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Chapter 91 : Poxviruses
Poxviruses are large double-stranded DNA viruses that have a wide range of susceptible host species. Monkeypox is of increased interest since its importation into the United States in 2003 and has increased concerns of zoonotic transmission of poxviruses. This chapter addresses molecular and immunological diagnostic issues for detection of viral infections associated with four genera of the Chordopoxvirinae that cause human disease and their public health significance. Diagnostic methods are similar for these viruses and are addressed cumulatively. Parapoxviruses are structurally distinct from other Chordopoxvirinae and commonly cause agricultural disease of sheep, goats, and cattle that may be transmitted by direct contact to humans. The basis for diagnosis of any poxviruses can be attributed historically to smallpox. Detection of humoral antibody responses by serology is an indirect approach to diagnosis and has been a hallmark for laboratory diagnosis of viral infections. The most pragmatic serology tests are reviewed and include hemagglutination inhibition (HI), plaque reduction neutralization testing (PRNT), and enzyme-linked immunosorbent assay (ELISA), with methods described for PRNT and ELISA.
This photograph is of a Bangladeshi boy with smallpox, revealing the distribution of maculopapular lesions. (Source: CDC Public Health Image Library, James Hicks, 1973.)
Close-up photograph of monkeypox lesions on the arm and leg of a 4-year-old female child in Liberia. (Source: CDC Public Health Image Library, 1971.)
Monkeypox lesions from the 2003 U.S. outbreak, showing primary inoculation reactions (A, B, and C), examples of smallpox-like (D) and umbilicated varicella-like (E) disseminated monkeypox lesions, and morphologic appearance of disseminated lesions over time (F, G, H, and I). Panel A shows a primary inoculation reaction at the site of a prairie dog bite, panel B shows a prairie dog scratch, and panel C shows a preexisting cat scratch. Panel F shows a disseminated lesion less than 24 h after its appearance, panel G shows lesions after 6 days, panel H shows a lesion after 96 h, and panel I shows a lesion after more than 9 days. (Reproduced from reference 44 with permission.)
Major (primary) reaction—expected vaccine site reaction and progression following primary smallpox vaccination or revaccination after a prolonged period between vaccinations. Vaccinia virus vaccination results in a take under normal circumstances. A take is used as a measure of vaccine efficacy. The inoculation site becomes pustular around day 4 and then vesicular by day 7 and begins to scab around day 14. (Source: CDC [http://www.cdc.gov].)
EM of vaccinia virus (A and B) and monkeypox virus (C and D) from clinical lesions collected during the 2003 U.S. outbreak. Bar equals 100 nm. (Source: CDC [vaccinia, Cynthia Goldsmith and Yasou Ichihashi; monkeypox, Cynthia Goldsmith and Christopher D. Paddock].)
EM of parapoxvirus (orf) from a human lesion. Bar equals 100 nm. (Source: CDC [Cynthia Goldsmith and Fred A. Murphy].)
PRNT using control sera positive for plaque reduction. Sera were tested at 20-, 40-, and 80-fold dilutions. Plaque counts are the lowest in the 20-fold dilution wells (far left) and increase with higher dilutions. (Source: CDC [Poxvirus Program, Kevin L. Karem].)