University of Edinburgh, Easter Bush, Midlothian, UK.
Transfusion. 2012 Jul;52(7):1482-9. doi: 10.1111/j.1537-2995.2011.03420.x. Epub 2011 Nov 2.
Human parvovirus 4 (PARV4) is a newly discovered parvovirus prevalent in injecting drug users and other groups with histories of parenteral exposure including persons with hemophilia exposed to non-virally inactivated clotting factor concentrates. To investigate its potential ongoing transmission to persons with hemophilia treated with plasma-derived, virally inactivated clotting factors, we screened a large cohort of persons with hemophilia for antibody seroconversion to PARV4 over a 5-year observation period.
Samples from 195 persons with hemophilia enrolled in the Hemophilia Growth and Development Study cohort were screened for PARV4 antibodies at the start and end of a 5-year period of treatment with exclusively virally inactivated clotting factor concentrates. Samples collected at intermediate time points from subjects seroconverting over the study period were screened to narrow down the seroconversion time and investigate immunoglobulin (Ig)M responses, duration of acute viremia, and clinical presentations.
PARV4 seroprevalence at the outset of the study was 44%. Over the observation period, nine subjects (seven human immunodeficiency virus positive) seroconverted for anti-PARV4 (incidence, 1.7%/year). Infected subjects showed relatively prolonged durations of viremia (mean, 7 months) and weak, transient IgM responses during acute infections. Clotting factors inactivated by solvent/detergent or by wet or dry heat were infectious. The most common clinical presentations were rashes and exacerbation of hepatitis.
This study identifies PARV4 as a transfusion-transmissible agent that is resistant to viral inactivation. Of concern, infections may still regularly occur in those exposed to plasma-derived blood products. Urgent evaluation of the incidence of PARV4 in treated individuals and disease associations of PARV4 infections is required.
人细小病毒 4 型(PARV4)是一种新发现的细小病毒,在注射吸毒者和其他有过注射暴露史的人群中流行,包括暴露于未通过病毒灭活的凝血因子浓缩物的血友病患者。为了研究其是否有可能继续传播给接受血浆源性、病毒灭活的凝血因子治疗的血友病患者,我们在 5 年的观察期内,对一个大型血友病患者队列进行了 PARV4 抗体血清转化筛查。
在一项为期 5 年的 exclusively virally inactivated clotting factor concentrates 治疗期间,对参加血友病生长和发展研究队列的 195 名血友病患者的样本进行了 PARV4 抗体筛查。在研究期间发生血清转化的受试者的中间时间点采集的样本进行了筛查,以缩小血清转化时间,并研究免疫球蛋白(Ig)M 反应、急性病毒血症的持续时间和临床表现。
研究开始时,PARV4 的血清流行率为 44%。在观察期间,有 9 名受试者(7 名 HIV 阳性)发生了抗-PARV4 血清转化(发生率为 1.7%/年)。感染的受试者表现出相对较长时间的病毒血症(平均 7 个月)和急性感染期间短暂的、弱的 IgM 反应。用溶剂/去污剂或湿热或干热灭活的凝血因子具有传染性。最常见的临床表现是皮疹和肝炎加重。
本研究将 PARV4 确定为一种对病毒灭活有抵抗力的可输血传播的病原体。令人担忧的是,暴露于血浆源性血液制品的人群仍可能经常发生感染。迫切需要评估治疗个体中 PARV4 的发生率和 PARV4 感染的疾病关联。