New Zealand Perspective on Rotavirus Disease

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New Zealand Perspective on Rotavirus Disease

• Keith Grimwood
• Wellington School of Medicine
• Health Sciences

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Duality of interest

• Consultancies, Advisory, Data Monitoring Boards
• MoH, NIH NIAID, HRC
• Viral Sexually Transmitted Infection Education
  Foundation
• Australian CF Association
• CF Association of NZ
• GlaxoSmithKline
• Merck Sharp Dohme
• Wyeth Pharmaceuticals

• Funded grants
• NHMRC, WHO, HRC
• Lottery Grants Board
• CHRF, WMRF, NZCFA
• ESR
• GlaxoSmithKline
• Merck Sharp Dohme

rotavirus-related
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NZ Perspective

• Global disease burden
• Case for immunisation
• NZ disease burden
• Serotype distribution
• Economic analysis
• Surveillance/Questions

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Global estimates of RV disease burden

• More than 600,000 children under 5yrs of age die
  annually
• Rotaviruses account for
• 8 (2.522) of all cases of diarrhoea in the
  community
• 28 of clinic visits
• 39 of hospitalisations

Vaccine 1999 17 2207 Emerg Infect Dis 2006 12
304
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Estimated global prevalence of RV disease
Event
Risk of Particular Event
1 205
610,000 deaths
1 50
2.4 million hospitalisations
1 5
24 million clinic visits
1 1
114 million domiciliary episodes
Emerg Infect Dis 2006 12 304
Lancet 2006 368 323
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Case for immunisation

• More than 90 of children by 3-years of age have
  had gt 1 RV infection
• independent of
• nationality or ethnicity
• hygiene level, sanitation, access to clean water
• Vaccines are seen as the only public health
  measure capable of controlling RV disease
• safety
• efficacy
• disease burden
• RV serotypes
• anticipated health benefits
• economic analyses

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Gastro disease burden in NZ

• 2500 NZ children lt 3yrs of age are hospitalised
  annually with gastroenteritis
• 3rd behind asthma and respiratory infections
• RV was 1st reported in NZ infants in 1975
• Dunedin 2/3 infants
• Dunedin 2/4 children
• Palmerston North 2/5 children

NZMJ 197581494 197582176
197683 22
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RV disease burden in NZ

• Small hospital-based studies
• Auckland
• 60 children (lt 6yrs) between June and July, 1977
• 43/60 (72) had RV in their stools
• Palmerston North
• 39 children (3-38 mths) between June and Sept,
  1978
• 26/39 (67) were RVve

J Infection 19791339 NZMJ 19799077
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RV disease burden in NZ

• Dunedin-based study
• 497 children, between June 1977 and Sept 1980
• 252 from Dunedin, 245 from other NZ centres
• RVs were detected in 45 of stool samples by EIA
• in some months up to 75 were ve for RV
• 98 were lt 5years of age

NZMJ 19829567
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RV disease burden in NZ

• Retrospective multicentre study
• Starship, Middlemore, Waikato and CHCH
• linked hospital admission and laboratory data
• children aged lt 5 yrs with acute diarrhoea for
  1994-96
• RVs accounted for 46.5 to 88.3 of the total
  ves
• Estimated that 35 of admissions were RV-related
• Mean (SD) LOS was 1.5 (2.35) days
• Between 1984-1993 there were 18 diarrhoea-related
  deaths

PIDJ 199918614
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RV disease burden in NZ

• Prospective hospital-based multicentre study
• Starship, Middlemore, Waikato, Wellington/Kenepuru
  , Hutt, CHCH and Dunedin
• children aged lt 3 yrs with acute diarrhoea (May
  1998 to April 2000)
• Overall, 1138/2019 (56) provided stools for
  testing
• centre range 38-88
• Stools were more often collected from
• infants lt 12mths of age
• non-Pacific ethnicity
• residing in less deprived neighbourhoods
• staying more than 48 hrs in hospital
• during the winter/spring mths
• centres outside Auckland

JPCH 200642 198-205
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RV disease burden in NZ

• RVs were detected in 43 of samples
• Mean (SD) LOS was 1.9 (1.9) days
• RV detection varied by age and season (not SES or
  ethnicity)
• peak detection rates 2nd yr of life
• winter/spring predominance
• 83 of cases
• monthly peaks in July to September
• 57-71
• Dehydration for RV vs non-RV cases 51 vs 37

JPCH 200642 198-205
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Age distribution of children lt 3yrs with acute
diarrhoea

• Ages
• 0-5 15
• 6-11 32
• 12-17 23
• 18-23 14
• 24-29 9
• 30-35 6

JPCH 200642 198-205
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Standardised age and ethniciy estimates for
annual RV hospitalisation in NZ children under
age 3yrs, 1998-2000
per 100,000 age-adjusted children
JPCH 200642 198-205
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Annual incidence of hospitalisation for RV
gastroenteritis in children under 5yrs of age
from selected industrialised countries
Emerg Infect Dis 2003 9 565 PIDJ 2006 25
S7 J Paediatr Child Health 2006 42 198
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RV disease burden in NZ

• Most recent study of RV-associated
  hospitalisation might have
  under-estimated the true burden of disease
• systematic under-sampling of older children with
  short LOS
• sensitivity of EIA method is only 90
• miscoding of hospitalisations was not taken into
  account
• Visits to the ED or GPs were not included
• No attempt was made to estimate nosocomial RV
  infections

Arch Virol 1995 140 1225
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National estimates of RV disease burden

• Assumptions
• ELISA-based methods under-estimate RV infection
  by 10
• for each hospitalisation, 8 children visit
  their doctor
• for each physician visit, 4 are treated at home

Arch Virol 1995 140 1225 Acta Paediatr
Suppl 1999 426 24 PIDJ 1987 6 1270 Arch
Pediatr Adolesc Med 2004 154 586
BMJ 1999 318 1046
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Estimated annual RV disease burden in NZ
Event
Risk of Particular Event
1 58,000
? 1 death
1 40
1,400 hospitalisations
1 5
11,200 GP visits
44,800 domiciliary episodes
1 1.3
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Goals for a rotavirus vaccine

• Aim to duplicate the degree of protection
  following natural infection
• prevent moderate to severe disease
• decrease numbers of children
• admitted to hospital
• seen in Emergency Departments
• presenting to the family doctor
• Rotarix (P8 G1) and RotaTeq (P8, G1-G4)
• 85-98 efficacy against severe RV disease

NEJM 2006 354 11 2006 354 23
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Efficacy of licensed RV vaccines

Efficacy from 3 pooled studies of 67, 95 CI
15,87
NEJM 2006 354 11 2006 354 23
22
Global distribution of human group A rotavirus
P-G types (1989-2004)
Rev Med Virol 2005 15 29
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Distribution of NZ and Australian RV G-serotypes
JCM 2003 41 3649 Unpublished NZ data
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NZ RV G serotypes 1998-99
Unpublished NZ data from JPCH 200642 198-205
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Distribution of RV G serotypes in New Zealand
1998-1999, 2005-2006
Unpublished NZ data from JPCH 200642
198-205 Current RV serotype survey
preliminary data
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NZ RV G serotypes 2005-6 in children lt 5yrs
Starship Waikato
Wellington Hutt MedLab Wellington
CHCH Hospital MedLab South
Current RV serotype survey preliminary data
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Health economics key NZ issues

• Primary burden of rotavirus disease is morbidity
  in children
• Rotavirus also has an economic impact on
• households
• healthcare systems
• society
• Questions asked by policy makers and payers
• is rotavirus an important problem?
• can we do something about it?

Hosp Pharm 1997 32 1480 Emerg Infect Dis
2003 9 565 Pediatrics 1999 103
556 Health Policy 1997 42 39 Ped Infect
Dis J 1993 12 897 BMJ 1983 287 575 and
1999 318 1046
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Economic analysis

• Burden of Disease
• what is the cost of rotavirus disease to the
  healthcare system and nation?
• Cost Effectiveness
• compare change in healthcare costs to a change in
  some intermediate health outcome measure
• is vaccination a good health investment?
• Cost Benefit
• compare monetary costs to monetary benefits
• is vaccination a good economic investment?

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Economic analysis Australian data

• Annual cost of rotavirus disease in Australia is
  AUD 26 m (1999)
• societal and health care costs
• the cost effectiveness ratios are sensitive to
  the unit price of the vaccine
• New Zealand in 2005 AUD 6.2
• population differences
• 2.5 annual inflation
• Need economic data for the New
• Zealand environment

ANZ J Pub Health 1999 23 611

Expert Rev Pharmacoeconomics Outcomes Res 2005
5 593
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Surveillance

• RV gastroenteritis surveillance
• not notifiable
• stool collection for RV testing is not routine
• need to develop surveillance systems to monitor
  effectiveness of a RV immunisation programme
• disease burden
• circulating RV serotypes
• emergence of new strains with loss of vaccine
  efficacy
• reassortment of vaccine strains with WT viruses
• adverse events AIS 1 in 4,000 by chance alone
  in 1st 6m
• Centre for Adverse Reactions Monitoring (CARM)
• NZPSU
• NZHIS database, linked with NIR

ADC 2005 90 1077
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Some remaining questions

• Ongoing trials
• Asia and Africa
• efficacy in these settings
• protection against P4G2
• immunogenecity in preterm infants
• transmission studies in twins
• safety in HIV infected infants
• long term efficacy 2-3 yrs
• Latin America, Europe and Asia
• ? Role in reducing nosocomial RV diarrhoea
  patients, families, staff, students

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RV vaccines do we need them in NZ?

• Yes, but can we afford them?
• overseas economic analyses demonstrate
• that an immunisation programme will
• not initially be cost saving
• direct health vs societal costs
• costs being sensitive to vaccine price
• competition from other new vaccines
• post licensure surveillance
• safety relating to IS
• efficacy, including strain surveillance

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Acknowledgements

• Auckland
• D Lennon, R. Pinnock, R. Nicholson
• Waikato
• D Graham
• Wellington/Hutt
• K Grimwood, A Farrell, P Leadbitter
• N Beamish, I Gosling
• CHCH/Dunedin
• G. Abbott, D Teele, M Dennis-Meates
• B Taylor, R Ikram

• Malaghan Institute
• J Kirman, C Cohet, N Redshaw
• S Hook, K Romeril, C Wood
• ESR
• S Huang

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Geographical and temporal clustering of G9 in
NZ in 1999
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Deciding NZ immunisation policy
Case made to Ministers for funding for
new/revised programme
Advises the Ministry of Health
Immunisation Technical Working Group (an
independent expert advisory panel)
Economic analysis
Epidemiology and disease burden Post-licensure
effectiveness and safety
Licensure