Hookworm dosing and response
This page discusses the therapeutic use of the human hookworm, Necator americanus (NA) [1]. The other species of human hookworm, Ancylostoma duodenale is not suitable for general therapeutic use because it takes an estimated nine times more blood than Necator, can infect a foetus by crossing the placenta, and is able to migrate via breast milk.
Therapeutic response
The success of hookworm therapy cannot be predicted
At the present time, it is not possible to predict who will benefit from hookworm therapy, nor to what extent a condition might respond, but factors that favour a better outcome include:
- being young
- having been ill for a shorter period of time
- having a less severe form of a disease
The severity of skin response to the initial inoculation is not a reliable guide to the likely extent of success with the therapy.
Early benefits are possible but not common, and they may fluctuate
A few people may begin to see benefits at an early stage, but these don't become consistent until at least 12 weeks.
Disease symptoms may worsen before improving
Disease symptoms frequently worsen during the first few months before beginning to improve. One individual, who had had daily headaches and frequent migraines for many years, saw his symptoms worsen slightly in the first 4 months after his first dose. [10]
Consistent improvement can begin anytime from 3 to 24 months
For the majority of those who do eventually respond, significant benefits do not usually materialise until at least 3 months after the first inoculation, with most people only seeing improvement in their condition between 3 and 6 months.
Some only start to improve between 6 and 12 months.
Others have to wait for more than a year.
In a few cases, the wait has stretched to around 2 years.
Diseases may continue to flare occasionally up to 18 months
Even when benefits appear early in the process, diseases can continue to flare periodically for no apparent reason until around 18 months.
The emergence of benefits can be a gradual process
The appearance of benefits can be a very gradual process in some people, and follows a natural progression in which the amount of time that worms have been hosted can be more important than the number of worms inoculated.
In another example, someone who had been unable to eat any normal foods for more than a decade began to tolerate a few foods for the first time at 12 weeks, but tolerance to other foods was only regained very gradually, over a period of 18 months. [28]
Provided that the colony is regularly refreshed, improvements often continue to appear into the third year, and even beyond that, albeit at a gradually slowing rate. The first comment below was written by someone with MS and food sensitivities after hosting hookworms for over 2½ years.
Different conditions in the same host may respond at different times
Where someone has more than one condition, these may take different lengths of time to respond. One subject experienced an unusually early response when his nasal congestion began to ease on the day after his first inoculation, but his Restless Leg Syndrome only began to reduce during week 5, and took 19 weeks to resolve completely. And, while a few of his food intolerances began to ease at 12 weeks, it was 18 months before he was able to eat all foods again.
A child with “terrible contact dermatitis and severe eczema from multiple food allergies” had mostly clear skin by 9 months after her first inoculation with hookworms, but her food allergies only began to disappear at 19 months. [34]
People with several conditions may not see improvement in all of them
Response may vary from one inoculation to another
The self-treater who reported this, added that, in her case, new symptoms which appear after an inoculation can last anywhere from a couple of days to 6 months. [37]
For benefits to last, a hookworm colony needs regular maintenance
Although it appears that a few individuals may be able to enjoy a continuation of some benefits after hookworms are lost, [38] benefits will only continue in the vast majority of cases for as long as the colony is actively maintained by adding periodic top-up doses.
See also
For more detail about what to expect at each stage of hookworm therapy, see the following page.
Introduction to hookworm dosing
Hookworm dosing cannot be reduced to a formula because everyone is different in how they respond to helminths.
It is not necessary to use the large doses that were advocated by the early pioneers of this therapy, typically starting with a dose of 25 or 35 hookworm larvae, followed in some cases by even larger supplementary doses.
A dose of 5 larvae has proved to be an effective introduction, and this number minimises the side effects that are a common feature of the early experience of hookworm therapy.
For more detail about the possible side effects, see the following page.
If starting with 5 larvae, most hookworm hosts should be free from side effects by 12 weeks, so would be able to add a further dose at this point. However, more worms should not be added until all the side effects caused by the first dose have completely subsided, along with any exacerbation of symptoms of the disease being treated. Otherwise, there could be an aggregation, or "stacking", of side effects from both doses. Apart from the host having to endure these side effects, along with any disease exacerbations caused by the introduction of hookworms, the increased inflammation caused by adding too many worms too quickly may be sufficient to prevent at least some of the new worms from attaching to the gut lining.
For someone who is very sick, it can be tempting to try to speed up the therapy process in the early stages by adding more worms as quickly as possible, but this can be counterproductive, possibly causing such severe side effects that it would be necessary to terminate the colony and start over.
Disease remission is brought about not so much by the number of worms being hosted as by the length of time that worms have been present. There is nothing to be gained by attempting to reach a notional maximum number of worms in any particular time frame. All that is required is that the colony is refreshed by periodic top-ups.
Once disease remission is achieved, the size and frequency of doses can be determined more accurately by observing how long it takes for signs of one’s disease to return after a dose, and using this information to establish a dosing regimen that will maintain uninterrupted remission. A period of experimentation is usually required, and hookworm hosts should keep a record of the size and dates of all their doses.
Hookworm dosing in a nutshell
1. Start with between 3 and 5 NA larvae. (For children, see Hookworm dosing in children below.)
- Anyone who is hypersensitive or has one of several particular conditions, should start with no more than 3 larvae.
- Doses larger than these are not necessary and may cause undue side effects, or may result in the flaring of symptoms of an existing disease, either of which might require termination of the colony and a fresh start. Too many larvae may even cause long-term harm.
2. Supplementary doses can be added at intervals of no less than 12 weeks, but not until all side effects from the previous dose have resolved.
- It can be tempting to quickly increase the number of hookworms being hosted by escalating the number in each dose, but doses of 5 NA will do everything that is needed in the first 6 months, and 10 can be too many for some people.
- Once small doses are well tolerated, the number of larvae in subsequent doses can, if necessary, be increased gradually while being careful to avoid overdosing, which can cause side effects.
- There is no need to aim for any particular colony size. All that is necessary is to regularly add fresh doses to ensure that there are always vibrant young adult worms present in the gut.
3. Once benefits have appeared (between 3 and 24 months), experiment to find the number of worms per dose, and the interval between doses, that will optimise those benefits.
- The ideal long-term dose size and frequency vary between self-treaters by a factor of 10.
4. Keep dosing under review indefinitely because the need for worms can change over time, requiring re-optimisation of the dosing regimen.
5. It is essential to continue to maintain a colony indefinitely, without breaks, because hookworms can only provide health benefits while they are present in the gut.
See the rest of this page for full details about each of the above steps.
The evolution of hookworm dosing
The early providers had limited evidence on which to base dosing
When the first company to sell hookworms online was established in 2007, researchers working with hookworms were still at the stage of carrying out preliminary experiments, including on themselves, in an attempt to establish what number of NA larvae might be suitable for use in reintroducing this species into helminth-naive subjects for experimental purposes. Their preliminary research had established that introductory doses of 50 NA were too much for the recipients, [42] but found that 10 larvae were well tolerated and elicited a modest host eosinophil response. [43] Beyond these experiments, there was little information to help the commercial hookworm providers in deciding what doses they should recommend to their customers.
The two individuals behind the first online hookworm vendor separated early in their association to form two separate companies - Autoimmune Therapies (AIT) and Worm Therapy - which recommended different doses for those commencing hookworm therapy. In the case of AIT, a first dose of 35 larvae was followed by two doses of 50 larvae at 12 week intervals. Worm Therapy started their new clients with a dose of 25 larvae, and based the size and timing of subsequent doses on the recipient’s response to their first dose.
Numerous early hookworm self-treaters who used these two regimens reported significant side effects from the doses they were supplied, especially clients of AIT. One self-treater had to contend with 19 weeks of intermittent diarrhoea from weeks 5 to 24 following an initial dose of 35 larvae, and someone who used AIT’s full 35/50/50 sequence was hospitalised with organ damage that required medical treatment. [44]
For the first few years after hookworms became available commercially, the only online discussion about helminthic therapy was in a Yahoo forum created and run by AIT, where this company’s approach to dosing was accepted, largely without question.
The online community refined dosing based on collective experience
After the creation, in 2012, of the independent Helminthic Therapy Support group on Facebook, reports began to emerge of members who appeared to have inoculated with too many hookworms, causing a loss of benefits and a decline in health that necessitated termination of their hookworm colonies. In some cases, the resulting destabilisation of health caused ramifications that lasted for many months, and even several years for a few individuals. [45]
As more reports began to emerge of adverse side effects following the dosing protocols that were still in use, particularly by AIT, warnings were issued to Support group members about the risks of inoculating with too many hookworms, especially for those who have one of the conditions that are now listed as requiring a modified approach to helminth dosing.
When this Helminthic Therapy Wiki was founded, in January 2017, this Hookworm Dosing and Response page became the repository for all the details about hookworm dosing that had been collected from posts to the Support group and elsewhere. This material showed very clearly that the previous approach to hookworm dosing had been flawed, and that not only are much smaller introductory doses preferable from the point of view minimising side effects, but that they can often produce the same level of efficacy as larger introductory doses, and provide a solid foundation for longterm dosing which might, for some self-treaters, eventually include much larger supplementary doses.
New providers embraced the new approach to dosing
In 2014, a new breed of hookworm provider began to emerge, beginning with Wormswell (2014-2018), and followed by Symmbio (2016), YourSymbionts (2018) and Au NAturel (2019). These companies not only introduced a more user-friendly, pay-per-dose business model, but also worked more closely with the online community of helminth self-treaters than previous companies had done.
Once this wiki was available, the newer providers all recognised the site as the definitive database of information about all aspects of helminthic therapy, and contributed to the site's development. As the knowledge about hookworm dosing evolved, these companies adopted an increasingly more conservative approach in line with the evidence presented on this page.
AIT continued to apply their introductory 35/50/50 dosing protocol until 2017, except in the case of clients with fibromyalgia, whom they had come to realise require much lower doses. After the company’s attention was drawn to this page, they adopted a new dosing regimen and, by late 2017, had begun to introduce newcomers to the therapy with a dose sequence of 5/5/10/10/20/20 larvae. Worm Therapy, meanwhile, continued to start most of their new clients on a dose of 25 larvae, and persisted with this practice into at least the early part of 2019, even after their attention had been drawn to the data on this page, which they dismissed as being "merely anecdotal". The Llamas Clinic, which was closely associated with Worm Therapy between 2008 and 2018, also prefers to supply doses of 25 NA, and has refused to provide some clients with smaller numbers. In one case, the clinic did agree to send a client a dose of 3 NA, after initially being reluctant to do this, but then actually shipped a dose of 10.
Reports received by this wiki in 2020 and 2021 revealed that AIT had by that time reverted to recommending, and routinely supplying, doses of up to 50 NA larvae, even though dosing at this level had previously put at least one of their clients in hospital with potentially fatal side effects. AIT have apparently even suggested that some of their clients should take supplementary doses of up to 100 larvae if they have failed to achieve the results they had hoped for. Usually, in this situation, most providers of NA will recommend the addition of a different species - typically either TSO or HDC - rather than the use of an excessive number of hookworms, but AIT only sells NA, and appear to rely on this species alone rather than suggesting the use of any other.
Obsolete dosing practice is perpetuated outside the online community
Medical practitioners with an interest in helminthic therapy who follow the conversation in the Helminthic Therapy Support group had mostly modified their approach to hookworm dosing by the start of 2019, and the majority were starting new patients on a dose of 5 larvae. A few, however, continued to operate in isolation from the online community, and were not keeping up to date via this wiki. Consequently unaware of the reports of severe side effects experienced by some self-treaters, these doctors continued to use a variety of idiosyncratic dosing protocols that often involved excessively large doses, for example, introducing new patients to the therapy with between one and three doses of 25 larvae.
In late 2018, one naturopathic doctor was still starting most of his patients on an initial dose of 25-35 larvae, followed by 2 or 3 doses of 20 larvae at three month intervals and then 5-10 larvae at 2 month intervals, a schedule that is diametrically opposed to what is suggested by user experience, as reported on this page.
In late 2020, another naturopathic doctor who was obviously aware of the need to start with much smaller doses, was nevertheless introducing too many doses in the first 12 weeks. Starting her patients with a single larva, she was adding a second one a week later, then following these with a further 5 larvae every two weeks until a colony of 20 was reached in the tenth week.
There are some self-treaters who are not working with a doctor and who fail to find, or decide to overlook, the advice available on this page, and turn instead to obsolete information found on assorted sites across the internet, which leads them to seek larger hookworm doses than are advisable. Unfortunately, these individuals sometimes even turn a deaf ear to attempts by providers to encourage them to be more conservative in their dosing choices.
Hookworm dosing in research centres
The hookworm self-treaters who are members of the online community far outnumber the subjects who have taken part in the few formal clinical trials that have been mounted to investigate the therapeutic potential of hookworms, and the researchers involved in these studies have consequently had access to far less data to inform their understanding of the effects of different dose sizes.
Prior to 2006, researchers at Nottingham University had carried out a small dose-ranging study to identify a suitable dose size for their trials of therapeutic infection with NA in humans. [46] They concluded from this study that a dose of 10 NA larvae is well tolerated, elicits a modest eosinophilic and antibody response, and was potentially suitable for use in preliminary clinical therapeutic trials. However, after trials using single doses of 10 NA, the team at Nottingham then employed a single dose of 25 NA in their Worms in Relapsing Remitting Multiple Sclerosis (WiRMS) trial that ran from 2011 to 2016. [47] Other centres investigating the therapeutic effects of hookworms have used doses ranging from 10 to 40 larvae. [48] [49] [50]
The information on this page, condensed from the experience of thousands of citizen scientists in the online community, could be invaluable to medical researchers, if they chose to utilise it. For example, they would come to appreciate the need for implementation of a dose-finding scheme to establish the ideal dose for each individual trial subject, and they would discover the importance of maintaining a hookworm colony by continuing to add supplementary doses at appropriate intervals. Unfortunately, however, medical research has largely ignored the experience of helminth self-treaters and the data presented here.
Socio-medical research confirms established best dosing practice
Socio-medical research first published in 2020 [51] confirmed what had been learned by self-treaters over the previous decade, viz., that there is such wide variation between individuals in their ability to tolerate helminths, as well as in their therapeutic response to them, that the use of individualised dosing is essential. By 2020, this was already appreciated by the majority of helminth suppliers and those physicians who provide information to self-treaters, and the use of an initial dose-finding approach was being widely recommended and practised in preference to attempting therapy with a standard dose applied to all individuals.
As is explained in detail on the rest of this page, the dose-finding approach used initially in hookworm-naive individuals entails starting with a dose of 3-5 NA larvae and then gradually working up to higher doses until either symptoms are relieved or adverse side effects indicate a need to reduce dosage. Failure to start with low exposure levels of NA was described by one of the physicians interviewed by the researchers as being irresponsible and fraught with problems.
If future clinical trials are to effectively test the potential of helminthic therapy, they must address the challenge of implementing dose-finding schemes in their subject cohorts. And, if self-treaters are to be guided towards reaping the greatest benefits from this therapy without incurring undue side effects, all helminth providers and advising physicians must also adopt the dose-finding approach.
The perils of excessive hookworm dosing
Those who began with a dose of 50 or more NA have usually regretted it!
Early pioneers who inoculated with 50 larvae eventually wished they hadn’t! Prof David Pritchard of Nottingham University School of Pharmacy could not cope with a single inoculation of 50 hookworm larvae, [52] and Dr James Logan from the London School of Hygiene and Tropical Medicine, who inoculated with 50 hookworm larvae for a UK TV documentary, had to abort the experiment after 60 days, saying, "I just can't live with the symptoms and the stomach pains.” [53]
Others have expressed similar sentiments.
Doses of 30 or 35 larvae can cause severe side effects
Doses of 20 or 25 larvae can cause very unpleasant effects
Too many hookworms may cause Löffler’s (Loeffler's) syndrome
The side effects caused by large hookworm doses mostly affect the gastrointestinal tract, causing the typical diarrhoea, cramping and gas, etc., but, sometimes, they may involve the chest, and possibly result in Löffler’s (Loeffler's) syndrome, a type of eosinophilic pneumonia (inflammation of the lung) that is caused by the immune system attacking the larvae during their transit through the lungs. This reaction is similar to those that occur at the site of inoculation on the skin, and in the gut.
Löffler’s Syndrome is most likely to be seen in those with a history of asthma or allergy, and it can manifest as a productive cough and shortness of breath, but possibly also as sinus and other upper respiratory issues. These may last for several weeks, but not necessarily continuously, and, while they do not usually require treatment, they can be very unpleasant. It may therefore be wise to avoid the use of doses of 35 larvae or more in order to obviate the risk of inducing Löffler’s Syndrome.
It is also possible to experience Loffler’s syndrome following inoculation with much smaller doses of NA, especially in those with certain pre-existing conditions - particularly those affecting the lungs - or with certain genetic profiles.
Someone with pulmonary hypertension and interstitial lung disease associated with scleroderma, in addition to a pre-existing Strongyloides infection, developed Loffler’s syndrome after taking a dose of 15 NA following previous doses of 5 and 10, both of which had been side effect-free and produced some improvements in health. All three doses were taken at 12 week intervals. Following the third dose, this individual became so ill that she was hospitalised and required high dose prednisone, even after termination of her NA colony. [76] [77]
Someone else who developed Loffler’s syndrome following inoculation with NA subsequently discovered, as a result of extensive genetic testing, that she is essentially defenceless against most parasites, so needs to restrict the number of helminths she hosts. [78] (Amongst other genetic anomalies, she has an adverse variation of the LTF gene [79]. Her testing was carried out by GeneSavvy and reviewed by a doctor experienced in interpreting such tests.)
The latter individual was unaware of her genetic predisposition when she began helminthic therapy, and there will inevitably be others with similar genetic variations who may face severe effects from adding just a few too many NA. Her case is further evidence for why everyone who starts therapy with hookworms should commence with no more than the recommended 3-5 larvae, and should proceed thereafter with caution, only increasing the size of supplementary doses very gradually.
Excessive hookworm doses have caused long-term harm in a few cases
I had undiagnosed MCAS, which was quite mild when I started with NA. My first dose was supposed to be 35, but the provider (AIT) accidentally sent me 50. I was desperate to start because I didn’t want further permanent damage from my MS, so I inoculated with them.
It was a very rough ride, with zero benefits. I added a second dose of 40 on schedule at 12 weeks and all hell broke loose. But… about 11 weeks after that dose I started to see a glimmer of improvement. I wanted to just stick with that for awhile, but my provider insisted I needed my third dose on schedule.
So I took 35 more, and my health went downhill within hours. And I never fully recovered. I ended up with severe eosinophilic pneumonia, a terrible exacerbation of my MS, and MCAS that, to this day, is very difficult to control.
I took albendazole and wiped them all out, with zero improvement. I re-dosed with 6 and started a little recovery, but after a few more small doses, all of the overdose symptoms returned, and I again had to wipe them all out.
I definitely had more benefits from a larger colony, but now my immune system can’t tolerate more than 10-12 NA on board at any one time. I’m 7 years into this therapy, so my acquired hypersensitivity to NA appears to be permanent. I’m quite confident that if I’d taken smaller doses to start with, I could have gotten all the benefits of this therapy without the permanent damage. [80]Larger doses may potentially cause organ damage in rare cases
There has been one report in the scientific literature of a case of reversible damage to the heart myocardium (in addition to Loeffler’s syndrome affecting the lungs) as a result of hypereosinophilia following inoculation over 7 months with three large doses (35/50/50) of NA.
Prolonged side effects can mask other developing conditions
Apart from having to cope with the side effects of larger doses of hookworms, there is also a risk that these symptoms could mask other conditions that might develop during a prolonged side effect period, as happened in the following case.
The first dose
The first dose of NA is best restricted to a maximum of 5 larvae
In the first decade of self-treatment with hookworms (2007-2017), introductory doses of up to 35 larvae were recommended by helminth providers, but this quantity often causes severe side effects. Even a dose of 5 NA can produce some side effects, but these are usually manageable at this dosage.
Not only do very small doses keep any side effects to a minimum, but 5, or even 3, NA, are also effective, and start the process of bringing the host's immune system back into balance.
Patients with some conditions need to start with 3 larvae or less
Anyone with an increased level of sensitivity should start with no more than 3 larvae, especially if they have one of the conditions listed in the following page section.
Here are just two examples of the difficulties experienced by people with hypersensitivities who inoculate with too many hookworms.
Someone with mastocytosis who inoculated with 30 NA ended up in hospital after increasingly high doses of prednisone failed to relieve muscle spasms that were so severe and constant she was literally screaming. She could not even roll over in bed. [84]
And someone with narcolepsy reported as follows.
One therapist who works with hypersensitive patients has reported that a dose of 2 larvae appears to give the same benefit as 3, but that this even smaller number produces less of an initial dip in the individual's overall condition before they start to improve. [85] The effect of using doses of just 1 larva have been reported to be more "hit and miss". [86]
Even 3-5 larvae can cause significant side effects in some people
A first dose of 5 larvae can cause significant transient side effects in some people, and not only those who are hypersensitive.
Even a first dose of 3 NA can be a challenge for a few self-treaters, including some who are not on the hypersensitive spectrum.
Just 3-5 larvae can be surprisingly effective
It can be difficult to imagine that very small numbers of tiny hookworms would be capable of producing much benefit in a host many times their size, but it is clear that they are.
- This last individual then increased the size of her next two doses, but this brought no additional benefit.
- I did fine at 5HWs so went to 10 and then 25. My best benefit was at 5 so went back down. [113]
The absence of a rash may not indicate a failed inoculation
For full details, see the following page.
Other helminth species should not be added alongside a first dose of NA
Beginning helminthic therapy with more than one species of worm presents an increased challenge to the host’s immune system, resulting in a greater risk of side effects.
Once a host's immune system has become accustomed to the presence of one species, the addition of further species may provide extra benefits.
Supplementary doses
Helminthic therapy is not a one-dose fix. To reap the benefits offered by helminths, self-treaters need to maintain exposure to them indefinitely. The first dose is just the starter.
A supplementary dose can usually be added 12 weeks after the first dose, but only if all side effects from the first dose have ceased. In a few cases, side effects can persist beyond 12 weeks.
Once side effects have settled, and the first cohort of worms has been in place for at least 12 weeks, these mature worms will help to modulate the immune system’s response to the second dose. This will result in less side effects unless there is a large increase in the size of the second dose which would make side effects more likely, in a dose-dependent manner. It is therefore recommended that all self-treaters who are using NA should proceed cautiously and only increase the size of supplementary doses gradually, selecting the number of larvae in each new dose based on their experience with the previous dose.
If the first dose was 5, and side effects were absent or minimal during the first 12 weeks, the second dose might be 10. However, if a first dose of 5 larvae causes significant side effects, this should be followed by a further dose of 5, and this should only be added once the side effects from the first dose have subsided. The response to the second dose should then be assessed during the following 12 weeks before deciding on the size of the third dose, and so on until side effects are no longer being experienced.
The amount of time that worms have been hosted is more important for the treatment than the number of worms that have been inoculated, and there is therefore no urgency to reach any particular total number.
After a few doses have been added, side effects should cease to appear altogether, if they have appeared at all beyond the first dose. However, supplementary doses may occasionally continue to trigger a recurrence of the disease being treated, as happened in the following case after each of the first four doses.
Once supplementary doses are no longer causing side effects or exacerbating the disease being treated, the size of doses can be gradually and cautiously increased, while remaining vigilant for any return of adverse effects.
A few NA hosts may eventually tolerate doses of between 35 and 50 larvae
After the first few doses, a few hosts do best with larger supplementary doses in the long term, and tolerate them well.
Supplementary doses of 35 or more larvae may cause side effects
Even subjects who have been hosting hookworms for many years may continue to experience significant and quite long-lasting side effects following supplementary doses of 35 or more larvae.
Supplementary doses may be best kept under 20 or 25
For most of those who are not in the higher risk category, keeping supplementary doses below 25 larvae will reduce the risk of significant side effects.
Some people need to restrict supplementary doses to 5 larvae or less
Some self-treaters have found that they need to continue to use very small doses, and that these provide them with all the benefits they require. This is particularly true for those on the hypersensitivity spectrum, who should continue to inoculate with very low numbers for at least the first few doses, and possibly indefinitely. It is also true for a small number of individuals who are helminth permissive, so have a reduced ability to control helminths, probably due to their genetic profile. Often unaware that they have this characteristic, they accumulate worms rather than losing them to the attrition that limits worm numbers in most people.
A few people may need to pause treatment after just one or two doses
Not everyone needs to add supplementary doses routinely every 12 weeks, and doing this can prove counter-productive for some hypersensitive, or helminth-permissive, individuals.
Dosing in the long term
Hookworm survival
The length of time that hookworm hosts can go between doses in the long term depends on three factors.
- The rate of attrition, which is dependent on the strength of the host’s unique immune response to helminths. This is greatest in people with IBD and other intestinal disorders involving inflammation, and is partly determined by host genetics. [145] [146]. (The authors of one very small study that was reported in 2001 hypothesised that the longevity of adult hookworms is probably determined more by parasite genetics than by host immunity. [147] However, this opinion was based on research carried out in a far smaller sample than that available in the helminthic therapy community, where many hundreds of NA self-treaters have inoculated with larvae from the same stock, but reported losing their worms after widely differing lengths of time. This strongly suggests that host immunity is the major determinant of hookworm longevity.)
- The extent of any use of substances that impact the health of the worms. For details of these, see the Human helminth care manual.
- The number of hookworms that were previously inoculated may also affect the length of time before symptoms begin to return.
Hookworms are reported to survive for 3-10 years [148] but to be capable of living for up to 15 years, [149] and possibly even 18 years. [150] A few hookworm self-treaters have been able to enjoy remission from their diseases for more than 5 years after a single inoculation.
However, the experience of most self-treaters suggests that hookworms typically only survive for between 1 and 3 years.
Some hosts, especially those with digestive diseases, can lose their hookworms in as little as 2 or 3 months.
Long-term dosing is based on individual user experience
The frequency with which NA hosts need to reinoculate varies widely between individuals.
The size of doses required also varies considerably between individual users.
In order for hookworm hosts to establish the ideal dose size and dosing frequency for them, they should keep a record of the size and dates of all their doses while they are gradually introducing larvae within their individual tolerance. Once they have achieved remission, they should pause dosing and note the length of time that it takes between their last inoculation and the reappearance of symptoms of their disease. This will provide the best guide to the frequency with which they will need to re-inoculate in the long term in order to maintain uninterrupted remission.
People who have several conditions may find that, when their colony begins to need reinforcements, symptoms of these conditions may begin to return at different stages. As soon as there is an indication that one condition is returning, and it is clear that the symptoms are not being caused by something else, a top-up dose is likely to be required.
Waiting until disease symptoms begin to return is not usually a problem with hookworms because attrition is a gradual process, and a proportion of the colony should still be alive when symptoms begin to reappear. These existing residents will usually maintain a degree of immune modulation while a new cohort becomes established, and will themselves be perked up by the arrival of the newcomers, with the result that most people see a fairly rapid return of full benefits.
Once it has been established how long a dose will last (this may vary somewhat according to the size of the dose), future top-up doses should be added in time to prevent a recurrence of symptoms, and a reminder to do this should be set in a diary or phone. Otherwise, mild symptoms may not be recognised as an indication of the need to top up one's colony and could be overlooked, with the result that the self-treater might find themselves in desperate need of a dose.
Long-term dosing in practice
After a period of personal experimentation, the majority of hookworm hosts settle on a long-term re-inoculation rate equivalent to 1 or 2 larvae per week, added at intervals ranging from weekly to twice each year, e.g., 1 or 2 weekly, 2-4 fortnightly, 4-8 monthly, 12-25 quarterly, or 25-50 every six months. A few outliers at either end of the spectrum find that they need to add the equivalent of only 1 larva every 2 weeks, or as many as 5 larvae each week, but with a maximum of 50 larvae per dose.
The following comments illustrate the range of dose sizes and dosing frequency being used, and show that many self-treaters top up at least every 3-6 months.
12 months
Unless I take something that kills them, I probably only need 3 or so, once a year. [161]5-6 months
I inoculate with 15 each 5 months, because I swear my baseline symptoms start to return at about 6 months post-inoculation. [162]I need to re-dose every 20 weeks. If I wait longer, symptoms return and I go through worm flu again (though diminished). If I re-dose every 20 weeks, results are more consistent. [163]I need 25 every six months.I inoculate with 30 about every 6 months. [164]I need to take 50 every 6 months.3-4 months
I find 1-3 NA ok. Five is ok if (my colony is) low. But more than that I have symptoms... I will probably do 2 every 3 months as a topup. [165]I now take about 7-10 hookworms every 3-4 months. [166]I dose 20 NA at about 3 month Intervals. [167]I need 25 every 3 months. [168]I have to redose every three months also. 35 is my magic number. [169]I take 40 NA every 3 months. [170]2-3 months
I do best at 2-3 month redoses. If I wait longer, I wish I hadn't. [171]I tried 20 NA every 3 months - it gave me worm flu. Now i've gone to 10 NA every 2 months, and it seems to work better for me personally. [172]I need 40 NA every 8 weeks, for now. [173]I now dose with 40 every 2.5 months. I need a frequent high dose to keep my Crohn's under control. (Link expired)1-2 months
My brother is now doing 3 NA every 4 weeks and that seems to be good for him as at 10-12 weeks he has return of symptoms. [174]I have to dose with 5 NA per month to stay healthy. I kill them off quicker than most people. [175]I switched to a monthly dosage of 15 NA and that seems to solve the problems. [176]I take 5-10 NA every 7-8 weeks. [177]I do 5 NA every 7 weeks. If I do it more often, I feel sick and flared up. If I space it out more, my autoimmune symptoms return. I listen to my body and this is what it needs at this point. I journal my symptoms so I’m able to see the patterns. [178]I’m having good results so far with 1 hookworm every 8 weeks. [179]1-2 weeks
Several people who began to increase the frequency of doses, while reducing the number of larvae in each dose, have continued this process until they were dosing every one or two weeks.
Someone who is treating ankylosing spondylitis went first from dosing quarterly to adding 10-15 NA every other month. [180] Then, finally, she changed to adding 6 NA every two weeks. [181]
Someone who had begun inoculating with 30 NA roughly every 6 months, eventually tried adding 5 every month.
I've recently experimented with 5 every month. I've found that this new schedule is much better at keeping my sinuses clear. I'm beginning to think that the number of larva is much less important than the frequency of inoculation. [182]After noting the improvements gained from more frequent dosing, he adopted a fortnightly regimen.
And he has since changed to weekly dosing with just one larva.
The additional exposure to migrating larvae facilitated by more frequent inoculations may provide increased immune stimulation.
… the larval phase of infection rather than the persisting egg-laying adult worms may be largely responsible for the cytokine production and so responders may be the more frequently/more recently exposed individuals. [185]
Trickle dosing, and sensitisation to NA
In his book, An Epidemic of Absence, Moises Velasquez-Manoff mentions that light, transitory, hookworm infections may prime allergic disease, and some other commentators have suggested that trickle dosing with hookworms (adding one or two larvae every week or fortnight) could present a potential risk of increased sensitisation to them, perhaps reducing the maximum number that can successfully colonise. However, feedback from self-treaters suggests that trickle dosing does not cause sensitisation, but that the addition of too many worms too quickly can do, especially in hypersensitive individuals.
The individual whose experience is described in this last quote has found that inoculating with 8-10 NA larvae every 6-8 weeks also results in sensitisation to the worms. Foods then begin to cause the symptoms that she experienced prior to first using NA, and which she associates with allergy: brain fog, blurry vision, tiredness, grumpiness and lack of motivation.
The risk of sensitisation to hookworms is likely to be highest in hypersensitive subjects and those with allergies, and this is one reason why it is important to start hookworm therapy with no more than 5 larvae (just 3 for the hypersensitive and those with certain other conditions), and then only to increase the size of supplementary doses very gradually so that any side effects that do develop will appear at a manageable rate rather than become suddenly so severe that termination is needed.
Trickle dosing can work well for those who adopt this practice.
It might be assumed that those who choose to dose every week or fortnight would have an almost continuous rash, but the rash caused by 1-3 larvae is usually minimal. [190]
Dose size and frequency may need adjustment over time
Response to helminths may change over time, requiring some adjustment to dosing.
Some people may even experience seasonal changes in their response that also require adjustments to dosing.
Colony size
It is impossible to determine how many hookworms are being hosted at any given time because there is no reliable test for this. Neither can the size of a colony be ascertained by adding up the doses that have been inoculated previously, because attrition is constantly taking its toll on intestinal worms, killing them at widely varying rates in different individuals. So, rather than aiming for any notional colony size, the best approach is for individuals to observe their response to each of the doses they add over time and to use this knowledge to determine what size and frequency of top-up doses will enable them to keep their disease in remission.
Since a few hookworm hosts may not achieve remission for up to 2 years, it may not be possible for them to see any obvious connection during this time between the number of worms inoculated and their effects, so a lack of benefits within this period may not necessarily indicate a need to add more worms. However, people with a higher attrition rate may lose their worms long before they reach 2 years, so it is essential during this period to maintain the colony by adding supplementary doses as discussed above.
Some people do extremely well with a relatively small number of hookworms.
Others have claimed they needed to establish a colony of between 100 and 150, and even as many as 200 hookworms. However, since there is no reliable way to establish how many worms are being hosted, and since attrition rates very widely between individuals, it cannot be assumed that someone who has inoculated with 4 doses of 25 NA over a year will have a colony of 100 at the end of that period. Any improvement in such cases is much more likely to have been the result of the length of time that these individuals had been hosting worms, rather than the number inoculated. The benefits of hosting hookworms can continue to accrue gradually during the first two years, whatever dosing schedule has been employed.
Overdosing on hookworms
There is a risk that attempting to increase the size of a colony without an obvious need to do so may cause a loss of benefits.
This loss of benefits as a result of exceeding a personal dosing limit is seen particularly, but not exclusively, in those on the hypersensitivity spectrum.
In addition to a loss of benefits caused by overdosing on hookworms, there can also be excessive side effects.
In some cases, side effects - especially diarrhoea - can persist for some time after a colony has been terminated.
Reducing the size of a hookworm colony
If too many worms have been added, resulting in unmanageable side effects, it may not be necessary to terminate the entire colony. Carrying out a partial cull should reduce the severity of the side effects while leaving some worms to continue the therapy.
A partial cull can be achieved by using any of the substances categorised in the Human helminth care manual as being potentially lethal to human helminths (marked with an ❌), although the effects of these substances will not be as predictable as those of an anthelmintic drug. The details on the Terminating a helminth infection page can be used to tailor a cull to meet the individual self-treater’s particular needs. For example, a single 500mg dose of mebendazole may kill approximately 30% of a colony of NA and, if this doesn't provide sufficient relief from the side effects, further doses of the drug can be taken as required.
Is there a constitutive limit on colony size?
Croese, et al., observed that the size of hookworm colony returned to the pre-inoculation level by week 21 and, even though this study using capsule endoscopy had involved only two subjects, it’s authors opined that there is a colony size status quo that is constitutively set by the host.
This assertion by Croese, et al., appears to be contradicted by the findings of a more recent study in which a colony of NA observed in a patient was described as "massive".
There may also be different degrees of predisposition to hookworm infection in different groups, e.g., young/old, male/female, [203] and other influences on colony size may include blood group. [204]
Before these more recent studies were published, the earlier paper by Croese, et al., had prompted the following discussion in the Helminthic Therapy Support group on Facebook.
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If this is the rule for hookworm, though, such that a dose of 15 or 50 or 100 or repeated top up doses all result in the same worm load, I wonder how to account for a few things from the historical record.
1) The Italians building the Gotthard tunnel in the late 19th century - they not only got very sick, but many of them died of congestive heart failure. If the worm load is independent of repeated doses and only depends on the individual's predetermined load based on genetics or whatever, what would explain such an epidemic? The tunnel workers likely mostly already had hookworm (how else would it have got into the tunnel in the first place?), so if repeated doses did not increase their loads, why did they go from asymptomatic as a group to sick enough to lead to the discovery of AD?
2) I have the same question for the history of the southern US and NA. Hookworm overloading due to repeated dosing was supposed to be significant enough to cause anemia in enough people to decimate the economy and motivate founding of the rockefeller commission to combat it. Moreover, if repeated dosing does not increase the worm load for most of the population, why was the rockefeller solution, which primarily involved latrines to limit re-infection, so effective that the whole economy was successfully recovered. They did not give everyone multiple doses of mebendazole, so it's not like hookworm was being eliminated. The effect could only be due to reduced worm loads. If the ultimate equilibrium load is not affected by repeated dosing, how can it then go down so profoundly merely be stopping the repeat dosing?
If either hookworm species really behaves in such a benign way, it would also be unique among parasitic eukaryotes.
I suppose it's also possible that even if the adult equilibrium population is independent of dosing magnitude and frequency, that the therapeutic effect may still depend more on how many helminths you are dosed with than how many survive.
Then the situation with NA would be more analogous to TSO - in TSO it the immune response to the attempted infestation that must be doing the trick as there is no persistent infection with adult TS? The effects we get with NA may be similarly be related to the transit of larvae
So it does not follow that even if equilibrium worm load remains the same that it is useless to top up or that larger doses are not more effective.
But I still am skeptical that worm load is a zero order function with respect to dose magnitude and frequency. I'm sure it's not perfectly linear, but there is no other way to account for populations being devastated by poor sanitation than that there is some increase in load with increasing area under the curve for dose....
There is a way that I might trust to actually count worms and it would not be that hard to do. One could make a monoclonal antibody to NA and then bind it to radioactive technetium. Lay down under a gamma camera and you might be able to resolve the number of worms if they were somewhat spread out.
I am a bit skeptical that a pill cam will see them all, given the size of colonic lesions I've seen missed by colonoscopy.
And then there is the Pritchard dose ranging study. Although the numbers were small, the people getting larger doses were pretty reliably sicker and had larger immune responses to match. One would have to believe that the worms were having attrition well after the establishment of enteritis-causing adults in the gut - an attrition that is proportional to the initial dose. More than proportional to the initial dose, actually.
IOW, the immune response is more than proportional to the initial dose, but does not prevent adults attaching to the mucosa long enough to cause eosinophilic enteritis.
And then one would have to further believe that most of the adults attached to the mucosa are then later successfully eliminated, and that the higher the initial dose, the higher fraction of worms are killed by the immune system. Otherwise, the higher the initial dose, the higher the ultimate worm load and we are back to square one.JL
MD
So if we are capable of limiting HW number it is clear that even in someone who was malnourished the presence of approx 20 HW is going to have almost no effect, therefore either the observation that HW have historically been a major cause of morbidity and mortality is incorrect, and people were developing anaemia and other health problems attributed to HW but actually due to other causes.
Or final HW numbers are a direct result of the number of exposures and there is no limiting factor to the final population, allowing numbers that are large enough to cause or contribute to pathology. If this is the case, which I believe it is, there must simply be some factor or variable in Croese's experiments that resulted in numbers being limited. Just because something gets into print does not mean that it is not open to mistakes (experimental) and misinterpretation of experimental data.Colony collapse
Occasionally, hookworm hosts may experience the total loss of their colony, possibly as a result of taking certain antibiotics or consuming one of the other substances that are capable of harming hookworms. (For more details, see the Human Helminth Care Manual.) Colony collapse is uncommon, as is the need to deliberately terminate a colony and start over, but, if it does occur, disease symptoms may return rapidly.
Some subjects have reported a more gradual loss of benefits after a colony collapse, this difference perhaps being due to these individuals having hosted worms for a longer period.
When a colony is lost before any benefits have been experienced, the host may not know that their worms have succumbed. This is one reason why it's important to continue to add supplementary doses at 12 week intervals until benefits have become obvious.
Restocking after a loss of hookworms
In the absence of any existing worms to modulate the immune response to a replacement dose following a colony collapse, this dose should be of an appropriately limited size, perhaps similar to the dose that was used at the very beginning of treatment, if this proved to be effective without causing undue side effects.
A full return of benefits may take a while, and the length of time varies between individuals.
Some benefits may return more quickly than others.
Hookworm dosing in children
Children are usually introduced to hookworms with a first dose of 3, or possibly 5, larvae, but no more than 3 if they have one of the conditions that require a modified approach to helminth dosing.
Based on the child’s experience with the first dose, subsequent doses can be increased gradually, if required, using the approach described above in the Supplementary doses section.
Some children may eventually be able to tolerate doses of up to 25 larvae, and might benefit from being given these larger numbers, once they have an established hookworm colony.
Also see the following page.