Quantifying Quality of Life and Disability of Patients with
Advanced Schistosomiasis Japonica
Tie-Wu Jia1, Ju ¨rg Utzinger2,3, Yao Deng4, Kun Yang4, Yi-Yi Li5, Jin-Huan Zhu5, Charles H. King6,
1Key Laboratory on Biology of Parasites and Vectors, MOH, WHO Collaborating Center on Malaria, Schistosomiasis and Filariasis, National Institute of Parasitic Diseases,
Chinese Center for Disease Control and Prevention, Shanghai, People’s Republic of China, 2Department of Public Health and Epidemiology, Swiss Tropical and Public
Health Institute, Basel, Switzerland, 3University of Basel, Basel, Switzerland, 4Jiangsu Institute of Parasitic Diseases, Wuxi, People’s Republic of China, 5Hunan Institute of
Parasitic Diseases, Yueyang, People’s Republic of China, 6Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio,
United States of America
Background: The Chinese government lists advanced schistosomiasis as a leading healthcare priority due to its serious
health and economic impacts, yet it has not been included in the estimates of schistosomiasis burden in the Global Burden
of Disease (GBD) study. Therefore, the quality of life and disability weight (DW) for the advanced cases of schistosomiasis
japonica have to be taken into account in the re-estimation of burden of disease due to schistosomiasis.
Methodology/Principal Findings: A patient-based quality-of-life evaluation was performed for advanced schistosomiasis
japonica. Suspected or officially registered advanced cases in a Schistosoma japonicum-hyperendemic county of the
People’s Republic of China (P.R. China) were screened using a short questionnaire and physical examination. Disability and
morbidity were assessed in confirmed cases, using the European quality of life questionnaire with an additional cognitive
dimension (known as the ‘‘EQ-5D plus’’), ultrasonography, and laboratory testing. The age-specific DW of advanced
schistosomiasis japonica was estimated based on patients’ self-rated health scores on the visual analogue scale of the
questionnaire. The relationships between health status, morbidity and DW were explored using multivariate regression
models. Of 506 candidates, 215 cases were confirmed as advanced schistosomiasis japonica and evaluated. Most of the
patients reported impairments in at least one health dimension, such as pain or discomfort (90.7%), usual activities (87.9%),
and anxiety or depression (80.9%). The overall DW was 0.447, and age-specific DWs ranged from 0.378 among individuals
aged 30–44 years to 0.510 among the elderly aged $60 years. DWs are positively associated with loss of work capacity,
psychological abnormality, ascites, and active hepatitis B virus, while splenectomy and high albumin were protective factors
for quality of life.
Conclusions/Significance: These patient-preference disability estimates could provide updated data for a revision of the
GBD, as well as for evidence-based decision-making in P.R. China’s national schistosomiasis control program.
Citation: Jia T-W, Utzinger J, Deng Y, Yang K, Li Y-Y, et al. (2011) Quantifying Quality of Life and Disability of Patients with Advanced Schistosomiasis
Japonica. PLoS Negl Trop Dis 5(2): e966. doi:10.1371/journal.pntd.0000966
Editor: Nilanthi de Silva, University of Kelaniya, Sri Lanka
Received August 2, 2010; Accepted January 18, 2011; Published February 15, 2011
Copyright: ? 2011 Jia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This investigation received financial support from the Western Pacific Region/World Health Organization (WHO) (I.D. MVP/CHN/08/01), from the
UNICEF/United Nations Development Programme/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) (ID No. A30298), the
National Natural Science Foundation of China (ID No. 30590373), the National Important Project on Science and Technology (No. 2008ZX10004-011), and the
National Science and Technology Supporting Programs (No. 2009BAI78B07). The funders had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: firstname.lastname@example.org
Schistosomiasis, caused by infection with trematode blood flukes
of the genus Schistosoma, is one of the world’s most important
helminth infections in terms of the global burden of human
morbidity and mortality [1,2]. Advanced, or late-stage schistoso-
miasis japonica can be regarded as an extreme form of chronic
Asian schistosomiasis, one that is more serious than the advanced
hepatosplenic disease of Schistosoma mansoni infection found in
Africa and the Americas. In the People’s Republic of China (P.R.
China), advanced schistosomiasis is a chronic disabling condition
associated with portal hypertension, splenomegaly, ascites, and
gastro-oesophageal variceal bleeding, or with severe growth
retardation or granulomatous disease of the large intestine. In
this country, advanced cases are registered and managed
independently from patients with general chronic schistosomiasis.
Advanced schistosomiasis japonica is much more common in
highly endemic areas, because repeated, heavy exposure to
cercariae means that early-stage chronic cases may not be
effectively treated in routine control programs. The eggs of
S. japonicum retained in the intestine and liver tissue stimulate a
granulomatous response, leading to continuous fibrosis of the
periportal tissue and developing a pipestem fibrosis. Although
down-modulation of the granulomatous response, which could
prevent excessive chronic morbidity  after 2–5 years or more,
parasite-induced periportal fibrosis may progress to cause
www.plosntds.org1 February 2011 | Volume 5 | Issue 2 | e966
obstruction of the portal vessels and damage to the liver
parenchyma, leading to development of advanced schistosomiasis
. Mortality eventually results from bleeding of the upper
gastrointestinal tract, spontaneous bacterial peritonitis, and
hepatic failure, among others [5,6]. Based on its major symptoms,
advanced schistosomiasis japonica in P.R. China represents a
common, serious health burden, and has been classified into four
clinical sub-types, namely (i) ascites, (ii) megalosplenia, (iii) colonic
tumoroid proliferation, and (iv) dwarfism [5,6].
In the 1950s, it was estimated that 5–10% of the S. japonicum-
infected individuals in areas highly endemic for schistosomiasis
would develop to the advanced stages of disease. At that time,
there were approximately 500,000 advanced cases in P.R. China
. Terms like ‘‘villages of widows’’ and ‘‘villages where all is
dead’’ were used to describe the devastating impact of schistoso-
miasis across southern P.R. China . Over the past 60 years,
implementation of integrated control approaches has succeeded in
greatly reducing the burden due to schistosomiasis in P.R. China
and, at present, dwarfism and colonic tumoroid proliferation are
rarely found [8,9]. However, ascites and megalosplenia are still
common, typically in foci of high transmission intensity, but also in
areas where the transmission of schistosomiasis has been controlled
and interrupted for several decades, such as Shanghai municipality
and Zhejiang province [10,11]. By the end of 2008, a total of
412,927 cases of schistosomiasis were found in P.R. China, and
among them, 30,030 (7.3%) suffered from the advanced form of
chronic schistosomiasis japonica .
Schistosomiasis represents a serious, but under-recognized,
disease burden in many developing countries . Unfortunately,
in the World Health Organization/World Bank Global Burden of
Disease (GBD) study, active schistosome infection was the only
health state evaluated in the assessment of schistosomiasis-
associated disease burden. Based on older, unfounded notions of
‘minimal to absent symptomatology’ in uncomplicated chronic
schistosomiais, the GBD assigned a schistosomiasis disability
weight (DW) of 0.005 (on a scale from 0 (no disability) to 1
(death)) for school-aged children, and 0.006 for those aged $15
years . More recent studies suggest, however that this is a
serious underestimation of the ‘true’ disability due to schistosomi-
In the mid-2004s, we successfully introduced a patient-based
evaluation, the so-called EQ-5D plus questionnaire, as a measure
of health-related quality of life to assess the disability impact of
early stage chronic schistosomiasis japonica . Of note, the EQ-
5D plus questionnaire had been widely used in different settings
for measuring population health status [19–21]. We concluded
that the overall DW for early stage chronic schistosomiasis was, on
average, 0.191 and age-specific weights ranged from 0.095
(children aged 5–14 years) to 0.246 (elderly aged $60 years)
. In 2006, another independent study carried out in Hubei
province on the basis of disability weighting definitions of the GBD
study  obtained a similar DW of 0.122 . These estimates
supported findings from two meta-analyses performed by King
and colleagues [15,18], and a disability-adjusted life year (DALY)-
based life-path model developed by Finkelstein et al. .
However, these studies were all limited to a general valuation of
the disabling sequelae of chronic schistosome infection. In view of
the considerable magnitude and fatal clinical outcomes of
advanced schistosomiasis japonica, and relatively independent
case management in P.R. China, we considered it important to
explore the independent contribution of advanced schistosomiasis
japonica to the national and global disease burden. Although there
are many studies on the topic of advanced schistosomiasis, very
few studies have attempted to assess the patients’ disability in terms
of overall quality of life [10,24].
Study area and population
This study was carried out between October 2007 and January
2008 in Hanshou county, Hunan province, which is hyperendemic
for S. japonicum, and where a considerable number of patients with
advanced schistosomiasis still reside. All suspected or officially
registered advanced schistosomiasis cases in Hanshou county were
eligible for enrolment. A short questionnaire was administrated
and a physical examination was carried out to screen for advanced
cases. Those who had reached ‘clinical cure’, or those who were
clearly co-morbid with other serious diseases such as tuberculosis,
diabetes, cardiopathy, nephropathy, and hepatic cirrhosis, were
excluded from the present study.
According to the national standardized diagnostic criteria for
schistosomiasis (WS261-2006), the inclusion criteria for advanced
schistosomiasis cases were as follows: (i) repeated or long-term
exposure to cercaria-infested water or a history of chemotherapy
against schistosomiasis; (ii) positive serological test (enzyme-linked
immunosorbent assay (ELISA)); and (iii) portal hypertension
syndrome resulting from hepatic fibrosis, e.g., ascites, splenomegaly
reaching Hackett grade 3 or higher, or splenomegaly of Hackett
grade 2 but with hypersplenism, dilatation of oesophageal or gastric
varices, or upper gastrointestinal bleeding. Based on the major
symptoms, advanced schistosomiasis is classified into four clinical
types, namely (i) ascites; (ii) megalosplenia; (iii) colonic tumoroid
proliferation; and (iv) dwarfism [5,6,25], each type of which was
qualified for the study. Those subjects who had undergone
splenectomy but who had persistent signs and symptoms of
abdominal pain, diarrhea, or weakness (i.e., not having reached a
status of ‘clinical cure’) were also eligible for inclusion.
Questionnaire and diagnostic procedures
The study subjects were first interviewed using a standardized
and pre-tested questionnaire and, subsequently, participants were
Advanced schistosomiasis japonica, an extreme form of
chronic schistosomiasis that occurs in Asia, is more serious
than the advanced hepatosplenic disease of schistosomi-
asis encountered in Africa and the Americas. The advanced
schistosomiasis japonica is a chronic disabling condition
associated with portal hypertension, splenomegaly, asci-
tes, and gastro-oesophageal variceal bleeding, or with
severe growth retardation or granulomatous disease of the
large intestine. However, the actual disability caused by
advanced schistosomiasis japonica is unknown. We carried
out a patient-based quality-of-life evaluation employing a
standardized and widely used questionnaire (known as
‘‘EQ-5D plus’’), coupled with ultrasonography and labora-
tory tests on advanced schistosomiasis japonica cases in a
hyperendemic area of China. Among 215 confirmed cases
of advanced schistosomiasis japonica, we found an overall
disability weight of 0.447 with age-specific weights
ranging from 0.378 to 0.510. Importantly, advanced
schistosomiasis japonica is not only associated with heavy
disability weights, but also with high morbidity and poor
self-reported quality of life. Our results provide valuable
data for the current revision of the Global Burden of
Disease (GBD) study, as well as for evidence-based
decision-making in China’s national schistosomiasis control
Quality of Life and Disability of Schistosomiasis
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subjected to a physical examination, ultrasonography, and labora-
tory testing. Regarding interviews, an individual questionnaire was
used to obtain information on sociodemographic variables (i.e., age,
sex, educational attainment, and occupation), exposure to cercaria-
infested water, history of anti-schistosomal treatment (including
chemotherapy or splenectomy), and self-reported symptoms and
signs during the past 12 months, including fatigue, anorexia,
abdominal distension or pain, diarrhea, blood in the stool, as well as
any partial or complete loss of working capacity. Additionally, the
EQ-5D plus questionnaire was employed to assess the respondents’
health-related quality of life in six relevant dimensions, namely (i)
mobility; (ii) self-care; (iii) participation in usual activities; (iv) the
presence of pain or discomfort; (v) the presence of anxiety or
depression; and (vi) altered cognition. For each dimension, three
possible outcomes were considered: no problems, moderate
problems, or extreme problems. The questionnaire also included
a 20 cm visual analogue scale (VAS) for the self-rated valuation of
patient’s own general health status on a continuous scale from best
imaginable (100) to the worst imaginable (0) [20,21,26,27]. This
VAS was subsequently used to derive the individual subject’s
disability score (see details below).
Abdominal ultrasonography was performed with the subject in
a fasting state (i.e., no food intake 4 hours prior to examination).
Subjects were horizontally-positioned and organometric measure-
ments were taken during relaxed inhalation. Pathology was graded
according to standardized criteria . Hepatic fibrosis was
graded from 0 (normal) to grade III (severe). Hepatomegaly was
defined as a protrusion of the liver of .3 cm under the xiphoid
process or palpable (.0 cm) under the right costal margin at the
midclavicular line. Inner diameter of main portal vein was
measured by ultrasonography and compared to established
normal values (10.961.1 mm for individuals aged 30–39 years,
11.161.1 mm for people aged 40–49 years, 10.761.2 mm for
individuals aged 50–59 years, and 10.660.9 mm for elderly aged
Figure 1. Flow chart, detailing how many advanced cases of schistosomiasis japonica were included and excluded in the study. Of
note, there were 66 advanced cases of schistosomiasis japonica with comorbidities, such as diabetes, cardiopathy, nephropathy, and hepatic cirrhosis.
Quality of Life and Disability of Schistosomiasis
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$60 years) . Splenomegaly was determined by physical
examination using the Hackett classification (grade 1–5). The
presence of ascites was confirmed by ultrasonography and graded
clinically as none, mild, moderate, or severe .
With regard to laboratory testing, a blood sample was obtained
for measurement of hepatitis B virus-related antigens and
antibodies, anti-schistosomal antibody, blood hemoglobin, and
serum albumin concentration.
Although participants were not specifically examined for other
diseases, those with clinical symptoms and signs clearly attribut-
able to conditions other than schistosomiasis were excluded from
the study. The number of advanced cases of schistosomiasis
japonica were included and excluded in the study with the study
flow chart showed in Figure 1.
An anonymous database was created and all entries double-
checked. Statistical analyses were performed using SAS software
version 8.1 (SAS Institute; Cary, USA). The x2test was used to
examine differences between categories, and the Cochran-Mantel-
Haenszel x2test was employed to explore linear associations
between outcome variables and age. The DW for each individual
was computed, based on the self-rated health score on the linear
VAS using the following formula: DW=12(VAS score / 100),
where DW is the estimated disability weight for that subject.
The mean DWs were also calculated for subgroups stratified by
age or clinical type. Analysis of variance (ANOVA) was used to test
for differences in mean DWs among all groups, and the Bonferroni
t-test was used for pairwise comparisons. Two multivariate
regression models were developed to explore the morbidity
indicators associated with DW. Model 1 assessed the relationship
between age, exposure, the separate dimensions of the EQ-5D plus
questionnaire, and the subject’s DW outcome, whilst model 2
assessed the association between morbidity indicators, socioeco-
nomic status, and DW. Independent variables showing no
statistical significance (P.0.05) were removed by a backward
stepwise elimination procedure. Age, occupation, educational
attainment, hepatic fibrosis, loss of work capacity, and ascites were
specified as categorical variables, with a designated reference
category and a set of contrasted dummy variables.
The study protocol was approved by the institutional review board
of the National Institute of Parasitic Diseases, Chinese Center for
Disease Control and Prevention in Shanghai, and the WHO
Research Ethics Review Committee. The objectives, procedures,
and potential risks were explained to all participants. Written
informed consent was also obtained from each participant or a
literate relative. Individuals who were seropositive for anti-schisto-
somal antibody were treated with praziquantel, free of charge,
according to Chinese national guidelines for schistosomiasis control.
Characteristics of study cohort
During the initial screening, a total of 506 suspected or officially
registered cases were examined. Among them, 221 were
confirmed as advanced schistosomiasis japonica cases and 215
were evaluated. Males represented 71.6% (154/215) of the total
study cohort, and 80.5% (173/215) were older than 44 years
(mean age: 57.1 years, standard deviation: 12.6 years; range: 30–
The observed proportions of the different clinical categories of
advanced schistosomiasis were: 64.2% (138/215) for ascites (type
I), 34.4% (74/215) for megalosplenia (type II), 0.5% (1/215) for
colonic tumoroid proliferation (type III), and 0.9% (2/215) for
dwarfism (type IV). There was no significant difference in the
distribution of clinical categories between males and females
Table 1 shows the number and percentage of patients having
schistosomiasis-related clinical symptoms or signs, stratified by age,
among all the enrolled patients with advanced schistosomiasis.
There were no statistically significant differences in the rates of
history of prior treatment, fatigue, anorexia, abdominal pain,
diarrhea, or blood in the stool among the different age groups.
There was no statistically significant difference in the rate of
splenectomy between those aged 30–44 years and those aged 45–
59 years (P.0.05), but there was a statistically significant
difference between those aged 30–59 and those aged $60 years
(P,0.001). Overall, 84.9% (62/73) of the patients who had
undergone splenectomy were below the age of 60 years. The
prevalence of ascites increased with age from 23.8% (10/42)
among those aged 30–44 years to 36.3% (47/101) among those
aged $60 years (P,0.01).
The prevalence of self-reported impairment of work capacity
(partial or complete loss) also showed a strong increase with age,
Table 1. Clinical symptoms or signs in advanced cases of schistosomiasis japonica, stratified by age group (n=215).
Number (%) of clinical symptoms and signs
30–444222 (52.4)36 (85.7)39 (92.9)30 (71.4) 30 (71.4)18 (42.9) 13 (31.0)6 (14.3)32 (76.2)10 (23.8)
45–597240 (55.6) 67 (93.1)69 (95.8)58 (80.6)48 (66.7)39 (54.2)26 (36.1)7 (9.7)66 (91.7)21 (29.2)
$60 10111 (10.9)88 (87.1)96 (95.1)82 (81.2)91 (90.1)63 (62.4)45 (44.6)22 (21.8)100 (99.0) 47 (46.5)
All21573 (34.0)191 (88.8)204 (94.9)170 (79.1)169 (78.6)120 (55.8) 84 (39.1)35 (16.3)198 (92.1)78 (36.3)
aSignificant difference between age groups for general association (P,0.001), without statistically significant differences in the rate of splenectomy between individuals
aged 30–44 years and those aged 45–59 years (P.0.05), but with statistically significant difference between the age groups 30–59 years and $60 years (P,0.001).
bSignificant difference between age groups for general association (P,0.001) and a linear association between abdominal distension and age (P,0.01).
cSignificant difference between age groups for general association (P,0.001) and a linear association between work capacity and age (P,0.001).
dSignificant difference between age groups for general association (P,0.05) and a linear association between ascites and age (P,0.01).
Quality of Life and Disability of Schistosomiasis
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rising from 76.2% (32/42) among those aged 30–44 years to
99.0% (100/101) among those aged $60 years (P,0.001). Among
all enrolled subjects, 29.8% (64/215) had complete loss of work
capacity (by age group: 30–44 years, seven cases; 45–59 years,
nine cases; and $60 years, 48 cases), whilst an additional 62.3%
(134/215) of subjects had partial loss of work capacity (by age
group: 30–44 years, 25 cases; 45–59 years, 57 cases; and
$60 years, 52 cases).
Laboratory and ultrasonographic findings
Table 2 shows the results of laboratory and ultrasonography
testing for the study subjects. The mean hemoglobin level was
9.73 g/dl (standard deviation (SD)=2.11 g/dl) among males and
8.83 g/dl (SD=1.68 g/dl) among females. The hemoglobin level
of males was 0.89 g/dl higher than that of females (F value=7.61,
P,0.01). In comparison to normal levels (12–16 g/dl for males,
and 11–15 g/dl for females), the mean hemoglobin of males was
2.27 g/dl lower than average (t=213.04, P,0.001), while the
mean hemoglobin of females was found to be 2.17 g/dl lower than
average (t=29.31, P,0.001). The measured albumin levels for
the study subjects were within normal limits (35–55 g/l; t=1.81,
P=0.072) and there were no significant difference among age
groups in albumin levels (F=2.98, P=0.053). The rates of
circulating HBsAg and anti-HBc antibody positivity were
relatively high in the study cohort, but circulating HBeAg was
observed in only 2.0% (4/198). An inverse association with age
was found for hepatomegaly; the prevalence declined from 46.0%
(17/37) among those aged 30–44 years to 25.8% (25/97) among
those aged $60 years (P,0.05).
The mean inner diameter of the main portal vein was 3.9 mm
(SD=2.9 mm) larger than normal values (10.6–11.1 mm for those
aged $30 years; t=18.92, P,0.001) with no significant difference
among age groups (F=0.32, P=0.726). Hepatic fibrosis was
detected by 96.5% (191/198) of the study subjects, with 6.1% (12/
198) having grade II, and 61.1% (121/198) having grade III
fibrosis. We did not observe a significant difference in the
distribution of hepatic fibrosis severity scores among the different
age groups (P.0.05).
Self-rated quality of life
The results obtained through the EQ-5D plus questionnaire are
summarized in Tables 3 and 4. Almost all the patients with
advanced schistosomiasis japonica complained of some impair-
ment. Moderate impairment was reported by 54.4% (117/205),
extreme impairment by 41.9% (90/215), with the highest
prevalence of reported disability found in the pain or discomfort
dimension (90.7%, 195/215). Impairment in performance of usual
activities is a typical sequela of advanced schistosomiasis and this
form of disability was common in our study cohort (87.9%, 189/
215). Impaired mobility and self-care are considered more extreme
forms of disability, and these were reported fairly frequently by the
advanced schistosomiasis patients (31.6% (68/215) and 30.7%
(66/215) of subjects, respectively). The prevalence of impairment
in each of the six dimensions increased with age (P,0.001), such
that, among subjects $60 years, 100% (101/101) reported
impairment in at least one dimension of performance.
The overall DW derived for all of the subjects with advanced
schistosomiasis japonica was 0.447. Age-specific DWs were 0.378,
0.399 and 0.510 for those aged 30–44 years, 45–59 years and
$60 years, respectively. The difference among the age-specific
DWs was found to be highly significant (ANOVA F=17.77,
P,0.001). Pair-wise comparisons between age groups showed that
Table 2. Physical and ultrasonographic abnormalities in advanced cases of schistosomiasis japonica, stratified by age group (n=198).
(SD) in g/dla
(SD) in g/l
Mean inner diameter
of portal vein (SD)
Hepatic fibrosis (%)Grade I
15.3 (5.6) (n=36)
14.8 (1.9) (n=61)
15.1 (1.6) (n=95)
15.0 (2.9) (n=192)
From the 215 cases with advanced schistosomiasis japonica, 17 observations were excluded owing to missing values.
aAnalysis of variance was performed for means of hemoglobin (F value=8.03, P,0.001). Bonferroni t-test was performed for comparisons between age groups. The mean of hemoglobin of those aged $60 years was significantly
different from those aged 30–44 years and those aged 45–59 years at a level of 5%, and there were no statistical significance between those aged 30–44 years old and those aged 45–59 years at a level of 5%.
bThe mean of inner diameter of portal vein was 3.9 mm (SD=2.9 mm) larger than the normal value (10.6–11.1 mm for those aged $30 years; t=18.92, P,0.001) and there was no significant difference of means between age
groups (F=0.32, P=0.726).
cHepatitis B surface antigen. Significant difference between age groups for general association (P,0.01).
dSpecific antibody to hepatitis B core antigen. Significant difference between age groups for general association (P,0.01).
eHepatitis B antigen appearing during weeks 3 to 6 indicates an acute active infection at the peak infectious period, and means that the patient is infectious. Persistence of this virological marker beyond 10 weeks shows
progression to chronic infection and infectiousness.
fA linear association between hepatomegaly and age (P,0.05).
Quality of Life and Disability of Schistosomiasis
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there were no statistical significance between those aged 30–
44 years and those aged 45–59 years, but the mean DW of those
aged $60 years was significantly higher than those aged 30–
44 years and those aged 45–59 years (Table 5).
The mean DWs of each clinical type of advanced schistosomi-
asis japonica are summarized in Table 6. The mean DW was
0.495 for those with ascites (type I) and 0.360 for those with
megalosplenia (type II). The DW with ascites was 0.135 (95%
confidence interval (CI): 0.093–0.176) higher than for megalos-
plenia (ANOVA F=41.35, P,0.001). There was only one case of
colonic tumoroid proliferation and two cases of dwarfism, their
associated DWs were calculated at 0.400 (Table 6).
In assessing the combined impact of different patient attributes
on the DW score, we developed two multivariable regression
models presented in Tables 7 and 8. In model 1, following stepwise
comparison of nested models, we found that the dimensions of self-
care and cognition could be removed from the model (P.0.05),
while the remaining four dimensions of the EQ-5D plus
questionnaire each remained positively associated with DW
outcomes after adjustment for age, duration of water contact,
P,0.001). The older subjects tended to have a higher DW and
those with a longer duration of contact with cercaria-infested
water (expressed by the ratio of years of contact with infested water
to age) tended to have a lower DW. In model 2, examining other
demographic and clinical attributes, the independent variables,
including sociodemographic data, the number of previous anti-
schistosomal treatments, most reported symptoms, grade of
hepatic fibrosis, hepatomegaly, splenomegaly, hemoglobin, and
positive HBsAg, failed to predict the DW, and hence were
removed from the final model. Splenectomy and a higher albumin
level were negatively associated with DWs (adjusted R2=0.50,
P,0.05); DW was positively associated with the findings of
abdominal distension, abdominal pain, loss of work capacity,
ascites, and positive in HBeAg. After multiple adjustments, a
complete loss of work capacity and the presence of severe ascites
were the strongest predictors of an elevated disability level (highest
DW values) (Tables 7 and 8).
Although the general impact of schistosome infection has been
well reviewed in recent years, there is no special attention paid to
advanced hepatosplenic disease due to schistosomiasis in the GBD
study [15,18,28,29]. As a late-stage of chronic schistosomiasis, the
harms of advanced schistosomiasis are more extensive, intensive
and fatal with a protracted course [10,24,30,31]. Undoubtedly, the
language gap is an important issue explaining the limited
application of the Chinese literature in the updating of the
schistosomiasis burden in the GBD study [32,33]. Moreover, only
few studies attempted to assess the patient’s disability in terms of
overall quality of life [10,24,30,31]. In our preceding investiga-
tions, we concluded that the DW of chronic schistosomiasis
Table 3. Results obtained from EQ-5D plus questionnaire in 215 patients with advanced schistosomiasis japonica, stratified by
degree of health problem.
Dimension Degree of health problem, number (%)Any problem
Mobility 147 (68.4) 64 (29.8)4 (1.9) 68 (31.6)
Self-care 149 (69.3) 58 (27.0) 8 (3.7)66 (30.7)
Usual activities26 (12.1)127 (59.1)62 (28.8) 189 (87.9)
Pain or discomfort20 (9.3) 179 (83.3)16 (7.4) 195 (90.7)
Anxiety or depression41 (19.1) 118 (54.9) 56 (26.1)174 (80.9)
Cognition72 (33.5) 89 (41.4)54 (25.1)143 (66.5)
Any dimension8 (3.7) 117 (54.4) 90 (41.9)207 (96.3)
Table 4. Results obtained from EQ-5D plus questionnaire in patients with advanced schistosomiasis japonica, stratified by age
casesDimension, number (%)
30–44 427 (16.7) 10 (23.8)32 (76.2)33 (78.6)28 (66.7) 16 (38.1)36 (85.7)
45–59 7213 (33.5) 14 (19.4)59 (81.9)65 (90.3)53 (73.6) 40 (55.6)70 (97.2)
$60 10148 (47.5)42 (41.6)98 (97.0)97 (96.0)93 (92.1)87 (86.1)101 (100.0)
Total21568 (31.6)66 (30.7)189 (87.9) 195 (90.7)174 (80.9) 143 (66.5) 207 (96.3)
aSignificant difference between age groups for general association (P,0.001) and a linear association between health outcome and age (P,0.001).
bSignificant difference between age groups for general association (P,0.01) and a linear association between health outcome and age (P,0.01).
cSignificant difference between age groups for general association (P,0.001) and a linear association between health outcome and age (P,0.001).
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japonica (early stage) is considerably higher than that put forth by
expert opinion, which fed into the original GBD study in the 1990s
. The current study clearly shows that advanced schistosomi-
asis japonica is associated with poor self-reported quality of life,
high morbidity, and heavy disability.
As a whole, the overall DW of advanced schistosomiasis
japonica is 0.447, 2.34 times higher than that of chronic cases
and 4.30 times higher than that of the advanced hepatic disease
due to schistosomiasis (DW=0.104) used in the GBD 2004
update, which could be classified as ‘moderate and severe’
disability in the disability classes for the GBD study (see Table 5)
. The multivariate regression models indicate that DW is
positively associated with psychological abnormality, ascites,
impaired work capacity, and co-infection by active hepatitis B
virus (HBeAg positive), whereas splenectomy is a protective factor
for quality of life (see Tables 7 and 8).
Abdominal ultrasonography is considered as a specific and
sensitive examination for diagnosis of advanced schistosomiasis
. In this study, although 88.8% (191/215) of cases had been
subjected to etiologic and symptomatic treatment, more than half
(61.1%; 121/198) were detected with hepatic fibrosis of grade III
characterized by ‘fish-scale’, ‘turtle-back’, or ‘map-like’ pathogno-
monic pattern of ultrasonography in parenchyma of the liver,
obviously different from post-hepatitis cirrhosis . The enlarge-
ment of portal vein is a typical indicator of portal hypertension,
which implies the risk of upper gastrointestinal hemorrhage [25,36].
Referring to normal values obtained from the general population,
the mean of inner diameter of the major portal vein was 3.9 mm
larger than that of the normal value . Anemia is a common
outcome of Schistosoma infection and is further aggravated by the
emergence of hypersplenism in the advanced stage . It is showed
that the mean hemoglobin of advanced cases is far less than that of
the normal population (see Table 2).
The EQ-5D is a valid generic questionnaire that is frequently
used for describing and measuring health-related quality of life
[21,27,37,38]. Our study showed that the impairment rates of
advanced cases in each of six health dimensions of EQ-5D+C
questionnaire are all significantly higher than those of early-stage
chronic cases we had assessed (all P,0.001) (see Tables 3 and 4)
. Moderate or extreme problems were reported by 55.8%
(787/1410) of the chronic cases and by 96.3% (207/215) of the
advanced cases. Severe impairments in each of health dimensions
contributed considerably to the severe disabilities seen in advanced
cases. Activity restriction such as impairment of mobility or self-
care is a severe disability, especially for people living in remote
areas who are primarily engaged in agriculture. Some character-
istics of advanced schistosomiasis – such as long duration, frequent
relapse of ascites, impaired work capacity, and worsening family
economic status – could induce severe psychological problems
[24,30,31]. Our study shows that the reported rates of pain or
discomfort, or anxiety or depression among advanced schistoso-
miasis japonica cases are very high, reaching 90.7% and 80.9%,
respectively, which explains most of the variation of DW in model
1. Impaired usual activities or work capacity were reported in
87.9% or 92.1% of the patients, which could be explained as the
combined effect of anemia, ascites, impaired liver function,
splenomegaly, and other complications.
Ascites means a serious impairment and disability affecting a
person’s ability to work or take part in family and community
activities. In the current study, it has been shown that the DW of
Table 5. Mean disability weights (DWs) of advanced schistosomiasis japonica, stratified by age group.
No. of cases
SD 95% CI
(no. of cases)
(no. of cases)
30–44 42 0.3780.150 0.331–0.4250.05 (1)0.70 (2)
45–59 72 0.399 0.1380.367–0.4320.00 (1) 0.70 (2)
$60101 0.510 0.1510.480–0.540 0.20 (3)1.00 (1)
All 215 0.447 0.1580.426–0.468 0.00 (1) 1.00 (1)
CI, confidence interval; SD, standard deviation.
aAnalysis of variance was performed for mean scores (P,0.001). Bonferroni t-test was performed for comparisons between age groups (a=0.05). The mean DW of those
aged $60 years was significantly different from those aged 30–44 years and those aged 45–59 years, and there were no statistical significance between those aged
30–44 years and those aged 45–59 years.
Table 6. Mean disability weights (DWs) of advanced schistosomiasis japonica, stratified by clinical type.
No. of cases
scoreSD 95% CI
(no. of cases)
(no. of cases)
0.152 0.469–0.5200.05 (1)1.00 (1)
II 74 0.360b
0.1330.329–0.391 0.00 (1) 0.70 (1)
III1 0.400-- 0.40 (1) 0.40(1)
IV2 0.400-- 0.40 (2)0.40 (2)
All 215 0.447 0.1580.426–0.4680.00 (1) 1.00 (1)
CI, confidence interval; SD, standard deviation.
aBased on the major symptoms, advanced schistosomiasis japonica was classified into four clinical types, namely ascites (I), megalosplenia (II), colonic tumoroid
proliferation (III), and dwarfism (IV).
bAnalysis of variance was performed for mean scores. The DW of type I was 0.135 (95% CI: 0.093–0.176) higher than type II (ANOVA F=41.35, P,0.001).
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ascites is 0.135 higher than that of megalosplenia. Compared with
megalosplenia type cases, those suffering from ascites manifest
themselves with lower quality of life, longer duration of disability,
higher reoccurring rates, worse treatment outcomes, and greater
overall family burden . In P.R. China, splenectomy, either
with or without portosystemic anastomosis, is a general surgical
intervention for the treatment of portal hypertension due to
hepatosplenic schistosomiasis, which would help to reduce the risk
of upper gastrointestinal hemorrhage, cure refractory ascites,
recover work capacity, and remove hypersplenism .
P.R. China is one of the most highly endemic areas for chronic
HBV infection in the world . Superimposed HBV infection
has been suggested to play a role in the development of the more
severe form of liver disease among cases with schistosomiasis
[4,40]. There is a general agreement that the association of HBV
and S. japonicum infection are associated with higher morbidity and
mortality compared with either infection alone [40,41]. In this
study, 32.8% of advanced cases were found to be positive for
HBsAg and HbeAg. Positivity was positively related with DW in
advanced schistosomiasis, revealing that there is an active
interaction between HBV and schistosome infection.
The current investigation suffers from several limitations that
are offered for consideration. First, co-morbidity was inevitably
included in this disability assessment. Although hepatitis with
clinical features was excluded after a physical examination, four of
198 cases were detected to be HBeAg positive and kept in the
statistical analysis. However, given this small number, it is unlikely
that exclusion of these four cases would have substantially changed
the overall DW of advanced schistosomiasis japonica. Second, a
control group (absence of advanced schistosomiasis japonica,
matched for age and sex) was not available. The quality of life has
been defined as a person’s subjective sense of wellbeing, derived
from current experience of life as a whole. The use of a VAS, as an
approach of psychometrics, allows visualizing, and hence estimat-
ing the gap between the ‘real’ health and an ideal, hypothetical
stage of health (best imaginable) of the respondents. Hence, the
respondent becomes the control of him- or herself [26,38].
Additionally, it is not always easy to obtain representative
population samples of health states associated with a given
sequelae, particularly those with a low population prevalence
. We had tried to focus our attention on advanced
schistosomiasis japonica, and avoided administering a similar
questionnaire twice on the chronic cases (early stage). However, in
a subsequent study, the current results obtained from patients with
advanced schistosomiasis japonica could be readily compared with
those obtained from chronic cases reported in our previous work
 or from other inpatients without schistosomiasis. Third, the
general health condition of people is likely to deteriorate as they
become older. It should be noted, however that this effect could be
offset by a lower health expectation of the elderly .
We conclude that uncertainty remains while assessing DWs,
particularly for burden estimates due to neglected tropical diseases
[13,43–45]. There is a pressing need to incorporate new findings
from studies as the one reported here into the current revisions
and updates of the GBD study [14,18,44–47]. Re-evaluation and
recalibration of health burden of helminthic parasite infection
would highlight the strong potential of integrated parasite control
that are likely to go hand-in-hand with efforts for poverty
alleviation [13,28,48]. We therefore believe that the results
presented here provide valuable data for a revision of the local,
regional, and global burden of schistosomiasis, as well as for
Table 7. The relationship between the disability weight and
the EQ-5D plus questionnaire in multivariate regression model
error t valuea
Age0.0017 0.0006 2.79 0.006
Duration of contact
with infested watera
Mobility 0.08420.0168 5.00
Usual activities 0.03330.0147 2.27 0.024
Pain or discomfort0.0607 0.0201 3.020.003
Anxiety or depression0.0827 0.0138 5.99
Data derived from 215 patients with advanced schistosomiasis japonica.
aThis parameter was expressed by the ratio of years of contact with cercariae-
infested water to age.
Table 8. The relationship between the disability weight (DW) and related morbidity in multivariate regression model 2.
ParameterCoefficient Standard error t valuea
Intercept 0.35740.0579 6.17
Abdominal distension0.0455 0.02182.08 0.039
Abdominal pain 0.05710.01653.46
Partial loss of work capacity 0.1075 0.0297 3.63
Complete loss of work capacity0.21860.03236.78
Moderate ascites 0.0847 0.03162.68 0.008
Severe ascites0.2532 0.07743.270.001
Positive of HBeAg 0.1235 0.05452.27 0.025
Data are based on 198 patients with advanced schistosomiasis japonica (17 observations had missing values, and hence were omitted from this model).
Quality of Life and Disability of Schistosomiasis
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evidence-based decision making in P.R. China’s national schisto- Download full-text
somiasis control program.
We thank the patients with advanced schistosomiasis japonica for their
willingness to participate in the current study. We gratefully acknowledge
Paul Chinnock and Sara Melville from Cambridge University, and
Minggang Chen from the National Institute of Parasitic Diseases, Chinese
Center for Disease Control and Prevention, for their helpful comments on
earlier drafts of this manuscript.
Conceived and designed the experiments: T-WJ YD X-NZ. Performed the
experiments: T-WJ YD Y-YL J-HZ. Analyzed the data: T-WJ JU YD KY
Y-YL J-HZ CHK X-NZ. Contributed reagents/materials/analysis tools:
T-WJ JU YD KY J-HZ CHK X-NZ. Wrote the paper: T-WJ JU YD CHK
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