Shigella spp. Surveillance in Indonesia: the Emergence or Reemergence of S. dysenteriae.

From June 1998 through November 1999, Shigella spp. were isolated in 5% of samples from 3,848 children and adults with severe diarrheal illness in hospitals throughout Indonesia. S. dysenteriae has reemerged in Bali, Kalimantan, and Batam and was detected in Jakarta after a hiatus of 15 years.

Shigella spp. cause acute, debilitating diarrheal disease in humans (particularly young children) worldwide (1). In developing countries, where affected populations are immunologically compromised by poor nutrition and background infections, deaths attributed to shigellosis are common. Four Shigella species are recognized as pathogenic to humans: S. sonnei, S. boydii, S. flexneri, and S. dysenteriae. Both S. sonnei and S. boydii are usually associated with mild illnes of short duration in which the stool may be watery or bloody (2). S. flexneri is generally more severe, lasts longer, and causes blood in stools S. dysenteriae, particularly type 1, causes the most severe diarrheal illness, reflected in high death rates (3). S. flexneri is a principal cause of endemic shigellosis in many developing countries, while shigellosis in both endemic and epidemic form has been attributed to S. dysenteriae type 1 (2). Changes in the worldwide epidemiology of Shigella spp. have been documented in the last decades of the 20th century. In industrialized regions, S. dysenteriae was first replaced by S. flexneri, and then by S. sonnei (4,5); S. flexneri remains the leading cause of shigellosis in most of the developing world (2,6-8).

In Indonesia, the last cases of S. dysenteriae diarrhea were reported in 1985 from Jakarta (8,9). This report, based on a study using a systematic surveillance approach that included a standardized detailed bacteriologic examination, provides an Indonesia-wide geographic profile of Shigella spp.

The Study

From June 1998 through November 1999, a total of 3,848 children and adults seeking treatment for debilitating diarrheal disease were identified from eight hospital sites in Medan, North Sumatra; Padang, West Sumatra; Batam, Riau Island; Jakarta, Java Island; Denpasar, Bali (two hospitals); Pontianak, West Kalimantan; and Makassar, South Sulawesi. Rectal swabs were obtained from patients in the study before antibiotic therapy was administered. Specimens were placed in Cary-Blair transport medium, held at 4 [degrees] C, and sent on wet ice within 2 to 4 days after collection to the U.S. Naval Medical Research Unit No. 2, Jakarta. Bacteriologic evaluation was performed by standard culture method (10). Species was confirmed by using API 20E (Biomerieux, Marcy l'Etoile, France) and slide agglutination with specific Shigella antisera (Difco Laboratories, Detroit, MI). Antibiotic susceptibility testing was accomplished by the disk-diffusion method (11).

Overall, bacterial isolates of Shigella spp. were identified in 180 (5%) of 3,848 rectal swabs. The proportional contribution of S. flexneri, S. sonnei, and S. dysenteriae among shigellosis cases was 80%, 12%, and 8%, respectively. No S. boydii was detected. The percentage of representation among the three species did not vary substantially by geographic location. Notable was the reemergence of S. dysenteriae in Bali, West Kalimantan, and Batam, as well as in Jakarta after a hiatus of [is greater than] 15 years (Table). The proportional distribution of S. flexneri, S. sonnei, and S. dysenteriae for the 5- to 12-year-old and [is greater than] 12-year-old groups was similar. There appeared to be no consistency in the seasonal distribution patterns of Shigella spp. (Figure). S. flexneri was the most frequently isolated organism, followed by S. sonnei and S. dysenteriae.

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Other enteric pathogens isolated were Salmonella spp. (95, 2.5%), Vibrio cholerae (80, 2.1%), V. parahaemolyticus (38, 1%), V. cholerae non-O1 (9, 0.2%), and Campylobacter spp. (27, 0.7%). Enterotoxigenic Escherichia coli were detected in 225 (18.1%) of 1,240 specimens tested by the GM1 enzyme-linked immunoassay (12). Of the 541 specimens examined for rotavirus in the age groups [is less than or equal to] 5 years, 191 (35.3%) were positive. Tests to detect parasites showed Ascaris lumbricoides in 8 (2%), Blastocystis hominis in 23 (5.6%), Giardia lamblia in 3 (0.7%), and Endolimax nana in 2 (0.5%) of 407 stool specimens examined.

Clinical presentations associated with non S. dysenteriae included abdominal cramping (79%), vomiting (56%), and fever (48%); for S. dysenteriae, percentages of the same symptoms were 100%, 64%, and 27%, respectively. Stool samples from patients with S. flexneri, S. sonnei, and S. dysenteriae were principally characterized by mucus in the absence of blood (45%) or mucus and visible blood (27%).

Overall, antibiotic susceptibility patterns showed greater resistance to ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline for S. flexneri (85%, 59%, 82%, and 98%, respectively, from examination of 144 isolates) and S. sonnei (32%, 79%, 37%, and 100%, respectively, from examination of 22 isolates), than for S. dysenteriae (36%, 43%, 7%, and 29%, respectively, from examination of 14 isolates). There was no evidence of resistance to ceftriaxone, norfloxacin, ciprofloxacin, or nalidixic acid, regardless of Shigella species. Antimicrobial resistance was only apparent among isolates obtained from Jakarta, Bali, and Pontianak.

Conclusions

Our study showed that a substantial proportion (5%) of acute, debilitating diarrheal illness throughout Indonesia can be ascribed to shigellosis; moreover, S. dysenteriae was documented from various geographic locations. Both findings suggest that greater attention should be paid to highlighting the endemic and epidemic community impact of this pathogen and that laboratory detection capabilities need to be enhanced. Recognition of emerging and or reemerging disease pathogens requires reliable baseline and ongoing surveillance data.

Shifting patterns of antimicrobial-drug resistance, particularly in much of the developing world, are generally a function of overuse and misuse of antibiotic drug therapies. The spread of drug resistance is the result of poorly regulated and enforced policies. Resistance to nalidixic acid (100%) among isolates of S. dysenteriae has been reported in Bangladesh (13); however, we found no such resistance. Nevertheless, other data from Indonesia indicate increasing resistance. In a previous report (81, 72% of Shigella spp. were resistant to tetracycline, but less than 30% were resistant to chloramphenicol, trimethroprimsulfamethoxazole, or ampicillin. Previous studies from Bangladesh and Tanzania (13,6) showed that almost all tested isolates were resistant to the antibiotics used for treatment. Similar antimicrobial resistance profiles for Shigella spp. were reported from Thailand (14), where high resistance to ampicillin, trimethroprimsulfamethoxazole, chloramphenicol, and tetracycline was documented.

The reemergence of S. dysenteriae from several locations in Indonesia should prove cause for concern to health officials, particularly in monitoring acute, debilitating diarrheal outbreaks. The epidemic potential attributed to S. dysenteriae, as documented in Central America, Asia, and Africa, in conjunction with notably high death rates, warrants close attention to this reemerging pathogen in Indonesia (13,15,16).

This research was supported by the U.S. Naval Medical Research and Center Command (work unit numbers 61101A-00101.EAX 2401 and 623002A810.0101.HIX.3411).

Dr. Subekti is a microbiologist and medical research scientist who heads the Molecular Microbiology Section of the Enteric Diseases Program at U.S. Naval Medical Research Unit No. 2, Jakarta, Indonesia.

References

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(8.) Subekti D, Lesmana M, Komalarini S, Tjaniadi P, Burr D, Pazzaglia G. Enterotoxigenic Escherichia coli and other causes of infectious pediatric diarrheas in Jakarta, Indonesia. Southeast Asia J Trop Med Public Health 1993;24:420-4.

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(12.) Svennerholm AM, Wikstrom M, Lindbland M, Holmgren J. Monoclonal antibodies against E. coli heat stable toxin (Sta) and their use in a diagnostic ST ganglioside GM1-enzyme-linked immunosorbent assay. J Clin Microbiol 1986;24:585-90.

(13.) Sack RB, Rahman M, Yunus M, Khan EH. Antimicrobial resistance in organisms causing diarrheal disease. Clin Infect Dis 1997;24 (Suppl 1):S102-S105.

(14.) Moolasart P. Shigellosis in Thai people. JAMA Southeast Asia 1994;5:9-10.

(15.) Malakooti MA, Alaii J, Shanks GD, Phillips-Howard PA. Epidemic dysentery in western Kenya. Trans R Soc Trop Med Hyg 1997;91:541-3.

(16.) Mendizabal-Morris CA, Malta L, Gangarosa EJ, Guzman G. Epidemic Shiga-bacillus dysentery in Central America. Derivation of the epidemic and its progression in Guatemala, 1968-69. Am J Trop Med Hyg 1971;20:927-33.

Decy Subekti,(*) Buhari A. Oyofo,(*) Periska Tjaniadi,(*) Andrew L. Corwin,(*) Wita Larasati,(*) Maidy Putri,(*) Cyrus H. Simanjuntak,([dagger]) Narain H. Punjabi,(*) Jufri Taslim,([double dagger]) Budhi Setiawan,([sections]) Anak Agung G.S. Djelantik,([paragraph]) Luh Sriwati,(**) Atiek Sumardiati,([dagger][dagger]) Eka Putra,([double dagger][double dagger]) James R. Campbell,(*) and Murad Lesmana(*)

(*) U.S. Naval Medical Research Unit No. 2, Jakarta, Indonesia; ([dagger]) National Institute of Health Research and Development, Jakarta, Indonesia; ([double dagger]) Municipal Health Service, North Jakarta, Indonesia; ([sections]) Friendship Hospital, Jakarta, Indonesia; ([paragraph]) Sanglah Hospital, Denpasar, Bali, Indonesia; (**) Wangaya Hospital, Denpasar, Bali, Indonesia; ([dagger][dagger]) Regional Office of Health Ministry, Pontianak, Indonesia; and ([double dagger][double dagger]) Otorita Hospital, Batam, Indonesia

Address for correspondence: LCDR Buhari A. Oyofo, American Embassy Jakarta, Unit 8132 NAMRU TWO, FPO, AP 965208132, Indonesia; telephone: [phone]; fax: [phone]; e-mail: [e-mail].