Effect of micronutrient supplementation on diarrhoeal disease among stunted children in rural South Africa.

BACKGROUND/OBJECTIVE: The efficacy of zinc combined with vitamin A or multiple micronutrients in preventing diarrhoea is unclear in African countries with high prevalence of human immunodeficiency virus (HIV)-exposed children. Potential modifying factors, such as stunting, need to be addressed. The objective of this study was to determine whether adding zinc or zinc plus multiple micronutrients to vitamin A reduces diarrhoea incidence, and whether this differs between the strata of stunted or HIV-infected children. METHODS: We analyzed data from a randomized, controlled, double-blinded trial (ClinicalTrials.gov NCT00156832) of prophylactic micronutrient supplementation to children aged 6-24 months. Three cohorts of children: 32 HIV-infected children, 154 HIV-uninfected children born to HIV-infected mothers and 187 uninfected children born to HIV-uninfected mothers, received vitamin A, vitamin A plus zinc or multiple micronutrients, which included vitamin A and zinc. The main outcome was incidence of diarrhoea. Poisson regression was used in intent-to-treat analyses. Stratified analyses followed testing for statistical interaction between intervention and stunting. RESULTS: We observed no significant differences in overall diarrhoea incidence among treatment arms. Stunting modified this effect with stunted HIV-uninfected children having significantly lower diarrhoea incidence when supplemented with zinc or multiple micronutrients compared with vitamin A alone (2.04 and 2.23 vs 3.92 episodes/year, respectively, P=0.024). No meaningful subgroup analyses could be done in the cohort of HIV-infected children. CONCLUSIONS: Compared with vitamin A alone, supplementation with zinc and with zinc and multiple micronutrients, reduced diarrhoea morbidity in stunted rural South African children. Efficacy of zinc supplementation in HIV-infected children needs confirmation in studies that represent the spectrum of disease severity and age groups.

The effect of nutritional support on weight gain of HIV-infected children with prolonged diarrhoea.

AIM: To examine the effect on growth and immunity of enhanced calorie and protein provision to HIV-infected children presenting with prolonged diarrhoea. METHODS: A total of 169 HIV-infected children aged 6-36 months with diarrhoea for 7 days or more were randomly assigned to either standard nutrition support for children with prolonged diarrhoea or an enhanced diet started during hospitalisation and continued after discharge. The change in weight between enrolment and 8, 14 and 26 weeks and changes in plasma HIV-RNA and CD4 cell count at 8 and 26 weeks were estimated. RESULTS: Children receiving enhanced nutrition achieved significantly more weight gain (p < 0.001) between enrolment and 8 weeks than children on the standard diet (median increase in weight-for-age standard deviation score +1.02 vs. +0.01). After 8 weeks median weight velocity was normal and similar in both groups. The change in median CD4 count was similar in both groups. The 26-week mortality rate was high in both groups (standard support: 22%, enhanced support: 29%). CONCLUSIONS: Nutrition support of children with advanced HIV infection and prolonged diarrhoea resulted in significant and sustained weight gain, but did not improve CD4 counts or survival. These results support integrated nutrition interventions for HIV-infected children.

Mortality, morbidity, and microbiology of endemic cholera among hospitalized patients in Dhaka, Bangladesh.

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.

Central nervous system manifestations of childhood shigellosis: prevalence, risk factors, and outcome.

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)

Randomised comparison of ciprofloxacin suspension and pivmecillinam for childhood shigellosis.

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.

Typhoid fever vaccines: a meta-analysis of studies on efficacy and toxicity.

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.

Treatment of shigellosis: V. Comparison of azithromycin and ciprofloxacin. A double-blind, randomized, controlled trial.

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.

Hyperglycemia during childhood diarrhea.

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.

Randomised controlled comparison of single-dose ciprofloxacin and doxycycline for cholera caused by Vibrio cholerae 01 or 0139.

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.

Clinical features, antimicrobial susceptibility and toxin production in Vibrio cholerae O139 infection: comparison with V. cholerae O1 infection.

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.

Medical practitioners' knowledge of dysentery treatment in Bangladesh.

PIP: Interviews conducted with four groups of medical practitioners in Bangladesh revealed widespread deviation from the treatment protocol for dysentery established by the World Health Organization (WHO). Questioned were 136 doctors (46 of whom had postgraduate training), 87 drug dispensers, and 50 medical students from Dhaka; also included were 150 drug dispensers from Matlab. Each respondent was presented with a hypothetical case of a 2-year-old with bloody diarrhea of 3 days' duration and asked to identify the treatment they would offer. Less than half of the medical practitioners in each group identified the WHO-approved regimen of use of oral rehydration solution and a single antibacterial drug appropriate for shigellosis (e.g., ampicillin and co-trimoxazole). Provision of the correct answer ranged from a low of 8% among urban and 11% among rural drug dispensers to a high of 46% among medical students and doctors without postgraduate training. 398 of the 423 respondents recommended use of at least one antibiotic; 155 advised use of two or more such drugs. The drug dispensers were most likely to recommend use of the antibacterial agents metronidazole or furazolidone, neither of which are appropriate choices for children with dysentery. Of particular concern is the low level of correct knowledge of dysentery management among drug dispensers given the fact that private pharmacies are the main source of acute medical care in Bangladesh.^ieng

Treatment of shigellosis: IV. Cefixime is ineffective in shigellosis in adults.

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.

C reactive protein and prealbumin as markers of disease activity in shigellosis.

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.

Fatal renal failure caused by diethylene glycol in paracetamol elixir: the Bangladesh epidemic.

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.

Shigellosis in neonates and young infants.

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.

PIP: Findings are reported from a study conducted to determine the clinical features and outcome of shigellosis in young infants. The authors reviewed the hospital records of 159 infants of no greater than age 3 months and those of 159 children aged 1-10 years with shigellosis who were admitted to the Diarrhea Treatment Center in Dacca, Bangladesh. 82.8% of infants had a history of nonbloody diarrhea, 59.9% moderate or severe dehydration, 12% bacteremia, 32.7% fever, 1.9% abdominal tenderness, and 0% rectal prolapse. 42.7% of children had a history of nonbloody diarrhea, 32.1% moderate or severe dehydration, 5.0% bacteremia, 58.6% fever, 12.6% abdominal tenderness, and 8.3% rectal prolapse. Infections caused by Shigella boydii and Shigella sonnei were more common in infants, while Shigella dysenteriae type 1 infections were less common in infants than in older children. There was an equivalent proportion of Shigella flexneri infections in the two groups. Infants were twice as likely to die as older children. Only 17 infants were being exclusively breastfed at the onset of their illness. Multiple logistic regression analysis identified the independent predictors of death among infants to be gram-negative bacteremia, ileus, decreased bowel sound, hyponatremia, hypoproteinemia, and a lower number of erythrocytes detected on the microscopic examination of stool specimens. Diarrhea management algorithms which rely exclusively upon clinical findings of dysentery to diagnose and treat shigellosis are likely to be unreliable in this high-risk age group.