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Saturday, August 1, 2009

Va. Labworker Infected w/ SmallPox

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International Society for Infectious Diseases

Date: Thu 30 Jul 2009
Source: MMWR 31 Jul 2009 / 58(29);797-800 [edited]

Laboratory-Acquired Vaccinia Virus Infection -- Virginia, 2008
Vaccinia virus (VACV) is the live viral component of smallpox
vaccine. Inadvertent exposure to VACV can result in infection, and
severe complications can occur in persons with underlying risk
factors (e.g., pregnancy, immunodeficiencies, or dermatologic
conditions) (1). The Advisory Committee on Immunization Practices
(ACIP) recommends smallpox vaccination for laboratory workers who
handle nonhighly attenuated VACV strains or other orthopoxviruses
(e.g., monkeypox, cowpox, or variola) (2). On 8 Jul 2008, the CDC was
notified by a Virginia physician of a suspected case of inadvertent
autoinoculation and VACV infection in an unvaccinated laboratory
worker. This report describes the subsequent investigations conducted
by the Virginia Department of Health and the CDC to identify the
source of infection and any cases of contact transmission. Of the
patient's 102 possible contacts, 7 had underlying risk factors for
developing serious vaccinia infection. Investigators found no
evidence of contact transmission and, based on the results of
molecular typing, further concluded that the patient had been exposed
to a VACV strain that had contaminated the seed stock from the
laboratory where the patient worked. This case underscores the
importance of adherence to ACIP vaccination recommendations for
laboratory workers and use of safety precautions when working with
nonhighly attenuated VACV (3).

Case Report
On 5 Jul 2008, a man in his twenties who worked in a laboratory at an
academic institution in Virginia went to a local urgent care clinic.
He reported swelling of cervical lymph nodes and pain and
inflammation of his right earlobe associated with purulent discharge
beginning 2 Jul 2008, followed on 3 Jul 2008 by a feverish feeling
and swelling of his left eye with no change in his vision. The
patient was prescribed cephalexin for presumed bacterial infection
and prednisone for swelling. However, on July 6, his symptoms
worsened, and he went to a hospital emergency department. The patient
was given bacitracin for his eye and discharged. That night, he noted
pustular lesions at similar stages of development on his right ear
and left eye ( see image in the original text), and also on his
chest, shoulder, left arm, and right leg.

On 7 Jul 2008, the patient returned to the emergency department with
increasing eye pain and mild photophobia and received a diagnosis of
right auricular/pinnal cellulitis and suspected periorbital
cellulitis. Prednisone was discontinued, and he was admitted to the
hospital for treatment with intravenous vancomycin, ceftriaxone, and
pain medications. The same day, an ophthalmology consultation was
obtained for left-sided severe preseptal cellulitis, confirmed by
computed tomography scan. Biopsy of the conjunctival lesion revealed
acute necrotizing conjunctivitis. Slit lamp examination revealed no
apparent corneal abrasions and a clear anterior chamber in the left
eye, with slight loss of visual acuity. Because the patient's eye
infection appeared consistent with keratitis, ceftriaxone was
discontinued, vancomycin was continued, and the patient was started
on piperacillin/tazobactam and clindamycin.

On 8 Jul 2008, an infectious disease physician who was consulted
raised the possibility of suspected VACV infection, among other more
common viral or bacterial etiologies, because of histopathologic
changes noted in the patient's eye specimens. The consulting
physician elicited from the patient that he worked in a cancer
research laboratory that handled mice infected with VACV. The
physician contacted the CDC, which contacted the Virginia Department
of Health. Upon further investigation, the patient was determined to
have worked with VACV during 29-28 Jun 2008, 4-6 days before symptom
onset. This information was inconsistent with the patient's statement
during his initial interview on admission the previous day, when he
said he recalled last working with VACV in mid-May. Specimens from
the patient's eye, ear, arm, and chest were sent to the Virginia
Laboratory Response Network. The patient met the CDC surveillance
case definition for ocular vaccinia (1).

On 9 Jul 2008, a computed tomography scan revealed worsening of the
left preseptal infectious process with intraorbital involvement. On
10 Jul 2008, pending receipt of viral testing, 800 mg acyclovir was
administered to the patient intravenously. After receipt of
diagnostic testing results, vaccinia immune globulin was not
administered because the patient was improving. The patient went on
to make a full recovery and returned to his laboratory work in August 2008.

Laboratory Analysis
On 9 Jul 2008, the Virginia Laboratory Response Network tested lesion
scrapings from the patient using real-time polymerase chain reaction
and detected the presence of nonvariola orthopoxvirus DNA signatures.
The CDC subsequently confirmed the VACV infection. However, molecular
typing of VACV from the patient specimens, performed at the CDC,
indicated that the patient was infected with a strain (VACV Western
Reserve strain) that differed from the VACV strain reportedly used in
the laboratory's experiments (the recombinant construct OVA-vac).
Because the patient and laboratory VACV strains did not match,
investigators had to consider the possibility that the patient might
have acquired his VACV infection from another source, most likely
within the institution's laboratory complex.

Additional VACV specimens were collected both from the laboratory in
which the patient worked and from other laboratories in the academic
institution's research complex, and an investigation was launched to
identify the source of exposure. The CDC analyzed samples of all the
virus stocks used at the academic institution and detected a
contaminant virus in the OVA-vac stock from the laboratory in which
the patient worked that closely resembled the VACV strain isolated
from the patient.

Occupational Health Investigation
During 4-5 Aug 2008, investigators interviewed 3 persons separately
regarding experiments performed at the laboratory during June and
July: the patient, the laboratory director, and a student who worked
with the patient during 26-28 Jun 2008, when the patient's exposure
to VACV was thought to have occurred. Although the academic
institution's occupational health clinic annually provided education
on workplace safety and offered smallpox vaccination to all
laboratory workers who handled nonhighly attenuated VACV strains or
other orthopoxviruses, neither the patient nor the student had plans
to be vaccinated. The laboratory director was not up-to-date with his
VACV vaccination (last vaccinated >10 years previously).

Representatives of the occupational health and biosafety team at the
academic institution were interviewed to review their biosafety,
VACV-use, and vaccination policies for laboratory personnel.
Investigators found that safety protocols were in place. However, as
a result of this incident, changes in laboratory procedures regarding
VACV were made. Before the incident, the academic institution offered
VACV counseling and vaccination only to personnel who specifically
requested vaccination, even if the employee's written work profile
indicated VACV use. As a result of the incident, the academic
institution now offers counseling and education to all personnel with
occupational exposure to VACV. Vaccination is then offered to
laboratory workers without medical contraindications, and a
declination form is completed for laboratory workers who decline the
vaccine. In addition, changes have been made to the academic
institution's laboratories to better reflect CDC biosafety recommendations (4).

Contact Investigation
Recognizing that inadvertent transmission of VACV can occur through
contact with lesion exudates, investigators interviewed the patient
to identify his potential close contacts from 2 Jul 2008, when
symptoms began, through the period he was hospitalized. A close
contact was defined as any person with direct physical contact with
the patient or his linens, trash, or clinical specimens. Initially,
102 persons with possible exposure to the patient's lesions were
identified: 8 personal contacts, 12 laboratory workers, and 82
hospital workers.

A total of 55 (54 percent) of the 102 possible contacts were
identified as potentially having contact with the patient's lesion
exudates and were interviewed by the Virginia Department of Health or
members of the institution's infection control staff regarding
symptoms of possible VACV infection (e.g., fever, malaise, myalgia,
and lymphadenopathy) and risk factors for severe infection. These 55
close contacts included 8 personal contacts, 12 laboratory workers,
and 35 hospital workers. All were asked to report any symptoms or
illnesses for 14 days after their exposure. 7 of the 55 (4 personal
contacts and 3 hospital workers) had risk factors for severe
infection (i.e., pregnancy, immunodeficiencies, or dermatologic
conditions). However, no secondary VACV infections were detected.

[Reported by: E Davies, MPH, L Peake, MD, D Woolard, PhD, C Novak,
MD, Virginia Dept of Health; K Hall, MD, RT Leonard, PhD, R Allen,
PhD, Virginia. M Reynolds, PhD, W Davidson, MPH, C Hughes, MPH, V
Olson, PhD, S Smith, MS, H Zhao, MD, Y Li, PhD, K Karem, PhD, I
Damon, MD, PhD, Div of Viral and Rickettsial Diseases, National
Center for Zoonotic, Vector-Borne, and Enteric Diseases; A MacNeil,
PhD, A Roess, PhD, EIS officers, CDC.]

MMWR Editorial Note
In 1972, routine childhood vaccination against smallpox was halted
because of a declining probability of smallpox importation, reduced
likelihood of spread following importation, and occasional untoward
side effects of vaccination (5). In 2003, members of the military,
selected health-care workers, public health personnel, and 1st
responders began receiving smallpox vaccinations as part of
bioterrorism preparedness (6). From 1972 to 2003, laboratory workers
were the only group recommended for periodic smallpox vaccination in
the United States. ACIP currently recommends smallpox vaccination at
least every 10 years for laboratory workers who handle cultures or
animals infected with nonhighly attenuated VACV or other
orthopoxviruses (e.g., monkeypox, cowpox, or variola)* (7).

Laboratory-acquired VACV infections are not nationally notifiable
conditions but often are reported to CDC when virus confirmation is
required for diagnosis. These laboratory-acquired infections
typically occur in unvaccinated workers (2). During 2005-2007, 5
cases of laboratory-acquired VACV infection were reported to the CDC
(1). No known contact transmission of VACV was reported from these
laboratory-acquired infections; however, instances of contact
transmission of VACV from smallpox vaccinees to close contacts,
including children and intimate partners, has occurred (8). Adherence
to ACIP recommendations by laboratorians often is dependent on
interpretations of the risks for VACV laboratory exposure by
laboratory directors (who might not be fully aware of the pathogenic
properties of VACV in humans), concerns over adverse events
associated with vaccination, and the extent of VACV education
provided to laboratory workers (2). After the incident described in
this report, VACV laboratory procedures were changed, and counseling
and education was extended to all laboratory workers with
occupational exposure to VACV.

Laboratory-acquired exposure to VACV can be associated with a high
inoculum and can occur through a route (e.g., ocular) with a high
risk for complications (9). In the event of an exposure, the affected
body part should be washed immediately; eyewash protocols should be
followed for ocular exposure. The laboratory worker should then
report the incident to the laboratory director or to the occupational
health clinic. Depending on the timing and circumstances of the
exposure and status of the inoculated site, administration of
postexposure vaccination, vaccinia immune globulin, or antivirals
might be indicated to attenuate adverse clinical outcomes associated
with VACV infection (7).

Clinicians should maintain a high index of suspicion for VACV
infection when evaluating vesiculopapular rashes in patients who are
laboratory workers handling nonhighly attenuated VACV strains or are
their close contacts. Suspected cases of VACV infection should be
reported to state or local health departments for diagnostic
guidance. Further characterization of viruses can be performed at
specialized reference laboratories such as the poxvirus laboratory at
the CDC. Contact VACV transmission is uncommon (5.9 cases per 100 000
vaccinations) (3,6,10), and infection control measures are effective
in preventing such transmission (7); therefore, contact
investigations should be limited to persons who might have had
contact with lesion exudates, whether or not they have risk factors
for severe VACV infection.

(1) CDC. Surveillance guidelines for smallpox vaccine (vaccinia)
adverse reactions. MMWR 2006;55(No. RR-1).
(2) CDC. Laboratory-acquired vaccinia exposures and infections-United
States, 2005-2007. MMWR 2008;57:401-4.
(3) Sepkowitz KA. How contagious is vaccinia? N Eng J Med 2003;348:439-46.
(4) US Department of Health and Human Services, CDC, National
Institutes of Health. Biosafety in microbiological and biomedical
laboratories. 5th ed. Washington, DC: US Department of Health and
Human Services, CDC, National Institutes of Health; 2007. Available at
(5) CDC. Supplement: collected recommendations of the Public Health
Service Advisory Committee on Immunization Practices. MMWR 1972;21.
(6) CDC. Secondary and tertiary transfer of vaccinia virus among U.S.
military personnel-United States and worldwide, 2002-2004. MMWR 2004;53:103-5.
(7) CDC. Recommendations for using smallpox vaccine in a pre-event
vaccination program: supplemental recommendations of the Advisory
Committee on Immunization Practices (ACIP) and the Healthcare
Infection Control Practices Advisory Committee (HICPAC). MMWR
2003;52(No. RR-7).
(8) CDC. Household transmission of vaccinia virus from contact with a
military smallpox vaccinee-Illinois and Indiana, 2007. MMWR 2007;56:478-81.
(9) Lewis FM, Chernak E, Goldman E, et al. Ocular vaccinia infection
in laboratory worker, Philadelphia, 2004. Emerg Infect Dis 2006;12:134-7.
(10) Neff JM, Lane JM, Fulginiti VA, Henderson DA. Contact
vaccinia-transmission of vaccinia from smallpox vaccination. JAMA

Communicated by:

[Laboratory-acquired exposure to VACV can be associated with a high
inoculum and can occur through a route (e.g., ocular) with a high
risk for complications [see reference (9)].

Smallpox vaccination is no longer recommended (in the USA) for
laboratory workers handling highly attenuated poxvirus strains
because these strains either are unable to replicate or replicate
poorly in mammalian host cells and, therefore, do not create
productive infections in healthy persons. Clinicians should maintain
a high index of suspicion for VACV infection when evaluating
vesiculopapular rashes in patients who are laboratory workers
handling nonhighly attenuated VACV strains or are their close contacts.

Adherence to ACIP recommendations by laboratorians often is dependent
on interpretations of the risks for VACV laboratory exposure by
laboratory directors. In the light of this incident a good case can
be made for compulsory vaccination of all laboratory workers employed
in laboratories using any strain of VACV. It is a matter of concern
that the molecular typing of VACV from the patient specimens,
indicated that the patient was infected with a strain (VACV Western
Reserve strain) that differed from the VACV strain reportedly used in
the laboratory's experiments (the recombinant construct OVA-vac).
This is indicative of a general laxity in the handling of viruses in
the laboratory concerned. - Mod.CP]

[see also:
Smallpox vaccination, adverse events - USA: prog. vaccinia 20090520.1886
Rabies-vaccinia infection from oral vaccine - USA 20010825.2010
Vaccinia virus infections - Russia: WHO confirmation 20000620.1008
Vaccinia virus infections - Russia (Far East) 20000619.0996
Vaccinia recombinants, risk management: RFI 19980819.1658]

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