Rat-to-Elephant-to-Human Transmission of Cowpox Virus

To the Editor: Despite the eradi-cation of smallpox in the past century , other orthopoxviruses, such as monkeypox virus, vaccinia virus in Brazil, and cowpox virus (CPXV) in Europe (1), still infect humans. CPXV has been restricted to the Old World with wild rodents as its natural reservoir (2,3). Human CPXV infections are commonly described in relation to contact with diseased domestic cats, rarely directly from rats (2,4). Human infections usually remain localized and self-limiting but can become fatal in immunosuppressed patients (5). CPXV infections in captive exotic animals have been reported to be transmitted by rodents (2,6). In February 2007, a circus elephant (Elephas maximus) in northern Germany exhibited disseminated ulcerative lesions of the skin and mucosal membranes (Figure, panel A) caused by CPXV infection; the elephant was euthanized after treatment attempts failed. Electron mi-crographs of negative-stained biopsy specimens of tongue lesions showed orthopoxvirus particles. The presence of orthopoxvirus after routine virus isolation in Hep2 cells was confi rmed in direct immunofl uores-cence assay with orthopox-specifi c antibodies. The morphologic feature of hemorrhagic pocks on the chorioal-lantoic membrane (CAM) of infected embryonated hen's eggs indicated CPXV. This fi nding was confi rmed by sequence analysis of the complete hemagglutinin (HA) open reading frame (ORF), which showed 99% ho-mology of 921 bp to CPXV isolated in 1984 from an elephant in Hamburg, Germany (Figure, panel B). A serum sample was drawn from the elephant 2 weeks before euthanasia. An indirect fl uorescent antibody test (IFAT) detected immunoglobulin (Ig) G anti-bodies against the new corresponding elephant virus isolate (termed CPXV GuWi) with a titer of 1,260. According to the owner, the >40-year-old female elephant had never been vaccinated with vaccinia virus. Eight days after the elephant's death, a circumscribed lesion developed on the back of the right hand of a 19-year-old immunocompetent, healthy, unvaccinated animal keeper. CPXV was isolated from lesion fl uid and was found to be homologous by using the HA ORF to CPXV GuWi. A convalescent-phase serum sample from the keeper taken 3 weeks later showed a signifi cant increase in IgM 670 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 14, No. 4, April 2008 Figure. Route of cowpox virus (CPXV) transmission and phylogenetic analysis of orthopoxviruses. A) Disseminated ulcerative lesions of the skin around the eye of the circus elephant. Although transmission of CPXV has been confi rmed from cats and cows to humans (1,2), transmission from …