Zika Virus and Related Arbovirus Infections in Deferred Blood Donors

寨卡病毒(ZIKV)是一种伊蚊传播的黄病毒，由蚊子传播，导致加勒比海地区以及北美、中美洲和南美洲20多个国家和地区持续流行。除了通过蚊子传播外，寨卡病毒还可能通过输血和与感染寨卡病毒的男子发生性接触而传播。已知其他黄病毒，包括黄热病病毒和登革热病毒(DENV)可通过输血传播，并已导致严重后果。基孔肯雅病毒(CHIKV)是一种甲型病毒，理论上与输血有关的传播风险很高。在因前往疫区或与前往疫区的伴侣发生性接触而推迟的美国献血者中，ZIKV、DENV和CHIKV的感染率尚不清楚。此外，ZIKV、DENV和CHIKV在延期献血者中的自然病史还没有明确界定。 这项研究于2016年6月中旬在NIH血库的NIH临床中心部输血医学部开始招募。迄今为止，已登记了25名前往寨卡病毒流行地区的旅行延期或潜在献血者，并使用基于高灵敏度和特异性的RT-PCR检测ZIKV、DENV1-4和CHIKV(Altona诊断公司；根据FDA紧急使用授权)进行检测。参与者的平均年龄为40岁，其中56%是女性，72%是白人或高加索人，32%的人献血10年。捐赠者和潜在捐赠者前往了23个寨卡病毒流行的国家或地区，包括：阿根廷、巴西、哥伦比亚、哥斯达黎加、厄瓜多尔、萨尔瓦多、墨西哥、巴拿马和秘鲁；加勒比地区：巴哈马、多米尼加共和国、牙买加、马提尼克岛、波多黎各和美属维尔京群岛；其他地区：印度、印度尼西亚、尼日利亚、塞内加尔、新加坡、坦桑尼亚、阿联酋和越南。 我们使用临床样本对ZIKV RT-PCR试剂盒进行了内部验证，并确定了每毫升约100个拷贝的检测极限。到目前为止，在33名延期或潜在的献血者中，有32人的血浆和尿液中ZIKV、DENV和CHIKV呈阴性。一位潜在的捐献者在访问厄瓜多尔期间出现轻微的CHIKV相关症状两周后，尿液中的基孔肯雅RNA呈阳性(血液呈阴性)。这名患者将轻微的CHIKV症状归因于她在厄瓜多尔为一家援助机构所做的艰苦的志愿者工作，在献血者筛查期间不会被报告为疾病。 我们正在采购临床样本，以验证我们基于微阵列的病原体芯片可以同时检测ZIKV、DENV和CHIKV。 我们预计将与大型地区性血液采集系统合作，该系统将转介旅行延迟的献血者、最近前往ZIKV、DENV和/或CHIKV高危地区的献血者，以及在ZIKV、DENV和/或CHIKV的RNA检测呈阳性的献血者。

Zika virus (ZIKV) is an Aedes species, mosquito-transmitted Flavivirus responsible for an ongoing epidemic in over twenty countries and territories in the Caribbean, and in North, Central and South America. In addition to mosquito-borne transmission, ZIKV can likely be transmitted via blood transfusion and by sexual contact with a ZIKV-infected man. Other Flaviviruses, including yellow fever virus and dengue virus (DENV) are known to be transfusion-transmitted and have resulted in severe outcomes. Chikungunya virus (CHIKV), an alphavirus, has a high theoretical risk of transfusion-related transmission. The ZIKV, DENV and CHIKV infection rates are unknown among U.S. blood donors deferred either for travel to an endemic area or for sexual contact with a partner who travelled to an endemic area. Further, the natural history of ZIKV, DENV and CHIKV among deferred blood donors is not well-defined. Enrollment for this study began in mid June 2016 at the NIH Blood Bank, in the NIH Clinical Center Department of Transfusion Medicine. To date, 25 travel-deferred or potential blood donors who traveled to Zika virus endemic areas have been enrolled and tested using highly sensitive and specific RT-PCR-based assays for ZIKV, DENV1-4 and CHIKV (Altona Diagnostics; under FDA emergency use authorization). Enrollees have mean age of 40, 56% are female, 72% are white or Caucasian and 32% had been blood donors >10 years. Donors and potential donors traveled to 23 different countries or territories with endemic Zika virus, including: Argentina, Brazil, Colombia, Costa Rica, Ecuador, El Salvador, Mexico, Panama and Peru; in the Caribbean: the Bahamas, Dominican Republic, Jamaica, Martinique, Puerto Rico and the US Virgin Islands; elsewhere: India, Indonesia, Nigeria, Senegal, Singapore, Tanzania, UAE and Vietnam. We performed internal validation of the ZIKV RT-PCR kit using clinical samples and determined a limit of detection of approximately 100 copies per mL. Thus far, thirty-two of thirty-three deferred or potential blood donors were negative for ZIKV, DENV and CHIKV in plasma and urine. One potential donor was positive for Chikungunya RNA in urine (negative in blood) >2 weeks after mild, CHIKV-related symptoms began during a visit to Ecuador. The patient attributed the mild CHIKV symptoms to strenuous volunteer work she was doing for an aid agency in Ecuador, and would not have been reported as an illness during blood donor screening. We are in the process of procuring clinical samples for validation of our microarray-based pathogen chip for simultaneous ZIKV, DENV and CHIKV detection. We anticipate collaboration with a large regional blood collection system who will refer travel-deferred donors, donors who have recently traveled to ZIKV, DENV and/or CHIKV high-risk areas and donors who have tested RNA positive for ZIKV, DENV, and/or CHIKV.