AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Rotavirus is one of several viruses known to cause gastroenteritis. The rotavirus genome consists of 11 segments of double-stranded RNA enclosed in a double-shelled capsid. It is classified in the Reoviridae family. Although it is a self-limited infection, fluid stool losses may be dramatic, and death from dehydration is not uncommon, particularly in developing countries.

This infection most commonly strikes during the winter months (November through May), but it occurs year round in developing countries. In the United States every year, rotavirus first appears in the Southwest and spreads to the Northeast. Almost every child 5 years and younger at some point will be infected with rotavirus in both developed countries and developing countries.

For a related CME activity, see Rotavirus: Pillars of Care -- A Comprehensive Overview of Rotavirus: Understanding Virology and Epidemiology to Effectively Manage and Prevent Disease.

Pathophysiology

Rotavirus, like other viruses that cause enteritis, primarily infects the cells of the small intestinal villi, especially those cells near the tips of the villi. Because these particular cells have a role in the digestion of carbohydrates and in the intestinal absorption of fluid and electrolytes, rotavirus infections lead to malabsorption by impaired hydrolysis of carbohydrates and excessive fluid loss from the intestine. A secretory component of the diarrhea is present, with increased motility further exacerbating the illness; this increased motility appears to be secondary to virus-induced functional changes at the villus epithelium.

The pathologic changes to the intestinal lining may not correlate well with the clinical manifestations of the illness. In normal hosts, infections rarely occur in another organ system, although extraintestinal infections have been seen in immunocompromised hosts.

The virus is shed in high titers in the stool starting before the onset of symptoms and persists for up to 10 days after symptom appearance.

Frequency

United States

According to estimates, rotavirus causes 2.7 million diarrheal illnesses each year, with 80,000 of these requiring hospitalization annually.

International

Worldwide incidence of rotavirus is estimated to cause more than 125 million cases of diarrhea annually. Rotavirus is the foremost cause of childhood dehydrating gastroenteritis worldwide.

Mortality/Morbidity

• Rotavirus may cause as many as 100 deaths annually in the United States.
• Approximately 352,000-592,000 deaths are seen worldwide due to this disease. Virtually all these deaths occur as a result of hypovolemia.
• Significant morbidity is rare, but dehydration and shock can result in ischemic injury to the kidneys or the central nervous system.
• Children who become severely dehydrated may develop deep venous thromboses or cerebral venous thromboses.

Race

Race is not a factor in rotavirus infection, although socioeconomic class plays an important role. The disease is more prevalent among children in lower socioeconomic classes.

Sex

Rotavirus affects males and females equally.

Age

Rotavirus can cause illness in adults and children; however, adults are less severely affected.

• Adults usually have a few days of nausea, anorexia, and cramping pain. Diarrhea is a less significant symptom in adults than in children.
• Young children aged 4-24 months, particularly those in group daycare settings, are at increased risk for acquiring this infection.
• Newborn infants seem more resistant to this disease than their slightly older peers. They may shed the virus without being symptomatic. This phenomenon occurs in both breastfed babies and formula-fed babies; therefore, the protective effect of breastfeeding does not explain this phenomenon.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Often, a history of exposure to other children with diarrhea is reported.
• Symptoms usually begin within 2 days of exposure and include the following:
• • Anorexia
  • Low-grade fever
  • Watery, bloodless diarrhea
  • Vomiting
  • Abdominal cramps
• Stool output can be copious during the diarrheal phase of the illness, and dehydration is a common presenting complaint.

Physical

The physical examination findings are often unremarkable except for signs of dehydration.

• The most common finding is hyperactive bowel sounds.
• Rectal examination may stimulate the production of watery, heme-negative stools.
• Tachycardia disproportionate to temperature
• Sunken eyes and/or anterior fontanelle
• Dry or sticky-appearing mucosa
• Rough skin
• Depressed sensorium
• Significantly decreased urine output is an important sign, but it may be difficult to identify in diapered infants because the massive watery stool output makes it difficult to determine the amount of urine output.
• Weight loss

Causes

The most significant risk factor appears to be participation in group daycare, presumably because the virus is spread through fecal-oral contact by the children themselves and by the daycare workers who are responsible for diapering. Also, fomites serve as important vectors.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Food poisoning
Cholera
Salmonella

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Rotavirus may be identified by several means (ie, latex agglutination, enzyme immunoassay, electron microscopy, culture); however, in most cases, identification of the virus is important for public health purposes only. In general, use of such testing is unlikely in the ED.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• Prehospital care of affected infants should be directed toward identification of circulatory compromise and maintenance of adequate circulation. Field personnel may not be able to achieve access in the child with a contracted circulatory volume.
• • Infants who appear significantly dehydrated ideally should have 20 mL/kg isotonic sodium chloride solution or Ringer lactate solution administered en route to the hospital.
  • Patients who are less severely affected need only monitored transport.
  • The destination ED should be an ED approved for pediatrics (EDAP) or a pediatric critical care center (PCCC).

Emergency Department Care

• Identification and treatment of dehydrated infants is most important. In many cases, appropriate rehydration may be accomplished using established oral rehydration protocols. Lethargic children require a fingerstick glucose level initially.
• • For severely dehydrated children, IV access (often via an IO line) is required.
  • Administer 20 mL/kg boluses until volume is restored. A total requirement of 60-80 mL/kg is not uncommon.
  • If more than 40 mL/kg is necessary, consider electrolytes, BUN, and creatinine levels.
• Maintenance of hydration is the key issue for children who are not dehydrated. Selection of an appropriate fluid is crucial.
• • Infants who receive hyperosmolar fluids (eg, commercial soft drinks, sports drinks, gelatin) and those who are fed high salt-content solutions (eg, commercial soup, boiled milk) are at risk for significant hypernatremia.
  • Ideal maintenance beverages for dehydrated infants with viral enteritis are commercial infant solutions such as Pedialyte and Rice-Lyte. These beverages contain a small amount (usually 2-3%) of glucose and the correct balance of sodium and potassium.
    • Rehydrating infants with these beverages may be particularly difficult within the first 2 days of the illness because vomiting frequently occurs.
    • If the infant is vomiting, administer small, frequent feedings.
  • Once vomiting has resolved, the baby may be given a standard soy-based infant formula. This formula provides adequate energy intake for intestinal healing.
  • Supplemental feedings of oral maintenance solutions may be administered if fluid losses are excessive.
  • Avoid sports drinks and other hyperosmolar beverages for the reasons previously stated. Similarly, excessive free-water intake may predispose the infant to hyponatremia.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

In most cases, no medication is required. Instead, attention should be directed to appropriate fluid intake. Antiemetic and antidiarrheal medications have some risks for children in the age group typically affected by rotavirus and should be avoided. Some recent studies have used antidiarrheals in children with success, but this practice is not widely accepted. Antibiotics are not indicated.

A rotavirus vaccine (RotaShield) was released for general use in 1998-1999. Despite promising initial results, vaccination was withdrawn in 1999 because of a causal relationship between the vaccine and several cases of intussusception. The risk was observed 3-14 days following administration of the first dose of the RotaShield vaccine in infants older than 3 months.

Clinical trials are currently ongoing for production of a new vaccine without significant adverse effects. Promising oral vaccines that have been shown to be efficacious in preventing rotavirus diarrhea and in reducing the severity of the disease are being studied.

In February 2006, the United States Food and Drug Administration (FDA) approved one of the aforementioned oral vaccines known as RotaTeq. RotaTeq administration has been recommended for children as 3 separate oral doses at ages 2, 4, and 6 months. On February 21, 2006, the American Academy of Pediatrics (AAP) and the Advisory Committee on Immunization Practices (ACIP) recommended RotaTeq to be part of regularly scheduled childhood immunizations.

In April 2008, the FDA approved Rotarix, another oral vaccine, for prevention of rotavirus gastroenteritis. Rotarix administration is currently recommended as 2 separate doses to patients between 6 and 24 weeks of age.¹ Rotarix was efficacious in a large study showing that it protected patients with severe rotavirus gastroenteritis as well as decreasing the rate of severe diarrhea or gastroenteritis of any cause.²

Other vaccines may eventually be released in the United States, although a definitive date has not yet been set. In addition, side effects, such as intussusception, will be closely monitored for RotaTeq and any other future rotavirus vaccines. Between February 3, 2006, to January 31, 2007, 28 cases of intussusception after RotaTeq administration have been reported to the FDA.³ However, this number does not exceed the basal expected number of cases of intussusception. The cases have developed after the first, second, or third dose of RotaTeq. Fortunately, no deaths were reported, but 16 of the 28 case patients required hospitalization and surgery, while the other 12 patients were treated with a contrast or air enema. 

A study involving more than 63,000 patients who received Rotarix versus placebo at ages 2 and 4 months showed a decreased risk of intussusception for those patients receiving Rotarix.² The intussusception data were determined over a 31-day observation period (inpatient or outpatient) after each dose of the Rotarix vaccine, and this also included a 100-day surveillance period for all serious adverse events.² Although more patients who received Rotarix were observed to have seizures or pneumonia-related deaths, this link has not been directly established to Rotarix.^{2, 1} In addition, the FDA is requiring the Rotarix manufacturer to report data on postmarketing safety that involves more than 40,000 patients.¹

In June 2007, the FDA also revised the RotaTeq Adverse Reactions and Post-Marketing sections of the label to include Kawasaki disease, as 6 cases of Kawasaki disease were reported in the phase 3 clinical trial of RotaTeq.⁴ Five of the cases occurred in patients who received RotaTeq, while the other case was reported in a patient who received the placebo. No cause and effect relationship has been established with this and Kawasaki disease.

Although more research is necessary, nitazoxanide was shown to reduce rotavirus diarrhea and gastroenteritis in a small study of 38 patients.⁵ Time to resolution of illness was 31 hours for the group who received nitazoxanide compared with 75 hours for the placebo group. Nitazoxanide is currently approved by the FDA for treatment of diarrhea in pediatric and adult patients with diarrhea from Giardia or Cryptosporidium.

Drug Category: Vaccines

Elicit active immunization to increase resistance to infection. Vaccines consist of microorganisms or cellular components, which act as antigens. Administration of the vaccine stimulates the production of antibodies with specific protective properties.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Inpatient care is usually not needed unless the child is dehydrated, cannot tolerate oral liquids, has a poor social network, or appears toxic.

Transfer

• Transfer may be indicated for the dehydrated child who requires admission to a pediatric ICU.

Deterrence/Prevention

• Rotavirus is contagious. Parents who have more than one young child or who help care for several small children should be cautioned about good hand-washing technique. Children who are asymptomatic should not play with children who are symptomatic during the diarrheal phase of the illness.
• Daycare centers should keep symptomatic children together and separated from those who are not symptomatic. Ideally, the staff should be segregated as well, so that some staff members care for only the symptomatic children, and some staff members care for the others. Fomites should also be disinfected as viral spread from these objects has also been demonstrated.
• Health care workers can be vectors for this illness. Extra vigilance with regard to hand washing and housekeeping is warranted during rotavirus outbreaks.

Complications

• The most important complication of rotavirus infection is dehydration.
• Multisystem organ failure is possible when dehydration leads to shock.

Prognosis

• The prognosis is excellent as long as adequate hydration is maintained.
• Most children recover within a week of symptom onset.
• Rotavirus enteritis has virtually no important long-term sequelae.
• Reinfection is a common phenomenon.

Patient Education

• Parents should be taught the signs and symptoms associated with dehydration and should be instructed to seek care immediately upon noticing any of these signs or symptoms in a child.
• Parents must know which fluids should and should not be given and how to administer these fluids to young children who are vomiting.
• Parents should be informed about early refeeding with a soy-based infant formula and a bland, general diet, which may include lactose-free milk for toddlers.
• Diarrhea can last for 5-7 days.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Discharge instructions should include the signs of dehydration and clear instructions to return if any of these signs are noticed. Instructions also should warn against use of very osmolar or very salty fluids for the maintenance of hydration. On the other hand, excessive use of free water may be detrimental as well.
• Inadequate volume resuscitation with associated organ failure may result in shock and even death.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. FDA Approves New Vaccine to Prevent Gastroenteritis Caused by Rotavirus. US Food and Drug Administration; April 3, 2008. [Full Text].
2. Ruiz-Palacios GM, Perez-Schael I, Velazquez FR. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med. Jan 5 2006;354(1):11-22. [Medline].
3. Information on RotaTeq and Intussusception. US Food and Drug Administration; February 13, 2007. [Full Text].
4. Information Pertaining to Labeling Revision for RotaTeq. US Food and Drug Administration; June 15, 2007. [Full Text].
5. Rossignol JF, Abu-Zekry M, Hussein A, Santoro MG. Effect of nitazoxanide for treatment of severe rotavirus diarrhoea: randomised double-blind placebo-controlled trial. Lancet. Jul 8 2006;368(9530):124-9. [Medline].
6. Bass DM. Rotavirus and other agents of viral gastroenteritis. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 2004:1081-3.
7. Bines JE. Rotavirus vaccines and intussusception risk. Curr Opin Gastroenterol. Jan 2005;21(1):20-5. [Medline].
8. Hamilton JR. Viral enteritis. Pediatr Clin North Am. Feb 1988;35(1):89-101. [Medline].
9. Kombo LA, Gerber MA, Pickering LK, et al. Intussusception, infection, and immunization: summary of a workshop on rotavirus. Pediatrics. Aug 2001;108(2):E37. [Medline].
10. Peter G, Myers MG. Intussusception, rotavirus, and oral vaccines: summary of a workshop. Pediatrics. Dec 2002;110(6):e67. [Medline].
11. Pickering LK, Cleary TG. Infections of the gastrointestinal tract. In: Gershon AA, Hotez PF, Katz SL, eds. Krugman's Infectious Diseases of Children. 2004:220-1.
12. Ramig RF. Pathogenesis of intestinal and systemic rotavirus infection. J Virol. Oct 2004;78(19):10213-20. [Medline].
13. Santosham M, Foster S, Reid R, et al. Role of soy-based, lactose-free formula during treatment of acute diarrhea. Pediatrics. Aug 1985;76(2):292-8. [Medline].
14. Vesikari T, Matson DO, Dennehy P, et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med. Jan 5 2006;354(1):23-33. [Medline].
15. Widdowson MA, Bresee JS, Gentsch JR, Glass RI. Rotavirus disease and its prevention. Curr Opin Gastroenterol. Jan 2005;21(1):26-31. [Medline].

Article Last Updated: Aug 18, 2008