What follows is a series of brief reports about varying aspects of human interaction with the parasite Enterobius vermicularis.

The Biology, Transmission and Treatment of Enterobiasis

Enterobiasis is a condition of helminth infestation affecting the intestinal tract. It is caused by the nematode Enterobius vermicularis, commonly known as the human pinworm (CDC, 2004). There are three main points of relevance concerning human interaction with this parasite: 1) The biology and characteristics of the pathogen, including the stages of the infection process, along with their corresponding symptoms. 2) How the pathogen is spread from one individual to another, as well as the role of the environment in facilitating or complicating transmission. 3) The diagnosis, treatment and prognosis of infected individuals. A solid grasp of each of these aspects is crucial in understanding the nature of the human pinworm and its relationship with human beings.

Compared to other microorganisms, pinworms are rather large. Adult females range in length from eight to thirteen millimeters. Males are notably smaller at two to five millimeters (CDC, 2004). Without regard to size, adult specimens look fairly similar in appearance to ordinary earthworms. The additional length of female specimens may be attributed to an anatomical structure that bares a striking resemblance to a lizard tail, extending to a point. This tail aids the in locomotion of females during their nightly migration to the perianal region to lay eggs which have been described as “colorless . . . smooth, thin eggshell[s] with one flattened side” (CDC, 2003, 2004). According to Lindsay (1997), Enterobius vermicularis has a direct life cycle, e.g. there is no intermediate host or vector involved. After the ingestion of eggs by the host, pinworms grow and develop in the large intestine where adult worms can live for 90 or more days (MMWR, 1993). While the infected individual is sleeping, the female worm uses its powerful tail to migrate through the intestinal tract to the rectum, where eggs containing larvae are deposited around the anus (MMWR 21, 1993). After only a few hours, these eggs may become infective, ready to reinfect the host, or spread to another individual.

While the presence of eggs may cause discomfort, primarily anal itching and general irritability, symptoms are generally mild or nonexistent (CDC, 1999). Additionally, pinworm eggs can survive independent of a host for up to two weeks, depending upon the nature of the surrounding environment (CDC, 1999; MMWR 21, 1993). The Centers for Disease Control and Prevention (2004) indicates that additional complications may occur in severe cases, including bacterial infection, due to unhygienic scratching of the perianal area, anorexia, caused by lack of appetite and vulvovaginitis, in the case that larvae “invade the female genital tract.” Vulvovaginitis is the inflamation of the vaginal mucosa in females. The mere presence of Enterobius vermicularis in the proximity of the vagina is often enough to trigger symptoms, however, bacterial infections can also easily result from agressive scratching.

While pinworm infestation is a worldwide pandemic, it holds the distinctive title of being the most common worm infection in the United States (CDC, 1999). For the most part, it affects young children and those living with or in close proximity to infected individuals. This is because young children are less likely to thouroughly wash their hands, and more likely to touch everything within their reach. Because of its mode of transmission, pinworm is commonly found circulating between children in preschool and grade school settings. Young children, in particular, are likely to be less reserved in their scratching, thus eggs may become caught beneath unwashed fingernails, in turn, contaminating anything they touch. The parasite is spread most commonly through accidental ingestion following contact with contaminated surfaces, such as clothing, bedding or fingers (CDC, 1999). Interestingly enough, the parasite may also be spread through the air by means of eggs attaching to dust particles, which may then be inhaled and ingested (MMWR, 1993).

If an individual’s symptoms suggest enterobiasis, a laboratory diagnosis may be used to verify the presence of infection (CDC, 1999). According to the Centers for Disease Control (2004), the laboratory diagnosis, must be performed first thing in the morning, prior to bowel movements or washing, and consists of the application of adhesive tape to the perianal region. The tape is then placed on a slide and examined under a microscope for the presence of eggs. Both bowel movements and washing have a high probability of removing the majority of eggs present in the anal region, potentially resulting in a falsely negative diagnosis. Alternative methods of diagnosis include the use of adhesive anal swabs which serve to collect any traces of eggs. Additionally, if adult worms are detected during an ano-rectal or vaginal examination, diagnosis is positive.

Generally, barring any bacterial complications, the prognosis for a full and quick recovery is good, i.e. there is no mortality. The drug mebendazole is used in a two-dose course to treat enterobiasis (CDC, 2004). Mebendazole works by systematically shutting down glucose uptake in the metabolism the worms, consequently leading to their death. Treatment with the drug has a success rate in the range of 90 to 95% (Infomed, 2005). Furthermore, taking the necessary steps to prevent reinfection is essential in the treatment of enterobiasis. These steps incorporate many of the rules of basic hygiene: bathe in the morning, change clothing and underwear daily, and wash hands frequently. Additional steps include trimming fingernails, and the avoidance of nail-biting and the scratching of bare anal areas, as the disease infects its hosts from hand to mouth (CDC, 1999). Furthermore, family members living in the same house as the infected individual should be treated with the same course of medication, to prevent further propagation of the disease. A follow-up test may be performed four weeks after the initial treatment begins, to make sure that no traces or eggs of the parasite remain (Infomed, 2005).

Enterobiasis is a mild but widespread disease that will not disappear any time soon (MMWR 9, 1993). While it rarely if ever seriously debilitates or kills an infected individual, pinworm is a nuisance that can cause severe discomfort prior to treatment. However, simply educating and convincing those at risk (school age children) to wash their hands frequently, especially before eating and after using the bathroom, could effectively reduce the number of annual cases.

The History and Geographic Distribution of Enterobiasis

Today, Enterobius vermicularis, or pinworm, is the most common intestinal parasite of humans in temperate climates with modern sanitation (Ashford, Hart and Williams, 1988). However, enterobiasis (pinworm infection) has likely affected human populations throughout the world for more than 10,000 years (Fry and Moore, 1969; Song, Cho, Kim and Choi, 2003). The parasite has such broad scope both historically and geographically, that it would be difficult to find a time in human history when pinworm was not present.

Written accounts of the disease throughout history, combined with archaeological data provide evidence for this lasting pandemic. Early medical writings verify the presence of human pinworm in China, India, the Middle East, and the Mediterranean. For example, Hippocrates (circa 460 BC–380 BC) was familiar with the clinical manifestations of the parasite, including the nightly migration of females to the perianal region to lay eggs, resulting in anal pruritus, irritation of the skin around the anus. These symptoms remain unchanged today (Fry and Moore, 1969; CDC, 2004). Coprolites positive for pinworm have been obtained through archaeological investigation at geographically distinct sites across North America and South America. The abundance of New World finds contrasts directly with a scarcity of Old World coprolite specimens positive for the parasite. Only three geographically distinct sites, located in Germany, China and Egypt, have yielded positive fecal samples in the Old World, although Horne (2002) suggests that this may be attributable to deficient inspection of coprolites from other Old World archaeological sites.

The finding of E. vermicularis eggs dating to 7837 BC ± 630 years in Danger Cave in western Utah marks the earliest recorded association of man with this “ubiquitous and exclusively human parasite” (Fry and Moore, 1969). Other specimens from nearby Hogup Cave date from around 4000 BC to as late as 600 BC, demonstrating that infestation was consistently present over a large span of time. Despite the fact that only 2.8 percent of coprolites from the caves contained pinworm eggs, the rate of infestation was probably much higher. Compared to modern studies of E. vermicularis employing the cellophane tape and swab technique to test for the presence of eggs, fecal examination shows less 5 percent of the actual infestation rate (Fry and Moore, 1969). Of the Old World coprolite specimens, the findings from the Dakhleh Oasis, in Egypt, are the oldest and most revealing, dating from 30 BC to AD 395. They represent the only known findings of E. vermicularis in ancient Africa (Horne, 2002). Thus, pinworm has had a presence on almost every continent, the notable exception being Antarctica.

While enterobiasis may affect human populations in nearly all climates, E. vermicularis is different from most other worms, it thrives in temperate regions (Juckett, 1995). According to Penner (1941), the viability of pinworm is reduced in environments where the temperature never falls below 62º Fahrenheit. This accounts for the lower rate of infestation in tropical and subtropical climes. While the parasite is spread mainly at the community and household levels, transmission of E. vermicularis also occurs between regions (global transmission) and between communities (regional transmission). The parasite could easily spread during travel or through trade. E. vermicularis eggs can survive independent of a host for up to two weeks, depending on the nature of the surrounding environment (CDC, 1993; CDC, 1999). Therefore, it is plausible to believe that the parasite could stow away on the surface of a package (ideally something that passes through many pairs of hands) in an aircraft or ship and spread to different areas. However, because of the high prevalence of E. vermicularis in nearly all temperate regions, travel and trade are not likely to affect the overall geographic distribution of the parasite. Within temperate regions, the parasite is endemic in nearly all communities. Which is to say, while E. vermicularis is spread between communities and regions, it doesn’t make a difference from a public health standpoint. In tropical regions, I suspect the parasite is more common in areas that are more or less developed and participate in frequent trade with countries in temperate regions.

At the community level, pinworm infection occurs more frequently in school-aged children (ages 5-14) than in the average population (Song, Cho, Kim and Choi, 2003). According to Rahman (1991), evidence suggests that the overall rate of infestation in the middle class residential community of Penang, Malaysia in 1991 was 30.6 percent (97 infected of 317 examined). The rate infestation for children ages 1-10 in the same community is 57.8 percent (37 infected of 64 examined; Figure 1).

Figure 1.  Presence of E. vermicularis eggs in Penang, Malaysia (Rahman, 1991)
        Age (years)	No. examined	No. positive
        1-10	        64	        37 (57.8 %)
	11-20		72		28 (38.9 %)
	21-30		78		12 (15.4 %)
	30-40		60		11 (18.3 %)
	> 40		43		9 (20.9 %)
	Total		317 		97 (30.6%)

Therefore, there is a definite correlation between the age of an individual and the prevalence of infestation, the greatest prevalence occurring in pre-adolescents. In urban and metropolitan areas, young children are more likely to be enrolled in preschools. These children are at a particular risk for enterobiasis, because of the ease of transmission in the preschool environment (Song, Cho, Kim and Choi, 2003). Young children are less likely to thoroughly wash their hands than older individuals when using the restroom. Moreover, young children are more likely to touch everything they can see and reach. This type of behavior and other juvenile habits such as nail biting and thumb sucking are significant factors facilitating the fecal-oral transmission of E. vermicularis. Juckett (1995) suggests that pinworm infections are often more severe in institutionalized patients than in the general population, however, he makes it clear that the parasite does not discriminate between people of different groups and socioeconomic levels. Furthermore, a study of risk factors for enterobiasis among preschool children in metropolitan Seoul in 2003 revealed that infection was more common in children ages 6-7 than in children ages 2-5. The researchers concluded that the older children had more opportunities for physical contact, facilitating the spread of the parasite (the younger children slept during recess). Additionally, infection rates were higher in preschools near traditional markets than those in residential areas, suggesting that sanitation and cleanliness also play important roles (Song, Cho, Kim and Choi, 2003).

Enterobiasis presents an interesting case at the household level. When one family member becomes infected, there is a high probability that all other family members will become infected. This high level of cross-infection is the result of an enormous number of eggs being produced in a short period of time, contaminating bedding, clothing and other surfaces around the home. Treatment is generally prescribed to the entire family, regardless of symptoms (Juckett, 1995). Reinfection is common within the household, thus rigorous cleaning is often recommended (Rahman, 1991). Again, enterobiasis is most common in schoolchildren, so one might expect that it would have greater prevalence in households with schoolchildren. Figure 1 shows that the parasite is least common in people between the ages of 21 and 30. Individuals within this age range are least likely to live in a household with children, and/or to have children of their own. Overcrowded living conditions may also contribute to a higher risk-factor for infestation (Song, Cho, Kim and Choi, 2003).

The relationship between humans in pinworms likely extends far into our past. Within communities and regions today, the public health issues surrounding enterobiasis are less related to the actual condition, and have more to do with the social stigma of having worms. Thus, widespread treatment is still worthwhile (Song, Cho, Kim and Choi, 2003). Although pinworm infection is mild, The Centers for Disease Control and Prevention (1993) maintains E. vermicularis is resilient, pervasive, and will not disappear any time soon.

Enterobiasis and the Hygiene Hypothesis

Enterobiasis has affected human populations for more than 10,000 years (Fry and Moore, 1969). However, in the last 50 years, infestation rates have dropped in industrialized countries. Around the middle of the 20th century, nearly half of Europe’s children were thought to be infested. Yet, recent data from Sweden suggests that infestation rates are now between 5% and 24% (Gale, 2002). These numbers reflect a broader trend of reduced helminth infestation among individuals in Western industrialized nations. On the other hand, rates of childhood asthma and childhood Type I (insulin-dependent) diabetes mellitus have risen risen in those nations(Gale, 2002). The hygiene hypothesis proposes that exposure to infectious agents (including Enterobius vermicularis) yields protection from developing those types of inflammatory diseases. Exposure to infectious agents is considerably reduced in Western industrialized nations when compared to developing nations, and this may explain the correlations between reduced helminth infestation rates and increased rates of allergic and autoimmune diseases in Western industrialized nations (Gale, 2002; Wilson and Maizels, 2004; Yazdanbakhsh and Matricardi, 2004).

While the exact role of parasites within the hygiene hypothesis remains controversial and is not fully understood, several studies have found a correlation between helminth infestation and inflammatory disease (Huang et al., 2002). In laboratory rodents, pinworm has been found to effectively inhibit the development of diabetes and other autoimmune diseases (Gale, 2002). According to Huang et al. (2002), there is also a negative association between enterobiasis and diseases such as asthma and rhinitis. They attribute this negative association to the protective effect of pinworm infestation against the development of inflammatory disease, though they do not rule out other possible mechanisms of association. In their study, 14.1% of individuals negative for pinworm infestation were diagnosed asthmatics, while only 9.3% of individuals positive for pinworm infestation had asthma. Additionally, 38.3% of individuals negative for pinworm infestation had been diagnosed with allergic rhinitis, but only 27.4% of individuals positive for pinworm infestation had received a diagnosis of allergic rhinitis.

As suggested in Wilson and Maizels (2004), cytokine modulation is central to the protective effect of parasite infestation against inflammatory disease. A cytokine is a protein responsible for “regulating the growth and activation of immune cells and mediating normal and pathologic inflammatory and immune responses”(Harrison’s Online, 2005). The cytokines responsible for dealing with immune responses to parasites include IL-10, as well as others. IL-10 is crucial in keeping the body’s immune responses under control and making sure that the presence of a parasite or other antigen does not provoke an overreaction. It is believed that helminths such as pinworm have the ability to stimulate production of regulatory cytokines like IL-10, ensuring that both host and parasite survive. These raised levels of IL-10 may also inhibit inflammatory responses to triggers such as allergens, protecting the individual from developing allergic and autoimmune diseases (Wilson and Maizels, 2004).

However, the mere presence of a parasitic infection does not guarantee a reduced likelihood of allergic and autoimmune diseases in an individual. The length of infestation must be prolonged enough for the body to adequately develop such a resistence. In populations where infestation is endemic and untreated, individuals are largely unaffected by allergic diseases. Helminth infestation in such areas may be characterized by either continuous infestation, or by a series of repeated episodes (Capron et al., 2004). However, even though Enterobius vermicularis is common throughout the industrialized world, it is often treated before any effective changes in the immune system can take place. According to Capron et al. (2004), the systematic eradication of helminth parasites in the West over the last 40 years, and the subsequent rise of allergic and autoimmune diseases, raises serious medical questions, particularly towards those scientists who have dedicated their lives to eliminating these parasites. Is it better to spend money treating a condition like enterobiasis, which is largely asymptomatic and harmless, thereby increasing the likelihood that rates of allergic and autoimmune disease will continue to rise, or to treat only those cases which are severe, in turn, decreasing rates of allergic and autoimmune disease? The diagnosis of parasitic infestation often carries a stigma, most people are not keen on the idea of a worm living inside them, but, there are points both for and against both sides of the issue.

The importance of this research lies in what it offers to immunologists. Understanding how the immunomodulatory properties of Enterobius vermicularis and other parasites influence the human immune response could be of great benefit to scientists developing treatments for immune-mediated diseases (Gale, 2002). Additionally, because it is the most common parasite in the industrialized West, a fuller understanding of the effects of Enterobius vermicularis on the human body would be a significant addition to the science of medicine.

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