New pentavalent rotavirus vaccine shows little efficacy against diarrhea

Vaccine. 2018 Jun 13. pii: S0264-410X(18)30772-2. doi: 10.1016/j.vaccine.2018.05.105. Available online 13 June 2018

Lalit Kumar, Jacob Puliyel

Letter to the Editor
New pentavalent rotavirus vaccine shows little efficacy against diarrhea
Lalit Kumar
Jacob Puliyel
Department of Pediatrics, St Stephens Hospital, Delhi 110054, India
⁎Corresponding author.
Keywords: Rotarix; Bovine human-reassortant pentavalent vaccine; Serum Institute of India
Rotavirus vaccine is recommended as a means of reducing diarrheal morbidity and deaths in developing countries [1]. The original efficacy studies with the presently licensed vaccines were done in the USA and Europe. Efficacy against severe rotavirus infection was around 90% (95% confidence interval (CI) : 85.·1‒–94.·1) and against all-cause severe gastroenteritis it was about 50% (CI: 39.·8‒–57.·8) [2]. Efficacy was less in Africa and Asia. In Africa it was 61% (CI: 44.0‒0–73.2) 2) against severe rotavirus diarrhoea and 30% (CI: 15.0‒–42.6) against all-cause severe diarrhoea [3].
The journal Vaccine has now published the results of a Phase-III randomized-control-trial, of a newly developed pentavalent rotavirus vaccine (BRV-PV). Vaccine efficacy against rotavirus diarrhoea ,(39.5% efficacy against severe rotavirus gastroenteritis (SRVGE) in the per protocol analysis) is emphasized in the report. However, the incidence of ‘all-cause severe gastroenteritis’ was not reduced by vaccination – vaccine efficacy was reported as 4.6% (95% CI: -−5.1‒ to 13.4) [4].
From the standpoint of the scientific record, additionally highlighting the clinically relevant aspect of their findings - namely efficacy against all-cause diarrheal morbidity, would enable decision makers to make choices about the vaccine, considering costs and benefits.
The same vaccine was studied in Niger. An efficacy of 66.7% against severe rotavirus gastroenteritis was reported in the per protocol population [5]. However severe gastroenteritis due to any etiology was not significantly lower among the vaccinated (difference in rate 1.97 cases per 100 person years confidence interval [CI](CI: –- 1.,28 to –5.22) [6]. The authors did post-hoc analysis of efficacy against ‘very severe diarrhoea’ (which they defined as Vesikari score of 15 or more) and reported a difference in rate of 3.08 per 100 person years (CI: 1.79 to –4.36) among the vaccinated. As efficacy against ‘very severe diarrhea’ has not been studied previously, comparable data for other rotavirus vaccines is not available.
[1] Rotavirus vaccines. WHO position paper -January 2013. Wkly Epidemiol Rec 2013;88(5):49–64.
[2] T. Vesikari, A. Karvonen, R. Prymula, V. Schuster, J.C. Tejedor, R. Cohen, et al., Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind T controlled study, Lancet 370, 2007, 1757–1763.
[3] S.A. Madhi, N.A. Cunliffe, D. Steele, D. Witte, M. Kirsten, C. Louw, et al., Effect of human rotavirus vaccine on severe diarrhea in African infants, N Engl J Med 362 (4), 2010 Jan 28, 289–298.
[4] P.S. Kulkarni, S. Desai, T. Tewari, A. Kawade, N. Goyal, B.S. Garg, et al., Flores J; SII BRV-PV author group. A randomized Phase III clinical trial to assess the efficacy of a bovine-human reassortantpentavalent rotavirus vaccine in Indian infants, Vaccine 35, 2017, 6228–6237.
[5] S. Isanaka, O. Guindo, C. Langendorf, A. Matar Seck, B.D. Plikaytis, N. Sayinzoga-Makombe, et al., Efficacy of a low-cost, heat-stable oral rotavirus vaccine in Niger, N Engl J Med 376, 2017, 1121–1130.
[6] J. Kaur and J. Puliyel, Heat-stable oral rotavirus vaccine, N Engl J M