Optimizing Metabolism

by Ingrid Kohlstadt, MD, MPH

Emerging Global Changes in Rotavirus Epidemiology

Overview

The epidemiology of diarrheal disease is different than it was 20 years ago and even 2 years ago. The biggest factor leading to this change is immunization against rotavirus. In this Townsend Letter on gastroenteritis and travel health, I reflect on the Vaccine Day 2015–2016 keynote talk given by Roger Glass, MD, PhD, of NIH at Johns Hopkins Bloomberg School of Public Health. The column does not focus on the vaccine itself or the risks and benefits of vaccines, but on immunization’s impact.

The Hospitals Have Fewer Admissions for Diarrhea

The FDA website states, “Background: Before the introduction of rotavirus vaccines, most children in the United States became infected with rotavirus before two years of age, causing an estimated 55,000-70,000 hospitalizations and 20-40 infant deaths in the United States each year.”

For Glass, this statement holds a personal story. His wife, Barbara Stoll, MD, is a neonatologist who was chief of pediatrics at the time that he began researching rotavirus. While she was bringing patients to the hospital, he was working just as diligently at getting them discharged.

The Epidemic Curve Has Changed

Hospital admissions for diarrheal diseases peak in winter. Most of those cases were called “idiopathic.” meaning the cause was unknownspital admissions have been attributed to rotavirus. Rotavirus immunization has been steadily flattening the winter peak for diarrheal disease admissions. In developing countries such as in Bangladesh, where Dr. Glass began his clinical stof diarrheal disease, the monsoon season was the peak of the epidemic curve. That, too, has flattened.

Herd Immunity Is Conferred

Herd immunity reduces the severity of disease even among those individuals who didn’t get immunized. The infection doesn’t spread in communities as quickly or extensively as it did prior to immunization.

Immunizing Against One Strain of Rotavirus Confers Protection Against All Strains

Unlike influenza and dengue, with rotavirus the immunization with one strain is cross-protective. Only one strain is needed for protection and exposure to another strain doesn’t increase severity.

Intussusception As a Vaccine Risk

The first rotavirus vaccine was stopped because of intussusception. Intussusception remains a risk and having had intussusception from any cause in the past contraindicates rotavirus vaccine.

Here’s what the FDA notes on its website about intussusception risk:

RotaShield (Wyeth Laboratories) was the first vaccine licensed for the prevention of rotavirus gastroenteritis in infants. RotaShield was voluntarily withdrawn from the market by the manufacturer after studies suggested an elevated risk of intussusception, estimated at approximately 1 case per 10,000 vaccine recipients. Prior to licensing RotaTeq and Rotarix, the risk of intussusception was assessed in large clinical trials of more than 60,000 children for each vaccine. No increased risk for intussusception was observed for either vaccine. However, several post-licensure studies conducted in other countries subsequently suggested potential increased risk of intussusception after both Rotarix and RotaTeq.

Maternal Antibodies Can Interfere with Vaccine Effectiveness

The rotavirus vaccines are more effective in the US than in India. From a scientific standpoint, this is an intriguing question for ongoing research. One hypothesis is that maternal antibodies may interfere with disease effectiveness.

From the lens of public health, oral vaccines have worked less well in the places that they are needed the most – where the disease morbidity and mortality are highest. India has put forward an innovative approach, which I describe in the next section.

Psychosocial Factors

In India, Bharat Biotech produced a vaccine from a rotavirus strain isolated in that country. The clinical trials have taken place in India and are of equal or greater effectiveness for the Indian population. They are making the vaccine available for $1 a dose. Immunization against rotavirus has become a matter of national pride, and vaccine uptake is very high. Disease mortality in India has decreased 8-fold.

Probiotics Can Influence Disease Response

Prior to the vaccines, probiotics reduced susceptibility for rotavirus among high-risk individuals. In 1993 Dr. Jose (Pepe) Saavedra proposed using a strain of probiotics in pediatric gastroenterology patients, and observed a reduction in diarrheal disease. Specifically, it reduced rotavirus infection. I think that Saavedra’s study was the first clinical probiotics study at Johns Hopkins Hospital. Many have built on his work, including the study of probiotics in travelers. Probiotics may also reduce rotavirus incidence in travelers.

Summary

Immunization is changing the epidemiology of rotavirus worldwide. The rates and severity of diarrheal disease in young children and the community at large is changing in response to immunization. The immunization is enabling science to deepen its understanding of rotavirus disease. However, much remains unknown, such as how the lower rates of rotavirus in our population will influence the immune system in the future. To be vigilant about such unknowns, research into the gut microbiome and ongoing epidemiology will be important. In other words, alternative-medicine approaches to health and healing, which have long considered the gut–immune system connection, may be readily applicable to vaccine safety.

Ingrid Kohlstadt, MD, MPH, FACPM, FACN

Faculty Associate, Johns Hopkins Bloomberg School of Public Health

Executive Director, NutriBee National Nutrition Competition Inc.

Editor, Advancing Medicine with Food and Nutrients (CRC Press; 2013)