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Rotavirus vaccine is a vaccine used to protect against rotavirus infections. These viruses are the leading cause of severe diarrhea among young children. The vaccines prevent 15 to 34% of severe diarrhea in the developing world and 37 to 96% of severe diarrhea in the developed world. The vaccines appear to decrease the risk of death among young children due to diarrhea. Immunizing babies appears to decrease rates of disease among older people and those who have not been immunized.
The World Health Organization (WHO) recommends that rotavirus vaccine be included in national routine vaccinations programs, especially in areas where the disease is common. This should be done along with promoting breastfeeding, handwashing, clean water and good sanitation. It is given by mouth and requires two or three doses. It should be given starting around six weeks of age.
Safety of the currently available vaccines is good. This includes in people with HIV/AIDS. A prior version of the vaccine that is no longer available was linked to intussusception, but the current versions are not clearly linked. Due to a potential risk they are not recommended in babies who have had intussusception. The vaccines are made from weakened rotavirus.
The vaccine first became available in the United States in 2006. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system. The wholesale cost in the developing world is between US$6.96 and $20.66 per dose as of 2014. In the United States it is more than US$200. As of 2013 there are two types of vaccine available globally, Rotarix and RotaTeq, with a number of others available in certain countries.
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 US$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.
Safety and efficacy trials 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 concluded that they are effective vaccines.
Rotavirus vaccines are licensed in more than 100 countries, and more than 80 countries have introduced routine rotavirus vaccination. 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. Recent studies in developing countries that have introduced rotavirus vaccines have supported these findings, showing significant decreases in deaths and hospitalizations from rotavirus diarrhea after introduction.
Additionally, the vaccines may also prevent illness in non-vaccinated children by limiting exposure through the number of circulating infections. A 2014 review of available clinical trial data from countries routinely using rotavirus vaccines in their national immunization programs found that rotavirus vaccines have reduced rotavirus hospitalizations by 49-92% and all-cause diarrhea hospitalizations by 17-55%.
The World Health Organization recommends the first dose of vaccine be given right after 6 weeks of age. Two or three doses more than a month apart should be given, depending on the vaccine administered. Because the majority of cases occur between six months and two years of age, the vaccine is not recommended for use in children over two years of age.
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. It was approved by the U.S. FDA in April 2008.
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.
Rotavac was licensed for use in India in 2014 and is manufactured by Bharat Biotech International Limited. It is a live attenuated, monovalent vaccine containing a G9P human strain isolated from an Indian child. It is given by mouth in a three-dose series, 4 weeks apart, beginning at 6 weeks of age up until 8 months of age.
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 eight years of delay until rival manufacturers were able to introduce new vaccines which 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 theoretically up to 4.2 million deaths worldwide could have been avoided during that 8 years. 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 1,300 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. WHO continues to recommend that rotavirus vaccine be included in all national immunization schedules because the risk of intussusception following rotavirus vaccination remains very low compared with the benefits of preventing the impact of severe and deadly diarrhea.
Society and culture
More than 80 countries have introduced routine rotavirus vaccination, almost half with the support of Gavi, the Vaccine Alliance. In order to make rotavirus vaccines available, accessible, and affordable in all countries—particularly low- and middle-income countries in Africa and Asia where the majority of rotavirus deaths occur—international non-governmental organization PATH, the WHO, the U.S. Centers for Disease Control and Prevention, and Gavi have partnered with research institutions and governments to generate and disseminate evidence, lower prices, and accelerate introduction. These and other organizations continue to work to improve coverage and public health impact of rotavirus vaccination today.
The cost of rotavirus vaccination varies depending on country, from a low of approximately US$0.50 in GAVI-eligible countries up to a high of US$185-$226 in the United States. Wholesale cost for GAVI has fallen by 67 percent between 2006 and 2011 to US$2.13-3.56 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.
The cost in developed countries, where it is not mandatory, is much higher. In France, for example, the vaccine is available to the public for EUR 60.38 (Jan 2016) fully at the user's charge. The following table shows current prices of rotavirus vaccines in various countries and regions:
The development of new vaccines intended to be offered at lower cost than the current globally approved vaccines is ongoing. Rotavac, manufactured by India-based Bharat Biotech and currently licensed only in India, plans to make the vaccine available for US$1 per dose for public markets. Vaccines from Serum Institute of India, Pvt., Ltd. and Sanofi affiliate Shantha Biotechnics are currently in Phase III clinical trials.
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 the finding of DNA from porcine circovirus-1 (PCV1) in the vaccine 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, stating 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. In May 2010 the suspension of the Rotarix vaccine was lifted.
Additional rotavirus vaccines are under development. 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 non-replicating rotavirus vaccine (NRRV) candidate made of the P2-VP8 fusion protein, which is currently undergoing development and trials in South Africa. Rotavirus antigens for parenteral delivery, such as the P2-VP8 candidate, can be expressed as virus-like particles prepared in baculovirus, expressed antigens, DNA vaccines, and killed virus. These novel approaches are being pursued using animal models and, in the case of the NRRV P2-VP8 candidate, clinical trials.
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