Biomedical subjects
Publications and source records attributed to T Butler.
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.
From three fatal cases of diarrhoeal illness in Bangladesh, Yersinia species were isolated from tissues at post-mortem examination. One patient was infected with Y. enterocolitica serotype 0:7, 8 and two patients were infected with Y. intermedia. These patients were infected also with other enteric pathogens. These findings suggest that Yersinia may be important as pathogens in tropical diarrhoea and as co-pathogens in serious disease.
The clinical efficacies of pivmecillinam and ampicillin were compared in a randomized double-blind trial in the treatment of acute shigellosis. Of 44 adult male patients, all culture positive for Shigella strains, 22 patients received 400 mg of pivmecillinam and 22 patients received 500 mg of ampicillin every 6 h. Both drugs were administered orally for 5 days. Four patients receiving ampicillin were infected with Shigella strains that were resistant to ampicillin but susceptible to pivmecillinam, and two patients receiving pivmecillinam were infected with Shigella strains resistant to both ampicillin and pivmecillinam. The mean duration of diarrhea in all patients receiving pivmecillinam was 3.3 days compared with 4.5 days in patients receiving ampicillin (P less than 0.05). When patients infected with the resistant strains were excluded, the mean duration of diarrhea in patients receiving pivmecillinam was 3.2 days compared with 4.1 days in patients receiving ampicillin. The patients infected with strains susceptible to both antibiotics had mean durations of fecal excretion of Shigella strains of 1.2 days for those treated with pivmecillinam and 1.4 days for those treated with ampicillin. The patients infected with organisms resistant to both drugs had longer durations of diarrhea and fecal excretion of Shigella strains. The results suggest that pivmecillinam is as effective as ampicillin and can be a useful drug for the treatment of shigellosis.
Overnight 1 mg dexamethasone suppression tests were performed on 37 hospitalized patients with unipolar major depression and 13 psychiatric controls: 62% of the depressives and 38% of controls failed to suppress below 6 micrograms/dl of plasma cortisol at least once on the day after dexamethasone. Specificity for depressive diagnosis was only 62% but rose to 100% when a plasma cortisol value of 10 micrograms/dl was used as the criterion for normal suppression. Depressed patients were significantly more likely to show normal suppression if they were under age 65 (56% vs. 24% in the geriatric sample). Other demographic and clinical variables examined in the depressed sample did not assort by suppressor status.
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To explore the clinical spectrum of rotavirus diarrhoea in Bangladeshi children, we reviewed surveillance data from randomly selected diarrhoeal cases who were intensively studied at the International Centre for Diarrhoeal Diseases Research--Bangladesh. Twenty-seven (29%) of children aged less than or equal to 4 years excreted rotavirus; rotavirus was the only pathogen isolated from 13 cases. Seven of these 13 cases displayed the typical features of rotavirus diarrhoea: occurrence in infancy, prominent vomiting, watery diarrhoea, and acid stools rarely exhibiting blood or leucocytes. In contrast, six of the 13 cases presented with non-watery diarrhoea. These cases were distinguished by older ages, infrequent vomiting, less acidic stools, faecal blood and leucocytes, and frequent left shifts on peripheral blood examination. We conclude that the clinical spectrum of rotavirus infections may include an invasive diarrhoeal syndrome that differs in several respects from the more widely appreciated watery diarrhoeal syndrome.
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Opsonic requirements for phagocytosis by human polymorphonuclear leukocytes (PMNLs) of a laboratory strain of Borrelia hermsii were examined. Intracellular localization of spirochetes was confirmed by electron microscopy and cinephotomicroscopy. Phagocytosis of 3H-labeled spirochetes was increased with higher concentrations of pooled human serum or greater ratios of spirochetes to PMNLs and was unaffected by diminished classical complement pathway activity. Immune rabbit serum markedly increased phagocytosis of spirochetes beyond levels observed with preimmune rabbit serum. Immune rabbit serum also demonstrated direct activity against B. hermsii, which decreased the motility and viability and increased agglutination of the spirochetes independently of complement. Both the direct activity against B. hermsii and the opsonic activity of immune rabbit serum were eliminated by immunoabsorption of immunoglobulins. These observations suggest a role for the alternative complement pathway and for immunoglobulins in the opsonization of spirochetes for phagocytosis by PMNLs. Immunoglobulins may also play a role in the direct clearance of spirochetes.
The activities of ceftriaxone, moxalactam, and ampicillin against Salmonella typhimurium LT-2 were compared in culture media at pH 5, 6, 7 and 8 and in mice inoculated intraperitoneally. The minimal inhibitory concentrations for strain LT-2 in Mueller-Hinton broth were 0.03 microgram of ceftriaxone per ml, 0.08 microgram of moxalactam per ml, and 0.4 microgram of ampicillin per ml. A comparison of minimal inhibitory concentrations in buffered broth at pH 5 with those in media at higher pH values showed that ceftriaxone was more acid stable than the other antibiotics. Groups of CF-1 female mice inoculated intraperitoneally with 3 X 10(4) colony-forming units received saline or each drug in fourfold decremental doses by the subcutaneous route every 8 h for 3 days, beginning at 24 h after challenge. The mean log 10 colony-forming units of S. typhimurium per spleen at the end of treatment and the mortality rates at 21 days after inoculation were measured for each treatment group. The mean log 10 colony-forming units per spleen was significantly reduced from that of the saline control by dosages of greater than or equal to 0.06 mg of ceftriaxone per kg, 64 mg of moxalactam per kg, or greater than or equal to 16 mg of ampicillin per kg (P less than 0.05). Mortality rates of infected mice were significantly reduced by dosages of greater than or equal to 1 mg of ceftriaxone per kg or greater than or equal to 64 mg of ampicillin per kg (P less than 0.05), whereas moxalactam in dosages as high as 16 mg/kg did not significantly reduce mortality rate. These results demonstrate the superiority of ceftriaxone to the other tested antibiotics on a weight basis in this model of experimental Salmonella infection.
To clarify the pathogenesis of oral plague infection, we studied the susceptibility of three species of rodents to intragastric inoculation of Yersinia pestis, described the pathology and progression of infection, and measured antibody responses to fraction IA antigen of Y. pestis. The 50% lethal doses of bacteria by intragastric inoculation for Mus musculus, Zygodontomys pixuna, and Rattus rattus were log10 = 6.32, 5.46, and 9.62, respectively, which were at least 1,000-fold higher than the values obtained by subcutaneous inoculation. M. musculus was shown to be susceptible to lethal infection also when bacteria were ingested in drinking water. Microscopic pathology was consistent with heavy systemic infection. Quantitative cultures of tissues at different times after intragastric inoculation revealed that infections of blood, liver, and spleen preceded infections of Peyer's patches and mesenteric lymph nodes. Stool cultures were negative. The strain of Y. pestis used for inoculation was killed when exposed to a buffered solution at pH less than or equal to 3. Antibody responses were observed in some of the surviving rodents after intragastric challenge. These results showed that Y. pestis was an effective oral pathogen that produced fatal systemic infections and self-limited infections with immunity but did not produce enteric pathology or lead to fecal excretion of bacteria.
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Relapsing fever caused by Borrelia spirochetes is characterized by episodes of spirochetemia, fever, and DIC. We examined the ability of Borrelia hermsii to induce production of leukocytic pyrogen and thromboplastin from human blood leukocytes in vitro. Organisms were found devoid of endotoxin by the Limulus assay. Human peripheral blood leukocytes were separated into MNC and PMN fractions and were incubated with two to five spirochetes per cell in 10% human serum. Supernatant fluids from MNC-spirochete mixtures produced mean increases in the temperature of rabbits of 0.80 degree to 1.35 degrees C, which were significantly higher than those caused by supernatant fluids of MNC or spirochetes alone (p less than 0.05). MNC-spirochete mixtures possessed seven to 15 times the thromboplastic activity of MNC suspensions alone, assayed with a modified one-stage prothrombin time. Supernatant fluids of PMNs and spirochetes, on the other hand, did not contain leukocytic pyrogen, and PMN suspensions did not produce thromboplastin. Cycloheximide (10 micrograms/ml), and inhibitor of protein synthesis, completely suppressed both pyrogen and thromboplastin production. Although intracellular spirochetes were observed within phagosomes of blood monocytes by electron microscopy, the production of leukocytic pyrogen and thromboplastin was not significantly altered by serum opsonins or by the inhibitors of phagocytosis cytochalasin B (5 micrograms/ml) or phenylbutazone (2 mg/ml). These results showed that Borrelia spirochetes stimulated human MNCs to produce increased amounts of leukocytic pyrogen and thromboplastin and that this stimulation required de novo synthesis of protein, was not mediated by endotoxin, and was not prevented by omitting opsonic proteins or by inhibiting phagocytosis.
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