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Biomedical subjects

R B Sack

Publications and source records attributed to R B Sack.

At least 19 recordsLinked to original sources

Enteropathogens associated with acute and persistent diarrhea in Bangladeshi children less than 5 years of age.

A longitudinal study of diarrhea was carried out from May 1988 to April 1989 by household surveillance of 705 children less than 5 years old in rural Bangladesh. Stool samples were examined for enteric pathogens at the beginning of each diarrheal episode. For persistent episodes, stool examination was repeated on days 15-17 of the illness. For each case of persistent diarrhea, stool samples from age-matched acute diarrheal and healthy controls were examined. Compared with healthy controls, cases of diarrhea were associated with Shigella species (P = .07) and rotavirus (P less than .05). Diffusely adherent Escherichia coli (P less than .05) and cryptosporidia (P = .07) were the only enteropathogens associated with persistent diarrhea in comparison with acute diarrhea. No more than 15% of children had the same class of pathogen identified from stool on both days 1-3 and days 15-17, indicating that persistent infection was uncommon. However, a different enteropathogen was frequently found on days 15-17, suggesting that sequential infection may be a cause of persistent diarrhea.

Bangladesh

Epidemiological and clinical characteristics of acute and persistent diarrhoea in rural Bangladeshi children.

A community-based longitudinal study of acute and persistent diarrhoea in 705 children less than five years old was carried out for a year in a rural area of Bangladesh. Diarrhoea morbidity data were collected from each study child every fourth day by home visit. Clinical features of diarrhoeal episodes and diarrhoeal management information were documented. The overall diarrhoeal incidence rate in the study children was 4.6 episodes per child per year. The incidence of persistent diarrhoea was 34/100 child-years. Persistent diarrhoea was positively associated with young age and more severe illness, characterized by the presence of clinical dehydration or blood in the stool in the first week. Use of ORT in the first week was positively associated and use of an antibiotic was negatively associated with the occurrence of persistent diarrhoea. Reduced breast-feeding and consumption of cow's milk at some time during the episode were also positively associated with persistence. This would suggest that appropriate fluid and dietary management for all episodes should be the goal. Children with more severe initial illness characterized by the presence of blood in the stool or clinical dehydration should have more careful follow-up to identify persistent episodes and adverse nutritional effects. Breastfeeding should be continued during acute diarrhoea, but the role of ORT, antibiotics and cow's milk deserves further investigation.

Acute Disease

Etiologic agents in acute vs persistent diarrhea in children under three years of age in peri-urban Lima, Perú.

In a longitudinal study of acute and persistent diarrhea in 677 children less than three years old in a peri-urban community of Lima, Perú, during 27 months of surveillance, stools were cultured at the beginning of each diarrheal episode and on each subsequent week of illness. Analyzing stool cultures only from children who had not received antibiotic treatment in the 48 h prior to the culture, no association was found between any enteropathogen and persistent diarrhea. We did not find any increase in mixed infections in persistent diarrhea episodes as compared with acute diarrhea, controlling for age, season and anthropometric status. The isolation rate for any given enteropathogen was similar during the first, second, third or later week of illness, but when the presence of a specific enteropathogen was sought in sequential stools within a single episode, no evidence of persistent infection was found. This study shows that in developing countries with a high incidence of diarrheal diseases frequent re-infections with enteropathogens prevalent in the population are one reason for prolonged illnesses. Host factors that increase susceptibility to infection or decrease recovery from illness may also play a role. Further studies of these factors, such as micronutrient deficiencies, are needed to identify a public health intervention to control persistent diarrhea, a condition associated with mortality in many developing countries.

Acute Disease

Human colonic epithelial cells, HT29/C1, treated with crude Bacteroides fragilis enterotoxin dramatically alter their morphology.

Bacteroides fragilis has been associated with causation of diarrheal disease in livestock and humans. To date, conventional tissue culture and animal assays used to detect the biologic activity of bacterial enterotoxins have failed with enterotoxigenic B. fragilis. Although enterotoxigenic B. fragilis stimulates intestinal secretion in lamb and calf ligated intestinal loops, infant rabbits, and adult rabbits with ligated ceca, these animal systems are costly and complicated, which limits their usefulness for identification of enterotoxigenic B. fragilis strains. Using the cloned human colonic-epithelial-cell line HT29/C1, we have developed an in vitro assay that is 89% sensitive and 100% specific in detecting enterotoxigenic B. fragilis strains as defined by the lamb ligated-intestinal-loop assay. Subconfluent HT29/C1 cells treated with concentrated bacterium-free culture supernatants of enterotoxigenic B. fragilis strains develop specific and striking morphologic changes including loss of cell-to-cell attachments, rounding, swelling, and, in some cases, pyknosis. These morphologic changes are initially visible at 1 h after treatment and progress over at least the first 24 h. This tissue culture assay should prove useful in epidemiologic studies of enterotoxigenic B. fragilis and may facilitate basic studies to identify the B. fragilis toxin(s) and its mechanism of action.

Bacterial Toxins

Differentiation of Shigella flexneri strains by rRNA gene restriction patterns.

We studied the restriction endonuclease cleavage patterns of rRNA genes (ribotypes) of 72 clinical isolates of Shigella flexneri representing eight serotypes to determine whether ribotyping could be used to distinguish S. flexneri strains and to compare the discriminating ability of the method with that of serotyping. By using a cloned Escherichia coli rRNA operon as the probe, Southern blot hybridization of restriction endonuclease-digested total DNA was carried out. Ribotyping of the isolates with each of the five restriction endonucleases BamHI, EcoRI, HindIII, PstI, and SalI generated reproducible restriction patterns. However, HindIII produced the optimum digestion pattern of the rRNA genes and was more useful than the other enzymes used in differentiating strains. Analysis of the 72 isolates showed 11 different HindIII cleavage patterns of their rRNA genes. Four of these HindIII-generated ribotypes could be further differentiated into two to four subribotypes by using PstI. The results indicate that ribotyping has an application for differentiation of S. flexneri strains and can complement serotyping. Definition of strains in terms of both serotype and ribotype may be of greater use in epidemiological studies.

Bacterial Typing Techniques

Rotavirus diarrhea in Bangladeshi children: correlation of disease severity with serotypes.

To improve the understanding of the relative importance of serotypes of rotavirus in dehydrating diarrhea, we examined the correlation of clinical characteristics and disease severity with serotype in 2,441 diarrheal episodes among children younger than 2 years of age in rural Bangladesh. Of 764 rotavirus-associated episodes, a single G type (serotype 1, 2, 3, or 4) was determined by oligonucleotide probe in 485 (63%), while 233 episodes were nontypeable. Episodes with G types 2 and 3 were associated with more-severe dehydration than episodes associated with G type 1 or 4 or with nontypeable rotavirus. Episodes did not differ by G type in prevalence of vomiting, copious diarrhea, fever, abdominal pain, or length of treatment center stay. Rotavirus reinfections were detected in seven children, with homologous reinfection (G type 2) in one. Twelve children with diarrhea who died had rotavirus detected in stool specimens within 30 days of death. Children who died were more likely to be malnourished than were surviving children with rotavirus diarrhea. Of 40 specimens tested by polymerase chain reaction, 29 (72.5%) were P type 1, 9 (22.5%) were P type 2, 1 (2.5%) was P type 3, and 1 (2.5%) was nontypeable. One severely symptomatic diarrheal episode was associated with P type 3 rotavirus, a serotype usually found in asymptomatic nursery infections. Although G types 2 and 3 were associated with more-severe dehydration than other serotypes, the differences do not appear to be of major clinical importance. Effective vaccines should protect against all four major G types.

Bangladesh

Cholera epidemics in Bangladesh: 1985-1991.

In 1991, a major epidemic of diarrhoea broke out in Bangladesh. To estimate the extent of cholera during diarrhoea epidemics and to focus on the public health issues related to cholera in Bangladesh, we have used the government figures of the 1991 epidemic and data from our own experience of epidemic interventions in nearly 400 rural upazilas (sub-district) between 1985 and 1989 and in 1991. Our data showed that V. cholerae 01 was the most frequently (40%) isolated enteropathogen during the epidemics. The disease is widely distributed in the country. Only 24% of the total 1,648 laboratory confirmed cholera patients were below 5 years of age, and children below 2 years of age accounted for only 10% of the total. Access difficulty to medical care and absence of a reliable surveillance were thought to be the constraints to early detection and appropriate intervention, thus, there were more deaths during the epidemics. We have shown that a high proportion (59%) of cholera patients during their illness in the rural areas were not visited by the government surveillance staff and that most (80%) were treated at home. Access to treatment by qualified physicians was limited to 23% of the patients, whereas a large proportion of the patients were treated by the unqualified rural practitioners (68%), and the others (9%) had no access to any health care providers. Our experience also indicated a higher case fatality ratio (14%) prior to intervention by qualified physicians during epidemics and an overall fatality ratio of 4%, despite the significant reduction (less than 1%) achieved by the intervention. Cholera is highly epidemic in Bangladesh.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Virulence properties of Enterobacteriaceae isolated from the small intestine of children with diarrhea.

Enterobacteriaceae isolated from the duodena of Peruvian children with persistent diarrhea (PD) have been examined for virulence factors and compared with Enterobacteriaceae isolated from children with acute diarrhea, those convalescent from PD and diarrhea-free controls. Escherichia coli were isolated from 42 of 186 (23%) of the aspirates. All 11 children with PD in whom multiple E. coli colonies were examined were colonized by a single serotype. DNA probes identified enterotoxigenic E. coli in 2 of 89 (2.2%) PD aspirates and 2 of 38 (5.3%) acute diarrhea aspirates and enteroaggregative E. coli in one PD and one control aspirate. Strains positive with the enteropathogenic E. coli adherence factor probe were identified from 2 of 89 (2.2%) patients with PD and 1 of 34 (2.9%) controls. A subset of 12 E. coli strains failed to show adhesion to human duodenal enterocytes although 5 of 9 showed sparse but polar attachment to ileal cells from a child with short bowel syndrome and PD. Three of 10 Enterobacteriaceae (two E. coli, one Klebsiella species) caused diarrhea in the reversible ileal tie adult rabbit model. Colonization with virulent Enterobactericeae did not explain the majority of episodes of PD. Examination of these duodenal bacteria in the rabbit model revealed some that caused diarrhea but were not recognized pathogens.

Bacterial Toxins

Enterotoxigenic Bacteroides fragilis: epidemiologic studies of its role as a human diarrhoeal pathogen.

Strains of Bacteroides fragilis which produce enterotoxin(s) (ETBF) have been associated with diarrhoeal diseases in young domestic animals and have also been isolated from humans with diarrhoea. We have determined epidemiologically that ETBF are significantly associated with diarrhoea in humans. We studied Apaches, primarily children, with diarrhoea attending an outpatient facility in Whiteriver, Arizona, from July 1986 through July, 1988. Stool cultures for isolation of ETBF and other diarrhoeal pathogens were taken from these persons as well as from age and time-matched control persons who did not have diarrhoea. ETBF were isolated significantly more often from persons with diarrhoea (12%) than from controls (6%), p = 0.03. Isolation was highest (20-24% of stool cultures positive) during the second and third years of life. The diarrhoeal syndrome associated with ETBF was non-specific, and most characteristic of a secretory, rather than inflammatory, type of diarrhoea. ETBF are significantly associated with acute diarrhoea in Apache children, and may be an important newly described cause of diarrhoea in humans.

Acute Disease

Methodological issues in diarrhoeal diseases epidemiology: definition of diarrhoeal episodes.

A review of the diarrhoeal disease literature reveals considerable variability in the definition of diarrhoeal episodes. The use of various definitions of diarrhoea and episodes leads to misclassification, affects the estimates of the disease burden in communities and reduces comparability of the findings from different studies. This study is an attempt to validate the definition of diarrhoeal episodes using prospectively collected community-based surveillance data. In comparative validation analyses, three or more loose stools or any number of loose stools containing blood in a 24-hour period seemed to be the best definition of diarrhoea. Three intervening diarrhoea-free days seemed to be the optimum to define a new episode. The implications of using differing definitions and the importance of using a validated definition are discussed.

Bangladesh

A field study of the safety and efficacy of two candidate rotavirus vaccines in a Native American population.

A double-blind, randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of a rhesus rotavirus vaccine and RIT 4237, a bovine rotavirus vaccine, in a Navajo population. Infants aged 2-5 months were randomized to receive one dose of either 10(4) pfu of the rhesus rotavirus vaccine or 10(8) pfu of the RIT 4237 vaccine or placebo. Eleven (10.2%) of 108 infants in the rhesus vaccine group, 11 (10.4%) of 106 in the RIT 4237 group, and 9 (8.4%) of 107 in the placebo group experienced rotavirus diarrhea during the follow-up period of 17 months. Thus, in this population, neither vaccine was efficacious in preventing rotavirus diarrhea.

Diarrhea, Infantile

Measles-associated diarrhea in hospitalized children in Lima, Peru: pathogenic agents and impact on growth.

Because the causes of measles-associated diarrhea are not well known, 0- to 5-year-old children presenting to the hospital with measles-associated diarrhea (cases, n = 77) or acute diarrhea only (controls, n = 77) were compared. Growth and diarrheal morbidity were evaluated for 1 month after acute illness. Campylobacter jejuni was more frequently isolated from cases (31%) than controls (16%; P = .03). Rotavirus was absent in all cases versus 28% of controls (P less than .001). Incidence density for new episodes of diarrhea was significantly greater in cases (6.5 vs. 4.1; odds ratio, 1.6; confidence intervals, 1.09-2.34; P = .01), as was duration of episodes (3 vs. 2 days, P = .02). Both groups showed similar positive cumulative percentage weight gains throughout follow-up. These data support the theory of measles as a risk factor for developing diarrhea. The bacteriologic and virologic findings may reflect the immunologic response of the host to measles infection.

Acute Disease

High frequency of coinfecting enteropathogens in Aeromonas-associated diarrhea of hospitalized Peruvian infants.

Rectal swabs from 391 infants less than 18 months of age who were hospitalized with acute diarrhea and from 138 similarly aged healthy infants were examined for the etiologic agents of diarrhea. Aeromonas spp. were recovered from 205 of 391 (52.4%) diarrheic patients, whereas they were recovered from 12 of 138 (8.7%) controls (P less than 10(-11). Among the 205 Aeromonas-positive diarrheic patients, 118 (57.6%) were found to be coinfected with other common enteropathogens. Of the 164 Aeromonas-positive initial diarrheic specimens, 82 (50.0%) had one or more other enteropathogens present; 30 patients were coinfected with rotavirus, 20 with enterotoxigenic Escherichia coli, 16 with Campylobacter spp., 14 with Shigella spp., 13 with enteropathogenic E. coli, 4 with Vibrio spp., 1 with Salmonella spp., and 1 with Plesiomonas spp. of Aeromonas strains from cases compared with that from controls supports an etiologic role for this organism. However, frequent concomitant infections with other well-recognized enteropathogens and a lack of disease correlation with common Aeromonas phenotypes suggest that only a subset of Aeromonas strains may be diarrhea causing and that such strains may be common to several of the existing species.

Aeromonas

Electrocardiographic changes in tetanus: a serial study.

Serial electrocardiograms (ECGs) were recorded in 20 consecutive male patients admitted to the Infectious Diseases Hospital, Calcutta with generalised tetanus. Age of patients varied from 5 to 40 years (mean age 20.4 years). Ten patients died. ECGs were recorded daily for the first week after admission and later every 2nd or 3rd day. Altogether, 167 ECGs were analysed. Sinus tachycardia was present in 17 (85%) patients, prolonged QT interval in 12 (60%) patients, non-specific ST-T abnormalities in 12 (60%) patients and P wave changes in 10 (50%) patients. Other abnormalities recorded, included short PR interval, supraventricular tachycardia, intraventricular conduction delay, sinus bradycardia, 1 degree A-V block, abnormal axis deviation, right ventricular hypertrophy and sino-atrial Wenckebach phenomenon, although all of the findings cannot clearly be attributed to tetanus. Spatial QRS-T angle was calculated in 18 of these patients to determine any possible change in this parameter of prognostic significance. Two out of 9 who survived had abnormally wide (greater than or equal to 55 degrees) spatial QRS-T angle on admission; the angle narrowed with recovery. In the non-survivor group, 4 patients had abnormally wide QRS-T angles on admission; further widening was noted in patients on whom follow-up tracings were available. The difference in spatial QRS-T angle between the survivor and the non-survivor groups was statistically significant (p less than 0.05). Spatial QRS-T angle changes have not been reported in tetanus before. Although non-specific, serial study in individual cases would be useful in assessing prognosis.

Adolescent

Role of a soy-based lactose-free formula in the outpatient management of diarrhea.

The introduction of a soy-based, lactose-free formula during the acute phase of diarrheal illness in infants has been shown to reduce stool output and duration of diarrhea in hospitalized patients. In the United States, most infants with acute diarrhea are treated as outpatients. In the present study, infants with diarrhea who were treated as outpatients were randomly assigned to receive either a soy-based, lactose-free formula alternating with oral rehydration solution from the beginning of therapy ("early feeding") or oral rehydration solution alone for the first 24 hours of therapy, followed by a soy-based, lactose-free formula alternating with oral rehydration solution (control group). Twenty-nine infants were randomly assigned to the early-feeding group and 27 to the control group. Twenty-one (72%) of 29 in the early-feeding group resolved their diarrhea at the end of 48 hours of therapy compared with 12 (44%) of 27 in the group fed oral rehydration solution only (P = .02). It is concluded that the introduction of a soy-based, lactose-free formula from the beginning of therapy for acute diarrhea in children treated as outpatients is safe and may shorten duration of diarrhea while maintaining adequate caloric intake.

Ambulatory Care

A comparison of rice-based oral rehydration solution and "early feeding" for the treatment of acute diarrhea in infants.

To compare the use of rice-based oral rehydration solution (R-ORS), with the introduction of food immediately after rehydration ("early feeding"), using standard glucose-based oral rehydration solution (G-ORS) in the management of acute diarrhea, we conducted a four-cell randomized, controlled trial among 200 hospitalized Egyptian infants between 3 and 18 months of age. During the rehydration phase (first 4 hours), three groups were given G-ORS and a fourth group was given R-ORS. During the subsequent maintenance phase, the control group was given a soy-based, lactose-free formula (G-ORS + SF), a second group (G-ORS + RF) was given a rice-based formula, and a third group (G-ORS + rice) was given boiled rice. The fourth group (R-ORS + SF) continued to receive R-ORS for the first 24 hours of the maintenance period, followed by a soy-based lactose-free formula. During the first and second 24 hours of the maintenance period, infants in the three treatment groups had a lower mean stool output in comparison with the control group (p = 0.006 and 0.03, respectively). The mean total stool output in the R-ORS + SF group was significantly lower than in the control group (p = 0.02). There were no statistically significant differences among the four groups in the mean duration of diarrhea. We conclude that (1) infants who were given R-ORS had reduced total stool output (by 35%) compared with the control group and (2) feeding of boiled rice or a rice-based formula immediately after rehydration therapy was as efficacious as treatment with R-ORS alone for 24 hours, followed by feeding with a soy-based, lactose-free formula.

Acute Disease

Rotavirus diarrhoea in Apache children: a case-control study.

A case-control study of rotavirus diarrhoea in Apache children up to two years old was conducted at the White Mountain Apache reservation from 1 May through 15 December 1985 to identify risk factors for rotavirus diarrhoea. The mothers of fifty cases, forty-five hospital controls and twenty-five neighbourhood controls participated in this study. Exposure to other children with diarrhoea stood out as the single most important factor for acquiring rotavirus diarrhoea (Odds ratio = 14.0). Other significant risk factors were living in homes with septic tanks and in homes with 'poor environmental sanitation.'. Minimizing contacts of children with diarrhoea therefore would be the most effective measure in preventing the spread of this disease in the community.

Arizona