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Mortality and morbidity associated with cholera acquired in a modern endemic setting have not been well defined. In Dhaka, Bangladesh from 1986 to 1996, we found that causative agents of cholera shifted over time, varying by serogroup, biotype, and serotype. At the International Centre for Diarrhoeal Disease Research (ICDDR,B: Centre for Health and Population Research) in 1996, 19,100 cholera patients were treated, 887 (4.6%) were admitted, and 33 died (mortality rate = 3.7% of cholera inpatients, 0.14% of all cholera patients). When cholera inpatients who were discharged improved were compared with those who died, bacteremia (odds ratio [OR] = 10.5, 95% confidence interval [CI] = 2.9-37.9), radiographic evidence of pneumonia (OR = 3.1, 95% CI = 1.2-7.7), and acidosis as estimated by the serum bicarbonate value (OR = 0.893, 95% CI = 0.825-0.963) were independently associated with death by multivariate analysis. Pneumonia was the leading cause of death and accounted for two-thirds of all deaths among individuals with cholera in this study. Death in hospitalized patients with cholera acquired in a modern endemic setting is, therefore, extremely rare, and most frequently due to concomitant infection, especially pneumonia.

Summary Background Effective antimicrobial therapy can reduce the duration and volume of cholera diarrhoea by half. However, such treatment is currently limited by Vibrio cholerae resistance to the drugs commonly prescribed for cholera, and by the difficulties involved in the administration of multi-drug doses under field conditions. Because of its favourable pharmacokinetics we thought it likely that single-dose ciprofloxacin would be effective in the treatment of cholera. Methods In this double-blind study treatment was either a single 1 g oral dose of ciprofloxacin plus doxycycline placebo, or a single 300 mg oral dose of doxycycline plus ciprofloxacine placebo. 130 moderately or severely dehydrated men infected with V cholerae O1 and 130 infected with V cholerae O139 were randomly assigned treatment. Patients stayed in hospital for 5 days. We measured fluid intake and stool volume every 6 h, and a sample of stool for culture was obtained daily. The primary outcome measures were clinical success-the cessation of watery stool within 48 h; and bacteriological success-absence of V cholerae from cultures of stool after study day 2. Findings Among patients infected with V cholerae O1, treatment was clinically successful in 62 (94%) of 66 patients who received ciprofloxacin and in 47 (73%) of 64 who receive doxycycline (difference 21% [95% CI 8–33]); the corresponding proportions with bacteriological success were 63 (95%) and 44 (69%) (27% [14–39]). Among patients infected with V cholerae O139, treatment was clinically successful in 54 (92%) of 59 patients who received ciprofloxacin and in 65 (92%) of 71 who received doxycycline ( V cholerae O1 or O139. All but one of the V cholerae O1 and all of the O139 isolates were susceptible in vitro to doxycycline, whereas 48 (37%) of the V cholerae O1 isolates and none of the O139 isolates were resistant to tetracycline. Treatment clinically failed in 14 (52%) of 27 doxycycline-treated patients infected with a tetracycline-resistant V cholerae O1 strain, compared with three (8%) of 37 patients infected with a tetracycline-susceptible strain (44% [23–65]). Interpretation Single-dose ciprofloxacin is effective in the treatment of cholera caused by V cholerae O1 or O139 and is better than single-dose doxycycline in the eradication of V cholerae from stool. Single-dose ciprofloxacin may also be the preferred treatment in areas where tetracycline-resistant V cholerae are common. In V cholerae , in-vitro doxycycline susceptibilities are not a useful indicator of the in-vivo efficacy of the drug.

Background and Objective. Alterations in consciousness, including seizures, delirium, and coma, are known to occur during Shigella infection. Previous reports have suggested that febrile convulsions and altered consciousness are more common during shigellosis than with other childhood infections. Those reports, however, have been from locations where S dysenteriae type 1 was not common, thus making it difficult to assess the specific contribution that S dysenteriae type 1 infection, and Shiga toxin, might make to the pathogenesis of altered consciousness in children with shigellosis. In this study we seek to determine the prevalence, risk factors, and outcome of altered consciousness in children with shigellosis in Bangladesh, a country where infection with all four species of Shigella is common. We particularly focus on the importance of metabolic abnormalities, which we have previously shown to be a common feature of shigellosis in this population.Methods. This study was conducted at the Diarrhea Treatment Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh in Dhaka, Bangladesh, which provides care free of charge to persons with diarrhea. During 1 year, a study physician identified all inpatients infected withShigella by checking the logs of the Clinical Microbiology Laboratory daily. Study physicians obtained demographic and historical information by reviewing the patient charts and by interviewing patients, or their parents or guardians, to confirm or complete the history of illness obtained on admission. Patients were categorized as being conscious or unconscious based on a clinical scale; having a seizure documented in the hospital; or having a seizure by history during the current illness that was not witnessed by medical personnel. Patient outcome was classified as discharged improved, discharged against medical advice, transferred to another health facility, or died in the Treatment Centre. Laboratory examinations were ordered at the discretion of the attending physician; all such information was recorded on the study form. Clinical management was by the attending physician. Factors independently predictive of a documented seizure, or of unconsciousness, were determined using a multiple logistic regression analysis. For this analysis variables associated with unconsciousness or a documented seizure in the analysis of variance or χ2 analyses were entered into the regression equation and eliminated in a backward stepwise fashion if the probability associated with the likelihood ratio statistic exceeded .10.Results. During this 1-year study, 83 402 persons with diarrhea came to the Treatment Centre for care, and 6290 patients were admitted to the inpatient unit. Shigella was isolated from a stool or rectal swab sample of 863 (13.7%) of the inpatients.Seventy-one (8%) of the inpatients with shigellosis were ≥15 years old; 61 (86%) were conscious; 10 (14%) were unconscious; none had either a documented seizure or a seizure by history during this illness. Seven hundred ninety-two patients were Clinical features that are known to cause altered consciousness—fever, severe dehydration, hypoglycemia, hyponatremia, or meningitis—were present in 38 (92.7%) of the 41 patients in whom a seizure was witnessed and in 67 (91.8%) of the 73 patients who were unconscious. Nineteen (46.3%) of the patients who had a seizure documented had two of these five features, 4 (9.8%) had three, and 1 (2.4%) had four of these features; among unconscious patients two of the features were present in 25 (34.2%) and three in 2 (2.7%). In a multiple regression analysis factors independently associated with a documented seizure in patients Patients who were unconscious (death rate 48%) or had a documented seizure (death rate (29%) were at significantly increased risk of death compared with conscious patients (death rate 6%) or patients who had a seizure by history (no deaths). There were no deaths among patients 15 years or older.Conclusions. This study had a substantially larger number of patients than any of the previously published clinical studies on seizures or altered consciousness during shigellosis. The results of this study suggest that seizures in shigellosis in the population studied occur in an age group—children 5 years of age or less—known to be at increased risk of seizures from fever or metabolic alterations. This study also suggests that, at least in the majority of these inpatients, altered consciousness is not related to Shiga toxin, which is produced in appreciable amounts only by the S dysenteriae type 1 serotype. Direct infection of the central nervous system also was not a major cause of altered consciousness in these patients. Both diminished consciousness and documented seizures are associated with a poor outcome in Bangladeshi children with shigellosis. Prompt attention to fever reduction and metabolic alterations may help reduce these potentially lethal complications, but often this is not easy to accomplish in the poor countries where shigellosis is endemic.

Summary Background Infections caused by multiply resistant Shigella species are a major cause of childhood morbidity and mortality in Third World countries. The fluoroquinolone agent ciprofloxacin is active in vitro against these strains of bacteria, but has not been routinely used to treat acute childhood infections because of concern that quinolones may cause arthropathy in children. We undertook a randomised double-blind study to test the effects of ciprofloxacin treatment in children with shigella dysentery. Methods We compared the efficacy and toxic effects of ciprofloxacin suspension (10 mg/kg every 12 h for 5 days, maximum individual dose 500 mg) with those of pivmecillinam tablets (15–20 mg/kg every 8 h for 5 days, maximum individual dose 300 mg). We enrolled 143 children aged 2–15 years with dysentery of 72 h or less duration. Patients stayed in hospital for 6 days, and were followed up 7, 30, and 180 days after hospital discharge. Joint symptoms and function were assessed daily for 6 days. Clinical success was defined as the absence of frank dysentery on day 3, and on day 5 no bloody-mucoid stools, one or no watery stool, six or fewer total stools, and no fever. If no shigella were isolated from faecal samples on day 3 or thereafter, treatment was judged bacteriologically successful. Findings 13 patients were excluded since they did not meet eligibility criteria; 10 withdrew before day 5. Thus 120 patients (60 in each group) completed the study. Treatment was clinically successful in 48 (80%) of 60 patients who received ciprofloxacin and in 39 (65%) of 60 patients who received pivmecillinam (p=0·10). Treatment was bacteriologically successful in all of the patients receiving ciprofloxacin, and in 54 (90%) of the patients receiving pivmecillinam (p=0·03). Joint pain after treatment began in 13 (18%) of 71 patients who received ciprofloxacin and 16 (22%) of 72 patients who received pivmecillinam (p>0·2), and no patient had signs of arthritis. Interpretation In our trial, ciprofloxacin suspension and pivmecillinam had the same clinical efficacy. Ciprofloxacin had greater bacteriological efficacy and was not associated with the development of arthropathy. We conclude that ciprofloxacin is an effective and safe drug for use in multiply resistant childhood shigellosis.

Treatment of shigellosis is currently limited by the high prevalence of multidrug-resistant strains of Shigella. Objective: To determine the efficacy of azithromycin in the treatment of shigellosis. Design; Randomized, double- blind clinical trial. Setting: Diarrhea treatment center in Dhaka, Bangladesh. Patients: 70 men with shigellosis that had lasted 72 hours or less. Interventions: Patients stayed in the hospital for 6 days. Thirty-four patients were randomly assigned to receive 500 mg of azithromycin on study day 1, followed by 250 mg once daily for 4 days; 36 patients were assigned to receive 500 mg of ciprofloxacin every 12 hours for 5 days. Measurements: Clinical treatment failure was considered to have occurred if frank dysentery persisted for 72 hours after therapy began or if on study day 5 a patient had more than six stools, had any bloody-mucoid stools, had more than one watery stool, or had an oral body temperature exceeding 37.8 °C. Bacteriologic treatment failure was considered to have occurred if Shigella strains could be isolated from a stool sample after study day 2. Therapy was considered either clinically or bacteriologically successful in patients who completed therapy and did not meet criteria for failure. Results: Therapy was clinically successful in 28 (82%) patients who received azithromycin and 32 (89%) patients who received ciprofloxacin (difference, 7% [95% CI, 23% to 10%]). Therapy was bacteriologically successful in 32 (94%) patients receiving azithromycin and 36 (100%) patients receiving ciprofloxacin (difference, 6% [CI, 14% to 2%]). Peak serum concentrations of azithromycin were equal to the minimum inhibitory concentration (MIC) of the infecting Shigella strains, whereas serum concentrations of ciprofloxacin were 28 times the MIC. Stool concentrations of both drugs were more than 200 times the MIC. Conclusion: Azithromycin is effective in the treatment of moderate to severe shigellosis caused by multidrug-resistant Shigella strains.

We prospectively compared the clinical features of cholera due to Vibrio cholerae O1 and V. cholerae O139 in 242 men 18-60 years of age, with a history of diarrhoea of 24 h or less, and moderate or severe dehydration. The antimicrobial susceptibility of all of the V. cholerae strains isolated from these patients was determined, and in vitro cholera toxin production determined for 68 isolates. On admission, the 110 patients infected with V. cholerae O1 significantly more often had body temperature36 degrees C (85% vs. 66%, Por = 0.05), faecal leucocyte count50/high power microscope field (40% vs. 12%), and lower mean faecal chloride content (94 vs. 103 mmol/L) than did the 132 patients infected with V. cholerae O139. Patients infected with V. cholerae O1 also initially had significantly higher median volumes of stool (13 vs. 11 mL per kg body weight per h), vomitus (1 mL/kg/h vs. nil), and intravenous fluid requirements (23 vs. 21 mL/kg/h). All V. cholerae O1 and O139 isolates were susceptible to ciprofloxacin, all but one were susceptible to doxycycline and erythromycin, and the majority of both serogroups were resistant to co-trimoxazole (95% and 97%, respectively). V. cholerae O1 and O139 susceptibilities differed for tetracycline (58% vs. 100%) and furazolidone (27% vs. 93%) (P0.001 in both cases). The amount of cholera toxin produced in vitro by strains of V. cholerae O1 and O139 was similar, and did not correlate with stool volume. The results demonstrated that V. cholerae O139 does not cause more severe, or more invasive, disease than V. cholerae O1, as had been previously suggested, but that clinically important differences in antimicrobial susceptibility do exist among strains isolated in Bangladesh.

Acute bacterial meningitis (ABM) is a medical emergency and a global health problem associated with significant mortality and neurologic sequelae (1, 2). An aetiologic diagnosis and determination of the antimicrobial susceptibility require good laboratory services that are lacking in most developing countries. We have retrospectively reviewed 448 patients admitted to our hospital from January 1988 to June 1994 with suspected meningitis...

Serotyping of Vibrio cholerae is based on the somatic '0' antigen. Cholera is caused by the 01 serotype ev. cholerae 01), and there were pre­ viously a total of 138 serotypes identified. A new serotype of V. cholerae has recently been identified as the pathogen responsible for explosive outbreaks of severe dehydrating diarrhoea in India and Bangladesh. This has been designated V. cholerae 0139. [1] Since it produces an illness that is clinically indistinguishable from cholera, it is considered to be another serotype of V. cholerae that can cause cholera.[2] The synonym 'Bengal' has been proposed because the serotype was first isolated along the Bay of Bengal. Replacement of fluid and electrolyte losses is the most important part of tbe management of patients with cholera caused by V. cholerae 01 or V. cholerae 0139. Treatment of cholera due to V. cholerae 01 with effective antimicrobials has been useful in shortening the duration of diarrhoea and faecal excretion of the pathogen, and in reduc­ ing the volume of watery stools, with subsequent decreased requirement for rehydration fluids. This randomised clinical trial was conducted at the Diarrhoea Treatment Centre of the Interna­