Is There Any Good News On The Infectious Disease Front?
It might seem like all the news surrounding Infectious Diseases is pretty grim these days—so I will start this week’s report with some of the most hopeful information we have had in a long time. SARS2-Cov19 wasn’t my first pandemic, in 1981 I took care of some of the earliest AIDS patients in New York, and spent a very significant portion of my career in medicine directly involved with this disease, caring for patients, and closely following the trajectory of treatment. Today, and for quite a long while, there has been highly effective, life saving treatments for HIV—but the regimens have been cumbersome and sometimes difficult to adhere to, with significant aide effects, expensive, and out of reach for many people in poorer countries. In addition, despite years of Public Health education efforts, there are over 1.3 million new HIV infections a year, with a majority of them occurring in Africa and disproportionally affecting women. An oral drug combination pill, Truvada, was approved for pre-exposure prophylaxis (PrEP) in 2012, and has been moderately successful in men, but significantly less effective in women. The spectacularly good news is that a study in South Africa and Uganda of 5000 sexually active young women demonstrated that a newer anti-viral lenacapavir, which is given as a subcutaneous injection every six months, was 100% effective in preventing infection. This double blinded study compared the new treatment to two different formulations of Truvada which had failure rates of 1.5% and 1.8%, statistically significant. This medication is currently approved for treatment and hopefully will quickly be adopted by the WHO and various governments as the new standard in prophylaxis.
Far worse news is easy to find on the Infectious Disease front, so let’s have at it. The highly pathogenic Avian Influenza H5N1 has spread explosively in the Colorado dairy herds over the last 2 months and 25% of the cows are now infected. A fourth US dairy worker has been infected with the virus as a result of contact with the bovines, and this was another case of conjunctivitis without serious disease. So far there have been 3 cases with the mild symptom of eye infection only, and one with respiratory symptoms, but again not severe. Meanwhile, Cambodia has just reported 2 young children in the same household infected with H5N1 and receiving “intensive care” in hospital. I have previously touched on this apparent dichotomy between the severity of human H5N1 cases Southeast Asia and China, and what we are seeing here in the cow associated cases, but I think it’s worth another look. The disease as reported over the last decade in Asia has a mortality rate of 40-50%. Have we just not had enough cases yet, and a few more will begin to incur some episodes of severe illness? Are there so many cases of mild or asymptomatic disease in Asia which go unreported that the apparent mortality of the disease is exaggerated? Many of the severe and fatal cases in Asia occurred in children; is this virus one that is particularly lethal in children rather than adults—the complete inverse of SARS2 where we dodged a bullet? Perhaps the virus, in acquiring the ability to infect mammals, and in particular cows, lost some virulence factor for human infection—that would be nice. Do humans have some unique resistance to any forms of the virus which have adapted to other mammals, and we won’t experience mass death events like marine mammals? H5N1 certainly is lethal for many species of mammals, and the particular clade infecting cows has already shown it’s ability to kill cats, dogs and other animals around these farms. There are many unanswered questions; but we do know that this particular mutant of H5N1 infecting the cows has some unique genetic changes from the run of the mill clades found in wild and domestic birds, and this has allowed construction of a viral “evolutionary tree”, pointing to a single spill-over event from bird to cow, and subsequent spread of descendants of that single virus to the over 135 infected dairy herds in 12 states.
Charting the course of this epidemic, determining how the virus spread from farm to farm, and the true magnitude of human infection has been hampered by a flat-footed slow initial response from CDC, and also by uncooperative farm owners and workers refusing testing. The CDC responded by beginning to measure influenza A virus in the system of wastewater surveillance initially established to measure SARS2-Cov19 (CDC National Wastewater Surveillance System). This was not specific for H5N1 (the assay measures any A Influenza virus), but the thought was summer is not the time of year for normal influenza activity, and any unusual increases would likely be a signal of H5N1. Now building off work done at Stanford University’s WastewaterSCAN, the CDC is recommending that specific testing for H5N1 be adopted across all the sites doing this monitoring. Stanford’s WastewaterSCAN is currently monitoring many sites around the country, and currently is quantifying over a dozen different pathogens. Below is a graph of COVID virus RNA averaged around the US, showing that the current summer surge has surpassed levels seen in February of this year. Following that is a second graph of RSV activity—interesting because I believe that so far, it is suggesting that RSV has returned (or is returning) to it’s usual fall then winter peak, without the bizarre summer surges seen in the two years following the Pandemic lockdowns. Parents and pediatricians should rejoice!
Standard pasteurization has now been confirmed, at least in the laboratory, to inactivate virtually every trace of the H5N1 virus, a welcome bit of data. I would caution however that industrial scale pasteurization, occurring in a myriad of sites around the US, can be subject to breaks in technique—and as they say at Boeing, “Stuff happens, so you pays your money and you takes your chance”. Under the circumstances I would propose that drinking unpasteurized milk (never a smart idea) has moved up in the ranking of stupid things you can do. In fact I’m placing it just below going to the Dominican Republic for some rock bottom price plastic surgery. (I have some direct experience in dealing with negative outcomes there). We humans do lots of unsafe things, frequently for the dopamine reward and adrenaline rush, but I’m finding it hard to imagine there is a great deal of either in a cold glass of milk with undisclosed pathogens such as: tuberculosis, salmonella, listeria, brucella species, E.coli, Streptococcus zooepidemicus and campylobacter species. Given the CDC and FDA’s strongly worded warning against consuming unpasteurized milk, you might be surprised to learn that last week the Delaware State Legislature passed a bill making it perfectly legal to sell unpasteurized milk and other dairy products. The timing of this new law in Delaware is really something else—perhaps dementia is contagious.
H5N1 continues to take a tremendous toll on avians around the world. This week the governor of Colorado declared an emergency in Weld county where 1.8 million egg producing chickens will be slaughtered because of infection. It’s been a while since the virus struck so heavily here—but the last time it did in 2022, the price of standard eggs hit $7/dozen, if you could find them. Should this virus acquire the ability to spread from person to person, the federal government is counting on the combination of vaccination and anti-viral agents to combat the epidemic which might ensue. BARDA (Biomedical Advanced Research Development Authority) has just announced $174 grant to Moderna for research into development of an RNA based pan-influenza vaccine. That is potentially quite significant since current influenza vaccine production requires gigantic numbers of eggs, which could be in short supply at an inopportune moment, and is much more time consuming than RNA platform based vaccine production. So far influenza anti-virals have been remarkably broadly active and durable against the emergence of resistance, but that of course could change, and seriously impact our ability to respond to an outbreak of Avian Influenza. The current edition of Emerging Infectious Diseases has a CDC study on the spontaneous emergence of H1N1 strains from 5 continents with moderate levels of resistance to olsetamivir (Tamiflu). This neuraminidase inhibitor is the most widely used influenza drug, and emerging resistance is a real concern. I will link to the study below for those with in depth interest in the topic. There are a couple of other anti-virals which retain activity against these mutant influenza strains—but Tamiflu is the primary drug which has been stockpiled by the government in case of an Influenza pandemic. If you’re into acquiring your own emergency stash, I’d go with balovavir, a single oral dose medication with a different mechanism of action against the virus, and not effected by Tamiflu resistance.
https://wwwnc.cdc.gov/eid/article/30/7/24-0480_article Multicountry Spread of Influenza A(H1N1)pdm09 Viruses with Reduced Oseltamivir Inhibition, May 2023–February 2024
Mpox (Monkey Pox) is still around, and causing a rising number of infections. In the US there were 511 cases reported through the end of March, approximately a doubling of the rate in 2023, and so far infections have all been caused by the less severe pandemic clade 2, which spread around the world in 2022. Recently Mpox has ramped up in South Africa, which surprisingly saw very few cases during the world wide epidemic two years ago. Last month 20 cases were reported among men who have sex with men across South Africa, with three deaths. That high fatality rate would make you wonder if these cases were the more lethal Congo basin clade I of the virus, which has also recently acquired the ability to transmit through sex, and has been spreading in a remote mining region of Congo, fueled by the sex trade. However, the South African Health Ministry reports these new cases are the less severe clade 2 virus of 2022. The high mortality rate likely reflects the very high incidence of HIV infection in this population. The wrong virus in the wrong person at the wrong time is often a prescription for disaster. For the record I don’t think it will be long before the more lethal clade 1 makes it’s way out of Congo’s Heart of Darkness, first into surrounding African nations following the trucking routes, and eventually into the European party circuit. Jynneos vaccine has been moderately protective in people with intact immune systems, but the percentage of at risk folks vaccinated in the US is estimated to be low by the CDC, and of course much lower in most areas of the world. Also the duration of protection is unknown presently, and once this genie popped out of the bottle there was no way to contain it. Properly used condoms are pretty effective in blocking transmission of several sexually transmitted diseases, but likely far less so with Mpox. Also experience has taught us that human behavior in this sphere being what it is, counting on “properly used” condoms to contain a novel sexually transmitted virus is like making the Tooth Fairy your retirement plan.
There’s no editorial this week—the apocryphal Chinese curse, “May you live in interesting times”, should suffice. According to Wiki, there is no evidence this was ever a Chinese saying, but might have been an English politician’s invention. The closest Chinese proverb being, “Better to be a dog in times of tranquility than a human in times of Chaos”—I’d have to ask Fido about that. In any event with uncertainty about the functioning and future of the Executive Branch, it is comforting to know we have steady, highly intelligent members of Congress like AOC, Margery Taylor Green, or Jamaal Bowman (ok he’s out very soon, and looking to be a volunteer fireman) to steer the ship of state. Every push of the like button will get you a coffee for $5 at Starbucks, but every time you forward this post to a new person you will be eligible to vote an extra 10 times for the candidate of your choice.
Thank you for your continued news !
Good news about RSV and relieved not to have it floating around this summer in addition to COVID and adenovirus !