Etiology of Nodding Syndrome: an Epileptic Disorder of East African Children

项目摘要 点头综合征（NS）是一种病因不明的癫痫性脑病， 东非健康儿童和青少年，坦桑尼亚、南苏丹报告了确诊病例， 和乌干达的2014年，在冲突后北方乌干达的NS疫情结束后，我们进行了一项 病例对照研究显示NS病例与报告的既往麻疹感染显著相关， 在肮脏的国内流离失所者营地， 传染病流行，免疫接种不稳定。麻疹病毒感染（MVI）是否正确 诊断是不确定的，因为一些符合MVI病例定义的乌干达人已经证明， 有风疹病毒感染（RVI或德国麻疹）。MVI和RVI都可能与NS相关 因为婴儿患上任何一种病毒的急性疾病， 疾病（SSPE，PRP）与Nodding综合征临床重叠。MV触发的SSPE（亚急性 硬化性全脑炎）和SSPE样RVI引发的进行性风疹全脑炎（PRP），如 NS，排尿相关神经系统疾病，SSPE中记录有点头。我们建议开设 并装备一个小型生物流体筛选实验室，提高乌干达的技术能力， 马凯雷雷大学健康科学学院（MCHS）的研究人员将测试 假设NS是一种与这些（SSPE/PRP）迟发性脑疾病相当的慢性病毒性疾病 疾病他们将从临床定义的乌干达NS病例（n=50）中筛选现有血清样本， 对照组（n=50），用于既往MV、RV或其他嗜神经病毒感染足迹。他们还将 筛选NS和非NS受试者、住院患者的血液和脑脊液（CSF） 因其他医学原因接受CSF分析。编码的血清和CSF标本将通过以下方法进行盲态检测： 与慢病毒（MV、RV）相关的IgG抗体的酶联免疫吸附试验（ELISA）， 其他嗜神经病毒（HSV、CMV、EBV和B19）。逆转录聚合酶链反应 将用于检测病毒基因组并确认ELISA结果。来自MCHS的研究员将获得 个性化的研究培训和实验室为基础的分析经验，在俄勒冈州健康与科学 大学（OHSU）将允许他们独立地在OHSU和MCHS进行平行分析， 从NS病例和对照中获得的生物样品（血清和CSF）。沿着其他感兴趣的健康 乌干达研究员将参加定制的研讨会和讲习班， 解决点头综合征和其他脑部疾病目前在乌干达，参加有关生物医学 在非洲大陆的会议，并参加在美国国家卫生研究院国际中心举行的受赠方年会。 !

PROJECT SUMMARY Nodding syndrome (NS) is an epileptic encephalopathy of unknown etiology that manifests in previously healthy children and adolescents in eastern Africa, with confirmed cases reported in Tanzania, South Sudan and Uganda. In 2014, after the NS epidemic in post-conflict northern Uganda had terminated, we carried out a case-control study that revealed significant NS case association with reported prior measles infection and family dependence on moldy food during their wartime residence in squalid internal displacement camps where infectious disease was rife and immunization erratic. Whether measles virus infection (MVI) was correctly diagnosed is uncertain because some Ugandans who meet the case definition for MVI have proven instead to have rubella virus infection (RVI or German measles). MVI and RVI are both potentially relevant to NS because infants who develop acute illness from either virus occasionally develop many years later brain diseases (SSPE, PRP) that overlap clinically with Nodding syndrome. MV-triggered SSPE (subacute sclerosing panencephalitis) and SSPE-like RVI-initiated progressive rubella panencephalitis (PRP) are, like NS, seizure-associated neurological disorders, with head nodding recorded in SSPE. We propose to create and equip a small biofluid screening laboratory and enhance the technical capacity of Ugandan Research Fellows from Makerere University College of Health Sciences (MCHS), who will test the hypothesis that NS is a slow virus disorder comparable to these (SSPE/PRP) delayed-onset brain diseases. They will screen existing serum samples from clinically defined Ugandan NS Cases (n=50) and Controls (n=50) for footprints of prior viral infection with MV, RV or other neurotropic viruses. They will also screen blood and cerebrospinal fluid (CSF) from subjects with NS and non-NS, hospital-based patients undergoing CSF analysis for other medical reasons. Coded serum and CSF specimens will be tested blind by enzyme-linked immunosorbent assay (ELISA) for IgG antibodies associated with slow viruses (MV, RV) and other neurotropic viruses (HSV, CMV, EBV and B19). The Reverse Transcriptase Polymerase Chain Reaction will be used to detect viral genomes and confirm ELISA results. Research Fellows from MCHS will receive individualized research training and laboratory-based analytical experience at Oregon Health & Science University (OHSU) that will allow them independently to conduct parallel analyses at OHSU and MCHS on the biological samples (serum and csf) obtained from NS Cases and Controls. Along with other interested health professionals, the Ugandan Research Fellows will participate in customized seminars and workshops that address Nodding syndrome and other brain diseases present in Uganda, attend relevant biomedical meeting(s) on the African continent, and participate in the annual meeting of grantees in the USA at NIH FIC. !