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What is the History of Rotavirus in America and Other Countries?


rotavirus

While diarrheal infections have always been present, identification of the rotavirus as one cause of the illness was only recently discovered. In 1973, a team of Australian researchers examining the intestinal tissues and feces of children with diarrhea through electron micrography discovered the presence of a novel wheel-shaped virus fragment. This virus was given the name “rotavirus” after the Latin word for wheel - rota.1 2

By 1980, the CDC had declared rotavirus to be the most frequent cause of serious gastrointestinal illness in infants and toddlers and estimated that the virus caused between 20 and 60 deaths annually in the United States. It was also estimated to cause 400,000 physician visits, 200,000 emergency room visits, and between 55,000 and 70,000 hospitalizations.3 The infection, however, was not, and still is not, a nationally notifiable disease, therefore the exact numbers of infections and deaths from rotavirus are not known.4

It was also noted in 1980 that most infants developed the illness during the winter months in non-tropical regions. Many cases of rotavirus were also preceded by respiratory symptoms which included nasal congestion, cough, and ear infections. Vomiting was found to occur prior to the onset of diarrhea, and when infants and children were given only clear fluids, vomiting ceased within 24 hours. Researchers also reported that while gastrointestinal illnesses were common, deaths were rare. In 1980, it was still not known exactly how the virus was spread but it was assumed that this occurred through the fecal-oral route. Transmission through respiratory droplets was also suspected; however, scientists had been unable to isolate the virus in the respiratory tract.5

By 1983, researchers were still uncertain about the prevalence of the virus in the environment, and the incidence of infections in communities. They were also not sure how long the virus could persist in the environment, and whether it was readily transmitted through food, water, air, or additional sources. Research priorities included the development of a test that could rapidly identify the specific virus, the establishment of a universal classification for each group and type of rotavirus, and the development of a vaccine against the virus.6

The most common serotypes of rotavirus were noted to be G1, G2, G3, and G4 and they accounted for more than 80 percent of all human rotavirus strains.7

In January of 1989, the CDC established the National Rotavirus Surveillance System (NRSS) to collect data on rotavirus incidence and epidemiology. The surveillance system consisted of 99 laboratories who began providing data on confirmation of rotavirus. For a 23-month period, from January 1989 to November 1990, only 20 percent of the over 48,000 samples collected were positive for rotavirus. During the data collection period, rotavirus occurred most frequently in February and least often in October. Researchers also noted that approximately 500 children died each year from diarrheal disease and estimated that 20 percent of these deaths were attributable to rotavirus. Health officials also reported that hospitalizations and deaths from rotavirus were preventable by aggressive oral hydration – but stated that this strategy was under-utilized.8

By 1992, public health officials reported that rotavirus infections began in western states in November and reached its peak in December and January; however, in eastern states, rotavirus activity began in January and peaked in February and March.  They had no explanation for this occurrence as it was not tied to rotavirus strain variation.9

Between 1986 and 1999, published studies reported that approximately 22 percent of childhood diarrhea hospitalizations were due to rotavirus. Globally, 440,000 yearly rotavirus deaths in children under the age of 5 were estimated. However, this was noted to be a significant decrease from 1985, when approximately 873,000 infants were estimated to die from the illness.10

Rotavirus serotype G9 was first detected in the United States in 1987 and by 1995, it was believed to be the fifth most common serotype and was found in multiple countries including India, Brazil, Italy, and more.11

Rotavirus Vaccine Introduced

On August 31st, 1998, the first vaccine targeting rotavirus, RotaShield, received FDA approval for use in children. At this time, health officials estimated that 2.7 million children under the age of five developed the illness each year, which resulted in 50,000 hospitalizations and 500,000 physician appointments. The rates were reported to be much higher in developing countries, with public health officials estimating that the virus caused about 800,000 deaths each year.

The approved reassortant (mix of genetic material from different species) vaccine, a tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) contained a rhesus monkey rotavirus with serotype G3 specificity and reassortant rhesus-human rotaviruses with G1, G2, and G4  specificity to target the four common serotypes of rotavirus. The vaccine was reported to be between 49 and 68 percent effective against any rotavirus diarrhea and between 61 and 100 percent effective against severe rotavirus diarrhea.12

At the time of the vaccine’s recommendation by the CDC’s Advisory Committee on Immunization Practices (ACIP), it was noted that few cases of rotavirus occurred in infants younger than 3 months of age, while infants and children between four and 36 months were most affected. Rotavirus was rarely symptomatic in adults; however, it was still found at times to cause illness in parents of children with the infection, those with immunocompromising conditions, travelers to underdeveloped countries, and the elderly.13

RotaShield Vaccine Suspended

By the spring of 1999, however, several reports of intussusception following RotaShield vaccine administration had been made to the Vaccine Adverse Events Reporting System (VAERS) and on July 16, 1999, the CDC announced that it was suspending its recommendation of RotaShield due to the increasing number of reported intussusception cases.14 15 Later that year, at the CDC’s October ACIP meeting, the committee voted to withdraw its recommendation in light of evidence which found that intussusception occurred in one out of every 5,000 infants who received the vaccine.16 17

RotaTeq Vaccine Introduced

In 2006, when RotaTeq, the second oral live rotavirus vaccine received approval for use in the United States, the most common rotavirus serotypes were P1A[8]G1, P1B[4] G2, P1A[8] G3, P1A[8] G4, P1A[8] G9,and P2A[6] G9. It was reported that in infants between three and 35 months of age, the first rotavirus infection would likely be the most severe and 40 percent of children would not have any further rotavirus infections. Seventy-five percent of children would be protected against subsequent rotavirus gastroenteritis, and 88 percent would be protected against subsequent severe rotavirus gastroenteritis. The initial first natural infection was reported to protect an infant against severe rotavirus gastroenteritis in the future but that asymptomatic or mild infections might still occur.18

These same six distinct rotavirus serotypes were also noted to be the predominant circulating strains in the United States when ROTARIX, the third oral live rotavirus vaccine was recommended for use by ACIP in 2008.19

Surveillance of rotavirus serotypes in the United States following the introduction of RotaTeq found that G3 replaced G1 as the strain most frequently detected and that additional uncommon serotypes had also been detected. Additionally, by the 2007-2008  season, the mean age of rotavirus cases in children less than 3 years had increased significantly. The authors concluded that “These findings underscore the need for careful monitoring of strains to assess possible vaccine pressure-induced changes and vaccine effectiveness against various rotavirus genotypes.”20>

G12 rotaviruses were first detected in the Philippines in 1987 among children under the age of two, but then not detected again until 1998. However, since 1998, G12 rotavirus strains have been detected globally.21 One of the first outbreaks of G12 rotavirus in the U.S. occurred in Rochester, New York in 2006-2007 and this strain contributed to a 72 percent increase in the number of rotavirus cases. Since this first large outbreak, G12 strains have continued to be detected in the U.S. and abroad.22 23 24 25

Rotavirus Vaccine Shedding

Since the introduction of vaccines targeting rotavirus, vaccine-derived rotavirus strains have also been detected and studies have found that shedding of these viruses do occur and can persist for weeks to months.26 27 28 29 Additionally, vaccine strain and vaccine-derived rotaviruses have been found to cause gastrointestinal illness in both immunocompromised and immunocompetent infants.30 31 32 33

While rotavirus gastroenteritis has decreased following the introduction of RotaTeq and ROTARIX vaccines, norovirus gastroenteritis has emerged and is currently the most common cause of gastroenteritis in children.34 35 Norovirus, or Norwalk virus, was first identified in 1929 and initially referred to in the medical literature as “winter vomiting disease”. Symptoms of the illness included nausea, vomiting, diarrhea, stomach cramps and fever.36

Reports of norovirus outbreaks began increasing in 200237 and the CDC currently estimates that norovirus is responsible for 19 to 21 million cases of acute gastroenteritis, 109,000 hospitalizations and 900 deaths annually, with most deaths occurring among the elderly.38

The exact number of rotavirus cases in the U.S. is unknown as the virus is not considered nationally notifiable.39 The World Health Organization (WHO) estimates that 215,000 children under age five will die from the illness, with most deaths occurring in developing countries.40
 

IMPORTANT NOTE: NVIC encourages you to become fully informed about rotavirus and rotavirus vaccines by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

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References

1 Communication and Education Branch, National Center for Immunization and Respiratory Diseases (NCIRD) and the Centers for Disease Control (CDC). Rotavirus  In: Epidemiology and Prevention of Vaccine-Preventable Diseases. 13th ed. Centers for Disease Control (CDC) 2015; Pg. 311. Updated November 2020. Accessed Apr. 4, 2021.

2 Bishop R. Discovery of rotavirus: Implications for child health. J Gastroenterol Hepatol. Oct. 2009;24 Suppl 3:S81-5.

3 U.S. Centers for Disease Control and Prevention. Rotavirus in the U.S. In: Rotavirus. Mar. 26, 2021.

4 Communication and Education Branch, National Center for Immunization and Respiratory Diseases (NCIRD) and the Centers for Disease Control (CDC). Rotavirus  In: Epidemiology and Prevention of Vaccine-Preventable Diseases. 13th ed. Centers for Disease Control (CDC) 2015; Pg. 311. Updated November 2020. Accessed Apr. 4, 2021.

5Rotavirus infections in infancy Br Med J. Nov. 1980; 281(6249): 1162–1163.

6 U.S. Centers for Disease Control and Prevention. Diarrheal Diseases Control Program: Rotavirus Diarrhea. MMWR June 1983; 32 (24): 311-318.

7 Cunliffe NA, Dove W, Bunn JE, et al. Expanding global distribution of rotavirus serotype G9: detection in Libya, Kenya, and Cuba. Emerg Infect Dis Sep-Oct. 2001;7(5):890–892.

8 U.S. Centers for Disease Control and Prevention. Rotavirus Surveillance – United States, 1989-1990. MMWR Feb. 8, 1991; 40(5): 80-87.

9 U.S. Centers for Disease Control and Prevention. Laboratory – Based Surveillance For Rotavirus – United States, January 1989 – May 1991. MMWR Aug. 28, 1992; 41(34): 629.

10 Parashar UD, Gibson CJ, Bresee JS. et al. Rotavirus and severe childhood diarrhea. Emerg Infect Dis Feb. 2006;12(2):304–306.

11 Cunliffe NA, Dove W, Bunn JE, et al. Expanding global distribution of rotavirus serotype G9: detection in Libya, Kenya, and CubaEmerg Infect Dis Sep – Oct. 2001;7(5):890–892.

12 Parashar UD, Bresee JS, Gentsch JR. et al. Rotavirus. Emerg Infect Dis Oct-Dec. 1998; 4(4):561-570.

13 Parashar UD, Bresee JS, Gentsch JR. et al. Rotavirus. Emerg Infect Dis Oct-Dec. 1998; 4(4):561-570.

14 Schwartz JL The first rotavirus vaccine and the politics of acceptable risk. Milbank Q June 2012;90(2):278-310.

15 U.S. Centers for Disease Control and Prevention. Intussusception Among Recipients of Rotavirus Vaccine —United States, 1998–1999. MMWR July 1999; 48(27): 577-581.

16 U.S. Centers for Disease Control and Prevention. Withdrawal of Rotavirus Vaccine Recommendation. MMWR Nov. 5, 1999; 48(43): 1007.

17 Schwartz JL. The first rotavirus vaccine and the politics of acceptable risk. Milbank Q June 2012;90(2):278-310.

18 U.S. Centers for Disease Control and Prevention. Prevention of rotavirus gastroenteritis among infants and children : recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Aug. 11, 2006; 55(RR-12): 1-16.

19 U.S. Centers for Disease Control and Prevention. Prevention of Rotavirus Gastroenteritis Among Infants and Children Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Feb. 6, 2009; 58(RR02):1-25.

20 Hull JJ, Teel EN, Kerin TK, et al. United States rotavirus strain surveillance from 2005 to 2008: genotype prevalence before and after vaccine introduction. Pediatr Infect Dis J Jan. 2011;30(1 Suppl):S42–S47.

21 Rahman M, Matthijnssens J, Yang X, et al. Evolutionary history and global spread of the emerging g12 human rotaviruses. J Virol Mar. 2007;81(5):2382–2390.

22 Mijatovic-Rustempasic S, Teel EN, Kerin TK, et al. Genetic analysis of G12P[8] rotaviruses detected in the largest U.S. G12 genotype outbreak on record. Infect Genet Evol Jan. 2014;21:214–219.

23 Cunliffe NA, Ngwira BM, Dove W, et al. Serotype g12 rotaviruses, Lilongwe, Malawi. Emerg Infect Dis Jan. 2009;15(1):87–90.

24 Pietsch C, Liebert UG. Human infection with G12 rotaviruses, Germany. Emerg Infect Dis Sep. 2009;15(9):1512–1515.

25 Soares Lda S, Lobo Pdos S, Mascarenhas JD, et al. Identification of lineage III of G12 rotavirus strains in diarrheic children in the Northern Region of Brazil between 2008 and 2010. Arch Virol 2012;157(1):135–139. 

26 Markkula J, Hemming M, Vesikari T. Detection of vaccine-derived rotavirus strains in nonimmunocompromised children up to 3-6 months after RotaTeq® vaccination. Pediatr Infect Dis J Mar. 2015;34(3):296-8.

27 Gower CM, Dunning J, Nawaz S, et al. Vaccine-derived rotavirus strains in infants in England Arch Dis Child. 2020; 105:553-557.

28 Ye S, Whiley DM, Ware RS, et al. Multivalent Rotavirus Vaccine and Wild-type Rotavirus Strain Shedding in Australian Infants: A Birth Cohort Study. Clin Infect Dis May 2018;66(9):1411–1418.

29 Bowen MD, Payne DC. Rotavirus vaccine-derived shedding and viral reassortants. Expert Rev Vaccines. Jan. 2012;11(11):1311–1314.

30 Donato CM, Ch'ng LS, Boniface KF, et al. Identification of strains of RotaTeq rotavirus vaccine in infants with gastroenteritis following routine vaccination. J Infect Dis May 2012;206(3):377–383.

31 Boom JA, Sahni LC, Payne DC, et al. Symptomatic infection and detection of vaccine and vaccine-reassortant rotavirus strains in 5 children: a case series. J Infect Dis Aug. 2012;206(8):1275–1279.

32 Hemming M, Vesikari T. Vaccine-derived human-bovine double reassortant rotavirus in infants with acute gastroenteritisPediatr Infect Dis J Sep. 2012;31(9):992–994.

33 Than VT, Jeong S, Kim W. Characterization of RotaTeq® vaccine-derived rotaviruses in South Korean infants with rotavirus gastroenteritis. J Med Virol May 2015;87(1):112–116.

34 Communication and Education Branch, National Center for Immunization and Respiratory Diseases (NCIRD) and the Centers for Disease Control (CDC). Chapter 13: Rotavirus - Disease Description. In: Manual for the Surveillance of Vaccine-Preventable Diseases. Centers for Disease Control (CDC) May 18, 2019.

35 Payne DC, Vinj√© J, Szilagyi PG, et al. Norovirus and medically attended gastroenteritis in U.S. children. N Engl J Med. Mar. 2013;368(12):1121–1130.

36 Widdowson MA, Monroe SS, Glass RI. Are noroviruses emerging? Emerg Infect Dis May 2005;11(5):735–737.

37 Widdowson MA, Monroe SS, Glass RI. Are noroviruses emerging? Emerg Infect Dis May 2005;11(5):735–737.

38 U.S. Centers for Disease Control and Prevention. Burden of Norovirus Illness in the U.S. In: Rotavirus. Mar. 5, 2021.

39 U.S. Centers for Disease Control and Prevention. 2021 National Notifiable Conditions National Notifiable Diseases Surveillance System (NNDSS) No Date. Accessed Apr. 4, 2021.

40 World Health Organization (WHO). Rotavirus.  In: Immunizations, Vaccines and Biologicals. October 2020.


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