Enteric fever burden in North Jakarta, Indonesia: a prospective, community-based study.

INTRODUCTION: We undertook a prospective community-based study in North Jakarta, Indonesia, to determine the incidence, clinical characteristics, seasonality, etiologic agent, and antimicrobial susceptibility pattern of enteric fever. METHODOLOGY: Following a census, treatment centre-based surveillance for febrile illness was conducted for two-years. Clinical data and a blood culture were obtained from each patient. RESULTS: In a population of 160,261, we detected 296 laboratory-confirmed enteric fever cases during the surveillance period, of which 221 (75%) were typhoid fever and 75 (25%)  were paratyphoid fever.  The overall incidence of typhoid and paratyphoid cases was 1.4, and 0.5 per thousand populations per year, respectively. Although the incidence of febrile episodes evaluated was highest among children under 5 years of age at 92.6 per thousand persons per year, we found that the burden of typhoid fever was greatest among children between 5 and 20 years of age. Paratyphoid fever occurred most commonly in children and was infrequent in adults. CONCLUSION: Enteric fever is a public health problem in North Jakarta with a substantial proportion due to paratyphoid fever. The results highlight the need for control strategies against enteric fever.

Etiology of acute, non-malaria, febrile illnesses in Jayapura, northeastern Papua, Indonesia.

We conducted a prospective, inpatient fever study in malaria-endemic Papua, Indonesia to determine non-malaria fever etiologies. Investigations included malaria blood films, blood culture, paired serologic samples analysis for dengue, Japanese encephalitis, leptospirosis, scrub typhus, murine typhus, and spotted fever group rickettsia. During 1997-2000, 226 patients (127 males and 99 females) 1-80 years of age (median age = 25 years) were enrolled. Positive blood cultures (n = 34, 15%) were obtained for Salmonella Typhi (n = 13), Escherichia coli (n = 8), Streptococcus pneumoniae (n = 6), Staphylococcus aureus (n = 5), Streptococcus pyogenes (n = 1), and Klebsiella pneumoniae (n = 1). Twenty (8.8%) patients were positive for leptospirosis by polymerase chain reaction. Eighty (35.4%) of 226 patients had ≥ 1 positive serology, diagnostic for 15 rickettsial and 9 dengue cases. Acid-fast bacilli-positive sputum was obtained from three patients. Most common confirmed (81 of 226, 35.8%)/suspected diagnoses were typhoid fever (n = 41), pneumonia (n = 29), leptospirosis (n = 28), urinary tract infections (n = 20), rickettsioses (n = 19), dengue (n = 17), and meningitis/encephalitis (n = 15). There were 17 deaths, 7 (46.7%) were caused by meningitis/encephalitis. Multiple positive serologic results and few confirmed diagnoses indicate the need for improved diagnostics.

Standard WHO-ORS versus reduced-osmolarity ORS in the management of cholera patients.

The study compared the safety and efficacy of an oral rehydration salts (ORS) solution, containing 75 mmol/L of sodium and glucose each, with the standard World Health Organization (WHO)-ORS solution in the management of ongoing fluid losses, after initial intravenous rehydration to correct dehydration. The study was conducted among patients aged 12-60 years hospitalized with diarrhoea due to cholera. One hundred seventy-six patients who were hospitalized with acute diarrhoea and signs of severe dehydration were rehydrated intravenously and then randomly assigned to receive either standard ORS solution (311 mmol/L) or reduced-osmolarity ORS solution (245 mmol/L). Intakes and outputs were measured every six hours until the cessation of diarrhoea. During maintenance therapy, stool output, intake of ORS solution, duration of diarrhoea, and the need for unscheduled administration of intravenous fluids were similar in the two treatment groups. The type of ORS solution that the patients received did not affect the mean serum sodium concentration at 24 hours after randomization and the relative risk of development of hyponatraemia. However, patients treated with reduced-osmolarity ORS solution had a significantly lower volume of vomiting and significantly higher urine output than those treated with standard WHO-ORS solution. Reduced-osmolarity ORS solution was as efficacious as standard WHO-ORS solution in the management of cholera patients. The results indicate that reduced-osmolarity ORS solution is also as safe as standard WHO-ORS solution. However, because of the limited sample size in the study, the results will have to be confirmed in trials, involving a larger number of patients.

Immunogenicity and safety of four different doses of Haemophilus influenzae type b-tetanus toxoid conjugated vaccine, combined with diphtheria-tetanus-pertussis vaccine (DTP-Hib), in Indonesian infants.

Widespread use of Haemophilus influenzae type b (Hib) conjugated vaccine in industrialized countries has resulted in a dramatic decline in the incidence of invasive Hib diseases, but the vaccine's cost has prevented its inclusion in basic immunization programs in developing countries. To overcome this problem, combination with diphtheria-tetanus-pertussis (DTP) vaccine or reduction in the dose of Hib vaccine has been proposed. To evaluate the immunogenicity and adverse reactions from lower doses of Hib-polyribosylphosphate (PRP) conjugated with tetanus toxoid (PRP-T), a double-blind study was conducted in Jakarta, Indonesia, and its suburbs. A total of 1048 infants 6 weeks to 6 months of age received three doses of DTP vaccine combined with the usual 10 microg dose or with a reduced dose of 5, 2.5 or 1.25 microg of PRP-T at two-monthly intervals. Antibodies were measured prior to the first dose and 4-6 weeks following the third dose. Adverse reactions were similar among all four groups. The only significant difference was a higher rate of irritability (p<0.02) and of temperature elevation >38 degrees C (p<0.009) after doses 1 and 2 in the lowest dose group (1.25 microg PRP-T) compared to the other groups. All participants tested had a 4-fold increase in antibodies against all DTP antigens. In addition, after a fourth booster dose of Hib, 99.6% of infants produced >or=0.15 microg/ml of antibody to Hib-PRP, and 96.4% showed levels >or=1.0 microg/ml after primary immunization, level that correlate with short- and long-term immunity, respectively. Antibody titers to the PRP antigen showed no significant differences among dosage groups with the exception of the 5.0 microg group, which had a significantly higher GMC than the 1.25 microg group (p<0.012). This study demonstrates that primary vaccination with half, one-fourth, or one-eighth of the usual dose of PRP-T, combined with DTP vaccine, produces protective immune responses, and has side effects that are comparable to DTP vaccination alone. In these lower dosages, PRP-T conjugate vaccine can lower vaccine costs to a level that is affordable for infant immunization programs in developing countries.

A multi-country cluster randomized controlled effectiveness evaluation to accelerate the introduction of Vi polysaccharide typhoid vaccine in developing countries in Asia: rationale and design.

Phase-III vaccine efficacy trials typically employ individually randomized designs intended to ensure that measurements of vaccine protective efficacy reflect only direct vaccine effects. As a result, decisions about introducing newly licensed vaccines into public health programmes often fail to consider the substantially greater protection that may occur when a vaccine is deployed in public health programmes, due to the combination of direct plus indirect vaccine protective effects. Vaccine total protection can be better evaluated with cluster randomized trials. Such a design was considered to generate policy relevant data to accelerate the rationale introduction of the licensed typhoid fever Vi polysaccharide (PS) vaccine in Asia by the Diseases of the Most Impoverished (DOMI) typhoid fever programme. The DOMI's programme multi-country study is one of the largest cluster randomized vaccine trials ever mounted in Asia, which includes approximately 200,000 individuals. Its main objective is to determine the effectiveness of a licensed Vi PS vaccine. The rationale and design of this study are discussed. Preliminary results are presented that determined the final planning of the trial before immunization. Important methodological and practical issues regarding vaccine cluster randomized designs are illustrated.

The burden of diarrhoea, shigellosis, and cholera in North Jakarta, Indonesia: findings from 24 months surveillance.

BACKGROUND: In preparation of vaccines trials to estimate protection against shigellosis and cholera we conducted a two-year community-based surveillance study in an impoverished area of North Jakarta which provided updated information on the disease burden in the area. METHODS: We conducted a two-year community-based surveillance study from August 2001 to July 2003 in an impoverished area of North Jakarta to assess the burden of diarrhoea, shigellosis, and cholera. At participating health care providers, a case report form was completed and stool sample collected from cases presenting with diarrhoea. RESULTS: Infants had the highest incidences of diarrhoea (759/1,000/year) and cholera (4/1,000/year). Diarrhea incidence was significantly higher in boys under 5 years (387/1,000/year) than girls under 5 years (309/1,000/year; p < 0.001). Children aged 1 to 2 years had the highest incidence of shigellosis (32/1,000/year). Shigella flexneri was the most common Shigella species isolated and 73% to 95% of these isolates were resistant to ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol and tetracycline but remain susceptible to nalidixic acid, ciprofloxacin, and ceftriaxone. We found an overall incidence of cholera of 0.5/1,000/year. Cholera was most common in children, with the highest incidence at 4/1,000/year in those less than 1 year of age. Of the 154 V. cholerae O1 isolates, 89 (58%) were of the El Tor Ogawa serotype and 65 (42%) were El Tor Inaba. Thirty-four percent of patients with cholera were intravenously rehydrated and 22% required hospitalization. V. parahaemolyticus infections were detected sporadically but increased from July 2002 onwards. CONCLUSION: Diarrhoea causes a heavy public health burden in Jakarta particularly in young children. The impact of shigellosis is exacerbated by the threat of antimicrobial resistance, whereas that of cholera is aggravated by its severe manifestations.

Diarrhoea episodes and treatment-seeking behaviour in a slum area of North Jakarta, Indonesia.

Visits to household during a census in an impoverished area of north Jakarta were used for exploring the four-week prevalence of diarrhoea, factors associated with episodes of diarrhoea, and the patterns of healthcare use. For 160,261 urban slum-dwellers, information was collected on the socioeconomic status of the household and on diarrhoea episodes of individual household residents in the preceding four weeks. In households with a reported case of diarrhoea, the household head was asked which form of healthcare was used first. In total, 8,074 individuals (5%)--13% of children aged less than five years and 4% of adults--had a diarrhoea episode in the preceding four weeks. The two strongest factors associated with a history of diarrhoea were a diarrhoea episode in another household member in the four weeks preceding the interview (adjusted odds ratio [OR] 11.1; 95% confidence interval [CI] 10.4-11.8) and age less than five years (adjusted OR 3.4; 95% CI 3.2-3.5). Of the 8,074 diarrhoea cases, 1,969 (25%) treated themselves, 1,822 (23%) visited a public-health centre (PHC), 1,462 (18%) visited a private practitioner or a private clinic, 1,318 (16%) presented at a hospital, 753 (9%) bought drugs from a drug vendor, and 750 (9%) used other healthcare providers, such as belian (traditional healers). Children with diarrhoea were most often brought to a PHC, a private clinic, or a hospital for treatment. Compared to children, adults with diarrhoea were more likely to treat themselves. Individuals from households in the lowest-income group were significantly more likely to attend a PHC for treatment of diarrhoea compared to individuals from households in the middle- and higher-income groups.

Antimicrobial resistance of bacterial pathogens associated with diarrheal patients in Indonesia.

The antimicrobial susceptibility patterns for 2,812 bacterial pathogens isolated from diarrheal patients admitted to hospitals in several provinces in the cities of Jakarta, Padang, Medan, Denpasar, Pontianak, Makassar, and Batam, Indonesia were analyzed from 1995 to 2001 to determine their changing trends in response to eight antibiotics: ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline, cephalothin, ceftriaxone, norfloxacin, and ciprofloxacin. Vibrio cholerae O1 (37.1%) was the pathogen most frequently detected, followed by Shigella spp. (27.3%), Salmonella spp. (17.7%), V. parahaemolyticus (7.3%), Salmonella typhi (3.9%), Campylobacter jejuni (3.6%), V. cholerae non-O1 (2.4%), and Salmonella paratyphi A (0.7%). Of the 767 Shigella spp. isolated, 82.8% were S. flexneri, 15.0% were S. sonnei, and 2.2% were S. dysenteriae (2.2%). The re-emergence of Shigella dysenteriae was noted in 1998, after an absence of 15 years. Shigella spp. were resistant to ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline. Salmonella typhi and Salmonella paratyphi A were susceptible to all antibiotics tested, while Salmonella spp. showed various resistance patterns according to species grouping. A small number of V. cholerae O1 were resistant to ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline; however, they were still sensitive to ceftriaxon, norfloxacin, and ciprofloxacin. Similar results were shown for V. cholerae non-O1. Campylobacter jejuni showed an increased frequency of resistance to ceftriaxone, norfloxacin, and ciprofloxacin, but was susceptible to erythromycin. This study shows that except for C. jejuni and V. parahaemolyticus, which appeared to be resistant to ciprofloxacin, the majority of the enteric pathogens tested were still susceptible to fluoroquinolones.

Transmission of epidemic dengue hemorrhagic fever in easternmost Indonesia.

In April 2001, a second suspected outbreak of dengue hemorrhagic fever in the easternmost region of Indonesia was investigated in Merauke, a town located in the southeastern corner of Papua, by the Indonesian Ministry of Health and the U.S. Naval Medical Research Unit No. 2. Principal case criteria of hemorrhagic disease provided for a study enrollment of 15 clinically acute and 37 convalescing subjects. Additionally, 32 comparable age/sex controls were selected from neighboring households. Laboratory diagnosis involved three testing methodologies: virus isolation by cell culture, a reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and serologic assays. Antibody (IgM) to dengue virus was detected in 27% of the acute clinical cases, 30% of the convalescing cases, and only 3% of the matched controls. Dengue 3 was the only viral serotype detected from acute serum samples by the RT-PCR. The mean +/- SD age of the acute and convalescing cases was 7.8 +/- 5.4 years. Overall hospital records accounted for 172 suspected outbreak cases, all urban residents of Merauke with no recent travel history outside the area. The estimated outbreak-associated case fatality rate among all suspected dengue cases was 1.2%. A seven-year retrospective review of hospital records in Merauke showed negligible disease reporting involving hemorrhagic disease prior to the outbreak.

Surveillance of bacterial pathogens of diarrhea disease in Indonesia.

Emerging or reemerging infections due to bacterial disease may be a local, regional or global problem. Bacterial acute gastroenteritis is a potential cause of substantial morbidity in travelers and deployed U.S. military personnel. A surveillance study was conducted over a two-year period in Indonesia among 6760 patients with debilitating diarrheal diseases. Of the 6,760 patients, 587 (9%) of the patient stools were positive for bacteria. The proportions of bacteria isolated from the 587 patients were: Shigella flexneri (39%), Salmonella spp. (26%), Vibrio spp. (17%), S. sonnei (7%), Campylobacter jejuni (4.4%), Salmonella typhi (3%) and S. dysenteriae (2.3%). Shigella flexneri was the most prevalent pathogen isolated, over Vibrio spp. No V. cholerae was isolated in the cities of Pontianak, Padang or Batam in Indonesia. Shigella dysenteriae reemergence was noted in Bali, Kalimantan, Batam and Jakarta after an absence of 15 years. Isolation of a high proportion of S. flexneri, and Vibrio spp. occurred during the rainy months. All bacterial isolates were susceptible to quinolones, with the exception of C. jejuni and Salmonella spp., which were resistant to ciprofloxacin, norfloxacin and nalidixic acid. Our findings highlight the decline of V. cholerae, the rise of S. flexneri and the reemergence of S. dysenteriae in Indonesia. The study also documents the emergence of quinolone-resistant Campylobacter spp. in the Indonesia archipelago.

The importance of leptospirosis in Southeast Asia.

The importance of leptospirosis in Southeast Asia was assessed in conjunction with other studies supported by the U.S. Naval Medical Research Unit No. 2 (US NAMRU-2), Jakarta, Republic of Indonesia. These included studies of hospital-based, acute clinical jaundice in Indonesia, Lao PDR, and Socialist Republic of Vietnam; nonmalarial fever in Indonesia; and hemorrhagic fever in Cambodia. Background prevalence estimates of leptospiral infection were obtained by a cross-sectional, community-based study in Lao PDR. Laboratory testing methods involved serology, microscopic agglutination test, and reverse-transcriptase polymerase chain reaction. Suggestive evidence of recent leptospiral infections was detected in 17%, 13%, and 3% of patients selected on the basis of non-hepatitis A through E jaundice, nonmalarial fever, and hemorrhagic fever (in the absence of acute, dengue viral infections). Leptospiral IgG antibody, reflective of prior infections, was detected in 37% of human sera, collected in Lao PDR. The predominant leptospiral serogroups identified from cases with clinical jaundice were Hurstbridge, Bataviae, and Icterohaemorrhagiae tonkini LT 96 69. Among the nonmalarial febrile cases, Bataviae was the most frequently recognized serogroup. Pyrogenes and Hurstbridge were the principal serogroups among the hemorrhagic fever case subjects. These findings further attest to the relative importance of clinical leptospirosis in Southeast Asia. The wide spectrum of clinical signs and symptoms associated with probable, acute, leptospiral infections contributes to the potential of significant underreporting.

Enteropathogens associated with acute diarrhea in community and hospital patients in Jakarta, Indonesia.

The prevalence of bacteria, parasite and viral pathogens in 3875 patients with diarrhea in community and hospital settings from March 1997 through August 1999 in Jakarta, Indonesia was determined using routine bacteriology and molecular assay techniques. Bacterial pathogens isolated from hospital patients were, in decreasing frequency, Vibrio cholerae O1, Shigella flexneri, Salmonella spp. and Campylobacter jejuni, while S. flexneri, V. cholerae O1, Salmonella spp. and C. jejuni were isolated from the community patients. V. cholerae O1 was isolated more frequently (P<0.005) from the hospital patients than the community patients. Overall, bacterial pathogens were isolated from 538 of 3875 (14%) enrolled cases of diarrhea. Enterotoxigenic Escherichia coli were detected in 218 (18%) of 1244 rectal swabs. A small percentage of enterohemorrhagic E. coli (1%) and of Clostridium difficile (1.3%) was detected. Parasitic examination of 389 samples resulted in 43 (11%) positives comprising Ascaris lumbricoides (1.5%), Blastocystis hominis (5.7%), Giardia lamblia (0.8%), Trichuris trichiura (2.1%) and Endolimax nana (0.5%). Rotavirus (37.5%), adenovirus (3.3%) and Norwalk-like virus (17.6%) were also detected. Antimicrobial resistance was observed among some isolates. Bacterial isolates were susceptible to quinolones, with the exception of some isolates of C. jejuni which were resistant to ciprofloxacin, nalidixic acid and norfloxacin. Data obtained from this community- and hospital-based study will enable the Indonesian Ministry of Health to plan relevant studies on diarrheal diseases in the archipelago.

Spectrum of vibrio species associated with acute diarrhea in North Jakarta, Indonesia.

Vibrio spp was isolated from 1024 (21.2%) of 4820 diarrhea patients admitted to a community hospital in North Jakarta from 1996 through 1998. Vibrio cholerae O1 (49.5%) and V. parahaemolyticus (30.1%) comprised the major species isolated, followed by V. cholerae non-O1 (16.9%), and V. fluvialis (9.4%). In 938 (19.4%) patients, Vibrio was found as single isolate. Multiple infections were detected in 86 (1.8%) patients. A small number of V. furnisii, V. metschnikovii, V. mimicus and V. hollisae were also isolated. No V. cholerae O139 was detected. The majority of patients with Vibrio spp. infections were adults between the ages of 20 to 45 years. No Vibrio spp. was isolated from infants <1 year old in this study. In vitro antibiotic susceptibility testing revealed no antibiotic resistance associated with the 507 V. cholerae O1 isolates tested, except for colistin (100%). These data implicate Vibrio spp. as a major cause of diarrhea in this region.