Thursday, June 30, 2022

Eurosurveillance: Surface Contamination in Hospital Rooms Occupied by Patients Infected with Monkeypox

 

Monkeypox Virus - Credit CDC PHIL  

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Three weeks ago the CDC - while admitting there were still some unknowns - adjusted their guidance on the transmission of Monkeypox (see CDC Statement On Monkeypox Transmission), relaxing some of their their recommendations on isolation and hospital infection control procedures. 

This new guidance now only called for a private room (no special air handling required) and de-emphasized the potential airborne spread of Monkeypox. They provided some examples of how Monkeypox can and can't spread: 

    • No: Casual conversations. Walking by someone with monkeypox in a grocery store. Touching items like doorknobs.
    • Yes: Direct skin-skin contact with rash lesions. Sexual/intimate contact. Kissing while a person is infected.
    • Yes: Living in a house and sharing a bed with someone. Sharing towels or unwashed clothing.
    • Yes: Respiratory secretions through face-to-face interactions (the type that mainly happen when living with someone or caring for someone who has monkeypox).
    • Maybe/Still learning: Contact with semen or vaginal fluids.
    • Unknown/Still learning: Contact with people who are infected with monkeypox but have no symptoms (We think people with symptoms are most likely associated with spread, but some people may have very mild illness and not know they are infected).
Other than the caution over sharing linens, towels, or a bed, very little mention is made about the potential for transmission via contaminated surfaces or fomites.  

In fact, their example (abovespecifically rules out transmission by touching objects like doorknobs. 

Which brings us to a new study, published today in Eurosurveillance, on evidence of surface contamination in and around hospital rooms inhabited by Monkeypox patients in Germany, including places not touched by the patient and in the adjacent anteroom where HCWs donned and doffed their PPE. 

Among the most contaminated surfaces they found were door knobs, cabinet door handles, faucets, and light switches.  

Viral DNA may be detected, of course, even when the virus is no longer viable, or in concentrations too low to be infectious.  But these researchers were able to successfully isolate viable virus from 3 of the samples, suggesting transmission of the Monkeypox virus by fomite is at least possible

How likely that is to occur, and whether additional infection controls are needed, isn't known yet. But we have a history of underestimating the ability of viruses to get around. 

This is a lengthy and detailed report, and you'll want to read it in its entirety.  I've only posted some brief excerpts. 


Evidence of surface contamination in hospital rooms occupied by patients infected with monkeypox, Germany, June 2022 




Since 4 May 2022, the largest west-African-clade-monkeypox outbreak to date in countries with non-endemic occurrences has been described [1]. The outbreak involves transmission among people in close physical contact with symptomatic cases [1,2], in contrast to previous outbreaks, where zoonotic transmission was reported as the main mechanism of spread [3]. Nevertheless, events of person-to-person transmission have been previously described [3,4]. Additionally, transmission to personnel taking care of patients was reported on rare occasions [5,6]. 
Indirect transmission via contaminated objects is also discussed in the literature [6,7]. However, there are insufficient data on the environmental contamination of surfaces with monkeypox virus. We systematically examined surfaces of two hospital rooms occupied by monkeypox patients and the adjacent anterooms, which are used for donning and doffing personal protective equipment (PPE), for monkeypox virus contamination using PCR. In addition, we assessed the infectivity on cell culture of the collected samples by virus isolation.

          (SNIP)

Discussion 

Besides zoonotic transmission, monkeypox virus infections have been reported after person-to-person transmission [3]. To our knowledge, the highest rate of secondary cases described to date was in a central African outbreak in 1996–1997, where 65 (73%) of 89 case-patients with available data had had contact to another case-patient within 7–21 days before their onset of illness [4]. Person-to-person transmission with nosocomial transmission from a patient to three healthcare workers was reported in another African outbreak [5]. One nurse who evaluated the patient, and who later became ill, had removed the patient’s clothing, taken the patient’s temperature, and drawn blood without adequate PPE. Nosocomial transmission was also reported related to an imported case from Nigeria to the United Kingdom [6]. In this case, the infected healthcare worker changed potentially contaminated bed linen without adequate PPE.

There are no definite data on the required infectious dose with monkeypox virus in humans. However, in contrast to variola virus [9], a significantly higher dose is assumed to be required to trigger infection [10]. In non-human primates, infection could be initiated by intrabronchial application of 5×104 plaque-forming units (PFU) [11]. Orthopoxviruses are reported to remain infectious under dry conditions and different temperatures [12]. Dried vaccinia virus is stable up to 35 weeks (at 4 °C) without loss of infectivity [12]. In this study monkeypox virus was successfully isolated from three different samples, each with a total of at least 106 virus copies. Thus, contaminated surfaces with such viral loads or higher, could potentially be infectious and it cannot be ruled out that their contact with especially damaged skin or mucous membranes, could result in transmission.

Detection of up to 1.1×106 viral copies on gloves is consistent with the detection of viral DNA on surfaces typically handled only by medical staff such as the door handles of the anteroom. The detection of the virus at very low concentrations even outside the isolation unit indicates that containment protocols may not have been fully adhered to.

The findings in this report are subject to some limitations. As DNA is an environmentally stable molecule, detection of viral DNA by PCR cannot be equated with infectious virus. Despite high contamination with up to 105 cp/cm2 as well as the successful recovery of monkeypox virus from samples with a total of > 106 copies, our findings do not prove that infection can occur from contact with these surfaces. No secondary case in the context of clinical care of the two patients in our study has been observed so far. The study was performed only for two cases and might not be generalised to other cases. In particular, in certain cases, depending on the skin regions mainly affected and the number of lesions, the levels of contamination of different surfaces may vary.

Overall, these data underscore the importance to remind hospital personnel of the need to follow recommended protection measures for monkeypox. Sufficient time and attention must be given to the careful doffing of PPE and personnel must be properly trained in these procedures. Regular disinfection of frequent hand and skin contact points during the care processes additional to regular room cleaning and surface disinfection using products with at least virucidal activity against enveloped viruses can reduce infectious virus on surfaces and thereby risk of nosocomial transmission [13]. 

Suitable strategies for preventing the spread of the virus outside the patient's room must be individually adapted to the situation of the respective medical facility. The application of the double-gloving method [14] with discarding of the outer glove layer or disinfection of the gloved hand [15,16] before entering an anteroom can contribute to this. After the final doffing of the PPE, proper hand hygiene must be performed immediately. Pre-exposure vaccination for healthcare workers [17,18] as well as early post-exposure vaccination in the case of probable or confirmed contamination in the absence of or incorrectly applied protective equipment [18,19] may be considered.

Those living in the same households of affected individuals should be advised that, in addition to avoiding close physical contact, disinfection of shared skin- and hand-contact surfaces might be useful to prevent transmission [20,21]. At the present time, the viral load on inanimate surfaces required for disease transmission is unknown. Therefore, future studies should also investigate the dose dependent infectivity of such surfaces.


New Zealand Revises Testing Guidance For Suspected COVID Reinfection

 

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Early in the pandemic conventional wisdom held that once you have been infected with COVID, you were protected against reinfection - probably for years - and potentially forever.  While there were reasons to question this `best case scenario' (see COVID-19: From Here To Immunity), many people believed we could `infect ourselves out of this pandemic'. 

By the summer of 2020, reinfections - while rare - were beginning to appear, and their numbers only increased with the arrival of Alpha in late 2020, and Delta in the spring of 2021.  

Vaccines, which were also expected to provide `durable' protection, were showing decreased longevity with the arrival of each new variant.  `Breakthrough' infections, particularly after the emergence of Omicron, took off (see MMWR: Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19).

But even with this changing viral landscape many countries have set an arbitrary 60, 90, or even 180 day `window' following infection (or vaccination) where they assume a person is `protected', and re-testing for COVID is not generally recommended. 

Last week, in EID Journal: Early SARS-CoV-2 Reinfections within 60 Days and Implications for Retesting Policies, we looked at multiple documented cases of reinfection (by different lab-confirmed variants) well within the 60-day window, and a call to re-evaluate these arbitrary (and optimistic) assumptions about the duration of immunity. 

In light of these recent findings, yesterday New Zealand's Ministry of Health lowered their threshold for re-testing following COVID infection from 90 days to just 30 days

I'll return with a postscript after the break. 


Getting reinfected with COVID-19

The latest evidence shows that getting reinfected with COVID-19 can occur within a short period of time. Reinfection will become more likely as new variants spread among the community

Last updated: 30 June 2022

We have updated our advice on getting infected again with COVID-19 after a previous COVID-19 infection and when people should take a rapid antigen test (RAT).  

If a person develops new symptoms consistent with COVID-19, and it’s 29 days or more since a previous infection, it’s possible they have a reinfection with COVID-19 and they should test using a RAT.

This reflects a change from our earlier advice which was that people would not need to re-test if they had tested positive for COVID-19 within the past 90 days.  

It is unclear how common it is to be reinfected with COVID-19. We are constantly monitoring international and national data and updating our reinfection guidance as new evidence becomes available.

Anyone reinfected with COVID-19 will have access to the same advice, help and support as they would receive for a new COVID-19 infection.

Advice for people who have had COVID-19 before and get new symptoms 28 days or less since your last infection

If COVID-19 symptoms return and it is 28 days or less since your last COVID-19 infection:there is no need to take a rapid antigen test (RAT) you should stay home and recover until 24 hours after you no longer have symptoms.

Some people recovering from COVID-19 may have symptoms that come and go for some time afterwards or they may be caused by other infections like the common cold, flu or a chest infection.

If you have an underlying health condition or your symptoms are getting worse, seek advice from a health practitioner or call Healthline on 0800 358 5453.

COVID-19 symptoms

29 days or more since your last infection

If you develop new COVID-19 symptoms and it is 29 days or more since your last COVID-19 infection:it is possible that you have COVID-19 again and you should take a RAT. if you test positive, this will be considered a reinfection and you should follow the standard COVID-19 isolation guidelines.

COVID-19 symptoms

Self-isolation requirements if you have COVID-19

Your household contacts will also need to isolate, unless they have either:had COVID-19 in the last 90 days and are recovered been a household contact in the last 10 days.

Isolation requirements for household contacts.

If your result is negative

If your result is negative, your symptoms could be another infection, such as the flu or another virus. If your symptoms continue you should repeat a RAT 48 hours later. If this is still negative, then stay at home until at least 24 hours after your symptoms resolve.

If you have an underlying health condition or symptoms that are getting worse, you should call Healthline on 0800 358 5453 or your local healthcare provider.

Reinfection with COVID-19 – what we know so far

Reinfection refers to the detection of a second or subsequent COVID-19 infection, regardless of the variant involved.

You are more likely to become reinfected as your immune response from the vaccine, or your previous COVID-19 infection, decreases over time.

It is still unclear how common reinfections are but they’re likely to become more common as new variants and subvariants spread across New Zealand.

For most people illness caused by reinfection is likely to be no more severe than a previous infection, but they can experience different symptoms.

Changing from 90 days to 29 days or more

Early in the COVID-19 pandemic, many countries chose to advise not to test within a 90-day period of an initial infection, when reinfection was thought to be unlikely and difficult to diagnose with PCR.

Evidence now shows that reinfection can occur within 90 days, particularly with new variants.

In recognition of this evidence our advice is now to test from day 29, if you experience new COVID-19 symptoms following a previous infection.

Within 29 days of a previous infection it is very difficult to diagnose reinfection because symptoms, viral levels and test positivity can continue to vary for some weeks following an infection with COVID-19.

Evidence on reinfections is evolving rapidly. We will continue to monitor emerging information on reinfection and update this advice as new evidence becomes available.

COVID-19 infection and immunity

Monitoring reinfection in the community

When someone uploads a positive RAT into My Covid Record, if it is 29 days or more since their last infection, they will be categorised as a reinfection and given the same advice and support as for a new infection.

Using this data from My Covid Record we can now monitor the number of people with a reinfection with COVID-19. Information on the number of reinfections will be included in the daily COVID-19 updates published on our website.

Latest COVID-19 current cases in New Zealand.

Guidance for clinicians

We have updated our clinical guidance for healthcare providers about how to manage patients who present with symptoms consistent with COVID-19, or a positive COVID-19 RAT, after a previous COVID-19 infection.

Guidance on reinfection for clinicians.

Downloads
Clinical guidance on testing for possible covid-19 reinfection (docx, 409 KB)
Clinical guidance on testing for possible covid-19 reinfection (pdf, 231 KB)

Everything we know about the BA.4/BA.5 Omicron variants (see NEJM: Neutralization Escape by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4, and BA.5) suggests they have an even greater ability to evade prior immunity, making `breakthrough infections' and reinfections even more likely in the months ahead. 

The SARS-CoV-2 virus has shown a remarkable ability to adapt to humans (and other hosts), and as it has evolved its abilities have changed. 

As the COVID threat changes, we need to be nimble enough in our response to pivot when needed, if we are to bring this pandemic under control.  

Hopefully more countries will follow New Zealand's lead.

Wednesday, June 29, 2022

NIH Begins Clinical Trial On A Universal Flu Vaccine Candidate

 

 #16,853

For as along as I've been writing this blog (nearly 17 years), we've supposedly been `5 years away' from having a safe and effective `universal flu vaccine'. While better flu vaccines have been developed (cell culture-propagated vaccines, adjuvanted and high dose vaccines), today's vaccines far too often provide only moderate protection against a virus that kills tens of thousands of Americans every year.

Long considered the holy grail of vaccinology, a `universal flu vaccine'  it is often fancifully described in the popular press as being a `one time (or every few years) shot' that would convey nearly full protection against all flu subtypes.  

While that would be ideal, the NIH has set a more realistic goal; a 75%+ VE (Vaccine Effectiveness) across multiple (seasonal & novel) subtypes that would last at least a year (see J.I.D.: NIAID's Strategic Plan To Develop A Universal Flu Vaccine).


Despite these reduced goals, the road to a universal flu shot is a long one, and success - at least in the near term - is far from guaranteed (see Scripps Research: Study Suggests Some Flu Viruses May Be Less Susceptible To A `Universal' Flu Vaccine).

Based on some promising animals studies (see An inactivated multivalent influenza A virus vaccine is broadly protective in mice and ferrets), the NIH is ready to begin Phase I human trials of a candidate vaccine (BPL-1357).

This press release comes from the NIH. 

Trial of potential universal flu vaccine opens at NIH Clinical Center

Tuesday, June 28, 2022
A Phase 1 clinical trial of a novel influenza vaccine has begun inoculating healthy adult volunteers at the National Institutes of Health Clinical Center in Bethesda, Maryland. The placebo-controlled trial will test the safety of a candidate vaccine, BPL-1357, and its ability to prompt immune responses. The vaccine candidate was developed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID). The single-site trial can enroll up to 100 people aged 18 to 55 years and is led by NIAID investigator Matthew J. Memoli, M.D.

“Influenza vaccines that can provide long-lasting protection against a wide range of seasonal influenza viruses as well as those with pandemic potential would be invaluable public health tools,” said NIAID Director Anthony S. Fauci, M.D. “The scientific community is making progress on this pressing global health priority. The BPL-1357 candidate influenza vaccine being tested in this clinical trial performed very well in pre-clinical studies and we look forward to learning how it performs in people.”

BPL-1357 is a whole-virus vaccine made up of four strains of non-infectious, chemically inactivated, low-pathogenicity avian flu virus. A study in animals(link is external), led by NIAID investigator Jeffery K. Taubenberger, M.D., Ph.D., and posted online as a pre-print, found that all mice receiving two doses of BPL-1357 vaccine delivered either intramuscularly or intranasally survived later exposure to lethal doses of each of six different influenza virus strains, including subtypes that were not included in the vaccine. Similar results were obtained in challenge experiments with BPL-1357-vaccinated ferrets.

In the Phase 1 trial, volunteers will be randomized in a 1:1:1 ratio into three groups and will receive two doses of placebo or vaccine spaced 28 days apart. Group A participants receive BPL-1357 intramuscularly along with intranasal saline placebo; Group B will receive doses of the candidate vaccine intranasally along with intramuscular placebo; volunteers in Group C receive intramuscularly and intranasally delivered placebo at both visits to the clinic. Neither the study clinicians nor the volunteers know the group assignments. Volunteers must not have received any type of flu vaccination in the eight weeks prior to enrollment and must agree to forego seasonal flu vaccination for approximately two months after the second vaccine (or placebo) dose.

The study duration for each participant is approximately seven months. In addition to the two clinic visits to receive vaccine (or placebo), volunteers will be asked to return to the clinic seven times to provide blood and nasal mucosal samples that will be used by the investigators to detect and characterize immune responses.

“With the BPL-1357 vaccine, especially when given intranasally, we are attempting to induce a comprehensive immune response that closely mimics immunity gained following a natural influenza infection,” said Dr. Memoli. “This is very different than nearly all other vaccines for influenza or other respiratory viruses, which focus on inducing immunity to a single viral antigen and often do not induce mucosal immunity.”

“Our study will examine the safety of BPL-1357 and also will allow us to assess the importance of mucosal immunity against flu and whether a strategy of inducing both the cellular and antibody arms of the immune system can provide broader protection against the ever-changing influenza virus,” he added.

For additional information about the trial, visit clinicaltrials.gov and search on the trial identifier NCT05027932.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

CDC Opens EOC for Monkeypox Response - HHS Unveils Targeted Vaccine Plan


Credit CDC

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While Monkeypox isn't expected to present a society-wide epidemic threat like COVID or pandemic flu, without a coordinated national and international response, it still has the ability to spread potentially serious illness and become firmly entrenched in humans with unpredictable results. 

Yesterday the CDC announced 60 new cases (n=306), while internationally the number now exceeds 3,000.  Both numbers are thought to be significantly under-counted, and are expected to continue to rise as testing increases.  

Later today the CDC will hold a COCA Call for clinicians on clinical diagnosis, treatment, and reporting of cases, while yesterday the CDC activated their EOC (Emergency Operations Center).

CDC Activates Emergency Operations Center for Monkeypox Response
Media Statement
For Immediate Release: Tuesday, June 28, 2022
Contact: Media Relations
(404) 639-3286

Today, CDC continues to lean forward with an aggressive public health response to the monkeypox outbreak by activating its Emergency Operations Center (EOC). This action stands up the CDC’s command center for monitoring and coordinating the emergency response to monkeypox and mobilizing additional CDC personnel and resources. CDC’s activation of the EOC allows the agency to further increase operational support for the response to meet the outbreak’s evolving challenges. It is home to more than 300 CDC staff working in collaboration with local, national, and international response partners on public health challenges. The activation of the EOC will serve to further supplement the ongoing work of CDC staff to respond to this outbreak.

Globally, early data suggest that gay, bisexual, and other men who have sex with men make up a high number of monkeypox cases. CDC continues to provide guidance and raise awareness among frontline healthcare providers and public health. CDC is also raising awareness of the current situation with the public through its website and social media in addition to direct partner and community outreach.

In June, CDC updated and expanded the monkeypox case definition and continues to encourage health care providers to consider testing for all rashes with clinical suspicion for monkeypox. Health care providers who see a patient with a rash that resembles monkeypox or might be more characteristic of more common infections (e.g., varicella zoster, herpes zoster, or syphilis) should carefully evaluate the patient for monkeypox and should consider testing. Anyone who has risk factors for monkeypox, and a new rash should seek care and testing.

Last week, CDC began shipping orthopoxvirus tests to five commercial laboratory companies, including the nation’s largest reference laboratories, to quickly increase monkeypox testing capacity and access in every community. This development will facilitate increased testing, leverage established relationships between clinics, hospitals and commercial laboratories, and support our ability to better understand the scope of the current monkeypox outbreak.

Please visit the CDC website, which is updated daily, for the latest information related to our response.

Late yesterday the HHS and White House held a press call where they unveiled the HHS's plan to acquire, and distribute, over 1.6 million doses of Monkeypox (JYNNEOS) vaccine over the coming months, and to expand the nation's testing capacity. 

This vaccination plan is targeted at the highest risk individuals, and those who may have been exposed, and since it requires 2-shots, will be enough for about 800,000 individuals. 

The HHS press release follows, after which I'll have a bit more about the JYNNEOS vaccine. 

HHS Announces Enhanced Strategy to Vaccinate and Protect At-Risk Individuals from the Current Monkeypox Outbreak


The U.S. Department of Health and Human Services (HHS) today announced an enhanced nationwide vaccination strategy to mitigate the spread of monkeypox. The strategy will vaccinate and protect those at-risk of monkeypox, prioritize vaccines for areas with the highest numbers of cases, and provide guidance to state, territorial, tribal, and local health officials to aide their planning and response efforts.

Under the strategy, HHS is rapidly expanding access to hundreds of thousands of doses of the JYNNEOS vaccine for prophylactic use against monkeypox in areas with the highest transmission and need, using a tiered allocation system. Jurisdictions can also request shipments of the ACAM2000 vaccine, which is in much greater supply, but due to significant side effects is not recommended for everyone.

“Within days of the first confirmed case of monkeypox in the United States, we quickly began deploying vaccines and treatment to help protect the American public and limit the spread of the virus,” said HHS Secretary Xavier Becerra. “While monkeypox poses minimal risk to most Americans, we are doing everything we can to offer vaccines to those at high-risk of contracting the virus. This new strategy allows us to maximize the supply of currently available vaccines and reach those who are most vulnerable to the current outbreak.”

HHS will provide 296,000 doses of JYNNEOS vaccine. Of that amount, 56,000 doses will be made available immediately, and an additional 240,000 doses will be made available in the coming weeks. HHS expects more than 750,000 additional JYNNEOS doses to be made available over the summer, and an additional 500,000 doses will undergo completion, inspection, and release throughout the fall, totaling 1.6 million doses available this year.

JYNNEOS vaccine will be allocated using a four-tier distribution strategy that prioritizes jurisdictions with the highest case rates of monkeypox. Within each tier, doses of JYNNEOS will be allocated based on the number of individuals at risk for monkeypox who also have pre-existing conditions, like HIV.

The Advisory Committee on Immunization Practices currently recommends vaccination for those at high risk following a confirmed monkeypox exposure. Given the large number of contacts and difficulty in identifying all contacts during the current outbreak, vaccine will now be provided to individuals with confirmed and presumed monkeypox exposures. This includes those who had close physical contact with someone diagnosed with monkeypox, those who know their sexual partner was diagnosed with monkeypox, and men who have sex with men who have recently had multiple sex partners in a venue where there was known to be monkeypox or in an area where monkeypox is spreading.

“We are focused on making sure the public and health care providers are aware of the risks posed by monkeypox and that there are steps they can take –through seeking testing, vaccines and treatments – to stay healthy and stop the spread,” said Centers for Disease Control and Prevention (CDC) Director Rochelle Walensky, M.D., M.P.H.

To date, the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR), in coordination with the CDC, has responded to requests from 32 jurisdictions, deploying more than 9,000 doses of vaccine and 300 courses of antiviral treatments. HHS will continue to evolve and strengthen its vaccine supply and distribution strategy to ensure the communities most in need have access to vaccinations to combat monkeypox. This includes being in regular communication with states and jurisdiction to monitor case rates and be responsive to requests made by jurisdiction to ensure the vaccine strategy continues to meet needs in real-time.

Today’s expanded vaccine strategy is part of the Biden-Harris Administration’s broader monkeypox outbreak response plan to mitigate the spread of the virus and protect those at highest risk. From day one of the outbreak, the Biden Administration acted with urgency to deploy testing and treatments to communities most impacted, scaling testing capacity to more than 70 labs in 48 states and began shipping its FDA-cleared orthopoxvirus tests last week to five major commercial labs to further increase testing capacity and convenience in every community. The Administration is also communicating regularly with community leaders, health care providers, and stakeholders in high-risk communities to raise awareness of the outbreak, and increase access to tests, vaccines, and treatments.

“We have vaccines and treatments to respond to the current monkeypox outbreak thanks to years of sustained investment and planning,” said HHS Assistant Secretary for Preparedness and Response Dawn O’Connell. “Our goal right now is to ensure that the limited supply of JYNNEOS vaccine is deployed to those who can benefit from it most immediately, as we continue to secure additional vaccine doses.”


The JYNNEOS vaccine - which we first looked at in 2019 (see FDA Approves 1st live, Non-replicating Vaccine to Prevent Smallpox & Monkeypox) - was designed to be primarily a replacement for the smallpox vaccine, but is believed will be effective against Monkeypox as well. 


In 2019, FDA licensed JYNNEOS, a replication-deficient MVA vaccine, for prevention of smallpox or monkeypox disease in adults aged ≥18 years determined to be at high risk for infection with these viruses. JYNNEOS is administered by subcutaneous injection as a 2-dose series delivered 28 days apart. There is no major cutaneous reaction, also known as a “take” (a vaccine site lesion often used as a marker of successful vaccination with replication-competent vaccines such as ACAM2000), following vaccination with JYNNEOS and consequently no risk for inadvertent inoculation or autoinoculation. The effectiveness of JYNNEOS was inferred from the immunogenicity of JYNNEOS in clinical studies and from efficacy data from animal challenge studies.

The older ACAM2000 smallpox vaccine is still available, but is a live-virus vaccine, and carries a higher risk of adverse side effects and cannot be given to everyone.  

 

Tuesday, June 28, 2022

CDC Nowcast: BA.4/BA.5 Now More Than Half Of All Cases In The United States


#16,851


As expected, the tag-team combo of Omicron BA.4 and BA.5 have eclipsed BA.2.12.1 as the dominant COVID variants in the country.  Both carry the L452R and F486V mutations in their viral spike protein which help them evade prior immunity (either from infection or vaccine, or both), but BA.5 continues to outperform BA.4 and will likely become the dominant strain.

BA.5 is already dominant in Denmark and in the UK, and while it doesn't appear to have caused more severe illness, its increased infectivity has sparked a rise in infections and hospitalizations in both nations. 

Everything we're seeing suggests that BA.5 (and BA.4) are more likely to evade prior immunity than earlier variants, meaning that even those who have (even recently) recovered from the virus - or have received their booster vaccination - may be at risk of infection.  

Vaccination (and boosters), along with prior infection, are still expected to reduce the severity of COVID illness, even if they provide relatively little protection against infection. 

As a result, we are starting to see more places recommend wearing face masks again, as an additional layer of protection against infection.

Given the limits of surveillance, testing, and genomic sequencing around the country, all of the following numbers should be viewed as rough estimates, and we may see further revisions to the data in the weeks ahead.



Given what we know about the often devastating effects of `long COVID', and recent evidence of risks to unborn children in the womb from maternal infection, and a report (Outcomes of SARS-CoV-2 Reinfection) suggesting that successive reinfections with COVID can lead to higher all-cause mortality, it makes sense not to trivialize the risks from COVID. 

Even though I'm fully vaccinated, and topped off with my 2nd booster this month, I'm continuing to wear a face mask in public, carry (and use) hand sanitizer, and avoid crowds when possible. 

Your mileage may vary. But for me, it seems well worth the hassle if it will reduce my chances of having a bad outcome.  And with influenza likely to return on top of COVID this fall, I don't expect to be changing my routine anytime soon. 


Preprint: Human infection With a Novel Reassortment Avian Influenza A H3N8 Virus: An Epidemiological Investigation Study



Two H3N8 cases in Henan Province roughly 400 miles apart

#16,850

Two months ago (Apr 26th), we saw the first confirmed human infection by avian H3N8 reported by Chinese officials in Henan Province (see China: NHC Confirms Human Avian H3N8 Infection In Henan Province). The patient - described as a 4 year-old boy from Zhumadian City - fell ill in early April - and at the time was reported to be in critical condition with respiratory failure.

A month later (May 26th), I wrote about a 2nd case - also in Henan Province - which was eventually  confirmed by Hong Kong's CHP (see Hong Kong CHP Finally Notified Of 2nd H3N8 case).

H3N8 is of particular concern because it remains a plausible cause of a flu pandemic that spread out of Russia in the late 1800s, and because we've seen it jump successfully from birds to other species (equines, canines, and aquatic mammals) in recent decades (see overview in FAO/OIE/WHO Joint Rapid Risk Assessment Human infection with Influenza A(H3N8)).

Last fall, in CCDC Weekly: Epidemiological and Genetic Characteristics of the H3 Subtype Avian Influenza Viruses in China, we looked at a rare, detailed, and highly informative overview of avian H3 viruses detected in wild birds and poultry across China. One which highlighted both H3N2 and H3N8 as growing threats.

More recently, in Adaptation of Two Wild Bird-Origin H3N8 Avian Influenza Viruses to Mammalian Hosts, we looked at a study investigating the transmissibility and pathogenicity of two H3N8 LPAI viruses (GZA1 & XJ47) isolated from wild birds in China.

Both strains were subjected to a serial passage experiment, and both developed much higher virulence, and picked up known mammalian adaptations (PA T97I and D701N in PB2).

So far, the details on these two human H3N8 cases have been relatively sparse.  But today we have a preprint describing the epidemiological investigation into the first case.  Perhaps most notably, the family dog and cat both tested positive for H3N8, and a full-length HA sequencing revealed the HA to be identical to the boy's. 

It isn't possible to ascertain who infected who.  The child could have contracted the virus from an avian exposure, and passed it on to these companion animals.  Or, or one of these animals could have contracted it, and passed it on to the child. 

First the link, abstract, and an abstract from the preprint.  Most will want to read the report in its entirety.  I'll have a bit more after the break.  


Human infection with a novel reassortment avian influenza A H3N8 virus: an epidemiological investigation study

Pengtao Bao, Yang Liu, Xiao-Ai Zhang, Hang Fan, Jie Zhao, Mi Mu, and 16 more
This is a preprint; it has not been peer reviewed by a journal.

https://doi.org/10.21203/rs.3.rs-1754198/v1
This work is licensed under a CC BY 4.0 License


Abstract

A four-year-old boy developed recurrent fever and severe pneumonia in April, 2022. High-throughput sequencing on his bronchoalveolar lavage fluid revealed a novel reassortant avian influenza A-H3N8 virus (A/Henan/ZMD-22-2/2022(H3N8). Both HA and NA genes of the virus were of avian origin, with the HA gene most closely related to H3N2 and H3N8 viruses detected in ducks in Guangdong Province, and NA gene most closely related to wild bird H3N8 influenza viruses detected in the USA and Japan.

The six internal genes were acquired from Eurasian lineage H9N2 viruses. Molecular substitutions analysis revealed the haemagglutin retained avian-like receptor binding specificity but PB2 genes possessed sequence changes (E627K) associated with increased virulence and transmissibility in mammalian animal models. 

The patient developed respiratory failure, liver, renal, coagulation dysfunction and sepsis. Endotracheal intubation and extracorporeal membrane oxygenation were administered. 

Positive detection of the novel A(H3N8) RNA was obtained from nasopharyngeal swab of a dog, anal swab of a cat, and environmental samples collected in the patient’s house. The full-length HA sequence from the dog and cat was identical to sequence from the patient

No influenza like illness developed and no H3N8-RNA was identified from the family members. Serological test revealed neutralizing antibody induced against ZMD-22-2 virus in the patient and three of his family members.

 Our results suggest a novel triple reassortant H3N8 caused severe human disease. There is some evidence of mammalian adaptation, possible via an intermediary mammalian species, but no evidence of person to person transmission. The potential threat from avian influenzas viruses warrants continuous evaluation and mitigation.

          (SNIP)

         Discussion 

         (Excerpt)

It’s notable that H3N8 virus was also detected from the domesticated cat and dog that were in close contact with the patient. Both dogs and cats are known to be susceptible to human influenza and avian influenza strains. Dogs are particularly susceptible to influenza A viruses, including H3N2, H3N8, H5N1, and H6N1. In Asia, respiratory disease caused by influenza virus H3N2 was documented in dogs, and fatal infection with the highly pathogenic avian influenza virus (HPAIV) H5N1 has also been reported29. 

A number of single cases of H5N1 HPAI infections in cats have also been reported in different parts of the world, mainly associated with recent avian outbreaks30. Here we observed the H3N8 infected dog developed mild clinical signs, moreover, laboratory abnormality of elevated LDH was observed, possibly indicating a systematic infection. The infected dog excreted virus not only via the respiratory tract but also possibly via the digestive tract as evidenced by positive detection of H3N8 specific RNA in the drinking water. Therefore, both the respiratory and gastrointestinal routes of infection may cause horizontal transmission among dog, cat and the human being. 

However, it is not possible to infer the direction of transmission, since both dogs and cats are naturally susceptible to influenza virus strains from other hosts, including birds and mammals. Under current situation, both cat and dog are semidomesticated and may highly likely come in contact with wild birds, ducks in the nearby pond, on the other hand, frequently exposed to human and poultry. Spillover of H3N8 virus into dog and cat further to human, or the otherwise manner can both occur, and it’s impossible to determine mamallian adaptation happened first in dog, cat or human.

 The potential ability of cat and dog to be a “mixing vessel” of diverse origin influenza strains into novel reassortant might be indicated. Unfortunately, the lack of poultry specimens from the household of the patient, and the unsuccessful sampling of the duck in the neighboring pond means we cannot firmly establish the original zoonotic source of infection nor determine the genetic sequence of the original virus.



It will be interesting to see if any similar details emerge on the 2nd case, reported in May. 

In the meantime, we've looked at the potential for dogs and cats to serve as `mixing vessels' for influenza many times in the past, including:
Pathogens: Emergence and Characterization of a Novel Reassortant Canine Influenza Virus Isolated from Cats

J. Clin. Microb: Serological Screening Of Dogs & Cats For Influenza A - Europe

China: Avian-Origin Canine H3N2 Prevalence In Farmed Dogs

Seroprevalence Of Influenza Viruses In Cats - China

Study: Dogs As Potential `Mixing Vessels’ For Influenza

J. Virology: Zoonotic Risk, Pathogenesis, and Transmission of Canine H3N2

Access Microbiology: Inter-Species Transmission of Avian Influenza Virus to Dogs
Perhaps the biggest wake up call came in late 2016 when we saw an avian H7N2 virus sweep through hundreds of cats housed at multiple New York Animal shelters - while also infecting at least two people - demonstrating that that cats can become efficient transmitters of a novel flu virus as well.

While spillover events such as these two H3N8 infections are rare, this is a reminder that nature never stops tinkering, and has as much time as it needs to create the next global health crisis. 

Upcoming COCA Call (June 29th): Monkeypox: Updates about Clinical Diagnosis and Treatment




#16,849

With 244 confirmed cases of Monkeypox across the country (see map below), and thousands more around the globe, the odds of a clinician being confronted by a case of this exotic and formerly rare infection rises with every passing day. 


Tomorrow the CDC will hold a 1-hour COCA Call (webinar) for clinicians on diagnosing, treating, and reporting Monkeypox cases (details below).  

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

I suspect this will be a heavily attended event. If you are unable to attend the live presentation, these (and past) webinars are always archived and available for later viewing at this LINK.  
Monkeypox: Updates about Clinical Diagnosis and Treatment

Overview

This COCA Call will present what clinicians need to know about monkeypox including guidance about the typical clinical presentation, treatment options, pre- and post-exposure prophylaxis, and reporting to public health authorities.

Presenters

Agam Rao, MD, FIDSA
CAPT, U.S. Public Health Service
Medical Officer, Poxvirus and Rabies Branch
National Center for Emerging and Zoonotic Infectious Diseases
Centers for Disease Control and Prevention

Leandro A. Mena, MD, MPH, FIDSA
Director, Division of STD Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Centers for Disease Control and Prevention

Brett Petersen, MD, MPH
CAPT, U.S. Public Health Service
Deputy Chief, Poxvirus and Rabies Branch
National Center for Emerging and Zoonotic Infectious Diseases
Centers for Disease Control and Prevention

Call Materials


To be posted. Please check back.

Call Details

When:
Wednesday, June 29, 2022,
2:00 PM – 3:00 PM ET


Webinar Link:
https://www.zoomgov.com/j/1615907540

Passcode: 189531

Dial In:
US: +1 669 254 5252
or +1 646 828 7666
or +1 551 285 1373
or +1 669 216 1590

International numbers

One-tap mobile:
US: +16692545252,,1615907540#,,,,*189531# or +16468287666,,1615907540#,,,,*189531#

Webinar ID: 161 590 7540

Monday, June 27, 2022

HK CHP Monitoring Human H5N6 Infection On The Mainland (Jiangxi)


 

#16,848

As I mentioned in my previous blog (see China NIC Report: Summer Influenza Surge In Southern China) there was one H5N6 human infection reported during week 24 by China's National Influenza Center.  

While no details were provided, within the past hour Hong Kong's CHP has published the following statement:
CHP closely monitors human case of avian influenza A(H5N6) in Mainland
 
The Centre for Health Protection (CHP) of the Department of Health is today (June 27) closely monitoring a human case of avian influenza A(H5N6) in the Mainland, and again urged the public to maintain strict personal, food and environmental hygiene both locally and during travel.

The case involves a 58-year-old male living in Ganzhou, Jiangxi, who had exposure to poultry from the market. He developed symptoms on June 2 and was admitted for treatment on June 5. He is in critical condition.

From 2014 to date, 79 human cases of avian influenza A(H5N6) have been reported by Mainland health authorities.

"All novel influenza A infections, including H5N6, are notifiable infectious diseases in Hong Kong," a spokesman for the CHP said.

Travellers to the Mainland or other affected areas must avoid visiting wet markets, live poultry markets or farms. They should be alert to the presence of backyard poultry when visiting relatives and friends. They should also avoid purchasing live or freshly slaughtered poultry, and avoid touching poultry/birds or their droppings. They should strictly observe personal and hand hygiene when visiting any place with live poultry.

Travellers returning from affected areas should consult a doctor promptly if symptoms develop, and inform the doctor of their travel history for prompt diagnosis and treatment of potential diseases. It is essential to tell the doctor if they have seen any live poultry during travel, which may imply possible exposure to contaminated environments. This will enable the doctor to assess the possibility of avian influenza and arrange necessary investigations and appropriate treatment in a timely manner.

While local surveillance, prevention and control measures are in place, the CHP will remain vigilant and work closely with the World Health Organization and relevant health authorities to monitor the latest developments.

The public should maintain strict personal, hand, food and environmental hygiene and take heed of the advice below when handling poultry:
  • Avoid touching poultry, birds, animals or their droppings;
  • When buying live chickens, do not touch them and their droppings. Do not blow at their bottoms. Wash eggs with detergent if soiled with faecal matter and cook and consume the eggs immediately. Always wash hands thoroughly with soap and water after handling chickens and eggs;
  • Eggs should be cooked well until the white and yolk become firm. Do not eat raw eggs or dip cooked food into any sauce with raw eggs. Poultry should be cooked thoroughly. If there is pinkish juice running from the cooked poultry or the middle part of its bone is still red, the poultry should be cooked again until fully done;
  • Wash hands frequently, especially before touching the mouth, nose or eyes, before handling food or eating, and after going to the toilet, touching public installations or equipment such as escalator handrails, elevator control panels or door knobs, or when hands are dirtied by respiratory secretions after coughing or sneezing; and
  • Wear a mask if fever or respiratory symptoms develop, when going to a hospital or clinic, or while taking care of patients with fever or respiratory symptoms.
The public may visit the CHP's pages for more information: the avian influenza page, the weekly Avian Influenza Report, global statistics and affected areas of avian influenza, the Facebook Page and the YouTube Channel.


Ends/Monday, June 27, 2022
Issued at HKT 17:50
NNNN
 
While reports of H5N6 cases from Mainland have gone eerily silent in recent weeks, last week in The Lancet: Resurgence of H5N6 Avian Influenza Virus in 2021 Poses New Threat to Public Health we looked at the continual evolution of the virus, and its continually growing threat to public health. 


China NIC Report: Summer Influenza Surge In Southern China

 

Figure 9 Weekly distribution of reported ILI outbreaks in southern provinces  (CHINA)

#16,847

Influenzas A's dramatic return after a nearly 2-year absence continues with an early, and strong showing in Australia and New Zealand (see Australia's Early and Impressive Flu Season), and reports of an unseasonable summer flu outbreak in Southern China (see Southern China: Several Provinces Issue H3N2 Influenza Alerts), prompting concerns over this fall's flu season in the Northern Hemisphere. 

Over the weekend Chinese media have been reporting that outpatient clinics are filled with suspected flu patients, often queuing up overnight, and that oseltamivir (aka Tamiflu) is in short supply in many places. 

According to the latest report from China's National Influenza Center (NIC), this flu outbreak is predominantly A/H3N2, and almost all of the activity is centered in the Southern half of the country.  While not entirely unheard of (we saw an outbreak in the summer of 2017), large influenza epidemics on the Mainland are uncommon during the summer months (see chart below).

Figure 1 % of influenza-like cases reported by sentinel hospitals in southern provinces in 2019-2022

From this week's NIC report:

In the 24th week of 2022 (June 13, 2022 - June 19, 2022), the ILI% reported by sentinel hospitals in southern provinces was 6.8%, Higher than the previous week (5.8%) and higher than the same period in 2019-2021 (4.2%, 3.1% and 4.3%). 
 
In the 24th week of 2022, a total of 6,542 influenza-like case surveillance samples were detected by the influenza surveillance network laboratories nationwide (excluding Hong Kong, Macao and Taiwan regions, the same below). 

In southern provinces, 1403 influenza virus-positive specimens were detected, of which 1389 were A(H3N2) subtype influenza, 13 were B(Victoria), and 1 was B unsegmented. Six influenza virus-positive specimens were detected in northern provinces, of which five were subtype A (H3N2) and one was B (Victoria). 

While China hasn't publicly acknowledged an HPAI human infection since late April, this update informs us of 1 human infection with HPAI H5N6 and 1 with LPAI H9N2 in week 24.

During week 24, WHO reported no cases of human infection with H5N1 highly pathogenic avian influenza. 2. distributed area. 

In the 24th week, Jiangxi Province reported one case of human infection with H5N6 highly pathogenic avian influenza.

In week 24, Sichuan Province reported one case of human infection with H9N2 avian influenza.

All of this comes as China continues to battle (successfully, according to their NHC) against Omicron, with only 5 local cases (3 in Beijing and 2 in Shanghai) reported in their latest update.  Since China often releases bad news `strategically', these reports should be weighed accordingly. 

Meanwhile, the surge in flu and COVID continues in Australia, with their latest (No. 06, 2022) update from the Australian Government showing influenza's impressive rise during the first half of June.  

Activity

• Influenza-like-illness (ILI) activity in the community this year has increased since March 2022. 

• In the year to date in 2022, there have been 147,155 notifications reported to the National Notifiable Diseases Surveillance System (NNDSS) in Australia, of which 55,101 notifications had a diagnosis date this fortnight. 

• From mid-April 2022, the weekly number of notifications of laboratory-confirmed influenza reported in Australia has exceeded the 5 year average. 

Severity 

• In the year to date, of the 147,155 notifications of laboratory-confirmed influenza, 54 influenza-associated deaths have been notified to the NNDSS. 

• Since commencement of seasonal surveillance in April 2022, there have been 989 hospital admissions due to influenza reported across sentinel hospitals sites, of which 6.1% were admitted directly to ICU. 

Despite the slight downward hook shown in the last 2 weeks - which may simply indicate a lag in reporting -  it is too soon to know if Australia's flu season has peaked. 

The return of influenza A at the same time that a new wave of (BA.4/BA.5) Omicron is gaining momentum around the globe complicates matters for everyone.  

Not only does it increase the possibility of seeing potentially severe dual infections (influenza and COVID), it will make it much harder to differentiate between flu and COVID infections. 

Influenza seasons are highly unpredictable, and what happens now in China or in the Southern Hemisphere doesn't guarantee a harsh season for Northern Hemisphere this fall.  

But between presumed low community immunity to influenza after 2 years of social distancing - and what we can see happening elsewhere in the world - I certainly wouldn't bet against it.