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Biomedical subjects

J D Clemens

Publications and source records attributed to J D Clemens.

At least 109 records · Page 6Linked to original sources

Evidence for natural reassortants of human rotaviruses belonging to different genogroups.

Of 335 rotavirus isolates associated with diarrheal disease in Bangladesh that were culture adapted and subsequently characterized for electropherotype, subgroup, and serotype, 9 had properties that suggested they may be natural reassortants between human rotaviruses belonging to different "genogroups." Two of these were examined in greater detail by RNA-RNA hybridization with prototype strains representative of each of the three proposed human rotavirus genogroups. One subgroup II isolate, 248, with a "long" electrophoretic pattern was neutralized by hyperimmune antisera to both serotype 2 and 4 strains. Consistent with these results, seven RNA segments of this isolate formed hybrids with human strains belonging to the Wa genogroup and four segments hybridized with strains belonging to the DS-1 genogroup. The second isolate examined, 456, belonged to subgroup II and had a long electrophoretic pattern but was found to be a serotype 2 strain. This isolate also appeared to be an intergenogroup reassortant because three of its segments formed hybrids with strains belonging to the Wa genogroup and eight hybridized with viruses of the DS-1 genogroup. On the basis of the relative migration rates of these RNA-RNA hybrids during gel electrophoresis, a suggested origin for each gene segment was proposed which was consistent with the results expected from electrophoretic, subgroup, and serotypic analyses.

Blotting, Northern↗

Impact of measles vaccination on childhood mortality in rural Bangladesh.

This study examines the impact of measles vaccination on childhood mortality, based on longitudinal data from the Matlab maternal and child health/family planning programme in rural Bangladesh. It analyses the mortality experience of 8135 vaccinated and 8135 randomly matched nonvaccinated children aged 9-60 months, who were observed from March 1982 to October 1985. The results indicate that measles vaccination had a pronounced impact on both short- and long-term survival--the mortality rates for vaccinated children were as much as 46% less than those for nonvaccinated children. Immunization of children aged up to 3 years with measles vaccine appears to improve significantly their subsequent chances of survival. The findings underscore the need to give greater priority to measles vaccination within primary health care programmes in settings such as rural Bangladesh.

Bangladesh↗

Association of antecedent malnutrition with persistent diarrhoea: a case-control study.

To determine the effect of nutritional state on persistent diarrhoea a case-control study was carried out on 756 children followed up prospectively for 18 months. Children who developed persistent diarrhoea were compared with population controls and controls with acute diarrhoea. The mean weight for age in the children with persistent diarrhoea (69.9%) was significantly lower than that in the population controls (77.0%) and the diarrhoeal controls (76.2%). Weight for age of less than or equal to 70% was associated with persistent diarrhoea in both case-control analyses (population controls, matched odds ratio 3.25; diarrhoeal controls, matched odds ratio 2.46). The corrected odds (multiple logistic regression) in the two analyses were 3.2 (95% confidence interval 1.3 to 8.1) and 3.4 (1.2 to 9.1). Weight for age of less than or equal to 70% increases the risk of persistent diarrhoea. In an underweight child there is a higher risk of diarrhoea becoming persistent. Prevention of malnutrition and intensive management of acute diarrhoea in malnourished children should help reduce the risk of the diarrhoea persisting.

Age Factors↗

Oral cholera vaccines containing B-subunit-killed whole cells and killed whole cells only. I. Cross-reacting antigens of members of family Vibrionaceae and the vaccines.

Antigenic similarity between the oral cholera B subunit-whole cell (BS-WC) and whole-cell only (WC) vaccines and strains of the family Vibrionaceae was studied by crossed immunoelectrophoresis. A reference system consisting of Vibrio cholerae Inaba E1 Tor antigenic extract and homologous rabbit antiserum was applied in the study. The system was represented by 30 anodically migrating antigens forming distinct precipitation bands. Antigenic extracts of other members of the family Vibrionaceae showed the following numbers of cellular antigens shared in common with the reference system: Vibrio cholerae non-01-30, V. mimicus-23, V. fluvialis-15, V. parahaemolyticus-10, Aeromonas hydrophila-7, A. sobria-5, A. caviae-4 and Plesiomonas shigelloides-5 antigens. Homologous rabbit antiserum reacted with 11 antigens of BS-WC vaccine and 10 antigens of WC vaccine. The number of antigens which members of the family Vibrionaceae shared in common with those preserved in the WC component of the vaccines were as follows: Vibrio cholerae non-01, 7; V. mimicus, 5; V. fluvialis, 3; V. parahaemolyticus, 3; Aeromonas hydrophila, 2; A. sobria, 2; and A. caviae, 2; Plesiomonas shigelloides, 1. None of the strains produced an antigen reacting with anti-cholera toxin antibodies. The presence of common antigens in the vaccine and among members of family Vibrionaceae indicates that the oral cholera vaccine could stimulate immunity effectively against other members of the family.

Administration, Oral↗

Oral cholera vaccines containing B-subunit-killed whole cells and killed whole cells only. II. Field evaluation of cross-protection against other members of the Vibrionaceae family.

Because of demonstrable cross-reactivity of cellular antigens contained in B subunit-killed whole-cell (BS-WC) and killed whole-cell-only (WC) oral cholera vaccines with antigens of various non-cholera species of the family Vibrionaceae (NCV), the protection conferred by the vaccines against diarrhoea associated with NCV was evaluated during a randomized, double-blind field trial in Bangladesh. Children aged 2-15 years and women aged greater than 15 years (62,285 in number) received three doses of BS-WC vaccine, WC-only vaccine, or a placebo consisting of Escherichia coli K12 strain (K12). During 1 year of follow-up, the incidence of treated episodes of diarrhoea associated with non-cholera vibrios known to be enteric pathogens (non-01 Vibrio cholerae, V. fluvialis, V. parahaemolyticus, V. mimicus) in the placebo group was low (1.9 cases per 10,000 recipients) and identical to that for the two vaccine groups combined. The incidence (per 10,000 recipients) of treated diarrhoeal episodes associated with Aeromonas species was considerably higher, but nearly identical in the three groups (26.1 cases for BS-WC, 26.0 cases for WC; 25.9 cases for K12). Pleisiomonas shigelloides was not isolated from any participant. It is concluded that NCV other than Aeromonas were rarely isolated from diarrhoeal patients in our study population and that killed oral vaccines which were effective against cholera exhibited no detectable cross-protection against diarrhoea associated with NCV organisms.

Administration, Oral↗

Exclusion of clinically atypical or microbiologically mixed diarrhoeal episodes from outcome events in a field trial of oral cholera vaccines.

We investigated whether alternative clinical and microbiological criteria for outcome events affected estimates of vaccine efficacy in a randomized, double-blind field trial of B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) oral cholera vaccines among 62,285 rural Bangladeshi participants. At one year of follow-up estimates of vaccine protective efficacy (PE = 60%, P less than 0.0001 for BS-WC; PE = 54%, P less than 0.0001 for WC) against all treated diarrhoeal episodes associated with V. cholerae 01 were similar to estimates of efficacy against only those episodes which were clinically typical and unassociated with additional enteric pathogens (PE = 62%, P less than 0.0001 for BS-WC; PE = 52%, P less than 0.0001 for WC). In contrast, estimates of vaccine cross-protection against episodes associated with each of several agents antigenically related to V. cholerae 01 (LT-ETEC, non-cholera Vibrio sp, Aeromonas sp) were substantially reduced when mixed infections with V. cholerae 01 were excluded. We conclude that restrictive criteria intended to improve the specificity of the definition of cholera did not increase the detectability of vaccine efficacy against V. cholerae 01, but that exclusion of mixed infections with V. cholerae 01 was necessary to avoid false-positive conclusions about vaccine cross-protection against other potential target pathogens.

Administration, Oral↗

The use of phage-sensitivity patterns for tracing heat labile toxin-positive (LT+) Escherichia coli.

The heat-labile toxin (LT) positive Escherichia coli colonies from 785 stool specimens obtained during a cholera vaccine trial were examined for their phage-sensitivity pattern to 31 E. coli phages. These specimens originated from 105 index cases and their contacts. Isolates with common phage-sensitivity patterns were grouped and were studied further both serologically and for their plasmid profile. The largest group (42 isolates) belonged to serogroup O78 and the second largest group (19 isolates) belonged to serogroup O6. There were 23 index cases which had E. coli with the same phage-sensitivity pattern as some of their contact strains. The identity of isolates from 16 index cases with strains from their respective contacts could be verified serologically. For the remaining seven index cases and their contacts, the isolates did not agglutinate with available antisera. However, subsequent studies demonstrated that, when the phage-sensitivity pattern among the strains matched, the plasmid profiles of these strains also matched. This further indicates the ability of phage-sensitivity patterns to serve as markers in tracing strains.

Bacterial Toxins↗

Chronic diarrhoea: a methodologic basis for its apparent heterogeneity.

The etiologic and epidemiologic patterns of chronic diarrhoea vary extensively between studies. While undoubtedly some of this heterogeneity reflects the complexity of the disease entity, inconsistencies in methodology between studies may result in some of the variation. To illustrate this problem we examined 44 papers on chronic diarrhoea for comparability of the age range of subjects under study and for the use of standardized definitions of 'chronic' and 'diarrhoea'. There was wide variation in the age ranges examined, extending from two weeks to 91 years. No definition or description of 'diarrhoea' was provided in 13 (30%) studies while 'chronic' remained undefined or undescribed in 11 (25%) papers. Among the 14 (32%) studies providing a definition of 'diarrhoea', four different sets of criteria were used and among the 22 (50%) papers defining 'chronic', eight different definitions were employed.

Adolescent↗

Impact of B subunit killed whole-cell and killed whole-cell-only oral vaccines against cholera upon treated diarrhoeal illness and mortality in an area endemic for cholera.

The impact of B subunit killed whole-cell (BS-WC) and killed whole-cell-only (WC) oral cholera vaccines was assessed in a randomised double-blind trial in rural Bangladesh. 62,285 children aged 2-15 years and women aged over 15 ingested three doses of one of the vaccines or placebo. During the first year of follow-up there was a 26% reduction of all visits for treatment of diarrhoea in the BS-WC group and a 22% reduction in the WC group. The reduction of all admissions for fatal or severely dehydrating diarrhoea was 48% in the BS-WC group and 33% in the WC group. Overall mortality rates were 26% lower in the BS-WC group and 23% lower in the WC group during the first year, and reductions of mortality were observed only in women vaccinated at ages over 15 years. However, no differences in cumulative mortality were evident at the end of the second year of surveillance.

Administration, Oral↗

Discontinuation of breast-feeding during episodes of diarrhoea in rural Bangladeshi children.

Discontinuation of breast-feeding during an episode of childhood diarrhoea is widely regarded as a common, high-risk practice in the developing world. We studied cessation of breast-feeding in a rural Bangladeshi population under comprehensive surveillance for medically treated diarrhoeal episodes. Among 2129 episodes in children aged under 36 months and breast-fed before the onset of diarrhoea, there were only 33 (2%) in whom breast-feeding had stopped before presentation for care. Children in whom breast-feeding had stopped (cases) differed little from those in whom it had not (controls) in respect to exclusive vs partial breast-feeding, age, gender, or several maternal characteristics (maternal age, education, and recent maternal diarrhoeal illness). In contrast, cases were more likely to have presented with clinically severe illness or to have died within 30 d of presentation (odds ratio = 2.20, P less than 0.05). We conclude that discontinuation of breast-feeding during diarrhoea is an infrequent phenomenon in this population. However, the association of cessation of breast-feeding with severe clinical outcomes may be of considerable importance, particularly in countries where discontinuation of breast-feeding is more common.

Bangladesh↗

Educational intervention for altering water-sanitation behavior to reduce childhood diarrhea in urban Bangladesh: impact on nutritional status.

We evaluated whether an educational intervention that was effective in reducing childhood diarrhea also improved childhood nutritional status. Fifty-one communities of 38 families each were randomized to receive the intervention or no intervention. During 1 y of follow-up the rate of diarrhea (per 100 wk) in children less than 6 y in the intervention group was 5.89 episodes whereas that in the nonintervention group was 7.55 episodes (protective efficacy 22%; p less than 0.0001). During the same follow-up period children in both groups exhibited comparable patterns of weight gain; 1 y after the intervention the mean weight for age of children in both groups was 76% of the NCHS standard. No significant differences were observed in the proportion of each group that experienced a major deterioration or improvement of nutritional status. We conclude that an intervention that reduces rates of childhood diarrhea may not necessarily also improve nutritional status.

Bangladesh↗

The influence of gender on determinants of urban childhood mortality in Bangladesh.

To assess sociodemographic characteristics predicting childhood mortality in urban Bangladesh, we conducted a case-control study of subjects selected from 51 low and middle class areas of urban Dhaka between 14 October 1984 and 13 October 1985. Cases were the 38 children who died aged under six years during the study interval; six surviving controls aged under six years were selected for each case. Factors associated with childhood deaths included being under one year of age (OR (odds ratio) = 11.80; p less than 0.0001), and several direct and indirect indicators of poor economic status: ie head of household earning a daily wage rather than a salary (OR = 2.63; p less than 0.01); residence in a single-room dwelling (OR = 2.63; p less than 0.05); or residence in a structure of inferior construction (OR = 2.58; p less than 0.05). There were important gender-specific differences in the risk factors. Having one or more male siblings was associated with an increased risk of death for male children (OR = 2.78; p less than 0.05), while having at least one female sibling was suggestively associated with the risk of death for female children (OR = 2.47; p less than 0.10). Family dependence on daily wages rather than on a salary was associated with male deaths (OR = 6.24; p less than 0.001) but not with female deaths (OR = 1.38). Other indices of poverty (poor construction of house and single-room dwellings) were also associated with an increased risk of male but not female deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Bangladesh↗

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

We assessed the protective efficacy (PE) of three doses of B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) oral cholera vaccines in a randomized, double-blind trial among 62,285 children and women residing in rural Bangladesh. After one complete year of surveillance, 110 cases of cholera were detected in the placebo group, 52 in the WC group (PE, 53%; P less than .0001), and 41 in the BS-WC group (PE, 62%; P less than .0001). Protection was greater for BS-WC recipients than for WC recipients only during the initial eight months of observation. Both vaccines conferred equivalent protection against cholera associated with life-threatening dehydration and against less severe cholera. High-grade, sustained protection was observed in persons vaccinated when older than five years; in younger persons protection was transient. We conclude that BS-WC and WC vaccines confer significant protection against cholera, particularly in persons vaccinated when older than five years.

Administration, Oral↗

Cross-protection by B subunit-whole cell cholera vaccine against diarrhea associated with heat-labile toxin-producing enterotoxigenic Escherichia coli: results of a large-scale field trial.

The B subunit (BS) of cholera toxin and that of the heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC) are antigenically similar. We therefore assessed whether a combined cholera toxin BS/whole-cell (BS-WC) oral vaccine against cholera conferred cross-protection against LT-producing ETEC (LT-ETEC) diarrhea in a randomized, double-blind field trial among rural Bangladeshi children and women. The 24,770 persons who ingested two or more doses of BS-WC vaccine were compared with 24,842 controls who took two or more doses of killed whole-cell (WC) oral cholera vaccine. Sixty-seven percent fewer episodes of LT-ETEC diarrhea were noted in the BS-WC group than in the WC group during short-term (three-month) follow-up (P less than .01), but no reduction was evident during the ensuing nine months. Short-term protection was particularly notable against LT-ETEC diarrhea causing life-threatening dehydration (protective efficacy, 86%; P less than .05).

Adolescent↗

Measles vaccination and childhood mortality in rural Bangladesh.

To ascertain whether measles vaccination was associated with reduced mortality rates in rural Bangladeshi children, the authors conducted a case-control study in four contiguous areas, two of which had participated in an intensive measles vaccination program which began in the spring of 1982. Cases were 536 children who had died in the four-area region at the age of 10-60 months between April 1982 and December 1984. Two age- and sex-matched controls were selected from the four-area region for each case; each control had survived at least through the date of death of the matched case. Measles vaccination was associated with a 36% (95% confidence interval 21%-48%) proportionate reduction in the overall rate of death and a 57% (95% confidence interval 43%-67%) reduction in the rate of deaths directly attributed to measles or ascribed to diarrhea, respiratory illness, or malnutrition. The association of measles vaccination and reduced mortality remained unchanged after the authors restricted controls to children who had survived at least one year after the deaths of their matched cases. Moreover, children vaccinated in 1982 exhibited a sustained reduction in the rate of death in 1983 and 1984. The authors concluded that measles vaccination was associated with a pronounced and sustained reduction in the rate of death among children in this study.

Bangladesh↗