Management of Guillain-Barré syndrome in Bangladesh: Clinical practice, limitations and recommendations for low- and middle-income countries.

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.

Validation and adjustment of modified Erasmus GBS outcome score in Bangladesh.

OBJECTIVE: We have assessed and improved the performance of the modified Erasmus GBS Outcome Score (mEGOS) among patients with Guillain-Barré syndrome (GBS) from Bangladesh. METHODS: Validation cohort consisted of patients with GBS from two prospective cohort studies in Bangladesh. Poor outcome was defined as being unable to walk independently at week 4 and week 26. We excluded patients able to walk independently, patients who died within the first week, or with missing GBS disability scores. Performance of mEGOS at entry and week 1 was determined based on the discriminative ability (ability to differentiate between patients able and unable to walk independently; measured using the area under the receiver operating characteristic curves [AUC]) and calibration (observed probability versus predicted probability of poor outcome). RESULTS: A total of 506 patients aged ≥6-year-old were enrolled, with 471 and 366 patients included in mEGOS validation analysis at entry and week 1, respectively. The AUC values for predicting poor outcome (1) at week 4 were 0.69 (mEGOS entry) and 0.78 (mEGOS week 1) and (2) at week 26 were 0.67 (mEGOS entry) and 0.70 (mEGOS week 1). Mean predicted probabilities of poor outcome corresponded with observed outcomes except for the probability of poor outcome at week 4 which was overestimated by mEGOS week 1. This was resolved by updating the model intercept. INTERPRETATION: The mEGOS shows valid outcome predictions among patients with GBS from Bangladesh. The model can aid the identification of patients at high risk of poor outcome and help to adequately allocate healthcare resources in low-resource settings.

Draft Genome Sequences of Four Strains of Campylobacter jejuni Isolated from Patients with Axonal Variant of Guillain-Barré Syndrome in Bangladesh.

Four Campylobacter jejuni strains (Z191005RS, Z191005SS, Z201020RS, and Z201020SS) isolated from the axonal variant of Guillain-Barré syndrome (GBS) were sequenced using Illumina technology. The average genome size was from 1.61 to 1.63 gb, with a very high coverage ranging from 654× to 758×, which facilitates the possibility of rare variant calling.

The Etiology of Childhood Pneumonia in Bangladesh: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study.

BACKGROUND: Pneumonia remains the leading infectious cause of death among children <5 years, but its cause in most children is unknown. We estimated etiology for each child in 2 Bangladesh sites that represent rural and urban South Asian settings with moderate child mortality. METHODS: As part of the Pneumonia Etiology Research for Child Health study, we enrolled children 1-59 months of age with World Health Organization-defined severe and very severe pneumonia, plus age-frequency-matched controls, in Matlab and Dhaka, Bangladesh. We applied microbiologic methods to nasopharyngeal/oropharyngeal swabs, blood, induced sputum, gastric and lung aspirates. Etiology was estimated using Bayesian methods that integrated case and control data and accounted for imperfect sensitivity and specificity of the measurements. RESULTS: We enrolled 525 cases and 772 controls over 24 months. Of the cases, 9.1% had very severe pneumonia and 42.0% (N = 219) had infiltrates on chest radiograph. Three cases (1.5%) had positive blood cultures (2 Salmonella typhi, 1 Escherichia coli and Klebsiella pneumoniae). All 4 lung aspirates were negative. The etiology among chest radiograph-positive cases was predominantly viral [77.7%, 95% credible interval (CrI): 65.3-88.6], primarily respiratory syncytial virus (31.2%, 95% CrI: 24.7-39.3). Influenza virus had very low estimated etiology (0.6%, 95% CrI: 0.0-2.3). Mycobacterium tuberculosis (3.6%, 95% CrI: 0.5-11.0), Enterobacteriaceae (3.0%, 95% CrI: 0.5-10.0) and Streptococcus pneumoniae (1.8%, 95% CrI: 0.0-5.9) were the only nonviral pathogens in the top 10 etiologies. CONCLUSIONS: Childhood severe and very severe pneumonia in young children in Bangladesh is predominantly viral, notably respiratory syncytial virus.

Reply to Fabre et al. Comment on "Tanmoy et al. CRISPR-Cas Diversity in Clinical Salmonella enterica Serovar Typhi Isolates from South Asian Countries. Genes 2020, 11, 1365".

We respectfully thank Fabre et al. [...].

Draft Genome Sequences of Three Strains of Campylobacter jejuni Isolated from Patients with Guillain-Barré Syndrome in Bangladesh.

Campylobacter jejuni is the pathogen most commonly associated with Guillain-Barré syndrome (GBS). The present work describes the draft genome sequences of 3 C. jejuni strains, BD39, BD67, and BD75, isolated from stool specimens of patients with C. jejuni-triggered GBS using Illumina technologies.

Guillain-Barré syndrome in low-income and middle-income countries: challenges and prospects.

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.

Tracking the Emergence of Azithromycin Resistance in Multiple Genotypes of Typhoidal Salmonella.

The rising prevalence of antimicrobial resistance in Salmonella enterica serovars Typhi and Paratyphi A, causative agents of typhoid and paratyphoid, have led to fears of untreatable infections. Of specific concern is the emerging resistance against azithromycin, the only remaining oral drug to treat extensively drug resistant (XDR) typhoid. Since the first report of azithromycin resistance from Bangladesh in 2019, cases have been reported from Nepal, India, and Pakistan. The genetic basis of this resistance is a single point mutation in the efflux pump AcrB (R717Q/L). Here, we report 38 additional cases of azithromycin-resistant (AzmR) Salmonella Typhi and Paratyphi A isolated in Bangladesh between 2016 and 2018. Using genomic analysis of 56 AzmR isolates from South Asia with AcrB-R717Q/L, we confirm that this mutation has spontaneously emerged in different Salmonella Typhi and Paratyphi A genotypes. The largest cluster of AzmR Typhi belonged to genotype 4.3.1.1; Bayesian analysis predicts the mutation to have emerged sometime in 2010. A travel-related Typhi isolate with AcrB-R717Q belonging to 4.3.1.1 was isolated in the United Kingdom, increasing fears of global spread. For real-time detection of AcrB-R717Q/L, we developed an extraction-free, rapid, and low-cost mismatch amplification mutation assay (MAMA). Validation of MAMA using 113 AzmR and non-AzmR isolates yielded >98% specificity and sensitivity versus phenotypic and whole-genome sequencing assays currently used for azithromycin resistance detection. With increasing azithromycin use, AcrB-R717Q/L is likely to be acquired by XDR strains. The proposed tool for active detection and surveillance of this mutation may detect pan-oral drug resistance early, giving us a window to intervene.IMPORTANCE In the early 1900s, with mortality of ∼30%, typhoid and paratyphoid ravaged parts of the world; with improved water, sanitation, and hygiene in resource-rich countries and the advent of antimicrobials, mortality dwindled to <1%. Today, the burden rests disproportionately on South Asia, where the primary means for combatting the disease is antimicrobials. However, prevalence of antimicrobial resistance is rising and, in 2016, an extensively drug resistant Typhi strain triggered an ongoing outbreak in Pakistan, leaving only one oral drug, azithromycin, to treat it. Since the description of emergence of azithromycin resistance, conferred by a point mutation in acrB (AcrB-R717Q/L) in 2019, there have been increasing numbers of reports. Using genomics and Bayesian analysis, we illustrate that this mutation emerged in approximately 2010 and has spontaneously arisen multiple times. Emergence of pan-oral drug resistant Salmonella Typhi is imminent. We developed a low-cost, rapid PCR tool to facilitate real-time detection and prevention policies.

Changes in motor nerve excitability in acute phase Guillain-Barré syndrome.

BACKGROUND: The most common subtypes of Guillain-Barré syndrome (GBS) are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). In the first days after the onset of weakness, standard nerve conduction studies (NCS) may not distinguish GBS subtypes. Reduced nerve excitability may be an early symptom of nerve dysfunction, which can be determined with the compound muscle action potential (CMAP) scan. The aim of this study was to explore whether early changes in motor nerve excitability in GBS patients are related to various subtypes. METHODS: Prospective case-control study in 19 GBS patients from The Netherlands and 22 from Bangladesh. CMAP scans were performed within 2 days of hospital admission and NCS 7-14 days after onset of weakness. CMAP scans were also performed in age- and country-matched controls. RESULTS: CMAP scan patterns of patients who were classified as AMAN were distinctly different compared to the CMAP scan patterns of the patients who were classified as AIDP. The most pronounced differences were found in the stimulus intensity parameters. CONCLUSIONS: CMAP scans made at hospital admission demonstrate several characteristics that can be used as an early indicator of GBS subtype.

Electrophysiology of Guillain-Barré syndrome in Bangladesh: A prospective study of 312 patients.

OBJECTIVE: To describe the electrophysiological features in relation to clinical and serological findings of Guillain-Barré syndrome (GBS) in the national neuroscience hospital in Bangladesh. This is one of the few studies that investigated GBS patients using standardized electrophysiology in low-income countries. METHODS: In a prospective and observational study, we investigated 312 GBS patients by standardized clinical, serological and electrophysiological methods. Unilateral motor and sensory nerve conduction studies (NCS) were performed within two weeks of onset of weakness. Follow up NCS were performed in 189 patients and classified according to eight sets of established GBS criteria. Serology included assessment of anti-GM1 antibodies and anti-campylobacter jejuni lipo-oligosaccharide (LOS) antibodies. RESULTS: Depending on the criteria used, 44-59% patients had axonal GBS with anti-GM1 antibodies being present in 55-58% and 9-42% patients had demyelinating GBS with anti-GM1 antibodies being present in 7-35%. Conduction block (CB) with demyelinative slowing in the same nerve segment was found in 24% (74/312) patients, and CB without demyelinative slowing in the same nerve segment was found in 18% (56/312) patients, of whom anti-GM1 antibodies were found in 27% and 57% patients respectively. Follow-up NCS showed a change in GBS classification in 11-26% of patients, mainly from demyelinating to axonal GBS. CONCLUSIONS: The predominant subtype of GBS in Bangladesh is axonal but demyelinating GBS also occurs with classification being strongly dependent on the applied criteria. SIGNIFICANCE: The present study demonstrates the importance of reaching international agreement on GBS criteria that should be based on the best evidence.

CRISPR-Cas Diversity in Clinical Salmonella enterica Serovar Typhi Isolates from South Asian Countries.

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a global health concern and its treatment is problematic due to the rise in antimicrobial resistance (AMR). Rapid detection of patients infected with AMR positive S. Typhi is, therefore, crucial to prevent further spreading. Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated genes (CRISPR-Cas), is an adaptive immune system that initially was used for typing purposes. Later, it was discovered to play a role in defense against phages and plasmids, including ones that carry AMR genes, and, at present, it is being explored for its usage in diagnostics. Despite the availability of whole-genome sequences (WGS), very few studied the CRISPR-Cas system of S. Typhi, let alone in typing purposes or relation to AMR. In the present study, we analyzed the CRISPR-Cas system of S. Typhi using WGS data of 1059 isolates obtained from Bangladesh, India, Nepal, and Pakistan in combination with demographic data and AMR status. Our results reveal that the S. Typhi CRISPR loci can be classified into two groups: A (evidence level >2) and B (evidence level ≤2), in which we identified a total of 47 unique spacers and 15 unique direct repeats. Further analysis of the identified spacers and repeats demonstrated specific patterns that harbored significant associations with genotype, demographic characteristics, and AMR status, thus raising the possibility of their usage as biomarkers. Potential spacer targets were identified and, interestingly, the phage-targeting spacers belonged to the group-A and plasmid-targeting spacers to the group-B CRISPR loci. Further analyses of the spacer targets led to the identification of an S. Typhi protospacer adjacent motif (PAM) sequence, TTTCA/T. New cas-genes known as DinG, DEDDh, and WYL were also discovered in the S. Typhi genome. However, a specific variant of the WYL gene was only identified in the extensively drug-resistant (XDR) lineage from Pakistan and ciprofloxacin-resistant lineage from Bangladesh. From this work, we conclude that there are strong correlations between variations identified in the S. Typhi CRISPR-Cas system and endemic AMR positive S. Typhi isolates.

Protocol for a prospective, observational, hospital-based multicentre study of nosocomial SARS-CoV-2 transmission: NOSO-COR Project.

INTRODUCTION: The newly identified SARS-CoV-2 can cause serious acute respiratory infections such as pneumonia. In France, mortality rate in the general population was approximately 10% and could reach higher levels at the hospital. In the current context of high incidence rates of SARS-CoV-2 in the community, a significant increase in the rate of nosocomial transmission is expected. The risk of nosocomial transmission could even be higher in low-income countries that have fragile healthcare systems. This protocol is intended to estimate the prevalence and incidence of suspected or confirmed cases of nosocomial SARS-CoV-2 infection, the clinical spectrum and the determinants (risk factors/protective) at participating hospitals. METHODS AND ANALYSIS: This will be an international multicentre prospective, observational, hospital-based study in adults and children. It will include volunteer patients and healthcare professionals in France and hospitals affiliated with the GABRIEL network. Demographic and clinical data will be collected using case report forms designed especially for the purpose of the project. A nasopharyngeal swab will be collected and tested for SARS-CoV-2 by reverse-transcriptase PCR. Characteristics of the study participants, the proportion of confirmed nosocomial SARS-CoV-2 infections relative to all patients with syndromes suggestive of SARS-CoV-2 infection, will be analysed. Appropriate multivariate modelling will be used to identify the determinants associated with nosocomial onset. ETHICS AND DISSEMINATION: This study was approved by the clinical research and committee of all participating countries. The findings will be submitted to peer-reviewed journal for publication and shared with national health authorities. TRIAL REGISTRATION NUMBER: NCT04290780.

Crimean-Congo hemorrhagic fever virus replication imposes hyper-lipidation of MAP1LC3 in epithelial cells.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a virus that causes severe liver dysfunctions and hemorrhagic fever, with high mortality rate. Here, we show that CCHFV infection caused a massive lipidation of LC3 in hepatocytes. This lipidation was not dependent on ATG5, ATG7 or BECN1, and no signs for recruitment of the alternative ATG12-ATG3 pathway for lipidation was found. Both virus replication and protein synthesis were required for the lipidation of LC3. Despite an augmented transcription of SQSTM1, the amount of proteins did not show a massive and sustained increase in infected cells, indicating that degradation of SQSTM1 by macroautophagy/autophagy was still occurring. The genetic alteration of autophagy did not influence the production of CCHFV particles demonstrating that autophagy was not required for CCHFV replication. Thus, the results indicate that CCHFV multiplication imposes an overtly elevated level of LC3 mobilization that involves a possibly novel type of non-canonical lipidation. Abbreviations: BECN1: Beclin 1; CCHF: Crimean-Congo hemorrhagic fever; CCHFV: Crimean-Congo hemorrhagic fever virus; CHX: cycloheximide; ER: endoplasmic reticulum; GFP: green fluorescent protein; GP: glycoproteins; MAP1LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; n.i.: non-infected; NP: nucleoprotein; p.i.: post-infection; SQSTM1: sequestosome 1.

Analysis of isolates from Bangladesh highlights multiple ways to carry resistance genes in Salmonella Typhi.

BACKGROUND: Typhoid fever, caused by Salmonella Typhi, follows a fecal-oral transmission route and is a major global public health concern, especially in developing countries like Bangladesh. Increasing emergence of antimicrobial resistance (AMR) is a serious issue; the list of treatments for typhoid fever is ever-decreasing. In addition to IncHI1-type plasmids, Salmonella genomic island (SGI) 11 has been reported to carry AMR genes. Although reports suggest a recent reduction in multidrug resistance (MDR) in the Indian subcontinent, the corresponding genomic changes in the background are unknown. RESULTS: Here, we assembled and annotated complete closed chromosomes and plasmids for 73 S. Typhi isolates using short-length Illumina reads. S. Typhi had an open pan-genome, and the core genome was smaller than previously reported. Considering AMR genes, we identified five variants of SGI11, including the previously reported reference sequence. Five plasmids were identified, including the new plasmids pK91 and pK43; pK43and pHCM2 were not related to AMR. The pHCM1, pPRJEB21992 and pK91 plasmids carried AMR genes and, along with the SGI11 variants, were responsible for resistance phenotypes. pK91 also contained qnr genes, conferred high ciprofloxacin resistance and was related to the H58-sublineage Bdq, which shows the same phenotype. The presence of plasmids (pHCM1 and pK91) and SGI11 were linked to two H58-lineages, Ia and Bd. Loss of plasmids and integration of resistance genes in genomic islands could contribute to the fitness advantage of lineage Ia isolates. CONCLUSIONS: Such events may explain why lineage Ia is globally widespread, while the Bd lineage is locally restricted. Further studies are required to understand how these S. Typhi AMR elements spread and generate new variants. Preventive measures such as vaccination programs should also be considered in endemic countries; such initiatives could potentially reduce the spread of AMR.

Salmonella enterica Serovar Typhi in Bangladesh: Exploration of Genomic Diversity and Antimicrobial Resistance.

Typhoid fever, caused by Salmonella enterica serovar Typhi, is a global public health concern due to increasing antimicrobial resistance (AMR). Characterization of S Typhi genomes for AMR and the evolution of different lineages, especially in countries where typhoid fever is endemic such as Bangladesh, will help public health professionals to better design and implement appropriate preventive measures. We studied whole-genome sequences (WGS) of 536 S Typhi isolates collected in Bangladesh during 1999 to 2013 and compared those sequences with data from a recent outbreak in Pakistan reported previously by E. J. Klemm, S. Shakoor, A. J. Page, F. N. Qamar, et al. (mBio 9:e00105-18, 2018, https://doi.org/10.1128/mBio.00105-18), and a laboratory surveillance in Nepal reported previously by C. D. Britto, Z. A. Dyson, S. Duchene, M. J. Carter, et al. [PLoS Negl. Trop. Dis. 12(4):e0006408, 2018, https://doi.org/10.1371/journal.pntd.0006408]. WGS had high sensitivity and specificity for prediction of ampicillin, chloramphenicol, co-trimoxazole, and ceftriaxone AMR phenotypes but needs further improvement for prediction of ciprofloxacin resistance. We detected a new local lineage of genotype 4.3.1 (named lineage Bd) which recently diverged into a sublineage (named Bdq) containing qnr genes associated with high-level ciprofloxacin resistance. We found a ceftriaxone-resistant isolate with the blaCTX-M-15 gene and a genotype distinct from the genotypes of extensively drug-resistant (XDR) isolates from Pakistan. This result suggests a different source and geographical origin of AMR. Genotype 4.3.1 was dominant in all three countries but formed country-specific clusters in the maximum likelihood phylogenetic tree. Thus, multiple independent genetic events leading to ciprofloxacin and ceftriaxone resistance took place in these neighboring regions of Pakistan, Nepal, and Bangladesh. These independent mutational events may enhance the risk of global spread of these highly resistant clones. A short-term global intervention plan is urgently needed.IMPORTANCE Typhoid fever, caused by Salmonella enterica serovar Typhi, is responsible for an estimated burden of approximately 17 million new episodes per year worldwide. Adequate and timely antimicrobial treatment invariably cures typhoid fever. The increasing antimicrobial resistance (AMR) of S Typhi severely limits the treatment options. We studied whole-genome sequences (WGS) of 536 S Typhi isolates collected in Bangladesh between 1999 and 2013 and compared those sequences with data from a recent outbreak in Pakistan and a laboratory surveillance in Nepal. The analysis suggests that multiple ancestral origins of resistance against ciprofloxacin and ceftriaxone are present in three countries. Such independent genetic events and subsequent dissemination could enhance the risk of a rapid global spread of these highly resistant clones. Given the current treatment challenges, vaccination seems to be the most appropriate short-term intervention to reduce the disease burden of typhoid fever at a time of increasing AMR.

Small volume plasma exchange for Guillain-Barré syndrome in resource-limited settings: a phase II safety and feasibility study.

OBJECTIVE: To assess the safety and feasibility of small volume plasma exchange (SVPE) for patients with Guillain-Barré syndrome (GBS). DESIGN: Non-randomised, single-arm, interventional trial. SETTING: National Institute of Neurosciences and Hospital, Dhaka, Bangladesh. PARTICIPANTS: Twenty adult (>18 years) patients with GBS presented within 2 weeks of onset of weakness who were unable to walk unaided for more than 10 m. INTERVENTIONS: SVPE involves blood cell sedimentation in a blood bag and removal of supernatant plasma after blood cells are retransfused. This procedure was repeated three to six times a day, for eight consecutive days. Fresh frozen plasma (FFP) and normal saline were used as replacement fluid. OUTCOME MEASURES: Serious adverse events (SAEs) were defined as severe sepsis and deep venous thrombosis related to the central venous catheter (CVC) used during SVPE. SVPE was considered safe if less than 5/20 patients experienced an SAE, and feasible if 8 L plasma could be removed within 8 days in at least 15/20 patients. RESULTS: Median patient age 33 years (IQR 23-46; range 18-55); 13 (65%) were male. Median Medical Research Council (MRC) sum score was 20 (IQR 0-29; range 0-36); three (15%) patients required mechanical ventilation. One patient developed SAE (severe sepsis, possibly related to CVC). The median plasma volume exchanged was 140 mL/kg (range 110-175) and removal of 8 L plasma was possible in 15 (75%) patients. Patients received a median 1 g/kg IgG via FFP although a substantial proportion of IgG was probably removed again by the SVPE sessions. GBS disability score improved by at least one grade in 14 (70%) patients 4 weeks after SVPE started. No patients died. CONCLUSION: SVPE seems a safe and feasible alternative treatment to standard plasma exchange (PE) or intravenous immunoglobulin (IVIg) for GBS; further studies of clinical efficacy in low-income and middle-income countries are warranted. TRIAL REGISTRATION NUMBER: NCT02780570.

Zika virus and Guillain-Barré syndrome in Bangladesh.

OBJECTIVE: Previous studies have associated Guillain-Barré syndrome (GBS) with Zika virus (ZIKV) outbreaks in South America and Oceania. In Asia, ZIKV is known to circulate widely, but the association with Guillain-Barré syndrome is unclear. We investigated whether endemic ZIKV infection is associated with the development of GBS. METHODS: A prospective study was conducted from 2011 to 2015 in Bangladesh. A total of 418 patients and 418 healthy family controls were included in the study. Patients were diagnosed with GBS prior to inclusion according to established criteria. Detailed information on the epidemiology, clinical presentation, electrophysiology, diagnosis, disease severity, and clinical course were obtained during a follow-up of 1 year using a predefined protocol. RESULTS: ZIKV-neutralizing antibodies were detected in our study from 2013 onwards. The prevalence of ZIKV-neutralizing antibodies was not significantly higher in patients with GBS compared to healthy controls (OR 2.23, P = 0.14, 95% CI 0.77-6.53). Serological evidence for prior ZIKV infection in patients with GBS was associated with more frequent cranial, sensory, and autonomic nerve involvement compared to GBS patients with Campylobacter jejuni, the predominant preceding infection in GBS worldwide. Nerve-conduction studies revealed that ZIKV antibodies were associated with a demyelinating subtype of GBS, while C. jejuni infections were related to an axonal subtype. INTERPRETATION: No significant association was found between ZIKV infection and GBS in Bangladesh, but GBS following ZIKV infection was characterized by a distinct clinical and electrophysiological subtype compared to C. jejuni infection. These findings indicate that ZIKV may precede a specific GBS subtype but the risk is low.