Correlates to Increased Lethality of Attenuated Venezuelan Encephalitis Virus Vaccine for Immunosuppressed Hamsters

Abstract

Splenectomy or pretreatment of adult hamsters with cyclophosphamide (Cytoxan) increased the lethality of the TC-83 vaccine strain of Venezuelan encephalitis virus (VEE), inoculated subcutaneously, from 12% for normal hamsters to 75 and 76%, respectively. Neither splenectomy nor cyclophosphamide treatment significantly increased the lethality of Pixuna virus. Cytoxantreated (Cy) hamsters developed and maintained levels of TC-83 virus higher than normal infected controls in blood, brain, spleen, and femoral bone marrow; splenectomy had a similar but less intense effect. A severe myeloid necrosis of femoral bone marrow developed 4 to 9 days after TC-83 virus inoculation in 78% of the Cy hamsters and in 48% of the splenectomized (Sx) hamsters. In contrast, only 13% of normal TC-83-infected hamsters developed this lesion. Extensive hemorrhagic lesions in the olfactory lobes and adjacent areas of the brain also developed more frequently in Cy or Sx hamsters than in normal infected controls. Lethally infected hamsters developed and maintained a severe thrombocytopenia, which may be related to the bone marrow lesion and to the hemorrhagic manifestations of lethal VEE infections.