Rotavirus:
A Major Cause of Childhood Morbidity and Mortality
By Kelly A. Reynolds, Ph.D.

Rotavirus is a pathogen of the gastrointestinal tract that causes severe acute gastroenteritis and diarrhea among infants and children, and is the most common cause of severe vomiting and diarrhea in children worldwide. Rotavirus is capable of long term survival and infections are highly contagious. Although repeat infections appear to be less severe, children may become infected several times with rotavirus.

The virus has a characteristic wheel and spoke shape and shares a number of features with the influenza virus. With a wide variety of types and subtypes of the virus group-and the ability to change their surface proteins over time-a number of different rotaviruses may be present in communities at the same time. In addition, like influenza infections, rotavirus illness has a seasonal fluctuation, with infections in North America peaking in the winter.

There are six distinct serological groups of the virus, labeled A through F. Group A rotaviruses typically cause infections in humans; and also primates, horses, pigs, dogs, cats, rabbits, mice, cattle and birds. Other groups infect pigs (B, C, E), cattle (B), sheep (B), rats (B), ferrets (C), and chicken (D, F, G). Groups B and C rotaviruses have been known to cause infections in humans, and may be associated with transfer of the pathogen from their animal hosts.

Public health impact
Enteric illness continues to be a rampant problem worldwide resulting in significant morbidity and mortality. Officials estimate that by the age of four, nearly every child will have been infected with rotavirus. Sadly, more than 870,000 deaths throughout the world each year are due to rotaviral gastroenteritis. Death is usually due to severe dehydration and loss of electrolytes, treatable symptoms in regions with access to medical supplies and clean water. Although 3.5 million cases of rotaviral diarrhea are estimated to occur yearly in the U.S., the death rate is much lower than in developing countries, with up to 125 deaths and 104,000 hospitalizations. In the United States, it's estimated that rotavirus illness costs in excess of $1.4 billion per year.

Marked by vomiting, high fever, and diarrhea, rotavirus illness typically manifests after 12 hours to four days of exposure and lasts from 4-to-8 days. Humans of all ages are susceptible to rotavirus infections; however, children under age two and the immunocompromised are more likely to experience severe symptoms from the infection.

Waterborne transmission
Many rotavirus infections may not result in noticeable disease symptoms, and are thus termed asymptomatic. Spread by the fecal-oral route, an infected person may excrete up to 10 billion viruses per gram of feces, providing a source for water contamination via sewage or fomites (inanimate objects) and food contamination via tainted hands. Waterborne outbreaks of rotavirus have been recorded and rotavirus continues to be found in sewage, source waters and shellfish harvest areas. One study found rotavirus present in 20 percent of the shellfish in the test area. What's more alarming is that no relationship was found between viral contamination and bacterial indicators-the routine test to determine the overall water quality.

As mentioned, rotavirus may also be transmitted by air, hands, fomites and food. Known to survive for weeks in potable and recreational waters, and for at least four hours on human hands, the potential for cross-contamination to other surfaces and unsuspecting individuals is high. Outbreaks are common in childcare centers and in pediatric hospitals and have been documented in elderly nursing homes. In January 1989, the Centers for Disease Control (CDC) established a National Rotavirus Surveillance System in the United States to monitor the presence of rotavirus. During the 23-month survey period, rotavirus was detected in 20 percent of 48,035 specimens from pediatric, community, commercial, hospital and public health laboratories. A similar survey conducted in 1998 revealed an incidence rate of 23 percent in 22,912 fecal specimens examined.

Avoiding infection and disease
Typical of many virus infections, there's no treatment for rotaviral gastroenteritis other than supportive therapy. Keeping the patient hydrated either by intravenous fluids or oral rehydration (electrolyte replacement) formulas drastically reduces the chance for death by dehydration. Although nursing babies may still become infected, asymptomatic infection is more likely in the first three months of life due to the passive immunity of transplacental antibodies and human breast milk.

According to the results of a new study, rotavirus may cause symptoms by stimulating the nervous system in the wall of the gut, leading to increased secretion of salts and water. Targeting the mechanism of rotavirus infection and illness may lead to the development of drugs to combat the disease. One example of this is from Dr. Ove Lundgren, of Goteborg University in Sweden. His study gave drugs to mice that inhibited the nervous system of the gut, finding that within two days of being infected with rotavirus, only six out of 14 mice receiving treatment developed diarrhea, compared to 14 out of 15 mice that were infected but didn't receive the medicine.

On August 1998, a vaccine known as Rotashieldâ was developed and released for the prevention of rotavirus infections. Proven to decrease the morbidity and mortality of rotavirus infections, the new vaccine was touted as a miracle shot that may save the lives of thousands of children. Unfortunately, in July 1999, the CDC recommended use of the vaccine be halted due to the potential link with intussusception, a type of bowel obstruction that occurs when the bowel folds in on itself, possibly requiring surgery to repair.

Although this link has not yet been proven, Wyeth Laboratories Inc. of Marietta, Pa., voluntarily ceased further distribution of the vaccine, in consultation with the U.S. Food and Drug Administration. Scientists at Children's Hospital Medical Center in Cincinnati have developed a new rotavirus vaccine that appears to be up to 89 percent effective at preventing the disease, but is still being tested.

Microbiologists are working on the development of a reliable and consistent method for the detection of rotavirus in water that will also provide a practical means of routine monitoring. The use of molecular-based methods that target viral genomes appears to be the most likely means of virus detection in water in the future. Other methods being investigated include: combined use of cell culture and the molecular polymerase chain reaction (PCR) approach, microscopic methods and flow cytometry. Risk assessment modeling, a mathematical approach to predicting the risks of infection from waterborne pathogens, is also being streamlined for rotavirus.

Conclusion
As always, it's best to avoid infection with viral pathogens in the first place rather than rely on post-infection treatments. Prevention includes the improvement of sanitary conditions, health education and better nutrition. Good hygiene, including frequent handwashing, is a necessary step for infection control of rotavirus and a variety of other human pathogens. Finally, chemical disinfection and water purification methods effective against viruses are necessary to prevent virus transmission from contaminated waterborne routes.

References
1. Abad, F.X., R.M. Pinto and A. Bosch, "Flow cytometry detection of infectious rotaviruses in environmental and clinical samples," Applied Environmental Microbiology, 64: 2392-2396, 1998.
2. Gale, P., "Developments in microbiological risk assessment models for drinking water-a short review," Journal of Applied Bacteriology, 81: 403-410, 1996.
3. LeGuyader, F., E. Dubois, D. Menard, and M. Pommepuy, "Detection of hepatitis A virus rotavirus and enterovirus in naturally contaminated shellfish and sediment by RT-seminested PCR," Applied Environmental Microbiology, 60: 3665-3671, 1994.
4. Lundgren O., A.T. Peregrin, K. Persson, S. Kordasti, I. Uhnoo and L. Svensson, "Role of the Enteric Nervous System in the Fluid and Electrolyte Secretion of Rotavirus Diarrhea," Science, Jan. 21; 287: 491-495, 2000.
5. U.S. Centers for Disease Control & Prevention (CDC), "Withdrawal of rotavirus vacine recommendation," Morbidity and Mortality Weekly Report (MMWR), 48:1007, 1999.
6. CDC, "Rotavirus surveillance-United States, 1989-1990," MMWR, 40: 1991.
7. CDC, "Rotavirus surveillance-United States, 1997-1998," MMWR, 47:978-980, 1999.

Acknowledgment
Images in this article can be found on the website: www.rotavirus.com


 Dr. Kelly A. Reynolds About the author
Dr. Kelly A. Reynolds is a research scientist at the University of Arizona with a focus on the development of rapid methods for detecting human pathogenic viruses in drinking water. She is also a member of the WC&P Technical Review Committee.