Correlation Between Japanese Encephalitis Virus Infection And Guillain-barré Syndrome

Objective In 2018,suspicious cases of Japanese encephalitis(JE)broke out in northern Ningxia,and some patients developed new features of the outbreak of Guillain-Barré syndrome(GBS).In order to further clarify the outbreak of the pathogen,summarize its epidemiological,clinical characteristics and treatment observations,clarify the causal relationship between the pathogen infection and GBS,provide scientific basis for clinical diagnosis and treatment,and for the Japanese encephalitis virus(JEV)prevention and control and future scientific research provide laboratory basis.Methods According to the JE diagnostic criteria(WS214-2008)and the diagnostic criteria issued by the Brighton GBS Working Group,47 acute JE(heavy and very heavy)patients with GBS were collected from the 161 confirmed JE patients as the study group,and 20 normal outpatients were collected.Cases served as the control group.Enzyme-linked immunosorbent assay(ELISA)technology was used to detect JEV-IgM and West Nile Virus(WNV)IgM in blood and / or cerebrospinal fluid of all patients collected;Detection of WNV-RNA and Zika virus(ZIKV)RNA by fluorescent quantitative polymerase chain reaction(FQ-PCR).Virus culture,isolation and identification were performed on patients' blood and cerebrospinal fluid.The isolated virus strains were subjected to whole genome sequencing and phylogenetic analysis.Peripheral nerve autoantibody lineage was detected in the blood and / or cerebrospinal fluid of 44 patients by ELISA.The epidemiological characteristics,clinical symptoms and signs,cerebrospinal fluid examination,sural nerve biopsy,neuroelectrophysiology and imaging characteristics,and follow-up observation results after 8 months of treatment were summarized.Results(1)Epidemiological analysis shows that the outbreak of GBS occurred in the 28 th week to the 35 th week of 2018,and the epidemic area was in the northern region of Ningxia,which is consistent with the literature report on the geographical distribution of Culex pipiens tricuspidatum in Ningxia.70% of the above areas are Culex pipiens tricuspids.After carrying out mosquito killing and live attenuated JE virus vaccine,as of December 2019,there were only 3 cases of mild JE patients in Ningxia.All of them recovered after one week of treatment,and no peripheral nerves were seen.Damage cases and similar outbreaks are prevalent.(2)The blood and / or cerebrospinal fluid immunoassay of 47 GBS patients confirmed the presence of JEV infection,and the symptoms were consistent with JEV infection before the onset of GBS.One virus strain was isolated from the cerebrospinal fluid of one of the severe patients,and the whole genome was sequenced and identified as the JEV gene type ?b(G?b),which belongs to the same clade as the JEVs isolated from mosquitoes in Ningxia.BLAST comparison analysis with the GenBank100 genomic sequence,suggesting that it is closest to the phylogenetic tree of Jiangsu Lianyungang isolate KX357114.1,with 99.38% homology,and is homologous to Guangdong isolates MH184574.1,MH184576.1,MH184575.1 Sex is 99.17%,99.16%,99.03%,suggesting that JEV in our district may originate in southern cities where JEV is frequent.(3)Fifty-seven patients had fever,headache,or nausea,vomiting,and varying degrees of disturbance of consciousness,respiratory failure,and flaccid paralysis of the extremities.Twenty-three cases of craniocerebral MRI showed multiple and new lesions in bilateral thalamus and / or midbrain.38 cases of cerebrospinal fluid had protein cell separation.(4)The electromyogram of 47 patients showed peripheral nerve and nerve root damage.According to the GBS classic and variant classification,it was divided into 4 cases of acute inflammatory demyelinating polyradiculoneuropathy(AIDP),22 cases of acute motor axonal neuropathy(AMAN),18 cases of acute motor sensory axonal neuropathy(AMSAN),and 3 Acute sensory neuropathy(ASN).(5)The gastrocnemius nerve biopsy of 2 patients with AMSAN showed that myelinated nerve fibers had thickened and layered myelin,and most of the axons were highly edema,mitochondrial vacuoles,and some axons atrophy.(6)The blood and / or cerebrospinal fluid peripheral nerve autoantibody lineage of 44 GBS patients was tested,and about 30% of the patients were positive for anti-GM1,GM2,GD1 a,and GD1 b antibodies.(7)Evaluation of the recovery of respiratory muscle strength and limb muscle strength showed that the hormone combined with gamma globulin group was significantly better than the hormone alone group(P <0.01).Conclusions(1)The outbreak of the virus in Ningxia was JEV GIb,which changed the previous JEV-GIII type,which is the first report in China.(2)The outbreak of GBS may be related to JEV infection.(3)Axonal injury is the main type of peripheral nerves in patients with JE and GBS,mainly AMAN and AMSAN subtypes.There are different types of antiganglioside antibodies in blood and cerebrospinal fluid(mainly GM1,GM2,GD1 a and GD1b).(4)Early application of immunoglobulin may have a certain therapeutic effect.(5)Immunization against mosquitoes and susceptible people is still the key to prevent the disease.