:phosphatidylserine and/or anti-GT1a:GM1 heteromeric complex antibodies were strongly positive in cases (92.9% sensitivity and 68.3% specificity). Genomic analysis showed that the C jejuni strains were closely related and had the Asn51 polymorphism at cstII gene. Conclusions Our study indicates that the 2019 Peruvian GBS outbreak was associated with C jejuni infection and that the C jejuni strains linked to GBS circulate widely in different parts of the world.