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.

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.

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.

Guillain-Barré syndrome following varicella-zoster virus infection.

We describe the frequency, clinical features, and electrophysiological and immunological phenotypes of Guillain-Barré Syndrome (GBS) patients treated at a single institution in Bangladesh who had preceding chicken pox (primary Varicella-zoster virus [VZV] infection) within 4 weeks of GBS onset. A literature review of GBS cases preceding VZV infection is also provided. Diagnosis of GBS was based on the National Institute of Neurological Disorders and Stroke criteria for GBS. Serum anti-VZV IgM and IgG antibodies were quantified by indirect chemiluminescence immunoassay (CLIA); anti-Campylobacter jejuni IgG, IgM, and IgA antibodies and anti-ganglioside GM1 IgM and IgG antibodies, by enzyme-linked immunosorbent assays. Neurophysiologic subtypes were categorized following the Hadden criteria. Of 536 patients with GBS, 7 (1.3%) had chicken pox within 4 weeks before GBS onset. Four of the seven cases were male (age range, 23 to 40 years old). All seven patients were bed-bound, six had sensory symptoms, and three required mechanical ventilation for respiratory failure. All seven patients had CSF albuminocytologic dissociation and evidence of demyelination in nerve conduction studies. Anti-VZV IgM antibodies were present and anti-GM1 and anti-Campylobacter jejuni lipo-oligosaccharides (LOS) were negative in all cases. All patients had excellent outcome at 1 year (able to run). A systematic literature review of GBS cases related to VZV revealed 39 previously reported patients with comparable clinical presentations and outcomes, of which 36 had neurophysiologic evidence of demyelination. VZV infection is associated with the demyelinating subtype of GBS, clearly distinct from the axonal form of GBS that predominate in countries like Bangladesh.

Standardization of Laboratory Methods for the PERCH Study.

The Pneumonia Etiology Research for Child Health study was conducted across 7 diverse research sites and relied on standardized clinical and laboratory methods for the accurate and meaningful interpretation of pneumonia etiology data. Blood, respiratory specimens, and urine were collected from children aged 1-59 months hospitalized with severe or very severe pneumonia and community controls of the same age without severe pneumonia and were tested with an extensive array of laboratory diagnostic tests. A standardized testing algorithm and standard operating procedures were applied across all study sites. Site laboratories received uniform training, equipment, and reagents for core testing methods. Standardization was further assured by routine teleconferences, in-person meetings, site monitoring visits, and internal and external quality assurance testing. Targeted confirmatory testing and testing by specialized assays were done at a central reference laboratory.

Association of C-Reactive Protein With Bacterial and Respiratory Syncytial Virus-Associated Pneumonia Among Children Aged <5 Years in the PERCH Study.

BACKGROUND.: Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. METHODS.: We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for "confirmed" bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to "RSV pneumonia" (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. RESULTS.: Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. CONCLUSIONS.: Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study.

Environmental Spread of New Delhi Metallo-ß-Lactamase-1-Producing Multidrug-Resistant Bacteria in Dhaka, Bangladesh.

Resistance to carbapenem antibiotics through the production of New Delhi metallo-ß-lactamase-1 (NDM-1) constitutes an emerging challenge in the treatment of bacterial infections. To monitor the possible source of the spread of these organisms in Dhaka, Bangladesh, we conducted a comparative analysis of wastewater samples from hospital-adjacent areas (HAR) and from community areas (COM), as well as public tap water samples, for the occurrence and characteristics of NDM-1-producing bacteria. Of 72 HAR samples tested, 51 (71%) samples were positive for NDM-1-producing bacteria, as evidenced by phenotypic tests and the presence of the blaNDM-1 gene, compared to 5 of 41 (12.1%) samples from COM samples (P < 0.001). All tap water samples were negative for NDM-1-producing bacteria. Klebsiella pneumoniae (44%) was the predominant bacterial species among blaNDM-1-positive isolates, followed by Escherichia coli (29%), Acinetobacter spp. (15%), and Enterobacter spp. (9%). These bacteria were also positive for one or more other antibiotic resistance genes, including blaCTX-M-1 (80%), blaCTX-M-15 (63%), blaTEM (76%), blaSHV (33%), blaCMY-2 (16%), blaOXA-48-like (2%), blaOXA-1 (53%), and blaOXA-47-like (60%) genes. Around 40% of the isolates contained a qnr gene, while 50% had 16S rRNA methylase genes. The majority of isolates hosted multiple plasmids, and plasmids of 30 to 50 MDa carrying blaNDM-1 were self-transmissible. Our results highlight a number of issues related to the characteristics and source of spread of multidrug-resistant bacteria as a potential public health threat. In view of the existing practice of discharging untreated liquid waste into the environment, hospitals in Dhaka city contribute to the potential dissemination of NDM-1-producing bacteria into the community.IMPORTANCE Infections caused by carbapenemase-producing Enterobacteriaceae are extremely difficult to manage due to their marked resistance to a wide range of antibiotics. NDM-1 is the most recently described carbapenemase, and the blaNDM-1 gene, which encodes NDM-1, is located on self-transmissible plasmids that also carry a considerable number of other antibiotic resistance genes. The present study shows a high prevalence of NDM-1-producing organisms in the wastewater samples from hospital-adjacent areas as a potential source for the spread of these organisms to community areas in Dhaka, Bangladesh. The study also examines the characteristics of the isolates and their potential to horizontally transmit the resistance determinants. The significance of our research is in identifying the mode of spread of multiple-antibiotic-resistant organisms, which will allow the development of containment measures, leading to broader impacts in reducing their spread to the community.

High mortality from Guillain-Barré syndrome in Bangladesh.

Although Guillain-Barré syndrome (GBS) has higher incidence and poor outcome in Bangladesh, mortality from GBS in Bangladesh has never been explored before. We sought to explore the frequency, timing, and risk factors for deaths from GBS in Bangladesh. We conducted a prospective study on 407 GBS patients who were admitted to Dhaka Medical College Hospital, Dhaka, Bangladesh from 2010 to 2013. We compared deceased and alive patients to identify risk factors. Cox regression model was used to adjust for confounders. Of the 407 GBS patients, 50 (12%) died, with the median time interval between the onset of weakness and death of 18 days. Among the fatal cases, 24 (48%) were ≥40 years, 36 (72%) had a Medical Research Council sum score ≤20 at entry, 33 (66%) had a progressive phase <8 days, and 27 (54%) required ventilation support. Ten patients (20%) died due to unavailability of ventilator. The strongest risk factor for deaths was lack of ventilator support when it was required (HR: 11.9; 95% confidence interval [CI]: 4.6-30.7). Other risk factors for death included age ≥40 years (HR: 5.9; 95% CI: 2.1-16.7), mechanical ventilation (HR: 2.3; 95% CI: 1.02-5.2), longer progressive phase (>8 days) (HR: 2.06; 95% CI: 1.1-3.8), autonomic dysfunction (HR: 1.9; 95% CI: 1.05-3.6), and bulbar nerve involvement (HR: 5.4; 95% CI: 1.5-19.2). In Bangladesh, GBS is associated with higher mortality rates, which is related to lack of ventilator support, disease severity, longer progressive phase of the disease, autonomic dysfunction, and involvement of the bulbar nerves.

A CRISPR-Cas system enhances envelope integrity mediating antibiotic resistance and inflammasome evasion.

Clustered, regularly interspaced, short palindromic repeats-CRISPR associated (CRISPR-Cas) systems defend bacteria against foreign nucleic acids, such as during bacteriophage infection and transformation, processes which cause envelope stress. It is unclear if these machineries enhance membrane integrity to combat this stress. Here, we show that the Cas9-dependent CRISPR-Cas system of the intracellular bacterial pathogen Francisella novicida is involved in enhancing envelope integrity through the regulation of a bacterial lipoprotein. This action ultimately provides increased resistance to numerous membrane stressors, including antibiotics. We further find that this previously unappreciated function of Cas9 is critical during infection, as it promotes evasion of the host innate immune absent in melanoma 2/apoptosis associated speck-like protein containing a CARD (AIM2/ASC) inflammasome. Interestingly, the attenuation of the cas9 mutant is complemented only in mice lacking both the AIM2/ASC inflammasome and the bacterial lipoprotein sensor Toll-like receptor 2, but not in single knockout mice, demonstrating that Cas9 is essential for evasion of both pathways. These data represent a paradigm shift in our understanding of the function of CRISPR-Cas systems as regulators of bacterial physiology and provide a framework with which to investigate the roles of these systems in myriad bacteria, including pathogens and commensals.

Guillain-Barré syndrome in Bangladesh: validation of Brighton criteria.

Guillain-Barré syndrome has a diverse clinical phenotype related to geographical origin. To date, the majority of large-scale studies on Guillain-Barré syndrome (GBS) have been conducted in developed countries. We aimed to evaluate the key diagnostic features and assess the suitability of the Brighton criteria in 344 adult GBS patients from Bangladesh. All patients fulfilled the National Institute of Neurological Diseases and Stroke (NINDS) diagnostic criteria. Standardized data on demographic characteristics and clinical features, cerebrospinal fluid (CSF) analysis, and nerve conduction study (NCS) results were elaborated to measure the sensitivity of Brighton criteria. Most patients (88%) were admitted to hospital after the nadir weakness. Symmetrical weakness and reduced reflexes were found in 98% of patients. CSF albuminocytologic dissociation was detected in 238/269 (89%) cases and abnormal nerve physiology in 258/259 (>99%) cases. Only 27 (8%) patients received either intravenous immunoglobulin (IVIg) or plasmapheresis. In total, 200 (58%) patients met level 1 of the Brighton criteria; 97 (28%) patients met level 2; 42 (12%) patients met level 3; and 5 (2%) patients met level 4. This analysis showed that despite the heterogeneity of GBS in Bangladesh, the Brighton criteria showed a high sensitivity in the diagnosis of GBS.

Enhanced, sialoadhesin-dependent uptake of Guillain-Barre syndrome-associated Campylobacter jejuni strains by human macrophages.

Molecular mimicry between Campylobacter jejuni sialylated lipooligosaccharides (LOS) and human nerve gangliosides can trigger the production of cross-reactive antibodies which induce Guillain-Barré syndrome (GBS). To better understand the immune events leading to GBS, it is essential to know how sialylated LOS are recognized by the immune system. Here, we show that GBS-associated C. jejuni strains bind to human sialoadhesin (hSn), a conserved, mainly macrophage-restricted I-type lectin. Using hSn-transduced THP-1 cells, we observed that C. jejuni strains with α(2,3)-sialylated LOS, including strains expressing GM1a- and GD1a-like epitopes, bind to hSn. This observation is of importance, as these epitopes are frequently the targets of the cross-reactive antibodies detected in GBS patients. Interestingly, the Sn binding domains were not constitutively exposed on the surface of C. jejuni. Heat inactivation and the environmental conditions which food-borne C. jejuni encounters during its passage through the intestinal tract, such as low pH and contact with bile constituents, exposed LOS and facilitated Sn binding. Sn binding enhanced bacterial uptake and increased the production of interleukin-6 (IL-6) by primary human Sn-expressing monocyte-derived macrophages compared to control conditions, where Sn was blocked using neutralizing antibodies or when nonsialylated C. jejuni was used. Sn-mediated uptake has been reported to enhance humoral immune responses. As C. jejuni strains expressing ganglioside mimics GD1a and GM1a are closely associated with GBS, Sn binding may be a determining event in the production of cross-reactive antibodies and the development of GBS.

Evaluation of a D-amino-acid-containing fluorescence resonance energy transfer peptide library for profiling prokaryotic proteases.

Bacterial proteases play an important role in a broad spectrum of processes, including colonization, proliferation, and virulence. In this respect, bacterial proteases are potential biomarkers for bacterial diagnosis and targets for novel therapeutic protease inhibitors. To investigate these potential functions, the authors designed and used a protease substrate fluorescence resonance energy transfer (FRET) library comprising 115 short d- and l-amino-acid-containing fluorogenic substrates as a tool to generate proteolytic profiles for a wide range of bacteria. Bacterial specificity of the d-amino acid substrates was confirmed using enzymes isolated from both eukaryotic and prokaryotic organisms. Interestingly, bacterial proteases that are known to be involved in housekeeping and nutrition, but not in virulence, were able to degrade substrates in which a d-amino acid was present. Using our FRET peptide library and culture supernatants from a total of 60 different bacterial species revealed novel, bacteria-specific, proteolytic profiles, although in-species variation was observed for Pseudomonas aeruginosa, Porphyromonas gingivalis, and Staphylococcus aureus. Overall, the specific characteristic of our substrate peptide library makes it a rapid tool to high-throughput screen for novel substrates to detect bacterial proteolytic activity.

Hygiene intervention reduces contamination of weaning food in Bangladesh.

OBJECTIVE: This study was conducted to measure the impact of a hygiene intervention on the contamination of weaning food in Bangladesh. METHODS: Sixty households were selected: 30 study and 30 control households. Samples of weaning food were collected from all the 60 households at baseline and examined for faecal coliforms (FC), faecal streptococci (FS) and Clostridium perfringens (CP) following standard procedures. After cooking, food samples were collected on three occasions before feeding. Following Hazard Analysis Critical Control Point (HACCP) procedures, critical control points were determined. The mothers in the 30 study households were then trained for 4 weeks in how to attain the control point conditions. Then, again the food samples were collected and analysed. RESULTS: At baseline, weaning foods from study and control households were heavily contaminated with FC and FS. The FC and FS counts were 1.84 log(10) and 1.92 log(10) colony-forming unit (cfu)/g, respectively, in the study households, and 0.86 log(10) and 1.33 log(10)  cfu/g, respectively, in the control households in the first feeding. After the intervention, the FC and FS counts in study households had dropped to 0.10 log(10) and 0.09 log(10)  cfu/g, respectively, a statistically significant reduction (P < 0.001). Monitoring the sustainability of the behaviour change after 3 months showed that the mothers were maintaining food hygiene. CONCLUSIONS: A hygiene intervention following the HACCP approach reduced the weaning food contamination significantly. Awareness building among mothers about weaning food hygiene could be an important intervention for preventing weaning food-related diarrhoea in Bangladesh.

Campylobacter jejuni translocation across intestinal epithelial cells is facilitated by ganglioside-like lipooligosaccharide structures.

Translocation across intestinal epithelial cells is an established pathogenic feature of the zoonotic bacterial species Campylobacter jejuni. The number of C. jejuni virulence factors known to be involved in translocation is limited. In the present study, we investigated whether sialylation of C. jejuni lipooligosaccharide (LOS) structures, generating human nerve ganglioside mimics, is important for intestinal epithelial translocation. We here show that C. jejuni isolates expressing ganglioside-like LOS bound in larger numbers to the Caco-2 intestinal epithelial cells than C. jejuni isolates lacking such structures. Next, we found that ganglioside-like LOS facilitated endocytosis of bacteria into Caco-2 cells, as visualized by quantitative microscopy using the early and late endosomal markers early endosome-associated protein 1 (EEA1), Rab5, and lysosome-associated membrane protein 1 (LAMP-1). This increased endocytosis was associated with larger numbers of surviving and translocating bacteria. Next, we found that two different intestinal epithelial cell lines (Caco-2 and T84) responded with an elevated secretion of the T-cell attractant CXCL10 to infection by ganglioside-like LOS-expressing C. jejuni isolates. We conclude that C. jejuni translocation across Caco-2 cells is facilitated by ganglioside-like LOS, which is of clinical relevance since C. jejuni ganglioside-like LOS-expressing isolates are linked with severe gastroenteritis and bloody stools in C. jejuni-infected patients.

Calicivirus from novel Recovirus genogroup in human diarrhea, Bangladesh.

To identify unknown human viruses in the enteric tract, we examined 105 stool specimens from patients with diarrhea in Bangladesh. A novel calicivirus was identified in a sample from 1 patient and subsequently found in samples from 5 other patients. Phylogenetic analyses classified this virus within the proposed genus Recovirus.

TLR4-mediated sensing of Campylobacter jejuni by dendritic cells is determined by sialylation.

In Guillain-Barré syndrome (GBS), ganglioside mimicry of Campylobacter jejuni lipo-oligosaccharide (LOS) drives the production of cross-reactive Abs to peripheral nerve gangliosides. We determined whether sialic acid residues in C. jejuni LOS modulate dendritic cell (DC) activation and subsequent B cell proliferation as a possible mechanism for the aberrant humoral immune response in GBS. Highly purified sialylated LOS of C. jejuni isolates from three GBS patients induced human DC maturation and secretion of inflammatory cytokines that were inhibited by anti-TLR4 neutralizing Abs. The extent of TLR4 signaling and DC activation was greater with LOS of the wild type isolates than with nonsialylated LOS of the corresponding sialyltransferase gene knockout (cst-II mutant) strains, indicating that sialylation boosts the DC response to C. jejuni LOS. Supernatants of LOS-activated DCs induced B cell proliferation after cross-linking of surface Igs in the absence of T cells. Lower B cell proliferation indices were found with DC supernatants after DC stimulation with cst-II mutant or neuraminidase desialylated LOS. This study showed that sialylation of C. jejuni LOS enhances human DC activation and subsequent B cell proliferation, which may contribute to the development of cross-reactive anti-ganglioside Abs found in GBS patients following C. jejuni infection.

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.

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.

Detection of antibodies in neuropathy patients by synthetic GM1 mimics.

Antibodies to the ganglioside GM1 are associated with various forms of acute and chronic immune-mediated neuropathy, including Guillain-Barré syndrome (GBS) and multifocal motor neuropathy. In diagnostics and research, these antibodies are usually detected by GM1 preparations derived from bovine brain tissue, which are non-covalently attached to solid carriers such as enzyme-linked immunosorbent assay (ELISA) plates. Such brain-derived GM1 preparations are potentially contaminated with other glycolipids. In the current study, uncontaminated mono- and divalent synthetic analogs of the ganglioside GM1 were successfully attached via covalent bonds onto the surface of ELISA plates. The resulting modified diagnostic tool showed strong affinities and good specificities for binding of monoclonal mouse and human anti-GM1 antibodies and cholera toxin, as well as for the anti-GM1 antibodies in serum samples from neuropathy patients. While these proof-of-principle experiments reveal the potential of synthetic ganglioside mimics in diagnostics, they show the necessity of further studies to overcome certain limitations, specifically the non-specific interactions in the negative control assays with synthetic GM1.