Increased Cases of Rotavac-Induced Intussusceptions After the Third Dose Explained by Background Rates

Historical Context: Rotavirus is a leading cause of severe diarrhea among infants and young children globally. The introduction of rotavirus vaccines, such as Rotavac, has significantly reduced the incidence of rotavirus-related hospitalizations and deaths. However, concerns about vaccine safety, particularly the risk of intussusception (a form of bowel obstruction), have been a topic of ongoing research and debate. Intussusception is a condition where a part of the intestine folds into another section, which can be life-threatening if not treated promptly. The historical context of this issue dates back to the early 2000s when the first rotavirus vaccine, RotaShield, was withdrawn from the market due to its association with intussusception. Subsequent vaccines, including Rotavac, have been closely monitored for similar risks.

Article Summary: In response to the article “Increased Cases of Rotavac-Induced Intussusceptions” by Brian Hooker and Jacob Puliyel, published on July 5, 2024, in the International Journal of Risk & Safety in Medicine (IJRSM), this analysis delves into the increased risk of intussusception following the third dose of Rotavac. The key findings and explanations are as follows:

1. Increased Risk Post-Third Dose:

   • The risk of intussusception increased nearly 2.5 times within 21 days after the third dose when unvaccinated individuals were excluded from the analysis.
   • The third dose administration peaked at 16-17 weeks and then declined sharply until 20-21 weeks, tapering off by 26-27 weeks.

2. Delayed Administration:

   • The third dose is scheduled for 14 weeks of age, but children often received it at a median age of 18 weeks, overlapping with the peak age for intussusception.
   • This delay in administration explains the higher number of cases observed after the third dose.

3. High-Risk Period Analysis:

   • The bar chart in Figure 2 of the NEJM paper illustrates the distribution of intussusception cases among vaccinated infants during the first 21 days (high-risk period) and up to 59 days post-vaccination.
   • The large number of cases during and after the high-risk period following the third dose correlates with the delayed administration.

4. Temporal Association:

   • SCCS studies worldwide have used the 1-21 days post-vaccination as the high-risk period.
   • The IJRSM paper’s choice of two time windows (0-30 days and 31-60 days) to detect temporal association appears misleading, as cases do not abruptly stop after 60 days.

5. Intussusception Cases Beyond 60 Days:

   • Cases of intussusception continue beyond 60 days, as shown in Figure 2 and Table 1 of the NEJM paper.
   • The number of cases during the high-risk window (1-21 days) and beyond (22-59 days) is significant, indicating that restricting analysis to 180 days is misleading.

6. Age Distribution:

   • Intussusception cases peak around 7 months in unvaccinated children, with a median age of 4-8 months in Asia.
   • A retrospective surveillance in India found the median age for intussusception to be eight months, with a peak between four and six months.

7. Misleading Timeframe:

   • The NEJM paper shows that intussusception cases remain high until the end of the first year, with cases appearing even at 50-51 weeks.
   • Limiting the analysis to six months does not accurately reflect the risk of intussusception post-vaccination.

Summary in Bullet Points:

• Increased Risk: Intussusception risk increased 2.5 times within 21 days post-third dose.
• Delayed Administration: Third dose often given at 18 weeks, overlapping with peak intussusception age.
• High-Risk Period: Significant cases observed during 1-21 days and up to 59 days post-vaccination.
• Temporal Association: Misleading to use only 0-30 and 31-60 days windows for analysis.
• Cases Beyond 60 Days: Intussusception cases continue beyond 60 days post-vaccination.
• Age Distribution: Peak intussusception age is 4-8 months, with a median of eight months in India.
• Misleading Timeframe: Six-month analysis period does not fully capture intussusception risk.

This detailed analysis provides a comprehensive understanding of the increased cases of Rotavac-induced intussusceptions, emphasizing the importance of accurate timing and risk assessment in vaccination programs.