Infectious agents in biological samples from patients with Guillain-Barré syndrome in Peru, 2018-2019. / Agentes infecciosos en muestras biológicas de pacientes con síndrome de Guillain-Barré en Perú, 2018-2019.

OBJECTIVE: To describe the results of laboratory tests performed on biological samples from patients with Guillain-Barré syndrome (GBS) submitted to the Instituto Nacional de Salud (INS) between 2018 and 2019. MATERIALS AND METHODS: We conducted an observational study on patients with GBS, by using data from the epidemiological surveillance system. Biological samples, previously analyzed at the INS, were obtained to study arboviruses, respiratory viruses, enteroviruses and enterobacteria, among others. RESULTS: A total of 2,051 specimens were obtained from 906 patients with GBS. Three patients tested positive for dengue and three for Zika. In 19 patients, the stool culture was positive for Campylobacter jejuni. Phylogenetic analysis of 10 Campylobacter jejuni strains classified them as genotype ST2993, which was previously reported in China and associated to a GBS outbreak. Twelve cerebrospinal fluid samples tested positive for enterovirus by PCR in 2018, but none could be verified by culture or complete genome sequencing during the study. One patient was positive for influenza A, two for influenza B, two for adenovirus, five for respiratory syncytial virus, and ten for rinovirus. CONCLUSION: Several pathogens were found in samples from patients with GBS. However, we found that the genotype ST2993 of Campylobacter jejuni was the most likely causal agent, a pathogen that is related to GBS outbreaks in different continents. It is necessary to confirm this hypothesis with additional analytical studies and it is important to describe the transmission mechanism of C. jejuni genotype ST2993 in order to implement prevention and control measures.

OBJETIVO: Describir los resultados de los exámenes de laboratorio realizados en muestras biológicas de pacientes con síndrome de Guillain-Barré (SGB), recibidas en el Instituto Nacional de Salud (INS) entre los años 2018 y 2019. MATERIALES Y MÉTODOS: Se realizó un estudio observacional en pacientes con SGB notificados en el sistema de vigilancia epidemiológica. Se obtuvieron muestras biológicas analizadas en el INS para investigar arbovirus, virus respiratorios, enterovirus y enterobacterias, entre otros. RESULTADOS: Se recibió un total de 2051 especímenes clínicos de 906 pacientes con SGB. Tres pacientes dieron positivo al dengue y tres pacientes al Zika. En 19 pacientes, el cultivo en heces fue positivo para Campylobacter jejuni. El análisis filogenético de diez cepas de Campylobacter jejuni las clasificó como genotipo ST2993, reportado previamente en China y asociado a un brote de SGB. En 2018, hubo 12 muestras que habían dado positivo al PCR para enterovirus en el líquido cefalorraquídeo, pero ninguna pudo corroborarse con el cultivo respectivo ni con secuenciamiento de genoma completo. Un paciente dio positivo por virus de la influenza A, dos por virus de la influenza B, dos por adenovirus, cinco por virus respiratorio sincicial, y diez por rinovirus. CONCLUSIÓN: Se han encontrado diversos agentes patógenos en especímenes de pacientes con SGB, sin embargo, la presencia de Campylobacter jejuni genotipo ST2993, un patógeno relacionado a brotes de SGB en varios continentes, sería el probable agente causal. Es necesario confirmar esta hipótesis con estudios analíticos y determinar la cadena de transmisión de este agente para implementar las medidas de prevención y control.

[The most frequent causative agents of Guillain-Barre syndrome in a Mexican general hospital]. / Agentes causales mas frecuentes del sindrome de Guillain-Barre en un hospital de Veracruz, Mexico.

INTRODUCTION: After Zika virus outbreak and the increase in the incidence of Guillain-Barre syndrome (GBS), the causal relationship has been studied, however a full etiological correlation has not been found. PATIENTS AND METHODS: From January 1 to December 31, 2017, patients with GBS were included. In addition to the basic serologies, enterovirus, herpes, Campylobacter, hepatitis B and C, TORCH, HIV, Brucella and Salmonella were requested. RESULTS: Cohort of seven male patients. Five patients analyzed cerebrospinal fluid reporting normal; all of them underwent brain scan, reporting normal. Neuroconduction was performed, resulting in acute inflammatory demyelinating polyneuropathy in four cases and acute motor axonal neuropathy in one case. All received intravenous immunoglobulins, five cases had a good prognosis and two deaths. No positive cases were reported to Zika virus. A positive case was reported to dengue and another to chikungunya. Five positive cases were reported to Campylobacter. One case positive to enterovirus. Dengue + Campylobacter coinfections were reported in one case and chikungunya + Campylobacter in another case. CONCLUSIONS: The present cohort shows that it was not possible to establish a causal relationship between GBS and Zika virus, but other viral and bacterial causal agents were identified, such as dengue, chikungunya and enterovirus, with the identification of Campylobacter cases even more remarkable.

TITLE: Agentes causales mas frecuentes del sindrome de Guillain-Barre en un hospital de Veracruz, Mexico.Introduccion. Con posterioridad a la oleada del virus del Zika y el incremento en la incidencia de sindrome de Guillain-Barre (SGB), se ha estudiado la relacion causal, pero no se ha encontrado una plena correlacion etiologica. Pacientes y metodos. Del 1 de enero al 31 de diciembre de 2017, se incluyeron pacientes con SGB. Ademas de las serologias basicas, se solicitaron determinaciones de enterovirus, virus del herpes, Campylobacter, hepatitis B y C, TORCH, virus de la inmunodeficiencia humana, Brucella y Salmonella. Resultados. Cohorte de siete pacientes de sexo masculino. A cinco pacientes se les analizo el liquido cefalorraquideo, que era normal. A todos se les realizo una tomografia encefalica, tambien normal, y se realizo neuroconduccion, que mostro polineuropatia inflamatoria desmielinizante aguda en cuatro casos y neuropatia motora axonal aguda en uno. Todos recibieron inmunoglobulinas intravenosas; tuvieron buen pronostico cinco casos y hubo dos defunciones. No se informo de casos positivos al virus del Zika. Hubo un caso positivo al dengue, uno al chikungunya, cinco a Campylobacter y uno a enterovirus. Se informo de coinfecciones de dengue + Campylobacter en un caso y de chikungunya + Campylobacter en otro. Conclusiones. La presente cohorte demuestra que no fue posible establecer una relacion causal entre el SGB y el virus del Zika, pero se identificaron otros agentes causales viricos y bacterianos, como dengue, chikungunya y enterovirus, y fue aun mas destacable la identificacion de los casos de Campylobacter.

Guillain-Barré syndrome, transverse myelitis and infectious diseases.

Guillain-Barré syndrome (GBS) and transverse myelitis (TM) both represent immunologically mediated polyneuropathies of major clinical importance. Both are thought to have a genetic predisposition, but as of yet no specific genetic risk loci have been clearly defined. Both are considered autoimmune, but again the etiologies remain enigmatic. Both may be induced via molecular mimicry, particularly from infectious agents and vaccines, but clearly host factor and co-founding host responses will modulate disease susceptibility and natural history. GBS is an acute inflammatory immune-mediated polyradiculoneuropathy characterized by tingling, progressive weakness, autonomic dysfunction, and pain. Immune injury specifically takes place at the myelin sheath and related Schwann-cell components in acute inflammatory demyelinating polyneuropathy, whereas in acute motor axonal neuropathy membranes on the nerve axon (the axolemma) are the primary target for immune-related injury. Outbreaks of GBS have been reported, most frequently related to Campylobacter jejuni infection, however, other agents such as Zika Virus have been strongly associated. Patients with GBS related to infections frequently produce antibodies against human peripheral nerve gangliosides. In contrast, TM is an inflammatory disorder characterized by acute or subacute motor, sensory, and autonomic spinal cord dysfunction. There is interruption of ascending and descending neuroanatomical pathways on the transverse plane of the spinal cord similar to GBS. It has been suggested to be triggered by infectious agents and molecular mimicry. In this review, we will focus on the putative role of infectious agents as triggering factors of GBS and TM.

Binational outbreak of Guillain-Barré syndrome associated with Campylobacter jejuni infection, Mexico and USA, 2011.

In June 2011, a cluster of suspected cases of Guillain-Barré syndrome (GBS), which can follow Campylobacter jejuni infection, was identified in San Luis Río Colorado (SLRC), Sonora, Mexico and Yuma County, Arizona, USA. An outbreak investigation identified 26 patients (18 from Sonora, eight from Arizona) with onset of GBS 4 May-21 July 2011, exceeding the expected number of cases (n = 1-2). Twenty-one (81%) patients reported antecedent diarrhoea, and 61% of 18 patients tested were seropositive for C. jejuni IgM antibodies. In a case-control study matched on age group, sex, ethnicity, and neighbourhood of residence, all Arizona GBS patients travelled to SLRC during the exposure period vs. 45% of matched controls (matched odds ratio 8·1, 95% confidence interval 1·5-∞). Exposure information and an environmental assessment suggested that GBS cases resulted from a large outbreak of C. jejuni infection from inadequately disinfected tap water in SLRC. Binational collaboration was essential in investigating this cross-border GBS outbreak, the first in mainland North America since 1976.

[Guillain Barré syndrome in association with Brucellosis]. / Síndrome de Guillain Barré asociado a Brucelosis.

We describe a case of a 47 years old male, with a history of 2 days of progressive, ascendant, symmetrical weakness in the lower extremities; a lumbar puncture was performed after the brain CT scan, as well as an electromyography, evidencing pure motor polyradiculopathy with axonal pattern, compatible with Guillain Barre syndrome. Afterwards, he received four plasmapheresis sessions, with clinical improvement from the second session. Due to his epidemiological background, Brucella set testing was done. Rose Bengal was positive, antibiotic treatment with rifampin and doxicicline was initiated, as well as rehabilitation. Three months later the patient recovered completely. The relevance of early treatment with plasmapheresis and the definition of the etiologic diagnosis determine that the prognosis of the Guillain Barre syndrome is favorable.

Patterns of Guillain-Barre syndrome in children: results from a Mexican population.

BACKGROUND: Guillain-Barré syndrome (GBS) is an acute, immune-mediated flaccid paralysis frequently associated with Campylobacter infection. Of two predominant GBS subtypes, a demyelinating subtype (acute inflammatory demyelinative polyneuropathy [AIDP]) predominates in the United States and Europe, and axonal subtype (acute motor axonal neuropathy [AMAN]) is the predominant form in China. Previous clinical studies suggested that AMAN also occurs in Mexican children. The purpose of this study was to describe the subtypes of GBS in children from Mexico City. METHODS: We prospectively studied 121 children admitted to two pediatric hospitals in Mexico City from 1996 to 2002. Clinical histories were obtained, electrophysiologic studies were performed to determine GBS subtype, and microbiologic studies were performed. RESULTS: Of the 121 children, 46 had AMAN and 32 had AIDP. The male to female ratio was 1.3 for AMAN cases (mean age = 6.3) and 3.0 for AIDP cases (mean age = 7.0). There was a strong seasonal distribution of AMAN cases in July to September. Children with AMAN, but not AIDP, had worsening of illness during hospitalization as judged by peak severity scores. Vomiting was more likely in AIDP (28.1%) vs AMAN (6.5%) (p = 0.012) and diarrhea was more common in AMAN (32.6%) than AIDP (12.5%) (p = 0.06). IgG anti-GM1 antibody titers were higher in patients with AMAN vs AIDP (p = 0.067). Anti-GD1a antibodies were equally present in both groups. Anti GQ1b titers were higher in AMAN vs AIDP (p = 0.009). Campylobacter antibody responses were positive in 44.1% of patients with AMAN and 37.0% of patients with AIDP. Twenty patients (14 = AMAN, 6 = AIDP) had positive stool cultures for C jejuni. Two serotypes, HS:19 and HS:41, accounted for 6 of 10 Campylobacter isolates available for serotyping from these cases. CONCLUSIONS: This study confirms that acute motor axonal neuropathy is an important Guillain-Barré syndrome subtype in Mexican children, is associated with diarrhea, and occurs seasonally.

Molecular evidence for dissemination of unique Campylobacter jejuni clones in Curaçao, Netherlands Antilles.

Campylobacter jejuni isolates (n = 234) associated with gastroenteritis and the Guillain-Barré syndrome (GBS) in the island of Curaçao, Netherlands Antilles, and collected from March 1999 to March 2000 were investigated by a range of molecular typing techniques. Data obtained by pulsed-field gel electrophoresis (PFGE), amplified fragment length polymorphism (AFLP) analysis, multilocus sequence typing (MLST), automated ribotyping, and sequence analysis of the short variable region of the flagellin gene (flaA) were analyzed separately and in combination. Similar groupings were obtained by all methods, with the data obtained by MLST and AFLP analysis exhibiting the highest degree of congruency. MLST identified 29 sequence types, which were assigned to 10 major clonal complexes. PFGE, AFLP analysis, and ribotyping identified 10, 9, and 8 of these clonal groups, respectively; however, these three techniques permitted subdivision of the clonal groups into more different types. Members of seven clonal groups comprising 107 isolates were obtained from November 1999 to February 2000, and no distinguishing characteristics were identified for two GBS-associated strains. The sequence type 41 (ST-41), ST-508, and ST-657 clonal complexes and their corresponding AFLP types have been rare or absent in the Campylobacter data sets described to date. We conclude that several clonal complexes of C. jejuni are associated with human disease in Curaçao, and some of these have not been reported elsewhere. Furthermore, given the observation that C. jejuni-associated diseases appear to be more severe from November to February, it can be speculated that this may be due to the presence of virulent clones with a limited span of circulation.

Anti-ganglioside antibodies and clinical outcome of patients with Guillain-Barré Syndrome in northeast Brazil.

OBJECTIVES: The goal of this study was to investigate the frequency of GM1 antibodies and to assess whether exposure to Campylobacter jejuni was associated with a distinct clinical variant of Guillain-Barré Syndrome (GBS) or disease outcome in Rio Grande do Norte, Brazil. MATERIAL AND METHODS: Forty-one patients with a presumed diagnosis of GBS were enrolled and prospectively studied between June 1994 and November 1999. RESULTS: Anti-GM1 was present in 51.2% (n = 21) of patients. The presence of anti-GM1 was significantly associated with acute axonal motor neuropathy when compared to acute inflammatory demyelinating polyneuropathy (P = 0.01). Patients with anti-GM1 antibodies presented distal muscle involvement and fewer sensory deficits. Age, time to nadir and ventilatory assistance were not associated with anti-GM1 antibodies. Eight out of 21 patients (32%) presented with anti-C. jejuni antibodies. Clinical features were similar for patients with GBS with positive and negative C. jejuni antibodies. Anti-GM1 antibodies were associated with C. jejuni infection (P = 0.0005). Presence of anti-GM1 and C. jejuni antibodies did not indicate a worse prognosis. CONCLUSION: Patients with GBS and anti-GM1 antibodies had more distal muscle weakness, fewer sensory deficits, more axonal degeneration and C. jejuni infection, but these findings were not associated with a worse prognosis.

Absence of clonality of Campylobacter jejuni in serotypes other than HS:19 associated with Guillain-Barré syndrome and gastroenteritis.

Guillain-Barré syndrome (GBS) is recognized as a complication that occurs after Campylobacter infection. Certain Penner serotypes, such as HS:19, are linked particularly to GBS in some parts of the world, and there is good evidence for restricted genetic diversity in these isolates. However, GBS also occurs after Campylobacter infection due to other serotypes. Therefore, we asked whether Campylobacter jejuni non-HS:19 serotypes associated with GBS have a clonal structure and differ from strains isolated from patients with Campylobacter gastroenteritis. A worldwide selected population of C. jejuni non-HS:19 strains associated with GBS and gastroenteritis was analyzed by use of multilocus enzyme electrophoresis, automated ribotyping, pulsed-field gel electrophoresis, and flagellin gene typing. The results show that these isolates represent a heterogenic population and do not constitute a unique population across serotypes. No epidemiologic marker for GBS-associated strains was identified.

Molecular population genetic analysis of Campylobacter jejuni HS:19 associated with Guillain-Barré syndrome and gastroenteritis.

Infection with Campylobacter jejuni serotype HS:19 is associated with the development of Guillain-Barré syndrome (GBS). To determine whether a particular HS:19 clone is associated with GBS, multilocus enzyme electrophoresis (MLEE) was used to analyze a worldwide collection of isolates. There were 34 electropherotypes (ETs) in 3 phylogenetic clusters among 83 C. jejuni isolates. Cluster I contained all HS:19 strains, and a single ET (ET4) accounted for most HS:19 strains. HS:19 strains did not occur in any of the other clusters. ET4 contained isolates from different geographic locations, indicating global spread of this clone. Furthermore, ET4 contained isolates from patients with uncomplicated enteritis and GBS, as well as isolates from animal sources. The results of this study show that HS:19 strains comprise a clonal, although not monomorphic, population, which is distinct from non-HS:19 strains within C. jejuni. A unique clone associated with GBS was not identified by use of MLEE.

Flagella as a potential marker for Campylobacter jejuni strains associated with Guillain-Barré syndrome.

Campylobacter jejuni recovered from patients with Guillain-Barré syndrome (GBS) in different geographical locations and bearing different heat-labile and heat-stable antigens were found to have identical amino acid sequences in their flagellar flaA short variable region, suggesting that it may be a potentially useful marker for GBS association.

Determinación de enterovirus en casos con diagnóstico de síndrome de Guillain-Barré mediante la utilización de la técnica de concentración ácida / Determination of enterovirus in cases with a Guillain-Barré syndrome diagnosis using the acid concentration technique

El propósito de este trabajo fue determinar la presencia de enterovirus en materia fecal mediante la utilización de la técnica de concentración ácida (TCA). Para esto se analizaron muestras de 58 niños menores de cinco años con diagnóstico de Síndrome de Guillain-Barré (SGB), tanto por la técnica de rutina como por la técnica propuesta. Se utilizaron como testigos nueve muestras que salieron positivas con la técnica de rutina. En estas nueve muestras y en 22 más (31 casos) se aislaron e identificaron enterovirus tipo no polio mediante la TCA (53 por ciento), por lo tanto, se obtuvo 38 por ciento más de aislamientos utilizando la TCA. El aislamiento celular fue más exitoso en la línea celular RD (59 por ciento) que en la Hep-2c (41 por ciento), aunque los títulos virales que se obtuvieron fueron bajos en su mayoría (71 por ciento). La TCA mejora la detección de enterovirus, sin embargo, por ser más costosa y más laboriosa, únicamente se recomienda su uso en casos de importancia epidemiológica como: los compatibles a polio y cuyo resultado sea negativo al utilizar la técnica de rutina o en casos cuya muestra proviene de un caso de fallecimiento; siempre y cuando las muestras sean tomadas en los primeros 15 días después del inicio de la sintomatología.