Fever and multisystem organ failure associated with 17D-204 yellow fever vaccination: a report of four cases
Fever and multisystem organ failure associated with 17D-204 yellow fever vaccination: a report of four cases
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DOI：
10.1016/s0140-6736(01)05327-2
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发表时间：
2001-07-14
期刊：
影响因子：
168.9
通讯作者：
Cetron, MS
中科院分区：
文献类型：
--
作者：
Martin, M;Tsai, TF;Cetron, MS
1998年，美国疾病控制和预防中心接到通知，有三名患者在接种黄热病疫苗几天后出现严重疾病。1996年也发生过类似的情况。4例患者年龄均在63岁以上。方法分别从2例患者的血浆和1例患者的脑脊液中分离出黄热病病毒疫苗株，对其进行基因组测序。临床样本进行了中和试验，并对活检获得的一个肝脏样本进行了免疫组织化学分析。临床表现为发热、肌痛、头痛、意识不清，随后出现严重的多系统疾病。3名患者死亡。在一名疫苗接种者的血浆和脑脊液中发现了黄热病病毒的疫苗相关变异。两名疫苗接种者的恢复期血清样本显示抗体应答率至少为1:10 240。肝组织免疫组化检测显示，肝样本库普弗细胞中存在黄热病抗原。临床特征及其与疫苗接种的时间相关性。疫苗相关病毒的恢复、抗体反应和免疫组织化学分析共同提示疾病与黄热病疫苗接种之间可能存在因果关系。黄热病仍然是南美洲和非洲的一个重要致病和致死原因；因此，应保持疫苗接种，直到这些事件的频率被量化。
Background In 1998, the US Centers for Disease Control and Prevention was notified of three patients who developed severe illnesses days after yellow fever vaccination. A similar case occurred in 1996. All four patients were more than 63 years old.Methods Vaccine strains of yellow fever virus, isolated from the plasma of two patients and the cerebrospinal fluid of one, were characterised by genomic sequencing. Clinical samples were subjected to neutralisation assays, and an immunohistochemical analysis was done on one sample of liver obtained at biopsy.Findings The clinical presentations were characterised by fever, myalgia, headache, and confusion, followed by severe multisystemic illnesses. Three patients died. Vaccine-related variants of yellow fever virus were found in plasma and cerebrospinal fluid of one vaccinee. The convalescent serum samples of two vaccinees showed antibody responses of at least 1:10 240. Immunohistochemical assay of liver tissue showed yellow fever antigen in the Kuppfer cells of the liver sample.Interpretation The clinical features, their temporal association with vaccination. recovery of vaccine-related virus, antibody responses, and immunohistochemical assay collectively suggest a possible causal relation between the illnesses and yellow fever vaccination. Yellow fever remains an important cause of illness and death in South America and Africa; hence, vaccination should be maintained until the frequency of these events is quantified.