Unintentional transfer of vaccinia virus associated with smallpox vaccines

Figures & data

Figure 1. ACAM2000® Blackbox warning.¹²

Figure 2. Case definitions adapted from the smallpox vaccine adverse reactions surveillance guidelines¹¹ and Brighton Collaboration Vaccinia Virus Vaccine Adverse Events Working Group.^31aExamples include: erythema multiforme, urticaria, non-viral pustulosis, viral exanthem. ^bConjunctivitis: inflamed membrane that lines the inner surface of the eyelid and exposed surface of the eyeball excluding the cornea with serous or mucopurulent discharge and the presence of vesicles, ulcerations, or “moist appearing” white lesions. ^cBlepharitis: pustules, edema, hyperemia of eyelid +/− lymphadenopathy (periauricular or submandibular), cellulitis, fever. ^dPeriocular area: papules, vesicles or pustules above the brow or below the inferior occipital rim, but not involving adnexa, lids, lid margins or canthi

Figure 3. Flow diagram illustrating selection, exclusion, and classification of VAERS reports that were reviewed as potential cases of unintentional transfer of vaccinia.

Table 1. Characteristics of persons report vaccinated between 1 March 2008 and 31 August 2010 with ACAM2000® vaccinees with a VAERS adverse event report that included signs or symptoms consistent with a rash, lesion or eye involvement.

	Case Classification, no. (%)
Characteristic	Confirmed^a autoinoculation		Suspect autoinoculation		Possible autoinoculation		Total autoinoculation		Not a Case		Unclassified
Gender
Male	2	(67)	23	(88)	53	(83)	78	(84)	101	(73)	50	(86)
Female	1	(33)	3	(12)	10	(15)	14	(15)	34	(25)	8	(14)
Unknown	―^c		―		1	(2)	1	(1)	3	(2)	―
Age Group
3–5^b	―		―		―		―		―		1	(2)
6–17	―		―		―		―		―		―
18–29	3	(100)	21	(81)	47	(73)	71	(83)	93	(67)	42	(72)
30–39	―		3	(11)	13	(20)	16	(17)	30	(22)	11	(19)
40–49	―		1	(4)	3	(5)	4	(4)	11	(8)	4	(7)
50–59	―		―		―		―		1	(1)	―
60+	―		―		1	(2)	1	(1)	―		―
Unknown	―		1	(4)	―		1	(1)	3	(2)	―
Military
Yes	3	(100)	6	(23)	15	(23)	24	(26)	43	(31)	10	(17)
Unknown	―		20	(77)	49	(77)	69	(74)	95	(69)	48	(83)
Total	3		26		64		93		138		58

^a Includes a case that may be generalized vaccinia distribution and stage of lesions not clearly described; ^bNo one under 17 has been recommended for smallpox vaccination since 1972, most likely an error in the report. ^c — designates zero cases identified for this category.

Table 2. Rate of unintentional transfer per 100,000 vaccinations by vaccine type, study year, and age group vaccinated.

Transfer type	Vaccine type, study year, and age group vaccinated
	Dryvax®					ACAM2000®		Dryvax® and ACAM2000
	1963^3	1963^4	1968^5	1968^6	2004^9	2010		2011^19
	All ages	All ages	All ages	All ages	≥ 17 y old	≥ 17 y old		≥ 17 y old
						Suspect, confirmed and possible	Suspect and confirmed only
Auto-inoculation	0.7	—	1.1	23.4	14.5	20.6	6.4	—
Contact	0.6	—	0.8	2.7	7	4.4	3.5	5.4
Not Specified	—	41.7	—	—	—	—	—	—

Table 3. Characteristics of persons with contact vaccinia associated with persons vaccinated with ACAM2000® between 1 March 2008 and 31 August 2010 reported to VAERS or recorded in CDC’s consultation log.

	Case Classification, no. (%)
Characteristic	Confirmed		Possible		Total Contact
Gender
Male	8	(50)	2	(50)	10	(50)
Female	8	(50)	2	(50)	10	(50)
Age Group
6–17	2	(13)	―^a		2	(10)
18–29	12	(75)	1	(25)	13	(65)
30–39	1	(6)	1	(25)	2	(10)
Unknown	1	(6)	2	(50)	3	(15)
Military Vaccinee
Yes	11	(69)	1	(25)	12	(60)
Unknown	5	(31)	3	(75)	8	(40)
Patient a Civilian
Yes	14	(87)	1	(25)	15	(75)
No	2	(13)	1	(25)	3	(15)
Unknown	―		2	(50)	2	(10)
Type of Contact
Sports	8	(50)	1	(25)	9	(45)
Intimate	7	(44)	2	(50)	9	(45)
Towel	1^b	(6)	1	(25)	2	(10)
Total	16		4		20

^a Designates zero cases identified for this category; ^bTertiary case, initial event was sports.

Table 4. Location^a of lesions or rash for all possible, suspect, and confirmed cases of inadvertent transfer of vaccinia virus reported to VAERS or recorded n CDC’s consultation log associated with persons vaccinated with ACAM2000® between 1 March 2008 and 31 August 2010 by inoculation type.

	Autoinoculation, no. (%)								Contact, no. (%)						ALL, no. (%)
	Confirmed		Suspect		Possible		Total		Confirmed		Possible		Total
Number of Cases	3		26		64		93		16		4		20		113
Location
Abdomen	—		—		5	(8)	5	(8)	—		—		—		5	(4)
Arm/elbow/shoulder	1	(33)	8	(31)	19	(30)	28	(30)	5	(31)	3	(75)	8	(40)	35	(31)
Back	—		5	(19)	6	(9)	11	(12)	—		—		—		11	(10)
Chest	—		—		2	(13)	2	(2)	2	(13)	—		2	(10)	12	(11)
Diffuse	—		—		13	(20)	13	(14)	—		—		—		13	(12)
Eye^b	1	(33)	3	(12)	—		4	(4)	2	(13)	—		2	(10)	6	(5)
Face	1	(33)	8	(31)	6	(8)	15	(16)	7	(44)	2	(50)	8	(40)	24	(21)
Foot/Toe	—		2	(8)	5	(7)	7	(8)	—		—		—		7	(6)
Genital	1	(33)	2	(8)	2	(3)	5	(5)	5	(31)	—		5	(25)	10	(9)
Hand/Finger	—		6	(23)	7	(11)	13	(14)	2	(13)	—		2	(10)	15	(13)
Joints	—		—		3	(4)	3	(3)	—		—		—		3	(3)
Leg/knee/thigh	1	(33)	1	(4)	10	(14)	11	(12)	2	(13)	—		2	(10)	14	(12)
Neck	—		2	(8)	7	(10)	9	(10)	2	(13)	1	(25)	3	(15)	12	(11)
Scalp	—		1	(4)	1	(1)	2	(2)	—		—		—		2	(2)
Torso	1	(33)	2	(8)	12	(19)	15	(16)	1	(6)	—		1	(5)	16	(14)
Unknown	—		1	(4)	4	(6)	5	(5)	2	(13)	—		2	(10)	7	(6)

^a One case may have multiple sites of involvement; ^bFits the case definition of ocular vaccinia (Fig. 2).

Sanofi Pasteur. ACAM2000 Package Insert. September 2009. Available at http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm180810.htm. Accessed 13 April 2012.

 Google Scholar

Casey C, Vellozzi C, Mootrey GT, Chapman LE, McCauley M, Roper MH, et al, Vaccinia Case Definition Development Working Group, Advisory Committee on Immunization Practices-Armed Forces Epidemiological Board Smallpox Vaccine Safety Working Group. Surveillance guidelines for smallpox vaccine (vaccinia) adverse reactions. MMWR Recomm Rep 2006; 55:RR-1 1 - 16; PMID: 16456528

 PubMedGoogle Scholar

Wenger P, Oleske JM, Kohl KS, Fisher MC, Brien JH, Graham PL, et al, Brighton Collaboration Vaccinia Virus Adverse Event Working Group for Inadvertent Inoculation. Inadvertent inoculation as an adverse event following exposure to vaccinia virus: case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 2007; 25:5754 - 62; http://dx.doi.org/10.1016/j.vaccine.2007.02.087; PMID: 17537553

 PubMedGoogle Scholar

Neff JM, Lane JM, Pert JH, Moore R, Millar JD, Henderson DA. Complications of smallpox vaccination. I. National survey in the United States, 1963. N Engl J Med 1967; 276:125 - 32; http://dx.doi.org/10.1056/NEJM196701192760301; PMID: 4381041

 PubMed Web of Science ®Google Scholar

Neff JM, Levine RH, Lane JM, Ager EA, Moore H, Rosenstein BJ, et al. Complications of smallpox vaccination United States 1963. II. Results obtained by four statewide surveys. Pediatrics 1967; 39:916 - 23; PMID: 4381735

 PubMed Web of Science ®Google Scholar

Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968. N Engl J Med 1969; 281:1201 - 8; http://dx.doi.org/10.1056/NEJM196911272812201; PMID: 4186802

 PubMed Web of Science ®Google Scholar

Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968: results of ten statewide surveys. J Infect Dis 1970; 122:303 - 9; http://dx.doi.org/10.1093/infdis/122.4.303; PMID: 4396189

 PubMed Web of Science ®Google Scholar

Neff J, Modlin J, Birkhead GS, Poland G, Robertson RM, Sepkowitz K, et al, Advisory Committee on Immunization Practices, Armed Forces Epidemiological Board. Monitoring the safety of a smallpox vaccination program in the United States: report of the joint Smallpox Vaccine Safety Working Group of the advisory committee on immunization practices and the Armed Forces Epidemiological Board. Clin Infect Dis 2008; 46:Suppl 3 S258 - 70; http://dx.doi.org/10.1086/524749; PMID: 18284367

 PubMed Web of Science ®Google Scholar

Wertheimer ER, Olive DS, Brundage JF, Clark LL. Contact transmission of vaccinia virus from smallpox vaccinees in the United States, 2003-2011. Vaccine 2012; 30:985 - 8; http://dx.doi.org/10.1016/j.vaccine.2011.12.049; PMID: 22192851

 PubMedGoogle Scholar