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Vaccine 29 (2011) 7801– 7806

Contents lists available at ScienceDirect

Vaccine

jou rn al h om epa ge: www.elsev ier .com/ locate /vacc ine

ospital-based study of the economic burden associated with rotavirus diarrhean eastern China

ui Jina,c, Bei Wanga,c,∗, Zhaoyin Fangb,∗∗, Zhaojun Duanb, Qian Gaoa, Na Liub, Lijie Zhangb,uan Qiand, Sitang Gonge, Qirong Zhuf, Xiaona Sheng, Qingbin Wuh

Department of Epidemiology and Health Statistics, Southeast University, Nanjing 210009, ChinaChinese Center for Disease Control and Prevention, National Institute for Viral Disease Control and Prevention, Viral Gastroenteritis Division, Beijing 100052, ChinaKey Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, ChinaLaboratory of Virology, Beijing Municipal Laboratory of Infection and Immunity, Capital Institute of Pediatrics, Beijing 100020, ChinaGuangzhou Children’s Hospital, Guangzhou 510120, ChinaChildren’s Hospital of Fudan University, Shanghai 200032, ChinaFujian Centers for Disease Control and Prevention, Fuzhou 350001, ChinaThe Children’s Hospital of Soochow University, Suzhou 215003, Jiangsu, China

r t i c l e i n f o

rticle history:eceived 18 March 2011eceived in revised form 22 July 2011ccepted 23 July 2011vailable online 16 August 2011

eywords:otavirusconomic burden

a b s t r a c t

Rotavirus infection is one of the most common causes of severe diarrhea in China. To evaluate the eco-nomic burden associated with rotavirus infection of children in China, we combined data on the diseaseburden of rotavirus-associated costs for samples comprising 832 outpatients and 604 inpatients fromfive seaside cities. The average social costs and direct medical costs for rotavirus-associated admissionswere calculated to be US $61.64 and US $40.73 for outpatients, and US $684.15 and US $559.48 forinpatients, respectively, from October 1, 2006 to December 1, 2007. On average, the private cost rangedfrom US $54.64 for outpatients to US $454.24 for inpatients when children suffered from rotavirus infec-tion. Accordingly, this cost accounted for 35.19–293% of the monthly income of an unskilled or service

iarrheahina

worker. We estimated that the annual number of children with rotavirus diarrhea was 12.10 million.Consequently, the total annual direct cost, total annual social cost, and total annual private cost were US$271.4 million, US $365.0 million, and US $290.0 million, respectively. Furthermore, rotavirus diarrheaaffected children’s behavior and emotions, which had a great influence on the caretakers’ quality of life.These data indicate the potential requirement for a safe and effective rotavirus vaccine to reduce the

ted w

economic burden associa

. Introduction

Rotavirus is one of the most common causes of severe diarrhean children worldwide and is estimated to cause >500,000 deaths,2 million hospitalizations, and >25 million clinic visits each yearmong children aged <5 years [1]. Almost 85% of these deaths occurn low-income countries in Africa and Asia. In addition to pain

nd suffering, these rotavirus-associated events result in increasededical expenses, lost productivity, and other costs to society and

amilies. The global annual burdens of rotavirus gastroenteritis in

∗ Corresponding author at: Department of Epidemiology and Health Statistics,outheast University, Nanjing, China. Tel.: +86 25 83272569.∗∗ Corresponding author.

E-mail addresses: jinhui hld@163.com (H. Jin), wangbeilxb@seu.edu.cnB. Wang), fangzhyn@263.net (Z. Fang), zhaojund@126.com (Z. Duan),qianbjc@263.net (Y. Qian), gongsitang@hotmail.com (S. Gong),rzhu@shmu.edu.cn (Q. Zhu), shenxnfjcdc@yahoo.com.cn (X. Shen),ingbin6638@yahoo.com.cn (Q. Wu).

264-410X/$ – see front matter © 2011 Elsevier Ltd. All rights reserved.oi:10.1016/j.vaccine.2011.07.104

ith rotavirus disease.© 2011 Elsevier Ltd. All rights reserved.

children aged <5 years were estimated to be 111 million, 25 million,and 2 million gastroenteritis episodes requiring home care, clinicvisits, and hospitalizations, respectively [2].

Recent licensed rotavirus vaccines have shown efficacy againstsevere rotavirus diarrhea in clinical trials and have been intro-duced into routine vaccination programs in numerous countries[3]. Although clinically effective rotavirus vaccines have becomeavailable, policy makers still need to make decisions regarding therelative higher cost and benefit of vaccination. It is necessary forthem to consider the economic burden of the disease, the impactof vaccination on health and economic outcomes, and the net costof vaccination compared with the health benefits. Although diar-rhea diseases are highly endemic in China [4,5], despite continuouseconomic progress and radical improvements in infrastructure,there are limited data showing the relative importance of the eco-

nomic burden resulting from rotavirus diarrhea in China [6]. Twoseries studies showed that rotavirus was responsible for ∼50% in2001–2003 [4] and ∼47.8% in 2003–2007 [5] of hospitalizations ofchildren with diarrhea at 6 and 11 sentinel hospitals (SHs) in China,

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espectively. However, to assist the decision makers in consideringhe need for the introduction of a rotavirus vaccine in the future,

ore data are required with consideration of the disease burdennd the economic cost of the disease, and to compare strategies forrevention with a rotavirus vaccine against other new vaccines inhe pipeline and alternative strategies to control diarrhea diseasesn children. It will be hard for pediatricians and policy makers tossess whether or not rotavirus vaccines should be licensed andvailable for disease prevention and improvement of children’sealth without these data.

Therefore, this prospective study was initiated to evaluatehe economic burden of rotavirus gastroenteritis associated withospitalization or outpatient visits of children aged <5 years

n China, including the direct costs of health care services forotavirus-specific diarrhea, indirect costs, and intangible costs tohe individual patients. These data are essential for decision mak-rs regarding the introduction of routine rotavirus vaccination intohe national childhood immunization program.

. Materials and methods

.1. Study population

Data on the disease burden associated with rotavirus infec-ion were estimated from SH surveillance. SH surveillance wasstablished at five hospitals in Beijing (Capital Institute for Pedi-trics), Shanghai (Pediatric Hospital of Fudan University), SuzhouSuzhou’s Children Hospital), Fuzhou (Department of Pediatrics ofujian Provincial Hospital), and Guangzhou (Guangzhou Children’sospital) in China. These hospitals were selected on the basis of

heir geographic location, the experience of their investigators withurveillance, and the ability of local clinicians to collect patient datand test clinical specimens.

From October 2006 through December 2007, we evaluated chil-ren with diarrhea using standardized clinical criteria, obtained

nformation from their parents and collected fresh stool specimensrom the children for rotavirus testing in the SHs. The criteria fornclusion of children in this study were (1) age <5 years, (2) pres-nce of diarrhea at the time of clinical presentation, and (3) diarrheaefined as ≥3 liquid stools in a 24-h period. Both outpatientsnd inpatients were included. Each month, the study investiga-ors received data forms from the patients enrolled at each SH,eviewed the data forms for completeness, periodically monitoredhe surveillance sites to ensure data quality, and retested a part ofhe samples to verify infection with rotavirus.

All stool specimens were stored at −20 ◦C immediately after col-ection in each SH. Rotavirus-positive specimens were identifiedy enzyme-linked immunosorbent assay using a group A rotavirusetection kit (IDEIA Rotavirus; Dako) in accordance with the man-facturer’s instructions.

The study was approved by the Ethics Committee of each partic-pating hospital and written informed consent was obtained fromll individuals.

.2. Data collection

Diarrhea economic expenditure from the WHO criteria wasdopted to design the questionnaire. A case report form with demo-raphic, clinical, and laboratory information was completed, andecal specimens were collected for etiologic diagnosis. Informationor the cost related to patient’s diarrhea episode was obtained from

heir family, who were given a symptom list to fill out that wasntended to document all direct non-medical costs, indirect costsnd intangible costs related to the diarrhea symptoms under thenstructions of a research assistant. The families were encouraged

2011) 7801– 7806

to return the lists directly to the local physicians in the hospital or ina prestamped preaddressed envelope after 10 days. The informa-tion recorded included the length of hospital stay, visits to otherhealth care providers, extra travel costs, additional diapers used,other miscellaneous costs (e.g., food supplements for nonprescrip-tion remedies), time off work required by family members as resultof the child’s illness, and the respective estimated hourly, daily,weekly, and monthly income losses.

2.3. Data analysis

The cost analysis incorporated both monetary and time costswhenever applicable. In this study, rotavirus diarrhea-related costsincluded direct expenditures for direct medical costs and directnon-medical costs, indirect expenditures for time loss by caretakersand intangible expenditures. Indirect costs arising from morbidityand mortality included the value of time lost from work by thecaretakers. Here, indirect costs mainly included the loss of workinghours, which was turned into indirect economic losses based onthe local average wage multiplied by the time lost according to thehuman capital approach.

Costs were estimated from two perspectives, social costs (totaldirect cost + total indirect cost) and private costs (0.5 × direct med-ical cost + direct non-medical cost + total indirect cost). Noticeably,0.5 was the insurance coverage proportion, which represented one-half of the direct medical cost and was charged to the children’sparents’ working units or local Medical Insurance Bureau accord-ing to local health insurance policy. Each of the aforementionedcosts was calculated as follows:

(1) Total direct costs included total SH cost (or direct medical cost)and total family expenditure (or direct non-medical cost): totalSH cost for inpatients = SH inpatient cost + SH outpatient cost;total SH cost for outpatients = SH outpatient cost. All directmedical costs, including drug costs, treatment costs, laboratorytest costs, and other costs, were calculated based on the datafrom the hospital record rooms. All five SHs conducted similarcalculations.

Total family expenditure = family travel costs + family othercosts.Family travel costs = actual cost of bus fare, taxi, or mileageto visit hospitals (SH or non-SH) or other outpatient services(SH or non-SH services) because of the child’s illness.Family other costs = actual cost of co-payment for any otherprovider costs, including cost of non-SH hospital treatment,actual cost for food supplements and nonprescription reme-dies + actual cost for additional day care + actual cost forextra diaper use + actual cost for miscellaneous items.

(2) Total indirect costs were calculated as the total caretaker’s timecost, where the caretaker’s time cost = (hours/days off work)(estimated hour/day salary). Caretakers were asked to recordin the symptom diary all the time taken off from paid employ-ment.

(3) Intangible costs for inpatients were calculated as the loss ofdegree of quality of life, based on a Quality of Life questionnaire,including children’s behavior changes, caretaker’s emotion andbehavior changes, and caretaker’s degree of worry. Based onspecified rating rules (no = 0, sometimes = 1, and often = 2), theindividual variable values were turned into total scores andcompared with one another.

Annual national direct costs and indirect costs were calculatedbased on epidemiological literature [7] and the Chinese HealthStatistics Yearbook (2008).

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.4. Statistical analysis

Data were double entered using Epidata4.0 after logical recti-cation, and categorical comparisons were performed using SPSStatistical software, version 11.5. Little’s MCAR test was used toudge the mechanism for missing data about Not Missing At Ran-om (NMAR). The logarithmic values of missing data for cost were

nput as the logarithmic mean of the existing data from the sameospital. Cost data are reported as the mean value and standardeviation (SD). The costs were classified and calculated by etiolog-

cal groups (rotavirus positive, rotavirus negative and untested),mong which the comparisons were performed using a t-test anal-sis or the Wilcoxon signed-rank test without equal variances andormal distributions.

. Results

From October 2006 through December 2007, a total of 1436hildren (832 outpatients and 604 inpatients) were enrolled inur study. Among them, the complete symptom records amountedo 92%. Missing data included the number of households, travelxpenses, treatment expenses for outpatients, etc. However, Lit-le’s MCAR test showed there was no NMAR in the missing data�2 = 1520.97, P < 0.001).

There were 406 males aged 12.82 ± 8.17 months and 198emales aged 13.38 ± 9.50 months in the inpatients, and 548 malesged 13.88 ± 9.81 months and 284 females aged 14.33 ± 10.91onths in the outpatients. One female child died of severe dehy-

ration in Shanghai hospital.

.1. Average direct and indirect costs

Outpatients infected with rotavirus incurred higher mean costshan those without rotavirus infection, especially in the medicalosts, direct costs and social costs (P < 0.05), although there wereimilar median values for some costs (Table 1). The longest averagearetaker’s time was observed in the rotavirus diarrhea outpatients2.05 days) among the different groups. The average social cost and

rivate cost for rotavirus-associated visits were calculated to be US61.64 and US $54.64 for outpatients, respectively, correspondingo 39.70% and 35.19% of the monthly income of an unskilled orervice worker (US $155.25).

able 1verage direct and indirect costs of the rotavirus diarrhea disease burden in outpatients.

Cost variables RV(+)N = 144

RV(−)N = 97

Direct costd 40.73(48.59) 29.29(40.09)

Direct medical costa 13.99(14.04) 8.86(8.79)

Travel costb 14.85(31.71) 12.24(30.94)

Other costsc 11.89(16.18) 8.19(9.22)

Indirect coste 20.90(20.07) 17.62(19.05)

Delay days 2.05(2.04) 1.86(1.75)

Caregiver’s time costse 20.90(20.07) 17.62(19.05)

Total social costf 61.64(57.36) 46.91(50.64)

Total private costg 54.64(53.94) 42.48(48.73)

ote: Data are shown as mean (SD). Data are normalized in US $. The currency exchange

a Direct medical cost.b Caregiver travel cost + other visitor travel cost.c Total costs of co-payments to other health care providers paid by the family, such as

d a + b + c.e Annual incomes are 34,191 in Beijing, 34,345 in Shanghai, 25,016 in Suzhou, 18,314 in

o the total caretaker time multiplied by the local annual average income from the local Sf Outpatient direct cost + outpatient indirect cost.g 0.5 × outpatient direct medical cost + outpatient direct non-medical cost (travel cost +h Wilcoxon signed-rank test.

2011) 7801– 7806 7803

In contrast, it was found that inpatients with rotavirus infectionhad lower costs than those without rotavirus infection (Table 2),except for travel costs (US $35.83 with rotavirus infection vs US$31.25 without rotavirus infection). Noticeably, for the indirectcosts, rotavirus-infected inpatients had a similar caretaker’s timebut fewer indirect costs than those without rotavirus infection (lat-ter: P = 0.032). The average social cost and direct medical cost forrotavirus-associated admissions were calculated to be US $684.15and US $454.24 for inpatients, respectively, corresponding to 441%and 293% of the monthly income of an unskilled or service worker(US $155.25).

3.2. National annual direct and indirect costs for rotavirusdiarrhea

According to the data from the Chinese Health StatisticsYearbook (2008), there were 66.69 million children aged <5years in China, and their acute diarrhea incidence was 2.0times/person/year [8]. Therefore, the annual number of diar-rhea times was 133 million/year (66.69 million children × 2.0times/person/year [7]). Based on a rotavirus detection rate of 9.1%[7] among children with diarrhea, we estimated that the annualnumber of rotavirus diarrhea times was 12.10 million (133 mil-lion/year × 9.1%) in 2007 in China.

National rotavirus diarrhea outpatient visits in 2007: 163.8million with outpatient visits in 2007, multiplied by an 8.08%admission rate in the pediatric department and then by 85%children aged <5 years, and a 13% diarrhea incidence rate,giving a final rotavirus detection rate of 23.8% in outpatientswith diarrhea [7]. The final result was 3.48 million (163.8 mil-lion × 8.08% × 85% × 13% × 23.8%) children with rotavirus diarrheaat outpatient visits in 2007. Under this assumption, it is estimatedthat for the direct cost, the annual cost related to rotavirus diarrheawas US $141.7 million (total direct cost, US $40.73 × 3,480,000). Thecorresponding estimates of the annual social cost and annual pri-vate cost were US $214.5 million (US $61.64 × 3,480,000) and US$190.1 million (US $54.64 × 3,480,000), respectively.

National rotavirus diarrhea inpatient visits in 2007: 66.69million children aged <5 years in 2007, multiplied by a 3.33%

admission rate among them and then by a 20% acute diarrheaadmission rate, giving a rotavirus diarrhea detection rate of 50%in inpatients with diarrhea [7]. The final result was 220 thou-sand (66.69 million × 3.33% × 20% × 50%) children with rotavirus

UntestedN = 591

RV(+) vs RV(−)

t P

54.04(75.46) −2.335h 0.01915.85(16.56) 0.632 0.52823.17(51.23) 2.040 0.04215.02(28.34) 1.993 0.04719.07(16.17) 0.756 0.451

1.71(1.43) 1.272 0.20419.07(16.17) 0.756 0.45173.11(80.74) 2.048 0.04265.18(78.67) 1.784 0.076

rate is 1 US $ to 7.4 Yuan. RV, rotavirus; N, number of patients.

diapers and medications.

Fuzhou, and 34,328 in Guangzhou. Indirect costs (caregiver’s time costs) are equaltatistical Bureau and divided by 365 days.

other costs) + outpatient indirect cost.

7804 H. Jin et al. / Vaccine 29 (2011) 7801– 7806

Table 2Average direct and indirect costs of the rotavirus diarrhea disease burden in inpatients.

Cost variables RV(+)N = 350

RV(−)N = 154

UntestedN = 100

RV(+) vs RV(−)

t P

Direct costd 589.48(369.32) 618.39(501.70) 578.26(335.93) −0.736 0.462Direct medical costa 459.83(286.69) 484.83(466.96) 427.51(231.80) 1.422 0.156Travel costb 35.83(38.89) 31.25(30.59) 38.58(41.36) −2.829h 0.005Other costsc 93.82(116.12) 102.31(83.41) 112.18(160.29) −0.722 0.471

Indirect coste 94.68(60.50) 132.20(166.34) 118.64(73.20) −2.143h 0.032Delay days 6.36(5.56) 6.58(4.72) 6.36(4.66) −0.411 0.681Caregiver’s time costs 94.68(60.50) 132.20(166.34) 118.64(73.20) −2.143h 0.032

Total social costf 684.15(394.48) 750.59(587.04) 696.90(370.95) −1.283 0.201Total private costg 454.24(265.20) 508.17(381.49) 483.14(273.31) −1.593 0.113

Note: Data are shown as mean (SD). Data are normalized in US $. The currency exchange rate is 1 US $ to 7.4 Yuan. RV, rotavirus; N, number of patients.a Direct medical cost including clinic visits and hospitalization.b Caregiver travel cost + other visitor travel cost.c Total costs of co-payments to other health care providers paid by the family, such as diapers and medications.d Direct medical cost + travel cost + other cost.e Annual incomes are 34,191 in Beijing, 34,345 in Shanghai, 25,016 in Suzhou, 18,314 in Fuzhou, and 34,328 in Guangzhou. Indirect costs (caregiver’s time costs) are equal

to the total caretaker time multiplied by the local annual average income from the local Statistical Bureau and divided by 365 days.f Inpatient direct cost + inpatient indirect cost.

cost +

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g 0.5 × inpatient direct medical cost + inpatient indirect non-medical cost (travel

h Wilcoxon signed-rank test.

iarrhea admitted to hospital in 2007. Under this assumption, its estimated that for the direct cost, the annual cost related tootavirus diarrhea was US $129.7 million (total direct cost, US589.48 × 220,000). The corresponding estimates of the annualocial cost and annual private cost were US $150.5 million (US684.15 × 220,000) and US $99.9 million (US $454.24 × 220,000),

espectively.

Therefore, based on the above national rotavirus diarrhea out-atient and inpatient visits in 2007, we estimated that the totalnnual direct cost, total annual social cost, and total annual pri-

able 3hanges in family members’ behavior and emotions for 311 inpatients.

Variables RV (+)N = 152

RV (−)N = 80

Children behavior changeLessening food intake 138(90.79) 72(90)

Reducing sleeping 113(74.34) 74(92.5)

Crying more than usual 135(88.82) 70(87.5)

Easy irritability 98(64.47) 44(55)

Inactivity 129(84.87) 68(85)

Exhaustion 136(89.47) 70(87.5)

Need extra consolation 126(82.89) 71(88.75)

Caretakers’ behavior affectedWorking 128(84.21) 66(82.5)

Sleeping 144(94.74) 76(95)

Dining 133(87.5) 71(88.75)

Leisure activity 121(79.61) 65(81.25)

House-keeping 133(87.5) 68(85)

Caretakers’ worrying aboutDiarrhea 151(99.34) 80(100)

Vomit 130(85.53) 52(65)

Fever 128(84.21) 66(82.5)

Dehydration 120(78.95) 60(75)

Bellyache 119(78.29) 64(80)

Inappetency 133(87.5) 68(85)

Lose weight 126(82.89) 68(85)

Caretakers’ emotion changeUpset 135(88.82) 78(97.5)

Anxious 152(100) 79(98.75)

Helpless 87(57.24) 34(42.5)

Exhausted 93(61.18) 32(40)

Sad 73(48.03) 23(28.75)

ote: Data are shown as number (percentage).a Fisher’s exact method.

other costs) + inpatient indirect cost.

vate cost were US $271.4 million, US $365.0 million, and US $290.0million, respectively.

3.3. Intangible costs

Inpatient intangible costs were calculated as the loss of quality

of life of inpatients based on the Quality of Life Scale, including thechanges in family members’ behavior and emotions. A total of 311cases were collected from four hospitals, except for Guangzhou,among which 152 cases were rotavirus-positive (Table 3). Regard-

UntestedN = 79

RV(+) vs RV(−)

�2 P

73(92.41) 0.038 0.84554(68.35) 11.054 0.00171(89.87) 0.088 0.76656(70.89) 1.981 0.15966(83.54) 0.001 0.97967(84.81) 0.205 0.65165(82.28) 1.403 0.236

71(89.87) 0.112 0.73878(98.73) – 1a

64(81.01) 0.077 0.78167(84.81) 0.089 0.76571(89.87) 0.283 0.595

79(100) – 1a

57(72.15) 13.062 0.000361(77.22) 0.112 0.73852(65.82) 0.470 0.49359(74.68) 0.092 0.76269(87.34) 0.283 0.59568(86.08) 0.170 0.681

72(91.14) 5.257 0.02276(96.20) – 0.345a

43(54.43) 4.562 0.03348(60.76) 9.466 0.00235(44.30) 8.029 0.005

H. Jin et al. / Vaccine 29 (

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ig. 1. The life quality score based on children with diarrhea and caretakers. *Thereere statistically significant difference between RV-pos and RV-neg (P < 0.015).

ess of whether the inpatients were infected with rotavirus, thehildren showed similar behavior changes, such as lessening foodntake and crying more than usual, although reduced sleepingiffered significantly between those with and without rotavirus

nfection. The children’s diarrhea affected their parents’ sleeping,ining, and housekeeping, followed by working and leisure activity.he syndromes that the parents of children with rotavirus diarrheaorried about were inappetency (87.50%), followed by vomiting,

ever, and weight loss (82.89%), while the parents of children with-ut rotavirus diarrhea worried about inappetency (85.00%) andeight loss (85.00%), followed by fever (82.50%) (Table 3). The emo-

ional changes in the parents of children with rotavirus diarrheaere significantly higher than ones without rotavirus diarrhea, inelpless, exhausted and sad (P < 0.05).

Based on the rating rules (no = 0, sometimes = 1, and often = 2),he individual variable values were turned into total scores. Ashown in Fig. 1, almost all the scores of the children and caretak-rs exceeded 0.5 after the occurrence of diarrhea. Furthermore, thecores for rotavirus infection were obviously higher than the scoresithout rotavirus infection, especially for the caretakers’ behavior

nd emotions (P < 0.015).

. Discussion

The present study has provided insights into the rotavirusisease burden in China by assessing the costs of rotavirus gastroen-eritis, including outpatients and inpatients. The results showedhat the average direct medical cost for outpatients was US $13.99,imilar to a previous finding of US $13.51 [9], while the averageirect medical cost for inpatients was US $459.83, and higher than arevious finding of US $108.96 [9]. In the previous study, Wang et al.9] included county-level hospitals, which are different from city-evel hospitals. We also estimated that the average social costs andrivate costs for rotavirus-associated admissions were US $61.64nd US $54.64 for outpatients, and US $684.15 and US $454.24 fornpatients, corresponding to 39.70% and 35.19% for outpatients,nd 441% and 293% for inpatients of the monthly income of annskilled or service worker. In China, routine immunizations ofhildren are funded by the government through a system of pub-ic health centers. Only a small percentage of children receive theiroutine vaccinations privately. The rationale for approaching theresent study from the social perspective was that, if the cost toHs could be shown to be substantial, it would indicate greatereasibility for the government to consider introducing a rotavirusaccine into the routine immunization schedule in the future.

The results of this study extend the findings of previous research

rom Asian countries [10–15]. The estimated burden of rotavirusisease-associated hospitalization appeared to be similar to that

n Taiwan [10], and lower than those in Hong Kong [11] andapan [15], reflecting differences in the estimations of the direct

2011) 7801– 7806 7805

cost. These studies also demonstrated that rotavirus-infected inpa-tients incurred lower costs than those without rotavirus infection.However, the researchers never considered collecting data fromoutpatient departments or from emergency rooms without subse-quent hospitalization besides the hospitalized patients’ costs. Ourstudy showed that rotavirus-infected outpatients had higher coststhan those without rotavirus infection. This is very meaningful forChina, because Chinese urban children were more willing to accepttreatment in a clinic compared with staying in a hospital [7].

In addition, intangible costs were considered in this study as anessential supplement to the total costs, based on behavior and emo-tion changes in the patients and caretakers. Since hospitalizationsaccount for the largest proportion of costs for rotavirus-associatedillness in the health care system, it might be important to assessthe effects of a rotavirus vaccine on the rates of hospitalization ifmore data become available. Our results showed that children’sdiarrhea caused serious impacts on the children and their caretak-ers (most of the scores were >0.5). More interestingly, the scores forrotavirus infection were obviously higher than the scores withoutrotavirus infection, especially for caretakers’ behavior and emo-tions (P < 0.015).

Based on the present study, we estimated that the annual num-ber of children with rotavirus diarrhea was 12.10 million, with 3.48million visits and 220 thousand hospitalizations, and that the totalannual direct cost, total annual social cost, and total annual pri-vate cost were US $271.4 million, US $365.0 million, and US $290.0million, respectively. Similarly, a report from the United Statessuggested that more than 2.7 million children were infected withrotavirus with about 60 thousand children hospitalized each yearbefore initiation of the rotavirus vaccination programme [16]. Moreimportantly, the health care costs arising from rotavirus infectionreached US $3.52–10 million. In Hong Kong, the cost of rotavirusdiarrhea in hospitals was US $430 million for only 700 million peo-ple [17]. In addition, we found the estimated costs of outpatientswere higher than ones of inpatients, which had been neglected inthe disease burden of rotavirus diarrhea.

However, the present study has potential limitations and wemust be cautious in its interpretation. Usually, it is hard to quantifythe cost per unit of service as well as the value of resources usedin the treatment of diarrhea with sufficient accuracy. For exam-ple, in the calculation of private costs, the insurance coverage ofurban residents was limited and varied in the different cities. Part ofthe undetected fecal infection could be a potential bias for the costestimation of rotavirus diarrhea patients. Fortunately, this studyand other studies [9,17] showed there were no statistically signifi-cant differences for most costs between patients with and withoutrotavirus diarrhea. In addition, although our study indicates thatrotavirus-associated diarrhea adversely affected the health-relatedquality of life of the children and their parents, the conclusion wasbased on a questionnaire, not a real scale. The reason for basingthe description on the change in family members’ behavior andemotions is that many methodological challenges are related tothe estimation of health-related quality of life or QALYs (Quality-Adjusted Life Years) in young children with short-lived and milddiseases. Recently, a Canadian prospective study [18] reported sim-ilar results. Rotavirus diarrhea mainly affected children’s emotionsand pain/discomfort, and the parents paid more attention to thechildren’s activities, pain/discomfort, and anxiety/depression. Fur-thermore, those authors used Health Utilities Indexes and Europeanquality of life, most commonly used instruments of health related-quality of life, to assess the QALYS of the children and parents. TheQALYs lost per 1000 patients were estimated to be 2.2 for chil-

dren and 1.8 for parents. However, considering the incompletepsychologies of children, these questionnaires still need to be vali-dated for infants and children with acute disease [18]. Finally, it isnoteworthy that, although we could provide a rough estimation of

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he annual national cost based on the limited data, it may not beepresentative of the entire population, because these five hospi-als were located in the economically developed cities in easternhina. Therefore, the conclusion could be overestimated becausehese costs were from these high-level hospitals with more chanceo encounter serious patients.

In summary, rotavirus infection imposes a tough economic bur-en in China. Although the introduction of a safe and effectiveotavirus vaccine may not prevent all rotavirus-associated visitsnd hospital admissions, it might result in significant cost reduc-ions for the Chinese government and families.

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