Nucleic acid testing in high-risk blood donors may help catch hepatitis B virus (HBV) infections that might otherwise be missed.
Nine HBV cases were identified in 3.7 million donors screened at three of the American Red Cross’s five National Testing Laboratories in 2008 — triple the expected infection rate, according to Susan L. Stramer, PhD, of the American Red Cross in Rockland, M.D., and colleagues.
“This study showed a higher-than-expected rate of HBV infection with the use of triplex nucleic acid testing, mainly in donors who had been vaccinated against HBV and who would not have been identified by routine screening,” the researchers wrote in the New England Journal of Medicine.
Current HBV screening tests for hepatitis B surface antigen (HBsAg) or for antibodies against HBV core antigen (anti-HBc), but these methods are unable to detect HBV in donors in time frame before seroconversion.
To see if they could improve detection rates, the researchers performed combination nucleic acid testing for HBV, hepatitis C virus (HCV) and HIV using a single triplex assay among 3.7 million donors.
They identified nine samples that were positive for HBV DNA, but negative for HBsAg and anti-HBc. Although this only translates into one case per 410,540 donations, modeling estimates projected a much lower occurrence rate at two to four cases in the entire sample.
“These acute HBV infections rapidly resolved and are of inconsequential significance, but their potential for transmission remains unresolved,” the researchers wrote.
Six of the nine samples identified came from donors who had been vaccinated against HBV and had developed subclinical infections that resolved. Only one of these donors was infected with HBV subgenotype A2, the most frequent HBV strain in the United States and the primary vaccine strain.
The three additional identified cases occurred among donors who had not been vaccinated against HBV and experienced acute infection with A2 subtype. Overall, two cases of liver injury occurred in the nine samples among donors who had not been vaccinated.
“The blood of donors with acute HBV DNA-positive infection during the window period is likely to be highly infectious in transfusion recipients,” the researchers wrote. “The significance of infection in vaccinated donors is less clear.”
The data emphasize the efficacy of the HBV vaccine, according to the researchers, who noted that the vaccinated donors had “brief, transient” courses of infection, “with no evidence of disease and very low or absent expression of HBsAg.” However, they warned that the vaccine might be less effective against non-A2 HBV subtypes.
Despite the lack of cost-efficacy in routine nucleic acid screening because of the low overall number of transfusion-transmitted infections, the researchers noted that 25 of the 75 seronegative blood samples identified were confirmed positive for HBV, HBC or HIV.
“Because of the high cost of introducing new screening assays for blood donors and the inability to document cost-effectiveness similar to that of other medical interventions, the continued development of new tests either to replace older tests or detect newly identified agents is in question,” the researchers wrote.