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DIARRHEA AS A MAJOR PROBLEM IN PEDIATRCS

Rotavirus and the Burden of Diarrhoeal Disease in Indonesia

Yati SoenartoDeptartment of Pediatrics

Gadjah Mada University/Sardjito HospitalYogyakarta, Indonesia


POPULATION DENSITY IN THE WORLD

Central Bureau, 2003


0

5

10

15

20

25

30

35

ARI diarrhoea nervoussystem

parasitic& otherinfection

tetanus thyphoid

1995

2000

MOH, 2003

LEADING CAUSES OF DEATHIN CHILDREN U 5


CASE MANAGEMENT OF DIARRHEACASE MANAGEMENT OF DIARRHEACASE MANAGEMENT OF DIARRHEACASE MANAGEMENT OF DIARRHEA

1. Fluid and food management

2. Use of drugs

3. Communication:

Physicians - Patients - parentsPhysicians - Patients - parents


bb

Intravenous“All”

Fasting

AntibioticAntidiarrhea

• ORT: ORS• Limited

IVbbFeeding:

Continue during & increase after diarrhea

Zn Suplementation

ANTIMICROBA

New formula ORS

ANTIDIARRHEA

Patient-Physician Communication

Incidence

& severitySelective

Past’70-’80

Present’80-now

Progress: management of diarrhea

ANTIMICROBA

ANTIDIARHEA

Duration, volume &IV

MostRecent

Patient safety+ Patient safety“No” P-D

communication


Problems on diarrhea case Problems on diarrhea case managementmanagement

ORT:ORT:ORS fails to reduce stool volume & durationNot always available / acceptable

Not palatableToo costlyNot fulfilling energy requirement

NUTRITION :NUTRITION :Loss appetiteNutrient lost: vomit & stool lossesLoss of intestinal saccharidases

malabsorptionWithholding of foodCatabolic effect of the infection


THE INCREASE OF ORT USE FOR DIARRHEA 1991 - 2000

65

70

75

80

85

90

95

1991 1994 1997 2000

SOURCE : Indonesian Demographic Health Survey (IDHS)


1.NGO:Coord.Board of Ped Gastr

Community based program

2.Prof.Association

3.Universities

Research development

Curriculum innovation

THE ROLE OF INDONESIAN PEDIATRIC GASTROENTEROLOGY

PEER GROUP

1972 : with NGOs, Community and private sectors

Support program (MOH) activities :

1975 : Rehydration Centre at Teaching Hospitals

Rehydration Corner at Health Centers

1997 : Working group of breast feeding promotion

1985 :Diarrhea Training Unit (DTU)at 7 Medical Schlools

1986 : MEDIAC implementation to Medical Schools : 6 14 35 (all) Medical Schools Nursing Program

1996 : MED-IMCI

2000 :

DIARRHEA CASE MANAGEMENT


1994 1997 2000

Increased fluids: IDHS (2003) 56,5 57,0 96.7 * Urban 90,5 61,7 - Rural 53,5 56,5 -

Continued feeding: IDHS 52,0 49,6 -

Increased fluids and continued feeding: MCHS (2003) 31,9 Urban 27,3 Rural 36,0

MCHS : Mother & Child Health SurveyIDHS : Indonesian Demography & Health Survey

HOME MANAGEMENT OF DIARHEA


Drugs given by HC personal in cases with bloody & watery stool

(1991-1992)

Drugs given by HC personal in cases with bloody & watery stool

(1991-1992)

Drugs given to 168 diarrhea attacks/ from 141 U5childen (out of 497 children living at 2 villages)

DysenteryDysentery WateryWatery

NN %% nn %%

Antibiotics & Antibiotics & antidiarrheaantidiarrhea

AntibioticsAntibiotics

Anti DiarrheaAnti Diarrhea

No drugsNo drugs

3

19

0

0

13.6

86.486.4

0

0

19

84

3

8

16.5

73.073.0

2.6

7.07.0


Causative

agents

’78 – ’79%

(n:338)

’90 – ’92%

(n=131)

’04 – ’05% (n=638)

Enteropathogens

Rotavirus

ETEC (LT&ST)

Salmonella

Shigella

Cryptosporidium

E. Histolytic

Mix enteropahogens

56

38

11.5

6

4

0.3

7.6

80

66

NE

2.1*

1.8*

1.3**

0

3

29

Not yet analyzed

NE (not examined)

6

1

NE

NE

NE

Studies on the etiology of Diarrhea


2005 : Sardjito teaching hospital: ISO 20002006 : Study on “Patient safety study on diarrheal disease management”. Preliminary result (n 121):• IV Fluids

– No dehydration: 12.3%;Vomit: 83.2%– Some dehydration: 12.7%;Vomit: 93%– Severe dehydration: 100%Guidelines: IV Fluid only for severe

dehydration & Profuse Vomit. • Antibiotics

- Acute watery diarrhea:0.6% - Intolerance: 0%- Persistent: 75%- Dysentery: 90%- Intolerance: 0%Guidelines: Antibiotics only for dysentery &

persistent diarrhea.

Rotavirus and the Burden of Diarrhoeal Disease in IndonesiaCourtesy of U. Parashar

1 dot = 1000 deaths

GLOBAL DISTRIBUTION OF RV MORTALITYIN CHILDREN U 5


• 1 in 5 outpatiened; 1 in 65 hospitalized; 1 in 293 die due to RV; • 20%-85% of all hospitalization of children for diarrhea;

20% of all deaths in children <5 yrs in developing countries

- U.S: $560 mill/yr, & $ 200 mill loss of productivity- PERU: $ 2.6 thsnds /yr- India:severe Diarrhea: $2,663/prson

median 440,000 death in <5yrs

RVWorldwide


Longitudinal (1/> yr) hospital studies;RV diarrhea: ‘80 – ‘84: 21% – 42% (8 long.studies); ‘78 – ‘79: 38%; Strain: G1 – G4;’00 – ‘05: 53%; Strain: G1,3,4; G9

Cost: ?

40

24.9

16

7.5 7.4

0

10

20

30

40

50

1972 1980 1986 1992 1996

Deaths: Diarrhea :2nd causeRV: ?

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1989 1990 1991 1992 1993 1996 2000 2003

Economic crisis

Mortality Morbidity

RVIndonesia


1970’s 1980’s 1990’s 2000’s

70 71 72

73 74 75

76 77 78

79

80 81 82

83 84 85

86 87 88

89

90 91 92

93 94 95

96 97 98

99

00 01 02

03 04 05

06 07 08

09

30 YEARS JOURNEY(UniMelb/RCH - GMU/ Sardjito)


1973 : Rotavirus discovery (R. Bishop, RCH/Unimelb) 1976 : Pilot study, in which RV was found in 12% of children with acute diarrhea in Jogjakarta,Indonesia(Lancet).GMU-RCH,

Introduced by J.Rohde (Rockefeller F)1976 : Asymptomatic excretion of RV (RCH, Melbourne) 1978 : A case control hospital & a cohort

community design (GMU-RCH) published:

1979 : RV in Yogya, Indonesia – 38% of admissions – J Clin Microbiol

1973 : Rotavirus discovery (R. Bishop, RCH/Unimelb) 1976 : Pilot study, in which RV was found in 12% of children with acute diarrhea in Jogjakarta,Indonesia(Lancet).GMU-RCH,

Introduced by J.Rohde (Rockefeller F)1976 : Asymptomatic excretion of RV (RCH, Melbourne) 1978 : A case control hospital & a cohort

community design (GMU-RCH) published:

1979 : RV in Yogya, Indonesia – 38% of admissions – J Clin Microbiol


1983 : Neonatal infection shown to protect against community strains (RCH, Melbourne)

1989 : Funding to prepare RV3 as an oral vaccine – Flow Labs, USA (RCH)

1994 : Phase I trial started – funded by AMRAD (RCH)

1997 : Phase II trial started – funded by AMRAD & Australian Government (RCH)


2001 – 04 : Hospital-based system & strain surveillance for rotavirus diarrhoea and estimate of disease burden in Indonesia. A Multi Country Study on Rotavirus Surveillance, Coordinated by CDC Atlanta. Funded by PATH (GMU)

2002 – 04 : An Extending Surveillance to Estimate the Disease Burden of Rotavirus

Gastroenteritis in Yogyakarta and Central Java Indonesia (GMU).

2006 – 08 : Multicenter Study (6 teaching hospitals): Extention for Hospital Based

Surveillance and Strain Characterization of Rotavirus Diarrhoea in Indonesia. Funded by PATH & Biofarma (GMU).

2001 – 04 : Hospital-based system & strain surveillance for rotavirus diarrhoea and estimate of disease burden in Indonesia. A Multi Country Study on Rotavirus Surveillance, Coordinated by CDC Atlanta. Funded by PATH (GMU)

2002 – 04 : An Extending Surveillance to Estimate the Disease Burden of Rotavirus

Gastroenteritis in Yogyakarta and Central Java Indonesia (GMU).

2006 – 08 : Multicenter Study (6 teaching hospitals): Extention for Hospital Based

Surveillance and Strain Characterization of Rotavirus Diarrhoea in Indonesia. Funded by PATH & Biofarma (GMU).


Author Years/City Duration(mos)

Detection assay

Number Age (mos) % with rotavirus

Yati Soenarto(collaborator UniMelb)

1978-1979Yogyakarta

13 EM, IEM & Electrophoresis of Genome RNA

4230334

< 1< 11 mo 12 yrs

1.4037.8

Simanjuntak 1980-19811981-1982Jakarta

1212

ELISAELISA

466113

All agesAll ages

34.838.1

Sutoto 1980-1981Jakarta

13 ELISA 287 All ager 20.9

LONGITUDINAL RV STUDIES IN INDONESIA1978 - 2008


Author Years/City Duration(mos)

Detection assay

Number Age (mos) % with rotavirus

Soeparto PWasito EB

198419961997

Surabaya

12601212

LXLXLX

113144319

0-240-240-24

31.334.536.142.0

Yati Soenartocollaborators CDC Atlanta, UniMelb)

2001 -2004Jogjakarta & Central Java

32 ELISA 1321 0-36 53.4

Yati Soenarto collaboratorUniMelb)

2005 – 2008Multicenter surveillance

On going ELISA 785 0-60 Not yet analyzed


Study Characteristics Patient Characteristics

Authors Years/City

Duration/ months

DetectionAssay

Number Age (month)

% withRotavirus

Yuwono D 1990Bandung

5 RPHA 89*86**

0-36 40.9*24.3**

*: urban health center** : rural health center

A RV STUDY IN RURAL AND URBAN HEALTH

Study Characteristics Patient Characteristics

Author Years/City Duration/ months

Detection assay

Number Age (months)

Rotavirus seroprevalence

Sutoto ’80 – ‘81Jakarta

13 ELISA 136 All ages 16.2

A RV STUDY IN COMMUNITY


Hospital-based system and strain surveillance for rotavirus diarrhoea and

estimate of disease burden in Indonesia. A Multi Country Study on

Rotavirus Surveillance.

Aug 2001 - April 2004

Hospital-based system and strain surveillance for rotavirus diarrhoea and

estimate of disease burden in Indonesia. A Multi Country Study on

Rotavirus Surveillance.

Aug 2001 - April 2004


RV DISEASE BURDEN IN YOGYAKARTAAND CENTRAL JAVA (2001 – 2004)b

8929 cases of < 5 children

1397 diarrheal cases(100%)

705 rotavirus diarrhea(53.4%)

36 severe dehydration(5.1%)

2 deaths (RV positive)(0.03%)

440 dehydration(62.4%)


0

50

100

150

200

250

300

350

400

450

No Some Severe

Negative

Positive

Not Tested

No Yes

0

50

100

150

200

250

300

350

400

450

500

Rotavirus Negative

Rotavirus Positive

Dehydration

N valid = 1397

P=0.005

N valid = 1321

P=0.024


Rotavirus by SeasonAugust 2001 - April 2004

02468

101214161820222426283032

nu

mb

er o

f ro

tavi

rus

det

ecti

on

0

10

20

30

40

50

60

RainfallE-RainTemperatureE-TemperatureRotavirus

Rainfall 5.3 3.2 6.8 6.7 5.2 17.116.35.3 4.0 3.2 4.8 7.7 1.5 4.8 1.5 8.7 7.7 5.6 16.67.5 1.5 4.2 4.8 8.4 1.5 4.8 1.5 9.5 9.7 10.85.5 8.6 0.6

E-Rain 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4 6.4

Temperature 25. 27. 27. 27. 26. 26. 26. 27.127.127. 26. 25. 25.126. 27. 27. 27. 26. 26. 27. 27. 27. 26. 24. 25. 25. 27.126. 27 28. 26. 26. 28.1

E-Temperature 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27 27

Rotavirus 55 36 12 7 13 23 31 23 29 12 21 47 45 37 18 10 7 11 13 13 18 25 39 43 36 18 5 8 5 1 7 16 21

A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A

2001 2002 2003 2004


Costs and Virus Types Mean Standard

Deviation

t-Test P-Values

Direct Medical Cost Expenditure

Rotavirus +

Rotavirus -

415

310

480.1

227.8

3.77 0.00

Direct Non Medical Cost Expenditure

Rotavirus +

Rotavirus -

101

84

133.2

122.1

1.77 0.08

Total Cost

Rotavirus +

Rotavirus -

517

394

512.6

275.4

3.99 0.00

Direct vs Indirect Cost


0.94.5

28.1

18.92

46.85

56.73

9.62

0

15.38

6.73

0

20

40

60

1978-1979 2001-2003

G1 G2 G3 G4 Non-typ.

G-type comparison: 1978-1979 and 2001-2003


Rotavirus diarrhea: previous studies in Indonesia(53.4% vs 37.8%) Peak age: 12-24 months; Male > female (1.4:1) RV caused more dehydration significantly Obvious seasonal variation: highest RV during dry

season with lowest temperature. Change in the RV strain circulating in Indonesia?. Change in the dominant strain? Where is G3? Was the G9 just recently identified? G1 was the least (1 in 57) in 78-79majority in 01-

03? Was non-type able In 78-79 G1? And Why?

SUMMARY (1)


1. Attempts have been made to produce more representative data of RV in Indonesia. An IRSN (Indonesian Rotavirus Surveillance Network) involving 7-10 teaching hospitals & surrounding (smaller/rural/district) hospitals is being set up (Indonesian map)followed by conducting the surveillance started at year 2006.

2. Current data is hospital based, is community based data required?

3. To ascertain the change in the strain prevalence, study of stool samples collected during that period of 1979-2001 is necessary.

What is next??


EXTENTION FOR HOSPITAL-BASED SURVEILLANCE AND STRAIN CHARACTERIZATION

OF ROTAVIRUS DIARRHOEA IN INDONESIA

January 2006 – January 2008

Multi Center Surveillance

Indonesian Rotavirus Surveillance Network (IRSN)Palembang, Jakarta, Bandung, Yogyakarta, Denpasar, Mataram


PalembangJakarta

Bandung

Yogyakarta

Denpasar

Mataram

Aceh Irian


INCIDENCE OF RV IN INDUSTRILIZED = IN DEVELOPING COUNTRIES IMPROVEMENT IN: WATER SUPPLY, HYGIENE & SANITATION: NOT ↓ RV DIARRHEA VACCINE IS NEEDED the 2nd breakthrough after ORT?Diarrheal Disease:•ORT reduced mortality•RV vaccine reduced morbidity


COLLABORATORS


• Partnership system• Priority research program• Specific projects

• Partnership system• Priority research program• Specific projects

Partnership & networking on research, Partnership & networking on research, education & clinical practice– could education & clinical practice– could

translational research being implemented?translational research being implemented?

Partnership & networking on research, Partnership & networking on research, education & clinical practice– could education & clinical practice– could

translational research being implemented?translational research being implemented?

COMMUNITIESCOMMUNITIES GOVERNMENTGOVERNMENT

UNIVERSITIESUNIVERSITIES

International collab.&

network PRODUCTS

IMPROVED HEALTH/QUALITY OF LIFEIMPROVED HEALTH/QUALITY OF LIFE

Career Career developmentdevelopment

linkageslinkages

inputinput Out putOut put

CAPACITIES

Diarrheal case management

Patient safety study on Diarrheal Disease

management


Diarrhea Cases

• Diarrhea morbidity in Indonesia at 2005 : 1.343.276 (19 provinces)

• Diarrhea mortality in Indonesia at 2005 : 119 (14 provinces)(Subdit.Ditjen Diare P4D, 2005)

• Diarrhea morbidity in DIY at 2006 : 11.460 (without Gunung Kidul)(Dinkes DIY, 2006)

• The highest morbidity : NTB 193.759• The highest mortality : Sulsel 49??

(Subdit.Ditjen Diare P4D, 2005)


Terima Kasih

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