Interleukin-1 beta (IL-1 beta), IL-1 receptor antagonist, and TNF alpha production in whole blood.

The ability of an individual to mount defense responses to infection depend in part on the capacity to produce cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF). The specialized equipment, labor intensity, and sterile practice required for the standard in vitro evaluation of cytokine production can make such evaluation impractical in some clinical situations. We report a method for stimulating whole blood to produce cytokines that can be implemented in laboratories without tissue culture facilities and requires minimal sample preparation. IL-1 beta and TNF alpha production in whole blood samples was stimulated with endotoxin and/or phytohemagglutinin in standard EDTA-containing vacuum collection tubes. After incubation, plasma was removed and frozen for later assay. Comparison of this whole blood method with isolated mononuclear cell cultures indicated a significant correlation for IL-1 beta production (r = 0.746, P = 0.005). This technique also produced the newly described cytokine, IL-1 receptor antagonist. We conclude that the whole blood method is an acceptable alternative to isolated cell culture methods for measuring IL-1 beta in situations that preclude the standard in vitro approach.

Cavitation in acute histoplasmosis.

Cavitary lung lesions in histoplasmosis are usually associated with the chronic form of the disease. This report describes a ten-year-old boy with the clinical and serologic pattern of acute Histoplasma capsulatum infection who had multiple cavitary lesions.

False localization of site of endocarditis by cardiac catheterization with quantitative cultures.

The authors present a patient with relapsing Pseudomonas aeruginosa endocarditis in whom cardiac catheterization with quantitative cultures falsely localized the infection to the tricuspid valve, probably because the patient was having intermittent rather than continuous bacteremia. After catheterization the patient developed mitral insufficiency and congestive heart failure. This experience suggests that quantitative cultures during cardiac catheterization may give misleading results and that the procedure may have significant complications.

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.

Serological evidence for chlamydial infection in patients with acute diarrhoea.

Anti-chlamydial antibodies were detected in 25 of 93 patients with diarrhoea in Bangladesh. This first report of evidence for chlamydial infection in this country should stimulate a search for a causal relationship between chlamydiae and prevalent diseases of Bangladesh.

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.

Health related response to natural disasters: the case of the Bangladesh cyclone of 1991.

This paper evaluates the health related response to large natural disasters using the example of the recent Bangladesh cyclone of 1991. After providing a description of the extent of the health response, it focuses on three major issues: (i) assessment of needs (ii) coordination of major groups involved in health relief and rehabilitation efforts and (iii) appropriateness and effectiveness of the health response in terms of definable outcome criteria. The conclusions are that in the case of the Bangladesh cyclone: (a) the assessment of needs was more reactive rather than anticipatory and was not based on any systematic data gathering from the field; (b) in contrast to previous disaster situations there was excellent coordination of the major groups involved in the aid process (the government, the armed forces and non-governmental organizations) and (c) given the caveat of inadequate baseline information, it appears that the health response was prompt and effective in preventing any increase in mortality from diarrheal diseases and measles. The reasons for the deficiencies and successes of the health response are analysed and finally a list of detailed recommendations to facilitate future disaster/cyclone management and response is provided.

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.

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.