Burden of Severe Rotavirus Diarrhea in Indonesia

S188 • JID 2009:200 (Suppl 1) • Soenarto et al

S U P P L E M E N T A R T I C L E

Burden of Severe Rotavirus Diarrhea in Indonesia

Yati Soenarto,1 Abu. T. Aman,2 Achirul Bakri,3 Herman Waluya,3 Agus Firmansyah,4 Muzal Kadim,4 Iesje Martiza,5

Dwi Prasetyo,5 Nenny S. Mulyani,1 Titis Widowati,1 Soetjiningsih,6 I. Putu Gede Karyana,6 Wayan Sukardi,7

Joseph Bresee,8 and Marc-Alain Widdowson8

Departments of 1Child Health and 2Microbiology, Faculty of Medicine, Gadjah Mada University, Sardjito Hospital, Yogyakarta, 3Department ofPediatrics, Faculty of Medicine, Sriwijaya University, Muhammad Hussein Hospital, Palembang, 4Department of Pediatrics, Faculty of Medicine,University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, 5Department of Pediatrics, Padjajaran University, Hasan Sadikin Hospital,Bandung, 6Department of Pediatrics, Faculty of Medicine, Udayana University, Sanglah Hospital, Bali, and 7Department of Pediatrics, Faculty ofMedicine, Mataram University, Mataram Hospital, Mataram, Indonesia; and 8National Center for Immunizations and Respiratory Diseases, Centersfor Disease Control and Prevention, Atlanta, Georgia

Globally, rotavirus is the leading cause of diarrhea-related hospitalizations and deaths among young children,but the burden of rotavirus disease in Indonesia is poorly documented. From January through December2006, we conducted prospective surveillance (inpatient and outpatient) among children aged !5 years at 6hospitals in 6 provinces of Indonesia, using standardized methodology. Of 2240 enrolled children hospitalizedfor diarrhea, 1345 (60%) were rotavirus positive. Of 176 children enrolled in outpatient clinics in 3 hospitals,73 (41%) were rotavirus positive. Among children hospitalized for diarrhea, dehydration was more commonamong those who tested positive for rotavirus than among those who did not (91% vs 82%; ), as wasP ! .05vomiting (86% vs 67%; ). Children aged 6–23 months experienced 72% of all rotavirus episodes.P ! .05Rotavirus prevalence increased slightly in the cool, dry season. The most commonly detected genotypes wereG9 (30%) and P[6] (56%). G1P[6] and G9P[6] accounted for 34% and 21% of strains, respectively. A highproportion of genotype P[6] was detected, in combination with the common G types G1 and G9. Availablerotavirus vaccines would likely be efficacious against the most common circulating strains, but continuedmonitoring of uncommon genotypes is needed.

Rotavirus is the leading cause of severe acute diarrhea

in children throughout both developed and developing

countries. Every year, rotavirus is estimated to cause

1500,000 deaths worldwide among children aged !5

Potential conflicts of interest: none reported.Financial support: PATH and Biofarma.Supplement sponsorship: This article was published as part of a supplement

entitled “Global Rotavirus Surveillance: Preparing for the Introduction of RotavirusVaccines,” which was prepared as a project of the Rotavirus Vaccine Program, apartnership between PATH, the World Health Organization, and the US Centersfor Disease Control and Prevention, and was funded in full or in part by the GAVIAlliance.

The findings and conclusions in this article are those of the authors and donot necessarily represent the views of the US Centers for Disease Control andPrevention.

Presented in part: 6th Workshop of the Asian Rotavirus Surveillance Network,Bangkok, Thailand, December 2007; and Annual Scientific Meeting, Gadjah MadaUniversity, Yogyakarta, Indonesia, March 2008.

Reprints or correspondence: Dr. Yati Soenarto, Dept. of Child Health, Facultyof Medicine, Gadjah Mada University, Sardjito Hospital, Jl. Kesehatan no. 1,Yogyakarta, Indonesia ([email protected]).

The Journal of Infectious Diseases 2009; 200:S188–94� 2009 by the Infectious Diseases Society of America. All rights reserved.0022-1899/2009/20009S1-0025$15.00DOI: 10.1086/605338

years, with 180% of these deaths occurring in devel-

oping nations [1]. Furthermore, rotavirus infection

causes 2.1 million hospitalizations, 25 million outpa-

tient visits, and 111 million episodes of diarrhea world-

wide annually [2]. Surveillance of rotavirus in several

countries in the Asian region has found rotavirus to be

associated with 30%–70% of diarrhea-related hospi-

talizations among children [3, 4].

In Indonesia, few longitudinal studies on the burden

of rotavirus disease have been conducted since the

1970s [5–7]. These older studies used various meth-

odologies and may no longer reflect the etiologies of

acute diarrhea in Indonesia today. The annual number

of diarrhea-related deaths among children in Indonesia

has decreased during the past 20 years, largely because

of the successful use of oral rehydration salt. Further-

more, the incidence of bacterial gastroenteritis has de-

creased because of improvements in sanitation, hygiene,

and the availability of antibiotics, which would have

had little effect on the rates of rotavirus infection.

To reduce the burden of rotavirus gastroenteritis, ro-

by guest on October 18, 2016

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Rotavirus Diarrhea in Indonesia • JID 2009:200 (Suppl 1) • S189

Figure 1. Map of the hospital locations.

tavirus vaccines have been developed and introduced for rou-

tine immunization in several countries in the Americas and

Europe. In Indonesia, a lack of data on rotavirus burden and

circulating strains has led to poor recognition of the magnitude

of the problem and low prioritization of rotavirus vaccines as

a prevention strategy [8]. To inform a future decision about

rotavirus vaccine introduction in Indonesia, we conducted stan-

dardized surveillance for severe rotavirus diarrhea and circu-

lating rotavirus strains in 6 health care facilities throughout

Indonesia as part of the Asian Rotavirus Surveillance Network.

MATERIALS AND METHODS

This study followed guidelines laid out in a generic protocol

for rotavirus surveillance published by the World Health Or-

ganization; the protocol was designed to standardize surveil-

lance efforts in different countries [9].

Population and sample. The study population consisted

of all children aged !5 years who presented with acute diarrhea

from January through December 2006 at any of 6 teaching

hospitals. The participating hospitals are located in 6 different

provinces of Indonesia, on the islands of Sumatra, Java, Bali,

and West Nusa Tenggara (Figure 1). The hospitals were Mu-

hammad Hussein Hospital (Palembang, South Sumatra), Cipto

Mangunkusumo Hospital (Jakarta, Capital City Special Terri-

tory), Hasan Sadikin Hospital (Bandung, West Java), Sardjito

Hospital (Yogyakarta, Yogyakarta Special Territory Province),

Sanglah Hospital (Denpasar, Bali), and Mataram Hospital (Ma-

taram, West Nusa Tenggara).

Inpatients. All children aged !5 years who were admitted

to the participating hospitals with a primary diagnosis of di-

arrhea were screened for study eligibility. Acute diarrhea was

defined as �3 loose stools within 24 h and for a duration of

!2 weeks [10]. A standardized clinical form was completed to

obtain detailed information on the date of admission, age and

sex of the patient, nutritional status, previous treatment, status

of dehydration, symptoms of illness, and final diagnosis. A fresh

fecal specimen was obtained from enrolled children within 24

h after admission, was placed in a clean container, and was

stored at 4�C–8�C until laboratory testing for rotavirus.

Outpatients. Children aged !5 years who received treat-

ment at outpatient clinics for acute diarrhea (as defined above)

in 1 of 3 participating hospitals—Hasan Sadikin Hospital, Sard-

jito Hospital, and Mataram Hospital—were enrolled. A stan-

dardized clinical form similar to the one described above was

completed.

Fecal samples were collected at presentation by a nurse or

at home within 2 days after the clinic visit by parents or care-

takers, who were given small containers for that purpose. Sam-

ples were sent to the hospital immediately or were kept in the

refrigerator until the next day.

Laboratory examination. Stool specimens were trans-

ported in refrigerated boxes either to the Microbiology Labo-

ratory, Gadjah Mada University, Faculty of Medicine, Yogya-

karta (specimens from Sardjito, Sanglah, and Mataram

hospitals), or to the Biofarma Laboratory, West Java (specimens

from Muhammad Hussein, Cipto Mangunkusumo, and Hasan

Sadikin hospitals). In the laboratory, the sample was aliquoted

and stored at �70�C. Rotavirus was detected using an enzyme

immunoassay (Dakopatts; Dako International) in accordance

with the manufacturer’s instructions. All rotavirus-positive

stool specimens were sent to the Gadjah Mada University Lab-

oratory for rotavirus strain characterization. Forty randomly

selected strains from each participating hospital (240 in total)

were typed during the study period.



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Table 1. Enrollment of Patients with Diarrhea and Results of Rotavirus Testing among ChildrenAged !5 Years at 6 Hospitals in Indonesia, 2006

Patient group,location Hospital

No. ofpatientsenrolled

No. (%) ofpatients

tested forrotavirus

Patients with rotavirus-positive diarrhea

No.Percentage of tested

patients (95% CI)

InpatientsPalembang Muhammad Hussein 534 513 (96) 326 64 (60–68)Jakarta Cipto Mangunkusumo 106 99 (93) 66 67 (58–76)Bandung Hasan Sadikin 138 137 (99) 70 51 (43–59)Yogyakarta Sardjito 262 246 (94) 95 39 (33–45)Denpasar Sanglah 557 557 (100) 339 61 (57–65)Mataram Mataram 710 688 (97) 449 65 (61–69)

Subtotal … 2307 2240 (97) 1345 60 (58–62)Outpatients

Bandung Hasan Sadikin 27 27 (100) 11 41 (22–58)Yogyakarta Sardjito 38 29 (76) 3 10 (1–21)Mataram Mataram 123 120 (98) 59 49 (41–59)

Subtotal … 188 176 (94) 73 41 (34–48)

NOTE. CI, confidence interval.

Ethical considerations. This study was approved by the

Ethical Committee of Research in Medical Health at Faculty of

Medicine, Gadjah Mada University, and by PATH (Seattle,

Washington). Informed consent was obtained from parents or

caretakers of eligible children before enrollment in the study.

RESULTS

Hospital-based surveillance. From January through Decem-

ber 2006, a total of 2870 children aged !5 years were hospi-

talized for acute diarrhea in the 6 participating hospitals. Of

these, 2307 children (80%) were enrolled in this study. Stool

specimens were tested for 2240 (97%) of all children enrolled.

The remaining 67 children either were discharged before a stool

sample was obtained or provided an inadequate amount of

stool specimen for testing. Of the 2240 stool samples tested,

1345 (60%) were positive for rotavirus. The percentage of chil-

dren whose samples tested positive for rotavirus ranged from

39% to 67% at the different study sites (Table 1). Of the enrolled

children, 2 died as a result of severe diarrhea (both were ro-

tavirus negative) and another 7 died of causes other than

diarrhea.

The percentage of rotavirus-positive cases was high in all age

groups but was highest among children aged 6–11 months

(64%) and 12–23 months (67%). We found an unexpectedly

high prevalence of rotavirus (32%) among infants aged !3

months. Children aged !2 years accounted for 1185 (88%) of

the 1345 inpatients with rotavirus-positive diarrhea during the

study period. The median age of enrolled children and of chil-

dren with rotavirus-positive diarrhea was 11 months. Overall,

male individuals were more likely to be hospitalized for diarrhea

than were female individuals (60% vs 40%), but this sex dif-

ference was not statistically significant between rotavirus-pos-

itive and rotavirus-negative children. Rotavirus-positive chil-

dren were more likely to experience dehydration (odds ratio

[OR], 2.3; 95% confidence interval [CI], 1.7–2.9) and vomiting

(OR, 3.0; 95% CI, 2.4–3.6) and were less likely to have bloody

diarrhea (OR, 0.3; 95% CI, 1.7–4.6) than were rotavirus-neg-

ative children. The prevalence of fever or mucus in the stool

was not significantly different between rotavirus-positive and

rotavirus-negative patients. Before hospitalization, 61% of chil-

dren who tested positive for rotavirus had received oral re-

hydration salt, 28% had received antibiotics, 17% had received

antiemetics, and 14% had received antidiarrheal agents (Table

2).

Rotavirus infection occurred year-round at all sites, with a

peak during the colder months of June and July, when the

rotavirus prevalence rose to 70%–75%, after which the prev-

alence steadily decreased until December (33%) (Figure 2)

Outpatient surveillance. Three of the participating hos-

pitals also enrolled children who presented with diarrhea for

outpatient care. Of 27, 29, and 120 stool specimens collected

from outpatients in Hasan Sadikin Hospital, Sardjito Hospital,

and Mataram Hospital, respectively, 11 (41%), 3 (10%), and

59 (49%) tested positive for rotavirus (Table 1). Similar to the

findings among hospitalized patients, the majority of outpatient

rotavirus cases (86%) occurred in children aged !24 months,

and rotavirus prevalence increased in the months of May

through July. Among the outpatients, the 73 rotavirus-positive

children were more likely to present with vomiting (71% vs

34%; OR, 4.8; 95% CI, 2.5–9.2) and dehydration (69% vs 26%;



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Figure 2. Seasonality of rotavirus infection among children in 6 hos-pitals in Indonesia, 2006.

Table 2. Characteristics and Clinical Symptoms of Hospitalized Children Aged !5 Years with Rotavirus Diarrhea,Indonesia, 1 January–31 December 2006

Characteristic

No. (%) of patientsenrolled

( )n p 2240

No. (%) of patientswith rotavirus-positive

diarrhea( )n p 1345

No. (%) of patientswith rotavirus-negative

diarrhea( )n p 895 Odds ratio (95% CI)

SexMale 1348 (60) 827 (61) 521 (58) 1.1 (1.0–1.4)Female 892 (40) 518 (39) 374 (42)

Age, months0–2 139 (6) 44 (3) 95 (11) 0.7 (0.3–1.5)3–5 313 (14) 168 (12) 145 (16) 1.8 (0.9–3.6)6–11 765 (34) 490 (36) 275 (31) 2.7 (1.4–5.4)12–23 718 (32) 483 (36) 235 (26) 3.1 (1.6–6.2)24–35 193 (9) 115 (9) 78 (9) 2.3 (1.0–4.7)36–47 69 (3) 28 (2) 41 (7) 1.0 (0.5–2.5)48–59 43 (2) 17 (1) 26 (3) 1.0 (reference)

Clinical symptomDehydration 1953 (87) 1223 (91) 730 (82) 2.3 (1.8–2.9)a

Vomiting 1750 (78) 1152 (86) 598 (67) 3.0 (2.4–3.7)a

Stool mucous 658 (29) 377 (28) 281 (31) 0.9 (0.7–1.0)Bloody stool 78 (3) 24 (2) 54 (6) 0.3 (0.2–0.5)a

Fever 986 (44) 591 (44) 395 (44) 1.0 (0.8–1.2)

NOTE. CI, confidence interval.a Statistically significant ( ).P ! .05

OR, 6.1; 95% CI, 3.2–11.8) and were less likely to have blood

in the stool (3% vs 16%; OR, 0.2; 95% CI, 0.03–0.69), compared

with the 103 rotavirus-negative children.

Genotyping. Molecular characterization was performed on

240 specimens that were positive for rotavirus by enzyme im-

munoassay, to determine G and P genotypes. G genotypes of

rotavirus were detected for 199 (83%) of the samples. The

majority of strains had genotypes G1 and G9, which accounted

for 73 (30%) and 69 (29%) of the 240 samples, respectively,

followed by G2, which accounted for 34 specimens (14%).

Other genotypes included G3 (0.4%) and G4 (0.4%). The re-

maining samples were mixed types (9%) (Figure 3A). Of the

240 samples, 189 (79%) were successfully P genotyped. P[4]

and P[8] antigens were present in 31 (16%) and 33 (17%) of

the 189 typed strains, respectively, but an unexpectedly high

prevalence (105 [56%] of 189) of genotype P[6] was detected.

Mixed infections and untypeable infections accounted for 9%

and 21% of samples, respectively (Figure 3B). The median age

of children infected with P[6] genotype strains was the same

as those infected with strains of other P types (11 months).

Both G and P genotypes were established for 123 (51%) of

the 240 rotavirus-positive samples. G1P[6] and G9P[6] ac-

counted for 34% and 21% of samples, respectively. Other ge-

notypes included G2P[4] (17%), G1P[8] (11%), and G9P[8]

(9%). The remaining genotypes were G1P[4], G2P[6], G9P[4],

and G3P[4], which accounted for 2%, 3%, 2%, and 1%, re-

spectively (Figure 4).

DISCUSSION

This study demonstrates that rotavirus infection is the most

common cause of severe acute diarrhea among children aged

!5 years in Indonesia. Rotavirus was identified in 60% of the

2240 children hospitalized with acute diarrhea and in 41% of



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Figure 3. Distribution of G genotypes (A) and P genotypes (B) of rotavirus strains at 6 sites in Indonesia, 2006.

Figure 4. Rotavirus strain distribution in Indonesia, 2006.

the children who presented with diarrhea at the outpatient

clinics. The majority (88%) of all cases of rotavirus disease

occurred in children aged !2 years. Rotavirus-positive gastro-

enteritis was associated with more vomiting and dehydration,

compared with rotavirus-negative gastroenteritis. Our study

found a high prevalence of P[6] type strains—which were pre-

dominately the relatively unusual G1P[6] and G9P[6] strains—

and untypeable strains. The currently available vaccines do not

contain G9 or P[6] antigens, so these results highlight the im-

portance of continued strain monitoring in Indonesia and ad-

ditional laboratory efforts to type strains before and after vac-

cine introduction, to measure vaccine effectiveness against all

strains.

Previous studies conducted in Indonesia in the late 1970s

detected rotavirus in 15% of patients with mild diarrhea and

up to 38% of children with severe acute diarrhea. These results

are considerably lower than both our initial findings from 3

sites (57%) and our current findings [3, 5–7]. A recent study

reported that the overall prevalence of rotavirus among children

aged !5 years who seek care for diarrhea in Indonesia was

45.5% [11], but the results of that study are difficult to compare

with those of our study, because the age groups were a little

different, and outpatient visits were included with hospitali-

zations. Reasons for the increased prevalence of rotavirus di-

arrhea in recent years include the use of more-sensitive diag-

nostic tests and decreases in the number of bacterial and

parasitic gastrointestinal infections, as a result of improvements

in sanitation and water safety, which would reduce the fre-

quency of all-cause diarrhea but increase the proportion of

disease caused by rotavirus.

Very few data have been collected on children who present

with diarrhea for outpatient care in Asia. A community-based

study in Thailand found that 12% of children with diarrhea at

a clinic tested positive for rotavirus, whereas the percentage of

children hospitalized with acute diarrhea who tested positive

for rotavirus was 43% [12]. The percentage who tested positive

for rotavirus in our study was high, compared with that in the

Thai study and also with reported prevalences of 10%–20%



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among outpatients in the United States and Chile [13, 14]. Our

findings are nonetheless consistent with the general finding that

the prevalence of rotavirus among hospitalizations for diarrhea

is higher than that among episodes of milder diarrhea treated

in clinics.

Our findings confirm that children aged !3 months are less

likely to have rotavirus diarrhea, which is likely to be partly

but not exclusively because of transplacental neutralizing im-

munoglobulin G antibodies and immunoglobulin A in breast

milk. Human breast milk also contains several components,

including milk mucin, that have been shown to inhibit rotavirus

replication and infection by binding to the virus [15]. One

study showed that exclusive breast-feeding provides better pro-

tection against severe rotavirus infection than partial or no

breast-feeding [16]. Furthermore, a longitudinal study involv-

ing US children showed a reduced risk of diarrhea among those

who were mostly breast-fed during the first 6 months of life

[17].

Countries with tropical climates usually show little seasonal

variation in rotavirus, compared with those with temperate

climates [12, 18]. We found that rotavirus-positive diarrhea

occurred year-round but that there was an apparent increase

in rotavirus prevalence in the cool, dry season. This is consistent

with our previous study in 2001–2004 that showed a clear

seasonal trend of rotavirus infection occurring in the dry season

(authors’ unpublished data). A study in Myanmar also reported

that rotavirus infection was highest during the cool, dry season

and decreased in the hot, dry and the hot, wet seasons [19].

The increased frequency of vomiting and dehydration in

rotavirus infection may pose challenges to the administration

of oral rehydration salt and may increase reliance on intrave-

nous fluid therapy, thus leading to higher treatment costs. Cost

estimation from one of our studies revealed that the rotavirus-

associated economic burden from a health care system per-

spective was US$14.536 million per year (US$3.46 per birth

annually) [20]. A substantial proportion of children with ro-

tavirus diarrhea received antibiotics, antivomiting agents, and

antidiarrheal agents before they visited the hospital. However,

almost 40% of children with diarrhea had not received oral

rehydration salt, which is the primary treatment for any de-

hydrating diarrheal illness, which emphasizes the need for ed-

ucation among parents and primary health care providers about

appropriate initial treatment for watery diarrhea.

Overall, P[6] was the most common P type, accounting for

56% of the strains typed. P[6] strains have been reported to

be very common among neonates in Bangladesh [21]; they were

also found in 29 (21%) of 137 children of all ages in India

[22]. In 1996–1999, P[6] strains were reported to be the most

predominant P type, in association with G1 and G3 types, in

a survey of circulating strains in Africa [23].

The globally common genotypes G1P[8] and G2P[4] were

not represented strongly in this study and accounted for only

11% and 17% of all strains, respectively. Also, the genotypes

G3 and G4 were found only in Yogyakarta, at low prevalences

(0.4% each). These findings are in contrast to those of a study

conducted in 2001–2004 that showed that G1P[8] represented

62.5% of all strains in Indonesia (authors’ unpublished data).

The results also differ from those of an older study in Yogya-

karta that found that the 4 globally common G types (G1, G2,

G3, and G4) were predominant [24]. The finding of a high

proportion of G9 in our study corresponds with recent reports

that G9 is an emerging serotype in Indonesia [11] and world-

wide [23, 25, 26]. Of interest, genotype G9 was found to be

predominant in Palembang and Mataram, where rotavirus

prevalence was highest.

A high percentage of strains were untypeable (21%), perhaps

because of a slight mismatch between primers and strains. Ad-

ditional laboratory studies will be needed to assess whether

these untypeable strains represent G3 and G4 genotypes or

perhaps unusual genotypes.

Both the monovalent attenuated human rotavirus vaccine

and the pentavalent human-bovine rotavirus reassortant vac-

cine have demonstrated good efficacy against types G1–G4 and

G9. However, with the exception of G2P[4], the G types are

frequently in combination with P[8], which is the VP4 protein

contained in both vaccines, and this will elevate vaccine efficacy

against heterologous G types [27–29]. Although trial data sug-

gest some efficacy of both vaccines against strains comprising

G and P types not present in the vaccines, the degree of pro-

tection afforded against heterologous strains, such as G9P[6]

found in this study, remains unclear.

Overall, our results highlight the high burden of rotavirus

disease, the changing diversity of rotavirus strains circulating

in Indonesia by location and year, and the currently high prev-

alence of globally unusual strains. Although the overall disease

burden in Africa and Asia is well recognized, the World Health

Organization is waiting for the results of vaccine clinical trials

in poorer countries of these regions before they will extend the

current recommendations for the routine use of available ro-

tavirus vaccines in the Americas and Europe. Studies have

shown that, in Asia, rotavirus vaccines are highly cost-effective

and are projected to have a large impact on the burden of

severe rotavirus gastroenteritis [30]. Moreover, as a GAVI Al-

liance–eligible country, Indonesia should qualify for a large

subsidy for the vaccine cost for a period of 5 years.

To complement this study, research on the economic burden

of rotavirus in Indonesia would further support policy makers

in making a decision about the introduction of rotavirus vac-

cine, by helping to assess the relative affordability of the new

rotavirus vaccines. Finally, raising community awareness about

rotavirus infection and rotavirus vaccines will be important in

complementing primary strategies for reducing the disease bur-



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den. Recent qualitative research has shown a low awareness of

rotavirus disease among policy makers, health care practition-

ers, and the community in Indonesia [8]. This suggests that,

in addition to epidemiological and laboratory data, educational

campaigns need to be targeted at the medical and nonmedical

communities, to increase awareness about the danger of ro-

tavirus infection and to garner broad support from these groups

before vaccine introduction.

Acknowledgments

We thank Carl Kirkwood, Ruth Bishop, and Graeme Barnes (MurdochResearch Institute); Roger Glass (Fogarty International Center), for sup-port; Hera Nirwati (Faculty of Medicine, Gadjah Mada University) and I.P. Sukanto (PT Bio Farma), for the laboratory work; Abdul Wahab andAlthaf Setyawan (Community Health and Nutrition Research Laboratory,Faculty of Medicine, Gadjah Mada University), for data analysis; doctors,nurses, and administrative staff at all study sites, for helping with the study;and Etty Indriati (Department of Anthropology, Gadjah Mada University),for her comments and suggestion. We are grateful to all the research as-sistants in the Child Health Department, Faculty of Medicine, Gadjah MadaUniversity: A. W. Erlin Mulyadi, Era Agustin, Muhammad Bayu Sasongko,Dara Rosmailina Pabittei, Diarum Puspasari, Lucia Simbolon, Retno Palupi,Vicka Oktaria, Rachman Edi Santoso, Endy Widya Putranto, Diatrie An-indyajathie, Tri Budi Hartomo, Maya Indriati, Emmy Choirina, and Har-yanto, for their valuable contributions to this study.

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