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Epidemiology & Disease Burden : Asian Rotavirus
Surveillance NetworkTony Nelson
Department of PaediatricsThe Chinese University of Hong Kong
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1st ARSN MeetingBangkok Feb 1999
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Messages
• Rotavirus vaccine now available in US• Decision makers will need disease
burden data• What data do we have?• What data do we need?
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Are decision-makers aware of rotavirus disease burden ?
• Diarrhoea recognised as leading cause of morbidity and mortality BUT most doctors & policy makers often don’t appreciate importance of rotavirus
• Aetiology does not usually alter management –thus diagnosis of rotavirus often not made
• Policy makers may think improving water and sanitation may prevent rotavirus - incorrect
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WHO’s Generic Protocol
Hospital-based surveillanceSimple data collectionOutcomes:
rates of diarrhoeahospitalisationsand/or % RV positive
Strain characterisation
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Back home ...
Planning surveillance & cost study
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• Reinvigorating the competition– Big pharma (GSK, Merck)– Local producers (China/India)
• Parallel testing in both developed & developing countries
• Increasing awareness of the potential for rotavirus vaccines
Glass. Lancet 2004;363:1547
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Will intussusception occur with other rotavirus vaccines?
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Hong Kong : Intussusception (Jul 1997-Jun 2003) & Rotavirus (Apr 2001-Mar 2003)
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The Asian Rotavirus Surveillance Network: Phase 1
ChinaHong KongIndonesiaMalaysiaMyanmarSouth KoreaTaiwanThailandVietnamGAVI eligible
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2nd Workshop of ARSNBangkok, May 2002
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Publication of 1st year results
• August 2001 to July 2002• South Korea started in June 2002• 33 hospital in 8 countries• Data of 16,000 hospitalisations for
diarrhoea during 1st year• Data collation by CDC
Bresee. Emerg Infect Dis. 2004;10:988
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Stools Tested
• 11,498 stools from 16,1173 patients = 71%
• 45% of tested specimens positive for rotavirus
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Rates of Rotavirus DetectionAug 2001–Jul 2002
Sites Tested RV+ % RangeChina 2079 44 24-65Taiwan 1532 49 43–53Hong Kong 2986 28 18–35Vietnam 1570 59 47–67Myanmar 388 53 53Thailand 992 44 38–49Malaysia 1374 57 52–59Indonesia 577 52 47–57
Overall 11,498 45 18–67
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Figure 1. Seasonality of rotavirus in member countries of theAsian Rotavirus Surveillance Network
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Malaysia
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Vie tnam
Indonesia
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Spring 2003 Meeting
of the
Asian Rotavirus Surveillance Network
ASIAN ROTAVIRUS SURVEILLANCENETWORK
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Workshop of the Members of the Asian Rotavirus Surveillance Network
Manila, Philippines21-22 October 2003
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Launch of Phase 2 of ARSNChina (8)Indonesia (5)Myanmar (1)Thailand (2)
GAVI eligible
Bangladesh (2)Cambodia (1)Kyrgyzstan (2)Lao PDR (1)Mongolia (2)Nepal (1)Pakistan (2)Philippines (7)Sri Lanka (1)Uzbekistan (2)
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Sep 2005• Disease Burden :
Taiwan, Korea, Hong Kong, Malaysia, Thailand, China, Japan, Myanmar, India, Vietnam
• Economic Burden : HK & Japan, cost-effectiveness projections for Asia
• Vaccine updates : RIX4414, Pentavalent & Hexavalent human-bovine, Indian neonatal strains
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Taiwan RV disease burden
• Enrolled 2600• RV+ rate 43%• Bacteria 11%• Adenovirus 2.5%• RV + other 3.9% RV+RV+
RVRV--
Chen et al. JID. 2005;192:S44-48
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Kim et al. JID. 2005;192:S49-56
Korea RV disease burdenRV+ rate (4106 children)• INPATIENTS = 73%• OUTPATIENTS = 18%Incidence of hospitalisation for RV:
11.6 per 1000 children < 5yrsOverall incidence of RV:
57 per 1000 children < 5yrs
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Hong Kong RV disease burden
RV+ rate = 30%Incidence of hospitalisation for RV• 8.8 per 1000 children < 5yrs• 4x previous “passive” estimate
1 in 24cumulative risk of hospitalisation
for RV by age 5 yearsNelson et al. JID. 2005;192:S71-79
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Malaysia RV disease burden
• Ministry of Health Data• ~14,000 GE admissions• RV+ rate for hospitalised RV = 50%
Hsu et al. JID. 2005;192:S80-86
1 in 61cumulative risk of hospitalisation
for RV by age 5 years
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Thailand RV disease burden
• Enrolled 4057• RV+ rate 43%
• Community RV+ rate 12%
Jiraphongsa et al. JID. 2005;192:S87-93
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China RV Disease Burden
• 6 sentinel hospitals• n= 3149• RV+ rate 50%
Fang ZY et al. JID. 2005;192:S94-99
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Japan RV disease burden
• 3 sentinel hospitals (n=443)• RV+ rate = 58%Incidence of hospitalisation for RV• ~ 15 per 1000 children < 5yrs
1 in 15cumulative risk of hospitalisation
for RV by age 5 yearsNakagomi T et al. JID. 2005;192:S106-110
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Myanmar RV disease burden
• Diarrhea 18% of hospitalisations• n=1736 • RV+ rate = 53%
Moe K et al. JID. 2005;192:S111-113
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Vietnam RV disease burden
• n=5809 (2000-2003)• RV+ rate = 55%
Nguyen Van Man et al. JID. 2005;192:S127-132
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India RV disease burden
• Passive surveillance study• 6 hospitals (~65% admissions)• RV+ rate = 24%
Incidence of hospitalisation for RV• 3.4 per 1000 children < 5yrs
Bahl R et al. JID. 2005;192:S114-119
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Asian Rotavirus Disease BurdenSites % RV+Korea 73 (180/249)Japan 58 (256/443)Vietnam 55 (3195/5809)Myanmar 53 (920/1736) China 50 (1590/3149) Taiwan 47 (1118/2600)Thailand 43 (1745/4057) Hong Kong 30 (1760/5881)
Overall 45
Data from JID. 2005;192:
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Asian RV Disease Burden
“Much higher than anticipated”
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Variation in peak age of onset
GDP/capita
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Asian Rotavirus Serotypes (%)
Sites n G1 G2 G3 G4 G9 M/O/U
China 470 14 5 67 <1 5 10Hong Kong 300 49 15 23 4 5 5India 137 23 13 6 - 15 42Korea 203 25 13 19 2 39 2Taiwan 300 31 10 9 4 37 9Thailand 838 1 17 <1 5 55 22Vietnam 499 47 15 - 10 22 6
Data from JID. 2005;192:
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Economic Burden of Rotavirus and Potential Cost-effectiveness of
Vaccination in Asia
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Economic Burden in Hong Kong
• Sub-sample of 471 children admitted with diarrhoea
• Hospital costs & Outpatient costs– Government costs– Family costs
• Out of pocket expenses• Indirect costs
Nelson et al. JID. 2005;192:S64-70
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Cost estimations for Hong Kong
• Total social cost USD 4.3 M• Total direct medical cost USD 4 M • 4 x higher than previous estimate
• Government cost ~ USD 1800• Family cost USD 120
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Preliminary cost-effectiveness analysis for Hong Kong
• High disease burden (1 in 24)• High cost of hospital admission (USD1800)• Depending on vaccine price, a universal
immunization programme for rotavirus could be cost saving for government
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Japan Economic Burden of rotavirus-associated admissions
• Direct medical cost USD 1236• Extrapolated total direct medical
cost USD 96 M
Nakagomi T et al. JID. 2005;192:S106-110
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Projected cost-effectiveness RV vaccines in Asia
• In Asia by 5 years of age– 171,000 will die (109,000)– 1.9 M hospitalisations (1.4M)– 13.5 M outpatient visits (7.7M)
• Medical cost $191 M• Cost-effectiveness depends on
income level, vaccine price & standard used
Podewils L et al. JID. 2005;192:S133-145
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Prospects for the early introduction of rotavirus
vaccines into universal programmes in Asia ?
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What we have ...• Good local disease burden data from a
mix of developed & developing countries in the ARSN
• More data on its way• Evidence of a safe & effective vaccines
including data from regional trials• Some information on economic burden
and cost effectiveness
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What Asia still needs ...
• More LOCAL data on cost-effectivenss• More support of local opinion leaders• More high-level regional support
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Thank you
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Acknowledgements• 1st Phase Members of ARSN
– Roger Glass, Joe Bresee, Umesh Parashar, Zhao-Yin Fang, Bei Wang, John Tam, Yati Soenarto, SiswantoAgus Wilopo, Paul Kilgore, Jung Soo Kim, Wong SweeLan, Chan Lee Gaik, Kyaw Moe, Kow-Tong Chen, Chuleeporn Jiraphongsa, Yaowapa Pongsuwanna, Nguyen Van Man, Phan Van Tu, Le Thi Luan, Erik Hummelman.
• Funding support – World Health Organization– Children’s Vaccine Program at PATH– CDC Foundation– GlaxoSmithKline– Merck
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India epidemiological profile
• Data from 9 studies
• RV+ rate = 23%
• Marked diversity of strains circulating
Kang G et al. JID. 2005;192:S120-126
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