August 15, 2011

Strain Stopper
By Carolyn Gutierrez
For The Record
Vol. 23 No. 15 P. 24

Updated norovirus guidelines aim to further bolster infection control.

In response to recent advances made concerning the epidemiology, immunology, diagnostic techniques, and infection control of noroviruses, the Centers for Disease Control and Prevention (CDC) published the “Updated Norovirus Outbreak Management and Disease Prevention Guidelines” in the March 4 edition of Morbidity and Mortality Weekly Report.

In addition to the latest guidelines for managing and preventing outbreaks, state-of-the-art IT developments such as the National Outbreak Reporting System (NORS) and an electronic norovirus outbreak surveillance network called CaliciNet are described, giving public health professionals a modern edge in containing these wide-reaching viruses. By consolidating norovirus outbreak data using IT tools, public health professionals can more efficiently detect and monitor norovirus activity across the country.

According to epidemiologist Ben Lopman, MSc, PhD, one of the seven experts from the CDC’s Division of Viral Diseases who prepared the new recommendations, the guidelines “are a review of the current evidence on the biology and epidemiology of norovirus” and “provide guidance to states for reporting outbreaks to the CDC. … This is the first new set of guidelines on norovirus that has been published in a decade in the U.S.”

In 1968 in Norwalk, Ohio, a group of viruses that would later be known as Norwalklike viruses was first identified as the source of a gastroenteritis outbreak. Found within the Caliciviridae family, this group of single-stranded RNA, nonenveloped viruses is now known by its genus name norovirus.

Noroviruses are typically the culprit in large gastroenteritis epidemics, commonly referred to as food poisoning or stomach flu (although not related to influenza). According to the CDC guidelines, “In the United States, approximately 21 million illnesses attributable to norovirus are estimated to occur annually.”

Symptoms and Transmission
Following an incubation period of 12 to 48 hours, norovirus symptoms emerge, including the sudden onset of nonbloody diarrhea, nausea, vomiting, and abdominal pain. A patient may also experience body aches and fever. In otherwise healthy patients, the illness may resolve itself without treatment in one to three days, but in elder, pediatric, and immunocompromised populations, the illness can last four to six days, causing acute dehydration.

Although sometimes found in the vomit of infected patients, noroviruses are shed predominantly in the stool, generally two to five days after infection. However, the virus can remain in the stool for up to four weeks.

The updated CDC guidelines underscore how highly transmittable the norovirus particles are, noting that “approximately 5 billion infectious doses might be contained in each gram of feces during peak shedding.”

There are three paths of norovirus transmission: person to person, foodborne, and waterborne. Person-to-person transmission may occur through close interactions with infected persons or exposure to contaminated inanimate or environmental surfaces. According to the guidelines, “Norovirus is now recognized as the leading cause of foodborne disease outbreaks in the United States.”

Foodborne transmission may occur either through infected food handlers or by the food having been contaminated by sewage or human waste at some point in the food’s distribution or processing. The guidelines mention raspberries, oysters, and delicatessen meats having caused outbreaks in this fashion. Contaminated well water and breakdowns in the chlorination of municipal water systems have caused prodigious waterborne community outbreaks of norovirus.

When norovirus is suspected, the guidelines recommend prompt and thorough investigations, “including collection of clinical and epidemiologic information to help identify predominant mode of transmission and possible source.”

Outbreaks
Norovirus has cast its net over large populations, from infants in child care facilities and college students to prisoners and U.S. Marines during Operation Iraqi Freedom. Institutional settings such as hospitals and nursing homes are most vulnerable to outbreaks due to the lack of long-term immunity combined with the variety of insidious routes of transmission the virus may take. Large group settings such as restaurants and cruise ships are at risk as well. According to the updated guidelines, most norovirus outbreaks are caused by person-to-person transmission, but multiple routes of transmission can occur within an outbreak.

Citing statistics from a study by Zheng et al published in the Journal of Clinical Microbiology in 2010, the guidelines state, “Of the 660 norovirus outbreaks laboratory confirmed by CDC during 1994-2006 that indicated the setting, 234 (35.5%) were from long-term care facilities (eg, nursing homes); 205 (31.1%) were from restaurants, parties, and events; 135 (20.5%) were from vacation settings (including cruise ships); and 86 (13%) were from schools and communities.”

Norovirus outbreaks in healthcare facilities may be the most troubling as they tend to be severe and prolonged, increasing vulnerable patients’ risk of death. The updated guidelines recommend excluding ill staff that may be exposed to patients until 48 to 72 hours after symptom resolution and isolating ill residents or patients for 24 to 48 hours after symptom resolution.

In addition to noroviruses, pathogens such as rotavirus, sapovirus, and astrovirus have reportedly caused gastroenteritis outbreaks in child care centers due to insufficient immunity in the pediatric population.

Diagnostic Methods
In the past 10 years, refinements have been made in molecular diagnostic techniques, enabling scientists to detect viral strains more effectively. To identify noroviruses, most clinical virology labs perform real-time reverse transcription-polymerase chain reaction (RT-PCR) assays, in particular, TaqMan-based real-time assays. In a study published in the Journal of Clinical Microbiology in 2006, researchers examining the use of TaqMan-based real-time assays found that the technique demonstrated a higher sensitivity in detecting norovirus compared with a conventional RT-PCR assay, including the ability to detect the virus in water. Sensitive assays such as TaqMan could potentially decrease all-important turnaround times for identifying and managing norovirus strains responsible for public health epidemics.

The guidelines recommend collecting “whole stool specimens from at least five persons during the acute phase of illness (≤ 72 hours from onset) for diagnosis by TaqMan-based real-time reverse transcription…, perform genotyping on norovirus-positive stool specimens, and report results to CDC via CaliciNet.” Although stool specimen testing is preferred, vomit may also be collected for testing during an outbreak. Specimen testing must be done quickly in an epidemiologic investigation while the viral excretion is at its peak.

Prevention and Disinfection
“Norovirus is spread through a variety of transmission routes so no single means of prevention will tackle all cases, but personal hygiene, including hand washing, is probably the best single method, at least for preventing person-to-person transmission,” Lopman says. “Proper food handling, including thorough washing of raw vegetables, is useful for preventing foodborne transmission. Those are probably the two key prevention methods.”

The simple practice of hand washing is paramount to controlling the transmission and prevention of disease. The guidelines cite a study described in Pediatrics in 2008 in which “an intervention study in elementary schools demonstrated that improved hand hygiene and surface disinfection can lead to lower rates of absenteeism caused by nonspecific gastroenteritis and reduced surface contamination with norovirus.”

Frequent washing with soap and running water for a minimum of 20 seconds is recommended. Alcohol-based sanitizers (more than 70% ethanol) can be used for additional protection but should not be used in lieu of hand washing.

The updated norovirus guidelines underscore the importance of disinfecting potentially contaminated surfaces to prevent disease transmission. A chlorine bleach solution with a concentration of 1,000 to 5,000 ppm is recommended, and all cleaning products and disinfectants used in healthcare settings should be Environmental Protection Agency registered. Employees should be well versed in preventive controls and practices such as hand washing, cleaning, sanitizing equipment and surfaces, and, if applicable, proper food handling.

HIT’s Role
The CDC recommends swift reporting of all acute gastroenteritis outbreaks to state and local health departments. Norovirus reporting procedures have been streamlined thanks to NORS and CaliciNet, electronic surveillance systems created within the last two years. These systems have been beneficial in tracking new variants of the GII.4 strain that seem to evade population immunity. As the guidelines note, “These emergent GII.4 strains rapidly replace existing strains predominating in circulation and can sometimes cause seasons with unusually high norovirus activity, as in 2002-2003 and 2006-2007.”

According to Lopman, “NORS collects information on all outbreaks, including those spread from person to person, which is the majority of norovirus outbreaks, and it collects basic epidemiological outbreak data. CaliciNet is a national data system of genetic sequences of noroviruses that are found to cause outbreaks, and this system is used to identify new strains of norovirus when they emerge and also to link outbreaks that may be caused by a genetically identical virus. Both of these systems are fully online and state health departments access them to the Web and can report and access data online through these systems.”

A large compilation of norovirus data can give scientists a national perspective, an overview from which to discern emerging viral strains and disease patterns.

“Similar to influenza, new strains of norovirus emerge every couple of years,” says Lopman, “and when they do emerge, most people don’t have immunity to them and so they can cause big outbreaks. I think at this stage, what scientists do now is try to understand immunity to norovirus, and one aspect of that is to understand the emergence of these new strains. Ultimately, that sort of understanding could lead to new interventions, including vaccines.”

— Carolyn Gutierrez is a freelance writer based in New York City.