Immunizations

Background

Immunizations have been widely used to prevent and even eradicate diseases globally. Their use for diarrheal disease is subject to debate; Rotavirus is the most common cause of severe diarrheal disease, especially in children, and has therefore been the focus of most vaccination attempts (Zwane, 2007, pg. 5). Most individuals assume that providing clean drinking water and improving sanitation and hygiene will significantly reduce the spread of rotavirus.  However, what most people do not know is that they can not assume that the rotavirus can be controlled like other water borne diseases.  The rotavirus is found in all countries of the world, no matter how well the infrastructure of a country is at providing clean water and sanitary living conditions.  This is one of the most dangerous information gaps because it can undermine the development of effective rotavirus control strategies.  Fortunately, over the past several decades, much research has been conducted by public universities and pharmaceutical companies’ world wide on the rotavirus focusing on the development of a vaccination. 

• 4,500 children die each day from unsafe water and lack of basic sanitation facilities. Over 90 percent of deaths from diarrheal diseases, mainly in children below 5 years of age, are due to unsafe water and sanitation in the developing world.
• More than 125 million cases of diarrhea each year are attributed to the rotavirus, which causes an estimated 25% of all deaths due to diarrheal disease and 6% of all deaths in children under the age of five. The World Health Organization has given the development of a safe and effective vaccine against rotavirus infection high priority for improving global health.
• Rotavirus is associated with 25 million clinic visits, 2 million hospitalizations, and more than 600,000 deaths worldwide among children younger than five years of age.
• It is estimated that every child in the world will have at least one rotavirus infection before the age five, and each year in industrialized nations like the U.S., around 70 child deaths are attributed to this diarrheal disease. In developing countries nearly 1,400 children die from rotavirus infections each day.
• In the United States alone, the rotavirus affects roughly 80% of the approximately 4 million infants born each year.  On an annual basis, about 500,000 infants require medical attention and 50,000 are hospitalized. The economic burden in the U.S from rotavirus is estimated at over $1 billion in direct medical and indirect societal costs.
• Children 6 months to 2 years of age are most vulnerable to rotavirus infection, along with premature infants, the elderly, and those with weakened immune systems. 
• The rotavirus can be spread in high concentrations from the stools of infected children and is transmitted primarily by a fecal-oral route, both through close person-to-person contact and potentially through fomites.

 

Recomendations

Most bacteria or viruses that cause diarrheal diseases do not meet the necessary criteria to have viable vaccinations.  Normally, the disease is not prevalent enough and thus it is not cost effective for major pharmaceutical companies to develop them.  However, the rotavirus, as stated above, is very prevalent worldwide and thus, several vaccinations have been developed and found effective to combat the issue.  The rotovirus can be found in a multitude of strains which vary from continent to continent. This is problematic due to the fact that vaccines have primarily been developed in the United States and Europe. Further research to develop region specific vaccines for the strains found in untended areas is imperative.

Evidence

Rotavirus Immunization

• A human-bovine reassortant rotavirus vaccine, RotaTeq, has been developed by Merck Pharmaceuticals and FDA approved and licensed for Sale in the U.S. on February 3, 2006. Just recently on April 3, 2008, another diarrheal disease vaccination, Rotarix, has been marketed by GlaxoSmithKline; it is derived from a live attenuated human rotavirus containing the RIX4414 strain of the virus.  The efficacy of both vaccines has been thoroughly tested in many different cohorts from several different countries.

  RotaTeq

• The vaccine has been tested in three phase III trials, including a large-scale clinical trial of approximately 70,000 infants in 11 countries, with the United States and Finland accounting for approximately 80% of all enrolled persons.
• The efficacy of RotaTeq after completion of a 3-dose regimen against rotavirus gastroenteritis of any severity was 74% and against severe rotavirus gastroenteritis was 98%.
• RotaTeq reduced the incidence of office visits by 86%, ED visits by 94%, and hospitalizations for rotavirus gastroenteritis by 96%.
• Efficacy against all gastroenteritis hospitalizations of any etiology was 59%.  The efficacy of RotaTeq in the second rotavirus season postvaccination was 63%, and against rotavirus gastroenteritis of any severity was 88%.
• RotaTeq would be administered at ages 2, 4, and 6 months; it would result in 255,000 fewer physician visits, 137,000 fewer ED visits, 44,000 fewer hospitalizations, and 13 fewer deaths per year in children aged <5 years in the United States.
• From the societal perspective, vaccination is likely to be cost-saving at a total cost per child of up to $156 per child in the United States (approximately $42 per dose).

Rotarix

• Several clinical trials with the Rotarix vaccine were completed in Finland and Latin American (Brazilian, Mexican, and Venezuelan) where 63,255 healthy infants who received two oral doses of either the Rotarix vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age.
• The efficacy of the Rotarix vaccine against severe rotavirus gastroenteritis and against rotavirus associated hospitalization was 85% and reached 100 percent against more severe rotavirus gastroenteritis.
• Hospitalization for diarrhea of any cause was reduced by 42%.
• Ruiz-Palacios et al concluded that two oral doses of the live attenuated Rotarix vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception.

References

UNICEF Children and Water, Global Statistics retrieved from http://www.unicef.org/wes/index_31600.html on June 14, 2008

Malek, M. MD, Curns A. MPH,  Holman R. MS, et al Diarrhea- and Rotavirus-Associated Hospitalizations Among Children Less Than 5 Years of Age: United States, 1997 and 2000 Pediatrics 2006;117;1887-1892

Butz AM, Fosarelli P, Dick J, Yolken R. Prevalence of rotavirus on high-risk fomites in day-care facilities. Pediatrics 1993;92:202–5.

Vesikari T, Matson DO, Dennehy P, et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med 2006;354:23–33.

CDC Prevention of Rotavirus Gastroenteritis Among Infants and Children. MMWR. 2006. 55

Block VT, Goveia M, Rivers S, et al. Efficacy, immunogenicity, and safety of a polyvalent rotavirus vaccine (RotaTeq) at expiry potency in healthy infants. In: National Immunization Conference. Washington, DC; 2005.

Ruiz-Palacios G. MD, Pérez-Schael I. MSc, Velázquez R. MD. Safety and Efficacy of an Attenuated Vaccine against Severe Rotavirus Gastroenteritis. The New England Journal of Medicine. January 5, 2006 vol. 354 no. 1