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Biomedical subjects

D A Sack

Publications and source records attributed to D A Sack.

At least 163 records · Page 9Linked to original sources
PubMed1983

Rotavirus diarrhoea: an expanding clinical spectrum.

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.

Adolescent↗
PubMed1983

Current status of an oral B subunit whole cell cholera vaccine.

Purified B subunit of cholera toxin retains membrane-binding capacity and protective immunogenicity and yet has no toxic activity as tested in animals. These properties suggest that B subunit might be a promising immunogen, particularly as an oral vaccine, for stimulating protective antitoxic immunity against cholera in man. A method has been elaborated which allows preparation of +/- 10 grams of pure B subunit per fermentor culture cycle. As tested in both Swedish and Bangladeshi volunteers purified B subunit alone or in combination with conventional whole cell vaccine gives no side-effects at all when given orally and only very mild local reactions after parenteral administration. A single peroral or intramuscular immunization with B subunit has given significant intestinal IgA antitoxin antibody formation in 75-85% of Bangladeshi women tested; however, the duration of the response was longer after the oral route. The preliminary results of a recent study (Svennerholm, A.M., Jertborn, M., Gothefors, L., Karim, A., Sack, D. and Holmgren, J., to be published) have further shown that two peroral immunizations of Bangladeshi volunteers with a combined B subunit--whole cell cholera vaccine give rise to mucosal IgA antitoxin as well as anti-lipopolysaccharide antibody formation which closely resemble these antibody responses in cholera convalescents. The combined vaccine also evoked a local immunologic memory comparable to that induced by clinical disease.

Antibody Formation↗
PubMed1982

Intestinal antibody responses after immunisation with cholera B subunit.

In about 80% of Bangladeshi volunteers a single oral or intramuscular immunisation with a new cholera toxoid immunogen (B subunit) gave rise to a local intestinal secretory immunoglobulin A (IgA) antitoxin response as measured in intestinal-lavage fluid by enzyme-linked immunosorbent assay methods. The rise in IgA antitoxin titre was similar for both immunisation routes and was comparable to that seen after clinical cholera; however, the response persisted longer after oral than intramuscular immunisation. A second immunisation by either route evoked an antitoxin response which usually closely resembled that seen after the first immunisation.

Administration, Oral↗
PubMed1982

Carbohydrate malabsorption in infants with rotavirus diarrhea.

We studied a group of patients with rotavirus diarrhea to determine the association of carbohydrate malabsorption during diarrhea with the degree of acidosis and severity of purging. Unlike enterotoxigenic diarrhea in which the metabolic acidosis is due to loss of bicarbonate in an alkaline stool, patients with rotavirus develop a metabolic acidosis while passing an acid stool with little detectable bicarbonate. Also unlike enterotoxigenic diarrhea, rotavirus stool contains large quantities of reducing substances suggesting significant carbohydrate malabsorption. Our findings are consistent with the hypothesis that carbohydrate malabsorption is an important secondary pathophysiological mechanism in the rotavirus diarrhea syndrome. This model for rotavirus diarrhea helps to explain the electrolyte and acid-base pattern of the rotavirus stool and stresses the importance of further nutrition balance studies to determine the optimal dietary management of patients with rotavirus diarrhea.

Acidosis↗
PubMed1982

The use of chlorpromazine in the treatment of cholera and other severe acute watery diarrheal diseases.

Four hundred and ten patients with severe watery diarrhea; including 316 patients with cholera, were studied in a double-blind, randomized, placebo controlled trial to determine if chlorpromazine (1 mg/kg) would be useful in the management of such patients. All patients were at least 7.5% dehydrated on admission into the study; all received intravenous fluids followed by oral rehydration solution and all received tetracycline. In addition, one-half of the patients received chlorpromazine, 1 mg/kg, orally as a single dose 2 h after admission. Effectiveness of the chlorpromazine was determined by comparing oral therapy failure rates, purging rates, vomiting rates, i.v. fluid requirements and hospitalization time in groups of the patients receiving and not receiving the drug. In children with severe cholera, e.g., with shock on admission or with very high purging rates, chlorpromazine lowered the oral therapy failure rate by about 50%. However, children with less severe cholera, adults with cholera, and patients of all ages with noncholera diarrhea could not be demonstrated to benefit significantly from the drug. In these groups of patients, oral therapy failures were rare irrespective of whether or not chlorpromazine had been given. We, therefore, do not recommend chlorpromazine in the routine management of patients with watery diarrhea, however, it may be useful in treatment of children with severe cholera when added to standard treatment of hydration and tetracycline.

Acute Disease↗
PubMed1981

Stool electrolyte content and purging rates in diarrhea caused by rotavirus, enterotoxigenic E. coli, and V. cholerae in children.

One hundred twenty children below 5 years of age with diarrhea caused by Vibrio cholerae, enterotoxigenic Escherichia coli, or rotavirus were studied for stool electrolyte composition and purging rates. The mean purging rate in cholera was 60.1 ml, in ETEC 39.2 ml, and in rotavirus infection 31.4 ml/kg/8 hour. The mean stool sodium concentration in cholera was 88.9 mMol/L, in ETEC 53.7 mMol/L, and in rotavirus infection 37.2 mMol/L. Stool potassium concentration did not show much variation, Mean CO2 concentration in rotavirus infection was 6 mMol/L, significantly lower than in cholera and in ETEC diarrhea. In cholera, stool sodium concentration increased significantly with increase in purging rates; the same was not true in rotavirus and ETEC diarrhea. These differences are considered important factors in formulating replacement therapy in diarrhea.

Child, Preschool↗
PubMed1981

Glucose vs sucrose in oral rehydration solutions for infants and young children with rotavirus-associated diarrhea.

The use of oral rehydration solutions containing essential electrolytes and either glucose or sucrose of equal osmolality was compared in a double-blind sequential trial of 784 children with rotavirus-associated diarrhea treated at a center in rural Bangladesh. The oral fluid failure rate was 11.5% for the sucrose-containing solution group and 7.3% for the glucose-containing group (P = NS). Vomiting was a significantly more common cause of failure for the group treated with sucrose-containing oral rehydration solution and was associated with an increased rate of intake of the sweeter sucrose-containing solution. The purging rate was not different for the two groups. The oral fluid failure rates for children in the most underweight category (less than 60% of expected weight for age) were not different from those for other groups, although, as assessed by purging rate and initial dehydration, the stool losses of members of this group constituted a greater proportion of their body weight. Glucose is the preferred carbohydrate for oral electrolyte solutions, although sucrose can be substituted with only minimum loss of efficacy.

Child, Preschool↗
PubMed1981

Enterotoxigenic Escherichia coli diarrhoea: acquired immunity and transmission in an endemic area.

Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrhoea in developing countries. Studies were made, in an endemic area of Bangladesh, of household contacts of patients with diarrhoea associated with E. coli producing heat-stable and heatlabile toxins (ST/LT) or heat-stable toxin (ST) only. It was found that 11% of contacts were infected in the 10-day study period, and that both the rate of infection and the proportion of infected persons with diarrhoea decreased with increasing age, suggesting the development of immunity. ETEC of the same serotype as that of the index patient were found in 9% of water sources used by index households, in a small number of food and drinking water specimens from the index homes, and in faeces from 3 healthy calves. The rate of infection of household members was highest in houses where there was contaminated food or water, which suggests that infection may take place in the home when contaminated water is brought in.

Bangladesh↗
PubMed1980

Oral therapy in children with cholera: a comparison of sucrose and glucose electrolyte solutions.

We performed a double-blind trial comparing sucrose electrolyte oral solution with glucose electrolyte oral solution in children less than 5 years of age with severe cholera-like diarrhea. Of 111 patients studied (102 with bacteriologically confirmed cholera), 55 received sucrose solution and 56 received glucose solution. The success rates, as defined by the absence of the need to give unscheduled intravenous therapy, were similar in the two groups (73% and 77% in the sucrose and glucose groups, respectively). There was no difference in purging rates between the two groups. The primary determinant of success for oral fluid regardless of the sugar was the purging rate. Sucrose malabsorption was responsible for oral therapy failure in one child. This study demonstrates that sucrose is an effective alternative to glucose in the oral therapy solution, but either must be used in conjunction with intravenous solution when treating severe dehydrating diarrhea.

Administration, Oral↗
PubMed1980

Immunobead enzyme-linked immunosorbent assay for quantitating immunoglobulin A in human secretions and serum.

We have developed an enzyme-linked immunosorbent assay for quantitating human immunoglobulin A in human secretions and serum. The procedure uses Immunobeads as the solid phase, has a sensitivity of 10 ng/ml, and can be completed in 1 day. Since there is no diffusion through agar, the assay does not require a correction factor when measuring secretory immunoglobulin A. This method should be useful in studies of local mucosal immunity in humans, especially when a very sensitive assay is needed.

Cholera↗
PubMed1980

Microtiter ganglioside enzyme-linked immunosorbent assay for vibrio and Escherichia coli heat-labile enterotoxins and antitoxin.

We have developed a microtiter enzyme-linked immunosorbent assay method for detecting the heat-labile enterotoxins of Vibrio cholerae and Escherichia coli using GM1 ganglioside as the base coat. This method compares favorably with a similar assay using anticholera toxin as the base coat, and with the Y1 adrenal cell assay. The assay should be useful in detecting enterotoxin production in E. coli and vibrios (including non-agglutinating Vibrio), in quantitating the toxin, and in determining binding properties of enterotoxins to ganglioside. The assay can also be used to quantitate antibodies which block the attachment of the toxin to the ganglioside.

Antitoxins↗
PubMed1980

Seroepidemiology of rotavirus infection in rural Bangladesh.

A prospective seroepidemiological study of rotavirus infection was performed in children in a village in rural Bangladesh. Ninety-three percent of the children had detectable antibodies during the study, and there were 66 significant rises in titer occurring in 57 of the 85 children. Antibody titer rises occurred in older children and younger children with equal frequency. Nine children (11%) had evidence of multiple infections during the 16-month period. Winter infections were most frequent, although one summer (monsoon) season was also associated with a large cluster. Subjects with high titers (greater than 1:8) of antibody less frequently developed a titer rise than did subjects with lower titers.

Antibodies, Viral↗