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Introduction
Japanese encephalitis (JE) is an acute infectious zoonosis disease
caused by infection with Japanese encephalitis virus (JEV) through
mosquito bites [1,2,3,4,5]. Infection results in damage to the
central nervous system. Symptoms such as sustained high fever,
disturbance of consciousness, and convulsions appear after
infection with JEV, and the mortality rate can be more than
30%. Furthermore, ,30% of the survivors may have neurological
sequelae, such as severe consciousness disturbance, dementia,
aphasia, and limb paralysis [2,6,7]. JE is an internationally
recognized public health problem and has been a cause for
concern globally [3]. According to a report by the World Health
Organization (WHO), ,69000 JE cases occur annually worldwide
and JE is prevalent in 24 countries and territories in Asia and
Oceania. Thus, ,3000 million people live in the JE-endemic area
and are at risk of JEV infection [2,3,8].
JE is a vaccine-preventable disease, and immunization pro-
grams can prevent JEV infection [2]. Historically, Japan, Korea,
and China had high incidence of JE. However, with the
implementation of JE vaccination programs in the 1960s, both
Japan and Korea have almost achieved a state of JE ‘‘elimina-
tion’’[8]. China began implementing a JE vaccination program in
the 1980s, and the incidence of JE has since been substantially
reduced [9,10]. After 2000, with the help of the WHO and
Program for Appropriate Technology in Health (PATH), as well
as other international organizations, other JE endemic counties in
Asia have begun to implement JE vaccination programs [8]. On
the other hand, as a natural focal disease transmitted by
mosquitoes, the incidence of JE can be affected by several climatic
factors, such as temperature and rainfall [11,12,13,14,15]. The
research conducted in Malaysia confirmed that the effects of
climatic factors on JE were masked by vaccination programs and
cannot be estimated precisely [16]. Therefore, the JE data derived
from the period without JE vaccination are of great significance to
reveal the authentic epidemiology of JE and influences of climatic
factors on JE incidence.
PLOS ONE | www.plosone.org 1 June 2014 | Volume 9 | Issue 6 | e99183
China is a highly endemic area of JE. In addition, there was a
nationwide JE epidemic in China during the 1960s and 1970s, and
tens of thousands cases were reported, with an incidence of over
15/100000 per year in this era of no JE vaccine intervention
[9,10]. As China was experiencing the ‘‘Cultural Revolution’’ at
that time, the functions of government were weakened and the
public health authorities almost failed to implement any interven-
tions. Thus, China experienced a natural JE epidemic period with
no interventions from the 1960s to 1970s. Then, there comes the
question that what the epidemiology of JE was in the absence of
vaccine interventions during that period in China. In this study,
we examined the spatial and temporal distribution of JE cases
during the period 1963 to 1975 in mainland China. By combining
with meteorological data, the effects of rainfall and temperature on
JE in several geomorphic units are also discussed. The results not
only provide data supporting the prevention and control of JE in
endemic regions that have not widely implemented JE vaccination
programs, but are also of practical significance for prevention and
control of JE in potentially endemic regions.
Materials and Methods
Data collection and management
Since 1950, JE has been included in the national notifiable
infectious diseases list [9]. The data on reported cases and annual
incidence of JE from 1963 to 1975 were obtained from the China
Information System for Disease Control and Prevention
(CISDCP) [17], and covered the whole nation, including 29
provinces, municipalities, and autonomous regions (the national
administrative divisions consisted of 29 provinces, municipalities,
and autonomous regions during this period), among which
Xinjiang, Tibet, and Qinghai had no reported cases during the
study period and were classified as JE-free areas.
The meteorological data, including the monthly precipitation
and monthly mean temperature, from 1963 to 1975 were obtained
from the China Meteorological Data Sharing Service System in a
grid format [18]. Due to the obvious seasonal distribution of JE
cases, which clustered in June, July, and August in China, the
temperature and rainfall in summer are more sensitive than the
annual values in terms of evaluating the effects on JE. In this study,
the average monthly rainfall and temperature in June, July, and
August were used to represent summer rainfall and summer
temperature, respectively.
Division of geomorphic units
To further analyze the effects of climatic factors in different
geographical environments on the incidence of JE, China was
divided into eight geomorphic units and the boundaries of each
geomorphic unit are represented with the boundaries of the major
provincial administrative regions included (Figure 1). These
geomorphic units were as follows: the Qinghai-Tibet Plateau
(QTP), which consists of Qinghai and Tibet; the Loess Plateau
(LP) consisting of Shaanxi, Gansu, and Ningxia; the Inner
Mongolian Plateau (IMP), which consists of the Inner Mongolian
Autonomous Region; the Yunnan-Guizhou Plateau (YGP) con-
sisting of Yunnan, Guizhou, and Sichuan; the Northeast China
Plain (NECP), which consists of Heilongjiang, Jilin, and Liaoning;
the North China Plain (NCP) covering Hebei, Beijing, Tianjin,
Shanxi, Shandong, and Henan; the Yangtze River Plain (YRP),
which consists of Hunan, Hubei, Anhui, Jiangsu, Jiangxi,
Zhejiang, and Shanghai; and the Pearl River Delta Plain (PRDP),
which mainly includes Guangdong province. The annual
incidence of JE in each plateau or plain was calculated from the
sum of reported JE cases within the regions divided by the
population size in the corresponding year. In addition, the summer
temperature and summer rainfall for each region were derived
from the gridded meteorological datasets using the zonal statistics
to summarize the values within each region. Zonal statistical
analyses were conducted using the Spatial Analyst module in the
ArcGIS software (version 9.3; ESRI, Redlands, CA).
Cluster analysis
The Local Indicators of Spatial Association (LISA) was used to
describe the spatial clusters of JE incidence at the provincial level
between 1963 and 1975. The spatial correlations or spatial clusters
between the value of a given location and the average of
neighboring values in the surrounding locations were represented
on the LISA cluster maps by calculating the Local Moran’s I,
which ranged from 21 to 1[11,17,19]. In addition, the Z-score
was used to measure the significance of the spatial correlations
indicated by Local Moran’s I. A high positive Z-score indicates
that the surrounding features have either similar high values
(High-High) or similar low values (Low-Low), while a low negative
Z-score indicates a significant (P,0.05) spatial outlier (High-Low
or Low-High) [20]. The spatial statistics module in ArcGIS
software (version 9.3; ESRI) was applied to perform LISA analysis
at the provincial level to identify the cluster pattern during the JE
epidemic period.
Results
Japanese encephalitis in mainland China in 1963–1975
There were more than 1.4 million reported JE cases in China
from 1963 to 1975, accounting for almost 60% of the total
reported JE cases since 1950. With the exception of Xinjiang,
Tibet, and Qinghai, all provinces, municipalities, and autonomous
regions in China have reported cases of JE. In addition, the
incidence of JE during this period was between 8.32/100000 and
20.92/100000 (Figure 2A). The epidemic peaked in 1966 and
1971, with about 150000 and 170000 cases of JE reported,
representing annual JE incidence rates of 20.58/100000 and
20.92/100000, respectively.
The spatial distribution of JE around the country in 1971 is
shown in Figure 2B. The incidence of JE in each province was
between 1.59/100000 and 53.06/100000, and there were 10
provinces with JE incidence higher than the national average
(20.92/100000). Figure 2B shows that the endemic regions can be
divided into three classes including high, medium, and low
prevalence regions, according to the prevalence rates. The high-
prevalence regions, including Shandong, Henan, Anhui, Hunan,
Hubei, Jiangsu, Jiangxi, Zhejiang, Shanghai, Fujian, Guangdong,
and Guangxi, have JE incidence greater than 20/100000, and
these 12 provinces are distributed in mainly the North China
Plain, the Yangtze River Plain, and the Pearl River Delta Plain.
Regions with medium JE incidence of between 10/100000 and
20/100000 include Liaoning, Hebei, Shaanxi, and Sichuan, which
are located in central and southwestern China. The low-
prevalence regions with incidence less than 10/100000 consist of
10 provinces; i.e., Heilongjiang, Liaoning, Inner Mongolia,
Beijing, Tianjin, Shanxi, Ningxia, Gansu, Yunnan, and Guizhou,
which are located mostly in the Northeast China Plain, the Inner
Mongolian Plateau, the Loess Plateau, and the Yunnan-Guizhou
Plateau.
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