Invited commentary: dynamics of Helicobacter pylori infection in childhood.
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Adolescent↗
Biomedical subjects
D N Taylor
Publications and source records attributed to D N Taylor.
A placebo-controlled trial of Lactobacillus GG to prevent diarrhea in undernourished Peruvian children.
OBJECTIVE: Lactobacillus GG (L-GG), an acid- and bile-resistant strain that colonizes the intestinal mucosa, has been used to manage diarrhea in children. Our objective was to evaluate the prophylactic use of L-GG to prevent diarrhea in children at high risk from a developing country in a randomized, placebo-controlled trial. STUDY DESIGN: Two hundred four undernourished children 6 to 24 months old from an indigent peri-urban Peruvian town received either L-GG or placebo in flavored gelatin once daily, 6 days a week, for 15 months. Episodes of diarrhea were documented by daily home visits, and diagnostic studies were done in a subset of cases. Recovery of L-GG in stool from subjects and from family contacts was examined. RESULTS: Subjects in the L-GG group had significantly fewer episodes of diarrhea (5.21 episodes diarrhea/child/year ['ecy'] L-GG group, 6. 02 ecy placebo group; P =.028). The decreased incidence of diarrhea in the L-GG group was greatest in the 18- to 29-month age group (P =. 004) and was largely limited to nonbreastfed children (Breastfed: 6. 59 ecy L-GG, 6.32 ecy placebo, P =.7; Nonbreastfed: 4.69 ecy L-GG, 5. 86 ecy placebo, P =.005). The duration of diarrhea episodes and the causes of diarrhea were similar in both groups, except adenovirus was more common in the placebo group. CONCLUSION: L-GG supplementation may be useful as a prophylactic measure to control diarrhea in undernourished children at increased risk, especially nonbreastfed children in the toddler age group.
Breast Feeding↗
Enteropathogens and other factors associated with severe disease in children with acute watery diarrhea in Lima, Peru.
To evaluate enteropathogens and other factors associated with severe disease in children with diarrhea, 381 children <5 years of age with diarrhea and moderate to severe dehydration (in-patients) and 381 age-, sex-, and date-of-visit-matched children with mild diarrhea (out-patients) presenting to a hospital in Peru, were studied. Rotavirus was detected in 52% of the in-patients and 35% of the out-patients (odds ratio [OR]=2.3, 95% confidence interval [95% CI]= 1.6-3.2); 95% of the rotaviruses among in-patients were of serotypes G1-G4. The risk of severe diarrhea was particularly great in children who were not exclusively breast-fed in early infancy and who also lacked piped water in their homes (for children with both characteristics OR=6.8, 95% CI=3.6-12.8). The high prevalence of rotavirus and its association with severe diarrhea underscores the need for rotavirus vaccines. Interventions to educate mothers and improve access to safe water should augment the impact of rotavirus vaccines in preventing severe diarrhea.
Animals↗
Expanded safety and immunogenicity of a bivalent, oral, attenuated cholera vaccine, CVD 103-HgR plus CVD 111, in United States military personnel stationed in Panama.
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. A total of 170 partially-immune American soldiers stationed in Panama received one of the following five formulations: (a) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(7) CFU, (b) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(6) CFU, (c) CVD 103-HgR alone at 10(8) CFU, (d) CVD 111 alone at 10(7) CFU, or (e) inactivated Escherichia coli placebo. Among those who received CVD 111 at the high or low dose either alone or in combination with CVD 103-HgR, 8 of 103 had diarrhea, defined as three or more liquid stools. None of the 32 volunteers who received CVD 103-HgR alone or the 35 placebo recipients had diarrhea. CVD 111 was detected in the stools of 46% of the 103 volunteers who received it. About 65% of all persons who received CVD 103-HgR either alone or in combination had a fourfold rise in Inaba vibriocidal titers. The postvaccination geometric mean titers were comparable among groups, ranging from 450 to 550. Ogawa vibriocidal titers were about twice as high in persons who received CVD 111 as in those who received CVD 103-HgR alone (600 versus 300). The addition of CVD 111 improved the overall seroconversion rate and doubled the serum Ogawa vibriocidal titers, suggesting that the combination of an El Tor and a classical cholera strain is desirable. While CVD 111 was previously found to be well tolerated in semiimmune Peruvians, the adverse effects observed in this study indicate that this strain requires further attenuation before it can be safely used in nonimmune populations.
Cholera↗
Chronic diarrhea in the returned traveler.
The persistence of gastrointestinal symptoms after travel to a developing country is one of the most common and troublesome post-travel illnesses. Few data exist to document the extent of this problem, but anecdotal examples abound among travel medicine practitioners, internists, and gastroenterologists. This article presents an approach to the patient with persistent gastrointestinal symptoms after travel.
Bacterial Infections↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗