Parasitic worm

Parasitic worms or helminths are a division of eukaryotic parasites that, unlike external parasites such as lice and fleas, live inside their host. They are worm-like organisms that live and feed off living hosts, receiving nourishment and protection while disrupting their hosts' nutrient absorption, causing weakness and disease. Those that live inside the digestive tract are called intestinal parasites. They can live inside humans as well as other animals.

Helminthology is the study of parasitic worms and their effect on their hosts. The word helminth comes from Greek hélmins, a kind of worm.

Categorization
Parasitic worms are categorized into three groups: cestodes (tapeworms), nematodes (roundworms), and trematodes (flukes). The following table shows the principal morphologic differences of these different families of helminths:

Note that ringworm (dermatophytosis) is actually caused by various fungi and not by a parasitic worm.

Reproduction and proliferation
Parasitic worms are sequential hermaphrodites and reproduce depending on the species of worm, either with the presence of a male and female worm, joining sperm and eggs, producing fertile eggs, such as hookworms, or by breaking off segments that contain both male and female sex organs that are able to produce fertile eggs without the presence of a male or female (e.g., tapeworms).

All worm offspring are passed on through poorly-cooked meat, especially pork, wild fish, and beef, contaminated water, feces and mosquitoes. However, it is estimated that 40 million Americans are infected with the most common roundworm in the United States, the pinworm.

Worm eggs or larvae or even adults enter the human body through the mouth, anus, nose, or skin, with most species attaching themselves to the intestinal tract. With the presence of digestive enzymes, worm egg shells are dissolved, releasing a brand-new worm; unlike its egg shell, the parasitic worm is protected from the body's powerful digestive enzymes by producing a protective keratin layer.

Acquisition
Helminths often find their way into a host through mosquito transmission, eating infected food, drinking contaminated water, and walking on infected soil. This is especially a problem in the developing world where food and water is usually unclean, and many people simply do not own shoes. Many walk miles barefoot only to collect contaminated water for their families, and as a result contract diseases and helminths.

Immune response
Response to worm infection in humans is a Th2 response in the majority of cases. Inflammation of the gut may also occur, resulting in cyst-like structures forming around the egg deposits throughout the body. The host's lymphatic system is also increasingly taxed the longer helminths propagate, as they excrete toxins after feeding. These toxins are released into the intestines to be absorbed by the host's bloodstream. This phenomenon makes the host susceptible to more common diseases such as seasonal viruses and bacterial infections.

Intestinal helminths
Intestinal helminths are a type of intestinal parasite that reside in the human gastrointestinal tract. They represent one of the most prevalent forms of parasitic disease. Scholars estimate that over a quarter of the world’s population is infected with an intestinal worm of some sort, with roundworm, hookworm, and whipworm infecting 1.47 billion people, 1.05 billion people, and 1.30 billion people, respectively. Furthermore, the World Bank estimates that 100 million people may experience stunting or wasting as a result of infection.

Because of their high mobility and lower standards of hygiene, school-age children are particularly vulnerable to these parasites. Overall, it is estimated that 400 million, 170 million, and 300 million children are infected with roundworm, hookworm, and whipworm. Children may also be particularly susceptible to the adverse effects of helminth infections due to their incomplete physical development and their greater immunological vulnerability.

Symptoms
In patients with a heavy worm load, parasite infection is frequently symptomatic. Conditions associated with intestinal helminth infection include intestinal obstruction, insomnia, vomiting, weakness, and stomach pains; while the natural movement of worms and their attachment to the intestine may be generally uncomfortable for their hosts. The migration of Ascaris larvae through the respiratory passageways can also lead to temporary asthma and other respiratory symptoms.

In addition to the low-level costs of chronic infection, helminth infection may be punctuated by the need for more serious, urgent care; for example, the World Health Organization found that worm infection is common reason for seeking medical help in a variety of countries, with up to 4.9% of hospital admissions in some areas resulting from the complications of intestinal worm infections and as many as 3% of hospitalizations attributable to ascariasis alone.

Also worth considering is the fact that the immune response triggered by helminth infection may drain the body’s ability to fight other diseases, making affected individuals more prone to co-infection. There are reasonable evidences indicating that helminthiasis is responsible for the unrelenting prevalence of AIDS and tuberculosis in developing, particularly African, countries. A review of several data clearly revealed that effective treatment of helminth infection reduces HIV progression and viral load, obviously by improving helminth-induced immune suppression.

Nutrition
One way in which intestinal helminths may impair the development of their human hosts is through their impact on nutrition. Intestinal helminth infection has been associated with problems such as vitamin deficiencies, stunting, anemia, and protein-energy malnutrition, which in turn affect cognitive ability and intellectual development. This relationship is particularly alarming because it is gradual and often relatively asymptomatic.

Parasite infection may affect nutrition in several ways. On the one hand, some scholars argue that worms may compete directly with their hosts for access to nutrients; both whipworm and roundworm are believed to impact their hosts in this way. Nonetheless, Watkins and Pollitt argue that the magnitude of this effect is likely to be minimal; after all, the nutritional requirements of these intestinal worms is small when compared with that of their host organism.

A more probable source of infection-induced malnutrition is the nutrient malabsorption associated with parasite presence in the body. For example, in both pigs and humans, Ascaris has been tied to temporarily induced lactose intolerance and Vitamin A, nitrogen, and fat malabsorption. Impaired nutrient uptake may result from direct damage to the intestine’s mucosal walls as a result of the worms’ presence, but it may also be a consequence of more nuanced changes such as chemical imbalances caused by the body’s reaction to the helminths. Alternatively, Watkins and Pollitt suggest that the worms’ release of protease inhibitors to defend against the body’s digestive process may impair the breakdown of other, nutritious substances as well. Levinger mentions this briefly in the case of whipworm. Finally, worm infections may also cause diarrhea and speed “transit time” through the intestinal system, further reducing the body’s opportunity to capture and retain the nutrients in food.

Worms may also contribute to malnutrition by creating anorexia. A decline in appetite and food consumption due to helminthic infection is widely recognized by the literature, with a recent study of 459 children in Zanzibar reporting that even mothers noticed spontaneous increases in appetite after their children underwent a deworming regime. Although the exact cause of such anorexia is not known, researchers believe that it may be a side effect of body’s immune response to the worm and the stress of combating infection. Specifically, some of the cytokines released in the immune response have been tied to anorexic reactions in animals.

Helminths may also affect nutrition by inducing iron-deficiency anemia. This is most severe in heavy hookworm infections, as N. Americanus and A. Duodenale feed directly on the blood of their host. Although the impact of individual worms is limited (each consumes about .02-.07 ml and .14-.26 ml of blood daily, respectively), this may nonetheless add up in individuals with heavy infections, since they may carry hundreds of worms at a given time. One scholar went so far as to predict that “the blood loss caused by hookworm was equivalent to the daily exsanguination of 1.5 million people,” while a study in Zanzibar showed that a 15¢ triannual application of Mebendazole could avert 0.25 l of blood loss per child per year.[25] Although whipworm is milder in its effects, it may also induce anemia as a result of the bleeding caused by its damage to the small intestine.

The connection between worm burden and malnutrition is further supported by studies indicating that deworming programs lead to sharp increases in growth; the presence of this result even in older children has led some scholars to conclude that “it may be easier to reverse stunting in older children than was previously believed.” Other, less clearly causal studies (see Oberhelman 1998) also show a strong correlation between worm burden and malnourishment among school-age children.

Delayed intellectual development
Once the links between helminth infection and various forms of malnutrition are established, there are a number of pathways by which parasite burden may affect cognition. For example, poor performance on normal growth indicators appears to be correlated with lower school achievement and enrollment, worse results on some forms of testing, and a decreased ability to focus; on the other hand, iron deficiency may result in “mild growth retardation,” difficulty with abstract cognitive tasks, and “lower scores...on tests of mental and motor development...[as well as] increased fearfulness, inattentiveness, and decreased social responsiveness” among very young children. Anemia has also been associated with reduced stamina for physical labor, a decline in the ability to learn new information, and “apathy, irritability, and fatigue.”

These connections are supported by a number of deworming studies. For example, using 47 students from the Democratic Republic of the Congo, Boivin and Giardani (1993) found that iron supplements acted as a complement to deworming medication, producing better effects on mental cognition when they were applied in conjunction than when they were individually administered. He hypothesized that this result was due to the fact that iron supplements may “improve [students’] physical well-being to the point of enhancing attentional or arousal mechanisms influential in learning and cognitive performance,” with deworming medication only acting to extend these benefits by further reducing the tendency to anemia.

Perhaps even more fascinating are a number of papers that take the study of intestinal helminth beyond the malnutrition-cognition link to focus on the connections between worm infections and memory formation. For example, Nokes et al. (1992) find that interventions to reduce whipworm infection in 159 Jamaican schoolchildren led to better “auditory short-term memory” and “scanning and retrieval of long-term memory;” particularly fascinating was his discovery that a nine-week period was all that was necessary for dewormed students to “catch up” to their worm-free peers in test performance. Nokes’ optimistic conclusion that “whipworm infection[‘s]...adverse effect on certain cognitive functions...is reversible by therapy” is particularly significant because it suggests that the effects of worms on intellectual performance may not be restricted to the mechanism of long-term malnutrition, since the physical and developmental effects of such malnutrition would theoretically be irreversible.

Also worth noting are the studies of Ezeamama et al. (2005) and Sakti et al. (1999), which studied worm burden in the Philippines and Indonesia, respectively. Both authors found significant negative impacts of helminthic infection on memory and fluency, findings that are particularly meaningful because they included controls for socioeconomic status, hemoglobin levels, and proxies of nutrition (nutritional status and stunting, respectively). As Ezeamama observes, these studies suggest “that undernutrition is not the primary mediator of the observed relationships” between worm infection and intellectual performance, particularly because their findings were significant in aspects of intellect that went beyond mere cognition and reaction time.

Finally, Watkins and Pollitt observe that, much as physical activity is “nutritionally mediated” as patients with heavy worm burden struggle to preserve energy and fight malnutrition, so too could “the poorly nourished mind similarly adapt...by reducing mental effort in the form of arousal and sustained attention.” While they find little evidence that this adaptation would provide benefits in the form of energy conservation, it is clear that the active course of ongoing parasitic disease could impose other, more direct limitations on an individual’s attention span.

School attendance and outcomes
The day-to-day costs of illness provide a strong explanation for yet another negative consequence of helminth infection, or the observation that it acts as “a very real barrier to children’s progress in school” as quantified by “outcome measures such as absenteeism, under-enrollment, and attrition.” Parasite-heavy students may be too weak to attend classes, or their families may be too indebted by medical bills and low worker productivity to pay for school enrollment fees. This effect may be conceptually distinct from previous findings about the impact of parasitism on cognition and learning; for example, Miguel and Kremer (2004) find that deworming programs improve school attendance by 25% without affecting test outcomes at all. Nonetheless, these effects may also be related: Bleakley (2007) found that school attendance and enrollment grew significantly in the school-age populations that benefited most from the Rockefeller Foundation’s deworming programs, leading to a long-term increase in income as well as a rise in literacy rates.

History
Public health campaigns to reduce helminth infections in the US may be traced as far back as 1910, when the Rockefeller Foundation began the fight against hookworm – the so-called “germ of laziness” – in the American South. This campaign was enthusiastically received by educators throughout the region; as one Virginian school observed: “‘children who were listless and dull are now active and alert; children who could not study a year ago are not only studying now, but are finding joy in learning...for the first time in their lives their cheeks show the glow of health.’” From Louisiana, a grateful school board added:" As a result of your treatment...their lessons are not so hard for them: they pay better attention in class and they have more energy...In short, we have here in our school-rooms today about 120 bright, rosy-faced children, whereas had you not been sent here to treat them we would have had that many pale-faced, stupid children."

Similar (albeit somewhat more imperialist) reports emerged from various other regions of the developing world at the time; for example, two scholars in Puerto Rico found that: "Over all the varied symptoms with which the unfortunate jibaro [peasant], infected by uncinaria [hookworm], is plagued, hangs the pall of a drowsy intellect, of a mind that has received a stunning blow...There is a hypochondriacal, melancholy, hopeless expression, which in severe cases deepens to apparent dense stupidity, with indifference to surroundings and lack of all ambition.’

Such observations made an intuitive connection between worm burden and intellectual performance, but even today this link is anything but well-established. While it seems that worms may impair cognition in some way, the mechanisms driving this relationship are still hotly debated.

Current efforts
One popular approach to intestinal helminth control is school deworming programs. These programs have a number of advantages. On the one hand, they allow health policymakers to take advantage of existing infrastructure and institutions for the dispensation of medical treatment; students already plan to attend school on a somewhat regular basis, and teachers can easily distribute the medication to their students without receiving any medical training.

School deworming programs have also been shown to have strong positive externalities. Miguel and Kramer (2004) used a difference-in-difference model to prove that deworming programs in some schools reduced the burden of disease in neighboring, untreated schools; other evidence suggests that deworming children also has strong benefits for adult infection rates, since children are a significant source of transmission.

The nature of the intestinal helminths and the medications available to treat them also favor universal deworming programs. Infection is generally diffuse, so it is worth treating a wide sample of the population; furthermore, a drug like albendazole is a cheap, safe intervention that is not particularly specific, and so can be used fairly effectively against all three of the main intestinal helminths (or any coinfection of them). Finally, because these worms cannot replicate inside of their hosts, reducing transmission may be the best way to reduce prevalence, and mass interventions on an annual or biannual basis may in fact be a reasonable means of achieving this goal.

Use in medicine
Parasitic worms have been used as a medical treatment for various diseases, particularly those involving an over active immune response. As humans have evolved with parasitic worms, proponents argue that they are needed for a healthy immune system. Scientists are looking to see if there is a connection between the prevention and control of parasitic worms and the increase in allergies such as hay-fever in developed countries. Parasitic worms may be able to damp down the immune system of their host, making it easier for them to live in the intestine without coming under attack. This may be one mechanism for their proposed medicinal effect.

The authors of a study published in Science magazine in April of 2011 suggest that there may be a link between the rising rates of metabolic syndrome in the developed worlds and the largely successful efforts of Westerners to eliminate intestinal parasites. The authors' work suggest that eosinophils (a type of white blood cell) in fat tissue play an important role in preventing insulin resistance by secreting interleukin 4, which in turn switches macrophages into "alternative activation". Alternatively activated macrophages are important to maintaining glucose homeostasis (i.e., blood sugar regulation). Helminth infection causes an increase in eosinophils. In the study, the authors fed rodents a high-fat diet in order to induce metabolic syndrome, and then injected them with helminths. Helminth infestation improved the rodents' metabolism. The authors concluded:

"Although sparse in blood of persons in developed countries, eosinophils are often elevated in individuals in rural developing countries where intestinal parasitism is prevalent and metabolic syndrome rare. We speculate that eosinophils may have evolved to optimize metabolic homeostasis during chronic chronic infections by ubiquitous intestinal parasites…."