Reoviridae: Rotavirus

Rotavirus belongs to the Reoviridae family and is a non-enveloped, double-stranded RNA virus. Transmission occurs through the fecal-oral route. Rotavirus is a common cause of severe gastroenteritis in children. Severe infections can result in dehydration and death. Diagnostic testing is not usually required, but the virus can be detected in stool samples using ELISA or PCR. Oral rehydration therapy is the mainstay of treatment. A live-attenuated vaccine is available to prevent rotavirus infections.

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Classification

RNA Viruses Flowchart Classification

RNA virus identification:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA or RNA. RNA genome viruses can be further characterized by either a single- or double-stranded RNA. “Enveloped” viruses are covered by a thin coat of cell membrane (usually taken from the host cell). If the coat is absent, the viruses are called “naked” viruses. Viruses with single-stranded genomes are “positive-sense” viruses if the genome is directly employed as messenger RNA (mRNA), which is translated into proteins. “Negative-sense,” single-stranded viruses employ RNA dependent RNA polymerase, a viral enzyme, to transcribe their genome into messenger RNA.

Image by Lecturio. License: CC BY-NC-SA 4.0

General Characteristics and Epidemiology

Basic features of Rotavirus

  • Taxonomy:
    • Family: Reoviridae
    • Genus: Rotavirus
  • RNA virus:
    • Double stranded
    • Positive- and negative-sense strands
    • Linear
    • Segmented (11 segments)
  • Structure:
    • “Wheel like”
    • Non-enveloped virus
    • 3-layered icosahedral capsid
    • Protein spikes
  • Can remain viable for weeks to months in the environment
Transmission electron micrograph of multiple rotavirus virions

Transmission electron micrograph of multiple rotavirus virions

Image: “Transmission electron micrograph of multiple rotavirus particles” by Dr Graham Beards. License: CC BY 3.0

Associated diseases

Rotaviruses causes gastroenteritis.

Epidemiology

  • Leading cause of acute gastroenteritis in children < 5 years old
  • Worldwide distribution
  • Children have a more clinically apparent disease than adults.
  • More common during winter in temperate climates

Pathogenesis

Reservoir

Humans are the primary reservoir.

Transmission

Transmission occurs through the fecal-oral route:

  • Ingestion of contaminated food or water
  • Contact with contaminated surfaces/fomites

Host risk factors

  • Young children
  • Individuals who have not been immunized
  • Immunocompromised individuals
  • Individuals living in long-term care facilities

Pathophysiology

  • Virions penetrate the cells of the small intestinal villi. 
  • Cholera toxin-like protein production → destruction and blunting of the microvilli → disruption in electrolyte and water absorption
  • ↓ Disaccharidase activity → malabsorption of lactose and D-xylose → osmotic influx into the intestine 
  • Active water secretion and impaired absorption → watery diarrhea
  • Virions are shed in feces → allows transmission
pathogenesis of rotavirus infection flowchart

Flowchart summarizing the pathogenesis of rotavirus infection

Image by Lecturio. License: CC BY-NC-SA 4.0

Clinical Presentation

Timeline:

  • Incubation period < 48 hours
  • Duration: 4–5 days

Symptoms:

  • Fever
  • Malaise
  • Abdominal pain
  • Vomiting
  • Diarrhea
    • Watery
    • Noninflammatory
    • Nonbloody
    • Can be severe and lead to serious dehydration

Signs of dehydration:

  • Tachycardia
  • Dry mucous membranes
  • ↓ Urine output
  • ↓ Skin turgor
  • Sunken eyes

Diagnosis and Management

Diagnosis

Rotavirus infections are difficult to distinguish from other diarrheal diseases on the basis of clinical exam alone.

  • Lab testing is generally not needed.
  • Detection of rotavirus in the stool can be performed (if necessary):
    • ELISA 
    • PCR

Management

  • The disease is self-limiting.
  • Symptomatic therapy 
  • Oral rehydration
  • IV fluids in patients with severe dehydration

Prevention

Live attenuated vaccines have been developed to prevent rotavirus infections: 

  • Given to all children before 8 months of age 
  • Contraindications:
    • SCID
    • History of intussusception
    • Allergy to vaccine components

Differential Diagnosis

  • Norovirus: a non-enveloped, positive-sense, ssRNA virus belonging to the Caliciviridae family. Norovirus is a common cause of acute diarrhea worldwide. Transmission is via the fecal-oral route. Patients with norovirus infections present with nausea, vomiting, and diarrhea. The diagnosis is usually based on clinical suspicion. Treatment is symptomatic. 
  • Campylobacter jejuni: curved, gram-negative bacilli. Common symptoms of infection are fever, headache, severe abdominal pain, myalgias, and diarrhea, which is sometimes bloody. Rarely, patients may exhibit arthritis, endocarditis, or meningitis. The diagnosis can be made with a stool culture. Treatment includes rehydration therapy and antibiotics (e.g., macrolides or fluoroquinolones).
  • Shigellosis: an acute bacterial infection of the GI tract caused by the gram-negative Shigella species. Patients develop symptoms of fever, tenesmus, and bloody diarrhea. Shigellosis is diagnosed clinically and confirmed by stool culture. Management can include rehydration therapy and antibiotics (in severe cases or in high-risk patients).
  • Non-typhoidal Salmonella: an infection caused by the gram-negative bacilli, S. enteritidis or S. typhimurium. Vomiting, abdominal cramping, fever, and inflammatory diarrhea may be present. Stool cultures can provide the diagnosis. Management is supportive, and antibiotics are only used for systemic manifestations or severe diarrhea.
  • Giardiasis: an infection of the intestinal tract caused by Giardia lamblia, a flagellated protozoan. The hallmark symptom of giardiasis is foul-smelling steatorrhea. Patients who develop chronic infections may experience weight loss, failure to thrive, and vitamin deficiencies resulting from malabsorption. The diagnosis is made through the detection of Giardia organisms, antigens, or DNA in the stool. Management includes supportive treatment and antimicrobial therapy with metronidazole, tinidazole, or nitazoxanide.

References:

  1. Hallowell, B.D., Parashar, U.D., Curns, A., DeGroote, N.P., Tate, J.E. (2019). Trends in the Laboratory Detection of Rotavirus Before and After Implementation of Routine Rotavirus Vaccination. MMWR, 68(24), 539–543. https://www.cdc.gov/mmwr/volumes/68/wr/mm6824a2.htm?s_cid=mm6824a2_w
  2. Dennehy, P.H. (2015). Rotavirus Infection: A Disease of the Past? Infectious Disease Clinics of North America. 29(4):617–635. https://pubmed.ncbi.nlm.nih.gov/26337738
  3. Burke, R.M., Tate, J.E., Barin, N., et al. (2018). Three Rotavirus Outbreaks in the Post Vaccine Era. MMWR 67:470–472.
  4. Grimwood, K., Lambert, S.B. (2009). Rotavirus Vaccines: Opportunities and Challenges. Human Vaccines. 5(2):57–69.
  5. Tate, J.E., Burton, A.H., Boschi-Pinto, C., Parashar, U.D. (2016). Global, Regional, and National Estimates of Rotavirus Mortality in Children < 5 Years of Age, 2000–2013. https://doi.org/10.1093%2Fcid%2Fciv1013
  6. Aliabadi, N., Tate, J.E., Haynes, A.K., Parashar, U.D. (2015). Sustained Decrease in Laboratory Detection of Rotavirus After Implementation of Routine Vaccination-United States, 2000–2014. MMWR, 64(13):337–342. https://www.ncbi.nlm.nih.gov/pubmed/25856253
  7. Centers for Disease Control and Prevention. (2011). Rotavirus surveillance—Worldwide, 2009. MMWR, 60(16):514-516. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6016a5.htm
  8. Crotese, M.M., Parashar, U. (2009). Prevention of Rotavirus Gastroenteritis Among Infants and Children: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR, 64(13):337–342. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5802a1.htm
  9. Payne, D.C., Englund, J.A., Weinberg, G.A., et al. (2019). Association of Rotavirus Vaccination With Inpatient and Emergency Department Visits Among Children Seeking Care for Acute Gastroenteritis, 2010–2016. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2752101
  10. Cortese, M.M., et al. (2013). Effectiveness of Monovalent and Pentavalent Rotavirus Vaccine. Pediatrics, 132(1):e25–33. https://www.ncbi.nlm.nih.gov/pubmed/23776114
  11. Bishop, R. (2009). Discovery of Rotavirus: Implications for Child Health. Journal of Gastroenterology and Hepatology. 24 (Suppl 3): S81–S85. https://doi.org/10.1111%2Fj.1440-1746.2009.06076.x
  12. Ruiz-Palacios, G., et al. (2006). Safety and Efficacy of an Attenuated Vaccine Against Severe Rotavirus Gastroenteritis. The New England Journal of Medicine. 354(1):11–22. http://www.nejm.org/doi/full/10.1056/NEJMoa052434
  13. Vesikari, T., et al. (2006). Safety and Efficacy of a Pentavalent Human-Bovine (WC3) Reassortant Rotavirus Vaccine. The New England Journal of Medicine. 354(1):23–33. http://www.nejm.org/doi/full/10.1056/NEJMoa052664
  14. O’Ryan, M.G. (2020). Clinical Manifestations and Diagnosis of Rotavirus Infection. UpToDate. Retrieved May 24, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-rotavirus-infection
  15. LeClair, C.E., and Budh, D.P. (2020). Rotavirus. StatPearls. Retrieved May 24, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK558951/
  16. Nguyen, D.D., Henin, S.S., and King, B.R. (2018). Rotavirus. Medscape. Retrieved May 24, 2021, from https://emedicine.medscape.com/article/803885-overview
  17. Centers for Disease Control and Prevention. (2021). Rotavirus. Retrieved May 24, 2021, from https://www.cdc.gov/rotavirus/index.html

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