Table 1.
Clinical endpoints in TD-vaccine field studies
| Publication | Vaccine candidate | Study population (n) | Primary endpoint definition | Vaccine efficacy (VE) |
|---|---|---|---|---|
| Scerpella et al., 199529 | Killed whole-cell Vibrio cholerae O1 with a recombinant B-subunit of cholera toxin (WC/rBS) | Student travellers to Mexico (n = 502) | ≥4 loose stools in 24 h (or 3 in 8 h) plus an additional symptom | VE against ETEC = 50% (95% CI, 14–71%) beginning 7 days after the second dose. However, no efficacy was demonstrated within 7 days of the second vaccination when 74% of ETEC cases occurred |
| Wiedermann et al., 200030 | Inactivated whole-cell ETEC and cholera vaccines plus recombinant B-subunit of cholera toxin (rCTB) | Austrian travellers to tropical or subtropical destinations (44 different countries in Africa, Asia, Latin-America) (n = 250) | ≥3 liquid stools and ETEC-only pathogen detected in stool | ETEC vaccine VE = 79% (P = 0.119) Cholera vaccine VE = 82% (P = 0.0496) |
| Leyten et al., 200531 | Live-attenuated oral cholera vaccine strain CVD 103-HgR | Travellers to Indonesia, India, Thailand and West Africa (n = 134) | ≥3 loose stools in 24 h, or 2 loose stools plus additional symptoms | Study terminated early as the primary endpoint ≥50% VE not achieved at point of interim analysis |
| Sack et al., 200732 | Inactivated whole-cell ETEC vaccine plus recombinant B-subunit of cholera toxin (rCTB) | Travellers to Mexico and Guatemala (n = 672) | Primary vaccine preventable outcome (VPO): ≥3 loose stools in 24 h plus ≥1 gastrointestinal symptom caused by homologous ETEC vaccine strain | VE = 24% (n.s.) |
| Bourgeois et al., 200733 | Inactivated whole-cell ETEC vaccine plus recombinant B-subunit of cholera toxin (rCTB) | Travellers to Mexico and Guatemala (n = 1406) | VPO-ETEC TD: ≥5 unformed or liquid stools in 24 h plus ≥1 gastrointestinal symptom and homologous ETEC vaccine strain isolated within 24 h of episode | VE = −59 (95% CI, −384, 48) |
| Frech et al, 200847 | Heat-labile toxin LT-patch | Travellers to Mexico and Guatemala (n = 170) | Mild TD: 3 loose stools in 24 h Moderate TD: 4–5 loose stools in 24 h and ETEC LT, LT/ST or ST positive Severe TD: ≥6 loose stools in 24 h and ETEC LT, LT/ST or ST positive |
VE against moderate-to-severe TD = 75% (P = 0.007) VE against severe TD = 84% (P = 0.0332) |
| Steffen et al., 201334 | Heat-labile toxin LT-patch | Travellers to India (n = 723) | Mild TD: 3 loose stools in 24 h Moderate TD: 4–5 loose stools in 24 h and ETEC LT, LT/ST or ST positive Severe TD: ≥6 loose stools in 24 h and ETEC LT, LT/ST or ST positive |
VE near zero (P = 1.000) |
| Behrens et al., 201435 | Heat-labile toxin LT-patch | Travellers to Mexico and Guatemala (n = 1644) | VE against moderate-to-severe TD = 34.6% (95% CI, −2.2, 58.9) |