TY - JOUR
T1 - Secondary efficacy endpoints of the pentavalent rotavirus vaccine against gastroenteritis in sub-Saharan Africa
AU - Tapia, Milagritos D.
AU - Armah, George
AU - Breiman, Robert F.
AU - Dallas, Michael J.
AU - Lewis, Kristen D.C.
AU - Sow, Samba O.
AU - Rivers, Stephen B.
AU - Levine, Myron M.
AU - Laserson, Kayla F.
AU - Feikin, Daniel R.
AU - Victor, John C.
AU - Ciarlet, Max
AU - Neuzil, Kathleen M.
AU - Steele, A. Duncan
N1 - Funding Information:
This research study was funded by PATH's Rotavirus Vaccine Programme under a grant from the GAVI Alliance, and was co-sponsored by Merck . The study was designed by scientists from Merck & Co., Inc., with substantial input from PATH staff and site investigators. PATH staff independently monitored study execution at sites and participated in pharmacovigilance and data analyses. We also acknowledge the sincere effort of all our study staffs and the support of the community members throughout the study area without which this study would never have been materialized. Conflict of Interest Statement : SOS received Merck funding as a member of the Advisory Board for Pediatric Vaccines and Vaccine New Products; MC was an employee of Merck when the clinical trial was conducted and owned equity in the company. MML is a paid advisory board member for NIH Vaccine Center, Center for Clinical Vaccinology and Tropical Medicine at Oxford University, AlphaVax, International Vaccine Institute, Centre de Recerca en Salut Internacional de Barcelona, AfriChol, and the Pasteur Institute STOPENTERICS program, and has received consultancies from Novartis and Merck. No other conflicts of interest are declared.
PY - 2012/4/27
Y1 - 2012/4/27
N2 - The efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq®, was evaluated in a double-blind, placebo-controlled, multicenter Phase III clinical trial conducted (April 2007-March 2009) in 3 low-income countries in Africa: Ghana, Kenya, and Mali. In total, 5468 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age; concomitant administration with routine EPI vaccines, including OPV, was allowed. HIV-infected infants were not excluded. The primary endpoint, vaccine efficacy (VE) against severe-rotavirus gastroenteritis (RVGE), as measured by Vesikari scoring system (VSS, score ≥11), from ≥14 days following Dose 3 through a follow-up period of nearly 2 years in the combined 3 African countries, and secondary endpoints by total follow-up period have been previously reported. In this study, we report post hoc subgroup analyses on secondary endpoints of public health importance. VE against RVGE of any severity was 49.2% (95%CI: 29.9, 63.5) through the first year of life and 30.5% (95%CI: 16.7, 42.2) through the complete follow-up period. VE against severe-gastroenteritis of any etiology was 21.5% (95%CI: <0, 38.4) through the first year of life and 10.6% (95%CI: <0, 24.9) through the complete follow-up period. Through the complete follow-up period, VE against severe-RVGE caused by (i) vaccine-contained G and P types (G1-G4, P1A[8]), (ii) non-vaccine G types (G8, G9, G10), and (iii) non-vaccine P types (P1B[4], P2A[6]) was 34.0% (95%CI:11.2, 51.2), 81.8% (95%CI:16.5, 98.0) and 40.7% (95%CI:8.4, 62.1), respectively. There was a trend towards higher VE with higher disease severity, although in some cases the numbers were small. In African countries with high under-5 mortality rates, PRV significantly reduced RVGE through nearly 2 years of follow-up; more modest reductions were observed against gastroenteritis of any etiology. PRV provides protection against severe-RVGE caused by diverse rotavirus genotypes, including those not contained in the vaccine.
AB - The efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq®, was evaluated in a double-blind, placebo-controlled, multicenter Phase III clinical trial conducted (April 2007-March 2009) in 3 low-income countries in Africa: Ghana, Kenya, and Mali. In total, 5468 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age; concomitant administration with routine EPI vaccines, including OPV, was allowed. HIV-infected infants were not excluded. The primary endpoint, vaccine efficacy (VE) against severe-rotavirus gastroenteritis (RVGE), as measured by Vesikari scoring system (VSS, score ≥11), from ≥14 days following Dose 3 through a follow-up period of nearly 2 years in the combined 3 African countries, and secondary endpoints by total follow-up period have been previously reported. In this study, we report post hoc subgroup analyses on secondary endpoints of public health importance. VE against RVGE of any severity was 49.2% (95%CI: 29.9, 63.5) through the first year of life and 30.5% (95%CI: 16.7, 42.2) through the complete follow-up period. VE against severe-gastroenteritis of any etiology was 21.5% (95%CI: <0, 38.4) through the first year of life and 10.6% (95%CI: <0, 24.9) through the complete follow-up period. Through the complete follow-up period, VE against severe-RVGE caused by (i) vaccine-contained G and P types (G1-G4, P1A[8]), (ii) non-vaccine G types (G8, G9, G10), and (iii) non-vaccine P types (P1B[4], P2A[6]) was 34.0% (95%CI:11.2, 51.2), 81.8% (95%CI:16.5, 98.0) and 40.7% (95%CI:8.4, 62.1), respectively. There was a trend towards higher VE with higher disease severity, although in some cases the numbers were small. In African countries with high under-5 mortality rates, PRV significantly reduced RVGE through nearly 2 years of follow-up; more modest reductions were observed against gastroenteritis of any etiology. PRV provides protection against severe-RVGE caused by diverse rotavirus genotypes, including those not contained in the vaccine.
KW - G genotype
KW - Gastroenteritis
KW - P genotype
KW - Rotavirus
KW - Vaccine efficacy
UR - http://www.scopus.com/inward/record.url?scp=84860009433&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2012.01.022
DO - 10.1016/j.vaccine.2012.01.022
M3 - Article
C2 - 22520141
AN - SCOPUS:84860009433
SN - 0264-410X
VL - 30
SP - A79-A85
JO - Vaccine
JF - Vaccine
IS - SUPPL. 1
ER -
