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Biomedical subjects

D Mahalanabis

Publications and source records attributed to D Mahalanabis.

At least 19 recordsLinked to original sources

Role of Shigella flexneri 2a 34 kDa outer membrane protein in induction of protective immune response.

Emergence of Shigella vaccine is in great need in developing countries. In this paper we have shown that 34 kDa Shigella flexneri 2a outer membrane protein has a role in eliciting immune responses. When injected parentarally this protein gives significant protection against challenge with virulent Shigella flexneri 2a. Macrophages activated with the 34 kDa protein resulted in the dose dependent production of nitric oxide, the highly reactive free radical responsible for killing of invading bacterial pathogen. Also, treatment of murine peritoneal macrophages with the 34 kDa protein showed dose dependent increase in the production of tumor necrosis factor-alpha and interleukin-12. However, there was no dose dependent increase in interleukin-10 production. These data indicated that the 34 kDa outer membrane protein has the ability to modulate the protective immune response against the invading bacterial pathogen, mainly through TH1 mediated pathway. So, the 34 kDa outer mebrane protein can be one of the major components for developing subunit vaccine against shigellosis.

Animals↗

Antioxidant vitamins E and C as adjunct therapy of severe acute lower-respiratory infection in infants and young children: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of antioxidant Vitamins E and C as adjunct therapy of severe acute lower respiratory infection (ALRI) in children. DESIGN: Randomized double-blind placebo-controlled clinical trial. SETTING: A large childrens' hospital serving the urban poor in Kolkata, India. SUBJECTS: Children aged 2-35 months admitted with severe ALRI. INTERVENTION: In total, 174 children were randomly assigned to receive alpha-tocopherol 200 mg and ascorbic acid 100 mg twice daily or placebo for 5 days. All children received standard treatment for severe ALRI. Outcome measures were: time taken to recover from a very ill status, fever, tachypnoea, and feeding difficulty; and improvement in oxidative stress and immune response indicated by thiobarbituric acid reacting substances (TBARS) and response to skin antigens, respectively. RESULTS: Recovery rate ratios (95% CI) using proportional hazards model were 0.89 (0.64-1.25), 1.01 (0.72-1.41), 0.86 (0.57-1.29), and 1.12 (0.77-1.64) for very ill status, feeding difficulty, fever, and tachypnoea, respectively. TBARS values were high and similar in the two groups at admission, discharge, and at 2 weeks follow-up. Serum alpha-tocopherol significantly increased in treated group at discharge. Immune response to skin antigens were very poor at admission and after 2 weeks, in both groups. CONCLUSION: Infants with severe ALRI failed to benefit from two antioxidant nutrients as adjunct therapy. Severe ALRI in infants may cause cell-mediated immune dysfunction. We need a better understanding of oxidative processes in growing infants to help us better design interventions with antioxidant therapy.

Acute Disease↗

Protective efficacy of oral immunization with heat-killed Shigella flexneri 2a in animal model: study of cross protection, immune response and antigenic recognition.

Oral immunization of rabbits with four doses of 10(11) heat-killed Shigella flexneri 2a showed 100% protection against challenge with virulent S. flexneri 2a. After orally immunizing Guinea pigs with four doses of heat-killed S. flexneri 2a 100% protection could be shown against ocular challenge with the same virulent S. flexneri 2a strain but this conferred no protection against challenge with Shigella dysenteriae type 1. In enzyme-linked immunosorbent assay (ELISA) and immunoblot experiments both whole cell lysate-envelope (WCL-E) fraction and outer membrane proteins (OMPs) were recognized by the antisera. Though protective mechanism in shigellosis is not established with certainty, outer membrane proteins (specially 38, 34, 23 and 20kDa proteins) may be the major antigens in the induction of protective immune responses as indicated by this observation.

Administration, Oral↗

Lean body mass in preschool aged urban children in India: gender difference.

OBJECTIVE: To estimate lean body mass (LBM) in preschool aged boys and girls in India and explore gender difference. DESIGN: Crossectional. SETTING: Immunization clinic of a charitable Government General Hospital in Kolkata, India. SUBJECTS: Two-hundred and forty-five children (147 boys and 98 girls) aged 1-5 y from among the urban poor were admitted in the study between July 1999 and December 2000. Children with acute or chronic illness or congenital malformation were excluded. METHOD: Length/height to the nearest 0.1 cm, weight to the nearest 10 g and total body resistance using multifrequency bioelectrical (Xitron 4000B) impedance analyzer (BIA) at 50 kHz were measured. Their nutritional status was compared with National Center for Health Statistics (NCHS) median data and lean body mass (LBM) was calculated using anthropometry and BIA equations. The groups were compared using analysis of variance and multiple linear regression. RESULTS: Girls were more stunted (P<0.001) and underweight (P<0.047), while the degree of wasting was similar. Mean LBM percentage was higher in boys compared with girls by anthropometry (P<0.001) and BIA (P<0.005), which persisted after adjusting for age. With increasing age, LBM percentage declined in girls (P<0.02) in contrast to reference girls, in whom it increased. In boys LBM percentage increased with age as is in reference boys. CONCLUSIONS: In addition to the girls being more stunted and underweight, LBM% decreased in girls with increasing age but steadily increased in boys, suggesting hidden deprivation of female children.

Age Factors↗

Risk factors for pneumonia in infants and young children and the role of solid fuel for cooking: a case-control study.

We evaluated the risk factors for childhood pneumonia with particular reference to indoor air-pollution associated with solid fuel use for cooking (e.g. coal, wood, dung), using a case-control study in a children's hospital in Calcutta. Cases were 127 children aged 2-35 months of either sex admitted with pneumonia and controls were 135 children attending their immunization clinic. Solid fuel use (odds ratio = 3.97, CI = 2.00-7.88), history of asthma in the child (OR = 5.49, CI = 2.37-12.74), poor economic status indicator (OR = 4.95, CI = 2.38 to 10.28), keeping large animals (OR = 6.03, CI = 1.13-32.27) were associated with high risk of pneumonia after adjusting for confounding (logistic regression analysis). Nearly 80% of people in India use such smoke producing fuel and the population attributable risk would be very high. This finding has important health policy implications. Furthermore, history of asthma is a useful prognostic indicator for early action for prevention of severe pneumonia.

Air Pollution, Indoor↗

Folic acid supplementation on red kidney bean-induced diarrhoea and enteric bacterial translocation into mesenteric lymph nodes in rats: a pilot study.

UNLABELLED: Deaths following childhood diarrhoea, a major health problem in developing countries, are often associated with malnutrition and septicaemic complications. Folic acid has been used in the treatment of acute and chronic diarrhoea in the tropics. Using a rat model, we evaluated the protective effect of large doses of folic acid on diarrhoea, small intestinal bacterial overgrowth and translocation of enteric bacteria into mesenteric lymph nodes induced by a raw red kidney bean-based diet containing lectin (phytohemagglutinin). Long-Evans rats in 2 groups of 5 each (60 g to 70 g in weight, 28 d old) were used. All 10 rats, individually kept in metabolic cages, received a raw red kidney bean-based diet for 10 d, and 5 of them also received a daily folic acid supplement (160 microg/g feed) both during and for 10 d before the experiment. The faecal weight was measured and a quantitative aerobic bacterial culture of the small intestinal mucosal scrapings and of the mesenteric lymph nodes was made. Folic acid supplementation did not reduce faecal output nor did it prevent loss of body weight associated with lectin-induced diarrhoea. However, the mean total count of enteric bacteria translocated to the mesenteric lymph nodes was significantly reduced in the supplemented rats (1.27 +/- 0.61 vs 2.66 +/- 0.84, p = 0.028) and a trend towards reduced bacterial count in the small intestinal mucosal scrapings (0.40 +/- 0.89 vs 1.42 +/- 1.31, p = 0.16) was documented. A significant positive correlation was also seen between the bacterial count in the jejunal mucosal scrapings and in the mesenteric lymph nodes. CONCLUSION: Although large-dose folic acid supplementation did not prevent diarrhoea and malnutrition induced by a lectin-based diet, it substantially reduced the count of enteric bacteria translocated into the mesenteric lymph nodes and showed a trend towards a reduction in indigenous bacteria adhering to jejunal mucosa. These findings could be of relevance in the prevention of septicaemic complications following many clinical conditions, including diarrhoea with malnutrition in children known to have bacteraemic and septicaemic complications.

Animals↗

Persistent diarrhoea: associated infection and response to a low lactose diet.

Children aged 4-23 months with persistent diarrhoea received a low lactose diet, multivitamins, minerals and antibiotics for infection. Sixty-one (57 per cent) children improved with low lactose diet while 46 (43 per cent) failed. Children who failed were younger (8.9 +/- 3.5 vs. 11.3 +/- 4.4 months), had higher initial purging rate (146 +/- 102 vs. 109 +/- 102 g/kg/day) and consumed more ORS (138 +/- 77 vs. 95 +/- 79 g/kg/day). A higher proportion of children in the failure group needed unscheduled intravenous fluid (48 vs. 20 per cent) and lost body weight (24 vs. 0 per cent). Single and multiple stool pathogen were isolated from 44 and 45 per cent cases, respectively. Diarrhoeagenic Escherichia coli (66 per cent) was the most common pathogen isolated. Half of all pathogens including Campylobacter, rotavirus, cholera and non-typhoidal Salmonella were nosocomially acquired. Sixty four per cent of children had extraintestinal infections including acute lower respiratory infection (50 per cent), urinary tract infection (29 per cent) and septicaemia (11 per cent). The presence of extraintestinal infections were significantly associated with failure. Overall, 91 per cent of children had either intestinal and/or extraintestinal infections.

Age Factors↗

Tetracycline in the treatment of severe cholera due to Vibrio cholerae O139 Bengal.

Vibrio cholerae O139 synonym Bengal, recognized in 1993, is the second member in the list of about 200 serogroups of V. cholerae with epidemic and pandemic potential. Although replacement of fluids and electrolytes remains the cornerstone in the management of cholera, antimicrobial therapy can significantly shorten the duration of diarrhoea, and reduce stool volume and requirements ofrehydration fluids. The role of antimicrobial therapy on the natural course of the disease caused by this relatively new pathogen has not been systematically assessed. A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy of tetracycline in the treatment of adults with severe cholera due to V. cholerae O139 Bengal. Forty-three adult males with severe cholera were randomly allocated to receive either 500 mg of tetracycline (n=21) or placebo (n=22) for three consecutive days. Demographic and clinical characteristics of these patients on admission were comparable. Tetracycline therapy was associated with significantly reduced total median (inter-quartile range) stool volume [216.48 (90.18-325.22) mL/kg vs 334.25 (215.12-537.64) mL/kg; p=0.001], higher rates of clinical cure (81% vs 27%; p<0.001), and shorter median (inter-quartile range) duration of diarrhoea [32 (24-48) hours vs 80 (48-104) hours; p<0.001]. The mean +/- (SD) requirement of intravenous fluid was not significantly different between the two groups [146.42 +/- 42.12 mL/kg vs 150.44 +/- 27.21 mL/kg; p=0.70]. The median (inter-quartile range) duration of faecal excretion of V. cholerae O139 was significantly shorter in the tetracycline group than the placebo group [1(1-2) day vs 5 (3-6) days; p<0.001]. The results of the study indicate that tetracycline therapy is clinically useful in the treatment of severe cholera due to V. cholerae O139 Bengal.

Adolescent↗

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.

Bicarbonates↗

Micronutrients as adjunct therapy of acute illness in children: impact on the episode outcome and policy implications of current findings.

Role of micronutrients namely vitamin A, zinc and folate, as adjunct therapy of illness episodes in children in developing countries have been discussed in the light of health policy. Apart from a selective review, attempts have been made to statistically combine results of several studies to address policy issues. In children, vitamin A supplementation during illness has (a) a profound effect in reducing mortality in measles, (b) possibly a significant effect in reducing persistent diarrhea episodes in children with acute diarrhea, and (c) no benefit in pneumonia. Use of large dose vitamin A is recommended during measles episodes but not in non-measles pneumonia. Its use in acute diarrhea is debatable but recommended in persistent diarrhea and in severe malnutrition as a component of a micronutrient mixture. Large dose vitamin A supplementation should be used with caution in young infants as there are unresolved concerns about its safety particularly, bulging fontanelle observed in infants when co-administered at immunization. In children, zinc supplementation during illness, (a) had a marked effect in reducing prolonged episodes and a modest effect on episode duration in acute diarrhea, (b) resulted in reduced rate of treatment failure and death in persistent diarrhea, (c) had no effect in measles and non-measles pneumonia, and (d) probably had a detrimental effect of increasing death rate when a large dose was used in severely malnourished children. The desirability of routine zinc supplementation therapy of undernourished children with acute diarrhea should be assessed further. Concerning policy, zinc supplementation as a component of a micronutrient mixture is recommended in the rehabilitation of severely malnourished children and in persistent diarrhea. However, recommendation for its routine use in all cases of acute diarrhea in children needs additional studies on effectiveness, cost, operations and safety. In two randomized controlled trials folate has been evaluated in acute and persistent diarrhea and found to have no beneficial effect. Folate is not recommended as adjunct therapy of diarrhea. Role of folate in preventing severe disease and/or death deserves further evaluation.

Acute Disease↗

Hyperimmune bovine colostrum in the treatment of shigellosis in children: a double-blind, randomized, controlled trial.

UNLABELLED: Immunological approaches have been considered as an alternative therapeutic option for the treatment of enteric infections over the past few years. Hyperimmune bovine colostrum (HBC) is a potentially innovative immunological option in the management of shigellosis together with traditional antibiotic therapy. Children aged 1-12 y with a history of bloody mucoid diarrhoea of less than 5 d duration were enrolled after their stool specimen was found to be positive for Shigella dysenteriae type I antigen by a rapid diagnostic fluorescent antibody staining test. They were randomized to receive either HBC containing very high titres of antibody against S. dysenteriae type I antigen or bovine colostrum (BC) without any antibody. The study group received 100 ml of HBC three times a day orally for 3 d and control group received BC. Children also received pivmecillinam in a dose of 50 mg kg(-1) d(-1) in four divided doses orally for 5 d. Admission characteristics of the 34 children in the HBC group and 35 in the BC group were comparable. No significant differences were observed in duration of diarrhoea, fever, anorexia, abdominal pain, tenesmus, stool frequency or visible blood in the stool between the groups. Two (6%) children in the study and five (14%) in the control group remained stool culture positive for S. dysenteriae type 1, even after 5 d of sensitive antimicrobial therapy. CONCLUSION: The results indicate that HBC as an adjuvant is unable to show any beneficial effect in reducing the stool frequency, duration or severity of childhood shigellosis due to S. dysenteriae type I infection.

Amdinocillin Pivoxil↗

Sodium and water homeostasis in children with shigellosis.

UNLABELLED: Studies in Bangladesh have shown that the mortality in shigellosis is significantly higher in hyponatraemic (HN) than in normo- (NN) or hypernatraemic children. The aim of this study was to describe the effect of shigellosis on renal haemodynamics and sodium and water homeostasis before treatment was started. Twenty-one moderately ill children infected with Shigella dysenteriae type I were studied. Eight of them had a serum sodium concentration below 130 mmol/L. Renal function was determined by glomerular filtration rate measured by clearances of inulin and iohexol. Effective renal plasma flow was estimated by clearance of para-aminohippuric acid. Plasma renin, aldosterone and anti-diuretic hormone were also studied. The HN children had significantly higher haemoglobin and haematocrit levels than the NN group. There was an inverse correlation between serum sodium and haemoglobin, and a direct correlation between serum sodium and urinary sodium and urinary chloride. Direct correlations were found between serum aldosterone and haemoglobin, plasma renin and systolic blood pressure and an inverse correlation between serum aldosterone and serum sodium. Clearances of inulin and iohexol were normal. Detectable levels of ADH were found in both groups, despite low serum osmolalities. CONCLUSION: The HN state seems to be triggered by multiple factors. The normal glomerular filtration rate excludes a volume expansion secondary to reduced renal function. Inappropriate or a physiological increase of anti-diuretic hormone secretion may be of importance. The higher sodium losses in stools of the HN children might also be a factor contributing to the HN.

Body Mass Index↗

Screening of patients with acute infectious diarrhoea: evaluation of clinical features, faecal microscopy, and faecal occult blood testing.

BACKGROUND: For optimal management of acute infectious diarrhoeal diseases, it is necessary to utilize a screening process to distinguish between invasive and non-invasive diarrhoeas. The aim of this study was to compare the diagnostic utilities of clinical features, faecal microscopy (FM), and faecal occult blood testing (FOBT) in distinguishing invasive diarrhoeas from non-invasive ones. METHODS: A total of 1008 patients with acute diarrhoea were evaluated. Rectal swabs were cultured for Salmonella, Shigella, and Vibrio species; rectal swabs from 109 of these patients were also examined for Campylobacter, enterotoxigenic Escherichia coli, and rotavirus species. Isolation of faecal enteropathogens served as the gold standard. FOBT was performed with a commercial modified guaiac test. Specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and likelihood ratio were compared. RESULTS: Among the 1008 patients 402 with a single identified enteropathogen were available for analysis. Invasive and non-invasive enteropathogens were isolated from 262 (65.2%) and 140 (34.8%) cases, respectively. The presence of visible blood in faeces was almost a pathognomonic sign of invasive diarrhoea but had poor sensitivity. Clinical features were useful but inadequate in differentiating patients with non-bloody diarrhoea (74% of patients) into invasive and non-invasive categories. The sensitivities, specificities, PPVs, and NPVs of FM and FOBT were 75%, 77%, 58%, 88%, and 85%, 68%, 53%, and 91%, respectively. CONCLUSION: The presence of visible blood in faeces is a highly specific clinical feature of invasive diarrhoea but suffers from low sensitivity. In non-bloody diarrhoea FOBT is a valuable screening test and is comparable to FM, particularly when interpreted in the clinical context.

Acute Disease↗

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.

Acute Disease↗

Vibrio cholerae O139 Bengal: a descriptive study.

A prospective study was conducted to determine the clinical and laboratory characteristics and the clinical course of cholera due to Vibrio cholerae O139 Bengal. The study subjects included 22 adult males with stool culture-proven V. cholerae O139. On enrollment, mean +/- SD concentrations (mmol/L) of serum sodium, potassium, chloride, and bicarbonate were 134 +/- 3, 4 +/- 1, 102 +/- 4, and 13 +/- 4 respectively, and stool sodium, potassium, chloride, and bicarbonate concentrations were 120 +/- 24, 18 +/- 6, 93 +/- 16, and 37 +/- 9 respectively. Seventeen patients (7.8%) had faecal leukocytes ranging from 11 to 50 per high-power field. All V. cholerae O139 isolates (100%) were susceptible to tetracycline, erythromycin, and ciprofloxacin, 92% to furazolidine, and only 5% to trimethoprim-sulphamethaxazole. The median (interquartile) volume of liquid stool during the first 24 hours was 9 (5-12) litre. The median (interquartile) volume of liquid stool and the amounts of intravenous and oral rehydration fluids required during the entire study period were 16 (9-24) litre, 9 (6-18) litre, and 14 (9-20) litre respectively. The median (interquartile) duration of diarrhoea was 80 (48-104) hours. The median (interquartile) duration of excretion of V. cholerae O139 in stool was 5 (3-6) days. Clinical and laboratory features, and case management of cholera due to V. cholerae O139 are very similar to conventional cholera due to V. cholerae O1.

Adolescent↗