Evaluation of Intussusception After Oral Monovalent Rotavirus Vaccination in South Africa

Abstract

Background Postlicensure studies have shown an association between rotavirus vaccination and intussusception. We assessed the risk of intussusception associated with Rotarix (RV1) administration, at 6 and 14 weeks of age, in an upper-middle-income country, South Africa. Methods Active prospective surveillance for intussusception was conducted in 8 hospitals from September 2013 through December 2017. Retrospective case enrollment was done at 1 hospital from July 2012 through August 2013. Demographic characteristics, symptom onset, and rotavirus vaccine status were ascertained. Using the self-controlled case-series method, we estimated age-adjusted incidence rate ratios within 1–7, 8–21, and 1–21 days of rotavirus vaccination in children aged 28–275 days at onset of symptoms. In addition, age-matched controls were enrolled for a subset of cases (n = 169), and a secondary analysis was performed. Results Three hundred forty-six cases were included in the case-series analysis. Post–dose 1, there were zero intussusception cases within 1–7 days, and 5 cases within 8–21 days of vaccination. Post–dose 2, 15 cases occurred within 1–7 days, and 18 cases within 8–21 days of vaccination. There was no increased risk of intussusception 1–7 days after dose 1 (no cases observed) or dose 2 (relative incidence [RI], 1.71 [95% confidence interval {CI} .83–3.01]). Similarly, there was no increased risk 8–21 days after the first (RI, 4.01 [95% CI, .87–10.56]) or second dose (RI, .96 [95% CI, .52–1.60]). Results were similar for the case-control analysis. Conclusions The risk of intussusception in the 21 days after the first or second dose of RV1 was not higher than the background risk among South Africa infants. Clinical Trials Registration South African National Clinical Trial Register (DOH-27-0913-4183).

Risk of intussusception after monovalent rotavirus vaccine (Rotavac) in Indian infants: A self-controlled case series analysis

“…In this study no case was observed before 6 weeks, one case before 10 weeks and 11 cases before 14 weeks of ages. This observation is similar to that from African countries [23] , [28] . The median or peak ages of intussusception in children from the countries with increased risk were also comparable to the Indian and African children.…”

“…Our results are comparable to the reports of intussusception after RV1 (Rotarix™) vaccination in several African countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, Zimbabwe and South Africa), where no increased risk of intussusception after any dose of RV1 were observed [23] , [28] . However, increased risks of intussusception were documented in the 1–7 days following dose 2 of RV1 in Brazil (IR 2.6; 95% CI 1.3–5.2; OR 1.9; 95% CI 1.1–3.4) and after dose 2 (IR 5.3; 95% CI 3.0–9.3 and OR 5.8; 95% CI 2.6–13) and dose 1 (IR 6.49; 95% CI 4.17–10.09) in Mexico [9] , [10] .…”

“…As no external controls are used, this method automatically controls for time-invariant confounding [25] . The SCCS has been used in several studies investigating the risk of intussusception with RVV vaccine [9] , [10] , [11] , [14] , [23] , [26] , [27] , [28] , [29] with the pseudo-likelihood method [30] . We limited the analysis to the first occurrences of intussusception that met the level-1 Brighton collaboration criteria and children aged 28–364 days at the onset of symptoms, considering the minimum and maximum ages at which RVV could be given in India.…”

Intussusception after Rotavirus Vaccine Introduction in India

“…Despite the hypothesis that intussusception might be an adverse event associated with all rotavirus vaccines 11 , the World Health Organization (WHO) recommended rotavirus vaccine introduction into childhood vaccination programs as cases and deaths averted due to diarrhea are greater than the additional intussusception, resulting in a favourable risk benefit analysis 12 . Recently, our understanding of the safety of rotavirus vaccination in specific populations was further informed by the finding that in seven low-income African countries and South Africa, where vaccine efficacy has been lower than that seen in high-income countries, there was no increased risk of intussusception following Rotarix® vaccination 13 , 14 .…”

Prospective surveillance for intussusception in Indian children aged under two years at nineteen tertiary care hospitals

“…Some increased risk of intussusception after the first (relative risk, RR: 4.7–13.8) and second (RR: 1.3–5.3) doses of RVVs was reported from several countries (Mexico, Brazil, Australia, United Kingdom, United States, Spain and Singapore) [ 1 – 8 ]. But no increased risk of intussusception after any dose of RVV was observed in some countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, Zimbabwe and South Africa) [ 9 , 10 ]. The impact of RVV on diarrhoea morbidity and mortality outweigh the risk of intussusception and associated mortality [ 11 ].…”