Norovirus - Avoid It If You Can

 

Norovirus is an Increasing Problem

Norovirus is a non-enveloped single strand RNA virus.  One of the critical features of Norovirus is infectivity.  Infected individuals secrete the virus in feces, saliva, and oral mucus.  Virus can be detectable in the saliva for up to 2 weeks after infection even though most of the guidelines for food preparers suggests that they can go back to work 2-3 days after the acute illness has passed.  The infective dose for Norovirus is as little as 18 viral particles (1).  An infected person is excreting billions of these particles. For comparison, influenza virus requires a dose of about 1.95-3.0 x 10³ infectious particles, and most common respiratory viruses including SARS-CoV-2 are on par with Norovirus. 

The clinical syndrome develops rapidly after exposure resulting in abdominal cramping, vomiting and diarrhea.  It creates significant mortality and morbidity causing an estimated 213,000 deaths world-wide (2).  In the US 900 people die per year out of 21 million infections. Most of the fatalities occur in the elderly and immunocompromised. Rapid fluid loss and dehydration is most likely a causative factor especially in the case of pre-existing medical problems. There is a bias toward advising all people like they are healthy young adults and that this syndrome is a self-limited 2-3 day episode of stomach flu.

There is an asymptomatic carrier state with anywhere from 11.6-49.2% of measured populations carrying the virus. This also extends to 1-3.4% of food handlers.  Humans were previously the only known reservoir for this virus, but a recent review looked at modern data and concluded that it may be a reverse zoonosis with human to animal transmission in lab animals and the wild (3, 4). 

Outbreaks of the virus are getting more common especially in environments where there is close contact and contact with contaminated surfaces like schools, universities, elderly homes, and cruise ships.  In the US there are about 2,500 outbreaks per year and poor granularity in terms of geographic locations. In other words, unless a local news channel picks up the story of an outbreak – you probably will not know until you get there.  The distribution of outbreaks over the calendar year for the last 4 years is given at the top of this post.  Outbreaks tend to intensify in the winter months where there is more aggregation.   

The most common advice given to prevent Norovirus infection is hand washing and cleaning contaminated surfaces.  The virus remains physically stable in pH 3-7 condition and temperatures up to 60 degrees C (140 degrees Fahrenheit) but that conventional wisdom may not be enough.  The virus is aerosolized presumably by coughing, sneezing, and toilet flushing and has been detected in the air around hospitalized patients (8). The particles detected were in the droplet nuclei/aerosol range but that may be an artificial dichotomy (9).  The main point in this research is that the droplets detected contained sufficient virus to cause infection. Current CDC precautions for Norovirus do not include masking except where there is a risk of “splashes to the face during the care of patients, particularly among those who are vomiting.”  This is reminiscent of the reluctance to declare respiratory viruses including SARS-CoV-2 and influenza airborne. 

6.6% of the US population are immunosuppressed based on taking immunosuppressant drugs or having a health condition that affects immunity and that number is increasing (10).  Women are more likely to be affected than men. In addition to the immunocompromised - 39% of the population has at least one serious chronic illness any number of which can affect innate immunity (11).  In addition, many of these diseases or their management can end up compromised by severe acute gastroenteritis.  Common examples would be blood glucose management in diabetes mellitus and electrolyte and fluid management in hypertension, arrhythmias, and renal disease.  Since 42% of the population has 2 or more chronic conditions it is highly likely that recommended management of rehydration will need to be personalized to that patient.  

There are also nebulous recommendations about the quarantine necessary following an episode of this illness.  The CDC web site provides an example, in order:

“Most people with norovirus illness get better within 1 to 3 days; but they can still spread the virus for a few days after.”

“You can still spread norovirus for 2 weeks or more after you feel better.”

“Stay home when sick for 2 days (48 hours) after symptoms stop.”

Apparently, Norovirus has been detected in saliva for up to 2 weeks after infection – leading to this mixed recommendation. There is some additional information at a public health link – but not much more. This link has interesting information on clinical criteria without biological confirmation that a probable Norovirus outbreak is occurring. In a 2013 review, Norovirus was the second most common infection disease outbreak affecting psychiatric hospitals (13).  This review looks at infection control procedures that may be unique to psychiatry as well as those that address the difficult to destroy nature of the virus.  It is resistant to common hand sanitizers and the need for contact cleaning with hypochlorite while masked and gowned to prevent infection of staff.  The reference on the possible airborne nature of the virus also applies. A description of a psychiatric hospital with 4 previous Norovirus outbreaks and how that was stopped by a specific infection control program is also described (14).

That is currently the state-of-the-art on Norovirus. I have some additional information posted below.  The best defense at this point is to know that this is a highly infectious virus that is nothing to fool around with, especially if you are elderly, have chronic medical conditions, or are immunocompromised.  I don’t think it is my place to make specific rehydration recommendations because of the complexity I describe in the above paragraphs – but your personal physician certainly can.  No matter what you read – avoiding dehydration is the most important aspect.  Your physician can best describe how to do that given any other medical conditions. 

There are currently no vaccines or antiviral medications for Norovirus.  Vaccines are complicated by several factors discussed in this paper (15) that projected vaccine availability 5-10 years out from 2014.  Here we are 10 years out. Like the current SARS-CoV-2 vaccines early trials show a limited duration of immunity, but that can eliminate many cases in more vulnerable populations.

 

George Dawson, MD

 

Supplementary 1:

For 2025 – I decided to separate out my anecdotal experience from the published scientific data.   Readers of this blog know that my intent is generally to include it as additional relevant information and I have joked about trying to learn more about diseases by trying to get most of them.  That is no different with Norovirus.  The actual clinical syndrome I have seen many times dating back to my days as a Peace Corps volunteer travelling in East Africa.  It was referred to as “Traveler’s Diarrhea” and the theory was that it was caused by “enterotoxigenic E. Coli.”  Various remedies were suggested including Pepto Bismol (bismuth salicylate) or a prophylactic course of sulfamethoxazole/trimethoprim (SMX/TMP) – an antibiotic that I subsequently prescribed many times as an intern and resident.  

All Peace Corps volunteers were issued a medical kit and the two primary medications were a large bottle of Lomotil (diphenoxylate/atropine) and another large bottle of Benadryl (diphenhydramine).  So most acute diarrheal diseases were treated with Lomotil.  We also got IM cholera vaccines that interestingly were discontinued shortly after my Peace Corps tour because “they were more painful than protective.”  The only currently approved cholera vaccine is an oral vaccine.

My wife recently had a complicated course of appendicitis and there was concern about the possibility of an intraabdominal abscess.  As she recovered slowly from the surgery she had residual right upper quadrant pain and suddenly developed an acute illness again very similar to the appendicitis. I convinced her to go to free-standing emergency department where she was treated for nausea and rapidly given 1 liter of normal saline in less than 30 minutes. She was hypotensive and had a lot of vomiting and diarrhea in the hours before this assessment.  A CT scan of the abdomen was negative and a PCR test of a stool sample confirmed no C. difficile toxin and positive for Norovirus (see test panel below).

Returning home she recovered over the next two days – but I contracted it and am recovering on day 3.  I will post the symptom course in this note when I am fully recovered.  I will note that my wife has had 2 episodes of SARS-CoV-2 infections in the past 3 years and I did not get them from the airborne route but was masked and using a UV air cleaner at the time.  This time I was not masked – but I was using all of the CDC recommended contact precautions, the same UV air cleaner, and handwashing.       

Supplementary 2:

Sometimes it pays to be a hoarder. I found this book in my auxiliary library today.  It was sent to me by a friend who was attending Harvard Medical School when he heard I was definitely headed to Africa.  I regaled my Peace Corps colleagues with tales of possible infections in Africa. The most interesting section for this post is that it provides an anchor point for diarrheal disease classification in 1975. It lists invasive and enteropathogenic E. coli as the primary pathogens detectable by culture and bioassay or an assay set up to detect the toxin.  Epidemic viral gastroenteritis is attributed to Norwalk virus in the same book.  The name originated from immune electron microscopy of a viral particle identified as a causative agent in Norwalk, Ohio.  Episodic viral gastroenteritis at the time was attributed to rotavirus, duovirus, and orbivirus.

Supplementary 3:

I resumed working out on day #7 and have charted the symptoms using my invention of a malaise index.  Note that APAP here means acetaminophen that I take for symptoms that are generally caused by cytokines from the inflammatory response caused by viral and bacterial infections.  The index itself is included below the graphic of the course of the illness to explain what was rated.  For research purpose a Likert scale approach for every item would probably be used.  Even though the symptom descriptions are fairly basic - the underlying pathophysiology is not.  There are also some symptoms that I experienced that were not included like a sensory lack of taste for food. 

Supplementary 4: 

The Minnesota Department of Health came out with the following release on Norovirus today.  Apparently there have been 40 outbreaks in the state of Minnesota.  No specific locations are given and the general advice has the limitations I outlined in the above blog post.

All of the details can be found at this link.

Supplementary 5:

EPA Registered Products that will kill Norovirus:  Chlorox and Lysol products are the most recognizable names but there are many (386).  Note the necessary contact time in the table necessary to effectively eliminate the virus.

https://www.epa.gov/pesticide-registration/epas-registered-antimicrobial-products-effective-against-norovirus-feline

References:

1:  Winder N, Gohar S, Muthana M. Norovirus: An Overview of Virology and Preventative Measures. Viruses. 2022 Dec 16;14(12):2811. doi: 10.3390/v14122811. PMID: 36560815; PMCID: PMC9781483.

2:  Pires SM, Fischer-Walker CL, Lanata CF, Devleesschauwer B, Hall AJ, Kirk MD, Duarte AS, Black RE, Angulo FJ. Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food. PLoS One. 2015 Dec 3;10(12):e0142927. doi: 10.1371/journal.pone.0142927. PMID: 26632843; PMCID: PMC4668836.

3:  Robilotti E, Deresinski S, Pinsky BA. Norovirus. Clin Microbiol Rev. 2015 Jan;28(1):134-64. doi: 10.1128/CMR.00075-14. PMID: 25567225; PMCID: PMC4284304.

4: Villabruna N, Koopmans MPG, de Graaf M. Animals as Reservoir for Human Norovirus. Viruses. 2019 May 25;11(5):478. doi: 10.3390/v11050478. PMID: 31130647; PMCID: PMC6563253.

5:  Karimzadeh S, Bhopal R, Nguyen Tien H. Review of infective dose, routes of transmission and outcome of COVID-19 caused by the SARS-COV-2: comparison with other respiratory viruses. Epidemiol Infect. 2021 Apr 14;149:e96. doi: 10.1017/S0950268821000790. Erratum in: Epidemiol Infect. 2021 May 14;149:e116. doi: 10.1017/S0950268821001084. PMID: 33849679; PMCID: PMC8082124.

6: CDC.  Norovirus Facts and Stats.  (accessed on 12/15/2024): https://www.cdc.gov/norovirus/data-research/index.html

8:  Alsved M, Fraenkel CJ, Bohgard M, Widell A, Söderlund-Strand A, Lanbeck P, Holmdahl T, Isaxon C, Gudmundsson A, Medstrand P, Böttiger B, Löndahl J. Sources of Airborne Norovirus in Hospital Outbreaks. Clin Infect Dis. 2020 May 6;70(10):2023-2028. doi: 10.1093/cid/ciz584. PMID: 31257413; PMCID: PMC7201413.

9:  Drossinos Y, Weber TP, Stilianakis NI. Droplets and aerosols: An artificial dichotomy in respiratory virus transmission. Health Sci Rep. 2021 May 7;4(2):e275. doi: 10.1002/hsr2.275. PMID: 33977157; PMCID: PMC8103093.

10:  Martinson ML, Lapham J. Prevalence of Immunosuppression Among US Adults. JAMA. 2024 Mar 12;331(10):880-882. doi: 10.1001/jama.2023.28019. PMID: 38358771; PMCID: PMC10870224.

11:  Benavidez GA, Zahnd WE, Hung P, Eberth JM. Chronic Disease Prevalence in the US: Sociodemographic and Geographic Variations by Zip Code Tabulation Area. Prev Chronic Dis 2024;21:230267. DOI: http://dx.doi.org/10.5888/pcd21.230267

12:  Fukuta Y, Muder RR. Infections in psychiatric facilities, with an emphasis on outbreaks. Infect Control Hosp Epidemiol. 2013 Jan;34(1):80-8. doi: 10.1086/668774. Epub 2012 Nov 27. PMID: 23221197.

13: Tseng CY, Chen CH, Su SC, Wu FT, Chen CC, Hsieh GY, Hung CH, Fung CP. Characteristics of norovirus gastroenteritis outbreaks in a psychiatric centre. Epidemiol Infect. 2011 Feb;139(2):275-85. doi: 10.1017/S0950268810000634. Epub 2010 Mar 25. PMID: 20334730.

14:  Tseng CY, Chen CH, Su SC, Wu FT, Chen CC, Hsieh GY, Hung CH, Fung CP. Characteristics of norovirus gastroenteritis outbreaks in a psychiatric centre. Epidemiol Infect. 2011 Feb;139(2):275-85. doi: 10.1017/S0950268810000634. Epub 2010 Mar 25. PMID: 20334730.

15:  Gupta SS, Bharati K, Sur D, Khera A, Ganguly NK, Nair GB. Why is the oral cholera vaccine not considered an option for prevention of cholera in India? Analysis of possible reasons. Indian J Med Res. 2016 May;143(5):545-51. doi: 10.4103/0971-5916.187102. PMID: 27487997; PMCID: PMC4989827.

16:  Benenson AS (ed).  Control of communicable diseases in man – 12^th Edition. American Public Health Association. Washington, DC.  1975:  96-101, 125-129.

17:  CDC.  Confirmed norovirus outbreaks submitted by state.  Good source of data from CaliciNet updated every months.  Gives number of outbreaks per state in the past year and rough data on virus genotype.  https://www.cdc.gov/norovirus/php/reporting/calicinet-data.html

 

The Importance of Malaise...

About a year ago – a good friend of mine shared his observations about death and dying. 

“I have known 5 people who told me that they ‘felt the worst they had ever felt in their life’ and by that afternoon – they were dead.”  The “people” were all men.

He went on to describe what happened to our long-time mutual acquaintance and what he said on that fateful morning.  He described a man who went to work at a local factory despite his wife’s suggestion that he stay home and see a doctor. In every case the “worst I have ever felt in my life” predicted death in a few hours and did not deter these men from their usual daily routine.  Most of these men died of heart attacks.  They had atypical symptoms rather than chest pain – but my friend is not a physician and was not interested in the details only what they all said on the morning of their deaths.

The only time I felt that badly was when I sustained a ruptured and gangrenous appendix at age 18.  I had a very complicated course that included a Penrose drain being placed in my side to drain the remnants of the necrotic appendix. Even as I was healing, I felt horrible. I felt so badly that I did not care if I lived or died at that point. I was not depressed, nauseated, or in pain – just a very intense sick feeling.

That may be why I have had an interest in malaise as a syndrome.  I equate malaise with flu-like illnesses and that feeling you get from a severe case of the flu or flu-like viruses.  I had malaria once back in the 1970s and was very ill for several days.  That bout of illness was characterized by low energy, fever, and severe chills associated with the fever.  I can remember crawling across the floor of my house draped in a sleeping bag and into a tub of hot water just to warm up.  That was about 6 years after the appendicitis and the disease features were clearly different, but again not nausea, depression, or pain. 

Steadman’s medical dictionary defines malaise as:  A feeling of general discomfort or uneasiness, an out-of-sorts feeling, often the first indication of infection or other disease.  That definition captures the general experience but not the intensity.  I could tell that something was wrong in the early stages of appendicitis.  But in the space of 2 or 3 hours something was really wrong and the sick feeling was amplified a hundred-fold.  Are they both malaise?  Can malaise occur during a chronic condition – can you have acute and chronic malaise?  This semantic confusion may be why not many people seem interested in using the term. 

Interestingly there is a Malaise Inventory and it is in the psychiatric literature (1-3).  It was originally conceived by Michael Rutter as a measure of psychological well-being and the associated physical components.  It was adapted from the 195-item Cornell Medical Index Health Questionnaire.  The inventory itself consists of 24 self-competed questions and can be viewed here.  Many of the items (eg. Do you often feel miserable or depressed?) decrease item specificity.  Many of the items (eg. Do you often get worried about things?) are not specific for physical illnesses.  That may be why some authors found that psychological dimensions accounted for the more variance than physical ones.  It has generated very little research interest and is generally referenced once or twice a year in PubMed except for the year 2021 where there were 10 references.  In more recent studies it is used as a measure of psychological distress rather than malaise associated with a physical illness.

Why might it be important to have a more physically defined malaise? It could lead to earlier recognition of serious physical illnesses.  Based on what we currently know about pathophysiology – I would not be surprised if there were subtypes of malaise.  For example, the severe illnesses I have experienced were all most likely related to inflammatory signaling and the well documented effects of some of those molecules like cytokines. On the other hand, hyperadrenergic states associated with acute cardiovascular diseases could produce a different type of illness feeling.  We are generally limited by knowing the possible presentations (typical and atypical) to not miss a serious problem without reference to any non-specific illness feeling.  It may also allow for treatment of those associated symptoms. One of the striking features of the modern approach to appendicitis is rapid symptomatic treatment or pain and nausea. Are there better ways to treat acute infectious inflammatory conditions than NSAIDs and acetaminophen?  Are there better ways to treat chronic malaise?

My proposed analysis of malaise does not replace the need for common sense and recognizing the dangers of denial.  I am fully aware of the difficulty getting timely emergency care in the US health care system unless you need a trauma surgeon or interventional cardiologist.  But – if you are experiencing the “worst I have ever felt in my life” feeling you owe it to yourself and your family to get it checked out as soon as possible.  EMTs are called for a lot less.  I have talked to too many people who in retrospect would have called the EMTs instead of driving themselves to the hospital while they were having a heart attack.  

 

George Dawson, MD, DFAPA

 

References:

1:  Grant G, Nolan M, Ellis N. A reappraisal of the Malaise Inventory. Social psychiatry and psychiatric epidemiology. 1990 Jul;25:170-8.

2:  Rutter M, Graham R Yule W (1970a) A neuropsychiatric study in childhood. London, Heinemann.

3:  Rutter M, Tizard J, Whitmore K (1970 b) Education, health and behaviour. Longmans, London.

 

Photo Credit:  Eduardo Colon, MD - Thunderstorm over Minneapolis.

Supplementary 1: The Malaise Inventory

How are you feeling generally…

1. Do you often have backache?

2. Do you feel tired most of the time?

3. Do you often feel miserable or depressed?

4. Do you often have bad headaches?

5. Do you often get worried about things?

6. Do you usually have great difficulty in falling or staying asleep?

7. Do you usually wake unnecessarily early in the morning?

8. Do you wear yourself out worrying about your health?

9. Do you often get in a violent rage?

10. Do people often annoy and irritate you?

11. Have you at times had twitching of the face, head or shoulders?

12. Do you often suddenly become scared for no good reason?

13. Are you scared to be alone when there are no friends near you?

14. Are you easily upset or irritated?

15. Are you frightened of going out alone or of meeting people?

16. Are you constantly keyed up and jittery?

17. Do you suffer from indigestion?

18. Do you suffer from an upset stomach?

19. Is your appetite poor?

20. Does every little thing get on your nerves and wear you out?

21. Does your heart often race like mad?

22. Do you often have bad pains in your eyes?

23. Are you troubled with rheumatism or fibrositis?

24. Have you ever had a nervous breakdown?

 

Supplementary 2: 

I put the following questionnaire together based on some of my previous inventories for tracking flu-like illnesses.  

The Minnesota Malaise Index (MNMI)

1:  I have a fever

2:  I am fatigued

3:  I feel physically sick like I have the flu or another serious infection

4:  I have a difficult time concentrating on tasks and thoughts that I need to focus on and this is a new problem.

5:  I have a difficult time making decisions that used to be easy for me.

6:  I have a cough

7:  I have a runny nose

8:  My nose is congested to the point that it blocks or partially blocks air flow.

9:  I have a headache

10:  I have a sore throat

11:  My muscles are sore

12:  My joints are sore

13:  I am sneezing

14:  I am sleeping less than 6 hours per night

15:  I am sleeping more than 9 hours per day

16:  I have no appetite

17:  I have nausea, vomiting, or diarrhea

18:  I am in pain

19:  My activity level has changed and I am hardly doing anything

20:  Severity level:

A.       Some impairment in daily activity due to illness.

B.       Moderate impairment postpones desired activity.  No longer able to exercise.

C.       Severe impairment – need to rest due to illness and feeling physically ill

D.       Very severe impairment-cannot stand or sit due to severe illness and in some cases indifferent to living or dying due to illness severity

 

Supplementary 3:

Minnesota Malaise Index Tracker