Rotavirus vaccination programmesBMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e5286 (Published 08 August 2012) Cite this as: BMJ 2012;345:e5286
- Manish M Patel, medical epidemiologist
- 1National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta GA 30333, USA
In a linked research paper (doi:10.1136/bmj.e4752), Braeckman and colleagues analyse the effectiveness of a monovalent rotavirus vaccine after its routine introduction in Belgium.1 This is the first study of its kind from Europe, and the new data offer robust evidence on the effectiveness of the vaccine in a real life setting.
Public health problems are tackled by defining the extent of the problem, developing an intervention, and then deploying and evaluating the intervention. Each step is necessary for optimal control of the problem. Belgium is one of several countries that has recently implemented a nationwide rotavirus vaccination programme for controlling severe diarrhoea in children and it is currently evaluating the programme.1
Efforts to control rotavirus began in 1973, when Ruth Bishop identified wheel shaped (rota) virus-like particles in the intestinal mucosa of infants with diarrhoea.2 In the ensuing decades rotavirus was confirmed as the main cause of severe diarrhoea in children under 5 years, accounting for nearly 40% of hospital admissions and 450 000 deaths related to diarrhoea every year.3 Several decades of research resulted in the development of two new rotavirus vaccines (monovalent and pentavalent vaccines), which are now recommended by the World Health Organization for all children worldwide.4 Around 30 countries now include rotavirus vaccines in their routine childhood immunisation programmes, with more countries intending to include them in future programmes.5
Rotavirus vaccines were effective when tested in large clinical trials, but these trials were conducted under stringent conditions where vaccines were given to healthy children at a set age.6 7 As these vaccines are routinely introduced, national evaluations will shed light on aspects of the vaccine’s efficacy that could not be assessed fully by the clinical trials. This will ensure that protection is sustained year after year as changes in disease and strain epidemiology are monitored and the vaccine’s efficacy against diverse strains is evaluated. This last aspect is particularly relevant for the G1P monovalent vaccine because rotavirus strains come in many combinations of G and P proteins that vary each year.8 The monovalent vaccine protects children adequately against strains that are partially heterotypic from the vaccine strain (strains with P), but stronger evidence is needed before we know whether it protects against fully heterotypic strains (strains with neither G1 nor P).8
Braeckman and colleagues’ analysis of data from a random selection of 39 Belgian hospitals over two years showed that rotavirus vaccine prevented most (90%, 95% confidence interval 81% to 95%) hospital admissions for rotavirus in children. The vaccine was equally effective in children under and over 1 year of age, indicating a sustained level of protection during the ages 0-5 years, when children are at highest risk. Perhaps the most reassuring aspect was that the vaccine conferred similarly high protection against fully heterotypic G2P strains (85%, 64% to 94%) and homotypic G1P strains (95%, 78% to 99%).
Perhaps one of the more salient unstated reasons for evaluating these vaccines is to gain a better understanding of the benefit-risk balance. Because a previous rotavirus vaccine (RotaShield) was withdrawn from the market in the United States after studies discovered an association with intussusceptions in infants, the current vaccines have been subject to a high level of scrutiny. In fact, large post-marketing studies for current vaccines in Mexico and Australia have uncovered a low level risk of intussusception.9 10 In addition, post-marketing detection of non-pathogenic DNA or DNA fragments of porcine circovirus in both vaccines has also raised concerns about vaccine safety globally, although no links to human disease have been seen to date.11 Many studies, like the current one by Braeckman and colleagues, have contributed evidence that has facilitated informed decision making. WHO, the European Medicines Agency, and the US Food and Drug Administration have deemed that real world benefits of rotavirus vaccines greatly outweigh potential safety concerns. In no uncertain terms, evaluation has mattered.
This success is encouraging, but nearly 90% of the world’s children do not yet have access to rotavirus vaccines. Cost effectiveness is a concern for wealthy countries with few diarrhoea related deaths, particularly in western Europe, where only four countries have added a rotavirus vaccine to their routine programmes. However, new findings from post-marketing studies may tilt the cost-benefit ratio in favour of rolling out the vaccine. Studies in middle income and high income countries have convincingly shown that rotavirus vaccine provides indirect benefits to those who are too old to be vaccinated, and that the population burden of rotavirus is greater than that predicted before the introduction of vaccine.5 That said, after six years of vaccine use in many large countries, vaccine manufacturers should have recovered their costs, and reduced vaccine prices would facilitate more equitable access to these vaccines.
Meanwhile, the GAVI Alliance has agreed to purchase vaccines for eligible low income countries, but the efficacy of these vaccines is substantially lower in such settings than in wealthier countries. The real world performance of rotavirus vaccines needs to be tested in countries funded by GAVI. Ways to improve efficacy, such as modifying the schedule to avoid interference by maternal antibodies or adding another dose of vaccine, also need to be tested. These are potentially simple solutions that might drastically improve the life saving potential of these vaccines.12
A legitimate concern is that the early enthusiasm that has led to rapid uptake of rotavirus vaccines by some countries might hamper evaluation of the health impact of rotavirus vaccination and research to improve vaccine performance. Undeniably, efforts to control rotavirus have produced remarkable dividends. These early successes should be a springboard to progress. Improving affordability, maintaining the momentum of vaccine introductions and evaluations, and searching for ways to improve efficacy will be crucial if the rotavirus problem is to be resolved globally.
Cite this as: BMJ 2012;345:e5286
Competing interests: The author has completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Commissioned; not externally peer reviewed.