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A rotavirus vaccine protects children from rotaviruses, which are the leading cause of severe diarrhea among infants and young children. Each year an estimated 453,000 children die from diarrhoeal disease caused by rotavirus, most of whom live in developing countries, and another two million are hospitalised. Rotavirus is highly contagious and resistant and, regardless of water quality and available sanitation, nearly every child in the world is at risk of infection.
There are two effective rotavirus vaccines: Rotarix by GlaxoSmithKline and RotaTeq by Merck. The development of a vaccine called Rotavac that is intended to be offered at lower cost than the others was announced in India in 2013, and has been tested in Phase III trials.
On June 5, 2009, the World Health Organization (WHO) recommended that rotavirus vaccine be included in all national immunization programs. The Rotavirus Vaccine Program and the Accelerated Vaccine Introduction initiative have worked to study rotavirus vaccines among developing-country populations to assist developing countries in introducing rotavirus vaccines into routine immunization programs. These partnerships are spearheaded by international non-governmental organization PATH, WHO, the U.S. Centers for Disease Control and Prevention, and the Global Alliance for Vaccines and Immunization. It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.
Rotarix is a monovalent, human, live attenuated rotavirus vaccine containing one rotavirus strain of G1P specificity. ROTARIX is indicated for the prevention of rotavirus gastroenteritis caused by G1 and non-G1 types (G3, G4, and G9) when administered as a 2-dose series in infants and children. On March 22, 2010, FDA provided an early communication regarding Rotarix, manufactured by GlaxoSmithKline Biologicals (GSK) At that time, FDA recommended that clinicians and public health professionals in the United States temporarily suspend the use of Rotarix while the agency and manufacturer investigated the finding of DNA from porcine circovirus-1 (PCV1) in the vaccine. Since that time, both FDA and GSK have confirmed the presence of PCV1 in the vaccine. Although this contamination was thought to be benign, vaccines are supposed to be sterile. In May 2010 the suspension of the vaccine was lifted.
RotaTeq is a live, oral pentavalent vaccine that contains five rotavirus strains produced by reassortment. The rotavirus A parent strains of the reassortants were isolated from human and bovine hosts. Four reassortant rotaviruses express one of the outer capsid, VP7, proteins (serotypes G1, G2, G3, or G4) from the human rotavirus parent strain and the attachment protein VP4 (type P7) from the bovine rotavirus parent strain. The fifth reassortant virus expresses the attachment protein VP4, (type P1A), from the human rotavirus parent strain and the outer capsid protein VP7 (serotype G6) from the bovine rotavirus parent strain. In February 2006, the U.S. Food and Drug Administration approved RotaTeq for use in the United States. In August 2006, Health Canada approved RotaTeq for use in Canada. Merck is working with a range of partners including governmental and non-governmental organisations to develop and implement mechanisms for providing access to this vaccine in the developing world.
On March 22, 2010, the detection of DNA from porcine circovirus types 1 and 2 within RotaTeq and Rotarix prompted the FDA to suspend the use of rotavirus vaccines while conducting an investigation in collaboration with the 12 members of the Vaccines and Related Biological Products Advisory Committee (VRBPAC). On May 6, 2010, the FDA announced its decision to revoke the suspension, asserting that porcine circovirus types 1 and 2 pose no safety risks in humans and concluded that health risks involved did not offset the benefits of the vaccination.
An Indian-made rotavirus vaccine, Rotavac, was developed and announced in 2013. If approved by the Drugs Controller General of India, it would be available at Rs. 54 per dose, more affordable than the two vaccines now available costing more than Rs. 1,000 per dose.
Vaccines in development
Other vaccines are undergoing clinical trials. These include: a human neonatal PG3 strain, RV3, developed by Ruth Bishop and colleagues in Australia, a human bovine reassortant vaccine developed by Albert Kapikian and presently undergoing development and trials in different countries and a neonatal strain vaccine (G9P11) being developed by Bharat Biotech in India. This G9P(11) virus strain has the VP4 of bovine rotavirus origin, and all other segments of human rotavirus origin. Other approaches to the development of rotavirus vaccines are also being pursued. Rotavirus antigens for parenteral delivery have received some attention as virus-like particles prepared in baculovirus, expressed antigens, DNA vaccines, and killed virus. These novel approaches are being pursued using animal models.
Effectiveness and cost
A 2009 review estimated that vaccination against rotavirus would prevent about 45% of deaths due to rotavirus gastroenteritis, or about 228,000 deaths annually worldwide. At $5 per dose the estimated cost per life saved was $3,015, $9,951 and $11,296 in low-, lower-middle-, and upper-middle-income countries, respectively. The cost of rotavirus vaccination has fallen by 67 percent between 2006 and 2011 to USD 2.50 per dose, as part of an offer made by a pharmaceutical company to the GAVI Alliance. However, the vaccine is still more expensive than most other childhood vaccines included in the WHO's Expanded Programme on Immunization.
Safety and efficacy trials of Rotarix and RotaTeq in Africa and Asia found that the vaccines dramatically reduced severe disease among infants in developing countries, where a majority of rotavirus-related deaths occur. A 2012 Cochrane review of 41 clinical trials that included 186,263 participants concluded Rotarix and RotaTeq are effective vaccines. Additional rotavirus vaccines are under development.
Rotavirus vaccines are licensed in more than 100 countries, but only 31 countries have introduced routine rotavirus vaccination as of 2011. The incidence and severity of rotavirus infections has declined significantly in countries that have acted on the recommendation to introduce the rotavirus vaccine. In Mexico, which in 2006 was among the first countries in the world to introduce rotavirus vaccine, the diarrheal disease death rates from rotavirus dropped by more than 65% among children age two and under during the 2009 rotavirus season . In Nicaragua, which in 2006 became the first developing country to introduce the rotavirus vaccine, investigators recorded a substantial impact, with rotavirus vaccine preventing 60% of cases against severe rotavirus and cutting emergency room visits in half. In the United States, vaccination has reduced rotavirus-related hospitalizations by as much as 86% since 2006. The vaccines may also prevent illness in non-vaccinated children by limiting exposure through the number of circulating infections. In September 2013, the vaccine will be offered to all children in the UK, aged between two and three months, and it is expected to halve the cases of severe infection and reduce the number of children admitted to hospital because of the infection by 70 percent.
In 1998, a rotavirus vaccine (RotaShield, by Wyeth) was licensed for use in the United States. Clinical trials in the United States, Finland, and Venezuela had found it to be 80 to 100% effective at preventing severe diarrhea caused by rotavirus A, and researchers had detected no statistically significant serious adverse effects. The manufacturer of the vaccine, however, withdrew it from the market in 1999, after it was discovered that the vaccine may have contributed to an increased risk for intussusception, or bowel obstruction, in one of every 12,000 vaccinated infants. There then followed 8 years delay until rival manufacturers were able to introduce new vaccines which due to different adjuvant were shown to be more safe and effective in children: Rotarix by GlaxoSmithKline and RotaTeq by Merck. Both are taken orally and contain disabled live virus.
The experience, however, provoked debate about the relative risks and benefits of a rotavirus vaccine. This is because rotavirus is responsible for 29% of deaths from diarrhea in children below 5 years worldwide, and thus 4.2 million deaths could be avoided during that 8 years in different parts of the world. Meanwhile, other countries such as Brazil and Mexico undertook their own independent epidemiological studies which demonstrated that 4 deaths were attributable to vaccine, while it had prevented approximately 80,000 hospitalization and 1300 deaths from diarrhea each year in their countries. This example shed light on the importance of careful country-specific epidemiology which enables rational balancing between benefit and risk.
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