Biomedical subjects

J D Clemens

Publications and source records attributed to J D Clemens.

At least 91 records · Page 5Linked to original sources

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

Response to initial therapy and new onset as predictors of prognosis in patients hospitalized with congestive heart failure.

Clinical predictors of in-hospital fatality were assessed in 191 persons admitted to the Yale-New Haven Hospital Intensive Care Unit with a diagnosis of congestive heart failure. In the 17 (8.9%) patients who died, the most important individual predictors among the presenting clinical features were absence of dyspnea, presence of anterior chest pain or jugulovenous distension, and cardiac severity due to ischemia, valvular disease, or arrhythmia. Two important predictors, largely neglected in previous literature, were a prior history of congestive heart failure and a poor clinical response after 24 h of therapy. Multivariable analysis led to the identification of 6 features (age greater than 70 y, prior history of congestive heart failure, jugulovenous distension, chest pain, cardiac severity, and poor early response to therapy) that could be combined into a simple clinical predictive index. The new index identified 5 prognostic groups with fatality rates of 0, 3.5, 7.4, 19.2, and 85.7 percent. An advantage of the clinical index is the identification of a subgroup of patients, with low risk for fatality, who may not need prolonged treatment in an intensive care unit.

Aged↗

PubMed1991

The protective efficacy of polyvalent pneumococcal polysaccharide vaccine.

BACKGROUND: Although the protective efficacy of pneumococcal polysaccharide vaccine has been demonstrated in randomized trials in young African gold miners, there has been controversy about its efficacy in older Americans at risk for serious pneumococcal infections. To assess the vaccine's protective efficacy against invasive pneumococcal infections, we conducted a hospital-based case-control study of the efficacy of pneumococcal vaccine in adults with a condition recognized to be an indication for receiving the vaccine. METHODS: From 1984 to 1990, adults in whom Streptococcus pneumoniae was isolated from any normally sterile site were identified by prospective surveillance in the microbiology laboratories of 11 large hospitals; those with an indication for pneumococcal vaccine were enrolled as case patients. For each case patient, one control was matched according to age, underlying illness, and site of hospitalization. We contacted all providers of medical care to ascertain each subject's history of immunization with pneumococcal vaccine. Isolates of S. pneumoniae were serotyped by an investigator unaware of the subject's vaccination history. RESULTS: Thirteen percent of the 1,054 case patients and 20 percent of the 1,054 matched controls had received pneumococcal vaccine (P less than 0.001). When vaccine was given in either its 14-valent or its 23-valent form, its aggregate protective efficacy (calculated as a percentage: 1 minus the odds ratio of having been vaccinated times 100) against infections caused by the serotypes represented in the vaccine was 56 percent (95 percent confidence interval, 42 percent to 67 percent; P less than 0.00001) for all 983 patients infected with a serotype represented in the vaccine, 61 percent for a subgroup of 808 immunocompetent patients (95 percent confidence interval, 47 percent to 72 percent; P less than 0.00001), and 21 percent for a subgroup of 175 immunocompromised patients (95 percent confidence interval, -55 percent to 60 percent; P = 0.48). The vaccine was not efficacious against infections caused by serotypes not represented in the vaccine (protective efficacy, -73 percent; 95 percent confidence interval, -263 percent to 18 percent; P = 0.15). CONCLUSIONS: Polyvalent pneumococcal vaccine is efficacious in preventing invasive pneumococcal infections in immunocompetent patients with indications for its administration. This vaccine should be used more widely.

Adolescent↗

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

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↗

PubMed1991

Assessment of the prevalence and risk factors for human immunodeficiency virus type 1 (HIV-1) infection among college students using three survey methods.

To evaluate the seroprevalence and risk factors for human immunodeficiency virus type 1 (HIV-1) infection among undergraduate college students, the authors simultaneously conducted three types of surveillance on a large university campus (27,902 undergraduates) in the Baltimore-Washington metropolitan area: a voluntary HIV-1 serosurvey with a linked risk assessment questionnaire (n = 3,394), a blinded serosurvey using blood specimens collected for routine purposes in the Student Health Center (n = 1,829), and a random sample risk assessment and case identification mail survey (n = 1,017 respondents of 3,000 solicited). The proportion of students belonging to a known risk group (a homosexual or bisexual man, intravenous drug user, or a sexual partner of a bisexual man, an HIV-1-infected person, a female prostitute, or an intravenous drug user) was 5.9% in the mail survey and 8.8% in the voluntary serosurvey. Whereas no infections were detected in the blinded serosurvey, two infected persons were identified in the mail survey (0.2%) and two in the voluntary serosurvey (0.06%), all among high-risk persons. Although derived from independent samples and subject to different biases, these three survey methods yielded a consistent pattern of HIV-1 epidemiology on this campus, whereby the overall prevalence of infection was low and confined to members of high-risk groups, despite the common occurrence of behaviors that might facilitate sexual transmission of HIV-1 among many other students.

Data Collection↗

PubMed1991

Reactivities of serotyping monoclonal antibodies with culture-adapted human rotaviruses.

Rotaviruses collected in Bangladesh during 1985 to 1986 were culture adapted and used in a comparative serotyping study with three groups of monoclonal antibodies, all of which reacted with the major neutralization protein (VP7) of serotype 1, 2, 3, or 4. The goals were to determine which monoclonal antibodies most accurately predicted the serotype and why large variations in serotyping efficiencies have occurred with these monoclonal antibodies in previous studies. The 143 rotavirus isolates used in this study belonged to 69 different electropherotypes; and 44, 23, 21, and 55 isolates were identified as serotype 1 through 4, respectively, by neutralization with serotype-specific hyperimmune antisera. Serotyping specificity by enzyme-linked immunosorbent assay with monoclonal antibodies was 100% consistent with results found by neutralization with polyclonal antisera, but large differences were observed in the sensitivities of the different monoclonal antibodies. Monoclonal antibodies 5E8 (serotype 1), 1C10 (serotype 2), 159 (serotype 3), RV3:1 (serotype 3), ST-3:1 (serotype 4), and ST-2G7 (serotype 4) reacted with all the isolates of the corresponding serotype for which there were sufficient infectious particles. Monoclonal antibody 2F1 (serotype 2) was much less sensitive and reacted with only five serotype 2 isolates, but these were among those with the highest titers. Monoclonal antibodies RV4:2 (serotype 1), KU6BG (serotype 1), RV5:3 (serotype 2), and S2-2G10 (serotype 2), on the other hand, failed to react with between one and three isolates of the corresponding serotypes which had high titers, apparently because of epitope changes in these isolates. Effects of epitope variation were, however, most apparent with monoclonal antibodies 2C9 (serotype 1) and YO-1E2 (serotype 3), which reacted with one and no isolates of the corresponding serotypes, respectively. Cross-neutralization of escape mutants indicated that the serotype 1 monoclonal antibodies 5E8, 2C9, and RV4:2 reacted with different but probably overlapping epitopes, as did serotype 2 monoclonal antibodies 2F1, 1C10, and RV5:3, finding that were consistent with the enzyme-linked immunosorbent assay data. Because of epitope variations between rotavirus strains, serotyping with several monoclonal antibodies directed at different epitopes may increase the sensitivity of the method.

Antibodies, Monoclonal↗

PubMed1991

Culture adaptation and characterization of group A rotaviruses causing diarrheal illnesses in Bangladesh from 1985 to 1986.

Group A rotaviruses collected between 1985 and 1986 during comprehensive surveillance of treated diarrheal episodes occurring in a rural Bangladesh population were culture adapted and characterized by electropherotype, serotype, and subgroup. Of 454 episodes of rotavirus-associated diarrhea, rotaviruses were culture adapted from 381 (84%), and 335 contained 11 electrophoretically identical segments in unpassaged and cultured preparations. These 335 comprised 69 different electropherotypes with between 1 (32 isolates) and 79 representatives. The persistence of specific rotavirus strains within the study population, as defined by the detection of viruses with particular electropherotypes, was generally limited to a period of only a few months. All 335 isolates were serotyped by neutralization with hyperimmune antisera to prototype rotavirus strains representative of serotypes 1 to 4, i.e., Wa, DS-1, P, and ST-3. It was found that 80, 48, 119, and 88 isolates belonged to serotypes 1 to 4, respectively. The concentrations of hyperimmune antisera required to neutralize these isolates, however, were at least threefold greater than those needed to neutralize the homologous strains. Therefore, the isolates appeared to have altered neutralization epitopes from their prototype strains. Furthermore, the serotype 4 isolates were consistently shown to be much more closely related to the serotype 4B VA70 strain than the serotype 4A ST-3 strain. All but two isolates identified as serotypes 1, 3, or 4 had long electropherotypes and were subgroup II, and all but one serotype 2 isolate were subgroup I and had short electropherotypes. The three disparate strains appeared to be genetic reassortants. Evidence is presented that dual infections required for reassortant formation were not uncommon. Thus, formation of multiple reassortants may have been a cause for the observed rapid shift in viral strains within the study population.

Age Factors↗

PubMed1991

Formation and selection of intergenogroup reassortants during cell culture adaptation of rotaviruses from dually infected subjects.

A previous study showed that intergenogroup reassortants of human rotaviruses can persist in nature (R.L. Ward, O. Nakagomi, D.R. Knowlton, M.M. McNeal, T. Nakagomi, J.D. Clemens, D.A. Sack, and G.M. Schiff, J. Virol. 64:3219-3225, 1990), but the mechanisms involved in their formation and selection had not been determined. In this study it was shown that, during cell culture adaptation of rotaviruses belonging to different genogroups from stools of dually infected subjects, intergenogroup reassortants were formed and selected, presumably mimicking the processes that occur in nature.

Animals↗

PubMed1990

Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up.

The protective efficacy (PE) of B subunit killed whole-cell (BS-WC) and killed whole-cell-only (WC) oral cholera vaccines was assessed in a randomised double-blind field trial among children aged 2-15 years and women over 15 years in rural Bangladesh. Among the 62 285 subjects who received three doses of BS-WC, WC, or Escherichia coli K12 strain placebo, cumulative PE at 3 years of follow-up was 50% for BS-WC and 52% for WC. PE was similar against severe and non-severe cholera, but was significantly lower in children who were vaccinated at 2-5 years (26% for BS-WC; 23% for WC) than in older persons (63% for BS-WC; 68% for WC). Among persons vaccinated at 2-5 years, protection at 4-6 months of follow-up was similar to that for older persons, but rapidly waned thereafter and was not evident during the third year of follow-up. In contrast, persons vaccinated at older ages were protected even in the third year of follow-up (PE 40% for BS-WC; 62% for WC). PE was substantially higher against classical cholera (58% for BS-WC; 60% for WC) than against El Tor cholera (39% and 40%).

Administration, Oral↗

PubMed1990

Developing improved observational methods for evaluating therapeutic effectiveness.

Therapeutic efficacy is often studied with observational surveys of patients whose treatments were selected nonexperimentally. The results of these surveys are distrusted because of the fear that biased results occur in the absence of experimental principles, particularly randomization. The purpose of the current study was to develop and validate improved observational study designs by incorporating many of the design principles and patient assembly procedures of the randomized trial. The specific topic investigated was the prophylactic effectiveness of beta-blocker therapy after an acute myocardial infarction. To accomplish the research objective, three sets of data were compared. First, we developed a restricted cohort based on the eligibility criteria of the randomized clinical trial; second, we assembled an expanded cohort using the same design principles except for not restricting patient eligibility; and third, we used the data from the Beta Blocker Heart Attack Trial (BHAT), whose results served as the gold standard for comparison. In this research, the treatment difference in death rates for the restricted cohort and the BHAT trial was nearly identical. In contrast, the expanded cohort had a larger treatment difference than was observed in the BHAT trial. We also noted the important and largely neglected role that eligibility criteria may play in ensuring the validity of treatment comparisons and study outcomes. The new methodologic strategies we developed may improve the quality of observational studies and may be useful in assessing the efficacy of the many medical/surgical therapies that cannot be tested with randomized clinical trials.

Adrenergic beta-Antagonists↗

PubMed1990

Field trial of oral cholera vaccines in Bangladesh: evaluation of anti-bacterial and anti-toxic breast-milk immunity in response to ingestion of the vaccines.

In a field trial conducted in Bangladesh, ingestion of either B subunit-killed whole cell (BS-WC) or killed whole cell (WC) oral cholera vaccines by mothers was associated with a 47% reduction of the risk of cholera in their non-vaccinated children aged under 36 months. Because vaccine-induced breast-milk immunity seemed a possible explanation for these findings, we evaluated anti-lipopolysaccharide (LPS) and anti-cholera toxin (CT) IgA antibody responses in breast milk collected during the trial from 53 lactating women who ingested three doses of BS-WC, WC, or an Escherichia coli K12 strain (K12). Despite induction of moderate vibriocidal (1.4 to 2.0-fold) and anti-CT (4.5-fold) serum antibody responses, the vaccines did not elicit significant rises of anti-LPS or anti-CT IgA breast-milk antibodies. The failure of the vaccines to elicit significant levels of breast-milk anti-cholera antibodies suggests an alternative explanation for protection of young children by maternal vaccination, such as interruption of maternal-child transmission of Vibrio cholerae 01.

Administration, Oral↗

PubMed1990

Low gastric acid as a risk factor for cholera transmission: application of a new non-invasive gastric acid field test.

Although gastric acid is thought to be an important host defense against certain enteric infections, field studies of the role of gastric acid in preventing enteric infections have been hampered by the lack of a suitable non-invasive test. Because low gastric acid output (GAO) is an established risk factor for cholera, we assessed after validation, whether a new non-invasive test which estimates GAO by measuring breath hydrogen excess after ingestion of magnesium and a stimulant of gastric acid secretion, could discriminate between persons at high and at low risk of developing cholera. Fifteen age-matched pairs, participants in the field trial of two oral cholera vaccines in rural Bangladesh, were tested. In each pair the "case" was a person who had recovered from severe cholera at least 6 months before testing and the "control" was a person who resided in the home of a cholera patient but remained uninfected. The stimulated breath hydrogen was higher in controls (median hydrogen excess = 369 mumol/80 min) than in cases (median hydrogen excess = 150 mumol/80 min) (p less than 0.05) and was higher in controls in 12 out of 15 pairs. The results, which are consistent with past invasive assessments of the association between hypochlorhydria and cholera, suggest that this non-invasive test may be useful in evaluating GAO in epidemiological field studies.

Adult↗

PubMed1990

Methodological considerations in defining chronic diarrhoea using a distributional approach.

Attempts to develop effective treatment and preventive strategies for chronic diarrhoea have been confounded by inconsistencies in defining the disorder. In the present paper, we illustrate some of the methodological considerations encountered in using a distributional approach to define chronic diarrhoea. We employ data obtained from 3470 children aged less than six years residing in Dhaka, Bangladesh, between January 1985 and January 1986. The importance of defining the age of the target population is demonstrated by the inverse correlation between age and duration of episodes required to reach or exceed the 95th percentile, ranging from 27 days in children aged less than 12 months to 18 days in children aged over four years. Altering the percentile cut-off qualifying as 'chronic' from the 95th percentile to the 90th percentile changed the minimum qualifying duration from 24 to 16 days. We also demonstrate the impact of altering criteria for termination of an episode and of altering the duration of the monitoring period on the resultant length of episodes classified as 'chronic'.

Bangladesh↗

PubMed1990

Seroepidemiologic evaluation of anti-toxic and anti-colonization factor immunity against infections by LT-producing Escherichia coli in rural Bangladesh.

To evaluate serologic immunity against clinical infections by heat-labile enterotoxin-producing Escherichia coli (LT-ETEC) in rural Bangladesh, 124 children and adult women with LT-ETEC diarrhea (cases) were compared with 347 age-matched community controls. In paired acute-convalescent sera from the cases, IgG anti-CFA I and anti-CFA II antibody titers increased eight-to ninefold after infection by LT-ETEC with the homologous CFA, and IgG anti-LT antibody titers increased fourfold for all LT-ETEC infections. Anti-CFA and anti-LT titers peaked in controls aged 12-23 months, the age group with the highest incidence of ETEC infections. However, antibody titers were similar in acute sera from cases and in sera from controls. Although serum IgG anti-CFA and anti-LT antibodies rose in response to LT-ETEC infections and paralleled the age-specific incidence of ETEC in the community, these antibodies were not associated with a lower risk of LT-ETEC diarrhea.

Adolescent↗

PubMed1990

Breast feeding and the risk of severe cholera in rural Bangladeshi children.

The association between breast feeding and the risk of severe cholera was examined in a case-control study of rural Bangladeshi children under 36 months of age who were studied in 1985-1986 during a field trial of killed oral cholera vaccines. A total of 116 cases who were treated for severe cholera were compared with 464 age-matched community controls without severe cholera. Overall, the odds ratio relating breast feeding to severe cholera (0.30, p less than 0.0001) reflected a 70% reduction in the risk of severe cholera among breast-fed children. The estimated reduction of risk declined with age, but was clearly evident in children up to 30 months of age. Although the association between breast feeding and a reduced risk of severe cholera was not significantly greater in children of mothers who had received cholera vaccine than in children whose mothers had received placebo during the trial, maternal vaccination per se was suggestively associated with a reduced risk of severe cholera in their nonvaccinated children (odds ratio = 0.53, p = 0.05). These results indicate that breast feeding was associated with a substantial reduction of the risk of severe cholera and raise the possibility that vaccination of mothers may provide protection to their young children in endemic settings.

Bangladesh↗