Astral Codex Ten

Loa loa

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Loa loa

Article

Loa loa is a recurring concept in the Astral Codex Ten archive, appearing 2 times across 2 issues between November 17, 2021 and November 24, 2021. The archive places it in contexts such as “possible Loa loa infection (endemic in West and Central Africa)”; “a species of parasitic worm called Loa loa”; “There’s a species of parasitic worm called Loa loa”. It most often appears alongside Alexandros Marinos, COVID, hydroxychloroquine.

Metadata

  • Category: Concepts
  • Mention count: 2
  • Issue count: 2
  • First seen: November 17, 2021
  • Last seen: November 24, 2021

Appears In

Source Context

Recovered passages from the original issue text. When the raw archive preserved outbound links inside the source passage, they are listed directly under the quote.

Ivermectin: Much More Than You Wanted To Know
November 17, 2021 · Original source
Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body. Being full of worms may impact your ability to fight coronavirus. Gluchowska et al write: Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases. Treatment of worm infections might reduce the negative effect of COVID-19! And ivermectin is a deworming drug! You can see where this is going… The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die. According to the WHO: The current COVID-19 pandemic serves to highlight the risk of using systemic corticosteroids and, to a lesser extent, other immunosuppressive therapy, in populations with significant risk of underlying strongyloidiasis. Cases of strongyloidiasis hyperinfection in the setting of corticosteroid use as COVID-19 therapy have been described and draw attention to the necessity of addressing the risk of iatrogenic strongyloidiasis hyperinfection syndrome in infected individuals prior to corticosteroid administration. Although this has gained importance in the midst of a pandemic where corticosteroids are one of few therapies shown to improve mortality, its relevance is much broader given that corticosteroids and other immunosuppressive therapies have become increasingly common in treatment of chronic diseases (e.g. asthma or certain rheumatologic conditions). So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas. And how might you address this, WHO? Treatment of chronic strongyloidiasis with ivermectin 200 µg/kg per day orally x 1-2 days is considered safe with potential contraindications including possible Loa loa infection (endemic in West and Central Africa), pregnancy, and weight <15kg. Given ivermectin’s safety profile, the United States has utilized presumptive treatment with ivermectin for strongyloidiasis in refugees resettling from endemic areas, and both Canada and the European Centre for Disease Prevention and Control have issued guidance on presumptive treatment to avoid hyperinfection in at risk populations. Screening and treatment, or where not available, addition of ivermectin to mass drug administration programs should be studied and considered. This is serious and common enough that, if you’re not going to screen for it, it might be worth “add[ing] ivermectin to mass drug administration programs” in affected areas! Dr. Avi Bitterman carries the hypothesis to the finish line: First two images are with all relevant studies; second two are a sensitivity analysis that removes some of the most dubious. The good ivermectin trials in areas with low Strongyloides prevalence, like Vallejos in Argentina, are mostly negative. The good ivermectin trials in areas with high Strongyloides prevalence, like Mahmud in Bangladesh, are mostly positive. Worms can’t explain the viral positivity outcomes (ie PCR), but Dr. Bitterman suggests that once you remove low quality trials and worm-related results, the rest looks like simple publication bias: This is still just a possibility. Maybe I’m over-focusing too hard on a couple positive results and this will all turn out to be nothing. Or who knows, maybe ivermectin does work against COVID a little - although it would have to be very little, fading to not at all in temperate worm-free countries. But this theory feels right to me. It feels right to me because it’s the most troll-ish possible solution. Everybody was wrong! The people who called it a miracle drug against COVID were wrong. The people who dismissed all the studies because they F@#king Love Science were wrong. Ivmmeta.com was wrong. Gideon Meyerowitz-Katz was…well, he was right, actually, I got the worm-related meta-analysis graphic above from his Twitter timeline. Still, an excellent troll. Also, the best part is that I ignorantly asked, in my description of Mahmud et al above: And it was! It was a fluke! A literal, physical, fluke! For my whole life, God has been placing terrible puns in my path to irritate me, and this would be the worst one ever! So it has to be true! The Scientific Takeaway About ten years ago, when the replication crisis started, we learned a certain set of tools for examining studies. Check for selection bias. Distrust “adjusting for confounders”. Check for p-hacking and forking paths. Make teams preregister their analyses. Do forest plots to find publication bias. Stop accepting p-values of 0.049. Wait for replications. Trust reviews and meta-analyses, instead of individual small studies. These were good tools. Having them was infinitely better than not having them. But even in 2014, I was writing about how many bad studies seemed to slip through the cracks even when we pushed this toolbox to its limits. We needed new tools. I think the methods that Meyerowitz-Katz, Sheldrake, Heathers, Brown, Lawrence and others brought to the limelight this year are some of the new tools we were waiting for. Part of this new toolset is to check for fraud. About 10 - 15% of the seemingly-good studies on ivermectin ended up extremely suspicious for fraud. Elgazzar, Carvallo, Niaee, Cadegiani, Samaha. There are ways to check for this even when you don’t have the raw data. Like: The Carlisle-Stouffer-Fisher method: Check some large group of comparisons, usually the Table 1 of an RCT where they compare the demographic characteristics of the control and experimental groups, for reasonable p-values. Real data will have p-values all over the map; one in every ten comparisons will have a p-value of 0.1 or less. Fakers seem bad at this and usually give everything a nice safe p-value like 0.8 or 0.9.
Inline links: source, Gluchowska et al, the WHO, carries, https://substackcdn.com/image/fetch/$s_!xExE!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2F5da21781-249c-4e59-b616-9f23d83cc044_2048x1184.jpeg, https://substackcdn.com/image/fetch/$s_!4SMr!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2Fdcd6e4b2-37f7-4602-93d5-2581c3b27a60_700x432.png, https://substackcdn.com/image/fetch/$s_!-6n2!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2F7fd6e8f4-093e-4e02-bce7-363615146c9c_2228x1346.jpeg, https://substackcdn.com/image/fetch/$s_!CPZs!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2Fb0425847-198a-4bd3-a63b-149f15d147ba_700x432.png, https://substackcdn.com/image/fetch/$s_!H3rK!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2F9972491b-25b0-4c06-8aca-86fce102ae63_666x147.png, even in 2014, The Carlisle-Stouffer-Fisher method
Pascalian Medicine
November 24, 2021 · Original source
Is anything ever truly safe? There’s a species of parasitic worm called Loa loa. Usually it hides from the immune system. But if you take ivermectin for some unrelated reason, the loa loa dies en masse, the immune system notices the corpses, it freaks out and massively overreacts, and sometimes your brain gets fried in the crossfire. If you get this, kudos - it’s one of the most esoteric ways to die, and any medical professionals in the vicinity will be impressed. But my point is, “this drug has no side effects” is a fraught statement. In principle ivermectin is perfectly safe; in practice, the world is full of weird stuff that can make harmless drugs kill you unexpectedly.
Does Pascalian medicine beat our current strategy of only using drugs that are proven to work? I don’t know. I think the current strategy makes sense on a social level, but I’m not sure that the Pascalian strategy wouldn’t work for an individual. At least an individual who is able to reliably identify which low-but-nonzero-probability-of-benefit drugs really do have very few potential side effects (if you didn’t already know about loa loa encephalopathy, consider that this might not be you; I am very much not-recommending that any reader here do this on their own).