Addressing the Current Vaccine Disinformation

Let’s get a few matters out of the way before we dive in.

  1. I do not receive any financial benefit whatsoever whether you receive or refuse any vaccine currently on the market or in development. I do not own stock in any pharmaceutical companies, vaccine developers, or companies that are involved in producing, distributing or selling ingredients for vaccines that I know of. (I qualify with the statement “that I know of,” because I do invest in mutual funds that include large numbers of companies and these investments are managed and moved around by professional fund managers, so I couldn’t even tell you which companies they are investing in or whether they might buy or sell shares at any given time.)
  2. I am retired, so I am not administering vaccines to anyone and therefore, do not stand to gain financially from patients receiving vaccines or from treating patients who get ill as a consequence of not being vaccinated.
  3. I am not on the boards of any companies that have a financial interest in or receive a financial benefit from people receiving vaccines or from spreading vaccine disinformation.
  4. I do not receive any compensation or have any sponsorships for my blog, my social media, my media appearances, or my views on scientific, medical or public health issues.
  5. I do not receive payment for appearing on the weekly local Boise State Public Radio show Idaho Matters hosted by Gemma Gaudette, and the views I express on that show are strictly my own.
  6. I do not speak at political events, partisan-sponsored conferences, or on cable network shows or podcasts that have political or ideological leanings.
  7. I am not paid speaker’s fees for any talks on COVID-19, vaccines, or related issues.
  8. I am a life-long, conservative Republican who has never run for or held a political position, nor do I have any desire or ambition to do so.
  9. I am a Christian and raised my children in the Southern Baptist Church.
  10.  Bottom line – everything I do with respect to my attempts to educate the public about health issues is to give back to the community the benefit of my education, training, years of medical practice, and many more years of experience and learning as I have served in leading a large teaching hospital and then a large health system, because I feel blessed to have had all the opportunities that I have had, the tremendous opportunity to help people in their time of need, the many lessons I have learned, and I refuse to let all of it go to waste now that I am retired. Further, as a practical matter, I don’t care whether you get vaccinated or not. Chances are, I don’t even know most of the people reading this. But, here is what I do care about:
  11. I think people should make informed decisions about their health care choices. That means we doctors provide you with the information – pros, cons, risks, benefits – about medical interventions and then, you the patient, or someone on your behalf if you are unable to make the decision, get to decide whether to accept or refuse the intervention. I respect it when patients make their decisions – those are decisions for them to make. What I deeply resent is doctors who manipulate patients into making a decision in favor or opposed to an intervention for their own best interests, not the patient’s. Most recently, I am appalled at the doctors who knowingly spread COVID-19 disinformation because they could not honestly answer the conflicts of interest questions above the way that I did, and yet they don’t disclose those conflicts. These doctors may be motivated by greed, political aspirations, commitments to ideology over science, notoriety, the funding to travel all over the U.S. and world to appear at conferences as a speaker, or other reasons or combinations of reasons, but it is abhorrent to the oaths we took as physicians, it is antithetical to the teachings of the Bible, and it is a terrible embarrassment to the profession.
  12. I think truth still matters. Without truth, and people to stand up to lies and disinformation loudly and clearly, we breed distrust. And, with distrust of science, medicine, public health, etc., people get hurt. As one of the current anti-vaxxers stated, the best way to disrupt public health is from within. This may be one of the few truths uttered by this disinformation purveyor. I never imagined that I would see the day when antivaxxers would be on public health boards, serve as state public health officials or even be proposed for political appointment to head or oversee our federal public health agencies. Most people do not understand the terrible threat this poses, and frankly, those threats will be in greatest part to our children and grandchildren and their successors, which is the most appalling thing about all of this, because we should protect those who cannot yet make decisions for themselves.
  13. I am old enough to have seen the amazing progress that modern science and medicine has made. I was in training when we were first seeing patients with HIV, but didn’t know what that was, and every patient, young adults for the most part, died, usually in a short amount of time. We now have patients living out long lives due to antiretroviral treatments, and, as of last year, we even have three patients cured of this disease and several in long-term remission. When I started practice, the majority of children died of acute leukemias; today, the majority of these children can be successfully treated and survive. We have more understanding of diseases, more treatment options, new technologies available to us, and research is coming up with more treatment options. I don’t want to go back, and I don’t want children to have to suffer from preventable illness. It is the children who suffer the greatest impacts of the antivaxx movement.

Okay, with that out of the way, let’s dive in.

I can’t possibly address all the lies and disinformation being spread out there, but let’s take some of the big ones, and then I may tackle some of the other ones in future blog posts. My objective is not going to be to give you a complete treatise, listing every reason and every scientific proof to show beyond a shadow of a doubt that every particular item of disinformation is completely false, but rather, show you the clearest and most convincing proofs that are easy to understand why the assertions made by those promoting disinformation are false. I would certainly hope that when I can convincingly prove that a number of the main points being spread are false, that would be enough for you to realize those persons spreading those lies should not be trusted with the other statements they are spreading.

  1. The COVID-19 vaccines are not vaccines.

This is a very common refrain from at least one doctor who promotes disinformation. When you hear this, you can be confident that the physician is purposefully trying to deceive you and manipulate you, because even antivaxxers don’t buy this argument, and certainly no reputable physician does. Any first-year medical student can tell you that a vaccine is a substance (usually a protein, a toxin, or a part or the whole of a pathogen [e.g., virus or bacterium] that is introduced by nasal spray, swallowing or injection, to stimulate a reaction from the immune system so as to prime the immune system to respond faster to a future exposure to that pathogen in order to prevent severe disease and death. Since the development of mRNA vaccines, the definition needed to be expanded to not require the direct introduction of the antigen (that substance that triggers an immune response), but to include the injection of mRNA that provides the code for cells to produce the protein (antigen) that will then in turn stimulate the immune response.

In other words, a vaccine, as opposed to antibiotics or other medications, trains the body’s immune system to be on the look-out for, respond faster, and attack a particular pathogen to minimize the harm if and when that person is exposed to that infectious pathogen. It is an advantage for the person to get a “sneak peek” to the future invader, to recognize it, and to be prepared in advance.

This is exactly what the currently authorized and approved COVID-19 vaccines in the U.S. do, although two of them utilize mRNA technology (Pfizer and Moderna) and one uses a long-used and traditional protein subunit technology (Novavax).

Those who try to promote the idea that COVID-19 vaccines are not vaccines often point to the fact that the vaccine does not always prevent infection, transmission of the infection to others and/or illness. However, this represents a lack of understanding of vaccines or intentional deceit, and would mean that the majority of vaccines (that they have acknowledged in the past are vaccines and in fact often have acknowledged that they and their families have received) are not vaccines.

Many vaccines – for example, the polio virus vaccines, RSV vaccines, rotavirus vaccines, influenza vaccines and COVID-19 vaccines – are intended to prevent people from getting seriously ill, ending up in the hospital or dying. They do not provide for “sterilizing immunity” – the prevention of infection and the onward transmission of infection to others, and frankly, most vaccines cannot achieve this much higher standard that disinformation purveyors want you to believe is characteristic, and in fact, a condition of being a vaccine.

Prevention of severe disease is a tremendous benefit of vaccines. It saves lives and it relieves the burdens on our health care infrastructure during times of high levels of community spread of that infection. However, if the vaccinated person does get infected, he or she will reproduce virus and can potentially spread the infection to others.

Sterilizing immunity generally requires the maintenance of high levels of neutralizing antibodies (these are antibodies that can attach to the virus to block its entry into cells) and these antibodies must be located in the tissues lining that part of the body in which the virus invades. This is difficult for any vaccine to achieve, and it is even more difficult when the virus is mutating, recombining or reassorting rapidly (these changes in the virus protein can cause conformational changes to the protein [change its shape or configuration] such that the antibody cannot bind as tightly or cannot attach at all), which occurred with the SARS-CoV-2 virus due to uncontrolled spread due to low levels of adoption of nonpharmaceutical measures and low vaccination rates (including lack of access to vaccines).

Bottom line: The COVID-19 vaccines are vaccines. Every study has shown an antibody response following vaccination in immunocompetent individuals. They use the spike protein of the SARS-CoV-2 virus (Novavax) or mRNA to instruct cells to produce spike protein (Pfizer and Moderna) in order to stimulate an immune response (development of antibodies, among other things) so that if the person is infected subsequently, the illness will be less severe and less likely to require hospitalization or result in death. That is a vaccine – you introduce a substance that induces an immune response that helps protect against severe disease.

  • The vaccine is not safe.

The current vaccines are safe and we know this because we monitor for adverse effects and hundreds of millions of doses of vaccine have been administered in the U.S. (that number was 676 million doses as of a year and a half ago). Safe does not mean there are no side effects. Injection site soreness, redness and mild symptoms are common to almost all injections whether vaccines or medications. Safe does also not mean that there are no adverse effects in certain individuals, even serious ones. If you review the package inserts of every prescription medication you can see that some people will experience adverse effects even with medications that we consider to be very safe. There is no over-the-counter medication or supplement that has not caused adverse effects in some people who take them (aspirin and acetaminophen (Tylenol) have caused death under certain circumstances). Safe means that adverse effects are infrequent, generally mild or resolve completely, and for serious adverse effects they are rare, not higher than the background rates in the general population, or they occur infrequently enough that a reasonable person would weigh the risks of the vaccine against the risks of severe disease and still opt to have the vaccine. Unfortunately, any vaccine or medication can cause harms and some people will be harmed. It is terrible for someone to be harmed when given something to try to help them, and efforts are made to make vaccines and medications as safe as possible. Anytime a vaccine is given or a medication prescribed the doctor and patient must weigh the benefits against the harms. Oftentimes, as with the COVID-19 vaccines, the potential harms with the vaccine are far less common and less serious than those same harms caused by actual infection (e.g., the risk of myocarditis).

  • Infections are good for us and help build healthy immune systems. Vaccines harm us.

Here is the truth in graphs:

Poliomyelitis:

Note that the graph below has a logarithmic scale, not linear.

It shows the number of cases (solid line) of poliomyelitis (this number is far less than the number of infections, because few infections result in poliomyelitis paralytic disease and other manifestations of polio that are recognizable) expressed as the rate of disease in the population per 100,000 people, and this is only the numbers for the United States. It also shows the number of deaths also expressed as a rate per 100,000 people (dotted line). It is dramatic to see the decline in number of cases and in the death rate following the introduction of polio vaccines (first, the injectable vaccine – IPV, and then the oral vaccine – OPV, which those of us my age will remember as the “sugar cube”). It was because of these vaccines that we eliminated polio from the U.S.

Smallpox

Smallpox in its usual form (accounting for approximately 90% of cases) had a case fatality rate of around 30 percent. About 5 percent of cases were of the flat form (instead of the more classic fluid-filled blisters) that was fatal in 97 percent of cases. A hemorrhagic form accounted for about 3 percent of cases and was universally fatal.

The smallpox vaccine was the earliest vaccine to be developed. In North America, through use of vaccination, smallpox was eliminated in 1952. It was finally eliminated in Africa in 1977, the last country in the world to achieve this goal and as a result, smallpox has now been eradicated across the globe, a remarkable achievement.

I could, of course, provide you with similar graphs of the reduction in number of cases and mortality rates due to vaccine-preventable diseases once those vaccines were developed and deployed, but for simplicity’s sake, here is some of that data in tabular form:

Effectiveness of Vaccination for some common Infectious Diseases in the U.S.

DiseaseMax. # Cases/Year# Cases in 2019
Diphtheria206,939 (1921)2
Measles894,134 (1941)1,192
Mumps152,209 (1968)3,780
Pertussis (whooping cough)265,269 (1934)18,617
Paralytic Polio21,269 (1952)0
Rubella (German measles)57,686 (1969)6
Tetanus1,560 (1923)26
Hemophilus influenzae type BApprox. 20,000 (1984)18
Hepatitis B26,611 (1985)3,563

Source: Basic Immunology, Abbas, Lichtman, and Pillai, Elsevier 7th ed., Figure 1.2, page 3.

Vaccines have been one of the most successful public health interventions. In the pre-vaccine era, roughly half of all newborns died before their first birthday, largely from vaccine-preventable diseases. In the most recent data, that 50% mortality rate pre-vaccines in the first year of life is now 0.56%. Infant Deaths Have Risen for the First Time in 20 Years – The New York Times.

The truth is that our immune system is an intricate and very complicated system that serves to protect us from infection. Many infections can threaten our health and our lives. Vaccines are a way to prepare our immune systems to successfully fight off infections that might otherwise cause hospitalization and even death.

Vaccines can cause adverse effects in some people, however, at a population level, vaccines have saved hundreds of millions of lives.

  • The COVID-19 vaccines were not effective.

The COVID-19 vaccines are in fact effective, and while I could provide mountains of evidence, I will just show you some data points that make this clear:

The above graph shows the effect of a COVID-19 booster in 2021 (this was the dose of vaccine given after the 2-dose priming series) on the cumulative incidence of COVID-19. Those who received the booster had a low number and relatively flat incidence of COVID-19, whereas those who did not receive the booster (received a placebo instead) had a steep increase in COVID-19 occurrences over the next three months.

As stated above, the primary purpose of the COVID-19 vaccines was to prevent severe disease. The vaccines were rolled out in 2021. Data from a six-month time period in 2021revealled that the average daily deaths per 100,000 people who tested positive for COVID-19 was 1.3 in unvaccinated individuals and only 0.1 in those who were vaccinated. Source: Basic Immunology, Abbas, Lichtman, and Pillai, Elsevier 7th ed., Figure 1.2, page 3. Further, throughout the time that the CDC reported hospitalizations and deaths from COVID-19 and compared those rates in patients who were unvaccinated versus those who were vaccinated, the rates in the unvaccinated were significantly higher.

The COVID-19 vaccines certainly can be improved upon, but it is clearly erroneous to state that they were not effective.

  • The COVID-19 vaccines are causing “turbo” cancers.

This is a wild and baseless claim that asserts that the mRNA vaccines are causing a surge in fast-growing cancers, a claim that one particular disinformation doctor made soon after the vaccines became available (which in of itself made no scientific, medical or pathophysiological sense) indicating that he had seen a 20-fold increase in the number of cancers in his practice, even though he never produced the evidence for the claim and no laboratory anywhere in the world other than his had reported an increase in cancer diagnoses. There are many reasons that this assertion is nonsense, and only intended to promote fear of the vaccines, but here are some key reasons why this is ridiculous:

  1. The disinformation purveyors have made no effort to account for confounding variables. To understand confounding variables, let’s take an example. Suppose that I conduct a study that attempts to correlate student grades on the final exam in a college biology course with the number of hours the students spent studying for the exam. What I find is that those students who studied the greatest number of hours actually received lower grades than those students who studied fewer hours. I might very well make an incorrect conclusion that the longer one studies for a biology exam, the worse they will perform. Of course, that could be true, if for example, the students that performed worse, stayed up all night, were sleep-deprived and as a result, unable to concentrate and focus on the exam, whereas those who studied fewer hours were better rested. But, on the other hand, perhaps the reason that these students studied more hours is that they were cramming for the exam, whereas the other students had been studying all semester-long. Or, it could be that students who studied less had taken biology courses in high school and came into the course with a greater fund of knowledge. This is why we emphasize that correlation does not necessarily mean causation.

So, what confounding variables do the doctors touting “turbo cancers” disregard? First, let’s take a look at Differences in cancer rates among adults born between 1920 and 1990 in the USA: an analysis of population-based cancer registry data – The Lancet Public Health. The authors of this study examined the cancer incidence for 34 types of cancer and mortality trends for 25 types of cancer, by birth cohorts in the U.S. from age 25 to 84 for the period January 1, 2000 to December 31, 2019 (this is prior to the first identification of cases of COVID-19 in the U.S., and the vaccines wouldn’t be available to any Americans until a year later).

The authors found that the incident rates increased with each successive birth cohort for eight of the 34 cancers. These investigators found that there was an increasing incidence of 17 of 34 cancers in younger birth cohorts, adding to the growing evidence of increased cancer of increased cancer risk in younger generations. Thus, cancer risk was already increasing among younger Americans before COVID-19 and certainly before COVID-19 vaccines were made available to the public. Thus, any credible assertion that cancer rates are increasing or “turbo cancers” are developing requires that data account for this already increasing cancer risk. The problem is that those who spread the disinformation of turbo cancers offer no data. In fact, laughably, one such purveyor of this vaccine nonsense simply asks the room for a show of hands as to how many people know someone who was unexpectedly diagnosed with cancer, and then exclaims, “wow!” But, we don’t collect data by anecdotes or a show of hands. I suspect that most people reading this blog knew of someone who developed cancer even before the pandemic began since cancer is very common and is a leading cause of death.

Further, even if these doctors had data to show a significant increase in cancers after vaccines became available, there would also be the confounding factor that the vaccines were introduced because we had a novel virus infecting and sickening many more Americans than those that received the vaccine. Currently, there are seven viruses known to contribute to the development of cancer – Epstein-Barr Virus (EBV), Human Papillomavirus (HPV), Hepatitis B and C viruses (HBV and HCV), Human T-cell lymphotropic virus-1 (HTLV-1), Human Herpesvirus-8 (HHV-8), and Merkel Cell Polyomavirus (MCPyV). https://pmc.ncbi.nlm.nih.gov/articles/PMC5742800/. On the other hand, no vaccine has ever been demonstrated to contribute to the development of cancer.  Thus, the burden rests with those trying to stoke fears about the COVID-19 vaccines to show evidence that it is the vaccines, rather than the SARS-CoV-2 contributing to the “turbo cancers” they assert are occurring, if in fact they have any evidence to support their claim of “turbo cancers.”

The attribution of any increase in cancers to vaccines has become even more difficult of a hurdle to meet because unlike the virus, for which there is accumulating evidence for possible persistence of virus, or at least viral proteins https://directorsblog.nih.gov/2024/10/31/many-people-with-long-covid-have-signs-of-persistent-sars-cov-2-proteins-new-findings-show/; all the evidence to date supports that the vaccine viral protein is cleared very promptly from the body. Thus, this presents even a greater challenge for those making the assertion of cancers due to the vaccines to explain why our long-standing concept that prolonged exposure (cigarette smoke, asbestos, and other carcinogens) is necessary for the development of cancer is wrong, and how a brief exposure to a substance could cause cancer and what animal model they can point to where that has ever been shown.

Without any data to support the notion of “turbo cancers,” without any accounting for the background rates of increasing cancer risk among younger Americans, without any explanation as to why if there was an unexpected increase it would be more likely due to the vaccines than to the infections themselves, without any explanation as to how a brief exposure to the spike protein in the vaccine would cause cancer but the much longer exposure to the virus proteins and in much greater amounts wouldn’t cause cancer, and with no experimental animal model to point to, these assertions can not be taken seriously and amount to complete fabrication by unethical doctors intent on stoking harmful and unjustified vaccine fears.

In closing, if you don’t want to get vaccinated, Godspeed. But, don’t let someone trick you and manipulate you into not protecting yourself and your family. Look at the facts and make an informed decision for yourself. But, if you don’t trust or want the COVID-19 vaccine, please don’t stop getting your children vaccines that have been used for decades, that we know are effective, and as you can clearly see for yourself have saved the lives of so many children.  

Other Sources:

  1. Plotkin’s Vaccines, Plotkin, Orenstein, Offit, and Edwards. 7th edition. Elsevier. 2018
  2. Pollard, A.J., Bijker, E.M. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol 21, 83–100 (2021). https://doi.org/10.1038/s41577-020-00479-7.
  3. Explaining how vaccines work. https://www.cdc.gov/vaccines/basics/explaining-how-vaccines-work.html.

Understanding Influenza – Part II

There are four types of influenza viruses – A, B, C and D. Types A and B are responsible for the annual influenza epidemics that occur in humans, and type A viruses are the only influenza viruses known to cause pandemics. The general requirement for an influenza virus to cause a pandemic is for the virus to be sufficiently different from prior circulating viruses such that there is little to no immunity in the population. Influenza C viruses cause such mild illness in humans that we rarely identify those infections and we do not consider influenza C viruses to pose a pandemic threat. Influenza D viruses primarily infect cattle and can spillover to other animals, but pose little threat to humans.

Influenza viruses are RNA viruses and thus are prone to replication errors and the accumulation of mutations. Under normal circumstances, these mutations are incremental and do not result in wholly antigenically distinct viruses (meaning that our immune systems would not recognize them). This is referred to as antigenic drift, and it happens frequently enough that we experience yearly epidemics during the flu season. Antigenic drift involves minor changes in the hemagglutinin (HA) and neuraminidase (NA) proteins of the circulating influenza A viruses, such that it is necessary for us to update the influenza vaccines every year, however, not so significant of changes that some degree of cross-reactive immunity would not exist or that a new subtype of virus would emerge (the latter developments would represent antigenic shift, as opposed to drift).

Subtypes of influenza A viruses are characterized by their hemagglutinin and neuraminidase protein characteristics. There are 18 known subtypes of hemagglutinin proteins that are represented by the letter H followed by a number (H1 – H18), and 11 known subtypes of neuraminidase proteins that are represented by the letter N followed by a number (N1 – N11). The subtypes of influenza A viruses are then described by the combination of the hemagglutinin and neuraminidase subtypes. The influenza A subtypes that contribute to our seasonally recurring flu seasons are H1N1 or A(H1N1) and H3N2 or A(H3N2).

All known influenza A subtypes exist in aquatic birds, which serves as the reservoir for influenza A viruses. These aquatic birds are migratory birds and they can carry and spread the virus along their flyways.

In wild ducks, these viruses replicate in the cells lining their gastrointestinal tracts, but do not make the ducks sick. The ducks excrete very high levels of the virus and can contaminate fresh water ponds, lakes and rivers, as well as land that they fly over or dwell on, which in turn often leads to infections of domestic birds and poultry. Large numbers of baby ducks are hatched each year, and they can be infected by virus in the water, and further contribute to the spread of the virus.

It is believed that all mammalian influenza viruses derive from the aquatic bird (avian) influenza reservoir, and phylogenetic analyses (the study of the evolution of genetic sequences) suggests that both swine and human influenza A viruses evolved from avian influenza viruses.

Besides accumulating mutations as a result of errors in transcription (the process of copying the virus’ genetic material during virus replication in order to make copies of the virus’ proteins, which in turn can be assembled into new virus progeny), influenza viruses can undergo the process of reassortment.

The diagram above shows one such example that lead to the H7N9 virus that infected humans in China back in 2013.

The influenza virus has eight genes coding for eight influenza A proteins (PA, PB1, PB2, nucleoprotein, hemagglutinin, neuraminidase, nuclear export protein and membrane protein. If a host is infected with two or more different influenza viruses, these viruses can exchange genes resulting in a new virus that has genes from more than one influenza virus. In the above example, the H7N9 virus got its hemagglutinin protein H7 from a domestic duck and its neuraminidase protein N9 from wild birds, while the other genes came from multiple H9N2 viruses in domestic poultry. The significance of this is that the new resulting virus can have much more antigenic variation from that of previously circulating influenza viruses (antigenic shift) and the new collection of proteins may confer biological changes to the virus that might result in enhanced transmission to humans, and even more concerningly, the capability for enhanced forward transmission (human-to-human spread).

The first human influenza virus was isolated in 1933. The largest influenza pandemic in just over 100 years was the Spanish flu pandemic of 1918 – 1919. That was an H1N1 virus, and there is evidence to suggest that it was an intact avian influenza virus (not the result of reassortment) that appeared in humans or swine before 1918 and then replaced the previously circulating strains when it caused the pandemic.

The Asian influenza virus (H2N2) replaced the 1918 H1N1 virus in 1957 when it caused a pandemic. The Hong Kong influenza virus (H3N2) appeared in 1968 when it sparked a pandemic, and then the H1N1 virus reappeared in 1977.

Sources

https://www.cdc.gov/flu/about/virusestypes.html#:~:text=Influenza%20A%20viruses%20are%20divided%20into%20subtypes%20based,%28H1%20through%20H18%20and%20N1%20through%20N11%2C%20respectively%29.

Influenza: An Emerging Disease. https://pmc.ncbi.nlm.nih.gov/articles/PMC2640312/.

More on my Update on Avian Influenza from yesterday

In my post last night on avian influenza, I mentioned a recently published article (yesterday) that I thought should give us pause about many of the assumptions being made about the current H5N1 outbreak in dairy cattle, and that should cause us to increase and improve our response to containing this outbreak. Today, we will review that study in greater detail.

That article – “A human isolate of bovine H5N1 is transmissible and lethal in animal models” https://www.nature.com/articles/s41586-024-08254-7 – was published in Nature on October 28, 2024.

In this study, the investigators examined the H5N1 virus circulating in dairy cattle that had infected a farm worker. This is very important because we need to know whether this was just an isolated occurrence that happened by chance related to the closeness of the farm worker and length of time working with these infected animals that represents a very low risk to the general population that is not at such occupational risk, or alternatively, whether the virus is evolving in such a way as to be able to more efficiently spread to humans, and even more concerning would be if the virus is developing more effective transmission from infected humans to their human close contacts. Thus far, we have seen no evidence of the latter, which would be the most concerning as to risk to the general population and as to pandemic potential.

Somewhat surprising (at least to me) was that the virus could grow well on human lung cells (alveolar epithelial cells), but it did not grow well in eye cells (corneal epithelial cells) – both cells have the receptor type used by avian influenza viruses [my surprise being in part because the most common presentation of infected farm workers has been conjunctivitis, an infection of the lining over the eye].

We don’t test these viruses on human subjects for ethical reasons, so animal models are used, including mice. However, ferrets are one of the best animal models because they most closely mirror influenza infections in humans, so they were used in this study, as well.

When directly infected with the virus recovered from the farm worker’s eye, the infection caused rapid and deadly infections in the mice and ferrets, in fact, all of the ferrets died. This tells me that we may very well be lulled into thinking that the current H5N1 only causes mild illness in humans since that is what we have observed in the 36 humans that are known to have been infected thus far. But we need to keep in mind that is likely only because it infected their eyes and not their lungs. Our upper airways have different receptors that are not amenable to H5N1 binding, so the virus is not finding a way to get to our lungs just yet. However, to me, this means we must contain the spread of this infection in cattle and other animals so that the virus does not continue to evolve in such a way as to be able to infect our upper airways and eventually our lungs.

Another very concerning finding was that the recovered H5N1 virus was able to spread (though not terribly efficiently) through the air 17 – 33% of the time from directly infected ferrets to healthy ferrets in a separate, but nearby cage in the same room. Five of the six infected ferrets who became infected from these respiratory droplets died. This is concerning because the USDA has been telling us that cow-to-cow and cattle-to-poultry transmission is likely occurring predominantly through fomites (virus on inanimate objects such as workers clothing or the equipment used to milk the cows) and not through respiratory means, and it is further concerning, because even though not highly transmissible through respiratory droplets, this represents an increase in transmissibility compared to prior strains of the bovine H5N1 virus.

We know from our prior studies of avian influenza viruses that while avian influenza viruses generally only cause sporadic infections in mammals, including humans, that a mutation named PB2-E627K (the PB2 is a designation for one of the H5N1 proteins, the E and K specify the amino acid substitution (lysine) that is present in the protein, and the 627 specifies the exact location in the amino acid sequence of the protein where the mutation occurs. This mutation has been known to increase transmissibility of avian influenza viruses in mammals, increase the polymerase (the enzyme necessary to replicate (make more of) the virus’ proteins) activity, and to increase virulence. Thus, there is concern that the H5N1 virus circulating cattle might be evolving to better infect mammals, including humans.

Another mutation was also observed – PB2-M631L. This mutation increased polymerase activity in human cells, and this is another concerning indicator of potential evolution of the virus to adapt to enhanced mammalian transmission.

Fortunately, the mutations have not resulted in resistance to all of our available antiviral medications for influenza A, although the virus has become less sensitive to the antiviral medication that has been our standard treatment for these patients.

My take-a-way from this research is that we are likely underestimating the risks of the current outbreak of H5N1 among dairy cattle in the U.S. both in terms of the potential for spread to humans and the risk for severe disease. This does not mean that either of these are imminent, but there is a progression of warning signs that I look for with any outbreak of a novel virus.

The threshold question is whether the virus is capable of infecting humans (the answer for H5N1 is yes) and is there already existing immunity in the population (likely no, although there is one study showing that people infected with the 2009 pandemic influenza A virus might have some degree of cross-reactive antibodies, but keep in mind that that particular pandemic did not cause a large proportion of the U.S. population to become infected, so this may not be a significant mitigating factor.)

The progression of risk factors in my mind then goes as follows:

Is there a large and sustained outbreak of the virus in its natural host (in the case of H5N1 that would be wild aquatic birds and ultimately domesticated birds and poultry)?  Yes

Next level of concern: Do humans have significant interactions with those natural hosts? Yes, with respect to poultry farm workers and those who cull flocks in which infection has occurred.

Next level of concern:  Have the infections extended to other animal species, especially mammals? Yes.

Next level of concern: Do humans have significant interactions with any of those species? Yes.

Next level of concern: Have there been any documented spillover (zoonotic) infections from infected animals to humans? Yes.

Next level of concern: Is the virus showing genetic evidence of evolution to more efficient transmission to humans? Yes.

Next level of concern: Is there evidence that the virus can be transmitted by respiratory droplets and/or aerosols? Possibly.

Next level of concern: Have any of the humans infected by animals infected other humans (in other words, is there evidence of onward human-to-human transmission)? Thus far, no.

So, I cannot predict whether this virus will cause an epidemic or pandemic in humans, but certainly, to me, the warning signs and risk factors have steadily been accumulating. This is the time to contain the spread of the infection, and frankly, we are failing to do so. The number of cattle herds infected continues to grow, the number of poultry flocks infected continues to grow, and we are detecting more human infections in the past few weeks than we did for the entire year up to then. We are failing to contain this epizootic (epidemic in animals) and if we don’t get serious about containing this outbreak, we do so at the potential peril to the entire world.

To elaborate on a point that I have made previously, as well as in yesterday’s blog post, this is also an increasingly dangerous time for us not to intervene aggressively. The reason is that our human seasonal influenza season is upon us. Soon we can expect to see many humans, and presumably those who work on farms with cattle, poultry and swine getting infected with our seasonal H1N1 and H3N2 viruses. With large numbers of cattle infected with H5N1, we now have the potential to infect those cattle with the human H1 and H3 viruses. We now know that infected cattle have very high levels of the H5 virus in their utters and that those utters have the cell receptor types needed for avian influenza viruses, as well as those needed for human influenza viruses. That means that cattle could be infected with both. That then increases the risk for a “reassortment” event.

Influenza viruses have eight segments of genetic material. When a host is infected with two different influenza viruses, the viruses can swap one or more of those eight segments. This results in a reassortment – an influenza virus with some genetic material from the avian virus and some genetic material from the human virus. This can result in changes to the intrinsic properties of the virus and could result in increase transmissibility, infectiousness, virulence and/or an enhanced ability for the virus to transmit from humans to other humans. This has been at play in at least three prior influenza pandemics. It is especially of concern because, as we have seen in trying to identify cases of avian influenza infections in farm workers, many workers do not seek medical attention when ill because they may not have health benefits, but even more often, they are concerned that missing work will result in loss of pay or even loss of their jobs. Conversely, as we get to this flu season and need to reduce the risk that infected farm workers with seasonal influenza will transmit those viruses to animals, we will be undermined by the same challenges that will result in workers working even while sick. To address this would require symptomatic screening of workers, rapid testing, and isolation of those who have influenza, but this would be a huge challenge without cooperation from farmers, and likely significant incentives from the government.

Thus, it is imperative that we increase testing to identify infected animals and humans, increase the genetic surveillance of the virus to detect these genetic changes that may increase these risks, increase testing of close contacts to ensure that we are not seeing human-to-human transmission, increase containment efforts of infections within and between herds, increase the availability of testing to health care providers because it may be difficult to distinguish an avian influenza infection from the human seasonal influenza that we see at this time of the year, increase the cooperation of farmers, and increase our research into effective vaccines and antivirals.

Update on Avian Influenza (H5N1) Outbreak in US.

In my last update, I expressed concern that something has changed (for the worse) with this virus. We were seeing a change in virulence to cattle in California with prior reports of case fatality rates in infected dairy cattle being 1 – 2%, but in California herds, the case fatality rates were being reported in the press as 10 – 15%. Further, while we were told that prior to the identification of the California outbreaks, symptomatically ill cattle seemed to be recovering within about a week, we were now seeing evidence in California herds that it was taking several weeks for recovery of those that survived.

In the latest update from the CDC, H5 Bird Flu: Current Situation | Bird Flu | CDC, it states:

While the current public health risk is low, CDC is watching the situation carefully and working with states to monitor people with animal exposures.

CDC is using its flu surveillance systems to monitor for H5 bird flu activity in people.

Both the USDA and the CDC have commented as to how the H5N1 virus is spreading. The USDA provides:

HPAI (HPAI stands for highly pathogenic avian influenza) is a very contagious and often deadly respiratory disease of poultry, such as chickens, turkeys, and geese. It is often spread by wild birds and can make other animals sick, too. It’s a major threat to the poultry industry, animal health, trade, and the economy worldwide. Caused by influenza type A viruses, the disease varies in severity depending on the strain and species affected. 

HPAI H5N1 (this is now a reference to the specific avian virus that is spreading in dairy cattle in the US) viral infection was first confirmed on a dairy premises on March 25, 2024. USDA, in coordination with States, took immediate action to conduct additional testing for HPAI, as well as viral genome sequencing, to learn more about the virus and how it was spreading among dairy cattle. USDA and State teams conducted extensive epidemiological work to investigate the links between HPAI-affected dairy premises and evidence of spillover into poultry premises.

Continued disease transmission regionally within the country is due to several factors. In addition to the movement of livestock, transmission between farms is likely related to normal business operations such as numerous people, vehicles, and other farm equipment frequently moving on and off an affected premises and on to other premises. Importantly, it is not currently believed that the disease is spread onto dairy or poultry premises by migratory waterfowl—this is supported by both genomic and epidemiological data analysis.

The CDC provides the following graphic to describe routes of transmission to various species:

But, as you can see for yourself, this leaves many questions unanswered, as to how the virus is spreading within herds and how people are infected by cattle. Further, while both agencies emphasize that no human-to-human spread of H5N1 has been detected (a true statement), many of us feel that the CDC has not done enough testing to assure us this is the case.

There is one troubling case of note. A patient in Missouri in August of this year with a chronic respiratory illness was admitted to the hospital with gastrointestinal symptoms. Testing was positive for influenza A and the CDC confirmed that the patient had H5N1. The patient had no history of exposure to infected humans or animals and we are told that the patient had not ingested raw (unpasteurized) milk. The epidemiological investigation revealed that seven persons (1 family member and 6 health care workers) had symptoms that warranted investigation given their exposure to this patient. Five of the six health care workers were tested by serology (testing for antibodies to the H5N1 virus that would provide evidence of prior infection) and all tested negative, suggesting that their symptoms were due to something other than infection with the H5N1 virus. Several different tests were conducted on the index patient (the patient who was hospitalized and first identified as having H5N1 infection) and the household contact. Testing results of the sera from the index case and their household contact were similar: both showed evidence of an antibody immune response to H5 in only one assay (that detects H5 neutralizing antibodies), but not on the other serologic assays used to detect infection. The CDC interprets the results as follows:

The weak immune signal suggests that it is possible that both of these people may have been exposed to H5 bird flu despite the fact that they did not meet accepted thresholds for seropositivity. These similar immunologic results coupled with the epidemiologic data that these two individuals had identical symptom onset dates support a single common exposure to bird flu rather than person-to-person spread within the household. Intensive epidemiologic investigation has not identified an exposure to an animal or animal product exposure to explain these possible infections, and these serologic data cannot further elucidate the exposure leading to these possible infections.

While I personally think that there likely is little or no human-to-human spread, neither agency has advised us of the plan to ensure that remains the case, particularly as we prepare to enter the human influenza season with the risk of transmission of human influenza viruses to cattle and the risk for reassortments that might result in an avian influenza virus with more efficient transmission to and between humans. Further the failure to contain the spread of the virus among cattle after 7 months is not reassuring most of us that the response to this event is as vigorous as it needs to be. Poultry outbreaks have been identified in 48 states, and 14 states have outbreaks among dairy herds.

Finally, the CDC is reporting 36 human infections thus far this year, but my concern is that more than half of these were just detected in the past 2 – 3 weeks coincident with the changes that we have noted in the virus virulence among cattle. Further, many of us following this matter closely strongly suspect that many infections have gone undetected and that there still is not adequate testing being done. We do know that there are more cases awaiting confirmation that will likely be added to this tally of human infections. The Seattle Times reported on Friday that

the number of workers at a Franklin County commercial egg farm who have now tested positive for bird flu has increased to eight, according to preliminary test results.

These are the first known human cases of H5N1 in the state of Washington. If these are confirmed, this will bring the total of human infections to 23 just from this month. Fortunately, all cases thus far have been considered to be “mild.”

KFF Health News on Friday reporters cannot determine why we are seeing this spike in cases, because surveillance in humans “has been patchy for seven months.”

KFF Health News obtained hundreds of emails from state and local health departments through an open records request. They report:

Despite health officials’ arduous efforts to track human infections, surveillance is marred by delays, inconsistencies, and blind spots.

Several documents reflect a breakdown in communication with a subset of farm owners who don’t want themselves or their employees monitored for signs of bird flu.

Other emails hint that cases on dairy farms were missed.

Researchers worldwide are increasingly concerned.

“I have been distressed and depressed by the lack of epidemiologic data and the lack of surveillance,” said Nicole Lurie, formerly the assistant secretary for preparedness and response in the Obama administration.

Maria Van Kerkhove, head of the emerging diseases unit at the World Health Organization, said, “We need to see more systemic, strategic testing of humans.”

Contributing to the problem are (1) the fact that the USDA cannot force dairies or poultry farms to cooperate, (2) it has been reported that some veterinarians have been threatened by some farmers with loss of their employment if they report the illnesses, (3) many of the workers have no health insurance and/or lack the ability to take time off to see a doctor without loss of pay and possibly even their jobs, and (4) the CDC cannot come in to investigate unless invited by the involved state. Additionally, many local health departments are underfunded and understaffed to be able to conduct the investigations thoroughly.

Personally, I fear that there is also a sense of complacency given that no human-to-human transmission has been documented thus far and that the illnesses have so far been mild. But, if we allow this spread to continue, that could change over night.

A newly published article indicates that the H5N1 influenza virus obtained from an infected worker was capable of being transmitted through respiratory droplets in a high-containment laboratory environment to mice and ferrets (influenza infections in ferrets more closely resemble human influenza infections than those in mice), and that the infection in the ferrets that were directly inoculated with the virus was 100% lethal, in contrast to studies with prior bovine H5N1 virus, which caused severe disease in ferrets, but limited mortality. Further, the investigators determined that the virus may be capable of binding to and replicating in human respiratory tract cells. The isolated virus has the mutation PB2-E627K, known to increase the efficiency of transmission of avian influenza viruses in mammalian species. This study suggests that we need to carefully monitor this situation, be careful before concluding that there is no respiratory droplet transmission, and be alert for the potential of this virus to cause severe disease in humans.

Finally, many of us remain concerned that there simply is not enough transparency by both the USDA and the CDC.

I do not know whether H5N1 will eventually spark a new pandemic, but I know that if you were watching a pandemic unfold before our very eyes, which we almost never do, this is the progression of evolution that you might expect to see.

Understanding Influenza – Part I

How Does the CDC conduct influenza surveillance?

Are we seeing an increase in influenza activity yet?

Is it time to get my flu shot?

How Does the CDC conduct influenza surveillance?

First, there is virologic surveillance, i.e., testing by a network of laboratories for the influenza virus and reporting to the CDC of those results. This network of laboratories consists of the U.S. World Health Organization (WHO) Collaborating Laboratories System and the National Respiratory and Enteric Virus Surveillance System (NREVSS). Together, this accounts for approximately 100 public health and approximately 300 clinical laboratories located throughout all 50 states, Puerto Rico, Guam, and the District of Columbia that participate in virologic surveillance for influenza throughout the year.

The public health laboratories primarily help determine the specific strains of influenza virus in circulation (A and B) and for influenza A the subtypes and for influenza B the lineages, while the clinical laboratories provide the CDC with data as to the timing of increases and decreases in seasonal influenza activity and the amount of influenza activity. Both kinds of laboratories report the age of the person who was tested, if known, so that the CDC can also track and report influenza activity by age group (0-4 years, 5-24 years, 25-64 years, and ≥65 years).

In addition, the state and public health laboratories send samples of the influenza A and B viruses they identify so that the CDC can do further genetic and antigenic analysis of the viruses to determine how closely they are aligned to the viruses used in preparation of that season’s flu vaccine, as well as to identify how the viruses are evolving, as they continually are doing so.

Another use of these samples is for the CDC to test the ongoing effectiveness of our antiviral treatment options in order for the CDC to advise physicians if the virus is developing resistance to one or more of our treatment options.

Human seasonal influenza A viruses are of the H1 or H3 type (in my prior posts, I have explained that we often refer to specific influenza A viruses by the antigenic characterization of their two primary proteins – neuraminidase and hemagglutinin, which results in a designation of H_N_, where the blanks are filled in with a number that correlates to the specific antigen identification. For our seasonal influenza outbreaks, we expect to see influenza A viruses of the H1N1 and the H3N2 types. Thus, an additional goal of antigenic characterization of circulating influenza A viruses is to identify any novel viruses (e.g., an H5, H7 or H9 virus) that might emerge such as swine or avian influenza A viruses that might have pandemic potential (in large part because there would not be preexisting population immunity) so that public health measures can be put in place as early as possible. The avian (bird) influenza virus currently circulating in dairy cattle is of the H5N1 type.

The second component to the surveillance system is outpatient illness monitoring. Data on outpatient visits to health care providers for respiratory illness [fever (temperature of 100°F [37.8°C] or greater) and a cough and/or a sore throat] referred to as influenza-like illness (ILI) is collected through the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet). ILINet consists of outpatient healthcare providers in all 50 states, Puerto Rico, the District of Columbia, and the U.S. Virgin Islands. These providers also report the total number of visits so that the CDC can monitor for increases or decreases in the percentage of visits for influenza-like illness. Note that this surveillance component is not specific for influenza, since it does not require confirmatory testing to validate that the respiratory illness is caused by influenza; nevertheless, this has proved to be a valuable indicator for the onset and scale of illness during the respiratory virus season. We consider an increase in influenza-like illnesses to be occurring when visits for ILI are >2.9% nationally for a reporting week. For Idaho (Region 10), the CDC considers an increase to be occurring when these visits account for more than 1.9% of visits (due to a lower baseline level of influenza compared to nationally).

The CDC then assigns one of 13 levels of influenza activity for each reporting week in comparison to the mean level during non-seasonal weeks. Activity levels are classified as minimal (levels 1-3), low (levels 4-5), moderate (levels 6-7), high (levels 8-10), and very high (levels 11-13). An activity level of 1 corresponds to an ILI percentage below the mean, level 2 corresponds to an ILI percentage less than 1 standard deviation above the mean, level 3 corresponds to an ILI percentage more than 1 but less than 2 standard deviations above the mean, and so on, with an activity level of 10 corresponding to an ILI percentage 8 to 11 standard deviations above the mean. The very high levels correspond to an ILI percentage 12 to 15 standard deviations above the mean for level 11, 16 to 19 standard deviations above the mean for level 12, and 20 or more standard deviations above the mean for level 13.

The third part of the surveillance system is the hospitalization monitoring. Laboratory-confirmed influenza-associated hospitalizations are monitored through the Influenza Hospitalization Surveillance Network (FluSurv-NET). The current network of hospitals covers over 90 counties or county equivalents in the 10 Emerging Infections Program (EIP) states (CA, CO, CT, GA, MD, MN, NM, NY, OR, and TN) and four additional states through the Influenza Hospitalization Surveillance Project (MI, NC, OH, and UT). The network represents approximately 9% of US population (~30 million people). New hospital admissions are defined as patients who were admitted to an inpatient bed on the previous calendar day and had a positive influenza test at admission or during the 14 days prior. Laboratory confirmation includes detection of influenza virus infection through molecular tests (e.g., polymerase chain reaction [PCR], nucleic acid amplification [NAAT]), antigen detection tests, immunofluorescence tests, and virus culture. 

During the COVID-19 pandemic, all hospitals were required to report COVID-19 and influenza information on laboratory testing, capacity and utilization, and patient flows to facilitate the public health response to the pandemic. As of December 15, 2022, these data are required to be reported to CDC’s National Healthcare Safety Network (NHSN), which monitors national and local trends in healthcare system stress, capacity, and community disease levels for approximately 6,000 hospitals in the United States.

The final component of the surveillance system is mortality monitoring. The National Center for Health Statistics (NCHS) collects death certificate data from state vital statistics offices for all deaths occurring in the United States. Deaths included in this component of the U.S. Influenza Surveillance System are those which are classified based on the various ICD-10 (this is the set of codes that doctors and hospitals use to characterize a patients’ illness) codes used to for cause of death such as those associated with influenza. Data are aggregated by the week of death occurrence. 

Pediatric influenza-associated deaths are also tracked. For surveillance purposes, an influenza-associated pediatric death is defined as a death in a person less than 18 years of age, resulting from a clinically compatible illness that was confirmed to be influenza by an appropriate laboratory diagnostic test. There should be no period of complete recovery between the illness and death. 

Together, all of these components of influenza surveillance give us a general understanding of when the flu season is beginning, when it is ending, how much transmission we are seeing and how severe the season seems to be.

The beginning of the annual “Flu season” — as determined by elevated flu activity – varies from season to season. During most seasons, activity begins to increase in October, most often peaks between December and February and can remain elevated into May. The flu season is said to have started after consecutive weeks of elevated flu activity are registered in the various CDC influenza surveillance systems.

It can be very confusing for the uninitiated as to how to identify specific dates of the influenza season reporting because the reporting period for each influenza season begins during Morbidity and Mortality Weekly Report (MMWR) week 40 and ends week 39 of the following year.

Text Box: If you are dying to know how to number the weeks or translate the numbered weeks to dates, here is how it is done: The first day of any MMWR week is Sunday. MMWR week numbering is sequential beginning with 1 and increases with each week to a maximum of 52 or 53. MMWR week #1 of an MMWR year is the first week of the year that has at least four days in the calendar year. For example, if January 1 occurs on a Sunday, Monday, Tuesday or Wednesday, the calendar week that includes January 1 would be MMWR week #1. If January 1 falls on Thursday, Friday or Saturday, the calendar week of January 1 would be included as the last week of the prior MMWR year (week #52 or #53).

Are we seeing an increase in influenza activity yet?

The short answer is no. We have data as of week 42 (the third week of flu season reporting)

From the virologic surveillance standpoint, the percent positivity for influenza testing is only 0.7% from the reporting clinical laboratories and remaining stable. (This means that of those presenting with influenza-like illnesses for which diagnostic testing was performed, less than 1 percent of the tests are returning positive for influenza.) The public health labs have identified that two influenza A strains are predominantly circulating – influenza A(H1N1)pdm2009 (we’ll discuss this in greater detail in subsequent blog posts, but basically, this is the designation for the current influenza A virus that has the antigenic designation of H1N1 based upon the two main proteins [H for hemagglutinin and N for neuraminidase]and the pdm2009 indicates that this particular strain is a descendent of the 2009 pandemic strain) and influenza A(H3N2) (which is also an influenza A virus, but with different proteins (H3 and N2). Both of these viruses are included in this year’s seasonal flu vaccine.

Influenza-like illness surveillance also reflects low activity. Currently, only 2.1% of visits are for influenza-like illness, and this rate is not on the increase, so we have not yet seen an increase over baseline.

Further, weekly hospitalizations for influenza-associated illness are very low at 0.1 per 100,000 people.

Finally, influenza-associated mortality is also low currently (0.05%), meaning that 0.05% of all reported deaths for that week were attributed to influenza. Fortunately, none of those deaths were in children less than age 18.

As expected, the majority of influenza viruses identified that are currently circulating are A, but there were some B viruses isolated, and all of these are of the Victoria lineage. We previously had influenza B/Yamagata circulating until it appears to have been eliminated with the respiratory precautions taken early in the COVID-19 pandemic, though we can’t rule out its eventual return just yet.

Is it time to get your flu shot?

Not unless you are travelling internationally or you have an opportunity to get your shot now and know that if you don’t get it now, you won’t.

On the other hand, if you are willing to wait a bit and know that you can go in and get your shot with little notice, it may be advisable to wait until we see that increase because the flu vaccine effectiveness does wane a bit each month, and as mentioned above, the flu activity often peaks between December and February and can remain at elevated levels through May, so we want to have people maximally protected at the end of this year and beginning of next, as well as some protection persisting through the spring.

Additional Update on the Marburg Virus Disease Outbreak

Be sure to read my update from this weekend on the Marburg virus disease outbreak in Rwanda.

The Ministry of Health of Rwanda has updated its outbreak numbers today. The total number of confirmed cases is now 56, an increase of seven new cases over the weekend. Thirty-six patients are in isolation and receiving treatment. Fortunately, there are no new deaths, so the death count remains at 12. Thus far, only 8 patients have recovered from the disease. This outbreak is the third largest outbreak of Marburg virus disease ever reported anywhere in the world.

Today, the U.S. Department of Health & Human Services announced (https://www.hhs.gov/about/news/2024/10/07/fact-sheet-hhs-actions-to-support-response-marburg-outbreak-in-rwanda.html) that the CDC will begin “public health entry” screening of travelers to the U.S. who have been in Rwanda in the past 21 days. HHS states that “This screening aims to reduce the risk of importation of Marburg cases into the United States and the spread within U.S. communities,” however, it does not elaborate on what this screening would entail.

The track record for airport screenings to keep infected persons out of the U.S. has not been good. My co-author and I write about why this strategy failed early on in the COVID-19 pandemic in our book, “Preparing for the Next Global Outbreak” https://www.press.jhu.edu/books/title/12896/preparing-next-global-outbreak. Nevertheless, overall, I am pleased with the U.S. response to this current outbreak, and I believe that the Ministry of Health for Rwanda has also responded very well to this outbreak.

Marburg Virus Disease Outbreak Update

I have previously written about the Marburg virus, the timeline and history of outbreaks, and the recent outbreak in Rwanda. This is an update. Marburg virus is one of the deadliest viruses known to infect humans. Much of the background information below comes from “Key information about Rwanda’s deadly Marburg outbreak is still missing” https://www.science.org/content/article/key-information-about-rwanda-s-deadly-marburg-outbreak-still-missing.

This is the first outbreak of Marburg virus disease in Rwanda. It was announced on September 27, 2024 after the virus was detected in a blood specimen the day before. It is common for infectious disease outbreaks in African countries to be dismissed as inconsequential to those living in the U.S. But, time and time again, history should have taught us that this is flawed thinking. Human immunodeficiency virus, Ebola virus, and Monkeypox virus are just three viruses off the top of my head that first began as isolated outbreaks in Africa, but then caused disease to appear in the United States, with HIV and MPox being the largest in scale. In large part, this is due to the large amount of international travel and the long incubation periods of these viruses.

Instead, what we should have learned is that Africa is a great laboratory for us to learn about emerging pathogens (to give credit to the CDC, we do have CDC workers stationed in Africa) and that even if we don’t do it for altruistic reasons, researching these organisms, developing therapeutics and vaccines, and assisting Africa to contain these outbreaks is in our best interest to avoid the much more difficult and expensive undertaking of containing disease outbreaks in the U.S. and the rest of the world.

We refer to the first known case of an outbreak as the “index” case. Identifying the index case of a novel or rare virus infection, especially when the infection transmission is zoonotic (transmitted from an animal to the human), when possible is extremely helpful because the epidemiological links are fewer with a greater opportunity to discover when the first infection likely occurred and what the potential sources of that infection were.

In the case of this outbreak, we have little information about the index case, but we have some. First, it was an adult male. Second, he died from the infection on September 8. Third, the wife did not become infected after observation for a full incubation period (up to 21 days).

Piecing together information from reliable, but unofficial sources, we learn that the index case had traveled in Rwanda prior to falling ill. He was treated at King Faisal Hospital in Kigali (a very good hospital, especially for these tropical diseases). He actually (as have been several other subsequent cases) was co-infected with malaria and Marburg virus. Doctors diagnosed the malaria, which they commonly see, but did not realize that he also was infected with the Marburg virus as this virus had never been detected in Rwanda before and early signs and symptoms of these two infections overlap, thus, the malaria diagnosis appeared to explain the index case’s illness.

It was only after several health care workers from the hospital’s intensive care unit became ill that the concern for a spreading hemorrhagic fever illness grew (malaria is not transmitted from human-to-human). Tests subsequently confirmed that the index patient had Marburg virus disease (MVD).

Most of the cases in this outbreak are in health care workers. Infected health care workers likely also infected more health care workers. It is possible that some people were been exposed to the virus from contact with the dead body of the index case and at the funeral.

Concerningly, there are some infected in this outbreak who have not been able to be traced to another known infected person. That suggests that some cases of infection have likely been missed.

Health care workers are at especially high risk for transmission of this virus from infected patients because they may be in close contact with the patient’s secretions (saliva, vomitus, blood, urine, stool, sweat) before the diagnosis is made and appropriate precautions are in place. Additionally, as patients become more ill, the amount of virus increases in the blood, further increasing the risk of transmission to those caring for the patient if proper precautions and personal protective equipment are not in use.

To my knowledge, we still do not have the sequencing of the recovered virus samples to determine which strain of Marburg virus this is and to determine whether this outbreak is the result of a single spillover event or multiple ones. Answering the question as to which strain this is is important because the mortality rates are different, the response to monoclonal antibodies are different, and the effectiveness of our current experimental vaccines appears to be different.

As of yesterday, the Republic of Rwanda Ministry of Health has reported that the outbreak has resulted in 46 confirmed cases with 12 deaths. Five people have recovered from the infection, while 29 people are still in isolation and being treated.

The U.S. has sent investigational vaccines (the Sabin chAd-3 vaccine which is in phase 2 trials) and monoclonal antibodies (MappBio’s MBP-091 mAb) (well, maybe we are learning the lessons from history!) to Rwanda on condition that the country conduct clinical trials to establish their safety and effectiveness. There are currently no licensed vaccines or therapeutics to prevent or treat this disease.

No cases have been identified in the U.S. or other countries outside of the continent of Africa, however, the WHO does note in its most recent situation update https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON537 that due to the outbreak involving the capital of Rwanda that has an international airport, the potential for travelers to be infected while in Rwanda, but then manifest their disease in another country due to the long incubation period is a possibility. The CDC also sent out a health alert (https://emergency.cdc.gov/han/2024/han00517.asp) to U.S. physicians last Thursday. (I applaud the CDC for this. Many of us recall the case of Ebolavirus disease that appeared in a Dallas emergency room following travel from Africa that resulted in the infection of two nurses there, who fortunately survived their illness.

Avian Influenza Update

I have written before about our country’s lethargic public health response (with notable exceptions for the states of California, Colorado and Michigan) to the A(H5N1) avian influenza outbreak among U.S. poultry and dairy farms, and some of the developments that should be increasing our concern for the potential of this epizootic (epidemic in animals) to develop into an epidemic or pandemic among humans. In brief summary of these concerning developments, we start with the fact that we are dealing with a novel influenza virus for which there is little to no existing population immunity and that avian influenzas have already demonstrated their ability to contribute to the development of human pandemics (1918, 1957, and 1968) and have been recognized by public health authorities to be viruses with pandemic potential for decades. The outbreak of H5N1 among many animal (both land and marine mammals) species over the past two years is unprecedented, whereas in the past, few mammalian species have been known to be infected and those infections were sporadic and incidental in nature. Then, this year, for the first time, we have an outbreak occurring in dairy cattle, and that outbreak has been sustained, growing and unable to be contained with the current measures put in place by the USDA and CDC. Of even greater concern is that there have been an unprecedented number of infections in dairy and poultry workers in the U.S. Finally, the concerns heightened even more when a person in Missouri was diagnosed as infected with H5N1 who had no occupational work exposure to likely animals, no ingestion of raw milk or dairy products and no other risk factors for exposure, raising the concerning potential that there might be community spread.

New developments are again increasing concern that this virus is changing in concerning ways.

For much of the past six months, there were no known dairy herd infections in California. They were only recently discovered and the number of herds infected in California has now grown to 56. However, reports coming out of California describe a far more virulent infection in the cattle. Until now, we have had few details about the percentage of cattle in herds infected (according to the article it has previously been estimated to be about 10 percent of the herd), and we have been led to believe that most cattle were recovering from the infection with few deaths among the cattle. The LA Times is now reporting that although farmers were told to expect less than 2 percent mortality for infected cattle, preliminary reports suggest that 10 – 15 percent of the infected cows in the California outbreaks are dying. A veterinarian described the infected cows as appearing much more clinically ill than the descriptions we have been provided with in the past outbreaks, though he qualified that the abnormally high temperatures may be playing a role. He also indicated that many of the deaths were due to complications such as pneumonia or bloat. He also described that many of the cattle stop eating during the illness. As a consequence, the digestive tract doesn’t empty well, and in turn, the cattle can suffocate form the increased pressure on their diaphragm.

Another change appears to be in the duration of illness. We were previously led to believe that the infections in other states resulted in a week-long, or perhaps two, of mild illness. Now cattle are often sick for several weeks. This veterinarian estimates that as much as 50 – 60 percent of the cattle in the herds with these outbreaks are clinically ill. And, while we were led to believe that recovered cattle seemed to be completely recovered in other states, this veterinarian stated that the recovered cattle seemed to only recover about 60 – 70 percent of their milk production. https://www.latimes.com/environment/story/2024-10-04/bird-flu-deaths-increasing-among-california-dairy-cows.

To add to the concerns, three new human infections of H5N1 (suspected, but awaiting confirmatory testing) were detected this past week in California (the first two were reported on Friday and the third was reported today) – all in dairy workers with direct contact with cattle. None of these three had any contact with each other, so these were three separate spillovers. All thee had conjunctivitis (pink eye), with one worker having reported splashing of milk in his or her eye.

These developments could be in part explained by the fact that California has seemed to be much more aggressive and transparent in their response to these outbreaks, but many of us have an unsettledness that something has changed with the virus given that 3 human infections have been detected in just the past week (prior to this, there have only been 14 human cases detected this year across the entire country) and that the clinical severity in cattle appears to have changed significantly. Our main concern is whether the virus is adopting through mutations and reassortments an increased ability to infect humans and ultimately, the biggest concern would be for the virus to acquire increased efficiency in human-to-human transmission, which until the Missouri case, has seemed to be a remote possibility. And, a number of us are concerned for the upcoming human influenza season and the potential that dairy workers could transmit human seasonal influenza virus (H1 or H3) to cattle while there already appears to be such high levels of H5N1 infection in cattle that could result in co-infections that could facilitate reassortments (swapping of one or more of the eight genetic segments in influenza viruses) allowing the H5 virus to acquire genetic material from the human seasonal virus that would in turn give the H5 virus increased efficiency in human transmission.

We need much more testing, we need testing that does not have to be sent to the CDC in Atlanta and can be done with a faster turnaround time, we need genetic sequences for comparison to see if the virus has picked up mutations associated with enhanced mammalian spread, we need a reliable serological test so that we can assess the degree of spread among cattle and among workers and their close contacts, we need studies that help us understand the transmission modes of the virus, we need research to be done on vaccines against H5N1 and a we need more antiviral options for treatment, especially in the event of the development of oseltamivir resistance. In a nutshell, we need to shake off the sense of complacency, develop some greater sense of urgency, increase the transparency from USDA and CDC, engage academic and commercial laboratories in the development of faster and cheaper tests that can be more accessible, devote funding for research, make more serious and intensified efforts at containment of the spread of the virus, and we need a plan to minimize the risks of human-to-cattle spread of the upcoming seasonal influenza viruses.

Mpox Update

There is good news and bad news. I’m a glass half-full kind of guy, so let’s start with the good news.

But, first, a situation update from the World Health Organization (WHO) though this includes data only up through 9/22/24 (Multi-country outbreak of mpox, External situation report #38 – 28 September 2024 (who.int)). A large outbreak of Mpox has been taking place in 15 African countries, particularly in the Democratic Republic of Congo (DRC), Burundi, and Nigeria with more than 30,000 suspected cases so far just for 2024, but it is likely the number is far higher.

There are two clades (strains) of Monkeypox virus contributing to the current outbreak – clade IIb (newly recognized at that time) that previously spread globally to at least 123 countries beginning in May of 2022 and was declared a Public Health Emergency of International Concern (PHEIC) at that time, but was brought under relative control a year later, at which time the PHEIC was terminated. While clade IIa, the ancestor clade had a mortality rate in African outbreaks on the order of 1 percent, the case fatality rate for clade IIb globally was fortunately only about 0.2 percent. Whether the virus evolution to a more transmissible clade IIb involved a trade-off in virulence, or whether the reduction in mortality was related to better access and better health care systems outside of Africa, or both, is not currently known.

Clade IIb has been noted to be primarily affecting and spread by men who have sex with men. For reasons that are not totally understood, this year has seen an uptick in clade IIb cases again. Then, earlier this year, a new clade Ib emerged, which has spread outside of the DRC to neighboring countries that had not previously had Mpox cases, and it is believed that, in part, to have occurred through heterosexual sex workers. However, clade Ib has disproportionately affected young children (not seen with clade IIb) and has caused high morbidity and mortality in children, raising concern transmission may also be occurring through direct contact with infected animals and through close contact with infected adults. While the case fatality rate for clade Ia, the ancestor to this new clade, ranged between 4 and 10 percent, the case fatality rate for suspected cases this year (a mix of clade Ib and IIb, but probably dominated by the large increase in Ib) is almost 2.7 percent.

The Mpox outbreak continues to grow in each African country that has detected cases. Guinea just reported its first case after Gabon had recently reported its first case. Clade II cases have been detected in all six WHO regions of the world. The U.S. has reported 113 cases in 2024 through August. Fortunately, confirmed cases of clade 1b have only been reported in three countries outside of Africa thus far, all in travelers to Africa, except for the most recent case who is reported to have only traveled to the UAE.

On to the good news. First, yesterday, the WHO approved the first diagnostic test for the monkeypox virus for emergency use (https://news.un.org/en/story/2024/10/1155351).  The newly approved test is the Alinity m MPXV assay and this is a real-time PCR (polymerase chain reaction) test that enables detection of monkeypox virus DNA from human skin lesion swabs.  The test is made by Abbott Molecular, a U.S. company. While this is a tremendous advancement in our ability to diagnose MPox cases, this test will still require being performed in clinical laboratories with trained laboratory technicians (as opposed to point-of-care testing that can be done at home or in a doctor’s office).

Prompt diagnosis is important in isolating infected patients and minimizing further spread to those in close contact with the infected patient.

The second piece of good news is that vaccines have arrived in Africa (finally!) and immunizations began today in the DRC in the North Kivu province, beginning with high-risk persons (including health care workers, first responders, and close contacts of infected persons). On September 13, WHO announced the MVA-BN (Modified vaccinia Ankara – Bavarian Nordic) vaccine as the first vaccine against mpox to be added to its prequalification list https://www.who.int/news/item/13-09-2024-who-prequalifies-the-first-vaccine-against-mpox.

MVA-BN is a highly attenuated virus vaccine utilizing the Chorioallantois Vaccinia virus Ankara poxvirus, which was previously created as a safer alternative smallpox vaccine, that is also effective against the monkeypox virus. Unlike the original smallpox vaccine, this modified virus is incapable of replication and therefore does not produce disease in the recipients, nor does it pose a risk of transmission to those in close contact of vaccinees. The vaccination schedule includes two doses administered a month apart. The WHO reports that the MVA-BN vaccine given before exposure has an estimated 76% effectiveness in protecting people against mpox, with the 2-dose schedule achieving an estimated 82% effectiveness.

On the bad news front, a report on a recent outbreak of Mpox in Australia (New South Wales) since June of 2024 included 433 cases, of whom 26 required hospitalization. The concerning news is that 14 percent of those infected had previously received one dose of vaccine, and 40 percent of cases had been fully vaccinated with two doses.

Two days ago, a research letter was published in JAMA Network reporting the decline in antibody responses following MVA-BN vaccination https://jamanetwork.com/journals/jama/fullarticle/2824688. (Keep in mind that antibody levels always decrease following vaccination or acute infection. The real concern is whether immunological memory is long-lived so that antibodies can be quickly produced recalled and produced in response to infection or reinfection.) The authors cited research demonstrating that two doses of MVA-BN vaccine provided 66% effectiveness and 1 dose provided 36% effectiveness at peak immunity during the 2022 mpox outbreak, which clearly demonstrates that the vaccine is immunogenic and provides the population of those vaccinated with some degree of protection. Thus, the concern is not one of immunogenicity, but rather the longevity of protection and whether further booster doses may be necessary. Of note, the current recommendation in the U.S. is only for the initial two-shot series in those at risk for Mpox.

High levels of neutralizing antibodies were seen after infection, but not after vaccination. However, it is difficult to know the clinical significance of this because the correlates of immune protection are not known for Mpox, and not all infections require neutralizing antibodies for prevention of infection. Even if neutralizing antibodies are required, we don’t know what level of antibodies are required.

Thus, it is a bit difficult to know whether the findings of this study are of concern in and of themselves, however, coupled with the report above out of Australia, as well as a report of a cluster of MPox infections in persons previously vaccinated do suggest that boosters in high-risk individuals may be necessary within a year of the initial series. If public health officials determine this to be the case, it will pose a challenge in Africa given that vaccine is in short supply and there is not enough to vaccinate all those in the countries involved in the current outbreak even with just the first dose of the initial series.

We clearly need more research on MPox vaccines, and given a study suggesting that our only antiviral against the monkeypox, TPOXX (tecovirimat) did not appear effective in accelerating recovery in clade Ib cases (though it did not rule out that it might be effective in preventing more severe disease if given earlier and to higher risk individuals) https://www.biospace.com/drug-development/mid-stage-study-finds-only-mpox-drug-ineffective-against-current-outbreak#:~:text=SIGA%20Technologies%20%E2%80%99%20antiviral%20drug%20TPOXX%20%28tecovirimat%29%20is,topline%20readout%20of%20the%20Phase%20II%20PALM007%20trial, we also need more research into effective antivirals.

Some Helpful Resources for Followers of my Blog

Free COVID-19 rapid antigen tests

If you have not already done so in the past week, each household can order 4 free tests to be mailed to you by going to https://covidtests.gov/. It is fast and easy.

Help in finding COVID-19 vaccines:

  1. https://www.vaccines.gov/en/.

Use this site if you need to find a pharmacy in your area or you are looking for a particular pharmacy that is in your area. When you land on the website, you will enter your zip code and it will return a list of pharmacies, with their address, phone number, and a link to their website if you want to sign up for a COVID-19 vaccine.

Use this website if you are looking for a pharmacy with the Pfizer 2024 – 2025 updated COVID-19 vaccine in your area. After you enter your zip code, it will provide you with a list of pharmacies that have that particular vaccine available, along with their addresses, phone numbers and links to their websites where you can schedule a visit for the vaccine.

Use this website if you are looking for a pharmacy with the Moderna 2024 – 2025 updated COVID-19 vaccine in your area. After you enter your zip code, it will provide you with an option to select a list of pharmacies that have that particular vaccine available, along with their addresses, phone numbers and links to their websites where you can schedule a visit for the vaccine or a map view of the pharmacies in your area.

Use this website if you are looking for a pharmacy with the Novavax 2024 – 2025 updated COVID-19 vaccine in your area. After you arrive at the landing page, you will need to click near the top in the center of the page where it states: “Use the Novavax Finder.” Once you are redirected, enter your zip code, and then you will need to scroll down to see a list of pharmacies that have that particular vaccine available, along with their addresses, phone numbers and links to their websites where you can schedule a visit for the vaccine.