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.
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.
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.
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.
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.
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.
Our long history of ignoring diseases that emerge in Africa as solely of concern to the African continent has been proven wrong time and time again, but yet, we still haven’t learned. We must gain an appreciation for how interconnected the world is today. The CDC has already acknowledged that Marburg virus has spread to other parts of the world through international travel. https://www.cdc.gov/marburg/outbreaks/index.html.
I remember well, when a similar disease caused by Ebola virus that was seemingly isolated to Africa, presented to a hospital in Dallas, Texas in September of 2014 in a traveler from Liberia. Two nurses at that Dallas hospital were exposed to the patient and came down with Ebola virus disease. Fortunately, despite the high mortality rate, both nurses survived.
Marburg virus was first detected in 1967 through simultaneous outbreaks in laboratories working with African green monkeys imported from Uganda in Marburg and Frankfurt, Germany and in Belgrade, Yugoslavia. In addition to the 31 reported cases, an additional primary case was later diagnosed by blood test. There were 31 cases and 7 deaths (23 percent fatality rate).
In 1975, a man with a recent travel history to Zimbabwe was admitted to a hospital in South Africa. Infection spread from the man to his traveling companion and a nurse at the hospital. The man died, but both women eventually recovered (33 percent fatality rate).
In 1980, a patient who had recently traveled to Kenya was hospitalized with Marburg virus disease in Nairobi and subsequently died. A doctor who attempted to revive the patient developed symptoms nine days later but recovered. There were two cases and one death (50 percent fatality rate).
In 1987, a 15-year-old Danish boy was hospitalized with a 3-day history of headache, malaise, fever, and vomiting. Nine days prior to symptom onset, he had visited Kitum Cave in Mount Elgon National Park in Kenya. Despite aggressive supportive therapy, the patient died on the 11th day of illness. No further cases were detected. (100 percent fatality rate).
There was a large outbreak of Marburg virus disease between 1998 and 2000. Most cases occurred in young male workers at a gold mine in Durba, in the northeastern part of the Democratic Republic of Congo, which proved to be the epicenter of the outbreak. Cases were later detected in the neighboring village of Watsa. There were 154 cases and 128 deaths (83 percent fatality rate).
Between 2004 and 2005, an outbreak of Marburg virus disease is believed to have begun in Uige Province in Angola in October of 2004. Most cases detected in other provinces have been linked directly to the outbreak in Uige. There were 252 cases and 227 deaths (90 percent fatality rate).
In 2007, there was a small outbreak, with four cases in young males working in a lead and gold mine in Uganda. To date, there have been no additional cases identified. There was one death (25 percent fatality rate).
In 2008, a U.S traveler returned from Uganda in January 2008, became ill and fortunately survived. A diagnosis of Marburg virus disease was confirmed.
Also in 2008, a 40-year-old Dutch woman with a recent history of travel to Uganda was admitted to hospital in the Netherlands. She had visited a cave in Maramagambo forest in Uganda, at the southern edge of Queen Elizabeth National Park. Three days before hospitalization, the first symptoms (fever, chills) occurred, followed by a rapid deterioration in her health. The woman died on the 10th day of the illness (100% fatality rate).
In 2012, testing at CDC/UVRI identified a Marburg virus disease outbreak in the districts of Kabale, Ibanda, Mbarara, and Kampala in Uganda over a 3-week period. There were 15 cases and 4 deaths (27 percent fatality rate).
In 2014, one case was confirmed (fatal) and 197 contacts were followed for 21 days. Out of these 197 contacts, eight developed symptoms similar to Marburg, but all tested negative at the Uganda Virus Research Institute (UVRI) with support from CDC (100 percent fatality rate).
In 2017, a blood sample from Kween District in Eastern Uganda tested positive for Marburg virus. Within 24 hours of confirmation, a rapid outbreak response was begun. This outbreak occurred as a family cluster with no additional transmission outside of the four related cases. There were four cases and three deaths (75 percent fatality rate).
In 2021, in Guinea, one case was reported and confirmed by the Guinean Ministry of Health in a patient who was diagnosed after death. No additional cases were confirmed after more than 170 high-risk contacts were monitored for 21 days (100 percent fatality rate).
In 2022, a fatal case of Marburg disease was identified in the Ashanti region of Ghana on July 7, 2022. Marburg disease was initially detected through testing at Ghana’s national laboratory marking the first detection of Marburg disease in Ghana. Shortly after, two additional family members were also confirmed to have Marburg disease. No additional cases outside the family cluster were identified. The outbreak was declared over in September. There were three cases and 2 deaths (67 percent fatality rate).
And, now, for the first time involving this country, there is a large outbreak in Rwanda. There have already been 27 cases identified, but sadly nine of them have died. Disturbingly, more than 70 percent of these cases are in health care workers who work at either of two hospitals in the capital city of Rwanda – Kigali (population 1.7 million people). That suggests to me that the health care workers were likely exposed to Marburg virus by patients in whom the diagnosis was missed, and thus, there may be many more cases in the community. In addition, three hundred close contacts are being monitored for signs or symptoms of the disease.
The other concern is that Kigali is the home to both a regional and international airport with destinations to nearly 20 countries, including in the Middle East and Asia.
Marburg virus causes rare, but deadly infections in humans, of the hemorrhagic fever type. Marburg virus can also infect primates. Symptom onset is often sudden and can consist of fever, rash (often on the chest, back and abdomen) and severe bleeding. The natural host for Marburg virus is the Egyptian rousette bat (Rousettus aegyptiacus) and bats can then transmit the infection to people, i.e., this is a zoonotic infection. The incubation period ranges from 2 – 21 days.
The infection spills over from infected bats to humans through bat saliva, urine or feces. An infected person may then transmit the infection to a close contact who comes in contact with the infected person’s secretions or body fluids (including in the postmortem period) or contact with fomites (bedding, clothing, needles, or medical equipment used by the patient). As has been documented for the Ebola virus, Marburg virus may persist in the testes of recovered male patients and then be transmitted through sex even after the male’s recovery.
Despite the repeated outbreaks over nearly sixty years, the severity of the disease, the risk to health care workers, the emergence of infection in new African countries, and now the assessment by the World Health Organization that the risk for spread to neighboring countries is high and the acknowledgement of the risk of spread beyond East Africa (specifically, national level – high; regional level – high; global level – low), there are no approved treatments or vaccines for this disease.
This occurs at the same time that the WHO has declared a Public Health Emergency of International Concern due to an outbreak of monkeypox clade Ib virus and Mpox cases in Africa that is affecting some of Rwanda’s neighboring countries. Rwanda itself has had 4 confirmed cases as of the last update I could find from almost two weeks ago. Monkeypox clade IIb already caused a global outbreak in 2022.
Hopefully, we will devote some funding to better understanding the biology of this virus, investigating antiviral treatments, and developing vaccines. We should have learned that it is far easier and far less expensive to contain outbreaks than to respond to them on a global level.
Surveillance and Containment of Novel Infectious Agents with Pandemic Potential – We are Not Good at This
The old saying, “An ounce of prevention is worth a pound of cure,” is no more apt than in the field of global outbreaks and pandemics. In other words, the cost of responding aggressively to novel infectious agents with pandemic potential, even if they ultimately do not cause an epidemic or pandemic is far less costly (in terms of dollars, societal costs and health care costs) than if we respond lethargically and allow the infection to spread among animals and eventually to humans and beyond the initial geographic borders before we decide to get serious about it. We need only look the past two years at our non-response to Mpox outbreaks in Africa over decades that ultimately became a Public Health Emergency of International Concern with global spread in 2022. You would think “well, surely we learned our lesson from that,” but now two years later, we are faced with a second Public Health Emergency of International Concern with another outbreak in Africa with yet a different strain of Mpox that is now showing up in countries that have never had cases of Mpox before and appears to potentially cause higher morbidity and mortality, and unlike the strain involved in 2022 that appeared to be largely spreading among communities of men who have sex with men, this one appears to infect a much broader range, including children and heterosexual adults.
In addition to early interventions being cost-effective and potentially sparing many lives, just undergoing a systematic epidemiological investigation, as well as studies of the infectious agent and its biological properties, receptor affinities, mode of transmission, and pathogenesis (the mechanisms by which it produces disease) as well as studies of the immune response of those who are infected and potential vaccines or therapies, would generate tremendously valuable information about the specific infectious agent, but also potentially add to our knowledge about related infectious agents (e.g., our studies and knowledge of smallpox have accelerated our knowledge and vaccine options against monkeypox) and contribute to our general understanding of bacteria, viruses, fungi, prions, or whatever the infectious threat turns out to be.
Now, for at least the third time, in just two years, we appear to be making all the same mistakes and omissions again as we are faced with a new strain of avian influenza virus that is spreading largely uncontrolled among U.S. dairy farms.
In late 2000, when my soon-to-be coauthor contacted me about the idea of writing a book, after my wife had already planted that idea in my head six months earlier, I became convinced that there was a need for us to write that book (Preparing for the Next Global Outbreak: Lessons from the Schoolhouse to the White House), because it was already becoming clear to me that we were making many mistakes and appeared not to be learning from these. That book was the opportunity for us to chronicle our learnings from the COVID-19 pandemic and to capture the learnings, as well as laying out 117 specific recommendations with the hopes that the next time we were threatened with a global outbreak, hopefully it would be unnecessary to repeat all these mistakes.
An article was published in Nature two days ago in which some influenza experts offered a review and their perspective on the global H5N1 (this is the scientific reference to a particular avian influenza [bird flu] virus) influenza panzootic (this is the term for a pandemic in animals) in mammals The global H5N1 influenza panzootic in mammals | Nature. I think this will be of interest to readers on my blog, so I will summarize it below:
In their introduction, they call out a point that I have made a number of times on the radio show I appear on weekly (Idaho Matters with Gemma Gaudette, Boise State Public Radio https://www.npr.org/podcasts/605235114/idaho-matters): Influenza A (this group includes some human seasonal influenza viruses, as well as avian influenza viruses) has been responsible for more pandemics among humans than any other organism in history to our knowledge, but definitely in the past century. Thus, any outbreak of influenza A among humans or animals deserves our attention, at the very least.
While generally we think of avian influenza viruses as causing infections in waterfowl and wild birds that then contaminate feed or feeding grounds and infect domestic birds, especially poultry, the current global outbreak is different and concerning due to: (1) the rapid global spread of the virus including to South America and Antarctica for the first time; (2) the rapid evolution and changes to the virus resulting from reassortment (this is a process characteristic of influenza viruses whose genetic material largely consists of 8 segments, of which one or more can be easily swapped with another influenza virus when a human or other animal is infected with, for example, one avian influenza virus and one human influenza virus, resulting in a significant change in the virus that can lead to adaptation of the avian virus to better infect mammals, which otherwise the avian influenza virus is quite limited in its ability to do), and (3) the frequent spillover to land and marine mammals, many of which we have never detected H5N1 infections in before.
For the first time in the decades that we have been aware of the virus, the H5N1 virus has demonstrated sustained mammal-to-mammal transmission among very diverse species, including most recently (first detected in March of this year) outbreaks among dairy cattle farms in a growing number of herds in a growing number of states in the U.S.
All of these factors should be increasing our assessment of risk for spillover to humans (and we have now detected 15 such cases in the U.S., with concern that there could be many more undetected cases) and the potential (even though currently thought to be low) for this virus to develop the potential to cause a human pandemic.
In the past, with one notable exception (see below) avian influenza viruses have caused human pandemics, but only after first infecting swine that served as the “mixing bowl” for reassortment of the avian influenza virus with other influenza A viruses that gave the avian influenza virus the ability to efficiently infect humans and the ability for efficient human-to-human transmission. These authors lay out information that we have learned that raises the potential that the currently uncontrolled spread of the virus in other mammals, particularly dairy cows, may serve the “mixing bowl” function that swine have done in the past.
The authors include the graphic below to demonstrate how the H5N1 highly pathogenic avian influenza A virus has spread from being isolated to Asia to encompassing the United States within 15 years, and several years later, throughout much of the world.
This next graphic depicts the range of mammalian species that have been infected by the virus, most of these for the first time in the virus’ history to our knowledge:
We need to keep in mind that spread of the virus to and among a greater number of mammals presents the virus with many more opportunities to evolve in ways that increase transmissibility and that equip the virus with more defenses against mammalian immune responses. Both of these, in turn, increase the threat of more efficient spread to humans, and ultimately could result in more efficient transmission among humans, the final step between this remaining a panzoonotic event and becoming a human pandemic.
The authors point out that the change in threat level occurred in 2020 when a new genotype (genetic form of the virus) developed that is referred to as clade 2.3.4.4b (you can think of clade as another word for strain). That lead to greater spread around the world and greater spread to a wider range of animals.
In the past, when a different avian influenza virus spread to the U.S. from Asia, outbreaks were contained with surveillance and culling of infected poultry. This time is different. Culling of infected poultry has not stopped the spread of this virus and now, for the first time, outbreaks are occurring on an increasing number of dairy farms in a growing number of states. It appears that wild migratory birds are continuing to introduce the virus on dairy and poultry farms as they fly over, including during migration.
The current clade spreading among dairy cattle in the U.S. is the clade 2.3.4.4b – the result of the virus having undergone a number of reassortments (swapping of segments of the genetic material with other influenza viruses the host was infected with) – going back to a reassortment between an H5N8 avian influenza virus and a Eurasian low pathogenic avian influenza virus.
Initially, there was a single spillover event of the H5N1 virus from wild birds to U.S. dairy cattle (in Texas), likely in late 2023 or early 2024, after which there was onward transmission from cattle to other cattle likely through virus on milking machines, though the contribution of respiratory transmission remains unclear. There was subsequent spread to other dairy farms by transport of infected cattle, as well as spillover events from cattle to other animals and wildlife, most notably cats that drank raw milk spillage on these farms.
The authors then pose and try to answer the critical question: Could this virus spark a pandemic?
The authors point out that for an influenza virus to spark a pandemic, it must fulfill two key criteria. First, the main attachment protein of the virus (i.e., hemagglutinin, from which each virus is given the “H” designation – in this case, H5) must be antigenically novel (meaning that the immune systems of a sufficiently large portion of the population have not previously been exposed to it and would not be able to recall prior immune memory to make a rapid antibody response). This criterion is fulfilled, as human seasonal influenza viruses are of the H1 or H3 type, predominantly. H5 has never before circulated in humans, and thus, it would be antigenically novel, and further, there is no evidence to support that humans would have cross reactive immunity from any of our past hemagglutinin protein exposures.
The second criterion is a much higher, but not impossible, bar to meet: efficient transmission between humans.
Based on our current understanding, we believe that would require three changes to an avian influenza virus (and these would most likely occur through the reassortment process). The first change is in the viral polymerase (PB2, PB1, and PA proteins) that helps the virus exploit mammalian host machinery to replicate (make the viral proteins necessary to assemble new virions) by way of enabling the avian viral protein able to work with and direct the human cellular components it needs for the process of protein synthesis. A second change must occur in the hemagglutinin protein (remember, this gives the influenza virus its H designation) to help the virus bind strongly to cell surface receptors abundant in the human upper respiratory tract (URT) since avian influenza viruses preferentially use cell receptors with α 2, 3 -sialic acids attached to their cell surface glycoproteins, whereas humans do not generally have this configuration in the upper respiratory tract (rather, we have α 2, 6 -sialic acids on our cell surface glycoproteins). This is critical because levels of virus are highest in respiratory secretions and aerosols when the virus is present in the upper respiratory tract of the person emitting the secretions and aerosols. The third change must stabilize the hemagglutinin protein to tolerate lower pH (a more acidic environment) to prevent destruction of the virus when transiting between hosts through the air. For H5N1 viruses, the highest hurdle appears to be the second criterion. The virus’ polymerase is more prone to adaptation than is the ability for the virus to change receptor affinities.
In 1957, this trifecta occurred during dual infection of an individual animal — probably a human, but possibly another species, such as a pig — with an avian H2N2 influenza virus and a human H1N1 influenza virus that resulted in the emergence of a new influenza virus containing the hemagglutinin, the neuraminidase, and the gene for one of the polymerase proteins (PB1) from the avian virus, along with the remaining five genetic segments from the human H1N1 influenza virus, and it sparked a pandemic.
The remnants of that reassortment H2N2 pandemic virus circulated in humans until 1968, when it was replaced by another reassortment virus, the H3N2 Hong Kong virus — created by the replacement of the hemagglutinin (H2) and polymerase (PB1) genes of the H2N2 virus with two new avian genes, H3 and a new PB1 that triggered another pandemic. The Origins of Pandemic Influenza — Lessons from the 1918 Virus | New England Journal of Medicine (nejm.org)
However, while much less common, and perhaps only a once-in-a-century or longer event, we should keep in mind that the most deadly pandemic (in terms of American deaths on a per capita basis) since the late twentieth century was the influenza pandemic of 1917 -1918 (the COVID-19 pandemic killed a greater number of Americans, however, in 1917-1918, the U.S. population was roughly a third of what it is now, so on a per capita basis, the U.S. mortality rate was higher for the influenza pandemic) was caused by an H1N1 virus for which there is no evidence of reassortment, meaning that this avian virus most likely infected humans and then evolved within humans to acquire these necessary mutations and enhanced transmission.
I am concerned that we have uncontrolled spread of the H5N1 virus among dairy cattle. As we approach our seasonal influenza season, will those working on dairy farms transmit our seasonal virus to these animals, where we know that coinfection can occur in cow utters, and will this potentially serve as the “mixing bowl” to allow mutations and reassortments necessary for the three criteria above to be met?
But while this is a concern yet to materialize, there is already a concerning development that further demonstrates how bad we are at surveillance and containment of novel infectious agents with pandemic potential beyond the fact that thus far, six months later, we still are unable to prevent further spread of H5N1 to more dairy farms in more states (the latest being California). This development gives rise to concern that perhaps the second criterion is becoming closer to being met, while public health and agriculture agencies have largely been mounting a response without any sense of urgency, and in some respects, without any sense.
Here is what happened. An individual in Missouri, with a number of underlying health problems, was hospitalized on August 22 of this year. On September 6, the CDC announced that this person was confirmed to have an avian influenza (H5 – reportedly the sample was inadequate to allow for identification of the neuraminidase “N” component) that was detected through the state’s seasonal flu surveillance system. The patient was treated with antiviral therapy and was able to be discharged from the hospital and has since recovered. This was the 14th case of H5 infection in a human in the U.S. in 2024 (15th case in total – there was a case in Colorado in 2022 in a worker involved in culling infected poultry birds). What was particularly concerning about this case was that the person, unlike all the other reported cases, had no occupational exposure to poultry or dairy cows. https://www.cdc.gov/media/releases/2024/s0906-birdflu-case-missouri.html.
The significance of lack of exposure history is the concern for whether the patient was infected through community spread of infection – a clear concern that the second criterion that we discussed above may have been met unbeknownst to us. At that point in time, I was hoping that the patient had ingested raw milk, and it seemed an obvious oversight that the CDC didn’t state whether the patient did so in the announcement. It was not until later that the CDC would confirm that the patient had not ingested raw (unpasteurized) dairy products.
Since then, information has been slow to be updated and has dripped in in an ever-increasingly concerning manner, despite the reassurances from public health agencies that the risk to the public remains low. One week later it was disclosed that a “close contact” was also sick at around the same time as this patient. That person was not tested for influenza. In perplexing statements, the CDC stated that it did not believe that there had been spread of H5N1 between the infected patient and any close contact, without offering any basis for that somewhat surprising statement. “There is no epidemiological evidence at this time to support person-to-person transmission of H5N1 though public health authorities continue to explore how the H5N1-positive individual in Missouri contracted the virus.”
Let me explain why this feels like gas-lighting to those of us not privy to all the information that the CDC has about this case, and can only go on the basis of the drips of information made public. So first let me acknowledge that the investigation is disjointed in that the state has original jurisdiction and the CDC can only insert itself to the extent it is invited by the state. Further, I acknowledge that if we had all the information that the state investigators and CDC have, perhaps I would come to the same conclusion that they have. But, with the limited amount of information that has been made public, the CDC’s statements make no sense. First of all, they state that “there is no epidemiological evidence” to support person-to-person transmission. Well, one key tool of an epidemiological investigation is to do contact tracing. They state that a “close contact” was also sick around the same time as the patient, but was not tested for influenza. So, that is concerning evidence. It is not proof, by any means, but we are being told that someone who was in close contact with the patient was also sick, but we don’t know what illness they had because they were not tested and we don’t know the nature of the close contact. That raises four possibilities: (1) Close contact infected patient; (2) patient infected close contact: (3) patient and close contact were infected by a common unidentified source; or (4) patient had avian influenza infection, but close contact has a contemporaneous, but different and unrelated illness. Despite having no answers, these are not unanswerable questions. The fourth possibility is the most important to answer, and the way you answer that in someone who is no longer sick and therefore cannot be tested with our influenza tests that we use on sick patients is to do a serological test, i.e., we check the person for antibodies to H5N1 in their blood. In response to questioning about this, we are told that the public health authorities were contemplating such testing. (You have to read this next sentence as if I am yelling it, because I was in my head). Contemplating it, good heavens, it takes me 5 minutes to contemplate that kind of testing in my medical practice! All you need is a tourniquet, gloves, a specimen tube, an alcohol swab, a needle and syringe or vacuum device and a band aid. We all have had blood drawn like this and it is no big deal except for those of us with aversions to needles. This simple test would answer the most important question. If the contact (which was later disclosed to be a household contact, which makes this even more likely to be related infections) is negative for antibodies, then great; we can let this go. But, if positive, then we need to explore the timing of onset of their respective symptoms and a detailed review of their activities and contacts during the days leading up to their infections to better understand did one infect the other or did they most likely have a common source exposure.
Another week later the CDC informs us that no source has been identified for the patient’s avian influenza infection (this means that this case is distinctly different than all the other known cases, and remains concerning for community spread because there has been adequate time for the epidemiological investigation to be completed). Now we are told that there were two health care workers who were exposed to the index case (the hospitalized patient) who subsequently developed respiratory symptoms after caring for the patient before respiratory precautions were put in place. One tested negative for influenza during the illness, serology testing was pending for the second case.
Then, we get a bombshell update on September 27 from the CDC. An additional four (i.e., now total of 6) health care workers developed respiratory symptoms following the identification of the index case (hospitalized patient), and 3 of the 4 (5 of the 6) were exposed to the index patient. However, unlike the initial two health care workers who were exposed prior to the institution of respiratory precautions (droplet), the subsequent three had exposures after those precautions were instituted. Drawing some inferences from the statement, it appears that serological tests (antibody testing) is pending for five of these health care workers (apparently, serology is not being performed on the first health care worker who is the only one who had PCR testing for influenza [that individual tested negative]). Frustratingly, the serology testing for the household contact of the index case is still pending.
We are also told that a total of 94 people were exposed to the patient while hospitalized.
So, why am I frustrated and why are so many experts troubled by this situation?
The fact that the CDC must be invited in to an outbreak investigation by the individual state is reminiscent of the frustration the world experienced as the WHO was unable to investigate the SARS-CoV-2 outbreak in China until it was invited in.
Similarly, the CDC and USDA have limited ability to surveil and manage the H5N1 outbreak on U.S. dairy cattle farms, which has resulted in undertesting, delays in identifying cases, a lack of ability to determine the full extent of the outbreak, and a failure of containing the outbreak.
The fact that we are still waiting on serological testing results from the household close contact of the index case at 3 weeks now indicates the bottleneck in testing (apparently this testing can only be done at the CDC lab reminiscent of the bottleneck in testing and marked delays in obtaining results that we experienced at the beginning of the COVID-19 pandemic, which blinded us to the extent of community spread of the disease at the time). It also suggests inefficiency of testing. I can generally get serology tests back in 48hours to a week. If there is a reason that this testing takes weeks to perform, then again, the CDC should just tell us. Otherwise, it feels as though they have the results and are not disclosing them, or they are slow-walking the testing.
The fact that it has taken so long to identify health care workers exposed to the index case and those who experienced symptoms suggests a lack of a sense of urgency in the investigation.
We are now told that the serological testing of the newly identified symptomatic health care workers will be delayed due to the weather conditions created by hurricane Helene. This is another problem with having only one laboratory (in Atlanta) that can perform this testing. I do not mean to imply that serologic testing is simple, however, it is done many times a day in thousands of laboratories across the country. If there is a reason that this testing can only be performed at the CDC in Atlanta, then just explain that to us. Otherwise, there are many laboratories across the country certified to conduct complex testing, and an effort should be made to speed up this testing and increase its availability now that we have a case that should be considered evidence of community spread, until proven otherwise. (We assume community spread when we cannot identify a source of the infection).
Recall, that at the time of this patient’s hospitalization August 22, we were at very high levels of COVID-19 across the country. In fact, it would not be surprising that some of these symptomatic health care workers had COVID and not bird flu. However, this is emblematic of the unexplainable, and I think, indefensible, abandonment of infection control practices in hospitals.
Let’s go a little deeper. So, we are told 94 health care workers were exposed to the patient. That means the patient was exposed to 94 health care workers when COVID levels were extremely high.
We are also told that initially no respiratory precautions were in place upon the patient’s admission. We aren’t told what the patient’s presenting signs and symptoms were (something that frustrates many of us that are trying to learn from these cases), but we are told that the avian influenza infection was picked up through the state’s seasonal flu surveillance system. So far, I have not been able to locate the exact criteria used for selection of patients to screen for influenza under Missouri’s surveillance system, but it would make sense that specimens would be obtained from patients with influenza-like illnesses (acute respiratory illnesses, fever, cough, etc.). It can certainly be difficult to distinguish influenza, COVID-19, RSV and a number of other respiratory infections early on in the course of hospitalization. Assuming this to be the case, and I fear that this hospital is no different from most across the country, patients with potentially contagious respiratory infections are being admitted without respiratory precautions, repeatedly exposing staff. And, of course, this also means that patients who already are vulnerable due to the illness they are hospitalized with are exposed to staff and to patients with respiratory infections for whom no respiratory precautions are in place.
Further, note of the 6 health care workers that so far were identified as developing respiratory symptoms after exposure to the patient, only one was tested while ill. That means that we don’t even know the extent that infections are being passed around in hospitals from patients to other patients or health care workers, or vice versa. We also aren’t provided with any information from the CDC’s update as to whether any of these symptomatic health care workers continued to work while they were symptomatically ill (spread to other patients or staff who were now contacts of the health care worker, but not the index patient?), and if they did, whether they were required to wear a respirator mask (I might fall out of my chair if the answer is yes).
It’s not like this is just all academic. If there is human-to-human transmission of this avian influenza, this is critical to know. It should inform farm and hospital infection control practices and how we handle infections. If there are sustained chains of transmission, then this is of paramount importance, because this means there is a pandemic threat and this calls for an active public health response and an updated pandemic response plan.
The CDC tells us that the public threat remains low. That is very possibly the case. However, that is an assessment based on very sparse and insufficient data. If the seven symptomatic close contacts are all negative on their serology testing, I would totally agree. If the seven symptomatic close contacts are all positive on their serology, then we have either got a highly infectious disease with an effective reproduction number of near 7 (the index case infected 7 people; for a pandemic to occur, one only needs this number to be greater than 1 if the other criteria we discussed above are met) or there is far greater community spread (i.e., not all of these people were infected by the index case, therefore there are many other undetected sources of infection out there) that we don’t know about. If it is the latter, and we simply have 6 out of 94 health care workers previously infected by someone other than the index patient (and we are not told that any of the remaining 88 health care workers are being tested in the event they had asymptomatic infections, or were pauci-symptomatic and their symptoms were so mild that when questioned weeks later they forgot about them), then we have already lost control of this.
For now, we will just wait for the drips of continued updates and try to piece this altogether as we get additional information that we should already have by now.
I do not recall a time that a college football game was cancelled due to a pertussis (whooping cough) outbreak, but that was just recently the case when an outbreak occurred among members of the Portland State football team just before they were scheduled to play South Dakota. That game was cancelled, and for a while, it was uncertain whether Portland State would have to cancel its scheduled match-up with Boise State, as well, but that game was able to go forward on September 21 – this past weekend.
Meanwhile, here in Idaho, the Bonner County Daily Bee Pertussis outbreak continues in region | Bonner County Daily Bee is reporting on a pertussis outbreak in the Panhandle – northern Idaho. According to reports from the Panhandle Health District as reported in the article, “Since April, the number of reported pertussis cases in North Idaho has grown from a few dozen to 166 as of mid-September, and that number is continuing to increase.” Keep in mind, the number of actual cases is almost certain to be far more than the number of cases reported, as not everyone with pertussis seeks or requires medical attention.
For comparison, Panhandle Health District only had nine total cases of pertussis over the past three years — five in 2023, three in 2022, and one in 2021.
The CDC also reports that cases of pertussis in the U.S. are on the rise this year. So far this year, cases are about three-times that reported in 2023.
One reason I was surprised about the outbreak among members of the Portland State football team, besides the fact that I had never heard of a college game being cancelled for this reason, is that although people of all ages can get pertussis, it is largely a disease that affects children and adolescents. Babies younger than one year old are at greatest risk of getting pertussis and developing severe complications. Of infants who develop whooping cough, roughly one-third need to be treated in the hospital. Whooping cough is particularly dangerous for these babies and infants because their airways are smaller and less well developed and generally, they have no prior existing immunity unless their mothers were vaccinated against pertussis during the pregnancy.
Pertussis is highly infectious. It is caused by bacteria called Bordetella pertussis. It is transmitted through respiratory droplets, predominantly, by coughing, sneezing, or even normal breathing when in close contact with others. This bacterium attaches to cells lining the upper airways that have hair-like extensions that act to help mobilize secretions and debris that we breath in from the air – these hair-like structures are called cilia (pronounced sil-E-ah). However, this bacterium releases a toxin when it infects cells and this toxin damages the cilia and often causes the airways to swell. This can cause choking, paroxysms of coughing sometimes severe enough and prolonged enough to cause vomiting, and in these young children, it can lead to a characteristic sign that gives the disease its name – whooping. Often, after one to two weeks of first presenting as a cold-like illness, the coughing phase begins and these infants may have a series of coughing fits followed by what seems like a prolonged effort to get a deep breath in that is accompanied by this “whoop” sound and the infant’s chest may cave in a bit. Even more worrisome is that some babies don’t develop these signs, but rather may have periods in which they stop breathing (apneic spells). While most of these children will recover, tragically, about 20 babies die per year from this infection.
While older children and adults don’t generally develop compromised breathing, the coughing can be quite bothersome and, in some cases, pneumonia can develop. Pertussis can be treated with antibiotics. Often times, a physician will make the diagnosis empirically, i.e., simply based upon typical signs and symptoms being present, especially when an increase in cases have been reported in the community. However, pertussis can be confused with other illnesses like RSV (respiratory syncytial virus), COVID-19, and influenza, so when in doubt, testing for this bacterium can be done with a PCR test from a nasal swab, like most persons experienced early on in the COVID-19 pandemic when testing for the SARS-CoV-2 virus. Given how contagious this infection is, the decision may be made to treat others in the family with antibiotics who are not yet showing signs or symptoms of the disease prophylactically when someone in the household is infected.
We begin DTaP vaccinations for babies at two months old and use this vaccine for children up to age 7. The “D” stands for diphtheria, another bacterial (Corynebacterium diphtheriae) infection that results from the toxin produced by this bacterium that can cause a grayish membrane to form in the back of the throat that can interfere with swallowing and breathing and cause an emergency. The “T” stands for tetanus toxoid, the stimulus for the immune system to protect the body from the life-threating toxin produced by the bacterium (Clostridium tetani) that causes the disease tetanus or more colloquially known as “lockjaw.” Finally, the “aP” stands for acellular pertussis, and this component of the vaccine consists of several protein antigens (antigens are recognized by the body as not part of the body and stimulate an immune reaction and the production of antibodies and the development of cellular immunity) from the bacterium and is referred to “acellular” to distinguish it from earlier vaccines that contained the entire cell of the bacterium. The acellular form of the vaccine is used in most developed countries because it results in far fewer side effects.
We then shift to the Tdap vaccine once children are around 11 or 12 years of age, and continue with this vaccine every ten years to boost the immune response, which does wane over time. The lower-case letters for “D” and “P” reflect that the dosage (amount of the vaccine component) has been reduced. This is also the formulation we often recommend for pregnant women during the 27th – 36th weeks of pregnancy in order for the mother to form antibodies that are then transferred to the infant and help protect that newborn until we can begin the baby’s vaccination series at 2 months of age. Many physicians will also recommend that the father and grandparents who are going to be in close contact with the baby get this vaccine to reduce the likelihood that they get infected and then pass the infection on to the vulnerable infant.
My role of trying to educate the public about this developing pandemic and the actual and potential risks that SARS-CoV-2 infection presented back in the first two years, when misinformation and disinformation were rampant, and when the evidence was still unfolding, and especially prior to the availability of vaccines, was greatly challenging.
On one hand, there was the loud voice of minimizers who likened COVID-19 to a cold or possibly even the flu and discouraged precautionary measures, and on the other hand, but not mutually exclusive, a group of physicians with more promotion on social media, cable networks, and even some of the mainstream media, who advocated for the unhealthy and elderly to stay home, but to have children and young adults return to all their normal activities, including those known to be high-risk for infection, to promote infection with the pronouncement that our country would then achieve herd immunity and COVID-19 would no longer present a significant threat to society. One well-known and nationally renowned physician even wrote an article for a major news outlet that predicted that we would achieve herd immunity as a country by April of 2021. I tried to warn the public that that prediction was not based upon any sound facts or science and was completely unreasonable. In fact, nearly 3 ½ years later, we still have not achieved “herd immunity.” I wrote at length about what herd immunity is, what factors are necessary to achieve herd immunity, and why herd immunity was not a reasonable expectation with the SARS-CoV-2 virus, at least for the foreseeable future in our book, Preparing for the Next Global Outbreak: A Guide to Planning from the Schoolhouse to the White House, https://www.press.jhu.edu/books/title/12896/preparing-next-global-outbreak.
Another challenge that was frustrating and challenging to deal with was the fact that the public’s and government’s focus and attention was on hospitals being overwhelmed and people dying from the disease. I tried repeatedly to raise the point that it often takes years after we first recognize a new virus to determine the long-term health consequences of infection, and sometimes these consequences can be serious and even disabling. I urged people to consider that we may learn of such health consequences from infection with SARS-CoV-2, so those who were being encouraged to take a cavalier approach to this virus because they were not in any of the identified high-risk groups, might still want to take reasonable steps to minimize the risks of infection, or at least guard against multiple reinfections, which would very likely increase any such long-term health risks. It is hard to know if my warnings made much of an impact.
Unfortunately, since then, we have learned that there are many potential long-term health risks, some that I had not even contemplated, and that these risks do, in fact, appear to increase with increasing number of infections.
In this blog post, I am only going to review two studies (more to come). The first is a study that would never be approved in the U.S. because the study took healthy individuals and exposed them (we call this a challenge study) to SARS-CoV-2 to study the effects of infection. Published by The Lancet, the investigators of this study, Changes in memory and cognition during the SARS-CoV-2 human challenge study – eClinicalMedicine (thelancet.com), took 34 healthy volunteers who had no history of COVID-19 and who were tested by serology (antibody testing) to ensure that they had no antibodies to the virus that would suggest prior asymptomatic or pauci-symptomatic infection of which the subjects were unaware, and inoculated them (introduced the virus directly into their nasal passage) with the wild type (original strain) of SARS-CoV-2. The investigators then conducted cognitive tests on the subjects (some who developed evidence of infection: measurable and sustained viral loads by PCR testing and some who did not become infected who then served as the comparison group) during their period of quarantine and at 30, 90, 180, 270, and 360 days following their artificially-induced infections in order to compare the results to their pre-infection, baseline cognitive testing. Of the eighteen subjects that developed laboratory evidence of infection, one was asymptomatic and all the others suffered only mild illness (i.e., not severe enough to require medical attention or intervention).
The infected subjects demonstrated statistically significant lower global composite cognitive scores than uninfected volunteers, and this difference occurred both during the acute infection, as well as through the follow-up period of 1 year. Memory and executive function tasks showed the largest between-group differences and this was despite the subjects generally having no awareness of the cognitive decline.
Although this was a small number of subjects tested, it was concerning that cognitive decline was detected in all cases, whether the infection was asymptomatic or mild. It remains an unanswered question as to how many of these subjects ever returned to their baseline level of cognitive functioning. While these subjects were not aware of their cognitive decline, it is not uncommon for people during and after COVID-19 to report “brain fog,” which generally refers to loss of memory, difficulty focusing, and difficulty maintaining attention for prolonged periods of time. Keep in mind that these subjects ranged in age between 18 and 30; these were not elderly individuals, but rather young adults in the prime of their lives. It also raises concern that with this impact on young adults, what is the impact on children with still developing brains?
The second study was a review article published in the New England Journal of Medicine in February of this year: Long Covid and Impaired Cognition — More Evidence and More Work to Do | New England Journal of Medicine (nejm.org). I have previously written about some of the neurologic and psychiatric sequelae of COVID-19, but this study looks further into a recent analysis of the U.S. Current Population Survey that showed that after the start of the Covid-19 pandemic, one million U.S. residents of working age reported having “‘serious difficulty’ remembering, concentrating, or making decisions” than at any time in the preceding 15 years. While in the previous paper, the investigators established cognitive decline with infection with the original strain of SARS-CoV-2 that occurred even with asymptomatic or mild infection and persisted at least a year, these authors point to the fact that cognitive decline has been reported with every variant since the original 2019 virus.
Concerningly, these researchers state:
As compared with uninfected participants (control), cognitive deficit — commensurate with a 3-point loss in IQ — was evident even in participants who had had mild Covid-19 with resolved symptoms. Participants with unresolved persistent symptoms had the equivalent of a 6-point loss in IQ, and those who had been admitted to the intensive care unit had the equivalent of a 9-point loss in IQ.
They go on to point out:
Memory, reasoning, and executive function (i.e., planning) tasks were the most sensitive indicators of impaired function, and scores on these tasks tended to correlate with brain fog. Vaccinations provided a small cognitive advantage. Reinfection contributed an additional loss in IQ of nearly 2 points, as compared with no reinfection.
It is hard to know the significance of these findings without longer follow-up and surveillance. But, these findings are concerning enough that I believe it prudent to try to protect our children is schools with better air handling, ventilation, and filtration. It is frustrating to me that minimizers, promoters of herd immunity, disinformation purveyors, and even our own public health messaging no doubt contributed to such a high population infection burden. I hope all of these changes in cognitive function reverse over time, but given that prior studies have shown that imaging can detect structural alterations to the brain, including loss of brain tissue, I am skeptical that all persons will experience recovery.
Starting tomorrow (Monday, September 23, 2024), all U.S. households can once again request 4 free at-home rapid antigen tests for COVID-19 on the website www.COVIDTests.gov.
Before throwing out tests you may have at home already, keep in mind that for many, the expiration dates have been extended beyond the date printed on the packaging. To see if your tests’ expiration dates have been extended, go to At-Home OTC COVID-19 Diagnostic Tests | FDA.
UPDATE (9/23/24)
I tried to submit my own order today, but apparently there is a delay. The government now states that you will be able to order them by the end of the month (1 week from today), but I cannot find anywhere where they specify the exact day.
One caution: Be sure you use COVIDTests.gov and not COVIDTests.com (the latter is an active website for a private company).
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