Bonheur Ashley N, Thomas Sarah, Soshnick Sara H, McGibbon Emily, Dupuis Alan P, Hull Rene, Slavinski Sally, Del Rosso Paula E, Weiss Don, Hunt Danielle T, McCabe Megan E, Dean Amy B, Folkerth Rebecca, Laib Anne M, Wong Susan J
Division of Pediatric Critical Care Medicine, The Children's Hospital at Montefiore/Albert Einstein College of Medicine, Bronx, NY, USA.
Office of the New York City Chief Medical Examiner, New York, NY, USA.
BMC Infect Dis. 2021 Aug 4;21(1):749. doi: 10.1186/s12879-021-06482-0.
Dengue virus (DENV) is endemic in many parts of the world. Antibody dependent enhancement (ADE) in DENV infections occurs when a person with primary immunity is infected by a second, different DENV strain. Antibodies to Zika virus (ZIKV), which emerged in the Western Hemisphere in 2015, are cross reactive with DENV and theoretically could provoke ADE in a DENV naïve individual.
DENV infection was suspected in a child who had recently returned from a one-month stay in the Dominican Republic. The child presented with fever, vomiting, abdominal pain, and in hypovolemic shock. Volume and pressor resuscitation were unsuccessful, and the child died less than 24 h after hospitalization. Laboratory results suggested an early acute first DENV infection since serum, plasma, and spinal fluid had DENV1 detected by polymerase chain reaction (PCR), yet the serum lacked IgG antibodies to DENV nonstructural protein 1 (NS1) of all four DENV serotypes. This acute DENV infection occurred in the presence of a remote ZIKV infection as determined by antibodies to ZIKV NS1 envelope by multiplex microsphere immunoassay and an exceptionally high plaque reduction neutralization titer to ZIKV. ZIKV IgG avidity index was high, confirming a past infection. DENV1 RNA was detected in all ten organs and tissues examined by PCR. The severe and fatal complications reported here suggest that a remote ZIKV infection may provoke an exaggerated immune response leading to hypovolemic shock when primarily infected by DENV1.
We report the first known patient in the United States with a rapidly progressive and fatal case of travel-associated DENV in which prior exposure to ZIKV likely played a role in triggering an ADE phenomenon. This association of prior ZIKV immunity and subsequent new dengue infection is a worrisome phenomenon and an important contribution to the body of knowledge on immunity to flaviviruses.
登革病毒（DENV）在世界许多地区流行。当具有初次免疫的人被第二种不同的DENV毒株感染时，就会发生DENV感染中的抗体依赖性增强（ADE）现象。2015年在西半球出现的寨卡病毒（ZIKV）抗体与DENV具有交叉反应，理论上可能在未感染过DENV的个体中引发ADE。
一名儿童最近在多米尼加共和国停留了一个月后返回，怀疑感染了DENV。该儿童出现发热、呕吐、腹痛，并处于低血容量性休克状态。液体复苏和使用升压药均未成功，该儿童在住院后不到24小时死亡。实验室结果提示为早期急性初次DENV感染，因为通过聚合酶链反应（PCR）在血清、血浆和脑脊液中检测到了DENV1，但血清中缺乏针对所有四种DENV血清型的DENV非结构蛋白1（NS1）的IgG抗体。通过多重微球免疫测定法检测到针对ZIKV NS1包膜的抗体以及对ZIKV异常高的空斑减少中和滴度，确定该急性DENV感染发生在既往有ZIKV感染的情况下。ZIKV IgG亲和力指数较高，证实为既往感染。通过PCR在所有十个检查的器官和组织中均检测到了DENV1 RNA。此处报告的严重和致命并发症表明，既往ZIKV感染可能会引发过度免疫反应，导致在初次感染DENV1时发生低血容量性休克。
我们报告了美国首例已知的与旅行相关的DENV快速进展且致命的病例，其中既往接触ZIKV可能在触发ADE现象中起了作用。既往ZIKV免疫与随后新的登革热感染之间的这种关联是一个令人担忧的现象，对黄病毒免疫知识体系有重要贡献。
