An ongoing dialogue on HIV/AIDS, infectious diseases,
February 21st, 2025
The Language Grouch Returns
Plaster anatomic head, 1900.
If you’re an ID doctor, there’s a lot to be grouchy about these days. This. This. THIS! The list is long — and growing. Longtime readers with an interest in ID: I ask that you please contact your members of Congress to convey the harmful impacts of the workforce cuts at the CDC, NIH, VA, and other agencies. Thank you.
Now, on to the topic of today’s post — a break from the news but maintaining the grouchy mood to discuss some words or phrases I deeply dislike. We’ll come to a new one in a minute, but first a review of a few others already in my penalty box:
- HAART. I sense this one is vanishing, especially among us ID and HIV specialists — either that or people are afraid to say it in front of me. Seems that ART, standing for “antiretroviral therapy,” has finally triumphed. Hooray! Whether my campaign against HAART has anything to do with its demise is unknown, but I’m happy to take credit. In fact, I’ll add that to my CV now.
- Thanks in advance. As a reminder, I vastly prefer (even welcome!) a simple “Thank you” or “Thanks” when a person asks for something. My wife thinks this pet peeve of mine is beyond petty, saying “You want people to thank you and be appreciative, but at the same time you don’t approve their way of doing so. That’s not fair.” Good point — but a Thanks in advance innocently placed at the bottom of an email reminding me to complete my annual HealthStream modules, or a request for 3 learning objectives for an upcoming talk, still rankles. Oh well.
- Quick question. It’s possible every ID doctor gets hives when they hear this one, since the range of complexity in these “quick questions” is vast — and truly unknowable when someone starts out by greeting you with Can I ask you a quick question? I shared this distaste for the “quick question” prelude with an experienced (and excellent) nurse, and she told me I have misinterpreted the intent of the “quick” — it’s not to meant to demean the knowledge of the queried person, but to soften the impact of the curbside to follow. She’s no doubt right — people are trying to be nice! — so I’ve become much more tolerant of this one. Preemptive antihistamines are no longer required to prevent the hives.
But this is just a partial list. So today I’m bringing back the Language Grouch to introduce another unfavorite phrase — and this time it’s a common request:
Can I pick your brain?
Every time I see this one, I immediately think about what it means literally. This would involve cracking open someone’s skull, rooting around inside, and then using a sharp tool to pick at what most people consider the most important organ in the body. The fact that neurosurgeons do this routinely is still unfathomable to me, all these decades of being a doctor later.
But, as the saying famously goes, I’m no neurosurgeon (or rocket scientist), which puts me with roughly 99.999% of the population. And for us non-neurosurgeons, being an active brain picker would not only be inappropriate — it would also get us arrested. Don’t do it.
But of course the request is metaphorical — people who say, Can I pick your brain? aren’t asking to perform a craniotomy. What they’re after is information, not chipping away at your white or gray matter. I know this because I distinctly remember the first time I got the request, which occurred way back in my senior year of college, and no doubt explains my distaste for it. Pull up a chair, here’s the story:
I was taking a wonderful history of music course, the kind of broad survey that completely changes your life by introducing you to something you never really understood. It was the second semester, and we were on to some of the heavy hitters — Mozart, Beethoven, Mendelssohn, Schubert, Chopin, Brahms. The standard classical music canon.
Our “homework,” if you could call it that, consisted of going to the music library and listening to the greatest music of Western civilization in the listening lab, along with an annotated score. Homework! I distinctly recall listening to the opening notes of Beethoven’s Fourth piano concerto as one of my assignments, heard through the special headphones they gave us when we checked out the recordings. Hearing those gentle notes, then the early key change from the orchestra right after the opening, and reading along in the score — it literally gave me chills!
For some context, the early 20-something me had mostly been listening to Led Zeppelin, Blondie, Steely Dan, Elvis Costello, and The Pretenders — Genesis and Yes were the closest I’d come to classical music. Discovering these 19th century great works of music was a revelation. To call me an enthusiastic student barely begins to describe how happy this class made me. I couldn’t get to the lectures fast enough.
The course also had weekly small sections, taught by a fun and funny graduate student memorably named “Fla.” (It must have stood for something. I wonder where he is now. Definitely not picking brains.) I was the kind of student who, if you’re not really into this music stuff, you’d find annoying. In our weekly small teaching sections, I sat at the front of the class and actively engaged with Fla, absorbing his every word.
In the same class was a (sort of) friend of mine, who I’ll call Brian to protect his identity. I’m not saying his large size and ability to push people around and knock them over while wearing pads and a helmet helped him get into college, but just sharing that “talent” of his shows that I have my suspicions.
Not only was Brian indifferent to the charms of the music course, but he also teased me about what he considered my very teacher’s pet-like behavior. Most of the teasing happened in our dorm’s dining hall because he stopped going to the small sections early in the course.
But when it came to prepare for our final exam, Brian reached out to me because there was simply no way to cram the listening assignments into the time he had remaining before the test. Listening to music takes time — you can’t speed it up, they’re not digital podcasts.
Not only that, one of the goals of the small sections was to highlight the most important material, always a harbinger of what was to be on the tests. And Brian had only attended a tenth of the classes — and I’m being generous with that estimate. Fla held no charms for him.
So here’s what Brian said (he was a last-name-first user):
Hey Sax — can I come over sometime and pick your brain about the key material for the music final?
How would you have responded?
Take it away, Ludwig. This music still gives me chills.
The views and opinions expressed in this blog do not represent those of NEJM Journal Watch, NEJM Group, or the Massachusetts Medical Society.
February 14th, 2025
This Year Influenza Came Back to Remind Us It’s Not Messing Around
If it seems like pretty much everyone you know either has the flu or is recovering from it, it’s because we’re in the middle of the worst flu season in over a decade.
Take a look at this figure, from our state’s surveillance data, updated yesterday:
The result of all this “influenza-like illness”? Patients are deluging outpatient clinicians with messages about fevers, sore throats, coughs, and related symptoms. Hospital beds and ICUs fill up with chronically ill people whose condition has worsened due to the flu. Emergency rooms, already overstrained, park sick people in hallways awaiting evaluation and treatment.
Yes, it’s bad out there, folks. This week, we heard that our hospital has four times as many people hospitalized with the flu than as those hospitalized with COVID-19, the first time this has happened since the pandemic.
One of the most common questions we ID doctors get when the flu season is bad, or late, or just strange, is, “Why this year?” The honest answer is this humble three-word sentence:
We don’t know.
Some have blamed the cold weather this winter without much in the way of a significant thaw. Maybe, but other cold winters haven’t necessarily had this much flu. Plus there’s plenty in southern states.
Others cite the low rate of influenza vaccination, in reaction to overzealous (in some views) COVID-19 vaccine recommendations. Perhaps, but this has never been a popular vaccine.
A third theory is the fact that masking and other infection prevention activities in the community have ended. I doubt it’s this because masking was pretty much over last year and even the year before.
Some have asked me if this year’s strain of flu is somehow different, and the answer is that surveillance molecular data do not so far suggest this is the case. This is in contrast to the 2009 H1N1 influenza pandemic, where during April (!) flu cases surged because of the emergence of a novel H1N1 variant to which younger people had little immunity.
Related, one cause of this year’s high number of cases emphatically isn’t a flood of cases of “highly pathogenic” avian influenza, H5N1. Despite active surveillance at the state level, we still are not seeing this illness from this strain to a significant degree — fortunately!
Note that I put the words “highly pathogenic” in quotes. H5N1 is of course of great concern because we have no natural immunity to it. If it emerges as a human-to-human pathogen, we’re looking at an explosion of cases, analogous to or worse than 2009. That’s bad enough.
But another major worry is that it might be intrinsically more virulent, more likely to cause severe disease per case. But the cases of H5N1 reported thus far in the United States from animal sources have had a wide spectrum of severity. At one extreme there has been a death, and at least one ICU admission; at the other end of the spectrum, many have had mild illness (conjunctivitis seems particularly common), and a recent serologic study in 150 bovine veterinary practitioners found 3 positive cases — all asymptomatic.
So I’d propose we remove the two-word phrase “highly pathogenic” as a common modifier of H5N1 until we really know whether it deserves this scary label — not just in birds and cats, but also in humans.
And please, let’s press on with the following:
- Active influenza surveillance, with transparent reporting of data. This recent government action to reduce the CDC workforce will not make this easier. To quote one of my former colleagues who works there right now, “It’s a very sad time for public health.” 100% agree.
- Re-invigorated research to improve the flu vaccine. That universal flu vaccine can’t come soon enough.
- Further drug development to improve flu treatment. Can I interest anyone in interferon lambda again, which was effective in COVID but never developed? It’s a potential treatment for respiratory viruses that may be agnostic to etiology.
Here’s hoping.
The views and opinions expressed in this blog do not represent those of NEJM Journal Watch, NEJM Group, or the Massachusetts Medical Society.
February 6th, 2025
Could This Be the End of PEPFAR?
Short email from a longtime colleague, working in Africa at a PEPFAR site:
Without USAID, PEPFAR is essentially dead.
I got chills reading this.
PEPFAR, the abbreviation for the President’s Emergency Plan for AIDS Relief, started in 2003 under the direction of President George W. Bush. To say it’s been a resounding success undersells the impact of the program. Take a look at these two graphs, first the trend in life expectancy in several African countries (all PEPFAR recipients) before access to HIV therapy:
Now let’s look at what happened after the broad roll-out of HIV treatment, greatly facilitated by PEPFAR:
The PEPFAR program shows what happens when you pour resources into a devastating problem with a highly effective solution — in this case, a rapidly progressive and fatal disease of younger people (AIDS), with subsequent halting of that disease with antiretroviral therapy. Widely cited — and credible — estimates are that PEPFAR has saved more than 26 million lives. It has been so effective that for years it garnered bipartisan support from U.S. politicians who otherwise agreed on hardly anything.
What does USAID have to do with PEPFAR? USAID collaborates with PEPFAR and local partners to implement HIV programs, ensuring the delivery of antiretroviral therapy and other critical services. The sudden freeze in aid disrupts these efforts, potentially jeopardizing the health of countless individuals who rely on consistent HIV care. To quote again my colleague:
USAID manages the supply chain with multiple donors and products — drugs, reagents, equipment. They represent a substantial portion of the PEPFAR budget in my country.
Some have argued that provision of HIV care internationally should shift to be the responsibility of the host countries, especially now that ART has become so inexpensive and widely available. While I understand this argument, isn’t the sensible approach to make this transition gradually, or at least with some warning? And what about the other essential work of USAID? If this action is done solely to save the Federal government money, it’s not going to have much effect. As a reminder, only around 1% of the Federal budget goes to economic foreign aid, and not all of that to USAID.
Beyond the primary concern, which is the health of individuals receiving care and treatment through this program, there’s the reputation cost for our country. A country that supports effective foreign aid in poor nations is considered generous and kind; one that suddenly pulls such aid the polar opposite — selfish and cruel. Another communication from a colleague in a different country:
As a result of the PEPFAR/USAID freezes, we lost a third of our staff in our HIV clinic, mostly people who dedicated their entire professional lives to the clinic. The offices are empty and corridors echo where they didn’t before.
Let’s contrast this with the joy this program engendered when it started. I distinctly remember meeting a doctor from Nigeria in the early days of PEPFAR; he was smiling broadly at the extraordinary effectiveness of ART that he could now give to literally hundreds of his patients. Shaking my hand, he said — “We cannot thank you enough. Please tell President Bush.”
I never met the former President, but I certainly would do so if I had the chance.
The views and opinions expressed in this blog do not represent those of NEJM Journal Watch, NEJM Group, or the Massachusetts Medical Society.
January 25th, 2025
Let’s Hope the MMWR Resumes Publication Sooner Rather Than Later
To us specialists in Infectious Diseases, there are certain verities we hold near and dear to our hearts:
- Antibiotics are miracle drugs, but the bugs will become resistant if we don’t use them responsibly.
- Certain childhood vaccines (e.g., measles, polio, H flu type B) stand as some of the greatest scientific accomplishments in human history.
- To understand infectious risks, you have to have good data, carefully sourced and analyzed.
Number 3 is why this week’s non-publication of the Morbidity and Mortality Weekly Report (MMWR) came as such a shock. MMWR is the CDC’s primary way of publishing and communicating important data for public health. It didn’t go out because of a communications pause at federal health agencies issued by the new administration. The gap in publication marks the first time in its more than 60-year history that the CDC didn’t release a new issue.
Want an example of how useful the MMWR is for us ID people? Here’s a good one:
Highlighted in red, dear friends, is the first report of the disease now known as AIDS occurring in five previously healthy gay men in Los Angeles. The text from this account has always struck me as a perfect example of careful but prescient scientific reporting:
The occurrence of pneumocystosis in these 5 previously healthy individuals without a clinically apparent underlying immunodeficiency is unusual … All the observations suggest the possibility of a cellular immune dysfunction related to a common exposure that predisposes individuals to opportunistic infections.
Spot-on accurate. The second MMWR detailing more AIDS cases occurred less than a month later. Remember, these publications appeared 2 years before the discovery of HIV, the virus that causes the disease.
Subsequent MMWR reports on the rising incidence of AIDS, the populations at risk, and the strong epidemiologic evidence for modes of transmission played key roles in figuring out what was happening on a national and global level. We knew even before the virus was discovered that sexual, perinatal, and blood-borne infection were all implicated, and that household and other “casual” contact posed little, if any, risk.
Want more recent examples of infectious threats all reported in MMWR? A partial list:
- SARS
- MERS
- Zika
- Ebola
- Chikungunya
- Candida auris
- Mpox
- H5N1 avian influenza
- Innumerable food-borne outbreaks
- And yes, of course, COVID-19
I put COVID-19 last because I strongly believe this is the primary motivation for the communications pause issued by the new administration. The pandemic was so horrifically disruptive — so traumatic — to our society that we’re still grappling with the best way to deal with it.
And one unfortunate coping mechanism is the urge to scapegoat individuals and organizations for what happened. The CDC and its publications were often in the center of this storm, and some now want to blame them for all that they were unhappy about.
Was CDC perfect? Of course not. But they tirelessly worked to get things right, and reported abundant COVID-19 data on case numbers, hospitalizations, deaths, and vaccinations that we all turned to regularly. To expect, in hindsight, that they would do so infallibly is setting an impossible standard — one no organization, government or otherwise, can meet.
Apparently, the MMWR staff are still at work, so let’s hope that the pause in communication is brief. There always will be infectious threats out there, with H5N1 avian influenza now being foremost on our minds. It’s only through careful and regular reporting of data that we can face these threats responsibly.
January 11th, 2025
Ten Interesting Things About Norovirus Worth Knowing
For reasons unclear to all, we’ve had quite the run (!) on norovirus cases in the United States this winter. Seems like everyone knows someone who’s been taken down by this nasty illness, and this crowd of miserable people includes one of my medical school classmates, a good friend who texted us about her experience.
Thanks for sharing, Diane, speedy recovery!
So here are ten interesting facts worth knowing as you wisely head to the sink to wash your hands again before eating:
1. It is the leading cause of acute gastroenteritis in the world. This chart-topping characteristic of norovirus is probably even more impressive now that the rotavirus vaccine is available, dropping childhood cases from that virus dramatically.
In case you’re wondering, “acute gastroenteritis” just means diarrheal disease of sudden onset that lasts less than 2 weeks and may be accompanied by nausea, vomiting, abdominal pain, and fever.
2. It was discovered after studying stored stool specimens collected during a community outbreak from 1968. That outbreak involved half (!) the students at a school in Norwalk, Ohio — hence the name, “Noro” gets its first syllable from “Norwalk”. I guess the citizens of that town didn’t want to be remembered for this dismal week.
Before the identification of virus, scientists strongly suspected a transmissible agent for this illness for obvious reasons. Not only was the attack rate so high in that school, but some of the family members of those students (who had not been in the school) came down with a similar illness.
Researchers then conducted some highly disturbing (from an ethical standpoint) human challenge experiments from specimens collected during this same outbreak, proving that it was, in fact, contagious. Can you imagine trying to get studies like this through a human subjects committee today? Awful.
The actual publication of the pivotal paper documenting discovery of the virus wasn’t until 1972, when advances in electron microscopy allowed identification of the culprit critters from four years earlier, shown in this image:
3. Cases of norovirus peak in the winter months. In fact, the illness was once called “winter vomiting illness” due to this seasonal peak, with this generic term used prior to the discovery of the causative agent. Why winter? Humans gather indoors, huddling together against the cold, passing respiratory viruses between each other in the air, and viruses like norovirus in contaminated food, water, and surfaces. Fun times!
It was also called “non-bacterial gastroenteritis” to distinguish it from salmonella, shigella, and other causes of diarrhea that could be diagnosed by cultures. These “non” labels in medicine have always amused me — describing something by what it is NOT. You know, “non-A, non-B hepatitis” before we knew about hepatitis C, or “non-tuberculous mycobacteria (NTM),” a term still in broad use despite way more NTMs than TMs. Weird.
(I still miss NASH — non-alcoholic steatohepatitis — for fatty liver, an entity that seems to change its name every week.)
4. Infamous sites for norovirus outbreaks include cruise ships, daycare centers, recreational water parks, military barracks, nursing homes, and college dormitories. But especially cruise ships — go ahead, check out that link, I’ll be here when you get back.
… (waiting patiently) …
OK, now that you’ve seen the list of reported cruise ship outbreaks just in the past year, do you still want to take that winter cruise? Fact: any place or situation that people gather in close settings, and where contaminated food, water, and surfaces are hard to control, can trigger these outbreaks. How about particular foods? Oysters are often mentioned, which is no surprise at all, giving me an additional reason to avoid these slimy beasts*.
(*Easy for me to say since I don’t like them. Hardly a sacrifice. Feel very fortunate it’s not chocolate, or pizza.)
5. The incubation period is typically 24–48 hours after exposure. However, this doesn’t mean a person is “in the clear” after a couple of days if they don’t catch it in a household, on a cruise ship, or a dormitory that has active cases, for reasons that will be plainly evident in the next scary facts about the durability and ubiquity of norovirus in our world.
6. While norovirus shedding peaks during the acute illness, the virus can still be detected in stools for weeks in many people, small amounts can cause disease, and it’s devilishly hard to kill. The median time to loss of the virus is a month. Wow. A decent proportion of asymptomatic children shed the virus — nearly half in a study of kids in Mexico.
Plus, it’s an incredibly hardy virus — it resists freezing, heating to 60°C, and is not eradicated by alcohol-based hand sanitizers. I’ve heard this last phenomenon is because of the durable norovirus capsid, versus the much more fragile envelopes in other viruses, such as SARS-CoV-2 and influenza. I’m sure virologists have a much more sophisticated explanation.
One might wonder, reading these facts, why everyone doesn’t get norovirus all the time, or at least once every year. It comes down to those basic principles of infectious diseases, which are host factors (immunity, genetics, stomach acidity), inoculum size (how much virus found its way to you), and luck. Secondary attack rates might be high, but remember that sentinel outbreak in Norwalk — “only” half the students got it.
(For the record, my friend Diane’s husband is doing just fine. So far.)
7. After 1–2 days of utter misery from norovirus gastroenteritis, most people start to improve. During recovery, it’s not uncommon to have a week or so of feeling wiped out as one regains hydration and nutrition, but the general trend is favorable despite some ongoing gastrointestinal symptoms.
As with all infections, the disease is more severe for those at the extremes of age and people who are immunocompromised. For the latter group, illness can be prolonged, lasting weeks or even months, leading to profound weight loss.
8. There is no antiviral treatment for norovirus. Treatment is “supportive”, with the goal of maintaining hydration and getting at least some calories in during the acute phase. Remember, even people with cholera — the most notorious and life-threatening diarrheal disease of humankind — can absorb fluids when given liberally. So hydration is key.
What about during recovery? There’s lots of advice out there on the interweb, with variously recommended diets (e.g., bananas, rice, applesauce, toast — “BRAT” — clear broths, avoiding dairy products and spicy foods, etc.), but the reality is that we don’t have good evidence for any particular diet. I tell patients basically to eat what they want, in moderation, and to listen to what their bodies are telling them. The return of hunger is an excellent sign a person is on the mend.
9. The diagnostic test of choice for norovirus is stool PCR. Many laboratories now do molecular tests first — not cultures — to evaluate the causes of diarrhea. Since it’s so common, norovirus is included in all the multiplex panels that test for multiple pathogens.
The increased use of molecular testing no doubt explains at least in part the increased incidence of this infection. But on the flip side, the vast majority of cases are never diagnosed — so whatever figures we see on incidence are no doubt a massive underestimate.
10. Prevention strategies include frequent hand washing, cleaning contaminated surfaces, and isolation of symptomatic patients. As noted above, despite both pre- and post-symptomatic viral shedding, the highest risk time for transmission is during the symptomatic phase of the illness. Will we ever have a norovirus vaccine? Perhaps, though there are plenty of obstacles.
So that’s 10. Actually way more than 10, see how your subscription brings you added value?
And as an additional bonus, listen to my brilliant colleague Dr. Mike Klompas speak in our postgraduate course. Check out his #1 tip for infection control — for norovirus, it’s gold!
January 3rd, 2025
On the Inpatient ID Consult Service, Oral Antibiotics Have a Rocky Road to Acceptance
Home IV antibiotics are not fun — just look at her face. (Image: Pixabay)
Having just completed a stint doing inpatient ID consults, I came away impressed with three things:
- Staph aureus remains the Ruler of Evil Invasive Pathogens in the hospital setting.
- You can “jinx” a holiday season by saying it’s usually quiet on Christmas. This year it sure wasn’t quiet, hoo boy.
- Some surgeons aren’t ready to accept the evidence about oral antibiotics being just as good as intravenous (IV) for their patients with severe infections.
Note I wrote some surgeons — not all. But with apologies to authors of the POET and OVIVA studies, and in particular to Dr. Brad “Oral is the New IV” Spellberg, who has been a leader in this space, I bring you now a blended version of several conversations I had with surgical colleagues when I recommended oral antibiotics for their patients:
Me: I heard from your resident that you wanted a PICC line for Mr. Smith. Did you see our consult note?
Surgeon: Thanks for following him. No, didn’t read it — what did it say?
Me, not at all surprised that the attending surgeon didn’t read our Masterpiece: We recommended that he go home on trim sulfa, one double-strength tablet twice daily. (I might have said Bactrim. Ok, I did.) The organism is susceptible, and it has excellent oral absorption. That way we can spare him the PICC line and all the risks and hassles of home IV therapy.
Surgeon: This was a very severe infection — I’d prefer we be as aggressive as possible in treating it.
Me: Understood. But there’s literature now showing that oral antibiotics are comparable to and safer than IV. I’m especially comfortable in recommending it when there is a high GI-absorption option like Bactrim, a susceptible bug, and there has been source control, as in this case.
Surgeon: Thanks for sharing that — I’m not up on the ID literature, but this infection threatened to get into the joint (or bloodstream or CNS — it’s a generic conversation). In the OR, we drained frank pus*, and had to copiously** irrigate the site with 3 liters of sterile saline.
(*I always felt bad for people named “Frank” when I hear this expression.)
(**Surgeons frequently use the word “copiously” when they irrigate infections. And how do they decide on the number of liters to use?)
Me: Yes, I understand it was bad. But it sounds like you got it all — that’s probably the most important thing. Another thing, he’s taken Bactrim before, and we know he tolerates it well.
Surgeon: Maybe use orals for a milder infection, but not for an infection this severe. I told him after the surgery he’d be going home on IVs. If we use oral antibiotics and it fails, I’d feel bad we didn’t attack this as hard as possible with IV antibiotics.
Me: Ok, we’ll set up the home antibiotics.
Surgeon: Great, thanks so much. Really appreciate your help.
Me: No problem. He’ll go home on 6 weeks of IV colistin.
(That’s an ID joke, ha ha. It really was ceftriaxone.)
A few comments about this exchange.
- It’s entirely friendly. We both want what’s best for the patient.
- The surgeon has already made up his mind before consulting us that IV is preferred over oral antibiotics.
- There is deep anxiety about oral antibiotics not being “aggressive” enough with a “severe” infection, with the concern about an error of omission rather than commission. Meaning, a bad outcome by doing less outweighs concerns about a bad outcome by doing more, which is why I bolded this sentence, and repeat it here: “If we use oral antibiotics and it fails, I’d feel bad we didn’t attack this as hard as possible with IV antibiotics.”
This last point gets to the core of this debate. Surgeons, who by their very nature are quite active in their day-to-day practice, may not comfortable with what they consider a less invasive approach. Intravenous antibiotics are more challenging, more intensive, typically reserved for inpatients or critically ill people, hence (they think) they must be better.
This is a particularly tough nut to crack. And I get it — if an infection is severe, don’t we want to treat it as aggressively as possible?
The problem with this line of thinking is that it ignores good clinical evidence (including randomized trials and well-done observational studies); it does not factor in the risks, hassles, and cost of IV therapy; and it forgets the important principle Brad often cites, which is that the bacteria don’t care how the antibiotic got there — just that it got there.
In some ways, we’ve fostered the surgeon’s view by taking on the management of home IV therapy — often called Outpatient Parenteral Antimicrobial Therapy, or OPAT — as a core responsibility of us specialists in Infectious Diseases. After all, who knows antibiotics better than we do?
But this has insulated them from the problems. If we had each surgeon manage OPAT for their patients, it would open their eyes about misplaced monitoring labs, clotted and infected lines, upper extremity DVTs, failed home deliveries of medications, confused care providers at home, capricious vancomycin levels, and miscellaneous other mess-ups that are an unwelcome part of home IV therapy.
I have a hunch that if Dr. Orthopod P. Neurosurgeon had to manage these and myriad other OPAT issues, they’d be quite willing to consider an oral option if we told them a good one existed.
December 28th, 2024
Notes from a Trip to China
Thanks to Glenn, tour guide extraordinaire, for this picture of the Forbidden City! (Yes, it was cold.)
Here are some observations from a recent trip to China, a country I’d never visited before. It was an 8-day trip related to my editor role at Clinical Infectious Diseases (there is a Chinese edition) and my particular area of focus within Infectious Diseases (HIV), so I’ll start with some epidemiology and medical stuff and wrap up with some non-medical observations.
Big picture — it’s an amazing country, well worth visiting, with dynamic city life, historic sites, incredible food, and so many people. Very grateful for the opportunity to visit.
Two caveats ahead of time — this was just one trip, an “academic exchange,” with lectures and hospital visits. So my experience can hardly be considered fully representative of this complex and giant country. Second, that 13-hour time difference scrambles the brain a bit, so it’s possible (likely) I got some of this wrong. Corrections welcome from the true China experts out there!
Medical and Epidemiology Section
Over 1.4 billion people live in China — that’s over a billion more than in the USA (334 million), in a country roughly the same geographic size. Must keep that in mind when interpreting any epidemiologic data.
China lost the “most populous country in the world” title recently to India, which just edged it out. Population growth has stopped, even after the end of the one-child policy. Like many prosperous nations, young adults in China don’t want to have big families anymore.
China still has just over 100,000 new HIV diagnoses a year. If you think about our 38,000 new cases/year in the USA, and adjust for our respective country’s populations, their incidence appears to be similar to ours, perhaps a bit lower.
Sexual transmission of HIV dominates the current China HIV epidemic in most regions. People told me it was, like the USA, predominantly in men who have sex with men — but it’s hard to find this information in official figures. It’s an enigma!
Despite a big scale-up and wide availability of HIV testing, the late diagnosis of HIV remains a huge problem. Approximately a third of new HIV cases are diagnosed when the CD4 cell count is < 200. As a result, they still have plenty of people diagnosed during a hospitalization for opportunistic infections.
The spectrum of opportunistic infections they see includes the full range of bacterial, fungal, mycobacterial, and viral pathogens. One difference is that southern China is an endemic region for Talaromyces, which is quite uncommon in North America.
There’s very little use of PrEP. This is a big opportunity for HIV prevention, as late HIV diagnosis means not just symptomatic HIV disease and opportunistic infections, it also implies many years of potential HIV transmissions prior to getting on suppressive HIV therapy.
The doctors in clinical practice are unbelievably busy, busy in ways we could never endure in the USA. Doctors told me that some days they saw 50 or more patients. Overnight shifts in the hospital had similar numbers.
One Chinese doctor cited a visit to the USA where she heard doctors complain about being too busy with an HIV clinic that had 10 patients scheduled during an afternoon in clinic. She found that highly amusing.
(Hey — I’d find that busy too!)
The incredibly high demand for medical services, and the required brevity of the clinical visits, has engendered a strain between doctors and patients, and plenty of distrust. Several people mentioned this to me.
The government provides ART and laboratory monitoring for all people with HIV. This includes standard lab tests and more sophisticated molecular tests, if indicated.
The default government-supplied first-line treatment is a four-pill tenofovir DF, lamivudine, and efavirenz regimen. (The efavirenz comes as two 200 mg pills.) This is why a randomized clinical trial comparing it to BIC/FTC/TAF was ethical — efavirenz-based therapy is still standard of care in China.
People can pay to get integrase-inhibitor based first-line regimens that include either bictegravir or dolutegravir. The price is much lower than in the USA.
Transmitted HIV drug resistance is a growing problem. Not surprisingly, it’s NNRTI resistance that’s the issue, which is exactly what happened here in the 2000s.
Non-Medical Section
Cash in China is gone. Everyone pays for things electronically. This is true in the fanciest hotels, shops, and restaurants, at the humblest street stalls selling inexpensive souvenirs, marinated tofu rolls, and chili noodles, and everything in between. The only “cash” I saw was a replica of a bill on a decorative airline ticket.
An app does everything. That app is WeChat — it pays for things, yes, but so much more. It also consolidates your spending history, chats, shared photos, locations, call records, probably your dog’s birthday. It’s all there in one multi-purpose location.
The government monitors everything, and everyone knows this. That includes, of course, WeChat. Sure must make it convenient for them to see what you’re up to!
Cameras are everywhere. I walked into a hotel for a meeting, one I wasn’t staying at, and a camera quickly picked up my face in the elevator, projecting it on a screen next to the number pad and highlighted it.
The cities I visited were unbelievably clean. I visited Guangzhou, Hangzhou, and Beijing. These are big cities, with plenty of people and high population density. You’d think that would lead to plenty of garbage on the streets and overflowing trash cans, but I saw zero of both. It was wonderful.
(Quick aside: Interesting contrast to my hometown New York, where bags of garbage are put out on the street on a regular basis, and trash bins are few and far between or over capacity — or non-existent! New York’s garbage certainly must be quite a shock for visitors from China.)
The cities are unbelievably safe. It was wonderful (again). I strolled down some packed pedestrian passages, brimming with people looking at shops, tasting street food, watching the occasional public dancing group. I asked the person I was walking with — who was wearing his backpack on his back — if he ever worried about pickpockets. “Doesn’t happen here,” he said.
(Another aside — Barcelona is one of my favorite cities in the world. But can you imagine how long your wallet or cell phone would last in your backpack if you wore it on your back on Las Ramblas?)
The quality of rail travel — subways and high-speed trains — is light years better than ours. Public transportation is very affordable and (not surprisingly) very crowded. The airports are gleaming and efficient.
Car traffic in the big cities is quite dense (like ours) but exacerbated by an enormously wide range of vehicles (cars, trucks, scooters, mopeds, bicycles both manual and electric) using the same roads. Seems like half the cars are electric (green license plates), featuring many brands not available here.
Tourist sites are very popular, with most of the tourists Chinese — book ahead! And don’t be fooled by the “empty” look of the Forbidden City in the picture at the top of this post — that was due to the skilled photography work of Glenn, my erudite tour guide, who knew the perfect vantage point for every photo. The place is huge, by the way — that picture is probably 10% of the total area.
Intense security is part of the process of entering famous sites. Don’t forget your passport, which will be scanned or at the very least reviewed.
Tea is ubiquitous. This is the drink that accompanies every meal.
Starbucks is ubiquitous. This and the previous comment are not oxymorons. Tea is for meals, Starbucks for other times of day. In all of my foreign travels, I have never seen a higher density of this chain. There are nearly 8,000 Starbucks in China, and the number has grown fast. Not surprisingly, domestic coffee production has risen up as a competitor.
If you ask for water at a restaurant, it will be hot. Granted, I was there in the winter. But I was told this is typical year-round. It’s actually quite pleasant once you get used to it.
Restaurant meals have no “courses.” The food comes out when it’s ready, even when there are multiple dishes to be shared.
If there’s tipping at hotels, restaurants, or taxis, I didn’t see it. They assume the payment is also for the service. Gosh, that’s a better system.
Family ties are ironclad. Grandparents, children, and grandchildren all occupy the center of life — even if it means lots of travel to make it work and living situations that could strain privacy. Multi-generational households are the bedrock of social life in China.
The work ethic and ambition of young professionals is off-the-charts high. Conversations invariably included numbers of hours worked, salary targets, and promotion goals — plus an acknowledgment that there would be no short cuts to success.
I traveled through Hong Kong on my way and was surprised to learn that people need an “Entry Permit” (EEP) on their Chinese passport to enter the region from mainland China — even today, 27 years after the transfer to Chinese sovereignty.
The control of the internet is a real thing. Google, YouTube (owned by Google), most social media, and the vast majority of western news sites are blocked. There is an English-language, China-sanctioned version of CNN that is available online and on television. Interesting to observe what news is given the go-ahead.
They are enormously proud of the economic progress and poverty alleviation their country has made in the last several decades. They also expressed, at least to me, admiration for resources that our country offers. Several mentioned family members who studied or worked in the USA.
MLB in China stands for “Major League Baseball,” but not really. It’s a fashion label first and foremost. And New York Yankees and Los Angeles Dodgers logos dominate (90% of the team insignias, based on my quick tally). To the Red Sox and Giants fans out there, don’t worry — they are fans only of the logos, not the teams!
It was a fascinating trip — looking forward to going back!
(H/T to Joseph Tucker, Jonathan Li, and Kevin Zhang for helpful feedback on this post, and enormous thanks to the organizers of my trip and my medical hosts, Christoph in particular, who made it possible.)
December 12th, 2024
Dr. Thomas O’Brien — Expert in Antimicrobial Resistance and Giant in His Field (Literally)
Dr. Thomas (Tom) O’Brien was born in January 1929, in between the discovery of penicillin (September 1928) and the publication of the findings in a medical journal (May 1929). As noted by his longtime mentee Dr. John Stelling, Tom physically embodied the antibiotic era — quite appropriate for someone best known for his groundbreaking work in antimicrobial resistance. He died this week at the age of 95.
A longtime faculty member here at Harvard Medical School and Brigham and Women’s Hospital, Tom inspired a crowd of people like me who knew him as a wonderful colleague and mentor. Regularly fielding questions about tricky drug-resistant bugs, he also radiated enthusiasm about the entire field of Infectious Diseases in a way that was never boastful or showy.
I can easily still picture his smiling face towering over the rest of us during weekly plate rounds in the microbiology laboratory, taking such pleasure in the minutiae of a surprising isolate or advance in diagnostics. “Look at this plate of VRE,” he once memorably said. “It grows better with vancomycin. How about that?”, followed by a quick chuckle of amazement at the smarts of microbes.
Tom also was the person whom I first heard describing the framework for thinking about patient care, leading to the The Four States of Clinical Medicine and the perfect two-by-two table. Just wonderful — I think about this all the time.
Here are a couple of personal anecdotes, if I may:
Way back when I was just starting out as a faculty member, still in my early 30s, I received a consultation on a patient with slow-to-resolve severe cellulitis. (Some details in the case have been changed for confidentiality.)
She had chronic leg edema, so was vulnerable to these infections, and this was the second hospitalization for this problem. She also was a high-powered professional here in Boston, a leader in her company; when I first met her, the most striking thing was the pile of impressive-looking documents and thick reports on her hospital tray table as she continued to work despite the infection.
(This was before we had laptop computers or the internet. I told you it was “way back when.”)
I introduced myself as the ID attending, and she shot me a glance over her reading glasses that could not have expressed disappointment more clearly. You? the look communicated, all but telling me, I am not optimistic that you can help me — you’re too young.
After completing the history and physical exam, I told her that the antibiotics the medical team had chosen were fine, but that sometimes these infections — which are usually caused by strep, the same or similar bacteria that cause strep throat — can take a long time to improve. Elevating the leg as much as possible could help speed the process.
Well! This was clearly not what she wanted to hear. Sighing with frustration, she told me this was unacceptable and requested a second opinion — and here’s the kicker: “… from someone older, more experienced.”
Tom O’Brien to the rescue! I saw Tom in the microbiology laboratory and explained the situation. Smiling — he was always smiling — he generously said, “Let’s go up there together and speak with her. My gray hair might reassure her.”
(He did have impressive hair. Family trait, I guess.)
To say that Tom’s kind, gentle manner helped diffuse a tense encounter barely begins to describe how calming his presence in the room was. Lowering himself down from his 6-foot, 5-inch (estimate) vantage point, and sitting by her bed, he gently gave her his thoughts in friendly, easy-to-understand terms, reinforcing what I said without in any way diminishing or ignoring her concerns. It was a master class in doctor-patient communication, and I’m grateful to this day for it.
The rest of her hospitalization she was pleasant — and patient — both with me and the slow improvement. But improve she did!
Here’s a second anecdote: My wife and I were at a divisional holiday party a year or so after the birth of our second child. Struggling big-time with two careers and two little kids, we asked Tom and his impressive wife Ruth (a corporate lawyer) how they managed — especially since they had six (!) children.
“Oh, you do your best,” he said. “Just make sure you show up for their big events. And there’s no shame in getting help.” He then proceeded to tell us that they had an account with a local cab company (this was before Uber), and that their kids happily shuttled from activity to activity using taxis while their parents were at work.
It’s not that opening an account with a cab company solved all our problems. It was his acknowledgment, in such a friendly, unpretentious way, that this parenting thing was tough but that you get by, somehow. If they could do it with six kids, certainly we could do it with two. Something about his calm and cheerful demeanor in the face of this challenge made everything seem better — an approach Tom had about many problems.
(Someone told me that he sometimes said he raised five, not six children — “the sixth one we just threw in there with the rest, and let them take care of raising number six.”)
Dr. Thomas O’Brien, you will be missed! And though I started this piece writing that he is “best known for his groundbreaking work in antimicrobial resistance,” some would argue that perhaps another fact about Tom should take that top spot. I’m speaking, of course, about his son.
Conan, my condolences to you, your mother, Ruth, and your whole family. He was a great one.
(Edit: I learned after posting this that Conan’s mother Ruth, age 92, died 3 days after her husband Tom.)
December 8th, 2024
Who’s Going to Get Lenacapavir for HIV Prevention?
At the International AIDS Conference this past summer, Dr. Linda-Gail Bekker brought down the house presenting the results of the PURPOSE 1 trial of twice-yearly injectable lenacapavir for prevention of HIV in women. The results — zero infections out of over 2000 participants — demonstrated clear superiority over oral PrEP with TDF/FTC. The study simultaneously appeared in the New England Journal of Medicine; always wonderful timing when that happens.
Now, with a similar study design (without the TAF/FTC arm), we have the results of PURPOSE 2, which tested lenacapavir for HIV prevention in men who have sex with men and people who are gender diverse. Again, the injectable approach significantly beat out oral PrEP, with only two infections occurring among nearly 2000 lenacapavir recipients, around a 10-fold lower rate than in the TDF/FTC arm.
These studies highlight one of the great joys of HIV medicine, in that occasionally we get a study result that’s so dramatic it makes everyone in the field wake up and go wow. To jog your memory, here are five previous 5 wow-moments, at least in my opinion:
- Zidovudine during pregnancy markedly reduces mother-to-child transmission.
- Triple therapy with protease-inhibitor/dual NRTI-based ART improves survival — a lot.
- Integrase inhibitor–based salvage treatment gives nearly everyone a chance at viral suppression, even those with multi-drug resistance.
- Pre-exposure prophylaxis works for prevention of HIV in people at high risk for HIV.
- Suppressive HIV treatment is 100% effective for prevention of HIV transmission.
After each of these studies appeared, everything changed — and changed fast. Guideline writers scrambled to update their recommendations, and HIV treaters, clinical researchers, and community activists strongly advocated for changes to the standard of care.
Will the spectacular results of the PURPOSE 1 and 2 trials meet with the same rapid change in guidelines and rapid adoption? There are reasons to think they will, and reasons to think they won’t.
On the favorable side are, obviously, the incredibly good results — so good that many media reports incorrectly cited these twice-yearly injections as a “vaccine”. Hey, quick fact check, it’s not a vaccine!
(Though parenthetically, one does speculate that something this effective will make HIV vaccine research even harder than it is already. How can one demonstrate better protection with a vaccine than seen in the PURPOSE studies?)
The contrarians will cite the current high cost of lenacapavir as treatment, especially compared to generic TDF/FTC, which CostPlus drugs now lists at $32 for a 3-month supply, and many government-sponsored programs will pay for entirely.
Plus, we have the cabotegravir experience in the “real world”, a sobering reminder that efficacy does not equal effectiveness — or at least not if the breakthrough treatment isn’t put into practice. Remember, cabotegravir was also significantly more effective than TDF/FTC in two blinded clinical trials, demonstrated 100% efficacy in women (if one excludes the participants with HIV at baseline), and has been FDA approved for HIV prevention since December 2021.
And our use of cabotegravir so far in the USA? Based on a recently published CDC report of national prescription trends for PrEP, it was around 3% of those on PrEP in 2023; someone who works on PrEP implementation research told me that it’s only a bit higher today. And its adoption in the parts of the world with the highest HIV incidence is, sadly, essentially zero.
FDA approval of lenacapavir for PrEP is pretty much a sure thing, and expected some time in 2025. Who will get it for HIV prevention promises to be one of the more fascinating stories in HIV medicine over the next couple of years. Stay tuned.
November 27th, 2024
Some ID Things to Be Grateful for This Holiday Season — 2024 Edition
Not a fan.
The calendar says it’s nearly the fourth Thursday of November, so here in the United States, the Thanksgiving holiday is upon us. It’s a day when we gather with family and friends to express thanks, to eat plenty (usually too much), to watch a bunch of spectacular athletes bash themselves to smithereens in the name of sport, and to wonder why anyone would eat sweet potatoes with marshmallows.
(Must be the same people who eat candy corn during Halloween. Yuck on both accounts. And no, I cannot be convinced otherwise.)
It’s also time for me to take stock of our ID world, citing some things in our field that I’m grateful for — an annual tradition on this site. Off we go:
Twice-yearly lenacapavir was really effective for HIV prevention. How could this not garner first mention? While it awaits FDA approval for this indication, and making it broadly available will be a critically important challenge, this should a major advance in pre-exposure prophylaxis (PrEP) for HIV.
We’re about to get a bunch of new drugs for treatment of urinary tract infections. The FDA already approved sulopenem etzadroxil with probenecid and pivmecillinam, and they granted gepotidacin priority review (approval expected by March, 2025). Since UTIs are increasingly caused by resistant organisms, I count this as progress. Naysayers will say, “But what about resistance, side effects, cost, and access?”, so allow me to cite the ID doc’s consistent ambivalence about new antimicrobial agents.
But since this is a gratitude post, I’ll just go with the glass half full here — and hope I can figure out how to say sulopenem etzadroxil with probenecid without using the trade name (it might be impossible).
Three additional studies confirmed the remarkably high resistance barriers of dolutegravir and bictegravir. The results of D2EFT (pronounced “DEFT”), VISEND, and a study from the GHESKIO treatment center in Haiti all gave the same message — that these two integrase inhibitors could be used with tenofovir/3TC or FTC and still achieve or maintain viral suppression, regardless of the degree of baseline NRTI resistance. Amazing! Great to have confirmatory data in support of the prior NADIA and 2SD studies.
Seven days of antibiotics was noninferior to fourteen days in the treatment of bloodstream infections. What a great clinical trial — ask an important and common clinical question, set up the primary and secondary endpoints to be of substantial interest, and then power it appropriately to answer the question. The results provide some solid evidence for The Rules, at least if Staph aureus and endocarditis aren’t in the picture. Why can’t we have more clinical trials like this? Can’t wait to hear what they find in secondary analyses, and in their follow-up BALANCE+ studies.
Metagenomic sequencing and other advanced molecular techniques are slowly making their way into clinical practice. I’d bet good money that if I asked 100 practicing ID docs whether they’ve had at least one case where one of these tests provided a solid, practice-changing diagnosis — rapidly and without an invasive procedure — more than 90% would raise their hand. Maybe 99%.
Rwanda appears to have contained the Marburg virus outbreak. In doing so, the country provided a model for pathogen response, involving enhanced testing, rapid initiation of isolation policies, and scaling up supportive care. If there are no further cases by December 21, the outbreak will be declared over.
The DHHS HIV treatment guidelines removed abacavir from its list of recommended initial treatment regimens. If you combine abacavir’s deficiencies (hypersensitivity, cardiovascular risk, lack of hepatitis B activity, pill size) with the remarkably high effectiveness of dolutegravir/lamivudine and the renal and bone safety of tenofovir alafenamide, there’s hardly any reason to use abacavir anymore — you really have to do some mental acrobatics to come up with a compelling indication. Nonetheless, I suspect HLA-B*5701 will live rent-free in our brains forever.
Non-ID gratitude section:
eBikes are now widely available, in many different styles and at a broad range of price points*. If you haven’t tried one yet, what are you waiting for? They are miraculous machines, allowing you to ride unthinkable distances and zoom up steep hills, so therefore can replace cars on many routes. I already have over a thousand miles on mine and have had it only around a year. (*What’s the difference between a “price” and a “price point”. Gosh if I know.)
Andrea Petkovic is a very fine writer. Two things I’m obsessed about are tennis and great writing. How exciting it’s been, therefore, to discover a professional tennis player (now retired) who provides both? Her writing alternates topics breezy and serious, the tone is deft, human, and humorous, and every week there’s a new selection — the most recent example a beautiful rumination on the retirement of Rafael Nadal. The strength of self-published newsletters comes to life in examples like this.
I discovered at least one thing that Microsoft Teams does better than Zoom. Perhaps unsurprisingly, it’s sharing a Powerpoint presentation. Here’s the brief summary: if you share the file rather than sharing your screen, it gives you a great look at your upcoming slides and other features. It’s the “Presenter View” without having to do anything. Transformative!
Jim Gaffigan is skinny now, and even better, he has a new comedy special. He naturally starts out by explaining how he got his new sleeker physique (this will be no surprise), and the responses he’s received from others — all A+ comedy material from this brilliant and prolific comedian. But he quickly veers off into much broader territory, in particular parenting (he has 5 kids) and, in one particularly funny bit, technology.
Take it away, Jim!
Hey, I’ve been doing this post for years now and expect that I’ve missed one of your favorites. What are you grateful for this year?
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
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