In 2003, a zoonotic outbreak of human monkeypox occurred in North America. The outbreak was the first time that this virus caused human disease outside Africa. Subsequent investigation confirmed that the source of the outbreak was an imported consignment of African mammals from the West African nation of Ghana. Subsequently, the virus moved to captive native North American species, including Cynomys species (prairie dogs) (10,21,23). Human cases were infected through contact with infected animals, principally prairie dogs (19,23). Viral isolates associated with the outbreak were genetically characterized as West African variants of monkeypox distinct from Central African viruses (20). During the outbreak, and in a follow-up study, specimens from suspected cases and their contacts were submitted to the Centers for Disease Control and Prevention (CDC) for laboratory testing. Laboratory testing included virological testing (culture and PCR) of presumptive virus-containing specimens for case confirmation and analysis of immunological markers from blood or serum samples. Immunological analysis included serologic testing for orthopoxvirus (OPX)-specific antibodies (immunoglobulin G [IgG] and IgM) and virus-specific cellular (CD4, CD8, and B-cell) immunity evaluation in cases and contacts.In this study, we evaluated human monkeypox cases and household contacts of monkeypox-infected animals and report the characterization of the convalescent and long-term memory (1-year) immune response to monkeypox infection during this outbreak. Correlations between immunological markers, smallpox vaccination status, and infection outcomes are evaluated, as well as memory immune responses in previously vaccinated individuals within this cohort.
MATERIALS AND METHODS
Specimens.Response to the 2003 U.S. monkeypox outbreak involved the collection of information related to lab results, exposure characteristics, clinical features of illness, and other epidemiologic features. Teams of clinicians, epidemiologists, and microbiologists from the CDC and the six affected states collected information and samples from cases and contacts of cases. Patient specimens were sent to the CDC as a part of the outbreak investigation, and confirmation of suspect cases was based on identification of virus in tissuederived specimens (21). As an extension of the outbreak investigation, a followup, household-based, Institutional Review Board-approved, case control study was initiated to assess exposures, clinical markers of disease severity, and immune responses at 7 to 14 weeks (convalescent) and at 1 year postexposure. Specimens were collected at convalescent and 1-year time points, and clinical and epidemiologic information was collected with a standardized questionnaire. A total of 92 persons enrolled in the study. Eighteen of those enrolled were excluded from the analysis due to unknown vaccination status or unwillingness to provide biological samples. A total of 72 individuals were considered in these analyses. Enrolled individuals were categorized into ...