- Author: Nikesh A Patel; Chief Editor: Mark R Wallace, MD, FACP, FIDSA more...
VIG is the only drug available for amelioration of some vaccinia-related complications. VIG is produced from pooled human sera taken from vaccinia-immunized individuals and is available only from the CDC. VIG has been effective when administered early in cases of vaccinia necrosum and eczema vaccinatum. VIG has not been effective in cases of encephalopathy. The use of VIG for generalized vaccinia reactions is usually unnecessary. Vaccinia immune globulin, intravenous (VIGIV) has recently been approved by the US Food and Drug Administration.
Cidofovir (Vistide, Gilead Sciences, Foster City, Calif), a nucleotide analogue of cytosine, has demonstrated antiviral activity against certain orthopoxviruses in cell-based in vitro and animal model studies. The CDC proposes an investigational use of cidofovir in the treatment of vaccinia-related complications, which has not been studied among humans; thus, the benefits are uncertain.
These agents are used for passive immunity. Therapy consists of administration of immunoglobulin pooled from serum of immunized subjects.
Produced from the pooled sera of vaccinia-immunized individuals. Preparation contains antibodies targeted against vaccinia virus. Indicated for the treatment of vaccinia necrosum and eczema vaccinatum.
Derived from human plasma and manufactured from pooled plasma donors who received booster immunizations with smallpox vaccine (Dryvax). Contains increased antibody levels against vaccinia virus. Indicated to treat rare adverse reactions and aberrant infections caused by vaccinia virus, including aberrant infections (eg, accidental implantation in the eyes, mouth, other potentially hazardous areas), eczema vaccinatum, progressive vaccinia, severe generalized vaccinia, and vaccinia infections in immunocompromised individuals.
Cidofovir will be released for civilian use by the CDC and for military use by the Department of Defense if the patient meets the following criteria: (1) VIG treatment fails to elicit a response, (2) a patient is near death, or (3) all inventories of VIG have been exhausted. This proposed use of cidofovir is investigational, and its effectiveness in the treatment of vaccinia-related complications among humans is unknown.
Not licensed for use as a treatment for smallpox. Currently approved for treatment of CMV retinitis in AIDS. Cidofovir is the first member of a group of antivirals known as acyclic phosphonate nucleotide analogs. Cidofovir diphosphate, the active intracellular metabolite of cidofovir, inhibits herpes virus polymerases at concentrations that are 8- to 600-fold lower than those needed to inhibit human cellular DNA polymerases alpha, beta, and gamma. Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis. Adefovir, cidofovir, and ribavirin are under investigation for smallpox. Ribavirin as an aerosol treatment for pediatric respiratory syncytial virus is under investigation.
Vaccines, Live, Viral
Before the eradication of smallpox disease, live vaccinia virus smallpox vaccine was administered routinely in all pediatric age groups, including neonates and infants. It is now used only as routine vaccination for laboratory personnel who directly handle cultures or animal care personnel whose occupations place them at risk for exposure to vaccinia and other orthopoxviruses, including recombinant vaccinia viruses.
Indicated for routine active immunization against smallpox disease for persons determined to be at high risk for smallpox infection.
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].
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].
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].
Rimmelzwaan GF, Sutter G. Candidate influenza vaccines based on recombinant modified vaccinia virus Ankara. Expert Rev Vaccines. 2009 Apr. 8(4):447-54. [Medline].
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].
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].
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].
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].
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].
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].
Artenstein AW. New generation smallpox vaccines: a review of preclinical and clinical data. Rev Med Virol. 2008 Jul-Aug. 18(4):217-31. [Medline].
Baxby D. Indications for smallpox vaccination: policies still differ. Vaccine. 1993. 11(4):395-6. [Medline].
Breman JG, Henderson DA. Diagnosis and management of smallpox. N Engl J Med. 2002 Apr 25. 346(17):1300-8. [Medline].
Buller RM, Palumbo GJ. Poxvirus pathogenesis. Microbiol Rev. 1991 Mar. 55(1):80-122. [Medline].
Carroll MW, Moss B. Poxviruses as expression vectors. Curr Opin Biotechnol. 1997 Oct. 8(5):573-7. [Medline].
[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].
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].
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.
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.
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].
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].
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.
Grabenstein JD, Winkenwerder W Jr. US military smallpox vaccination program experience. JAMA. 2003 Jun 25. 289(24):3278-82. [Medline].
Haga IR, Bowie AG. Evasion of innate immunity by vaccinia virus. Parasitology. 2005. 130 Suppl:S11-25. [Medline].
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].
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].
Lane HC, Fauci AS. Microbial bioterrorism. Kasper, et al, eds. Harrison's Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2005.
Lane JM, Millar JD. Risks of smallpox vaccination complications in the United States. Am J Epidemiol. 1971 Apr. 93(4):238-40. [Medline].
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].
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].
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].
Moss B. Poxvirus entry and membrane fusion. Virology. 2006 Jan 5. 344(1):48-54. [Medline].
Moss B. Vaccinia virus: a tool for research and vaccine development. Science. 1991 Jun 21. 252(5013):1662-7. [Medline].
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.
Notice to Readers: Newly Licensed Smallpox Vaccine to Replace Old Smallpox Vaccine. MMWR Morb Mortal Wkly. 2008. 57:207-208.
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].
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].
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].
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].
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].
Sepkowitz KA. How contagious is vaccinia?. N Engl J Med. 2003 Jan 30. 348(5):439-46. [Medline].
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].
Stark JH, Frey SE, Blum PS, Monath TP. Lack of transmission of vaccinia virus. Emerg Infect Dis. 2006 Apr. 12(4):698-700. [Medline].
Townsley AC, Moss B. Two distinct low-pH steps promote entry of vaccinia virus. J Virol. 2007 Aug. 81(16):8613-20. [Medline].
|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.|