Review
Fulfilling the promise of rotavirus vaccines: how far have we come since licensure?

https://doi.org/10.1016/S1473-3099(12)70029-4Get rights and content

Summary

Rotavirus is the most common cause of fatal and severe childhood diarrhoea worldwide. Two new rotavirus vaccines have shown efficacy against severe rotavirus disease in large clinical trials. Between 2006 and 2010, 27 countries introduced rotavirus vaccination into national immunisation programmes and, subsequently, the burden of severe rotavirus disease in these countries has decreased substantially in both vaccinated and unvaccinated children. Rotavirus vaccination has led to large, sustained declines in childhood deaths from diarrhoea in Brazil and Mexico, which supports estimates that rotavirus was the leading cause of diarrhoeal deaths in these countries. Studies after licensing have provided new insights into these vaccines, such as the duration of protection, relative effectiveness in poor populations, and strain evolution after vaccine introduction. The challenge for policy makers worldwide is to analyse the effect of vaccination in early adopter countries and to assess whether the benefits outweigh the costs and encourage wider dissemination of these vaccines.

Introduction

Rotavirus-related diarrhoea is one of the most common illnesses in children worldwide, causing 453 000 deaths and 2·4 million hospital admissions every year in children younger than 5 years.1, 2, 3 Identification of rotavirus in 19734 led to several decades of targeted research5 that culminated in the development of two live oral rotavirus vaccines. Results of two pivotal trials done in Europe and the Americas showed these vaccines to be safe and efficacious.6, 7 In 2006, WHO recommended these vaccines—Rotarix (two-dose series; GlaxoSmithKline Biologicals) and RotaTeq (three-dose series; Merck)—for use in children in these regions.8 A similar recommendation was not made for low-income settings in Africa and Asia where most of the yearly rotavirus deaths occur because of a shortage of efficacy data from these regions. Phase 2 studies showed that children in Bangladesh, India, and South Africa had a low immune response to oral rotavirus vaccines.9, 10, 11 The reduced efficacy of oral vaccines against poliomyelitis,12, 13 cholera,14 and typhoid15 in some low-income settings was also taken into account. In anticipation of vaccine introduction, we previously reviewed the global epidemiology of rotavirus disease, described the 20 year scientific development of rotavirus vaccines, and discussed the challenges facing their global use.16

Since then, the two licensed rotavirus vaccines have passed several crucial milestones, bringing them closer to the desired goal of reducing diarrhoea-related hospital admissions and death in children worldwide. First, the efficacy of both rotavirus vaccines was shown in trials in low-income countries in Africa and Asia.17, 18 Second, on the basis of these trials, WHO expanded their initial regional recommendation for rotavirus vaccination to all children worldwide.19, 20 Third, donor funding for rotavirus vaccination became available to the poorest countries through the GAVI Alliance, a public–private partnership created in 2000 to increase access to immunisation.21, 22 Fourth, 27 countries worldwide made these vaccines available through the public sector between 2006 and 2010 by including them in their routine national immunisation programmes (table 1).25 Rotavirus vaccination is generally initiated in children aged 2–4 months and completed by the time the child is about 7–8 months old.

In this Review, we assess the reported postlicensure data from the first countries to integrate rotavirus vaccination into their national immunisation programmes.

Section snippets

Rotavirus-related hospital admissions

Soon after rotavirus vaccines were introduced into publicly funded immunisation programmes, their rapid uptake in some high-income countries was noted, with vaccination coverage ranging from 54% to 93% in children younger than 1 year, and 37% to 90% in children younger than 2 years (table 2). The effects of rotavirus vaccination have been substantial (figure) and include reductions in the number of direct medical events (eg, admissions to hospital, deaths, doctor visits)25 and improvements in

Safety of rotavirus vaccines

A previously licensed rotavirus vaccine, RotaShield, was withdrawn 9 months after its introduction in the USA after postlicensure safety monitoring discovered that the vaccine was associated with intussusception, a rare but life-threatening form of bowel obstruction in infants.97 Both RotaTeq and Rotarix were assessed in large clinical trials with more than 60 000 infants each, but they were not associated with a rise in intussusception when compared with placebo.6, 7 However, monitoring of

Future challenges

Since the development and successful testing of the first rotavirus vaccine in the early 1980s,5, 105 research and development efforts have produced two new rotavirus vaccines prequalified for global use by WHO and recommended for the routine immunisation of all children. In the past 5 years, these vaccines have been adopted in national immunisation programmes in a number of mostly high-income and middle-income countries. Several of these countries have documented dramatic declines in severe

Search strategy and selection criteria

We searched PubMed with the primary search terms “rotavirus” and “vaccine” or “rotavirus” and “impact” between Jan 1, 2006, and Sept 1, 2011. We did not limit our search by language. We included all studies that measured the effect of rotavirus vaccination on rotavirus events, the number of people admitted to hospital for gastroenteritis, or deaths after routine use of rotavirus vaccine. We excluded clinical trials from the pooled data.

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