Table 1.

Factors influencing uptake of rotavirus vaccines

Concern	Issue	Major findings	Reference
Safety	Intussusception	1–6 excess cases/100 000 recipients. Vaccine benefits outweigh risks.	[21–30]
	Age restriction of 15 weeks (dose 1) in vaccine schedule	Risk of intussusception may be related to older age at vaccination. Restriction may reduce vaccine coverage 5–10% in developed but as much as 30–40% in some developing countries. Lifting restriction could potentially prevent 47 200 AGE deaths while causing an additional 294 intussusception deaths. In view of the benefits exceeding risks in high AGE mortality settings, the upper limit of 15 weeks on dose 1 was relaxed by WHO, and vaccination is allowed concurrently with other childhood vaccines up to 24 months of age.	[31–41]
	NICU patients	NICU patients may miss opportunity to receive vaccine because they may be age ineligible by discharge. No definite attributable risk of AGE after vaccination of infants in NICU documented.	[42–44]
	Porcine circovirus	2010 RV1/RV5 found with PCV contamination, leading to a suspension of RV1 vaccination for short period. After thorough review, FDA panel found no evidence of risk from vaccination and deemed it safe to resume.	[45–49], http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm205540, http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/02/WC500162147.pdf, http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm212140, http://www.who.int/immunization/newsroom/news_rotavirus_vaccine_use/en/index.html, http://venice.cineca.org/Venice2_WP3_Report_December2010.pdf
	Vaccine-derived strains	~1/140 000 RV5 vaccinees have vaccine-derived rotavirus strain that could cause severe rotavirus disease. Risk outweighed by the large health benefits of rotavirus vaccination.	[50–52]
Other	Lower efficacy in developing countries	Modest vaccine efficacy of 40–64% in developing countries still demonstrates impact in higher-burden settings. Presence of transplacental maternal antibodies, chronic malnutrition, coinfections, coadministration with oral poliovirus, may contribute to decreased vaccine effectiveness in developing world. Breast-feeding not shown to be a factor linked with lower vaccine uptake. Vaccine schedules with additional dosing underway to determine if boosting improves vaccine effectiveness.	[54–70]
	Emergence of strains escaping vaccine immunity	RV1/RV5 show similar effectiveness to heterotypic/homotypic strains. No sustained dominance of any strain since vaccine introduction. Further surveillance is warranted.	[74–81]
	Financing	Some developed countries cite low burden and high cost as barrier to universal introduction. GAVI subsidizes eligible countries, 37 to date have introduced rotavirus vaccine. As countries transition out of GAVI assistance, evaluation of sustainability of vaccine programs needed.	[84–87], http://venice.cineca.org/Venice2_WP3_Report_December2010.pdf

AGE, acute gastroenteritis; FDA, US Food and Drug Administration; GAVI, Global Alliance for Vaccines and Immunization; NICU, neonatal intensive care unit; PCV, porcine circovirus; RV, rotavirus; WHO, World Health Organization