Rotavirus vaccine efficacy: current status and areas for improvement

Carvalho, Miguel F.; Gill, Davinder

In the aftermath of the voluntary withdrawal of RotaShield from the market in 1999 due to increased risk of intussusception, the safety and benefits of Rotavirus vaccines have been the subject of substantial scrutiny and comment. A USAbased report evaluated the occurrence of intussusception in 19 states in infants aged 1 to 12 months and noted that 429 had developed the condition, 74 of which had also been vaccinated with RotaShield. The incidence was greater 3--14 days after vaccination, especially after the first dose (43 accounts; 9 after second and 1 after third) with an estimated 28% increase in cases of intussusception if the vaccination program were fully implemented (1 in 4,670 to 9,474 infants vaccinated). Overall the study showed strong temporal and specific association between vaccine administration and intussusception and concluded that vaccines with better safety profile are required. 42 Another study evaluated the impact of age in incidence of intussusception after RotaShield administration and noted that infants over 90 days old at first dose represent 80% of all cases (despite having received solely 38% of first doses). Overall, vaccination schedules could be completed by 60 days of age in 2 doses so as to reduce intussusception incidence. 43 This strategy was tested with RRV-TV in Ghana (despite being withdrawn from European and USA markets) and based on data from 500 infants in vaccine and 498 in placebo groups, efficacy was 63.1% against RGE of any severity for serotypes present in vaccine and 60.7% for all serotypes. No cases of intussusception were reported 44 . A post-licensing evaluation of intussusception risk in the USA comprised 1,277,556 doses for RotaTeq (of which 507,874 were first doses) and 103,098 doses for Rotarix (of which 53,638 were first doses). The authors performed two analyses and for RotaTeq the primary analysis indicated an association between vaccination and intussusception (highest at 3-7 days after first dose; 1.1 excess cases/100,000 infants receiving the first dose for the 7-day risk window and 1.5 excess cases/ 100,000 infants receiving the first dose for the 21-day risk window); the secondary analysis identified an attributable risk of 1.2 excess cases/100,000 infants receiving the first dose for the 21-day risk window (no risk attributable to doses 2 and 3). The limited number of Rotarix doses did not allow for precise estimation of intussusception risks therefore preventing a direct comparison with RotaTeq. The secondary analysis indicated a significant attributable risk after the second dose of 7.3 excess cases/100,000 infants for the 21-day risk window 34 It will be important to continue monitoring risks associated with Rotavirus vaccines in low income nations as data from high income settings may not directly compare. 45 Ironically, although efficacy of Rotavirus vaccination is lower in developing nations, it is also in such regions that the benefits are of greater magnitude due to higher burden of disease. 33, [46] [47] [48] [49] Taking into consideration the disease burden and associated costs of hospitalization as well as the mortality of Rotavirus gastroenteritis, the impact of vaccination is predicted to be very significant. 47 It is estimated that in GAVI-eligible countries, vaccination could prevent 2.46 million child deaths and 83 million disability-adjusted life years. 46 According to Troeger et al., from 2005 to 2015 there was a decrease in mortality of 43.6% among children