China NHC Statement: A Fatal Case of H3N2 and H10N5 Mixed Infection Discovered in Zhejiang Province

Zhejiang Province – Credit Wikipedia

Editor's note: I'm 14 hours post cataract surgery and supposedly taking a break, but Sharon Sanders on FluTrackers has picked up an interesting report from China on a fatal dual infection with Avian H10N5 and seasonal H3N2 influenza in a woman from Anhui province (hospitalized in Zhejiang province).

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First the (translated) statement as it appears on China's NHC website, after which I'll have more on the timeline, along with a brief review of H10 human infections and the ever-present concerns from dual influenza A infections.

A case of H3N2 and H10N5 mixed infection discovered in Zhejiang Province
Date: 2024-01-30 Source: Emergency Response Department

The National Administration for Disease Control and Prevention reported that a case of H3N2 and H10N5 mixed infection was discovered in Zhejiang Province.

The patient is a 63-year-old female from Xuancheng, Anhui Province. She has multiple underlying diseases in the past. Symptoms such as cough, sore throat, and fever developed on November 30, 2023; on December 2, he was admitted to a local medical institution for treatment due to his worsening condition; on December 7, he was transferred to a medical institution in Zhejiang Province for hospitalization. Died on the 16th.

During a retrospective study of fatal cases, Zhejiang Province isolated seasonal H3N2 subtype and avian H10N5 subtype influenza viruses from case specimens on January 22, 2024. On January 26, the China Centers for Disease Control and Prevention conducted a re-examination and testing of specimens submitted for inspection in Zhejiang, and the results were consistent with previous results. Zhejiang and Anhui provinces have conducted medical observation on all close contacts, and no abnormalities were found, and nucleic acid screening was negative; through retrospective case searches, no suspicious cases were found during the same period.

The National Administration of Disease Control and Prevention has guided Zhejiang and Anhui provinces to carry out prevention and control in accordance with relevant plans and organized experts to conduct risk assessments. Experts assessed that the complete genetic analysis of the virus showed that the H10N5 virus was of poultry origin and did not have the ability to effectively infect humans. The epidemic was an occasional cross-species transmission from poultry to humans. The risk of the virus infecting humans is low and no human-to-human transmission has occurred.

Experts suggest that the public should avoid contact with sick and dead poultry in daily life and try to avoid direct contact with live poultry; pay attention to dietary hygiene and improve self-protection awareness. If you have fever and respiratory symptoms, you should wear a mask and seek medical treatment as soon as possible.

This cases was apparently only discovered 7 weeks after her initial hospitalization, and 5 weeks after her death, due to a policy of retrospectively testing samples from fatal flu cases in China.  This delay makes the  `negative results' from close contacts somewhat less probative than they may appear. 

The reality is, it takes more than a bit of luck for a novel flu case to be picked up by surveillance in China, or anywhere else.  Most people with flu-like symptoms never seek medical help, and of those that do, only a small percentage (usually only in sentinel hospitals) end up tested for subtype.

We've seen studies suggesting that surveillance is lucky if it picks up 1 in 200 novel flu cases (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012), and seroprevalence studies of poultry workers showing very high titers to various subtypes of avian flu.

 

Ten months ago, in UK Novel Flu Surveillance: Quantifying TTD, we looked at a UKHSA assessment stating that it could take hundreds of community cases, over several weeks, before HPAI H5N1 might be picked up by routine passive surveillance.

In countries or regions with less sophisticated testing, surveillance and reporting capabilities, limited community transmission might take much longer to detect.  Absence of evidence isn't the same as evidence of absence. 

Although it tends to get less attention than H5, H7, or even H9 subtypes, avian H10 viruses have also shown a proclivity for spilling over into mammals (see Avian H10N7 Linked To Dead European Seals), and occasionally, infecting humans.  

A few past blogs include:

J.I.A.:Genetic and Biological Properties of H10Nx influenza viruses in China

CHINA NHC Reports 1st Human H10N3 Avian Flu Infection - Jiangsu Province

HK CHP: A Cryptic Report of A 2nd H10N3 Case On the Mainland

Cell Host & Microbe: Avian H10N7 Adaptation In Harbor Seals

Jiangxi Province Reports 3rd H10N8 Case

While the number of reported H10 infected humans remains small - possibly due to a lack of surveillance and testing - in 2014's BMC: H10N8 Antibodies In Animal Workers – Guangdong Province, China, we saw evidence that some people may have been infected with the H10N8 virus in China long before the first case was recognized.

While this mixed H3N2/H10N5 infection appears to have been a dead-end - with no recognized onward transmission of H10N5 or a H10/N3 reassortment detected - humans (like birds, pigs, and other hosts) have the potential to act as mixing vessels for influenza viruses. 

Twice in my lifetime (1957 and 1968) avian flu viruses have reassorted with seasonal flu and launched a human pandemic.

• The first (1957) was H2N2, which According to the CDC `. . . was comprised of three different genes from an H2N2 virus that originated from an avian influenza A virus, including the H2 hemagglutinin and the N2 neuraminidase genes.'

• In 1968 an avian H3N2 virus emerged (a reassortment of 2 genes from a low path avian influenza H3 virus, and 6 genes from H2N2) which supplanted H2N2 - killed more than a million people during its first year - and continues to spark yearly epidemics more than 50 years later.

This is the reason why yearly flu vaccination is strongly recommended for people who raise pigs, or work with poultry, although in far too many places these precautions are not commonly adopted.

While a seasonal flu/avian flu hybrid might not be as deadly as full-on avian virus, it might spread a lot easier in humans  (see The `Other Mixing Vessel' For Pandemic Influenza). 

While this is likely a rare, or `one-off' event, it reminds us that nature throws the genetic dice countless times every day around the world, and it only has to get `lucky' once to plunge us into another public health crisis. 

For the next day or so (or until my post-op vision improves) you'll want to check back with Flutrackers for the latest updates. 

A Brief Hiatus

 

I'll be leaving in a couple of hours to have my first (of two) cataract operations (next one in late Feb.), and as such I probably won't be blogging again until tomorrow afternoon (or possibly) Thursday morning.  

In the meantime, you can check in with FluTrackers and with CIDRAP  or Crof for the latest infectious disease news.

Cheers, and thanks for all the visits to this humble blog over the years.  

Updating the Caspian Sea Seal Die Off

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In early December of 2022 there were reports in the Russian media of the discovery of a large number (700) of dead seals near on the coast of the the Caspian Sea near Dagestan (see map above). 

Within a few days another report estimated 2,500 seal deaths, and discussed the possibility that they had died from oxygen starvation due to gas (methane) emissions due to seismic activity.  

A similar event two years earlier in that region had been attributed to that scenario. 

A month later, in Russia: Mass Mortality Event (Seals) In Caspian Sea Linked To Avian Flu, we looked at a (translated) press release from the Dagestan State University which stated that (as yet unsubtyped) avian influenza A virus was detected in the carcasses of these seals, although it was too soon to say whether the virus was the actual cause of death.

In early February Russia's Federal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor) announced they were unable to confirm those test results, and had asked the Dagestan State University to provide biological samples of what they tested. 

Since then, Russian media has been filled with conflicting reports and opinion pieces on the cause of this mass mortality event.

Some blame illegal and/or poorly run landfills, runoff from which have allegedly polluted the waters of the Caspian sea, while others have suggested gas and oil pollution or military operations are to blame. 

As Caspian seals are considered endangered, this has become a bit of a political `hot potato'. 

Again, last December we began to see reports of die offs of seals in the Caspian Sea due to `an unknown disease' (see sample below).

Seals are again dying en masse on the Turkmen coast of the Caspian Sea

December 14, 2023

On the Turkmen coast of the Caspian Sea, mass deaths of seals from an unknown disease are again observed. Experts have caught dozens of dead seals in recent days. The Turkmen authorities ordered the military to shoot seals swimming to the shore. A Radio Azatlyk correspondent reported this on December 12.

“Navy specialists are destroying seal carcasses caught at sea. Serving sailors are also involved in this,” said one of the local specialists in an anonymous conversation with our correspondent.

About 10 days ago the COMPASS Foundation - which was founded in 2022 with the stated aim to `become the single coordinator of environmental activities in Russia' - published a press release where they describe a huge drop in the population of Caspian Seals in 2023, and once again indicate that avian flu may be the cause. 

The Caspian seal population is in critical condition

19.01.2024 

As part of the program, from April to December 2023, 6 expeditions were carried out to areas of seasonal concentration and feeding of seals.

During the expeditions, leading Russian scientists collected information about the size, age and sex structure of the seal population. The survey showed a catastrophically low density of seals in their seasonal places and a complete absence in the island rookeries in the spring, which is uncharacteristic during this period.

For objective assessment and monitoring, 4 stationary camera traps were installed in different parts of Maly Zhemchuzhny Island. According to materials from August to October, only one individual was recorded on the island.

The census results showed that the average age of dead individuals was 7.7 years - this indicates an increase in the mortality of young individuals, including pregnant females.

In December, information appeared in the media about a new wave of dumping of dead seal carcasses. For a prompt response, the working group, led by Foundation expert Vladimir Lifantiev, with the support of the oil service company NaftaGaz, went on an expedition to the Caspian coast and the island of Chechen.

Candidate of Biological Sciences, Associate Professor at the Institute of Ecology and Sustainable Development of DSU Alimurad Gadzhiev, while exploring the coast, said:

The population is not just in a critical condition, it has already passed that red line, after which it is unlikely to be restored in the near future.

The main version of the death of Caspian seals, according to the scientific group, is their infection with highly pathogenic avian influenza.

The Foundation took the initiative to include the seal in the list of rare and endangered objects of the animal world that require priority measures for restoration and reintroduction. Corresponding proposals have been sent to the Russian Ministry of Natural Resources, as well as to Rosprirodnadzor.

We've certainly seen massive die offs of seals elsewhere around the world due to avian flu (see a few examples below), making it the logical suspect.  But so far, we've seen very little concrete information on this ongoing event in the Caspian sea. 

SGSSI Statement: HPAI Confirmed in Mammals in Sub-Antarctica For The First Time

Chile: SERNAPESCA Updates Marine Mammal Deaths From Avian Influenza

Denmark: SSI Reports H5N1 In Dead Seals

CDC EID Journal: HPAI A(H5N1) Virus Outbreak in New England Seals, United States

Beyond the horrendous loss of so many mammals - and its unpredictable knock-on impacts to the ecosystem - each mammalian infection is another opportunity for this avian influenza virus to better adapt to - and potentially transmit among - mammalian hosts.

Six months ago, in Avian Flu's New Normal: When the Extraordinary Becomes Ordinary, I wrote about the numbing effect that comes with the constant barrage of HPAI H5 reports from around the world.

Things that were nearly unthinkable two years ago (e.g. Repeated trans-Atlantic introduction of avian flu from Europe, the proliferation of HPAI H5 across the length of South America, or the repeated spillovers of H5 into mammalian species) have now become commonplace.

Although the future course and impact of HPAI H5 remains unknown, nature's laboratory is open and operating 24/7, which suggests that complacency is a luxury we cannot afford.

Bangladesh: Media Reports Of Two Nipah Deaths

Nipah Epi Curve In Bangladesh (2001-2023)

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Last spring, after seeing a decline in Nipah cases for the previous 7 years (see IEDCR chart above), Bangladesh reported a significant uptick (14 cases, 10 deaths) in the disease. We also saw an outbreak in Kerala, India in September of last year (see Kerala: Media Reports 5th Confirmed Nipah Case - Awaiting Test Results On 11 Others).

Carried by fruit bats, Nipah outbreaks often occur in Bangladesh between December and May - which is date palm sap harvesting season - as infected bats like to roost at night at the top of date palm trees, and collection containers can become contaminated with bat saliva and feces.

Date Palm Sap Collection – Credit FAO

There are other routes of infection, as we saw in Malaysia in 1998 when the virus spread first from bat to pigs - and then from pigs to humans - eventually infecting at least 265 people, killing 105 (see Lessons from the Nipah virus outbreak in Malaysia).

Human-to-human transmission has also been reported, as in India in 2018 (see Nipah Transmission In Kerala Outbreak) where we saw apparently robust household and nosocomial transmission of the virus in Southern India, eventually infecting 19 people.

While the IEDCR hasn't updated its website/dashboard as of this writing, overnight there are numerous Bangladeshi media reports of two recent Nipah deaths.  One such example comes from The Business Post, which describes 2 men (ages 38 and 27) who fell ill after consuming raw date juice, with both dying in a Dhaka hospital.

Nipah virus: 2 patients from Manikganj die in Dhaka

TBP Desk
29 Jan 2024 11:51:27 | Update: 29 Jan 2024 12:14:16

Two people from Manikganj, who were infected with Nipah virus after consuming raw date juice, died in Dhaka while undergoing treatment.

Given the limits of testing and surveillance, it is likely that some number of cases in Bangladesh, and in neighboring countries, go unidentified each year, as the geographic range of the fruit bat that carries the virus is quite large (see map below).

Outbreaks in humans since the virus was first identified in the late 1990s have tended to be sporadic, and small - with the Malaysian outbreak (1998-1999) being the largest.  But in the 2013 paper The pandemic potential of Nipah virus, the author Stephen P. Luby wrote (bolding mine):

Characteristics of Nipah virus that increase its risk of becoming a global pandemic include:

• humans are already susceptible; many strains are capable of limited person-to-person transmission;
• as an RNA virus, it has an exceptionally high rate of mutation
• and that if a human-adapted strain were to infect communities in South Asia, high population densities and global interconnectedness would rapidly spread the infection.

After the 2018 outbreak in Kerala, India, concerns over larger, urban outbreaks of the virus have increased (see Enhancing preparation for large Nipah outbreaks beyond Bangladesh: Preventing a tragedy like Ebola in West Africa by Halsie Donaldson, Daniel Lucey).

Whether Nipah has - or will ever accrue - the `right stuff' to pose a genuine pandemic threat is unknowable, but it 2019 it ranked #20 in the CDC's list of Zoonotic concerns, well ahead of MERS-CoV (#27) and Mpox (#29). 

Also in 2019 the WHO published their List Of Blueprint Priority Diseases, detailing 8 disease threats in need of urgent accelerated research and development. And Nipah, along with its Australian cousin Hendra, were among them. 

Almost exactly a year ago, in EID Journal: Nipah Virus Exposure in Domestic and Peridomestic Animals Living in Human Outbreak Sites, Bangladesh, 2013–2015, we looked at a dispatch that described the detection of NiV antibodies in cattle, dogs, and cats in proximity to known outbreaks in humans

While Nipah remains more of a regional concern than a global threat, each new human infection and every spillover event provides the virus with another opportunity to better adapt to a new host. 

A reminder that while we continue to struggle with COVID, the next global health crisis may already be simmering in a bat, a rat, or a cat somewhere in the world, just waiting for the right conditions to allow it to start its world tour.

A Review Of H5N1 Clade 2.3.2.1c Infections In Cambodia

 
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Over the past 48 hours we've seen two new H5N1 infections reported from Cambodia (see here and here), bringing the total number reported over the past year to 8. The two most recent cases are currently alive, and being treated in the ICU, but we know that 4 of the 6 earlier cases died (see CDC chart above). 

All four of the fatalities in 2023 were children, while the two survivors were both adults (one was only mildly affected). 

Although the reasons aren't clear, younger people  (< 40) seem to be more susceptible to H5 infections while the opposite appears true for H7N9 (see H7N9: The Riddle Of The Ages). Childhood immune imprinting, however (see Nature: Declan Butler On How Your First Bout Of Flu Leaves A Lasting Impression), is believed to be a possible factor.

The newer clade 2.3.4.4b H5N1 virus - which has conquered much of the world and has killed tens of thousands of mammals since 2021 - has (thus far) proven far less lethal in humans.  

Of the 13 cases reported since 2022 (see chart above), 7 were asymptomatic, 4 had critical illness, and 1 died. 

The caveat being, that we only know about the cases that get reported. It is quite likely that some (perhaps, many) cases (both mild & severe) have occurred and have simply gone unrecognized or unreported around the world.  

Previously we've seen seroprevalence studies on poultry workers in Asia (see PLoS One: Seroprevalence Of H5N1 Among Bangladeshi Poultry Workers) that suggest human infection with H5N1 is probably a lot more common than we know. 

This idea was revisited again last August in a BMJ Global Health Journal commentary (see below) which reported on human seropositivity in 5 live bird markets in Egypt - a country which hasn't reported a human infection since 2017 - which found increasing evidence of previous infection with H5N1.

We are underestimating, again, the true burden of H5N1 in humans
Mokhtar Gomaa1, Yassmin Moatasim1, Ahmed El Taweel1, Sara H Mahmoud1, Amira S El Rifay1, Ahmed Kandeil1,2, Pamela P McKenzie2, Richard J Webby2, Rabeh El-Shesheny1,

Mohamed Ahmed Ali1,Ghazi Kayali3 

https://doi.org/10.1136/bmjgh-2023-013146

Summary box

• From mid-2021, a dramatic increase in activity and geographical distribution of clade 2.3.4.4b H5N1 viruses in animals occurred.
• The extent of clade 2.3.4.4b human infections is unknown, but almost certainly more than the reported number, especially as this virus has shown an ability to infect several non-human mammals on a large scale.
• Our study in five live bird markets showed that human seropositivity appeared to follow virus detection in wild and domestic birds sold live in the markets suggesting this as source of virus exposure.
• Our estimate of 4.6% clade 2.3.4.4b H5N1 seroprevalence is more than double that of our earlier clade 2.2 seroprevalence estimate suggesting that the currently circulating viruses are more infectious to mammalian hosts.
• The scale, geographical scope and increasing list of infected species with clade 2.3.4.4b viruses urge the conduct of additional seroprevalence studies.

The reality is, mild or even moderate cases are less likely to seek medical care, making it unlikely they will be tested, or reported. Some severe cases may go undetected as well, but on average, they are more likely to be picked up by surveillance. 

Similarly, in China we've followed the spillover of HPAI H5N6 to humans, where roughly 90 cases have been reported since 2014 (see map below).  Of those, roughly half (of the cases where we have an outcome) proved fatal. 

But once again, we have no idea how many mild or moderate cases go unreported.  Since we don't have a good handle on the denominator - the total number of people infected - we can't reliably calculate the CFR. 

This chronic lack of data has sparked many debates over the years on the true lethality of H5 (see mBio: Mammalian-Transmissible H5N1 Influenza: Facts and Perspective).

Raw data suggests that H5N1 clade 2.3.2.1c and HPAI H5N6 currently pose more of a threat to human health than does H5N1 clade 2.3.4.4b, but we missing a lot of critical information.  

The oft-quoted `factoid' that H5N1 kills 50% of those it infects is, thankfully, highly unlikely. Of course, even a 2% CFR would be disastrous in a pandemic. 

What we can say is that some strains of HPAI H5 can kill up to 50% of those who are sick enough to be hospitalized. But there could easily be 10 - or perhaps 100 - milder cases for every severe case.  

While we haven't seen any detailed reviews of the more recent H5N1 cases from Cambodia, last August the Journal Emerging Microbes & Infections published an analysis of the viruses detected in first (father/daughter) cluster reported nearly a year ago. 

Reassuringly, they found that virus did not bind efficiently to human receptor cells, limiting its zoonotic potential. 

Characterization of the haemagglutinin properties of the H5N1 avian influenza virus that caused human infections in Cambodia

Pengxiang Chang, Jiayun Yang, Thusitha K. Karunarathna, Mehnaz Qureshi, Jean-Remy Sadeyen & Munir Iqbal
Article: 2244091 | Received 13 Apr 2023, Accepted 30 Jul 2023, Published online: 25 Aug 2023

https://doi.org/10.1080/22221751.2023.2244091

ABSTRACT

High pathogenicity avian influenza (HPAI) H5N1 is a subtype of the influenza A virus primarily found in birds. The subtype emerged in China in 1996 and has spread globally, causing significant morbidity and mortality in birds and humans. In Cambodia, a lethal case was reported in February 2023 involving an 11-year-old girl, marking the first human HPAI H5N1 infection in the country since 2014. 

This research examined the zoonotic potential of the human H5N1 isolate, A/Cambodia/NPH230032/2023 (KHM/23), by assessing its receptor binding, fusion pH, HA thermal stability, and antigenicity. Results showed that KHM/23 exhibits similar receptor binding and antigenicity as the early clade 2.3.2.1c HPAI H5N1 strain, and it does not bind to human-like receptors. Despite showing limited zoonotic risk, the increased thermal stability and reduced pH of fusion in KHM/23 indicate a potential threat to poultry, emphasizing the need for vigilant monitoring.

Of course, with influenza viruses, the only constant is change.  So we'll be watching Cambodia closely for more cases.

Stay tuned. 

Cambodia: MOH Announces 2nd H5N1 Case of 2024

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Two days ago Cambodia reported their 1st H5N1 infection of 2024 - detected in a 3 y.o. boy in Prey Veng Province - and today their MOH has announced a 2nd case - this time in a 69 y.o. man - residing more than 150 miles to the north and west of Friday's case, in Siem Reap Province. 

After having gone 9 years without reporting any H5N1 infections, this makes the 8th case to be reported by Cambodia in less than a year.  

The reasons behind this recent uptick are unknown, but a recent study  (see Preprint: A Timely Survey of Knowledge, Attitudes, and Practices Related to Avian Influenza (H5N1) in Rural, Cambodia)  found very lax attitudes regarding avian flu among the rural population (e.g. 23% of participants cooked sick or dead poultries for their families).

As with the previous 6 cases, these two latest infections most likely stem from a clade 2.3.2.1c H5N1 virus - an older lineage of avian flu which predates our current clade 2.3.4.4b epizootic.   

The translated Press Release from the Cambodian MOH follows, after which I'll return with more.

Kingdom of Cambodia, Nation, Religion, King
Ministry of Health
Press Release
On

          69-year-old man infected with bird flu

The Ministry of Health of the Kingdom of Cambodia would like to inform the public that there is another case of bird flu in a 69-year-old man and was confirmed positive for H5N1 bird flu virus (H5N1) from the National Institute of Health. Public on January 27, 2024, residing in Pbat village, Prey Chrouk commune, Puok district, Siem Reap province. The patient is currently receiving intensive care from a team of doctors. According to the survey, the patient has raised about 50-60 chickens at home and has been dying for about two weeks.

The National and Sub-National Emergency Response Team of the Ministry of Health has been cooperating with the working groups of the Ministry of Agriculture, Forestry and Fisheries and the Ministry of Environment, local authorities at all levels to actively investigate the outbreak of bird flu and respond. Respond to methods and technical protocols, continue to search for sources of transmission on both animals and humans, and continue to search for suspected cases and affected people to prevent transmission to others in the community, and distribute Tamiflu to affected people. Close and conduct health education campaign for the people in the village where the incident occurred.

The Ministry of Health would like to remind all citizens to be careful about bird flu because H5N1 bird flu continues to threaten the health of our people and also would like to inform you if there are symptoms. Fever, cough, runny nose or shortness of breath and a history of contact with sick or dead chickens during the 14 days prior to the onset of symptoms, do not visit crowded places and seek consultation and examination. Get treatment at the nearest health facility as soon as possible. 

Transmission: H5N1 bird flu is a flu virus that is usually transmitted from sick birds to other birds, but can sometimes be transmitted from birds to humans through close contact with sick or dead birds. Avian influenza in humans is a serious disease that requires treatment at Hospital on time. Although it is not easily transmitted from person to person, if it can metabolize it can be as contagious as the seasonal flu.

Preventive measures: Government education messages include: Wash hands frequently with soap and water before eating and after contact with birds, keep children away from birds and keep birds away from living, do not eat birds. Sick or dead and all birds made for eating must be well cooked.

The Ministry of Health will continue to inform the public about information related to public health issues through the Telegram Channel and the official Facebook page of the Ministry of Health, as well as the official Facebook page of the Department of Infectious Diseases and the website www.cdcmoh.gov.kh.

This site has health education materials that can be downloaded and used. For more information, contact the Ministry of Health's hotline number 115 for free.

Days Sunday, 3 Roach Khe Bos, Chhnang Thao, Panchasak, BE 2567, Phnom Penh, January 28, 2024

 

So far, we haven't seen any evidence of sustained or efficient human-to-human transmission of H5N1, but this recent uptick in clade 2.3.2.1c infections warrants our attention.  The more times the virus spills over into humans, the more opportunities it will have to `figure us out', and better adapt to a human host. 

As we've seen the past few years with clade 2.3.4.4b, the `right' reassortment or combination of antigenic changes can breathe new life into an existing lineage.

Whether that has happened with clade 2.3.2.1c remains to be seen. But this is a reminder that while we are watching one threat (H5N1 clade 2.3.4.4b), we could always get blindsided by something unexpected (e.g. H5N6, H10N3, H3N8, etc.) coming from out of left field.

CIDRAP: Debate Over the Updated WHO COVID Prevention Guidance

 

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The origins of the next major global health crisis - what many health officials have dubbed as `Disease X' (a placeholder name, not a specific disease) - is completely unknown, but we can make some educated guesses as to its nature.

1st, it will be primarily a respiratory disease, spread via droplets or fine aerosols.  We know that, because non-respiratory diseases (e.g. vector borne, or spread by direct contact) tend to produce regional, not global, outbreaks. 

2nd, it will have the ability to be spread - as does influenza and COVID - from asymptomatic (or pre-symptomatic) carriers.  The primary reason why the 2002-2003 SARS-CoV outbreak was contained was because it lacked this ability, which allowed for easier containment. 

Lastly,  nosocomial transmission will not only injure patients and healthcare workers, but degrade the ability of healthcare facilities to provide essential services during the crisis. 

Even though we knew all of this before SARS-CoV-2 emerged, the world prepared for something far less formidable. After going nearly 100 years and seeing only infrequent and mild-to-moderate influenza pandemics, many planners simply assumed we were past the age of truly severe pandemics. 

As a result, we were woefully unprepared for the pandemic we eventually got. 

Our Strategic National Stockpile was far less well equipped than advertised, with warnings (see Caught With Our Masks Down) about inevitable PPE shortages and inadequate ventilators (see Pandemic Realities: Ventilator Shortages) having gone unheeded. 

WHO pandemic guidance, published just months before the pandemic, recommended against the wearing of masks (of any type) by the public (see graphic below); a policy which remained in place until the summer of 2020. 

The following infamous Feb 29th, 2000 tweet by the U.S. Surgeon General also sought to discourage the use of masks by the general public. 

By early April of 2020 the CDC reversed their position on face covers for the public (see The CDC's Cloth Face Cover Recommendations), and the WHO would follow suit a couple of months later. Once surgical mask supplies improved, they were recommended over cloth face covers. 

Even though the airborne spread of COVID was becoming increasingly obvious (see COVID-19: The Airborne Division), officially it remained  primarily a `droplet' infection, and many healthcare facilities relied on (cheaper, and more readily available) surgical masks to protect their staff and patients. 

The World Health Organization's recommendations for PPE for HCWs in contact with COVID cases recommended the wearing of `medical masks' defined as `surgical or procedure masks that are flat or pleated (some are like cups); they are affixed to the head with straps'.

WHO guidance reserved the use of N95 or FFP2 respirators for use when performing aerosol generating procedures.  In the United States, the CDC preferentially recommended more protective N95s (when available) for exposure to all COVID patients, but due to shortages proposed an `acceptable alternative'.

 

Fast forward 4 years, and the WHO has released their latest set of guidelines (see Infection prevention and control in the context of COVID-19: a guideline, 21 December 2023) for healthcare workers dealing with COVID patients; guidelines that many public health experts still considered inadequate. 

Last night CIDRAP published a lengthy review of the debate (see link and excerpts below), which includes quotes from a number of well known public health experts.  Follow the link to read it in its entirety, I'll have a bit more after the break. 

Highly recommended.

Updated WHO COVID prevention guidance may endanger rather than protect, some experts say

Mary Van Beusekom, MS
January 26, 2024
COVID-19

The World Health Organization's (WHO's) newly updated COVID-19 prevention and control guidelines purport to protect healthcare workers, patients, and the community, but some experts say they may encourage risky behavior by propagating long-disproven ideas about how viruses spread.

"I think they put healthcare workers and patients and the community at significant risk," said Lisa Brosseau, ScD, CIH, an expert on respiratory protection and infectious diseases and a CIDRAP research consultant.

One of the main problems, said Raina Macintyre, MBBS, PhD, professor and head of the biosecurity program at the Kirby Institute in Sydney, Australia, is that the document doesn't incorporate many of the lessons learned during the pandemic—such as the major role of COVID-19 spread among people with no symptoms.

"The guidelines suggest using symptoms to screen people," she said via email. "This is seen in health guidelines in many countries—emphasis on symptoms ('wear a mask if you feel unwell'), when we know a substantial proportion of transmission is asymptomatic, which is a major rationale for universal masking in high-transmission settings."

          (Continue . . . ) 

I know a lot of health care workers felt betrayed by the lack of PPEs during the opening months of the COVID pandemic.  It was very much a repeat (only worse) of the opening months of the relatively mild 2009 H1N1 pandemic, when sporadic PPE shortages were reported (see California Nurses Association Statement On Lack Of PPE). 

In the wake of those shortages, we saw numerous calls for better pandemic preparedness, including:

• In 2009 the Minnesota Center for Health Care Ethics and University of Minnesota Center for Bioethics released draft ethical pandemic guidelines on the rationing of scarce resources, where they estimated their were only enough PPE’s in the state of Minnesota to last 3 weeks into a severe pandemic.
• In 2014 in NIOSH: Options To Maximize The Supply of Respirators During A Pandemic, we looked at strategies to try and cope with the expected shortfall in PPEs during a severe pandemic.
• A 2015 CID Journal report Potential Demand for Respirators and Surgical Masks During a Hypothetical Influenza Pandemic in the United States estimated in the U.S. alone, we'd need billions of respirators and masks.

We saw numerous conflicting studies on the relative effectiveness of surgical masks vs N95s (see A Surgical Mask Strike and JAMA: Surgical Masks vs N95 Respirators), with a strong lobby pushing for using far less expensive face masks.

But despite countless promises and having a full decade to prepare, when COVID emerged, the cupboards were nearly bare for both types of PPEs. 

While I'd like to believe the last 4 years have taught us the folly of underestimating pandemic threats, and the need for maintaining robust pandemic preparedness, the evidence suggests otherwise.  

We no longer report COVID hospitalizations or deaths, and seek to minimize its risks at every turn, despite ample evidence of `Long COVID' and the potential for seeing more dangerous variants emerge in the future. 

Whether we are faced with a new pandemic threat, or a emergence of a new COVID variant, health care and other front line workers are deserving of the best gear, and guidance, that we can provide.  

Not the least we can get away with.

ISIRV: Comparative Mortality in Patients Hospitalized With influenza A/B virus, RSV, Rhinovirus, Metapneumovirus or SARS-CoV-2

 
#17,881

While it is apparent that - due to increased immunity from vaccination and/or infection, and changes in the SARS-CoV-2 virus - that COVID's fatality rate has dropped significantly since 2020, it continues to infect millions of people each month, hospitalizing (and killing) thousands. 

Roughly 80% of countries no longer regularly report COVID infections, hospitalizations, or deaths to the WHO, yet in their latest monthly epidemiological update they report:

Many countries have adopted the attitude that COVID infection is now comparable to influenza in terms of severity, but studies continue to suggest that morbidity and mortality from the SARS-CoV-2 virus still exceeds that of seasonal flu. 

There are also studies that show that long-term sequelae (aka `Long COVID') is more frequent, and more severe than with other post-viral syndromes from respiratory illnesses (see NIH Preprint: Comparing The Impact Of `Long Flu' to `Long COVID').

While most people use Influenza A as the benchmark for comparison, over the years we've seen evidence that other common respiratory infections (including Influenza B, RSV, metapneumovirus, etc.) may have equally severe outcomes. 

ERJ: When “B” becomes “A” : The Emerging Threat of Influenza B Virus

California: Orange County Declares Public Health Emergency Over Rise In Pediatric RSV

CDC HAN #00473: Severe Respiratory Illnesses Associated with Rhinoviruses and/or Enteroviruses Including EV-D68 – Multistate, 2022

CMAJ: Burden of Noninfluenza Respiratory Viral Infections in Adults Admitted to Hospital

But the lack of testing and reporting on all of viral infections makes direct comparisons difficult.  While far from perfect, one compromise is to study outcomes in those who are sick enough to be hospitalized.  Which is exactly what today's study does.

Based on 30-day outcomes among hospitalized patients, researchers found that the risks of death from Influenza A, Influenza B, RSV, and metapneumovirus were roughly comparable, and that even after the arrival of Omicron (spring 2022), COVID continued to carry a 70% higher case fatality rate (CFR) than influenza A. 

This study is subject to a number of limitations (see full text), but it does illustrate that in addition of influenza A and COVID, other common viral illnesses can produce significant morbidity and mortality in the hospitalized patient.

I've reproduced the abstract and some excerpts, but you'll want to follow the link to read it in its entirety.

ORIGINAL ARTICLE

Open Access

Comparative analysis of mortality in patients admitted with an infection with influenza A/B virus, respiratory syncytial virus, rhinovirus, metapneumovirus or SARS-CoV-2

Abstract

Background

While influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are recognised as a cause of severe illness and mortality, clinical interest for respiratory syncytial virus (RSV), rhinovirus and human metapneumovirus (hMPV) infections is still limited.

Methods

We conducted a retrospective database study comparing baseline characteristics and 30-day mortality in a large cohort of adult patients admitted for an overnight stay or longer with an influenza virus (A/B), rhinovirus, hMPV, RSV or SARS-CoV-2 infection. For non-SARS-CoV-2 viruses, data were included for the period July 2017–February 2020. For SARS-CoV-2, data between March 2020 and March 2022 were included.

Results

Covariate-adjusted 30-day mortality following RSV, hMPV or rhinovirus infections was substantial (crude mortality 8–10%) and comparable with mortality following hospitalisation with an influenza A virus infection.

Mortality following a SARS-CoV-2 infection was consistently higher than for any other respiratory virus, at any point in time (crude mortality 14–25%). Odds of mortality for SARS-CoV-2 compared with influenza A declined from 4.9 to 1.7 over the course of the pandemic. Patients with SARS-CoV-2 infection had less comorbidity than patients with other respiratory virus infections and were more often male. In this cohort, age was related to mortality following hospitalisation, while an association with comorbidity was not apparent.

Conclusions

With the exception of SARS-CoV-2 infections, we find the clinical outcome of common respiratory virus infections requiring hospitalisation more similar than often assumed. The observed mortality from SARS-CoV-2 was significantly higher, but the difference with other respiratory viruses became less distinct over time.

(SNIP)

The aim of this study was to provide a comparative analysis of 30-day mortality following hospitalisation with an infection with influenza A/B, RSV, rhinovirus, metapneumovirus or SARS-CoV-2. 

In this retrospective cohort study, we found that, once hospitalisation is required, covariate-adjusted mortality for RSV, hMPV or rhinovirus infections was comparable and not different from mortality following hospitalisation with an influenza A/B virus infection. 

Throughout the year, RSV, rhinovirus and hMPV infections made up a substantial proportion of total respiratory virus infections requiring hospitalisation. RSV is increasingly recognised as a cause of severe illness and mortality in high-risk older adults,4, 5, 18-20 while clinical interest for rhinovirus and hMPV infections is still limited. In our study, 30-day mortality was not different between influenza and RSV, hMPV or rhinovirus infections (8–10%) and in line with previously published influenza and RSV data on adults.4, 21, 22

Lower mortality rates have been reported by some6, 23 and might be explained by a shorter follow-up time when in-hospital mortality rather than 30-day mortality is used as an outcome, or by less stringent criteria for hospital admission. In line with the general consensus, we found that elderly are particularly vulnerable for poor outcomes of respiratory virus infections.2, 20, 24 In our dataset, however, comorbidity registered as CCI was not associated with mortality following hospitalisation with a respiratory virus infection. This may seem in contrast to other findings;25-27 however, this discrepancy might in part be explained by a mitigating effect of influenza vaccination in high-risk individuals, or by a lower admission threshold for those with expected severe progression of disease.

Few studies have compared SARS-CoV-2 mortality during winter 2021/2022 with mortality following hospitalisation with several other common respiratory virus infections. In the last half year of the study period (1 September 2021 to 1 March 2022), odds of mortality following hospitalisation with a SARS-CoV-2 infection were 1.7 times greater than following an influenza virus infection. 

(Continue . . . )

  

Cambodia MOH Reports Another H5N1 Infection

#17,880

Overnight the Cambodian MOH posted an announcement on their Facebook page (see below) indicating that they have detected another H5N1 infection - the first of 2024 and the 7th in the past 12 months - this time in a 3 y.o. boy who is currently being treated in the ICU.

It is worth noting that this case is being reported from Prey Veng province, which reported 2 cases in 2023  (one in October and another in February).  Four other cases were reported in 2023 after a 9 year hiatus. 

As with the previous 6 cases, this is most likely  another clade 2.3.2.1c H5N1 infection - an older lineage of avian flu which predates our current clade 2.3.4.4b epizootic.  

The translation of today's announcement follows.  I'll have a postscript after the break.

Kingdom of Cambodia, Nation, Religion, King
Ministry of Health
Press Release

On Cases of bird flu in 3-year-old boys

The Ministry of Health of the Kingdom of Cambodia would like to inform the public that there is another case of bird flu in a 3-year-old boy and was confirmed positive for H5N1 bird flu virus from the National Institute. Public Health and Institut Pasteur du Cambodge on January 25, 2024, located in Ta Bruy village, Prek Poun commune, Kampong Trabek district, Prey Veng province. The patient is currently receiving intensive care from a team of doctors. According to inquiries, about 10 days ago, there were dead chickens in the village and around the patient's house.

The National and Sub-National Emergency Response Team of the Ministry of Health has been cooperating with the working groups of the Ministry of Agriculture, Forestry and Fisheries and the Ministry of Environment, local authorities at all levels, the police and partner organizations, to actively investigate the occurrence of Avian Influenza will respond to methods and technical protocols, continue to search for sources of transmission in both animals and humans, and continue to search for suspected and affected cases to prevent the spread of the disease to others in the community, as well as distribute Tamergo. Educate the health of the people in the village where the incident took place.

The Ministry of Health would like to remind all citizens to be careful about bird flu because H5N1 bird flu continues to threaten the health of our people and also would like to inform you if there are symptoms. Fever, cough, runny nose or shortness of breath and a history of contact with sick or dead chickens during the 14 days before the onset of symptoms, do not visit crowded places or seek consultation and examination. Get treatment at the nearest health facility as soon as possible.

Transmission: H5N1 bird flu is a flu virus that is usually transmitted from sick birds to other birds, but can sometimes be transmitted from birds to humans through close contact with sick or dead birds. Avian influenza in humans is a serious disease that requires treatment at Hospital on time. Although it is not easily transmitted from person to person, if it can metabolize it can be as contagious as the seasonal flu.

Preventive measures: Government education messages include: Wash hands frequently with soap and water before eating and after contact with birds, keep children away from birds and keep birds away from living, do not eat birds. Sick or dead and all birds made for eating must be well cooked.

The Ministry of Health will continue to inform the public about information related to public health issues through the Telegram Channel and the official Facebook page of the Ministry of Health, as well as the official Facebook page of the Department of Infectious Diseases and the website www.cdcmoh.gov.kh, which has Health education materials that can be downloaded, viewed and used. For more information, please contact the Ministry of Health Hotline 115 for free.

Friday, January 1, 2024, Phnom Penh, January 26, 2024

Rochak King saute

Office of the Ministry of Health, Lot 80, Samdech Pen Nuth (St. 289), Phnom Penh Tel: Fax: (855-23) 885 970/884 909

While the reasons behind this sudden resurgence after 9 years remain a mystery, a recent study (see Preprint: A Timely Survey of Knowledge, Attitudes, and Practices Related to Avian Influenza (H5N1) in Rural, Cambodia)  found very lax attitudes regarding avian flu among the rural population (e.g. 23% of participants cooked sick or dead poultries for their families).

Despite our recent preoccupation with HPAI H5N1 clade 2.3.4.4b, which has been spreading with remarkable speed via migratory birds for the past couple of years, HPAI H5Nx viruses remain a diverse, and evolving threat. 

All of which makes this resurgence of clade 2.3.2.1c infections very much worthy of our attention.