Michael Chudy

A new cluster of hepatitis A infection in hemophiliacs traced to a contaminated plasma pool.

Recently, several clusters of hepatitis A have been observed among hemophiliacs linked to factor VIII concentrates treated for virus inactivation solely with the solvent/detergent (S/D) method, a procedure that does not affect nonenveloped viruses such as the hepatitis A virus (HAV). A new outbreak of hepatitis A in six hemophiliacs treated with the same lot of a factor VIII preparation occurred recently in Germany. The objective of the study was to clarify whether these diseases were caused by the administration of the S/D‐treated plasma product, rather than a community‐acquired infection. Polymerase chain reactions designed to detect HAV nucleic acid have been carried out in the implicated factor VIII lots, in the corresponding plasma pools, and in serum samples of four out of six infected individuals. The nucleic acid sequences were determined in samples that resulted in positive amplification products. HAV sequences were found in one of the two plasma pools used for manufacture of the incriminated product, in the incriminated lot itself, and in all recipient sera tested so far, although the latter were collected up to 7 weeks after the onset of jaundice. The sequences obtained were completely identical, revealing a unique HAV strain of genotype IA. This study provides conclusive evidence that hepatitis A can be transmitted by factor VIII concentrates treated solely by the S/D procedure for virus inactivation. This inactivation method is not effective against nonenveloped viruses. Since a number of hepatitis A transmission episodes have been described with such preparations during the past 10 years, their continued use seems to be questionable unless additional virus removal or inactivation steps are introduced to prevent the transmission of nonenveloped viruses. Molecular approaches again proved to be reliable tools for elucidating the chain of virus transmission. J. Med. Virol. 57:91–99, 1999.

Sensitivity of HCV core antigen and HCV RNA detection in the early infection phase

BACKGROUND : Various countries have introduced HCV NAT to exclude infectious donations collected during the preseroconversion window phase (PWP). For the same purpose, an ELISA has also been developed to detect HCV core antigen (cAg).

Infectivity of blood products from donors with occult hepatitis B virus infection

Occult hepatitis B virus (HBV) infection (OBI) is identified in 1:1000 to 1:50,000 European blood donations. This study intended to determine the infectivity of blood products from OBI donors.

Anti-HBc screening of blood donors: a comparison of nine anti-HBc tests

Background and Objectives  Since voluntary introduction of hepatitis B virus (HBV) minipool nucleic acid amplification technology (NAT) at the German Red Cross, the expected residual risk of a transfusion‐associated HBV infection has been estimated to be 1 : 500 000 – about 10 times higher than for human immunodeficiency virus (HIV) or hepatitis C virus (HCV) infection. Donors demonstrating chronic positivity for antibody to hepatitis B core antigen (anti‐HBc), negativity for hepatitis B surface antigen (HBsAg) and polymerase chain reaction (PCR)‐negative with a low virus load are a major cause of this increased risk.

First transmission of human immunodeficiency virus Type 1 by a cellular blood product after mandatory nucleic acid screening in Germany

BACKGROUND: In February 2007, a 63‐year‐old man underwent surgery. Retrospective testing with nucleic acid testing (NAT) showed that the patient was human immunodeficiency virus Type 1 (HIV‐1) positive 10 days after transfusion. The transfusion‐transmitted infection had been identified by a donor‐related lookback started in April 2007 after anti‐HIV seroconversion.

Multicenter performance evaluation of a transcription-mediated amplification assay for screening of human immunodeficiency virus-1 RNA, hepatitis C virus RNA, and hepatitis B virus DNA in blood donations

BACKGROUND: The performance of the recently launched Procleix Ultrio (Chiron/Gen‐Probe) human immunodeficiency virus‐1 (HIV‐1), hepatitis C virus (HCV), and hepatitis B virus (HBV) blood screening assay was evaluated in a European multicenter study.

Hepatitis B virus genotype G monoinfection and its transmission by blood components

An acute hepatitis B virus (HBV) infection was diagnosed in a regular apheresis (plasma/platelet) donor by the hepatitis B surface antigen (HBsAg) assay and minipool nucleic acid amplification technology (NAT). The acute infection was confirmed by detection of anti‐HBc (IgM) and anti‐HBs 2 weeks later. The donor showed no clinical symptoms and had normal alanine aminotransferase levels. He had a history of weekly apheresis plasma or platelet donations. Archived material from the donor and the respective recipients was investigated by sensitive HBV NATs as part of a look‐back procedure. HBV DNA was detectable in previous donations as well as in two recipients transfused with platelet concentrates. The rare HBV genotype G was identified in all HBV‐DNA‐positive samples. Strong evidence of genotype G monoinfection was obtained by clonal sequencing, HBV genotype line probe assay, genotype‐specific NATs, and restriction pattern analysis. In contrast to previously described genotype G infections, which all appeared as coinfections with genotype A, neither the hepatitis B e antigen (HBeAg) nor anti‐HBe was detectable in any of the samples. This shows that HBeAg is dispensable for viral replication. The delay in detecting HBsAg in both the donor and recipient samples may be explained by either decreased genotype G–specific synthesis of incomplete viral forms in early HBV infection or the lower sensitivity to genotype G of the current HBsAg assays. In conclusion, this reported case of an HBV infection was caused exclusively by genotype G. (HEPATOLOGY 2006;44:99–107.)

Experience of mandatory nucleic acid test (NAT) screening across all blood organizations in Germany: NAT yield versus breakthrough transmissions.

BACKGROUND: Mandatory nucleic acid test (NAT) blood screening was introduced in Germany in 1999 for hepatitis C virus (HCV) RNA and in 2004 for human immunodeficiency virus Type 1 (HIV‐1) RNA. Minimal sensitivity limits of 5000 IU HCV RNA/mL and 10,000 IU HIV‐1 RNA/mL were defined for the individual donation facilitating testing of minipools (MPs). The NAT yield obtained from all blood organizations is summarized. Transfusion‐associated virus transmissions despite NAT screening (“breakthrough transmissions”) are analyzed.

First case of hepatitis C virus transmission by a red blood cell concentrate after introduction of nucleic acid amplification technique screening in Germany: a comparative study with various assays

Background and Objectives  Pooled nucleic acid amplification techniques (NAT) and donor screening for anti‐hepatitis C virus (HCV) have reduced the diagnostic window period of HCV infection in the blood donor population from about 12 to 1 or 2 weeks. During that time, HCV RNA is hardly detectable by pooled or individual donation NAT. Here we describe a case of transfusion‐acquired HCV infection from an extremely low‐titre donation. After a repeat donor tested positive for HCV, a look‐back procedure was initiated. A recipient of a red cell concentrate from the previous donation was identified and found to be infected with HCV as well. We compared several commercial NAT systems for their ability to detect the viraemic plasma.

Blood screening nucleic acid amplification tests for human immunodeficiency virus Type 1 may require two different amplification targets.

BACKGROUND: Five cases of human immunodeficiency virus Type 1 (HIV‐1) RNA–positive blood donations are described that escaped detection by three different CE‐marked nucleic acid amplification technique (NAT) screening assays. These events were associated with two HIV‐1 transmissions to recipients of blood components. The implicated NAT assays are monotarget assays and amplify in different viral genome regions (group‐specific antigen or long terminal repeat). Investigations into the cause of the false‐negative test results were initiated.