The clinically observed HBV infection risk caused by blood components from occult HBV carriers with low anti-HBc titers who slip through the JRC screening system is more than 10-fold lower than the transmission risk by donations in the pre-HBsAg and/or MP-NAT window phase.

Although the CID50 of approximately 10 copies was similar for the two HBV genotypes, the doubling time and pre-HBV nucleic acid amplification technology (<100 copies/mL) window period in chimps infected with the lowest infectious dose seemed to be shorter for genotype C than for genotype A.

Studies of hepatitis B virus (HBV) infection in non-human primates such as chimpanzees are no longer possible due to ethical considerations and the endangered status of chimpanzees since April 2007 in Japan. A human hepatocyte transplanted chimeric mouse was used to characterize HBV infectivity in serial stages of acute infection. Chimeric mice were inoculated intravenously with serum samples obtained from an experimentally infected chimpanzee with HBV. Sera from the pre-acute phases (i.e., rump-up viremia prior to anti-HBc) and late acute phases (i.e., declining phase of HBsAg and anti-HBcAb positive) were collected from the chimpanzees 57 and 244 days after inoculation. These sera contained 2.6 x 10(6) and 2.8 x 10(6) copies/ml of HBV DNA, respectively. Three chimeric mice inoculated intravenously with 100 microl of pre-acute serum (equivalent to 10(0) copy of HBV DNA) developed an HBV infection. The three chimeric mice that received 100 microl of pre-acute serum (equivalent to 10(1) copies of HBV DNA), developed high levels of serum HBV DNA. None of the three chimeric mice inoculated with 100 microl of 1:10(4) dilution (equivalent to 10(1) copies of HBV DNA) of late-acute serum was infected, while only one of three chimeric mice inoculated with 100 microl of 1:10(3) dilution (equivalent to 10(2) copies of HBV DNA) of late-acute serum developed an HBV infection. Based on these results, chimeric mice can be used as animal models for the study of HBV infectivity, pathogenesis and control. The results show that pre-acute phase HBV serum is about 100-times more infectious than late acute phase serum.

Objective: To determine the copy number of hepatitis C virus (HCV) RNA, determined by nucleic acid amplification test (NAT) for screening blood units in Japan, that can transmit infection to chimpanzees. Methods: Fresh-frozen plasma with markers of HCV infection, as well as inocula pedigreed from 1 of them, were evaluated for the infectious activity in chimpanzees. Results: One unit each (273–282 ml) of fresh-frozen plasma from 2 blood donors or a pool from 13 donors to make a unit, which contained high-titered antibody to HCV but without HCV RNA detectable by NAT, did not infect any of 3 chimpanzees. Two chimpanzees were infected, however, when they were inoculated with 1 ml of serum from a blood donor in the ‘window period’ of HCV infection and containing 7.0 × 10⁶ copies/ml of HCV RNA. The preacute phase serum from 1 of them harvested 7 weeks after the inoculation was titrated in 2 chimpanzees, and an inoculum containing approximately 2 × 10¹ copies of HCV RNA could transmit infection to both of them. Conclusion: Approximately 20 copies of HCV can transmit infection to recipients, which needs to be taken into consideration in planning the screening of blood units for HCV RNA by NAT. Although the sensitivity of present NAT could be improved further, there would be a limit of it in detecting a low-level HCV RNA in the window period of donors with the infectious capacity in recipients.

The sensitivity of the 50-sample pool MPX NAT system was higher than that of individual HBsAg screening by CLIA. By adopting this NAT-screening system, the JRC has improved the safety of the blood supply and maintained supply across Japan.

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