title: Secondary efficacy endpoints of the pentavalent rotavirus vaccine against gastroenteritis in sub-Saharan Africa.
abstract: 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.
authors.affiliation: Centre pour le Développement des Vaccins, Bamako, Mali. mtapia@medicine.umaryland.edu
authors.forename: Milagritos D
authors.initials: MD
authors.lastname: Tapia
authors.forename: George
authors.initials: G
authors.lastname: Armah
authors.forename: Robert F
authors.initials: RF
authors.lastname: Breiman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dallas
authors.forename: Kristen D C
authors.initials: KD
authors.lastname: Lewis
authors.forename: Samba O
authors.initials: SO
authors.lastname: Sow
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Rivers
authors.forename: Myron M
authors.initials: MM
authors.lastname: Levine
authors.forename: Kayla F
authors.initials: KF
authors.lastname: Laserson
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Feikin
authors.forename: John C
authors.initials: JC
authors.lastname: Victor
authors.forename: Max
authors.initials: M
authors.lastname: Ciarlet
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Neuzil
authors.forename: A Duncan
authors.initials: AD
authors.lastname: Steele
mesh_terms: D000284:Administration, Oral; D017954:Africa South of the Sahara / Q000453:epidemiology; D004311:Double-Blind Method; D005260:Female; D005759:Gastroenteritis / Q000453:epidemiology / Q000473:pathology* / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D012400:Rotavirus Infections / Q000453:epidemiology / Q000473:pathology* / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D012720:Severity of Illness Index; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D010919:Placebos; C492535:RotaTeq; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated