Concerned about Crypto?

This is the fourteenth of 16 student posts, guest-authored by Caroline Rauschendorfer. 

Cryptosporidiosis, known more commonly as crypto, is a gastrointestinal (GI) disease caused by parasites of the Cryptosporidium genus. If infected with crypto you may experience diarrhea, nausea, vomiting, fever, and abdominal cramps that can last up to two weeks. Definitely something you want to avoid, if possible, but at least it usually resolves on its own without medical intervention and is rarely fatal in otherwise healthy individuals. [3]

The most common disease causing organisms for crypto are C. hominis and C. parvum. C. hominis is a version of the parasite that sticks mainly to humans. Historically, large outbreaks of crypto tend to be caused by drinking water that has been contaminated with wastewater. In 1993 a large outbreak of crypto occurred in Milwalkee, Wisconsin, making 403,000 people ill. It was thought to be caused by a failure of drinking water purification. It is also possible to get crypto from a variety of other places as well: swimming in contaminated water, eating contaminated food, or from infected livestock. [3]

It is this last possibility for transmission that I am most concerned with. As I said earlier, C. hominis sticks primarily to people; but C. parvum, another type of Cryptosporidium, has the ability to infect most major domestic livestock. [2] As a second year veterinary student, this is a health concern for me. C. parvum is particularly common in cattle, and frequently causes infection in young calves. Crypto infected calves either come into a large animal clinic or are seen by a veterinarian on farm for being a “poor-doer” and having watery diarrhea. Veterinarians and veterinary students often come in close contact with these sick calves during treatment and can become infected themselves. As a matter of fact, contracting crypto as a veterinary student during your large animal rotation is practically a right of passage.

Many studies have been done looking at the prevalence of crypto in cattle, with a variety of results. One similarity between most studies, however, is that the prevalence of crypto is generally higher in calves than in adult cattle. Results from different studies ranged from 7.5 to 49% of U.S. dairy calves infected with crypto. [2] This means that working with calves puts you at an even greater risk of becoming infected with crypto.

No need to freak out yet, though. One thing that should be noted is: it is possible to come in contact with cryptosporidium and not become sick. Crypto is not difficult to kill, and will be removed from water by boiling it for at least 1 minute; however, routine chemical disinfection alone may not kill it. According to one study, crypto contaminates 65% to 95% of surface water and 45% to 65% of ground water in the U.S. This probably doesn’t sound like a good thing, but it actually might be.  According to another study, 35% of the U.S. population has antibodies to crypto. Repeated exposure to small doses of crypto may help build immunity against it. [4]

The body’s immune system fights disease in two ways: adaptive and innate immunity. Innate immunity is the part of your immune system that you are born with and involves the cells that patrol and recognize any type of foreign cell or molecule that might be inside your body, such as bacteria, viruses and parasites. Adaptive immunity is something that the immune system builds over time as your body is invaded by various infectious agents (viruses, bacteria, parasites, etc.). The cells that are part of the adaptive system produce a memory when they are exposed to these infectious agents so that if they encounter them again, they can mark them to be killed by other cells. In other words, innate immunity works very generally and very quickly, whereas adaptive immunity adapts to the specific infectious agent, but it takes longer to kick in. This works for crypto in that if your body is exposed to the parasite for the first time as a small amount in your drinking water, it may not be enough to make you sick, but if your adaptive immune system finds it and makes a memory it can fight off the parasite much better if you are ever exposed to it again. This would also be true if you were infected with crypto and had all the gross symptoms that go with it, it would just be more unfortunate. [5]

Immunity is also the reason why crypto, although not serious for health individuals, can be very harmful for the immunocompromised such as those on chemo drugs for cancer treatment, or people with HIV/AIDS. The number of immune cells in an immunocompromised person can be so low that they do not have enough to fight off an infection. If someone with HIV/AIDS becomes infected with crypto, it is much more likely to be lethal. [3]

Treatment of crypto for someone who is immunocompromised would be to administer blood serum, which contains immune cells, from a healthy person. This has been shown to help in some cases. Unfortunately there is no treatment for otherwise healthy individuals who become infected with crypto. Your only option is to wait out the two miserable weeks until your body fights off the parasite. In some cases, IV fluids may be helpful for people who become dehydrated from severe diarrhea. [3]

Thankfully, there are many ways to help protect yourself from crypto. The CDC recommends, as always, washing your hands, especially before eating or preparing food, after gardening, after using the bathroom, after changing children’s diapers, after tending to someone who is ill with diarrhea, or after handling animals and animal waste. The also recommend keeping your child out of daycare if they have diarrhea. At pools, lakes, and any other recreational water source, they recommend: not swimming if you have diarrhea, especially children with diapers; showering before entering the water; washing children thoroughly after changing their diaper or after they use the toilet before allowing them in the water; and not changing diapers at the poolside. The CDC recognizes livestock handling as a potential risk for crypto infection and have special recommendations for these people: minimize contact with animal feces, particularly young animals; always wear disposable gloves when cleaning up animal waste and wash hands when finished; and wash hands after contact with animals or their living areas. As a veterinary student these are all things I will have to keep in mind while treating animals to help prevent two weeks of misery for myself. [1]

References

1. Centers for Disease Control. http://www.cdc.gov/parasites/crypto/gen_info/index.html. Updated 2010.

2. Dixon B, Parrington L, Cook A, et al. The potential for zoonotic transmission of giardia duodenalis and cryptosporidium spp. from beef and dairy cattle in ontario, canada. Vet Parasitol. 2011;175(1-2):20-26.

3. Leitch GJ, He Q. Cryptosporidiosis-an overview. J Biomed Res. 2012;25(1):1-16.

4. Preiser G, Preiser L, Madeo L. An outbreak of cryptosporidiosis among veterinary science students who work with calves. J Am Coll Health. 2003;51(5):213-215.

5. Tizard IR. Veterinary immunology. 8th ed. Philadelphia, PA: Saunders; 2008.

Spotlight on Nasty Parasites: Echinococcus granulosus

This is the fifth of 16 student posts, guest-authored by E. Jane Kelley.

Did you know that some dogs might have a tapeworm in their small intestine that can cause the development of large cysts in people’s livers, lungs, and brains? This is not very common in the United States currently, though there are cases reported periodically (2), but in some areas of the world it is a huge problem. An infection that can spread from animals to humans or vice-versa is called a zoonotic infection.

The tapeworm is called Echinococcus granulosus and the cystic disease it causes is called hydatid disease (http://www.cdc.gov/parasites/echinococcosis/) .  Human beings are considered a “dead-end” host because they are not usually the host of the parasite. The most common life cycle of the tapeworm involves dogs as the definitive host (which means that the adult tapeworm lives in their intestine) and sheep as the intermediate host (which means that they have the immature stage of the parasite, called a metacestode, in their bodies). As you can imagine, this means that this infection is more common in areas of the world where there is extensive sheep-raising. There are other definitive hosts (such as foxes, wolves, coyotes, wolves and cats) and there are other intermediate hosts (cattle, goats, deer, rabbits, and rodents for instance), but the dog-sheep cycle is globally the most important as far as human disease.

Back to the life-cycle: the adult tapeworm is small and lives quite innocuously in the small intestine of the dog, not usually causing any problem for the dog. Tapeworm eggs are shed in the dog’s feces and, in the usual scheme of things, are ingested by sheep as they graze. The eggs develop into an immature stage of the parasite, which travels in the bloodstream from the small intestine to other organs such as liver and lung. After a while, the immature stage develops into a cyst in the liver and/or lung and the life cycle is complete when a dog eats organs from a dead sheep. In most cases, multiple small cysts (3-4 cm in diameter and they are fluid-filled) develop in the liver or lung of the sheep, but, remarkably, affected sheep do not usually show any clinical signs and the cysts are found at slaughter.

Sometimes humans ingest the eggs accidentally (this parasite is spread by what is called fecal-oral transmission from the dog to the human, use your imagination, enough said) and the cysts can form in the liver, lung, brain or other places in the human. In human beings, the infection tends to result in a single large cyst rather than multiple small cysts like the sheep. These can take years to develop and can become very large (20 cm in diameter or more). Some cysts in the liver do not cause problems, but cysts in the lung may cause respiratory problems such as coughing and shortness of breath and cysts in the brain are not good for obvious reasons. The treatment is surgical removal of the cyst.

Again, we don’t have much problem with hydatid disease in this country currently but there is potential for it to become more prevalent. It was believed to have been introduced in the early 1900s with infected livestock. Interestingly, the infection initially established itself in a domestic dog/domestic pig cycle (not sheep) in the east (8) and by the 1920s was in Mississippi, Louisiana, Tennessee, and Arkansas. By the 1970s, it was fairly prevalent in the sheep-raising areas of the west (Utah, Arizona, California, and New Mexico)(4) and there is a cervid (elk, moose, deer) cycle in wildlife in Canada, Alaska, and Minnesota (6). Recently in Montana and Idaho, approximately 60% of gray wolves sampled had adult tapeworms in their intestine and cysts were found in organs of elk, mule deer, and a mountain goat (5).

Let’s focus on Utah for a moment. Echinococcus granuosus was believed to have been introduced into the state in 1938 in sheep dogs from Australia (3). Sanpete County in central Utah is the area where most of the sheep-raising went on (and still does). In the 1970s Echinococcus granulosus was endemic in sheep and dogs in central Utah. Endemic means that the disease is constantly present in a certain area. About 25-30% of the dogs were infected and 13% of sheep carcasses examined had cysts (1,7). In addition, during this time period, there were several human cases. The close contact between sheep-herders and their families and the sheep dogs and sheep kept the cycle going. Also, the sheep were range sheep with common grazing allotments and contact with other dogs and sheep. Control measures such as proper disposal of dead sheep, hand-washing, regular deworming of the dogs and educating the families were implemented and greatly decreased the incidence of infection in dogs, sheep and people (1,3,7). However, there are occasional cases still in Utah so either control measures were not 100% effective and/or there is a wildlife reservoir of infection (such as coyotes). There have been 3 cases in humans reported to the Utah Department of Health since the 1970s and multiple liver and lung cysts were found in a slaughtered sheep in 2008.

In some areas of the world, such as China (11), Echinococcus granulosus is a serious and increasing public health concern. In China, it is considered an emerging or re-emerging disease (a disease that was at a low level but is recently causing many more infections). Eradication of hydatid disease has been achieved in some island countries such as Iceland, New Zealand and Tasmania (10). It is certainly an easier task to control infection on a relatively small island with a single government than in other areas. Control of infection involves measures previously mentioned such as  regular deworming of dogs, proper disposal of sheep and cattle carcasses, stray dog control, education about the importance of hand-washing, and elimination of wildlife reservoirs if present. This is not as easy as it sounds and requires long term commitment which may be a problem in countries with economic and political unrest. For example, in Kazakhstan (a country in central Asia), after independence from the Soviet Union in 1991, social and economic changes have brought about changes in animal husbandry (from large collective farms to smaller farms with closer contact between people, dogs, and livestock) such that incidence of Echinococcosis has been increasing in people, dogs, and livestock (9).

In the United States, hydatid disease is less likely to become a serious problem because we have a relatively stable government and the infrastructure for the handling of carcasses and stray dog control. However, there are parts of the country where this still exists and, I don’t know about you, but I don’t relish the thought of having a huge cyst in my liver or brain. For those of you who kiss your dogs, have you seen what dogs eat?  Add this disease to the list of reasons that it’s not a good idea.  Don’t let your dogs defecate in children’s playgrounds because small children are not very discerning about what goes in their mouth.

References:

  1. Barbour AG, Everett JR, Andersen FL, et al. Hydatid disease screening: Sanpete County, Utah, 1971-1976. Am J Trop Med Hyg 1978 Jan; 27: 94-100.
  2. Bistow BN, Lee S, Shafir S, et al. Human echinococcosis mortality in the United States, 1990-2007. PLos Negl Trop Dis 2012 Feb; 6: e1524.
  3. Crellin JR, Andersen FL, Schantz PM, et al. Possible factors influencing distribution and prevalence of Echinococcus granulosus in Utah. Am J Epidemiol 1982 Sep; 116: 463-474.
  4. Donovan SM, Mickiewicz N, Myer RD, et al. Imported echinococcosis in southern California. Am J Trop Med Hyg 1995 Dec; 53: 668-671.
  5. Foreyt WJ, Drew ML, Atkinson M, et al. Echinococcus granulosus in gray wolves and ungulates in Idaho and Montana, USA. J Wildl Dis 2009 Oct; 45: 1208-1212.
  6. Himsworth CG, Jenkins E, Hill JE, et al. Emergence of sylvatic Echinococcus granulosus as a parasitic zoonosis of public health concern in an indigenous community in Canada. Am J Trop Med Hyg 2010 Apr; 82: 643-645.
  7. Loveless RM, Andersen FL, Ramsay MJ, et al. Echinococcus granulosus in dogs and sheep in central Utah, 1971-1976. Am J Vet Res 1978 Mar; 39: 499-502.
  8. Pappaioanou M, SchwabeCW, Sard DM. An evolving pattern of human hydatid disease transmission in the United States. Am J Trop Med Hyg 1977 Jul; 26: 732-742.
  9. Shaikenov BS, Torgerson PR, Usenbayer AE, et al. The changing epidemiology of echinococcosis in Kazakhstan due to transforming of farming practices. Acta Trop 2003 Feb; 85: 287-293.
  10. Torgerson PR, Budke CM. Echinococcosis- an international public health challenge. Res Vet Sci 2003 Jun; 74: 191-202.
  11. Yang YR, McManus DP, Huang Y, et al. Echinococcus granulosus infection and options for control of cystic echinococcosis in Tibetan communities of Western Sichuan Province, China. PLos Negl Trop Dis 2009 April; 3: e426.

Worms: Are they good or bad for us?

Student guest post by Shylo Wardyn

“Of all the parasites I’ve had over the years, these worms are among the… hell, they are the best”.

Was Fry from the animated show ‘Futurama’ right in his assessment of worms being good for him? Did he know something about parasitic worm infections that I was unaware of? Well, in the show, his parasites were doing remarkable things for his body, but does this translate to real life at all? Some people think so. Altman reviews the idea that over evolutionary time, our ancestors were infected with all sorts of parasites and this led to an interaction between the worm gene products and the immune system. These interactions led to modulation of dendritic cells and establishment of T-cell networks. It has been hypothesized that in an environment without these interactions, as is the case for most people living in “Westernized” countries, there is a loss of the ‘fine tuning’ of the adaptive immune system.

In another review, Jackson et al. discuss how this mechanism could have co-evolved. It is generally believed that the T helper cell type 2 (Th2) evolved to counter infections with parasitic worms. These cells are activated in response to parasitic worm infection, which leads to a large regulatory T cell response. Our response to worms seems to involve an immune response that is less inflammatory than our response to microbes, and it also takes much longer to reach the peak of effectiveness. This is due in large part to an initial systemic suppression of innate and adaptive immunity in the host. This is likely caused by regulatory CD4+ and CD25+ T cells producing suppressive cytokines or other suppressor T cell subsets. Anti-inflammatory responses are also caused by alternatively activated macrophages. These macrophages secrete anti-inflammatory cytokines and express genes whose functions relate to wound healing and repair. Therefore, being infected with parasitic worms leads to a down-regulation of proinflammatory responses, while allowing mechanisms for wound repair and a controlled development of the Th2 response. This Th2 and T regulatory response is beneficial for both the worm and the host. For us, the regulated Th2 response is less costly than the generation of a strong immune response, which often can be detrimental to our own cells. For the parasites, they are able to survive the initial immune response and therefore reproduce, while later parasites would not be able to survive the developed immune response.

The overall thought is that since parasitic worm infections are ubiquitous in mammals and have been since mammals first evolved, there would be a positive selective pressure for those individuals whose immune systems respond well to worm infections. Our immune systems may have been selected to anticipate a chronic exposure to Th2 and T regulator inducing pathogens. Since our ancestors were chronically infected by worms, their immune systems would have developed to work well in this context, while not necessarily working as well in the absence of worms. This scenario may explain why in some cases the immune system goes haywire in populations that are free from parasitic worms.

So is there any strong evidence linking parasites with populations free from allergies and autoimmune diseases? There have been many ecological studies which show an inverse correlation between the parasite load and allergy level for a particular region. Does this prove anything? Not really, the data is simply correlative. There have been other studies showing that treatment of worm infections is accompanied by an increase in skin test reactivity to allergens and IgE antibody levels. It appears that in the absence of worms, the immune system overreacts to allergens to which it normally wouldn’t mount a response in the presence of worms. This gives us a better idea about the link between parasitic worms and immune responses. While the evidence is still shaky, it is biologically plausible that the lack of worms in our environment has led to the massive increase in the amount of immune related diseases, such as asthma, multiple sclerosis, type 1 diabetes, and general allergies. However, the immune system is incredibly complex, as are those diseases, and I’ve barely scratched the surface of it for this topic. So while it seems being infected with worms may prevent immune system diseases, I doubt anyone would trade their asthma for a tapeworm. It does make for an interesting hypothesis (and Futurama episode) though and should be researched more thoroughly.

References

Altmann D. M. (2008). Review series on helminths, immune modulation and the hygiene hypothesis: Nematode coevolution with adaptive immunity, regulatory networks and the growth of inflammatory diseases. Immunology, 126(1); 1-2.

Jackson J. J., Friberg I.M., Little S. and Bradley J. E. (2008). Review series on helminths, immune modulation and the hygienehypothesis: Immunity against helminths and immunological phenomena in modern human populations: coevolutionary legacies? Immunology, 126(1); 18-27.

Weiss S.T. (2000). Parasites and asthma/allergy: What is the relationship? Journal of Allergy and Clinical Immunology, 105(2); 205-210.