Human Monkeypox Infection: A Family Cluster in the Midwestern United States

Abstract

The outbreak of monkeypox in the Midwestern United States during June 2003 marks the first documented human infection in the Western Hemisphere. Consistent with those in outbreaks in Africa, most cases in this outbreak were associated with febrile rash illness. We describe a cluster of monkeypox in a family with a spectrum of clinical illness, including encephalitis, and outline the laboratory confirmation of monkeypox. Standardized patient information was collected by questionnaire and medical chart review; all cases described were laboratory confirmed. Laboratory methods included nucleic acid detection, viral culture, serologic testing, histopathologic evaluation, and immunohistochemical testing. Of 3 family members with monkeypox, 2 had rash illness only, and 1 required hospitalization for severe encephalitis. The family member with the mildest clinical course had previously received smallpox vaccination. Diagnostic testing by both polymerase chain reaction and culture revealed infectious monkeypox virus in skin lesions of all 3 patients; 2 patients had orthopoxvirus detected by immunohistochemistry in skin lesions. The patient with encephalitis had orthopoxvirus-reactive immunoglobulin M (IgM) in cerebrospinal fluid. All patients had detectable IgM responses to orthopoxvirus antigens. These 3 patients illustrate a spectrum of clinical illness with monkeypox despite a common source of exposure; manifestation and severity of illness may be affected by age and prior smallpox vaccination. We report that monkeypox, in addition to causing febrile rash illness, causes severe neurologic infection, and we discuss the use of novel laboratory tests for its diagnosis.