An overview of rotavirus vaccination programs in developing countries

ABSTRACT

Introduction

Rotavirus is the leading cause of acute diarrhea among children <5 years worldwide. As all children are equally susceptible to infection and disease development, rotavirus vaccination programs are the best upstream approach to preventing rotavirus disease, and the subsequent risk of hospitalization or death.

Areas covered

We provide an overview of global rotavirus vaccine policy, summarize the burden of rotavirus disease in developing countries, review data on the effectiveness, impact, safety, and the cost-effectiveness of rotavirus vaccination programs, and identify areas for further research and improvement.

Expert opinion

Rotavirus vaccines continue to be an effective, safe, and cost-effective solution to preventing rotavirus disease. As two new rotavirus vaccines enter the market (Rotasiil and Rotavac) and Asian countries continue to introduce rotavirus vaccines into their national immunization programs, documenting vaccine safety, effectiveness, and impact in these settings will be paramount.

KEYWORDS:

• Rotavirus
• rotavirus vaccine
• vaccines
• vaccine implementation
• low and middle-income countries
• developing countries
• diarrhea

Article highlights

• In 2006 the World Health Organization’s (WHO) Strategic Advisory Group of Experts (SAGE) first recommended the inclusion of rotavirus vaccines into national immunization programs in Europe and the Americas, and in 2009 SAGE recommended the integration of rotavirus vaccine into all immunization programs worldwide.

• Currently, four rotavirus vaccines have been pre-qualified by WHO for use globally. In developing countries, WHO recommends the use of Rotarix vaccine in a 2-dose schedule given at 6 and 10 weeks of age, and RotaTeq, Rotavac, and Rotasiil in a 3-dose schedule at 6, 10, and 14 weeks of age, with vaccine doses given concurrently with other childhood vaccines given at these ages.

• WHO currently recommends that the rotavirus vaccine series can be started at 6 weeks of age and subsequent vaccine doses can be given until 24 months of age. However, on-time vaccination at as early of an age as possible is strongly encouraged to achieve protection against rotavirus disease early in life.

• In 2013, an estimated 214,664 deaths were attributed to rotavirus infection in developing countries, and in the absence of rotavirus vaccine introduction, 38% of all hospitalized diarrhea cases among children <5 years globally are due to rotavirus infection.

• As of December 2019, 100 countries have introduced a rotavirus vaccine into their national immunization programs; an additional 6 low-income countries with a gross national product of <US$1,580 per capita have been approved for funding support for vaccine introduction from Gavi, the Vaccine Alliance and are awaiting national introduction and another 13 countries are preparing to introduce independent of Gavi support.

• A systematic review that analyzed post-licensure vaccine effectiveness data stratified by a country’s childhood mortality rates aligned with these findings, with Rotarix vaccine effectiveness at 84% (13 studies), 75% (8 studies), and 57% (9 studies) in countries with low, medium, and high childhood mortality rates, and RotaTeq vaccine effectiveness at 90% (20 studies) and 45% (7 studies) in countries with low and high child mortality rates, respectively.

• Rotavirus vaccine introduction has reduced the global proportion of hospitalized diarrhea cases attributed to rotavirus among children <5 years from 38% in the pre-vaccine period, to 23.0% in the post-vaccine period, a 39.6% relative decline. While the magnitude of the decline varies by WHO region, due to varying vaccine effectiveness and vaccine coverage, overall reductions remain relatively consistent.

• Post-marketing surveillance conducted in several high and middle-income countries has identified a slight increase in risk of intussusception 1-7 days following vaccination for both Rotarix and RotaTeq at a rate of 1 excess case per 20,000 – 100,000 vaccinated infants. The WHO Global Advisory Committee on Vaccine Safety has reviewed all of these data and reaffirmed the recommendation for continued rotavirus vaccine use.

• Currently, minimal data have been published on the effectiveness or intussusception risk associated with Rotavac or Rotasiil in routine use.

• When looking at all countries, previous work has found that at $5 per dose, the cost effectiveness of rotavirus vaccine per DALY averted in low, low-middle, and upper-middle-income countries was $88, $291, and $329, respectively. While occasionally some countries have found rotavirus vaccine not to be cost effective, this generally occurred when only direct medical costs were considered, and not those incurred by the family or society.

Author contributions

B Hallowell, J Tate, and U Parashar were involved in the conception, design, drafting, and revising of the manuscript. All authors provide final approval of the version of the study to be published and take accountability for all aspects of the work.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.