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Biomedical subjects

R B Sack

Publications and source records attributed to R B Sack.

At least 37 records · Page 2Linked to original sources
PubMed2000

Enterotoxin-specific immunoglobulin E responses in humans after infection or vaccination with diarrhea-causing enteropathogens.

Cholera toxin (CT)-specific antibody responses of the immunoglobulin E (IgE) isotype in the sera of adult patients suffering from infection with either Vibrio cholerae O1, V. cholerae O139, or enterotoxigenic Escherichia coli (ETEC) were analyzed and compared with those in the sera of volunteers immunized with a bivalent B subunit O1/O139 whole-cell cholera vaccine. A significant IgE response to CT was observed in 90% of the patients with V. cholerae O1 infection (18 of 20; P = <0.001) and 95% of the patients with V. cholerae O139 infection (19 of 20; P = <0.001). Similarly, the majority of the patients with ETEC diarrhea (83%; 13 of 15) showed a positive IgE response to CT. Eight of 10 North American volunteers (80%) orally challenged with V. cholerae O1 showed CT-specific IgE responses (P = 0.004). In contrast, Swedish volunteers immunized with the oral cholera vaccine showed no IgE responses to CT (P value not significant). During the study period, total IgE levels in the sera of the diarrheal patients, the North American volunteers, and the Swedish cholera vaccinees alike remained unchanged. However, the total IgE levels in the sera of patients and healthy Bangladeshi controls were on average 89-fold higher than those in the sera of the healthy Swedish volunteers and 34-fold higher than those in the sera of the North American volunteers.

Adolescent↗
PubMed2000

Prevalence of toxin types and colonization factors in enterotoxigenic Escherichia coli isolated during a 2-year period from diarrheal patients in Bangladesh.

The prevalence of toxin types and colonization factors (CFs) of enterotoxigenic Escherichia coli (ETEC) was prospectively studied with fresh samples (n = 4,662) obtained from a 2% routine surveillance of diarrheal stool samples over 2 years, from September 1996 to August 1998. Stool samples were tested by enzyme-linked immunoassay techniques and with specific monoclonal antibodies for the toxins and CFs. The prevalence of ETEC was 14% (n = 662), with over 70% of the strains isolated from children 0 to 5 years of age, of whom 93% were in the 0- to 3-year-old age range. Of the total ETEC isolates, 49.4% were positive for the heat-stable toxin (ST), 25.4% were positive for the heat-labile toxin (LT) only, and 25.2% were positive for both LT and ST. The rate of ETEC isolation peaked in the hot summer months of May to September and decreased in winter. About 56% of the samples were positive for 1 or more of the 12 CFs that were screened for. The coli surface antigens CS4, CS5, and/or CS6 of the colonization factor antigen (CFA)/IV complex were most prevalent (incidence, 31%), followed by CFA/I (23.5%) and coli surface antigens CS1, CS2, and CS3 of CFA/II (21%). In addition, other CFs detected in decreasing order were CS7 (8%), CS14 (PCFO166) (7%), CS12 (PCFO159) (4%), CS17 (3%), and CS8 (CFA/III) (2.7%). The ST- or LT- and ST-positive ETEC isolates expressed the CFs known to be the most prevalent (i.e., CFA/I, CFA/II, and CFA/IV), while the strains positive for LT only did not. Among children who were infected with ETEC as the single pathogen, a trend of relatively more severe disease in children infected with ST-positive (P < 0.001) or LT- and ST-positive (P < 0.001) ETEC isolates compared to the severity of the disease in children infected with LT only-positive ETEC isolates was seen. This study supports the fact that ETEC is still a major cause of childhood diarrhea in Bangladesh, especially in children up to 3 years of age, and that measures to prevent such infections are needed in developing countries.

Antigens, Bacterial↗
PubMed2000

Prevalence of enterotoxin genes in Aeromonas spp. isolated from children with diarrhea, healthy controls, and the environment.

Aeromonads are causative agents of a number of human infections. Even though aeromonads have been isolated from patients suffering from diarrhea, their etiological role in gastroenteritis is unclear. In spite of a number of virulence factors produced by Aeromonas species, their association with diarrhea has not been clearly linked. Recently, we have characterized a heat-labile cytotonic enterotoxin (Alt), a heat-stable cytotonic enterotoxin (Ast), and a cytotoxic enterotoxin (Act) from a diarrheal isolate of Aeromonas hydrophila. Alt and Ast are novel enterotoxins which are not related to cholera toxin; Act is aerolysin related and has hemolytic, cytotoxic, and enterotoxic activities. We studied the distribution of the alt, ast, and act enterotoxin genes in 115 of 125 aeromonads isolated from 1, 735 children with diarrhea, in all 27 aeromonads isolated from 830 control children (P = 7 x 10(-4) for comparison of rates of isolation of aeromonads from cases versus those from controls), and in 120 randomly selected aeromonads from different components of surface water in Bangladesh. Aeromonas isolates which were positive only for the presence of the alt gene had similar distributions in the three sources; the number of isolates positive only for the presence of the ast gene was significantly higher for the environmental samples than for samples from diarrheal children; and isolates positive only for the presence of the act gene were not found in any of the three sources. Importantly, the number of isolates positive for both the alt and ast genes was significantly higher for diarrheal children than for control children and the environment. Thus, this is the first study to indicate that the products of both the alt and ast genes may synergistically act to induce severe diarrhea. In 26 patients, Aeromonas spp. were isolated as the sole enteropathogen. Analysis of clinical data from 11 of these patients suggested that isolates positive for both the alt and ast genes were associated with watery diarrhea but that isolates positive only for the alt gene were associated with loose stools. Most of the isolates from the three sources could be classified into seven phenospecies and eight hybridization groups. For the first time, Aeromonas eucrenophila was isolated from two children, one with diarrhea and another without diarrhea.

Aeromonas↗
PubMed2000

New insights on the emergence of cholera in Latin America during 1991: the Peruvian experience.

After a century of absence, in late January 1991, Vibrio cholerae invaded the Western Hemisphere by way of Peru. Although a number of theories have been proposed, it is still not understood how that invasion took place. We reviewed the clinical records of persons attending hospital emergency departments in the major coastal cities of Peru from September through January of 1989/1990 and 1990/1991. We identified seven adults suffering from severe, watery diarrhea compatible with a clinical diagnosis of cholera during the four months preceding the cholera outbreak, but none during the previous year. The patients were scattered among five coastal cities along a 1,000 km coastline. We postulate that cholera vibrios, autochthonous to the aquatic environment, were present in multiple coastal locations, and resulted from environmental conditions that existed during an El Nino phenomenon. Once introduced into the coastal communities in concentrations large enough for human infection to occur, cholera spread by the well-known means of contaminated water and food.

Cholera↗
PubMed1999

Intestinal immune responses in patients infected with enterotoxigenic Escherichia coli and in vaccinees.

Immune responses against enterotoxigenic Escherichia coli (ETEC) were examined in Bangladeshi adults with naturally acquired disease and compared to responses in age-matched Bangladeshi volunteers who had been orally immunized with a vaccine consisting of inactivated ETEC bacteria expressing different colonization factor antigens (CFs) and the B subunit of cholera toxin. B-cell responses in duodenal biopsy samples, feces, intestinal washings, and blood were determined. Because most of the patients included in the study were infected with ETEC expressing CS5, immune responses to this CF were studied most extensively. Vaccinees and patients had comparable B-cell responses against this antigen in the duodenum: the median numbers of antibody-secreting cells (ASC) were 3,300 immunoglobulin A (IgA) ASC/10(7) mononuclear cells (MNC) in the patient group (n = 8) and 1,200 IgA ASC/10(7) MNC in the vaccinees (n = 13) (not a significant difference). Similarly, no statistically significant differences were seen in the levels of duodenal B cells directed against enterotoxin among vaccinees and patients. A comparison of the capacities of the various methods used to assess mucosal immune responses revealed a correlation between numbers of circulating B cells and antibody levels in saponin extracts of duodenal biopsy samples (r = 0.58; n = 13; P = 0.04) after vaccination. However, no correlation was seen between blood IgA ASC and duodenal IgA ASC after two doses of vaccine. Still, a correlation between numbers of CF-specific B cells in blood sampled from patients early during infection and numbers of duodenal B cells collected 1 week later was apparent (r = 0.70; n = 10; P = 0.03).

Adolescent↗
PubMed1999

Case-control study of enteropathogens associated with childhood diarrhea in Dhaka, Bangladesh.

The International Centre for Diarrhoeal Disease Research, Bangladesh, is a major center for research into diarrheal diseases. The center treats more than 100,000 patients a year. To obtain useful information representative of all patients, a surveillance system in which a 4% systematic sample of all patients is studied in detail, including etiological agents of diarrhea, was installed in October 1979. The first paper on etiology for the surveillance patients was published in 1982, which identified a potential enteric pathogen in 66% of patients. In subsequent years, several new agents of diarrhea have been identified. To assess the importance of a broader spectrum of diarrheal agents including the ones identified relatively recently, we studied 814 children with diarrhea. The children were up to 5 years of age and were part of the surveillance system. They were matched with an equal number of community controls without diarrhea. The study was conducted from February 1993 to June 1994. A potential enteric pathogen was isolated from 74.8% of diarrheal children and 43.9% of control children (P = 0.0001). Even though the first study was not a case-control study, it identified rotavirus, Campylobacter jejuni, enterotoxigenic Escherichia coli, Shigella spp. , and Vibrio cholerae O1 as major pathogens. The present study identified these pathogens as being significantly associated with diarrhea. In addition, the study also identified six additional agents, including enteropathogenic E. coli, Aeromonas spp., V. cholerae O139, enterotoxigenic Bacteroides fragilis, Clostridium difficile, and Cryptosporidium parvum, as being significantly associated with diarrhea. Plesiomonas shigelloides, Salmonella spp., diffusely adherent E. coli, enteroaggregative E. coli, Entamoeba histolytica, and Giardia lamblia were not significantly associated with diarrhea. Enteroinvasive E. coli, enterohemorrhagic E. coli, and Cyclospora cayetanensis were not detected in any of the children. The major burden of diseases due to most pathogens occurred in the first year of life. As in the previous study, seasonal patterns were seen for diarrhea associated with rotavirus, V. cholerae, and enterotoxigenic E. coli, and infections with multiple pathogens were common. With a few exceptions, these findings are in agreement with those from other developing countries. This knowledge of a broader spectrum of etiological agents of diarrhea in the surveillance patients will help us plan studies into various aspects of diarrheal diseases in this population.

Bangladesh↗
PubMed1999

Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae strains causing childhood infections in Bangladesh, 1993 to 1997.

Three hundred sixty-two Streptococcus pneumoniae strains were isolated from children under 5 years of age at Dhaka Shishu (Children) Hospital from 1993 to 1997. The strains were isolated from blood (n = 105), CSF (n = 164), ear swab (n = 61), eye swab (n = 20), and pus (n = 12). Of the 362 isolates, 42 (11.6%) showed intermediate resistance (MIC, <0.1 microgram/ml) and only 4 (1.1%) showed complete resistance (MIC, >2.0 microgram/ml) to penicillin. Penicillin resistance exhibited a strong relationship with serotype 14; 47.8% of the penicillin-resistant strains belonged to this type. A remarkably high (64.1%) resistance to co-trimoxazole was observed, along with a significant increase during the time period studied; there was no relationship to capsular type. By way of contrast, penicillin resistance did not show any significant change during the study period. Resistance to chloramphenicol (2.2%) and erythromycin (1.1%) was rare. The high resistance to co-trimoxazole and its increasing trend demand elucidation of the clinical impact of pneumonia treatment by this antimicrobial and reconsideration of the World Health Organization recommendation for co-trimoxazole administration to children with community-acquired pneumonia at the health care worker level in Bangladesh.

Bangladesh↗
PubMed1999

Molecular characterization of a new ribotype of Vibrio cholerae O139 Bengal associated with an outbreak of cholera in Bangladesh.

Vibrio cholerae O139 Bengal initially appeared in the southern coastal region of Bangladesh and spread northward, causing explosive epidemics during 1992 and 1993. The resurgence of V. cholerae O139 during 1995 after its transient displacement by a new clone of El Tor vibrios demonstrated rapid changes in the epidemiology of cholera in Bangladesh. A recent outbreak of cholera in two north-central districts of Bangladesh caused by V. cholerae O139 led us to analyze strains collected from the outbreak and compare them with V. cholerae O139 strains isolated from other regions of Bangladesh and neighboring India to investigate their origins. Analysis of restriction fragment length polymorphisms in genes for conserved rRNA (ribotype) revealed that the recently isolated V. cholerae O139 strains belonged to a new ribotype which was distinct from previously described ribotypes of toxigenic V. cholerae O139. All strains carried the genes for toxin-coregulated pili (tcpA and tcpI) and accessory colonization factor (acfB), the regulatory gene toxR, and multiple copies of the lysogenic phage genome encoding cholera toxin (CTXPhi) and belonged to a previously described ctxA genotype. Comparative analysis of the rfb gene cluster by PCR revealed the absence of a large region of the O1-specific rfb operon downstream of the rfaD gene and the presence of an O139-specific genomic region in all O139 strains. Southern hybridization analysis of the O139-specific genomic region also produced identical restriction patterns in strains belonging to the new ribotype and those of previously described ribotypes. These results suggested that the new ribotype of Bengal vibrios possibly originated from an existing strain of V. cholerae O139 by genetic changes in the rRNA operons. In contrast to previously isolated O139 strains which mostly had resistance to trimethoprim, sulfamethoxazole, and streptomycin encoded by a transposon (SXT element), 68.6% of the toxigenic strains analyzed in the present study, including all strains belonging to the new ribotype, were susceptible to these antibiotics. Molecular analysis of the SXT element revealed possible deletion of a 3.6-kb region of the SXT element in strains which were susceptible to the antibiotics. Thus, V. cholerae O139 strains in Bangladesh are also undergoing considerable reassortments in genetic elements encoding antimicrobial resistance.

Bangladesh↗
PubMed1999

Effects of environmental factors on child survival in Bangladesh: a case control study.

The need for further studies on relationships between deaths and environmental variables has been reported in the literature. This case-control study was, therefore, carried out to find out the associations between several social and environmental variables and deaths of children due to infectious diseases such as those leading to diarrhoea, acute respiratory infection, measles and other diseases. Six hundred and twenty-five deaths (cases) and an equal number of matched living children (controls) aged 1-59 months, were studied in rural Matlab. An analysis of crude and adjusted odds ratio showed differential associations. Sources of drinking water, amount of stored water, conditions of latrines, number of persons sleeping with the child and the type of cooking site were statistically significantly associated with deaths due to infectious diseases after controlling for breast feeding, immunization, and the family size. Significant associations were also observed between: (i) the sources of drinking water and deaths due to ARI, and (ii) conditions of latrines and deaths due to diarrhoeal diseases, after controlling for the confounding variables. Several other environmental factors also showed associations with these various death groups, but they were not statistically significant. The size of the samples in death groups (small) and the prevalence of more or less homogeneous environmental health conditions probably diminished the magnitude of the effects. The results of the study reconfirm the importance of environmental health intervention in child survival, irrespective of breast-feeding, immunization, and selected social variables.

Bangladesh↗
PubMed1998

Maternal measles antibody decay in rural Bangladeshi infants--implications for vaccination schedules.

Considerable numbers of measles cases occur below the target age for vaccination in the Indian sub-continent. The immunogenicity of measles vaccine in infancy is dependent on the rate of decay in maternal antibody since this antibody interferes with vaccine induced seroconversion. This study investigated maternal antibody decay in a rural population in Bangladesh and evaluated possible risk factors for early decay. Measles antibodies were assessed using both ELISA and Plaque Reduction Neutralization (PRN) test in 330 infant-mother pairs in a cross-sectional survey. PRN was more sensitive method than ELISA for determining antibody levels. Antibody levels decreased rapidly in infants with increasing age. By the age of 5 months, 67% (28/42) infants had practically no protective antibody left (30 mIU ml-1 or below). Only 12% infants at 5 months of age, and 5% at 8 months, had levels greater than 120 mIU ml-1--stated to 'protect' children. Multiple regression showed that maternal age was the only variable associated with the level of antibody (maternal weight, height and MUAC were not associated), decreasing by 1.06 mIU ml-1 for each year of age (P = 0.002). Infant's antibody concentration decreased with age by an average 2 mIU mL-1 for every month of life (P < 0.0001), and was determined by the maternal antibody concentration (P < 0.0001) (child's length, weight, MUAC, mother's gestational age and parity were not associated). The relatively rapid antibody decay suggests that the target age for measles vaccination might be reduced. Further, as the cohort of vaccinated mothers enters reproductive age in Bangladesh, a more rapid decay of antibody may be expected in future generations of Bangladeshi children. The information presented here suggests that a formal trial of standard measles vaccine at younger ages is justified in this population as it could confer considerable benefit in reducing infant measles.

Adult↗
PubMed1998

Increasing frequency of mecillinam-resistant shigella isolates in urban Dhaka and rural Matlab, Bangladesh: a 6 year observation.

A total of 14,915 shigella isolates obtained in 1991-1996 from patients attending the Dhaka (urban) and Matlab (rural) treatment centres of the International Centre for Diarrhoeal Disease Research, Bangladesh were examined for susceptibility to ampicillin, co-trimoxazole, nalidixic acid, mecillinam and ciprofloxacin by a disc diffusion method. There were no ciprofloxacin-resistant shigella isolates. The prevalence of resistance to ampicillin, co-trimoxazole and nalldixic acid varied between isolates. It increased to similar degrees in isolates from both Matlab and Dhaka. However, resistance to mecillinam was more prevalent among isolates from Matlab than from Dhaka. The increase in mecillinam-resistant shigellae in the community may have grave implications for the empirical treatment of shigellosis in Bangladesh and other developing countries.

Amdinocillin↗
PubMed1998

Induction of fimbriated Vibrio cholerae O139.

Several fimbriated phases of Vibrio cholerae O139 strains were selectively induced and compared immunologically and biochemically with those of V. cholerae O1. Fimbrial antigens were detected on the surfaces of vibrio cells colonizing the epithelial cells of a rabbit small intestine. Convalescent-phase sera from six individuals infected with V. cholerae O139 revealed the development of antibody against the fimbrillin. These findings suggest that the fimbriae of V. cholerae O1 and O139 are expressed in vivo during infection and that consideration must be given to the use of fimbrial antigens as components of vaccines against cholera.

Animals↗
PubMed1998

Validation of a volunteer model of cholera with frozen bacteria as the challenge.

To evaluate a standardized inoculum of Vibrio cholerae for volunteer challenge studies, 40 healthy adult volunteers were challenged at three different institutions with a standard inoculum prepared directly from vials of frozen, virulent, El Tor Inaba V. cholerae N16961, with no further incubation. Groups of 5 volunteers, with each group including 2 volunteers with blood group O, were given a dose of 10(5) CFU, and 34 of the 40 volunteers developed diarrhea (mean incubation time, 28 h). Transient fevers occurred in 15 (37.5%) of the volunteers. V. cholerae was excreted by 36 of 40 volunteers. Five additional volunteers received 10(4) CFU, and four developed diarrhea but with a lower average purging rate than required for the model. Of the 40 volunteers, 37 developed rises in their vibriocidal and antitoxin titers similar to those in previous groups challenged with freshly harvested bacteria. We conclude that challenge with frozen bacteria results in a reproducible illness similar to that induced by freshly harvested bacteria. Use of this model should minimize differences in attack rates or severity when groups are challenged at different times and in different institutions.

Adolescent↗
PubMed1997

Evaluation of Peru-15, a new live oral vaccine for cholera, in volunteers.

A new live oral cholera vaccine, Peru-15, was studied for safety, immunogenicity, and excretion in 2 groups of healthy volunteers. Twelve inpatient volunteers received freshly harvested vaccine in doses of either 10(7) or 10(9) cfu. Subsequently 50 outpatient volunteers received freeze-dried vaccine in doses of 10(8) or 10(9) cfu or placebo in a three-cell, double-masked, placebo-controlled trial. The strain was well tolerated at all dose levels, and it stimulated high levels of vibriocidal antibodies in most inpatient volunteers and in all outpatient volunteers. Although antitoxin responses were less frequent and of lower magnitude than the vibriocidal responses, antitoxin responses were seen in >60% of the outpatient volunteers. About 60% of the volunteers excreted the vaccine in their feces; however, fecal excretion did not correlate with serologic responses. It is concluded that Peru-15 is a safe and immunogenic oral vaccine for cholera.

Administration, Oral↗
PubMed1997

Antimicrobial resistance in organisms causing diarrheal disease.

Antimicrobial resistance is becoming increasingly important in the treatment of enteric infections, particularly those due to Shigella, Vibrio cholerae, enterotoxigenic Escherichia coli (associated with traveler's diarrhea), and Salmonella typhi. The rate of antimicrobial resistance is highest in the developing world, where the use of antimicrobial drugs is relatively unrestricted. Of greatest immediate concern is the need for an effective, inexpensive antimicrobial that can be used safely as treatment for small children with dysentery due to Shigella, primarily Shigella dysenteriae type 1.

Campylobacter jejuni↗
PubMed1997

Acute respiratory infections in children: a community-based longitudinal study in rural Bangladesh.

A community-based logitudinal study conducted in Matlab, a rural area in Bangladesh, investigated acute respiratory infections (ARI) among children. A cohort of 696 children under 5 years of age was followed for 1 year yielding 183,865 child-days of observation. Trained field workers visited the study children every fourth day. Data on symptoms suggesting ARI, such as fever, cough, and nasal discharge, were collected for the preceding 3 days by recall. To determine the type and severity of ARI, the field workers conducted physical examinations (temperature, rate of respiration, and chest indrawing) of children reporting cough and/or fever. The overall incidence of ARI was 5.5 episodes per child-year observed; the prevalence was 35.4 per hundred days observed. Most of the episodes (96 per cent) were upper respiratory infections (URI). The incidence of acute lower respiratory infections (ALRI) was 0.23 per child per year. The incidence of URI was highest in 18-23-month-old children, followed by infants 6-11 months old. The highest incidence of ALRI was observed in 0-5-month-old infants followed by 12-17-month-old children. Among 559 children who were followed for 6 months or longer, about 9 per cent did not suffer any URI episode and about 16 per cent suffered one or more ALRI episodes. About 46 per cent of URI and 65 per cent of ALRI episodes lasted 15 days or more. The incidence rates of URI were higher during the monsoon and pre-winter periods, and that of ALRI at the end of the monsoon and during the pre-winter periods. Sociodemographic variables were not associated with the incidence of URI or ALRI. The study documents ARI to be a major cause of morbidity among rural Bangladeshi children.

Bangladesh↗