Burden of of Paediatric Paediatric Burden Pierre VAN DAMME - - PowerPoint PPT Presentation

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Burden of of Paediatric Paediatric Burden Pierre VAN DAMME - - PowerPoint PPT Presentation

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Burden of of Paediatric Paediatric Burden Pierre VAN DAMME Rotavirus Rotavirus University of Antwerp Gastroenteritis in in Gastroenteritis Belgium Europe Europe REVEAL Study Study REVEAL Rotavirus gastroenteritis R Epidemiology

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Burden Burden of

  • f Paediatric

Paediatric Rotavirus Rotavirus Gastroenteritis Gastroenteritis in in Europe Europe REVEAL REVEAL Study Study

Pierre VAN DAMME

University of Antwerp Belgium

R Rotavirus gastroenteritis E Epidemiology & V Viral types in E Europe A Accounting for L Losses in Public Health & Society

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Study Study objectives

  • bjectives

– – Annual rate of consultation due to acute Paediatric Rotavirus Annual rate of consultation due to acute Paediatric Rotavirus Gastroenteritis (RVGE) in: Gastroenteritis (RVGE) in:

  • hospitals

hospitals

  • emergency rooms

emergency rooms

  • GP, FP or Paediatricians practices

GP, FP or Paediatricians practices – – Age and seasonal distribution of RVGE Age and seasonal distribution of RVGE – – Comparison of clinical and management characteristics of RVGE v Comparison of clinical and management characteristics of RVGE vs. s. characteristics of acute gastro characteristics of acute gastroe enteritis (AGE) other then RVGE nteritis (AGE) other then RVGE – – Serotyping Serotyping of RV strains

  • f RV strains

– – Costs of RV disease Costs of RV disease

REVEAL study

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Sweden France Spain Italy Germany U.K. Belgium

Prospective multicentre observational study 7 European regions Study population:

  • children <5 years of age
  • living in the defined study area
  • meeting the case definition of AGE
  • informed consent obtained

Study period: Oct 1, 2004 – Sept 30, 2005 3 Settings

  • all Hospitals in study area (ntotal=12)
  • all Emergency Room in study area (ntotal =16)
  • sample of GPs and/or Peadiatricians (ntotal=139)

Study Design Study Design

REVEAL study

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Sweden France Spain Italy Germany U.K. Belgi um

Belgium - Antwerp 2 Hospitals 2 Emergency rooms 22 GPs or Pediatricians France - Dijon 2 Hospitals 6 Emergency rooms 22 GP or Pediatrician Germany - Rostock 2 Hospitals 0 Emergency rooms 34 GPs or Pediatricians Italy - Padova 1 Hospital 1 Emergency room 13 GPs or Pediatricians

Study sites Study sites

Spain - Gandia+Denia (Valencia) 2 Hospitals 3 Emergency rooms 23 GPs or Pediatricians Sweden - Umea 2 Hospitals 3 Emergency room 13 GP or Pediatricians UK - Wirral (Liverpool) 1 Hospital 1 Emergency room 12 GPs or Pediatricians

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Study area NOT country data Study area NOT country data

12 12 13 13 23 23 13 13 34 34 22 22

22 22 Number of Number of primary care primary care participant participant

1 H 1 H 1 EW 1 EW 2 H 2 H 3 EW 3 EW 2 H 2 H 3 EW 3 EW 1 H 1 H 1 EW 1 EW 2 H 2 H 0 EW 0 EW 2 H 2 H 6 EW 6 EW

2 H 2 H 2 EW 2 EW Number of Number of hospitals (H) and hospitals (H) and emergency wards emergency wards (EW) (EW)

5.8 5.8 15.2 15.2 4.9 4.9 6.9 6.9 3.7 3.7 6.3 6.3

5.7 5.7 % of children < % of children < 5y 5y

17 488 17 488 15 206 15 206 14 856 14 856 16 000 16 000 15 844 15 844 15 050 15 050

14 193 14 193 Number of Number of children < 5 y children < 5 y

300 000 300 000 100 000 100 000 305 000 305 000 180 000 180 000 432 740 432 740 238 309 238 309

250 243 250 243 Number of Number of Inhabitants in Inhabitants in study area study area

Wirral Wirral Peninsul Peninsul a a City of City of Umea Umea Cities of Cities of Gandia Gandia et et Denia Denia City of City of Padova Padova Rostock Rostock Great Great Dijon Dijon

City of City of Antwerp Antwerp Study area Study area UK UK Sweden Sweden Spain Spain Italy Italy Germany Germany France France Belgium Belgium m15

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Pre-defined selection criteria of investigators are as follows:

  • preference for a previous involvement in research studies
  • preference for a routine use of computerized medical records
  • investigators able to estimate an accurate denominator of patients

followed in his/her practice

  • agreement to follow the quality control procedures defined in the

protocol

  • full-time practitioners
  • investigators who have a refrigerator suitable for specimen storage

at their office or agree to use a freezer provided by the CRO for the study duration

mkulig, 11/30/2005

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Swe Fra Spa Ita Ger U.K. Bel

At Baseline

  • all children presenting with symptoms of AGE screened physician diagnosed AGE
  • inclusion of a subset of screened children
  • questionnaires: by physician and by parents

Follow-up procedures

  • physician visit : only if sought by parents
  • questionnaires: by parents after child’s recovery

Stool sample collection

  • at health care contact or
  • at home, shipped to treating physician
  • Immunochromatographic assay (ICG) testing (VIKIA – BioMerieux)

Study Procedures Study Procedures

Visit to physician Qs: parents + physician Stool sample End of symptoms Qs: parents (+ nurse) (mean duration)

REVEAL study

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Case definition of AGE Case definition of AGE

  • A child who had within a 24

A child who had within a 24-

  • hour period:

hour period:

  • at least

at least 3 loose stools or 3 loose stools or

  • 3 watery stools or

3 watery stools or

  • forceful vomiting with no other cause

forceful vomiting with no other cause

  • symptoms in the last 7 days before a medical visit

symptoms in the last 7 days before a medical visit

  • preceded by a symptom

preceded by a symptom-

  • free period of 14 days

free period of 14 days

Exclusion criteria Exclusion criteria: : nosocomial nosocomial RVGE, chronic gastrointestinal tract disease with symptoms simi RVGE, chronic gastrointestinal tract disease with symptoms similar to lar to GE (i.e. GE (i.e. coeliac coeliac disease, disease, Hirschsprung Hirschsprung) )

Lab test: Lab test:

  • Immunochromatographic assay (ICG) testing (VIKIA – BioMerieux) ( by physician) (on fresh stool)

( by physician) (on fresh stool)

  • ELISA testing (central lab) (frozen stools sent to Cincinnati Ch

ELISA testing (central lab) (frozen stools sent to Cincinnati Children ildren’ ’s Hospital) s Hospital)

– – Genotyping (G Genotyping (G-

  • serotypes by RT

serotypes by RT-

  • PCR and sequencing) (Merck Research Laboratories)

PCR and sequencing) (Merck Research Laboratories)

REVEAL study

RVGE RVGE-

  • case = AGE plus ELISA testing +

case = AGE plus ELISA testing +

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RV+ 40.4% RV- 59.6%

Rotavirus is a major cause of Paediatric Rotavirus is a major cause of Paediatric Gastroenteritis Gastroenteritis

Kapikian AZ, Jama 1996

Rotavirus Unknown Adenovirus Bacteria Astrovirus Calicivirus

Industrialised countries Proportion (%) of Rotavirus positive samples (RV+) vs. Rotavirus negative samples (RV-) in the REVEAL study

NRV+ = 1102, NRV- = 1610

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Incidence rate Incidence rate calculation calculation for 3 settings for 3 settings

  • Children go to primary care or ER and may be referred:

Children go to primary care or ER and may be referred: – – Primary care Primary care → → ER : incidence ER ER : incidence ER – – Primary care Primary care → → Hosp : incidence hospital Hosp : incidence hospital – – Primary care Primary care → → ER ER → → Hosp : incidence hospital Hosp : incidence hospital

  • Each study area: inclusion of all hospitals, all ER & sample of

Each study area: inclusion of all hospitals, all ER & sample of primary care physicians primary care physicians – – Need take into account Need take into account sample fraction sample fraction of primary care physicians

  • f primary care physicians
  • Proportion of included children in each setting is not the same:

Proportion of included children in each setting is not the same: – – Take into account Take into account participation rate participation rate

  • For incidence rate calculation all eligible children are needed

For incidence rate calculation all eligible children are needed ( (Number Number of

  • f observed
  • bserved AGE/RVGE) + (

AGE/RVGE) + (Number Number of

  • f estimated

estimated AGE/RVGE) AGE/RVGE) Number Number of

  • f children

children <5 y. living in the <5 y. living in the study study area area

REVEAL study

Incidence:

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Example Spain: Flow of children in hospital Example Spain: Flow of children in hospital

Eligible children screened at hospital 181 Not included in the study 80 Estimated RV+ 42 RV+ 54 Included in the study 101

53.4 % 53.4 % AGE Incidence: AGE Incidence: 14856 14856 101 + 80 101 + 80 x100 =1.22 % RVGE Incidence: RVGE Incidence: 14856 14856 54 + 42 54 + 42 x100 = 0.65 %

REVEAL study 95% CI (1.04-1.40) 95% CI (0.53-0.77)

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Incidence rate of AGE/RVGE per 1000 Incidence rate of AGE/RVGE per 1000 children children/ /year year in in each each area area stratified stratified by setting by setting

20 40 60 80 100 120 140 160 180 Belgium France Germany Italy Spain Sweden UK 10 20 30 40 50 60 70 Belgium France Germany Italy Spain Sweden UK 5 10 15 20 25 Belgium France Germany Italy Spain Sweden UK

Hospital GP/FP Emergency room

# children # children # children country country country

Distribution of incidence rate in 3 settings is dependent on country Health Care System

AGE RVGE AGE AGE RVGE RVGE

REVEAL study

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10 20 30 40 50 60 70 80 Belgium France Germany Italy Spain Sweden UK

Hospital Emergency Primary Care

Percentage of RVGE among AGE in each study area stratified by se Percentage of RVGE among AGE in each study area stratified by setting tting

More than 50% of hospitalizations (and ER visits) for AGE are due to RV

REVEAL study

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Distribution of RVGE cases by Distribution of RVGE cases by month month of age

  • f age

( (corrected corrected for participation rates and for participation rates and sampling sampling fraction) fraction)

1 2 3 4 5 6

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36

Age (months)

% of RVGE cases

~95% of cases is > 6 months of age

REVEAL study

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Percentage Percentage of RVGE

  • f RVGE children

children per per month month

( (corrected corrected for participation rates and for participation rates and sampling sampling fraction) fraction)

N Peak Peak of AGE in

  • f AGE in winter

winter mainly mainly due to RVGE due to RVGE

REVEAL study

200 400 600 800 1000 1200 Oct. 04 Nov. 04 Dec. 04 Jan. 05 Feb. 05 Mar. 05 Apr. 05 May. 05 Jun. 05 Jul. 05 Aug. 05 Sept. 05 10 20 30 40 50 60 70

%

RV neg RV pos

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Distribution of circulating serotypes among RVGE positive childr Distribution of circulating serotypes among RVGE positive children en

(corrected for participation rates and sampling fraction) (corrected for participation rates and sampling fraction)

G3 9.3%

G8 0.5% G6 0.4%

G4 14.3%

G12 0.4% G10 0.1%

G2 3.4% G9 38.7% G1 32.9%

G1 G2 G3 G4 G6 G8 G9 G10 G12

The five main circulating RV serotypes are: G1, G2, G3, G4 and G9, representing more than 98% of RVGE children.

REVEAL study

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Circulating Serotypes Circulating Serotypes – – Distribution by study area Distribution by study area

(corrected for participation rates and sampling fraction) (corrected for participation rates and sampling fraction)

Belgium

24.18 11.5 9.62 28.4 26.29 G1 G2 G3 G4 G9

France

7.8 33.62 54.77 1.73 1.04 1.04 G2 G3 G4 G6 G8 G9

Germany

56.07 5.92 28.99 0.89 8.14 G1 G3 G4 G8 G9

REVEAL study

Italy

0.3 1.92 0.44 0.44 0.44 11.69 0.89 83.88 G1 G2 G3 G4 G6 G8 G9 G12

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Circulating Serotypes Circulating Serotypes – – Distribution by country Distribution by country

(corrected for participation rates and sampling fraction) (corrected for participation rates and sampling fraction) Spain

0.49 0.98 6.23 2.46 0.33 28.52 60.98 G1 G2 G3 G4 G6 G9 G10

Sweden

1.57 37.01 57.09 2.76 1.57 G1 G2 G4 G9 G12

REVEAL study

UK

0.36 1.07 13.21 85.36 G1 G3 G4 G9

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Average Average amount amount of

  • f days

days in in hospital hospital for for each each study study area area

4.3 3.6 5.0 3.7 3.7 2.5 2.8

0,5 1 1,5 2 2,5 3 3,5 4 4,5 5 BE FR GER IT SP SW UK

days

3-5 days are required for hospitalisation due to RVGE

REVEAL study

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Percentage Percentage of parents

  • f parents who

who stopped stopped working working at at least one least one day day due to due to child child’ ’s s RVGE RVGE

64.3 50.0 40.0 42.1 44.0 43.0 36.4 53.0 44.0 64.4 81.0 31.9 44.1 68.0 38.5 58.0 73.0 20.0 50.0 91.0 10 20 30 40 50 60 70 80 90 100 Hospitalised cases Emergency cases GP/Paediatrician cases Belgium France Germany Italy Spain Sweden UK

Considerable days of work lost for parents due to RVGE

REVEAL study

% of parents with work day lost

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Average Average number number of

  • f days

days at at home of parents due to home of parents due to child child’ ’s s RVGE RVGE in in the the different different settings settings

4,2 7,0 4,8 2,3 2,5 3,4 6,4 0,0 5,3 5,4 3,8 3,7 4,6 4,4 4,1 3,8 4,3 4,6 4,0 2,9 7,5 1 2 3 4 5 6 7 8 Hospitalised cases Emergency cases GP/Paediatrician cases Belgium France Germany Italy Spain Sweden UK

Considerable days of work lost for parents due to RVGE

REVEAL study

Mean number of workdays lost

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Conclusions (1/2) Conclusions (1/2)

REVEAL: First large REVEAL: First large-

  • scale epidemiological study on RV in Europe

scale epidemiological study on RV in Europe

  • Strengths:

Strengths:

  • same methodology for all study areas

same methodology for all study areas

  • covering an entire season in 7 different countries/regions

covering an entire season in 7 different countries/regions

  • covering 3 different health care settings

covering 3 different health care settings

  • use of central laboratory for serotype analyses

use of central laboratory for serotype analyses

  • high number of children included

high number of children included

  • Limitations:

Limitations:

  • only children seeking health care identified
  • nly children seeking health care identified
  • not all children presenting with symptoms were included

not all children presenting with symptoms were included

  • for incidence: calculation (observed + estimated) was done

for incidence: calculation (observed + estimated) was done

REVEAL study

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Conclusions (2/2) Conclusions (2/2)

  • Distribution of incidence rate in 3 settings is dependent on country Health

Care System

  • More than 50% of hospitalizations for AGE is due to RV

More than 50% of hospitalizations for AGE is due to RV

  • 3

3-

  • 5 days are required for hospitalisation due to RVGE (consistent

5 days are required for hospitalisation due to RVGE (consistent with the with the literature) literature)

  • P

Peak eak in in winter winter months months AGE AGE mainly mainly due to RV due to RV

  • Majority of community acquired RVGE in children > 6 months of ag

Majority of community acquired RVGE in children > 6 months of age e

  • The five main ( > 98%) circulating RV serotypes are: G1, G2, G3, G4 and G9.
  • Considerable

Considerable numer numer of

  • f days

days of

  • f work

work lost lost for parents due to RVGE for parents due to RVGE RVGE: Significant disease burden in Europe merits preventive mea RVGE: Significant disease burden in Europe merits preventive measure sure

REVEAL study

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Acknowledgement Acknowledgement

Principal Investigators Principal Investigators

  • P. van
  • P. van Damme

Damme – – Belgium Belgium

  • F. Huet
  • F. Huet -
  • France

France C.

  • C. H

Hü ül lß ße e – – Germany Germany

  • C. Giaquinto
  • C. Giaquinto -
  • Italy

Italy J.

  • J. Paricio

Paricio -

  • Spain

Spain M.

  • M. Tom

Tomà às s -

  • Spain

Spain L.

  • L. Gothefors

Gothefors -

  • Sweden

Sweden

  • P. Todd
  • P. Todd -
  • UK

UK Other contributors Other contributors FA.

  • FA. Allaert

Allaert

  • N. Vernet
  • N. Vernet
  • N. Largeron
  • N. Largeron

F.

  • F. A

Aï ït t-

  • Belghiti

Belghiti A.

  • A. Moren

Moren M.

  • M. Trichard

Trichard

  • O. Van der Hel
  • O. Van der Hel

REVEAL study

All participating physicians and parents in the 7 different countries

Sponsored by Sanofi Pasteur MSD