Biomedical subjects

D A Sack

Publications and source records attributed to D A Sack.

At least 55 records · Page 3Linked to original sources

PubMed1994

Is protection against shigellosis induced by natural infection with Plesiomonas shigelloides?

Shigellosis due to Shigella sonnei is rare among people growing up and living in developing countries; however, infections due to S sonnei becomes more common than those due to S flexneri as societies develop economically. The relation between risk of S sonnei infection and economic development may be explained by the exposure of developing-country populations to Plesiomonas shigelloides. P shigelloides is often found in surface water, and one serotype (serotype 17) possesses a cell-wall lipopolysaccharide identical to that of S sonnei. Thus, exposure to P shigelloides by drinking contaminated water may immunise populations to S sonnei. As economic development occurs, water quality improves and populations become susceptible to S sonnei. Although drinking water has many advantages, immunisation against S sonnei may be one benefit of traditional water sources.

Developing Countries↗

PubMed1994

The significance of enteroaggregative Escherichia coli in the etiology of hospitalized diarrhoea in Calcutta, India and the demonstration of a new honey-combed pattern of aggregative adherence.

Previous studies have identified enteroadherent Escherichia coli that exhibit localized adherence, diffuse adherence and atypical diffuse adherence as diarrhoeagenic agents associated with infantile diarrhoea in Calcutta, India. In this study, a DNA probe specific for enteroaggregative adherence was used to determine the etiological significance of enteroaggregative E. coli in the causation of diarrhoea. From a total of 330 strains of E. coli recovered from 159 cases of acute secretory diarrhoea and 174 cases of invasive diarrhoea, 20 strains hybridized with the probe, whereas of the 25 E. coli strains recovered from 25 healthy controls only 1 strain hybridized with the probe. Of the 21 probe positive strains, 19 adhered to HeLa cells in the typical stacked-brick pattern while 2 strains recovered from 2 cases of secretory diarrhoea adhered to the glass surface in a hitherto undescribed formation which we have termed, based on the appearance, as the honey-comb pattern. The enteroaggregative E. coli strains identified in this study did not produce any conventional enterotoxins and were significantly associated with patients with secretory diarrhoea (10.7%) than with invasive diarrhoea (1.7%). The results of this study indicate that enteroaggregative E. coli play a causal role in acute secretory diarrhoea in this part of the world which lends credence to the involvement of a potent toxin in the pathogenesis of EAggEC mediated infections.

Bacterial Adhesion↗

PubMed1993

Evaluation of conventional media for detection of colonization factor antigens of enterotoxigenic Escherichia coli.

Strains of enterotoxigenic Escherichia coli producing either colonization factor antigen (CFA) I or II were tested for expression of CFA when grown on 16 different agar media by using agglutination and coagglutination with monoclonal antibodies, mannose-resistant hemagglutination, and a salt aggregation assay. CFA was detected from the CFA-positive strains when CFA agar was used, and it was also detected when other commercially available media were used, notably nutrient agar. CFA was not detected when other commercial media such as MacConkey agar were used. The use of nutrient agar with monoclonal antibody-based coagglutination reagents offers a potentially simple and rapid method for detecting E. coli which express CFA I or II.

Agglutination↗

PubMed1993

Comparison of Vibrio cholerae serotype 01 strains isolated from patients and the aquatic environment.

Vibrio cholerae 01 strains of El Tor and Classical biotypes and Ogawa and Inaba serotypes were isolated from both patients and pond water, the latter used by the patients from whom the V. cholerae 01 strains had been isolated. Paired strains, i.e. from the patient and from the pond used by the patient, were compared. All strains were found to be non-hydrophobic and agglutinating in ammonium sulphate (2.0-2.5 M). They demonstrated similar antibiogram patterns and plasmids were not detected. Except for one clinical and one environmental strain, all strains caused fluid accumulation in the rabbit ileal loop (RIL). The outer membrane protein profiles of both clinical and environmental strains were nearly identical, except for the presence of an additional 22 kDa polypeptide, observed only in environmental strains. The protein profiles of two environmental isolates, analysed after passage through rabbits by oral feeding, were altered, demonstrating a significant decrease in the number of protein bands after animal passage but with the major protein band pattern remaining unchanged. Each passaged strain, however, demonstrated properties similar to the non-passaged culture in cell surface hydrophobicity, plasmid profile, antibiogram patterns, and enterotoxin production.

Animals↗

PubMed1992

Nonparticipation as a determinant of adverse health outcomes in a field trial of oral cholera vaccines.

The authors estimated the incidence rates of cholera and death between 1985 and 1988 for 32,642 age- and sex-eligible persons who did not participate in a randomized, placebo-controlled field trial of killed oral cholera vaccines in rural Bangladesh. As compared with 20,744 placebo recipients, the relative risk of cholera for all nonparticipants, adjusted for potentially confounding demographic variables, was 1.20 (95% confidence interval (CI) 1.03-1.41); this adjusted relative risk reflected elevated adjusted relative risks in nonparticipants who were medically ineligible (RR = 1.65; 95% CI 1.22-2.22) or refused to participate (RR = 1.19; 95% CI 1.01-1.41), but not in persons absent at the time of vaccination (RR = 1.00; 95% CI 0.78-1.28). The adjusted relative risk of death was also elevated in nonparticipants as compared with placebo recipients (RR = 1.28; 95% CI 1.10-1.48), with the same pattern of adjusted relative risks for different categories of nonparticipants: for ineligible subjects, 2.64 (95% CI 2.12-3.29); for refusers, 1.20 (95% CI 1.02-1.41); and for absentees, 0.95 (95% CI 0.75-1.22). The authors concluded that nonparticipation was associated with clinically cogent adverse health outcomes, but that the magnitude of these associations varied according to the reason for nonparticipation. These findings underscore the caution required in assessing vaccine efficacy with controls who are not vaccinated because of choices made by patients or vaccinators.

Administration, Oral↗

PubMed1992

An oral B subunit: whole cell vaccine against cholera.

During the last decade there has been a rapid progress in the development of new, much improved vaccines against cholera. These vaccines, which are given orally to stimulate the gut mucosal immune system, are based on either a combination of purified cholera toxin B (binding) subunit and killed cholera vibrios of Inaba and Ogawa serotypes and El Tor and classical biotypes (B subunit-whole cell vaccine, B-WC) or on a live attenuated mutant strain of Vibrio cholerae producing the B subunit (CVD 103-HgR). The safety of the oral B-WC cholera vaccine and the immunogenicity and protective efficacy of this vaccine against both cholera and diarrhoea caused by enterotoxigenic Escherichia coli have been extensively documented, e.g. in a large randomized, placebo-controlled field trial in 90,000 persons living in a cholera endemic area. The potential for inexpensive large-scale manufacturing of the B-WC vaccine has recently been much facilitated by the introduction of recombinant DNA technology for production of the B subunit component. This now gives promise that this vaccine could become a useful, cost-effective tool in future strategies to control cholera both in endemic situations and in relation to acute epidemic outbreaks.

Administration, Oral↗

PubMed1992

Crossed immunoelectrophoretic analysis of antigenic composition of B-subunit/whole-cell and whole-cell only killed oral cholera vaccines.

Crossed immunoelectrophoresis was used to identify antigens preserved in the whole-cell component of oral cholera vaccines tested in the field trial in Bangladesh. The composition and immunogenicity of the vaccine antigens were compared with those of antigens obtained from live cells of Vibrio cholerae 01 of both biovars and serovars. The whole-cell component of the vaccine contained ten antigens in comparison with the live Vibrio cells which revealed the presence of 30 antigens. The whole-cell component contained lipopolysaccharide, flagellar antigen, one cell-bound haemagglutinin and at least six outer membrane protein antigens.

Administration, Oral↗

PubMed1992

Seroepidemiologic evaluation of antibodies to rotavirus as correlates of the risk of clinically significant rotavirus diarrhea in rural Bangladesh.

A case-control study was conducted among children and adult women in rural Bangladesh to evaluate whether serologic immunity to rotavirus was associated with a lower risk of rotavirus diarrhea of sufficient severity to cause patients to seek medical care. Acute-phase sera from 219 cases of rotavirus diarrhea, detected among patients treated in three diarrheal treatment centers, were compared with sera from 477 contemporaneously selected community controls. Overall, serum IgG antirotavirus antibody titers were nearly one-fourth as high in cases as in controls (107 vs. 417 units/ml; P less than .001). Among persons aged greater than or equal to 8 months, in whom titers of maternal antirotavirus antibodies should have been negligible, even the lowest range of detectable titers (100-200 units/ml) was associated with a substantial (75%, P less than .05) reduction of the risk of rotavirus diarrhea. We conclude that titers of serum IgG antirotavirus antibodies induced by earlier infection were inversely related to the risk of clinically significant rotavirus diarrhea.

Adult↗

PubMed1992

Evidence that inactivated oral cholera vaccines both prevent and mitigate Vibrio cholerae O1 infections in a cholera-endemic area.

In a randomized, placebo-controlled field trial of B subunit-killed whole cell (BS-WC) and killed whole cell only (WC) inactivated oral cholera vaccines in rural Bangladesh, active surveillance of selected neighborhoods during the first year after vaccination identified 127 Vibrio cholerae O1 infections among 3285 three-dose recipients. For each vaccine, protective efficacy was greater against symptomatic (57%, P < .05 for BS-WC; 58%, P < .05 for WC) than against asymptomatic infections (46%, P < .05 for BS-WC; 32%, P = .09 for WC), and protection against each grade of infection was demonstrable for both the classical and El Tor biotypes. Although vaccine protection against symptomatic infections was evident in both young children and older persons, only persons vaccinated at age > 5 years were protected against asymptomatic infections. These results suggest that the inactivated oral vaccines acted both to protect against intestinal colonization by V. cholerae O1 and to interrupt the pathogenic sequence of established infections.

Adolescent↗

PubMed1992

Evidence that protection against rotavirus diarrhea after natural infection is not dependent on serotype-specific neutralizing antibody.

This case-control study sought to determine whether protection against clinically significant rotavirus diarrhea in children aged 4-35 months correlated with titers of serum neutralizing antibody and, if so, whether this protection was serotype-specific. Titers of acute-phase sera from 156 cases of treated rotavirus diarrhea in rural Bangladesh were contrasted with titers from 312 contemporaneously selected, age-matched controls. Analyses of the culture-adapted rotaviruses from the cases revealed that 24%, 15%, 43%, and 17% belonged to serotypes 1-4, respectively. Titers of both homologous and heterologous neutralizing antibody in acute blood specimens of cases were significantly lower than those of matched controls. However, multivariate logistic regression models demonstrated that only antibody titers to heterotypic rotaviruses were independently associated with protection against rotavirus disease. These data, which indicate that the correlation of protection with neutralizing antibody titers is not serotype-specific, suggest that immunity to rotavirus disease may be mediated by other factors.

Algorithms↗

PubMed1992

Protection from Shigella sonnei infection by immunisation of rabbits with Plesiomonas shigelloides (SVC 01).

Plesiomonas shigelloides, an organism commonly found in water, is only rarely associated with diarrhoea in man. P. shigelloides serotype O:17 (SVC O1), which is antigenically similar to Shigella sonnei, was found to be neither virulent nor toxic for rabbits. Rabbits immunised by feeding with P. shigelloides (SVC O1) were completely protected against an oral challenge with 10(10) cells of S. sonnei but non-immunised rabbits were not. P. shigelloides (SVC O1) may be a useful vaccine strain for shigellosis.

Animals↗

PubMed1992

Community-based evaluation of the effect of breast-feeding on the risk of microbiologically confirmed or clinically presumptive shigellosis in Bangladeshi children.

To assess the association between breast-feeding and the risk of microbiologically confirmed or clinically presumptive shigellosis, the authors performed a case-control analysis of Bangladeshi children younger than 3 years of age who were followed up for 1 month after exposure to Shigella in their residential neighborhoods. Two hundred sixty-nine cases with culture-confirmed shigellosis (n = 119) or clinically presumptive shigellosis (culture-negative dysentery, n = 150) were compared with 819 controls without Shigella diarrhea or other invasive diarrheal illnesses. The odds ratio relating breast-feeding to confirmed or presumptive shigellosis, adjusted for potentially confounding variables, was 0.48 (95% confidence interval = 0.32 to 0.72; P less than .001), suggesting a substantial protective effect. The protective association decreased with age but was still significant during the third year of life; appeared to be directly related to the degree of stunting; and was equivalent for confirmed and presumptive shigellosis. Notably, the protective association remained substantial against episodes due to Shigella which were resistant to at least one of the antibiotics customarily used for treatment of Shigella diarrhea (age-adjusted odds ratio = 0.40; 95% confidence interval = 0.22 to 0.74; P less than .01). These data suggest that breast-feeding confers a high level of protection against shigellosis throughout the first 3 years of life, especially among nutritionally compromised children, and thereby underscore the importance of promotion of breast-feeding as a central component of Shigella control programs in less developed settings.

Age Factors↗

PubMed1992

Occurrence of a large plasmid in a strain of Plesiomonas shigelloides with cross-reactivity against Shigella sonnei.

The plasmid profile of P. shigelloides SVC 01, strain with cross-reactivity with Sh. sonnei, (obtained from Dr Alf Lindberg, Stockholm University, Sweden), was assayed and compared with other local isolates of Plesiomonas spp. and also with Sh. sonnei. Diversity in occurrence of plasmids among different strains of P. shigelloides were observed. Further, the SVC 01 strain and Sh. sonnei differ in their plasmid profile.

Cross Reactions↗

PubMed1991

Biotype as determinant of natural immunising effect of cholera.

To test the hypothesis that clinical Vibrio cholerae O1 infections protect against recurrent cholera, treated cholera episodes in a rural Bangladesh population of 188,153 people who were followed between 1985 and 1988 were analysed. Of the 2214 people with initial episodes of cholera, 7 had a second episode. The incidence of cholera was 61% lower in subjects who had had an earlier episode than in those without such an episode. Whereas initial episodes of classical cholera were associated with complete protection against subsequent cholera, initial episodes of El Tor cholera were associated with negligible protection.

Adolescent↗

PubMed1991

Swedish Agency for Research Cooperation with Developing Countries. Prospects for public health benefits in developing countries from new vaccines against enteric infections.

The symposium participants concluded that vaccines with even moderate efficacy can be highly useful to prevent large numbers of severe illness episodes and deaths and that the decision of whether to initiate a vaccine program should be based on measures or estimates of public health effectiveness rather than only on protective efficacy. Studies of protective efficacy are of course critical to establish the vaccine's biologic activity, but additional aspects of public health effectiveness are also crucial in making these decisions. First-generation vaccines are available against typhoid, cholera, and soon rotavirus diarrhea, and vaccines against enterotoxigenic E. coli diarrhea and shigellosis are under development. The problems related to enteric diseases are enormous; the vaccines may soon be produced at low cost and promise to be relatively more easy to distribute than most previous vaccines. The number of illnesses and deaths averted from vaccine programs are potentially great. Pilot programs using the new vaccines should urgently be considered in areas where the disease burden is high, and steps should be taken to monitor effectiveness of the intervention in these programs. Such studies of vaccine effectiveness and costs in a "real world" situation are an essential step of the research process and should be used to guide the organization of larger-scale programs. Finally, many of the necessary research and development activities relevant to public health vaccinology must address country-specific problems. Developing countries should consider the role of vaccine-related research among the priorities for their essential national health research and build the necessary capabilities in applied and basic medical sciences and in the social sciences.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-Benefit Analysis↗

PubMed1991

Field trial of oral cholera vaccines in Bangladesh: serum vibriocidal and antitoxic antibodies as markers of the risk of cholera.

The relationship of serum vibriocidal (VC) and IgG anti-cholera toxin (CT) antibodies to the risk of cholera was evaluated during the first year of follow-up of recipients of three oral doses of B subunit (BS)-whole-cell vaccine, whole-cell vaccine, or Escherichia coli K12 strain placebo in Bangladesh. Acute sera from 121 cholera patients were compared with sera from 2592 contemporaneous community controls. Each doubling of VC titer was associated, on average, with a 22%-47% reduction of cholera risk in the three groups. In contrast, in the two groups that did not receive BS, anti-CT titers were directly associated with cholera and thus served as markers of higher cholera risk. Each vaccine conferred approximately 65% protective efficacy against cholera, but antibody titers did not correlate with vaccine efficacy, indicating that serum VC and anti-CT antibodies are poor markers of the longitudinal pattern of vaccine efficacy.

Administration, Oral↗

PubMed1991

ABO blood groups and the risk of diarrhea due to enterotoxigenic Escherichia coli.

To determine whether blood group O persons are at higher risk for enterotoxigenic Escherichia coli (ETEC) diarrhea, a case-control study was done for 17 months among rural Bangladeshis who were under systematic surveillance for diarrhea. Cases were children less than 3 years old who presented between 1 January 1985 and 1 June 1986 for care of heat labile (LT) or heat stabile toxin-producing ETEC diarrhea. Controls were of similar ages and were randomly selected from three community-based serosurveys between July 1985 and May 1986. No association between blood group O and ETEC diarrhea was found for the 510 cases and 641 controls, nor was an association evident for cases of each toxin phenotype. Further refinement of the case definition to include only patients with LT-ETEC diarrhea, without enteric copathogens, also failed to reveal a substantial association with blood group O. These data suggest that a strong association with ABO groups, analogous to that for cholera, does not exist for ETEC diarrhea.

ABO Blood-Group System↗

PubMed1991

Antibody responses after immunization with killed oral cholera vaccines during the 1985 vaccine field trial in Bangladesh.

Sera collected during the 1985 oral cholera vaccine trial in Matlab, Bangladesh, which demonstrated efficacy of a whole cell combined with cholera B subunit vaccine (WC/BS) and a whole cell only vaccine (WC), were analyzed for antitoxin and vibriocidal antibodies. Before vaccines were given, antitoxin titers were highest in children, especially those with O blood group, whereas vibriocidal titers rose throughout life. Two weeks after three doses of vaccine, geometric mean antitoxin titers were 2.5-4.5 times higher in vaccinees who received the WC/BS vaccine; the vibriocidal titers were 1.3-2.1 times higher in vaccinees who received either vaccine. The titer elevations were relatively brief and were barely detectable 7 months after the third dose even though significant levels of protection persisted greater than or equal to 3 years. Thus, the oral vaccines induced a serum response in this large field trial that was similar to that seen in earlier pilot studies, but the duration of the serum responses was much shorter than the duration of the protection.

Administration, Oral↗