Reinfection with a different Vi-phage type of Salmonella typhi in an endemic area.
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Biomedical subjects
Publications and source records attributed to T Butler.
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To evaluate the antisecretory activity of berberine sulfate (BS), we studied 165 adult patients with acute diarrhea due to enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae in randomized controlled trials. In patients with ETEC diarrhea who received 400 mg of BS in a single oral dose, the mean stool volumes were significantly less than those of the controls during three consecutive 8-hr periods after treatment (P less than .05). At 24 hr after treatment, significantly more patients who were treated with BS and had ETEC diarrhea stopped having diarrhea as compared with the controls (42% vs 20%, P less than .05). In patients with cholera who received 400 mg of BS, the mean 8-hr stool volume during the second 8-hr period after treatment declined to 2.22 liters, which was significantly less than the 2.79 liters found in the controls (P less than .05). However, patients with cholera who received 1200 mg of BS plus tetracycline did not have significant reduction in stool output compared with patients who received tetracycline alone. No side effects of BS were noted. These results indicated that BS is an effective and safe antisecretory drug for ETEC diarrhea, whereas the activity against cholera is slight and not additive with tetracycline.
To describe the pathology and clinical features of segmental necrotising enterocolitis (SNE) in children and adults, 22 diarrhoeal patients (median age two years, range two months to 50 years) in Bangladesh with this lesion detected at autopsy were examined and compared with two groups of diarrhoeal control patients. Gross pathology consisted of purplish or black mucosal or transmural discoloration with erosions or ulcerations in segments of the jejunum or ileum of 18 cases and of the colon alone in four cases. Two patients had intestinal perforations. Microscopically all specimens showed coagulation necrosis or haemorrhagic necrosis indicative of mucosal ischaemia. In 20 cases there was submucosal oedema and nine showed pneumatosis of the bowel. From 11, one or more of the invasive diarrhoeal pathogens Shigella, Campylobacter and Entamoeba histolytica were detected. From the comparison with controls significant associations were found for a long duration of diarrhoea, blood and mucus in stool, abdominal distension or tenderness, shock not attributable to hypovolaemia, septicaemia, and low concentration of serum protein (p less than 0.05). These findings indicated that segmental necrotising enterocolitis develops sometimes as a fatal complication of prolonged diarrhoeal illnesses associated with shock and hypoproteinaemia and is caused by ischaemic injury to the intestinal mucosa.
The cause of death (besides dehydration) for 140 diarrhoeal patients who died in hospital following rehydration was determined by autopsy examination. Children under 5 years comprised 74% of the patients. Diarrhoeal pathogens were identified as Shigella spp. in 27%, enterotoxigenic Escherichia coli in 17%, Entamoeba histolytica in 16%, Campylobacter jejuni in 12%, Salmonella spp. in 4%, Vibrio cholerae in 4%, and Giardia lambliain 4% of cases. The most frequent underlying causes of death were colitis in 44% and pneumonia in 38%. The most frequent immediate causes of death were septicaemia in 27%, hypoglycaemia in 9%, and hypokalaemia in 9%; multiple causes of death were present in 89% of cases. Kwashiorkor or marasmus was present in 59% and fatty degeneration of the liver was detected in 61% of cases. It is concluded that, in susceptible children, diarrhoeal pathogens produce destructive inflammation in the intestine and cause death or contribute to it by provoking disease in other tissues, especially septicaemia and fatty liver, or by combining these effects with antecedent or concomitant conditions, especially pneumonia and malnutrition.
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To study the metabolic acidosis that occurs during the diarrhea of cholera, we examined the serum anion gap in 21 patients with hypovolemic shock due to Vibrio cholerae infection. Measurements of serum electrolytes, as well as divalent cations and the anionic contributions of serum proteins, lactate, phosphate, and serum creatinine, were made at the time of admission, after rehydration, and during convalescence. At the time of admission, the mean serum concentration of sodium was 134.8 mmol (meq) per liter, that of chloride was 103.2 mmol per liter, and that of bicarbonate was 11.4 mmol per liter; the mean anion gap was 20.2 mmol per liter. The mean serum creatinine concentration was 2.48 mg per deciliter. The low serum bicarbonate level and the high serum anion gap were corrected by rehydration. The increased serum anion gap was caused by hyperproteinemia, lactic acidemia, and hyperphosphatemia, with anionic contributions to the rise in anion gap estimated as protein, 5.5 meq per liter; lactate, 2.5 meq per liter; and phosphate, 2.5 meq per liter. The hyperproteinemia was attributed to dehydration, the lactic acidemia to shock, and the hyperphosphatemia to acidosis and transient renal failure. The mean concentrations of serum calcium and magnesium were slightly elevated but did not affect the increased anion gap. These results indicate that severe cholera causes acidosis with relatively little change in serum chloride but an increased serum anion gap. The acidosis is more profound than would be expected on the basis of stool losses of bicarbonate, because of superimposed lactic acidemia and renal failure.
To study the function of the colon in cholera, 12 patients with acute cholera diarrhea were subjected to measurements of ileocecal flow rates, fecal flow rates, and ionic compositions of stool and ileocecal fluid. Subtraction of fecal flow rates from ileocecal flow rates was taken as a measure of net fluid absorption by the colon. Additionally, these patients underwent colonoscopic perfusion of the colon that measured net colonic absorption rates of water and ions. The mean ileocecal flow rate was 7.9 ml/min compared with a mean fecal flow rate of 7.6 ml/min, indicating a small mean net fluid absorption by the colon of +0.30 ml/min. By colonoscopic perfusion, 6 patients showed net colonic absorption of water and 6 patients net secretion of water with a slight mean net fluid secretion of -0.03 ml/min. The handling of ions by the colon showed mean net absorption of sodium (100 mu Eq/min) and chloride (127 mu Eq/min), and net secretions of potassium (-42 mu Eq/min) and bicarbonate (-112 mu Eq/min). During convalescence, 5 patients who were studied again all showed net colonic absorption of water, and the handling of potassium changed significantly from net secretion in acute disease to net absorption (p less than 0.05). These results showed that the colon contributes to the clinical expression of cholera by failing to absorb water normally, and by secreting potassium at high rates.
To study the pathogenesis of shigella diarrhea, we evaluated 11 patients for colonic fluid and electrolyte flux. Methods used were subtraction of the fecal flow rate from the ileocecal flow rate and colonoscopic perfusion of the colon. The mean ileocecal flow rate was 0.57 ml/min compared with a mean fecal flow rate of 0.48 ml/min, and the mean of the differences showed a slight net colonic water absorption of +0.09 ml/min. With use of perfusion, these patients showed an overall mean of slight net fluid secretion by the colon of -0.04 ml/min. Seven patients restudied during convalescence showed a mean net rate of colonic water absorption of +0.65 ml/min, which was significantly greater than in the acute phase (P less than .05), and a mean ileocecal flow rate of 0.56 ml/min. Ion transport by the colon during acute shigellosis showed net secretion of K+, which changed to net absorption in convalescence (P less than .05), and a decreased absorption of Cl-, which improved in convalescence (P less than .05). Patients with extensive colitis showed more impairment of net water absorption by the colon than did patients with colitis limited to the rectosigmoid colon. These findings demonstrate that shigella diarrhea results from colonic dysfunction, without evidence of increased small intestinal flow rate, and this colonic dysfunction consists of diminished net absorption of water and Cl- and increased secretion of K+.
To evaluate ceftriaxone for the treatment of shigellosis, 94 adult males with acute dysentery were randomly assigned to receive ceftriaxone (1 g), ampicillin (4 g), or saline placebo intravenously in single doses in a double-blind design. Stool cultures were positive for Shigella dysenteriae in 52 patients, S. flexneri in 38 patients, and other species in 4 patients. Both ceftriaxone and ampicillin caused reductions in the mean duration of fever and the means of daily stool frequency 2 to 4 days after therapy versus placebo (P less than 0.05). The ability of ceftriaxone to reduce stool frequency during 6 days after treatment was significant in patients with S. flexneri infections (P less than 0.05), whereas S. dysenteriae infections were relatively refractory to improvement by both antibiotics. Neither drug had a significant effect on overall duration of diarrhea, blood in stool, or tenesmus. Ampicillin reduced the mean duration of positive stool cultures after treatment from 2.6 days in the placebo group to 1.1 days (P less than 0.05), whereas ceftriaxone did not affect the duration of Shigella sp. excretion. These results indicate that single intravenous doses of ceftriaxone and ampicillin caused some clinical improvement in acute shigellosis but only ampicillin exerted a bacteriological effect on Shigella sp. excretion.
To compare the clinical efficacy of oral rehydration salts (ORS) from effervescent tablets containing citrate with the WHO recommended ORS for the treatment of dehydration due to acute diarrhoea, a randomized clinical trial was carried out in 57 adults and 58 children. These patients had mild or moderate degrees of dehydration and acidosis due to acute watery diarrhoea that was caused by enterotoxigenic Escherichia coli in 43-47% of the cases. Efficacies were compared by measuring oral fluid intake, stool output, gain in body weight, decrease in serum specific gravity and correction of acidosis during treatment. Successful rehydration and maintenance of hydration was achieved in 25 adults and 24 children treated with citrate containing ORS and 25 adults and 24 children treated with WHO ORS. The mean intake of ORS/kg body weight in children receiving WHO ORS was greater (p less than 0.05) and correction of acidosis was faster than the citrate group during the initial 24 h of therapy (p less than 0.05). By 48 h, however, both groups showed satisfactory and comparable intake of ORS and correction of acidosis. Thus ORS from effervescent tablets containing sodium citrate base is effective for management of diarrhoea in both adults and children and is a convenient stable form of ORS for use in the home and for travelers.
In a search for Yersinia infection in Bangladesh, one isolate of Y. enterocolitica serotype 0:3 was obtained from stools of 1,450 children with fever and diarrhea and one of Y. enterocolitica serotype 0:8 was recovered from intestinal contents of 80 fatal diarrheal cases during postmortem examination. These results suggest that Yersinia infection is an infrequent cause of tropical diarrhea.
A randomized, controlled trial was conducted to investigate the ability of indomethacin and chloroquine to reduce intestinal secretion in 29 adult patients with severe cholera. All patients received intravenous infusion to restore fluid balance, but no antibiotics were given. Patients treated with oral indomethacin (total 200 mg) and chloroquine (total 1.5 g) did not have significantly different stool output than untreated controls during the five 8-h posttreatment periods (40 h).
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.
To study the pathogenesis of diarrhea occurring with typhoid fever, we selected 42 patients with diarrhea and blood cultures positive for Salmonella typhi or Salmonella paratyphi A, but without diarrheal copathogens, for measurement of stool output and examination of fecal composition. The mean duration of fever before hospitalization was 9.5 days, and the mean duration of diarrhea was 5.8 days. All patients passed liquid stool on their first day in the hospital, ranging in volume from 4 to 172 ml/kg with a mean of 45 ml/kg. Red blood cells were in the stools of 57% of the patients. All patients had fecal leukocytes with a mean of 4,950 leukocytes/mm3, predominantly polymorphonuclear leukocytes. In the stools, the mean protein concentration was 9.3 g/liter; the mean pH was 6.1, and the mean concentration of electrolytes was as follows: sodium, 47 mEq/liter; potassium, 48 mEq/liter; and chloride, 43 mEq/liter. The mean total CO2 was 24 mmol/liter. During treatment with chloramphenicol, this group of patients showed daily improvement with a drop in both fever and stool output. The results indicate that patients with diarrhea during typhoid fever have a wide range of rates of purging, and the diarrhea is characterized by liquid stool containing large quantities of leukocytes and protein and is resolved by treatment with chloramphenicol.
The prevalence, presentation, and outcome of bacteremia due to Shigella and other gram-negative bacteria were determined by review of records of 2,018 inpatients with shigellosis who had their blood cultured in a Bangladeshi hospital in 1976-1983. Shigella bacteremia occurred in 82 (4.1%) patients; other bacteremia occurred in 102 (5.1%) patients. Patients with shigella sepsis more frequently (P less than .02) manifested severe dehydration, abdominal tenderness or ileus, agitation or lethargy, and leukocytosis than did nonbacteremic controls; they developed more frequently (P less than .05) renal failure (26%), leukemoid reaction (22%), thrombocytopenia (20%), and hemolytic-uremic syndrome (6%). The prevalence of all bacteremia was highest in the first year of life. Protein-energy malnutrition was a strong risk factor for shigella sepsis (P less than .01). The fatality rate in shigella bacteremia (21%) was higher (P less than .005) than in nonbacteremic shigellosis (10%) but lower (P less than .001) than in other bacteremia (51%). At highest risk of death from shigella bacteremia (P less than .01) were patients less than one year old, non-breast-fed, malnourished, and afebrile.
The dysgonic fermenter-2 bacterium is a newly recognized fastidious gram-negative bacillus that causes bacteremia and sometimes endocarditis in immunocompromised persons after they are bitten by dogs. To develop an experimental model of this infection, we placed polyethylene catheters across the aortic valves of New Zealand white rabbits, which were inoculated intravenously the next day with dysgonic fermenter-2 bacteria. After 1 week, the rabbits were killed and the endocardial vegetations were homogenized for quantitative culture. Large inocula (1.3 X 10(10) to 2.1 X 10(10) viable bacteria) were required to produce infected vegetations. All infected rabbits had negative blood cultures at the time of autopsy and most developed serum agglutinins against dysgonic fermenter-2 bacteria. Three daily injections of methylprednisolone (30 mg/kg), starting the day before inoculation, significantly increased the incidence of endocarditis and the number of bacteria per gram of infected vegetation (P less than 0.05). Treatment with methylprednisolone prolonged the initial bacteremia and caused significant increases in the numbers of bacteria per gram of blood, spleen, and liver compared with those of untreated controls (P less than 0.05). Rabbits that had previously undergone splenectomy showed prolongation of the initial bacteremia but no significant increase in the incidence of infected vegetations. These results showed that the dysgonic fermenter-2 bacterium is a pathogen that causes endocarditis in rabbits but that it requires a large inoculum and produces blood culture-negative infections. Treatment with methylprednisolone enhances infection by prolonging the initial bacteremia and probably by diminishing bactericidal activity in the vegetations.
To develop an animal model of the haemolytic-uraemic syndrome during shigellosis, rabbits were injected with lipopolysaccharides (LPS) extracted by the hot phenol-water method from Shigella dysenteriae I and from S. flexneri. Two intravenous injections of LPS spaced by 24 h elicited renal cortical necrosis in a generalized Shwartzman reaction characterized by fibrin deposition in glomerular capillaries and by elevated plasma creatinine concentration. Rabbits rendered leucopenic by busulphan treatment were protected against renal cortical necrosis after injection with LPS derived from S. dysenteriae I. Both LPS preparations derived from Shigella species were also active in producing fever in rabbits, death in rabbits, and gelation of limulus lysate with approximately the same potency as a standard LPS of E. coli 055:B5. These results demonstrated that the LPS of Shigella species given intravenously to rabbits produces renal cortical necrosis, which is caused by leucocyte-mediated intravascular fibrin deposition in renal blood vessels and which resembles histologically the renal lesion in the haemolytic-uraemic during shigellosis in humans.
Leukemoid reactions occurred in 136 patients (3.8%) hospitalized with shigellosis in Bangladesh. Sixty-eight percent of the patients with leukemoid reactions were children less than 4 years old. When compared with patients without leukemoid reactions, the leukemoid reactions were significantly associated with children aged less than 10 years. The most common serotype of Shigella in the patients with leukemoid reactions was Shigella dysenteriae 1, isolated from 96 patients (71%), whereas the most common species in patients without leukemoid reactions was Shigella flexneri, isolated from 2,119 patients (62%). The case fatality rate in patients with leukemoid reactions was 21% compared with 7.4% in patients without leukemoid reactions. These findings indicated that in patients with shigellosis, the leukemoid reaction was significantly associated with young children, isolation of S dysenteriae 1, and increased case fatality rate.