Session Title: VACCINE AND PREVENTION
EFFICACY OF HUMAN ROTAVIRUS VACCINE RIX4414 IN AFRICA DURING THE FIRST YEAR OF LIFE
N. Cunliffe1, M. Kirsten2, S. Madhi3, D. Witte1,4, B. Ngwira5, P. Bos6, J. Victor7, D. Steele8, K. Neuzil7, P.V. Suryakiran9, H.H. Han9
1Division of Medical Microbiology, University of Liverpool, Liverpool, UK, 2Department of Paediatric Surgery, University of Pretoria, Pretoria, 3Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of Witwatersrand, Johannesburg, South Africa, 4University of Malawi, College of Medicine, 5Department of Community Health, College of Medicine, University of Malawi, Blantyre, Malawi, 6MRC Diarrhoeal Pathogens Research Unit, University of Limpopo, Pretoria, South Africa, 7Rotavirus Vaccine Program, PATH, Seattle, USA, 8Initiative for Vaccine Research, WHO, Geneva, Switzerland, 9GlaxoSmithKline Biologicals, Rixensart, Belgium
Background: Rotavirus vaccination is a potential strategy for diarrhea prevention among children in Africa, where disease burden is high and access to primary care is limited. This double-blind, placebo-controlled, multi-center trial (102248/NCT00241644) was conducted in Malawi and South Africa to evaluate the clinical efficacy of the oral, live-attenuated human rotavirus vaccine RIX4414.
Methods: 4939 healthy infants were randomised(1:1:1) and received 2-doses of RIX4414 (at 10 and 14 weeks; placebo at 6 weeks), 3-doses of RIX4414 (at 6, 10 and 14 weeks) or 3-doses of placebo. Routine EPI vaccines including OPV were co-administered. HIV-infected infants were not excluded. Vaccine efficacy (VE) against severe rotavirus gastroenteritis (RVGE), defined as >=11 on the 20-point Vesikari scale, was calculated from 2 weeks post last dose to age 1 year.
Results: During the efficacy follow-up, mean duration 7.6 months, severe RVGE developed in 1.9% of RIX4414 (n=2974, pooled groups) and 4.9% of placebo recipients (n=1443); overall VE 61.2% (95%CI:44.0%-73.2%). Despite lower VE in Malawian (49.4%[95%CI:19.2-68.3]) compared to South African children (76.9%[95%CI:56.9-88.4]), the burden of severe RVGE prevented among Malawian children was greater; 3.9 versus 2.5 episodes per 100 infants vaccinated, respectively. There was no difference in VE between children receiving 2 (58.7%;[95%CI:35.7%-74.0%]) and 3 doses (63.7%;[95%CI:42.4%-77.8%]) of rotavirus vaccine.
Conclusions: In challenging settings in Africa, RIX4414 significantly reduced severe RVGE during the first year of life. Efficacy of 2 and 3 doses was similar. Overall public health impact in Africa is anticipated to be substantially higher than developed settings due to the high disease burden.