Options for controlling norovirus from farm-to. to-fork in ready-to food. NoV The Public Health Problem. NoV The Public Health Problem

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Options for controlling norovirus from farm-to to-fork in ready-to to-eat food. CAPT Wendy Fanaselle USPHS, FDA, CFSAN NoV The Public Health Problem NoV is the most common cause of gastroenteritis in people of all ages Responsible for < 50 % of all foodborne gastroenteritis outbreaks and 35% of all sporadic gastroenteritis outbreaks Estimated to be as frequent a cause of illness and death internationally as Salmonella foodborne illness The most significant diarrheal virus in terms of work/education days lost because it impacts all ages NoV The Public Health Problem Secondary Infections: Attack rate >50% in areas where a large population is enclosed within a static environment, such as: institutions, schools, military operations, hotels, recreational camps, or aboard cruise ships 1

NoV The Public Health Problem The greatest public health impact: In institutions such as hospitals and nursing homes, where NoV outbreaks commonly occur. Gastroenteritis: The most common illness experienced by ground troops during the Gulf War, and 70% of these cases were attributed to NoV NoV outbreaks on naval vessels have resulted in removing ships from active service for brief periods Norovirus Single stranded, non-enveloped RNA virus belonging to the family Caliciviridae July 1997 to June 2000: 232 NoV outbreaks reported to CDC: 57% were foodborne, 16% were due to person-to-person spread, and 3% were waterborne; in 23% undetermined cause. Bar = 50 nanometers Source: CDC Norovirus Technical Fact Sheet. See http://www.cdc.gov/ncidod/dvrd/revb/gastro/norovirusfactsheet.htm CDC s s EHSNET OUTBREAK/NONOUTBREAK STUDY 6/2002 6/2003 EFORS-Listed Outbreaks Evaluated by EHS-Net 179 Confirmed Outbreaks Unknown 13% Toxin 3% Viral Parasitic 47% 5% Viral Bacterial Parasitic Toxin Unknown/Missing 42% Norovirus Bacterial 32% 2

Transmission of Norovirus Fecal-Oral Route: : Primary route responsible for causing foodborne outbreaks Airborne Inhalation of microscopic droplets: Aerosols enhance dissemination of NV in the environment during an outbreak; has been important means of transmitting NV to staff Person-to to-person: Important means of sustaining & spreading an outbreak Environment-to to-person: Important means of sustaining & spreading an outbreak Norovirus Feeding Studies Dolin, 1971; Wyatt, 1974; Thornhill,, 1975; Graham, 1994 Symptoms: Nausea, vomiting, diarrhea, & stomach cramping- lasts 1-21 2 days Established the transmission of NoV via the fecal oral route Established peak viral shedding between 25 and 72h after inoculation Established longer viral shedding past 3 days as as long as 7 days 30 days past inoculation Established 32% asymptomatic infection rate, without any symptoms Graham found as many as 60% were positive NoV shedders 3 days after inoculation Characteristics of NoV Acute onset of vomiting (often explosive) and diarreah (also often explosive) Typically Lasts only 24 to 48 hours & rarely fatal, Seasonal virus: Peaks in Winter (Dec.- March) Can have a serious impact on healthy individuals of all ages, resulting in hospitalization and even intensive care, and Has been associated with serious complications or even fatalities in the elderly and immune compromised 3

Potential Transmission Level Norovirus Shed in the feces at levels up to 10,000,000 viral particles per gram of feces. One projectile vomiting incident can potentially contaminate the environment with 30,000,000 viral particles. Infectious dose of NoV is estimated from 10-100 100 viral particles. Environment to Person & Person- to-person Norovirus Transmission Contaminated fomites are the most likely factor responsible for sustaining a succession of outbreaks Hands play a significant role in NV transmission, either through direct fecal- oral contact, or through the contamination of ready-to to-eat food items Combination of High Levels Shed in the Feces and Low Infectious Dose Adds up to create a highly infectious microorganism The problem is compounded by the ability of NoV to survive in the environment and high resistance to disinfectants 4

RTE Food Produce Shellfish Environ. Surfaces Soil Water Airborne droplets Hands Vomit Feces Infected Human Figure 2. Conceptual Model of NoV Transmission Produce Shellfish Airborne droplets Irrigation Soil Vomit Water Surface Water Ground Water Environ. Surfaces Waste Water Hands Feces Infected Human Figure 3. Conceptual Model of NoV Transmission from Water Sources to Food NoV Stability in Water. Survives freezing conditions Survives exposure to acidity levels below ph 3 Presence of feces and viral aggregation prolongs NoV survival Survives in Salt water (0.5 and 1 M NaCl) for >6 days at room temperature (75.2 F F or 24 C) Survives in dechlorinated water for 25 days at 39.2 F or 4 C C and for 18 days at 77 F F or 25 C Inactivated by boiling at 212ºF F or 100 ºC May survive up to 1 year in bottled, sterile water stored in the dark. Impacted by microbial antagonism, sunlight, warmer temperature and the presence of oxygen 5

NoV in Wastewater Sampled from 4 Communities in France (da Silva, et. al., 2007) NoV Influent Influent Max Conc. Effluent Prior to Community Outbreak GI 43% 10 9 genome copies/ liter 24% GII 88% 6 x 10 7 genome copies/ liter 14% 10 5 genome copies/ liter Community Wastewater Sampling in 4 Communities in France: Continued Influent conc. Ranges of GI & GII were equivalent in all sample sites Highest conc. of GI and GII: December March GI conc. decreased in May GII conc. decreased in April Sept. Survival in Soil Soil Temperature Adsorptive Soils Have the most influence on virus survival in the soil soil moisture content, presence of aerobic microorganisms, soil levels of resin-extractable extractable phosphorus, exchangeable aluminum, and soil ph 6

Survival in Soil Sobsey, et al., 1989, reported that at least 12 weeks were required for a 99% reduction of HAV in soil at 41 F F or 5 C. 5 (Rzeżutka, A., et al., 2004): Viral decay for poliovirus & total cytopathic enteroviruses: Winter field conditions of 59 F F or 15 C (moisture levels of 25-15%): 92 days Summer field conditions of 27-33 33 C or 80.6 91.4 F F (moisture levels of 3-40%): 3 1.2 days NoV Survival on Hard Surfaces Presence of feces and viral aggregation on surfaces prolongs NoV survival Survival Hard Surfaces (RH 54-88%) 39.2 F/ 4 C 7 days 71.6 F/ 22 C 5 days 86 F/ 30 C < 24 hrs Characteristics of NoV Pertinent to its Stability in Food Survives freezing conditions Survives heating at 140 F/ 60 ºC C for 30 minutes Inactivated by boiling at 212 F/ 100 ºC Impacted by warmer temperature, sunlight, and oxygen Survives exposure to acidity levels below ph 3 Survives better under wet conditions than dry conditions Survives on produce longer than the shelf life of the produce item under refrigerated temperatures. May be susceptible to high pressure processing 7

NoV Survival on Hands If = to HAV: about 4 hrs Studies have shown at least 20 minutes Transfer Efficiency of Phage Rusin,, 2002: transfer rates of Phage PRD- 1 from fomites and from fomites to lips: Greatest from hard surfaces to hands: Faucet: 33.47% transfer efficiency Phone receiver: 65.8% transfer efficiency Dishcloth: 0.03% transfer efficiency Carrot: 0.01% transfer efficiency Transfer efficiency from finger to lip: 33.9% Transfer from Contaminated Fingers Barker (2004) found that NV can transfer from contaminated fingers, sequentially to 7 different environmental surfaces Secondary Transfer of NV (from contaminated surfaces to clean fingers, to other surfaces) can transfer sequentially to 4 different surfaces Detergent cleaning, followed by rinsing was not effective in cleaning contaminated surfaces, unless followed with a disinfectant. 8

Norovirus Transfer from Fingers to Food Virus is very difficult to control and highly resistant to disinfectants S. Bidawid (2004) J. Food Protect.- --Fingertip Fingertip transfer of FCV to ham, lettuce, and Food Virus stainless steel Item Transf er Reduced transfer rate significantly with: Ham 46 +/- 20.3% Soap and water wash - 0.9% Lettuce 18 +/- 75% ethanol soln.- 2.3% 5.7% Ethanol hand gel - 3.4% Stainles 13 +/- s Steel 3.6% NoV Environmental Contamination-- --RT-PCR Environmental surface tests-- --Hotel outbreak (Cheeseborough,( 2000) Surface Carpets (known recent vomit) Carpets (no known recent vomit) Toilet rims/seats Toilet handles, taps, basins & surfaces Horizontal surfaces below 1.5m (railings, switches, table tops, counters, phones) Horizontal surf. (light fittings, switches, wardrobe tops, counter tops) above 1.5m Phones, door handles, etc. Soft furnishings, cushions, curtains, ect. Total # Pos. 5 of 8 9 of 12 8 of 11 13 of 39 11 of 29 6 of 12 7 of 29 2 of 10 61 of 144 % Pos 62% 75% 73% 39% 37% 50% 24% 20% 42% Interrupting Human Transmission Pathway Handwashing & prohibiting bare hand contact with RTE food items is critical Removing food workers with active vomiting and/or diarrhea is critical Reducing airborne transmission, and treat as infectious material Cleaning Staff should use barriers, such as face masks, gloves, and aprons. Dispose materials used to clean-up vomiting incident, and thoroughly disinfect the area. 9

NoV Disinfection Chlorine: What is an effective concentration? Depends on: ph (HOCL) vs (OCL - ) concentration Presence of organic material Temperature Survives in a solution up to 3000 ppm hypochlorite for 10 minutes Agent Hypochlorou s acid solution (85-98% HOCl) Sodium hypochlorite Surface Stainless steel Melamine Stainless steel disc Petri dishes Disinfection of NoV Chlorine Surrog ate NoV NoV GII FCV FCV Dosage 188 ppm 38 ppm 18.8 ppm 5000 ppm 5000 ppm 1000 ppm Contact Time 1 min 10 min 5 min 1 min 10 min 10 min Fecal Contami nation No No Effect ive * Hydrogen peroxide and peroxyacetic acid Stainle ss steel disc FCV 11% H 2 O 2 and 15% C 2 H 4 O 3 10 min No Phenolic compnds Stainle ss steel disc FCV 4.75% o-benzyl p- chlorophenol and 4.75% o- phenylphenol (1:64 dilution) 10 min No 5% o-benzyl p- chlorophenol and 10.5% o- phenylphenol (1:50 dilution) 10 min No 10

Site Visits: Improves Risk Profile Commercial Cruise Ship Site Visit Site Visits: Improves Risk Profile Navy Battle Ship Lessons Learned from Site Visits Quarantine is important: Remove food workers with active vomiting and/or diarrhea from food preparation site Quarantine symptomatic personnel and passengers Reduce Hand Contamination: Find ways to prevent or reduce transmission in buffet areas Frequent hand washing No bare hand contact with RTE food Frequent replacement of serving utensils 11

Lessons Learned from Site Visits Vigorous clean-up or Environmental Disinfection is Vital: Cleaning Staff should use barriers, such as face masks, gloves, and aprons. Dispose materials used to clean-up vomiting incident, and thoroughly disinfect the area. Include testing for viruses in water and ice machines If possible, test suspect stool samples for norovirus Potential Control Options Identified for Further Consideration Surveillance: Need for Global Surveillance System Reportable Disease, Use of Biomarkers for Early Detection Interrupt Human Transmission Pathway: RTE Food Produce Shellfish Environ. Surfaces Airborne droplets Hands Soil Water Vomit Feces Infected Human Conceptual Model of NoV Transmission 12

Potential Control Options Identified for Further Consideration: Continued Interruption of Human Transmission: Hand Hygiene: : Handwash (with soap & water) before touching RTE Food Use Hand Barriers: Use utensils or Gloves to handle RTE food Isolate symptomatic humans & exclude from food harvest or preparation Potential Control Options Identified for Further Consideration: Continued Disinfect contaminated environmental surfaces: : Restrooms are Reservoirs Reduce potential airborne transmission Wash and dry produce as much as possible, without direct human contact, & avoid dark, anerobic storage conditions Conclusion Understanding the survival and transmission of NoV outside of the host can help us develop effective control mechanisms Wastewater sampling programs during peak NoV season may help prevent widespread outbreaks through early detection of NoV in the community 13

Conclusion Continued: Environmental controls such as disinfection are essential to interrupt the NoV pathway Focus on potential human fecal contamination of the environment and RTE Food (especially produce items) Focus on proper cleaning and disinfection of fecal contamination 14