Recent insights in testing for transfusion transmissible viral infections

Abstract

Since the advent of HIV in the early 80s there has been arapid evolution in the detection of transfusion transmissibleviral infections (TTVIs), first based on serologic screeningmethods and more recently on molecular diagnostics ornucleic acid amplification technology (NAT). For manyyears, transfusion centres have relied on serologic testingfor HBsAg, anti-HIV and anti-HCV to minimize the risk ofTTVIs, but since the late 1990s NAT for detection of HIV-RNA, HCV-RNA and HBV-DNA has been introduced in agrowing number of countries to provide a second layer ofsafety. Initially, NAT was performed on larger minipools(MPs) of typically 16–96 donations, but since 2005 auto-mated triplex NAT systems have become available for test-ing donations in smaller test pools ( 10% of the popula-tion has been exposed to the virus. Nevertheless, as anti-HBc-positive blood is known to be infectious some of thetime (<10%) if anti-HBs is not detectable [10,11] anti-HBcscreening has been introduced in a number of countrieswith a low HBV prevalence, well before NAT was intro-duced. More recently, a few European countries have intro-duced anti-HBc testing after MP-NAT had already beenintroduced [12], when it became clear that HBV transmis-sion cases by blood from donors with occult HBV infection(OBI) could still occur [13]. HBV-DNA levels in donors withOBI are generally low and can fluctuate around the detec-tion limit of the NAT systems in use. Recently, more sensi-tive ID-NAT technology for detection of HBV has beenintroduced, but it is unclear which proportion of HBVtransmission cases caused by occult HBV carriers wouldhave been detectable with these assays. HBV transmissionreports have shown that HBV-DNA positive blood in OBIcan be infectious if anti-HBs titres are below 10 mIU⁄ml[13], but the few systematic look back studies that havebeen performed so far indicate that the risk of HBV trans-mission from occult HBV carriers is relatively low [11,14].If anti-HBs antibodies are detectable the risk of anti-HBcpositive blood to be infectious is negligible [10,11], unlessviraemia breaks at relatively high level through a low anti-HBs titer as was observed in one case reports [15]. Thislatter case report showed that re-appearance of persistentlypresent HBV-DNA in OBI when it increased to approxi-mately 900 copies⁄ml at the time anti-HBs titres haddeclined to 12 mIU⁄ml was infectious in two recipients.