Viruses: Detection of a New Genetic Cluster of Influenza D Virus in Italian Cattle

Credit NIAID

#14,552


Influenza A & B  - due to their high burden of disease and (influenza A's, in particular) wide host range - remain the primary focus of influenza research and thus far, only influenza A has demonstrated the ability to spark a pandemic.

From the CDC's website (bolding mine):

Types of Influenza Viruses

There are four types of influenza viruses: A, B, C and D. Human influenza A and B viruses cause seasonal epidemics of disease almost every winter in the United States. The emergence of a new and very different influenza A virus to infect people can cause an influenza pandemic. Influenza type C infections generally cause a mild respiratory illness and are not thought to cause epidemics. Influenza D viruses primarily affect cattle and are not known to infect or cause illness in people.

But our knowledge of influenza is constantly changing. Until a few years ago, Influenza B was viewed as a far `less serious' infection than influenza A - affecting mainly children - and producing relatively mild illness in adults.

Not quite two years ago, in Influenza B: A Virus Not To Be Underestimated,  we looked at a number of studies over the past decade that have revised that perception, including:

Comparing Clinical Characteristics Between Hospitalized Adults With Laboratory-Confirmed Influenza A and B Virus Infection

Su Su, Sandra S. Chaves, Alejandro Perez, Tiffany D'Mello, Pam D. Kirley, Kimberly Yousey-Hindes, Monica M. Farley, Meghan Harris, Ruta Sharangpani, Ruth Lynfield ... Show more

Clinical Infectious Diseases, Volume 59, Issue 2, 15 July 2014, Pages 252–255, https://doi.org/10.1093/cid/ciu269

We challenge the notion that influenza B is milder than influenza A by finding similar clinical characteristics between hospitalized adult influenza-cases. Among patients treated with oseltamivir, length of stay and mortality did not differ by type of virus infection.

(Continue . . .)

But increasingly, attention is being paid to two other, lesser known, flu types; Influenza C (discovered in 1947) & influenza D (discovered in 2011).

Recently we've seen reports (see here and here) suggesting that Influenza C may not be quite as benign as previously advertised, and evidence suggesting that the more recently discovered Influenza D might have some zoonotic capabilities.

While it still isn't known whether Influenza D can cause symptomatic illness in humans, in 2016 - in Serological Evidence Of Influenza D Among Persons With & Without Cattle Exposure - researchers reported finding a high prevalence of antibodies against Influenza D among people with cattle exposure. They wrote:

IDV poses a zoonotic risk to cattle-exposed workers, based on detection of high seroprevalence (94–97%). Whereas it is still unknown whether IDV causes disease in humans, our studies indicate that the virus may be an emerging pathogen among cattle-workers.

In last February's blog  J. Clinical Med. : A Review Of The Emerging Influenza D Virus, the authors wrote:

The mixed reports for IDV infections in humans further make it important to study the zoonotic potential of IDV, especially in people with occupational exposure to susceptible livestock. Since IDV shows potential to infect a wide range of host after IAVs, its zoonotic potential is a global concern.

Last May, in Two New Influenza D Studies To Ponder, we saw evidence that Influenza D can infect Dromedary Camels, and a study that explored human cellular tropism, replication, and the development of antibodies to Influenza D. 

All of which brings us to a new study, published this week in the journal Viruses, which describes the detection of a new genetic cluster of the Influenza D virus circulating in Italy.

Detection of a New Genetic Cluster of Influenza D Virus in Italian Cattle 

by Chiara Chiapponi 1,*, Silvia Faccini 1, Alice Fusaro 2, Ana Moreno 1, Alice Prosperi 1, Marianna Merenda 1, Laura Baioni 1, Valentina Gabbi 1, Carlo Rosignoli 1, Giovanni L. Alborali 1, Lara Cavicchio 2, Isabella Monne 2, Camilla Torreggiani 1, Andrea Luppi 1 and Emanuela Foni 1
Viruses 2019, 11(12), 1110; https://doi.org/10.3390/v11121110 (registering DOI)
Received: 21 October 2019 / Revised: 21 November 2019 / Accepted: 27 November 2019 / Published: 30 November 2019
 
Download PDF

Abstract 

Influenza D virus (IDV) has been increasingly reported all over the world. Cattle are considered the major viral reservoir. Based on the hemagglutinin-esterase (HEF) gene, three main genetic and antigenic clusters have been identified: D/OK distributed worldwide, D/660 detected only in the USA and D/Japan in Japan. 

Up to 2017, all the Italian IDV isolates belonged to the D/OK genetic cluster. From January 2018 to May 2019, we performed virological surveillance for IDV from respiratory outbreaks in 725 bovine farms in Northern Italy by RT-PCR. Seventy-four farms were positive for IDV. A full or partial genome sequence was obtained from 29 samples. 

Unexpectedly, a phylogenetic analysis of the HEF gene showed the presence of 12 strains belonging to the D/660 cluster, previously unreported in Europe. The earliest D/660 strain was collected in March 2018 from cattle imported from France. Moreover, we detected one viral strain with a reassortant genetic pattern (PB2, PB1, P42, HEF and NP segments in the D/660 cluster, whilst P3 and NS segments in the D/OK cluster). 

These results confirm the circulation of IDV in the Italian cattle population and highlight the need to monitor the development of the spreading of this influenza virus in order to get more information about the epidemiology and the ecology of IDV viruses.

       (Continue . . . )

Although the zoonotic risk from Influenza D remains unquantified, this is obviously a virus that continues to evolve, and to spread globally.

For now, it doesn't appear to pose a significant human health threat, but it is important to learn what we can about it now - while we have the luxury of time - rather than waiting until it evolves into something more challenging.

Saudi MOH Announces 200th MERS Case Of 2019

#14,551


While 2019 is far from the most active MERS year we've seen, with more than a month left to go Saudi Arabia has already reported its 200th case, which is more than a 40% increase over all of 2018 (n=142).

Today's case (Epi Week 48) involves a 48 y.o. male - listed as a primary case with recent camel contact - from Medinah.  

This is the 12th case reported by KSA during the month of November.

Last summer, in The Global Seasonal Occurrence of MERS-CoV, we looked at a study that pegged June as the top month of the year for MERS cases (while January, July and November were the lowest).

 

These are averages, and not every year follows this pattern.  This year, for example, we saw more cases reported in July (n=9) than in June (n=7) or August (n=6) (note: reporting delays can sometimes skew when cases are reported).

While MERS-CoV hasn't taken off the way that SARS did 16 years ago, we've seen studies (see A Pandemic Risk Assessment Of MERS-CoV In Saudi Arabia) suggesting the virus doesn't have all that far to evolve before it could pose a genuine global threat.

As long as the virus continues to spill over from camels into the human population, that threat will continue.

WHO Update: Lassa Fever Outbreak In Sierra Leone

#14,550


On Monday, in Sierra Leone : Dutch Doctor Dies From Lassa Fever, Others Exposed, we looked at early reports of medical workers from the Netherlands and the UK who were exposed to Lassa Fever, which had resulted in the death of at least one doctor.

Overnight the WHO released a detailed narrative, which confirms at least 3 other positive Lassa cases have been identified among medical personnel, and expands the number of people who have been potentially exposed to several dozen.

Complicating matters, the doctor who died was initially thought to be infected with malaria or typhoid when he was repatriated for treatment, and so PPEs (other than gloves) were not used. He also attended a medical conference in Freetown shortly after he became symptomatic.

As result, in addition to Sierra Leone, the Netherlands, and the UK - Uganda, Germany, and Morocco are doing contact tracing and dealing with potentially exposed individuals.

The incubation period for Lassa runs from 10 days to 3 weeks, and the overall mortality rate is believed to be in the 1%-2% range, although it runs much higher (15%-20%) among those sick enough to be hospitalized.

The virus is commonly carried by multimammate rats, a local rodent that often likes to enter human dwellings - particularly during the dry season in West Africa - which runs from November to May.

Luckily, secondary transmission is far less common with Lassa than with many of the other Viral Hemorrhagic Fevers (VHF), including Ebola.

Due to its length, I've only included excerpts from the WHO update. Follow the  link to read it in its entirety.

Lassa Fever – The Netherlands (ex –Sierra Leone)

Disease outbreak news
28 November 2019

Sierra Leone health officials, supported by WHO, US Centers for Disease Control and Prevention (CDC) and other partners, are responding to an outbreak of Lassa fever.

On 20 November 2019, WHO was informed by The Netherlands’ International Health Regulations (IHR) National Focal Point of one imported case of Lassa fever from Sierra Leone. The patient was a male doctor, a Dutch national who worked in a rural Masanga hospital in Tonkolili district, Northern province in Sierra Leone.

The probable route of transmission is believed to be through exposures during a surgical procedure he performed on two patients in Masanga hospital on 4 November 2019. Both patients died following surgical interventions; one died on 4 November and the second on 19 November 2019. Both surgical patients are considered probable cases and the patient who died on the 4 November is believed to be the index case for this outbreak, who was likely the source of infection of the Dutch doctor.

The onset of the doctor’s symptoms started on 11 November, a week after performing the surgery, and included malaise and headache, followed by fever, diarrhoea, vomiting and cough. While symptomatic, he attended a surgical training event in Freetown, Sierrra Leone on 11-12 November. This event was also attended by several international participants from the Netherlands and United Kingdom, in addition to 35 local participants.

On 19 November, the symptomatic doctor was medically evacuated to The Netherlands after he did not respond to treatment with antimalarials and antibiotics. The evacuation was managed by a dedicated ambulance plane with four staff from a German organization. During the journey, the plane stopped in Morocco (Agadir Airport). As the illness was initially thought to be malaria or typhoid fever, personal protective equipment, other than gloves were not used and no specific containment procedures were used during the medical evacuation.

Laboratory specimens from the patient tested positive for Lassa fever by polymerase chain reaction (PCR) and sequencing at Erasmus University Medical Centre in Rotterdam on 20 November 2019.

The patient died on the night of 23 November 2019.

On 22 November 2019, WHO was informed of a second laboratory confirmed case of Lassa fever in another Dutch health care worker, who also worked in the Masanga hospital. Samples from this second case were sent to the Erasmus University Medical Centre in Rotterdam and tested positive for Lassa fever by PCR. The second case also participated in one of the surgical procedures performed by the medically evacuated Dutch doctor. The date of onset of symptoms of the second case was 11 November and was subsequently medically evacuated in high containment isolation to the Netherlands and is currently under treatment. Isolation precautions have been implemented.

The Masanga hospital in Sierra Leone, where the Dutch doctor worked is supported by several non-governmental organizations, with international health care workers including staff from countries including Denmark, The Netherlands and the United Kingdom, alongside national health care workers.

Contact tracing and monitoring activities have been initiated in these countries as required.

Sierra Leone

An outbreak investigation and response is ongoing under leadership of the Ministry of Health (MoH), supported by US Centres for Disease Control and Prevention (CDC) and WHO. As of 24 November 2019, in addition to the two Dutch cases, two further cases among national health care workers, one confirmed and another suspected, were reported from Masanga hospital. Both health care workers were involved in the management of the two surgical patients operated by the Dutch doctor on 4 November. All high-risk contacts in Masanga hospital are being monitored. 

The Netherlands

Several high and low risk contacts have been identified among personal contacts and health care workers. According to Dutch protocols, they will be monitored until 21 days after the last potential exposure. Five high-risk Dutch contacts who were in Sierra Leone have been repatriated through a dedicated flight and are now under monitoring. Dutch low risk contacts in Sierra Leone have been advised to perform self-monitoring in situ. 

Germany

The four medical evacuation flight staff (two pilots and two health care workers) spent eight (8) flight hours in a confined space in the ambulance plane, without any barrier between the cockpit and cabin. They have been assessed as moderate level risk contacts. According to German recommendations, they are being monitored for 21 days following the last potential exposure on 19 November (until 10 December 2019). 

United Kingdom (UK)

UK authorities have identified 18 UK nationals as contacts of the first Dutch case. Of these 18, eight are high risk contacts and were exposed in Masanga hospital while working alongside the doctor or possibly got exposed from the two patients he operated on 4 November. Of these eight high risk contacts, seven returned back to UK and one went to Uganda.

Additionally, 13 UK nationals attended a surgical training event in Freetown, Sierra Leone on 11-12 November, which was also attended by the first Dutch case, while already symptomatic. Of these 13 participants, three came from Masanga hospital and belong to the above group of eight high risk contacts. The rest 10 participants were possibly exposed during the training and are considered low risk contacts. Of these 18 contacts identified (eight high risk and ten low risk contacts), 17 have returned back to UK and are under public health follow up for 21 days; one high risk contact went to Uganda. There were also several Dutch and 35 local participants who attended this event. UK authorities are in contact with the organizers and the names of participants from Sierra Leone and The Netherlands have been shared with respective National IHR Focal Points. 

Uganda

One contact, a UK national, who may have been exposed in Masanga hospital on 15 November and subsequently travelled to Uganda on 16 November is now being followed up by the Uganda authorities, and the UK authorities are providing support remotely though public health and consular channels. 

The National IHR Focal Point of The Netherlands has also informed their counterpart in Morocco about the potential risk of exposure at the Agadir Airport. Morocco National IHR Focal Point confirmed that the investigation is conducted, and control measures have been implemented to ensure there was no transmission in Agadir.

Sierra Leone is endemic for Lassa fever. Previously, sporadic cases have been exported to Europe from endemic countries in Africa, such as Togo, Liberia and Nigeria.

In 2018, a total of 23 confirmed Lassa fever cases with 14 deaths (case fatality rate = 61%) were reported from two districts of Sierra Leone: Bo District (two cases with two deaths) and Kenema District (21 cases with 12 deaths).

From 1 January through 17 November 2019, of the 182 suspected cases, ten (10) cases with six (6) deaths (case fatality ratio 60%) have been confirmed for Lassa virus infection. All confirmed cases during this period were reported from Kenema district; which has been reporting cases of Lassa fever every year.

Public health response

The International Health Regulations Focal Points and Health Authorities in Denmark, Germany, Morocco, The Netherlands, Sierra Leone, Uganda and the United Kingdom have been collaborating to share information about this event, together with the WHO and US CDC.

Contact tracing and monitoring activities for 21 days following the last potential exposure have been initiated in Sierra Leone, Germany, The Netherlands, Uganda and the United Kingdom.

Investigations are ongoing in Sierra Leone in Masanga hospital and surrounding areas in Tonkolili district with a deployment of a national rapid response team, supported by US CDC and WHO.

WHO risk assessment

Lassa fever is an acute viral haemorrhagic fever illness that is transmitted to humans via contact with food or household items contaminated with rodent urine or faeces. Human-to-human infections and laboratory transmission can also occur through direct contact with the blood, urine, faeces, or other bodily secretions of a person with Lassa fever. The overall case fatality rate is 1%; it is 15% among patients hospitalized with severe illness.

Sierra Leone is endemic for Lassa fever and sporadic cases have been exported to Europe from endemic countries in Africa, such as Togo, Liberia and Nigeria in recent years. However, in general, the secondary transmission of Lassa fever through human contacts is rare.

Data from recent imported cases show that secondary transmission of Lassa fever is rare when standard infection control precautions are observed. Further, epidemiological investigations are ongoing: Human-to-human transmission occurs in both community and health-care settings, where the virus may spread by contaminated medical equipment. Health care workers are at risk if caring for Lassa fever patients in the absence of appropriate infection prevention and control measures. Considering the seasonal flare-ups of cases in humid zones between December and March, countries in West Africa that are endemic for Lassa fever are encouraged to strengthen their related surveillance systems.

(Continue .  . .)

Editor's Note: My previous blog post, on the OIE Notification of H5N6 in Nigeria mistakenly stated that it was an HPAI Strain. Obviously I need better reading glasses, as it was LPAI. 

Since it was published on Thanksgiving morning, and had received very few views, I removed it and the tweet announcing it to avoid any further confusion. My apologies for the error.

China: Inner Mongolia MOH Announces 5th Case Of Plague

Credit Wikipedia

#14,548


Two weeks ago, in HK CHP Notification Of Two Plague Cases Being Treated In China, we learned of two pneumonic plague cases (M 48, F 46) - originating from Inner Mongolia - who were being treated at a Beijing hospital.  

Bubonic plague is the most common - and most treatable - presentation of Plague, however in rare cases, Pneumonic Plague may develop. 

With Pneumonic Plague, the infected person develops a severe pneumonia, with coughing and hemoptysis (expectoration of blood), and may spread the disease by droplets from human-to-human.

Almost immediately we began to see (unconfirmed) reports of a wider outbreak, carried in the Chinese dissident press, and on social media. Reports that were quickly denied by the Chinese government, although they did report that contacts of the first two cases were `under observation'. 

Three days later (see China: Inner Mongolia Reports Another Plague Case) a 3rd case was announced - a 55 y.o. male who had caught and skinned a rabbit -  this time presenting as Bubonic plague. 

Despite intense censorship, social media (primarily Weibo) and the dissident press continued to report on (unconfirmed) roadblocks and quarantines in Inner Mongolia, with both Qinghai and Gansu Provinces also frequently mentioned.

Six days ago, in Taiwan CDC Reports 4th Mainland Plague Case of 2019, we learned - somewhat belatedly - of a Septicemic Plague case from Gansu Province, which reportedly occurred in September of this year.

Despite the furor in social media and in the dissident press, it is not unusual to see a handful of plague cases reported each year from China. 

We often see that many cases (or more) each year in the Western United States, and two years ago, Madagascar saw an epidemic involving hundreds of cases (see WHO WER: Plague Around The World).

Despite the denials of a larger problem, China does appear to be aggressively screening patients - particularly in Inner Mongolia - for plague symptoms, and has activated plague prevention and control plans.  

 This (translated) report from the Inner Mongolia Board of Health website.

Ordos City plague prevention and control of plague prevention and control of the joint meeting of the group held in the city 
Published: 2019-11-26 15:43:50　　 

Source: Wei Jian Committee Propaganda Department

November 25, Ordos City plague prevention and control of plague prevention and control of the joint meeting of the group held in the city. Ordos Municipal People's Government Vice Mayor Yu-jen masterpiece thematic deployment.

The meeting heard a report on the prevention and control of members of the unit plague the city health committee, city grass Bureau, the Municipal Transportation Bureau, the Municipal Public Security Bureau, Airport Group, railway civil aviation centers, to carry out plague prevention and control problems encountered in the work on the various sectors We proposed solutions.

The meeting urged all member units to further strengthen cooperation, implementation of joint prevention and control, long-term mechanism, and to increase supervision and inspection efforts to flag areas, strengthen the prevention and control of plague emergency training exercises, control public opinion to do the work. (Han Li Li Xiaomei feeds)

All of which brings us to a report from the Inner Mongolia MOH of a 5th plague case (4th from Inner Mongolia) since these reports began last September.  Once again, it is reportedly Bubonic plague, and it involves a herdsman from south-central Inner Mongolia.

(translated)

A case of bubonic plague confirmed in Siziwangqi of our district

Release time: 2019-11-27 23:40:00

Review: Liu Wei Editor: Edited by Huang Lihua: Emergency Office 

November 27, 2019, a herdsman on the bank of Sumu River, the bank of Siziwang Banner, Ulanchabu, was diagnosed as a bubonic plague during consultation with experts from the state and the autonomous region during the consultation at Siziwangqi People's Hospital.

The patient had been active in the source of the plague before he became ill. At present, the patient has been isolated and treated at the local hospital, and his condition is stable. The relevant prevention and control measures have been implemented. Four close contacts have been isolated for medical observation as required. At present, there are no abnormalities such as fever.

Wangsizizi Banner has completely killed the patient's residence and the surrounding herdsmen's residence, and carried out anti-rat and flea prevention and publicity education around the patient's residence.

Experts remind the general public:

1. Maintain good personal hygiene habits, avoid crowded places as much as possible, and wear masks in time when you go to a medical institution for treatment or if you have fever, cough and other related symptoms.

2. If you suspect that you have contact with the case, you can report to the local disease control department and obtain professional guidance. If you have symptoms such as fever, cough, lymph node pain, hemoptysis or bleeding, you should seek medical treatment in time.

3. Minimize contact with wild animals when traveling, do not hunt, strip, or carry epidemic animals without authorization, and take measures to prevent fleas from biting to avoid being bitten by fleas.

4. Field workers should raise awareness of plague prevention and strengthen personal protection measures. (Contributed by Lu Yakai)

China's penchant for censoring or suppressing `bad news' - particularly when it involves disease outbreaks - makes it difficult to assess the size, scope and significance of these plague cases. 

As previously mentioned, plague (Y. pestis) is endemic in rodents across much of China - including Inner Mongolia - and it is possible the shortage of pork due African Swine Fever (once again, badly under reported by the Chinese government) has driven more people to hunt, handle, and consume bushmeat, increasing the odds of human infection. 

Despite its fearsome reputation, Plague is treatable - if caught early enough - by modern antibiotics. While we may hear of more cases in the coming days, the more bombastic reports circulating on Chinese social media are unlikely to pan out. 

That said, large urban outbreaks of plague have (rarely) been reported in modern times - including in India in 1994 and Madagascar in 2017 - and so we'll continue to keep an eye on these reports in the coming days.

Vet. MicroB.: Eurasian Avian-Like Swine Influenza A (H1N1) Virus from Mink in China

#14,547

Conventional wisdom holds that the next pandemic influenza virus will most likely evolve in, and emerge from, either birds or pigs. Both species are hosts for a wide variety of novel flu subtypes, and both have contributed to the emergence of flu pandemics in the past.

Much further down the list we have an array of flu-susceptible mammals, including dogs, cats, horses, seals, and peridomestic animals like skunks, raccoons, and rabbits.

Dogs, cats, and to a lesser extent - horses - are of greatest concern because they generally have closer contact with humans, while seals, skunks, and rabbits usually do not.  We've looked at their potential role in a future pandemic a number of times, including:

Vet. Research: Host-range Shift of H3N8 Canine Influenza Virus

Study: Dogs As Potential `Mixing Vessels’ For Influenza

PLoS: Adaptation of H3N2 Canine Influenza Virus to Feline Cell Culture

J Infect Dis: Serological Evidence Of H7N2 Infection Among Animal Shelter Workers, NYC 2016

EID Journal: Equine Influenza - A Neglected, Reemergent Disease Threat

But over the years we've seen another small mammal, one that is susceptible to a remarkable variety of flu viruses, and - largely because they are farmed worldwide -  that could also serve as a plausible `mixing vessel' for influenza; mink. 

Mink farming has become big business in China over the past decade, with more than 60 million raised in 2012. Increasingly fox and raccoon dogs are raised on the same farms, increasing the odds of inter-species transmission of novel viruses.

In China, farmed animals are often fed a diet that includes raw poultry or poultry products (cite), which increases their risk of exposure to avian viruses, while wild mink may consume waterfowl, fish, frogs, and other small mammals.

A decade ago, in 2009's That Touch Of Mink Flu, we looked at a story out of Denmark, where at least 11 mink farms in the Holstebro were reported to be infected with a variant of the human H3N2 virus.

• Also in 2009, an H3N2 Swine Influenza was detected in Canadian Mink, reported in a Journal of Clinical Microbiology study called  Characterization of a Canadian Mink H3N2 Influenza A Virus Isolate Genetically Related to Triple Reassortant Swine Influenza Virus. 
• Three years earlier (2006) CIDRAP reported on a European mink found infected with an aggressive form of the H5 flu virus in the Blekinge region of southern Sweden near where H5N1 had been detected in wild birds.  
• And in 1984 a large outbreak in Swedish mink farms was found to be due to the H10N4 avian virus.

In 2015, we revisited mink flu in That Touch Of Mink Flu (H9N2 Edition), after a study was published in the Virology Journal on a serological survey of antibodies to H9N2 (along with H5 & H7 viruses) in Chinese farmed minks, along with the results of experimental infection of minks with the H9N2 virus.

We've returned to H9N2 in minks at least twice since then (see H9N2 Adaptation In Minks) and That Touch Of Mink Flu (H9N2) - Revisited.

We're mink simply conveyors the same flu virus that they acquired from humans or pigs, then their infection would be of little consequence. But since flu viruses tend to adapt to each new host, a species jump can introduce new, and unpredictable, evolutionary changes to the virus.

Although we only have the abstract available (the rest is behind a pay wall), we have fresh report - not surprisingly out of China - of a reassorted Eurasian Avian-like Swine Influenza H1N1 virus found in farmed mink.

First the link, and abstract, then I'll return with some background on the EA H1N1 virus.  

Emergence of an Eurasian Avian-Like Swine Influenza A (H1N1) Virus from Mink in China

Jiahui Liu, Zihe Li, Yanlei Cui, Haiyan Yang, ... Chuanmei Zhang

https://doi.org/10.1016/j.vetmic.2019.108509

Highlights

• We isolated and identified a swine origin triple-reassortant H1N1 influenza virus from the lungs of infected mink.

• Farmed minks were susceptible to H1N1 virus.

• This stain was lethal in mice and had low pathogenicity to mink.

• H1N1 virus could infect minks, replicated in vivo, was eliminated outwards.

Abstract

We evaluated the phenotype and genotype of a fatal influenza/canine distemper virus coinfection found in farmed mink in China. We identified a novel subtype H1N1 influenza virus strain from the lungs of infected mink designated A/Mink/Shandong/1121/2017 (H1N1).

The results of phylogenetic analysis of 8 gene fragments of the H1N1 strain showed the virus was a swine origin triple-reassortant H1N1 influenza virus: with the 2009 pandemic H1N1 segments (PB2, PB1, PA, NP and M), Eurasian avian-like H1N1 swine segments (HA and NA) and classical swine (NS) lineages.

The EID50/0.2 mL of this strain was 10-6.2 and pathogenicity tests were 100% lethal in a mouse model of infection. We found that while not lethal and lacking any overt signs of infection in mink, the virus could proliferate in the upper respiratory tracts and the animals were converted to seropositive for the HA protein.

        (Continue . . . .)


Since the influenza subtypes that commonly circulate in swine (H1, H2 & H3) are also the same HA subtypes that have caused all of the human pandemics going back at least 130 years (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), we pay particular attention to their evolution and spread in the wild.

Almost four years ago, Chen Hualan - director of China's National Avian Influenza Reference Laboratory - pegged the EA (Eurasian Avian-like) H1N1 swine virus (EAH1N1) as having perhaps the greatest pandemic potential of any of the novel viruses in circulation.

Avian-like H1N1 swine flu may "pose highest pandemic threat": study

WASHINGTON, Dec. 28 (Xinhua) -- The Eurasian avian-like H1N1 (EAH1N1) swine flu viruses, which have circulated in pigs since 1979, have obtained the ability to infect humans and may "pose the highest pandemic threat" among the flu viruses currently circulating in animals, Chinese researchers said Monday.

(Continue . . . )

Her comments came after the publication of her 2015 paper Prevalence, genetics, and transmissibility in ferrets of Eurasian avian-like H1N1 swine influenza viruses.  

In June of 2016, in Sci Rpts: Transmission & Pathogenicity Of Novel Swine Flu Reassortant Viruses we looked at a study where pigs were experimentally infected with one of these Eurasian-Avian H1N1 swine influenza viruses and the 2009 H1N1pdm virus.

Researchers generated 55 novel reassortant viruses spread across 17 genotypes, demonstrating not only how readily EAH1N1 SIV can reassort with human H1N1pdm in a swine host, but also finding:

`Most of reassortant viruses were more pathogenic and contagious than the parental EA viruses in mice and guinea pigs'. 

A few months later, in EID Journal: Reassortant EAH1N1 Virus Infection In A Child - Hunan China, 2016, we reviewed the case report on a 30-month old child from Hunan Province, who was infected with one of these reassortant EAH1N1 - H1N1pdm viruses.     

More recently, in Emerg. Infect. & Microbes: Novel Triple-Reassortant influenza Viruses In Pigs, Guangxi, China, we looked at the growing diversity of novel H1N1 and H3N2 flu viruses (including EA H1N1) in China's pig population.

The emergence of novel swine viruses is truly a global concern, yet  influenza surveillance in swine is minimal, and in many places it is nonexistent.

Even less studied is the evolution and spread of novel flu viruses in other farmed  species, like mink. The EA H1N1 virus in today's report was discovered more by happenstance, than design.

While mink may seem a long-shot, 3 months ago in Nature: Semiaquatic Mammals As Intermediate Hosts For Avian Influenza, we saw a study that suggested that mink be considered an important sentinel species for influenza surveillance.

The authors wrote:

It suggested that the semiaquatic mammals (riverside mammals), rather than pigs, might be the intermediate host to spread AIVs and serve as a potential mixing vessel for the interspecies transmission among birds, mammals and human.

In epidemic areas, minks, possibly some other semiaquatic mammals as well, could be an important sentinel species for influenza surveillance and early warning.

Of course, we'll never know how much of a role mink play in novel flu's ecology and evolution until we start seriously looking.

Nature MicroB.: Influenza A Variants with Reduced Susceptibility to Baloxavir Are Fit & Transmit Easily

Credit NIAID

#14,546

The new, one-dose influenza antiviral Baloxavir marboxil (trade name Xofluza®) was approved in the United States just over a year ago (see FDA Approval Of Xofluza : A New Class Of Influenza Antiviral, but has been approved for use in Japan since early 2018.

This new class of antiviral is particularly welcome as the two existing neuraminidase inhibitors - zanamivir and oseltamivir (Tamiflu ®) - have been in use now for 20 years, and there are always concerns over creeping resistance.

In early March of this year, however, we saw several reports - and a Eurosurveillance Rapid Communications - on the detection of a small number of Baloxavir resistant flu viruses among patients in Japan - including three that had not received the antiviral drug.

In August, in EID Journal: H-2-H Transmission Of A(H3N2) with Reduced Susceptibility to Baloxavir, Japan, we looked at a study that reported:

During the 2018–19 influenza season in Japan, we detected 32 mutant influenza A(H3N2) viruses carrying various types of PA I38 substitutions, 4 of which were isolated from children < 12 years of age without prior baloxavir exposure. 

The researchers concluded:  `These 4 children were probably infected with mutant viruses acquired from hosts previously treated with baloxavir.'


A month later, in J.I.D: Replicative Fitness of Seasonal Influenza A Viruses with Decreased Susceptibility to Baloxavir, we saw a study that evaluated the biological fitness of baloxavir resistant viruses collected last winter, and found them only mildly impaired.

The spontaneous development of resistant viruses in a patient who is already receiving antiviral drugs is a known - but relatively rare (roughly 1%) - complication. Usually, these mutated viruses suffer a fitness penalty' - making them less likely to be transmitted on to others.

Usually, but not always.  

In 2008 we saw the old seasonal H1N1 flu virus go from being nearly 100% sensitive to Oseltamivir to almost 100% resistant (see CIDRAP On the CDC Change Of Advice On Tamiflu) in a matter of months.

It was only the unexpected arrival of a new, oseltamivir-sensitive H1N1 pandemic virus in the spring of 2099 - one which supplanted the newly resistant strain - that salvaged Tamiflu's usefulness against H1N1.

All of which brings us to a new report that characterizes the fitness and transmissibility of one of last winter's baloxivir-resistant viruses, and finds that a single amino acid change was all that was needed to make it fit, and easily transmissible in humans.

While the full report is behind a paywall (link below), we've a press release from the University of Wisconsin-Madison providing more details.

Influenza A variants with reduced susceptibility to baloxavir isolated from Japanese patients are fit and transmit through respiratory droplets

Masaki Imai,Makoto Yamashita, […]
Yoshihiro Kawaoka Nature Microbiology (2019)

Here we report the isolation of the influenza A/H1N1 2009 pandemic (A/H1N1pdm) and A/H3N2 viruses carrying an I38T mutation in the polymerase acidic protein—a mutation that confers reduced susceptibility to baloxavir marboxil—from patients before and after treatment with baloxavir marboxil in Japan. These variants showed replicative abilities and pathogenicity that is similar to those of wild-type isolates in hamsters; they also transmitted efficiently between ferrets by respiratory droplets.

I've only included some excerpts from the press release (bolding mine), so follow the link to read it in its entirety.

New flu drug drives drug resistance in influenza viruses 

November 25, 2019 By Kelly April Tyrrell

On January 31, 2019, an 11-year old boy in Japan went to a medical clinic with a fever. The providers there diagnosed him with influenza, a strain called H3N2, and sent him home with a new medication called baloxavir.

For a few days, he felt better, but on February 5, despite taking the medication, his fever returned. Two days later, his 3-year-old sister also came down with a fever. She, too, was diagnosed with H3N2 influenza on February 8.

An analysis of flu samples collected from her and her brother show she was sickened by a strain of H3N2 harboring a new kind of mutation — one that Yoshihiro Kawaoka, University of Wisconsin–Madison professor of pathobiological sciences, says is resistant to baloxavir, is just as capable of making people sick as the non-mutated version, and is capable of passing from person to person.

He and colleagues describe this in a study published today [Nov. 25, 2019] in Nature Microbiology that examined the effects of baloxavir treatment on influenza virus samples collected from patients before and after treatment.

“We sequenced the entire viral genome of the 11-year-old boy with drug sensitive influenza virus (before treatment) and the sample from the girl that is drug resistant,” says Kawaoka. “Out of 13,133 nucleotides, there was only one nucleotide difference between the two.”

(SNIP)

Often, viruses that gain mutations such as drug resistance sacrifice their ability to survive and spread well among their hosts. To understand whether this was true of the baloxavir-driven mutation, the researchers grew the mutant viruses in cell culture and learned it grows just as well as the non-mutated form.

They then tested the mutant H1N1 and H3N2 viruses in hamsters and learned that once the virus mutates, that mutation continues to be copied as new virus grows.

The team also tested the mutated viruses in ferrets and found the mutated form was capable of transmitting from infected animals to healthy ones. The severity of their illness from flu was also similar to the non-mutated form.

While it’s unlikely the mutation will lead to widespread resistance around the world, Kawaoka says it could become a problem among family members in close proximity, and in facilities like hospitals and nursing homes. And, while children seem particularly prone to viral mutation with baloxavir treatment, it appears to occur less frequently in adults. It also quickly reduces the amount of virus in the systems of treated patients. “It’s a good drug for adults,” Kawaoka says.

And, he explains, patients with H1N1 or H3N2 that do develop resistance to baloxavir with treatment still do respond to other virus-fighting drugs.

“The drug resistant virus does transmit but there are so many influenza viruses worldwide and only a small population will be treated with this drug,” Kawaoka says. “The vast majority remain drug sensitive.”

        (Continue . . . )


So far, these early reports of baloxavir resistance - while concerning - remain highly scattered.  We should get a much better idea of its scope and significance this winter, as enhanced surveillance is planned in both Japan and the United States.

Stay tuned.

Netherlands: Multiple Farms Report LPAI H6

#14,545

Although LPAI H3 viruses aren't supposed to produce serious illness in poultry - and are not considered `reportable' by the OIE -  for several months over the spring and summer we followed an unusual outbreak of H3N1 in Belgium which produced significant losses to their poultry industry (see NL AVINED: LPAI H3N1 Updates).

Today, we are seeing reports of multiple outbreaks of a LPAI H6 virus in turkey farms across the Netherlands, which is also consider a non-reportable virus.

There are two broad categories of avian influenza; LPAI (Low Pathogenic Avian Influenza) and HPAI (Highly Pathogenic Avian Influenza).

• LPAI viruses are common in wild birds, cause little illness, and only rarely death.  They are not considered to be a serious health to public health (LPAI H7N9 being the exception). The concern is (particularly with H5 & H7 strains) that LPAI viruses have the potential to mutate into HPAI strains. 

• HPAI viruses are more dangerous, can produce high morbidity and mortality in wild birds and poultry, and can sometimes infect humans with serious result. Again, H5 and H7 viruses are of greatest concern, but other subtypes have also caused human illness and large poultry losses. 

Before the middle of the last decade, there was no uniform requirement to report or track LPAI infections.  That changed in 2006 when the OIE made reporting of LPAI H5 & H7 viruses mandatory.

While other LPAI subtypes are not currently reportable to the OIE (see Terrestrial Animal Code Article 10.4.1.), that doesn't make them entirely benign.

The most obvious, and worrisome loophole is for LPAI H9N2, which is common in Asia and the Middle East, and has recently moved into Africa. While not a notifiable virus, H9N2 has demonstrated its ability to infect humans and to reassort with other viruses, and is on the CDC's short list of novel viruses with pandemic potential (see CDC IRAT Score).

There are other non-notifiable LPAI viruses we keep a close eye on, including:

• LPAI H6N1 which caused a human infection in Taiwan in 2013 - jumped to Taiwanese dogs in 2014, and in 2015's EID Journal: Seropositivity For H6 Influenza Viruses In China, researchers found a a small, but significant number of people in their survey who tested positive for H6 influenza antibodies (indicating previous exposure).
• LPAI H4N6 - which while common in wild and migratory birds - has also been found in Chinese, Canadian (1999) and American swine (see Virology: Detection & Characterization Of Avian H4N6 In Midwestern Swine (2015)) and has shown signs of human adaptation (see Cell: Avian-to-Human Receptor-Binding Adaptation by Influenza A Virus Hemagglutinin H4).

 
Unlike H3N1 earlier this year, the LPAI H6 outbreaks in the Netherlands appear to be benign in poultry, and the risks of it mutating into into a more dangerous HPAI virus are believed negligible.

This (translated) report (Nov 25th) from the Netherlands AVINED.

Low pathogenic bird flu H6 in the Netherlands

It is currently quiet in the area of ​​the highly pathogenic bird flu and in the area of ​​the low pathogenic bird flu H3N1. In Belgium, screening at companies has been positive and no new cases of H3N1 have been detected. However, vigilance for bird flu remains necessary. Several cases of the low pathogenic bird flu of the (not subject to control) type H6 have recently been found in the Netherlands.

Several cases of low pathogenic avian influenza H6 have recently been found in laying farms and turkeys. This is a variant of bird flu that is not subject to control. Most cases were detected via monitoring (serologically positive) and a single case based on clinical symptoms. 

These were companies in the provinces of Overijsel, Flevoland, Gelderland, Friesland, Groningen and Noord-Brabant.Be carefulAVINED is happy to point out the importance of strict biosecurity and hygiene at your company. Also be aware of disease symptoms, so that an infection is discovered as early as possible. 

If in doubt, contact your veterinarian. And, in consultation with your veterinarian, make use of the possibility to send in Early Warning swabs. In the event of a failure of more than 0.5% during two days, or more than 3% per week per couple, a notification obligation applies to the NVWA (045 - 546 3188).

The lesson of Belgium's H3N1 outbreak earlier this year is that the conventional wisdom on avian flu is subject to change at any time.

LPAI H7 viruses were relatively recently thought to be a weak cousin of HPAI H5N1, and incapable of producing the same level of virulence in humans.

The emergence of LPAI H7N9 in China in 2013 - sporting a mortality rate (among those hospitalized) of 30% - has dispelled that notion.  A severe human infection with LPAI H7N4 in China last year showed this was not a fluke.

While the risks to poultry - and to human health - by this outbreak are likely very low, the fact that it has spread widely in the Netherlands is noteworthy.

Farmers are being urged to increase their biosecurity and to report any unusual symptoms or mortality in their flocks.

And this time of year, when migratory birds across the northern hemisphere are on the move, that is sound advice for all poultry operations.

Sierra Leone : Dutch Doctor Dies From Lassa Fever, Others Exposed

#14,544


Over the weekend it has emerged that a Dutch doctor, working in Sierra Leone, has died from Lassa fever after being repatriated back to the Netherlands, and that a second Dutch doctor is in isolation and receiving treatment (see BBC report Dutch doctor dies after contracting Lassa fever in Sierra Leone).

A second report - this time from Sky News - indicates that at least 3 Britons who may have been exposed have been repatriated to the UK for tests (see Lassa fever: Britons who came into contact with victims brought back to UK for tests).

While it doesn't get as much attention by the mainstream press as does its deadlier cousin Ebola, every year we see outbreaks of Lassa Fever in West Africa (see map above), often causing hundreds of infections and scores of fatalities (see

Eighteen months ago, in the WHO List Of Blueprint Priority Diseases, we looked at 8 disease threats in need of urgent accelerated research and development.

Number 3 on the list is Lassa Fever. 

List of Blueprint priority diseases

(SNIP)

The second annual review occurred 6-7 February, 2018. Experts consider that given their potential to cause a public health emergency and the absence of efficacious drugs and/or vaccines, there is an urgent need for accelerated research and development for*:

• Crimean-Congo haemorrhagic fever (CCHF)
• Ebola virus disease and Marburg virus disease
• Lassa fever
• Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS)
• Nipah and henipaviral diseases
• Rift Valley fever (RVF)
• Zika
• Disease X

Lassa fever is a Viral Hemorrhagic Fever (VHF), the virus for which is commonly carried by multimammate rats, a local rodent that often likes to enter human dwellings. Exposure is typically through the urine or dried feces of infected rodents, and roughly 80% who are infected only experience mild symptoms.

The incubation period runs from 10 days to 3 weeks, and the overall mortality rate is believed to be in the 1%-2% range, although it runs much higher (15%-20%) among those sick enough to be hospitalized.  

Like many other hemorrhagic fevers, person-to-person transmission may occur with exposure to the blood, tissue, secretions, or excretions of an individual (cite CDC Lassa Transmission).

Unfortunately, healthcare workers - particularly those working in austere or  less than ideal conditions - are often exposed.  In Nigeria, as of Nov 17th, 19 HCWs have been infected since January 1st.

While primarily a regional threat, during the last major outbreak (2016) exported cases turned up in several countries, including Germany and Sweden (see Germany's RKI Statement On Lassa Fever Cluster In Cologne & WHO Lassa Fever Update - Sweden (Imported)).

In 2016 the ECDC published a Rapid Risk Assessment on the spread of Lassa Fever out of  West Africa.  While the risk of seeing Lassa Fever outside of West Africa was determined to be low, they authors wrote:

The two imported cases of Lassa fever recently reported from Togo indicate a geographical spread of the disease to areas where it had not been recognised previously. Delays in the identification of viral haemorrhagic fevers pose a risk to healthcare facilities.

Therefore, Lassa fever should be considered for any patient presenting with suggestive symptoms originating from West African countries (from Guinea to Nigeria) particularly during the dry season (November to May), a period of increased transmission, and even if a differential diagnosis such as malaria, dengue or yellow fever is laboratory-confirmed.

A reminder that in this increasingly interconnected and mobile world that localized outbreaks - no matter how remote - aren't guaranteed to remain such, and that without a proactive response they can very quickly turn into public health threats anywhere in the world.

The WHO Pandemic Influenza NPI Guidance : Travel Measures

Scheduled airline traffic around the world, circa June 2009 – Credit Wikipedia

 















#14,543

Just over three weeks ago, in WHO Guidance: Non-pharmaceutical Public Health Measures for Mitigating the Risk and Impact of Epidemic and Pandemic Influenza, we took our first look at the World Health Organization's recently released 91-page NPI Guidance document.

Since then we've taken a closer look at the WHO's recommendations on Personal protective NPIs (hand hygiene, isolation, masks, etc.),  Social Distancing, and most recently Environmental Measures. 

NPIs - or Non-Pharmaceutical Interventions - are those actions (apart from taking vaccines & antivirals) that individuals and communities can do to help slow the spread of an infectious disease.  

None of these measures will stop a pandemic virus from spreading, or fully protect an individual from infection. Their combined use, however, can help slow the spread of the virus and (hopefully) reduce the impact of a severe pandemic.

The last category of NPIs to look at from this WHO document involves travel, both domestic and international. As the graphic at the top of this blog suggests, international airline traffic will play a big role in the rapid and efficient spread of the next pandemic virus.

The WHO NPI recommendations are divided into 4 categories.

• Travel Advice
• Entry & Exit Screening
• Internal Travel Restrictions
• Border closure

As with all of the other NPI recommendations, recommendations and timing are based on the severity of the pandemic; any severity, moderate, high, and extraordinary.

The least controversial of these recommendations is the issuance of travel advice, as we see this done routinely today, through the CDC's Traveler's Health website, through signage at airports, and other venues.

As with many of the other NPI recommendations we've looked at, there isn't a great deal of evidence of its effectiveness, but it is fairly easy to implement, has few downsides, and probably has some merit.

The second NPI considered is Entry and Exit Screening of travelers, which we've seen rolled out for the 2009 H1N1 pandemic, Ebola, MERS, and other localized outbreaks of exotic diseases.

While highly disruptive, and generally ineffective (see Why Airport Screening Can’t Stop MERS, Ebola or Avian Flu) it is often the first - and most visible - response by governments anxious to show they are `doing something'  to protect the populace.

Entry and exit screening

Summary of evidence

Ten articles related to entry and exit screening were included in this review (185, 220-228). Observational studies conducted at airports estimated that the sensitivity of entry screening was low (226-228). Among arriving international travellers, half of the influenza cases were identified more than a day after arrival (through passive case finding and contact tracing in the community), although 37% of the influenza cases were screened while passing through the border entry site (185). Simulation studies estimated that screening international travellers may help to delay the epidemic by less than 2 weeks (0–12 days) (220-222).

In 2010, in  Japan: Quarantine At Ports Ineffective Against Pandemic Flu, I wrote about a study that found between asymptomatic or mild H1N1 infections, and a silent incubation period of several days, there wasn’t much chance of long-term success.

For every person identified, and quarantined, by port authorities  - researchers estimate 14 others infected by the virus entered undetected.

In April of 2012, in EID Journal: Airport Screening For Pandemic Flu In New Zealand, we looked at a study that found that the screening methods used at New Zealand’s airport were inadequate to slow the entry of the 2009 pandemic flu into their country, detecting less than 6% of those infected.

While I suspect it will be widely ignored, the WHO's recommendation is against Entry and Exit Screening. 

Moving on, travel recommendation #3 involves Internal travel restrictions (note: This WHO NPI guidance document did not address International Travel Restrictions).  

Summary of evidence

One epidemiological study (231) and four simulation studies (114, 162, 232, 233) related to internal travel restrictions were included in this review. A time-series analysis study conducted in the USA showed that frequency of domestic airline travel is temporally associated with the rate of influenza spread, and following the September 11 attacks in 2001, a reduction in such travel delayed the epidemic peak by 13 days compared with the average for other years (231).

A simulation study predicted that implementation of a strict travel restriction (95% travel restriction, enforced for 4 weeks) could reduce the epidemic peak by 12%, and a moderate restriction (50% travel restriction, enforced for 2–4 weeks) could delay the pandemic peak by 1–1.5 weeks (162). Another simulation study predicted that an internal travel restriction of more than 80% could be beneficial (232). A strict internal travel restriction (90%) was also consistently found to delay the epidemic peak by 2 weeks in the United Kingdom, and by less than 1 week in the USA (114). However, a 75% restriction had almost no effect (114).

Presumably, very early in a pandemic, if a nation finds itself with a single hotspot of disease transmission, it might consider restricting travel to or from that area in an attempt to slow the outbreak.     

Frankly, it is hard to imagine this situation occurring more than a few weeks into any pandemic, but it nonetheless is conditionally recommended during the early stage of a localized and extraordinarily severe pandemic outbreak. 

And lastly, the WHO takes a very dim view of border closures of any kind, although they grant it might be effective for some small, self-sufficient island nations. 

Border closure

Summary of evidence

Eleven articles related to border closure were included in the systematic review (114, 135, 204, 231, 235-239). Two were epidemiological studies (135, 231) and nine were simulation studies (114, 204, 234-240). An epidemiological study suggested an important influence of international air travel on the timing of influenza introduction (231). Another historical analysis of the 1918–1919 pandemic suggested that strict border control was a successful method for delaying and preventing influenza from arriving in South Pacific islands (135).

A simulation study predicted that 99% restriction of cross-border travel between Hong Kong SAR and mainland China may delay the epidemic peak by about 3.5 weeks compared with non-travel restriction (235). Another simulation study conducted in Italy predicted that international air travel restriction would delay the peak of epidemic by about 1–3 weeks, depending on the transmission rate and the level of restriction (204). However, the attack rate was not significantly affected (204).

Furthermore, simulation studies based on a global scale model also predicted that international travel restriction would delay epidemics by about 2–3 weeks (236) and significantly delay its global spread (5–133 days) (237).

Strict border control of 99.9% may be effective in delaying the epidemic peak by 6 weeks, while 90% and 99% border control would delay the epidemic peak by 1.5 and 3 weeks, respectively (114). International travel restriction is estimated to slow the importation of infections (234, 238), but would not reduce the epidemic duration (238). 

Because the supply of essential items to a population, such as food and medical supplies, often relies on importation, strict border closures need to be carefully considered before implementation in island countries and territories (239).

 
Much like Entry and Exit Screening, border closures sound like a reasonable step during a pandemic (and I'm sure will be tried by some countries), but - at least with influenza - is unlikely to be effective. 

During the 1918 pandemic, when international travel was far less common, a few nations managed to block entry of the pandemic virus by imposing a strict quarantine of all arriving passengers (see Protective Effect of Maritime Quarantine in South Pacific Jurisdictions, 1918–19 Influenza Pandemic).

The four successful quarantines during the 1918 pandemic were in American Samoa (5 days' quarantine) and Continental Australia, Tasmania, and New Caledonia (all 7 days' quarantine).

• The Spanish Flu did not reach American Samoa until 1920, and had apparently weakened, as no deaths were reported.

• Australia's quarantine kept the influenza away until January of 1919, a full 3 months after the flu has swept New Zealand with disastrous effects. 

• Tasmania kept the flu at bay until August of 1919, and health officials believed they received an milder version, as their mortality rate was one of the lowest in the world.

• By strictly enforcing a 7-day quarantine, New Caledonia managed to avoid introduction of the virus until 1921. 

Eventually, once the quarantines were lifted, the virus did make it to these isolated regions of the world. But by that time, the virus often appeared to have weakened and its impact was lessened.

Eleven years ago, in New Zealand: Testing Pandemic Quarantine Plans, we looked at Exercise Spring Fever - a `war game' designed to test New Zealand's ability to cut themselves off from the rest of the world during a pandemic.

While no decision has ever been made regarding the quarantining of New Zealand during a pandemic, the option continues to be discussed.

Last year, a study published in Australia & New Zealand  Journal of Public Health, looked at the economic impact of a 180-day quarantine on the island nation of New Zealand.

Economic evaluation of border closure for a generic severe pandemic threat using New Zealand Treasury methods
Matt Boyd, Osman D. Mansoor, Michael G. Baker, Nick Wilson

First published: 08 August 2018

ABSTRACT 

Conclusions: This work quantifies the economic benefits and costs from border closure for New Zealand under specific assumptions in a generic but severe pandemic threat (e.g. influenza, synthetic bioweapon). Preparing for such a pandemic response seems wise for an island nation, although successful border closure may only be feasible if planned well ahead.

Implications for public health: Policy makers responsible for generic pandemic planning should explore how border closure could be implemented, including practical and legal frameworks. 

Whether New Zealand would actually `pull the trigger' is unknown, but they are probably the largest population island with a reasonable chance of success.

This 5-part series on the WHO's updated NPI guidance only covers the highlights of more than 200 pages of documentation.  Policy makers will want to delve deeper into the source documents. 

These recommendations are just that; recommendations.  

Not all will be adopted - or universally followed - by nations, communities, or individuals around the globe.  What may work in Europe or North America may not work nearly as well in Asia, or Africa.

In the opening weeks, and likely months, of the next influenza pandemic vaccines and antivirals will likely be either unavailable, or in very short supply.  NPIs, while far from perfect, offer us the `next-best'  thing we can do to reduce the spread, and impact of a pandemic.

EID Journal & IJID : Human Infection With LPAI H9N2 - India & Oman

Flu Virus binding to Receptor Cells – Credit CDC



#14,542

Although human infection with avian LPAI H9N2 remains only rarely reported (see FluTrackers List)) - and it has a reputation for producing substantially less severe illness in humans than its avian H5 & H7 counterparts - LPAI H9N2 is still considered an important player in the avian flu world.

• H9N2 has become widespread - even ubiquitous - among poultry across Asia and the Middle East, and has made recent inroads into Africa.
• Serological studies suggest human infection is far more common than standard surveillance would have us believe (see J. Infect & Public Health: High Seroprevalence Of Avian Influenza H9 Among Poultry Professionals In Pakistan)
• H9N2 reassorts easily with other viruses, and its internal genes are often found inside many HPAI viruses (including H5N1, H5N6, and H7N9) -  (see The Lancet's Poultry carrying H9N2 act as incubators for novel human avian influenza viruses) 
• H9N2 viruses continue to accrue evolutionary changes, which include mammalian adaptations, and increased binding to human receptor cells (see PLoS Path: Genetics, Receptor Binding, and Transmissibility Of Avian H9N2).
• Both the CDC and WHO consider the virus to have at least some pandemic potential  (see CDC IRAT SCORE), and several candidate vaccines have been developed over the years. 

The truth is, in areas where this virus circulates, few people with mild or moderate illness seek medical care or are ever tested for influenza. Fewer still have their samples forwarded to a laboratory capable of identifying novel flu subtypes like H9N2. 

The assumption is, human infection is more common than the reported cases would suggest.  And while most infections are mild or moderate, some severe cases have been reported. 

A couple of weeks ago, in Viruses: Characterization of the H9N2 Avian Influenza Viruses Currently Circulating in South China, we looked at a a new study, published in the journal Viruses, that reported that China's current crop of H9N2 viruses continues on an evolutionary path that increases its pandemic potential.

Until 2019, reports of human cases have been limited to (mostly) China and Hong Kong, plus a few cases from Bangladesh and Pakistan, and since 2015 - a handful of cases reported from Egypt.

This year, we've learned of two new countries reporting human H9N2 infections; India and Oman.  The Omani case was revealed last May in WHO Novel Flu Summary & Risk Assessment - May 2019.

Earlier this month, the CDC's EID Journal carried the following brief report of a human H9N2 infection from India, which was somewhat serendipitously discovered during an ongoing community-based surveillance study on RSV-associated deaths among children.

Volume 25, Number 12—December 2019
Research Letter

Laboratory-Confirmed Avian Influenza A(H9N2) Virus Infection, India, 2019

Potdar V, Hinge D, Satav A, Simões EF, Yadav PD, Chadha MS.

Abstract

A 17-month-old boy in India with severe acute respiratory infection was laboratory confirmed to have avian influenza A(H9N2) virus infection. Complete genome analysis of the strain indicated a mixed lineage of G1 and H7N3. The strain also was found to be susceptible to adamantanes and neuraminidase inhibitors.

Low-pathogenicity avian influenza A(H9N2) viruses have a wide host range, and outbreaks in poultry have been recorded since the 1990s in China (1). In India, avian specimens indicated no serologic evidence of H5N1 and H9N2 during 1958–1981 (2); however, 5%–6% persons with direct exposure to poultry had H9N2 antibodies (3). Human cases of influenza H9N2 virus infection have been observed in Hong Kong, China, Bangladesh, and Pakistan (4–7).

An institutional review board approved an ongoing community-based surveillance in 93 villages of Korku tribes in Melghat District, Maharashtra State, India, to determine incidence of respiratory syncytial virus (RSV)–associated deaths among children < 2 years of age.

A total of 2,085 nasopharyngeal swabs from children with severe or fatal pneumonia were transported to India’s National Institute of Virology to test for influenza, RSV, and other respiratory viruses. A nasopharyngeal swab from a 17-month-old boy received on February 12, 2019, tested positive by PCR for influenza A(H9N2) virus.

The child, a resident of Melghat, had fever, cough, breathlessness, and difficulty feeding for 2 days after illness onset on January 31, 2019. His high intermittent grade fever had no diurnal variation and no association with rash or mucocutaneous lesions. Examination revealed a conscious, restless child with a respiratory rate of 48 breaths/min and lower chest wall in-drawing with intermittent absence of breathing for >20 seconds. He was fully immunized for his age, with bacillus Calmette–Guérin, diphtheria, hepatitis B, poliovirus, and measles vaccines. Both length and weight for age were less than −3 SD. History of travel with his parents to a local religious gathering 1 week before symptom onset was elicited.

The father had similar symptoms on return from the gathering but could not undergo serologic testing because of his migrant work. No history of poultry exposure was elicited. The child received an antibacterial drug and antipyretics and recovered uneventfully.

(SNIP)

In conclusion, multiple introductions of H9N2 viruses in poultry have been observed in India. The identification of a human case of H9N2 virus infection highlights the importance of systemic surveillance in humans and animals to monitor this threat to human health.

Dr. Potdar is senior scientist heading the Influenza Group at the National Institute of Virology, Pune, India. Her primary research interest is molecular characterization and antiviral susceptibility of influenza viruses.

Today, the International Journal of Infectious Diseases (IJID) has published a report on the Omani infection reported by the WHO in May.

The first report of human infection with avian influenza A(H9N2) virus in Oman: the need for a One Health approach

Zayed Al-Mayahia,Hanan Al Kindib , C. Todd Davisc , Bader Al-Rawahid , Fatma Al-Yaqoubid , Yunho Janga,b,c,d,e,  Joyce Jonesc,  John R. Barnesa,b,c,d,e , William Davisc, Bo Shuc, Brian Lynchc , David E. Wentwortha,b,c,d,e , Zaina Al-Maskarie , Amal Al Maanid, Seif Al Abrid

DOI: https://doi.org/10.1016/j.ijid.2019.11.020
Abstract
 
Highlights

• First investigated human case in Oman of avian influenza A(H9N2) virus infection in a 14-month-old female.

• This single case raises the question of other possible mild unrecognized infections, especially among high risk groups such as poultry workers.

• This single case re-emphasizes urgent need for increased efforts to tackle the threat of avian influenza A(H9N2) virus infection by adapting a multisectoral, One Health approach.

Abstract

After detection of the first human case of avian influenza A subtype H9N2 in 1998, more than 40 cases were diagnosed worldwide. The spread of the virus, on the other hand, is more remarkable and significant in global poultry populations causing notable economic losses despite its low pathogenicity. 

Many surveillance studies and activities conducted in several countries proved the predominance of this virus subtype. We present a case report of A(H9N2) virus infection in a 14-month-old female from Oman. It is the first A(H9N2) human case reported from Oman and the Gulf Cooperation Countries and the second country outside of southern and eastern Asia, cases were also detected in Egypt. 

The patient had bronchial asthma and presented with high-grade temperature and symptoms of lower respiratory tract infection that necessitated admission to a high dependency unit in a tertiary care hospital. 

It is of urgency that a multisectoral One Health approach be established to combat the threat of avian influenza at the animal-human interface. In addition to enhancements of surveillance and control in poultry, there is a need to develop screening and preventive programs for high-risk occupations.

        (Continue . . . )


In this case, H9N2 was detected because this patient was severely ill, was admitted to a teriary hospital, and therefore met the criteria for testing under Oman's recently (2017) adopted National Acute Respiratory Illness (NARI) Surveillance program.  

How many others are infected, but never tested, across Asia and the Middle East remains unknown. As does the future evolutionary path of H9N2.

But what we do know is concerning enough to have inspired a good deal of research, some of which I've covered in these recent blogs.

Virology Journal: Mouse-adapted H9N2 Avian Influenza Virus Causes Systemic Infection in Mice

Viruses: A Global Perspective on H9N2 Avian Influenza Virus

OFID: Avian H5, H7 & H9 Contamination Before & After China's Massive Poultry Vaccination Campaign

J. Virology:Genetic Compatibility of Reassortants Between Avian H5N1 & H9N2 Influenza Viruses

Virology: Receptor Binding Specificity Of H9N2 Avian Influenza Viruses

EID Journal: Two H9N2 Studies Of Note