Mon 2022-Apr-18

# Ivermectin vs Strongyloidiasis Paper Published

Somebody asked me about the evidence associating putative ivermectin effects with worms, not COVID-19. Seems like it’s been finally published!

## Remember those ivermectin meta-analyses?

Remember last fall when we looked at claims ivermectin worked against COVID-19, but the effect was pretty hinky when we looked at credible reviews? One of the main findings from Scott Alexander’s review [1] was from Avi Bitterman, showing the studies that showed an effect were in parts of the world with worm infestations:

Basically, worm infestations make everything more terrible, including COVID-19; removing the worms if present makes surviving COVID-19 more likely. But if you don’t have worms, then ivermectin does nothing for you.

## Now it’s official!

Well, now Bitterman’s work has made it through peer review and is now officially in the scentific literature. [2] Let’s have a quick look through it:

• First, while there in theory a large number of studies available (199), only 12 made the final cut for inclusion, as we previously saw:
• 11 were duplicates,
• a whopping 175 were not proper randomized clinical trials (e.g., not randomized or no controls) or did not measure all-cause mortality as their primary outcome,
• 2 were excluded for outright fraud or randomization failure
• Statistically, the finding was pretty much that ivermectin looks like it might work if your COVID-19 patients might have worms, but does not work in patients unlikely to have worms. This is quantified by the Risk Ratio ($RR$), basically the ratio of rates of death in ivermectin vs control arms. To achieve statistical significance, you’d like to see $RR \le 1$ and the 95% confidence interval bounded below 1. This happenes only in studies conducted in areas of the world with high worm infestations:

Ivermectin trials performed in areas of low regional strongyloidiasis prevalence18,19,29-32,35,37 were not associated with a statistically significant decreased risk of mortality (RR, 0.84 [95% CI, 0.60 - 1.18]; P=.31). By contrast, ivermectin trials that took place in areas of high regional strongyloidiasis prevalence17,33,34,36 were associated with a significant decreased risk of mortality (RR, 0.25 [95% CI, 0.09 - 0.70]; P=0.008).

• Graphically, it looks like this: $RR$ is on the vertical axis, Strongyloides infestation rate is on the horizontal axis, and each study is a dot (circle proportional to study size).
• The curve is a regression model whose details I didn’t investigate (mixed-effects regression of $\log RR$ on Strongyloides infection rates). But note more importantly the confidence limits on $RR$: they’re only statistically significant in favor of ivermectin (i.e., below 1) in areas with more than about 8% of the population having worm infestations.
• The regression was statistically significance, and predicts a 38% drop in $RR$ for each 5% increase in worm prevalence.

## The Weekend Conclusion

There’s more in the paper, but as far as I can tell the conclusion is that this finally, definitively closes the door on ivermectin as a COVID-19 therapeutic.

Ivermectin is for worms.

For COVID-19, seek first vaccination! Then, if you still get sick: seek paxlovid, molnupiravir, fluvoxamine, and monoclonal antibodies (one of the few remaining ones still effective against the Omicron variant, like bebtelovimab).

## Notes & References

1: SA Siskind, “Ivermectin: Much More Than You Wanted To Know”, Astral Codex Ten Blog, 2021-Nov-07.

2: A Bitterman, CP Martins, and A Cices, “Comparison of Trials Using Ivermectin for COVID-19 Between Regions With High and Low Prevalence of Strongyloidiasis: A Meta-analysis”, JAMA Netw Open 5:3, 2022-Mar-21, e223079. DOI: 10.1001/jamanetworkopen.2022.3079

Written Mon 2022-Apr-18