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The Wide World of Vaccines

August 2019

Good News/Bad News about Rotavirus Vaccine and U.S. Pediatric Deaths from Diarrheal Disease

Dr. Harrison.jpg            

Christopher J. Harrison, MD, FAAP, FPIDS
 | Director, Infectious Diseases Research Laboratory | Director, Vaccine and Treatment Evaluation Unit | Professor of Pediatrics, UMKC School of Medicine

There has been a dramatic decrease in diarrheal disease due to rotavirus (RV) since the universal implementation of two RV vaccines. The first RV vaccine was put into use in 2005. Dr. Jackson’s Link column last month reviewed some of the data documenting the decline in RV disease. But new information published this month1 raises some concerns.

RV disease is not commonly thought of as having a fatal outcome in the U.S., but investigators from the Centers for Disease Control and Prevention (CDC) recently reviewed diarrhea-related mortality data of children 1 to 48 months old during 2005 to 2016.1 In their analysis, diarrheal-related fatalities decreased overall, but racial disparities persist for diarrheal death rates. Race was determined using U.S. Census data and diarrheal deaths were tallied using ICD-9 codes.

A prior 1995 CDC report2 from the pre-RV vaccine (1968 to 1991) era had shown that overall annual diarrheal death rates/100,000 population over the entire period averaged 8.3 for white race, 33.1 for African American race and 19.5 for race labeled as “other.” Figure 1.

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Figure 1

In the newest report from the RV vaccine era,2 diarrheal death rates from the two years just after RV vaccine implementation (2005 to 2006) were compared to the last two years for which complete diarrheal death data are available (2014 to 2016). Overall, annual diarrheal death rates declined 75% from the pre-vaccine era to 2.3/100,000 in 2005 to 2006, and even further to 1.7/100,000 in 2014 to 2016. Decreases were noted for both white and African American races, Figure 2, and were mostly in those less than 24 months old.

However, African American children still have a higher diarrheal death rate than white, American Indian and Asian American children. What are the reasons for this racial disparity? First we need to acknowledge that diarrheal deaths are not exclusively rotavirus related, so even a 100% effective RV vaccine would not eliminate all diarrheal deaths. Also, medical care for diarrheal disease has improved nationally since the 1960s due to oral rehydration, better access to care, improved child nutrition programs and better public health monitoring of outbreaks.

If one looks at the diarrheal death rate trends pre-vaccine, there was a gradual drop, Figure 1, likely related to these improvements in health care. So the major impact of RV vaccine for all but the African American race has been less hospitalizations and less diarrheal disease, not a major change in death rates. Nevertheless, RV vaccine use appears to have been associated with lower diarrheal death rates in African Americans. But the rate is still higher than for other races. Figure 2.      

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Figure 2

Among the likely multiple reasons for the disparity, access to medical care remains a concern for African American children, not just for diarrheal disease, but for health care in general. Alternatively, one could postulate genetic factors causing more severe disease in African Americans. However, FUT-2 nonsecretor status (the best defined genetic protective factor against RV and Norovirus) is as frequent in African Americans as in whites and Asians. FUT-2 is an epithelial receptor on gut mucosa that acts as the attachment point for some enteric viruses. Among African Americans and whites ~20% are nonsecretors (naturally protected against certain virus genotypes), whereas among Hispanics and American Indians, only ~10% are nonsecretors.3,4  

RV vaccine has a lower uptake overall than DTaP (~80-93%) uptake.5 Part of the issue with lower RV vaccine uptake is the restrictive window for administration in the package insert. This affects all races and hopefully that restriction can soon be reviewed by the FDA and made less restrictive. To improve the chances of completing the schedule, some clinicians have chosen to use the two-dose vaccine formulation in hopes two well visits can occur within the window.

Of note, however, is that African American race has been shown to be a predictor of a 20% less chance of having received RV vaccine.5 So, one approach to further reducing diarrheal death rates in African American children <5 years old may be additional targeted public health and private campaigns to allow easier access to RV vaccine for African American children during the restrictive window timeframe. Maximizing herd immunity is also something for which we can strive. Finally, we can also ensure we take advantage of every immunization opportunity so that the next CDC report can show that the diarrheal death rate in African American children drops to the same level as other races.    

References

  1. Diarrhea-Associated Mortality in Children Less Than 5 Years of Age in the United States, 2005–2016. Aliabadi N, Pham H, Curns AT, Rha B, Tate JE, Parashar UD. Pediatr Infect Dis J 2019 38(7): e153-e154.   

  2. Trends of Diarrheal Disease-Associated Mortality in U.S. Children, 1968 through 1991. Kilgore PE, Holman RC, Clarke MJ, et al. JAMA. 1995;274: 1143–1148. 
       
  3. Epidemiologic Association Between FUT2 Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States. Payne DC, Currier RL, Staat MA. JAMA Pediatr. 2015;169(11):1040-1045. 

  4. Innate Susceptibility to Norovirus Infections Influenced by FUT2 Genotype in a United States Pediatric Population. Currier RL, Payne DC, Staat MA, et al. 2015 CID 60(1):1631-1638. 

  5. Factors Associated With Rotavirus Vaccine Coverage. Aliabadi N, Wikswo ME, Tate JE, et al. Pediatrics 2019 143(2): e20181824.