Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 14, Number 4—April 2008

Retrospective Analysis of Monkeypox Infection

Melissa E. Dubois* and Mark K. Slifka*Comments to Author 
Author affiliations: *Oregon Health and Science University, Beaverton, Oregon, USA;

Main Article


Comparison of monkeypox-specific diagnostic tests*

Patient no. Serologic techniques Cellular techniques Direct viral detection Postadsorption ELISA Postadsorption Western blot†
Paired IgG Peptide ELISA 39 kDa 124 kDa 148 kDa
447 C C C C C + + +
452 C C C C C + + +
453 C C C P/S C + + +
461 C C C NA C + +
462 C C C C C +
481 C C C NA C + +
482 C C C NA C + +
484 C C C NA C +
489 C C C NA C + +
473 C C C NA C + +
519 C C C C C + +
520 C C C C C + +
446‡ C C C ND U
449‡ C C U ND U +
450 C C C P/S C +
451 C C C C C +
454 C C C P/S C + + +
455‡ C C C ND U +
463 C C C C C +
500 C C C ND C +

*These studies are based on persons who were infected with monkeypox during the 2003 outbreak in Wisconsin and who were tested by independent laboratories by using serologic (6), cellular (6), and virologic (4) techniques. Serologic techniques included identification of monkeypox peptide-specific immunoglobulin (Ig) G by peptide ELISA and kinetic analysis of IgG to orthopoxvirus in paired plasma samples (2–4 mo and 1 y postinfection) by endpoint ELISA. Orthopoxvirus-specific CD8+ T cells were measured by using intracellular cytokine staining analysis. Plasma samples were obtained 2–4 mo postinfection, except for patients 473 and 500 (6 mo), 519 and 520 (12 mo), and 557 (30 mo). Virologic confirmation was obtained by viral culture, PCR, electron microscopy, and immunohistochemical analysis of tissue samples (4). C, confirmed; P/S, probable/suspected; NA, not available; ND, not done; U, unconfirmed.
†A + indicates that at least 5/6 analysts scored the band of interest as positive.
‡Clinically inapparent monkeypox infection in previously vaccinated persons as determined by cellular and serologic retrospective diagnostic techniques (6).

Main Article

  1. Nalca  A, Rimoin  AW, Bavari  S, Whitehouse  CA. Reemergence of monkeypox: prevalence, diagnostics, and countermeasures. Clin Infect Dis. 2005;41:176571. DOIPubMedGoogle Scholar
  2. Rimoin  AW, Kisalu  N, Kebela-Ilunga  B, Mukaba  T, Wright  LL, Formenty  P, Endemic human monkeypox, Democratic Republic of Congo, 2001–2004. Emerg Infect Dis. 2007;13:9347.PubMedGoogle Scholar
  3. Jezek  Z, Fenner  F, eds. Human monkeypox. Basel: Karger; 1988.
  4. Reed  KD, Melski  JW, Graham  MB, Regnery  RL, Sotir  MJ, Wegner  MV, The detection of monkeypox in humans in the Western Hemisphere. N Engl J Med. 2004;350:34250. DOIPubMedGoogle Scholar
  5. Sejvar  JJ, Chowdary  Y, Schomogyi  M, Stevens  J, Patel  J, Karem  K, Human monkeypox infection: a family cluster in the midwestern United States. J Infect Dis. 2004;190:183340. DOIPubMedGoogle Scholar
  6. Hammarlund  E, Lewis  MW, Carter  SV, Amanna  I, Hansen  SG, Strelow  LI, Multiple diagnostic techniques identify previously vaccinated individuals with protective immunity against monkeypox. Nat Med. 2005;11:100511.PubMedGoogle Scholar
  7. Huhn  GD, Bauer  AM, Yorita  K, Graham  MB, Sejvar  J, Likos  A, Clinical characteristics of human monkeypox, and risk factors for severe disease. Clin Infect Dis. 2005;41:174251. DOIPubMedGoogle Scholar
  8. Lewis  MW, Graham  MB, Hammarlund  E, Hanifin  J, Slifka  MK. Monkeypox without exanthem. N Engl J Med. 2007;356:21124. DOIPubMedGoogle Scholar
  9. Jezek  Z, Marennikova  SS, Mutumbo  M, Nakano  JH, Paluku  KM, Szczeniowski  M. Human monkeypox: a study of 2,510 contacts of 214 patients. J Infect Dis. 1986;154:5515.PubMedGoogle Scholar
  10. Karem  KL, Reynolds  M, Hughes  C, Braden  Z, Nigam  P, Crotty  S, Monkeypox-induced immunity and failure of childhood smallpox vaccination to provide complete protection. Clin Vaccine Immunol. 2007;14:131827. DOIPubMedGoogle Scholar
  11. Seward  JF, Galil  K, Damon  I, Norton  SA, Rotz  L, Schmid  S, Development and experience with an algorithm to evaluate suspected smallpox cases in the United States, 2002–2004. Clin Infect Dis. 2004;39:147783. DOIPubMedGoogle Scholar
  12. Klein  KR, Atas  JG, Collins  J. Testing emergency medical personnel response to patients with suspected infectious disease. Prehosp Disaster Med. 2004;19:25665.PubMedGoogle Scholar
  13. Jezek  Z, Nakano  JH, Arita  I, Mutombo  M, Szczeniowski  M, Dunn  C. Serological survey for human monkeypox infections in a selected population in Zaire. J Trop Med Hyg. 1987;90:318.PubMedGoogle Scholar
  14. Baxby  D. The surface antigens of orthopoxviruses detected by cross-neutralization tests on cross-absorbed antisera. J Gen Virol. 1982;58:25162.PubMedGoogle Scholar
  15. Hutchinson  HD, Ziegler  DW, Wells  DE, Nakano  JH. Differentiation of variola, monkeypox, and vaccinia antisera by radioimmunoassay. Bull World Health Organ. 1977;55:61323.PubMedGoogle Scholar
  16. Lefkowitz  EJ, Upton  C, Changayil  SS, Buck  C, Traktman  P, Buller  RM. Poxvirus Bioinformatics Resource Center: a comprehensive poxviridae informational and analytical resource. Nucleic Acids Res. 2004;33:D3116. DOIPubMedGoogle Scholar
  17. Gispen  R, Brand-Saathof  B. Three specific antigens produced in vaccinia, variola, and monkeypox infections. J Infect Dis. 1974;129:28995.PubMedGoogle Scholar
  18. Arita  M, Tagaya  I. Virion polypeptides of poxviruses. Arch Virol. 1980;63:20925. DOIPubMedGoogle Scholar
  19. Turner  A, Baxby  D. Structural polypeptides of orthopoxvirus: their distribution in various members and location within the virion. J Gen Virol. 1979;45:53745.PubMedGoogle Scholar
  20. Harper  L, Bedson  HS, Buchan  A. Identification of orthopoxviruses by polyacrylamide gel electrophoresis of intracellular polypeptides. I. Four major groupings. Virology. 1979;93:43544. DOIPubMedGoogle Scholar
  21. Esposito  JJ, Obijeski  JF, Nakano  JH. The virion and soluble antigen proteins of variola, monkeypox, and vaccinia viruses. J Med Virol. 1977;1:95110. DOIPubMedGoogle Scholar
  22. Esposito  JJ, Obijeski  JF, Nakano  JH. Serological relatedness of monkeypox, variola, and vaccinia viruses. J Med Virol. 1977;1:3547. DOIPubMedGoogle Scholar
  23. Gispen  R. Analysis of pox-virus antigens by means of double diffusion: a method for direct serological differentiation of cowpox. J Immunol. 1955;74:13441.PubMedGoogle Scholar
  24. Gispen  R, Huisman  J, Brand-Saathof  B, Hekker  AC. Immunofluorescence test for persistent poxvirus antibodies. Arch Gesamte Virusforsch. 1974;44:3915. DOIPubMedGoogle Scholar
  25. Gispen  R, Brand-Saathof  BB, Hekker  AC. Monkeypox-specific antibodies in human and simian sera from the Ivory Coast and Nigeria. Bull World Health Organ. 1976;53:35560.PubMedGoogle Scholar
  26. Demkowicz  WE, Maa  JS, Esteban  M. Identification and characterization of vaccinia virus genes encoding proteins that are highly antigenic in animals and are immunodominant in vaccinated humans. J Virol. 1992;66:38698.PubMedGoogle Scholar
  27. Jones-Trower  A, Garcia  A, Meseda  CA, He  Y, Weiss  C, Kumar  A, Identification and preliminary characterization of vaccinia virus (Dryvax) antigens recognized by vaccinia immune globulin. Virology. 2005;343:12840. DOIPubMedGoogle Scholar
  28. Marennikova  SS, Malceva  NN, Habahpaseva  NA. ELISA—a simple test for detecting and differentiating antibodies to closely related orthopoxviruses. Bull World Health Organ. 1981;59:3659.PubMedGoogle Scholar
  29. Karem  KL, Reynolds  M, Braden  Z, Lou  G, Bernard  N, Patton  J, Characterization of acute-phase humoral immunity to monkeypox: use of immunoglobulin M enzyme-linked immunosorbent assay for detection of monkeypox infection during the 2003 North American outbreak. Clin Diagn Lab Immunol. 2005;12:86772. DOIPubMedGoogle Scholar

Main Article

Page created: July 13, 2010
Page updated: July 13, 2010
Page reviewed: July 13, 2010
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.