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Rotavirus Overview SUPPLEMENT Rotavirus Overview David I. Bernstein, MD, MA mately 70% during seasonal peaks of the disease.1 Figure 14 Abstract: Rotaviral gastroenteritis is a serious public health problem in illustrates the very large importance of rotavirus as an etiologic both developed and developing countries. The disease is ubiquitous, agent in severe diarrhea requiring hospitalization compared with affecting nearly all children by the age of 5 years. It is the most common other pathogens in both developing and developed countries.4 cause of hospitalizations for gastroenteritis among children in the United Several epidemiologic and clinical characteristics associ- States (30%–70% depending on the season) and is associated with direct ated with rotavirus argue for use of vaccination as the primary and indirect costs of approximately $1 billion per year. Symptoms of public health intervention for rotavirus.1 This includes the obser- rotaviral gastroenteritis are nonspecific (ie, diarrhea, vomiting, and fever), vations that the rates of rotavirus illness are similar in developed with disease severity varying considerably. Diagnostic confirmation of and less-developed countries, indicating that improved sanitation rotaviral gastroenteritis requires laboratory tests (most commonly enzyme will not decrease disease prevalence and the continued high rates immunoassay or latex agglutination); however, because specific diagnosis of hospitalization despite the widespread availability and use of is costly and does not affect treatment, laboratory tests are generally not oral rehydration solutions.1 In addition, natural history studies performed. Because no antiviral therapies are currently available, treatment suggest that mild, asymptomatic infection effectively protects of rotavirus infection is supportive and primarily aimed at the replacement against subsequent severe rotavirus gastroenteritis. Thus, the de- of fluid and electrolyte losses. Based on the observations that improved velopment of a vaccine that mimics a mild asymptomatic infection sanitation does not decrease disease prevalence and that hospitalizations has the potential to prevent the morbidity and mortality associated remain high despite the availability and use of oral rehydrating solutions, with severe rotavirus disease.1 the primary public health intervention for rotavirus infection is vaccination. Current vaccines (ie, RotaTeq, Merck and Company; Rotarix, GlaxoSmith- Kline) are effective for reducing rotaviral gastroenteritis (particularly DISEASE BURDEN severe disease), emergency department visits, and hospitalizations. Rota- Rotavirus gastroenteritis inflicts a devastating impact on virus vaccination is now included as part of the routine vaccination infants and young children, particularly in developing countries. It schedule for all infants in the United States. is estimated that the disease is associated with the deaths of more Key Words: rotavirus, gastroenteritis, rotavirus vaccine, diagnosis, than 600,000 children per year worldwide, with the majority of 5 treatment, epidemiology deaths occurring in Africa and Asia. Yearly death tolls are high in India (146,000), Nigeria (47,500), China (41,000), Pakistan (Pediatr Infect Dis J 2009;28: S50–S53) (36,500), Congo (29,000), and Ethiopia (29,000).5 Bangladesh has the highest per capita death rate from the disease.5 Although mortality rates in the United States are much lower (20–60 deaths/yr), the disease is still associated with substantial disease otavirus is the most common cause of severe diarrhea in infants burden. It is estimated that rotavirus gastroenteritis is associated Rand young children in both the United States and around the with 410,000 physician visits, 205,000 to 272,000 emergency 1 world. Rotavirus infection is nearly universal, with approximately department visits, and 55,000 to 70,000 hospitalizations each year 95% of children experiencing rotavirus gastroenteritis by age 5 1 2 in the United States. Thus, between 1 in 67 and 1 in 85 children years. There is no difference in the incidence of rotavirus infec- in the United States will be hospitalized with rotavirus by the age tion between developed and developing countries, indicating that of 5 years.6 Risk factors for rotavirus-induced hospitalization improved sanitation does not decrease the transmissibility of the 2 include no breastfeeding, low birth weight, being in child care, no virus. In the United States, rotavirus is responsible for 5% to 10% insurance or having Medicaid, and the presence of another child of cases of gastroenteritis among children Ͻ5 years of age, but it Ͻ 7 2 24 months in the house. is responsible for a much higher proportion of severe episodes. The direct and indirect costs associated with the disease are Compared with other causes of gastroenteritis, rotavirus is more estimated to be approximately $1 billion in the United States.1,2 A frequently associated with severe symptoms (eg, fever, vomiting, 3 study in 1993 calculated that the average total cost per episode of combined diarrhea/vomiting). Rotaviral gastroenteritis has been diarrhea presenting to a primary care physician was $289, with time shown to cause approximately 40% of all outpatient visits for acute missed from work by the parent/caretaker responsible for half of the gastroenteritis in infants and young children to pediatric primary 8 3 total cost (Fig. 2). The majority of parents missed at least 1 day of care practices. Furthermore, between 30% and 50% of all hospi- work (average 1.3 days).8 As expected, costs are much higher when Ͻ talizations for gastroenteritis among US children aged 5 years hospitalization is required. A study analyzing medical claims between are due to rotavirus infection. This value increases to approxi- 1993 and 1996 found that the cost of hospitalization (in 1998 dollars) was in excess of $2300, with a range of $648 to $79,886.9 Other studies of rotavirus-related hospitalizations have estimated median From the Cincinnati Children’s Hospital Medical Center; University of Cincin- charges per hospitalization of $2999 to $3399.6,10 Notably, because nati, Cincinnati, OH. Disclosure: Dr. Bernstein receives royalties for his work in the development of these analyses included only charges for medical services, these Rotarix and the patent for 89-12. He is also a consultant for GlaxoSmithKline. values did not include indirect costs (eg, lost time from work). Address for correspondence: David I. Bernstein, MD, MA, Cincinnati Chil- One large prospective study11 examined these indirect costs dren’s Hospital Medical Center; University of Cincinnati, 3333 Burnet between November 1997 and December 1999 at 3 pediatric med- Avenue, Cincinnati, OH 45229. E-mail: [email protected]. Copyright © 2009 by Lippincott Williams & Wilkins ical centers. The average nonmedical cost per case of severe ISSN: 0891-3668/09/2803-0050 rotavirus disease that required hospitalization was approximately DOI: 10.1097/INF.0b013e3181967bee $450–80% of which ($359) was attributed to missed work and S50 The Pediatric Infectious Disease Journal • Volume 28, Number 3, March 2009 The Pediatric Infectious Disease Journal • Volume 28, Number 3, March 2009 Rotavirus Overview EPIDEMIOLOGY The severity of rotavirus infection is age dependent. Al- though the disease can occur at any age, the disease most com- monly causes clinically significant disease in young infants and children.14,15 The first infection after 3 months of age is generally the most significant, with severe, dehydrating rotaviral gastro- enteritis primarily occurring among infants and children aged 3 to 35 months.1,2 The reasons for the reduced severity of disease in neonates are not completely understood, but because the onset of rotavirus disease corresponds with the decline of FIGURE 1. Role of etiologic agents in the pathogenesis of maternal antibody levels, early protection may be related to severe diarrheal illness requiring hospitalization in devel- transplacental antibodies that persist for the first months of 14,15 oped and developing countries. Reproduced with permis- life. sion from JAMA. 1993;269:627–629. Copyright 1993, Transmission of rotavirus is primarily via fecal-to-oral American Medical Association.4 spread, both through close person-to-person contact and contact with contaminated environmental surfaces.2,16 The virus is also probably transmitted via fecally contaminated food and water and/or respiratory droplets.2,16 Once established within the small intestine, the virus replicates in the villous epithelium, resulting in decreased intestinal absorption of sodium, glucose, and water, and decreased levels of intestinal lactase, alkaline phosphatase, and sucrase activity that may result in isotonic diarrhea.2 Rotavirus outbreaks exhibit a seasonal pattern. In temperate climates, rotavirus infections peak in winter months.1,2,17 In 1 study,18 the proportion of patients hospitalized with gastroenteritis who had confirmed rotavirus infection ranged from 25% during the off season to more than 70% during peak season. In the United States, annual epidemics begin in the Southwest during November and December, progressing north and east and reaching the North- east by April or May.14 A similar pattern has been identified in Europe, with the seasonal peak beginning in Spain in January, spreading to northern countries by March.14 Seasonality is less marked closer to the equator but the disease is more pronounced during drier and cooler months. The reason for this seasonality remains unknown.14,15 Recent data
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