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Vaccinia Follow-up

  • Author: Nikesh A Patel; Chief Editor: Mark R Wallace, MD, FACP, FIDSA  more...
Updated: Apr 25, 2016

Further Outpatient Care

Immunocompetent individuals with generalized vaccinia require supportive care and isolation from immunocompromised individuals until the infection resolves.

Less severe complications (eg, accidental infections) can be treated expectantly in an outpatient setting, provided the patient can avoid contact with high-risk individuals.


Further Inpatient Care

Patients with minor complications related to vaccinia immunization can usually be treated in an ambulatory setting. Severe complications require hospital admission and supportive intervention.

Infected patients should be isolated in a reverse airflow setting until the diagnosis is confirmed. These patients should avoid contact with other immunosuppressed persons (eg, persons with neutropenic cancer, HIV infection). These patients should also avoid contact with pregnant women, individuals with eczema, and young children.

Note that health care workers, including nurses, phlebotomists, house staff, and nutritionists, should also avoid direct contact with infected patients.



Routine vaccination with smallpox (vaccinia) vaccine, live (ACAM2000) is recommended by the CDC for occupations who directly handle cultures or animals contaminated or infected with replication-competent vaccinia virus, recombinant vaccinia viruses derived from replication-competent vaccinia strains (ie, those that are capable of causing clinical infection and producing infectious virus in humans), or other orthopoxviruses that infect humans (eg, monkeypox, cowpox, and variola).[2]

Health care personnel (eg, physicians and nurses) who currently treat or anticipate treating patients with vaccinia virus infections and whose contact with replication-competent vaccinia viruses is limited to contaminated materials (eg, dressings) and persons administering smallpox vaccine who adhere to appropriate infection prevention measures can be offered vaccination with ACAM2000, but vaccination is not recommended as routine.[2]

Avoiding vaccination of high-risk individuals (eg, immunosuppressed patients, pregnant women) can prevent vaccinia complications. Recent vaccinees also should avoid high-risk individuals for up to 21 days after vaccination. Recent evidence shows that TNF-alpha may play a role in resisting vaccinia virus infection of the skin; thus, patients on TNF-alpha-antagonists may also be at high risk.[10]

Avoid vaccination of children younger than 18 years unless indicated by a smallpox emergency.[2]

Current guidelines recommend that vaccinees defer blood donation for 21 days after vaccination or until the scab separates, whichever is later. Further studies indicate that extending the duration may be appropriate.

Contraindications to nonemergency use of smallpox vaccine include the following:[2]

  • Persons with a history or presence of atopic dermatitis or other active exfoliative skin conditions (eg, eczema, burns, impetigo, varicella zoster virus infection, herpes simplex virus infection, severe acne, severe diaper dermatitis with extensive areas of denuded skin, psoriasis, or Darier disease [keratosis follicularis])
  • Persons with conditions associated with immunosuppression (eg, HIV infection or AIDS, leukemia, lymphoma, generalized malignancy, solid organ transplantation, or therapy with alkylating agents, antimetabolites, radiation, tumor necrosis factor [TNF] inhibitors, or high-dose corticosteroids [≥2 mg/kg body weight or ≥20 mg/day of prednisone or its equivalent for ≥2 weeks], hematopoietic stem cell transplant recipients <24 months post-transplant or ≥24 months, but who have graft-versus-host disease or disease relapse, or autoimmune disease [eg, systemic lupus erythematosus] with immunodeficiency as a clinical component)
  • Children younger than 1 year
  • Women who are pregnant or breastfeeding
  • Persons with a serious allergy to any component of ACAM2000
  • Persons with known underlying heart disease with or without symptoms (eg, CAD or cardiomyopathy)
  • Primary vaccinees with 3 or more known major cardiac risk factors (ie, hypertension, diabetes, hypercholesterolemia, heart disease at age 50 years in a first-degree relative, and smoking)


Recovery from minor vaccinia complications is usually complete.

Severe complications, especially in immunocompromised hosts and young children with encephalopathy, carry significant mortality rates.


Patient Education

Patients should be instructed about proper wound care after vaccination with vaccinia virus. This includes changing any bio-occlusive dressings and avoiding inappropriate disposal of infected bandages.

Patients must be educated to avoid high-risk individuals during the period of maximal viral shedding, approximately 10 days after exposure to the virus.

Contributor Information and Disclosures

Nikesh A Patel Medical University of South Carolina College of Medicine

Nikesh A Patel is a member of the following medical societies: American Medical Association, South Carolina Medical Association

Disclosure: Nothing to disclose.


Dayna Diven, MD Professor, Department of Dermatology, University of Texas Southwestern Austin Programs

Dayna Diven, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Idaho Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Richard B Brown, MD, FACP Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine

Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, Massachusetts Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Mark R Wallace, MD, FACP, FIDSA Clinical Professor of Medicine, Florida State University College of Medicine; Clinical Professor of Medicine, University of Central Florida College of Medicine

Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, Florida Infectious Diseases Society

Disclosure: Nothing to disclose.

Additional Contributors

Brenda Jones, MD Associate Professor of Clinical Medicine, Division of Infectious Diseases, Keck School of Medicine of the University of Southern California

Disclosure: Nothing to disclose.


Ken Flanagan PhD Student, Department of Microbiology and Immunology, Albert Einstein College of Medicine

Ken Flanagan is a member of the following medical societies: American Association for Cancer Research

Disclosure: Nothing to disclose.

Howard L Kaufman, MD Chief, Division of Surgical Oncology, Columbia University College of Physicians and Surgeons

Howard L Kaufman, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American College of Surgeons, American Medical Association, Association for Academic Surgery, Illinois State Medical Society, Massachusetts Medical Society, New York Academy of Sciences, and Society of Surgical Oncology

Disclosure: Nothing to disclose.

Jennifer J Lee, MD Resident Physician, Department of Dermatology, University of Texas Southwestern at Austin

Jennifer J Lee, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, California Medical Association, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Thomas W McGovern, MD Dermatologist and Mohs Surgeon, Fort Wayne Dermatology, PC

Disclosure: Nothing to disclose.

Tasneem A Poonawalla, MD Physician, Department of Dermatology, Dean Clinic

Tasneem A Poonawalla, MD is a member of the following medical societies: American College of Physicians, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

  1. MacLeod DT, Nakatsuji T, Wang Z, di Nardo A, Gallo RL. Vaccinia Virus Binds to the Scavenger Receptor MARCO on the Surface of Keratinocytes. J Invest Dermatol. 2014 Aug 4. [Medline].

  2. Petersen BW, Harms TJ, Reynolds MG, Harrison LH. Use of Vaccinia Virus Smallpox Vaccine in Laboratory and Health Care Personnel at Risk for Occupational Exposure to Orthopoxviruses - Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2015. MMWR Morb Mortal Wkly Rep. 2016 Mar 18. 65 (10):257-62. [Medline]. [Full Text].

  3. Couch RB, Winokur P, Edwards KM, Black S, Atmar RL, Stapleton JT, et al. Reducing the dose of smallpox vaccine reduces vaccine-associated morbidity without reducing vaccination success rates or immune responses. J Infect Dis. 2007 Mar 15. 195(6):826-32. [Medline].

  4. Rimmelzwaan GF, Sutter G. Candidate influenza vaccines based on recombinant modified vaccinia virus Ankara. Expert Rev Vaccines. 2009 Apr. 8(4):447-54. [Medline].

  5. Tykodi SS, Thompson JA. Development of modified vaccinia Ankara-5T4 as specific immunotherapy for advanced human cancer. Expert Opin Biol Ther. 2008 Dec. 8(12):1947-53. [Medline]. [Full Text].

  6. Verheust C, Goossens M, Pauwels K, Breyer D. Biosafety aspects of modified vaccinia virus Ankara (MVA)-based vectors used for gene therapy or vaccination. Vaccine. 2012 Mar 30. 30(16):2623-32. [Medline].

  7. Perera LP, Waldmann TA, Mosca JD, Baldwin N, Berzofsky JA, Oh SK. Development of smallpox vaccine candidates with integrated interleukin-15 that demonstrate superior immunogenicity, efficacy, and safety in mice. J Virol. 2007 Aug. 81(16):8774-83. [Medline].

  8. Wertheimer ER, Olive DS, Brundage JF, Clark LL. Contact transmission of vaccinia virus from smallpox vaccinees in the United States, 2003-2011. Vaccine. 2011 Dec 19. [Medline].

  9. Centers for Disease Control and Prevention. Vulvar vaccinia infection after sexual contact with a military smallpox vaccinee--Alaska, 2006. MMWR Morb Mortal Wkly Rep. 2007 May 4. 56(17):417-9. [Medline].

  10. Tian T, Dubin K, Jin Q, Qureshi A, King SL, Liu L, et al. Disruption of TNF-a/TNFR1 function in resident skin cells impairs host immune response against cutaneous vaccinia virus infection. J Invest Dermatol. 2012 May. 132(5):1425-34. [Medline]. [Full Text].

  11. Redfield RR, Wright DC, James WD. Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease. N Engl J Med. 1987 Mar 12. 316(11):673-6. [Medline].

  12. Artenstein AW. New generation smallpox vaccines: a review of preclinical and clinical data. Rev Med Virol. 2008 Jul-Aug. 18(4):217-31. [Medline].

  13. Baxby D. Indications for smallpox vaccination: policies still differ. Vaccine. 1993. 11(4):395-6. [Medline].

  14. Breman JG, Henderson DA. Diagnosis and management of smallpox. N Engl J Med. 2002 Apr 25. 346(17):1300-8. [Medline].

  15. Buller RM, Palumbo GJ. Poxvirus pathogenesis. Microbiol Rev. 1991 Mar. 55(1):80-122. [Medline].

  16. Carroll MW, Moss B. Poxviruses as expression vectors. Curr Opin Biotechnol. 1997 Oct. 8(5):573-7. [Medline].

  17. [Guideline] Casey C, Vellozzi C, Mootrey GT, Chapman LE, McCauley M, Roper MH. Surveillance guidelines for smallpox vaccine (vaccinia) adverse reactions. MMWR Recomm Rep. 2006 Feb 3. 55(RR-1):1-16. [Medline].

  18. Casey CG, Iskander JK, Roper MH, Mast EE, Wen XJ, Török TJ. Adverse events associated with smallpox vaccination in the United States, January-October 2003. JAMA. 2005 Dec 7. 294(21):2734-43. [Medline].

  19. Clark J, Diven D. Poxviruses. Tyring S, Moore A, Lupi O, eds. Mucocutaneous Manifestations of Viral Diseases. 2nd ed. New York, NY: Informa HealthCare; In press.

  20. Damon I. Orthopoxviruses: Vaccinia (Smallpox Vaccine), Variola (Smallpox), Monkeypox, and Cowpox. Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 6th ed. Orlando, FL: Churchill Livingstone; 2005. 1742-55.

  21. Egan C, Kelly CD, Rush-Wilson K, Davis SW, Samsonoff WA, Pfeiffer H. Laboratory-confirmed transmission of vaccinia virus infection through sexual contact with a military vaccinee. J Clin Microbiol. 2004 Nov. 42(11):5409-11. [Medline].

  22. Franz DR, Jahrling PB, Friedlander AM, McClain DJ, Hoover DL, Bryne WR, et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA. 1997 Aug 6. 278(5):399-411. [Medline].

  23. Friedman HM. Smallpox, Vaccinia, and Other Poxviruses. Isselbacher, et al, eds. Harrison's Principles of Internal Medicine. 13th ed. New York, NY: McGraw-Hill; 1994. 798-9.

  24. Grabenstein JD, Winkenwerder W Jr. US military smallpox vaccination program experience. JAMA. 2003 Jun 25. 289(24):3278-82. [Medline].

  25. Haga IR, Bowie AG. Evasion of innate immunity by vaccinia virus. Parasitology. 2005. 130 Suppl:S11-25. [Medline].

  26. Harrop R, Ryan MG, Golding H, Redchenko I, Carroll MW. Monitoring of human immunological responses to vaccinia virus. Methods Mol Biol. 2004. 269:243-66. [Medline].

  27. Hopkins RJ, Lane JM. Clinical efficacy of intramuscular vaccinia immune globulin: a literature review. Clin Infect Dis. 2004 Sep 15. 39(6):819-26. [Medline].

  28. Lane HC, Fauci AS. Microbial bioterrorism. Kasper, et al, eds. Harrison's Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2005.

  29. Lane JM, Millar JD. Risks of smallpox vaccination complications in the United States. Am J Epidemiol. 1971 Apr. 93(4):238-40. [Medline].

  30. Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968. N Engl J Med. 1969 Nov 27. 281(22):1201-8. [Medline].

  31. Lewis FS, Norton SA, Bradshaw RD, Lapa J, Grabenstein JD. Analysis of cases reported as generalized vaccinia during the US military smallpox vaccination program, December 2002 to December 2004. J Am Acad Dermatol. 2006 Jul. 55(1):23-31. [Medline].

  32. Moss B. Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proc Natl Acad Sci U S A. 1996 Oct 15. 93(21):11341-8. [Medline].

  33. Moss B. Poxvirus entry and membrane fusion. Virology. 2006 Jan 5. 344(1):48-54. [Medline].

  34. Moss B. Vaccinia virus: a tool for research and vaccine development. Science. 1991 Jun 21. 252(5013):1662-7. [Medline].

  35. Neff JM. Vaccinia Virus (Cowpox). Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, Pa: Churchill Livingstone; 2000. 1553-5.

  36. Notice to Readers: Newly Licensed Smallpox Vaccine to Replace Old Smallpox Vaccine. MMWR Morb Mortal Wkly. 2008. 57:207-208.

  37. Ojeda S, Domi A, Moss B. Vaccinia virus G9 protein is an essential component of the poxvirus entry-fusion complex. J Virol. 2006 Oct. 80(19):9822-30. [Medline].

  38. Paoletti E. Applications of pox virus vectors to vaccination: an update. Proc Natl Acad Sci U S A. 1996 Oct 15. 93(21):11349-53. [Medline].

  39. Rotz LD, Dotson DA, Damon IK, Becher JA. Vaccinia (smallpox) vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001. MMWR Recomm Rep. 2001 Jun 22. 50:1-25; quiz CE1-7. [Medline].

  40. Savona MR, Dela Cruz WP, Jones MS, Thornton JA, Xia D, Hadfield TL, et al. Detection of vaccinia DNA in the blood following smallpox vaccination. JAMA. 2006 Apr 26. 295(16):1898-900. [Medline].

  41. Sejvar JJ, Labutta RJ, Chapman LE, Grabenstein JD, Iskander J, Lane JM. Neurologic adverse events associated with smallpox vaccination in the United States, 2002-2004. JAMA. 2005 Dec 7. 294(21):2744-50. [Medline].

  42. Sepkowitz KA. How contagious is vaccinia?. N Engl J Med. 2003 Jan 30. 348(5):439-46. [Medline].

  43. Stanley SL Jr, Frey SE, Taillon-Miller P, Guo J, Miller RD, Koboldt DC, et al. The immunogenetics of smallpox vaccination. J Infect Dis. 2007 Jul 15. 196(2):212-9. [Medline].

  44. Stark JH, Frey SE, Blum PS, Monath TP. Lack of transmission of vaccinia virus. Emerg Infect Dis. 2006 Apr. 12(4):698-700. [Medline].

  45. Townsley AC, Moss B. Two distinct low-pH steps promote entry of vaccinia virus. J Virol. 2007 Aug. 81(16):8613-20. [Medline].

This typical pustular lesion following vaccinia immunization usually appears within 5 days of vaccination and forms a scab by 10-14 days. Vaccination usually leaves a permanent indentation.
Table 1. Frequency of Complications Related to Vaccination
Complication Number of cases from 450,293 vaccinations administered between 12/13/2002 and 5/28/2003 Department of Defense rate per million vaccinees (95% confidence interval) Historical number of cases from 1950s and 1960s
Death 0 0 (0-3.7) Age 1 y at first vaccination - 5 per 1 million primary vaccinees
Age 1-4 y at first vaccination - 0.5 per 1 million primary vaccinees
Age 5-19 y at first vaccination - 0.5 per 1 million primary vaccinees
Age ≥ 20 y at first vaccination - No data
Encephalitis 1 2.2 (0.6-7.2) 3 per 1 million primary vaccinees
Vaccinia necrosum/progressive vaccinia 0 0 (0-3.7) Approximately 1 patient per million during primary or revaccination
Usually fatal over a period of several months
Eczema vaccinatum 0 0 (0-3.7) 1 per 100,000 primary vaccinees
1 per 1 million revaccinees
Generalized vaccinia 36 80 (63-100) Occasional occurrence in immunocompetent individuals
3 per 100,000 primary vaccinees
1 per 1 million revaccinees
Accidental vaccinia 48 107 (88-129) 3 per 100,000 to 1 million vaccinees
Erythematous rash 36 80 (63-100) Approximately 1 per 100,000 primary vaccinees*
Acute myopericarditis 37 82 (65-102) 100 per 1 million vaccinees
*Incidence was slightly higher when vaccination occurred before age 1 year.
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