Hepatitis A Virus Incidence Rates and Biomarker Dynamics for Plasma Donors, United States.

The United States is currently affected by widespread hepatitis A virus (HAV) outbreaks. We investigated HAV incidence rates among source plasma donors in the United States since 2016. Serial donations from HAV-positive frequent donors were analyzed for common biologic markers to obtain a detailed picture of the course of infection. We found a considerable increase in incidence rates with shifting outbreak hotspots over time. Although individual biomarker profiles were highly variable, HAV RNA typically had a high peak and a biphasic decrease and often remained detectable for several months. One donor had a biomarker pattern indicative of previous exposure. Our findings show that current HAV outbreaks have been spilling over into the plasma donor population. The detailed results presented improve our comprehension of HAV infection and related public health aspects. In addition, the capture of full RNA curves enables estimation of HAV doubling time.

Longitudinal changes in measles antibody titers in plasma donors and minimum antibody levels of immunoglobulin products for treatment of primary immunodeficiency.

BACKGROUND: To ensure that immunoglobulin (Ig) products have adequate functional antibody, the US Food and Drug Administration (FDA) requires that Ig lots contain minimum levels of measles neutralizing antibody; the current minimum is 0.48 x US Reference Ig 176. STUDY DESIGN AND METHODS: In the first part of the study, measles antibody titers were measured in donor plasma samples collected in 2007, 2011, and 2017. In the second part, trough or steady-state serum levels of measles neutralizing antibody were measured in two studies of patients with primary immunodeficiency (PID) who were treated with intravenous (Study 1; N = 46) or subcutaneous (Study 2; N = 18) Ig replacement therapy, meeting previous requirements for lot potency (≥0.6 x US Reference Ig 176). Serum measles neutralizing antibody titers were then estimated for conditions in which the potency of the Ig replacement product was 0.48 or 0.30 x US Reference Ig 176. RESULTS: Measles antibody titers in donated plasma samples declined in donors born after 1963. In the two studies of patients with PID who were treated with intravenous or subcutaneous Ig replacement therapy, all patients exhibited trough (intravenous Ig) or steady-state (subcutaneous Ig) measles neutralizing antibody titers above 0.12 IU/mL, which has been shown to protect against clinical measles in the general population. Estimates suggest that all patients except one would have continued to meet this standard if the Ig lot potency had been 0.48 or 0.30 x US Reference Ig 176. CONCLUSION: These studies provide supporting evidence that the lot release specification can be safely lowered from 0.48 to 0.30 x US Reference Ig 176, which will accommodate declining measles neutralizing antibody levels in donor plasma.