ISSN 0915-5813

IASR

National Institute of Infectious Diseases andTuberculosis and Infectious Diseases
Control Division,
Ministry of Health, Labour and Welfare

Vol. 41 No. 6 (No. 484) June 2020
Infectious Agents Surveillance Reporthttps://www.niid.go.jp/niid/en/iasr-e.html

Distribution, invasion and colonization of Aedes aegypti in Japan...... 91
Expansion of Aedes albopictus in Japan, 2018....................................... 92
Current global trends in dengue fever in 2019...................................... 93
Three autochthonous cases of dengue fever in Japan for the first timein five years, 2020................................................................................. 94
Suspected domestic case of dengue hemorrhagic fever in Naha city,
2019....................................................................................................... 96

A case of dengue fever caused by dengue virus type 1, reported as adomestic case in Nishinomiya City, 2014............................................. 97
Vaccine progress and prospects for dengue virus................................... 99
The risk of dengue fever epidemics and preparedness for vector
control in Japan.................................................................................. 100
Notice from MHLW: Decision on influenza virus strains to be used
for influenza HA vaccine in Japan, 2020/21 season.......................... 101
Report of leptospirosis cases, in Fukushima prefecture, 2019............. 102<THE TOPIC OF THIS MONTH>
Dengue fever and dengue hemorrhagic fever, 2015-2019
Dengue fever (DF) is an infectious disease caused by the dengue virus (DENV). DENV belongs to the genus Flavivirus of the family
Flaviviridae and consists of four serotypes, DENV-1, -2, -3, and -4. DENV is one of the mosquito-borne arboviruses, and the main vectors
are Aedes aegypti and Ae. albopictus. DENV is mainly maintained in the human-to-mosquito-to-human transmission cycle. Currently, Ae.
aegypti is not distributed in Japan, but Ae. albopictus inhabits a wide area excluding Hokkaido (see pp.91 & 92 of this issue). DENV infection
in humans causes symptoms, such as fever, exanthema, and joint and muscle pain, after an incubation period of approximately 4 to 14 days
(DF). In many cases, patients recover without sequelae. However, some DF patients develop severe symptoms, such as hemorrhage and/orneurological symptoms, including deterioration in consciousness, and may die due to multiple organ failure. Such a disease state is called
severe dengue fever (SDF), and includes dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). There is no specific treatmentfor DF. A dengue vaccine is licensed and available in some countries (see p.99 of this issue). DF is mainly endemic in tropical andsubtropical regions (see p.93 of this issue). Most DF patients in Japan were those, including returnees, infected with DENV in the endemic
regions. Autochthonous outbreaks of DF were reported in 2019 for the first time in five years since 2014 (see p.94 of this issue).
1. National Epidemiological Surveillance of Infectious Diseases (NESID)
DF is classified as a category IV infectious disease under the Infectious Diseases Control Law of Japan. Physicians who diagnosepatients with DF must immediately notify the cases to their prefectural governors via local public health centers.
The reported number of DF cases has increased since the 9 cases in 1999 when data collection started. The number of reported casesof DF and DHF between 2015 and 2018 ranged from 201 to 343. In 2019, the number of cases was at a record high of 463 (Fig. 1 and Table1). One hundred and sixty-two cases and four cases in 2014 and 2019, respectively, were reported to NESID as domestic cases of DF (seep.97 of this issue).
Cases of DENV infection by serotypes 1-4 are identified every year. Cases of DENV-1 infection were the most common in 2011-2015
and 2019, and cases of DENV-2 infection were the most common in 2016-2018. In more recent years, type DENV-3 has also been detected
in greater numbers (IASR 36: 33-35, 2015) (Table 2).
Figure 1. Monthly number of notified dengue fever and dengue hemorrhagic fever cases, January 2014December 2019, Japan
180
160

Domestic cases
Imported cases

No. notified cases

140
1201008060
40
20013572014

9 11 135

7

9 11 13520157

9 11 135

7

9 11 1

2016
2017
Month of diagnosis

35

7

9 11 135201879 11 Month2019

Year(National Epidemiological Surveillance of Infectious Diseases: as of 8 April 2020)

Table 1. Number of notified dengue cases by year of diagnosis,
2014-2019, JapanYear ofdiagnosis

No. notified cases
Dengue fever (Dengue Hemorrhagic Fever*)

2014
2015
2016
2017
2018
2019
Total
2019 cases (imported vs. domestic)
Imported
Domestic

Table 2. Dengue virus serotypes detected among dengue fever anddengue hemorrhagic fever cases, 2014-2019, Japan

341
292
343
245
201
463
1,885

(9)
(5)
(12)
(6)
(4)
(7)
(43)

459
4(6)
(1)

*Dengue hemorrhagic fever reported number out of dengue fever

UnknownNo.
notifiedcases

7192

341

20

129

292

Dengue virus serotype

Year ofdiagnosis

Type 1Type 2Type 3

2014

108

20

1420156356

242016556241

19

165

343*

2017

314034121282452018

2034263118201

2019

78734016256463

Total

355285

179

77988

1,885

78

71

4016254459-2--24Type 42019 cases (imported vs. domestic)
ImportedDomestic* There was a single case coinfected with serotypes 1 and 3 in 2016
(National Epidemiological Surveillance of Infectious Diseases: as of 8 April 2020)(National Epidemiological Surveillance of Infectious Diseases: as of 8 April 2020)

1′（ 89′）（Continued on page 90′）

IASR Vol. 41 No. 6（Jun. 2020） 2′（ 90′）
（THE TOPIC OF THIS MONTH-Continued）No. notified cases

Seasonality: The highest number of DF cases is reported to NESID Figure 2. Age and sex distribution of notified dengue fever anddengue hemorrhagic fever cases, 2015- 2019, Japan
during August and September (IASR 36: 33-35, 2015) (Fig. 1 in p.89). This150
（n=1,540）
is due to the increase in the number of travelers and the prevalence of140
Male
130
dengue fever at the destinations. Previous domestic DF cases wereFemale
120
110
observed during the summer and autumn seasons (Fig. 1 in p.89).
100
Suspected place of infection: Patients diagnosed with DF between
9080
2015 and 2019 (excluding cases of domestic infection) traveled to at least
7060
45 countries/regions (Table 3 in p.91). Of the 1,540 patients infected outside
50
40
Japan, 1,350 (88%) visited Asian countries. The majority visited Southeast
30
Asia, likely reflecting the prevalence of DF in these regions and the2010
increase in the number of people entering Japan. Other patients presumed
00- 5- 10- 15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65- 70to have been infected in Oceania, Latin America and the Caribbean, theAge group (Year)
Middle East and Africa, and Europe and the United States have also been
(National Epidemiological Surveillance of Infectious Diseases: as of 8 April 2020)
reported. In 2019, there were large outbreaks of DF in Southeast Asia andother parts of the world, and the number of imported cases from these regions increased (see pp.93 & 100 of this issue). In 2019,
autochthonous outbreaks of DF were found, and three out of four domestic DF patients were infected with DENV-1 in Japan (see p.96 ofthis issue).
Gender and age: Among 1,540 patients infected overseas who were reported to NESID in 2015-2019, 969 (63%) were men and 571(37%) were women. The number of patients in their 20s, 30s, and 40s was 259 (17%), 230 (15%), and 187 (12%), respectively. Males wereslightly more frequently infected and those in their 20s comprised the highest number of cases (Fig. 2).
Dengue hemorrhagic fever: There were 5 (1.7%), 12 (3.5%), 6 (2.4%), 4 (2.0%), and 7 (1.5%) cases of DHF reported to NESID in
2015, 2016, 2017, 2018, and 2019, respectively (Table 1 in p.89). The ages of patients in these 34 cases ranged from 13 to 79 years (median31.5 years). There was no difference between males and females, with 20 and 14 cases, respectively, accounting for 2% of the total numberof cases. One death due to SDF was reported in 2016.
2. Laboratory diagnosis
DENV isolation, RT-PCR-based DENV genome detection, and DENV nonstructural protein 1 (NS1) antigen detection methods are
the main virological tests for suspected DF in the early phase of the disease. Identification of the DENV serotype is possible by virus
isolation and viral genome detection. Using the NS1 antigen detection kit, results can be obtained quickly and easily. For serologicaldiagnosis, detection of specific IgM antibodies, and significant increases in specific IgG and neutralizing antibodies using paired sera fromthe acute and convalescent phases are useful (Table 4). However, as other flaviviruses that serologically cross with DENV are also prevalent
in dengue fever-endemic areas, antibody titers against these viruses should be examined as necessary. Prefectural and municipal publichealth institutes (PHIs) and the National Institute of Infectious Diseases (NIID, Department of Virology 1) conduct these laboratory testsfor DF.
3. Countermeasures in Japan
Japan is a non-endemic country for dengue fever. In 2014 and 2019, cases of dengue fever caused by DENV infection were reported inJapan, but both epidemics ended sporadically from late autumn to winter when the activity of the vector mosquito Ae. albopictus decreased.
As hundreds of imported DF cases have been reported annually in recent years, there is a risk of DF outbreaks in Japan during the seasons
when mosquitoes become active.
To prevent the spread of mosquito-borne infectious diseases, such as DF, chikungunya fever, and Zika virus disease, the Ministry of
Health, Labour and Welfare released guidelines to control mosquito-borne infectious diseases in 2015. The guidelines include encouraging
preventive measures against mosquito vectors on a routine basis, rapid identification of mosquito-borne diseases, measures against
mosquito vectors in the event of an outbreak of mosquito-borne infections, and providing patients with appropriate medical care.
In addition, “Clinical Examination Guidelines on
Table 4. Method of laboratory diagnosis among dengue fever and dengue hemorrhagic
the Mosquito-Borne Infections 5th Edition” wasfever cases*, 2014 -2019, Japan
released by the NIID. These guidelines provide aNo.
Virus detection
Serology
Year ofseries of practical procedures for epidemiology,
notified§diagnosis
NS1NTHIIgM
Isolation** PCR
cases
pathology, diagnosis, notification, treatment, and1128
188
2113412014
12
prevention of mosquito-borne infectious diseases.
19177
214292
201511National and local administrative agencies, medical1116
199
241343201615
institutions, and research institutes must cooperate
10132
19424520177
to take measures against mosquito-borne infectious
1292
144
201
2018
5121230343463201913
diseases such as dengue fever. The early detection
31206
1,018
1,347
1,885
Total
63
of domestic DF epidemics through surveillance is2019 cases (imported vs. domestic)
essential. As the number of imported DF cases has
Imported
1
21228
340
459
13
increased in recent years, it is important to prevent
Domestic
234
DENV infection by correctly using repellents when
* Includes testing by more than one method ** Isolation of infectious viral particles§
traveling to DF epidemic areas abroad.
DENV nonstructural protein 1 (NS1) antigen detection methods(National Epidemiological Surveillance of Infectious Diseases: as of 8 April 2020)

The statistics in this report are based on 1) the data concerning patients and laboratory findings obtained by the National Epidemiological
Surveillance of Infectious Diseases undertaken in compliance with the Act on the Prevention of Infectious Diseases and Medical Care for Patientswith Infectious Diseases, and 2) other data covering various aspects of infectious diseases. The prefectural and municipal health centers andpublic health institutes (PHIs), the Department of Environmental Health and Food Safety, the Ministry of Health, Labour and Welfare, andquarantine stations, have provided the above data.

Infectious Disease Surveillance Center, National Institute of Infectious Diseases
Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, JAPAN Tel (+81-3)5285-1111