Rotavirus vaccine: Is it worth doing?

August 2006

The FDA and the Vaccines for Children program both approved a new rotavirus vaccine (RotaTeq, Merck) in February.

The final Advisory Committee on Immunization Practices (ACIP) recommendations are scheduled for publishing in the Morbidity and Mortality Weekly Report on Aug. 11, 2006, but provisional recommendations are available at the CDC Web site. Three doses, to be given in two-month intervals, will cost $63.25. RotaShield, a previous rotavirus vaccine, was withdrawn because it was associated with an increased risk of intussusception. Whether parents will accept this expensive vaccine that causes a common but little known disease whose main association is intussusception is an interesting question.

Effects of infection

If you are the gaming sort and like to play the odds, it is estimated that four of five children are likely to be infected with a rotavirus before age 5. The disease is characterized by emesis, diarrhea and fever. The fever can be quite high and dehydration is a significant problem.

It is estimated that one in seven will require a medical visit, one in 78 will be admitted to the hospital and that one in 200,000 will die.

Viral shedding starts before the onset of diarrhea and relatively few virus particles are needed to infect. Thus, a lot of rotavirus infections occur in out-of-home care.

Rotavirus infections spread from the southwest United States late in the year and move east, reaching the northeast in the winter months. From a medical economist’s point of view, rotavirus infections are responsible for about a half-million physician visits and 50,000 hospitalizations annually.

Preclinical studies included tens of thousands of infants who were carefully observed for evidence of intussusception. It occurred in equal numbers in the vaccinated and the control groups.

Several hundred thousand infants have received the vaccine since licensure, and there is no suggestion that it will result in an excess number of cases of intussusception. A careful post-marketing surveillance program is in place to monitor for this condition.

The current vaccine is derived from a bovine strain of rotavirus. RotaShield was a rhesus virus derived strain. The new strain also appears to be somewhat less reactogenic than the previous one.

RotaTeq appears to be effective in preventing infection, reducing the incidence of diarrhea by about 74%; more importantly, it is protective against severe diarrhea leading to hospitalization. It is relatively free of adverse events; diarrhea and vomiting were found to be only marginally more common in vaccine recipients. It is recommended for use in infants born at least 32 weeks of gestation provided they have been discharged from the nursery, are at least 6 weeks of age and are in stable condition. Breast-feeding or concurrent administration of other vaccines are not contraindications nor is mild illness, including slight diarrhea or fever.

The vaccine is a live bovine-human recombinant vaccine. Administration to immunocompromised individuals or to people living with these individuals, or potential exposure of pregnant women — all of which are contraindications for many other live vaccines — are simply listed as “precautions” in the recommendations for RotaTeq. No special measures are required if vaccinated individuals are admitted to the hospital. There is some vaccine virus shedding after the first dose and negligible amounts after subsequent doses. Routinely, the vaccine is given at ages 2 months, 4 months and 6 months. It is not recommended for older infants and the third dose should not be given after 32 weeks. If emesis of a dose occurs, the vaccine need not to be repeated. It is stored at refrigerated temperatures.

The issue

The cost of this vaccine is an issue for parents, physicians and for developing countries. Its price is derived from a complicated formula, the incremental cost effectiveness ratio (ICER), which is calculated from the cost saved less cost of vaccine divided by the disability-adjusted-life-year (DALY) saved. These values obviously will vary from country to country. It is also obvious that the countries that most need this vaccine are least able to afford it.

It is estimated that there are 100 million episodes of gastroenteritis globally, of which 25 million require medical attention and 2 million are hospitalized. There are almost half a million deaths due to rotavirus (Emerg Infect Dis. 2003:9;565). The WHO establishes priorities for its programs based on the ICER for various countries. Vaccines are competing for resources with other programs, eg, mosquito netting, drugs for prevention of parasitic diseases, etc. Obviously money must be found to pay for these programs in countries that cannot afford them. In addition, companies reduce the prices of vaccines for these countries and alternative less costly vaccines are being developed in China and India.

The issue of how practitioners will pay up front for this and other expensive vaccines is also a major problem. I have been told that at least one company has extended the period for payment and that efforts are being made to obtain reimbursement from insurance companies in a timely manner.

Finally, at least one competing vaccine is expected in the near future (N Engl J Med. 2006:354;11).

For more information:

• Provisional recommendations for the Rotavirus vaccine provided by the Advisory Committee on Immunization Practices and the Vaccines for Children program can be found at www.cdc.gov/nip/vfc/acip_resolutions/0206rotavirus.txt