Efficacy of an Oral, Killed Enterotoxigenic Escherichia Coli Vaccine in Prevention of Diarrhea in Egyptian Infants and Young Children

U.S. Army Medical Research and Development Command356 enrolled

Overview

This is a randomized, double-blind, placebo-controlled clinical trial performed in Egyptian children 6-18 months of age. The primary aim of the study is to determine the protective efficacy of an oral, inactivated whole-cell enterotoxigenic Escherichia coli (ETEC) vaccine against diarrhea associated with excretion of ETEC that express a vaccine-shared antigen over a one year period of follow-up by active surveillance. The vaccine consists of a mixture of five formalin-killed ETEC bacteria expressing prevalent ETEC colonization factors and recombinant cholera toxin B-subunit (killed ETEC/rCTB vaccine). The placebo preparation is heat-killed Escherichia coli K-12 bacteria.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

356

Conditions

Diarrhea

Interventions

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 18 MonthsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Willingness of parent to have the child participate; 2. Plans to reside in catchment area continuously for at least one year Exclusion Criteria: 1. Global developmental delay 2. Severe malnutrition 3. Chronic bedridden status 4. Serious chronic disorder requiring chronic medication

Outcomes

Primary Outcomes

Time to first event of diarrhea due to vaccine-preventable ETEC (VP-ETEC) as defined below, and no other copathogen.

Time to first event of diarrhea associated with excretion of VP-ETEC (defined as ETEC expressing heat-labile \[LT\] and heat-stable enterotoxin \[ST\], or ST and a vaccine-shared colonization factor \[i.e., CFA/I, CS1, CS2, CS3, CS4, and/or CS5\]) and no other copathogen.

Time frame: 365-day period starting 14 days after the third vaccination

Secondary Outcomes

Time to first event of diarrhea due to ST-only ETEC expressing a vaccine-shared CF (ST-VCF-ETEC) as defined below, and no other copathogen..

Time to first event of diarrhea associated with excretion of ST-VCF-ETEC (defined as ETEC expressing ST-only plus any vaccine-shared colonization factor \[i.e., CFA/I, CS1, CS2, CS3, CS4, and/or CS5\]) and no other copathogen.

Time frame: 365-day period starting 14 days after the third vaccination

All events of diarrhea irrespective of etiology

All events (i.e., initial plus recurrent) of diarrhea associated with excretion of any ETEC, irrespective of phenotype, and no other copathogen.

Time frame: 365-day period starting 14 days after the third vaccination

IgG seroconversion

IgG seroconversion (≥ twofold increase in post-vaccination endpoint titer over baseline) against rCTB and vaccine-specific colonization factors CFA/I, CS2, CS4

Time frame: Baseline serum specimen is collected before first dose and post-vaccination specimen collected 14 days after third dose

IgA seroconversion

IgA seroconversion (≥ twofold increase in post-vaccination endpoint titer over baseline) against rCTB and selected vaccine-specific colonization factors CFA/I, CS2, CS4

Time frame: Baseline serum specimen is collected before first dose and post-vaccination specimen collected 14 days after third dose

Number of solicited adverse events

(i.e., diarrhea, vomiting, fever by caregiver report, poor feeding, and irritability)

Time frame: 3-day period after each dose