Jpn. J. Infect. Dis., 65, 94-97, 2012

Laboratory and Epidemiology Communications

An Isolated Incidence of Rubella Outbreakat a Workplace in Hokkaido, Japan
Masahiro Miyoshi1*, Rika Komagome1, Hideki Nagano1, Kenichi Takahashi1, Hiroshi Koba2,Yumiko Kaneko2, Yasuko Watanabe2, Fumiaki Suzuki2, Takashi Hiroshima2, Ichiro Aida3,
Sayaka Kitamura4, Naosuke Saji5, Ryo Yamaguchi5, and Motohiko Okano1
1Center for Infectious Diseases Control, Hokkaido Institute of Public Health, Sapporo 060-0819;
2Hokkaido Government Shiribeshi General Subprefectural Bureau, Kutchan 044-8588;
3Hokkaido Government Tokachi General Subprefectural Bureau, Obihiro 080-8588;
4Hokkaido Government Ishikari General Subprefectural Bureau, Sapporo 060-8558; and5Department of Health and Welfare, Hokkaido Government, Sapporo 060-8558, Japan

Communicated by Makoto Takeda(Accepted December 19, 2011)
Rubella is an acute and contagious disease that ismainly characterized by fever, rash, and cervical lymphadenopathy (1). Under the Law Concerning Prevention of Infectious Diseases and Medical Care forPatients with Infectious Diseases (the Infectious Dis-eases Control Law) in Japan, rubella has been classified
as a category V infectious disease and requires mandatory reporting instead of sentinel reporting since January
1, 2008 (2). Here, we report an isolated rubella outbreakthat occurred among adults in Hokkaido.
On May 14, 2011, some workers reported fever andrash (Table 1). Initially, we tested for the presence ofmeasles antibodies as a part of the process of eliminating measles in Japan. We obtained leukocyte (serum inthe case of some patients), throat swab, and/or urine
samples from 9 patients (Table 2) and analyzed thesesamples using enzyme immunoassay (EIA) for measles-*Corresponding author: Mailing address: Center for Infectious Diseases Control, Hokkaido Institute of Public
Health, North 19 West 12, Kita-ku, Sapporo 060-0819,
Japan. Tel: ＋81-11-747-2764, Fax: ＋81-11-747-2757,
E-mail: miyo＠iph.pref.hokkaido.jp
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Table 1. Epidemiological information of the patients
Patientno.

Age

Date of arrival inHokkaido

Accommodation

Date ofonset1)

Date of onset(rash)

Vaccination
status123456789101112131415161720s
30s
50s
40s
20s
40s
30s
40s
30s
30s
40s
30s
40s
40s
30s
30s
40s

2011/4/20
4/11
—
4/20
—
4/20
4/20
3/28
4/21
4/20
4/24
4/17
Resident of Hokkaido
Resident of Hokkaido
4/29
4/18
—

AB
Own home
COwn home
CFEC
B
D
G
HIJC
Own home

5/9
5/11
5/12
5/13
5/13
5/14
5/15
5/15
5/15
5/16
5/16
5/19
5/20
5/21
5/23
5/28
6/1

5/13
5/13
5/18
5/13
5/14
5/15
5/15
5/16
5/18
5/17
5/17
Unclear
5/23
5/21
5/23
6/2
6/2Unknown
Unknown
UnvaccinatedUnvaccinatedUnknown
UnvaccinatedUnvaccinatedUnknown
Unknown
Unknown
Unknown
Unknown
Unknown
Unknown
UnknownOnce
Unknown1):

Date indicates the day of onset including two or more of the following symptoms: fever (15), lymphadenopathy (3),headache (4), cough (3), sore throat (5), catarrh (5), malaise (5), arthralgia (4), inertia (1), fundus oculi pain (1),sputum (1), and diarrhea (1). Number in patenthesis indicates the number of cases having symptoms.

Table 2. Specific tests for rubella virus in this outbreak
Patient
no.*Days after
onset**

13

Rubella virus-specific antibodies
Specimen

IgM indexvalue1)

IgG indexvalue2)

87Serum
Plasma

0.44
0.64

0.15
1.07

7
822

Serum
Serum

2.16
0.02

0.16
0.13

94

Plasma

0.14

0.27

104

Plasma

2.36

0.31

111

Plasma

0.25

0.09

121

Plasma

0.07

0.12

13

4

Plasma0.2

0.06

RT-PCR
Specimen

NSE1

Serum
PBMC
TsU
Serum
PBMC
TsU
PBMC
TsU
PBMC
TsU
PBMC
TsU
PBMC
TsU
PBMC
TsU－－＋＋－＋＋＋＋＋－－＋＋＋＋＋－＋－－＋＋－－＋＋－＋＋＋＋＋－－＋－－＋＋－－－
ND＋－* and **: Case number and the date of onset are corresponded with Table 1.
1): IgM index value »1.21 is defined as positive.
2): IgG index value »1.0 is defined as positive.
PBMC, peripheral blood mononuclear cells; Ts, throat swab; U, urine; －, negative; ＋, positive;
ND, not done.

specific immunoglobulin (IgM) and tests for detecting
the genomes of measles virus. However, the results ofthese tests were negative. Rubella virus may cause theformation of rashes similar to those observed in measles(1). For this reason, we analyzed the collected samples
using an EIA kit (Denka Seiken Co., Tokyo, Japan)
with rubella virus-specific IgM and IgG antibodies
and/or evaluated the presence of both nonstructural95

ing May 9–16, and they stayed at 8 different accommodation facilities. Therefore, the epidemiological survey
suggests that several patients, including Nos. 1, 4, and11, were most probably exposed to the rubella virus ataround the same time.
A person with rubella can generally shed the virus
from 7 days before and after the onset of rash (1).
Patient No. 1 was considered as the earliest case because
the rashes in this patient were first notified on May 13.
Patients (Nos. 1–11) who showed onset of the symptoms
until May 16 were considered to be initially infected during similar period. Patients (Nos. 12–17) who showed
onset of the symptoms after May 19 were considered tohave been secondarily infected. Further, since patientNo. 16 (onset of symptoms on May 28) had used thesame accommodation facility that was used by patient
Nos. 4, 6, and 9 (onset of symptoms on May 13, 14, and15, respectively), he may have contracted the infection
from the workplace or the accommodation facility.
During and after this outbreak, no sporadic cases ofrubella were reported in Hokkaido.
Only patient No. 16 had a history of rubella vaccination, whereas the other patients were not aware of theirvaccination statuses (Table 1). Until the Immunization
Law in Japan was amended in 1994, routine immunization for rubella virus was performed only for female
students of junior high school from 1977; between 1989
and 1993, the measles-mumps-rubella vaccine was optionally administered to infants aged 12–72 months.
Therefore, adult men aged 30–40 years are presently
considered to be highly susceptible to rubella (6). The
present study supports this claim since the rubella virus
outbreak, which showed that the rubella virus-specific
IgG antibodies were absent in many male patients during the early phase of the infection.
Seven patients were negative for rubella virus-specific
IgM antibodies, and clinical specimens from 5 of themwere collected on the same day as the onset of rash.
During the early phase of the infection, it is difficult todiagnose the disease on the basis of serological findings
alone (7). The symptoms of rubella are often mild or
subclinical (1). However, rubella virus infection in pregnant women may cause congenital rubella syndrome(CRS) (1,8,9). The occurrence of CRS is most likely tocoincide with a rubella epidemic (10). Thus, improved
immunization and effective surveillance systems arecritical for preventing infection and eliminating rubella.

Fig. 1. Phylogenetic tree based on the 739-nucleotide region of
E1 gene of rubella virus. Bootstrap values above 75 are shown,and the samples obtained in this outbreak are marked withblack triangles.

protein (NS) and envelope protein 1 (E1) genes ofrubella virus using reverse-transcriptase polymerase
chain reaction (RT-PCR) (3) (Mori Y, personal communication). As shown in Table 2, the rubella virusspecific IgM antibodies were present in 2 patients (Nos.
7 and 10), while the rubella virus-specific IgG antibody
was present in only 1 patient (No. 3). In addition, 6
patients (Nos. 3, 8–11, and 13) were positive for both
NS and E1 genes and 1 patient (No. 12) was positive
only for the NS gene. Phylogenetic analyses using theneighbor-joining method were performed by direct sequencing of 739 nucleotides of E1 gene, which corresponded to the minimum acceptable window definedby the World Health Organization (4). Nucleotide sequences determined in this study have been submitted tothe DNA Data Bank of Japan (GenBank accession nos.
AB683468 and AB683469). Two groups of the sequence(RVi/Hokkaido.JPN/20.11/1 and RVi/Hokkaido.
JPN/20.11/2) were detected, and the genotypes of both
the groups were highly homologous to that of the 1E
strains of rubella virus. There was only one synonymoussubstitution between them (Fig. 1). The genotype 1E genome was also reported in an outbreak that occurred inNiigata Prefecture in the same year (5).
From the clinical manifestations and laboratory findings, total of 17 patients (men; age range, 20s–50s) werediagnosed as rubella (Tables 1 and 2). All the patients
had no history of travel to foreign countries. Five of thepatients were local residents, and the remaining werefrom areas outside Hokkaido. Fourteen patients, including 2 local residents, had stayed temporarily at accommodation facilities near the workplace. Threepatients (Nos. 1, 4, and 11) had arrived possibly during
the incubation period of the disease (12–23 days prior tothe onset of infection). The earliest case, patient No. 1,
showed onset of symptoms on May 9, after which morepatients fell ill on every day from May 11 to 16. Additionally, 11 patients showed the onset of symptoms dur-This article appeared in the Infectious Agents Surveillance Report (IASR), vol. 32, p. 254–255, 2011 inJapanese.
Acknowledgments The authors are grateful to the staff of theregional hospital for collecting the samples and providing theepidemiological data. The authors also thank Dr. Yoshio Mori of theNational Institute of Infectious Diseases of Japan for providing thetechnical advice.

Conflict of interest None to declare.
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