Large Outbreak of Guillain-Barre Syndrome, Peru, 2019.
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ABSTRACT:
SUBMITTER: Munayco CV
PROVIDER: S-EPMC7588531 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
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Large Outbreak of Guillain-Barré Syndrome, Peru, 2019.
Munayco César V CV Gavilan Ronnie G RG Ramirez Gladys G Loayza Manuel M Miraval Maria L ML Whitehouse Erin E Gharpure Radhika R Soares Jesus J Soplopuco Hans Vasquez HV Sejvar James J
Emerging infectious diseases 20201101 11
Outbreaks of Guillain-Barré syndrome (GBS) are uncommon. In May 2019, national surveillance in Peru detected an increase in GBS cases in excess of the expected incidence of 1.2 cases/100,000 population. Several clinical and epidemiologic findings call into question the suggested association between this GBS outbreak and Campylobacter. ...[more]
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Project description:ObjectiveTo identify the clinical phenotypes and infectious triggers in the 2019 Peruvian Guillain-Barré syndrome (GBS) outbreak.MethodsWe 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.ResultsThe 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.ConclusionsOur 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.
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Project description:BackgroundGuillain-Barre Syndrome (GBS) is considered a complex disorder with significant environmental effect and genetic susceptibility. Genetic polymorphisms in CD1E, CD1A, IL-17, and/or ICAM1 had been proposed as susceptibility genetic variants for GBS mainly in Caucasian population. This study explores the association between selected polymorphisms in these genes and GBS susceptibility in confirmed GBS cases reported in mestizo population from northern Peru during the most recent GBS outbreak of May 2018.MethodsA total of nine nonrelated cases and 11 controls were sequenced for the polymorphic regions of CD1A, CD1E, IL-17, and ICAM1.ResultsWe found a significant protective association between heterozygous GA genotype in ICAM1 (241Gly/Arg) and GBS (p < .047). IL-17 was monomorphic in both controls and patients. No significant differences were found in the frequency of SNPs in CD1A and CD1E between the group with GBS patients and healthy controls.ConclusionICAM1 polymorphisms might be considered as potential genetic markers of GBS susceptibility. Further studies with larger sample size will be required to validate these findings.
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Project description:Campylobacter jejuni infection is considered the most frequent factor associated with Guillain-Barré syndrome (GBS). In 2019, a large outbreak of GBS was detected in Peru, being associated with C. jejuni detected in stool samples from these patients. The aim of this study was to determine the molecular epidemiology of C. jejuni strains (ST-2993) associated with a large GBS outbreak in Peru. In this study, 26 C. jejuni strains belonging to the ST-2293, obtained from 2019 to 2020, were sequenced using Illumina technology. Five low-quality sequences were removed using bioinformatics, and 21 genomes (17 clinical strains and 4 chicken strains) were considered in the phylogenetic analysis and comparative genomics. Phylogenetic reconstruction, including genomes from international databases, showed a connection between Peruvian and Chinese GBS strains, both of them having lipooligosaccharides (LOS) locus genes related to molecular mimicry with gangliosides in peripheral nerves. Also, ST-2993 was detected in Amazon strains recovered many years before the 2019 outbreak, but with no epidemiological connection with GBS. Besides, a close relationship between human and chicken C. jejuni strains indicated chicken as one of the probable reservoirs. Finally, comparative genomics revealed differences between Chinese and Peruvian strains, including the presence of a prophage inserted into the genome. In conclusion, C. jejuni ST-2993 strains recovered from the GBS outbreak are closely related to Peruvian Amazon strains. Moreover, ST-2993 has been circulated in Peru since 2003 in the Peruvian Amazonia, showing the necessity to reinforce the epidemiological surveillance of C. jejuni to improve the prevention and control of future GBS outbreaks. IMPORTANCE This article describes the molecular epidemiology of C. jejuni strains (ST-2993) associated with a large Guillain-Barré Syndrome (GBS) outbreak in Peru, sequencing several strains recovered from GBS patients and chickens from 2019 to 2020. Phylogenetic analysis showed a connection between Peruvian and Chinese GBS strains, both of them having lipooligosaccharides (LOS) locus genes related to molecular mimicry with gangliosides in peripheral nerves. Also, ST-2993 strains were detected in isolates recovered many years before the 2019 outbreak, but with no epidemiological connection with GBS. Besides, a close relationship between human and chicken strains indicated those animals as a probable reservoir. This information will help to understand the real situation of GBS in Peru and its causal agent, C. jejuni ST-2993, showing the necessity to increase epidemiological tracking of these kinds of pathogens to detect them and avoid GBS outbreaks in the future.
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Project description:Background and purposeVarious electrodiagnostic criteria have been developed in Guillain-Barré syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria.MethodsFrom the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally.ResultsOf the 1137 studies, 68.3% (N = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%.Conclusions and discussionThis study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted.
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Project description:BackgroundGuillain-Barré syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain-Barré syndrome.MethodsAutoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We analysed the staining patterns of patients and controls. The prognostic value of anti-ganglioside antibodies was also analysed.ResultsNone of the GBS patients (n = 100) reacted against the nodo/paranodal proteins tested, and 61 (61%) were positive for, at least, one anti-ganglioside antibody. GBS sera reacted strongly against DRG neurons more frequently than controls both with IgG (6% vs 0%; p = 0.03) and IgM (11% vs 2.2%; p = 0.02) immunodetection. No differences were observed in the proportion of patients reacting against neuroblastoma-derived human motor neurons. Reactivity against monkey nerve tissue was frequently detected both in patients and controls, but specific patterns were only detected in GBS patients: IgG from 13 (13%) patients reacted strongly against Schwann cells. Finally, we confirmed that IgG anti-GM1 antibodies are associated with poorer outcomes independently of other known prognostic factors.ConclusionOur study confirms that (1) GBS patients display a heterogeneous repertoire of autoantibodies targeting nerve cells and structures; (2) gangliosides are the most frequent antigens in GBS patients and have a prognostic value; (3) further antigen-discovery experiments may elucidate other potential antigens in GBS.
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2011-07-28 | GSE31014 | GEO
Project description:BackgroundBetween October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barré syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain-Barré syndrome.MethodsIn this case-control study, cases were patients with Guillain-Barré syndrome diagnosed at the Centre Hospitalier de Polynésie Française (Papeete, Tahiti, French Polynesia) during the outbreak period. Controls were age-matched, sex-matched, and residence-matched patients who presented at the hospital with a non-febrile illness (control group 1; n=98) and age-matched patients with acute Zika virus disease and no neurological symptoms (control group 2; n=70). Virological investigations included RT-PCR for Zika virus, and both microsphere immunofluorescent and seroneutralisation assays for Zika virus and dengue virus. Anti-glycolipid reactivity was studied in patients with Guillain-Barré syndrome using both ELISA and combinatorial microarrays.Findings42 patients were diagnosed with Guillain-Barré syndrome during the study period. 41 (98%) patients with Guillain-Barré syndrome had anti-Zika virus IgM or IgG, and all (100%) had neutralising antibodies against Zika virus compared with 54 (56%) of 98 in control group 1 (p<0.0001). 39 (93%) patients with Guillain-Barré syndrome had Zika virus IgM and 37 (88%) had experienced a transient illness in a median of 6 days (IQR 4-10) before the onset of neurological symptoms, suggesting recent Zika virus infection. Patients with Guillain-Barré syndrome had electrophysiological findings compatible with acute motor axonal neuropathy (AMAN) type, and had rapid evolution of disease (median duration of the installation and plateau phases was 6 [IQR 4-9] and 4 days [3-10], respectively). 12 (29%) patients required respiratory assistance. No patients died. Anti-glycolipid antibody activity was found in 13 (31%) patients, and notably against GA1 in eight (19%) patients, by ELISA and 19 (46%) of 41 by glycoarray at admission. The typical AMAN-associated anti-ganglioside antibodies were rarely present. Past dengue virus history did not differ significantly between patients with Guillain-Barré syndrome and those in the two control groups (95%, 89%, and 83%, respectively).InterpretationThis is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome. Because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillain-Barré syndrome.FundingLabex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.
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Project description:The Guillain-Barré syndrome (GBS) has been previously associated with Zika virus infection. We analysed the data from all the patients with GBS diagnosis that were admitted to a referral hospital, in Tapachula City during the period from January 2013 to August 2016, comparing the incidence of GBS according to the temporality of the Zika outbreak in Southern Mexico. Additionally, we described the clinical and epidemiological characteristics of the GBS patients admitted before or after the Zika outbreak. We observed a sharp increase in the number of patients hospitalised due to GBS from the time the first confirmed Zika cases appeared in Mexico. Clinically we observed GBS cases before zika outbreak had more frequently history of respiratory/gastrointestinal symptoms and GBS during zika outbreak had significantly more frequently recent history of rash/conjunctivitis. Although we cannot affirm that the increased cases of GBS have a specific aetiologic association with Zika, our results suggest that this observed outbreak of in Tapachula, might have been associated to the emerging Zika epidemic, locally and suggests that rare complications associated with acute infections (such as GBS) might be useful in the surveillance systems for emerging infections.
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Project description:ObjectivePrevious 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.MethodsA 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.ResultsZIKV-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.InterpretationNo 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.
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