Population-Based Estimate of the Burden of Acute Gastrointestinal Illness in Jiangsu Province, China, 2010–2011

Epidemiol. Infect. (2013), 141, 944–952. f Cambridge University Press 2012 doi:10.1017/S0950268812001331

Population-based estimate of the burden of acute gastrointestinal illness in Jiangsu province, China, 2010–2011

Y. J. ZHOU 1,Y.DAI1,B.J.YUAN1,S.Q.ZHEN1,Z.TANG1,G.L.WU1,Y.WANG1, M. H. ZHOU 1* AND Y. CHEN 2*

1 Institute of Food Safety and Assessment, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of China 2 China National Center for Food Safety Risk Assessment, Beijing, People’s Republic of China

Received 31 October 2011; Final revision 28 April 2012; Accepted 31 May 2012; ﬁrst published online 16 July 2012

SUMMARY To determine the burden and distribution of acute gastrointestinal illness (AGI) in the population, a cross-sectional, monthly face-to-face survey of 10 959 residents was conducted in Jiangsu province between July 2010 and June 2011. The adjusted monthly prevalence was 4.7% with 0.63 AGI episodes/person per year. The prevalence was the highest in children aged <5 years and lowest in persons aged o65 years. A bimodal seasonal distribution was observed with peaks in summer and winter. Regional diﬀerence of AGI prevalence was substantial [lowest 0.5% in Taicang, highest 15.1% in Xinqu (Wuxi prefecture)]. Healthcare was sought by 38.4% of the ill respondents. The use of antibiotics was reported by 65.2% of the ill respondents and 38.9% took antidiarrhoeals. In the multivariable model, gender, education, season, sentinel site and travel were signiﬁcant risk factors of being a case of AGI. These results highlight the substantial burden of AGI and the risk factors associated with AGI in Jiangsu province, China.

Key words: Acute gastrointestinal illness, cross-sectional studies, epidemiology.

INTRODUCTION portant. In the USA about 179 million episodes of AGI occur each year and result in 600 000 hospital- Acute gastrointestinal illness (AGI), usually present- izations and 5000 deaths [3, 4]. Although AGI is ing as diarrhoea and vomiting, is a common and im- usually self-limiting, due to the high annual number portant public health problem worldwide [1]. It is of individuals aﬀected, illness imposes a substantial recognized as one of the leading causes of morbidity economic burden upon the population and healthcare and mortality in developing countries, especially for system [5]. children aged <5 years [2]. While AGI mortality is Although AGI is very common in the community, low in developed countries, AGI morbidity remains cases of AGI tend to be under-reported by traditional im- surveillance, which requires cases to present to the healthcare system. To address this, several * Author for correspondence: Dr Y. Chen, China National Center population-based studies have been conducted in for Food Safety Risk Assessment, 7 Panjiayuan Nanli, Chaoyang developed countries in order to obtain more accurate District, Beijing 100021, People’s Republic of China. (Email: [email protected]) [Y. Chen] estimates of incidence [6–9]. Measuring the actual (Email: [email protected]) [M. H. Zhou] disease burden within the population is important

Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.234, on 27 Sep 2021 at 12:51:08, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0950268812001331 Gastroenteritis in Jiangsu, China 945

Beijing CHINA Study area

Xuzhou

JIANGSU PROVINCE Yellow Sea

Yizheng Taizhou

Liyang Jiangyin Changshu Wuxi Taicang Suzhou

Sampling sites

Fig. 1. Map of the sampling sites in Jiangsu province, China.

for understanding of disease dynamics and guiding their suitability, willingness of local authorities and prevention strategies for gastroenteritis, especially feasibility of completing the studies. The sentinel sites foodborne diseases. were: (i) Xinqu (Wuxi prefecture) (population In China, information on AGI comes mainly 404 573), (ii) Quanshan (Xuzhou prefecture) (popu- from hospital-based or laboratory-based surveillance lation 615 007), (iii) Canglang (Suzhou prefecture) [10, 11]. To adjust hospital-based measurements of (population 325 696), (iv) Hailing (Taizhou prefec- the burden of AGI in China, the Chinese Center for ture) (population 374 267), (v) Jiangyin (population Disease Control and Prevention launched a national 1 420 105), (vi) Changshu (population 1 066 400), population-based study on AGI in 2010. The data (vii) Taicang (population 538 506), (viii) Liyang presented in this paper are from a subsample of par- (population 765 842) and (ix) Yizheng (population ticipants from Jiangsu province. We conducted the 608 092). The sentinel sites represent about 7.9% ﬁrst community survey to estimate the number of of the total Jiangsu permanent resident population cases of AGI in Jiangsu province, China between July (77 250 011) in 2009. 2010 and June 2011. The objectives of the present Each sentinel site was divided into several blocks study were to determine the temporal and demo- in terms of population proportioned distribution. graphic distribution of AGI in the population, inves- In total, we generated 693 blocks from the nine sen- tigate the burden of self-reported AGI, describe tinel sites. Households were randomly selected from healthcare-seeking behaviour for AGI and identify each block and the number of households surveyed risk factors associated with AGI. was proportional to population size. Within each household, one individual with the next birthday was selected to participate in the survey. Up to three at- METHODS tempts were made to contact the selected individual at diﬀerent times of the day to complete the survey. Study design and sample If the selected individual declined or no one lived at A cross-sectional, face-to-face survey was adminis- the residence, the neighbouring house (i.e. the nearest tered from July 2010 to June 2011 within nine residence), was selected as replacement. Proxy purposively selected sentinel sites in Jiangsu province respondents were used for all children aged <12 years (Fig. 1). The sentinel sites were selected based on and for individuals aged 12–18 years when parental

consent was not given to interview them directly. each sentinel site each month. All the data analyses Written and informed consent was obtained from all were performed using the software package SPSS, respondents before the interview. Surveys were ad- version 16.0 (SPSS Inc., USA). ministered in Chinese. Response rate was calculated by dividing the num- A target sample size of 1110 interviews per region ber of completed surveys by the number of house- was calculated to detect a prevalence of 7%, with a holds visited. The monthly prevalence of AGI was 5% level of precision and a 1.5% allowable error. calculated as the number of respondents reporting This translated into a total of 9990 interviews, with an AGI in the 4 weeks prior to the interview divided by overall allowable error of 0.5% (Epi Info v. 3.0.2; the total number of respondents. The incidence rate CDC, USA). To achieve this target, about 93 inter- of AGI/person per year was calculated using the ter- views were completed each month for each sentinel minology and formulae outlined by Rothman & site over a 12-month period. Greenland [7, 12, 13]. These estimates were adjusted for known differ- Data collection ences between the survey sample and the target population by weighting for age and sex using the fifth Household interviews were performed by trained national population census data of Jiangsu province healthcare workers using a standard questionnaire. as the reference population. The x2 test was used for The questionnaire was validated and developed testing the association between demographic factors specifically for the purposes of this study. All and the occurrence of AGI. Mean duration of diar- respondents were asked if they suffered from diarrhoea with respect to different age groups was rhoea, or vomiting in the 4 weeks prior to the inter- compared by analysis of variance (ANOVA). Values view. If the respondent reported diarrhoea or of P<0.05 were considered statistically significant. vomiting, they were asked for more details regarding Multivariable logistic regression was used to estimate symptoms and timing, what they thought had caused odds ratios (ORs) for each of the geographical, their illness, travel to other city/province, the use demographic variables. Weighting was not included of medical consultation and treatment, admission in the logistic regression since the purpose of the to hospital and whether a stool sample was sent analysis was to identify relative ORs among risk fac- for diagnostic purposes, the social and economic im- tors. In multivariable analysis, to determine the vari- pact of illness, and illness in other members of ables in the model we used the forward elimination the household. Additional questions were asked about method. Explanatory variables tested were gender, demographic factors, including the respondent’s sex, age, education, occupation, household size, house- age, information on household size and occupation. hold type, residence, season, sentinel site and travel history. Variables with P<0.05 were included in the Case definition final model. AGI was defined as diarrhoea of o3 loose stools in a 24-h period or significant vomiting with at least one other symptom (abdominal pain/cramps, fever). All RESULTS analyses excluded those persons who considered their Response rate and prevalence of AGI symptoms to be due to non-infectious causes of diarrhoea or vomiting such as Crohn’s disease, irritable The overall response rate was 87% with 10 959 bowel syndrome, ulcerative colitis, excess alcohol, completed interviews. Of the 10 959 persons in- . pregnancy, menstruation, or medication known to cluded in the survey, 490 (4 5%) reported having cause vomiting. A 7-day symptom-free interval was experienced symptoms of gastroenteritis in the pre- defined to distinguish multiple episodes. In case of vious 4 weeks. Of these respondents, 45 were de- multiple episodes, only the most recent episode of clared due to non-infectious causes and included in AGI was used. the non-case category, leaving 445 respondents to be identified as cases. After excluding these respondents, an overall prevalence of AGI in the Data analysis month before interview, adjusted for age and sex, Data were entered into EpiData version 3.1 (EpiData was 4.7% [95% confidence interval (CI) 4.4–5.1]. Association, Denmark) creating one database for This represents an average of 0.63 (95% CI

Table 1. Demographic characteristics and weighted monthly prevalence of reporting acute gastrointestinal illness (AGI) in the 4 weeks prior to interview in Jiangsu province, China, July 2010–June 2011

Proportion Monthly prevalence of AGI Proportion of survey Variable of residents respondents % (95% CI)

Gender Male 50.660.44.5(4.0–5.1) Female 49.439.65.0(4.4–5.5) Age (years)** 0–4 4.11.311.6(8.7–14.6) 5–14 15.52.26.2(5.0–7.3) 15–24 14.04.55.0(3.9–6.1) 25–44 35.632.43.8(3.2–4.4) 45–64 21.943.14.2(3.4–5.1) o65 8.916.53.6(2.4–4.8) Education** Preschool children 5.31.910.5(8.5–12.5) Illiterate 8.55.84.9(2.8–7.0) Primary 32.920.74.9(4.0–5.8) Secondary 46.551.64.0(3.5–4.6) Tertiary 5.412.84.0(3.1–5.0) University 1.47.23.8(2.6–5.0) Occupation** Labourer n.a. 20.03.6(2.8–4.5) Services n.a. 3.13.9(1.9–5.9) Administrator/director n.a. 3.02.4(0.5–4.3) Oﬃce staﬀ n.a. 6.04.2(2.8–5.6) Professional n.a. 5.95.3(3.5–7.1) Farmer n.a. 27.34.2(3.3–5.1) Self-employed n.a. 7.23.6(2.2–5.0) Retired n.a. 15.03.6(2.4–4.8) Unemployed n.a. 4.35.4(3.3–7.4) Too young to work n.a. 5.37.0(6.1–8.0) (including students) Others n.a. 2.82.9(1.0–4.8) Household size (no. of persons) 1–2 29.422.03.9(2.9–4.8) o370.678.04.9(4.5–5.3) Household type** No residents <18 years n.a. 50.13.8(3.3–4.4) At least one n.a. 49.95.3(4.8–5.8) resident <18 years Residence Urban 42.341.04.8(4.2–5.5) Rural 57.759.04.7(4.2–5.2) Travel* Yes n.a. 3.66.8(4.4–9.2) No n.a. 96.44.7(4.3–5.1)

CI, Conﬁdence interval; n.a., not available. * P<0.05, ** P<0.01.

0.62–0.64) occurrences of AGI/person per year. Distribution A total of 22 people still had symptoms of AGI at the time of interview, yielding a point prevalence of The demographic distribution of residents and survey 0.2%. respondents are shown in Table 1. In general, survey

14 Symptoms and severity Female 12 . Male Of the 445 cases who reported illness, 61 (13 7%) re- 10 spondents experienced both diarrhoea and vomiting. 8 Of the 439 cases with diarrhoea, four (0.9%) had . 6 bloody diarrhoea. Of the 445 cases, 17 (3 8%) cases reported more than one episode during the 28-day

Prevalence (%) Prevalence 4 period. 2 Overall the mean duration of diarrhoea was 0 . . 0–4 5–14 15–24 25–44 45–64 ኑ65 1 8 days (median 1 5 days). Children in the 0–4 years Age group (years) age group had a significantly longer mean duration of diarrhoea (3.4 days) than other age groups (P 0.01, Fig. 2. Monthly prevalence of acute gastrointestinal illness < by age and gender, in the 4 weeks prior to interview in ANOVA). On the worst day of symptoms, cases re- Jiangsu province, China, July 2010–June 2011. ported diarrhoea an average of 4.1 times (range 3–15 times) and vomiting an average of 2.7 times (range respondents were older, more educated and more 1–10 times). Twenty-three cases indicated that some- likely to be male than residents. Age was inversely one else within the household had similar symptoms associated with AGI prevalence. Children aged 0–4 at the same time. years had the highest prevalence (11.6%) of AGI and . the lowest prevalence (3 6%) was observed in the Suspected cause of illness o65 years age group. There were significant differences in AGI prevalence by education and occupation Cases were asked to report what they believed was the . status. Respondents living in a household with at least cause of their illness. Over half (57 1%) of those with AGI suspected their illness had been caused by con- one person aged <18 years were significantly more likely to have experienced AGI (5.3% vs.3.8%, suming contaminated food. Of those who suspected P 0.01, x2 test). Percentage of respondents reporting that their illness was due to eating contaminated food, < . AGI was significantly higher in those who had trav- 60 2% thought it was food consumed at home. elled (6.8%) than in those who had not (4.7%) (P<0.05, x2 test). In general, women had a higher Healthcare-seeking behaviour AGI prevalence than men (Fig. 2). Of the re- Healthcare-seeking behaviour of cases, medicines spondents, 78% households had o3 household used by cases and the source of the medicine are re- members, and AGI prevalence was higher (4.9%) in ported in Table 3. A physician was visited by 38.4% these larger households. There was no statistically of cases. Healthcare-seeking behaviour varied by age; significant difference in AGI prevalence between the the prevalence of seeking healthcare for AGI was urban residents and rural residents. highest (60.0%) in children aged <15 years. Of those The prevalence of AGI varied by sentinel sites, with who saw a doctor, 39.2% reported providing a stool the highest in Xinqu (Wuxi prefecture) (15.1%), and sample for laboratory testing. the lowest in Taicang (0.5%)(P<0.01, x2 test). There In total, 397 (89.2%) cases took medications to was a significant seasonal difference in AGI preva- treat or relieve symptoms for their illness. Sixty-five lence: summer had the highest prevalence, followed percent (65.2%) of those with acute gastroenteritis by winter (P 0.01, x2 test) (Fig. 3). < were estimated to have taken antibiotics, while 38.9% reported taking antidiarrhoeals. Of those who took Multivariable analysis medicine, only 42.8% reported that the medication In the final multivariable regression model, gender, was prescribed by a doctor, 43.1% obtained medicine education, season, sentinel site and travel were sig- from the family medicine chest, 21.7% purchased nificantly (P<0.01) associated with the occurrence of medicine from a pharmacy without prescription. AGI (Table 2). The odds of AGI was 1.9 times higher Antibiotics were taken by 77.2% of those who took in summer than in autumn. Respondents who lived in medicine from the family medicine chest. However, 86 Xinqu (Wuxi prefecture) (P<0.01) or those who had (21.7%) cases were estimated to have taken more travelled to other city/province were also significantly than one type of medication to treat or relieve symp- associated with reporting AGI. toms.

4 Prevalence (%) Prevalence

0 July Aug. Sep. Oct. Nov. Dec. Jan. Feb. Mar. Apr. May June Month Fig. 3. Monthly prevalence of acute gastrointestinal illness by study month in the 4 weeks prior to interview in Jiangsu province, China, July 2010–June 2011.

Impact on work and school in Ireland with 0.6 AGI episodes each year where a similar definition has been used [14]. Other retro- In total, 9.8% of those with AGI took time off work spective studies showed different rates: 1.4/person or school. The mean number of days taken off work per year in the USA [4], 1.4 in Denmark [8], and 1.3in was 2.0 days (range 1–5 days). Three children were Canada [13]. The observed difference could be in the absent from school as a result of their illness. The method of measurement or may be due to different mean and median numbers of days of school missed exposures based on lifestyle, possibly food or water were 1.4 and 1.0, respectively. preparation practices [9]. Recently, Majowicz et al. [15] proposed a standard symptom-based case defi- Standard case definition comparison nition for AGI, using this uniform definition is critical for facilitating accurate inter-country com- A summary of this study’s results using the sug- parisons and global burden-of-disease estimates. gested symptom-based case definition are outlined Using this symptom-based standard definition, we in Table 4. obtained similar results compared to those using the chosen definition in our primary analysis. We thus reported the suggested minimum set of results in this DISCUSSION article, in order to facilitate international compari- This study of AGI performed in the community in sons. Jiangsu province, China provides the demographic The estimates of disease burden in the community determinants and burden of AGI. Overall, AGI rep- differ substantially between retrospective and pro- resented a significant burden in Jiangsu province, we spective study designs even when using identical case estimated an overall adjusted monthly prevalence of definitions. In a UK study, the retrospective survey 4.7% and an average of 0.63 AGI episodes/person estimated disease incidence at 0.55 episodes/person per year. If extrapolated to the population, this per year and the prospective component at 0.19 [16]. amounts to over 3.6 million cases of AGI every month At the time this discrepancy was attributed to recall in Jiangsu, confirming that the magnitude of AGI in bias. One example of this is telescoping, with re- Jiangsu province is considerable. spondents remembering illness events as having oc- Comparison of AGI rates between countries is curred more recently than they actually did. But in complicated by the use of different case definitions other studies [6, 17, 18], it is reported that the shorter and methods in different studies. In this survey, a 7-day recall period yields significantly greater annual strict definition was used: diarrhoea of o3 loose estimates compared to the longer 15-day or 30-day stools in a 24-h period or vomiting with at least one recall periods, which is contrary to telescoping, other symptom (abdominal pain/cramps, fever). and the true burden of disease is underestimated. The estimated rate of AGI in Jiangsu province is Therefore, further investigation and research on this comparable to a similar retrospective study conducted potential bias is necessary.

Table 2. Final multivariable model of risk factors Table 3. Frequency of hospital consultation and associated with acute gastrointestinal illness in the medicine use by cases of acute gastrointestinal illness 4 weeks prior to interview in Jiangsu province, China, (n=445) in the 4 weeks prior to interview in Jiangsu July 2010–June 2011 province, China, July 2010–June 2011

OR (95% CI) P value No. of Variable cases (%) Gender <0.01 Male Ref. Ref. Ref. Sought medical care (n=445) Female 1.43 (1.17–1.75) <0.01 Yes 171 (38.4) . Education <0.01 No 274 (61 6) Preschool children 3.53 (2.18–5.71) <0.01 Submitted a stool sample stool (n=171) Illiterate 1.66 (1.11–2.50) <0.05 Yes 67 (39.2) Primary 1.10 (0.85–1.43) 0.45 No 104 (60.8) Secondary Ref. Ref. Ref. Took medicine (n 445) . . . . = Tertiary 0 85 (0 62–1 17) 0 31 Yes 397 (89.2) . . . . University 0 98 (0 66–1 45) 0 90 No 48 (10.8) . Season <0 01 Type of medicine (n 397)* . . . . = Summer 1 92 (1 49–2 49) <0 01 Antibiotics 290 (73.0) Autumn Ref. Ref. Ref. Antidiarrhoeals 173 (43.6) . . . . Winter 0 81 (0 60–1 10) 0 18 Analgesics 8 (2.0) . . . . Spring 0 82 (0 61–1 11) 0 20 Antipyretics 5 (1.3) Sentinel site <0.01 Antacids 2 (0.5) Wuxi 3.13 (2.31–4.26) <0.01 Other 5 (1.3) Xuzhou 0.43 (0.27–0.69) <0.01 Unknown 9 (2.3) . . . . Suzhou 0 30 (0 18–0 49) <0 01 Location of medicine purchase (n 397)* . . . . = Taizhou 0 77 (0 52–1 14) 0 19 Family medicine chest 171 (43.1) Jiangyin Ref. Ref. Ref. Hospitals with prescription 170 (42.8) . . . . Changshu 0 59 (0 39–0 90) <0 05 Pharmacy 86 (21.7) . . . . Taicang 0 14 (0 07–0 28) <0 01 Other 7 (1.8) Liyang 1.11 (0.77–1.59) 0.57 . . . . Yizheng 0 32 (0 19–0 54) <0 01 * Because some people took more than one type of medi- Travel <0.01 cation and some cases visited more than one location, the Yes 1.80 (1.21–2.69) <0.01 total percentage may exceeds 100%. No Ref. Ref. Ref. which may be more common, tending to peak during OR, Odds ratio; CI, Confidence interval. the winter months [26]. Moreover, seasonality of AGI was observed in this study; a bimodal distribution The gender distribution of AGI in our study is was observed, with peaks in September and March. In similar to that found in other reports [7, 9]. The higher Jiangsu province, Xinqu (Wuxi prefecture) had the rate of AGI in females may be due to differences in highest level of AGI. It is probable that the highly routes of exposure such as food preparation in the polluted Tai lake, which is the source of drinking kitchen. We observed significantly higher rates of water in Wuxi, contributes to this increased risk of AGI in children aged <5 years, and lower rates in AGI in Wuxi prefecture. adults aged o65 years, which is consistent with other In the present study, we found that AGI prevalence studies [13, 19, 20]. The reasons for this increase in decreased with increasing levels of education. Those children may be due to the naive immune system in that had not yet reached school age and the illiterate children of younger ages, and children aged <5 years were more likely to report illness. This may be due to being susceptible to rotavirus-infection diarrhoea higher AGI rates in children and different lifestyle [21–23]. Although the older group has the lowest AGI factors such as health habits, eating-out patterns or rate, they may suffer from higher morbidity and awareness of hygienic conditions. In the multivariable mortality when infected. In other studies, distribution model, respondents who had travelled were 1.8 times of AGI is reported to have a bimodal distribution more likely to report AGI than those who had not, [6, 13], with bacterial gastroenteritis tending to peak which is similar to other reported studies [14]. The in the summer [24, 25], while viral gastroenteritis, reason for this increase in people who had travelled

Table 4. Descriptive statistics of acute gastrointestinal illness following the proposed standard case deﬁnition of gastrointestinal illness in Jiangsu province, China, July 2010–June 2011

Annual incidence per person-year (95% CI) 0.63 (0.63–0.64) Annual incidence per person-year in males 0.61 Annual incidence per person-year in females 0.66 Mean age of cases (years) 46 Mean duration of illness (days)* 1.85 Cases with bloody diarrhoea (%) 0.89 Cases who sought medical care (%) 38.26 Cases submitting a stool sample 14.99 for testing (%) Cases with respiratory symptoms (%)# — Cases with symptoms still ongoing at 4.92 time of at interview (%)

CI, Conﬁdence interval. * Information on the duration of vomiting was not collected in the survey. Calculated by averaging the duration of illness among those had diarrhoea, regardless of whether the illness was still ongoing at the time of data collection. # Data not collected. Survey respondents were not asked about respiratory symptoms.

may be due to a greater opportunity of exposure to laboratory confirmation. It would be useful to carry gastrointestinal pathogens. out further work to measure the incidence of specific Healthcare was sought by 38.4% of respondents laboratory-confirmed infections in the community. with AGI. As disclosed in the present work, young The advantage of this study is that we used a face- children visited health facilities more often than per- to-face interview, which may reach the potential sons aged o15 years, which is in agreement with a participants who do not have access to a phone. A previous study in France [27]. The level of medicine high response rate of 87% was achieved compared to use (89.2%) found in this study was higher than that other telephone surveys looking at the same issues of the other countries, e.g. Ireland (47.0%) [14], [14, 27, 31]. Canada (63.9%) [7], France (76.3%) [27]. Because This is the first population-based study presenting more persons were treated with antibiotics than the incidence of community-acquired AGI in Jiangsu submitted a stool specimen and most episodes of province, China over a complete year, which provides gastroenteritis do not require antibiotic therapy [28], much needed information for planning control mea- it is clear that the results presented here may sures for gastroenteritis in an understudied and un- suggest possible over-prescribing of antibiotics. This is derreported part of the world. It demonstrates the of particular concern, especially in view of the increase substantial health burden of AGI in the region, the in antibiotic-resistant pathogens and the potential distribution of AGI estimates and the associations complications originating from taking antibiotics between AGI and demographic distribution. Further [29, 30]. In the present study, self-medication appears research is needed to estimate the proportion caused to be common, as less than half of the medication used by foodborne and other sources, and to identify types was prescribed by a doctor. The factors affecting of foods associated with AGI. the prescription and use of antibiotics require further research. ACKNOWLEDGEMENTS Limitations of this study are those common to other retrospective studies [6, 9, 18], it is possible that The authors thank the participating Regional Centers due to recall bias that retrospective studies may result for Disease Control and Prevention in Jiangsu prov- in over- or under-estimates of the true incidence ince, including the Wuxi, Xuzhou, Suzhou, Taizhou, of AGI. Another potential limitation of the study Jiangyin, Changshu, Taicang, Liyang and Yizheng may be that the AGI cases were defined based on Centers, for their support in the data collection. The self-reported symptoms without pathogen-specific authors also thank Dr Zumin Shi (University of

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