Jpn. J. Infect. Dis.

, 62, 331-336, 2009

Review
Japanese Encephalitis in Mainland China
Wang Huanyu, Li Yixing1, Liang Xiaofeng1, and Liang Guodong*
State Key Laboratory for Infectious Disease Control and Prevention, Department of Viral Encephalitis,
Institute for Viral Disease Control and Prevention and 1National Immunization Program,
Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China
(Received February 16, 2009. Accepted July 31, 2009)
CONTENTS:
1. Introduction 5. Age and gender distribution
2. Incidence and mortality 6. Occupational distribution
3. Seasonal distribution of cases 7. Prevalence of JEV isolates
4. Geographic distribution of cases 8. Control and prevention of JE
4-1. Highly endemic areas 8-1. JE vaccine
4-2. Moderately endemic areas 8-2. Surveillance of JE
4-3. Slightly endemic areas 9. Conclusion
4-4. Non-endemic areas
SUMMARY: Japanese encephalitis (JE) is a seasonal epidemic disease with a 50-year recorded history in China.
Its characteristics can be summarized as follows: (i) it is a seasonal epidemic disease; approximately 90% of
cases are recorded in July, August, and September each year. The peak of JE onset is 1 month earlier in South
China than in the north of the country; (ii) the disease is highly sporadic. It is rare for more than two cases to
appear simultaneously in one family; (iii) most affected children are under 15 years old; (iv) the disease is
widely distributed in all areas of the nation except Qinghai Province, Xinjiang Uygur Autonomous, and Tibet.
Due to widespread application of the JE vaccine, the number of JE cases has decreased significantly nationwide,
from 174,932 cases of morbidity in 1971 to 5,097 cases in 2005.

tending to expand. For instance, in 1995, an outbreak of JE

1. Introduction
Japanese encephalitis (JE) is an acute epidemic disease of
the central nervous system (CNS) caused by infection with
the Japanese encephalitis virus (JEV). JE mainly affects chil-
dren and adolescents. According to the World Health Organi-
zation (WHO) statistics, approximately 35,000 cases of JE are
reported each year, causing approximately 5,000 deaths---a
mortality rate of 5 - 40%. Approximately 50% of JE patients
present neurological and mental sequelae (1). JEV is trans-
mitted by mosquitoes and the genus Culex, which is major
vector. It is a perennial disease in tropical areas, but is clearly
seasonal in temperate zones, with a peak incidence period
between June and October each year. At present, JE is en-
demic in over 20 countries and areas, including the Pacific
coastal areas of Far East Russia, Japan, China, North and
South Korea, India, Vietnam, Laos, Myanmar, Thailand,
Cambodia, the Philippines, Malaysia, Singapore, Bhutan,
Indonesia, Nepal, Sri Lanka, Guam, Papua New Guinea, and
Australia (2,3). The traditional endemic areas of JE are mainly
distributed in the countries and regions of Asia, where epi-
demics are often reported. For example, an outbreak of JE in
India in 2005 involved 5,737 reported cases and resulted in
1,344 deaths (4). At present, the areas of JE endemism are
*Corresponding author: Mailing address: State Key Laboratory
for Infectious Disease Prevention and Control, Department of
Viral Encephalitis, Institute for Viral Disease Control and Pre-
vention, Chinese Center for Disease Control and Prevention,
100 Ying Xin Street, Xuan Wu District, Beijing 100052, People’s
Republic of China. Tel: +86 10 63510124, Fax: +86 10 63532053,
E-mail: gdliang@hotmail.com
occurred in Papua New Guinea and among the original
inhabitants of the northern islands of Australia, and even
appeared in the northern areas of Australian mainland (5,6).
JE has consequently become one of the most prominent pub-
lic health issues in the world.
China is the main region of JE endemism. Our data reveal
the occurrence and epidemic outbreaks of JE in all provinces
except Xinjiang Uygur Autonomous, Tibet, and Qinghai. JE
is one of four arbovirus diseases currently prevalent in China
(7). In this paper, we summarize the epidemics of JE in main-
land China in recent years and the prevention measures taken
there.
2. Incidence and mortality
JE case reporting is currently mandated by law in China.
Since the establishment of a case reporting system in 1951,
the incidence of JE has been recorded annually in China.
Further, since 2004, each JE case has been electronically
recorded and the data collected at the national level by the
Chinese Center for Disease Control and Prevention (China
CDC); the case reporting system has thus become both more
sensitive and more efficient.
Historically, there have been two major JE epidemics.
The first, in 1966, had an annual incidence of >15/100,000
nationwide, whereas the second, in 1971, was associated with
174,932 cases of morbidity and an incidence of 20.92/100,000
(8-10). Since the 1980s, JE vaccination has been widely used
in our country and, as a consequence, the number of mor-
bidities has declined gradually year by year. Prior to the 1990s,
the annual morbidities numbered between 20,000 and 40,000.

331
 Table 1. The incidence and death of JE in 1996 - 2005
No. of Incidence No. of Mortality
Year Case fatality (%)
JE cases (1/100,000) death cases (1/100,000)
1996 10,308 0.8660 379 0.0318 3.677
1997 10,060 0.8343 370 0.0307 3.678
1998 12,490 0.9977 510 0.0407 4.083
1999 8,556 0.6889 348 0.0280 4.067
2000 11,779 0.9489 375 0.0302 3.184
2001 9,795 0.7707 246 0.0194 2.511
2002 8,769 0.6548 229 0.0171 2.611
2003 7,860 0.5829 366 0.0271 4.6565
2004 5,422 0.4171 200 0.0154 3.6887
2005 5,097 0.3898 214 0.0164 4.1985
Total 90,136 – 3,237 – –

Fig. 1. JE incidence in 1951 - 2006, China.

However, the number of JE morbidities decreased from 11,779
to 5,097 between 2000 and 2005, the annual incidence de-
clined from 0.9489/100,000 to 0.3898/100,000, the number
of mortalities declined from 375 to 214, and the mortality
rate also decreased from 0.0302/100,000 to 0.0164/100,000.
Over this 6-year period, the annual mortality rate ranged
from 2.51 to 4.66% (11,12). The trends in the incidence and
mortality of JE in mainland China in recent years are illus-
trated in Figure 1 and Table 1.
3. Seasonal distribution of cases
JE cases are reported from January to December each year
nationwide and reveal a low incidence in the periods from
November to May. However, the number of morbidities in
June is typically double that occurring in May. The number
of morbidities occurring in July and August each year are
generally pooled. The number of morbidities in August accounts
for 41.14% of the total annual morbidities. The relatively high
morbidity level is maintained in September, declines in Oc-
tober, and then decreases significantly in November. The
number of morbidities between June and October accounts
for 97.42% of the total annual morbidity. A summary of 10
years’ data reveals that the monthly distribution trend of
morbidity is consistent (Figure 2 and Table 2). Thus, the inci-
dence of JE exhibits a clear seasonal distribution.
In addition, the monthly distribution data shows that both
the incidence and mortality rates increase significantly from
June, peak in July and August, and then decline from October
onwards, indicating a consistent annual pattern in the inci-
dence and mortality of JE (13).
The occurrences of JE cases in the north and south region
of China have been shown to be slightly different. In the south,
JE cases start to increase in July and decrease significantly in
August, whereas in the north, JE cases begin to increase in
August and clearly decrease in September (13-15).
4. Geographic distribution of cases
A total of 31 provinces in mainland China have reported
JE cases; the exceptions including Qinghai Province, Xinjiang
Uygur Autonomous, and Tibet. The cases are scattered in vari-
ous endemic localities with no obvious aggregation of the
disease. Based on the average annual incidence of JE between
1996 and 2005, the regions of endemism in mainland China
can be classified into the following four groups (Figure 3).
4-1. Highly endemic areas
The average incidence in these areas is considered to be
approximately >1/100,000. The areas include Sichuan Prov-
ince, Guizhou Province, Chongqing City, Shaanxi Province,
and Yunnan Province. Annually, the number of morbidities
in these five areas accounts for 50% of the total cases nation-
wide, comprised as much as 74.1% of the total cases in 2002.
The combined population of these areas, however, represents
only 26% of the national population (10,11,13-16).
4-2. Moderately endemic areas
The average incidence in these areas is considered to be
between 0.5/100,000 and 1/100,000. The areas include the

332
 Table 2. The incidence of JE cases by month in 1996 - 2005
Year
Month Total (%)
1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
JAN 20 17 43 24 16 10 25 18 7 2 182 (0.20)
FEB 9 6 20 10 7 12 20 10 11 2 107 (0.12)
MAR 21 37 40 18 15 21 45 30 27 12 266 (0.30)
APR 36 43 69 43 35 39 49 33 34 6 387 (0.43)
MAY 119 154 214 130 131 121 213 268 118 67 1,535 (1.70)
JUN 639 584 797 826 520 498 874 956 430 696 6,820 (7.57)
JUL 2,915 2,654 4,245 2,438 3,029 3,193 4,485 2,888 1,745 2,225 29,817 (33.08)
AUG 4,109 4,419 5,079 3,413 5,817 4,210 2,510 3,157 2,575 1,796 37,085 (41.14)
SEP 1,818 1,540 1,469 1,278 1,723 1,241 404 407 393 238 10,511 (11.66)
OCT 439 427 373 267 355 331 92 62 60 45 2,451 (2.72)
NOV 127 106 101 76 88 90 42 25 16 6 677 (0.75)
DEC 56 73 40 33 43 29 10 6 6 2 298 (0.33)
Total 10,308 10,060 12,490 8,556 11,779 9,795 8,769 7,860 5,422 5,097 90,136 (100.00)

cases nationwide (10,11,17-19).

Fig. 2. Seasonal distribution of JE case in China.
following seven provinces: Shanxi Province, Henan Prov-
ince, Anhui Province, Hubei Province, Hunan Province,
Jiangxi Province, and Guangxi Province. Between 2000 and
2002, the number of morbidities accounted for 20% of the
The five provinces with an incidence >1/100,000 are
located in southwest and middle China and lie adjacent to
each other. The seven provinces with incidence between 0.5/
100,000 and 1/100,000 are located on the eastern periphery of
the abovementioned five provinces and are closely adjacent
to them. The combined JE morbidities of these 12 provinces
account for 80% of the total cases nationwide, whereas their
combined population constitutes only 40% of the national
population. In addition, the total number of JE morbidities in
mainland China has decreased significantly in recent years
compared to those reported in historical records, and the 5,097
cases reported in 2005 was the lowest annual figure to date.
However, despite this downward trend, the ratio of the num-
ber of morbidities in the 12 high- and moderate-incidence
provinces as a percentage of the national total cases is in-

Fig. 3. Geographic distribution of JE in China.

333
creasing---from 82.7% in 1998 to 91.4% in 2002, and to
88.85% in 2005---demonstrating that the onset of JE is be-
coming more prevalent in these areas.
4-3. Slightly endemic areas
The average incidence in the slightly endemic areas is
considered to be between 0.1/100,000 and 0.5/100,000. The
areas include the following seven provinces: Shanxi Prov-
ince, Gansu Province, Jiangsu Province, Shandong Province,
Fujian Province, Guangdong Province, and Zhejiang Prov-
ince. In addition, there are a further 10 provinces and areas
with an incidence <0.1/100,000: Hebei Province, Ningxia
Province, Shanghai City, Liaoning Province, Inner Mongolia
Province, Hainan Province, Tianjin Province, Beijing City,
Jilin Province, and Heilongjiang Province (10,11,20-22).
4-4. Non-endemic areas
There have been no JE cases reported from three prov-
inces: Qinghai Province, Xinjiang Uygur Autonomous, and
Tibet. Although individual imported cases might be recorded
from these areas, they can still be regarded as non-endemic
(10,11,23).
According to the analysis of the annual incidence of JE
cases in each province, before the 1970s, the JE cases mainly
appeared in localities in the north of China, including Beijing
City, Tianjin City, Shandong Province, Shanghai City,
Zhejiang Province, Jiangxi Province, Fujian Province, and
Guangdong Province, and also from coastal areas in the east
(10). However, the incidence in these areas has undergone a
significant recent decline, and at present the average inci-
dence is approximately 0.1/100,000. This reveals that the
endemic areas of JE have shifted from the eastern coastal
areas to the southwest and middle provinces. The current low
incidence of JE in the eastern coastal areas is mainly attrib-
uted to the rapidly developing economy of this region that
has resulted in a relatively high coverage of JE vaccination
(10).
5. Age and gender distribution
In terms of the age distribution of JE morbidity, JE cases
have been recorded in subjects in infancy to those over 75
years old (Figure 4). The proportion of 2-, 3-, and 4-year-
olds is relatively high, accounting for 10.88, 12.88, and
12.33% of all cases, respectively. Young patients under 6 years
of age accounted for 68.10% of the total cases. In the years
between 2000 and 2005, young patients under 15 years of age
accounted for 91.19, 91.26, 91.06, 90.14, 89.80, and 90.6%
of the total cases nationwide, respectively (11).
The age distribution of JE deaths is similar to that of mor-
bidities. Death cases have been recorded in all age groups,
with the highest proportion in 2-, 3-, and 4-year-olds, account-
ing for 10.69, 11.95, and 10.84% of total JE death cases, re-
spectively. JE deaths in patients under 15 years of age account
Fig. 4. The proportion of JE cases by age 1996-2005, China.
334
for 83.7% of total deaths, and among these, deaths in patients
under 6 years of age account for 65.22% of JE fatalities.
The number of males among JE patients has exceeded that
of females, with a ratio of 1.3:1 in recent years (11).
6. Occupational distribution
The data on the occupational distribution of JE cases be-
tween 1996 and 2005 reveals that diaspora children account
for 54.51% of total morbidities and 54.72% of total mortali-
ties. According to reports in 2005, the occupation of morbid
patients is mainly diaspora children, students, and kindergar-
ten children, accounting for 88.5% of the total morbidities.
Among these, diaspora children accounted for 53.6%, stu-
dents for 23.4%, and kindergarten children for 11.5%, while
farmers accounted for 8.3% of all morbid patients. Mortalities
occurred mainly in diaspora children (50.3%), followed by
students (21.1%), farmers (15.8%), and kindergarten children
(7.0%) (11).
7. Prevalence of JEV isolates
JEV, a Flavivirus belonging to the family Flaviviridae, was
first isolated in Japan. JEV was first isolated in China in the
1940s (24-27). An inactivated form of the P-3 strain has been
used to develop a JE vaccine. Since its first discovery in China,
multiple strains of JEV have been isolated in the country.
Strain SA14 was isolated from mosquitoes in China and has
been used to develop a live attenuated JE vaccine.
In recent years, multiple strains of JEV have been isolated
from the cerebrospinal fluid (CSF) and blood of Chinese JE
patients, as well as from mosquitoes and midges collected in
areas including Shanghai City, Yunnan Province, Guizhou
Province, Henan Province, Sichuan Province, Fujian Prov-
ince, Liaoning Province, and Heilongjiang Province. More-
over, a molecular biological study of JEV has been launched
(28-38).
By tissue culture methods, seven strains of JEV have been
isolated from Culex tritaeniorhynchus collected in the
suburban area of Shanghai City. All seven newly isolated
strains exhibit a positive reaction with standard JEV anti-
bodies. A molecular biological study has demonstrated that
each of these strains belongs to genotype 1 of JEV (30). This
is the first report of the isolation of genotype 1 JEV in China.
Genotypic analysis of 100 JE strains isolated in mainland
China revealed that they possessed two JEV genotypes (geno-
types 1 and 3). JEV genotype 3 strains are primary epidemic
strains. JEV genotype 1 has been known since 1979 (37).
Two JEV genotypes were detected in specimens from JE pa-
tients and from mosquitoes simultaneous with a JE outbreak
in Yuncheng Prefecture, Shanxi Province, in 2006 (38). The
genome analysis of two JEVs from bats in Yunnan, China in
1980 showed both virus isolates belonging to genotype 3.
The viruses have a close relationship with JEVs isolated
between mosquitoes and humans in the same region over 2
decades (39).
8. Control and prevention of JE
8-1. JE vaccine
Inoculation with an inactivated vaccine (P-3 strain) was
developed and has been used in China for vaccination since
the beginning of the 1970s. A JE live attenuated vaccine
(SA14-14-2) has been used since the beginning of the 1990s,
and its safety and efficacy have been evaluated (40,41). A
total of 300,000,000 people have been vaccinated with this
attenuated vaccine. Prior to 2006, a total of 16 provinces had
used JE vaccination as part of their immunization program;
local governments provide the population with free JE vacci-
nation (42). Beginning in 2006, prevention and control of JE
in China has advanced with the integration of JE immuni-
zation into the Expanded Programme of Immunization (EPI)
in mainland China, especially in rural and underdeveloped
areas.
8-2. Surveillance of JE
In recent years, the government has paid great attention to
the prevention and treatment of JE. In 2004, the Ministry of
Health, China (MOH, China) advocated an increase in the
research on JE, and in 2006 announced a national surveil-
lance program for JE (43). At present, 22 surveillance sites
have been established in 13 provinces nationwide in order to
monitor JE epidemics, generally in areas with a high inci-
dence of JE. The surveillance includes case reports, close
monitoring of the nature of transmission media, pathogen
monitoring, and JE antibody monitoring among humans and
swine (43).
In recent years, the international society has augmented
the support to JE prevention in China. Since 2001, a program
of The Japan Health Science Foundation has supported
research in the “molecular epidemiological study of Japanese
encephalitis virus in China”. In 2005, the Program for Ap-
propriate Technology in Health (PATH) in America launched
a JE surveillance project in the highly endemic area of Shaanxi
Province, for which sera and CSF samples of local JE cases
have been collected for laboratory diagnosis. The WHO,
together with MOH, China, has launched an acute meningi-
tis and encephalitis surveillance (AMES) program in four
provinces (Hubei, Shandong, Guangxi, and Hebei).
9. Conclusion
The data indicate that the incidence of JE has been de-
creasing substantially; in 2008 for example, there were only
2,975 reported JE cases and 142 deaths in 25 provinces in
mainland China. The overall incidence of JE should decrease
even more due to the introduction of the JE vaccine into the
EPI system; nevertheless, JE currently remains also a high-
importance public health problem in China. Recently, the
tendency of the age distribution in JE morbidity has swung
toward teenage patients. The genotype of JEV has changed
from G3 only to G1 and G3, which means two genotypes are
circulating in China. Although the vaccine has been used in
newborns, the vaccine strategy should be adjusted according
to changes in the characteristics of the disease, especially in
terms of the local outbreaks of JE. Strengthening the sensi-
tivity of the surveillance system should also be an effective
way to control the disease.
ACKNOWLEDGMENTS
This work was supported by grants from the Ministry of Science and
Technology of China (No. 2003BA712A08-01) and the Japan Health Sci-
ence Foundation.
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