Efficacy of a travelers' diarrhea vaccine system in travelers to India

TY - JOUR

T1 - Efficacy of a travelers' diarrhea vaccine system in travelers to India

AU - Steffen, Robert

AU - Cramer, Jakob P

AU - Burchard, Gerd

AU - Jelinek, Tomas

AU - Schwarz, Ute

AU - Ramdas, Prabhugaunker

AU - Chatterjee, Santanu

AU - Jiang, Zhi-Dong

AU - DuPont, Herbert L

AU - Dewasthaly, Shailesh

AU - Westritschnig, Kerstin

AU - Behrens, Ronald H

N1 - © 2013 International Society of Travel Medicine.

PY - 2013

Y1 - 2013

N2 - BACKGROUND: A patch vaccine containing heat-labile toxin (LT) from enterotoxigenic Escherichia coli (ETEC) has demonstrated to be beneficial in reducing the rate and severity of travelers' diarrhea in Latin America. To evaluate the efficacy of this transdermal vaccine system in an area with a different diarrheal pathogen profile, an additional phase 2 study was conducted in European travelers to India.METHODS: For this multicenter, randomized, double-blinded, placebo-controlled field study 723 subjects were recruited; 603 (299 LT vaccine, 304 placebo) were included in the per-protocol-population (PPP).RESULTS: Although the LT patch induced a measurable LT immune response in recipients, it failed to protect against LT ETEC or all-cause diarrhea. In the PPP the incidence rate of diarrhea as per primary endpoint was 6.0% (18 of 299) in the vaccine group and 5.9% (18 of 304) in the placebo group. Additionally, lower than expected rates of LT ETEC diarrheas were observed in India. The vaccine delivery system frequently produced rash and pruritus at the site of application, long term hyperpigmentation persisted in a minority of LT recipients, and also few site reactions were noted in the placebo group.CONCLUSIONS: The evaluated patch vaccine failed to satisfy mainly with respect to protective efficacy. Noninvasive prophylactic agents against travelers' diarrhea, particularly vaccines against the most frequent pathogens, thus continue to be badly needed.

AB - BACKGROUND: A patch vaccine containing heat-labile toxin (LT) from enterotoxigenic Escherichia coli (ETEC) has demonstrated to be beneficial in reducing the rate and severity of travelers' diarrhea in Latin America. To evaluate the efficacy of this transdermal vaccine system in an area with a different diarrheal pathogen profile, an additional phase 2 study was conducted in European travelers to India.METHODS: For this multicenter, randomized, double-blinded, placebo-controlled field study 723 subjects were recruited; 603 (299 LT vaccine, 304 placebo) were included in the per-protocol-population (PPP).RESULTS: Although the LT patch induced a measurable LT immune response in recipients, it failed to protect against LT ETEC or all-cause diarrhea. In the PPP the incidence rate of diarrhea as per primary endpoint was 6.0% (18 of 299) in the vaccine group and 5.9% (18 of 304) in the placebo group. Additionally, lower than expected rates of LT ETEC diarrheas were observed in India. The vaccine delivery system frequently produced rash and pruritus at the site of application, long term hyperpigmentation persisted in a minority of LT recipients, and also few site reactions were noted in the placebo group.CONCLUSIONS: The evaluated patch vaccine failed to satisfy mainly with respect to protective efficacy. Noninvasive prophylactic agents against travelers' diarrhea, particularly vaccines against the most frequent pathogens, thus continue to be badly needed.

KW - Administration, Cutaneous

KW - Adolescent

KW - Adult

KW - Bacterial Vaccines

KW - Diarrhea

KW - Double-Blind Method

KW - Escherichia coli

KW - Escherichia coli Infections

KW - Female

KW - Germany

KW - Great Britain

KW - Humans

KW - Incidence

KW - India

KW - Male

KW - Middle Aged

KW - Travel

KW - Treatment Outcome

KW - Young Adult

U2 - 10.1111/jtm.12064

DO - 10.1111/jtm.12064

M3 - SCORING: Journal article

C2 - 24165382

VL - 20

SP - 374

EP - 379

JO - J TRAVEL MED

JF - J TRAVEL MED

SN - 1195-1982

IS - 6

ER -