Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled field trial

Sarah A. Frech, Herbert L. DuPont, Louis Bourgeois, Robin McKenzie, Jaime Belkind-Gerson, Jose F. Figueroa, Pablo C. Okhuysen, Norma H. Guerrero, Francisco G. Martinez-Sandoval, Juan HM Meléndez-Romero, Zhi Dong Jiang, Edwin J. Asturias, Jane Halpern, Olga R. Torres, Ana S. Hoffman, Christina P. Villar, Raniya N. Kassem, David C. Flyer, Bo H. Andersen, Kazem KazempourSally A. Breisch, Gregory M. Glenn

Research output: Contribution to journalArticle

Abstract

Background: Enterotoxigenic Escherichia coli (ETEC) is a major cause of travellers' diarrhoea. We investigated the rate of diarrhoea attacks, safety, and feasibility of a vaccine containing heat-labile enterotoxin (LT) from ETEC delivered to the skin by patch in travellers to Mexico and Guatemala. Methods: In this phase II study, healthy adults (aged 18-64 years) who planned to travel to Mexico or Guatemala and had access to a US regional vaccination centre were eligible. A centralised randomisation code was used for allocation, which was masked to participants and site staff. Primary endpoints were to investigate the field rate of ETEC diarrhoea, and to assess the safety of heat-labile toxins from E coli (LT) delivered via patch. Secondary endpoints included vaccine efficacy against travellers' diarrhoea and ETEC. Participants were vaccinated before travel, with two patches given 2-3 weeks apart. Patches contained either 37·5 μg of LT or placebo. Participants tracked stool output on diary cards in country and provided samples for pathogen identification if diarrhoea occurred. Diarrhoea was graded by the number of loose stools in 24 h: mild (three), moderate (four or five), and severe (at least six). Analysis was per protocol. The trial is registered with ClinicalTrials.gov, number NCT00516659. Findings: Recruitment closed after 201 participants were assigned patches. 178 individuals received two vaccinations and travelled and 170 were analysed. 24 (22%) of 111 placebo recipients had diarrhoea, of whom 11 (10%) had ETEC diarrhoea. The vaccine was safe and immunogenic. The 59 LT-patch recipients were protected against moderate-to-severe diarrhoea (protective efficacy [PE] 75%, p=0·0070) and severe diarrhoea (PE 84%, p=0·0332). LT-patch recipients who became ill had shorter episodes of diarrhoea (0·5 days vs 2·1 days, p=0·0006) with fewer loose stools (3·7 vs 10·5, p

Original languageEnglish (US)
Pages (from-to)2019-2025
Number of pages7
JournalThe Lancet
Volume371
Issue number9629
DOIs
StatePublished - 2008

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Diarrhea
Placebos
Enterotoxigenic Escherichia coli
Guatemala
Vaccines
Mexico
Vaccination
E coli heat-labile enterotoxin
Safety
Enterotoxins
Random Allocation
Hot Temperature
Skin

ASJC Scopus subject areas

  • Medicine(all)

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Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea : a phase II, randomised, double-blind, placebo-controlled field trial. / Frech, Sarah A.; DuPont, Herbert L.; Bourgeois, Louis; McKenzie, Robin; Belkind-Gerson, Jaime; Figueroa, Jose F.; Okhuysen, Pablo C.; Guerrero, Norma H.; Martinez-Sandoval, Francisco G.; Meléndez-Romero, Juan HM; Jiang, Zhi Dong; Asturias, Edwin J.; Halpern, Jane; Torres, Olga R.; Hoffman, Ana S.; Villar, Christina P.; Kassem, Raniya N.; Flyer, David C.; Andersen, Bo H.; Kazempour, Kazem; Breisch, Sally A.; Glenn, Gregory M.

In: The Lancet, Vol. 371, No. 9629, 2008, p. 2019-2025.

Research output: Contribution to journalArticle

Frech, SA, DuPont, HL, Bourgeois, L, McKenzie, R, Belkind-Gerson, J, Figueroa, JF, Okhuysen, PC, Guerrero, NH, Martinez-Sandoval, FG, Meléndez-Romero, JHM, Jiang, ZD, Asturias, EJ, Halpern, J, Torres, OR, Hoffman, AS, Villar, CP, Kassem, RN, Flyer, DC, Andersen, BH, Kazempour, K, Breisch, SA & Glenn, GM 2008, 'Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled field trial', The Lancet, vol. 371, no. 9629, pp. 2019-2025. https://doi.org/10.1016/S0140-6736(08)60839-9
Frech, Sarah A. ; DuPont, Herbert L. ; Bourgeois, Louis ; McKenzie, Robin ; Belkind-Gerson, Jaime ; Figueroa, Jose F. ; Okhuysen, Pablo C. ; Guerrero, Norma H. ; Martinez-Sandoval, Francisco G. ; Meléndez-Romero, Juan HM ; Jiang, Zhi Dong ; Asturias, Edwin J. ; Halpern, Jane ; Torres, Olga R. ; Hoffman, Ana S. ; Villar, Christina P. ; Kassem, Raniya N. ; Flyer, David C. ; Andersen, Bo H. ; Kazempour, Kazem ; Breisch, Sally A. ; Glenn, Gregory M. / Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea : a phase II, randomised, double-blind, placebo-controlled field trial. In: The Lancet. 2008 ; Vol. 371, No. 9629. pp. 2019-2025.
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abstract = "Background: Enterotoxigenic Escherichia coli (ETEC) is a major cause of travellers' diarrhoea. We investigated the rate of diarrhoea attacks, safety, and feasibility of a vaccine containing heat-labile enterotoxin (LT) from ETEC delivered to the skin by patch in travellers to Mexico and Guatemala. Methods: In this phase II study, healthy adults (aged 18-64 years) who planned to travel to Mexico or Guatemala and had access to a US regional vaccination centre were eligible. A centralised randomisation code was used for allocation, which was masked to participants and site staff. Primary endpoints were to investigate the field rate of ETEC diarrhoea, and to assess the safety of heat-labile toxins from E coli (LT) delivered via patch. Secondary endpoints included vaccine efficacy against travellers' diarrhoea and ETEC. Participants were vaccinated before travel, with two patches given 2-3 weeks apart. Patches contained either 37·5 μg of LT or placebo. Participants tracked stool output on diary cards in country and provided samples for pathogen identification if diarrhoea occurred. Diarrhoea was graded by the number of loose stools in 24 h: mild (three), moderate (four or five), and severe (at least six). Analysis was per protocol. The trial is registered with ClinicalTrials.gov, number NCT00516659. Findings: Recruitment closed after 201 participants were assigned patches. 178 individuals received two vaccinations and travelled and 170 were analysed. 24 (22{\%}) of 111 placebo recipients had diarrhoea, of whom 11 (10{\%}) had ETEC diarrhoea. The vaccine was safe and immunogenic. The 59 LT-patch recipients were protected against moderate-to-severe diarrhoea (protective efficacy [PE] 75{\%}, p=0·0070) and severe diarrhoea (PE 84{\%}, p=0·0332). LT-patch recipients who became ill had shorter episodes of diarrhoea (0·5 days vs 2·1 days, p=0·0006) with fewer loose stools (3·7 vs 10·5, p",
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T1 - Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea

T2 - a phase II, randomised, double-blind, placebo-controlled field trial

AU - Frech, Sarah A.

AU - DuPont, Herbert L.

AU - Bourgeois, Louis

AU - McKenzie, Robin

AU - Belkind-Gerson, Jaime

AU - Figueroa, Jose F.

AU - Okhuysen, Pablo C.

AU - Guerrero, Norma H.

AU - Martinez-Sandoval, Francisco G.

AU - Meléndez-Romero, Juan HM

AU - Jiang, Zhi Dong

AU - Asturias, Edwin J.

AU - Halpern, Jane

AU - Torres, Olga R.

AU - Hoffman, Ana S.

AU - Villar, Christina P.

AU - Kassem, Raniya N.

AU - Flyer, David C.

AU - Andersen, Bo H.

AU - Kazempour, Kazem

AU - Breisch, Sally A.

AU - Glenn, Gregory M.

PY - 2008

Y1 - 2008

N2 - Background: Enterotoxigenic Escherichia coli (ETEC) is a major cause of travellers' diarrhoea. We investigated the rate of diarrhoea attacks, safety, and feasibility of a vaccine containing heat-labile enterotoxin (LT) from ETEC delivered to the skin by patch in travellers to Mexico and Guatemala. Methods: In this phase II study, healthy adults (aged 18-64 years) who planned to travel to Mexico or Guatemala and had access to a US regional vaccination centre were eligible. A centralised randomisation code was used for allocation, which was masked to participants and site staff. Primary endpoints were to investigate the field rate of ETEC diarrhoea, and to assess the safety of heat-labile toxins from E coli (LT) delivered via patch. Secondary endpoints included vaccine efficacy against travellers' diarrhoea and ETEC. Participants were vaccinated before travel, with two patches given 2-3 weeks apart. Patches contained either 37·5 μg of LT or placebo. Participants tracked stool output on diary cards in country and provided samples for pathogen identification if diarrhoea occurred. Diarrhoea was graded by the number of loose stools in 24 h: mild (three), moderate (four or five), and severe (at least six). Analysis was per protocol. The trial is registered with ClinicalTrials.gov, number NCT00516659. Findings: Recruitment closed after 201 participants were assigned patches. 178 individuals received two vaccinations and travelled and 170 were analysed. 24 (22%) of 111 placebo recipients had diarrhoea, of whom 11 (10%) had ETEC diarrhoea. The vaccine was safe and immunogenic. The 59 LT-patch recipients were protected against moderate-to-severe diarrhoea (protective efficacy [PE] 75%, p=0·0070) and severe diarrhoea (PE 84%, p=0·0332). LT-patch recipients who became ill had shorter episodes of diarrhoea (0·5 days vs 2·1 days, p=0·0006) with fewer loose stools (3·7 vs 10·5, p

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