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Making this treatment more widely available

Travel to the tropics to infect oneself with hookworm is expensive, very dangerous and uncertain in outcome. It is as likely that one will return with malaria or some other horrible disease as it is that one will return with hookworm. Besides, if you visit a place like Cameroon you will be in constant state of fear of violence. That fear is more than justified. So, because I have gotten such good results and because the science behind it is so well-developed (see below) I wanted to make this therapy more easily available. For those who believe that they would benefit from helminthic therapy, but who do not want to undertake the expense and risk that I did in travelling to the tropics, I have started a clinic offering safe, sterile inoculation with hookworm. The hookworm larvae are extracted and purified using methods developed at British and Australian universities, methods they used to obtain larvae to inoculate their research subjects. You can visit my web site for that clinic here Autoimmune Therapies


Helminthic Therapy: How to put your Asthma, Colitis, IBD, Crohn's or Multiple Sclerosis into remission with hookworm.

This is my account of how I cured, or more correctly put into remission, my asthma and hayfever by deliberately infesting myself with the intestinal parasite hookworm.

This story is not for the faint hearted.

It involves a great deal of research, a trip to Cameroon and a lot of barefoot walking in open air latrines in equatorial West Africa.

If you have asthma or know someone who has asthma (or for that matter Crohn's Disease, Inflammatory Bowel Disease (IBD), multiple sclerosis or colitis) and are suffering badly, you owe it to yourself to consider this approach.

Because although it sounds strange and is repellant, it is founded on sound science and it has one other virtue.

It worked.

I have had severe allergies all of my life. As a child I suffered from hay fever so bad that my eyes would swell shut and mucus would stream from my nose. I would lie in a darkened room with a cold damp flannel over my face to quell the itching, almost inebriate from antihistamines. Spring was pure misery.

Later, I smoked cigarettes for seven years when I was a teenager and into my early twenties. I have been told that these two things are the prime markers for the development of adult-onset asthma. That is exactly what I started to get when I reached my early thirties.

As my asthma got worse I became increasingly reliant on inhalers, pills and antihistamines as well as upon the oral steroid prednisone to stay out of the hospital. I tried all the drugs and therapies available. As it was, by the time I was in my late 30s I was a frequent visitor to the emergency room. As anyone who has experienced a severe asthma attack can tell you, they are terrifying.

My use of prednisone increased, and as you may know, the side affects of prednisone are quite horrible, particularly with long-term use. I started to suffer from some of these side affects, particularly obesity, and despite all this these drugs were only marginally effective in controlling my asthma.

Soon, because of a change in employment, I was denied health insurance, so now I had the added burden of paying for all my medical care.

On a trip in the summer of 2004 to visit relatives in England, I learned of a BBC documentary about the connection between a variety of intestinal parasites and various autoimmune diseases. Visiting the BBC web site (go here to view the BBC article or go here to see the many articles on the same subject indexed and available through Google) I learned that not only did infestation with hookworm appear to cure (I use cure sometimes in this article where I should use remission because I find remission a clumsy word to incorporate into a sentence, and from my point of view my asthma has been cured. If it walks like a cure, looks like a cure and quacks like a cure, then...) hay fever and asthma but also IBD, Crohn's Disease and Colitis.

Some Links:

Wellcome Study into Asthma and Hookworm
ABC Science Online Asthma and Hookworm

Research at Nottingham - Asthma and Hookworm

Article about link between Asthma and Hookworm

New Scientist Article about Asthma and Hookworm

British Medical Journal on IBD & Crohn's treatment with hookworm

Crohn's & Ulcerative Coliltis research
Inflammatory Bowel Disease

Intrigued, I did more research and located some peer reviewed scientific papers published in the Lancet and the New England Journal of Medicine that demonstrated this link (membership is required to view these articles). I roped in some friends with graduate degrees in hard sciences and asked their opinions. After sifting their replies to remove the institutional bias, the consensus was that there seemed to be something there.

A Google search regarding the University of Nottingham study conducted in Ethiopia, as well as a recently undertaken study at Nottingham financed by Wellcome Laboratories indicates that hookworm may indeed cure asthma.

Obviously for the drug company that brings a new asthma therapy to market based on this research, there is the potential for billions in revenue. Unfortunately even if they are successful in identifying the mystery compound that hookworms secrete it will take around ten years to bring it to market, assuming they are successful in proving efficacy and safety.

The Decision to Infest Myself With Hookworms

Based upon what I read, and what I learned about the hookworms I decided that I was going to try and infest myself with hookworms in an attempt to cure my asthma. I was not willing to wait ten or more years for the drug companies to bring a drug to market. It was obvious to me that hookworms, for a healthy adult with a good diet, are quite benign. This account details my experiences, how I went about it, and the things I have done since infestation to calibrate my level of infestation so that in the end I was able to cure my asthma and hay fever with hookworms. These same techniques are of course applicable to any hookworm infestation, whether you want to control asthma, hay fever, colitis, Crohn's disease or IBD.

All about the worm

Ancylostoma duodenale, a face only a mother could love

Two species of hookworms commonly infest humans, Ancylostoma duodenale and Necator americanus. These species are found throughout the tropics. The distribution of each species significantly overlaps that of the other.

Hookworms are estimated to infect up to 1.3 billion people around the world depending on whose statistics you read. Most people who are infected are asymptomatic (without symptoms). Adult hookworms are very small, less than half an inch long and about half a millimeter wide. The most significant risk of hookworm infection is anemia secondary to loss of iron (and protein) into the gut but this only occurs in individuals with extremely high infestation levels or in those who are malnourished or immuno-compromised. Or all of the above.

A duodenale and N americanus are small (male: 8-11 mm, female: 10-13 mm), off-white worms. The sexes cannot be distinguished by the naked eye. Hookworm larvae (themselves invisible to the naked eye) emerge from embryos passed in stool within 24 hours and molt once to an infective filariform larval stage in another 24 hours. After molting, larvae are able to penetrate intact skin. The larvae can remain viable for up to two weeks on the ground.

Walking barefoot in soil contaminated with feces (the source of hookworm eggs/larvae) is the most common method of exposure. The other is inadvertent ingestion of contaminated feces. Note that the hookworms cannot proliferate in your gut, you can only increase your infestation level by coming into skin contact with larvae or ingesting contaminated feces. After skin penetration, the venous circulation carries larvae to the pulmonary bed, where they lodge in pulmonary capillaries. Within 3-5 days, the larvae break through into alveoli and travel up the ciliary escalator from the lungs into the bronchi, the trachea, and the pharynx. This often causes a violent cough such as I experienced. Upon reaching the pharynx, larvae are swallowed and gain access to the GI tract. Once in the GI tract, worms attach to the wall of the lower intestine and begin to feed on the blood of the host. They are intestinal leeches.

Eggs begin to appear in the stool approximately 4-6 weeks after initial infection (assay of stool is the primary means of diagnosis). The lifespan of the worm is up to 1 year for A duodenale and up to 5 years for N americanus. The female produces 10,000-25,000 eggs per day during this time. Per day baby! What a machine. I have also read that the larvae can travel up through up to six feet of soil to reach the surface of the ground if stool is buried. One has to appreciate the remarkable durability of these creatures.

Hookworm infection is rare in the US and western Europe. Simply having toilets and sewers does for them because without feces contaminated soil they are out of business. The prevalence of infection is as high as 80% in lesser-developed countries with moist tropical climates (and lacking toilets) but is only 10-20% in areas with drier climates. Hookworm infection rarely is fatal (mostly in very heavily infected and malnourished children) but anemia can be significant in the heavily infected.

But, hookworms cannot proliferate in your intestine, the only way to increase the worm load is to come into skin contact with stage one larvae.

Hookworms can be cured with a two-day course of very cheap oral medication that is widely available.

How I Obtained Hookworms and Cured my Asthma

Having decided that I was going to infest myself with hookworms I set about using internet resources to locate a supplier of hookworms embryos or larvae. The problem is that every government bureaucracy concerned with such things has been devoted to the elimination of hookworms since the 1920s. In addition it is a controlled organism (in Canada at least). None of the biological supply companies I was able to locate and contact carried live specimens of human hookworms, their larvae or embryos. The best I was able to locate were slides of dead examples.

Having hit a dead end I tried to contact the health departments in the southern states of the US, for Mississippi, Alabama, Georgia, etc, where hookworms used to be prevalent. The problem I ran into here is that hookworms are now very rare in the US and is not a reportable disease. So there is no requirement that health authorities track incidences of the disease. It undoubtedly exists I was told, but no one was able to tell me where. It is unlikely to be widespread anyway, just the introduction of toilets is likely to eliminate this parasite because it puts an end to the possibility that anyone might walk in contaminated soil. Puts the tropics in perspective.

I next contacted my doctor to ask his help. He turned me down after some consideration. The reason was that his malpractice insurance would have been revoked if he had helped me get infested. No insurance, no practice.

My requests to all my friends working as researchers, or the few graduate students I know were also denied. This was too far outside the then current orthodoxy for them to consider. WAY too far...

My attempts to enroll in the studies at Nottingham and Iowa were also fruitless.

At this point I came to the conclusion that short of bribing a research assistant or stealing samples from a lab I would have to go to the tropics and walk around barefoot in human excrement. Not an attractive proposition, but then neither is not being able to breathe, and the breathing thing was going to last the rest of my life.

But where to go to find these hookworms?

Intensive searches of the WHO website turned up just one map showing hookworm distribution in only one country: Cameroon.

I read extensively on Cameroon. By any measure it is one of the poorest places on the planet, although ironically relatively prosperous compared to most of its immediate neighbors. It is at best in the bottom quartile, but mostly in the bottom decile, for almost every measure of human welfare and economic well being that the UN and WHO measures.

Life expectancy is 47 years and declining, HIV/AIDs is approaching 20% which (given that half the population is under fifteen and presumably much less likely to be infected) means about about a third of the adult population has HIV). Hey baby!

The average annual wage is less than $700, it is at the epicenter for malaria and is afflicted with a legion of horrific diseases.

I found this ...off-putting... But I resolved to go. I spent almost a thousand dollars on vaccinations (although for the worst and most lethal diseases there are no preventive measures you can take, except to avoid the vectors of the disease, such as mosquitos for malaria and filharzia). For more information on the diseases prevalent in Cameroon you can start here. The highlights are malaria, dengue fever, river blindness, sleeping sickness, filharzia/elephantiasis, bilharzia (nasty!), rift valley fever, two varieties of hepatitis, cholera, typhoid and yellow fever. Filharzia is my least favorite, a mosquito born nematode (worm) that takes up residence in your lymphatic system and that if left untreated the worms proliferate and so clog your lymph system that your extremities swell with undrained lymph to produce elephantiasis. It is in incurable, but can be managed with treatment. I don't think I got it but I won't know until 2007.

Malaria and Dengue both have a mortality rate approaching 5%. Fortunately it appears that the only disease I caught was hookworms.

Still, I booked a ticket with Air France (flying with Air France was not a happy experience for me on this trip) from London to Paris, on to Douala and finally to the capital, Yaoundé. This was ridiculously expensive but there are effectively no choices for getting there. So I paid. First I had to get to London, I recommend Virgin Atlantic if you are flying from San Francisco or New York to London.

Being in the US I had to get my visa for Cameroon from the embassy in Washington DC. They are remarkably concerned with making sure visitors are going to leave their country and require far more documentation than the Americans ever did of me when I was an alien. Because time was short and because I live in California I used a visa facilitation service called Travisa to handle this for me, they got me the visa very promptly and for a reasonable fee. You can find their website here.

My Experiences in Cameroon in Brief

Cameroon is the third world, and the reality of statistics like those regarding incomes approaching a dollar a day are given a palpable reality as soon as you leave the airplane.

Africa is a constant assault on western sensibilities, from the open sewers or sewage running down the street, public urination, and lepers to the utter absence of law enforcement, EMT services, traffic lights and the insane and very dangerous driving habits of the locals. The only guidebook for Cameroon lists auto accidents as a leading danger for visitors. They aren't kidding. Having said that I loved it, but it probably isn't for most people.

Cameroon has no tourism infrastructure, its people being so poor (your pocket change represents two or three months wages) and the insane corruption make for a very challenging environment for a western traveler, particularly a conspicuous white one. You are a walking pile of cash, a visitor form another, much wealthier, planet. One feels very vulnerable and exposed. It can be very wearing and the danger of being robbed is constant.

This is a country where there is zero in the way of a safety net. If you are injured or beaten or robbed you are on your own. Dying, ignored in the street, is surely possible. Fortunately I met some very generous Cameroonians on the plane who invited me to stay with them. As they lived exactly where I wanted to go I headed for their place as soon as I woke up on my first day in Yaoundé, the capital. They had disembarked in Douala, the economic capital.

A nice street in the capital of Cameroon, Yaoundé
A leper, no fingers or toes, Yaoundé
Less than two dollars a day for an average wage translates to no light bulbs, never mind sewers and garbage collection
A small market in Yaoundé

Traveling to the west of the country meant taking a bus along the main road between the capital and the economic capital, Yaoundé and Douala. The road was a two lane highway in good condition about equivalent to an A road in the UK or a county road in the USA. From there it was another half day to Limbe, the regional capital of one of two Anglophone provinces in the West.

A wreck we encountered on the way to Douala from Yaoundé involving a truck, minibus and motorcycle.
The truck won.

A typical street scene in front of the main bus station in Douala. Keep your hand on your money and passport.

Our hosts were the most amazingly generous and kind people one can imagine. They  freely shared their house, knowledge and food, and showed us around. They were absolutely wonderful, as were most of the people I met in Cameroon. For instance they put a car and driver at my disposal, which proved invaluable in reaching the poorer and more remote areas where hookworms are prevalent. Without their help I am sure I would not have been successful. Thank you Richard and Sophie.

With the driver's help (I told everyone of my quest) I was able to visit a variety of villages and with practice learned to identify where the locals would defecate.

Almost no one owns a car, most cars are taxis, so everyone walks to work. Most workers are farmers or work in some kind of agriculture, and of course almost no one has plumbing never mind toilets, so when they leave the main road in the morning it is often time to relieve themselves.

So I looked for busy spurs off the main roads near population centers, villages. Sure enough, within about 50 meters of the main road there would be a variety of shared latrines. Meaning a clearing in the brush. I was able to avoid being stung or bitten by any of the worst types of insects, centipedes and reptiles while I was there, although the ants are enormous, aggressive and extremely painful. Luckily for me in the tropics excrement decays rapidly away to nothing, within 48 hours. Which is exactly the interval required for the hookworm embryos to become viable larvae. I have to admit that I stepped in a lot of excrement before I observed that. :-((

I became infested almost immediately, it must have been either the first or second day I spent walking barefoot through the latrines. When one thinks of it this was an enormous piece of luck. With an infection rate of below 20% even in this the most infected province of Cameroon, and the fact that infections are likely to be localized, and that a tiny fraction of one percent of the land is given over to contaminated soil, actually stepping in the right spot is quite a feat (no pun intended). Of course, I could not be sure without the tests almost two months later. So, I persisted with it for the remainder of my two-week stay. Having come that far I was not going to let my revulsion prevent my returning with hookworms in my body.

Seeing me the locals would often get fairly aggressive, wondering what the hell a white guy was doing walking around barefoot in their toilets. Still, I did get to meet a lot of interesting people. Unfortunately they were usually very intimidating, at least until they had calmed down. An angry man with a machete when you are standing isolated and alone in such an alien place is trying, particularly when you are compelled by circumstance to argue with him.

Five days after my first day walking barefoot I woke up at about 2 am coughing. For the next 2 hours or so I coughed, peaking in frequency and intensity about half an hour after I woke up. It built in intensity to the point that I vomited. It was a cough unlike any I have had. It was persistent and entirely unproductive (zero phlegm), and violent.

Six weeks after my return I tested positive for hookworms, but I still had asthma, so using the following techniques I increased my infestation level until my asthma and hay fever were cured. Helminthic Therapy: The Science behind what I did

How helminths like hookworm protect their hosts against Crohn's Disease, Asthma, Ulcerative Colitis and Multiple Sclerosis

Discovery of eosinophil and demonstration of its presence in both allergic disorders and helminth infestations provides a link between allergy and infection that was first observed in the late 1870's. Ehrlich observed and described the eosinophil in 1879 when noting that some cells containing numerous intracytoplasmic bodies stained strongly with the dye eosin.Shortly thereafter Muller and Rieder noted similar strong eosinophilia in hookworm infections, and others described numerous eosinophils in the phlegm and blood of asthma sufferers. Spurred by these observations, in 1913 Herrick wrote that 'Common to both bronchial asthma and Ascaris infestation is an increase of the eosinophils of the blood. One day we will ask the significance of this eosinophilia in this association'. Herrick may have been the first to recognize a possible association between asthma and helminthiasis. However, more than half-century would pass before this possible link was methodically investigated.

Two independent groups, in Sweden and the USA, discovered IgE in 1967, demonstrating its prominent role in both helminthiasis and allergic disorders. At around the same time several studies showed asthma (and other AI diseases) to be rare in the tropics. Godfrey investigated asthma in Gambia where the population was heavily infected with helminths and failed to find any cases of asthma.

Similar results were obtained from studies in Rhodesia (Zimbabwe) and Papua New Guinea. A recent meta-analysis of the data from these early surveys by Masters et al. demonstrated that the prevalence of parasitic infections was strongly negatively associated with the prevalence of asthma and allergic disorders. A supporting personal example of such a link was provided by Turton in the Lancet (1976), when he recounted how his longstanding hay fever did not recur after he had infected himself experimentally with hookworm.

While both disorders had been demonstrated to be linked by IgE and eosinophils the mechanism and factors involved directly were unknown. Many investigated the role of eosinophils whilst others studied the role of IgE in an attempt to understand and explain the precise relationship between helminthiasis and allergy. Investigators first thought that eosinophils damaged mast cell mediators, and their removal modulates the allergic process. However it was learned quite quickly that eosinophil granules are toxic for helminth larvae. By the 1980s eosinophils were shown to be the culprits in allergic reactions, and responsible for the tissue damage seen in asthma and related allergic diseases. Since then, as more data has been gathered, the picture is becoming more complex and less clear. Eosinophils appear to be pluripotential, displaying distinctly differing roles in various physiological processes, including tissue homeostasis, host defence and tissue damage. What they do depends on their context.

High IgE levels are seen in both helminth infections and atopic disorders such as asthma and seasonal rhinitis. Johansson et al. demonstrated that saturation of mast cells by the high levels IgE seen in myeloma patients inhibited the Prausnitz-Kustner reaction. These observations suggest that the paradoxically high IgE levels seen in parasitic infections prevent atopic diseases developing in such patients. Helminth- infested subjects are somehow protected from mast cell degranulation and inflammation by other allergens. The IgE blocking hypothesis explains this. A Lancet editorial in 1976 proposed that consequently a promising theoretical approach to prevention or treatment of allergic diseases would be deliberately to induce high IgE responsiveness, for example, by artificial infection with parasites'. Epidemiological studies of immune response have demonstrated that protection by helminth infections is conferred by high levels of polyclonal IgE.. This was demonstrated when patients lost their skin reactivity to allergens following helminthic infections.

Hygiene hypothesis and Th1-Th2 theory

Countless epidemiological studies have shown significant increases in the incidence and prevalence of allergic diseases and autoimmune disorders in the developed world in the past two decades. This trend in the clean and sterile developed world is not found in developing countries. There are also clear differences between rural and urban areas within many countries, particularly in the developed world. Only one factor has been demonstrated to have a significant effect. The number of early childhood infections is overwhelmingly and negatively associated with atopy. These may have a protective effect against atopic disorders. Matricardi et al. showed that childhood exposure to food and oro-faecal pathogens, such as hepatitis A, Toxoplasma gondii and Helicobacter pylori, reduced the risk of atopy in later life by more than 60 per cent. David Strachan observed a higher prevalence of atopic allergic disease in first born children compared to their younger siblings and on the basis of this and other studies introduced the term, 'hygiene hypothesis', in 1989. He proposed that lack of antigenic insults, due to cleaner environments, vaccination, and antibiotic use, would change the human immune system so that it responds inappropriately to otherwise benign environmental materials. Mosmann discovered that fully differentiated mouse CD4+ T cells secreted one of two different sets of cytokines, Th1 (e.g. INF-[gamma] and I1-2) and Th2 (e.g. I1-4 and I1-5) cytokines that determine the path of the inflammatory response. T-lymphocytes were stimulated by a normal granulomatous inflammatory response to produce Th1 cytokines. The majority of bacterial and viral infections have been demonstrated to produce a strong Th1 response. Lymphocytes expressing Th1 cytokines prevent the development of cells secreting Th2 cytokines; Th2 cytokines are associated with atopy and asthma development. The Th1 cytokines are viewed as the 'good' cytokines, which inhibit atopy immunopathology whereas Th2 cytokines are seen as the 'bad' cytokines. This concept of a balance between Th1 and Th2 responses is pivotal for the hygiene hypothesis.

This idea is supported by more recent studies that buttress the Th1-Th2 theory of atopy development and have provided further pointers to the aetiologic factors causing an adverse Th1-Th2 balance that lead to subsequent atopic disease development. The neonatal and early childhood periods are believed to be the critical periods for the establishment of the Th1-Th2 balance. Early infections are believed to establish a Th1-biased immunity and prevent the induction of the Th2 system that causes atopy. Intestinal microflora during infancy could be a cause of the induction of immune deviation. The composition of the flora may determine who will and will not develop allergy disorders.

Bjorksten et al studied newborns for the first two years of their lives from two countries with differing allergy prevalence, Estonia and Sweden. They demonstrated that in comparison with healthy children, the babies who developed allergy were less often colonised with enterococci, bifidobacteria and bacteroides in their stool cultures. Allergic infants had higher counts of staphylococcus aureus and clostridia counts. Many studies demonstrate that exposure to farming environments in childhood provides protection against development of allergies. Von Mutius et al. showed that this protective exposure derived from farm environments was most beneficial in the first six months of life and that the effect is enhanced if exposed until the age of five years old.

Some have speculated that endotoxin exposure in early life provides protection against atopy development by triggering Th1responses. Recently Bottcher et al studied infants from two countries that have a low (Estonia) and a high (Sweden) prevalence of allergy. They demonstrated endotoxin levels that were higher in Estonian than in Swedish house dust, which may account for the observed difference in atopy incidence. As well the levels of endotoxin inversely related to the development of atopy.

The hygiene hypothesis and the developing immunological model have been increasingly factors in selecting approaches to the prevention and cure of allergic diseases. One attempt to correct the reduction in microbial exposure in early life suggested by the hygiene hypothesis is the probiotic administration in infancy, and this has been studied. Probiotics are cultures of potentially beneficial bacteria of the healthy gut flora. Kalliomaki et al. performed a randomised controlled trial using Lactobacillus GG in prenatal mothers and newborns. The incidence of atopic eczema for the probiotic group was demonstrated to be half that of the placebo group. Probiotics may prove to be effective method of atopy prevention and may one day be administered routinely as part of well baby plans. Using bacterial products to induce Th1 stimulation may prove effective against atopy development. Heat-killed Mycobacterium vaccae (SRL 172), a potent down-regulator of Th2 cytokines and stimulator of Th1 response, has been shown to prevent allergic responses in mouse models and to minimize asthma during exposure to allergens.

More theories

Some research involving helminth infections suggests that the current Th1- Th2 model may be incomplete. Helminth infections were resolved in mice when Th1 cytokines were stimulated whereas the opposite occurred when Th2 cytokines were produced. Clarification proved that helminth infections were associated with the most potent Th2 cytokine responses. A major discrepancy in the hygiene hypothesis is that, although helminth infections and atopic diseases are associated with similar immunological phenomena, allergic responses were rarely observed in infected individuals. Rather, in contradiction, they are protected from allergy diseases by parasitic infestation. As a consequence, there has been some re-evaluation of the immunological explanation of the hygiene hypothesis and various adaptations and new theories have been forwarded to explain this and other theoretical discrepancies.

'Modified Th2' response

Asymptomatic helminth infections correlate with high serum levels of IgG4, another Th2 dependent isotype. It has been demonstrated that parasite specific IgG4 antibodies inhibit IgE-mediated degranulation. The concept of 'blocking antibodies' was proposed as a possible mechanism of allergen immunotherapy in the 1930s and 40s, by Cooke. One of the characteristics of successful immunotherapy is the induction of allergen-specific IgG4 antibodies. Platts-Mills et al. demonstrated that high exposure to cat allergens results in high IgG4 levels and decreased atopy when exposed to cat dander. This supports the role of IgG4 mediated down-regulating allergic responses. They suggested a modified Th2 response to reconcile the apparently contradictory protective Th2 response seen in helminth-infested patients.

Education of the immune system by pathogens

Chronic parasitic infections causes T-cell hypo-responsiveness, helminth infections are associated with poor T- cell responses. This hyporesponsiveness is thought to spill over to unrelated antigens. Studies on immunological responses to a purified protein derivative of TB, or tetanus toxoid after BCG, or tetanus vaccination demonstrates weaker responses in patients with concurrent helminth infection, when compared with healthy controls. Our immune system is trained towards an anti- inflammatory network by chronic pathogen exposure with associated down- regulatory molecules such as IL-10 and TGF-B possibly involved. Immunosuppression with raised IL-10 levels has been proven in studies on filarial and schistosomiasis patients in West Africa. Training the immune system in hosts exposed to a variety of long term or chronic helminth infestations may be different from those in subjects living in relatively sterile industrialized areas. There may be major implications for the manifestation of immune-related diseases, like allergy. A strong anti-inflammatory regulatory network, trained by exposure to multiple childhood infections, might help inhibit the chain reaction of events that lead to allergic inflammation.

Evolutionary by-product

It is speculated that the human immune system evolved the immediate- type hypersensitivity to respond primarily to a wide variety of parasites present in the environment. Under constant assault from a wide variety of parasites our immunological systems are calibrated to their presence. Parasites do not directly prevent atopy but the removal of the parasites leaves an immune mechanism without its usual target antigen. The IgE response to common airborne allergens becomes the default response absent helminths and other parasite infestations. This theory is consistent with the observed dissociation between very high IgE levels and reduced or non-existent skin test reactivity to aeroallergens seen in those from areas infested with helminths. Perhaps the high IgE levels bind to mast cell receptors and block the actions of aeroallergen.

A broader concept

Although it is proven that differences in infant and early child environment, such as childhood infections, pose significant risk factors for the development of allergic conditions like asthma and hayfever, many feel that is not enough to cause asthma alone. The evolving ideas for allergy development include post-natal risk factors, such as infections, to be only part of a greater scheme that includes fetal development and genetic predisposition. The idea that fetal experiences may have a significant impact on the development of illness was popularized by Barker et al. A well-known example is the increased risk of asthma and atopy seen in low birth weight infants. While Barker focused on fetal nutrition as the main factor, other factors are also important. Maternal illness and immune assaults during pregnancy has been strongly associated with subsequent asthma and atopy development. If the result of the interactions between genetics and the in-utero environment is a skewed Th2 immunophenotype in the neonate, these infants are more likely to develop allergic disorders.

Summary

An important relationship exists between parasite infections and the development of atopic disorders. Long-lived parasite infections offer protection against atopic diseases like asthma, Crohn's disease, ulcerative colitis, multiple sclerosis and hayfever by immunosuppression. This knowledge is the basis for helminthic therapy, the deliberate inoculation or infection of an atopic individual with helminths to achieve remission for their disorder, such as those listed above. They induce modulatory molecules that ameliorate host responses to enhance their survival. The precise linking element's are not known but both eosinophils and IgE globulins that occur so prominently in both disorders may be crucial to this relationship. Understanding the immunology of the host-parasite interaction and identifying the distinct parasite molecules with the immunomodulating effects may help to combat allergy more successfully.

The hygiene hypothesis re-emphasized the inverse relationship between infection and allergy. Helminth research has once again provided key insights into the possible immunological explanation. The initial Th1-Th2 dichotomy provided the earliest immunological explanation for the hypothesis but there are major discrepancies. Several researchers have forwarded alternative immunological concepts in an attempt to better explain the original hygiene hypothesis. Modified Th-2 responses seen in parasite infections may provide protective 'blocking IgG4 globulins' that inhibit allergic responses. Protective programming of the fetal immune system by exposure to early infections or other environmental factors may be the critical factor against later atopic conditions. The identification of superantigens in the development of atopic skin lesions provides further insight into this interesting relationship. Research may well show that allergy is an unfortunate by-product of an evolutionary mechanism developed to combat bacteria, parasites and other organisms. We have come around in a full circle. Allergy started with the study of infections and today we still look at infections for answers to allergic conditions. The exact link between allergy and infection may provide a means of effective and successful treatment of these two important human problems. Alternative approaches such as the use of Mycobacterium vaccae, Th1 adjuvants such as IL-12 or the use of immunostimulatory nucleotides (CpG) are examples of potential new therapies

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References

1 Wardlaw AJ, Moqbel R, Kay AB. Eosinophils: Biology and Role in disease. Adv Immunol 1995;60:151-238

2 Johansson SGO. Raised levels of a new immunoglobulin class (IgND) in asthma. Lancet 1967;2:951-3

3 Masters S, Barrett-Connor E. Parasites and asthma-predictive or protective? Epidemiol Rev 1985;7:49-58

4 Anderson HR. The epidemiological and allergic features of asthma in the New Papua Guinea Highlands. Clin Allergy 1974;4:171- 83

5 Stanworth DR, Humphrey JH, Bennich H, Johansson SG. Specific inhibition of the Prausnitz-Kustner reaction by an atypical human myeloma protein. Lancet 1967;2:330-2

6 Turton JA. IgE, parasites and allergy. Lancet 1976;2:686

7 Godfrey RC. Asthma and IgE levels in rural and urban communities in the Gambia. Clin Allergy 1975;5:201-7

8 Merrett TG, Merret J, Cookson JB. Allergy and parasites: the measurement of total and specific IgE levels in urban and rural communities in Rhodesia. Clin Allergy 1976;6:131-4

9 Lynch NR, Lopez RI, Di Prisco-Fuenmayor MC, Hagel I, Medouze L, Viana G, et al. Allergic reactivity and socioeconomic level in a tropical environment. Clin Allergy 1987;17:199-207

10 Matricardi PM, Rosmini F, Riondino S, Fortini M, Ferrigno L, Rapicetta M, et al. Exposure to foodbourne and orofecal microbes versus airbourne viruses in relation to atopy and allergic asthma. Br Med J 2000;320:412-7

11 Strachan DP. Hay fever, hygiene, and household size. Br Med J 1989;299:1259-60

12 Mosmann TR, Cherwinski H, Bond MW. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986;136:2348-57

13 Herz U, Lacy P, Renz H, Erb K. The influence of infections on the development and severity of allergic disorders. Curr Opin Immunol 2000;12:632-40

14 Bjorksten B, Sepp E, Julge K, Voor T, Mikelsaar M. Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 2001;108:516-20

15 Riedler J, Braun-Fahrlander C, Eder W, Schreuer M, Waser M, Maisch S, et al. ALEX Study Team. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 2001;358:1129-33

16 Von Ehrenstein OS Von Mutius E, Illi S, Baumann L, Bohm O, von Kries R. Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy 2000;30:187-93

17 Bottcher MR, Bjorksten B, Gustafson S, Voor T, Jenmalm MC. Endotoxin levels in Estonian and Swedish house dust and atopy in infancy. Clin Exp Allergy 2003;33:295-300

18 Von Mutius E, Braun-Fahrlander C, Schierl R, Riedler J, Ehlermann S, Maisch S, et al. Exposure to endotoxin or other bacterial components might protect against the development of atopy. Clin Exp Allergy 2000;30:1230-4

19 Kalliomaki M, Salminen S, Arvilommi H, Kero P, Koshinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 2001;357:1076-9

20 Smit J, Van Loveren H, Hoekstra M, Schijf M, Folkerts G, Nijkamp F. Mycobacterlum vaccae administration during allergen sensitization or challenge suppresses asthmatic features. Clin Exp Allergy 2003;33:1083-9

21 Camporota L, Corkhill A, Long H, Lordan J, Stanciu L, Tuckwell N, et al. The effects of Mycobacterium vaccae on allergen-induced responses in atopic asthma. Eur Respir J 2003;21:287-93

22 Heinzel FP, Sadick MD, Holaday BJ, Coffman RL, Locksley RM. Reciprocal expression of interferon-gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med 1989;169:59- 72

23 Scott P, Natovitz P, Coffman RL, Pearce E, Sher A. Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med 1988;168:1675-84

24 Gajewski TF, Pinnas M, Wong T, Fitch FW. Th1 and Th2 clones proliferate optimally in response to distinct antigen-presenting cell populations. J Immunol 1991;146:1750-8

25 Hussain R, Poindexter RW, Ottesen EA. Control of allergic reactivity in human filariasis. Predominant localisation of blocking antibody to the IgG4 subclasses. J Immunol 1992;148:2731-7

26 Ebner C, Siemann V, Scheiner O. Immunological change during specific immunotherapy of grass pollen allergy: reduced lymphoproliferative responses to allergen and shift from Th2 to Th1 in T-cell clones specific for Ph1p1, a major grass pollen allergen. Clin Exp Allergy 1997;27:1007-15

27 Platts-Mills T, Vaughan J, Squillace S, Woodfolk J, Sporik R. Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Lancet 2001;357:752-6

28 Elias D, Wolday D, Akuffo H, Petros B, Bronner U, Britton S. Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacilli Calmette-Guerin (BCG) vaccination. Clin Exp Immunol 2001;123:219-25

29 Cooper PJ, Espinel I, Paredes W, Guderian RH, Nutman TB. Impaired tetanus-specific cellular and humoral responses following tetanus vaccination in human onchocerciasis: a possible role for interleukin-10. Infect Dis 1998;178:1133-8

30 Doetze A, Satoguina S, Hoerauf A. Antigen-specific cellular hyporesponsiveness in a chronic human helminth infection is mediated by T(h)3/T(r)1-type cytokine IL-10 and transforming growth factor- beta but not by T(h)1 to T(h)2 shift. Int Immunol 2000;12:623-30

31 Van der Biggelaar AH, van Ree R, Rodrigues LC, Lell B, Deelder AM, Kremsner PG, et al. Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced IL-10. Lancet 2000;356:1723-7

32 Redpath S, Ghazal P, Gascoign NR. Hijacking and exploitation of IL-10 by intracellular pathogens. Trends Microbiol 2001;9:86-92

33 Barker DJ, Martyn CN. The maternal and fetal origins of cardiovascular disease. J Epidemiol Community Health 1992;46:8-11

34 Spinozzi F, Agea E, Russano A, Bistoni O, Minelli L, Bologni D, et al. CD4+IL13+T lymphocytes at birth and the development of wheezing and/or asthma during the 1st year of life. Int Arch Allergy Immunol 2001;124:497-501

35 Leyden JJ, Marples RR, Kligman AM. Staphylococcus aureus in the lesions of atopic dermatitis. Br J Dermatol 1974;90:525-30

36 Lever R, Hadley K, Downey D, Mackie R. Staphylococcal colonisation in atopic dermatitis and the effect of topical mupirocin therapy. Br J Dermatol 1988;119:189-98

37 White J, Herman A, Pullen AM, Kubo R, Kappler JW, Marrack P. The Vb-specific superantigen Staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell 1989;56:27-35

38 Leung DY, Hauk P, Strickland I, Travers JB, Norris DA. The role of Superantigens in human diseases: therapeutic implications for the treatment of skin diseases. Br J Dermatol 1998;139:17-29

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