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Biomedical subjects

R B Sack

Publications and source records attributed to R B Sack.

At least 127 records · Page 7Linked to original sources

Oral immunization of rabbits with enterotoxigenic Escherichia coli protects against intraintestinal challenge.

The development of a successful oral vaccine against enterotoxigenic Escherichia coli depends upon the identification of appropriate protective antigens which can be delivered effectively to intestinal mucosa. We have determined in a modified RITARD model the relative protection against intraintestinal challenge afforded by oral immunization with live enterotoxigenic E. coli carrying different candidate antigens. Studies were done with both wild-type strains and genetically manipulated strains of enterotoxigenic E. coli (parent strain E1392/75 2A) which carried plasmids containing intact heat-labile toxin (LT) gene sequences or various mutations of the LT genes. Immunizations were done by orogastric tube inoculation on days 0, 7, and 14; challenges were done on day 33. Protection against diarrhea with a homologous challenge was found to be 84 to 100% (P less than 0.01). Protection against diarrhea with challenges in which specific antigens could be tested included the following: (i) O and H antigens (O6:H16), 87 to 100% protection with different E. coli strains with identical O and H antigens (P less than 0.01) but no protection against a heterologous challenge; (ii) LT or the B subunit of LT only, approximately 50% protection (P less than 0.02). These findings suggest that O antigens are highly protective in this model but afford only serotype-specific protection and that the B subunit (with or without the A subunit) affords less protection but confers cross-protection against heterologous strains producing LT. This model should be useful in further defining appropriate protective antigens for candidate enterotoxigenic E. coli vaccine strains.

Administration, Oral↗

Comparison of noninvasive breath hydrogen test for gastric acid secretion to standard intubation test in adults.

We have developed a noninvasive test for gastric acid secretion based on the reaction of ingested magnesium metal with gastric acid to produce hydrogen gas, which is excreted in exhaled air and belches. This test was compared to the standard intubation test by performing both, on different days, in 36 adult Peruvian outpatients referred for gastric analysis; the correlation coefficient for this comparison was 0.71. The new test was repeated in nine subjects, and the resulting test-retest correlation coefficient was 0.83. The new test thus compares favorably with the standard intubation test. Because it is also noninvasive and should therefore be more acceptable to subjects, this new test may be useful for clinical evaluation and research studies on subjects in whom intubation would be difficult or unacceptable.

Adult↗

Comparison of noninvasive breath hydrogen test for gastric acid secretion to standard intubation test in infants and young children.

We have developed a noninvasive test of gastric acid secretion for use in infants and young children. It is based on the reaction of ingested magnesium metal with gastric acid to produce hydrogen gas, which is excreted in exhaled air and belches. This test was compared to the standard intubation test by performing both, on different days, in 20 children (5-37 months of age) without known gastric disease. The results of the two tests compared well: correlation coefficients were 0.78, 0.75, or 0.72 when exhaled air was collected for a total of 56, 81, or 31 min, respectively. Because the test is noninvasive, it should be more acceptable to children and their parents than the intubation test and thus could be used to conduct studies which are currently impractical.

Acute Disease↗

Isolation of enterotoxigenic Bacteroides fragilis from humans with diarrhea.

Enterotoxigenic Bacteroides fragilis was isolated from stool specimens of 8 of 44 diarrheic individuals (ages, 4 months to 69 years). The individuals had watery diarrhea and intestinal cramping; and infants had hyperthermia, vomiting, and blood in the stools. No recognized enteric pathogens were detected in seven of the eight diarrheic individuals positive for enterotoxigenic B. fragilis. The bacterium produced an enterotoxin detectable in concentrated broth that supported bacterial growth. Fifteen adult rabbits with ligated ceca developed fatal enteric disease following intraileal injection with 5 x 10(9) CFU of enterotoxigenic B. fragilis. Conversely, eight control rabbits injected with nonenterotoxigenic B. fragilis remained clinically normal. As few as 5 x 10(3) CFU of enterotoxigenic B. fragilis caused fatal enteric disease in the rabbit model. Disease in rabbits was characterized by mucoid, often hemorrhagic, diarrhea. The bacterium colonized the caudal small intestine and the colon of the rabbits and caused moderate to severe necrotizing colitis. Enterotoxigenic B. fragilis is widespread in the intestinal tract of diarrheic humans and is enteropathogenic in adult rabbits with ligated ceca. Its possible role in the enteric disease complex merits further study.

Adult↗

Early treatment with erythromycin of Campylobacter jejuni-associated dysentery in children.

To evaluate the efficacy of early treatment with erythromycin on the duration of fecal excretion and of diarrhea associated with Campylobacter jejuni, 170 patients, age 3 to 60 months, were randomly assigned in a double-blind fashion to receive either erythromycin ethyl succinate or placebo immediately after being seen at Cayetano Heredia Hospital because of acute dysentery. The groups' pretreatment characteristics were comparable. Of the 30 patients with stools positive for C. jejuni, 12 were in the placebo group and 16 in the treatment group. After 2 days of treatment, none of the patients in the placebo group and 36% of those in the erythromycin group had normal stools (P less than 0.05). After 5 days of treatment, 50% of the patients in the placebo group and 93% of those in the erythromycin group had normal stools (P less than 0.02). Fecal excretion of the organism continued significantly longer in the placebo group (P less than 0.01). There were no treatment failures in the treatment group compared with five (42%) in the placebo group (P less than 0.01). Thus, early administration of erythromycin significantly reduced the duration of both diarrhea and fecal excretion of the organism in infants and children with acute dysentery associated with C. jejuni.

Campylobacter Infections↗

Bicarbonate versus citrate in oral rehydration therapy in infants with watery diarrhea: a controlled clinical trial.

In a double-blind, randomized trial, we compared the efficacy of bicarbonate-containing oral rehydration solution vs citrate-containing solution in the treatment of infantile diarrheal dehydration and acidosis. Ninety-seven infants 3 to 24 months of age were entered in the study; 49 received bicarbonate-containing solution and 48 citrate-containing solution. The two groups were similar in all respects at the beginning of the study. Oral rehydration was successful (i.e., no intravenously administered fluids were required) in 85% of study patients; the success rate was similar in both treatment groups. Serum total CO2 concentration increased in a similar fashion in both groups, reaching near normal values at 48 hours after admission. We conclude that sodium citrate can be substituted for sodium bicarbonate in the formulation of the orally administered rehydration solution recommended by the World Health Organization for treatment of diarrheal dehydration in infants.

Bicarbonates↗

Enzootic bovine rotavirus is not a source of infection in Panamanian cattle ranchers and their families.

Vaccination of humans against rotavirus (RV) diarrhea may be accomplished by oral immunization with attenuated animal strains known to be antigenically very similar to human strains. To define better the degree of infectivity in nature of these animal strains for humans, we conducted surveillance for RV infection/diarrhea in 180 farm workers, their 161 family contacts, and the 566 animals (512 cattle, 35 pigs, and 19 sheep) on 14 farms in rural Panama. No correlation between the high infection rates in farm workers (72%) and their family contacts (78%) and in cattle (56%) could be demonstrated. Heads of families with four or more children with RV infection experienced a twofold greater rate of RV infection compared with heads of families of similar size without RV infection. Despite the close similarity between human and bovine RV, in Panama intrafamilial (particularly child-to-child or child-to-parent) rather than interspecies transmission appeared to be the most important route for the spread of this highly infectious virus.

Age Factors↗

Epidemiology and serology of Giardia lamblia in a developing country: Bangladesh.

The age-specific prevalence of Giardia lamblia was determined in two Bangladeshi villages and malnourished children in hospital in Dhaka City. Age-specific acquisition rates, the duration of infection and age-specific sero-positivity to (immunofluorescent assay) G. lamblia trophozoites were determined. Infection was acquired early (less than one year) and in 16% of infected children persisted for longer than three months. Prevalence was higher in 5 to 10-year-old village children (21%) and one to five-year-old malnourished children (51%). Over 40% of the children much less than 7 years acquired G. lamblia within 18 months; acquisition rates did not change with age. Positive antibody titres were acquired between six months and one year and the prevalence of sero-positivity remained high in all age groups No association was found between positive antibody titres and positive stool examinations. In developing countries serum antibodies are useful epidemiologically, but are not diagnostic in the individual patient.

Adolescent↗

Evidence of immunity induced by naturally acquired rotavirus and Norwalk virus infection on two remote Panamanian islands.

For better understanding of the role of humoral immunity in ameliorating infections with rotavirus (RV) and Norwalk virus (NW), 305 Cuna Indians living on two isolated islands located off Panama's Carribean coast were surveyed daily for diarrhea over a seven-month period. Nine (8%) of 108 persons with a baseline RV antibody titer of greater than 1:4 developed RV infection compared with 70 (46%) of 151 persons with a baseline RV antibody titer of less than 1:4 (P less than .001). Thirty-eight (25%) of 151 persons of all ages with baseline RV antibody titer of less than 1:4 had at least one episode of RV diarrhea compared with 6 (6%) of 108 persons who had baseline RV antibody titers of greater than 1:4 (P less than .001). Thirty-two (47%) of 68 persons of all ages who had a baseline NW antibody titer of less than 1:100 developed NW infection compared with 30 (13%) of 237 persons with a baseline NW titer of greater than 1:100 (P less than .001). The high NW and RV infection rates and the excellent levels of protection provided by specific preexisting humoral antibody to these agents should promote activities aimed at developing vaccines for preventing these infections.

Age Factors↗

Epidemiology of rotavirus diarrhea in a prospectively monitored American Indian population.

Rotaviral diarrhea is endemic in most areas of the world, yet community-wide epidemics have not been reported in prospectively monitored populations. This prospective study of the etiology of diarrhea included biweekly visits to the homes of 10% of the population of the White Mountain Apache Indians and began in April 1981. During a three-week period beginning 21 October, 1981, 342 new cases of diarrhea were identified on different parts of the reservation. Rotaviral antigen, detected by an enzyme-linked immunosorbent assay, was identified in 169 (73%) of the 233 stool samples that were tested. Rotavirus was not detected in any of the stool samples taken six months before or after the epidemic. During the epidemic, respiratory symptoms were present in 44 (33%) of 135 rotavirus-positive patients compared with 17 (17%) of 98 rotavirus-negative patients (P less than .05). This rapidly spreading epidemic involving all areas of the reservation, in the absence of a common source of exposure of ill persons, suggests the possibility of respiratory transmission.

Adolescent↗

Risk factors for fatal childhood diarrhea: a case-control study from two remote Panamanian islands.

Between September 1979 and March 1980, distinguishing features between fatal and nonfatal cases of diarrhea caused by the same etiologic agents were sought in a case-control investigation of Cuna Indian children living on the San Blas Islands located off Panama's Caribbean coast. The eight fatal cases of diarrhea (four associated with rotavirus, one with Giardia lamblia, and three without identifiable pathogens), which occurred in a cohort of 186 children aged less than five years who were followed for seven months, were matched with 24 contemporaneously occurring nonfatal cases of diarrhea. Weight-for-length measurements falling below the 90th percentile of the reference standard, reliance on traditional rather than equally as available Western medicine, and failure to receive oral rehydration solution were significantly more common among fatal than nonfatal cases. Incorporating traditional medicine men with their long-standing village-wide authority into expanded community health education programs that emphasize the importance of early treatment of diarrhea with oral rehydration solution would probably reduce mortality associated with diarrheal illness in this population.

Child, Preschool↗