It's unusually cool today in the Washington, DC, area, prompting my landscape designer wife to don her poison ivy hunting apparel and venture into the nether regions of our back yard to keep it safe for us.
We've had a lighter week in infectious diseases events. I'll take advantage of that to share a rare criticism of one of my favorite ID feeds. But first .....
Leptospirosis
This is a tough diagnosis most of the time; it's a relatively uncommon infection in the US, and the early stages don't have particularly novel signs and symptoms; it's just a nonspecific febrile illness. About 10% of cases can progress to a second and more severe stage, often called Weil's disease. It's important to remember that it can be a water-borne pathogen, as illustrated by these 2 recent reports.
First, this week's MMWR provides us with documentation of the leptospirosis outbreak in Puerto Rico following Hurricane Fiona in 2022. Leptospirosis is endemic in parts of Puerto Rico, and a disruption like flooding due to a hurricane increases its reach and can result in disease spikes. Look at these graphs of weekly rainfall and leptospirosis cases - it certainly fixes in my mind the tie between water and leptospirosis.
The MMWR article has a link to a nice clinician fact sheet.
Similarly, there's a new spike in leptospirosis infections in Thailand, so far just in news reports (you'll need Google translate again).
I first took a deep dive into leptospirosis as a medical student when I came upon a landmark article of detective work surrounding an outbreak in St. Louis. Two of the authors were mentors of mine, and they loved to regale me with (probably augmented) tales of tracking rats through the sewers of St. Louis. I'm sure this contributed to my choice of pediatric infectious diseases as a career, though not to the extent that I've chased sewer rats.
Mixed Messages About Vaccine Protection From Long Covid
A new article reached a different conclusion from several other reports showing that covid vaccination is somewhat protective against long covid, now better termed PASC (Post-Acute Sequelae of COVID-19). The new study is a retrospective cohort study mining an administrative database from a single (large) healthcare system. The bottom line is (of course!) towards the bottom of the table: no real differences in PASC rates based on vaccine status. Also note this was primarily a study of adults.
Is this a flawed study? Are the authors' conclusions wrong? Well, no to both. We will have differences in conclusions from such studies primarily when we are seeing retrospective studies that rely on administrative databases. The authors did a heroic job of attempting to adjust for various errors in how such data is recorded, but it's impossible to account for everything. Thus, we can have errors in diagnosis, diagnostic code assignment, and missing data, among other issues. Couple that with different definitions of PASC and the likely heterogenous pathogenesis of different forms of PASC, and it's a recipe for conflicting study results. I think we likely will have a clearer picture of PASC, including whether covid vaccination can offer some protection, but it will take prospective longitudinal studies which require more time for data collection and analysis. A longer discussion of the science of PASC is reviewed in Nature Medicine. In the meantime, studies like this one help us fine tune future studies.
Shame on CIDRAP
CIDRAP (Center for Infectious Disease and Research Policy at the University of Minnesota) is one of my favorite daily feeds. I think they blew it in mentioning FDA clearance of a new Lyme test; not only is it not newsworthy, but it could lead some individuals to chase harmful Lyme disease testing. I could be guilty of the same by even mentioning it here.
First of all, FDA clearance of diagnostic tests is a relatively low bar to clear. Although I couldn't find any FDA commentary on the test in question (I guess that would require a Freedom of Information Act request), I did link to the criteria that I think likely were used in this setting, because the particular methodology this test utilizes is nothing new. So, I believe the manufacturer would only need to show "substantial equivalence" to existing tests. This is not the same as showing the new test improved diagnostic accuracy or improved healthcare outcomes. Here's the summary of applicable FDA guidance:
"Studies to Demonstrate Substantial Equivalence
The types of studies typically used to demonstrate substantial equivalence may include the following:
- In the majority of cases, analytical studies using clinical samples (sometimes supplemented by carefully selected artificial samples) are sufficient.
- For some IVDs, the link between analytical performance and clinical performance is not well defined. In these circumstances, clinical information may be warranted.
- FDA rarely requires prospective clinical studies for IVDs, but regularly requests clinical samples with sufficient laboratory and/or clinical characterization to allow an assessment of the clinical validity of a new device. This is usually expressed in terms of clinical sensitivity and clinical specificity or agreement."
This new Lyme test is simply an immunoblot, a very common type of test utilized in multiple settings but with the drawback that interpretation is somewhat subjective - a human needs to decide if a band is prominent enough to be considered present.
When I dug deeper to find supporting studies for this particular test, I became more alarmed. While there are some preliminary studies that I think might have used this new immunoblot method, they don't answer any clinical performance questions. More worrisome is that the test will be sold by a California lab called IGeneX, a company that offers many Lyme tests that, in my opinion, have falsely diagnosed many of my patients with Lyme disease. They often rely on their own interpretations of what constitutes a positive test and provide no reliable scientific evidence to suggest their methodology is valid. In fact, the press release for this new test stated that "Results interpretation is based upon new criteria and not CDC criteria."
Even now on their website they steer providers and patients away from the standardized two-tier testing preferred by CDC. Here's a quote from the IGeneX website: "Lyme disease is typically diagnosed by a two-tiered testing (TTT) approach involving an enzyme-linked immunosorbent assay (ELISA) followed by a Western blot test. However, the sensitivity of these commercially available tests is poor, meaning they can miss active infections. Experts advise against this testing technique due to the ambiguity of its results." It's easy to find a so-called expert to say anything. Again, in my opinion, this lab is to be avoided, and you'll notice I didn't provide a link to them. I'm disappointed CIDRAP gave them free publicity.
Lyme disease testing is far from ideal, and it's certainly possible this new test is an improvement, though I doubt it. CDC explains diagnostic testing for Lyme disease, including the recommended two-tiered testing options. I suspect IGeneX might try to claim that their new immunoblot can fulfill CDC recommendations, but I'm concerned that they will use unsubstantiated rules for interpretation of a positive immunoblot result, as they have for similar tests in their lab.
COVID Crystal Ball
Last week my wife and I got our new covid vaccines, more based on upcoming travel plans rather than any immediate concerns about getting covid. In fact, things seem to be winding down. According to the latest CDC clairvoyance, "we estimate that COVID-19 infections are growing or likely growing in 7 states, declining or likely declining in 16 states, and are stable or uncertain in 25 states." (Not a totally reassuring conviction if half the states could be uncertain!)
I couldn't find a separate precise definition of cutoffs for their categories, but from viewing the data it appears that the Stable or Uncertain category is defined as a probability that the epidemic is growing in those states as between 0.5 and 0.75. By comparison, all the Growing states had probabilities of 0.93 and above.
Curmudgeon-in-Residence
I think I've paid my dues long enough to be entitled to curmudgeon status. The new Lyme test thing reminded me of my dismay that some of the children I've seen in my practice over the years were harmed by use of misleading diagnostic tests resulting in prolonged and unnecessary antibiotic use. I wear my Statler and Waldorf credentials proudly. I think I bear more of a resemblance to Statler.
Now, to cool off a bit, I'll take a quick stroll in my (safer) back yard.
