Disease factsheet about rotavirus

Rotaviruses are the single most important cause of severe diarrhoeal illness in infants and young children worldwide (1). By the age of five years most children irrespective of socioeconomic setting will have been infected at least once (2). While infected, many children will be in need of medical attention due to extensive fluid loss.

Rotavirus infections are not notifiable in most EU/EEA MSs with the exception of Germany. Hence, no EU/EEA-wide epidemiological or laboratory surveillance is conducted. As documented in burden of disease studies mortality is very low in EU/EEA countries (<0.2 per 100,000 children younger than 5 years) (3, 4) while hospitalisations in the pre-vaccine era range from 300 to 600 per 100,000 children less than 5 years of age (1-2% of each birth cohort) (5).

Rotavirus infections are vaccine-preventable following the EU/EEA approval of two oral, live attenuated rotavirus vaccines in 2006 for use in infants (6, 7).WHO recommends use of rotavirus vaccines in all infants (8) and EU/EEA countries that have introduced rotavirus vaccines into their national/regional immunization programmes have noted a significant reduction in number of children seeking medical attention for rotavirus infection (9-13).

Case definition

No EU case definition is available. 

The pathogen

  • The rotaviruses comprise the genus Rotavirus within the virus family Reoviridae;
  • The viral genome contains 11 segments of double-stranded RNA;
  • Classification of rotaviruses involves determination of serotype (antigenic characterization) and/or genotype (genetic characterization);
  • Most rotaviruses causing diarrhoeal illness in children worldwide belong to serogroup A, but rotaviruses group B and C may also cause disease in humans. Available vaccines provide protection against the most common group A rotaviruses;
  • Genetic characterization of rotaviruses uses the specificities of the two outer capsid proteins, VP4 (P-type) and VP7 (G-type). (14)

Clinical features and sequelae

  • Fever
  • Vomiting
  • Diarrhoea
  • Extensive nausea and vomiting in some children result in difficulties in providing oral rehydration and severe fluid loss in need of medical attention.
  • Complications include febrile seizures/seizures due to electrolyte disturbances but no residual sequelae due to seizures have been reported.
  • Severe dehydration may lead to shock and death if not corrected. This is rarely seen in the EU/EEA where access to health care and rehydration is available for all. However, if cases only come to the attention of health care after significant fluid loss a limited number of deaths are reported each year.
  • With symptomatic treatment, including rehydration, symptoms are commonly relieved within 3 to 8 days.(15)

Epidemiology

No formal surveillance of rotavirus infections or circulating strains is available in the EU/EEA.

From burden-of-disease studies it is noted that rotaviruses cause seasonal peaks of diarrhoeal disease between December and May in EU/EEA. However, sustained low-grade transmission is identified all year round (14).

Most children acquire their primary rotavirus infection between 6 and 36 months of age (15). Subsequent rotavirus infections occur throughout life but only rarely lead to severe disease leading to medical attention or hospitalisation.

Severe RV GE disease may develop in any child. However, a limited number of risk factors for development of severe disease have been identified including low-birth-weight infants (<2,500 g), another child <24 months of age in the household and severe immunodeficiency conditions (16). 

Circulating rotavirus genotypes vary by season and country and co-circulation of several genotypes are noted each year. However, the vast majority of human cases within EU/EEA and worldwide are caused by five genotypes within serogroup A rotavirus: G1P[8], G2P[4], G3P[8], G4P[8] and G9P[8] (17). See figure 1.

In addition, new emerging genotypes have been identified in EU/EEA countries with G12P[8] being the most common (Eurorotanet strain surveillance network 2015 Annual report) 

    Overall distribution of the six more frequent rotavirus genotypes by country between 2006 and 2013 (n=47,549 rotavirus strains analysed from 16 EU/EEA countries active within the EuroRotaNet surveillance network)
    Figure 1 Overall distribution of the six more frequent rotavirus genotypes by country between 2006 and 2013 (n=47,549 rotavirus strains analysed from 16 EU/EEA countries active within the EuroRotaNet surveillance network)

    Transmission

    • The incubation period is 1-2 days.
    • The infective period is 1-3 weeks. Asymptomatic carriers are common.
    • Rotaviruses are mainly transmitted from person-to-person through the faecal-oral route, but transmission may also occur through contaminated objects (e.g. door-handles, water-taps, toilet-seats and toys), airborne droplets and contaminated water or food. The infectious dose is small, an inoculum of as few as 10-100 virus particles is sufficient to produce illness in susceptible individuals while the typical excreted virus load is between 10 8 to 10 ^10 particles per millilitre (mL) faecal sample. (14)

    Diagnostics

     Excretion of rotaviruses may be confirmed by analysing stool samples using:

    • antigen-detecting assays (enzyme immunoassays, immunochromatographic rapid tests),
    • genome-detecting assays (PCR)
    • electron microscopy (14)

    Case management and treatment

    Clinical management is directed towards early replacement of fluid losses using oral rehydration at home. However, with more extensive fluid losses there may be a need for nasogastric and/or intravenous rehydration provided in hospital settings. Apart from fluid replacement, no other therapy is required in previously healthy individuals and the condition is self-limiting. No antiviral drugs are available. (15)

    Infection control, personal protection and prevention

    Children seeking medical attention in emergency departments/out-patient clinics or those hospitalized with rotavirus disease have the potential to be sources of nosocomially acquired infections.

    General protective measures for protection against rotavirus infections include meticulous hand hygiene by all caring for affected children. However, improved socioeconomic standard and hygiene in EU/EEA countries over the last 50-100 years have not decreased circulation of rotaviruses. Resistance to physical inactivation (along with the large number of viral particles shed in stool) contribute to the efficient transmission of human rotaviruses. Rotaviruses may persist on dry surfaces for up to two months. (15)

    Two live attenuated vaccines for oral use providing prevention against rotavirus disease   were authorised in the European Union in 2006; Rotarix, a monovalent vaccine (RV1) developed from a human rotavirus strain attenuated through serial passage in cell culture (GlaxoSmithKline Biologicals, Rixensart, Belgium) (7) and RotaTeq, a human-bovine rotavirus reassortant pentavalent vaccine (RV5) derived  from several cell culture adapted  human rotavirus strains and a bovine rotavirus strain  (Sanofi Pasteur MSD, Lyon, France) (6). The indication for these vaccines is active immunization of infants for prevention of gastroenteritis due to rotavirus infection.

    Vaccine efficacy has been evaluated in randomised, controlled clinical trials performed in low-mortality settings such as the EU/EEA countries (18) and both rotavirus vaccines were shown to be effective against hospitalisation due to G1P[8], G2P[4], G3P[8] and G4P[8] and G9P[8] rotavirus genotypes. In addition, RV5 has been shown to be effective against G12P (8). Vaccine efficacy against other genotypes has not been evaluated in rotavirus low-mortality settings. Vaccine effectiveness studies against rotavirus hospitalisation have shown protection in the range 80-90% upon introduction of rotavirus vaccines into the paediatric immunization programmes (5). Further, herd immunity contributes to the overall impact of vaccination programmes providing protection to e.g. older siblings of vaccinated individuals (19, 20).

    References

    1. Lanata C, Fischer-Walker C, Olascoaga A, Torres C, Aryee M, Black R. Global Causes of Diarrheal Disease Mortality in Children <5 Years of Age: A Systematic Review. PLoS ONE. 2013.
    2. Parashar U, Gibson CJ, Bresee J, Glass R. Rotavirus and severe childhood diarrhea. Emerging infectious diseases. 2006;12(2):304-6.
    3. Jit M, Pebody RG, Chen AC, Andrews N, Edmunds WJ. Estimating the number of deaths with rotavirus as a cause in England and Wales. Hum Vaccin. 2007;3(1):23-6.
    4. Berner R, Schumacher RF, Forster J. Survey on rotavirus infections in a German pediatric hospital. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 1997;16(6):479-81.
    5. ECDC. Draft Expert Opinion on rotavirus vaccination in infancy. 2016.
    6. European Medicines Agency: European Public Assessment Report Rotateq.
    7. European Medicines Agency: European Public Assessment Report Rotarix.
    8. Meeting of the immunization Strategic Advisory Group of Experts, April 2009--conclusions and recommendations. Releve epidemiologique hebdomadaire / Section d'hygiene du Secretariat de la Societe des Nations = Weekly epidemiological record / Health Section of the Secretariat of the League of Nations. 2009 Jun 5;84(23):220-36. PubMed PMID: 19499606. Epub 2009/06/09. eng
      fre.
    9. Castilla J, Beristain X, Martinez-Artola V, Navascues A, Garcia Cenoz M, Alvarez N, et al. Effectiveness of rotavirus vaccines in preventing cases and hospitalizations due to rotavirus gastroenteritis in Navarre, Spain. Vaccine. 2012;30(3):539-43.
    10. Leino T, Ollgren J, Salo H, Tiihonen P, Kilpi T. First year experience of rotavirus immunisation programme in Finland. Vaccine. 2012 Dec 17;31(1):176-82. PubMed PMID: 23122991. Epub 2012/11/06. eng.
    11. Braeckman T, Herck K, Meyer N, Pircon JY, Soriano-Gabarro M, Heylen E, et al. Effectiveness of rotavirus vaccination in prevention of hospital admissions for rotavirus gastroenteritis among young children in Belgium: Case-control study. BMJ (Online). 2012;345(7872).
    12. Marlow R, Muir P, Vipond B, Lyttle M, Trotter C, Finn A. Assessing the impacts of the first year of rotavirus vaccination in teh United Kingdom. Eurosurveillance. 2015;20(48).
    13. Hungerford D, Read J, Cooke RP, Vivancos R, Iturriza-Gómara M, Allen D, et al. Early impact of rotavirus vaccination in a large paediatric hospital in the UK. J Hosp Infect. 2016;93(2):117-20.
    14. Knipe D, Howley P. Chapter 25 Rotaviruses. Fields Virology 2012;  2.
    15. Long NT, Pickering AJ, Prober CG. Chapter 216 Rotavirus infections. Principles and practice of pediatric infectious diseases 4th edition. 2012;2:1094-7.
    16. Dennehy P, Cortese M, Bégué R, Jaeger J, Roberts N, Zhang R, et al. A case-control study to determine risk factors for hospitalization for rotavirus gastroenteritis in U.S. children. Pediatr Infect Dis J. 2006;25(12):1123-31.
    17. Hungerford D, Vivancos R, Read J, Pitzer VE, Cunliffe N, French N, et al. In-season and out-of-season variation of rotavirus genotype distribution and age of infection across 12 European coutnries before the introduction of routine vaccination 2007/2008 to 2012/13. Eurosurveillance. 2016;21(2).
    18. Soares-Weiser K, MacLehose H, Bergman H, Ben-Aharon I, Nagpal S, Goldberg E, et al. Vaccines for preventing rotavirus diarrhoea: vaccines in use. Cochrane Database of Systematic Reviews [Internet]. 2012; (11). Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008521.pub3/abstract.
    19. Mast T, Wang F, Su S, Seeger J. Evidence of herd immunity and sustained impact of rotavirus vaccination on the reduction of rotavirus-related medical encounters among infants from 2006 through 2011 in the United States. Pediatr Infect Dis J. 2015;34(6):615-20.
    20. Pollard S, Malpica-Llanos T, Friberg I, Fischer-Walker C, Ashraf S, Walker N. Estimating the herd immunity effect of rotavirus vaccine. Vaccine. 2015;33(32):3795-800.

    Disclaimer: The information contained in this factsheet is intended for the purpose of general information and should not substitute individual expert advice or judgement of healthcare professionals.