Incidence, management, and outcome of childhood empyema: a prospective study of children in Cambodian refugee camps.

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.

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.

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.

Eastern equine encephalitis presenting with a focal brain lesion.

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.

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

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.

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.

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.

Potentially lethal complications of shigellosis.

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.

Therapy for shigellosis. I. Randomized, double-blind trial of nalidixic acid in childhood shigellosis.

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.

Mortality due to shigellosis: community and hospital data.

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.

Antimicrobial therapy for shigellosis.

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.

Diagnosis and management of dysentery by community health workers.

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.

Intestinal obstruction during shigellosis: incidence, clinical features, risk factors, and outcome.

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.

Current practices for treatment of dysentery in rural Bangladesh.

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.

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.