Mousepox resulting from use of ectromelia virus-contaminated, imported mouse serum

Mousepox was identified in a single mouse-holding room in early 1999 after a group of 20 CAF1/Hsd mice were inoculated SC with a killed murine spindle cell tumor line, S1509A. The cell line had been used without complications multiple times and was determined to be free of viral contamination on the basis of results of mouse antibody production testing. Of the 20 mice inoc ulated, 12 mice died by postinoculation day 8. Severe lymphoid and hepatic necrosis was observed in select mice subjected to histologic examination. B allooning degeneration of epithelial cells with intracytoplasmic eosinophil ic inclusion bodies was observed in the skin overlying the inoculation site of the single mouse from which this tissue site was evaluated. Presence of ectromelia virus was confirmed by use of immunohistochemical and polymeras e chain reaction analyses, and the virus was isolated after serum, pooled f rom 5 of the index cases, was inoculated into an immune-naive mouse. Invest igation into the source of virus contamination included inoculating mice wi th aliquots of various S1509A freeze dates; chemically defined media and su pplements, including fetal bovine serum; and two lots of pooled commercial mouse sera, after heat inactivation at 56 degrees C for 30 minutes used as a medium supplement. One lot of pooled commercial mouse serum was identifie d as the source of ectromelia virus. This lot of serum was inadvertently us ed to feed S1509A cells that were subsequently inoculated into mice. We det ermined that the contaminated serum, which was purchased in late 1998, orig inated from China. The serum was imported into the United States as a batch of 43 L in early 1995. The serum was blended into a single lot and filtere d (0.2 mu m) before distribution to major suppliers throughout the country. The serum was sold or further processed to obtain a variety of serum-deriv ed products. Because murine serum is generally sold in small aliquots (10 t o 50 ml), we speculate that several thousand aliquots may have been derived from this batch of serum and, if inoculated into mice, would likely result in additional mousepox outbreaks.