Monday, February 13, 2012

Hookworm



This week at Infection Landscapes I will cover another of the soil-transmitted helminths, and another of the important neglected tropical diseases: hookworm. Hookworm is a major contributor to morbidity in the developing world, particularly with respect to growth and development in children.

The Worm. Human hookworm infections can be caused by two different species, both of which are nematodes. Necator americanus and Ancylostoma duodenale are the two main hookworm species that cause human infection. N. americanus has the greatest global distribution, and is responsible for the greatest prevalence of infection, whereas the prevalence of A. duodenale infection is more focally clustered across Africa, South Asia, China and a few foci in the Americas.

Ancylostoma duodenale (photo by Jay Reimer)

Necator americanus (photo by David Scharf)

Both species employ complex life cycles, as we saw with A. lumbricoides, however the pathway is somewhat different for the life cycle of hookworms and, subsequently, so is the resulting disease ecology. Let's describe the life cycle. The eggs of both species are deposited in the feces of an infected host and, following deposition, embryonate. The eggs require warm and moist soil that is sandy or loamy in composition. If these immediate ecologic needs are met, in about 2 days the eggs will develop into the first stage (L1), rhabditoform larvae, which are not infective and subsist on the microbial contents of the soil. These larvae will molt twice, the first time (L2) resulting in a second soil-stage rhabditoform, and the second time (L3) resulting in the infective filariform larvae. This stage of development no longer feeds, but its mobility increases dramatically so that it can remove itself from within the soil and relocate to high points above the soil horizon, such as rocks or grass. By moving above the soil horizon, the larvae are able to increase the likelihood that they will successfully engage the skin of their host. Once the larvae make contact with the skin, they penetrate by way of hair follicles or through open wounds or lesions on the skin's surface. Having achieved cutaneous and subcutaneous penetration, the filariform larvae must reach the lung to continue the next stage of the their life cycle. They do this by passive transfer through the venous circulation, which the larvae access by way of the capillary beds under the skin. The vasculature ultimately deposits these L3 larvae in the capillary beds of the lung from which they penetrate into the alveoli and migrate up the bronchii and trachea until they reach the throat. From here the larvae are swallowed and, thus, finally gain access to the alimentary tract of the host. In the small intestine the larvae molt for the third and final time forming the adult worm, which is the parasitic feeding stage of this worm. In this stage the adult worm targets the intestinal mucosa where it attaches and feeds on both the villi of the epithelium and the blood which it sucks from the blood vessels of the submucosa. The total infective process (skin penetration to intestinal feeding adult) typically requires 1 to 2 months to complete. Adult females and males mate in the host intestine and produce several thousand fertilized eggs per day. N. americanus females will produce up to 10,000 eggs each day, while A. duodenale females can produce three times as many eggs per day. These eggs are passed into the environment with the host's stool and the cycle continues. Below is a nice graph by the Centers for Disease Control and Prevention that depicts the complex life cycle of both hookworm species:


And here is another nice graph by MetaPathogen.com that nicely contextualizes the life cycle within transmission:


It is important to note that the life cycle stages above describe the strategies employed by both N. americanus and A. duodenale. Transmission by skin penetration is the only mode of transmission for N. americanus, and it is the most common mode of transmission for A. duodenale. However, A. duodenale can also transmit by ingestion of the larvae. When the latter strategy is employed the life cycle is shortened since the lung stage is bypassed and the larvae develop directly into the adult stage in the small intestine of the host.  

The Disease. Most hookworm infections are asymptomatic. When symptoms do occur, they typically involve 1) the subcutaneous migration of the larvae, 2) the larval development within the lungs, and/or 3) the attachment of the adult worms in the small intestine. Subcutaneous larvae migration can cause a hypersensitivity reaction in the course of the migrating worms that produces very itchy lesions on the skin:


Hypersensitivity reactions involving pruritic lesions are more common in hyperendemic areas following repeated infections over time. Larval infection in the lungs can produce cough and hypereosinophilia, and even mimic pneumonia with radiographically apparent chest infiltrates and fever. However, these more severe pulmonary symptoms are also usually only associated with high volume infections. Abdominal pain is the most common intestinal symptom, but irregular stool, with either diarrhea or constipation, and vomiting are also possible presentations. But again, symptomatic gut infection is more common in high volume infections.

The most important clinical consequence of hookworm infection at the population level is anemia. An iron-deficiency anemia results from the blood lost into the lumen of the gut, and which is ultimately passaged in stool, as the adult worms feed in the small intestine. Protein deficiency is also an important consequence of long-term or high volume infection. Because of the iron-deficiency anemia and protein deficiency, chronic hookworm infection is particularly damaging to children, often leading to arrested musculoskeletal growth and cognitive development. As such, children account for a large preponderance of the overall morbidity experienced by a population and so are typically the age group targeted in de-worming campaigns. This is the typical practice even though adults can often acquire higher volume infections under some circumstances. For example, due to the widespread use of human feces as fertilizer in farming among poor agricultural communities, adults working the fields contaminated by hookworm may have much more extensive exposures and subsequent infections.


The Epidemiology and the Landscape. There are likely close to one billion prevalent infections with hookworm in the world today. The vast majority of these occur in sub-Saharan Africa, Southeast, South and East Asia, and parts of South America:


As mentioned above, the morbidity associated with such a high burden of infection is predominantly manifested as impaired physical and cognitive development in children. When this morbidity is translated into disability-adjusted life years we can see below that sub-Saharan Africa and Southeast Asia are saddled with a disproportionate burden of disease, and we can also see that this burden is quite substantive:

Age-standardised disability-adjusted life year (DALY) rates from Hookworm disease by country (per 100,000 inhabitants).
   no data
   less than 10
   10-15
   15-20
   20-25
   25-30
   30-35
   35-40
   40-45
   45-50
   50-55
   55-60
   more than 60

The morbidity that attends hookworm infection in areas of high endemicity makes this one of the most significant infections currently affecting humans. This is further highlighted by the fact that this infection is one of the primary neglected tropical diseases, meaning it typically draws little consideration and/or resources in the overall global fight against infectious disease.

The range of hookworm species is determined by important aspects of the physical landscape and because of this, as well as critical overlapping characteristics of the human social landscape, the occurrence of hookworm in humans is distinctly delineated by geographic features. Soil and climate are two critical landscape features that determine the distribution of hookworm species. During the first two larval stages of development in the life cycle of both A. duodenale and N. americanus, the larvae require sandy, loamy soils in order to undergo the first two molts to the L3 stage, which can then infect humans. If the hookworm eggs hatch and find themselves in hard clay soils then the larvae will not reach the L3 developmental stage and thus they cannot infect humans and they cannot complete their life cycle. In addition, the soils must be moist and the temperature must be warm. As such, the specific climatic conditions limit the range of the worms to the tropical and subtropical regions of the world that receive significant amounts of precipitation on an annual basis, while the pedological and edaphological constraints further define the microgeography of these worms. Notice below the global distribution of soil morphology in the map produced by the Natural Resources Conservation Service (NRCS) of the United States Department of Agriculture:


And this NRCS map below depicting the global distribution of soil moisture:



And, finally, the map below by the United Nations Food and Agriculture Organization depicts the global distribution of the annual mean temperature:


It is worth noting how closely the global distribution of hookworm coincides with the global distributions of soil regimes, moisture, and temperature, with one exception: the southeastern Untied States. Indeed, this geographic region was, at one time, highly endemic for hookworm infection. Why no longer? The answer to this question lies within the context of the social landscape of this infection. 

There are three important factors from the hookworm life cycle that are critical to the landscape epidemiology of human transmission. First, the eggs pass out into the environment in the feces of the human host. Second, the larvae live in the soil during the first two larval stages of the life cycle. Third, the larvae must make contact with the skin of a new human host. These three factors determine how the social landscape intersects with the physical landscape to enable transmission to humans. 

Lack of sanitation infrastructure, and especially a means by which human waste can be removed from sites of human occupation, results in feces being distributed directly in the human environment or in proximal spaces. Conditions of poverty that are associated with the lack of municipal resources for infrastructural development often coincide with a lack of personal resources for adequate clothing. As such, a barefoot lifestyle may be ubiquitous in the same human environments (both the home and places of work) in which hookworm egg-laden human feces are deposited on a daily basis. This leads to an abundance of points of contact for transmission between hookworm larvae and human hosts in those intersecting landscapes of warm, moist, structurally rich soils and conditions of poverty. This intersection currently defines a geography that encompasses, almost exclusively, the developing world. However, this geography did include the southeastern United States where the same intersection of the key physical and social landscapes was present until the early 20th century. When adequate sanitation became widespread in this region of the US, human hookworm largely disappeared.

In many poor subsistence agricultural communities, farmers use human feces as a fertilizer to enhance the growth of their crops. This readily available fertilizer provides a cheap, yet very rich, source of critical nutrients to the soil, which can mean the difference between a crop yield that provides the farmer with a livelihood and a yield that does not. Unfortunately, in areas where hookworm is endemic, the use of human feces as fertilizer means a constant and widespread distribution of hookworm eggs throughout the farming community, and thus a steady source of new infections. 

Control and Prevention. Control and prevention of hookworm begins by following the usual guidelines: improving sanitation in resource poor areas. In most settings in the world where hookworm is a significant contributor to morbidity, improved infrastructure that can adequately remove human feces from the spaces of human occupation is a first priority in its prevention.

Where large-scale municipally-resourced sanitation infrastructure is not available, individual pit privies can be constructed for single homes, or clusters of homes. Here is a graphic that depicts the dimensions and structural components of such a privy:


Wearing good shoes without holes while outside in endemic areas is another critical step in the prevention of new hookworm infections. Unfortunately, footwear is often simply not available for those people who need it most, and as such this very simple transmission block cannot be utilized.

Photo by Peter Byrne

Finally, changing agricultural practices that rely on human feces for fertilization of crops could dramatically help reduce the widespread distribution of hookworm in soils in many agricultural subsistence communities.


Unfortunately this, too, can be a difficult practice to disengage since human feces serves as a very rich fertilizer and, thus, can form a critical component to subsistence farming in many parts of the world where other fertilizers or farming technologies are cost prohibitive. And, of course, without an affordable substitute refraining from human feces fertilization could very well lead to starvation. The massive scope of the problem presented by soil-transmitted helminths in general, and hookworm in particular, should now be coming into focus.

De-worming campaigns do offer some hope, since there are safe, effective, and fairly cheap anti-helminthic drugs available. However, as one might expect, there are obstacles to overcome in de-worming. First, these drugs are not free and, while cheap they may be, without adequate funding poor communities will not be able to prioritize the cost, especially since most infections are generally asymptomatic. Second, effective ways to deliver the de-worming medications to communities need to be implemented, which can be logistically challenging particularly in remote communities or during times of the year when travel may be restricted (i.e. during the rainy season). Third, the extensive use, or misuse, of these drugs will likely lead to antihelminthic-resistance in the worms, thus making the drugs ineffective. Nevertheless, if adequate resources can be put behind de-worming campaigns, and if delivery systems can be adapted to actively engage community members in the delivery and monitoring of these de-worming medications to simultaneously circumvent logistical obstacles and reduce the development of resistance, then substantial reductions in hookworm infections may still be possible.

26 comments:

  1. I have hookworm, but I still advocate the use of night soil. How else can we live with closed cycle systems. The nutrient should come from the ground into our bodies and from our bodies into the ground, not into a water treatment plant to be flushed into the sea and substituted with chemicals. Please, do not let a disaffection for soil-transmitted helminths and a lack of appreciation for natural cycles be the death knell to the worlds last sustainable agricultural practice. Please.

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    1. It is much easier to take this position when you are a functioning adult with the infection. One has to be especially mindful of the more severely affected- children. It is amazing how points of view can vary even when e are equipped with the same information. I can understand one's appreciation for the "natural cycles," however, let us not lose sight of a very real health issue here.

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  2. Diseases like hookworm (and malaria, etc.) remind me of how much the burden of disease can impact the economic development of countries. I recently read an article that this blog references, indicating that the UNTAPPED resources of the DR Congo are worth approximately the GDPs of the EU and US combined:

    http://www.newsaboutcongo.com/2009/03/congo-with-24-trillion-in-mineral-wealth-but-still-poor.html

    How is it that the DRC is not an economic powerhouse? Not only is it not an economic powerhouse, it is among the least developed countries on Earth.

    Diseases like hookworm, even though many cases are asymptomatic, occur in huge numbers. So the morbidity burden if only a fraction are symptomatic is still very high. And this morbidity burden includes symptoms that directly compromise the potential for labor and economic effort. How can someone start a business if they are profoundly anemic due to hookworm infection? All the natural resources in the world won't help if you don't have the social structure to sell them on the global market.

    Obviously, I am suggesting that hookworm, malaria, etc. is only a part of the reason why countries may not realize their full development potential. But I think that chronic diseases like these are important factors to consider in the context of efforts like microfinance, etc.

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    1. I agree that diseases such as hookworm with a large morbidity burden are extremely problematic in developing countries, and that solutions are hard to find. I just read an article about how a clinical trial of an experimental vaccine will be the first of its kind in Africa next year. The vaccine creates antibodies against certain enzymes the hookworm needs to live. Hopefully this effort will decrease the morbidity due to hookworm in Africa.

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  3. I grew up in the American South in the 1950's. In the small town where I lived, most people I knew had toilets, but a few still had out-houses. The problem was not lost on my mother, however, having grown up there a generation earlier. There were few mantras I heard more than "Put on your shoes, you will get ground itch." I don't think I EVER played in a mud puddle after a rain. But I never got hookworms and I am still, even though sanitation in that same town is 21th Century, will not walk outside barefooted after a rainstorm. Good habits die slowly, and thankfully so.

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    1. In reading this article it is fascinating to learn that a simple solution to the hookworm problem would be to wear shoes when outside. However in places such as sub-saharan Africa, this "simple solution" is actually quite difficult. Owning a pair of shoes is low on the priority list when you barely have enough food and water for yourself. Although the deworming campaign could decrease the risk of hookworm, perhaps general education and raising awareness of the problem can curb the risk of disease even more.

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  4. I can highly recommend the book An Epidemic of Absence for an alternative view of parasistes such as the hookworm and other parasites. Our relationship to many parasites appears to be not so simple as we once thought.

    http://www.moisesvm.com/

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  5. Hookworm infection is one of the infections that is considered a neglected tropical disease. One of the consequences of hookworm infection is anemia and protein deficiency. This is more dangerous for children which can lead to arrested musculoskeletal growth and cognitive development. 

    However many adults also are infected due to their occupation as farmers due to the use of human feces as fertilizer, this practice is common among poor agricultural communities such as sub-saharan Africa and Southeast Asia

    In poor communities such as sub-saharan Africa and Southeast Asia, a barefoot lifestyle and inadequate clothing is an issue due to the open entry for the worm to penetrate. Therefore there needs to be a change in agricultural practices such as using human feces as fertilizers and having proper clothing. There are anti-helminthic drugs that are very cheap and effective that can be used to fight off the infection.

    The issue with all of these concerns is that this is a poor community that may not be able to afford proper clothing, fertilizers and anti-helminthic drugs. Another concern is that walking barefoot and dressing a certain way is culturally embedded therefore it may not be easy to change. 

    It is difficult to approach a community that has strong cultural ties and who is very poor and can’t afford “cheap” drugs. 

    If shoes were donated, will the farmers wear them? and if drugs were also free, will the people take them adherently, not understanding the consequences of taking the drug properly due to lack of education?

    How can we approach communities such as these? 

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    1. It is difficult. When your life is on the line, something like hookworm (which is extremely prevalent in many poor areas) will not stop people from doing their daily work. Nicole, who responded to you as well, is correct in saying education is a key change that needs to be made; however, I do not think it would be too difficult. By finding educated local people, we can have them propagate the information to the rest of the communities. History has shown that natives are much more likely to follow the advice of someone from their area rather than strangers.

      Furthermore, I believe the main issue here is proper sanitation. A big way hookworm is being spread is by people walking barefoot in feces-ridden areas. This is unacceptable. By establishing good sanitation infrastructure, hookworm (among many other infectious) could easily be a thing of the past.

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  6. Nicole MastrogiovanniJuly 3, 2014 at 8:37 AM

    Difaa,

    You raise some excellent ideas on how to treat hookworm in underdeveloped communities such as sub-Saharan African and Southeast Asia by possibly creating an organization that donates shoes to them, specifically children who are prone to play in the dirt and farmers who work in the fields every day. I also think the “cheap” drugs would not be welcomed with open arms there even if they were free as you said due to their culture/religious beliefs and just from not understanding the reason of taking a pill or having a shot to protect them. Therefore I think we could tackle this issue in a public health approach by going into these third world areas and understanding their cultural views while trying to educate them on the protection factor of the shoes or drugs from hookworm. The only way we can help prevent these populations to comprehend the reasons behind the drugs is when we can start to open their viewpoints a little more and begin to help them. However, this is extremely time consuming because you would have to gain their trust in their community in order for them to accept you and respect you enough to follow suggestions on wearing shoes or taking drugs. But at least it would be a start to even save just a few people from the hookworm infection.

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  7. Nicole MastrogiovanniJuly 3, 2014 at 8:39 AM

    Difaa,

    You raise some excellent ideas on how to treat hookworm in underdeveloped communities such as sub-Saharan Africa and Southeast Asia by possibly creating an organization that donates shoes to them, specifically children who are prone to play in the dirt and farmers who work in the fields every day. I also think the “cheap” drugs would not be welcomed with open arms there even if they were free as you said due to their culture/religious beliefs and just from not understanding the reason of taking a pill or having a shot to protect them. Therefore I think we could tackle this issue in a public health approach by going into these third world areas and understanding their cultural views while trying to educate them on the protection factor of the shoes or drugs from hookworm. The only way we can help prevent these populations to comprehend the reasons behind the drugs is when we can start to open their viewpoints a little more and begin to help them. However, this is extremely time consuming because you would have to gain their trust in their community in order for them to accept you and respect you enough to follow suggestions on wearing shoes or taking drugs. But at least it would be a start to even save just a few people from the hookworm infection.

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  8. I grew up in Jamaica and we knew about hookworms as children because our parents constantly warned us about running around barefoot. The thing is, over the summer break, just before school started in September, it was assumed that we all (kids, that is) had "worms". As a result, we were given a herbal tea (way too early in the morning if you ask me) and soon enough "run" meant something different to us. I have no idea what that herb was called, but it seemed to have worked for us. Above all, it was cheaper than Western medicine. It would be interesting to see more research done to help determine the clinical value of certain cultural practices. In this case where the farmers who use human feces as manure are especially vulnerable, it might prove effective for them to grow the very thing that will help treat the infection. While it is more effective to treat the problem at the source, their choice of manure appears to be their only feasible option.

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    1. It sounds like the herbal tea you took acted like a laxative. It could be senna? But I feel like that wouldn’t necessarily “cure” hookworms since it only takes care of the GI tract and not the larvae in the lungs or the worms crawling up your skin. I’m also skeptical of using a laxative for treatment if the target population is already anemic from malnourishment.
      Im also very intrigued by the use of human feces as fertilizer. When I was in the Peace Corps in Senegal, we were taught that the human GI tract is actually very good at extracting nutrients and the stools that we pass are pretty devoid of nutrients. But after a quick google search, it seems like we were taught the exact opposite?
      Im curious what the newest data is on hookworm infection because cheap flip flops that cost less than $0.50 were available in West Africa back in 2012 and I think that’s a good starting point for footwear protection.

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  10. Hookworms affect not only humans but animals as well. It is confirmed that dogs especially puppies are more susceptible to hookworm infection in the developed countries. Veterinarians say that it is very important to vaccinate puppies and their mothers against hookworms. We know that hookworms cause a serious blood loss in puppies that eventually lead to the death. They should be seen by their veterinarian to check their feces two to four times when they are one year old and once or twice a year after.

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  11. One of my favorite things about hookworm is that there is some (limited) evidence that it can help treat allergies. This is a quote from a 2001 article on the topic: "Responses to both larval and adult worms have a characteristic T-helper type 2 profile, with activated mast cells in the gut mucosa, elevated levels of circulating immunoglobulin E, and eosinoophilia in the peripheral blood and local tissues, features also characteristic of type I hypersensitivity reactions. The longevity of adult hookworms is determined probably more by parasite genetics than by host immunity. However, many of the proteins released by the parasites seem to have immunomodulatory activity, presumably for self-protection." (The abstract can be found at http://cmr.asm.org/content/14/4/689.short.)
    More recently, there have been stories about a doctor who intentionally infected himself with hookworm in an effort to rid himself of his allergies...and it worked! Supposedly. (http://healthland.time.com/2012/04/18/doctor-infects-himself-with-parasites-for-health-experiment/, http://io9.com/5933615/why-doctors-are-treating-allergies-with-parasitic-worms) The current logic is that the immune response to parasitic infections is so similar to the overreaction that characterizes allergies--that is, eosinophilia and a release of IgE. In our developed, 21st century world, we don't have many hookworm infections (in the United States, anyway), but we still have this ability to respond to parasites and that ability is lying dormant until it turns against us by attacking neutral antigens, creating allergic hypersensitivity reactions.
    At this point, much of what I can find with a quick Google search is sensationalized versions of the parasites-as-allergy-cures story, but it will be interesting to see if this becomes more of a trend over the next few years.

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  12. One point that was very interesting to me was the use of anti-helminthic drugs for hookworm. Although these drugs, by themselves, seem effective, the context they are placed in may render them ineffective. For example, they may not be affordable to the communities that need them the most. In addition, due to lack of resources and oversight by healthcare providers, these drugs may be used improperly and lead to drug-resistant hookworms. Thus, it seems the most efficient way to tackle hookworm endemicity is via public health approaches rather than purely medical approaches. Some examples include developing proper sanitation infrastructure, campaigns for shoe donations, and proper construction of outhouses. Although costs may be high at first when ensuring proper sanitation infrastructure, these efforts will definitely pay off in the long run by decreasing morbidity from hookworm.

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    1. I agree that proper knowledge of how to build a latrine and wearing shoes can go a long way to curtailing the spread of hookworm. We may take for granted our indoor plumbing and ample supply of footwear, but these things are luxury items for most of the world. On a community level, shoe drives can go a long way by donating shoes to those in need to insulate feet from pathogens. At a government level, helping communities build proper latrines can go along way to curtailing hookworm as well as other pathogens like cholera.

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    2. That's a very good point to bring up! This problem and it's solution definitely needs to be looked at through different lenses. Great suggestions for campaigns as well. I like the multi-pronged approach to eradicating this. I agree that efforts will pay off in the long run but it is really unfortunate that when creating campaigns, if there is no immediate and tangible result, people will cut funding or not continue with the campaign.

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    3. I agree that interventions should focus on shoe donation campaigns. My dad could only afford one pair of shoes throughout his high school education in India. I have witnessed children and women walking around barefoot. They rather spend money on food and water than shoes, which is completely understandable. Therefore, shoe donations would be a great initiative.

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  13. http://www.cdc.gov/parasites/zoonotichookworm/gen_info/faqs.html

    Although different specious, zoonotic hookworm in humans from their pet dogs or cats still exist in our society. Same precautions of wearing shoes and curbing after dogs are effective in preventing the spread of the disease.

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  14. Very interesting! I didn't know that they go through the lungs, which is really scary. I also didn't know that they acted like some kind of leech and fed off human blood; I previously assumed they were in the intestine to eat the digested food.

    This also reminding me of a story on NPR's this American Life about a man who had severe allergies that were not lessened by Western medicine and was so desperate that he decided to go to a developing country to contract hookworms because he believed that
    it would alleviate his symptoms. He walked barefoot in areas that local people discarded their feces and contacted it. His allergy problem actually resolved and he made a business selling his hookworms around the world. I'm not sure which one he used but I will make an educated guess that it is the more common one, Necator americanus.

    If anyone is interested you can find it on here (it's the third story if you don't want to listen to the other ones:
    http://www.thisamericanlife.org/radio-archives/episode/404/enemy-camp-2010

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