SAN DIEGO – The potent synergistic benefits of coadministration of rotavirus vaccine and pneumococcal conjugate vaccine in young children are uniquely highlighted by a natural experiment conducted in southern Israel as described by Dr. Ron Dagan at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
Dr. Dagan is professor of pediatrics and infectious diseases at Soroka University Medical Center in Beersheba, Israel. It’s the sole hospital in a large, well-defined area of southern Israel. All children in that part of Israel are born in the hospital and receive their health care there, making it possible to generate highly reliable disease incidence data.
Dr. Ron Dagan
At any given time, physicians at the hospital are responsible for the care of roughly 30,000 children less than 2 years of age. So there’s a huge study population, comprehensive follow-up, and – the final element in this prospective, population-based study – the rotavirus and pneumococcal conjugate vaccines were introduced in Israel just a few years ago and at roughly the same time. This enabled Dr. Dagan and his coinvestigators to compare hospitalization rates and pediatric emergency department outpatient visits for diarrheal and lower respiratory viral illnesses among children less than 2 years old during the prevaccine period of April 2006-March 2009 with rates during April 2013-March 2014, when uptake of the two vaccines in that age group exceeded 90%.
This was an unusual study in that it looked at the global impact of two major vaccines. In contrast, vaccine clinical trials and postmarketing studies typically evaluate only those outcomes directly related to that particular vaccine.
The results of the Israeli study were startling: in the 3 years prior to introduction of the vaccines, one in five children under age 2 years admitted to the hospital had as an admitting diagnosis either rotavirus gastroenteritis confirmed by a positive stool ELISA test or pneumococcal pneumonia as evidenced by alveolar pneumonia on chest x-ray. After the vaccines became available, the hospitalization rates for rotavirus gastroenteritis and alveolar pneumonia plummeted by 78% and 46%, respectively. Moreover, outpatient pediatric emergency department visits for rotavirus gastroenteritis dropped by 71% and visits for alveolar pneumonia fell by 67%.
But that’s not all. Smaller yet clinically meaningful reductions were also documented in nonrotavirus gastroenteritis and nonalveolar lower respiratory tract infections. Specifically, the hospitalization rate for nonrotavirus diarrheal illnesses and nonalveolar pneumonia lower respiratory infections dropped by 21% and 7%, respectively, while outpatient emergency visits for those disorders fell by 16% and 14%.
This translates to an estimated 1,890 fewer hospitalizations and 4,030 fewer outpatient emergency department visits for diarrheal disease or lower respiratory infection per 100,000 children under age 2 per year, Dr. Dagan reported.
Michael Schmidt, Ph.D., who chaired a press conference highlighting the Israeli study, declared, “These data are absolutely phenomenal. It really shows the global value of these vaccines for society.”
Dr. Schmidt, professor and vice chairman of microbiology and immunology at the Medical University of South Carolina, Charleston, posed a question: What’s the explanation for the reductions in diseases not directly addressed by those two vaccines?
“We believe that one success can favorably affect the other. If you are weakened by diarrhea, you may be more likely to get pneumonia, and vice versa,” according to Dr. Dagan.
He added that the results actually pack a significantly greater wallop than is apparent at first look because rotavirus gastroenteritis and pneumococcal pneumonia in young children are seasonal diseases. They occur chiefly during October-March. So those 5,920 fewer hospitalizations and outpatient visits/100,000 per young children per year are concentrated during pediatricians’ busiest half of the year.
“In most places in the world, winter is a time of so much illness that pediatricians can’t deliver appropriate care. We knew that in our hospital we couldn’t deliver appropriate care to children in the winter because there were so many sick children piled on top of each other. But now, because of these two vaccines, we are less crowded in the winter, we have more time for children, we make fewer mistakes,” he said.
The study was funded by vaccine manufacturers and the Israel Ministry of Health. Dr. Dagan reported serving as a consultant, adviser to, and/or recipient of research grants from GlaxoSmithKline, Merck Sharp & Dohme, Pfizer, and Genocea.