F. Perry Wilson, MD, MSCE


June 14, 2022

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I'm Dr F. Perry Wilson of the Yale School of Medicine.

The weather is getting warmer, the birds are singing, the grass is growing, and as the shorts and skirts start appearing, so too, like clockwork, do rashes that look like this:


The target rash — erythema migrans — a pathognomonic sign of Lyme disease, named after a sleepy Connecticut town not more than a 40-minute drive from where I'm standing right now.

Lyme disease was first described in 1975 after a cluster of cases that looked like juvenile rheumatoid arthritis appeared in Lyme, Connecticut, associated with bites from the deer tick, but the disease has been around much longer. In fact, the oldest recorded sufferer is likely Ötzi the Iceman, who died more than 5000 years ago in the Alps between Italy and Austria; genetic analysis revealed Borrelia sequences. You'll recall that Borrelia burgdorferi is the most common spirochete that causes Lyme disease, at least in North America.


I have Borrelia on my brain — not literally, I hope — not only because of the nice weather and my tendency to shank golf balls into the tall grass, but also because of an article appearing in BMJ Global Health in which the authors do a ton of legwork to characterize the prevalence of exposure to bacteria causing Lyme disease around the world. And the numbers are quite a bit higher than what I expected.

The study is a meta-analysis, culling through papers from 1984 to 2021 that had one thing in common: They measured anti-Borrelia antibodies in humans' blood.

These antibodies arise shortly after infection and can persist for quite a long time, perhaps even for life. After screening, 89 articles presented data on how many people had those antibodies — how many people had been infected by a Borrelia spirochete.

The results? A lot of people. As many as 1 in 6 worldwide — 14.5% of the population, if you combine the results from all of these studies. That's 1.2 billion people. This number seems quite high.

Lyme disease is a reportable illness in the United States, and about 35,000 cases a year are reported in this country to the CDC. But the CDC acknowledges that the reporting system is passive and thus vastly undercounts the total cases. Using administrative data based on ICD-10 codes, the CDC estimates the true number of yearly cases in the US as somewhere around 450,000.

That's a lot of Lyme disease. It's no coronavirus, of course, but the yearly infection rate is about 10 times higher than a bad flu season.

The BMJ Global Health paper helps a bit to tell us where to look for all these infections. It's not rocket science. The authors show that antibody positivity is substantially higher among people in high-risk occupations (which includes farmers, soldiers, housewives — their word, not mine — and retirees, among others), people who live in more rural areas, and people who have recently been bitten by a tick.


The study also shows that the prevalence of Lyme disease is increasing, by about 50% from the 2000s to the 2010s. While it's not clear why that is, it is hard to miss the resonance with other infectious diseases that spill over into human populations as we encroach further into nature.

But if coronavirus has taught us anything, it is to have some healthy skepticism about antibody tests. Though the 89 studies the authors looked at all tried to look for Borrelia antibodies, the methods they used to do that were all over the map. The gold standard here is western blotting, and studies that used western blot to confirm antibody tests found substantially lower prevalence of Lyme disease — about 50% lower, in fact.

Which means, of course, that antibody tests can give false positives. In fact, some studies have shown that Epstein-Barr antibodies, something the vast majority of adults are walking around with, can cross-react to lead to false-positive Lyme tests.

The clinical lesson is one that has been reiterated by infectious disease societies for years: Lyme antibody tests are not good tests to guide treatment. At best, they may be used to do what the authors here are doing: give general estimates of the population burden of disease and trends over time.

But even using the low end of estimates of Lyme prevalence, it's clear that this disease has not gotten the attention it deserves. It is endemic to five out of seven continents, has affected millions, if not billions, of people alive today, and, given its varying presentations — 25% of kids don't even get the rash — might be easily missed.

So keep Borrelia on your brain as the weather warms. It's a great time to be a tick.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale's Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com.

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