Global norovirus pandemic emergence: maybe it’s in the polymerase

The perfect human pathogen has fantastic fitness because of lots of things: small hearty virus particles, millions of particles shed per gram of feces/vomit; induces projectile vomiting and according to new research in mSphere, fa_polymerase_figure4maybe the lack of fidelity in norovirus polymerase increases transmission between hosts.

Viruses are awesome.

Norovirus Polymerase Fidelity Contributes to Viral Transmission In Vivo 

oct.16

mSphere

1(5):e00279-16

A. Arias, L. Thorne, E. Ghurburrun, D. Bailey and I. Goodfellow

Intrahost genetic diversity and replication error rates are intricately linked to RNA virus pathogenesis, with alterations in viral polymerase fidelity typically leading to attenuation during infections in vivo. We have previously shown that norovirus intrahost genetic diversity also influences viral pathogenesis using the murine norovirus model, as increasing viral mutation frequency using a mutagenic nucleoside resulted in clearance of a persistent infection in mice. Given the role of replication fidelity and genetic diversity in pathogenesis, we have now investigated whether polymerase fidelity can also impact virus transmission between susceptible hosts. We have identified a high-fidelity norovirus RNA-dependent RNA polymerase mutant (I391L) which displays delayed replication kinetics in vivo but not in cell culture. The I391L polymerase mutant also exhibited lower transmission rates between susceptible hosts than the wild-type virus and, most notably, another replication defective mutant that has wild-type levels of polymerase fidelity. These results provide the first experimental evidence that norovirus polymerase fidelity contributes to virus transmission between hosts and that maintaining diversity is important for the establishment of infection. This work supports the hypothesis that the reduced polymerase fidelity of the pandemic GII.4 human norovirus isolates may contribute to their global dominance.

IMPORTANCE Virus replication fidelity and hence the intrahost genetic diversity of viral populations are known to be intricately linked to viral pathogenesis and tropism as well as to immune and antiviral escape during infection. In this study, we investigated whether changes in replication fidelity can impact the ability of a virus to transmit between susceptible hosts by the use of a mouse model for norovirus. We show that a variant encoding a high-fidelity polymerase is transmitted less efficiently between mice than the wild-type strain. This constitutes the first experimental demonstration that the polymerase fidelity of viruses can impact transmission of infection in their natural hosts. These results provide further insight into potential reasons for the global emergence of pandemic human noroviruses that display alterations in the replication fidelity of their polymerases compared to nonpandemic strains.

Norovirus sucks; here’s what it does to the body

It’s the perfect human pathogen.

A 2015 CDC report on noro burden by Ben Lopeman describes the virus as “ubiquitous, associated with 18% (95% CI: 17-20%) of diarrheal disease globally, with similar proportions of disease in high- middle- and low- income settings. Norovirus is estimated to cause approxi­mately 200,000 deaths annually worldwide, with 70,000 or more among children in developing countries.”10849902_719581291471357_3442145704847569295_n1-300x3001-300x300

Express describes what happens when the virus infects.

The viral particles hit the stomach first, but it is only when they travel into the small intestine that the virus begins to multiply.

It enters the cells lining the intestine, making copies of itself and then the cells die, release more virus particles, and the process is repeated.

The immune system recognises that cells are ‘dying’ and as an immune response, antibodies travel to the small intestine and deactivate the virus. Experts say this is when the body will start to feel the effects of the virus – such as fever and nausea.

The virus causes the gut to become inflamed or irritated – which leads to vomiting and watery diarrhoea. This, medics say, is the body’s way of fighting the infection and trying to clear it from the body.

 

OysterFest in Wellfleet MA to go on, without raw oysters, after 75 ill with noro

I’ve eaten exactly one raw oyster ever.

It was at a reception for a food safety meeting in New Zealand.

I picked up the shell, dumped the contents (salt water and a slimy shellfish meat) into my mouth, getting about 50% of it on my shirt. I spent the rest of the night smelling like the beach.raw_oyster

I didn’t get noro from the bivalve experience. According to capecod.com 75 folks around Cape Cod, MA are ill with norovirus after eating raw oysters harvested in a month that ends in ‘r.’

The state has closed all shellfish beds in Wellfleet Harbor following an outbreak of suspected norovirus believed to be linked to shellfish from that area.

It comes just two days before the Wellfleet OysterFest, which attracts tens-of-thousands of people to the Outer Cape.

An official from the festival said the event will go on planned, but without any raw shellfish.

The Massachusetts Department of Public Health issued the ban Thursday afternoon after receiving reports of approximately 75 suspect cases of norovirus over the past two days.

A statement from the DPH said they were all primarily associated with eating raw shellfish at weddings and restaurants in the Outer Cape area.

All shellfish harvesters in the area and Town of Wellfleet officials have been notified about the closure.

All affected shellfish that was harvested on or after September 26 has been recalled and ordered not to be used.

Norovirus outbreak sickens dozens linked to ‘party place’ in Hong Kong

Something was lost in translation, so I asked my friend from China, what’s a party place?

She told me it was a gathering spot that can cater to large events — 2-3,000 people — and called it an infection centre.
stephen_colbert_asian_friendAn ideal place to circulate Norovirus.

Health officials with Centre for Health Protection (CHP) of the Department of Health (DH) announced the investigation of a norovirus outbreak that has sickened at least two dozen in a party place in Sham Shui Po.

The 24 patients, including 13 children (six boys and seven girls) and 11 adults (three men and eight women) aged from 1 to 39, have presented with fever, vomiting and diarrhea since October 1. Among them, 18 sought medical attention while five of them have been discharged after hospitalization. All patients are now in a stable condition.

The stool specimen of one child tested positive for norovirus upon laboratory testing by the hospital concerned. Investigations are continuing.

In addition, health officials are investigating two outbreaks of acute gastroenteritis (AGE) in two kindergartens in Tai Po and Tin Shui Wai. An etiology has not been determined.

The outbreak at the kindergarten in Tai Po involves eight males and 13 females, comprising 18 pupils aged 3 to 5 and three staff members. They have presented with vomiting, diarrhea and fever since September 29. Fourteen of them sought medical attention and none required hospitalization.

The outbreak at the kindergarten in Tin Shui Wai involved eight boys and 13 girls aged between 2 and 5. They have presented with diarrhea and vomiting since October 3. Eleven pupils sought medical attention while one of them required hospitalization.

All three facilities have been visited by health officials and received advice concerning  proper and thorough disinfection, disposal of vomitus, and personal and environmental hygiene. The three places have been put under medical surveillance.

Check if there’s paper towels in the kids’ bathrooms: Evidence-based interventions of Norovirus outbreaks in China

In resource-limited settings where laboratory capacity is limited and response strategy is non-specific, delayed or inappropriate intervention against outbreaks of Norovirus (NoV) are common. Here we report interventions of two norovirus outbreaks, which highlight the importance of evidence-based modeling and assessment to identify infection sources and formulate effective response strategies.

norovirus-bathroomMethods

Spatiotemporal scanning, mathematical and random walk modeling predicted the modes of transmission in the two incidents, which were supported by laboratory results and intervention outcomes.

Results

Simulation results indicated that contaminated water was 14 to 500 fold more infectious than infected individuals. Asymptomatic individuals were not effective transmitters. School closure for up to a week still could not contain the outbreak unless the duration was extended to 10 or more days. The total attack rates (TARs) for waterborne NoV outbreaks reported in China (n = 3, median = 4.37) were significantly (p < 0.05) lower than worldwide (n = 14, median = 41.34). The low TARs are likely due to the high number of the affected population.

Conclusions

We found that school closure alone could not contain Norovirus outbreaks. Overlooked personal hygiene may serve as a hotbed for infectious disease transmission. Our results reveal that evidence-based investigations can facilitate timely interventions of Norovirus transmission.

BioMed Central Public Health

Tianmu Chen, Haogao Gu, Ross Ka-Kit Leung, Ruchun Liu, Qiuping Chen, Ying Wu and Yaman Li

DOI: 10.1186/s12889-016-3716-3

https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-016-3716-3

Norovirus GII.4 a new strain

A norovirus recombinant GII.P4_NewOrleans_2009/GII.4_Sydney_2012 was first detected in Victoria, Australia, in August 2015 at low frequency, and then re-emerged in June 2016, having undergone genetic changes.

norovirus-qmraAnalysis of 14 years’ surveillance data from Victoria suggests a typical delay of two to seven months between first detection of a new variant and occurrence of a subsequent epidemic linked to that variant. We consider that the current recombinant strain has the potential to become a pandemic variant.

A norovirus intervariant GII.4 recombinant in Victoria, Australia, June 2016: The next epidemic variant?

Euro Surveill. 2016;21(39):pii=30353. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2016.21.39.30353

L Bruggink, M Catton, J Marshall

http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=22594

Norovirus strikes hundreds at obstacle race in France

In June 2015, near Nice in the Alpes-Maritimes department, an acute gastroenteritis (AG) outbreak occurred among participants of an obstacle race. An investigation in 2 phases was conducted to identify the source of infection and document the extent of the outbreak.

tough_mudder_16-340x227During phase 1, a message on Facebook asked the racers to report by email any symptoms. In phase 2, a retrospective study was conducted through an interactive questionnaire for all participants. Cross-sectional descriptive studies were conducted, completed by an analytical study of the potential risks factors. Microbiological and environmental investigations were conducted in order to identify the responsible agent. An analysis of antidiarrhoeal drugs reimbursements was conducted with data from the French national health insurance to confirm the epidemiological investigation.

During phase 1, on 8229 registered participants, at least 1001 adults reported an AG, which was resolved in 48H.

In phase 2, the risks factors of AG identified were due to: younger participants, first hour of departure time and ingestion of mud. Twenty stool specimens traced were negative for bacteriological research. Only 4 stool specimens were sent to the CNR of enteric viruses. They were all positive for Norovirus genogroup1 and genotype 2 (GI.2), strain of human origin.

Indicator bacteria were negative in the drinking water and positive in the muddy water. Outbreak origin was due to human transmission: a norovirus possibly introduced by stools or vomiting from one or more persons infected, transmitted through contaminated muddy water.

For the future, recommendations for the organisation of such events should be proposed. The risks related to these races should be assessed to guide health authorities and to guide organizers in their awareness of potential risks factors.

Investigation of an outbreak of acute gastroenteritis among participants of an Obstacle Adventure Race Alpes-Maritimes

S Giron, C Six

http://invs.santepubliquefrance.fr/Publications-et-outils/Rapports-et-syntheses/Maladies-infectieuses/2016/Investigation-d-une-epidemie-de-gastro-enterites-virales-survenues-apres-une-course-a-obstacles

Blame Australia: 3 new noroviruses cause gastro outbreaks across Australia

University of New South Wales scientists have identified three new strains of highly contagious norovirus that are responsible for a major new epidemic of viral gastroenteritis that has affected hundreds of thousands of Australians over winter.

keep-calm-and-blame-it-on-australiaScores of outbreaks of nausea, vomiting and diarrhea have occurred in Sydney, the Hunter region and the ACT, mainly in closed settings including aged care facilities, hospitals, childcare centres and cruise ships. More cases are expected.

In 2012, Professor Peter White and his team in the UNSW Faculty of Science discovered a new strain of norovirus named Sydney 2012, which caused a worldwide pandemic of gastro, including major outbreaks in Australia.

This strain dominated cases of norovirus infection until this year, when it declined from 75 per cent of cases to 18 per cent of cases in Australia. Similar trends have also been seen in the US and New Zealand.

“Now that Sydney 2012 has declined, three new strains of norovirus have emerged as a new major health concern,” says Professor White.

“They are responsible for a big increase in the number of gastro cases in Australia in the past two months, and this new spate of infection is likely to continue to cause a wave of sick leave that will affect businesses and schools already reeling from the effects of the current influenza epidemic.”

UNSW PhD student and molecular virologist Jennifer Lun worked out the genetic typing of the new viral strains.

“I was surprised to find three new viruses, rather than a single one,” she says.

“Two of the viruses are hybrid strains that evolved from the previous pandemic Sydney 2012 strain, while the other new strain is likely to have come from Asia. It occurred to me immediately that there was a potential for them to cause an increase in outbreaks this winter, because people have not been exposed to them before.”

norovirus-2Each year, norovirus infects about two million Australians and kills about 220,000 people worldwide. The nausea, vomiting and diarrhoea usually last for two to three days.

“Norovirus is highly infectious and can spread through aerosol particles when people vomit,” says Professor White, of the UNSW School of Biotechnology and Molecular Sciences.

“During the past 20 years there have been six global epidemics of norovirus, in 1996, 2002, 2004, 2006, 2009 and 2012. Only time will tell how widely these three new strains will spread.”

The research on the new strains was carried out in collaboration with researchers at the Prince of Wales Hospital, Westmead Hospital, Canberra Hospital, the NSW Public Health Unit and medical testing service Douglass Hanly Moir.

Professor White established the Australian and New Zealand Norovirus Surveillance Network of testing laboratories in 2006, which has links with two similar organisations in Europe and North America to form a global surveillance network.

Probe launched after second ill pensioner dies after Scots staff send her on 450 mile taxi ride home

As Scotland grapples with 150 children sick from Norovirus at two schools, it has emerged that a second ill pensioner has died after being sent home hundreds of miles in a taxi from a Scottish hotel.

norovirus-elderly-womanThe Herald Scotland reports the Loch Achray Hotel in Callander, Stirlingshire, sent ill 79-year-old Norma Francis home on a 350-mile taxi journey to her home in Gnosall, Stafford, after showing symptoms of gastric illness. 

Norma fell unconscious during the journey and later died in hospital after paramedics were unable to waken her. 

Three weeks after Norma died on April 6, the hotel sent guest Carol Whymark, 70, and her husband, 73, home to Suffolk 450 miles in a taxi after it was suspected she was suffering from norovirus. 

The pensioner died of a heart attack in hospital the next day. 

Her daughter Sharone says the family have instructed lawyers to investigate Carol’s stay at the hotel, booked through Lochs and Glens Holidays Limited. 
Sharone, 47, said: “I just think it is terrible that this could have happened once, let alone twice. It’s disgusting. 

“I’ve lost my mum, my dad lost his wife and my daughter her nanny. I’m disgusted and this needs investigating. 

“I’m still numb really. I still feel angry.” 

Carol, who was on a coach tour of Scotland, woke up feeling unwell at the hotel on April 28. 

Her daughter said staff told husband Desmond that his wife had norovirus and offered him rubber gloves to clean the room and left food and water outside. 

The family claim no appropriate medical advice was given and the hotel simply offered a taxi home. 

A post mortem revealed she did not have norovirus in her system and died of the heart attack. 

Sharone said: “Mum said she didn’t feel 100 per cent – but there was no evidence of vomiting or loose stools. There was no medical attention at all. 

“They said to my dad there was a 90 per cent chance he will catch the virus. 

“Half an hour later they said she was fit to travel nine hours home. It’s so wrong. 
“When they came and said they would pay for a taxi, she said, ‘Yes, let’s go home’. 

“The poor lady who passed away three weeks before, she actually did have norovirus. 

“But my mum didn’t have it. 

“The hotel thought she had norovirus because the other lady did. 

32,000 hospitalized over contaminated water in Turkey

The number of people hospitalized due to contaminated water in the Elbistan district of the Mediterranean province of Kahramanmaraş has risen from 5,000 to some 32,000, while a group of officials announced a norovirus infection in caisson wells within the water supply network from Ceyhan River was the cause of the contamination. 

norovirus-2“We needed to find what the microorganism causing diarrhea was and the source of it. In light of the samples we took from the patients, we determined that what caused their diarrhea was a norovirus, which means bacteria and viruses together,” Health Ministry Health Services Department General Manager İrfan Şencan told journalists at a press briefing on Aug. 29, adding it can spread very easily.

“It’s a type of virus that can cause stomach ache, nausea, vomiting, fever and diarrhea. It can spread very easily and affects a lot of people. I need to stress that in addition to the infection occurring through drinking water directly, one can be infected through several other ways including kissing, washing hands, preparing meals, shaking hands and so on,” he added. 

Şencan noted there was no issue concerning the chemical quality of the water.