Poster Presentations

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. Witte^1,4, B. Ngwira⁵, P. Bos⁶, J. Victor⁷, D. Steele⁸, K. Neuzil⁷, P.V. Suryakiran⁹, H.H. Han^9
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.