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To evaluate serum C reactive protein (CRP) and prealbumin concentrations as markers of disease activity in shigellosis this study serially measured serum concentrations of CRP and prealbumin in 39 patients infected with Shigella spp, and a comparison group of 10 patients infected with Vibrio cholerae serotype 01. On admission, patients with shigellosis had significantly higher median concentrations of CRP (109 v 5 mg/l; p < 0.01) and significantly lower median concentrations of prealbumin (16 v 23 mg/l; p < 0.01) than did patient with cholera. Among Shigella spp infected patients, CRP concentrations were significantly lower, and prealbumin concentrations significantly higher, on study days 3 and 5 when compared with admission values. Among Shigella spp infected patients, those in whom treatment failed had higher admission CRP concentrations than those in whom treatment was successful (p = 0.142). An admission CRP concentration > or = 110 mg/l had a 70% sensitivity and a 61% specificity in predicting failure of treatment among patients infected with Shigella spp; the predictive value of a positive and negative test was 14% and 96% respectively. In summary, acute shigellosis elicits an acute phase response, the magnitude of which predicts clinical outcome. [ABSTRACT FROM PUBLISHER]

To determine if loperamide is effective and safe in treating watery diarrhoea, we randomly assigned 50 adult expatriates in Bangladesh with more than three unformed stools in the previous 24 hours and illness of less than 72 hours to receive loperamide or a placebo. On entry into the five day study patients took two capsules (one loperamide capsule = 2 mg) and one after each unformed stool up to a maximum of eight per day. The groups did not significantly differ in pretreatment features or pathogens identified. Mean number of stools on study day 1 was 2.6 in the loperamide group and 4.0 in the placebo group (p = 0.035); on day 2 it was 1.3 versus 3.4 (p less than 0.001). Differences in stool frequencies during the final three study days, or proportion of patients with cramps, nausea, or vomiting on any study day, were not significant. No serious side effects occurred in either group. We conclude that loperamide, by decreasing stool frequency during the early part of illness, may have a role in the symptomatic treatment of this self-limiting disease. [ABSTRACT FROM PUBLISHER]

Objective: To determine whether a single dose, or 2 doses, of ciprofloxacin are as effective as 5-day, 10-dose therapy for the treatment of shigellosis in adult men who are moderately to severely ill.Design: Randomized, double-blind clinical trial.Setting: A diarrhea treatment center in the capital city of a developing country, Bangladesh.Patients: A total of 128 adult men with dysentery of less than 96 hours duration. All had Shigella organisms isolated from a culture of stool.Interventions: Patients were randomly assigned to receive either a single 1-gram dose of ciprofloxacin at admission to the study (single-dose group; n = 40), a 1-gram dose of ciprofloxacin at admission and 24 hours later (2-dose group; n = 43), or 500 mg of ciprofloxacin every 12 hours for 5 days (10 dose group; n = 35). All patients were hospitalized for 6 days.Measurements: Stools were collected individually; their character and consistency were recorded and cultured daily. A physical examination and recording of symptoms were done daily, and the temperature was measured every 4 hours. Therapy was considered to have failed in patients who did not have improvement in the signs and symptoms of dysentery after 72 hours of therapy or in patients who on study day 5 had more than nine stools, or more than two watery stools, or were febrile.Results: There were no treatment failures in the 78 patients infected with species of Shigella other than Shigella dysenteriae type 1. Among the 40 patients infected with S. dysenteriae type 1, treatment failed in 4 of the 10 patients who received single-dose therapy, 2 of the 15 patients who received 2-dose therapy, and none of the 15 patients who received 10-dose therapy (P = 0.017, single-dose therapy group compared with 10-dose group; P = 0.15 for the single-dose group compared with the 2-dose group; P > 0.2 for the 2-dose group compared with the 10-dose group).Conclusions: A single 1-gram dose of ciprofloxacin is effective therapy for patients infected with species of Shigella other than S. dysenteriae type 1. Single-dose therapy is inferior to 10-dose therapy for treating patients infected with S. dysenteriae type 1. [ABSTRACT FROM AUTHOR]

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.

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 with Shigella 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 chi2 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 <15 years old (92%); 654 (83%) were conscious; 73 (9%) were unconscious; 41 (5%) had a documented seizure (compared with >/=15-year age group); 24 (3%) had a seizure by history during this illness. Of the 41 patients with documented seizures, 19 (46.3%) had a seizure at the time of admission, and 22 (53.7%) had a seizure after admission. Twenty-five (61.0%) of the 41 patients with documented seizures were reported to have a seizure during this illness before coming to the Treatment Centre. 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. (ABSTRACT TRUNCATED)

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.

Objective: To estimate the efficacy and toxicity of typhoid fever vaccines., Design: Meta-analysis of randomised efficacy trials and both randomised and non-randomised toxicity studies of the parenteral whole cell, oral Ty21a, and parenteral Vi vaccines., Subjects: 1,866,951 subjects in 17 efficacy trials; 11,204 subjects in 20 toxicity studies., Main Outcome Measures: Pooled estimates of three year cumulative efficacy, year specific efficacy, and incidence of adverse events., Results: Three year cumulative efficacy was 73% (95% confidence interval 65% to 80%) for two doses of whole cell vaccines (based on seven trials); 51% (35% to 63%) for three doses of Ty21a vaccine (four trials); and 55% (30% to 71%) for one dose of Vi vaccine (one trial). For whole cell and Ty21a vaccines, regimens of fewer doses were less effective. Efficacy was shown to be significant for five years for whole cell vaccines, four years for Ty21a vaccine, and two years for Vi vaccine. Neither the age of vaccine recipient nor the incidence of typhoid fever in the control group (varying from 6 to 810 cases per 100,000 person years) affected the efficacy of the whole cell or Ty21a vaccines. After vaccination, fever occurred in 15.7% (11.5% to 21.2%) of whole cell vaccine recipients, 2.0% (0.7% to 5.3%) of Ty21a vaccine recipients, and 1.1% (0.1% to 12.3%) of Vi vaccine recipients., Conclusions: Whole cell vaccines are more effective than the Ty21a and Vi vaccines but are more frequently associated with adverse events. Whether the added efficacy of the whole cell vaccines outweighs their toxicity will depend on the setting in which vaccination is used.

Background: 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 degrees 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% Cl, -23% to 10%]). Therapy was bacteriologically successful in 32 (94%) patients receiving azithromycin and 36 (100%) patients receiving ciprofloxacin (difference, -6% [Cl, -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.

Objective: To determine the cause of hyperglycemia in childhood diarrhea., Methods: During an 8-month period, patients admitted to a diarrhea treatment center in Bangladesh had their blood glucose concentrations determined. Sixteen patients aged 2 to 10 years with hyperglycemia (blood glucose concentration >10.0 mmol/L) and 20 patients in the same age group with a normal blood glucose concentration (3.3 to 9.0 mmol/L) had blood samples obtained on admission and 4 and 24 hours later for determination of glucoregulatory hormones and gluconeogenic substrates., Results: Prevalence of hyperglycemia among patients aged 2 to 10 years was 9.4%. Compared with the normoglycemic patients, hyperglycemic patients more often had severe dehydration (100% versus 10%, p <0.001), infection with Vibrio cholerae 0 1 or toxigenic Escherichia coli (94% vs 25%, p <0.001), and had similar duration of fasting (16 vs 14 hours, p = 0.677). Concentrations of epinephrine (7.15 vs 2.00 micromol/L), norepinephrine (10.35 vs 3.50 micromol/L), cortisol (1.38 vs 0.82 micromol/L), glucagon (36 vs 14 pmol/L), and C-peptide (1.22 vs 0.35 nmol/L) were all significantly (p < or = 0.014) higher in patients with hyperglycemia than in normoglycemic patients., Conclusions: The development of hyperglycemia in diarrhea is caused by a stress response to hypovolemia.

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 01 and 130 infected with V cholerae 0139 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 01, 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% Cl 8-33]); the corresponding proportions with bacteriological success were 63 (95%) and 44 (69%) (27% [14-39]). Among patients infected with V cholerae 0139, treatment was clinically successful in 54 (92%) of 59 patients who received ciprofloxacin and in 65 (92%) of 71 who received doxycycline (< 1% [-9 to 9]), and bacteriologically successful in 58 (98%) and 56 (79%), respectively (19% [9-30]). Total volume of watery stool did not differ significantly between ciprofloxacin-group and doxycycline-group patients infected with either V cholerae 01 or 0139. All but one of the V cholerae 01 and all of the 0139 isolates were susceptible in vitro to doxycycline, whereas 48 (37%) of the V cholerae 01 isolates and none of the 0139 isolates were resistant to tetracycline. Treatment clinically failed in 14 (52%) of 27 doxycycline-treated patients infected with a tetracycline-resistant V cholerae 01 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 01 or 0139 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.

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 temperature < 36 degrees C (85% vs. 66%, P < or = 0.05), faecal leucocyte count > 50/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%) (P < 0.001 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.

Objective: To compare the efficacy of cefixime with that of pivamdinocillin in the treatment of adults with acute dysentery caused by Shigella infection., Design: Randomized, double-blind clinical trial., Setting: A diarrhea treatment center in Dhaka, Bangladesh., Patients: 30 men with dysentery lasting 72 hours or less., Interventions: Patients were randomly assigned to receive either 400 mg of cefixime every 24 hours (n = 15) or 400 mg of pivamdinocillin every 6 hours (n = 15) for 5 days. All patients were hospitalized for 6 days. Patients in whom initial drug therapy failed received alternative antimicrobial therapy., Measurements: Physical examinations were done and symptoms were recorded daily, and body temperatures were measured every 6 hours. Stools were counted and examined for consistency and for the presence of blood and mucus. Therapy failed if symptoms of dysentery persisted for more than 72 hours or if, on study day 5, a patient had six stools, one watery or bloody-mucoid stool, or an oral temperature higher than 37.8 degrees C. Bacteriologic failure of therapy occurred if Shigella could be isolated from a stool sample on or after study day 3., Results: Therapy failed in seven (47%) patients given cefixime but in none of the patients given pivamdinocillin (P = 0.006). Patients given cefixime had longer duration of fever (median, 6 hours compared with 0 hours, P = 0.019), longer duration of the period with dysenteric stools (median, 4 days compared with 1 day, P = 0.001), and more stools during the 6 study days (median, 65 compared with 28, P = 0.002) than patients treated with pivamdinocillin. Bacteriologic failure of therapy occurred in 60% of patients (9 of 15) given cefixime and 13% of those (2 of 15) given pivamdinocillin (P = 0.009)., Conclusion: Cefixime is ineffective in treating shigellosis in adults when used in the standard recommended dosage.

Objective: To determine the cause of a large increase in the number of children with unexplained renal failure., Design: Case-control study., Setting: Children's hospital in Dhaka, Bangladesh., Subjects: Cases were all 339 children with initially unexplained renal failure; controls were 90 children with cause of renal failure identified; all were admitted to hospital during 35 months after January 1990., Main Outcome Measures: Differences between the case and control patients in clinical and histological features and outcome; toxicological examination of 69 bottles of paracetamol from patients and pharmacies., Results: Compared with children with an identified cause for their renal failure, children with initially unexplained renal failure were significantly (P < 0.05) more likely to have hepatomegaly (58% v 33%), oedema (37% v 20%), and hypertension (58% v 23%); to have a higher serum creatinine concentration (mean 519 mumol/l v 347 mumol/l) and lower serum bicarbonate concentration (10.1 mmol/l v 12.4 mmol/l); to have been given a drug for fever (91% v 31%); to have ingested a brand of paracetamol shown to contain diethylene glycol (20% v 0%); and to have died in hospital (70% v 33%). Diethylene glycol was identified in 19 bottles of paracetamol, from 7 of 28 brands tested. In the 12 months after a government ban on the sale of paracetamol elixir, new cases of renal failure decreased by 54%, and cases of unexplained renal failure decreased by 84%., Conclusion: Paracetamol elixirs with diethylene glycol as a diluent were responsible for a large outbreak of fatal renal failure in Bangladesh.

To determine the clinical features and outcome of shigellosis in young infants, we reviewed the hospital records of 159 infants < or = 3 months of age (including 30 neonates) and 159 children 1 to 10 years of age with shigellosis who were admitted to the Diarrhoea Treatment Centre in Dacca, Bangladesh. Infants more commonly had a history of nonbloody diarrhea (82.8% vs 42.7%; p < 0.001), moderate or severe dehydration (59.9% vs 32.1%; p < 0.001), or bacteremia (12.0% vs 5.0%; p = 0.027) and less commonly had fever (32.7% vs 58.6%; p < 0.001), abdominal tenderness (1.9% vs 12.6%; p < 0.001), or rectal prolapse (0% vs 8.3%; p = 0.001). Infections caused by Shigella boydii (20.8% vs 6.3%; p < 0.001) and Shigella sonnei (7.5% vs 1.3%; p = 0.006) were more common, and Shigella dysenteriae type 1 (9.4% vs 31.4%; p < 0.001) infections were less common in infants than in older children; the proportion of Shigella flexneri infections was equivalent in the two groups (59.1% vs 60.4%). Infants were twice as likely to die as older children (16.4% vs 8.2%; p = 0.026). Only 17 infants (14.3%) were being exclusively breast fed at the onset of their illness. In a multiple logistic regression analysis, independent predictors of death in infants were gram-negative bacteremia, ileus, decreased bowel sounds, hyponatremia, hypoproteinemia, and a lower number of erythrocytes detected on microscopic examination of stool specimens. Diarrhea management algorithms that rely only on clinical findings of dysentery to diagnose and treat shigellosis are likely to be unreliable in this high-risk age group.

To determine the incidence, outcome, and optimal management of empyema, all children less than 15 years of age admitted to Khao-I-Dang Hospital with a diagnosis of empyema during a 23-month period were prospectively studied. Khao-I-Dang Hospital provides care to 137,000 Cambodian children residing in eight refugee camps along the Thai-Cambodian border. Ninety-eight children with empyema were identified, for an annual incidence of 0.37 cases per 1,000 children. All patients had chest tubes inserted on admission, and all were treated with parenteral antibiotics, which included chloramphenicol in 92% of the patients and cloxacillin in 72%. Patients were hospitalized a mean of 30 days, and chest tubes were in place for a mean of 12 days. Surgery was performed on four patients who had bronchopleural fistulas that persisted for more than 14 days. Only one (1%) of the 70 patients treated with cloxacillin required thoracotomy, compared with three (11%) of the 28 patients who did not receive cloxacillin (P = 0.07). In a multiple regression analysis, the presence of pneumatoceles or mediastinal shift on admission chest radiograph, a history of tuberculosis in the family, and an age of more than five years were predictive of a longer duration of chest tube drainage. No patient died in the hospital, and only one patient died in the six months following discharge from the hospital. Chest radiographs that were obtained six months after discharge in 25 patients were all essentially normal, despite marked abnormalities on chest radiographs obtained at discharge. In summary, conservative medical management with the use of chest tubes for these 98 children with empyema resulted in a mortality rate of 1.0%, and should be considered as an effective alternative to the surgical management of patients presenting with this complication.

To determine whether protein-losing enteropathy occurs during shigellosis, we measured concentrations of alpha 1-antitrypsin in sequential stool samples from 110 adults hospitalized with acute dysentery due to Shigella infection. Mean stool concentrations of alpha 1-antitrypsin on admission were 10.9 micrograms/mg dry weight of stool. Stool alpha 1-antitrypsin concentrations were significantly (p < 0.001) lower on the 3rd and 5th study days (4.1 and 2.2 micrograms/mg, respectively) than on admission. Admission mean alpha 1-antitrypsin concentrations in patients with Shigella dysenteriae type 1 infection (14.4 micrograms/mg) were significantly (p < 0.05) higher than in patients infected with other species of Shigella (9.3 micrograms/mg). Stool alpha 1-antitrypsin concentrations were significantly correlated with the number of erythrocytes in the stool, and inversely correlated with serum protein concentration. Patients in whom antimicrobial treatment failed, most often because they were infected with a resistant strain of Shigella, had significantly higher concentrations of alpha 1-antitrypsin on all three study days. We conclude that Shigella infection is associated with a protein-losing enteropathy, that this enteropathy is more severe with S. dysenteriae type 1 infection, and that the enteropathy improves with appropriate antimicrobial therapy.

Eastern equine encephalitis (EEE) virus causes a severe meningoencephalitis with high morbidity and mortality. Despite numerous clinical reports of EEE, there are only 11 patients in whom cranial computed tomographic (CT) findings are described. In 6 patients, CT was normal and in 5 patients diffuse edema was present; none had a focal brain lesion. Based on these reports, it has been suggested that focal findings on CT support the diagnosis of herpes simplex encephalitis rather than EEE. The first patient with serologically-confirmed EEE and a focal lesion demonstrated by cranial CT and magnetic resonance imaging is described; these findings underscore the importance of including EEE in the differential diagnosis of encephalitides that can cause focal brain lesions on neuroimaging.

The susceptibility to ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ) was determined for 15,824 isolates of Shigella obtained from patients attending a treatment center in Dhaka, Bangladesh, from 1983 through 1990 and for 520 isolates obtained during community surveys from 1988 through 1990. Susceptibility to nalidixic acid was determined for isolates obtained after 1985. In 1983 13% of isolates were resistant to ampicillin, 23.5% to TMP-SMZ, and 0.8% to both drugs. By 1990 51.2% of isolates obtained at the Diarrhea Treatment Centre were resistant to ampicillin, 47.7% to TMP-SMZ, and 40.5% to both drugs (for comparison with figures for 1983, P less than .001). Resistance to nalidixic acid increased from 0.8% in 1986 to 20.2% in 1990 (P less than .001). In 1990 71.5% of Shigella dysenteriae type 1 isolates were resistant to ampicillin, 68.5% to TMP-SMZ, 67.7% to both drugs, and 57.9% to nalidixic acid. The resistance pattern of isolates obtained during community surveillance was similar to that of Treatment Centre isolates. In Bangladesh ampicillin and TMP-SMZ are no longer useful for treatment of infection with any species of Shigella, and nalidixic acid is no longer useful for treatment of infections due to S. dysenteriae type 1.

To determine the incidence and outcome of intestinal obstruction during shigellosis, the authors assessed 1211 consecutive patients with shigellosis admitted during a 15-month period to a diarrhea treatment center in Dhaka, Bangladesh. Obstruction was identified in 30 (2.5%) patients. Ten (33.3%) of these patients died, compared with 97 (8.2%) of the 1181 patients without obstructions (P less than 0.001; RR = 4.1). In a case-control study, patients with obstructions were compared with 30 control patients with shigellosis but without obstructions. Case and control patients were similar in age (median, 18 months vs. 24 months; NS). Before admission to the hospital, case patients had less often been breast-fed than control patients (33% vs. 85%; P = 0.006) and had more often received antimicrobial agents (53% vs. 13%; P = 0.001). Case patients more often had abdominal tenderness (73% vs. 13%; P less than 0.001), altered consciousness (50% vs. 17%; P = 0.006), and Shigella dysenteriae type 1 infection (73% vs. 27%, P = 0.001) and had a higher median blood leukocyte count (40 x 10(3)/microL vs. 14 x 10(3)/microL; P = 0.007) and serum potassium concentration (5.0 mmol/L vs. 4.3 mmol/L; P = 0.016), and lower median serum sodium (123 mmol/L vs. 131 mmol/L; P = 0.003) and total protein (52 g/L vs. 60 g/L; P = 0.025) concentrations than did control patients. Eight (27%) patients with obstructions developed the hemolytic-uremic syndrome, compared with none of the control patients (P = 0.003). It was concluded that obstruction is an ominous complication of shigellosis and that therapies in addition to provision of antimicrobial agents need to be evaluated.

In controlled clinical trials, which were first performed with use of the sulfonamides, antimicrobial agents have been shown to shorten the duration of symptoms and lessen the excretion of pathogens during episodes of shigellosis. Not all antimicrobial agents that are active in vitro against Shigella are effective in vivo, and efficacy of an agent can only be assessed by properly conducted clinical trials. Resistance to both ampicillin and trimethoprim-sulfamethoxazole, the drugs of choice for the treatment of shigellosis, is now common among Shigella dysenteriae type I isolates in Africa and Asia and is increasing among isolates of other Shigella species, including Shigella sonnei in the United States. Nalidixic acid, the newer quinolones, and amnidocillin pivoxil are additional agents that have been found to be effective in controlled clinical trials. There is a need, however, for more data on the safety of the quinolones before they can be routinely administered to children. Newer agents that deserve evaluation include the orally administered to children. Newer agents that deserve evaluation include the orally administered second- and third-generation cephalosporins, which are highly active in vitro against most strains of Shigella.

Almost all fatal cases of shigellosis occur in developing countries, and data on mortality are generally compiled from three sources: investigations of epidemics caused by Shigella dysenteriae type 1, surveillance of endemic diarrheal disease, and reports from hospitals. Attack rates during epidemics of dysentery due to infection with S. dysenteriae type 1 have ranged from 1% to 33%, and case-fatality rates have ranged from 1% to 7%. In Matlab, a rural district in Bangladesh, most diarrhea-related deaths and approximately 25% of all deaths among children 1 through 4 years of age are attributable to dysentery. In 1984, an epidemic of dysentery was associated with a 42% increase in the death rate in that age group. At the Dhaka Treatment Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh, the fatality rate for 970 inpatients with shigellosis was 11% in 1988, with most deaths occurring among malnourished children who were infected with Shigella flexneri. Control of mortality from shigellosis will require prevention of epidemic S. dysenteriae type 1 disease and endemic S. flexneri infections in children who live in countries with a high prevalence of malnutrition.

A rural area of Bangladesh with a population of 191,000 had 643 health care providers, of whom 324 (50%) practiced allopathic (Western) medicine, 152 (24%) were spiritualists, 109 (17%) were herbalists, and 58 (9%) were homeopaths. Two hundred eight (64%) of the allopaths had no formal training, and only 18 (6%) were graduates of medical school. In a community-based study of 480 children with bloody diarrhea and 480 children with nonbloody diarrhea, allopathic treatment was the most common care provided. Furazolidone and metronidazole were the two most commonly prescribed drugs, given to 26% and 23% of children, respectively, who were seen by a practitioner. Only 25% of children had received oral rehydration therapy. We conclude that in this region of Bangladesh care of acute diarrhea is provided mostly by private medical practitioners who have little or no training; that such care currently is largely irrational; and that the provision of rational care will require the development of simple algorithms that these practitioners can implement for treatment of this disease.

Complications that can lead to death during shigellosis include intestinal as well as systemic manifestations. The former include intestinal perforation, toxic megacolon, and dehydration, and the latter include sepsis, hyponatremia, hypoglycemia, seizures and encephalopathy, hemolyticuremic syndrome, pneumonia, and malnutrition. Data on the frequency of these complications come primarily from hospital-based studies, in which sepsis-either with Shigella or with other Enterobacteriaceae-and hypoglycemia are the most common causes of death. Management of these two complications requires broad-spectrum empiric antibiotic treatment of all severely ill, malnourished patients with shigellosis as well as frequent feedings to prevent hypoglycemia. Unfortunately, in developing countries, access to parenteral broad-spectrum antimicrobial agents is often limited, and frequent feedings are often precluded by the severe anorexia that is characteristic of shigellosis. Realistic approaches to the reduction of mortality from shigellosis must continue to focus on prevention and early antimicrobial therapy rather than on treatment of established complications.

To determine the importance of bacteremia in hospitalized patients with diarrhea in Bangladesh, from September 1982 through August 1983 the authors obtained blood for culture from 1,824 patients who were suspected of having sepsis (44% of all admissions). Nontyphoid bacteremia occurred in 243 patients. The most common pathogens were the Enterobacteriaceae (n = 66 episodes), Staphylococcus aureus (n = 65), Pseudomonas aeruginosa and other non-glucose-fermenting bacilli (n = 50), Streptococcus pneumoniae (n = 40), and Haemophilus influenzae (n = 16). When compared with an equal number of control patients without bacteremia, bacteremic patients were significantly (p less than 0.05) more likely to be under 1 year of age (46.5% of bacteremic patients vs. 30.0% of control patients) and more often had abdominal tenderness (20.1% vs. 11.5%), hypoproteinemia (a serum protein level less than 60 g/liter) (58.9% vs. 42.9%), and a prior intravenous infusion (49.0% vs. 30.9%). The case-fatality rate was 29.7% in bacteremic patients versus 7.8% in controls (relative risk (RR) = 3.8, p less than 0.001). Factors that were associated with an increased risk of death in bacteremic patients were infection with a Gram-negative pathogen (RR = 2.48), decreased peristalsis (RR = 2.66), hypoproteinemia (RR = 3.36), hypothermia (RR = 2.54), and hypotension (RR = 2.19). Bacteremia appears to be an important link between diarrheal illness and death in Bangladesh. In children with diarrhea who are suspected of being septic, early implementation of antimicrobial therapy that is effective against the broad range of pathogens identified appears to be indicated.

Ciprofloxacin, 500 mg every 12 h, was compared with ampicillin, 500 mg every 6 h, both given for 5 days, in the treatment of 121 adult males hospitalized with severe shigellosis. Treatment was randomized and double-blinded. At the completion of treatment, there was resolution or marked improvement in symptoms in 57 (95%) of 60 ciprofloxacin-treated patients, 23 (88%) of 26 ampicillin-treated patients infected with an ampicillin-susceptible strain of Shigella, and 15 (43%) of 35 ampicillin-treated patients infected with an ampicillin-resistant strain of Shigella (ampicillin-R group) (P less than .01, ciprofloxacin or ampicillin groups vs. ampicillin-R group). Bacteriologic failure was less common (P less than .025) in the ciprofloxacin group (0/60) than in the ampicillin (3/26, 12%) or ampicillin-R groups (5/35, 14%). Ciprofloxacin-treated patients had a mean of 29 stools during the study, compared with 46 for ampicillin-treated patients (P = .004). Thus ciprofloxacin seems to be an effective, and perhaps superior, alternative to ampicillin in treating patients with shigellosis.

To determine the frequency and outcome of hypoglycemia during diarrhea in childhood, we screened 2003 consecutive patients less than 15 years of age who were admitted to a diarrhea treatment center in Dhaka, Bangladesh. Hypoglycemia, defined as a blood glucose concentration less than 2.2 mmol per liter, was found in 91 patients (4.5 percent), 39 (42.9 percent) of whom died. We also measured the plasma concentrations of glucoregulatory hormones and gluconeogenetic substrates in 46 of the patients with hypoglycemia who were 2 to 15 years old and in 25 normoglycemic patients matched with them for age and weight. The patients with hypoglycemia had had diarrhea for less time than the normoglycemic patients (median, 12 vs. 72 hours; P less than 0.05), and their last feeding had been 18 hours before admission, as compared with 9 hours for the normoglycemic patients (P less than 0.05). The groups were similar in terms of nutritional status, the proportion of patients who had fever, and the types of pathogens recovered from stool samples. The plasma C-peptide concentrations were low (less than 0.30 nmol per liter) in all the hypoglycemic patients. As compared with the normoglycemic patients, the patients with hypoglycemia had elevated median plasma concentrations of glucagon (44 vs. 11 pmol per liter; P = 0.001), epinephrine (3400 vs. 1500 pmol per liter; P = 0.012), norepinephrine (7500 vs. 2900 pmol per liter; P = 0.002), and lactate (3.5 vs. 2.1 mmol per liter; P = 0.020) and similar alanine and beta-hydroxybutyrate concentrations. Eighteen hypoglycemic patients with severe malnutrition had been ill longer than 26 better-nourished patients with hypoglycemia (median duration of illness, 18 vs. 10 hours; P = 0.023) and had lower median plasma concentrations of lactate (1.9 vs. 3.9 mmol per liter; P = 0.021) and alanine (173 vs. 293 micromol per liter; P = 0.040). We conclude that hypoglycemia is a major cause of death in association with diarrhea. Because the glucose counterregulatory hormones were appropriately elevated in the children with diarrhea and hypoglycemia, whereas the gluconeogenetic substrates were inappropriately low, we further conclude that the hypoglycemia observed in such patients is most often due to the failure of gluconeogenesis.

The total number of admissions and deaths of patients with shigellosis were ascertained at the Dhaka Treatment Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh, 1974-1988, and the characteristics of 67 patients who died were compared with those of 134 discharged alive. Of 9780 Shigella-infected inpatients, 889 (9.1%) died; 32.3% of deaths occurred in children less than 1 year of age. Fatality rates were highest (10.3%) in Shigella sonnei-infected patients and lowest (6.7%) in Shigella dysenteriae type 1-infected patients. Age less than 1 year, lack of breast feeding in patients 1-2 years of age, hypothermia, severe malnutrition, severe dehydration, altered consciousness, abdominal distension, thrombocytopenia, hypoproteinemia, hyponatremia, hypoglycemia, renal failure, and bacteremia were all significantly more common in case patients. In a multivariate analysis, younger age, decreased serum protein, altered consciousness, and thrombocytopenia were predictive of death. Thus in Bangladesh the fatality rate for hospitalized patients infected with any species of Shigella remains high despite relatively intensive inpatient care, and young, hypoproteinemic patients are at greatest risk of fatal illness.

We compared nalidixic acid, 55 mg/kg/day, with ampicillin, 100 mg/kg/day, both given orally for 5 days, in the treatment of children with dysentery caused by shigellosis. All patients entered into the study had illness of less than 72 hours' duration and no prior allopathic drug therapy. Treatment was randomized and administered in double-blind fashion. Patients initially treated with ampicillin who were infected with a Shigella strain resistant to ampicillin were considered as a separate group (ampicillin-R). All isolates were susceptible to nalidixic acid. Similar percentages of patients treated with nalidixic acid (26/32, 81%) and with ampicillin (17/22, 77%) were clinically cured by the end of therapy; the rate in ampicillin-R (3/14, 21%) patients was significantly lower (p less than 0.001). Stool frequency in patients treated with nalidixic acid was significantly less than for ampicillin-treated or ampicillin-R patients during the final 3 study days. All patients treated with nalidixic acid and ampicillin had Shigella eradicated from their stool by day 3, compared with 77% (10/13) of ampicillin-R patients (p less than 0.05, ampicillin-R vs nalidixic acid or ampicillin). We conclude that nalidixic acid is an effective alternative to ampicillin in the treatment of shigellosis caused by nalidixic acid-susceptible strains.

We compared the efficacy and safety of a single polyelectrolyte solution, Dhaka solution (DS), containing 133 mmol/L sodium, 13 mmol/L potassium, 98 mmol/L chloride, and 48 mmol/L acetate with and without 139 mmol/L (25 gm/L) dextrose in the rapid (4 hours) rehydration of 67 patients with diarrhea and moderate or severe dehydration requiring parenteral fluid therapy. Of the 67 patient, 31 were randomly assigned to receive the dextrose-containing solution (DS + D) and 36 DS without dextrose. On admission to the hospital, the two groups of patients were similar with respect to enteric pathogens detected, proportion with hyponatremia, magnitude of dehydration as assessed by clinical criteria, serum protein or creatinine concentration, and plasma glucose levels. At the end of the 4-hour infusion, both groups of patients had similar decreases in serum creatinine and protein levels and similar volume of urine output, but patients receiving DS + D had a significantly higher plasma glucose level than patients receiving DS (7.8 mmol/L (140 mg/dl) vs 5.39 mmol/L (97 mg/dl), P less than 0.01). One patient in the DS group had hypoglycemia (plasma glucose 2.0 mmol/L (36 mg/dl) at 4 hours. No other complications were noted. Serum protein values 24 hours after admission were little changed from 4-hour values, suggesting that rehydration was complete at the end of 4 hours. We conclude that, in our patients, rehydration can be carried out safely and rapidly with the use of a single solution and that adding 139 mmol/L (25 gm/L) of dextrose to the solution can prevent hypoglycemia without producing an osmotic diuresis.

To develop guidelines for community health workers in the treatment of patients with diarrhoea, diarrhoea prevalence was actively surveyed for a year in a remote rural community of 915,000 persons, and the enteric pathogens and clinical features associated with diarrhoeal illness were determined in a sample of 300 patients. Bloody diarrhoea accounted for 39% of all diarrhoea episodes and 62% of diarrhoea-associated deaths. 51 (50%) of 101 patients with a history of bloody diarrhoea had Shigella infection, compared with 31 (16%) of 199 patients with other types of diarrhoea. A history of bloody diarrhoea was as predictive of the presence of shigella infection (positive predictive value 50%, negative predictive value 86%) as more complex prediction schemes incorporating other clinical features or stool microscopic examination. In the area of Bangladesh where the study was done reduction of diarrhoea-related morbidity and mortality will depend on control and treatment of shigellosis, and community health workers have been instructed to provide antibiotics for patients with a history of bloody dysentery.