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Clinical Trials

Artemisia Comes Through Again

Here’s an unusual twist for you. Many readers will be familiar – to their regret, most likely – with the story of T*ring Pharmaceuticals (name redacted slightly in order to not defame a great scientist whose name was tacked on to this outfit for no reason other than advertising). Their first idea was to go after praziquantel (PZQ, trade name Biltricide) as a likely acquisition – an old generic drug whose price could be jacked up in order to soak insurance payers. (That one didn’t work out for them, so they went on to do that for pyrimethamine (Daraprim) to great, er, fame).

Praziquantel itself now costs a two to four hundred dollars for a course of therapy in the US, but there are relatively few such courses of therapy here. That’s because it’s mostly used for schistosomiasis and other fluke-worm diseases, which are (thankfully) uncommon here, but these remain real problems in tropical regions, especially where access to clean water is difficult. The WHO estimates that the cost of treatment in sub-Saharan Africa is about $0.30, but the recommendation is for several courses in childhood, given across the at-risk population without individual diagnosis, so that adds up. Repeat treatment of those specifically identified with the infection is also beneficial. Merck Serono donates the drug to the WHO, who send it on to national treatment programs with enough resources to administer it, and USAID also pitches in.

But the cost is still an issue; there are too many people in Africa, South America, and Asia who would benefit, and there are not enough praziquantel doses to treat them with the funding available. Some 250 million people actually suffer from schistosomiasis itself, and the number of people you’d want to treat to keep the disease down is surely far higher than that. That last article article mentions that there are signs of resistance developing as well, which is not good news.

Interestingly, the compound’s mode of action is still somewhat unclear. It appears to disturb calcium ion channels in the worms themselves, and may also interfere with adenosine uptake (none of these species can make their own). As a side chemistry issue, I wrote here about a crowdsourcing project to find a good enantiospecific route to the compound, which is now given as a racemate although it’s the (R) enantiomer that does all the work. That next-to-last link has an interesting finding: one problem with dosing the drug is that it has a particularly bitter and foul taste, but that taste seems to be largely from the inactive enantiomer (!)

So this new paper could be of some interest. The authors, a multicenter team of researchers from the Democratic Republic of the Congo, Belgium, Luxembourg, and just down the road from me at Worcester Polytech, have gone back to an earlier treatment for such worm infections, tea infusions of Artemisia, which is known by the folk name of wormwood for a reason. Two Artemisia species were examined (200 patients for each), with tea give 3 times a day for seven days in comparison to the standard 6-tablet course of praziquantel in another 400 patients. There were some differences between the two tea treatments (particularly between male and female patients), but overall the Artemisia treatment appears to have actually been faster and more effective than praziquantel.

It’s quite reasonable to think that this is due to artemisinin, the well-known natural product from this genus that is also used to treat malaria. The compound was found in the 1980s to be an antihelminthic – in fact, I believe that was the research effort that then discovered its efficacy against the malaria parasites. Artemisinin and related compounds have been tried out in Africa for schistosomiasis, but malaria has been the main focus for the drug. The interesting thing is that only one of the two species used in this trial actually produce artemisinin itself, so there must be other compounds involved. Attempts to use Artemisia tea itself for malaria have not been that successful, with most patients appearing to be underdosed by this route. In this case, though, since the problem is confined to the GI tract and the liver, an oral infusion of this sort directly from the plant would seem to be enough to do the job.

Whether or not this can scale to use in affected areas, I do not know. But the Artemisia species involved are found in these parts of the world, and the hope is that growing and harvesting these could turn into a local industry that could be more beneficial and cost-effective than importing praziquantel. There’s going to be some arguing about the effectiveness of the tea route versus dried-plant tablets, etc., but those are the kinds of things that can be sorted out in real-world practice. For now, this looks like something that could help ease the burden of schistosomiasis and a number of other related diseases that human beings should not have to be infected with, and that’s an excellent thing.

27 comments on “Artemisia Comes Through Again”

  1. A Nonny Mouse says:

    An interesting commentary, which I was aware of, but there is also a major problem with Praziquantel in that the Chinese government has shut down most of the plants the were using the Reissert route as they were dumping cyanide residues into rivers…. Most producers have now switched to the Shin-Poong process which has resulted in the price of finished drug substance increasing from about $80-90/kg to about $140-150. It has also resulted in lowered production when there was already a lack of supply.

    The R-PZQ is being developed for paediatric use though it still will be 9 years to launch the product. (

    The open source (Synaptic Leap) which you mentioned has all but shut down now, though I personally have continued working on my own routes (having done R-PZQ for a client) when I have time, one of which could be very interesting from a cost perspective though I need high pressure hydrogenation to complete it!

    1. bb says:

      use a transaminse

      1. Algirdas Velyvis says:


        What do you mean by “use a transaminse”? Transaminase is not going to give you either of the two amide bonds.

        Do you mean to join N2-containing fragment with glyoxylate, to assemble N2-C3-C4 part of the molecule?

        I am genuinely curious, not being snarky.

      2. A Nonny Mouse says:

        Need to reduce an isoquinoline ring cleanly; Pd/C works, but it also takes the other side. Need copper chromite at high pressures and temperatures (which is how THIQ is made- neat with 98% selectivity).

        Nice thing about the process is using isoquinoline + a $2-3/kg intermediate which is made on 100s of tons.

  2. It is worth recalling that wormwood is also the distinguishing ingredient of absinthe, that which, the saying goes, “makes the tart grow fonder.” The active psychoactive component was thought to be thujone, which is a convulsant at high concentrations but which, apparently, never or rarely existed in such concentrations even in preserved antique versions of the liqueur. Nor does it appear to have psychoactive effects. Wormwood is now permitted to be used in the manufacture of absinthe. The URL beneath my name will lead you to a popular article.

    There is no pharmaceutical use for thujone listed in Wikipedia, but its basic pharmacological properties have been elucidated. It is certainly bioactive, and perhaps could itself be antihelminthic; but this is pure speculation on my part.

    1. Anonymous says:

      Absinthe: In the 1966 film version of Madame X, Holly (Lana Turner) has sunken into a life of depravity and is addicted to absinthe. Absinthe was banned from sale in the US from 1915 until 2007. But the way I heard it, “Absinthe makes the fart go Honda.”

    2. Skeptical says:

      There’s even more to the absinthe story; an environmental chemist played an important part in its renaissance. Story linked to my handle.

  3. t says:

    I remember seeing an episode in season 8(?) of River Monsters where two young girls in Brazil were given this tea as a treatment to clear either Malaria or schistosomiasis, and as a later they follow up, they mentioned that the girls were cured.

  4. a says:

    If you give ” 250 million people ” or some significant fraction of them Artemesia in lowish doses to help schistosomiasis and other fluke-worm diseases…….. will you end up enabling resistance in malaria with co-infected people?

    1. TCA says:

      Presumably not if you only use the Artemisia species that doesn’t produce artemisinin.

  5. Marie says:

    This story has gotten quite a bit of play on the airwaves of late. A pertinent point was raised on NPR’s All Things Considered on Jan 3: without treating the contaminated sources of drinking water from which most human hosts get the parasite, a human could be treated for worms one day and re-infected the next.

    Given the relative costs of the courses of treatment, getting people to drink a locally-grown tea regularly for the rest of their lives (which should, with luck and some work on sanitation and drinking-water infrastructure, significantly interrupt the parasite’s lifecycle) ought to be more cost-effective in the long run than occasional – even annual – dosing with a medication, even if the medication itself is more quickly effective in the short term.

    1. MCS says:

      To state the obvious, the proportion of African health problems that would be eliminated by universal access to clean drinking water is far larger than what wouldn’t. This has been known for 100-150 years and as far as I can see, is no closer than ever.

      1. loupgarous says:

        Reliably clean drinking water is something we got relatively late in world history, due to John Snow’s discovery that cholera could be traced to specific wells in London – he ended an outbreak by removing the handle for the pump where cholera victims got their water, inventing practical epidemiology while he was at it. It’s a harder problem in the Third World for a host of reasons, most to do with lack of the necessary energy to filter or boil enough water for everyone.

  6. as2o3 says:

    Derek; you misspelled the plant genus, it’s Artemisia with an i.

    1. Derek Lowe says:

      I managed not to notice that (taking my cues from the natural product’s name, I guess). But no one else seems to have noticed it before you, either! Fixed, thanks. . .

      1. Matthew K says:

        There’s a bit more fixing to do, the article uses “Artimesia” and “Artimisia” several times – neither is right, it’s “Artemisia”. But then I have been a proofreader in my time.

        1. Derek Lowe says:

          Arrg. Fixed, and I’m going to bed before I hose up anything else!

  7. Anonymous says:

    Merck donation: Merck also developed ivermectin (Mectizan) which is used to treat several third world diseases including river blindness. For many years they donated millions of dollars of drug and support. In some regions, the disease and its vector is almost eradicated.

    Merck site: about/ featured-stories/ mectizan.html

    1. Barry says:

      the eradication of the vector of river blindness was the goal of a rival WHO effort (lots of insecticides), not Merck’s ivermectin donations.
      In terms of eradications, “almost” can last an embarrassingly long time. See: “guinea worm”, “polio”…

      1. Isidore says:

        Why a “rival” effort? Treating a disease while simultaneously attempting to eradicate its causes are complementary, not rival efforts.

    2. MK says:

      It’s the other (American) Merck (MSD outside North America).. Praziquantel is donated by Merck KGaA (the original, German Merck).

  8. fred says:

    “…one problem with dosing [praziquantel] is that it has a particularly bitter and foul taste…”

    IIRC quinine has (had?) a similar problem. The preventative dosage was problematic as a result. It was solved with by dissolving it in a solution of ethyl-alcohol, water, juniper berry extract, and then had carbon dioxide dissolved into it under high pressure. I don’t quite recall the exact production order. And my reference is a bit shaky, James Burke’s Connection ep 7, series 1.

    I half wonder if it a direct substitution of praziquantel for quinine would be a worth while endeavour.

    I wonder if

    1. Scott says:

      Better known as Gin-and-Tonic.

      Which is still pretty foul by my tastebuds.

      1. loupgarous says:

        It’s odd how tastes change. I used to drink tonic water because I liked the taste. Somewhere in my fifties, I lost my liking for the tang of quinine. I wonder if lost liver function around then had anything to do with that.

  9. Takes me back….I was a post-doc in the then Dept of Protozoology, London School of Hygiene and Tropical Medicine during the 80s and recall the buzz around artemesia. Some of the history here:

  10. a. nonymaus says:

    Do praziquantel and this tea have any indications of cross-resistance? Would combination or alternating between the two offer better results?

  11. Barry says:

    developing artemisinin for malaria after finding it in an anti-helmintic screen seems no more odd than developing cyclosporin-A as a immunosuppresive after finding it in an anti-fungal assay.
    You won’t find what you’re not looking for.

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