Tuesday, January 12, 2010

Hookworms fail to cure asthma. Our hopes dashed.

I hate to report this news. One of the greatest hopes for a 'miracle cure' of asthma, allergy and possibly autoimmune disease has failed in a scientifically controlled clinical trial at the University of Nottingham in England.

As many of you know the group of researchers at Nottingham was the only research group in the world willing to clinically test HUMAN parasitic worms as a way to control or even cure asthma.

The idea of parasitic worms as therapy for our certain autoimmune and allergic diseases was first pioneered by Joel Weinstock then of the University of Iowa.

Weinstock used pig whipworms which could not survive in humans more than a few weeks. He claimed to have success in treating irritable bowel and colitis disorders with these pig parasitic worms. However, the worms being in the wrong host died in a few weeks and whatever benefit they gave to infected patients did not last. Weinstock could not get permission to use human worm parasites.

In the United States, Food and Drug Administration approval is needed for any clinical trial and the FDA insisted on parasites that could not survive in humans and possibly be retransmitted to others.

I like many of you was very disappointed that the US FDA refused requests for trials with human parasites or even with more trials with pig whip worms. We felt that the effects of parasites on calming a hosts immune system held great hope for our diseases. We especially felt that a HUMAN parasite would be much more likely to secret closer analogs to IL-10 and other human immune molecules that reduced inflammation and calmed our over active immune systems. We still held on to our hope that allergy, asthma and autoimmune disease could be helped by these parasites.

In stepped the courageous researchers at the Statens Serum Institut in Copenhagen Denmark who scientifically tested pig whipworms eggs (TSO's--Trichuris suis ovum) for efficacy in treating allergy. In October of last year, our Copenhagen friends released the disappointing results. The pig whipworms failed to help allergy. Perhaps there is still some slight hope that the pig whipworms might help various autoimmune digestive disorders like IBS, IBD, colitis and Crohn's. However their failure to help allergies seems to have thrown cold water even on this dimming hope.


Even after the Danish disappointment, there was still hope for sufferers of allergy, asthma, and autoimmune disease looking for a cure. Perhaps a very different kind of intestinal parasite might help--the hook worms.

Hookworms are in a completely different group of worms--the flat worm family (trematodes) as opposed to the round worm family (nematodes) that the whipworms are in. Perhaps this different family of parasites would work better than the whipworms especially if a HUMAN parasite was used.

Brave researchers at the University of Nottingham decided to give human hookworms a scientifically controlled clinical trial. We held out hope that these researchers would succeed in finally achieving clinical success. Our friends at Nottingham had somehow gained permission to conduct a real scientific trial of actual human parasite. Quick and easy cures with worm parasites still seemed possible.

Sadly our hopes are dashed again. The trial at the University of Nottingham failed to show a clinically significant difference between the group getting the human hookworms and the group who got sham shots of histamines as a control.

The hookworm larva do not enter the body through the mouth as do whipworms. They burrow through the skin which causes a mild rash and some itching. So the control group had to be given something that would duplicate this rash--histamine.

For a clinical trial to be valid neither the doctor nor the patients should know which group of patients received the 'treatment' and which group of patients did not (This process is called doing a "double blind, randomized" procedure.). Those who do not receive treatment must have similar symptoms initially as those that do, hence the histamine.

Sadly the truly infected hook worm group did not show any significantly better asthma control than the sham hook worm infected histamine group. What a huge disappointment!

Read more here:


I have put in bold face type the most significant sentences in the summary below of the University of Nottingham hookworm results for asthma patients:

Clin Exp Allergy. 2009 Dec 16. [Epub ahead of print]
Experimental hookworm infection: a randomized placebo-controlled trial in asthma.
Feary JR, Venn AJ, Mortimer K, Brown AP, Hooi D, Falcone FH, Pritchard DI, Britton JR.

Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
Summary Background Epidemiological studies suggest that hookworm infection protects against asthma, and therefore that hookworm infection may have a direct or an indirect therapeutic potential in this disease. We now report the first clinical trial of experimental hookworm infection in people with allergic asthma.

Objectives To determine the effects of experimental hookworm infection in asthma.

Methods Thirty-two individuals with asthma and measurable airway responsiveness to adenosine monophosphate (AMP) were randomized and double blinded to cutaneous administration of either ten Necator americanus larvae, or histamine solution (placebo), and followed for 16 weeks. The primary outcome was the change in provocation dose of inhaled AMP required to reduce forced expiratory volume in 1 s by 20% (PD(20)AMP) from baseline to week 16. Secondary outcomes included change in several measures of asthma control and allergen skin sensitivity and the occurrence of adverse effects.

Results Mean PD(20)AMP improved in both groups, more in the hookworm [1.49 doubling doses (DD)] than the placebo group (0.98 DD), but the difference between groups was not significant (0.51 DD; 95% confidence interval: -1.79 to 2.80; P=0.65). There were no significant differences between the two groups for other measures of asthma control or allergen skin sensitization. Infection was generally well tolerated.

Conclusions: Experimental infection with ten hookworm larvae in asthma did not result in significant improvement in bronchial responsiveness or other measures of asthma control in this study. However, infection was well tolerated and resulted in a non-significant improvement in airway responsiveness, indicating that further studies that mimic more closely natural infection are feasible and should be undertaken.

PMID: 20030661 [PubMed - as supplied by publisher]


Greg said...

I must disagree with your conclusion. The study has several flaws: it used a very small amount of hookworms (10 and most people treated for allergies get 30; the study only lasted 16 weeks and it takes 12 weeks for the worms to mature, having only an additional 4 weeks is not enough time to determine effectiveness- remodeling the immune system takes time; there was a small amount of improvement in the hookworm group. The study itself concludes with this statement: "However, infection was well tolerated and resulted in a non-significant improvement in airway responsiveness, indicating that further studies that mimic more closely natural infection are feasible and should be undertaken." They certainly do not conclude that helminthic therapy is not effective.

Anonymous said...

Yes, just underlining the above comment. This Nottingham study is of crucially flawed design. 10 worms is completely inadequate. 35 to 50 hookworms is what is indicated a standard dose by those practising this therapy and in some cases many more. Humans can safely host 250 worms with negligible risk of anaemia and for the purposes of a clinical study they could have easily done a 12 month follow up. I think there's a danger of this being a misleading clinical introduction to a very promising therapy for auto-immune disorders including asthma.

Anonymous said...

It's disappointing to read blogs like this - your conclusion did not accurately portray this study.

Ryan said...

I had some of the same thoughts as other commenters:
1) one study of 16 weeks seems a little short
2) Hookworm group showed a DD of 1.49, and control had a DD of .98. The study then said that this difference was insignificant. I admit I'm not familiar with this type of measurement - but it seems to me that a factor of 50% is pretty significant, unless the .98 and 1.49 values are absolute to a scale of something like 100.
3) At least the study indicated that future investigation is warranted.

Andrew W said...

It would be interesting to see the study design. For example, why did they choose 10 worms and not the standard "therapeutical" dose? Why such a small sample giving such low statistical power? And so on.


OmegaGX said...
This comment has been removed by the author.
Anonymous said...

I disagee with the study authors' decision to use 10 vs. 20-30, but their choice of 10 hookworms was the result of theoretical basis, and their previous small dose-finding study.

First, their claim is that epidemiologically, 50 eggs/gram feces may be enough to protect against asthma. They'd tested 10, 25, 50 or 100 N. americanus larvae. All increased eosinophils and IgE, IgG, and resulted in the 50eggs/gm output. The higher doses caused more of the temporary itching and GI symptoms, and some wheezing (the 10 l dose caused no wheezing). They do point out that the 10 larvae dose produced the lowest IgE increase, so the "greater tolerability is achieved at the expense of a lesser effect in provoking a potentially beneficial (anti-asthma) host immune response.

On the other hand, with only a 12 week study, and only 10 subjects total, they only had 3 pts/dose. At 25 larvae, 1 pt had 3 weeks of itching (one at 4/10), though the 50 larvae dose had less.. All doses had some diarrhea, but the 25 had one pt with a few weeks of low-grade diarrhea, and the 50 larvae dose had one subject with two episodes. Since the 50 and 10 larvae doses had fewer side effects than the 25, and both were pretty mild, it doesn't mean that one can't go higher than 10 larvae.

Given the suggestion of benefit even at the 10 larvae dose, it seems reasonable to redo the placebo-controlled trial with a higher dose and > 16 weeks, to better mimic the doses that the existing companies find therapeutic. If the IRB will allow it.

PS. Where did you find that the IRB in the US will not allow any more of these live helminth trials?

Anonymous said...

Please gets your facts straight. Hookworms are roundworms, and are in the Phylum Nematoda (as are whipworms). The Nottingham study used a human hookworm species, Necator americanus.

Anonymous said...

I'm looking for information on side effects of hook worms and came across this discussion. It's an important one and I just wanted to send out my appreciation of the topic. I have severe seasonal allergies and I'm interested in buying hookworms online. This will be difficult since i live in the states. I want to know about side effects from the hookworms from people that have bought them for this purpose. Sounds like diarrhea is a common side effect but nothing to be too concerned about as long as it's mild. I also wonder if the hookworms are transmittable? I know it's usually transmitted via feces. Anyone know of a person that has tried them for seasonal allergies?
Would it be transmittable via anal sex? I know that's borderline inappropriate but I had to ask.

Anonymous said...

I have severe seasonal allergies and I am looking for side effect info for hookworms in humans. I know you can buy hookworms from a guy in the UK. I live in the States and so I would have to have it shipped to a friend in Canada and then to me. I wonder if the hookworm is transmittable? I know this is borderline inappropriate but I wonder if it's transmittable via anal sex? Any thoughts?

Monika said...

The study is flawed, and there is hope...Here is a short write up about a patient who went to Thailand and took matters into his own hands, but got a doctor to follow him and publish the positive results:

Anonymous said...

The study said "resulted in a non-significant improvement in airway responsiveness".

There is no such thing as a non-significant IMPROVEMENT in airway response when you are constantly near death. Not enough worms, not enough time.

Having said that.. I'm still not convinced they do help asthma/allergies. Hundreds of people have tried helminthic therapy from autoimmunetherapies.com(according to them... but I can't find these people posting their exclamations of joy all over the net, coming up in google searches, surfacing on news programs. I see the guy who sells worms telling him miraculous story all over the place.. where are the others who have been cured? (seriously.. links please).
Cheers, Tim(AU)

Anonymous said...

australia's abc national radio ran a segment with the guy who had a serious asthma /allergy complex e.g. he couldn't put his head out a moving car window w/o suffering an attack.

he took himself to west africa. Hired a taxi and walked barefoot thru 24 outdoor latrines with the purpose of getting (innoculating?) hookworm.

After about three weeks into his return home he knew he was infested with hookworm because he could put his head outside the car window.

He was cured

Anonymous said...

I have to say this is Sad news.

I was on the original trial at Nottingham University in 06 for hayfever and I also get Asthma with hayfever.

I was cured for 2 years after being infected with hookworm. I was one of the people on the study that had a very good response to the worms.

I didn't need to take a single drug, eye drop nose spray or inhaler for 2 years.


Anonymous said...

Uhm... 32 test subjects, 16 infected... That is too few to draw any conclusions at all!

Anonymous said...

The antibodies to pollen, etc., will persist in the body for longer than the period of this trial. Even if the hookworm stopped production of the antibodies, as one possible route to a therapeutic response, then in that case this study would not detect that.

Anonymous said...

Significant in studies only mean they are 95% sure it didnt happen by chance. Medical variances are common in even controlled studies. I respect the scientists conclusion that he thought his results were statistically insignificant. It is a sign of good science. However, as stated above, the format is flawed in and of itself i.e more time, more larvae. But "significant" in science doesnt mean exactly the same thing as it does in our day-to-dat conversations.

Anonymous said...

Also one can argue that for many asthmatics measuring airway responsiveness to adenosine monophosphate (AMP) might not be that relevant. For some asthmatics forced expiratory volume does not correlate well with symptoms. Mild but still extremely annoying symptoms like excessive mucus do not necessarily show up in these types of tests, i.e. spirometry or PEF-measurement.

This means that in many countries in the West (with good asthma care) it is actually hard to find subjects that qualify for these experiments, because you can't even measure their symptoms using spirometry. But some of these people still suffer from their "mild" symptoms.

Anonymous said...

This was a trial about whether the body could tolerate hookworm it was not meant to cure. The researcher him self hosted over 300. The trials have continued to include a higher population. There are also many people self infesting via providers.

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