CHOLERA IN INDONESIA IN 1993-1999

788

Am. J. Trop. Med. Hyg., 65(6), 2001, pp. 788–797Copyright� 2001 by The American Society of Tropical Medicine and Hygiene

CHOLERA IN INDONESIA IN 1993–1999

CYRUS H. SIMANJUNTAK, WITA LARASATI, SUMARJATI ARJOSO, MAIDY PUTRI, MURAD LESMANA,BUHARI A. OYOFO, NONO SUKRI, DASWIR NURDIN, RATNA P. KUSUMANINGRUM, NARAIN H. PUNJABI,

DECY SUBEKTI, SUDEWA DJELANTIK, SUKARMA, SRIWATI, MUZAHAR, AZWIN LUBIS, HAROEN SIREGAR,BASTIAR MAS’UD, MURSAD ABDI, ATIEK SUMARDIATI, SUSANTO WIBISANA, HENDARWANTO, BUDI SETIAWAN,

WASIS SANTOSO, EKA PUTRA, SORITUA SARUMPAET, HANIFAH MA’ANI, CARLOS LEBRON,SRI ASTUTI SOEPARMANTO, JAMES R. CAMPBELL,AND ANDREW L. CORWIN

National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia; U.S. Naval Medical ResearchUnit No. 2, Jakarta, Indonesia; Sub-Directorate of Diarrheal Disease, Directorate General of Communicable Disease Control andEnvironmental Health Sanitation, Ministry of Health, Jakarta, Indonesia; Sanglah Hospital, Denpasar, Bali, Indonesia; Wangaya

Hospital, Denpasar, Bali, Indonesia; Dr. Pirngadi Hospital, Medan, North Sumatra, Indonesia; Labuang Baji Hospital, Makassar,South Sulawesi, Indonesia; Provincial Health Laboratory, Makassar, South Sulawesi, Indonesia; Provincial Health Authority

Office, Pontianak, West Kalimantan, Indonesia; Dr. Soedarso Hospital, Pontianak, West Kalimantan, Indonesia; PersahabatanHospital, Jakarta, Indonesia; Batam Authority Hospital, Batam, Riau, Indonesia; Dr. M. Djamil Hospital, Padang,

West Sumatra, Indonesia

Abstract. Cholera-specific surveillance in Indonesia was initiated to identify the introduction of the newly rec-ognizedVibrio cholerae non-O1, O139 serotype. Findings from seven years (1993–1999) of surveillance efforts alsoyielded regional profiles of the importance of cholera in both epidemic and sporadic diarrheal disease occurrencethroughout the archipelago. A two-fold surveillance strategy was pursued involving 1) outbreak investigations, and2) hospital-based case recognition. Rectal swabs were transported to Jakarta for culture and isolates were characterizedby serotypic identification. Outbreak findings showed thatV. cholerae O1, Ogawa serotype, was the predominantetiology in all 17 instances of investigated epidemic transmission. Monitoring of eight hospitals representing sevenprovinces provided 6,882 specimens, of which 9% were culture positive forV. cholerae: 589 (9%) for O1 and 20(� 1%) for non-O1 strains. Proportional representation ofV. cholerae O1 among cases of sporadic diarrheal illnesswas variable, ranging from 13% in Jakarta to� 1% in Batam. Overall, 98% ofV. cholerae O1 cases were the Ogawaserotype. There was no instance of non-O1, O139 serotype introduction in either epidemic or sporadic disease form.Anti-microbial drug susceptibility was consistently demonstrated, both temporally and spatially, except against colis-tin. Evidence is provided that epidemic and sporadic cholera occurrence in western Indonesia is associated withperiods of low rainfall. Conversely, in the more eastern portion of the country, heavy rainfall may have contributedto epidemic cholera transmission.

INTRODUCTION

Epidemic and sporadic diarrheal transmission worldwidehas been principally attributed to the O1 biotypes ofVibriocholerae.1,2 The two O1 serotypes associated with choleraoutbreaks and community acquired exposures are the clas-sical biotype and El Tor biotype.3–5 The first six cholera pan-demics of the last two centuries were believed to be largelyof the classical biotype, having originated on the Indian sub-continent. The current seventh pandemic, recognized in 1962from the port city of Makassar (formerly Ujung Pandang) insouthern Sulawesi, an island located in the eastern portionof the Indonesian archipelago, represents the first instanceof V. cholerae of the El Tor biotype occurring in epidemicform.6 Prior to the seventh pandemic, El Tor biotype wasknown in association with small outbreaks (non-epidemic)and sporadic cholera-like disease.7

From India and Bangladesh in the region surrounding theBay of Bengal, aV. cholerae non-O1 serotype was causa-tively identified for the first time in October 1992 in largeoutbreaks of cholera-like disease. This newV. cholerae non-O1 serotype was detected using a rabbit antiserum and des-ignated as the O139 serotype.1,8,9 Unlike most non-O1 se-rotypes, O139 uniquely shares the virulence trait of produc-ing cholera toxin usually associated with O1 serotypes.10 Thesharp increase in epidemic, cholera-like cases attributed tothe O139 serotype on the Indian subcontinent (more than100,000 episodes in January through March 1993 fromBangladesh alone), and the rapidity by which the O139 se-rotype of V. cholerae spread eastward into southeast Asia,

attested to the pandemic potential of this novel strain.8,11

Case reports of cholera-like disease involving the suspectedO139 serotype from Thailand and Malaysia suggested theregion could soon be overwhelmed by an eighth cholera pan-demic.11 Indonesia, a nation of islands, presents numerouspredisposing environmental and social conditions that favorexposure opportunities to both O1 and non-O1V. cholerae.These include frequent flooding, and poor hygiene and san-itation, such as use of untreated water for bathing and some-times for drinking purposes, and improper disposal of humanwaste. These conditions suggested that Indonesia could beparticularly susceptible to epidemic transmission associatedwith the spreading O139 serotype (Unpublished data; Indo-nesian Demographic and Health Survey, 1994).12

The unique epidemic profile ofV. cholerae O139 serotypeis characterized by debilitating, severe watery, dehydratingdiarrheal illness with accompanying vomiting in the absenceof fever, and high attack rates among young, nominallyhealthy adults from areas of highV. cholerae O1 endemic-ity.1,10,13 Unfortunately for countries like Indonesia, there isno apparent protective immunity againstV. cholerae O139associated with previous childhood exposures to O1 classicaland/or El Tor biotypes.1,10

In Indonesia, as throughout southeast Asia (but unlike onthe Indian subcontinent), the importance of cholera in acute,diarrheal illness among indigenous populations has not beenthoroughly investigated due to a lack of culture-based, lab-oratory diagnostic capabilities. Findings presented in this re-port reflect six years of organized cholera surveillance un-

789CHOLERA IN INDONESIA

FIGURE 1. Cholera Surveillance Network (CSN) and diarrheal outbreak occurrences throughout the Indonesian Archipelago.

dertaken in Indonesia for the purpose of 1) identifying theemergence ofV. cholerae O139 in the country; and 2) dif-ferentiating the relative importance ofV. cholerae O1 bio-types and serotypes in both epidemic and sporadic, acutediarrheal disease occurrence.

MATERIALS AND METHODS

Surveillance strategy. Targeted cholera surveillance wascollaboratively pursued by a multi-institutional consortiumcomprised of the National Institute of Health Research andDevelopment (NIHRD/LITBANGKES), Directorate Generalof Communicable Disease Control and EnvironmentalHealth and Sanitation (P2M-PLP) and the U.S. Naval Med-ical Research Unit No. 2 (NAMRU-2), all located in Jakarta.Additionally, local, district, and provincial health offices andselected area hospitals were integrally involved in all aspectsof surveillance activities. Cholera surveillance efforts wereinitiated in 1993 and have continued through 1999. A two-fold approach to comprehensive surveillance focused on in-vestigation of selected diarrheal outbreaks to ensure archi-pelago-wide coverage of epidemic and sporadic choleratransmission.

The area. As an archipelago nation that extends from thePacific Ocean to the Indian Ocean, Indonesia is made up of

17,000 islands, approximately 5,000 km from east to west.The country’s five principal island chains are characterizedby lush, tropical forests, and are crisscrossed by rivers andstreams. Most of the cities are congested, with significantovercrowding, particularly in impoverished areas lacking inbasic water and waste sanitation. Approximately 34% of In-donesia’s 205 million inhabitants live in urban areas.14 Sig-nificant population migrations resulting from economic, so-cial, and political upheavals have contributed to failures ininfrastructure development designed to provide an improvedliving environment.

Outbreak investigations. Seventeen investigations in-volving suspected diarrheal epidemic occurrence were con-ducted throughout Indonesia over a seven-year period of tar-geted cholera surveillance beginning in 1993 and continuingthrough 1999. Four outbreaks were in Sumatra, five in Java,two in Kalimantan (Borneo), two in Nusa Tenggara, three inPapua (formerly Irian Jaya), and one in Sulawesi (Figure 1).Outbreak selection for investigative purposes was predicatedon established criteria that included 1) suspected occurrenceinvolving � 25 persons, 2) associated (reported) fatalities,and 3) timely information allowing for a prompt responseduring actual epidemic transmission. Additionally, subjec-tive political and security considerations affected outbreakresponse decisions. Each selected outbreak was investigated

790 SIMANJUNTAK AND OTHERS

according to a prescribed protocol, which provided for vol-untary and informed consent of study subjects, systematiccase sampling (the ratio dependent on the overall number ofrecognized patients), and age/sex matched healthy controls.Also, a standardized questionnaire was administered in thelocal dialect by a trained interviewer, providing a demo-graphic and clinical profile of the affected population. Caseand control subjects were accessioned from both hospitaland community-based (with the household serving as theprincipal sampling unit) populations. Rectal swab sampleswere obtained by standard collection procedures and im-mediately placed in Cary-Blair transport medium for promptdelivery to NAMRU-2 and NIHRD/LITBANGKES, Jakarta.

Cholera surveillance in Indonesia was initiated followingprotocol driven review by the NAMRU-2 Committee forProtection of Human Subjects (CPHS). Additionally, insti-tutional reviews by the Indonesian Ministry of Health, name-ly (NIHRD/LITBANGKES) and P2M-PLP were carried outindependently, for human use consideration.

Hospital-based monitoring. Selection of hospital sitesfor the Cholera Surveillance Network (CSN) was intendedto provide the widest geographic representation of the ar-chipelago, in the absence of any standardized, laboratorysupported monitoring activities, to specifically target sporad-ic (community-acquired) cholera. Eight public hospitals pro-viding care to the general population were entered into theCSN: one from Java (Jakarta), two from Sumatra (Padangand Medan), one from the Riau Islands (Batam), one fromKalimantan (Pontianak), one from Sulawesi (Makassar), andtwo from Bali (Denpasar) (Figure 1). Findings represent pa-tient data from 6,882 case subjects enrolled from September1994 to November/December 1999.

Criteria used in the screening of diarrheal patients forstudy inclusion purposes reflected severity on actual caseadmission: debilitating diarrhea with dehydration. After in-formed, voluntary consent was obtained, demographic pa-tient information pertaining to age and sex was recorded.Two rectal swab samples were obtained from each subject,and placed in Cary-Blair transport medium. Specimens werethen transported overnight for isolation and identification atNAMRU-2/LITBANGKES in Jakarta, Indonesia).

Laboratory testing. Rectal swab samples were streakeddirectly onto a thiosulfate citrate bile sucrose (TCBS) agar,and also placed in alkaline peptone water enrichment broth,and incubated at 37�C. Inoculated enrichment broth was thensubcultured to TCBS after 24 hr of incubation.15 All TCBSplates were incubated at 37�C for 18–20 hr. Yellow coloniesresembling those ofV. cholerae were picked and identifiedby conventional biochemical and serologic methods.8,16 Vib-rio cholerae isolates were confirmed on the basis of the fol-lowing criteria: 1) found to be motile; 2) producing an al-kaline slant over an acid butt on Kligler’s iron agar; 3) ox-idase, sucrose, indole, ornithine, and lysine positive; and 4)arginine negative. Isolates agglutinating toV. cholerae O1polyvalent antiserum were further characterized by serologywith Ogawa- and Inaba-specific antisera. Susceptibility topolymyxin B17 and the CAMP test18 were used to differen-tiate El Tor from classical biotype.Vibrio cholerae isolatesthat did not agglutinate inV. cholerae O1 polyvalent anti-serum were subjected to the CAMP test for detectingV.cholerae non-O1, O139 serotype.19

All media used for biochemical testing ofV. parahae-molyticus contained 1% NaCl. Salt tolerance media wereprepared from 1% peptone, 0.1% glucose, 0.006% phenolred, pH 7.4, with (6.5%) and without NaCl. Identification ofV. parahaemolyticus was performed by a standard culturemethod.17 Briefly, isolates that produced an alkaline slantover acid butt on Kligler’s iron agar, and which were motile,and oxidase, indole, lysine, and ornithine positive, but su-crose and arginine negative, were described asV. parahae-molyticus. Isolates grew in medium with high salt content(6.5% NaCl), and did not grow in salt-free medium. Arabi-nose was generally fermented.

Climatic information. Rainfall data (mm) were obtainedfrom the Meteorology and Geophysics Institute, located inJakarta, Indonesia. Mean cumulative rainfall values fromarea-specific collection sites were averaged, providingmonthly comparative findings from 1993 through 1999.

RESULTS

Outbreak findings. The relative importance ofV. chol-erae O1 in epidemic diarrheal transmission is reflected inthe laboratory recognition of this bacterial pathogen in everyinstance of investigated outbreak occurrence. Uniformity inoutbreak causation is further demonstrated in that all 17 in-vestigated episodes of epidemic diarrheal disease were attri-buted toV. cholerae O1 of the El Tor biotype, Ogawa se-rotype. Overall, 27% (95% confidence interval [CI] for pro-portion � 0.241–0.303) of 788 diarrheal stool samples, rep-resenting outbreak specimen collections from throughout thearchipelago, cultured positive for the Ogawa serotype. Therecovery of Ogawa in stool specimens ranged from 6% of82 outbreak cases in Jakarta, Java, to 72% of 36 outbreakcases in Aceh, Sumatra (Table 1). Only in one instance in-volving epidemic diarrheal transmission, in Pontianak, WestKalimantan (1994), wasV. cholerae O1, Inaba serotype de-tected, although Ogawa was again implicated relative to out-break causation: 8% in Inaba versus 18% in Ogawa, among80 stool samples examined. NoV. cholerae non-O1 (includ-ing the O139 serotype) was identified from cultured isolates.

Overall, the proportional age distribution of outbreak af-fected case populations pooled from eight investigations was25%, 13%, 16%, 18%, 8%, 7%, and 3% for the ages� 5,5–9, 10–19, 20–29, 30–39, 40–49, and� 50 years, respec-tively. The overall mean age of outbreak cases was 21 years(95% CI for mean� 19–24), ranging from�1 to 80 years.However, mean age varied significantly (P � 0.0001) be-tween outbreaks, from a low of 14 years (95% CI for mean� 10–18), ranging from 1 to 80, for the Bandung/Kuningan,Java outbreak of 1997, to a high of 33 years (95% CI formean� 23–43), ranging from 2 to 80, for the Padang, Su-matra outbreak of 1998 (95% CI for difference betweenmeans� 10–29). The overall male-to-female ratio for out-break cases was 1:1.1.

Anti-microbial susceptibility ofV. cholerae O1 isolateswas 100% for all drug challenges (ampicillin, chloramphen-icol, tetracycline, trimethoprim-sulfamethoxazole, ceftria-xone, ciprofloxacin, norfloxacin, and nalidixic acid) exceptfor colistin, for which resistance among 235 isolates was100%.

Hospital-based findings. Overall, 9% (609) of 6,882 stool


TABLE 1Investigated diarrheal outbreaks in Indonesia, 1993–1999

Year Region SiteNo. ofsample

Age (yr)

Mean Range M:F

Percent positive for:

Vibrio choleraOgawa

S %

Vibrio choleraInaba

S % Period

1993 JavaIrian Jaya

GarutBiak

8729

NANA

NANA

NANA

299

3331

––

––

SeptemberNovember

1994 JavaJavaNusa TenggaraSumatraKalimantan

CiamisJakartaKupangPalembangPontianak

1282661280

NANANANANA

NANANANANA

NANANANANA

4585

14

336

214218

––––6

––––

7.5

OctoberSeptemberFebruaryOctoberSeptember

1995

1996

Nusa TenggaraIrian JayaIrian JayaSumatra

P. SumbaTimikaTimika 1Aceh

16355136

24NANA17

2–54NANA

2–60

0.6:1NANA

0.9:1

3253

26

19499

72

––––

––––

MarchMayJulyMarch

1997

19981999

JavaJavaSumatraKalimantanSumatraSulawesi

Bandung/KuninganTangerangPadang/S. Penuh Jmb.SamarindaPadangTakalar

881338542267

141526263323

1–802–401–771–732–801–70

1.3:11:1

0.7:10.8:10.8:10.8:1

373

111949

442529391813

––––––

––––––

AprilJuneJulySeptemberMarchMarch

TABLE 2Hospital-based cholera surveillance in Indonesia, 1993–1999

Isolate RegionMedan

(n � 649)Batam

(n � 272)Pontianak

(n � 1218)Jakarta

(n � 1423)Denpasar

(n � 2492)Padang

(n � 265)Makassar(n � 632)

Vibrio cholera Ogawa Culture positiveMean age (yr)

RangeM:F

324.6 � 3.4(n � 22)

1–131.5:1

(n � 28)

00

00

1613.3 � 15.0

(n � 11)1–502.2:1

(n � 16)

19128.8 � 12.6(n � 183)

2–820.8:1

(n � 182)

25325.9 � 18.8

(n � 19)1–861.4:1

(n � 207)

2625.0 � 18.2

(n � 20)1–650.7:1

(n � 26)

5722.1 � 19.1

(n � 50)1–821.5:1

(n � 52)Vibrio cholera Inaba Culture positive

Mean age

RangeM:F

114.6 � 3.4(n � 11)

1–100.8:1

(n � 11)

00

00

00

00

118.0 � 0(n � 1)18–18

0:1(n � 1)

242.5 � 24.7

(n � 2)25–60

1:1(n � 2)

00

00

00

00

specimens obtained from eight surveillance sites in Sumatra,Bali, Kalimantan, Sulawesi, and Java, representing acute,sporadic cases of debilitating diarrheal disease, were culturepositive for V. cholerae: 589 (9%) for O1 and 20 (� 1%)for non-O1 strains (Table 2). Significant (P � 0.0001) pro-portional variability inV. cholerae O1 representation amongrectal swab samples was recognized from different hospitalssites, ranging from 13% (191 of 1,423) in Jakarta, Java to0% of 272 from Batam, with a mean of 7% (95% CI for themean� 2.66–11.7). The largest number ofV. parahaemo-lyticus isolates (70) came from Bali, but the largest propor-tion relative to the overall collections came from Makassar(3% of 554). Ogawa serotype was recognized as the prin-cipal (98%) one amongV. cholerae O1 isolates, with a neg-ligible amount of Inaba. This mixture of Ogawa and Inabaserotypes was consistent at all hospital sites except in Me-dan, where Inaba accounted to 24% of allV. cholerae O1serotype. Additionally,V. parahaemolyticus was culturedfrom 2% (121) of the rectal swabs. Finally,V. cholerae non-O1 was cultured from rectal swabs reflecting sporadic casesof diarrheal disease throughout Indonesia: 12 from Bali, twofrom Padang, three from Jakarta, two from Makassar, and

one from Medan. None of the non-O1 isolates proved pos-itive for the V. cholerae non-O1, O139 serotype. Notably,no pathogenic vibrionaceae was isolated from 272 rectalswab specimens collected from Batam.

The overall mean age of patients from whomV. choleraeO1, V. cholerae non-O1, andV. parahaemolyticus isolateswere cultured was 25 years (95% CI for the mean� 23–24), 35 years (95% CI for the mean� 22–47), and 38 years(95% CI for the mean� 35–41), respectively. Diarrheal cas-es that proved ‘‘other than’’ cholera by culture method av-eraged 35 years of age (95% CI for mean� 29.8–39.5).There was significant (P � 0.001) geographic variability inmean age by hospital sites forV. cholerae O1, ranging fromfive years (95% CI for mean� 3.43–5.78) in Medan to 29years (95% CI for mean� 26.9–30.5) in Jakarta. Overalldifferences in gender case representation, expressed as male-to-female ratios involving diarrheal episodes of biotypesV.cholerae O1 (1.1:1),V. cholerae non-O1 (1.4:1),V. para-haemolyticus (1:1), and non-Vibrio bacterial pathogens andviral agents (1.1:1) showed little variation. ForV. choleraeO1 in particular, sex ratios differed from 0.8:1 in Jakarta to1:1.5 in Medan.


There was noin vitro drug resistance associated with the589 V. cholerae O1 isolates tested, except for colistin(100%). A similar antibiotic resistance profile was identifiedfor V. cholerae non-O1 andV. parahaemolyticus relative tocolistin: 83% of 20 isolates and 69% of 121 isolates, re-spectively. However, anti-microbial susceptibility was ob-served in 100% of the isolates for chloramphenicol, tetra-cycline, trimethoprim-sulfamethoxazole, ceftriazone, cipro-floxacin, norfloxacin, and nalidixic acid, whereas 30% ofV.cholerae non-O1 and 9% ofV. parahaemolyticus isolateswere found to be resistant to ampicillin.

Climatic and seasonal influences. Epidemic V. cholerae.Relatively low rainfall was recorded during outbreak periodsof V. cholerae in the western portion of Indonesia, exceptfor Sumatra, where there was no observed correlation be-tween rainfall and the four instances of epidemic occurrence.In Kalimantan, however, the mean cumulative rainfall duringthe two identified outbreak months was significantly (P �0.0001) less than for the non-outbreak months: 13 mm (rang-ing from 11 mm to 14 mm) versus 194 mm (ranging from2 mm to 331 mm). Similarly, the cumulative mean rainfallduring the five recognized outbreak periods (35 mm, rangingfrom 5 mm to 89 mm) in Java was significantly less thanfor the non-outbreak months (143 mm, ranging from 0 mmto 384 mm). East of this region, beyond the original 1863–1880 geographic/ecologic archipelago divide referred to asWallace’s Line20 (Figure 1), outbreaks were more, rather thanless, likely to occur during periods of heavy rainfall. Themean cumulative rainfall totals for outbreak versus non-out-break months varied substantially in Nusa Tenggara and Su-lawesi: 317 mm versus 119 mm (P � 0.05) and 385 mmversus 177 mm (P � 0.09), respectively. Finally, seasonalityassociated with outbreak occurrence was recognized assomewhat area specific in that two of four outbreaks occur-ring in Sumatra took place in March (1995 and 1997), fiveof seven in Kalimantan (1994 and 1997) and Java (1993,1994, and again in 1994) during September/October/Novem-ber, and three of three in Nusa Tenggara (1993 and 1994)and Sulawesi (1998) in March. There was less evidence ofseasonal clustering of outbreaks from Papua (Figure 2 A–F).

Sporadic V. cholerae. In Sumatra (Medan), negligible var-iability in rainfall over the 64 months of hospital-based sur-veillance precluded analysis relative to sporadic diarrhea at-tributed toV. cholerae. The only instance (September 1977)in which sporadicV. cholerae cases were detected in largenumbers, 16 cases from West Kalimantan (Pontianak), oc-curred when monthly rainfall totaled only 14 mm, comparedwith a cumulative monthly mean of 196 mm for the other81 months monitored (P � 0.0001). In the relatively shortperiod (42 months) of sporadic disease surveillance fromJava (Jakarta), there was evidence that notable spikes of spo-radic V. cholerae cases may have been a function of lowrainfall, whereas in more eastern Nusa Tenggara (Denpasar,Bali) and Sulawesi (Makassar), the relationship betweenrainfall and increases in sporadic case episodes ofV. chol-erae was less apparent (Figure 2 A–F).

However, two of the four outbreaks investigated from thisregion did occur during the month of March, both in 1996and 1998. In Kalimantan, the mean cumulative rainfall dur-ing the two identified outbreak months was significantly less

than for the non-outbreak months: 13 mm versus 194 mm.Notable is that both outbreaks also occurred during Septem-ber (1994 and 1997). Similarly, outbreak episodes in Javashared the same climatic and monthly characteristics withKalimantan in that cumulative rainfall (35 mm) averagedsignificantly less than for non-outbreak months, and three ofthe five described outbreaks took place during a September/October (1993 and 1994) temporal window (Figure 2 A–F).

Temporal relationships between 1.) sporadic and epi-demic V. cholerae and 2.) non-V. cholerae and V. cholerae.A pronounced temporal correspondence was evident be-tween epidemic and sporadicV. cholerae from Kalimantan,Java and Nusa Tenggara. Outbreak episodes were generallyframed against upward spikes of sporadic case detection.However, there was no observed temporal association be-tween epidemic and sporadic occurrence in Sumatra and Su-lawesi (Figure 2 A–F).

Although the small number of sporadicV. cholerae casesrelative to non-V. cholerae diarrheal episodes precludedquantitative comparative analysis of trends, patterns in Su-matra and Java parallel each other. Similarly, although lessobvious, was the pattern of occurrence observed in Kali-mantan, Nusa Tenggara, and Sulawesi.

DISCUSSION

Comprehensive surveillance for epidemic and sporadic di-arrheal case detection yielded noV. cholerae non-O1 of theO139 serotype. As late as 1995,V. cholerae O139 serotypewas feared to be an unstoppable juggernaut, displacing thedominant El Tor cholera biotype on its easterly progressionacross Southeast Asia.21 Indeed, an early report warned,‘‘Given the rapid spread ofV. cholerae O139 throughout andbeyond the Indian subcontinent, the pandemic potential ofthese strains seems assured’’.8 In Indonesia, this conclusionwas drawn against an environmental background alreadypredisposed to epidemic and endemicV. cholerae El Torbiotype, namely a poorly developed water sanitary infra-structure.12 However, such supposition has not been borneout in Indonesia, as reflected in our surveillance findings,nor elsewhere in the region.22

Outbreak investigation as an integral component of sur-veillance strategy provided a unique opportunity to identifythe cause of epidemic diarrheal disease. Most notable wasthe ubiquitous predominance of cholera, specifically theOgawa serotype, in epidemics throughout the archipelago.Comparative outbreak data from other countries/regions aresparse, since epidemic occurrence has not been investigatedin a systematic manner as part of a coordinated surveillanceactivity, particularly in developing areas. Surveillance find-ings presented in this report arm Indonesian health authori-ties with important etiologic information for mounting ap-propriate preventive and therapeutic actions, principally inpresumptive cholera outbreaks, in the absence of promptconfirmatory laboratory results. The findings also facilitateappropriate clinical case treatment and management strate-gies, as well as outbreak containment measures. Addition-ally, pre-emptive cholera vaccine (constructed for the Ogawaserotype) intervention in the early phases of outbreaks ofexplosive diarrhea may be warranted.

As with epidemic surveillance efforts, managed (hospital-


FIGURE 2. Climatic (rainfall) influences on epidemic and sporadicVibrio cholera diarrheal occurrence by location.

based) networks targeting sporadic cholera disease are stilla rarity in much of the developing world. Even along thegulf coast of the United States, an area historically plaguedby cholera, coordinated multi-stateVibrio surveillance wasonly initiated in 1989.23 In Indonesia, surveillance findings

show the proportional representation ofV. cholerae amongsporadic diarrheal episodes to be variable by location, al-though the El Tor, Ogawa serotype was ubiquitous. The ElTor biotype is spread by shedding of the organism into theenvironment from healthy persons, more so than the classical


FIGURE 2. continued.

biotype. This characteristic assures the predominance of ElTor relative to classical biotype, regardless of whether inepidemic or sporadic form.22,24

The relatively high proportion of sporadic cholera casesrecognized in Jakarta (13%) may reflect the notoriously pol-luted coastline along which much of the city’s human refuseis deposited. This provides a suitable warm, stagnant envi-ronment of high salinity favoring microbial growth and fe-

cal-oral spread via consumption of contaminated shellfish,fruits, and water.21 In another study, the rate of cholera inJakarta (1993–1997), identified from a ‘‘passive system’’ ofhospital-based surveillance for cholera vaccine evaluationpurposes, was 7,442 cholera cases/100,000 diarrheal epi-sodes, or 7%, of which all were the El Tor Ogawa serotype.12

In yet another study, targeting pediatric hospitalized diarrhe-al episodes in Jakarta in 1988–1989, less than 3% of cases


FIGURE 2. continued.


were attributed toV. cholerae.25 However, the comparabilityof these data may be limited because the proportional rep-resentation of cholera cases is likely a function of hospitalstudy geographic locations and associated catchment areaswithin Jakarta. Hospitals from northern Jakarta, where thehighest rates of cholera were observed, tend to serve a moreindigent population living in relatively poor environmentalsanitary conditions.

The importance of sporadic cholera occurrence in Bali(10%), second only to Jakarta, has also been highlighted bydocumented cases of acquired cholera in Singaporean andJapanese travelers to Bali in 1991.26 In contrast to findingsfrom three other surveys conducted in 1961–1980, 1965–1991, and 1975–1981 on travelers returning to Europe andNorth America, cholera rates were generally less than 1/100,000. Such vacations reflected few Bali travel destina-tions. The rate among Japanese tourists returning from Baliwas 13.1/100,000.27–29 However, these observations may beconfounded by a Japanese taste preference for local, rawseafood products. Nonetheless, this rate of imported cholerawas significantly higher than from for any other world-widetourist or business destination, regardless of the home regionsurveyed.26

Negligible drug resistance was identified among isolatesobtained from both epidemic and sporadic clinical settings.The exception to this was resistance to colistin, again, ininstances of both epidemic and sporadic cholera. Antimicro-bial resistance is becoming problematic in many areas of thedeveloping world, including Southeast Asia, because anti-microbial drugs are inexpensive and relatively unrestrictedin availability.30 In India, most cholera strains were shownto be resistance to co-trimoxazole, (trimethoprim-sulfameth-oxazole): 96% and 86% from Tamil Nadu and Calcutta, re-spectively, whereas 100% of isolates were susceptible to tet-racycline.31 Laboratory data from Bangladesh show high re-sistance (� 50%) in V. cholerae isolates to tetracycline andtrimethoprim-sulfamethoxazole, whereas negligible resis-tance was identified for doxycycline and diprofloxacin.30

High antimicrobial sensitivity from Indonesia did not allowfor analysis of trend over time.

Cholera occurrence has been shown to be a function ofpredisposing climatic influences such as water tempera-ture.32,33 Changes in local sea surface temperatures broughton by such weather anomalies as the El Nin˜o-Southern Os-cillation have been suggested to be related to the spread oftens of thousands of new cases of cholera.34,35 Increases insurface temperature brought on by El Nin˜o resulted in warm-er winter temperatures, which correlated with a doubling ofpediatric cases in Peru.36 Less clear has been the relationshipbetween rainfall and exposure opportunities associated withcholera risk. Certainly, heavy rains leading to excessiveflooding have the potential of contaminating water supplies,as described in numerous instances around the world.34,35

Conversely, subnormal rainfall may result in decreased di-lution and increased concentration ofV. cholerae bacteria,translating into increased risk of exposure.21 A similar phe-nomenon has been documented favoring epidemic transmis-sion of leptospirosis and hepatitis E virus.37,38

In Indonesia, differences in temperatures, particularlyalong coastal sections are slight, precluding causal analysis.Surveillance data coupled with rainfall measures afford a

unique opportunity to identify correlations between rainfalland cholera. In western Indonesia, in contrast with the east-ern part, epidemic and sporadicV. cholerae appear correlat-ed with periods of subnormal rainfall. A similar phenomenonwas discerned from surveillance findings reported from Ja-karta, where hospitalized cases peaked following and justprior to the ‘‘first’’ and ‘‘second’’ rainy seasons.39 Likewise,data extrapolated from hospital based surveillance in Jakarta(1993–1997) showed increases in detection of cholera casescoinciding with drier rather than wetter weather (Simanjun-tak C. and Punjabi N, unpublished data). However, this tem-poral relationship shifts in the more eastern portion of thearchipelago, where outbreak occurrence in fact appears dur-ing periods of heavy rainfall. Additionally, seasonal trendsin epidemic cholera vary with geography: September andOctober in the west, and February through April in the east.

The need for surveillance data, including targeted out-break findings, is essential in plotting the introduction andspread of endemic and pandemic cholera.40 Vigorous atten-tion to systematic, on-going collection efforts, particularly inmore developing areas traditionally associated with choleraoccurrence, requires a well coordinated and managed sur-veillance approach. This report describes the first such sys-tem implemented in Indonesia for recognizing the introduc-tion of the newV. cholerae non-O1, O139 serotype. Sur-veillance findings provided a unique geographic profile ofcholera, both in the epidemic and sporadic forms. Most no-table was the demonstration of cholera as the principal causeof epidemic diarrheal disease throughout the archipelago, theimplications of which are being factored into future inter-vention and control strategies.

Acknowledgments: We thank Colonel Patrick Kelly and CommanderMichael McCarthy (Global Emerging Infections System [GEIS]) fortheir cooperation in the completion of this research project.

Financial support: This work was supported by GEIS and STO.1B.

Disclaimer: The opinions and assertions contained herein are thoseof the authors and do not purport to reflect those of the U.S. Navyand Department of Defense, and Ministry of Health of the Republicof Indonesia.

Authors’ addresses: Cyrus H. Simanjuntak, Sumarjati Arjoso, andSri Astuti Soeparmanto, National Institute of Health Research andDevelopment, Ministry of Health, Jakarta, Indonesia. Wita Larasati,Maidy Putri, Murad Lesmana, Buhari A. Oyofo, Nono Sukri, RatnaP. Kusumaningrum, Narain H Punjabi, Decy Subekti, Carlos Lebron,James R. Campbell, and Andrew L. Corwin, U.S. Naval MedicalResearch Unit No. 2, Jakarta, Indonesia. Daswir Nurdin, Sub-Direc-torate of Diarrheal Disease, Directorate General of CommunicableDisease Control and Environmental Health Sanitation (P2M-PLP),Ministry of Health, Jakarta, Indonesia. Sudewa Djelantik and Su-karma, Sanglah Hospital, Denpasar, Bali, Indonesia. Sriwati, Wan-gaya Hospital, Denpasar, Bali, Indonesia. Muzahar and Azwin Lu-bis, Dr. Pirngadi Hospital, Medan, North Sumatra, Indonesia. HaroenSiregar, Labuang Baji Hospital, Makassar, South Sulawesi, Indone-sia. Bastiar Mas’ud and Mursad Abdi, Provincial Health Laboratory,Makassar, South Sulawesi, Indonesia. Atiek Sumardiati, ProvincialHealth Authority Office (KANWIL), Pontianak, West Kalimantan,Indonesia. Susanto Wibisana, Dr. Soedarso Hospital, Pontianak,West Kalimantan, Indonesia. Hendarwanto, Budi Setiawan, andWasis Santoso, Persahabatan Hospital, Jakarta, Indonesia. Eka Putraand Soritua Sarumpaet, Batam Authority Hospital, Batam, Riau, In-donesia. Hanifah Ma’ani, Dr. M. Djamil Hospital, Padang, West Su-matra, Indonesia.


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