Human rotavirus vaccine (Rotarix): focus on effectiveness and impact 6 years after first introduction in Africa

Abstract

A decade after licensure of the human rotavirus vaccine (HRV), a wealth of evidence supports a reduction of rotavirus (RV) gastroenteritis-associated mortality and hospitalizations following HRV inclusion in national immunization programs. Nevertheless, the majority of real-world data has been generated in high- or middle-income settings. Clinical efficacy trials previously indicated RV vaccine performance may be lower in less-developed countries compared with wealthier counterparts. Using recently published data from Africa, we examine the effectiveness and impact of HRV in resource-deprived areas, exploring whether vaccine performance differs by socioeconomic setting and the potential underlying factors. HRV vaccine effectiveness in early adopting African countries has proven to be similar or even superior to the efficacy results observed in pre-licensure studies.

Keywords:

• Africa
• developing countries
• RIX4414 vaccine
• Rotavirus vaccine
• vaccine effectiveness
• vaccine impact

Acknowledgments

Editorial assistance was provided by Julianna Solomons of Fishawack Communications, funded by GlaxoSmithKline.

Financial & competing interests disclosure

M O’Ryan has received no funding from GSK during the last 5 years; however, he received grant funding from GSK for the Latin American rotavirus vaccine trial between 2002 and 2006 and support for travel up to 2010 for study result communication and rotavirus talks. C Giaquinto has received research grants from GSK, Sanofi Pasteur-MSD and Merck, and honorarium for speaking or consultancy from GSK and Sanofi Pasteur-MSD. B Benninghoff is an employee of GlaxoSmithKline. The authors have no other 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 apart from those disclosed.

Key issues

• There are currently two widely licensed live, attenuated orally administered rotavirus vaccines. Rotarix^® (human rotavirus vaccine [HRV]) – a two-dose vaccine based on a single RV strain of the most commonly observed human genotype, G1P8, and RotaTeq^® a three-dose, human–bovine reassortant vaccine (HBRV) containing five different strains.

• As of March 2015, 28 countries in Africa have included RV vaccination in their NIPs (22 using HRV and six using HBRV). In 2009, South Africa became the first African country to introduce RV vaccines, and the first Gavi-funded RV vaccination program in Africa was rolled out in Sudan in 2011.

• Few studies have assessed the field effectiveness of HRV vaccination in lower-income settings; three African countries (South Africa, Ghana and Malawi) have now performed impact and effectiveness studies.

• There are two common methodologies used to assess the real-world performance of RV vaccines: Ecological (impact) studies, which monitor outcome trends over time, and case–control (effectiveness) studies, which compare the frequency of vaccination exposure among patients with RV disease and RV disease-free controls.

• European countries report HRV effectiveness of approximately 90% or more against RV gastroenteritis (RVGE) hospitalization compared with 76–96% in upper-middle-income and 76–77% in lower-middle-income countries.

• Current coverage rates in African countries range from 78% in Botswana to 99% in Rwanda.

• South Africa introduced HRV in August 2009 on a 6- and 14-week two-dose schedule. Three studies have reported 38–43% and 61–69% reduction in all-cause GE and RVGE, respectively, in children aged <12 months compared with 2009 data. Field effectiveness of HRV appears to be sustained in the 12- to 23-months age group.

• Ghana introduced HRV in May 2012 on a 6- and 10-week schedule. Surveillance data from two pediatric referral hospitals reported a decline in child hospitalizations from all-cause diarrhea by 51.6% from 2011 to 2012, and by a further 16.2% from 2012 to 2013. The proportion of diarrheal hospitalizations attributable to RVGE fell from 49.7–27.8% and for the <11 month olds from 73% to 46%.

• Malawi introduced HRV in October 2012 on a 6- and 10-week schedule. Pre-licensure clinical trials in Blantyre reported 49% efficacy against severe RVGE in the first year of life. A post-licensure impact study reported a 43.2% reduction in RV hospitalizations in children aged <12 months, while effectiveness of two doses of HRV against acute RVGE was approximately 64%.

• Similar to the experience with HRV in South Africa, vaccine effectiveness was notably higher in Malawi than previous estimates of the efficacy of the vaccine in the country.

• Efficacy and effectiveness studies have demonstrated robust protection against a range of homotypic and heterotypic RV types worldwide; nevertheless, there may be some degree of variation in the strength and/or nature of protection afforded by the vaccine against more phylogenetically divergent RV types.

• Determining a true epidemiological picture of intussusception in Africa will be challenging due to limited access to appropriate diagnostic equipment.

• The age of first RV infection is perhaps the most convincing explanation for discrepancies in vaccine efficacy and effectiveness between more developed and less developed settings.

• Data on reductions in mortality from RVGE in the post-vaccine era are still lacking in Africa.

• Whether herd effect increases the value of RV vaccination in Africa is yet to be documented, although impact data from South Africa suggest this is a possibility.

• Studies utilizing data from the African RV Surveillance Network initiative are expected to increase our current knowledge on RV impact in these settings.

Notes