Rotavirus (see the image below) is one of several viruses known to cause a self-limited gastroenteritis. Fluid stool losses may be dramatic, and death from dehydration is not uncommon, particularly in developing countries.
View Image | Transmission electron micrograph of rotavirus. Image courtesy of Centers for Disease Control and Prevention. |
Symptoms of rotavirus infection usually begin within 2 days of exposure and include the following:
Stool output can be copious during the diarrheal phase of the illness, and dehydration is a common presenting complaint.
See Clinical Presentation for more detail.
The physical examination findings for rotavirus infection are often unremarkable except for signs of dehydration. Other findings on examination may include the following:
Significantly decreased urine output is an important sign. However, this may be hard to identify in diapered infants, because the massive watery stool output makes it difficult to determine the amount of urine output.
Laboratory testing
Rotavirus may be identified by the following means[1] :
Other laboratory studies include measurement of electrolyte levels in patients with severe dehydration, alterations in mental status, associated seizures, or oral replenishment with excessive water or salt, as well as measurement of bedside glucose levels in very young infants and in any age child with associated lethargy.
See Workup for more detail.
In most cases, no medication is required for rotavirus infection. Instead, attention should be directed to appropriate fluid intake and other conservative measures.
Supportive care
Supportive care in infants with rotavirus infection includes the following:
There are currently 2 FDA-approved rotavirus vaccines to protect against rotavirus gastroenteritis (ie, RotaTeq and Rotarix). These vaccines are indicated in infants aged 6-32 weeks (RotaTeq) and those aged 6-24 weeks (Rotarix).
Note that in June 2013, the FDA approved required labeling for RotaTeq regarding intussusception data from the Mini-Sentinel’s Postlicensure Rapid Immunization Safety Monitoring (PRISM) program, the largest vaccine safety surveillance program in the United States.[2] The Mini-Sentinel PRISM study identified an increased risk of intussusception in the 21-day time period after the first dose of RotaTeq, with most cases occurring in the first 7 days after vaccination. No increased risk was found after the second or third doses. The findings translate into 1 to 1.5 additional cases of intussusception per 100,000 first doses of RotaTeq.[2]
The data from the Mini-Sentinel PRISM study regarding the risk of intussusception following the use of Rotarix were inconclusive.[2] Therefore, no labeling changes were required.
See Treatment and Medication for more detail.
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. Rotavirus is a self-limited infection. Fluid stool losses may be dramatic, and death from dehydration is not uncommon, particularly in developing countries.
View Image | Transmission electron micrograph of rotavirus. Image courtesy of Centers for Disease Control and Prevention. |
View Image | Transmission electron micrograph of intact rotavirus particles, double-shelled. Image courtesy of Centers for Disease Control and Prevention and Dr. E.... |
Rotavirus infection most commonly strikes during the winter months (December 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.[3] Almost every child 5 years and younger at some point will be infected with rotavirus in both developed countries and developing countries.
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 with increased motility can further exacerbate 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.[4]
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.
United States
Before the introduction of the rotavirus vaccines, this virus was estimated to cause 2.1-3.2 million diarrheal illnesses each year, with 55,000-70,000 of these requiring hospitalization annually.[1, 5, 6] In the 1990s and early 2000s, 410,000-600,000 office visits and 205,000-272,000 emergency department annual visits were attributed to rotavirus, and this resulted in yearly direct and indirect costs of the illness to be approximately $1 billion.[1, 6]
International
Worldwide incidence of rotavirus is estimated to cause more than 125 million cases of infantile diarrhea annually.[7] Rotavirus is the foremost cause of childhood dehydrating gastroenteritis worldwide.[1, 8] More than 2 million children younger than 5 years of age are hospitalized annually due to rotavirus gastroenteritis, and, of these, approximately 500,000-527,000 children die from this disease.[9, 10]
Before the introduction of the newer rotavirus vaccines, rotavirus was estimated to cause 20-60 deaths annually in the United States in children younger than 5 years.[1, 11]
Approximately 500,000-527,000 deaths in children younger than 5 years are seen worldwide due to rotavirus.[9, 10] Virtually all these deaths occur as a result of hypovolemia.
Significant morbidity is rare in the United States, 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 thrombosis.
Following introduction of the rotavirus vaccine in 2006, the incidence of severe gastroenteritis has declined significantly not only among children younger than 5 years but also in older age groups. A study using data from the Nationwide Inpatient Sample analyzed rotavirus-coded and cause-unspecified gastroenteritis discharges over a 10-year period and found there were significant reductions in rate ratios (RR) of rotavirus-coded gastroenteritis during 2008-2010 in the 0-4 year age group (RR, 0.20), those aged 5-14 years (RR, 0.30), and those aged 15-24 years (RR, 0.47).[12, 13] Moreover, significant reductions also occurred in cause-unspecified gastroenteritis in the 0-4 year age group (RR, 0.58), those aged 5-14 years (RR, 0.70), those aged 15-24 years (RR, 0.89), and those aged 25-44 years (RR, 0.94).[12, 13]
Race is not a factor in rotavirus infection, but one study did show that there was a reduced risk of hospitalization in infants born from Asian mothers in Washington State.[14] Socioeconomic class also plays an important role as this disease is more prevalent among children with Medicaid insurance.[14]
Rotavirus affects males and females equally, although males with viral gastroenteritis have been associated with an increased risk of hospitalization compared with females.[14]
Rotavirus can cause illness in adults and children. However, adults are often asymptomatic or less severely affected.
Adults, if affected, usually have a few days of nausea, anorexia, and cramping pain.[15] 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 rotavirus.
Low birth weight and prematurity as well as the paucity of breastfeeding have been associated with hospitalization from rotavirus.[16]
Almost every child worldwide is infected by rotavirus by the age of 3 to 5 years.[17]
In countries with relatively low incomes, the median age at which an infant develops rotavirus infectious symptoms is between 6 to 9 months with 80% of the infections occurring at < 1 year of age.[17]
In higher income countries, there is often a delay in rotavirus infectious symptoms until age 2-5 years, but there is a similarity with other countries in that the majority occur during infancy (65% occurring here in infants < 1 year of age).[17]
See the list below:
The physical examination findings for rotavirus infection are often unremarkable except for signs of dehydration.
The most significant risk factor for rotavirus infection 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 for viral transmission.
Rotavirus may be identified by several means (ie, enzyme immunoassay being the most common, latex agglutination, electron microscopy, culture).[1] However, in most cases, identification of the virus is important for public health or infection control purposes.[1] In general, use of such testing is less useful in the ED and can take significant time (days to weeks) for results to return.
View Image | This electron micrograph reveals a number of RNA rotavirus virions, and a number of unknown, 29nm virion particles. Image courtesy of Centers for Dise.... |
Electrolyte levels should be measured with severe dehydration, alterations in mental status, associated seizures, or oral replenishment with excessive water or salt.
Bedside glucose levels should be measured in very young infants and in any age child with associated lethargy.
Prehospital care of affected infants should be directed toward ensuring a secure airway, breathing, 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).
After ensuring proper airway and breathing and assessing circulation, identification and treatment of dehydrated infants is the main objective. In many cases, appropriate rehydration may be accomplished using established oral rehydration protocols. Lethargic children require a fingerstick glucose level immediately either by EMS or in the ED.
For severely dehydrated children, vascular 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 the key issue for children who are not dehydrated. Selection of an appropriate fluid is crucial. Some data show that administration of a bolus of 5% dextrose in 0.9% saline can help lower the level of serum ketones in dehydrated gastroenteritis patients.[18] A reduction in hospitalization rate, however, was not seen in this study comparing patients who received dextrose in 0.9% saline compared with those receiving 0.9% saline.[18]
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.
Antiemetics may be considered for children older than 6 months to control emesis.
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 if possible. Some recent studies have used antidiarrheals in children with success, but this practice is not widely accepted.[19, 20] Antidiarrheals are generally only recommended in cases of excessive or significantly prolonged diarrhea in which no other etiology has been determined.[21] Antiemetics have also been used with some success for vomiting in children with gastroenteritis.[22, 23] Antibiotics are not indicated if rotavirus gastroenteritis is suspected.[24]
A rotavirus vaccine (RotaShield) was released for general use in 1998-1999. Despite promising initial results, RotaShield was withdrawn from the market 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.
In February 2006, the United States Food and Drug Administration (FDA) approved RotaTeq. RotaTeq administration has been recommended for children as 3 separate oral doses at ages 2, 4, and 6 months.[1, 25] 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 at ages 2 and 4 months.[1, 25] Rotarix was efficacious in a large study showing that it protected patients against severe rotavirus gastroenteritis as well as decreasing the rate of severe diarrhea or gastroenteritis of any cause.[26]
Following the introduction of the rotavirus vaccine in 2006, a substantial decrease in hospitalization for diarrhea in children younger than 5 years has been observed.[27] Researchers from the US Centers for Disease Control and Prevention (CDC) analyzed hospital admission rates for rotavirus-related diarrhea and other measures of healthcare use. Results were compared with 5 years of data before 2006 (ie, before the introduction of the rotavirus vaccine). During 2007-2008, hospitalization rates for rotavirus-associated diarrhea decreased by 75% and hospitalizations for diarrhea of any cause decreased by 33% compared with the preceding 5-year period. Diarrhea-related incidence also decreased among age-matched unvaccinated children. The study estimated a $278 million reduction in hospital costs related to lower diarrhea-related admissions.[27]
The minimum recommended age for the first dose of either RotaTeq or Rotarix vaccine is 6 weeks, whereas the maximum age for the first dose of each is 14 weeks and 6 days.[1, 25] The minimum time recommended between each dose of either vaccine is 4 weeks, and the maximum age for the final vaccine dose is 8 months and 0 days.[1, 25] No maximum time between doses is specified by the Advisory Committee on Immunization Practices (ACIP).[1]
Either rotavirus vaccine can be given before, simultaneously, or after patient receipt of any blood product including those with antibodies.[1] In addition, a study involving 484 infants between the ages of 6-12 weeks were randomized to receive either Rotarix concurrently with their 2-month, 4-month, and 6-month vaccines or Rotarix separately at ages 3 months and 5 months.[28] The 2-month, 4-month, and 6-month vaccines were Haemophilus influenzae type b conjugate vaccine, 7-valent pneumococcal conjugate vaccine, and combined diphtheria-tetanus-acellular pertussis-hepatitis B-poliovirus vaccine. Serum antibodies were drawn one month after the third dose of the above vaccines, and it was determined that the antibody response was similar to all of the antigens in both study groups.[28]
Completion of the standard vaccination course is highly recommended,[1, 25, 29, 30] although even 1 or 2 doses of RotaTeq have been shown to significantly reduce ED visits and overall rotavirus gastroenteritis hospitalizations.[31] Regarding waning of immunity, one study evaluating patients younger than 5 years with acute gastroenteritis did not find any waning with RotaTeq for the first 4 years of life.[32] This study also did not find any waning of immunity for the first 2 years of life with Rotarix.[32] In addition, there has been documentation of herd immunity after rotavirus vaccinations.[33] In children less than one year old, the herd effect in the United States and Latin America was found to be 22% and 24.9%, respectively.[34]
Currently, ACIP, World Health Organization (WHO) (supported also by a large Cochrane Review), and American Academy of Pediatrics (AAP) recommend proper administration and usage of the vaccinations.[1, 25, 29, 30, 17] ACIP and AAP recommend that the vaccination be completed using the same product.[1, 25] However, if it is unknown which product was initially administered, the patient's vaccination series should still be completed with whichever vaccine is available.[1, 25] A randomized, multicenter, open-label study that included 1393 children reported that mixed rotavirus vaccine schedules were safe and induced comparable immune responses to administering a single vaccine formulation alone.[35]
ACIP and AAP do not directly state a preference for either RotaTeq or Rotarix.[1, 25] Owing to the use of different clinical scales defining severe rotavirus gastroenteritis in the trials of RotaTeq and Rotarix, a direct comparison of effectiveness often cannot be accurately made between the 2 vaccines.[25, 36] One study that enrolled patients younger than 5 years who had received the 3 doses of RotaTeq or 2 doses of Rotarix with acute gastroenteritis did show protection with either vaccine.[32] This same study also showed that after the 3 recommended doses of RotaTeq, 81% effectiveness against rotavirus-associated ED visits and 86% effectiveness against rotavirus-associated inpatient admissions was observed.[32] The authors also found that 2 recommended doses of Rotarix had 78% effectiveness against rotavirus-associated ED visits; however, the study was not powered enough to accurately assess Rotarix effectiveness for inpatient admissions.[32]
Other vaccines and newer agents such as oral anti-rotavirus proteins[37, 38] or antiviral thiazolides[39] 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 both RotaTeq and Rotarix 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 US Food and Drug Administration (FDA).[40] However, this number does not exceed the basal expected number of cases of intussusception in the general population. 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, whereas the other 12 patients were treated with a contrast or air enema.
According to a retrospective analysis of US insurance claims data for children aged 5 years or younger (N = 406,000), rotavirus vaccines reduced diarrhea-associated hospitalization by as much as 94% in the years after the vaccines were introduced. Both vaccinated and unvaccinated children benefitted; analysis showed an immediate decrease of 50% in hospitalization among unvaccinated children the first year vaccinations were available (2007-2008).[41, 42] Vaccines against rotavirus prevented more than 176,000 hospitalizations, 242,000 emergency department visits, and 1.1 million doctor's visits in the first four years they were available. Study authors estimate that this resulted in a cost savings of $924 million.
A study involving more than 63,000 patients who received Rotarix versus placebo at age 2 months and 4 months showed a decreased risk of intussusception for those patients receiving Rotarix.[26] 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.[26] Although more patients who received Rotarix were observed to have seizures or pneumonia-related deaths, this link has not been directly established to Rotarix.[26, 5] In addition, the FDA is requiring the Rotarix manufacturer to report data on postmarketing safety that involves more than 40,000 patients.[5]
Some studies from outside the United States have indicated a small but short-term increase in risks of developing intussusception following rotavirus vaccination. A study involving 615 patients over 69 hospitals in Mexico and Brazil reported an increased risk in intussusception with Rotarix in approximately 1 in 51,000-68,000 vaccinated infants.[43] This increased risk was seen in Mexico on days 1-7 after administration of the first dose of Rotarix, and this increase was also seen to a lesser extent in Brazil on days 1-7 after the administration of the second dose of Rotarix.[43] Another study from Australia showed an increased risk of intussusception within the first 3 weeks of receiving either RotaTeq or Rotarix in infants aged 1 month to less than 3 months, but they did not report an overall increase in the number of intussusception cases in infants aged 1-9 months after receiving the vaccine.[44]
Conversely, studies within the United States have not shown similar results to the aforementioned Mexico/Brazil[43] and Australian[44] studies.[45, 46] In addition, a serial cross-sectional analysis of American hospitals 4 years before vaccine reintroduction (1997, 2000, 2003, and 2006) and 1 year after vaccine reintroduction (2009) did not demonstrate an increase in the number of discharged patients younger than 1 year with a diagnosis of intussusception.[47] Another study involving 14 Latin American countries that currently use either Rotarix or RotaTeq compared the overall risk-and-benefit ratio of the vaccinations.[48] The authors of this study concluded that the benefits of the vaccination were clinically significant and easily outweighed the risks, including that of intussusception.[48]
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.[49] Five of the cases occurred in patients who received RotaTeq, while the other case was reported in a patient who received the placebo. Kawasaki disease has also been reported with Rotarix administration. In clinical trials, 17 cases of Kawasaki disease have been reported in those who received Rotarix, while 9 cases were reported in patients who received a placebo.[1]
The risks versus benefits of the available vaccines need to be evaluated for each individual patient. Based upon the current available data, it is generally accepted that the benefits of the vaccines significantly outweigh the risks of the vaccines including that of intussusception.[43, 50, 51, 48] With the introduction of RotaTeq and Rotarix, a significant amount of data have demonstrated the efficacy of the vaccines and overall decline of the rotavirus season not only in the United States but globally as well.[8, 10, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61] This has also lead to reduced use of resources and a significantly decreased need for hospitalizations and outpatient or emergency department visits.[8, 62, 63] In addition, specific studies on cost-effectiveness have also shown a benefit for rotavirus vaccination use.[64, 65, 66, 67, 68]
Although more research is necessary, nitazoxanide was shown to reduce rotavirus diarrhea and gastroenteritis in a small study of 38 patients between the ages of 5 months to 7 years.[69] 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 children and adults with diarrhea from Giardia or Cryptosporidium.
Clinical Context: Currently, 2 orally administered live-virus vaccines are marketed in the United States. Each is indicated to prevent rotavirus gastroenteritis, a major cause of severe diarrhea in infants.
RotaTeq is a pentavalent vaccine that contains 5 live reassortant rotaviruses and is administered as a 3-dose regimen against G1, G2, G3, and G4 serotypes, the 4 most common rotavirus group A serotypes. Also contains attachment protein P1A (genotype P[8]).
Rotarix protects against rotavirus gastroenteritis caused by G1, G3, G4, and G9 strains and is administered as a 2-dose series in infants between ages 6 and 24 wk.
Clinical trials found that each vaccine prevented 74-78% of all rotavirus gastroenteritis cases, nearly all severe rotavirus gastroenteritis cases, and nearly all hospitalizations due to rotavirus.
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 with the patient's primary physician is recommended to ensure patient improvement. The caretaker should also be instructed on clinical warning signs and the need to seek further care if the patient's symptoms worsen.
Breastfeeding can continue regularly before and after the patient receives the rotavirus vaccine.[25]
Inpatient care is usually not needed for rotavirus infection unless the child is dehydrated, cannot tolerate oral liquids, has a poor social network, or appears toxic.
Antiemetics have been used with some success in prevention of vomiting for gastroenteritis.[22, 23] Risk versus benefit of the medications must be determined by the treating clinician.
Transfer may be indicated for the dehydrated child who requires admission to a pediatric inpatient or ICU bed.
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.[70] Use of an alcohol-based hand sanitizer has been shown to reduce transfer of viruses to hands as well as to commonly contacted household surfaces.[71] Hand sanitizing wipes has also been shown to reduce infection risks of rhinovirus and rotavirus by 30-89%.[72]
Health care workers can be vectors for this illness. Extra vigilance with regard to hand washing, stethoscope cleaning, and housekeeping is warranted during rotavirus outbreaks.
The most important complication of rotavirus infection is dehydration.
Multisystem organ failure is possible when dehydration leads to shock and even death.
The prognosis for rotavirus infection 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.
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.