By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN

Dr. Fischer reports no financial relationships relevant to this field of study.

SYNOPSIS: Routine rotavirus vaccination of infants, when implemented broadly, is safe and is associated with reductions in diarrhea-related hospitalizations, mortality, and morbidity (such as malnutrition) in children.

SOURCE: Marquis A, Koch J. Impact of routine rotavirus vaccination in Germany: Evaluation five years after its introduction. Pediatr Infect Dis J 2020;39:e109-e116.

Two live attenuated, oral rotavirus vaccines became available in Germany in 2006, a time when rotavirus was the most common cause of gastroenteritis in preschool-age children and when rotavirus accounted for approximately 20,000 hospitalizations each year. However, there was concern that rotavirus vaccine increased the risk of intussusception, especially in older infants, so vaccination was initiated by the 12th week of life. Rotavirus vaccination became part of the standard immunization program in 2013, and Marquis and Koch looked back on outcomes of routine vaccination after five years of the use of these vaccines.

During the first five years of routine rotavirus immunization of infants in Germany, coverage by vaccination reached 80% of infants. The incidence of documented outpatient rotavirus gastroenteritis in preschool-age children dropped by 74% to 194 per 100,000 population, and the incidence of rotavirus-related hospitalizations dropped 70%. The improvements were most notable in the youngest age groups. The incidence of rotavirus infection also dropped in children who were too old to receive vaccination, suggesting some protection via herd immunity. Interestingly, the winter season of rotavirus infections shifted with vaccination to begin six weeks later.

There was no evidence for an increase in rotavirus disease in older populations, indicating that vaccination did not merely delay the onset of risk of becoming ill with rotavirus. With widespread rotavirus immunization in Germany, the incidence of intussusception during the first year of life actually dropped 28% (P < 0.001) to 48 per 100,000 children.

COMMENTARY

With so much bad health news in the world these days and with so much societal pressure for a new coronavirus vaccine, it is nice to be reminded of some good news. Routine vaccination works.

This new report from Germany represents valuable post-marketing evaluation of the vaccine and its programmatic implementation. As such, it is useful. Indeed, initial post-marketing evaluation of an earlier rotavirus vaccine revealed an increased risk of intussusception.1 The current vaccine and program being used in Germany has now been shown to be safe and effective. Routine rotavirus vaccination in Germany was associated with decreased incidences both of outpatient and inpatient rotavirus illnesses. The vaccine also was safe in a large population-level follow-up and was not associated with increased later-life rotavirus infections, suggesting mere delays in disease acquisition. Not only was there not an increased risk of intussusception, but vaccination also seemed to protect against intussusception.

Rotavirus was isolated and identified as a cause of childhood diarrhea in 1969.2 Since 2006, four live attenuated, oral rotavirus vaccines have been developed and used around the world.2 Overall, 107 countries have rotavirus vaccination programs, but 90 countries still do not have programs for routine rotavirus vaccination.2

Gastroenteritis is a significant cause of childhood death worldwide, and rotavirus-related diarrhea still accounts for huge cost, morbidity, and even some mortality in the United States. Initial rotavirus vaccine efforts were compromised with the finding of an increased risk of life-threatening intussusception after vaccination. Newer rotavirus vaccines, as seen in the study in Germany, do not have that problem.

Rotavirus vaccination is part of the current American routine childhood immunization series. Different rotavirus vaccines are made with different strains of human and bovine rotavirus antigens.1 Based on risks seen in older infants receiving previous versions of the vaccine, the vaccine series (two or three doses, depending on the specific vaccine) should not be started after 15 weeks of age, and no dose should be given after 8 months of age.1 Now, approximately 73% of U.S. infants receive a rotavirus vaccine, and the vaccine is credited with preventing about 50,000 hospitalizations for rotarvirus diarrhea in the United States each year.1

In the United States, for the past 25 years, the costs of routine childhood vaccines have been covered by the government for many children. The Vaccines for Children program accounts for half of all childhood vaccines in the United States and is credited with improving vaccination rates and reducing racial and ethnic disparities in vaccine coverage.3 This government-funded program has sustainably overcome legislative, access, and financial barriers to childhood vaccination. Nonetheless, the administration of vaccines against all 16 diseases covered by this program is estimated to cost approximately $2,000 per child.3 In India, rotavirus vaccine programs were instituted in 2016, with a phased approach including more states in each phase.4

Obviously, rotavirus vaccines are not just for Germany, the United States, and India. A recent review of the global impact of rotavirus vaccination evaluated pre-vaccine and post-vaccine data from 49 countries on six continents.5 Overall, among preschool-age children, there was a 59% reduction in rotavirus-related hospitalization, a 36% reduction in acute gastroenteritis-related hospitalization, and a 36% reduction in gastroenteritis-related mortality.5

Worldwide, more than one-third of childhood deaths are associated with malnutrition. Acute gastroenteritis and recurrent bouts of diarrhea both are causes and consequences of malnutrition. In Kiribati, a Pacific island nation where malnutrition was common, the rate of gastroenteritis-related hospital admissions dropped by 44% with implementation of a rotavirus vaccination program, and the incidence of severe acute malnutrition dropped by 24%.6

Since rotavirus vaccines are live, there has been concern about giving them to hospitalized children who might inadvertently spread live vaccine virus to compromised patients. Thus, it has been routine not to give the vaccine to babies in neonatal intensive care units until their day of discharge from the hospital, potentially limiting vaccine coverage in this vulnerable population. A recent review of 31 relevant papers shows that virus was shed by vaccinated children, but that transmission of infection was very rare and only occurred in household settings.7 It was suggested that it might not be necessary to preclude hospitalized newborns from vaccination at the normal age-based schedule times.7

REFERENCES

  1. Jacobson RM. Routine childhood vaccines given in the first 11 months of life. Mayo Clin Proc 2020;95:395-405.
  2. Folorunso OS, Sebolai OM. Overview of the development, impacts, and challenges of live-attenuated oral rotavirus vaccines. Vaccines 2020;8:E341.
  3. Schwartz JL, Colgrove J. The Vaccines for Children Program at 25 — access, affordability, and sustainability. N Engl J Med 2020;382:2277-2279.
  4. Malik A, Haldar P, Ray A, et al. Introducing rotavirus vaccine in the Universal Immunization Programme in India: From evidence to policy to implementation. Vaccine 2019;37:5817-5824.
  5. Burnett E, Parashar UD, Tate JE. Global impact of rotavirus vaccination on diarrhea hospitalizations and deaths among children < 5 years old: 2006-2019. J Infect Dis 2020; in press. doi: 10.1093/infdis/jiaa081.
  6. Lai J, Nguyen C, Babwaia B, et al. Temporal decline in diarrhea episodes and mortality in Kiribati children two years following rotavirus vaccine introduction, despite high malnutrition rates: A retrospective review. BMC Infect Dis 2020;20:207.
  7. Sicard M, Bryant K, Muller ML, Quach C. Rotavirus vaccination in the neonatal intensive care units: Where are we? A rapid review of recent evidence. Curr Opin Pediatr 2020;32:167-191.