WHO Multi-country Outbreak of Mpox : External Situation Report #34

 

Countries with endemic Mpox- Credit WHO

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Last week the CDC held a COCA Call : Mpox - Clinical Management & Outbreaks, as reports of sporadic infections (clade IIb) continue across the nation (see CBS News S.F. officials monitor rise in domestic mpox cases as global outbreak spreads)

At the same time a far more dangerous clade I mpox virus continues to rage in the DRC, which over the past 18 months has been blamed for more than 20,000 suspected mpox cases and more than 1,000 deaths.

The changing epidemiology and genetic evolution of mpox clade I in central Africa has sparked a number of risks assessments over the past six months, including:

CDC HAN Advisory #00501: Mpox Caused by H-2-H Transmission with Geographic Spread in the Democratic Republic of the Congo

ECDC Risk Assessment On Transmission & Spread of Clade I Mpox From The DRC

Last March a study was published Eurosurveillance: Ongoing Mpox Outbreak in South Kivu Province, DRC Associated With a Novel Clade I Sub-lineage, describing the first genomic analysis of samples from a previously unaffected region of the DRC (the city of Kamituga). 

That study revealed a novel clade I sub-linage had emerged - most likely from a zoonotic introduction - with changes that may render current CDC tests unreliable.

A month later, in Preprint: Sustained Human Outbreak of a New MPXV Clade I Lineage in Eastern Democratic Republic of the Congo, we saw a further analysis, which called for this new lineage to be named Clade Ib, and warned of its potential to spread globally.  

While that doesn't appear to have happened yet (based on limited reporting), we have been watching the incursion of Mpox into new regions, including a spike in cases recently reported in South Africa. 

As we've seen with COVID, and other infectious disease reporting around the globe, surveillance and reporting on Mpox is often limited, or sometimes missing entirely.  The WHO describes this situation below:

WHO continues to encourage all countries to ensure that mpox is a notifiable disease and to report mpox cases, including reporting when no cases have been detected (known as ‘zero-reporting’, as outlined in the Standing Recommendations on mpox issued by the WHO Director General).

This report does not highlight non-reporting countries. Therefore, it should be noted that an absence of reported cases from a country may be due to the country not reporting, rather than having no cases. Reporting to WHO has been declining, therefore, the decline in reported cases should be interpreted with caution.           

Two days ago the WHO released their monthly Situation Report (#34) on the Multi-country outbreak of Mpox, which includes details on the recent South African outbreak. I've provided some excerpts (below), but you'll want to follow the link to read the full 17-page report. 

Multi-country outbreak of mpox

External Situation Report 34, published 28 June 2024

Data as received by WHO from national authorities as of 31 May 2024

Report highlights

• In May 2024, a total of 646 new laboratory-confirmed cases of mpox and 15 deaths were reported to WHO from 26 countries, illustrating continuing transmission of mpox across the world. The most affected WHO regions, ordered by number of laboratory-confirmed cases, were the African Region, the European Region, the Region of the Americas, the Western Pacific Region and the South-East Asia Region. The Eastern Mediterranean region did not report any cases in May 2024.

• As reporting from countries to WHO has been declining, the current reported global data most likely underestimate the actual number of mpox cases.

• Within the African Region, the Democratic Republic of the Congo reported most (99%) of the confirmed mpox cases in the reporting month. With limited access to testing in rural areas, 18% of clinically compatible (reported as suspected) cases in the country are tested, therefore the confirmed case counts are underestimates of the true burden.

• This issue also features:An update on the mpox situation in South Africa;
• An update on vaccines and immunization for mpox, with information from partners.

• WHO welcomes the announcement by the Democratic Republic of the Congo national regulatory authority of the emergency authorization for use of MVA-BN and LC16 mpox vaccines, which will enable the country to import and deploy mpox vaccines for the national outbreak response.

         (SNIP)

Spotlight on South Africa

As of 26 June 2024, the Republic of South Africa had notified the WHO of 16 confirmed cases of mpox, including three deaths, during 2024. These cases were confirmed from 8 May 2024 to 23 June 2024 and 15 of the 16 patients were hospitalized. Prior to this, at the height of the multi-country outbreak, the Republic of South Africa had reported five mpox cases and no deaths from June 2022 to August 2022. The new reports represent the first mpox cases detected in the country since August 2022, and the first deaths altogether.

These cases have been reported from three (of nine) provinces: KwaZulu-Natal (eight cases; two deaths), Gauteng (seven cases; one death), and the Western Cape (one case). None of them had reported recent international travel or attendance at events or activities which may have introduced a higher risk of mpox.

The profiles of these cases reflect the well-described features of the 2022 - 2024 multi-country mpox outbreak. All these cases have been in men aged 23 to 43 years. Of these 16 cases, 11 cases were gay, bisexual or other men who have sex with men, and the most commonly reported context of likely exposure was sexual contact. 

For the five patients whose samples had been sequenced to date, clade IIb monkeypox virus (MPXV) was confirmed. These cases all experienced extensive skin lesions, and 15 out of 16 cases progressed to severe disease requiring hospitalization. Eleven cases have been reported to be persons living with HIV (PLHIV), with either unmanaged or only recently diagnosed HIV infection. There have been three deaths among the 16 confirmed cases, resulting in a case fatality ratio (CFR) of 19%, much higher than the clade IIb mpox global CFR which was 0.2% overall as at the end of May 2024. 

This disproportionate burden of HIV, severe mpox disease, and deaths suggests that MPXV is likely circulating in the community and has reached the most susceptible individuals. In a context where there may be stigma associated with sexual behaviour and/or HIV infection, limited access to health care services willbe compounded by hesitancy to seek early diagnosis and care for mpox.

In the face of this unusual epidemiological picture, the country has promptly responded to this outbreak, initiating action across several response pillars: surveillance and diagnostics; case management; risk communication and community engagement (RCCE); vaccination; infection prevention and control; operations, finance and logistics, and research. Actions include:

• activation of incident management teams at national and provincial levels to coordinate the response;

• development of national and provincial preparedness and response plans;

• case investigation, contact tracing and contact follow-up for identified cases;

• health worker training on mpox case management;

• securing an initial reserve of antiviral treatment courses for severe cases;

• establishment of a laboratory sample referral network for MPXV testing;

• risk messaging both within the general community and among risk groups;

• provision of policy guidance and initiation of processes to s

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ecure vaccines for high-risk groups;

• discussions on public health research objectives and studies to address key knowledge gaps.

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Nearly every WHO DON or disease Situation Report contains diplomatic reminders to member nations of their `duty to report' these types of cases under the IHR 2005 agreement, but compliance remains spotty at best. 

Increasingly, the `political' solution to the rise of inconvenient emerging infectious diseases - like Mpox, COVID, MERS-CoV, and novel influenza - is to limit testing, surveillance, and the reporting of cases, and even deaths.  

Like asking your doctor to `touch up your X-rays', this is a strategy that only works for the short term. 

CDC Issues Broader Influenza A Guidance For Agricultural Exhibits

Credit CDC

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Yesterday, in CDC FluView Wk #25: 2 New Novel Swine Flu Cases (H1N2v) In Pennsylvania, we looked at the latest among the more than 500 swine-variant influenza (H1N1v, H1N2v, or H3N2v) human infections reported in the United States since 2010.  

Many of these cases have been linked to participation in or attendance of agricultural exhibits at county and state fairs. 

Since swine-variant infections are usually mild - and testing is limited - these known cases probably represent only a fraction of the actual number of spillovers that have occurred (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012)).

Fortunately, these swine-variant viruses don't transmit efficiently in humans, and outbreaks have been limited. But, as we saw with the H1N1 2009 pandemic, occasionally these types of viruses are able to evolve sufficiently to overcome these constraints. 

The CDC's Assessment on Swine Variant Viruses reads:

Sporadic infections and even localized outbreaks among people with variant influenza viruses may occur. All influenza viruses have the capacity to change, and it’s possible that variant viruses may change such that they gain the ability to infect people easily and spread easily from person-to-person. The Centers for Disease Control and Prevention (CDC) continues to monitor closely for variant influenza virus infections and will report cases weekly in FluView and in the Novel Influenza A Virus Infections (cdc.gov) section of FluView Interactive.

Although the public health risks are considered low, the CDC advises those who are at higher risk of serious flu complications (including children under 5, adults over 65, pregnant women, and those with certain chronic medical conditions), to avoid pigs and the swine barn altogether.

While we've seen some restrictions (and a few outright bans) of poultry exhibits due to H5N1 in the past, since March of 2024 HPAI H5 has unexpectedly turned up in American livestock, including cattle, goats, and alpacas.

At least 3 mild human infections have been linked to cattle exposure, and we've seen reports of hundreds of peridomestic mammals (including cats, mice, raccoons, skunks, and foxes) infected, often fatally. 

 

Again, both are likely under-counts. 

We've already seen growing concerns over the risks of H5N1 transmission (animal-to-animal and animal-to-human) from livestock at agricultural exhibits, including:

County Fairs Debating Dairy/Poultry Exhibits Over H5N1 Concerns

Minnesota BOAH Announces Testing Requirements for Lactating Cattle Before Exhibition

This week the CDC released updated guidance for agricultural exhibits which now covers more than just swine-variant influenza, and pigs.  

Considerations and Information for Fair Organizers to Help Prevent Influenza

Considerations and Information for Fair Exhibitors to Help Prevent Influenza

The CDC and USDA continue to churn out advice and recommendations regarding HPAI H5 (see here, here, here, and here), but it is up to local jurisdictions to decide which to implement. 

Some, like the recommended PPE for farm workers have been a tough sell.

Due to their lengths (and overlaps) I've only included some excerpts from these new guidance documents.  Follow the links to read them in their entirety. 

Considerations and Information for Fair Organizers to Help Prevent Influenza

CDC keeps track of how many people get influenza (flu) caused by animal influenza A viruses throughout the year, including during exhibition season. As you organize your local or state agricultural fair or any other livestock exhibitions, be aware of important information to help protect visitors and livestock (e.g. pigs, poultry, cattle). This information can help prevent illnesses in public settings, like agricultural fairs, where people and animals from many places are in close contact.

Background

Livestock fairs and shows are an important learning opportunity for people of all ages interested in agriculture. Animals commonly exhibited at agricultural fairs and shows, including pigs, poultry (e.g., chickens, turkeys, ducks, geese), and cattle, can carry and spread influenza A viruses that are different from human seasonal influenza A viruses. Pigs can be infected with swine influenza A viruses, and poultry can be infected with avian influenza A viruses. In March 2024, avian influenza A(H5N1) virus in dairy cattle was first reported.

Influenza viruses are more likely to spread when people and animals from many places are in close contact, such as at fairs and shows. While rare, influenza A viruses can spread from people to animals (including pigs, poultry, and cattle) and from animals to people. The main way people get infected with animal influenza A viruses is by being around infected animals, especially if they have close contact with them. It is not very common for people to get sick from these viruses, but when they do, the sickness can vary from mild to severe. In some cases, it can even lead to hospitalization or death. CDC recommends fair organizers take actions to help prevent the spread of influenza A viruses between animals at fairs and animals and people.

Take action to prevent the spread of influenza viruses between animals and people at fairs

The risk of infection and spread of animal influenza A viruses to people can be reduced by taking simple actions. CDC recommends fair organizers consider the following actions:

Actions to consider when planning for fairs:

• Have available appropriate personal protective equipment (PPE) for staff and exhibitors to follow the CDC Updated Interim PPE Recommendations to Reduce Exposure to Novel Influenza A Viruses Associated with Disease in Humans in the event sick animals are identified during the fair

• This includes protective clothing, gloves, goggles, and a respirator or well-fitting mask that covers the mouth and nose.

• Control visitor traffic to prevent overcrowding. Create opportunities for one-directional traffic flow and limit public access to animals and animal bedding outside of designated areas when possible.
• Locate food service, concession stands, and dining/picnic tables away from animal areas.
• Place physical barriers between the public and animal displays to limit close contact with poultry, pigs, cattle, and other animals. Use alternatives to live-animal, hands-on exhibits that do not involve close contact with poultry, pigs, and cattle (i.e., milk a pretend cow exhibit).
• Provide adequate ventilation for both animals and humans. For enclosed or partially enclosed barns, increase the amount of clean outdoor air and direct clean air so that it flows over visitors and workers before animals and minimizes disturbing dust.
• Store animal feeding, watering, and cleaning equipment (e.g., buckets, shovels, wheelbarrows, and pitchforks) in designated areas that restrict public access. Avoid transporting soiled bedding through non-animal areas or transition areas. If this is unavoidable, take precautions to prevent spillage and clean up spillage right after it occurs.
• Locate longer-term exhibits (i.e., big bulls/boars, birthing center animals, breed exhibits) away from areas where competition livestock are housed.
• Limit the time animals are kept on the exhibition grounds (72 hours or less is ideal) to help prevent or interrupt the spread of flu between animals.
• Where feasible, clean and disinfect animal areas (e.g., flooring and railings) and equipment (e.g., gates, chutes, sort panels) at least once daily. Additionally, animal areas should be cleaned and disinfected between groups of animals. Use disinfectants effective against influenza A viruses that are safe for human and animal contact.
• Inform and educate exhibitors and visitors on the risks of infection and spread of animal influenza A viruses and how to prevent the spread between people and animals (including pigs, poultry, and cattle).

• Display or hand out educational materials to exhibitors at registration and to visitors when entering fairgrounds on how to prevent the spread of influenza viruses between people and animals (including pigs, poultry, and cattle).
• Post materials that show who may be at higher risk of serious flu complications and instruct them not to have close contact with animals that could carry influenza viruses (pigs, poultry, and cattle) and should not enter enclosures.
• Post signs or otherwise instruct visitors not to eat, drink, smoke/vape, touch or place their hands in their mouth, touch their eyes, or use bottles or pacifiers while in animal areas.
• Educate staff and exhibitors to instruct visitors not to carry toys, pacifiers, spill-proof cups, baby bottles, strollers, or similar items into animal areas. If possible, establish storage or holding areas for strollers and related items.
• Instruct visitors to supervise children closely to discourage touching of eyes, hand-to-mouth activities (e.g., nail-biting and thumb-sucking), and prevent contact with soiled animal bedding. Parents should also be instructed to prevent their children from sitting or playing on the ground in animal areas.
• Instruct visitors to limit contact with animals that can be infected with influenza viruses (including pigs, poultry, and cattle). Direct physical contact with the animal includes touching, holding, kissing, being bitten, licked, and scratched.
• Instruct parents and children to wash their hands with soap and water right after leaving animal areas, even if they did not touch an animal, and after coming in contact with contaminated environments or materials. If children’s hands become soiled, supervised hand washing should occur immediately.
• Post signs on hand hygiene and provide multiple hand-washing stations with running water, soap, and paper towels in transition areas between animal and non-animal areas and in food concession areas. Ensure hand-washing stations are accessible for all visitors, including children and persons with disabilities.
• Post all signs and other instructions in English, Spanish, and other appropriate languages, as well as in age-appropriate formats.

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The second document includes:

Considerations and Information for Fair Exhibitors to Help Prevent Influenza

          (Excerpt)

People at higher risk of serious flu complications

• Some people (e.g. children younger than 5 years, people 65 years and older, pregnant people, and people with certain chronic medical conditions, and others) are at higher risk of developing serious flu complications and should limit contact with animals (pigs, poultry, cattle) that could carry influenza viruses, if possible.
• If fair exhibitors at higher risk of developing serious flu complications cannot avoid exposure to, or direct contact with, pigs, poultry, cattle, or other animals, they should follow the CDC Updated Interim PPE Recommendations to Reduce Exposure to Novel Influenza A Viruses Associated with Disease in Humans. This includes wearing protective clothing, gloves, goggles, and a respirator or well-fitting mask that covers the nose and mouth. Parents and caregivers should review considerations for specific groups of people when selecting a respirator or mask for children.

What to do if you get sick

• Flu symptoms usually include fever, cough, sore throat, runny or stuffy nose, muscle or body aches, headaches, fatigue, and sometimes vomiting or diarrhea. Eye redness/irritation or eye discharge can also occur.
• If you get any of these symptoms, seek medical care and tell your provider about your contact with animals.
• A health care provider can decide whether influenza testing or antiviral treatment is needed.
• Influenza antiviral drugs can treat people with animal influenza virus infections as well as seasonal flu illness. These medications are recommended for treatment of people with swine or avian influenza symptoms.
• Antiviral drugs work better the sooner you start them after your symptoms begin, so seek medical care promptly if you get symptoms, especially if you are at higher risk of serious flu complications.

When people get infected with animal influenza A viruses, they may experience signs and symptoms that are similar to those caused by seasonal influenza A viruses, including:

• fever or feeling feverish
• cough
• sore throat
• runny or stuffy nose
• muscle or body aches
• headaches
• fatigue
• sometimes vomiting or diarrhea
• eye redness/irritation or eye discharge (This is more commonly reported with human infections with animal influenza viruses than seasonal influenza viruses.)

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There are more than 3000 county and state fairs in the United States, where every year tens of thousands of exhibitors draw tens of millions of visitors. Each operates under local or state rules, which can vary greatly between jurisdictions.  

Given the costs, inconvenience, and in some cases - impracticality - of some of these recommendations, I expect compliance will be limited.  I'm sure the CDC knows that. 

So far H5N1, and the current crop of swine-variant influenza viruses, haven't acquired the ability to spread efficiently in humans.  Hopefully, they never will.  

But venues like state and county fairs, and multi-species farms, can provide viruses with evolutionary opportunities they might otherwise not encounter. 

Since hope is not a plan, next month (July 16th) the CDC will hold a COCA call for clinicians and healthcare facilities on recognizing, treating, and reporting H5N1 in humans. 

Update on Highly Pathogenic Avian Influenza A(H5N1) Virus for Clinicians and Healthcare Centers

= Free Continuing Education

Overview

Highly Pathogenic Avian Influenza (HPAI) (H5N1) virus is widespread among wild birds and continues to cause outbreaks in poultry and spillover to mammals. In March 2024, HPAI A(H5N1) virus was detected in dairy cattle. To date, there have been three human cases of HPAI A(H5N1) virus infection identified in dairy farm workers in the United States.

 

The risk to the public from HPAI A(H5N1) viruses is low; however, people who have job-related or recreational exposure to infected birds or animals, including dairy cattle, are at greater risk of HPAI A(H5N1) virus infection. During this COCA Call, presenters will give an update on the current outbreak in the United States and current CDC surveillance and monitoring efforts. They will also provide information for clinicians on testing, using antivirals, and infection prevention and control recommendations.

Stay tuned.   

CDC FluView Wk #25: 2 New Novel Swine Flu Cases (H1N2v) In Pennsylvania

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While H5N1 in cattle is a relatively new concern, since 2010 we've seen over 500 swine-variant influenza (H1N1v, H1N2v & H3N2v) infections in humans reported to the CDC, often linked to direct or indirect contact with pigs.  

Just over 500 Cases in 15 Years in the United States 

Prior to 2016, the H1N2v subtype was only rarely reported (n=7), but since then it has been appearing with increasing frequency (n=40).  Two weeks ago, in Nature Comms: Potential Pandemic Risk of Circulating Swine H1N2 Influenza Viruses, we looked at growing concerns over this subtype. 

Swine variant influenza infections are indistinguishable from seasonal flu without highly specialized testing, which few countries tend to do.  Even here in the United States it is assumed we only detect a small percentage of cases (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012)).

Last March, in CDC FluView Wk #12: 1 Novel H1N2v Infection In Pennsylvania, we looked at the first reported swine variant case of 2024.  That patient (< 18 y.o) had contact with pigs, was hospitalized last March, but has since recovered.

Today the CDC's FluView #25 reports two more cases of the same subtype (H1N2v) reported from the same state.  In this case, both patients were > 18, had recently attended a livestock auction, and one was hospitalized but has since recovered. 

Novel Influenza A Virus:

Two human infections with a novel influenza A virus were reported by the Pennsylvania Department of Health. The patients, who are close contacts, were both infected with influenza A(H1N2) variant (A(H1N2)v) viruses. Both patients are ≥18 years of age and sought healthcare during the week ending June 22, 2024 (Week 25). One of the patients was hospitalized, and one was not. An investigation by state public health officials found that the patients had attended a livestock auction where swine were present prior to their illness onset. Investigation did not identify illness among additional close contacts of either patient. The investigation is ongoing.

Including these two reports there have been a total of three human infections with variant influenza A viruses reported in the United States in 2024.

When an influenza virus that normally circulates in swine (but not people) is detected in a person, it is called a “variant” influenza virus. Most human infections with variant influenza viruses occur following exposure to swine, but human-to-human transmission can occur. It is important to note that in most cases, variant influenza viruses have not shown the ability to spread easily and sustainably from person to person.

Early identification and investigation of human infections with novel influenza A viruses are critical so that the risk of infection can be understood, and appropriate public health measures can be taken.

Additional information on influenza in swine, variant influenza virus infection in humans, and guidance to interact safely with swine can be found at www.cdc.gov/flu/swineflu/index.htm.

Additional information regarding human infections with novel influenza A viruses:

Surveillance Methods  |  FluView Interactive

With few exceptions (i.e. the 2009 H1N1 pandemic virus), current swine influenza viruses don't appear to spread efficiently in humans. That said, the CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having at least some pandemic potential (2 added in 2019).

H1N2 variant [A/California/62/2018] Jul 2019 5.8 5.7 Moderate

H3N2 variant [A/Ohio/13/2017] Jul 2019 6.6 5.8 Moderate 

H3N2 variant [A/Indiana/08/2011] Dec 2012 6.0 4.5 Moderate

 The CDC currently ranks a Chinese Swine-variant EA H1N1 `G4' as having the highest pandemic potential of any flu virus on their list. But, as with avian flu, they all have barriers they must first overcome.

While our attentions this summer are understandably focused on H5N1 in cattle, it isn't the only novel flu threat we face. We are also entering in to what is traditionally `swine-variant season' - summer and fall - when we usually see the most spillovers into humans.  

These often occur at agricultural exhibits in county and state fairs, where large numbers of people have contact with livestock (see EID Journal: Shortening Duration of Swine Exhibitions to Reduce Risk for Zoonotic Transmission of Influenza A Virus). 

While most fairs have requirements the screening and barring of `sick pigs' from exhibition, over the years we've learned that many pigs may be infected asymptomatically (see EID Journal: Flu In Healthy-Looking Pigs and  Transmission Of Swine H3N2 To Humans At Agricultural Exhibits - Michigan & Ohio 2016).  

Although the public health risks are considered low, the CDC advises those who are at higher risk of serious flu complications (including children under 5, adults over 65, pregnant women, and those with certain chronic medical conditions), to avoid pigs and the swine barn altogether.

Last year the CDC held a webinar for clinicians on recognizing, treating, and reporting zoonotic influenza cases in the community (see COCA Call : What Providers Need to Know about Zoonotic Influenza), which remains available on their website.

CDC Updates & Revises RSV, COVID & Flu Vaccination Recommendations for Fall 2024

Credit ACIP/CDC 

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This week, following advice from ACIP (The Advisory Committee on Immunization Practices) the CDC has released updated recommendations for RSV, COVID, and seasonal flu vaccinations.  

As we noted at the end of May (see MMWR: Early Safety Findings Among Persons Aged ≥60 Years Who Received a RSV Vaccine — United States, May 3, 2023–April 14, 2024) there are some concerns over a higher-than-expected incidence of GBS (Guillain-Barré syndrome) among those who received this recent addition to the vaccine lineup.

The spike wasn't huge, and given the heavy impact of RSV infection on the elderly, pending more information, the advice from the CDC remained: 

RSV vaccination continues to be recommended for adults aged ≥60 years using shared clinical decision-making (9). CDC and FDA are conducting active safety evaluations to assess risks for GBS and other adverse events of special interest after RSV vaccination.

This week's recommendation scales back the recommendation for those aged 60-74, to those ` . . . who are at increased risk of severe RSV, meaning they have certain chronic medical conditions, such as lung or heart disease, or they live in nursing homes . . .'

The announcement from the CDC follows:

CDC Updates RSV Vaccination Recommendation for Adults

For the upcoming respiratory virus season, CDC recommends everyone age 75 and older receive the RSV vaccine

Media Statement

For Immediate Release, Wednesday, June 26, 2024
Contact: Media Relations
(404) 639-3286
media@cdc.gov


Today, CDC updated its recommendation for the use of Respiratory Syncytial Virus (RSV) vaccines in people ages 60 and older. For this upcoming respiratory virus season, CDC recommends:

• Everyone ages 75 and older receive the RSV vaccine.

• People ages 60–74 who are at increased risk of severe RSV, meaning they have certain chronic medical conditions, such as lung or heart disease, or they live in nursing homes, receive the RSV vaccine.

This recommendation is for adults who did not get an RSV vaccine last year. The RSV vaccine is not currently an annual vaccine, meaning people do not need to get a dose every RSV season. Eligible adults can get an RSV vaccine at any time, but the best time to get vaccinated is in late summer and early fall before RSV usually starts to spread in communities.

Today’s updated recommendation for people 60 and older replaces the recommendation made last year to simplify RSV vaccine decision-making for clinicians and the public.

Immunizations were available last year for the first time to protect people at increased risk for severe RSV, including infants and young children, and people ages 60 and older. Today’s updated recommendation is based on analyses of RSV disease burden among people 60 and older, as well as RSV vaccine effectiveness and cost-effectiveness studies. Those studies included the first real-world data since RSV vaccines were recommended for people 60 and older.

Healthcare providers should recommend RSV vaccines to their eligible patients, as well as discuss what other vaccines they will need this fall to help prevent respiratory infections.

The following is attributable to CDC Director Dr. Mandy Cohen:

“The CDC has updated its RSV vaccination recommendation for older adults to prioritize those at highest risk for serious illness from RSV,” said Mandy Cohen, M.D., M.P.H. “People 75 or older, or between 60-74 with certain chronic health conditions or living in a nursing home should get one dose of the RSV vaccine to provide an extra layer of protection.”

The advice this year for receiving both the flu and COVID vaccines is basically unchanged, although for the first time in a decade the quadrivalent vaccine will not be offered as they B/Yamagata strain has not been seen in 4 years. 

The CDC reports that COVID continues to claim more lives than influenza in the United States (75,500 in 2023).  Two weeks ago the FDA Updated COVID Vaccine Recommendations: Use KP.2 Strain If Feasible, due to its constant and rapid evolution. 

The full CDC announcement follows, I'll have a brief postscript after the break. 

CDC Recommends Updated 2024-2025 COVID-19 and Flu Vaccines for Fall/Winter Virus Season
 
Media Statement

For Immediate Release: June 27, 2024
Contact: Media Relations
(404) 639-3286

Today, CDC recommended the updated 2024-2025 COVID-19 vaccines and the updated 2024-2025 flu vaccines to protect against severe COVID-19 and flu this fall and winter.

It is safe to receive COVID-19 and flu vaccines at the same visit. Data continue to show the importance of vaccination to protect against severe outcomes of COVID-19 and flu, including hospitalization and death. In 2023, more than 916,300 people were hospitalized due to COVID-19 and more than 75,500 people died from COVID-19. During the 2023-2024 flu season, more than 44,900 people are estimated to have died from flu complications.

Updated 2024-2025 COVID-19 Vaccine Recommendation

CDC recommends everyone ages 6 months and older receive an updated 2024-2025 COVID-19 vaccine to protect against the potentially serious outcomes of COVID-19 this fall and winter whether or not they have ever previously been vaccinated with a COVID-19 vaccine. Updated COVID-19 vaccines will be available from Moderna, Novavax, and Pfizer later this year. This recommendation will take effect as soon as the new vaccines are available.

The virus that causes COVID-19, SARS-CoV-2, is always changing and protection from COVID-19 vaccines declines over time. Receiving an updated 2024-2025 COVID-19 vaccine can restore and enhance protection against the virus variants currently responsible for most infections and hospitalizations in the United States. COVID-19 vaccination also reduces the chance of suffering the effects of Long COVID, which can develop during or following acute infection and last for an extended duration.

Last season, people who received a 2023-2024 COVID-19 vaccine saw greater protection against illness and hospitalization than those who did not receive a 2023-2024 vaccine. To date, hundreds of millions of people have safely received a COVID-19 vaccine under the most intense vaccine safety monitoring in United States history.

Updated 2024-2025 Flu Vaccine Recommendation

CDC recommends everyone 6 months of age and older, with rare exceptions, receive an updated 2024-2025 flu vaccine to reduce the risk of influenza and its potentially serious complications this fall and winter. CDC encourages providers to begin their influenza vaccination planning efforts now and to vaccinate patients as indicated once 2024-2025 influenza vaccines become available.

Most people need only one dose of the flu vaccine each season. While CDC recommends flu vaccination as long as influenza viruses are circulating, September and October remain the best times for most people to get vaccinated. Flu vaccination in July and August is not recommended for most people, but there are several considerations regarding vaccination during those months for specific groups:

• Pregnant people who are in their third trimester can get a flu vaccine in July or August to protect their babies from flu after birth, when they are too young to get vaccinated. 

Children who need two doses of the flu vaccine should get their first dose of vaccine as soon as it becomes available. The second dose should be given at least four weeks after the first.

Vaccination in July or August can be considered for children who have health care visits during those months if there might not be another opportunity to vaccinate them.
For adults (especially those 65 years old and older) and pregnant people in the first and second trimester, vaccination in July and August should be avoided unless it won’t be possible to vaccinate in September or October.

Updated 2024-2025 flu vaccines will all be trivalent and will protect against an H1N1, H3N2 and a B/Victoria lineage virus. The composition of this season’s vaccine compared to last has been updated with a new influenza A(H3N2) virus.

For more information on updated COVID-19 vaccines visit: Coronavirus Disease 2019 (COVID-19) | CDC. For more information on updated flu vaccines visit: Seasonal Flu Vaccines | CDC.

The following statement is attributable to CDC Director Dr. Mandy Cohen:

“Our top recommendation for protecting yourself and your loved ones from respiratory illness is to get vaccinated,” said Mandy Cohen, M.D., M.P.H. “Make a plan now for you and your family to get both updated flu and COVID vaccines this fall, ahead of the respiratory virus season.”

Studies suggest strong links between influenza infection and cardiovascular events like heart attacks and strokes (see also Eur. Resp.J.: Influenza & Pneumonia Infections Increase Risk Of Heart Attack and Stroke).

And we've seen evidence suggesting that repeated influenza infections may be linked to an increase risk of developing Parkinson's later in life (see 2017's Nature Comms: Revisiting The Influenza-Parkinson's Link). 

In early 2023, in Neuron: Virus Exposure and Neurodegenerative Disease Risk Across National Biobanks, we also looked at a study published in Cell Neuron which found a statistical linkage between viral illnesses and developing neurodegenerative diseases later in life.

At an AAIC Meeting in 2020 (see Flu & Pneumonia Shots Appear To Reduce Dementia Risk In Elderly, researchers presented evidence suggesting:

● At least one flu vaccination was associated with a 17% reduction in Alzheimer’s incidence. More frequent flu vaccination was associated with another 13% reduction in Alzheimer’s incidence.

● Vaccination against pneumonia between ages 65 and 75 reduced Alzheimer’s risk by up to 40% depending on individual genes. 

While the current flu vaccine is nowhere near as effective as we'd like it to be, and the promise of a universal flu vaccine remains elusive (see  J.I.D.: NIAID's Strategic Plan To Develop A Universal Flu Vaccine), there is growing evidence to suggest the benefits of vaccination may extend beyond simply reducing the risk of influenza infection. 

I view getting a yearly flu shot like always wearing a seat belt in an automobile. It doesn't guarantee a good outcome in a car wreck, but it certainly increases your odds of walking away. 

 

Which is why I'll be rolling up my sleeve this fall for both the Flu and COVID vaccines.  Because at my age - and in my physical condition - I can use all the advantages I can get. 

Australia: 11th Avian H7 Outbreak, Now Reported in ACT

#18,154

The Australian Capital Territory (ACT) - which includes the city of Canberra - lies entirely within New South Wales and is a bit over 200 km from Hawkesbury district of Sydney, which reported two outbreaks of H7N8 last week.

For the past 48 hours there have been reports of an investigation into an egg farm in the ACT, and overnight H7N8 was confirmed by the ACT government.  

This outbreak is reportedly `directly linked' to the NSW farm outbreak, and  is not believed to be the result of another spillover from wild birds.

The official statement from ACT follows.

Avian Influenza

ALERT

Avian influenza (HPAI H7N8) was detected at a commercial farm in the ACT on 27 June 2024.

The ACT Government has implemented a quarantine order to manage the current case of avian influenza.

The impacted property is under quarantine and ACT Biosecurity is working closely with the property to manage the infection using national response arrangements.

The ACT Quarantine areas are available on the Legislation Register.

Avian influenza is not a food safety concern and it is safe to eat properly handled and cooked poultry meat, eggs and egg products.

If you see unusual signs of disease or suspect an exotic disease in your poultry, call the Emergency Animal Disease (EAD) Hotline immediately on 1800 675 888.

Current Situation

ACT quarantine arrangements

ACT Government has declared two quarantine areas: a restricted quarantine area and a control quarantine area. These quarantine areas are in place to reduce the movement of not only birds, but other materials, objects and equipment deemed as high risk.

Restrictions are especially important in the early period of this response. The situation will be monitored closely by the ACT Government and the restrictions may be amended or removed depending on the progression of the current outbreak.

ACT Biosecurity will continue to work closely with industry on good biosecurity practices. 

New South Wales

Avian Influenza (HPAI H7N8) has been detected at a number of poultry farms since June 2024. Details of the response, including movement controls can be found on the Department of Primary Industries website.

Victoria

Avian Influenza (H7N3 and H7N9) has been detected at a number of poultry farms since May 2024. Details of the response, including movement controls to prevent the spread of avian Influenza can be found on the Agriculture Victoria website.

COCA Call Today: Mpox - Clinical Management & Outbreaks

#18,153

Later today (2:00 PM – 3:00 PM ET) the CDC will hold a COCA call for clinicians on the continually evolving Mpox threat. The clade IIb outbreak which was declared a global health emergency in 2022 ended after only 10 months,  but we continue to see sporadic infections around the globe. 

At the same time a far more dangerous clade I mpox virus continues to rage in the DRC.

Last March a study was published Eurosurveillance: Ongoing Mpox Outbreak in South Kivu Province, DRC Associated With a Novel Clade I Sub-lineage, which contained the first genomic analysis of samples from a previously unaffected region of the DRC (the city of Kamituga). 

That study revealed a novel clade I sub-linage had emerged - most likely from a zoonotic introduction - with changes that may render current CDC tests unreliable.

In April, in Preprint: Sustained Human Outbreak of a New MPXV Clade I Lineage in Eastern Democratic Republic of the Congo, we saw a further analysis, which called for this new lineage to be named Clade Ib, and warned of its potential to spread globally. 

While that doesn't appear to have happened (yet), doctors are being asked to be particularly alert for cases with recent travel history to the DRC. 

These presentations are often technical, and are of greatest interest to clinicians and healthcare providers, but also may be of interest to the general public.

As always, If you are unable to attend the live presentation, these (and past) webinars are archived and available for later viewing at this LINK.

Mpox Update: Clinical Management and Outbreaks

= Free Continuing Education

Overview

The Centers for Disease Control and Prevention has been supporting the Democratic Republic of the Congo (DRC) in responding to its largest surge of clade I mpox (MPVX) cases ever recorded. Since January 1, 2023, DRC has reported more than 20,000 suspect mpox cases and more than 1,000 deaths. Clade IIb mpox continues to circulate in the United States but at much lower levels. The 2022 global clade IIb mpox outbreak caused more than 97,000 illnesses around the world, including more than 32,000 cases and 58 deaths in the United States.

During this COCA call, presenters will give updates on the clade I outbreak in DRC and remind clinicians to be alert for cases of mpox in patients with recent travel to DRC. Presenters will discuss when to suspect a case of mpox, provide updates on the clinical management and prevention of clade II mpox, discuss the epidemiology of clade II mpox, and cite vaccination data. They will also discuss the commercialization of the JYNNEOS vaccine and outline the update to the expanded access Investigational New Drug (EA-IND) for Tecovirimat (TPOXX).

Presenters

Agam Rao, MD
CAPT, U.S. Public Health Service
Chief Medical Officer for the Poxvirus and Rabies Branch
Division of High-Consequence Pathogens and Pathology
Centers for Disease Control and Prevention

Meghan Pennini, PhD
Chief Science Officer
HHS Coordination Operations and Response Element
Administration for Strategic Preparedness and Response
U.S. Department of Health and Human Services

Yon Yu, PharmD
CAPT, U.S. Public Health Service
Lead, Medical Countermeasures Regulatory Support Team
Office of Readiness and Response
Centers for Disease Control and Prevention

Call Materials

None at this time
Call Details

When:
Thursday, June 27, 2024
2:00 PM – 3:00 PM ET

Webinar Link:
https://www.zoomgov.com/j/1617016999

Webinar ID: 161 701 6999

Passcode: 059864

Telephone:
+1 669 254 5252, or, +1 646 828 7666

One-tap mobile:
+16692545252,,1617016999#,,,,*059864#

International numbers

JGV: H5N1 clade 2.3.4.4b Avian Influenza Viruses Replicate in Differentiated Bovine Airway Epithelial Cells Cultured at Air-liquid Interface

 
Credit USDA

#18,152

We are now more than 3 months since the initial detection of HPAI H5N1 (genotype B3.13) in American cattle, and yet there remain substantial (and frustrating) gaps in our understanding of this spillover event.   

The CDC and USDA have (diplomatically) indicated that they are often limited by a lack of cooperation on the part of farm owners, farm workers, and some state and local governments.

As a result - despite anecdotal reports of sick farm workers - fewer than 60 have actually been tested. Limited serology studies have only just begun (see CIDRAP Scientists expand H5N1 testing in dairy products, launch human serology study), and no one really knows how many cattle herds have been affected. 

Yesterday, Helen Branswell et al at STAT News published a special report that sums up the lackluster response to H5N1 in American cattle:  Three months into bird flu outbreak in U.S. dairy cows, experts see deep-rooted problems in response.

This week, in an HHS teleconference, USDA officials indicated that `unpublished' data suggests that H5N1 is primarily spread via mammary glands (see HogVet51's post) and not the respiratory route - which would be good news - assuming that data is correct. 

But limited testing, the glacial release of information - and what appears to be a tentative response to the outbreak by many state, local, and federal agencies - does little to inspire confidence.

While we wait for better data from the U.S., we've a study - conducted by researchers at Wageningen Bioveterinary Research, Lelystad, Netherlands - that suggests that bovine respiratory epithelial cells (AECs) are susceptible to H5N1 infection. 

Three points, going in.  

• These researchers used 3 European genotypes of H5N1 clade 2.3.4.4b, not the U.S. B3.13 genotype which is currently infecting cows, yet they achieved positive results.

• The cytopathogenic effect on bovine AECs was limited and infectious virus titres dropped rapidly, meaning respiratory infection might be sub-clinical and more difficult to detect. 

• This study involved a direct inoculation of bovine epithelial cells in a lab, and not a live-animal transmission study.  

While there are limitations to this study, it does at least raise the possibility that respiratory transmission in cattle may be a genuine concern.  

Due to its length, I've only posted some excerpts.  Follow the link to read the study in its entirety.  I'll have a brief postscript after the break.  

Research Article Open Access

H5N1 clade 2.3.4.4b avian influenza viruses replicate in differentiated bovine airway epithelial cells cultured at air-liquid interface  

Luca Bordes1​, Nora M. Gerhards1​, Stan Peters1​, Sophie van Oort1​, Marit Roose1​, Romy Dresken1​, Sandra Venema1​, Manouk Vrieling1​, Marc Engelsma1​, Wim H.M. van der Poel1​ and Rik L. de Swart1​

Published: 26 June 2024 https://doi.org/10.1099/jgv.0.002007

PDF

ABSTRACT

Highly pathogenic avian influenza (HPAI) H5N1 viruses are responsible for disease outbreaks in wild birds and poultry, resulting in devastating losses to the poultry sector. Since 2020, an increasing number of outbreaks of HPAI H5N1 was seen in wild birds. Infections in mammals have become more common, in most cases in carnivores after direct contact with infected birds.

Although ruminants were previously not considered a host species for HPAI viruses, in March 2024 multiple outbreaks of HPAI H5N1 were detected in goats and cattle in the United States. Here, we have used primary bronchus-derived well-differentiated bovine airway epithelial cells (WD-AECs) cultured at air-liquid interface to assess the susceptibility and permissiveness of bovine epithelial cells to infection with European H5N1 virus isolates.

We inoculated bovine WD-AECs with three low-passage HPAI clade 2.3.4.4b H5N1 virus isolates and detected rapid increases in viral genome loads and infectious virus during the first 24 h post-inoculation, without substantial cytopathogenic effects. Three days post-inoculation infected cells were still detectable by immunofluorescent staining.

These data indicate that multiple lineages of HPAI H5N1 may have the propensity to infect the respiratory tract of cattle and support extension of avian influenza surveillance efforts to ruminants. Furthermore, this study underscores the benefit of WD-AEC cultures for pandemic preparedness by providing a rapid and animal-free assessment of the host range of an emerging pathogen.

(SNIP)

DISCUSSION 

Here we investigated the susceptibility and permissiveness of bovine WD-AECs to infection with three different HPAI H5N1 viruses isolated in the Netherlands from poultry or a red fox, with either the avian PB2-627E or the mammalian PB2-627K adaptation [17]. Until the recent outbreaks of HPAI H5N1 in dairy cattle in the USA, avian influenza was not considered to spread to ruminants [15]. Reports on the clinical signs in cattle indicate rather mild disease in most of the animals [10]. High viral loads were detected in milk, supporting the possibility of cow-to-cow transmission via milk or milking machines [10, 11, 13].

The present study demonstrates that infection of bovine epithelial cells is not unique to the North American HPAI H5N1 lineage, as European HPAI H5N1 viruses readily replicated in bovine WD-AECs and generated infectious virus.

The cytopathogenic effect of the three HPAI H5N1 viruses on bovine AECs was limited and infectious virus titres dropped rapidly, suggesting that viral propagation was not very efficient. Virus replication was inversely correlated with the number of influenza virus-infected cells, which may indicate death of infected cells after 72 hpi for the H5N1-2021 PB2-627E and H5N1-2021 PB2-627K virus isolates but not the H5N1-2020 virus isolate. Nevertheless, within the first 24 h after inoculation a substantial increase in viral RNA (depicted as EID50 equivalents) and infectious titres was observed. The possibility of an abortive infection was disputed for the H5N1-2021 PB2-627E and H5N1-2021 PB2-627K viruses by the fact that the sum of the total number of collected infectious virus particles exceeded the inoculum dosage. For the H5N1-2020 virus the sum of the total number of collected virus particles was similar to the inoculum dose, which may indicate an abortive infection. However, more likely most of the inoculum was washed away during the five subsequent washes at 4 hpi and the H5N1-2020 virus replicated to a limited extent in WD-AEC. In addition, infected cells were still detectable by immunostaining 72 hpi. This is in contrast with an earlier study in which WD-AECs obtained from monkeys, cats, ferrets, dogs, rabbits or pigs were readily infected with influenza virus pH1N1, but infected cells were not detected in bovine or caprine WD-AECs [27].

Interestingly, the two H5N1 viruses isolated from a red fox in 2021 replicated more efficiently in bovine WD-AECs than the poultry isolate from 2020. We can only speculate if this may be related to the fact that these viruses were derived from a mammal, or to the evolutionary trajectory of European HPAI H5N1 strains. However, the mammalian isolates had a similar genetic composition as H5N1 viruses isolated during the 2021 epizootic from poultry and wild birds [17], supporting the likelihood of the latter. The increased genome production of the fox virus isolate with the PB2-627K mutation is not unexpected, as this mutation is widely associated with increased polymerase function in mammalian cells [28, 29].

Virus shedding in the respiratory tract of infected cattle was limited during sampling in the field [10], which may suggest the respiratory tract is not the primary replication site of HPAI in cattle. We hypothesize that this may be due to transient viral shedding in the respiratory tract preceding clinical signs in ruminants. Similar observations have been described for other mammals infected with HPAI H5N1, where disease is not observed in acutely infected subjects and overt clinical signs coincide with viral infection of the central nervous system [17, 30].

Further investigation will be required to assess potential differences in the capacity of North American or European lineage H5N1 isolates to infect ruminants and if the respiratory tract can act as potential entry site for these viruses. However, the data shown in the current study demonstrate that European H5N1 viruses are able to replicate in bovine airway epithelial cells, creating an opportunity for further viral adaptation to ruminants.

At present, surveillance of avian influenza is largely focused on wild birds, poultry and wild carnivorous mammals. However, the H5N1 outbreaks in ruminants in the USA and the results of the current study support extension of serological surveillance to include ruminants. Moreover, it urges to test ruminants showing disease signs as reported in the cases in the USA for highly pathogenic avian influenza infection. Detection of high viral loads in the milk of infected cows poses a potential risk for farmers or consumers of unpasteurized milk. Further investigation into the tropism, shedding and clinical symptoms of the recent HPAI H5N1 virus is required to provide an informed risk assessment for ruminants and the possible implications this may have for the zoonotic potential of HPAI H5N1 viruses.

This study has several limitations. The results cannot predict if the European HPAI H5N1 viruses may have spread to ruminants, or if transmission between ruminants is possible. However, this study shows first indications of amplification of infectious virus particles in bovine WD-AECs, with limited tissue damage, suggesting that subclinical infections may have occurred in cattle during the 2020–2024 European H5N1 epizootics.

Further comparison of North American and European HPAI H5N1 virus isolates in cells and tissues of ruminants and more extensive biological replicates are required to assess the translational value of our results. Screening cattle populations, that may have been exposed to HPAI infected birds, for avian influenza virus antibodies is indicated to confirm if these kind of infections have also occurred in Europe.

Our study concludes that European HPAI H5N1 isolates can replicate in bovine WD-AECs, refuting the general assumption that ruminants are not susceptible to infection with influenza A viruses. Our study underscores the benefit of WD-AEC cultures for the pandemic preparedness toolkit, providing a rapid assessment of the host range of an emerging pathogen.

         (Continue . . . )

Currently, lactating dairy cows are the primary focus for HPAI H5N1 testing in the United States, and even then, testing (except prior to interstate transport) is largely voluntary. 

While there is an assumption that non-dairy cows are immune - based primarily on a lack of clinical symptoms - our failure to test beef cattle remains a serious blind-spot.

Today's study suggests that H5N1 respiratory infection in cattle might well be sub-clinical, in which case we could be missing silent transmission of the virus. 

But even if bovine respiratory transmission should prove insignificant today, that could always change as the virus evolves and better adapts to mammals.

But the only way we'll know if that risk is genuine, or if changes are occurring, is by extensive and continued testing.  And so far, that doesn't seem to be a priority.