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D N Taylor

Publications and source records attributed to D N Taylor.

At least 37 records · Page 2Linked to original sources
PubMed1998

Diarrhea and Clostridium difficile infection in Latin American patients with AIDS. Working Group on AIDS in Peru.

Diarrhea and wasting are among the most debilitating and deadly manifestations of AIDS, yet only limited information is available regarding the etiology, clinical consequences, and immunologic effects of infection with diarrheal agents. Peruvian AIDS patients presenting with and without diarrhea were followed prospectively to examine the relations among diarrheal pathogens, clinical presentations, CD4 lymphocyte count, weight loss, and survival. Patients with chronic diarrhea had lower CD4 lymphocyte counts (P = .001) and lost more weight (P < .001). Weight loss and a decreased CD4 lymphocyte count were associated with increased mortality (P = .011 and P = .003, respectively). Mean CD4 lymphocyte count varied significantly by diarrheal agent. Clostridium difficile was the most prevalent pathogen and was associated with significantly increased mortality before and after adjustment for coinfection, length of follow-up, CD4 lymphocyte count, and weight loss (P = .006). C. difficile may be a more important and more prevalent etiologic agent in AIDS than previously recognized and may represent a preventable cause of death in patients with immunosuppression.

AIDS-Related Opportunistic Infections↗
PubMed1998

Phase 1 evaluation of Vibrio cholerae O1, serotype Inaba, polysaccharide-cholera toxin conjugates in adult volunteers.

Conjugate vaccines were prepared by binding hydrazine-treated lipopolysaccharide (DeALPS) from Vibrio cholerae O1, serotype Inaba, to cholera toxin (CT) variants CT-1 and CT-2. Volunteers (n = 75) were injected with either 25 microg of DeALPS, alone or as a conjugate, or the licensed cellular vaccine containing 4 x 10(9) organisms each of serotypes Inaba and Ogawa per ml. No serious adverse reactions were observed. DeALPS alone did not elicit serum LPS or vibriocidal antibodies in mice and only low levels of immunoglobulin M (IgM) anti-LPS in the volunteers. Recipients of the cellular vaccine had the highest IgM anti-LPS levels, but the difference was not statistically significant from that elicited by the conjugates. The conjugates elicited the highest levels of IgG anti-LPS (DeALPS-CT-2 > DeALPS-CT-1 > cellular vaccine). Both conjugates and the cellular vaccine elicited vibriocidal antibodies: after 8 months, recipients of cellular vaccine had the highest geometric mean titer (1,249), followed by DeALPS-CT-2 (588) and DeALPS-CT-1 (330). The correlation coefficient between IgG anti-LPS and 2-mercaptoethanol (2-ME)-resistant vibriocidal antibodies was 0. 81 (P = 0.0004). Convalescent sera from cholera patients had a mean vibriocidal titer of 2,525 that was removed by treatment with 2-ME. The vibriocidal activities of sera from all vaccine groups and from the patients were absorbed (>75%) by LPS but not by either CT-1 or CT-2. Conjugate-induced IgG vibriocidal antibodies persisted longer than those elicited by the whole-cell vaccine. Both conjugates, but not the cellular vaccine, elicited IgG anti-CT.

Adolescent↗
PubMed1998

Diarrheal disease incidence and morbidity among United States military personnel during short-term missions overseas.

Outpatient medical surveillance of U.S. troops was conducted during 11 different overseas missions between 1981 and 1990. In addition, at the end of each of 18 overseas missions during the same period, a sample of troops was queried regarding illnesses and exposures experienced in the preceding time overseas. Diarrhea was among the leading causes of morbidity during all of these short-term missions. Diarrhea incidence rates were found to be highest during summer months, and were higher during missions to Thailand (median = 25%, range = 20-29%), Latin America (median = 26%, range = 1-43%), and northeastern Africa and southwest Asia (median = 19%, range = < 1-52%). Rates were lowest in troops deployed to the Republic of South Korea (median = 16%, range = 8-27%). During April and May 1990, a focused surveillance and questionnaire study was conducted during a five-week, joint U.S.-Thai military training exercise in central Thailand. Among 2,600 U.S. personnel, diarrheal illness was found to be the most common medical problem for troops (estimated cumulative incidence = 29%). Travel outside of the base of operations and consumption of ice were found to be important risk factors. The 10-year database analyzed for this report is the largest, published summary showing the significant impact of diarrheal diseases on U.S. military forces during short-term deployments to less developed areas.

Africa, Northern↗
PubMed1997

Country-specific constancy by age in cagA+ proportion of Helicobacter pylori infections.

Helicobacter pylori strains may be either cagA+ or cagA-, and in logitudinal studies, infection with a cagA+ strain has been associated with increased risk for the development of atrophic gastritis and cancer of the distal stomach. We sought to determine the relative proportion of strains producing CagA in different geographic locales, and the extent to which CagA seroprevalence varied in countries with different gastric and esophageal cancer rates. Using an enzyme-linked immunosorbent assay (ELISA) to detect serum IgG to CagA, we examined sera from 468 asymptomatic H. pylori-infected adults from Canada, Peru, China, Thailand, The Netherlands and 3 different ethnic groups in New Zealand. The CagA seroprevalence in Peru and Thailand (82.2% and 78.8%, respectively) were each substantially higher than for the Chinese (37.9%), Canadian (41.9%), Dutch (39.0%) and New Zealand (28.2%) subjects, but within each population, rates were relatively constant across gender and age groups. Reported gastric but not esophageal cancer rates for the 8 studied populations were significantly associated with H. pylori seroprevalence. Variation in CagA positivity rates was not significantly associated with variation in either gastric or esophageal cancer rates. Our data suggest that CagA seroprevalence is not the major factor influencing gastric cancer rates.

Adult↗
PubMed1997

Cholera.

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Cholera↗
PubMed1997

Double-blind vaccine-controlled randomised efficacy trial of an investigational Shigella sonnei conjugate vaccine in young adults.

BACKGROUND: The aim of this double-blind randomised vaccine-controlled trial was to assess the efficacy of a conjugate vaccine composed of Shigella sonnei O-specific polysaccharide bound to Pseudomonas aeruginosa recombinant exoprotein A (S sonnei-rEPA) and of an oral, live-attenuated Escherichia coli/S flexneri 2a (EcSf2a-2) hybrid vaccine among military recruits in Israel at high risk of exposure to Shigella spp. We report here our preliminary findings on the efficacy of S sonnei-rEPA; we have not documented sufficient cases to assess the efficacy of EcSf2a-2. METHODS: Between April, 1993, and August, 1994, male Israeli Military recruits aged 18-22 years were asked to take part in our study. We enrolled 1446 soldiers from seven separate field sites (groups A-G). Soldiers were randomly allocated one injection of S sonnei-rEPA and four doses of oral placebo (n = 576), four oral doses of EcSf2a-2 and one injection of saline placebo (n = 580), or one injection of meningococcal tetravalent control vaccine and four doses of oral placebo (n = 290). Because there were no cases of S flexneri 2a, the EcSf2a-2 and meningococcal vaccines were the control group. We defined S sonnei shigellosis as diarrhoea with a positive faecal culture for S sonnei. Each group of soldiers was followed up for 2.5-7.0 months. The primary endpoint was protective efficacy of S sonnei-rEPA against S sonnei shigellosis. FINDINGS: Cases of culture-proven S sonnei shigellosis occurred in four groups of soldiers (groups A-D), which comprised 787 volunteers (312 received S sonnei-rEPA, 316 received EcSf2a-2, and 159 received meningococcal control vaccine). In groups A-C, cases of shigellosis occurred 70-155 days after vaccination, whereas in group D cases occurred after 1-17 days. In groups A-C, the attack rate of shigellosis was 2.2% in recipients of S sonnei-rEPA compared with 8.6% in controls (protective efficacy 74% [95% CI 28-100], p = 0.006). S sonnei-rEPA also showed significant protection against shigellosis in group D (43% [4-82], p = 0.039). Prevaccination and postvaccination ELISA measurements of antibody to S sonnei lipopolysaccharide among recipients of S sonnei-rEPA showed that the vaccinees who developed S sonnei shigellosis had significantly lower serum IgG and IgA responses to the homologous lipopolysaccharide than those who did not (p = < 0.05). INTERPRETATION: One injection of S sonnei-rEPA confers type-specific protection against S sonnei shigellosis. The high antibody concentration induced by the conjugate vaccine in volunteers who did not develop shigellosis suggests that there is an association between serum antibody titre and protection.

Adolescent↗
PubMed1997

Vibrio furnissii isolated from humans in Peru: a possible human pathogen?

During a cholera surveillance programme, Vibrio furnissii was isolated in late January and early February 1994 from stool samples collected from 14 persons of whom six had diarrhoea. The remaining eight persons were healthy family members or neighbours to cholera cases. No common source of infection was found. Strains isolated from stool samples each showed typical biochemical reactions of V. furnissii including gas production. Each isolate, except one, agglutinated O-antisera yielding a total of eight different serotypes. Most isolates were sensitive to 10 antibiotics tested, except to ampicillin and the vibriostatic agent O/129 (10 micrograms). Eight of 14 (57%) strains carried plasmids in the size range 2.6-88 kb, however, no correlation was found between antibiotic susceptibility patterns and plasmid content. Altogether, seven closely related HindIII ribotypes were observed among the 14 V. furnissii isolates studied. V. furnissii strains isolated from family members and other persons living close together often showed different ribotypes suggesting that the isolation was not associated with neighbourhood. Serotyping, plasmid profiling and ribotyping revealed a high strain diversity within V. furnissii, however, the importance of V. furnissii as an enteric pathogen remains to be elucidated.

Adolescent↗
PubMed1997

Helicobacter pylori infection in Desert Storm troops.

To determine whether military personnel deployed outside the United States are at increased risk of Helicobacter pylori infection, we evaluated U.S. Army personnel who served in the Persian Gulf from August 1990 to April 1991. Of 204 subjects from whom paired predeployment and postdeployment serum specimens were obtained, 76 (37%) were seropositive for IgG antibody to H. pylori before deployment by an enzyme-linked immunosorbent assay. Of the 111 initially seronegative subjects evaluated before and after a 7.5-month deployment, five (4.5%) seroconverted. The calculated annual seroconversion rate was 7.3%. In a postdeployment questionnaire, 62% of soldiers reported an episode of diarrhea while deployed, but there was not an increased rate of diarrhea or upper gastrointestinal symptoms in soldiers who were infected before deployment or in those who seroconverted. These data suggest that the risk of H. pylori infection increases during long-term deployment and that acute infection is not distinguishable from other gastrointestinal illnesses encountered during deployment.

Adult↗
PubMed1997

Evaluation of a bivalent (CVD 103-HgR/CVD 111) live oral cholera vaccine in adult volunteers from the United States and Peru.

To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1, a single-dose, oral cholera vaccine was developed by combining two live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber contained lyophilized bacteria, and the other contained buffer. In the first study, 23 U.S. adult volunteers received CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(8), 10(7), or 10(6) CFU, CVD 111 alone at 10(7) CFU, or placebo. In the second study, 275 Peruvian adults were randomized to receive CVD 103-HgR at 10(9) CFU plus CVD 111 at 10(9) or 10(8) CFU, CVD 111 alone at 10(9) CFU, CVD 103-HgR alone at 10(9) CFU, or placebo. Three of 15 U.S. volunteers who received CVD 111 at 10(7) or 10(8) CFU developed mild diarrhea, compared to none of 4 who received CVD 111 at 10(6) CFU and 1 of 4 who received placebo. Twelve (63%) of 19 vaccine recipients shed the El Tor vaccine strain. All but one volunteer developed significant Ogawa and Inaba vibriocidal antibody titers. Volunteers who received CVD 111 at 10(7) CFU had geometric mean Ogawa titers four to five times higher than those of volunteers who received the lower dose. In the second study, all dosage regimens were well tolerated in Peruvians. About 20% of volunteers who received CVD 111 at the high dose excreted the El Tor organism, compared to 7% in the low-dose group. CVD 111 was detected in the stools of two placebo recipients, neither of whom had symptoms or seroconverted. In all vaccine groups, 69 to 76% developed fourfold rises in Inaba vibriocidal antibodies. Among those who received the bivalent vaccine, 53 to 75% also developed significant rises in Ogawa vibriocidal antibodies. We conclude that it is feasible to produce a single-dose, oral bivalent vaccine that is safe and immunogenic against both biotypes (El Tor and classical) and both serotypes (Inaba and Ogawa) of cholera for populations in both developed and developing parts of the world.

Administration, Oral↗
PubMed1997

Distribution of colonization factor antigens among enterotoxigenic Escherichia coli strains isolated from patients with diarrhea in Nepal, Indonesia, Peru, and Thailand.

Samples (1,318) of enterotoxigenic Escherichia coli (ETEC) isolated in 1994-1995 from children with diarrhea from Nepal, Indonesia, Peru, and Thailand were examined for colonization factor antigen (CFA) and coli surface (CS) antigens. Fifty-five percent of 361 heat-labile and heat-stable (LT-ST), 14% of 620 LT-only, and 48% of 337 ST-only ETEC had CFA/CS antigens. LT-ST ETEC strains were predominantly in the CFA II group, and ST only strains were in the CFA IV group. Additional studies are needed to identify ETEC strains that do not have CFA/CS antigens.

Adult↗
PubMed1997

Molecular evolution of Vibrio cholerae O1 strains isolated in Lima, Peru, from 1991 to 1995.

Following the emergence of cholera in Lima, Peru, in 1991, isolates of Vibrio cholerae O1 biotype El Tor recovered from patients in various parts of Lima were selected and characterized. Ribotyping and pulsed-field gel electrophoresis (PFGE) revealed four BglI ribotypes and eight NotI PFGE types among 50 V. cholerae O1 strains recovered from patients with cholera in Lima from 1991 to 1995, with certain genotypes appearing to cluster geographically. While differences in ribotype and PFGE type patterns suggest that genetic changes are occurring in the strain responsible for the Latin American cholera epidemic, more frequently than previously reported, 40 (80%) O1 strains showed an identical ribotype pattern and 41 (82%) strains showed closely related PFGE types, types 1, 2, or 3, that differed by less than three restriction fragments. All strains were susceptible to nine antibacterial agents studied. In 1991, more than 95% of the clinical V. cholerae O1 strains were serotype Inaba, whereas from 1992, serotype Ogawa began to predominate, with more than 90% of the isolates being of the Ogawa serotype in 1995. The small differences in genotypes of V. cholerae O1 is remarkable because cholera is highly seasonal in coastal areas of Peru and support the hypothesis that the epidemic strain reemerges from an environmental source. However, the relative high rate of genetic changes within V. cholerae O1 as shown by ribotyping and PFGE should be taken into consideration when typing patterns of V. cholerae O1 associated with cholera in Latin America are evaluated.

Evolution, Molecular↗
PubMed1997

Nitric oxide production during Vibrio cholerae infection.

Vibrio cholerae induces massive intestinal fluid secretion that continues for the life of the stimulated epithelial cells. Enhanced regional blood flow and peristalsis are required to adapt to this obligatory intestinal secretory challenge. Nitric oxide (NO) is a multifunctional molecule that modulates blood flow and peristalsis and possesses both cytotoxic and antibacterial activity. We demonstrate that, compared with those in asymptomatic control subjects, levels of stable NO metabolites (NO2-/NO3-) are significantly increased in sera from acutely ill Peruvian patients with natural cholera infection as well as from symptomatic volunteers from the United States infected experimentally with V. cholerae. In a rabbit ileal loop model in vivo, cholera toxin (CT) elicited fluid secretion and dose-dependent increases in levels of NO2-/NO3- in the fluid (P < 0.01). In contrast, lipopolysaccharide (LPS) elicited no such effects when applied to the intact mucosa. NO synthase (NOS) catalytic activity also increased in toxin-exposed tissues (P < 0.05), predominantly in epithelial cells. The CT-induced NOS activity was Ca2+ dependent and was not suppressed by dexamethasone. In conclusion, symptomatic V. cholerae infection induces NO production in humans. In the related animal model, CT, but not LPS, stimulated significant production of NO in association with increases in local Ca(2+)-dependent NOS activity in the tissues.

Adult↗
PubMed1996

Cross-reactivity of Shigella flexneri serotype 2a O antigen antibodies following immunization or infection.

To study the cross-reactivity pattern of Shigella flexneri 2a O-antigen antibodies, sera from humans and monkeys challenged with S. flexneri 2a, and from humans and guinea pigs immunized with a recombinant vaccine expressing serotype 2a O-antigen, were tested against a panel of lipopolysaccharide extracted from heterologous S. flexneri. Sera from the two groups of humans, who were volunteers in either a clinical challenge or vaccination study, showed similar patterns: cross-reactivity was more often seen with IgA antibodies, and these were mostly cross-reactive with serotype 2b, which shares the type II antigen, and serotypes 1a, 5a, and Y, which share 4 or 3, 4 group antigen, with 2a. The majority of sera from immunized guinea pigs showed both IgG and IgA cross-reactivity with 1a, 5a, and Y, but not 2b. The majority of sera from challenged monkeys showed cross-reactivity with almost all flexneri serotypes tested, with 1a, 2b, and Y being recognized most often, and the cross-reactive antibodies were more often IgG than IgA. These results show that either immunization or challenge with the 2a serotype induces cross-reactive antibodies which recognize similar subsets of heterologous serotypes, and suggest that it may be possible to design multivalent vaccines against S. flexneri.

Adult↗
PubMed1996

Safety and immunogenicity of investigational Shigella conjugate vaccines in Israeli volunteers.

The safety and immunogenicity of investigational conjugates, composed of the O-specific polysaccharides of Shigella sonnei and Shigella flexneri type 2a covalently bound to Pseudomonas aeruginosa recombinant exoprotein A (rEPA), were evaluated in 192 Israeli soldiers. None had significant local reactions or fever. Fourteen days after injection, 90% of S. sonnei-rEPA recipients and 73 to 77% of S. flexneri-rEPA recipients had a fourfold or greater increase in serum immunoglobulin G (IgG) and IgA anti-lipopolysaccharide (anti-LPS) levels; at 2 years, these remained higher than at prevaccination (P < 0.01). There was a fourfold or greater increase in IgM anti-LPS in 20% of vaccinees at 2 weeks, but levels returned to prevaccination values at 6 to 12 months. IgG was the highest and most sustained class of LPS antibodies. Reinjection at day 42 did not boost antibody levels. Eighteen of 23 (78%) who received S. sonnei-rEPA and 13 of 19 (68%) who received S. flexneri-rEPA. had significant IgA-secreting cell responses. Significant IgG antibody-secreting cell responses were detected in 19 of 23 (83%) and 11 of 19 (58%) volunteers following vaccination with S. sonnei-rEPA and S. flexneri 2a-rEPA, respectively. On the basis of these data, further evaluation of the Shigella conjugates for protective efficacy in field trials in Israel was started.

Adolescent↗
PubMed1995

Safety, immunogenicity, and efficacy of live attenuated Vibrio cholerae O139 vaccine prototype.

New vaccines are needed to prevent cholera caused by Vibrio cholerae O139. Attenuated V cholerae O139 vaccines were made by deleting multiple copies of the cholera-toxin genetic element from two virulent strains of the organism, MO10 and AI4456. The deletion mutants were further modified by insertion of a construct that encoded the B subunit of cholera toxin, thus generating strains Bengal-3 and VRI-16. A stable spontaneous non-motile derivative of Bengal-3 was isolated and designated Bengal-15; VRI-16 is naturally non-motile. Bengal-3, Bengal-15, and VRI-16 were evaluated as oral single-dose cholera vaccine candidates in 4 volunteers each, and MO10 was given to 3 volunteers. 1 of 4 volunteers who received Bengal-3 and all 3 who received MO10 had diarrhoea. VRI-16 caused no significant symptoms but was not immunogenic. Bengal-15 produced few symptoms and was nearly as immunogenic as MO10. Subsequently, Bengal-15 was given to 10 volunteers at a dose of 10(8) colony-forming units. No volunteers had diarrhoea, and other subjective symptoms were as common in vaccinees as in 3 buffer recipients. 1 month after vaccination, 7 vaccinees, the 3 buffer recipients, and 3 unimmunised subjects were challenged with 5 x 10(6) colony-forming units of V cholerae O139. 5 of 6 controls had cholera-like diarrhoea. By contrast, 1 of 7 vaccinees had diarrhoea, which was mild and had a long incubation period. Vaccine protective efficacy was 83%. Our results indicate the Bengal-15 is a safe live attenuated vaccine candidate for cholera caused by the O139 serogroup.

Administration, Oral↗
PubMed1995

Evaluation of the safety, immunogenicity, and efficacy in healthy adults of four doses of live oral hybrid Escherichia coli-Shigella flexneri 2a vaccine strain EcSf2a-2.

In previous trials, live invasive Escherichia coli-Shigella flexneri 2a hybrid vaccine candidate EcSf2a-2, administered to adult volunteers as 3 doses of ca. 2 x 10(9) colony forming units (c.f.u.) spaced over one week, induced fever and/or diarrhea in 11% of subjects and provided only limited protection (36% efficacy) against illness following challenge with virulent S. flexneri 2a. We sought to improve the clinical safety of this vaccine by administering a lower inoculum, and to enhance protective immunity by administering additional booster doses at 2 weeks. Twenty-one healthy adults were immunized with ca. 7 x 10(8) c.f.u. of EcSf2a-2 on days 0, 3, 14, and 17. The vaccine consistently colonized the intestine without causing serious adverse reactions; mild diarrhea developed in one subject and low grade fever in another. Vaccination elicited an antibody secreting cell (ASC) response to lipopolysaccharide (LPS) in all subjects, which was highest on day 7 and notably diminished thereafter on days 10, 16, 21, and 24, suggesting that active mucosal immunity developed rapidly. The magnitude of the response was modest (geometric mean peak = 16 IgA ASC/10(6) peripheral blood mononuclear cells) and an IgG serological response to LPS was detected in only 19% of subjects. Following experimental challenge with virulent S. flexneri 2a administered with bicarbonate buffer, shigellosis (diarrhea, dysentery, or fever) developed in 10 of 16 vaccine recipients (63%) and in 12 of 14 unvaccinated controls (86%), resulting in a vaccine efficacy of 27% (95% confidence limits -197, 82, p = 0.15, 1-tailed).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗