Varicella (chickenpox), a common contagious disease
of childhood, is caused by the varicella zoster
virus (VZV) [Centers for Disease Control and Prevention
(CDC) 2005]. VZV is characteristic of the alpha
herpes viruses and establishes latency in the cells
of the dorsal root ganglia after primary infection
(Arvin 1996). The etiology of varicella and herpes
zoster was first reported by von Bo´kay in
1888 from the observation that susceptible children
often developed varicella after exposure to adults
with herpes zoster (Arvin 1996; CDC 2005; von Bo´kay
1909). Varicella results from the primary VZV infection,
whereas herpes zoster (shingles) is the result
of reactivation (Arvin 1996; CDC 2005; Jumaan et al.
2002). Primary varicella infection usually results
in lifetime immunity (CDC 2005), and second episodes
of varicella are uncommon (CDC 2005; Gershon et al.
1984), but they may occur (CDC 2005). VZV disease
history always indicates that varicella is the
primary infection, and herpes zoster is a recurrence
of the disease (Arvin 1996; CDC 1996, 1997, 2005;
Gershon et al.
1984; Jumaan et al.
2002), as well-documented second episodes of varicella
are rare (Gershon et al.
1984). Here we report a case of apparent VZV reinfection
with recurrent varicella infection in a nurse in
a teaching general hospital in Taiwan.
Case Presentation
A 25-year-old nurse, who had childhood chickenpox,
was diagnosed with varicella without mention of complication
[International Classification of Diseases, Revision
9 (ICD-9) code 052.9; World Health Organization
(WHO) 2001] by a dermatologic physician in a teaching
general hospital after she cared for a 62-year-old
male paraparesis patient who developed herpes zoster
during hospitalization. She graduated from nursing
school in July 2001, passed the licensing board,
and then started to work in the neurologic surgery
ward of a general teaching hospital in Taipei, Taiwan.
Toward the end of June, we conducted a study of
occupational VZV hazards to health care workers in
this hospital. The nurse was one of the volunteers
who carried an air sampler for several hours in rotation
with her colleagues on 9 July 2002. Saliva was collected
simultaneously. Nested polymerase chain reaction
(PCR) VZV DNA results were negative both in the personal
air samples and in saliva.
On 13 July 2002, a 62-year-old man was sent to
the emergency room due to paraparesis after he received
Chinese traditional chiropractic treatment from a
nonprofessional. He was diagnosed with spondylitis
with a T8 compression fracture and T9 myelopathy,
suspected tuberculosis (TB) of the spine, and paraparesis
and was transferred to a neurologic (internal medicine)
ward in the evening. The next day he underwent surgery
for total laminectomy (from T8 to T9) and hook system
(from T6 to T11), and was sent to the surgical intensive
care unit (SICU) for 5 days. On 18 July 2002, the
patient was transferred to the neurologic surgery
ward where the nurse worked.
Because the patient was suspected of having TB
of the spine, he underwent pleural and video-assisted
thoracoscopic surgery (VATS) biopsy on 1 August.
According to the nurse’s observation, the patient
was worried, anxious, and under a great deal of stress
regarding his health because his income was the primary
financial resource of his family. On 3 August, multiple
pruritic rash and vesicles were found over the patient’s
abdomen and lower back flank area. Herpes zoster
was confirmed by a dermatologic physician.
During the patient’s hospitalization in the
neurologic surgery ward, the nurse attended the patient
for several days (on 19-22 July, 29 July, 31 July-1
August, and 4-5 August 2002) before she resigned
from the job on 12 August. Her regular nursing care
tasks included measuring body temperature, blood
pressure, and pulse; administering medicine; asking
how the patient was feeling; and helping the patient
to change his bed rest position.
At the age of 5 years, the nurse had been infected
with chickenpox by her kindergarten-age sister, who
herself was previously infected by her kindergarten
classmates. At that time, the nurse, her sister,
and her brother had multiple chickenpox vesicles
on their faces simultaneously. Because of her previous
chickenpox history, it was supposed that the nurse
was immune to the VZV; while caring for the patient,
she did not wear gloves, a mask, or an isolation
gown before the herpes zoster was confirmed.
Because she had passed the admission examination
for graduate study in a medical school, the nurse
planned to resign her job to become a full-time student
by 15 August. Before she resigned, she took a short
vacation to her hometown in Ping-Tung County, in
the south of Taiwan, on 6 August. However, on 8 August,
she developed a high fever (39.5°C, 103.1°F),
malaise, and headache. She went to a private clinic
and was diagnosed with influenza by a physician in
her hometown. The next day, in addition to the prodromal
symptoms, pruritic rash started to appear on her
face, neck, and trunk. She came back to the teaching
general hospital in Taipei on 9 August and was diagnosed
with varicella without mention of complication (ICD-9
code 052.9) by another dermatologic physician (not
the herpes zoster patient’s dermatologic physician).
The nurse received treatment with Allegra (fexofenadine,
60 mg twice per day; Hoechst, Kansas City, MO, USA),
chlorpheniramine (4 mg three time per day; Mine Ta
Chemistry Pharmacy Co., Ltd., Tai Chung, Taiwan),
and Scanol (acetominophen, 500 mg three times per
day; Scanpharm, Birkerød, Denmark) for 14
days. Because her clinical symptoms were very clear,
no laboratory confirmation testing was performed
at that time. However, to confirm this second varicella
episode before reporting this case, we invited the
nurse to take serologic tests for varicella antibody
on 4 April 2005. The results indicated that VZV-specific
IgM was negative [< 1:20; Merifluor VZV IgM indirect
fluorescent antibody, (IFA); Meridian Bioscience
Inc., Cincinnati, OH, USA], but the VZV IgG was positive
(1:80 on the basis of > 1:10, Merifluor VZV IgG
IFA), with high sensitivity (93.9% for IgM and 100%
for IgG) and high specificity (100% for both antibodies)
according to the manufacturer’s instructions.
Negative specific serum IgM and positive specific
serum IgG indicated a past VZV infection. Because
varicella and herpes zoster both resulted from the
same antigen, the VZV IgG-positive reaction was excluded
from the herpes zoster. It was also excluded because
the nurse did not get herpes zoster from the second
episode of varicella on 9 August 2002 to 4 April
2005. The nurse is now convalescing.
The nurse was diagnosed with an acute chickenpox
infection by a dermatologic physician at the teaching
general hospital on the basis of her clinical symptoms
and signs, including a high fever (39.5°C), malaise,
and headache prior to the rash appearing on her face,
neck, and trunk. The duration of the high fever and
rash were 5 and 14 days, respectively. Fever and
malaise may appear 1-2 days before rash onset in
chickenpox primary infections in adults, whereas
rash is usually the first sign of the disease in
children (CDC 2005). According to the CDC case classification
(Jumaan et al.
2002), a confirmed case is defined as one that is
confirmed by laboratory testing or that meets the
clinical case definition and is epidemiologically
linked to a confirmed or a probable case (Jumaan
et al. 2002).
Recently, negative specific serum IgM and positive
specific serum IgG indicated a past VZV infection.
The nurse did not get herpes zoster from the second
episode of varicella on 9 August 2002 to 4 April
2005. Our case matches both definitions because the
vesicular illness preceded acute onset with diffuse
maculopapulovesicular rash and without other apparent
cause (Jumaan et al.
2002), and it was epidemiologically linked to the
care of a confirmed herpes zoster patient.
The air sampling study was performed on 9 July
2002 in the neurologic surgery ward, and the paraparesis
patient was admitted to the hospital on 13 July 2002
and transferred to the neurologic surgery ward on
18 July 2002. The patient’s rash was first
reported on 3 August 2002. It is not surprising that
the air sampling result was negative. In addition,
it is unlikely that the nurse was infected from the
air sampling equipment because the assembled cassettes
and sampling pump with tubing were put in a laminar
flow unit with ultraviolet light for 8 hr before
sampling, and sampled cassettes were replaced with
a new assembled cassette every day.
To investigate this uncommon case, we considered
four parameters: the agent (VZV), infectious routes,
the host (the nurse), and the hospital environment
(hospital ward).
Agent. Previous reports have mentioned
the same etiology of varicella and herpes zoster
(Arvin 1996; CDC 2005; von Bo´kay 1909). In
1925, children without varicella history developed
varicella after being inoculated with fluid recovered
from the herpes zoster lesions (infectious virus),
which demonstrated the transmissibility of the agent
(Arvin 1996; Kundratitz 1925). In the present case,
the nurse developed a recurrence of varicella after
nursing a herpes zoster patient, although she had
been infected by her sister when she was 5 years
of age.
Varicella has been reported as the disease most
commonly confused with smallpox (Jumaan et al.
2002); however, smallpox was eradicated from Taiwan
in 1955 (Center for Disease Control, Taiwan 2004a,
2004b), and the routine smallpox vaccination program
in Taiwan ended in 1979 after the disease was eradicated
worldwide following the WHO campaign (BiotechEast
2003; Center for Disease Control, Taiwan 2004a, 2004b;
Lee 2003). Because the nurse was born in 1978, it
is extremely unlikely that her rash at 5 years of
age was smallpox.
New variants of VZV have been reported recently,
including VZV-MSP, isolated in St. Paul-Minneapolis,
MN (Santos et al.
1998, 2000), and VZV-BC, isolated in British Columbia
(Tipples et al.
2002). We do not know whether there is a mutant strain
of VZV in Taiwan; thus this is a good index case
for further study. Another consideration is that
the nurse’s immunity was insufficient against
the second VZV attack, since she was infected initially
over 20 years earlier by her sister. Unfortunately,
it was not possible to check her VZV antibody titers
before her recurrent varicella episode.
Infection routes and incubation period. It
has been documented that cases of herpes zoster are
the infectious sources of chickenpox in susceptible
persons (Arvin 1996; CDC 2005). VZV is transmissible
by respiratory routes (Arvin 1996; CDC 2005). Possible
infection routes while the nurse was caring for the
patient included communicating with the patient and
helping the patient change his bed rest position
without employing protection such as a mask or gloves.
Previous PCR research showed that VZV is transmissible
for 24-48 hr before rash onset, which is consistent
with epidemiologic evidence (CDC 2005; Koropchak
et al. 1991),
or 4-5 days after a rash appears (CDC 2005).
The chickenpox incubation period is from 14 to
16 days after exposure (Arvin 1996; CDC 2005), with
a range of 10-21 days (CDC 2005). In this case, the
paraparesis patient had the rash on 3 August 2002.
The nurse had cared for him on 31 July and on 1,
4, and 5 August. The most likely infection dates
of this episode are 31 July and 1 August, since the
rash appeared on the nurse’s face, neck, and
trunk on 9 August, which is within the range of 10
days. In addition, recent VZV-IgG serologic tests
indicated that the antibody titer is still high (1:80
on the basis of 1:10 of a positive criterion). This
method was simple and highly sensitive and allowed
for the rapid and reliable determination of immunity
to VZV (Sauerbrei et al.
2004). Because varicella and herpes zoster resulted
from the same antigen, VZV, the VZV IgG-positive
reaction was excluded from herpes zoster. It was
also excluded because the nurse did not get herpes
zoster from the second episode of varicella on 9
August 2002 to 4 April 2005.
Host. In addition to a lack of protection
(gloves, mask) while caring for the patient, stress
may be another important host factor contributing
to recurrence. The nurse reported that before she
resigned from the hospital, she felt stress both
from the nursing practice and the logistics of her
resignation, as well as anxiety about her impending
study in graduate school. In fact, during our study
of occupational VZV hazards to healthcare workers
in early July 2002, the nurse reported performance
anxiety about graduate school and stress from multiple
clinical duties and logistic matters concerning her
resignation, such as the fact that she was on duty
on the date of graduate school registration, 5 August
2002. According to the nurse’s own report after
the recurrence, we believe that stress played an
important role in this recurrent varicella.
Environment. Documented environmental
VZV DNA included sampling from the air of the active
patient’s room (Sawyer et al.
1994), or the active patient’s family, including
air conditioner filter, table, television remote
control, and door handle (Asano et al. 1999). In
our study, 20.5% of the 44 air samples from different
departments of the same hospital were VZV DNA positive.
VZV is highly temperature sensitive (inactivated
at 56-60°C) in the environment and is not infectious
if the virion’s envelope is disrupted (Arvin
1996). The temperature in the hospital was controlled
by the central operation department at about 25°C.
The nurse was a young and unmarried female, with
only one year of work history. Her disease appears
to be recurrent varicella, which is very uncommon,
and it appears to be occupationally related. Documented
VZV infection may cause significant morbidity or
mortality, affecting the mother, the fetus, or the
newborn (Arvin 1996; CDC 1996, 1997, 2005; Harger
et al. 2002; Jumaan
et al. 2002),
as well increasing the risk of premature delivery
when infected during late pregnancy (Arvin 1996;
Paryani and Arvin 1986). We report this case to emphasize
that a varicella infection history may not be sufficient
for determination of VZV immunity, contrary to the
common belief that a reliable history of varicella
is a valid measure of immunity because the rash is
distinctive and subclinical cases rarely occur (CDC
1996, 2005; Jumaan et al.
2002). We think that VZV antibody testing may be
necessary for health care workers, especially for
new female workers.
Documented methods of VZV antibody detection include
complement fixation, IFA, fluorescent antibody to
membrane antigen (FAMA), neutralization, indirect
hemagglutination, immune adherence hemagglutination,
radioimmunoassay, latex agglutination, and enzyme-linked
immunosorbent assay (CDC 1996). Although IFA, FAMA,
neutrilization, and radioimmunoassay have been reported
to be sensitive but time consuming (CDC 1996), a
highly sensitive, specific, and rapid IFA test using
VZV-infected A549 cells as antigen has been developed
(Sauerbrei et al.
2004). The sensitivity and the specificity of this
method are 100%, compared to the FAMA test, with
the lowest limit of detection 50 mIU/mL versus 250
mIU/mL anti-VZV IgG for IFA and FAMA, respectively
(Sauerbrei et al.
2004).
Occupational VZV hazards exist in the health care
environment. The traditional concept of VZV lifetime
immunity after the primary varicella infection may
not be appropriate in a health care setting. We suggest
checking serologic titers for VZV antibody, followed
by a VZV vaccination for nonimmune health care workers.