Hospitalizations, deaths keep declining after rotavirus vaccine introduction

Researchers continue to note declines in deaths and hospitalizations after the implementation of routine rotavirus vaccination. If this pattern holds, greater population protection than expected may be attained in developing country settings.

Twelve studies published as a special supplement to The Pediatric Infectious Disease Journal summarized data on the decline in the number of children who are hospitalized due to rotavirus infection in countries that include rotavirus vaccines as part of their routine immunization programs.

“These studies add to the growing body of evidence that shows rotavirus vaccines are safe, effective and, most importantly, saving children’s lives,” Anne Schuchat, MD, who is director of the National Center for Immunization and Respiratory Diseases at the CDC, said in a press release about the studies. “Unfortunately, too many children around the world get severely ill or die from this preventable disease. We must continue to expand our efforts to ensure that children around the world have access to these vaccines.”

Infectious Diseases in Children Editorial Board member Fernando Guerra, MD, said: “The reduction in morbidity and mortality, let alone the severity of the disease, is nothing less than remarkable. Here in my own community of San Antonio, Texas, where the disease historically has been prevalent during the rotavirus season, the number of emergency department, clinic visits and hospital admissions has steadily declined during the past 3 to 4 years, as the uptake of the vaccine increases.”

Study highlights

Lucia Helena de Oliveira, RN, MSc, and colleagues of the Comprehensive Family Immunization Project, Pan American Health Organization in Washington, D.C., reported that 12 of 15 Latin American and Caribbean countries are using the vaccines, but “coverage levels need to increase to maximize the effect of the intervention,” they said. In this study, the researchers call for better rotavirus surveillance to “better assess the effect of vaccine use.”

In El Salvador, rotavirus hospitalization rates for children younger than 5 years declined by 69% to 81% in the 2.5 years after the introduction of rotavirus vaccine in October 2006. Led by Catherine Yen, MD, MPH, and colleagues from the El Salvador Ministry of Health, Pan American Health Organization and CDC, the researchers compared all-cause diarrhea and rotavirus-specific hospitalization rates in seven sentinel surveillance hospitals before the vaccine in 2006 with the years after vaccine introduction. The research showed that among sentinel surveillance hospitals, rotavirus hospitalization rates among children younger than 5 years declined by 81% (95% CI, 78-84) in 2008, when two-dose rotavirus vaccine coverage was 50% among newborns. The decline was about 69% (95% CI, 65-73) in 2009, when the two-dose vaccine coverage grew to 61% among newborns. The researchers also observed declines of 48% and 35% in 2008 and 2009, respectively, in the national diarrhea-related health care visits.

“When a new vaccine is introduced, it generally takes some time for vaccine compliance to rise to levels comparable to other well-established vaccines. Thus, vaccine compliance with rotavirus vaccine was not expected to have reached full coverage at the time these vaccine impact studies were completed,” Yen told Infectious Diseases in Children. “However, even at lower coverage levels, we were able to see a substantial positive impact of rotavirus vaccines on disease burden.”

In Mexico, which introduced the rotavirus vaccine in May 2007, there was a 40% decline in diarrhea-related hospitalizations in children younger than 5 years in the 2 years after vaccine introduction. In this study, led by Manjari Quintanar-Solares, MD, and colleagues from the CDC, the researchers obtained data from 306 Ministry of Health hospitals on diarrhea-related hospitalizations between January 2003 and June 2009, and they compared the median number of diarrhea-related hospitalizations during the 2008 and 2009 rotavirus seasons with the median number of diarrhea-related hospitalizations from 2003 to 2006. A median number of 10,993 diarrhea-related hospitalizations occurred each prevaccine rotavirus season from 2003 to 2006, but that number decreased to 9,836 in 2008 and again to 6,597 in 2009. The researchers noted no declines during 2008 or 2009 among unvaccinated children.

In Panama, Yadira Molto, MD, and colleagues from the CDC obtained monthly numbers of diarrhea-associated hospitalizations among children younger than 5 years in five health regions in Panama, representing 53% of the birth cohort. The researchers said during the prevaccine years of 2003 to 2006, diarrhea-associated hospitalizations averaged about 4,057 annually, but that number decreased to 3,159 in 2007 and to about 2,500 in 2008. This reduction in rotavirus coincided with increasing use of the rotavirus vaccine, from 63% at the end of 2006 to 94% by the end of 2008.

In the United States, Jacqueline Tate, PhD, and colleagues from the CDC reported there was a significant 58% to 86% reduction in rotavirus detections in the 3 years after vaccine introduction in July 2006. The researchers on that study concluded that: “Rotavirus vaccine has been widely accepted by pediatricians. Vaccine coverage is steadily increasing but remains lower than coverage levels of other routine infant immunizations.”

In an interview with Infectious Diseases in Children, Tate said: “There are many barriers for total compliance with rotavirus vaccines, and many of these are country specific. Individual countries need to assess what their particular barriers are and how best to address them.”

In Australia, Jim Buttery, FRACP, MSc, and colleagues from the Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Victoria, said after rotavirus vaccine introduction in July 2007, there was an 89% to 94% reduction in rotavirus-related hospitalizations in children younger than 5 years living in Queensland in the 2 years after vaccine introduction. Researchers in Australia also noted changes among dominating strains based on which vaccines were used in a specific location. In that study, the researchers noted, G1P[8] was the dominant genotype nationally, followed by G2P[4], G9P[8] and G3P[8].

“G2P[4] strains were more prevalent in states using Rotarix (Glaxo-SmithKline), whereas G3P[8] strains were more prevalent in states using RotaTeq (Merck),” the researchers concluded.

The Australian studies also suggested that there were large reductions in rotavirus disease among older, unvaccinated children, suggesting herd immunity played a role.

“The overall rates of reduction in rotavirus gastroenteritis that are being observed are beyond what can be attributed to the vaccine itself, as there are still many infants who are not vaccinated, nor have they completed the series,” Guerra said. “Also there seems to be limited transmission to older siblings as close household contacts, and who are of an age that would not have received the vaccine. As the Australian studies suggest that viral shedding and transmission of specific serotypes contribute to herd immunity in those defined populations, the same could be demonstrated in my community here. Such further attests to the efficacy and immunogenicity of the rotavirus vaccines, which definitely occupy an important place on infant immunization schedules.”

Rotavirus recommendations

Diarrhea is one of the top two killers worldwide of children younger than 5 years, and rotavirus is the leading cause of severe diarrheal disease in children. Each year, rotavirus-related diarrheal disease takes the lives of more than 500,000 children younger than 5 years and is responsible for millions of more hospitalizations.

In 2009, WHO officials recommended that all countries include rotavirus vaccines in their national immunization programs. Prevention and treatment of diarrhea also includes oral rehydration therapy, exclusive breast-feeding, zinc treatment, and improved hygiene and sanitation. Although most children in the world will be infected with rotavirus by their third birthdays, children in developing countries more often die of diarrhea caused by rotavirus because treatment for severe infections is often limited or inaccessible.

“Wherever we look, in both the developed and developing worlds, we see a rapid and impressive reduction in rotavirus infections following the roll-out of vaccine,” John Wecker, PhD, director of the Vaccine Access and Delivery Global Program at PATH, said about the studies in a press release. “Vaccine effectiveness often takes years to document; with rotavirus, there is an immediate dramatic impact — one which should compel decision-makers and donors to support and implement the WHO recommendation to introduce rotavirus vaccines today.” – by Colleen Zacharyczuk

For more information:

• Patel MM. Pediatr Infect Dis J. 2011;(suppl 1):S1-S66.

Disclosures: Drs. Guerra, Schuchat, Tate and Yen report no relevant financial disclosures.

Do you think the predominant strains of rotavirus will change as rotavirus vaccines are more commonly used? Will adjustments have to be made to the vaccines?

As far as the Australian findings, I don’t think we should be making adjustments to the current rotavirus vaccines just yet. The variation in the influenza strains requires yearly adjustments to these vaccines. Rotavirus strains do vary from year to year and location to location, but the most common serotypes tend to be seen yearly even though the proportion of each serotype varies. Trying to tailor which vaccine you use based on last year’s strains would be difficult to implement because, generally, pediatricians are going to stock whatever vaccines they have access to and also are the least costly to purchase. Unless there is a recognized difference in efficacy between vaccines, cost is a major factor in vaccine purchase. In Rhode Island, for instance, the state buys vaccines for all children, but in other areas, the individual pediatricians may buy based on what they are accustomed to giving and based on cost to them. Unless there is a clear difference in the ability of the current rotavirus vaccines to prevent infection in the United States, there is no indication at the present time to favor one rotavirus vaccine over the other.

It is interesting to note that there have been papers from Brazil that show predominance of a strain which might not have been well covered by the rotavirus vaccine program, so it really is too early to tell. Obviously, rotavirus strain variation needs to be closely followed over time to see if either vaccine has deficiencies and to see if there are any serotypes emerging that should be added to those already covered by the current rotavirus vaccines.

Penelope Dennehy, MD, is the director of the division of pediatric infectious disease at Hasbro Children’s Hospital, professor and vice chair for academic affairs in the department of pediatrics at Alpert Medical School, Brown University, Providence, R.I.

Disclosure: Dr. Dennehy reports no relevant financial disclosures.

Since we have been using the rotavirus vaccine here in the United States, it seems, at least in my experience, that we have had terrific results. I myself have not seen a case of rotavirus in 10 to 12 years, with the exception of two babies whose moms refused the vaccine.

As far as the data out of Australia, it is something to keep an eye on. Australia – population-wise – is small, but they have a decent-sized land mass, so if they are noticing these strains as a problem, it will be something to watch. If this data are duplicated, then we may have to look at the idea of changing strains in the vaccine, as is done with the influenza vaccine. However, before looking at changing strains year to year, the data have to be looked at and replicated across the world, particularly in Third World countries.

I would love to see the data coming out of India and China, and we will see this data emerge as many vaccine companies are scrambling to get into China. It is in these areas where you will see the greatest impact in terms of disease prevention and where you will also be able to see the predominating strains.

Richard Lander, MD, is a member of the Infectious Diseases in Children Editorial Board. He is in private practice in Livingston, N.J., and is the New Jersey Chairman of the AAP section on Administration and Practice Management; and is a clinical assistant professor of pediatrics at the University of Medicine and Dentistry of New Jersey.

Disclosure: Dr. Lander is a speaker for Merck.