Effectiveness of a multi-modal capacity-building initiative for upgrading biomedical waste management practices at healthcare facilities in Bangladesh: a 21st century challenge for developing countries.

INTRODUCTION: Biomedical waste management (BMWM) has attracted attention across the world as improper management can pose a serious threat for healthcare workers (HCWs), the general population and the environment. This study aimed to analyse the effectiveness of a multi-modal intervention (MMI) to upgrade BMWM practices at healthcare facilities across Bangladesh. METHODS: This quasi-experimental study, with a pre- and post-test design, was undertaken at nine healthcare facilities (five public, three private and one autonomous) over three phases, and concluded in 2019. The MMI included various strategies including: (i) system change; (ii) education and training; (iii) visual reminders; (iv) monitoring and feedback; and (v) ensuring sustainability at the study hospitals. Data collected from 2726 HCWs and waste handlers through direct observation were analysed using Statistical Package for Social Sciences Version 24. RESULTS: Significant improvements were seen in waste segregation practices using colour-coded bins (from 1% to 79%). The use of personal protective equipment during transportation and final management/disposal increased from 3% to 55%. Compliance with the use of standardized methods for collecting and transporting biomedical waste (BMW) increased substantially from 0% to 78%, while compliance with standardized methods for final management/disposal of BMW improved by 39%. CONCLUSION: Compliance with BMWM practices is very poor in Bangladesh due to a lack of knowledge, manpower and resources. Nevertheless, this MMI can be used as a tool to significantly improve BMWM practices in healthcare facilities. Initiatives such as this MMI will help the Government of Bangladesh to achieve Sustainable Development Goal 3.3 and universal health coverage by 2030.

L-isoleucine-supplemented oral rehydration solution in the treatment of acute diarrhoea in children: a randomized controlled trial.

Antimicrobial peptides represent an important component of the innate immune defenses of living organisms, including humans. They are broad-spectrum surface-acting agents secreted by the epithelial cells of the body in response to infection. Recently, L-isoleucine and its analogues have been found to induce antimicrobial peptides. The objectives of the study were to examine if addition of L-isoleucine to oral rehydration salts (ORS) solution would reduce stool output and/or duration of acute diarrhoea in children and induce antimicrobial peptides in intestine. This double-blind randomized controlled trial was conducted at the Dhaka Hospital of ICDDR,B. Fifty male children, aged 6-36 months, with acute diarrhoea and some dehydration, attending the hospital, were included in the study. Twenty-five children received L-isoleucine (2 g/L)-added ORS (study), and 25 received ORS without L-isoleucine (control). Stool weight, ORS intake, and duration of diarrhoea were the primary outcomes. There was a trend in reduction in mean +/- standard deviation (SD) daily stool output (g) of children in the L-isoleucine group from day 2 but it was significant on day 3 (388 +/- 261 vs. 653 +/- 446; the difference between mean [95% confidence interval (CI) (-)265 (-509, -20); p = 0.035]. Although the cumulative stool output from day 1 to day 3 reduced by 26% in the isoleucine group, it was not significant. Also, there was a trend in reduction in the mean +/- SD intake of ORS solution (mL) in the L-isoleucine group but it was significant only on day 1 (410 +/- 169 vs. 564 +/- 301), the difference between mean (95% CI) (-)154 (-288, -18); p = 0.04. The duration (hours) of diarrhoea was similar in both the groups. A gradual increase in stool concentrations of beta-defensin 2 and 3 was noted but they were not significantly different between the groups. L-isoleucine-supplemented ORS might be beneficial in reducing stool output and ORS intake in children with acute watery diarrhoea. A further study is warranted to substantiate the therapeutic effect of L-isoleucine.

Short-chain fatty acids and commensal microbiota in the faeces of severely malnourished children with cholera rehydrated with three different carbohydrates.

BACKGROUND: Short-chain fatty acids (SCFAs) liberated by fermentation of complex carbohydrates might stimulate water and salt absorption, and provide energy. The aim of the study was to assess the number and proportion of faecal bacteria and the concentration of SCFAs of severely malnourished children with cholera receiving oral rehydration solution (ORS) containing glucose, amylase-resistant starch (ARS) or rice. METHODS: Serial faecal samples were collected from 30 malnourished children with cholera until rehydration and partial nutritional recovery. SCFAs were identified and quantitated by high-performance liquid chromatography. In situ hybridization combined with flow cytometry was used to analyse the microbiota in the faeces. RESULTS: Before treatment the concentration of total SCFA in faecal sample of cholera children was found to be 4.7±0.6 mmol/kg and it increased steadily until 95.0±8.7 mmol/kg at day 28. Among different ORS groups, concentration was significantly higher in the Rice-ORS group at day 1 (P<0.011) and at day 2 (P<0.025). During recovery faecal output was significantly reduced and the number of bacteria also increased faster in the Rice-ORS group than in the glucose-ORS group at day 1 and day 2 (P<0.01), and a modest increase in bacterial number was observed in the glucose-ORS plus ARS group (day 1, P=0.07; day 2, P=0.09). CONCLUSION: Clinical recovery was associated with an increase in bacterial and SCFA concentrations with all three carbohydrates in ORS. However, the increases were significantly higher in children receiving Rice-ORS.

Differential expression of enteric neuroimmune-network in invasive and acute watery diarrhoea.

We aimed to evaluate the changes of nerve morphology and distribution of neurotransmitters and neuropeptides in the rectum of Shigella flexneri-infected patients and in the duodenum of Vibrio cholerae O1-infected patients. Nerve morphology was observed by transmission electron microscopy. Immunoreactivity of nerve growth factor (NGF), neurotransmitters and neuropeptides in tissues were studied by immunohistochemistry. Ultrastructural analysis of intestinal biopsy revealed persisting axons degeneration throughout the study period in all patients. Regeneration was already evident at the acute stage with marked increase at late convalescence. Both acute shigellosis and cholera were accompanied by increased expression of NGF and histamine and decreased expression of serotonin that was restored at convalescence. Immunoreactivity of vasoactive intestinal peptide (VIP) was increased during acute cholera, whereas in shigellosis VIP- and substance P-immunoreactive nerves appeared at early convalescence. Both shigellosis and cholera induced long-lasting degeneration of enteric neuronal axons, despite the presence of ongoing proliferation and regeneration processes. Neurotransmitters and neuropeptides may play differential roles in invasive and watery diarrhoea.

Efficacy of partially hydrolyzed guar gum-added oral rehydration solution in the treatment of severe cholera in adults.

BACKGROUND: Partially hydrolyzed guar gum (PHGG) is a water-soluble fiber if added to oral rehydration solution (ORS) and undergoes fermentation in the colon liberating short chain fatty acids (SCFAs). SCFAs potentiate the effect of ORS, reducing the severity of diarrhea. AIM: To examine the effect of PHGG-added ORS in reducing the stool output and duration of diarrhea in adult cholera. METHODS: 195 male patients were studied in a randomized controlled trial: (a) 65 received ORS + 25 g PHGG; (b) 65 received ORS + 50 g PHGG, and (c) 65 received ORS alone (control). Major outcomes were stool weight and duration of diarrhea. RESULTS: No significant differences were found in mean +/- SD stool weight (g/kg b.w.) during the first and second 24 h. In the subgroup analysis (excluding very high purging patients, stool weight in the first 24 h was >10 kg), the stool weight (g/kg b.w.) was significantly reduced in the first 24 h in both groups receiving PHGG (PHGG 25 g, 136 +/- 68 vs. PHGG 50 g, 144 +/- 49 vs. control, 176 +/- 43, p = 0.01). CONCLUSION: PHGG-added ORS might have a beneficial effect in moderately purging adult cholera. However, further studies are warranted to confirm the preliminary findings.

Day-care management of severe and very severe pneumonia, without associated co-morbidities such as severe malnutrition, in an urban health clinic in Dhaka, Bangladesh.

BACKGROUND: Management of severe and very severe pneumonia in children relies on hospital-based treatment, but practical barriers often prevent children in areas with the highest rates from receiving hospital care. OBJECTIVE: To develop and prospectively evaluate a day-care clinic approach, which provided antibiotics, feeding and supportive care during the day with continued care provided by parents at home, as an effective alternative to hospitalisation. METHODS: Children aged 2-59 months with severe or very severe pneumonia without associated co-morbidities, denied admission to hospital because of lack of beds, were enrolled at Radda Clinic, Dhaka and received antibiotics, feeding and supportive care from 08:00 to 17:00 every day, while mothers were educated on continuation of care at home during the night. RESULTS: From June 2003 to May 2005, 251 children were enrolled. Severe and very severe pneumonia was present in 189 (75%) and 62 (25%) children, respectively, and 143 (57%) were hypoxaemic with a mean (SD) oxygen saturation of 93 (4)%, which increased to 98 (3)% on oxygen therapy. The mean (SD) day-care period was 7 (2) days. Successful management was possible in 234 children (93% (95% CI 89% to 96%)), but 11 (4.4% (95% CI 2.5% to 7.7%)) had to be referred to hospital, and six (2.4% (95% CI 1.1% to 5.1%)) discontinued treatment. There were no deaths during the day-care study period; however, four children (1.6% (95% CI 0.6% to 4.0%)) died during the 3-month follow-up period, and 11 (4.4% (95% CI 2.5% to 7.7%)) required hospital admission. CONCLUSION: Severe and very severe pneumonia in children without associated co-morbidities such as severe malnutrition can be successfully managed at day-care clinics.

Day-care management of children with severe malnutrition in an urban health clinic in Dhaka, Bangladesh.

Management of severely malnourished children with associated complications relies on hospital-based treatment. Implementation of a standardized protocol at the Dhaka Hospital, ICDDR,B reduced case fatality approximately 50%. We developed and prospectively evaluated a day-care clinic approach that provided antibiotics, micronutrients and feeding during the day with continued care by parents at home at night as an alternative to hospitalization. Severely malnourished children aged 6-23 months denied admission to hospital were enrolled at Radda Clinic, Dhaka and received protocolized management with antibiotics, micronutrients and milk-based diet from 8:00 am to 5:00 pm each day, while mothers were educated on continuation of care at home. They were transitioned to the day-care nutrition rehabilitation (NR) unit of Radda Clinic following resolution of acute illness, received NR diet (Khichuri, halwa and milk-based) daily until children attained 80% weight-for-length. From February 2001 to November 2003, 264 children were enrolled; 52% were boys and 78%, 21% and 1% had marasmus, marasmus-kwashiorkor and kwashiorkor, respectively. Only 13% had severe malnutrition alone while 35% had pneumonia, 35% had diarrhea and 17% had both pneumonia and diarrhea. The mean (SD) duration of acute and NR phases were 8 (4) and 14 (13) days, respectively. Children gained weight [mean (SD) g/kg day] more rapidly during acute 10 (7) than NR phase 6 (5). Successful management was possible in 82% (95% CI 77-86%) children, 12% discontinued treatment and 6% referred to hospitals. Only one child died during NR phase. Severely malnourished children can be successfully managed at existing day-care clinics using a protocolized approach.

Three episodes of gracilis free muscle transfer under epidural anaesthesia.

The use of regional anaesthesia in major surgery is associated with a lower risk of complications. However, recent evidence suggests that a vascular steal phenomenon may result in a reduction of free flap blood flow in such patients. We report three cases of free gracilis transfer under epidural anaesthesia in patients who were considered high risk for general anaesthesia. Our experience suggests that there remains an important role for epidural anaesthesia in the management of patients undergoing lower limb free flap reconstruction. The inability to undergo general anaesthesia does not preclude free flap surgery in carefully selected patients.

Extended-interval gentamicin administration in malnourished children.

Malnourished children have several physiologic abnormalities that can affect drug distribution and elimination. The aim of this study was to determine the efficacy, safety and pharmacokinetics of a once-daily dose of gentamicin compared with conventional thrice-daily dosing in malnourished children. To our knowledge, it has not been investigated in this population so far. A total of 310 malnourished children of either gender aged 6 months to 5 years with diarrhea and pneumonia were randomized to receive intramuscular gentamicin 5 mg/kg/day once-daily (OD) (n=148) or the same total daily amount given in three divided doses (TD) (n=162) in addition to ceftriaxone 75 mg/kg/day. After 48 h at steady state, gentamicin pharmacokinetics was assessed by fluorescence polarization immunoassay in a subgroup of 59 children and 43 children in the OD and TD groups, respectively. The groups were equivalent in baseline demographic, clinical and laboratory characteristics. Good and partial clinical responses occurred in 64 per cent vs. 54 per cent and 25 per cent vs. 27 per cent in the OD and the TD children, respectively (p=NS for both comparisons). Five patients in each treatment group died. Renal toxicity defined by change in serum creatinine was not observed in any patient from either group. In the OD group, mean+/-SD serum gentamicin concentrations at 1 (peak), 3, 5, 8, 23, and 24 (trough value) hours after the dose were 11.7+/-4.1, 4.4+/-1.2, 2.08+/-0.9, 1.01+/-0.6, 0.31+/-0.09 and 0.29+/-0.07 mg/l respectively. In the TD group, mean +/-SD serum gentamicin concentration at 1 hour (peak) was 4.7+/-1.8 mg/l and the trough concentration was 0.48+/-0.21 mg/l. In OD group, the gentamicin trough concentration was significantly lower (p<0.001) and the peak concentration was significantly higher (p<0.001) compared to TD group. The results of this study indicate that once-daily gentamicin is effective and safe in malnourished children. Widespread implementation of once-daily dosing in malnourished children is appropriate and will reduce number of intramuscular injections and hospital costs.

Low osmolar oral rehydration salts solution in the treatment of acute watery diarrhoea in neonates and young infants: a randomized, controlled clinical trial.

To compare the efficacy and safety of low osmolar oral rehydration salts solution (ORS-75) (mmol/L: Na+ 75, osmolarity 245) with that of World Health Organization-recommended ORS (ORS-90) (mmol/L: Na+ 90, osmolarity 311 ) in the treatment of acute watery diarrhoea in neonates and very young infants, a randomized double-blind, controlled clinical trial was carried out at the Clinical Research and Service Centre of ICDDR,B: Centre for Health and Population Research, Dhaka, Bangladesh, during January 1998-December 1999. Infants, aged < or = 2 months, presenting with a history of watery diarrhoea of < or = 72 hours, with no or some dehydration and without any systemic illness, were randomly assigned to receive either ORS-75 or ORS-90 for the correction and subsequent prevention of dehydration. Infants were studied for a maximum of five days. Total stool output, stool frequency, and requirement for ORS were outcome measures. Serum electrolytes were measured at 24 hours after admission to monitor serum sodium imbalance. Seventy-three infants received ORS-75, and 71 received ORS-90. Both the groups were comparable in their baseline characteristics. Diarrhoea resolved within five days in 53% and 66% of infants receiving ORS-75 and ORS-90 respectively (p = 0.3). Total stool volume [median (inter-quartile range) 132 (65-280) vs 139 (70-259) g/kg, p = 0.9], during the study period, was not significantly different between the two groups. Total stool frequency [31 (16-51) vs 35 (16-53), p = 0.9] and total ORS intake [192 (96-374) vs 209 (134-317) mL/kg, p = 0.7] were similar between the groups. No infants developed late evidence of hypernatraemia, irrespective of treatment. The results of the study indicate that ORS-75 is as safe as standard ORS-90 in the treatment of acute watery diarrhoea in neonates and very young infants and is effective in correcting and preventing dehydration.

Partially hydrolysed guar gum supplemented comminuted chicken diet in persistent diarrhoea: a randomised controlled trial.

BACKGROUND: Partially hydrolysed guar gum (Benefiber) added to a diet is fermented in the colon, producing short chain fatty acids, which improve intestinal function, including colonic salt and water absorption. AIMS: To evaluate the effect of Benefiber supplemented comminuted chicken diet in the treatment of persistent diarrhoea. METHODS: One hundred and sixteen children (aged 5-24 months), presenting to Dhaka Hospital with a history of watery diarrhoea for more than 14 days (persistent diarrhoea), were randomised to receive either: (1) comminuted chicken diet with Benefiber (study diet); or (2) comminuted chicken diet without Benefiber (control diet). The study period was seven days. RESULTS: Of 116 children, 57 received the study diet and 59 received the control diet. Diarrhoea resolved in a greater number of children with the study than with the control diet (46/55 (84%) v 36/58 (62%); odds ratio 3.12, 95% CI 1.19 to 8.4). Survival analysis for the duration of diarrhoea also showed a reduced duration of diarrhoea in children receiving the study diet. There was also a trend in daily stool reduction in children receiving the study diet, significant on days 4-7. CONCLUSION: Results show that Benefiber supplemented comminuted chicken diet enhances recovery of children with persistent diarrhoea, indicating its therapeutic potential.

Acute dehydrating disease caused by Vibrio cholerae serogroups O1 and O139 induce increases in innate cells and inflammatory mediators at the mucosal surface of the gut.

BACKGROUND AND AIMS: The general concept is that as Vibrio cholerae is not invasive, it mediates a non-inflammatory type of infection. This is being re-evaluated based on available data that natural cholera infection or cholera toxin induces a Th2-type of immune profile and stimulates the humoral immune response, innate cells, and mediators in the host. METHODS: To perform a comprehensive analyses of the inflammatory components, we studied mucosal biopsies from patients, both adults and children with acute watery diarrhoea caused by V cholerae O1 and O139. Patients with cholera, adults (n = 30) and children (n = 18), as well as healthy controls (n = 24) were studied. Histochemical, immunohistochemical, and ultrastructural studies were carried out to elucidate the contribution of the different factors using paraffin and frozen duodenal and/or rectal sections as appropriate. Samples were collected during the acute stage and during early and/or late convalescence. RESULTS: Following natural cholera infection, patients responded with increases in neutrophil polymorphs during the acute stage (p<0.001) compared with healthy controls whereas mucosal mast cells (MMC) (p = 0.008) and eosinophils (p = 0.034) increased in the gut during convalescence. Electron microscopic analyses of duodenal biopsies from adult patients showed increased piecemeal degranulation in both MMC and eosinophils and accumulation of lipid bodies in MMC. Duodenal biopsies from V cholerae O1 infected patients showed upregulation of myeloperoxidase, lactoferrin, PGHS-1, SCF, tryptase, tumour necrosis factor alpha, alpha-defensin, and eotaxin during the acute stage and chymase, interleukin 3 and major basic protein during convalescence. CONCLUSION: We have shown that innate cells and their mediators are upregulated in acute watery diarrhoea. These cells and factors of the innate arm may be important in the host's defence against cholera. Such effects may need to be simulated in a vaccine to achieve long lasting protection from cholera.

Efficacy and safety of a modified oral rehydration solution (ReSoMaL) in the treatment of severely malnourished children with watery diarrhea.

OBJECTIVES: Efficacy, development of overhydration, and correction of electrolyte disturbances of severely malnourished children with acute diarrhea using a modified oral rehydration solution for malnourished children (termed ReSoMaL and recommended by the World Health Organization [WHO]) were evaluated and compared with standard WHO-oral rehydration solution (ORS). STUDY DESIGN: Children age 6 to 36 months with severe malnutrition and acute watery diarrhea were randomized to ReSoMaL (n=65) or standard WHO-ORS (n=65). Major outcome measures included the number of children who developed overhydration and the number who corrected hypokalemia. RESULTS: The numbers of children who developed overhydration were not significantly different (ReSoMaL vs WHO-ORS, 5% vs 12%, P=.2). ReSoMaL corrected basal hypokalemia in a greater proportion of children by 24 hours (36% vs 5%, P=.0006) and 48 hours (46% vs 16%, P=.004) compared with WHO-ORS. More children on ReSoMaL than WHO-ORS remained hyponatremic at 48 hours (29% vs 10%, P=.017). Three children in the ReSoMaL group developed severe hyponatremia by 24 hours, with one experiencing hyponatremic convulsions (serum sodium, 108 mmol/L). CONCLUSIONS: ReSoMaL has a large beneficial effect on potassium status compared with standard ORS. However, ReSoMaL therapy may result in symptomatic hyponatremia and seizures in patients with severe diarrhea.

Efficacy and tolerability of racecadotril in the treatment of cholera in adults: a double blind, randomised, controlled clinical trial.

BACKGROUND: The enkephalins, endogenous opiate substances, act as neurotransmitters along the entire digestive tract where they elicit intestinal antisecretory activity without affecting intestinal transit time or motility. Racecadotril, through inhibition of enkephalinase, reinforces the physiological activity of endogenous enkephalins and, therefore, shows intestinal antisecretory activity. AIM: We conducted the study to determine the role of racecadotril as an adjunct to the standard treatment of cholera in adults. METHODS: The study was a double blind, randomised, placebo controlled clinical trial involving 110 adult male cholera patients who received either racecadotril or placebo in addition to standard cholera treatment. The major outcome measures (stool output, oral rehydration solution (ORS) intake, requirements for unscheduled intravenous fluid infusion, and duration of diarrhoea) were compared between the groups. RESULTS: Of 110 patients enrolled, 54 received racecadotril and 56 received placebo. Admission clinical characteristics were comparable between the groups. There was no significant difference in (mean (SD)) total stool output (racecadotril v placebo 315 (228) v 280 (156) g/kg), total ORS intake (390 (264) v 369 (240) ml/kg), or duration of diarrhoea (35 (15) v 32 (13) hours) between the groups. Clinical success, defined as resolution of diarrhoea within 72 hours of initiation of study intervention, was similar in both groups (racecadotril v placebo 96% v 89%). The number of patients receiving unscheduled intravenous infusions was not significantly different between the groups (racecadotril v placebo 22% v 14%). No drug related adverse effect was noted. CONCLUSION: The study demonstrated that racecadotril therapy, although found to be safe, does not provide additional benefit in the treatment of severe cholera in adults.

Characteristics of children hospitalized with severe dehydration and persistent diarrhoea in Bangladesh.

The study analyzed data from a systematic sample of children, aged less than five years, who presented with persistent diarrhoea (diarrhoea of more than 14 days duration). It aims to differentiate (a) non-severe persistent diarrhoea (with no or mild dehydration) and (b) severe persistent diarrhoea (with moderate or severe dehydration), and to identify individual characteristics associated with severe persistent diarrhoea. In total, 7,505 patients, who represented a 4% systematic sample of the patient population, were seen during January 1993-December 1995. Of them, 297 (4%) presented with persistent diarrhoea. The male:female ratio was 2:1. Eighty-three percent of them had mild or no dehydration, and 17% had moderate or severe dehydration. Severe malnutrition of the study patients defined as weight-for-age z-score < -3, weight-for-length z-score < -3 and length-for-age z-score < -3 were 33.9%, 9.7%, and 22.7% respectively. Only 3% had oedematous malnutrition, and 11% had xerophthalmia. Factors independently associated with severe persistent diarrhoea by logistic regression analyses were: number of watery stool > 10 times during the last 24 hours prior to admission (OR, 10.0; CI, 1.2-87, p = 0.03), lower respiratory tract infection (OR, 111; CI, 4.2-2955, p = 0.004), and lack of mothers' education (OR, 7.8; CI, 1.4-41.9, p = 0.016) after controlling for confounders. Awareness and health education of mothers or caregivers and better case management during acute diarrhoeal episode might prevent the development of severe persistent diarrhoea in young children. In addition, children with severe persistent diarrhoea might need special attention to have adequate rehydration and control of extraintestinal infections, including respiratory tract infection.

Reduced osmolarity oral rehydration solution for persistent diarrhea in infants: a randomized controlled clinical trial.

OBJECTIVE: We evaluated and compared the efficacy of the World Health Organization (WHO) oral rehydration solution (ORS) and 2 different formulations of reduced osmolarity ORSs in infants with persistent diarrhea. STUDY DESIGN: Infants with persistent diarrhea (n = 95) were randomized to 1 of the 3 ORSs: WHO-ORS (control, n = 32), a glucose-based reduced osmolarity ORS (RORS-G, n = 30), or a rice-based reduced osmolarity ORS (RORS-R, n = 31) for replacement of ongoing stool losses for up to 7 days. Major outcome measures were stool volume and frequency, ORS intake, and resolution of diarrhea. RESULTS: Although there were variations from one study day to another, the stool volume was approximately 40% less in the reduced osmolarity ORS groups; consequently, these children required less ORS (22% for RORS-G and 27% for RORS-R groups). A higher proportion of children in the RORS-R groups also had resolution of diarrhea during the study period. No children in any of the treatment groups had hyponatremia. CONCLUSION: Reduced osmolarity ORS is clinically more effective than WHO-ORS and may thus be advantageous for use in the treatment of children with persistent diarrhea.

Treatment of enterotoxigenic and enteropathogenic Escherichia coli-induced diarrhoea in children with bovine immunoglobulin milk concentrate from hyperimmunized cows: a double-blind, placebo-controlled, clinical trial.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) and enteropathogenic Escherichia coli (EPEC) are important causes of diarrhoea in young children and are associated with significant mortality rates. Passive immunization with antibodies from immunized cows has previously been shown to be effective as prophylaxis against E. coli-induced diarrhoea and therapeutically against rotavirus and cryptosporidia-induced diarrhoea. METHODS: We tested the therapeutic efficacy of an oral bovine immunoglobulin milk concentrate (BIC) from cows hyperimmunized with ETEC and EPEC strains, in a randomized, placebo-controlled study in children with E. coli-induced diarrhoea. Eighty-six children between 4-24 months of age attending the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B) with E. coli-induced diarrhoea (63 EPEC/ETEC and 23 with other diarrhoeagenic E. coli) were randomly assigned to receive orally administered BIC (20 g) containing anti-ETEC/EPEC antibodies or a placebo preparation daily for 4 consecutive days. Daily stool output, intake of oral rehydration solution (ORS), stool frequency, and presence of diarrhoeagenic E. coli strains in the stool were monitored for 4 days. RESULTS: Children in the treatment group tolerated the BIC with no side effects. There were no significant differences between the two groups with regard to ORS intake, stool output, frequency of diarrhoea, or clearance of pathogen. Nor was there any significant alteration in the duration of diarrhoea. CONCLUSIONS: In contrast to the prophylactic efficacy of anti-E. coli BIC and the therapeutic efficacy of a similarly prepared anti-rotavirus BIC, antibodies from hyperimmunized cows appear to have no significant therapeutic benefit in the treatment of acute diarrhoea due to EPEC/ETEC.

Innate immune responses in children and adults with Shigellosis.

An array of pro- and anti-inflammatory mediators of the innate immune system was analyzed in stool, urine, and rectal mucosa samples from adults and children with shigellosis to better understand their role in recovery from and in the immunopathogenesis of the disease. Increased concentrations of lactoferrin (Lf), myeloperoxidase (MPO), prostaglandin E(2), and leukotriene B(4) (LTB(4)) in stool during acute shigellosis in both children and adults indicated that activated cells of the innate defense system at the mucosal site were secreting the mediators. Increased concentration of MPO and 8-iso-prostaglandin F(2alpha) and lower levels of superoxide dismutase (SOD) activity in stool during acute Shigella infection suggested increased formation of reactive oxygen species, free radical-catalyzed peroxidation of membrane lipids, and decreased scavenging of the reactive oxygen radicals. In children, lower expression of SOD in tissue with severe inflammation and lower levels of SOD activity in stool for longer periods compared to adults may further worsen the tissue damage and predispose the children to a lowered defense. Both adult and pediatric patients had significantly higher expression of inducible nitric oxide synthase (iNOS) in the rectum with severe inflammation, compared to that seen with mild inflammation, accompanied by persistently up-regulated iNOS mRNA, reflecting increased production of nitric oxide at the local site. However, in contrast to adults, reduced urinary nitrate levels in pediatric patients during acute shigellosis suggested lower production of nitric oxide in the renal compartment. Persistent production of Lf in pediatric patients may contribute to chronic inflammation in the rectum. In addition, increased production of proinflammatory mediators in the rectum of patients with severe histology suggested contribution of these molecules to the immunopathogenesis of severe colitis caused by shigellae.

Partially hydrolyzed guar gum-supplemented oral rehydration solution in the treatment of acute diarrhea in children.

BACKGROUND: Partially hydrolyzed guar gum (Benefiber; Novartis Nutrition, Minneapolis, MN, U.S.A.) is fermented by colonic bacteria liberating short-chain fatty acids (SCFAs), which accelerate colonic absorption of salt and water. The purpose of this study was to evaluate the effect of Benefiber (BF)-supplemented World Health Organization Oral Rehydration Solution (WHO ORS) in the treatment of acute noncholera diarrhea in children. METHODS: A double-blind, randomized, controlled clinical trial was performed at ICDDR,B in 150 male children aged 4 to 18 months who had watery diarrhea of less than 48 hours' duration. After admission, children were assigned to receive either WHO ORS or BF-supplemented WHO ORS until recovery. Major outcome measures, such as duration of diarrhea and amount of stool output, were compared between the treatment groups. RESULTS: Patients receiving BF-supplemented WHO ORS had significantly reduced duration of diarrhea compared with the control group (mean +/- SD, 74 +/- 37 vs. 90 +/- 50 hours, P = 0.03). Survival analysis for duration of diarrhea also showed a reduction the BF-supplemented WHO ORS-treated group (P = 0.025, log rank test). There was also less stool output daily from days 2 through 7 in the patients treated with BF-supplemented WHO ORS compared with that in the children treated with WHO ORS; the reduction was significant on day 7 only. CONCLUSION: Benefiber added to standard WHO ORS substantially reduces the duration of diarrhea and modestly reduced stool output in acute noncholera diarrhea in young children, indicating its potential as a new antidiarrheal therapy for acute diarrhea in children.

Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. CHOICE study group.

BACKGROUND: The effects of oral rehydration solution (ORS) with reduced osmolarity on children with acute watery diarrhoea are known, but little is known about the effects of such ORS on adults with cholera. We aimed to compare the efficacy and safety of an ORS with reduced osmolarity with that of standard WHO ORS in adults with cholera. METHODS: We undertook a double-blind, controlled clinical trial in adults with severe cholera at the International Centre for Diarrhoeal Disease Research, Bangladesh. Our primary outcomes were mean stool output in the 24 h after randomisation, proportion of patients who needed unscheduled intravenous therapy, and proportion of patients with biochemical hyponatraemia 24 h after randomisation. FINDINGS: 147 patients received ORS with reduced osmolarity and 153 received standard WHO ORS. There was no significant difference between the two groups in terms of main outcome variables: mean initial 24 h and total stool output (reduced osmolarity vs standard WHO ORS 212 [SE 8] vs 207 [8] and 284 [13] vs 273 [13] g/kg respectively), duration of diarrhoea (46 [1.5] vs 43 [1.5]). The proportion of patients vomiting during the first 24 h and the proportion who received unscheduled intravenous infusion during the first 24 h was similar between groups. More patients on reduced osmolarity ORS than on standard WHO ORS developed hyponatraemia during the first 24 h, defined as serum sodium concentration below 130 mmol/L (29 of 142 vs 16 of 150; odds ratio 2.1 [95% CI 1.1-4.1]). However, all hyponatraemic patients in both groups were symptom-free and the proportion of patients with serum sodium concentration below 125 mmol/L was similar between groups. INTERPRETATION: There was no difference in clinical outcome between cholera patients treated with reduced osmolarity ORS solution and those treated with standard WHO ORS. The risk of increased incidence of symptom-free hyponatraemia in patients with cholera treated with an ORS with reduced osmolarity should be further assessed by meta-analysis. The risk should be taken into account when choice of ORS is made in areas in which cholera is endemic.